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Current State of Infectious Diseases in Southern Africa

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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Current State of Infectious Diseases in Southern Africa

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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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)

  13. 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

  14. Reported TB Case Rate Botswana, 1975–2004 and HIV Prevalence Antenatal Women, 1992-2005 HIV TB 09/2006 TB Unit Ministry of Health Botswana

  15. Malawi illustrates this-- note increasing smear negative cases 30% treatment success and 60% mortality

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. What about other respiratory diseases? 09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling

  22. Pneumococcal invasive illness has escalated in our region… 09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling

  23. 09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling

  24. 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

  25. 09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling

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

  27. 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

  28. 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

  29. 09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling

  30. 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

  31. 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

  32. 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

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

  34. 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

  35. 09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling

  36. 09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling

  37. 09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling

  38. 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

  39. 09/2006 Facing the Challenges of Infectious Diseases in Africa- the Role of Mathematical Modelling

  40. 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

  41. 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

  42. 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

  43. 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

  44. 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

  45. 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

  46. 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

  47. 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

  48. 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

  49. 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

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