weather forecasting approach of transfusion services to new pathogen ( emerging infectious agents )...

66
Forecasting Forecasting Approach of Transfusion Approach of Transfusion Services to Services to New Pathogen ( Emerging New Pathogen ( Emerging Infectious Agents ) Infectious Agents ) Dr. R. N. Makroo Director & Sr.Consultant Dept. of Transfusion Medicine,Molecular Biology & Transplant Immunology Indraprstha Apollo Hospitals

Upload: abraham-erik-washington

Post on 26-Dec-2015

219 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Weather Forecasting Weather Forecasting Approach of Transfusion Services to Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) New Pathogen ( Emerging Infectious Agents )

Dr. R. N. Makroo Director & Sr.Consultant

Dept. of Transfusion Medicine,Molecular Biology & Transplant Immunology

Indraprstha Apollo Hospitals

Page 2: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Introduction

• Over the past 10 to 15 years the leading causes of allogeneic blood transfusion-related morbidity and mortality have shifted from being mainly due to transfusion-transmitted infections (TTIs) to the non-infectious events associated with blood transfusions

Page 3: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

• Nonetheless, despite many advances in the prevention of TTIs, TTIs continue to be associated with on-going morbidity and mortality.

• This is due to the emergence of new pathogens (or re-emergence of known pathogens) associated with TTIs.

Introduction

Page 4: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Components of Blood Safety

• National and local incidence/prevalence

• Criteria/Standards/

Guide-lines

• Selection of donor population

• Donor questioning

• Laboratory testing

• Product handling

• Record keeping

• cGMP/Quality

Page 5: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Outline• Status of blood donors• Current status of testing & risks • Emerging infections in Developed Vs Developing

countries– Background– Approach– Examples

• VIRUSES, BACTERIAS, PRIONS,PARASITES, TICK BORN etc.

Page 6: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Emerging Infections

“Clinically distinct conditions whose frequency in humans has increased over the past two decades”

Page 7: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Factors Contributing to Emergence of Infectious Disease

• Human demographics and behavior

• Technology and industry

• Economic development and land use

• International travel and commerce– Concept of global village

• Microbial adaptation and change

• Breakdown of public health measures

Page 8: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Wor

ld P

opul

atio

n in

billio

ns (

)

Day

s to

Circ

umna

viga

te (

) th

e Glo

be

Year1850

0

400

350

300

250

200

150

100

50

2000

0

1900 1950

1

2

3

4

5

6

Speed of Global Travel in Relation toWorld Population Growth

From: Murphy and Nathanson. Semin. Virol. 5, 87, 1994

Page 9: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Emerging Infections in Western World

• New Agent• Expanding Range• Imported• Re-emergent• Newly recognized• Patient changes

– BSE/vCJD– Babesia/Ehrlichia– Chagas disease, WNV– Malaria– HHV-6, 8, TTV, SENV.– CMV, B19?

NAT is performed on essentially all blood and plasma donations in the United States

The decrease in risk over time for HIV, HCV, and HBV hasbeen truly dramatic.

Page 10: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Concern High,Action Favored

Benefit HighAction Favored

vCJD

CJD

Lyme

HGV, etc

RMSF

HAV

Ehrlichia

B19

Babesia

T.cruzi

BacteriaHHV 8

HHV 6

HIV

Chlamydia, LeptospiraBartonella, etc

Ebola etc Leishmania

Malaria

WNV

HCV

HBV

Page 11: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

All volunteer donors

HBsAg test

AIDS high-risk exclusions

Anti-HIV test

ALT/HBcAb testsAnti-HCV test

Improved HCV tests

1965 1970 1975 1980 1985 1990 1995 2000

Year of Transfusion

% R

ecip

ien

ts I

nfe

cte

d

Tobler and Busch, Clin Chem 1997.

25

20

15

10

5

0

Blood is much safer, but is it safe enough?

NAT Implementation

11

Page 12: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services
Page 13: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Infections in India: our problems

• HIV, HCV, HBV AND MALARIA: Major problem to Blood safety

• NAT not Implemented to reduce the incidence

HIV, HCV AND HBV

New New VirusesViruses

Action Favored

Page 14: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

IS REALLY INDIA AT THE TOP IN BLOOD SAFETY ???

NO Very little concept of regular repeat V.B.D

Absence of Universal Hepatitis B core antibody Screening

WITH NO NAT No Uniformity in the Blood Transfusion Services

ITS REALLY A LONG WAY TO GO

AND IT’S A STEEP HILL TO CLIMB

Page 15: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Indian Scenario

• BTS in India is mainly hospital based

• Blood Banking is governed by Drugs & Cosmetic Act

• 2609 licensed blood banks under different?? control

• Gap in demand and supply of blood

• Majority of blood donors are still replacement donors

• Voluntary donors constitute only 65% (NACO 2011)

• Majority of voluntary blood donors are first time donors

• Little concept of regular repeat voluntary blood donation

15

Page 16: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Challenges of Blood Screening in India

• Population ~1.2 billion includes 2.5 million with HIV, 15million with HCV, and 43 million with HBV

• High blood donor seroprevalence of 0.3%,0.7%, and 1.4% for anti- HIV-1, anti-HCV, and HBsAg, respectively increases transfusion transmission risk of these viruses

• High percentage (~ 35%) of replacement donors compared to volunteer donors

• 2609 ( 36%) government , (28%)private hospitals, (14%) NGO & (21%)Stand alone private blood banks, many of which have poorly regulated practices, collect about ~ 8 million donations annually.

• Currently nucleic acid testing (NAT) for screening is not mandatory which would need to be adapted to our low volume setting

16

Page 17: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Threat to Safety of Blood Supply

• Current immunoassay blood screening tests detect virus-induced antibodies or viral antigens, not the virus itself – Window Period donations

• Window period between initial infection and detectable seroconversion

• Chronic carrier state in asymptomatic donor - test negative on antibody screen

• Atypical genetic variants of viruses• Laboratory errors (very low: zero-0.05%, further

reduction by >1 assays)

17

Page 18: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Window Period

Infection

Detection by Serology markers

Win

dow

Peri

od

HIV Ab Negative

HBsAg Negative

HCV Ab Negative

18

Page 19: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Closing the gap!-To enhance blood safety

• Implementation of new tests to narrow down the window period

• Combining >1 assays - 2 assays complement each other and decrease FP and FN results

• Increasing regular repeat voluntary donations (lower TTI incidence)

19

Page 20: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Why ID-NAT is preferred over Minipool?

• High prevalence countries – Greater number of reactives• Low Regular Repeat Voluntary Donors – Higher

percentage of reactives• Pooling results in a dilution of viremic samples

proportionate to the pool size• MP-Reduces sensitivity. Release of infected units.• MP requires additional process time, equipment,

manpower, lab space & environment for pooling and resolution of positive pool.

• High prevalence countries have higher number of pools reactive. Delayed release of negative blood units from a positive pool. 1-2 days delay.

• Higher contamination and error chance.

20

Page 21: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

In Asia: Why ID NAT

• Dr. J. P. Allain from Cambridge University- Global Expert on Hepatitis B in Blood Transfusions quotes:

• Study with 143 samples from South East Asia showed:

• 70.7% of these would be missed in pools of 6 and 87.5% in pools of 10 assuming a sensitivity of 5 IU per ml

• 37% of the donors had less than 5 IU/ml, and over 40% had between 5 and 30 IU/mL

• Additionally in India the predominant HBV is of genotype D which is characterized by low viral load with 10% having undetectable HBV DNA.

21

Page 22: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Why Nucleic Acid Testing? Reduction of Window Period

22Busch MP et al. Transfusion 2005;45:254-264, Assal A et al. Transfusion 2009;49:289-300, Weusten J et al, Transfusion 2011;51:203-15

Page 23: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

HIV-1 Minipool NAT Failures

Dwyre et al, Vox Sang 2011

23

Page 24: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

HBV detection superiority with ID-NAT

Dwyre et al, Vox Sang 2011

24

Page 25: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

TMA HCV superiority sensitivity

Sarrazin et al, Journal of Clinical Virology 2002

Comandor et al, Am J Gastroenterology 2001

20120919 25Dr. Makroo Novartis Symposia

Page 26: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

HCV Reactivity (April, 2006 – March 2012)Profile of 7 HCV NAT Yields Total tested: 117,622Need for NAT and IDT NAT

1. Makroo RN,Chowdhry M,Minimole, Rosamma NL & Thakur U. Six years Experience on Impact of Individual Donor Nucleic Acid Testing for Hepatitis C Viral RNA at a Tertiary Care Hospital of North India. 65th Annual AABB meeting Oct 6-9 Boston MA2. Raghuraman et al. Occurrence of False Positives during Testing for Antibodies to Hepatitis C Virus among Volunteer Blood Donors in India,” J .Clin. Microbiol. 2003; 41:1788-1790.

• The low viral load of 52-99 IU/mL indicates the requirement of ID-NAT testing

•0.39% (458) Sero prevalence for anti-HCV.•0.17% (191) concordant Sero and NAT positives•7 HCV NAT only yields1 , *4 Co-infections: HCV + HBV (ELISA HBV only)•267 Serology yields - High false positivity of HCV ab tests2 - Need for NAT

S/NUltrio Discrim Assay

Reactive Serology* Viral Load IU/ml

1 HCV Non Reactive 562 HCV Non Reactive 523 HCV HBsAg 974 HCV Anti HBc, Total 585 HCV Anti HBc, total 626 HCV Anti HBc, Total 997 HCV Non Reactive 53

26

Page 27: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

HBV Reactivity (April, 2006 – March 2012)Total tested: 94,247 recalculate numbersProfile of HBsAg, anti HBc and HBV DNA1

• Presence of HBV DNA is indicative of infectivity•99.85% of anti HBc reactive are negative by Procleix Ultrio HBV assay •Very high attrition of donations if excluded for anti HBc at 9.19% positivity

HBsAg ELISA Anti HBc ELISA Number Percentage HBV DNA- Percentage (Number)

Positive Non reactive 156 0.16

Positive Reactive 978 1.03

Negative Reactive 8660 9.19 0.15 (#13)

Negative Reactive 0.007(#9) Occult NAT yields*

Negative Non Reactive 0.006 (#8) WP NAT yields*

Positive ?? 0.75 (#887) Serology NAT* concordants

Positive ?? 0.37 (# 442) Sero yields*

27

Page 28: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

ID-NAT YIELDS

RN Makroo et al. Indian J Med Res 127, February 2008, pp 140-147

28

Multicenter evaluation of individual donor nucleic acid testing (NAT) for simultaneous detection of human immunodeficiency virus -1 & hepatitis B & C viruses in Indian blood donors

Page 29: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

29

ID NAT Yield: 1 in 1500

67 in 100,000 donations

6700 infected donors per 10 million donations

6700 X 3 =

app. 20000 infections per 10 million donations

Annual cost of medical management1.5-2.5 lacs/pt

= app. INR 400 crores annual expenditure

Cost of liver transplant = 20-25 lacs/pt + 10,000/month

If 2000 patients undergo LT/ yr

= app. INR 500 crores annual expenditure

= app. Cost for doing 10 million ID-NAT = 800 x 10 million= INR 800 crores

Each donor infects 3 patients

Page 30: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

30

Page 31: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

NAT and Hepatitis

• Most transfusion-transmitted infections are caused by blood donated during the early sero-negative window period, and for HBV also during Occult status.

• Direct detection of viral nucleic acids by using the NAT technologies significantly improves the blood safety by shortening the window period and detecting occult cases.

• Since 1999, all developed and increasing number of developing countries around the world have adopted routine NAT blood screening. Countries have moved to ID-NAT after including HBV.

• NAT on individual donations (ID NAT) provide the highest level of safety to the blood supply.

31

Page 32: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

HTLV-1 & 2

• HTLV-I identified in 1978 in a Japanese patient.

• Causes adult T-cell leukemia and lymphoma (ATL) and tropical spastic paraparesis (TSP) also known as HTLV-I-associated myelopathy or HAM.

• Prevalent globally but is endemic in Japan, the Caribbean, South

• America, and West and Central Africa, where infection rates are above 1%.

• HTLV-II identified in 1982 in a patient with hairy-cell leukemia

• HTLV-II is found in American Indian populations and in some populations of intravenous drug users

• The overall incidence in first-time donors in the United States is around 40 per 100,000. In repeat donors a rate of approximately 1.6 per 100,000 person years was identified from 1991 to 1996

• In India its prevalence was found to be 0.18% and was concluded that prevalence of HTLV-I/II carriers in India seems to be negligible and is not a major public health hazard. Hence, routine screening of Indian blood donors for antibody to HTLV-I/II is not warranted due to its low prevalence.

32

Rossi’s principle of Transfusion Medicine. 4th Ed

Kumar H, Gupta PK. Is seroprevalence of HTLV-I/II among blood donors in India relevant? Indian J Pathol Microbiol. 2006 Oct;49(4):532-4.

Page 33: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Malaria• Caused by plasmodium species

– P. Falciparum: IP is 12 days, 40-60% malaria cases worldwide, >95% of all malarial deaths

– P. vivax: 30-40% malaria cases, rarely fatal

– P. ovale: West Afica

– Others: P. malariae and P. knowlesi

• Transmitted by : female anopheles mousquito

• Transmitted by cellular blood components: whole blood or PRC or by components contaminated with red cells

• At 2-8 o C : P falciparum can survive for 2-3 weeks

• Post transfusion malaria (PTM): severe disease in pregnant women and immuno deficient individuals

33

Page 34: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Malaria

• Detection– Microscopic: blood films – gold standard– Macroscopic – Tests for malaria Ab: EIA, indirect immunofluoresence, western blot– Tests for malaria Ag: RIA, EIA– Tests for metabolic products: LDH ( all species) and HRP-2

( falciparum)- method of choice for screening of blood donors– Other : nucleic acid based tests and immunofluorscence for

detection of plasmodia within the erythrocytes

• Prevalence of Malaria at our centre in 2011: 0.019%

34

Page 35: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Cytomegalovirus

• It is a herpes virus; sub-family: betaherpesvirinae

• Incubation period: 4-8 weeks

• Also known as HHV-5

• CMV can manifest itself in many organs.

• Therefore, CMV is a major problem in immuno-suppressed patients requiring transfusion therapy.

• 95% of blood donors in India are sero positive for CMV

35

Page 36: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

36

95% of blood donors in India are sero positive for CMV

Page 37: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Cytomegalovirus

• Patients who should receive components that are selected or processed to minimize the risk of CMV infectivity include the following:

– Transplant recipients ( CMV negative)

– Patients with severe immunodeficiency

– Fetus (intrauterine transfusion)

– CMV-negative pregnant females

– Low birth weight premature infants and neonates

• It is essential for all blood banks to maintain a list of CMV negative donors

• Leukoreduced blood (<5 X 106 Leukocytes) = CMV negative blood

37

Page 38: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Cytomegalovirus• Donor testing

– ELISA ( IgM or IgG or IgM + IgG )

– Complement fixation test

– Heamagglutination

– Western blot

– PCR based assays

38Rossi’s principles of Transfusion Medicine, 4th ed

Page 39: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Trypanosomiasis (Chaga’s disease)

• Causative Agent : Trypanosoma cruzi

• Transmitted by triatomines or reduviid bugs (kissing bugs)

• Acute phase lasts 4 to 6 weeks, characterized by mild symptoms such as fever, malaise, and edema of the face, as well as lymphadenopathy and hepatosplenomegaly.

• The fatality rate in the acute phase is usually less than 5%.

• Up to decades later, 15% to 30% of carriers will develop serious sequelae involving the heart and gastrointestinal tract (mega-colon and mega-esophagus).

• Chagas’ disease kills an estimated 13,000 people annually, mostly from cardiac complications. Barrett MP, Burchmore RJS, Stich A, et al. The trypanosomiases. Lancet 2003;362:1469-80

• In India infections caused by T. evansi have been reported from Maharastra India. Joshi PP et al Am. J. Trop. Med. Hyg., 73(3), 2005, pp. 491–495

• Screening test: ELISA

• Confirmatory testing :RIPA (not FDA approved)

• Other methods: donor exclusion and pathogen inactivation

39

Page 40: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

• Are platelets of greatest risk?• few platelet units in look-backs• transfusion cases: almost all involved

platelets• survival and localization studies:

whole unit < 7 daysplatelets < 4 daysred cells < 2 daysplasma none

T. Cruzi in blood units

Page 41: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Transfusion Transmitted Leptospirosis

• Causative agent: Leptospira interrogans

• Incubation period : 2-21 days

• Endemic in : Maharashtra, West Bengal, Orissa, Gujarat, Tamil Nadu & Andaman islands

• Spreads by direct or indirect contact with urine of infected animals

• Symptoms: influenza like illness

• 80% clear infection spontaneously, 10% suffer from complications while it is fatal in another 10%

• Methods of detection

– Dark field microscopy

– culture

– Detection of IgM antibody

– PCR based assays

41

Page 42: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Transfusion Transmitted Leptospirosis

42

Of 794 DFM positive samples, 155 were cultured on liquid EMJH medium.

Results

Page 43: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Brucellosis

• Causative agent: B. melitensis, B. suis and B. abortus

• Zoonotic infection transmitted to humans primarily by consumption of unpasteurized milk and milk products

• Common presenting symptom are fever, fatigue, malaise, chills, sweats, headaches, myalgia, arthralgia, and weight loss

• Widespread in rural india

• Transfusion transmitted brucellosis: severe infection in immuno supressed, neonates and pregnant females

• Diagnostic methods– Blood cultures– Antigen detection by ELISA– Antibody detection: IgM and IgG – Agllutination : Rose Bengal Plate agg. (RBPT )and standard tube agg test (SAT) for screening

purposes

43

It is suggested that, in areas endemic for brucellosis, blood donors should be questioned about symptoms of brucellosis, and if suspected, serological tests for brucellosis should be indicated before blood transfusion. At the same time, the prevalence of the disease among animals should be reduced with effective animal disease control programs.Akçakus M et al. Brucella melitensis in blood cultures of two newborns due to exchange transfusion.Turk J Pediatr. 2005 Jul-Sep;47(3):272-4.

Page 44: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Creutzfeldt- Jakob disease (CJD)• It is transmissible spongiform encephalopathies (TSEs), comprise a spectrum

of diseases in animals and humans.

• In animals, these diseases include scrapie in sheep and goats, chronic wasting disease in deer and elk, and transmissible mink encephalopathy.

• Bovine spongiform encephalopathy (BSE) was first described in cattle in the United Kingdom (UK)

• In humans it causes fatal progressive dementia and motor disturbances

• Iatrogenic transmission of sporadic CJD has occurred via neurosurgical instrumentation and electroencephalogram (EEG) electrodes, corneal and dura mater grafts, and cadaveric pituitary-derived growth and follicular stimulating hormones.

• Blood transfusion results in Variant CJD (vCJD), first described in 1996.

44National CJD Surveillance Unit. CJD statistics Edinburgh, UK: NCJDSU, 2008. [Available at http://www.cjd.ed.ac.uk/fi gures.htm(May 16, 2008).]

Page 45: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Creutzfeldt- Jakob disease (CJD)

• Pathogenesis – presence of abnormal prion protein (PrPTSE) within the central nervous system and

also in the follicular dendritic cells of peripheral lymphoid tissues including tonsils, spleen, lymph nodes, and gut-associated lymphoid tissue

• Donor screening methods

– Permanent deferral of donors • family history of CJD• Recipients of growth hormone and FSH of human origin• Recipients of human dura matter and corneal grafts• Permanent residents of U.K.

– Detection of PRPTSE peripheral blood• Immunoblotting with proteinase K digestion and gel electrophoresis has been

enhanced using phosphotungstic acid precipitation and chemiluminescence• Capillary immunoelectrophoresis following proteinase K digestion and

competitive antibody binding45

Page 46: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Distribution of TSE Infectivity in Blood Components

Plasma 25 - 30%

Buffy Coat 35 - 45%

RBC 20 - 25%

Wh

ole

Blo

od

Page 47: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Newer viruses: Dengue • Dengue is one of the most serious mosquito borne viral disease of humans.

• Transmitted by : Aedes mosquito

• Estimated number of Dengue cases per annum worldwide :50–100 million

• Estimated number of severe forms of the disease: 500.000 (0.5% a 1%)

• Dengue like illness date back to more than 200 years ago

• 1779-1780 in Asia, Africa and North America

• Viral etiology established by the 1940s

• Global pandemic in Southeast Asia after World War II

47

Historical background

Page 48: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Dengue : the virus• There are 4 distinct serotypes: DENV-1, DENV-2, DENV-3, DENV-4• Family: Flaviviridae; Genus: Flavivirus• All serotypes produce a similar illness and induce a life-long immunity that is specific

to the infecting serotype.• However, although the four serotypes are related, the humoral immune response

does not provide cross protective immunity against each other.

48

Transmission by Blood Transfusion

•In the 2001 one case of dengue transmission through bone marrow transplantation in Puerto Rico

•In 2002 1 case transmitted by red blood cell transfusion were reported in Hong Kong.

•In both cases, donors made their donation during the viremic period but 1 to 2 days before the onset of symptoms.

•Later they developed classical dengue disease.

Page 49: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

A 52-year-old, asymptomatic, repeat blood donor gave blood on July 15, 2007. An investigation of all recipients of his blood products was initiated after he informed the blood bank that he had had a fever the day after donation. The stored serum sample was positive for dengue virus type 2, as ascertained by means of a polymerase-chain-reaction (PCR) assay.

Tambyah et al. Dengue Hemorrhagic Fever Transmitted by Blood Transfusion N Engl J Med 2008; 359:1526-1527

(National University of Singapore, Singapore 119074, Singapore)

49Highly prevalent nowPrevalent from centuries

Page 50: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Is there any impact of Dengue Epidemic on transfusion ?

• Do not have a precise information on the percentage of individuals who is asymptomatic during a given epidemic.

• Literature reports provide estimates from 30% to 70% of asymptomatic individual at an epidemic.

• Also largely unknown is the level and length of viremic period among asymptomatic individuals.

• It is obvious that a short and low level viremia will have a moderate impact on the risk of dengue transmission by transfusion.

Therefore, The asymptomatic carriers may act as a source of platelets to the symptomatic patients !

50

Page 51: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

West Nile Virus

• Causative agent: a flavivirus, first recognized in 1937

• Wide distribution: in Africa, Europe, Asia, Australia, and, in the past decade, in Northern America.

• WNV mainly infects birds and is normally transmitted by mosquito (Aedes)

• The incubation period is between 3 and 15 days in humans

• 80% of infections being asymptomatic or with a mild flu-like illness. In rare cases (fewer than 1% of those infected), a more severe disease results and fatal encephalitis can occur.

• Asking donors about pre-donation headache and fever was found to have no effect on blood safety. (Orton SL et al. Self-reported symptoms associated with West Nile virus infection in RNA-positive blood donors.Transfusion 2006;46:272-7).

• The risk of transfusion transmission is associated with a period of viremia occurring around 3 days after infection and lasting around a week.

• Since July 2003, the US and Canadian blood supply has been screened using WNV NAT

• Both minipool and ID-NAT assays are available.

51

Page 52: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

TT virus, SEN V, GBV-C/HGV• TT Virus

– DNA unenveloped , non hepatotropic virus

– named for the patient from whom it was first isolated in Japan

– Genus Circoviridae.

– Transmitted by orofecal and transfusion route

– Transfusion route is not significant in TTV epidemiology

• SEN V– SENV is not 1 virus but rather 8 diverse strains;

– 2 of these strains (SENV-D and SENV-H): causes of transfusion-associated non-A–E hepatitis

– SENV is clearly transmitted by Transfusion

– Although SENV is clearly transmitted by transfusion, these data are insufficient to establish a causal relationship between SEN V and TAH

• GBV-C/HGV– Enveloped RNA virus

– Virus genome similar to HCV

– Transmitted through blood transfusion

– High Risk groups:

• IV drug abusers

• Hemodialysis patients

• Multiple transfused patients52

Page 53: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Bacterial contamination of blood products

53

Popular organisms

•Y Enterocolitica•Pseudomonas•E. coli•Klebsiella•Proteus•Propionibacterium•Serratia sp•Coag neg staphylococcus•Staph aureus•streptococcus

•Staph Epidermidis•Bacillus sp•Staph aureus•Micrococcus•Diphtheroids

RBC Platelets

Bacterial contamination of plateletsis specially problematic as they are stored at RT

Page 54: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Sources of contamination

54

• Donor bacteremia

• Phlebotomy core

• Skin surface contaminants

• Containers and disposables

• Environment

Page 55: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Comparison of Residual Risks

HIV

HBVHCV

19961996199419941992199219901990198819881986198619841984

1:1001:100

1:10001:1000

1:101:10 000000

1:100 0001:100 000

1:1 000 0001:1 000 000

19981998 20002000

Transmission risk, per unit

Updated from: Goodnough LT Updated from: Goodnough LT e t al. NEJMe t al. NEJM 1999;341:126- 1999;341:126-77

20022002

BacterialBacterialContaminationContamination

(platelets)(platelets)

SepticSepticFatalitiesFatalities(platelets)(platelets)

ClinicalSepsis

(platelets)

Page 56: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

56

Page 57: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

• Donor deferral

• Skin decontamination before phlebotomy

• Diversion of first 15 ml of blood

• Closed system of component preparation

• Apheresis products

57

Page 58: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

• Storage time– 24 hour hold

• Storage temperature – Cool liquid stored platelets– Frozen platelets

58

Page 59: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

• Visual inspection– Discoloration– Clumping– Loss of swirling

• Biochemical parameters– Platelet pH– Glucose consumption– Limulus amebocyte lysate assay

(yersinia endotoxin)

• Microscopy– Gram stain– Acridine orange 59

Page 60: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

• Culture (gold standard)– BacT/Alert : CO2 production

– Pall BDS : O2 production

• Rapid tests– Verax PGD

• Others– PCR– Chemiluminesence based

universal bacterial rRNA probe60

Page 61: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

• Pathogen reduction technology

• Room temperature hold

• Filtration 61

Page 62: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

STRATEGIES TO PREVENT INFECTION

StorageStoragePathogen inactivationPathogen inactivationScreening testsScreening tests

Processing quality controlProcessing quality control Donor eligibilityDonor eligibility

Indications for transfusionIndications for transfusion

TracebilityTracebilityHemovigilanceHemovigilance

Page 63: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

Summary

63

• Emerging infections may impact blood safety

• Continuing, structured review of field needed

• Risk assessment is performed as required

• Selected agents are further evaluated in the field and the laboratory

• Interventions: testing, interview, call-back

• Partnerships with industry, public health agencies

Page 64: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

The Road Ahead

Commitment of blood banking community to provide safe blood.

Active involvement of health economists keeping in mind that good quality costs.

64

Page 65: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

BLOOD IS A PRICELESS GIFT.....

.....but the final product costs

65

Page 66: Weather Forecasting Approach of Transfusion Services to New Pathogen ( Emerging Infectious Agents ) Weather Forecasting Approach of Transfusion Services

THANK YOUTHANK YOU

Lets keep these unexpected passengers out