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HIV and Tropical Diseases Judd Walson, MD, MPH April 22, 2010

HIV and Tropical Diseases Judd Walson, MD, MPH April 22, 2010. Case #1. 23 year old female presents to HIV Care Clinic where she receives care complaining of fever for 1 day. Family lives in an area that is holoendemic for malaria.

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HIV and Tropical Diseases Judd Walson, MD, MPH April 22, 2010

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  1. HIV and Tropical Diseases Judd Walson, MD, MPH April 22, 2010

  2. Case #1 • 23 year old female presents to HIV Care Clinic where she receives care complaining of fever for 1 day. • Family lives in an area that is holoendemic for malaria. • She is anemic (Hb of 6.5), tachypneic, mildly confused and has fever to 40.1 C.

  3. Malaria and HIV

  4. Classification of endemicity http://www.malaria.am/eng/epidemiology.php

  5. Immunology • CD4 cells play a role in the development and maintenance of immunity against malaria • Shift towards a Th2 type response to clear chronic malaria infection • Induction of regulatory T cells with production of suppressive cytokines (hyporesponsiveness) • Poor B cell response leads to reduced clearance of parasites

  6. Effects of HIV-1 on Malaria Incidence and Severity Laufer MK et al. Impact of HIV-associated immunosuppression on malaria infection and disease in Malawi. The Journal of Infectious Diseases 2006; 193:872–8

  7. Laufer MK et al. Impact of HIV-associated immunosuppression on malaria infection and disease in Malawi. The Journal of Infectious Diseases 2006; 193:872–8 French N et al. Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults. AIDS 2001 vol. 15 (7) pp. 899-906.

  8. Case #1 • 23 year old female presents to HIV Care Clinic where she receives care complaining of fever for 1 day. • Family lives in an area that is holoendemic for malaria. • She is anemic (Hb of 6.5), tachypneic, mildly confused and has fever to 40.1 C.

  9. Case #1 • Any other info needed? • What testing needed? • What treatment needed?

  10. The diagnosis of Malaria • Malaria is often over diagnosed! • Most clinics and hospitals in Africa do NOT do any testing but make a clinical diagnosis of malaria

  11. The diagnosis of Malaria • The sensitivity and specificity of malaria thin and thick smears are 50% and 96% respectively. • The proportion of patients with positive smears DECREASES with age. • In endemic areas, a positive smear may confirm malaria…but is that why the patient is sick?? Malaria Journal 2006, 5:4, BMJ 2004; 329; 1212

  12. BMJ  2004;329:121

  13. Tanzanian Study • 4474 people admitted to hospital met criteria (clinical) for severe malaria. • 2062 (46.1%) had positive slides • 2375 were slide negative • 66.1% did NOT receive antibiotics • Case fatality rates were significantly different • 12.1% in the slide negative patients (16.5% in age>15) • 6.9% in the slide positive patients (10.7% in age>15) BMJ 2004;329;1212-

  14. Malaria and Bacteremia JID 2007;195; 985-904.

  15. Case #1 • Attending clinic since diagnosis 11 months ago. • CD4 count 437 cells/mm3 about 9 weeks ago. • ART naïve. • On co-trimoxazole for past 7 months. • Thin Smear POSITIVE for P. falciparum with a parasite density of 600 parasites per microL (7.5%).

  16. Treatment • 23 year old female with documented parasitemia, CD4 count of 437 cells/mm3, on co-trimoxazole. • What are the treatment options? • Doe the fact that she is on co-trimoxazole and NOT on ART matter?

  17. Co-trimoxazole? • Why do we use co-trimoxazole in Africa? • What are the implications for treatment of malaria in a patient on co-trimoxazole? • What other interventions can we add to prevent malaria? Are any of these beneficial if the patient is compliant with co-trimoxazole?

  18. co-trimoxazole • co-trimoxazole reduces MORTALITY in HIV infected individuals in Africa!!! (46% reduction in mortality in Uganda). • co-trimoxazole decreases rates of malaria, diarrhea and hospitalizations in those on prophylaxis. • co-trimoxazole taken for prophylaxis reduces mortality in family members (63% percent less mortality in children less than 10!) and reduces malaria, diarrhea and hospitalizations in family members as well! Lancet 2004; 364 (9443) pp. 1428-34, AIDS; 2005; 19 (10) pp. 1035-42

  19. Resistance • There is demonstrated in-vitro cross-resistance between SP (fansidar) and co-trimoxazole. • Most countries do NOT use SP as first line malaria treatment (except IPT for pregnant women!) • In a randomized trial of co-trimoxazole to prevent malaria, there was no demonstrated increase in resistant parasites over 12 weeks and co-trimoxazole was 99.5% effective in preventing clinical malaria. JID 2005;192;1823.

  20. Additional Interventions • Bednets – In Uganda, insecticide Treated Nets (ITN’s) resulted in a 40% reduction in the incidence of symptomatic malaria, OVER AND ABOVE the benefit seen with prophylactic co-trimoxizole. • ITN’s are simple, effective, and, in contrast to TMP/SMZ, do not pose risk to the individuals of drug toxicity or development of resistant microbial flora. Lancet. 2006;367:1256-61.

  21. Treatment and ART • Efavirenz is metabolized by CYP 3A4 and alters artesunate and amodiaquine levels (may result in increased liver toxicity) NOT DEMONSTRATED. • Ritonovir inhibits P450 and may increase mefloquine and artemisinin levels. (One study showed increased neutropenia in children on ART receiving artesunate plus amodiaquine. • Most protease inhibitors have direct anti-malarial activities (? Effective prophylaxis?) Clin. Infect. Dis. 46, 985–991, Trends in Parasitology. 24 (6) pp. 264-71

  22. Effects of Malaria on HIV-1 Hoffman IF et al. The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma concentration. AIDS 1999 vol. 13 pp. 487-494

  23. J . Kublin , P . Patnaik , C . Jere , W . Miller , I . Hoffman , N . Chimbiya , R . Pendame , T . Taylor , M . Molyneux. Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: a prospective cohort study. The Lancet , Volume 365 , Issue 9455 , Pages 233 – 240.

  24. Effect of modest VL reduction Gupta et al. JID 2007; 195 (Feb 15).

  25. Abu-Raddad LJ et al. Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa. Science 2006 vol. 314 (5805) pp. 1603-6.

  26. Summary Malaria and HIV • HIV infected individuals are at risk for more frequent and more severe malaria. Both are CD4 count dependent. • Malaria increases plasma viral load. This may have important implications for both HIV disease progression and transmission. • Co-trimoxazole works for patients and their families and benefits ALL HIV infected individuals in resource poor settings REGARDLESS OF CD4 COUNT.

  27. CASE # 2 • 38 year old man presents to clinic with complaints of weight loss. Slowly losing weight over past year (from about 60kg to 54kg). • No other complaints (no fever, cough, chills, etc.) • Says he has noticed large 6-7cm worms in his stool.

  28. CASE # 2 • Given weight loss, HIV testing advised and performed and patient is HIV positive. • Stool test done and is positive for eggs of Ascaris lumbricoides and hookworm species. WHAT SHOULD BE DONE (IF ANYTHING?).

  29. Distribution of helminths and HIV-1 in Africa Clinical Microbiology Reviews, October 2004, p. 1012-1030, Vol. 17, No. 4

  30. Epidemiology • Over 2 billion people are estimated to be infected with at least one species of helminths. • In fact, about 25% of the worlds population is infested with one or more soil transmitted helminth. • Of the approximately 25 million people infected with HIV-1 in Africa, as many as 50-90% may also be infected with a soil transmitted helminth.

  31. Helminth egg burden correlated with HIV-1 viral load J Acquir Immune Defic Syndr, Volume 31(1).September 1, 2002.56-62

  32. Walson JL, John-Stewart G. Treatment of helminth co-infection in HIV-1 infected individuals in resource-limited settings. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD006419. DOI: 10.1002/14651858.CD006419.pub2.

  33. AIDS 2008; 22:1–9.

  34. Effects on CD4 and Viral Load AIDS 2008; 22:1–9.

  35. Case #3 • An HIV infected mother brings her 1 year old son in to clinic because his sibling (age 3) has had “measles” (diagnosed at local facility). • The child is HIV positive by antibody testing. • Currently the child is well, playing and does not appear ill. • What can/should be done to protect the child? • What other interventions/testing could be done for the child?

  36. Measles and HIV • Measles is exacerbated by HIV infection. • HIV infected individuals shed the virus longer. • Vaccination is less effective in individuals with HIV. • Measles vaccine is a “live” virus vaccine so there may be risks with it’s use.

  37. HIV and Measles - Mortality Measles occurs at younger ages (more likely to occur at age <9 months) AND is associated with increased mortality even after controlling for age, sex, and measles vaccination status. CID 2008; 46:523-7.

  38. PREVENTION • In areas where there is a risk of measles transmission – ALL children (including those with HIV – regardless of degree of immunosuppression) should be vaccinated?? • Consider early vaccination in HIV infected children at 6-9 months • Where available, monthly IgG can be given to exposed children who have poor vaccine response. CID 2007. 45 (9) pp. 1214-20

  39. Treatment • Supportive care • Vitamin A – shown to reduce mortality and lead to more rapid resolution of pneumonia and diarrhea. Most data in children under 2. • ?Ribavirin where available for severe cases. No RCT data. N Engl J Med 1990 Jul 19;323(3):160, JAMA 1989 May 5;261(17):2512-6.

  40. Next session: May 6, 2010 HIV Dermatology – Most Interesting Case Contest Dr Roy Colven

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