Current State of Infectious Diseases in Southern Africa

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Current State of Infectious Diseases in Southern
Africa

• Diana Dickinson

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Overview

• HIV epidemic) already dealt with, just a few
  personal
• TB ) insights
• Pneumococcus in detail
• Other regional problems
• Malaria
• Hepatitis B
• Herpes Simplex
• Cervical cancer associated with HPV
• KS associated with HHSV8

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• Challenges of coping with the increases and
  changing pattern of disease
• How modellers fit in at every stage
• Planning
• Changing policy.
• Evaluating

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• People living with HIV.38.6 million
• Children
  2.3
• New HIV infections in 2005 4.1 million
• Children
  .54
• Deaths due to AIDS in 2005.. 2.8 million
• Children
  .38
• NB 1/3 of all HIV deaths are in Southern Africa

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Age-specific prevalence of HIV in pregnant women,
Botswana Sentinel Survey 2005
2003 22.8 38.6
49.7 45.9 41.5 34.4
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• So what influenced Botswana to be the trend
  setters???
• Obviously the foresight and wisdom of Botswanas
  leaders, but aided by
• Brian Gazzard, Lisbon IAS 1999
• -projection of reduction of costs when HIV is
  treated
• The Durban AIDS Conference with Jeffrey Sachs
  projection on how NO developing country could
  afford NOT to treat HIV
• Projected population graph with AIDS unchecked
• Lifetime risk of acquiring HIV of a 15 year old
  boy

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Projected population structure with and without
the AIDS epidemic, Botswana, 2020
80
Projected population structure in 2020
75
70
Males
Females
Deficits due to AIDS
65
60
55
50
Age in years
45
40
35
30
25
20
15
10
5
0
0
20
40
60
80
100
120
140
0
20
40
60
80
100
120
140
Population (thousands)
Source US Census Bureau, World Population
Profile 2000
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Lifetime risk of AIDS death for 15-year-old boys,
assuming unchanged or halved risk of becoming
infected with HIV, selected countries
100
90
Botswana
80
Zimbabwe
Botswana
70
South Africa
Zambia
Risk of dying of AIDS
60
Zimbabwe
50
Kenya
South Africa
risk halved over next 15 years
Zambia
Côte dIvoire
40
current level of risk maintained
Cambodia
Kenya
30
Côte dIvoire
Burkina Faso
20
Cambodia
Burkina Faso
10
0
0
5
10
15
20
25
30
35
40
Current adult HIV prevalence rate
Source Zaba B, 2000 (unpublished data)
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TB (CROI 2006)

• 2003
• 9,000,000 new cases
• 4,000,000 smear positive
• 2,000,000 deaths
• Global TB incidence growing at 1 per year
• Risk of TB 5-15 per year HIV (50x HIV-)

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Reported TB Case Rate Botswana, 19752004 and
HIV Prevalence Antenatal Women, 1992-2005
HIV
TB
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Malawi illustrates this-- note increasing smear
negative cases 30 treatment success and 60
mortality
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• 30-40 of all HIV deaths in Africa are due to TB
  usually diagnosed postmortem
• Lucas 1993 Cote dIvoire
• 40 of HIV wasted patients who died had TB
• Lewis 2005 Malawi
• 10 of HIV patients with severe anemia had
  disseminated TB diagnosed by bone marrow C/S

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• Malawi- 1999
• 2979 Health workers died- 50 TB
• - 40
  AIDS
• 105 TB control officers died

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Outcomes of TB in Malawi

• HIV ve only 20 still alive 2 years after
  diagnosis (No treatment for HIV then)
• HIV neg 50 only still alive at 7 yrs
• 11-12 of TB notifications recurrences/relapse-
  strong HIV association

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Outcomes of Isoniazid Prophylaxis (IPT) on
Incidence of TB

• IPT Reduces TB risk 40 (Wilkinson, BMJ 1998)
• IPT Reduces risk of recurrence 50-80 (Churchyard
  AIDS 2003, Fitzgerald Lancet 2000)
• HAART reduces TB risk but NOT back to normal
• If patient has NO HAART
• 9.7 risk of TB per 100 pt yrs
• If patient on HAART
• 2.4 TB cases /100 pt yrs- Badri Lancet 2001
• continues reducing to 1 by 5 yrs Lawn AIDS
  2005

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Deaths due to TB

• 60 of TB deaths in 1st 2 months
• Early HAART after 2 weeks reduces deaths
• However Increased IRIS with possible deaths with
  early HAART in first 3m
• A balance has to be struck

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• NOTE Smear neg patients transmit!!!
• 17 transmission rate
• NOTE
• With first diagnosis of HIV, risk of TB doubles
  in even that FIRST year of infection

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What about other respiratory diseases?
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• Pneumococcal invasive illness has escalated
  in our region

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Changing Patterns of Pneumococcal Infection in
Southern Africa

• Generally Increasing prevalence of invasive
  pneumococcal illness in developing countries. In
  RSA it seems to have replaced Haemophilus
  Influenza in LRTIs
• Now 74 vs 12.9 Hib- reverse ratio
• Increased prevalence of Paediatric (invasive)
  serotypes in HIV patients
• Increased mortality-65 with meningitis Malawi
  -20 with
  pneumonia
• Increased symptoms and signs with HIV patients
• Pleurisy, haemoptysis, diarrhoea, meningitis,
• Degree of risk CD4 driven
• average CD4 in patients who died was 110 vs 170
  in survivors

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

• Risks now have changed-
• HIV (Lost immunity to paediatric strains)
• Young women
• Small child in home
• Health worker
• Abuse of drugs,
• smoking or alcohol
• Antibiotic resistance and severity of illness
  increase with HIV

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• Morbidity reduced with HAART
• Spain, rate of invasive pneumococcal disease
  dropped from 24.1/1000 in 1985 to 2/1000 (We have
  yet to see those results in Southern Africa)
• However still increased risk X 30 to 35x

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Pneumococcal vaccine

• Normal paediatric pneumococcal vaccine reduces
  prevalence of paediatric serotypes and greatly
  reduces risk
• However other less virulent strains replace them
• Note- NOT the 23 valent vaccine- seemed to
  increase morbidity in Rakai- ? Due to severe
  immunocompromisation?

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

• Clinical Manifestations vary depending if occurs
  in stable or unstable transmission areas
• Unstable
• acute febrile disease, cerebral malaria and
  death
• still birth and abortion in pregnant women
• Stable
• Children chronic recurrent infections with
  anemia and growth retardation
• Adults acquired immunity, asymptomatic,
• Pregnant women, increased foetal growth
  retardation and increased infant mortality
• Severity in adults and children invariably
  aggravated by HIV, especially in unstable areas
  with increased risk of Intensive care and death
  (Cohen CID 2005, Grimwald Ped Inf Disease 2003)
• Infants in stable areas get more frequent and
  severe anaemia (van Eijke,AJTMH,2002)

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Cotrimoxazole Prophylaxis

• Ugandan cohort Lancet 2004 70 reduction of
  morbidity rate of severe malaria
• Mali 97 efficacy to prevent infection in HIV neg
  children
• Abidjan (Anglaret Lancet 1999) 5-6 reduction of
  morbidity
• W Kenya- decreases in level of parasitaemia

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Effect of HIV on malaria

• 3 million excess cases
• 5 increase of malaria deaths(65,000)
• Increases parasitaemia with increasing
  immunosuppression, reduced clearance ability
• Under 5 yrs of age, 1.7 fold increase in clinical
  disease
• Max impact in unstable transmission areas
• Botswana, Namibia, Zimbabwe. South Africa
• Incidence increased 28 (14-40.7)
• Deaths increased 114 (37-188)
• Emergent Infectious Diseases 2005

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Effect of Malaria on HIV

• Reversible increase viral load (2 fold in
  pregnancy)
• Malawi- increased neonatal mortality (AIDS 1999)
• Possible reduction in CD4
• No evidence of mother to child transmission
  increase

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Hepatitis B

• Worldwide huge burden
• 2 billion people infected
• 400 million chronic infection
• 500,000 to 1 million deaths annually
• Chronic hepatitis
• Cirrhosis
• Hepatocellular carcinoma

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Subsaharan Africa

• Horizontal transmission (Infected older siblings)
• Acquired mainly between 6 months and 5 yrs
• Some sexual transmission
• Most exposed to HBV as children before HIV
  exposure
• Some perinatal transmission ( or- HIV)
• Coinfection with HIV may result in
• Reactivation of infection in silent chronic
  carriers
• New HBV infection as protective immunity lost
  with HIV

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• HOWEVER
• Botswana our own stats show 40 incidence of
  exposure but lt1 hepB sAG positive
• Increased risk of Haart related hepatotoxicity
• Increased liver related mortality
• IDCC no longer screens for this as numbers are so
  small there is no impact on disease management
• South Africa 2 studies concur
• 41-43.3 evidence of previous or current
  infection Liver International 200525201-213
• AIDS Read 200414(3)122-137

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Kaposi Sarcoma

• HHSV8 associated
• Men more common in West
• Similar prevalence of HHSv8 in M and F in sub
  saharan Africa
• Incidence risen in Zimbabwe from
• 2.3/100,000 in males and 0.3/100,000 in females
  pre HIV
• Now 48/100,000 and 18/100,000 in 2001
• Incidence risen in Uganda by 20 or 30 times in
  the last 2 decades, 81 HIV
• Incidence increased in South Africa by 2 (??)
• Women seem to have more aggressive and
  symptomatic disease ?due to increased cytokines.
  Maybe biological difference?
• Meditz U Zimbabwe

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Cervical Cancer

• Associated with oncogenic Human Papilloma Virus
• Increases in Africa across all age groups
• Uganda, increases predate HIV epidemic
• An international Collaboration on HIV and Ca
  Cervix showed 1.88 increased incidence and no
  change with HAART
• HIV-infected women more likely than HIV-negative
  women to be coinfected with HPV 1
• (58 vs 24 P lt .01)
• HIV infected women more likely to have multiple
  strains of HPV (clearance of HPV affected)
• HIV-infected women more likely to have high-risk
  HPV infection 1
• (23 vs 14 P lt .01)
• 1 Duerr A, Paramsothy P, Jamieson DJ, et al.
  Effect of HIV infection on atypical squamous
  cells of undetermined significance. Clin Infect
  Dis. 200642855-861.

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Genital Herpes

• Herpes Simplex 2 responsible for recurrent
  outbreaks of genital herpes
• Increases HIV shedding in HIV patients
• Increases infectiousness of HIV and the
• likelihood of infection in HIV- patient
  exposed to HIV (upregulates mucosal immune
  activity)
• HIV increases severity of lesions and duration

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Other infectious diseases with differences

• Toxoplasmosis
• COMMON opportunistic Infection in the west
• lt1 among our HIV patients
• Cytomegalovirus
• Causes devastating disease in very immune
  compromised people, may result in blindness
• 50-65 previous exposure in the west
• 99.5 Botswana
• Cryptococcus
• Very common in our setting

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Diarrhoea in HIV patients

• Cryptosporidium
• Microsporidium
• Isospora Belli
• Salmonella, recurrent- not easily cleared
• As well as all the usual causes of diarrhoea
• Botswana has recently had a country wide epidemic
  of Cryptosporidium and enteropathogenic E Coli

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

• We need to be able to INFLUENCE POLICY- you can
  help us there
• We need to be able to
• predict the changing faces of the different
  diseases
• Evaluate different prevention strategies
• Evaluate different treatment interventions
• Prioritise

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We need you for

• Programme Planning
• Costs of prevention and testing
• Costs of treatment, both of HIV but other
  diseases
• Costs of laboratory tests, diagnostic and
  monitoring
• Human resource management, number of health
  workers required in different situations
• Education of Health Care Workers, costs and
  personnel needed
• Social programmes necessary
• Orphan care, education
• Feeding programmes

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And for the fun things?

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

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• I dont know what we could do without you! We
  would be struggling at an individual level to
  make an impact
• You paint the bigger picture
• With you we can crack this epidemic, you have
  already shown the way!

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• Thank You for listening
• Thankyou also to Florence Doualla Bell
• Who enabled you not to sit through 90 minutes
  today!!
• Sala Sintle