current state of infectious diseases in southern africa diana dickinson

Current State of Infectious Current State of Infectious Diseases in Southern AfricaDiseases in Southern Africa

Diana DickinsonDiana Dickinson

09/2006 Facing the Challenges of Infecti09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathous Diseases in Africa- the Role of Mathematical Modellingematical Modelling

OverviewOverview

HIV epidemic) HIV epidemic) already dealt with, just a few personalalready dealt with, just a few personal

TB ) TB ) insightsinsights

Pneumococcus in detailPneumococcus in detailOther regional problemsOther regional problems– MalariaMalaria– Hepatitis BHepatitis B– Herpes SimplexHerpes Simplex– Cervical cancer associated with HPVCervical cancer associated with HPV– KS associated with HHSV8KS associated with HHSV8


Challenges of coping with the increases Challenges of coping with the increases and changing pattern of diseaseand changing pattern of disease

How modellers fit in at every stageHow modellers fit in at every stage– Planning Planning – Changing policy.Changing policy.– Evaluating…Evaluating…

A global view of HIV infection38.6 million people [33.4‒46.0 million] living with HIV, 2005

2.4

HIV prevalence (%) in adults in Africa, 2005


People living with HIV……….38.6 millionPeople living with HIV……….38.6 million– Children 2.3Children 2.3

New HIV infections in 2005… 4.1 millionNew HIV infections in 2005… 4.1 million– Children .54Children .54

Deaths due to AIDS in 2005.. 2.8 millionDeaths due to AIDS in 2005.. 2.8 million– Children .38Children .38– NB 1/3 of all HIV deaths are in Southern NB 1/3 of all HIV deaths are in Southern

AfricaAfrica

Global HIV epidemic, 1990‒2005* HIV epidemic in sub-Saharan Africa, 1985‒2005*

Number of people living with HIV

% HIV prevalence, adult (15-49)

% HIV prevalence, adult (15‒49)

Number of peopleliving with HIV (millions)

0

10

20

30

40

50

1990 1995 2000 2005

0.0

1.0

2.0

3.0

4.0

5.0

1985 1990 1995 2000 2005

0

5

10

15

20

25

30

0.0

2.5

5.0

7.5

12.5

15.0

% HIV prevalence, adult (15‒49)

Number of peopleliving with HIV (millions)

Estimated number of people living with HIV and adult HIV prevalence

This bar indicates the range around the estimate

*Even though the HIV prevalence rates have stabilized in sub-Saharan Africa, the actual number of people infected continues to grow because of population growth. Applying the same prevalence rate to a growing population will result in increasing numbers of people living with HIV.

10.0

2.2

Impact of AIDS on life expectancy in five African countries, 1970–2010

Life expectancy at birth (years)

Source: United Nations Population Division (2004). World Population Prospects: The 2004 Revision, database.

Botswana

South Africa

Swaziland

Zambia

Zimbabwe

1970–1975 1975–1980

1980–19851985–1990

1990–19951995–2000

2000–20052005–2010

70

65

60

55

50

45

40

35

30

25

20

4.1

People in sub-Saharan Africa on antiretroviral treatment as percentage of those in need, 2002–2005

20022003

2004

2005

7.2Source: WHO/UNAIDS (2005). Progress on global access to HIV antiretroviral therapy: An update on “3 by 5.”


Age-specific prevalence of HIV in pregnant Age-specific prevalence of HIV in pregnant women, Botswana Sentinel Survey 2005 women, Botswana Sentinel Survey 2005 2003 22.8 38.6 49.7 45.9 2003 22.8 38.6 49.7 45.9

41.5 34.4 41.5 34.4


So what influenced Botswana to be the trend setters???So what influenced Botswana to be the trend setters???Obviously the foresight and wisdom of Botswana’s Obviously the foresight and wisdom of Botswana’s leaders, but aided by…leaders, but aided by…

Brian Gazzard, Lisbon IAS 1999Brian Gazzard, Lisbon IAS 1999-projection of reduction of costs when HIV is treated-projection of reduction of costs when HIV is treated

The The Durban AIDS ConferenceDurban AIDS Conference with Jeffrey with Jeffrey Sach’s projection on how NO developing country could Sach’s projection on how NO developing country could afford NOT to treat HIVafford NOT to treat HIV

Projected population graph with AIDS uncheckedProjected population graph with AIDS uncheckedLifetime risk of acquiring HIV of a 15 year old boyLifetime risk of acquiring HIV of a 15 year old boy

Projected population structure with and Projected population structure with and without the AIDS epidemic, Botswana, 2020without the AIDS epidemic, Botswana, 2020

80757065605550454035302520151050

020406080100120140 0 20 40 60 80 100 120 140

Males Females Deficits due to AIDS

Projected population structure in 2020

Population (thousands)

Ag

e in

yea

rs

Source: US Census Bureau, World Population Profile 2000

Lifetime risk of AIDS death for 15-year-old boys, Lifetime risk of AIDS death for 15-year-old boys, assuming unchanged or halved risk of becoming assuming unchanged or halved risk of becoming

infected with HIV, selected countriesinfected with HIV, selected countries

Source: Zaba B, 2000 (unpublished data)

Current adult HIV prevalence rate

Burkina Faso

Cambodia

Côte d’Ivoire

Kenya

South AfricaZambia

Zimbabwe

Botswana

Burkina FasoCambodia

Côte d’Ivoire

Kenya

South AfricaZambia

Zimbabwe

Botswana

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0% 5% 10% 15% 20% 25% 30% 35% 40%

Ris

k o

f d

yin

g o

f A

IDS

current level of risk maintained

risk halved over next 15 years

Anthony Harries Malawi, Ministry of HAnthony Harries Malawi, Ministry of Healthealth

TB (TB (CROI 2006) CROI 2006)

20032003

9,000,000 new cases9,000,000 new cases

4,000,000 smear positive4,000,000 smear positive

2,000,000 deaths2,000,000 deaths

Global TB incidence growing at 1% per yearGlobal TB incidence growing at 1% per year

Risk of TB 5-15% per year HIV + (50x HIV-)Risk of TB 5-15% per year HIV + (50x HIV-)

09/2006 TB Unit Ministry of Health Bot09/2006 TB Unit Ministry of Health Botswanaswana

0

100

200

300

400

500

600

700

Year

TB

Ca

se

Ra

te (

pe

r 1

00

,00

0)

0

5

10

15

20

25

30

35

40

45

HIV

se

rop

rev

ale

nc

e (%

)Reported TB Case Rate Botswana, 1975–2004Reported TB Case Rate Botswana, 1975–2004

and HIV Prevalence Antenatal Women, 1992-2005 and HIV Prevalence Antenatal Women, 1992-2005

TB

HIV

Malawi illustrates this-- note Malawi illustrates this-- note increasing smear negative cases increasing smear negative cases

30% treatment success and 60% mortality30% treatment success and 60% mortality


30-40% of all HIV deaths in Africa are due to 30-40% of all HIV deaths in Africa are due to TB usually diagnosed postmortemTB usually diagnosed postmortem

Lucas 1993 Cote d’IvoireLucas 1993 Cote d’Ivoire– 40% of HIV wasted patients who died had TB40% of HIV wasted patients who died had TB

Lewis 2005 MalawiLewis 2005 Malawi– 10% of HIV patients with severe anemia had 10% of HIV patients with severe anemia had

disseminated TB diagnosed by bone marrow disseminated TB diagnosed by bone marrow C/S C/S


Malawi- 1999Malawi- 1999– 2979 Health workers died- 50% TB2979 Health workers died- 50% TB

- 40% AIDS- 40% AIDS– 105 TB control officers died105 TB control officers died


Outcomes of TB in MalawiOutcomes of TB in Malawi

HIV +ve only 20% still alive 2 years after HIV +ve only 20% still alive 2 years after diagnosis (No treatment for HIV then)diagnosis (No treatment for HIV then)

HIV neg 50% only still alive at 7 yrsHIV neg 50% only still alive at 7 yrs

11-12% of TB notifications 11-12% of TB notifications recurrences/relapse- strong HIV recurrences/relapse- strong HIV associationassociation


Outcomes of Isoniazid Prophylaxis (IPT) on Outcomes of Isoniazid Prophylaxis (IPT) on Incidence of TBIncidence of TB

IPT Reduces TB risk 40% IPT Reduces TB risk 40% (Wilkinson, BMJ 1998)(Wilkinson, BMJ 1998)

IPT Reduces risk of recurrence 50-80% IPT Reduces risk of recurrence 50-80% (Churchyard (Churchyard AIDS 2003, Fitzgerald Lancet 2000)AIDS 2003, Fitzgerald Lancet 2000)

HAART reduces TB risk but NOT back to normalHAART reduces TB risk but NOT back to normalIf patient has NO HAART If patient has NO HAART

9.7 risk of TB per 100 pt yrs9.7 risk of TB per 100 pt yrs If patient on HAARTIf patient on HAART

2.4 TB cases /100 pt yrs- 2.4 TB cases /100 pt yrs- Badri Lancet 2001 Badri Lancet 2001

continues reducing to 1% by 5 yrs continues reducing to 1% by 5 yrs Lawn Lawn AIDS 2005AIDS 2005


Deaths due to TBDeaths due to TB

60% of TB deaths in 160% of TB deaths in 1stst 2 months 2 months

Early HAART after 2 weeks reduces Early HAART after 2 weeks reduces deathsdeaths

However Increased IRIS with possible However Increased IRIS with possible deaths with early HAART in first 3mdeaths with early HAART in first 3m

A balance has to be struckA balance has to be struck


What about other respiratory What about other respiratory diseases?diseases?


Pneumococcal invasive illness has Pneumococcal invasive illness has escalated in our region…escalated in our region…

Keith Klugman CROI 2006Keith Klugman CROI 2006

Changing Patterns of Pneumococcal Changing Patterns of Pneumococcal Infection in Southern AfricaInfection in Southern Africa

Generally Increasing prevalence of invasive Generally Increasing prevalence of invasive pneumococcal illness in developing countries. In RSA it pneumococcal illness in developing countries. In RSA it seems to have replaced Haemophilus Influenza in LRTIsseems to have replaced Haemophilus Influenza in LRTIs– Now 74% vs 12.9% Hib- reverse ratioNow 74% vs 12.9% Hib- reverse ratio

Increased prevalence of Paediatric (invasive) serotypes Increased prevalence of Paediatric (invasive) serotypes in HIVin HIV++ patients patientsIncreased mortality-65% with meningitis Malawi Increased mortality-65% with meningitis Malawi

-20% with pneumonia -20% with pneumoniaIncreased symptoms and signs with HIV+ patientsIncreased symptoms and signs with HIV+ patients– Pleurisy, haemoptysis, diarrhoea, meningitis,Pleurisy, haemoptysis, diarrhoea, meningitis,

Degree of risk CD4 driven Degree of risk CD4 driven – average CD4 in patients who died was 110 vs 170 in survivorsaverage CD4 in patients who died was 110 vs 170 in survivors

Pneumococcal pneumonia is a disease of the very young and very old giving a U shaped curve in Western countries

Percentage of distribution of deaths by age in southern Africa, 1985–1990 and 2000–2005

0–4 5–19 20–29 30–39 40–49 50–59 60+

40

35

30

25

20

15

10

5

0

1985-1990 2000-2005

Percentage of total deaths

Age-groups:

Source: Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat (2005). World Population Prospects: The 2004 Revision. Highlights. New York: United Nations. 4.2


Note, modellers!Note, modellers!

Risks now have changed-Risks now have changed-– HIV+HIV+ (Lost immunity to paediatric strains) (Lost immunity to paediatric strains)– Young womenYoung women– Small child in homeSmall child in home– Health workerHealth worker– Abuse of drugs,Abuse of drugs,– smoking or alcoholsmoking or alcohol

Antibiotic resistance and severity of illness Antibiotic resistance and severity of illness increase with HIVincrease with HIV


Morbidity reduced with HAARTMorbidity reduced with HAART– Spain, rate of invasive pneumococcal disease Spain, rate of invasive pneumococcal disease

dropped from 24.1/1000 in 1985 to 2/1000 dropped from 24.1/1000 in 1985 to 2/1000 (We have yet to see those results in Southern (We have yet to see those results in Southern Africa)Africa)

– However still increased risk X 30 to 35xHowever still increased risk X 30 to 35x

Mahdi et al CID 2005, 40,1511-18 Mahdi et al CID 2005, 40,1511-18

Pneumococcal vaccinePneumococcal vaccine

Normal paediatric pneumococcal vaccine Normal paediatric pneumococcal vaccine reduces prevalence of paediatric reduces prevalence of paediatric serotypes and greatly reduces riskserotypes and greatly reduces risk

However other less virulent strains replace However other less virulent strains replace themthem

Note- NOT the 23 valent vaccine- seemed Note- NOT the 23 valent vaccine- seemed to increase morbidity in Rakai- ? Due to to increase morbidity in Rakai- ? Due to severe immunocompromisation?severe immunocompromisation?


Burden of disease in adults reduced by Burden of disease in adults reduced by vaccination of children (USA)vaccination of children (USA)


MalariaMalaria

LaurenceSlutsker Kenya Med Res StatioLaurenceSlutsker Kenya Med Res Station, Kisumu CROI 2006n, Kisumu CROI 2006

MalariaMalaria

Clinical Manifestations vary depending if occurs in stable or Clinical Manifestations vary depending if occurs in stable or unstable transmission areasunstable transmission areas– UnstableUnstable

acute febrile disease, cerebral malaria and death;acute febrile disease, cerebral malaria and death; still birth and abortion in pregnant womenstill birth and abortion in pregnant women

– StableStable Children chronic recurrent infections with anemia and growth retardationChildren chronic recurrent infections with anemia and growth retardationAdults acquired immunity, asymptomatic,Adults acquired immunity, asymptomatic, Pregnant women, increased foetal growth retardation and increased infant Pregnant women, increased foetal growth retardation and increased infant mortalitymortality

Severity in adults and children invariably aggravated by HIV, Severity in adults and children invariably aggravated by HIV, especially in unstable areas; with increased risk of Intensive care especially in unstable areas; with increased risk of Intensive care and death (and death (Cohen CID 2005, Grimwald Ped Inf Disease 2003) Cohen CID 2005, Grimwald Ped Inf Disease 2003)

Infants in stable areas get more frequent and severe anaemiaInfants in stable areas get more frequent and severe anaemia (van (van Eijke,AJTMH,2002)Eijke,AJTMH,2002)


Cotrimoxazole ProphylaxisCotrimoxazole Prophylaxis

Ugandan cohort Ugandan cohort Lancet 2004Lancet 2004 70% reduction of 70% reduction of morbidity rate of severe malariamorbidity rate of severe malaria

Mali 97% efficacy to prevent infection in Mali 97% efficacy to prevent infection in HIV neg childrenHIV neg children

Abidjan Abidjan (Anglaret Lancet 1999)(Anglaret Lancet 1999) 5-6% reduction of 5-6% reduction of morbiditymorbidity

W Kenya- decreases in level of W Kenya- decreases in level of parasitaemiaparasitaemia


Effect of HIV on malariaEffect of HIV on malaria

3 million excess cases3 million excess cases5% increase of malaria deaths(65,000)5% increase of malaria deaths(65,000) Increases parasitaemia with increasing Increases parasitaemia with increasing immunosuppression, reduced clearance abilityimmunosuppression, reduced clearance abilityUnder 5 yrs of age, 1.7 fold increase in clinical Under 5 yrs of age, 1.7 fold increase in clinical diseasediseaseMax impact in unstable transmission areasMax impact in unstable transmission areas– Botswana, Namibia, Zimbabwe. South AfricaBotswana, Namibia, Zimbabwe. South Africa– Incidence increased 28% (14-40.7%)Incidence increased 28% (14-40.7%)– Deaths increased 114% (37-188%)Deaths increased 114% (37-188%)

– Emergent Infectious Diseases 2005Emergent Infectious Diseases 2005


Effect of Malaria on HIVEffect of Malaria on HIV

Reversible increase viral load (2 fold in Reversible increase viral load (2 fold in pregnancy)pregnancy)Malawi- increased neonatal mortality Malawi- increased neonatal mortality (AIDS (AIDS

1999)1999)

Possible reduction in CD4Possible reduction in CD4

No evidence of mother to child No evidence of mother to child transmission increasetransmission increase

Jean Nachega Jean Nachega

Hepatitis BHepatitis B

Worldwide huge burdenWorldwide huge burden– 2 billion people infected2 billion people infected– 400 million chronic infection400 million chronic infection– 500,000 to 1 million deaths annually500,000 to 1 million deaths annually

Chronic hepatitisChronic hepatitis

CirrhosisCirrhosis

Hepatocellular carcinomaHepatocellular carcinoma


Subsaharan AfricaSubsaharan Africa

Horizontal transmission (Infected older siblings)Horizontal transmission (Infected older siblings)Acquired mainly between 6 months and 5 yrs Acquired mainly between 6 months and 5 yrs Some sexual transmission Some sexual transmission – Most exposed to HBV as children before HIV Most exposed to HBV as children before HIV

exposureexposure

Some perinatal transmission (+ or- HIV)Some perinatal transmission (+ or- HIV)Coinfection with HIV may result inCoinfection with HIV may result in– Reactivation of infection in silent chronic carriersReactivation of infection in silent chronic carriers– New HBV infection as protective immunity lost with New HBV infection as protective immunity lost with

HIVHIV


HOWEVERHOWEVER– Botswana our own stats show 40% incidence Botswana our own stats show 40% incidence

of exposure but <1% hepB sAG positiveof exposure but <1% hepB sAG positiveIncreased risk of Haart related hepatotoxicity Increased risk of Haart related hepatotoxicity Increased liver related mortality Increased liver related mortality IDCC no longer screens for this as numbers are so IDCC no longer screens for this as numbers are so small there is no impact on disease management small there is no impact on disease management

– South Africa 2 studies concurSouth Africa 2 studies concur 41-43.3% evidence of previous or current infection 41-43.3% evidence of previous or current infection Liver International 2005;25:201-213Liver International 2005;25:201-213

AIDS Read 2004;14(3):122-137AIDS Read 2004;14(3):122-137

Robert Newton Univ of York UKRobert Newton Univ of York UK

Kaposi SarcomaKaposi Sarcoma

HHSV8 associatedHHSV8 associated– Men more common in WestMen more common in West– Similar prevalence of HHSv8 in M and F in sub saharan AfricaSimilar prevalence of HHSv8 in M and F in sub saharan Africa

Incidence risen in Zimbabwe fromIncidence risen in Zimbabwe from– 2.3/100,000 in males and 0.3/100,000 in females pre HIV2.3/100,000 in males and 0.3/100,000 in females pre HIV– Now 48/100,000 and 18/100,000 in 2001Now 48/100,000 and 18/100,000 in 2001

Incidence risen in Uganda by 20 or 30 times in the last 2 Incidence risen in Uganda by 20 or 30 times in the last 2 decades, 81% HIV+decades, 81% HIV+Incidence increased in South Africa by 2 (??)Incidence increased in South Africa by 2 (??)Women seem to have more aggressive and symptomatic Women seem to have more aggressive and symptomatic disease ?due to increased cytokines. Maybe biological disease ?due to increased cytokines. Maybe biological difference?difference?

Meditz U ZimbabweMeditz U Zimbabwe


Cervical CancerCervical Cancer

Associated with oncogenic Human Papilloma VirusAssociated with oncogenic Human Papilloma VirusIncreases in Africa across all age groupsIncreases in Africa across all age groups– Uganda, increases predate HIV epidemicUganda, increases predate HIV epidemic

An international Collaboration on HIV and Ca Cervix showed 1.88 An international Collaboration on HIV and Ca Cervix showed 1.88 increased incidence and no change with HAARTincreased incidence and no change with HAARTHIV-infected women more likely than HIV-negative women to be HIV-infected women more likely than HIV-negative women to be coinfected with HPV coinfected with HPV 1

– (58% vs 24%; (58% vs 24%; P P < .01)< .01)HIV infected women more likely to have multiple strains of HPV HIV infected women more likely to have multiple strains of HPV (clearance of HPV affected)(clearance of HPV affected)HIV-infected women more likely to have high-risk HPV infection HIV-infected women more likely to have high-risk HPV infection 1

– (23% vs 14%; (23% vs 14%; P P < .01)< .01)

1 Duerr A, Paramsothy P, Jamieson DJ, et al. 1 Duerr A, Paramsothy P, Jamieson DJ, et al. Effect of HIV infection on atypical squamous cells of undetermined significance. Clin Effect of HIV infection on atypical squamous cells of undetermined significance. Clin Infect Dis. 2006;42:855-861.Infect Dis. 2006;42:855-861.


Genital HerpesGenital Herpes

Herpes Simplex 2 responsible for Herpes Simplex 2 responsible for recurrent outbreaks of genital herpesrecurrent outbreaks of genital herpesIncreases HIV shedding in HIV+ patientsIncreases HIV shedding in HIV+ patientsIncreases infectiousness of HIV+ and theIncreases infectiousness of HIV+ and the

likelihood of infection in HIV- patient likelihood of infection in HIV- patient exposed to HIV (upregulates mucosal exposed to HIV (upregulates mucosal immune activity)immune activity)HIV increases severity of lesions and HIV increases severity of lesions and durationduration


Other infectious diseases with Other infectious diseases with differencesdifferences

ToxoplasmosisToxoplasmosis– COMMON opportunistic Infection in the westCOMMON opportunistic Infection in the west– <1% among our HIV patients<1% among our HIV patients

CytomegalovirusCytomegalovirus– Causes devastating disease in very immune Causes devastating disease in very immune

compromised people, may result in blindnesscompromised people, may result in blindness– 50-65% previous exposure in the west50-65% previous exposure in the west– 99.5% Botswana99.5% Botswana

CryptococcusCryptococcus– Very common in our settingVery common in our setting


Diarrhoea in HIV+ patientsDiarrhoea in HIV+ patients

CryptosporidiumCryptosporidium

MicrosporidiumMicrosporidium

Isospora BelliIsospora Belli

Salmonella, recurrent- not easily clearedSalmonella, recurrent- not easily cleared

As well as all the usual causes of diarrhoeaAs well as all the usual causes of diarrhoea

Botswana has recently had a country wide epidemic of Botswana has recently had a country wide epidemic of Cryptosporidium and enteropathogenic E ColiCryptosporidium and enteropathogenic E Coli


Where does all this lead to? Where does all this lead to? Where do modellers come in??Where do modellers come in??

We need to be able to INFLUENCE We need to be able to INFLUENCE POLICY- you can help us therePOLICY- you can help us there

We need to be able toWe need to be able to– predict the changing faces of the different predict the changing faces of the different

diseasesdiseases– Evaluate different prevention strategies Evaluate different prevention strategies – Evaluate different treatment interventionsEvaluate different treatment interventions– PrioritisePrioritise


We need you forWe need you for

Programme PlanningProgramme Planning– Costs of prevention and testingCosts of prevention and testing– Costs of treatment, both of HIV but other diseasesCosts of treatment, both of HIV but other diseases– Costs of laboratory tests, diagnostic and monitoringCosts of laboratory tests, diagnostic and monitoring– Human resource management, number of health Human resource management, number of health

workers required in different situationsworkers required in different situations– Education of Health Care Workers, costs and Education of Health Care Workers, costs and

personnel neededpersonnel needed– Social programmes necessarySocial programmes necessary

Orphan care, educationOrphan care, educationFeeding programmesFeeding programmes


And for the fun things?And for the fun things?

Modelling even paints fitness landscapes Modelling even paints fitness landscapes of individual HIV viruses and enables of individual HIV viruses and enables prediction of resistance mutation patternsprediction of resistance mutation patterns


I don’t know what we could do without you! I don’t know what we could do without you! We would be struggling at an individual We would be struggling at an individual level to make an impactlevel to make an impact

You paint the bigger pictureYou paint the bigger picture

With you we can crack this epidemic, you With you we can crack this epidemic, you have already shown the way!have already shown the way!


Thank You for listeningThank You for listening

Thankyou also to Florence Doualla BellThankyou also to Florence Doualla Bell– Who enabled you not to sit through 90 Who enabled you not to sit through 90

minutes today!!minutes today!!

Sala SintleSala Sintle

current state of infectious diseases in southern africa diana dickinson

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