hib vaccines: what is new ?? a review dr s g kasi bengaluru
TRANSCRIPT
Hib Vaccines What is new A Review
Dr S G KasiBengaluru
bull Improved Hib vaccinesbull New Hib Combos amp combos containing
DTaP+IPV+Hib combined with other infant vaccines
bull Effectiveness data on Hib vaccinesbull Cost-effectiveness data on Hib vaccines bull Changes in Hib epidemiology following use of
Hib vaccines
IMPROVED HIB VACCINES
Improved Hib vaccineshellip
bull Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid Glycoconjugate Journal Volume 28 Number 7 463-472
bull There is a need for a simple and high-yielding manufacturing process To improve the yield and rate of the reductive amination conjugation reaction used to make this vaccine some of the carboxyl groups of the carrier protein tetanus toxoid were modified to hydrazides which are more reactive than the ε -amine of lysine Other reaction parameters including the ratio of the reactants the size of the polysaccharide the temperature and the salt concentration were also investigated
Improved Hib vaccineshellip
bull Improved immune responses in mice using the novel chitosan adjuvant ViscoGel with a Haemophilus influenzae type b glycoconjugate vaccine VaccineVolume 29 Issue 48 8 November 2011 Pages 8965-8973
bull Mixing Act-HIB with ViscoGel induced significantly enhanced IgG1 and IgG2a titers in serum (p lt 005)
bull The antigen dose could be reduced ten-fold in combination with ViscoGel and the antibody titers observed were similar to 10 μg Act-HIB administered alone
bull The Act-HIB specific cellular response was stronger in mice vaccinated together with ViscoGel (p lt 005)
NEW COMBOS WITH HIB amp COMBOS CONTAINING DTAP+IPV+HIB COMBINED WITH OTHER INFANT VACCINES
bull A phase III randomized controlled study to assess and compare the immunogenicity and tolerability of single and multi-dose vials of DTwP-Hib a fully liquid quadravalent vaccine and their comparison with TETRAct-Hib vaccine in Indian infants aged 6ndash14 weeks Vaccine Vol 29 48 8 Nov 2011 8773-79
bull Postvaccination geometric mean titres for each component did not differ significantly between the single dose vial and multi dose vial subgroups and among the two study groups
bull Adverse events observed were within the range quoted in literature
Made in INDIA vs the ldquoForeign brandrdquo
bull Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children Vaccine Vol 7 4 2011451 ndash 57
bull Post-primary immunization 100 seroprotection was noted for Diphtheria Tetanus Hepatitis B and PRP-Hib components in both the vaccine groups
bull For pertussis response was 961 in SIIL and 954 in GSK groupbull The overall safety profile as well as persistence of antibodies against all vaccine
components up to the time of booster immunization was comparable between the SIIL and GSK groups
bull A marked rise of all antibody concentrations indicated effective primingbull The booster dose was safe well tolerated with a significant increase in antibody
concentrations of all the vaccine antigens in both the groups
bull One-year post-primary antibody persistence and booster immune response to a DTaP-IPVPRP~T vaccine (Pentaxim) given at 18 - 19 months of age in South African children primed at 6 10 and 14 weeks of age with the same vaccine S Afr Med J 2011101879-883
bull A DTaP-IPVPRP~T vaccinewas given to 182 healthy children in South Africa at 18 - 19 months of age following priming with the same vaccine plus a monovalent HBV at 6 10 and 14 weeks of age
bull One month after primary vaccination at least 943 of participants were seroprotected against tetanus diphtheria poliovirus and Hib infection
bull Before the booster dose the SP rates ranged from 657 to 100bull One month after the booster dose SP rates were 977 for Hib 1000
for diphtheria and 100 for tetanus and poliovirus types 1 2 3bull At least 957 of participants had fourfold post-booster increases in anti-
pertussis antibody titresbull The DTaP-IPVPRP~T vaccine booster was well tolerated with fever
ge390degC in only 17 of participants
DTwP+IPV+HBVHib
bull A randomized dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPw-HBV-IPVHib) vaccine versus co-administration of DTPw-HBVHib and IPV vaccines in 12 to 24 month old Filipino toddlers
bull Human Vaccines Volume 8 Issue 3 March 2012
DTwP+IPV+HBVHib
bull Three formulations of a combined candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPVHib GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose half-dose and one-third dose as compared to available stand-alone IPV vaccines) were evaluated when administered to healthy toddlers Controls received separately administered licensed DTPw-HBVHib and IPV vaccines
bull Three hundred and twelve Filipino children were vaccinated in their second year of life
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull Improved Hib vaccinesbull New Hib Combos amp combos containing
DTaP+IPV+Hib combined with other infant vaccines
bull Effectiveness data on Hib vaccinesbull Cost-effectiveness data on Hib vaccines bull Changes in Hib epidemiology following use of
Hib vaccines
IMPROVED HIB VACCINES
Improved Hib vaccineshellip
bull Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid Glycoconjugate Journal Volume 28 Number 7 463-472
bull There is a need for a simple and high-yielding manufacturing process To improve the yield and rate of the reductive amination conjugation reaction used to make this vaccine some of the carboxyl groups of the carrier protein tetanus toxoid were modified to hydrazides which are more reactive than the ε -amine of lysine Other reaction parameters including the ratio of the reactants the size of the polysaccharide the temperature and the salt concentration were also investigated
Improved Hib vaccineshellip
bull Improved immune responses in mice using the novel chitosan adjuvant ViscoGel with a Haemophilus influenzae type b glycoconjugate vaccine VaccineVolume 29 Issue 48 8 November 2011 Pages 8965-8973
bull Mixing Act-HIB with ViscoGel induced significantly enhanced IgG1 and IgG2a titers in serum (p lt 005)
bull The antigen dose could be reduced ten-fold in combination with ViscoGel and the antibody titers observed were similar to 10 μg Act-HIB administered alone
bull The Act-HIB specific cellular response was stronger in mice vaccinated together with ViscoGel (p lt 005)
NEW COMBOS WITH HIB amp COMBOS CONTAINING DTAP+IPV+HIB COMBINED WITH OTHER INFANT VACCINES
bull A phase III randomized controlled study to assess and compare the immunogenicity and tolerability of single and multi-dose vials of DTwP-Hib a fully liquid quadravalent vaccine and their comparison with TETRAct-Hib vaccine in Indian infants aged 6ndash14 weeks Vaccine Vol 29 48 8 Nov 2011 8773-79
bull Postvaccination geometric mean titres for each component did not differ significantly between the single dose vial and multi dose vial subgroups and among the two study groups
bull Adverse events observed were within the range quoted in literature
Made in INDIA vs the ldquoForeign brandrdquo
bull Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children Vaccine Vol 7 4 2011451 ndash 57
bull Post-primary immunization 100 seroprotection was noted for Diphtheria Tetanus Hepatitis B and PRP-Hib components in both the vaccine groups
bull For pertussis response was 961 in SIIL and 954 in GSK groupbull The overall safety profile as well as persistence of antibodies against all vaccine
components up to the time of booster immunization was comparable between the SIIL and GSK groups
bull A marked rise of all antibody concentrations indicated effective primingbull The booster dose was safe well tolerated with a significant increase in antibody
concentrations of all the vaccine antigens in both the groups
bull One-year post-primary antibody persistence and booster immune response to a DTaP-IPVPRP~T vaccine (Pentaxim) given at 18 - 19 months of age in South African children primed at 6 10 and 14 weeks of age with the same vaccine S Afr Med J 2011101879-883
bull A DTaP-IPVPRP~T vaccinewas given to 182 healthy children in South Africa at 18 - 19 months of age following priming with the same vaccine plus a monovalent HBV at 6 10 and 14 weeks of age
bull One month after primary vaccination at least 943 of participants were seroprotected against tetanus diphtheria poliovirus and Hib infection
bull Before the booster dose the SP rates ranged from 657 to 100bull One month after the booster dose SP rates were 977 for Hib 1000
for diphtheria and 100 for tetanus and poliovirus types 1 2 3bull At least 957 of participants had fourfold post-booster increases in anti-
pertussis antibody titresbull The DTaP-IPVPRP~T vaccine booster was well tolerated with fever
ge390degC in only 17 of participants
DTwP+IPV+HBVHib
bull A randomized dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPw-HBV-IPVHib) vaccine versus co-administration of DTPw-HBVHib and IPV vaccines in 12 to 24 month old Filipino toddlers
bull Human Vaccines Volume 8 Issue 3 March 2012
DTwP+IPV+HBVHib
bull Three formulations of a combined candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPVHib GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose half-dose and one-third dose as compared to available stand-alone IPV vaccines) were evaluated when administered to healthy toddlers Controls received separately administered licensed DTPw-HBVHib and IPV vaccines
bull Three hundred and twelve Filipino children were vaccinated in their second year of life
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
IMPROVED HIB VACCINES
Improved Hib vaccineshellip
bull Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid Glycoconjugate Journal Volume 28 Number 7 463-472
bull There is a need for a simple and high-yielding manufacturing process To improve the yield and rate of the reductive amination conjugation reaction used to make this vaccine some of the carboxyl groups of the carrier protein tetanus toxoid were modified to hydrazides which are more reactive than the ε -amine of lysine Other reaction parameters including the ratio of the reactants the size of the polysaccharide the temperature and the salt concentration were also investigated
Improved Hib vaccineshellip
bull Improved immune responses in mice using the novel chitosan adjuvant ViscoGel with a Haemophilus influenzae type b glycoconjugate vaccine VaccineVolume 29 Issue 48 8 November 2011 Pages 8965-8973
bull Mixing Act-HIB with ViscoGel induced significantly enhanced IgG1 and IgG2a titers in serum (p lt 005)
bull The antigen dose could be reduced ten-fold in combination with ViscoGel and the antibody titers observed were similar to 10 μg Act-HIB administered alone
bull The Act-HIB specific cellular response was stronger in mice vaccinated together with ViscoGel (p lt 005)
NEW COMBOS WITH HIB amp COMBOS CONTAINING DTAP+IPV+HIB COMBINED WITH OTHER INFANT VACCINES
bull A phase III randomized controlled study to assess and compare the immunogenicity and tolerability of single and multi-dose vials of DTwP-Hib a fully liquid quadravalent vaccine and their comparison with TETRAct-Hib vaccine in Indian infants aged 6ndash14 weeks Vaccine Vol 29 48 8 Nov 2011 8773-79
bull Postvaccination geometric mean titres for each component did not differ significantly between the single dose vial and multi dose vial subgroups and among the two study groups
bull Adverse events observed were within the range quoted in literature
Made in INDIA vs the ldquoForeign brandrdquo
bull Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children Vaccine Vol 7 4 2011451 ndash 57
bull Post-primary immunization 100 seroprotection was noted for Diphtheria Tetanus Hepatitis B and PRP-Hib components in both the vaccine groups
bull For pertussis response was 961 in SIIL and 954 in GSK groupbull The overall safety profile as well as persistence of antibodies against all vaccine
components up to the time of booster immunization was comparable between the SIIL and GSK groups
bull A marked rise of all antibody concentrations indicated effective primingbull The booster dose was safe well tolerated with a significant increase in antibody
concentrations of all the vaccine antigens in both the groups
bull One-year post-primary antibody persistence and booster immune response to a DTaP-IPVPRP~T vaccine (Pentaxim) given at 18 - 19 months of age in South African children primed at 6 10 and 14 weeks of age with the same vaccine S Afr Med J 2011101879-883
bull A DTaP-IPVPRP~T vaccinewas given to 182 healthy children in South Africa at 18 - 19 months of age following priming with the same vaccine plus a monovalent HBV at 6 10 and 14 weeks of age
bull One month after primary vaccination at least 943 of participants were seroprotected against tetanus diphtheria poliovirus and Hib infection
bull Before the booster dose the SP rates ranged from 657 to 100bull One month after the booster dose SP rates were 977 for Hib 1000
for diphtheria and 100 for tetanus and poliovirus types 1 2 3bull At least 957 of participants had fourfold post-booster increases in anti-
pertussis antibody titresbull The DTaP-IPVPRP~T vaccine booster was well tolerated with fever
ge390degC in only 17 of participants
DTwP+IPV+HBVHib
bull A randomized dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPw-HBV-IPVHib) vaccine versus co-administration of DTPw-HBVHib and IPV vaccines in 12 to 24 month old Filipino toddlers
bull Human Vaccines Volume 8 Issue 3 March 2012
DTwP+IPV+HBVHib
bull Three formulations of a combined candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPVHib GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose half-dose and one-third dose as compared to available stand-alone IPV vaccines) were evaluated when administered to healthy toddlers Controls received separately administered licensed DTPw-HBVHib and IPV vaccines
bull Three hundred and twelve Filipino children were vaccinated in their second year of life
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
Improved Hib vaccineshellip
bull Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid Glycoconjugate Journal Volume 28 Number 7 463-472
bull There is a need for a simple and high-yielding manufacturing process To improve the yield and rate of the reductive amination conjugation reaction used to make this vaccine some of the carboxyl groups of the carrier protein tetanus toxoid were modified to hydrazides which are more reactive than the ε -amine of lysine Other reaction parameters including the ratio of the reactants the size of the polysaccharide the temperature and the salt concentration were also investigated
Improved Hib vaccineshellip
bull Improved immune responses in mice using the novel chitosan adjuvant ViscoGel with a Haemophilus influenzae type b glycoconjugate vaccine VaccineVolume 29 Issue 48 8 November 2011 Pages 8965-8973
bull Mixing Act-HIB with ViscoGel induced significantly enhanced IgG1 and IgG2a titers in serum (p lt 005)
bull The antigen dose could be reduced ten-fold in combination with ViscoGel and the antibody titers observed were similar to 10 μg Act-HIB administered alone
bull The Act-HIB specific cellular response was stronger in mice vaccinated together with ViscoGel (p lt 005)
NEW COMBOS WITH HIB amp COMBOS CONTAINING DTAP+IPV+HIB COMBINED WITH OTHER INFANT VACCINES
bull A phase III randomized controlled study to assess and compare the immunogenicity and tolerability of single and multi-dose vials of DTwP-Hib a fully liquid quadravalent vaccine and their comparison with TETRAct-Hib vaccine in Indian infants aged 6ndash14 weeks Vaccine Vol 29 48 8 Nov 2011 8773-79
bull Postvaccination geometric mean titres for each component did not differ significantly between the single dose vial and multi dose vial subgroups and among the two study groups
bull Adverse events observed were within the range quoted in literature
Made in INDIA vs the ldquoForeign brandrdquo
bull Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children Vaccine Vol 7 4 2011451 ndash 57
bull Post-primary immunization 100 seroprotection was noted for Diphtheria Tetanus Hepatitis B and PRP-Hib components in both the vaccine groups
bull For pertussis response was 961 in SIIL and 954 in GSK groupbull The overall safety profile as well as persistence of antibodies against all vaccine
components up to the time of booster immunization was comparable between the SIIL and GSK groups
bull A marked rise of all antibody concentrations indicated effective primingbull The booster dose was safe well tolerated with a significant increase in antibody
concentrations of all the vaccine antigens in both the groups
bull One-year post-primary antibody persistence and booster immune response to a DTaP-IPVPRP~T vaccine (Pentaxim) given at 18 - 19 months of age in South African children primed at 6 10 and 14 weeks of age with the same vaccine S Afr Med J 2011101879-883
bull A DTaP-IPVPRP~T vaccinewas given to 182 healthy children in South Africa at 18 - 19 months of age following priming with the same vaccine plus a monovalent HBV at 6 10 and 14 weeks of age
bull One month after primary vaccination at least 943 of participants were seroprotected against tetanus diphtheria poliovirus and Hib infection
bull Before the booster dose the SP rates ranged from 657 to 100bull One month after the booster dose SP rates were 977 for Hib 1000
for diphtheria and 100 for tetanus and poliovirus types 1 2 3bull At least 957 of participants had fourfold post-booster increases in anti-
pertussis antibody titresbull The DTaP-IPVPRP~T vaccine booster was well tolerated with fever
ge390degC in only 17 of participants
DTwP+IPV+HBVHib
bull A randomized dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPw-HBV-IPVHib) vaccine versus co-administration of DTPw-HBVHib and IPV vaccines in 12 to 24 month old Filipino toddlers
bull Human Vaccines Volume 8 Issue 3 March 2012
DTwP+IPV+HBVHib
bull Three formulations of a combined candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPVHib GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose half-dose and one-third dose as compared to available stand-alone IPV vaccines) were evaluated when administered to healthy toddlers Controls received separately administered licensed DTPw-HBVHib and IPV vaccines
bull Three hundred and twelve Filipino children were vaccinated in their second year of life
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
Improved Hib vaccineshellip
bull Improved immune responses in mice using the novel chitosan adjuvant ViscoGel with a Haemophilus influenzae type b glycoconjugate vaccine VaccineVolume 29 Issue 48 8 November 2011 Pages 8965-8973
bull Mixing Act-HIB with ViscoGel induced significantly enhanced IgG1 and IgG2a titers in serum (p lt 005)
bull The antigen dose could be reduced ten-fold in combination with ViscoGel and the antibody titers observed were similar to 10 μg Act-HIB administered alone
bull The Act-HIB specific cellular response was stronger in mice vaccinated together with ViscoGel (p lt 005)
NEW COMBOS WITH HIB amp COMBOS CONTAINING DTAP+IPV+HIB COMBINED WITH OTHER INFANT VACCINES
bull A phase III randomized controlled study to assess and compare the immunogenicity and tolerability of single and multi-dose vials of DTwP-Hib a fully liquid quadravalent vaccine and their comparison with TETRAct-Hib vaccine in Indian infants aged 6ndash14 weeks Vaccine Vol 29 48 8 Nov 2011 8773-79
bull Postvaccination geometric mean titres for each component did not differ significantly between the single dose vial and multi dose vial subgroups and among the two study groups
bull Adverse events observed were within the range quoted in literature
Made in INDIA vs the ldquoForeign brandrdquo
bull Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children Vaccine Vol 7 4 2011451 ndash 57
bull Post-primary immunization 100 seroprotection was noted for Diphtheria Tetanus Hepatitis B and PRP-Hib components in both the vaccine groups
bull For pertussis response was 961 in SIIL and 954 in GSK groupbull The overall safety profile as well as persistence of antibodies against all vaccine
components up to the time of booster immunization was comparable between the SIIL and GSK groups
bull A marked rise of all antibody concentrations indicated effective primingbull The booster dose was safe well tolerated with a significant increase in antibody
concentrations of all the vaccine antigens in both the groups
bull One-year post-primary antibody persistence and booster immune response to a DTaP-IPVPRP~T vaccine (Pentaxim) given at 18 - 19 months of age in South African children primed at 6 10 and 14 weeks of age with the same vaccine S Afr Med J 2011101879-883
bull A DTaP-IPVPRP~T vaccinewas given to 182 healthy children in South Africa at 18 - 19 months of age following priming with the same vaccine plus a monovalent HBV at 6 10 and 14 weeks of age
bull One month after primary vaccination at least 943 of participants were seroprotected against tetanus diphtheria poliovirus and Hib infection
bull Before the booster dose the SP rates ranged from 657 to 100bull One month after the booster dose SP rates were 977 for Hib 1000
for diphtheria and 100 for tetanus and poliovirus types 1 2 3bull At least 957 of participants had fourfold post-booster increases in anti-
pertussis antibody titresbull The DTaP-IPVPRP~T vaccine booster was well tolerated with fever
ge390degC in only 17 of participants
DTwP+IPV+HBVHib
bull A randomized dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPw-HBV-IPVHib) vaccine versus co-administration of DTPw-HBVHib and IPV vaccines in 12 to 24 month old Filipino toddlers
bull Human Vaccines Volume 8 Issue 3 March 2012
DTwP+IPV+HBVHib
bull Three formulations of a combined candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPVHib GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose half-dose and one-third dose as compared to available stand-alone IPV vaccines) were evaluated when administered to healthy toddlers Controls received separately administered licensed DTPw-HBVHib and IPV vaccines
bull Three hundred and twelve Filipino children were vaccinated in their second year of life
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
NEW COMBOS WITH HIB amp COMBOS CONTAINING DTAP+IPV+HIB COMBINED WITH OTHER INFANT VACCINES
bull A phase III randomized controlled study to assess and compare the immunogenicity and tolerability of single and multi-dose vials of DTwP-Hib a fully liquid quadravalent vaccine and their comparison with TETRAct-Hib vaccine in Indian infants aged 6ndash14 weeks Vaccine Vol 29 48 8 Nov 2011 8773-79
bull Postvaccination geometric mean titres for each component did not differ significantly between the single dose vial and multi dose vial subgroups and among the two study groups
bull Adverse events observed were within the range quoted in literature
Made in INDIA vs the ldquoForeign brandrdquo
bull Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children Vaccine Vol 7 4 2011451 ndash 57
bull Post-primary immunization 100 seroprotection was noted for Diphtheria Tetanus Hepatitis B and PRP-Hib components in both the vaccine groups
bull For pertussis response was 961 in SIIL and 954 in GSK groupbull The overall safety profile as well as persistence of antibodies against all vaccine
components up to the time of booster immunization was comparable between the SIIL and GSK groups
bull A marked rise of all antibody concentrations indicated effective primingbull The booster dose was safe well tolerated with a significant increase in antibody
concentrations of all the vaccine antigens in both the groups
bull One-year post-primary antibody persistence and booster immune response to a DTaP-IPVPRP~T vaccine (Pentaxim) given at 18 - 19 months of age in South African children primed at 6 10 and 14 weeks of age with the same vaccine S Afr Med J 2011101879-883
bull A DTaP-IPVPRP~T vaccinewas given to 182 healthy children in South Africa at 18 - 19 months of age following priming with the same vaccine plus a monovalent HBV at 6 10 and 14 weeks of age
bull One month after primary vaccination at least 943 of participants were seroprotected against tetanus diphtheria poliovirus and Hib infection
bull Before the booster dose the SP rates ranged from 657 to 100bull One month after the booster dose SP rates were 977 for Hib 1000
for diphtheria and 100 for tetanus and poliovirus types 1 2 3bull At least 957 of participants had fourfold post-booster increases in anti-
pertussis antibody titresbull The DTaP-IPVPRP~T vaccine booster was well tolerated with fever
ge390degC in only 17 of participants
DTwP+IPV+HBVHib
bull A randomized dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPw-HBV-IPVHib) vaccine versus co-administration of DTPw-HBVHib and IPV vaccines in 12 to 24 month old Filipino toddlers
bull Human Vaccines Volume 8 Issue 3 March 2012
DTwP+IPV+HBVHib
bull Three formulations of a combined candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPVHib GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose half-dose and one-third dose as compared to available stand-alone IPV vaccines) were evaluated when administered to healthy toddlers Controls received separately administered licensed DTPw-HBVHib and IPV vaccines
bull Three hundred and twelve Filipino children were vaccinated in their second year of life
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull A phase III randomized controlled study to assess and compare the immunogenicity and tolerability of single and multi-dose vials of DTwP-Hib a fully liquid quadravalent vaccine and their comparison with TETRAct-Hib vaccine in Indian infants aged 6ndash14 weeks Vaccine Vol 29 48 8 Nov 2011 8773-79
bull Postvaccination geometric mean titres for each component did not differ significantly between the single dose vial and multi dose vial subgroups and among the two study groups
bull Adverse events observed were within the range quoted in literature
Made in INDIA vs the ldquoForeign brandrdquo
bull Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children Vaccine Vol 7 4 2011451 ndash 57
bull Post-primary immunization 100 seroprotection was noted for Diphtheria Tetanus Hepatitis B and PRP-Hib components in both the vaccine groups
bull For pertussis response was 961 in SIIL and 954 in GSK groupbull The overall safety profile as well as persistence of antibodies against all vaccine
components up to the time of booster immunization was comparable between the SIIL and GSK groups
bull A marked rise of all antibody concentrations indicated effective primingbull The booster dose was safe well tolerated with a significant increase in antibody
concentrations of all the vaccine antigens in both the groups
bull One-year post-primary antibody persistence and booster immune response to a DTaP-IPVPRP~T vaccine (Pentaxim) given at 18 - 19 months of age in South African children primed at 6 10 and 14 weeks of age with the same vaccine S Afr Med J 2011101879-883
bull A DTaP-IPVPRP~T vaccinewas given to 182 healthy children in South Africa at 18 - 19 months of age following priming with the same vaccine plus a monovalent HBV at 6 10 and 14 weeks of age
bull One month after primary vaccination at least 943 of participants were seroprotected against tetanus diphtheria poliovirus and Hib infection
bull Before the booster dose the SP rates ranged from 657 to 100bull One month after the booster dose SP rates were 977 for Hib 1000
for diphtheria and 100 for tetanus and poliovirus types 1 2 3bull At least 957 of participants had fourfold post-booster increases in anti-
pertussis antibody titresbull The DTaP-IPVPRP~T vaccine booster was well tolerated with fever
ge390degC in only 17 of participants
DTwP+IPV+HBVHib
bull A randomized dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPw-HBV-IPVHib) vaccine versus co-administration of DTPw-HBVHib and IPV vaccines in 12 to 24 month old Filipino toddlers
bull Human Vaccines Volume 8 Issue 3 March 2012
DTwP+IPV+HBVHib
bull Three formulations of a combined candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPVHib GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose half-dose and one-third dose as compared to available stand-alone IPV vaccines) were evaluated when administered to healthy toddlers Controls received separately administered licensed DTPw-HBVHib and IPV vaccines
bull Three hundred and twelve Filipino children were vaccinated in their second year of life
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children Vaccine Vol 7 4 2011451 ndash 57
bull Post-primary immunization 100 seroprotection was noted for Diphtheria Tetanus Hepatitis B and PRP-Hib components in both the vaccine groups
bull For pertussis response was 961 in SIIL and 954 in GSK groupbull The overall safety profile as well as persistence of antibodies against all vaccine
components up to the time of booster immunization was comparable between the SIIL and GSK groups
bull A marked rise of all antibody concentrations indicated effective primingbull The booster dose was safe well tolerated with a significant increase in antibody
concentrations of all the vaccine antigens in both the groups
bull One-year post-primary antibody persistence and booster immune response to a DTaP-IPVPRP~T vaccine (Pentaxim) given at 18 - 19 months of age in South African children primed at 6 10 and 14 weeks of age with the same vaccine S Afr Med J 2011101879-883
bull A DTaP-IPVPRP~T vaccinewas given to 182 healthy children in South Africa at 18 - 19 months of age following priming with the same vaccine plus a monovalent HBV at 6 10 and 14 weeks of age
bull One month after primary vaccination at least 943 of participants were seroprotected against tetanus diphtheria poliovirus and Hib infection
bull Before the booster dose the SP rates ranged from 657 to 100bull One month after the booster dose SP rates were 977 for Hib 1000
for diphtheria and 100 for tetanus and poliovirus types 1 2 3bull At least 957 of participants had fourfold post-booster increases in anti-
pertussis antibody titresbull The DTaP-IPVPRP~T vaccine booster was well tolerated with fever
ge390degC in only 17 of participants
DTwP+IPV+HBVHib
bull A randomized dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPw-HBV-IPVHib) vaccine versus co-administration of DTPw-HBVHib and IPV vaccines in 12 to 24 month old Filipino toddlers
bull Human Vaccines Volume 8 Issue 3 March 2012
DTwP+IPV+HBVHib
bull Three formulations of a combined candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPVHib GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose half-dose and one-third dose as compared to available stand-alone IPV vaccines) were evaluated when administered to healthy toddlers Controls received separately administered licensed DTPw-HBVHib and IPV vaccines
bull Three hundred and twelve Filipino children were vaccinated in their second year of life
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull One-year post-primary antibody persistence and booster immune response to a DTaP-IPVPRP~T vaccine (Pentaxim) given at 18 - 19 months of age in South African children primed at 6 10 and 14 weeks of age with the same vaccine S Afr Med J 2011101879-883
bull A DTaP-IPVPRP~T vaccinewas given to 182 healthy children in South Africa at 18 - 19 months of age following priming with the same vaccine plus a monovalent HBV at 6 10 and 14 weeks of age
bull One month after primary vaccination at least 943 of participants were seroprotected against tetanus diphtheria poliovirus and Hib infection
bull Before the booster dose the SP rates ranged from 657 to 100bull One month after the booster dose SP rates were 977 for Hib 1000
for diphtheria and 100 for tetanus and poliovirus types 1 2 3bull At least 957 of participants had fourfold post-booster increases in anti-
pertussis antibody titresbull The DTaP-IPVPRP~T vaccine booster was well tolerated with fever
ge390degC in only 17 of participants
DTwP+IPV+HBVHib
bull A randomized dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPw-HBV-IPVHib) vaccine versus co-administration of DTPw-HBVHib and IPV vaccines in 12 to 24 month old Filipino toddlers
bull Human Vaccines Volume 8 Issue 3 March 2012
DTwP+IPV+HBVHib
bull Three formulations of a combined candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPVHib GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose half-dose and one-third dose as compared to available stand-alone IPV vaccines) were evaluated when administered to healthy toddlers Controls received separately administered licensed DTPw-HBVHib and IPV vaccines
bull Three hundred and twelve Filipino children were vaccinated in their second year of life
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
DTwP+IPV+HBVHib
bull A randomized dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPw-HBV-IPVHib) vaccine versus co-administration of DTPw-HBVHib and IPV vaccines in 12 to 24 month old Filipino toddlers
bull Human Vaccines Volume 8 Issue 3 March 2012
DTwP+IPV+HBVHib
bull Three formulations of a combined candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPVHib GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose half-dose and one-third dose as compared to available stand-alone IPV vaccines) were evaluated when administered to healthy toddlers Controls received separately administered licensed DTPw-HBVHib and IPV vaccines
bull Three hundred and twelve Filipino children were vaccinated in their second year of life
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
DTwP+IPV+HBVHib
bull Three formulations of a combined candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPVHib GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose half-dose and one-third dose as compared to available stand-alone IPV vaccines) were evaluated when administered to healthy toddlers Controls received separately administered licensed DTPw-HBVHib and IPV vaccines
bull Three hundred and twelve Filipino children were vaccinated in their second year of life
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
DTwP+IPV+HBVHibbull Each DTPw-HBV-IPVHib formulation was non-inferior to control
in terms of pre-defined criteria for IPV immunogenicity Post-vaccination GMTs against each poliovirus type were increased between 42 and 379-fold over pre-vaccination titers
bull Non-inferiority to other vaccine antigens was also demonstratedbull The safety profile of the 3 DTPw-HBV-IPVHib formulations
resembled licensed DTPw-HBVHib and IPV in terms of the frequency and intensity of adverse reactions after vaccination
bull Further investigation of DTPw-HBV-IPVHib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
Co administration with Hep A vaccine
bull Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age Pediatr Infect Dis J 2011 Sep30(9)e164-9
bull Coadministration of the 3 vaccines did not impact immunogenicity of the HAV DTaP or Hib vaccines Vaccines were well tolerated in all groups
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6 10 and 14 Weeks of Age in Healthy South African Infants Vaccine April 2011 - Volume 30 - Issue 4 - pp e68-e74
bull Conclusions The new fully liquid investigational hexavalent vaccine in the Expanded Program on Immunization schedule withwithout hepatitis B at birth is highly immunogenic and safe compared with control vaccines warranting further development
bull
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
HibMenCYbull Immunogenicity and Safety of H influenza Type b N
meningitidis CY Conjugate Vaccine in Infants Pediatrics 2011 2011127e1375 Originally published online May 29
bull The HibMenCY was immunogenic against MenC and MenY and induced antindashpolyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
Hib CV in Adults with immunodeficiency
bull 32 patients with CRF and 19 controls were immunized with one dose of pediatric Hib vaccine
bull Serum antibody levels were assessed pre- and 1 6 9 months post-vaccine
bull Functional antibody activity was studied using a serum bactericidal assay
bull 4 week post-vaccination 97 developed protective antibody with a 14-fold increase in Ab titers
bull In 91 the antibody exhibited bactericidal activitybull In the majority of patients protective antibody persisted 9
months post-vaccine
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull The pediatric Hib vaccine is highly immunogenic in this group with higher response compared to other vaccines administered to such patients (hepatitis B and pneumococcal vaccines)
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
EFFECTIVENESS DATA ON HIB VACCINES
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull Effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine for Prevention of Meningitis in Senegal Pediatric Infectious Disease Journal May 2011 Vol 30 Issue 5 - pp 430-32
bull The adjusted vaccine effectiveness for ge2 doses was 958 (95 confidence interval 679ndash994)
bull Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
Chile amp Columbia No Booster Uruguay amp Argentina With Booster
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
COST-EFFECTIVENESS DATA ON HIB VACCINES
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull A decision analytic model was used to estimate morbidity and mortality from Hib meningitis Hib pneumonia and other types of Hib disease with and without the vaccine
bull Estimated costs per discounted DALY averted are US$ 9323 in Belarus and US$ 267 in Uzbekistan
bull The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull COST EFFECTIVENESS STUDY OF HIB VACCINATION FOR CHILDREN BELOW 5 YEARS IN JORDAN Issam al- KhawajaMD JMF
bull Effectiveness of Haemophilus influenzae Type b Conjugate Vaccine Introduction Into Routine Childhood Immunization in Kenya KD Cowgill M Ndiritu J Nyiro et al The effectiveness of the vaccine was 88 similar to other countries both developing and developed
bull Economic evaluation of Haemophilus influenzae type B vaccination in Indonesia a cost-effectiveness analysis Journal of Public Health | Vol 29 No 4 pp 441ndash448
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
CHANGES IN HIB EPIDEMIOLOGY FOLLOWING USE OF HIB VACCINES
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
CURRENT EPIDEMIOLOGY AND TRENDS IN INVASIVE HAEMOPHILUS INFLUENZAE DISEASEmdashUNITED STATES 1989ndash2008 CLIN INFECT DIS (2011) 53 (12) 1230-1236
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
Changes in Hib epidemiology 1
bull Between 1989 to 2008 for the general US popln 65 drop from 439 to 155100000 people
bull For children lt 5 years a 95 reduction from 3718 100000 children in 1989 to 309100000 children
bull 1989 Mean age- 28y 32lt 5y
bull 2008 Mean age- 63y 48 gt 65y
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
Changes in Hib epidemiology 2
bull Large increases in the incidence of infection caused by non-b types and nontypeable strains were observed
bull The largest increase in incidence was observed for serotype f (006 cases per 100 000 population in 1989 to 025 cases per 100 000 population in 2008 317 increase)
bull Serotype f was observed primarily among adults with 83 of cases reported in adults aged 18 years
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
Changes in Hib epidemiology in young children
bull 6324838(13) in lt5yrsbull 401632 (635) in lt1yrbull 175632 (277) in lt1 month
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull Invasive Haemophilus influenzae in British Columbia non-Hib and non-typeable strains causing disease in children and adults International Journal of Infectious DiseasesVolume 15 Issue 3 March 2011 Pages e167-e173
bull 98 isolates in 2008-09bull 66 were caused by non-typeable strains followed by
serotypes b (12) a (10) f (10) and e (1) bull Serotypes b and f and non-typeable strains caused disease
mainly in adults over 18 years of agebull Serotype a caused disease mainly in children under the age of 2
yearsbull 31 identified as genotypic β-lactamase-negative ampicillin-
resistant (BLNAR) strains
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination South Africa 2003ndash2009 Vaccine 201111066
bull S A started routine infant immunization against Hib vaccine in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose
bull After an initial rapid marked decline detection rates of Hib disease in children lt5 years increased from 07 per 100000 population in 2003 to 13100000 in 2009 (p lt 0001)
bull 51 were classified as vaccine failuresbull 53 were not HIV infectedbull Of vaccine failures 55 occurred among case patients ge18
months oldbull In November 2010 children in South Africa began receiving a
booster dose of HibCV as part of a pentavalent vaccine
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H influenzae type b in Brazil
bull 3910 H influenzae isolated from cerebrospinal fluid or blood from meningitis cases from 1990 to 2008 were analysed
bull Hib accounted for 98 of H influenzae meningitis isolates received during 1990ndash1999 versus 59 during 2000ndash2008
bull Non-b serotypes increased from 1 to 19 bull NTHi increased from 2 to 22 bull Higher proportions of non-b serotypes and NTHi than Hib
were isolated from blood rather than cerebrospinal fluid
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
4 important conclusionshellip
1 A shift in the distribution of capsular serotypes of invasive H influenzae disease has occurred with nontypeable strains replacing type b strains as the most common blood- stream isolates
2 Shift in the peak age incidence The most common disease manifestation of invasive H influenzae infection is bacteremia caused by nontypeable strains in adults
3 Infections caused by encapsulated non-type b serotypes especially serotypes a and f have been observed in selected geographic regions
4 Selected studies suggest an increasing incidence of invasive H influenzae infection particularly by nontypeable strains
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
IMMUNOGLOBULIN DEFICIENCY IN CHILDREN WITH HIB VACCINE FAILURE
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection
bull A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection
bull 19 (112) children had immunoglobulin deficiency including IgA (n = 12) IgM (n = 5) and all three immunoglobulin classes (n = 2)
bull Immunoglobulin deficiency was associated with younger age (lt2 years) at initial Hib disease amp
bull Parental reporting of their child receiving gt2 antibiotic courses annually in early childhood
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
Vaccine failure
bull Enhanced surveillance of Hib vaccine failure cases in the UK between 1992 and 1998 revealed that around 20 of children had co-morbidities including prematurity malignancy developmentaldelay Down syndrome and neutropenia
bull In addition enhanced national surveillance revealed that 21 of 106 children immunised with the Hib conjugate vaccine in infancy had Ig deficiency when tested after recovery from their acute infection
Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood Clin Infect Dis 200031973ndash80
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
bull Accelerating introduction of new vaccines barriers to introduction and lessons learned from the recent type b vaccine experience Haemophilus influenzae Rana Hajjeh Phil Trans R Soc B 2011 366 2827-2832
bull 3 major areas of focusbull communications to increase awareness about the various
factors needed for evidence-based decisions that meet a countryrsquos health goals
bull research activities to answer key questions that support vaccine introduction and long-term programme sustainability
bull coordination with the various stakeholders at global regional and country levels to ensure successful programme implementation
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-
- Hib Vaccines What is new A Review
- Slide 2
- Improved Hib vaccines
- Improved Hib vaccineshellip
- Slide 5
- New combos with hib amp Combos containing DTaP+IPV+Hib combined with other infant vaccines
- Slide 7
- Slide 8
- Slide 9
- DTwP+IPV+HBVHib
- Slide 11
- Slide 12
- Co administration with Hep A vaccine
- Slide 14
- HibMenCY
- Hib CV in Adults with immunodeficiency
- Slide 17
- Effectiveness data on Hib vaccines
- Slide 19
- Slide 20
- Cost-effectiveness data on Hib vaccines
- Slide 22
- Slide 23
- Changes in Hib epidemiology following use of Hib vaccines
- Current Epidemiology and Trends in Invasive Haemophilus influenzae DiseasemdashUnited States 1989ndash2008 Clin Infect Dis (2011) 53 (12) 1230-1236
- Changes in Hib epidemiology 1
- Changes in Hib epidemiology 2
- Changes in Hib epidemiology in young children
- Slide 29
- Slide 30
- Slide 31
- Slide 32
- 4 important conclusionshellip
- Immunoglobulin deficiency in children with hib vaccine failure
- Slide 35
- Vaccine failure
- Slide 37
- Slide 38
-