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Current State of Infectious Diseases in Southern Africa. Diana Dickinson. 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

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overview
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

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

slide3
Challenges of coping with the increases and changing pattern of disease
  • How modellers fit in at every stage
    • Planning
    • Changing policy.
    • Evaluating…

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

slide4
A global view of HIV infection

38.6 million people [33.4‒46.0 million] living with HIV, 2005

HIV prevalence (%) in adults in Africa, 2005

2.4

2.5

slide5
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

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

slide6
Estimated number of people living with HIV and adult HIV prevalence

Global HIV epidemic, 1990‒2005*

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

Number of people

living with HIV (millions)

% HIV prevalence,

adult (15‒49)

Number of people

living with HIV (millions)

% HIV prevalence,

adult (15‒49)

50

5.0

30

15.0

12.5

25

40

4.0

20

10.0

30

3.0

7.5

15

20

2.0

5.0

10

10

1.0

2.5

5

0

0.0

0

0.0

1990

1995

2000

2005

1985

1990

1995

2000

2005

*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.

Number of people living with HIV

% HIV prevalence, adult (15-49)

This bar indicates the range around the estimate

2.2

slide7
Impact of AIDS on life expectancy in five African countries, 1970–2010

70

65

60

Botswana

55

South Africa

Life

expectancy

at birth

(years)

50

45

Swaziland

40

35

Zambia

30

Zimbabwe

25

20

1970–1975

1980–1985

1990–1995

2000–2005

1975–1980

1985–1990

1995–2000

2005–2010

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

4.1

slide8
People in sub-Saharan Africa on antiretroviral treatment

as percentage of those in need, 2002–2005

2005

2002

2003

2004

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

7.2

slide9
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

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

slide10
So what influenced Botswana to be the trend setters???
  • Obviously the foresight and wisdom of Botswana’s leaders, but aided by…

Brian Gazzard, Lisbon IAS 1999

-projection of reduction of costs when HIV is treated

The Durban AIDS Conference with Jeffrey Sach’s 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

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

slide11
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

140

120

100

80

60

40

20

0

0

20

40

60

80

100

120

140

Population (thousands)

Source: US Census Bureau, World Population Profile 2000

slide12
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

70%

Botswana

South Africa

Risk of dying of AIDS

Zambia

60%

Zimbabwe

50%

Kenya

South Africa

risk halved over next 15 years

Zambia

Côte d’Ivoire

40%

current level of risk maintained

Cambodia

Kenya

30%

Côte d’Ivoire

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)

tb croi 2006
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-)

Anthony Harries Malawi, Ministry of Health

reported tb case rate botswana 1975 2004 and hiv prevalence antenatal women 1992 2005
Reported TB Case Rate Botswana, 1975–2004 and HIV Prevalence Antenatal Women, 1992-2005

HIV

TB

09/2006 TB Unit Ministry of Health Botswana

malawi illustrates this note increasing smear negative cases 30 treatment success and 60 mortality
Malawi illustrates this-- note increasing smear negative cases 30% treatment success and 60% mortality
slide16
30-40% of all HIV deaths in Africa are due to TB usually diagnosed postmortem

Lucas 1993 Cote d’Ivoire

  • 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

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

slide17
Malawi- 1999
    • 2979 Health workers died- 50% TB

- 40% AIDS

    • 105 TB control officers died

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

outcomes of tb in malawi
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

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

outcomes of isoniazid prophylaxis ipt on incidence of tb
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

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

deaths due to tb
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

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

what about other respiratory diseases
What about other respiratory diseases?

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

slide22
Pneumococcal invasive illness has escalated in our region…

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

slide24
09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling
changing patterns of pneumococcal infection in southern africa
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

Keith Klugman CROI 2006

slide26
09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling
slide27
Pneumococcal pneumonia is a disease of the very young and very old giving a U shaped curve in Western countries
slide28
Percentage of distribution of deaths by age in southern Africa,

1985–1990 and 2000–2005

40

35

30

25

Percentage

of total deaths

20

15

10

5

0

0–4

5–19

20–29

30–39

40–49

50–59

60+

Age-groups

:

1985-1990

2000-2005

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-
    • 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

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

slide30
09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling
slide31
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

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

pneumococcal vaccine
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?

Mahdi et al CID 2005, 40,1511-18

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

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

malaria
Malaria

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

malaria35
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)

LaurenceSlutsker Kenya Med Res Station, Kisumu CROI 2006

slide36
09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling
slide37
09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling
slide38
09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling
cotrimoxazole prophylaxis
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

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

slide40
09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling
effect of hiv on malaria
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

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

effect of malaria on hiv
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

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

hepatitis b
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

Jean Nachega

subsaharan africa
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

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

slide45
HOWEVER
    • Botswana our own stats show 40% incidence of exposure but <1% 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 2005;25:201-213

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

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

kaposi sarcoma
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

Robert Newton Univ of York UK

cervical cancer
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 < .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 < .01)

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

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

genital herpes
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

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

other infectious diseases with differences
Other infectious diseases with differences
  • Toxoplasmosis
    • COMMON opportunistic Infection in the west
    • <1% 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

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

diarrhoea in hiv patients
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

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

where does all this lead to where do modellers come in
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

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

we need you for
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

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

and for the fun things
And for the fun things?
  • Modelling even paints fitness landscapes of individual HIV viruses and enables prediction of resistance mutation patterns

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

slide54
I don’t 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!

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

slide55
Thank You for listening
  • Thankyou also to Florence Doualla Bell
    • Who enabled you not to sit through 90 minutes today!!
  • Sala Sintle

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

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