Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults

Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
AIDS (Impact Factor: 6.56). 05/2002; 16(7):1031-8. DOI: 10.1097/00002030-200205030-00009
Source: PubMed

ABSTRACT Despite the recognition of Cryptococcus neoformans as a major cause of meningitis in HIV-infected adults in sub-Saharan Africa, little is known about the relative importance of this potentially preventable infection as a cause of mortality and suffering in HIV-infected adults in this region.
A cohort study of 1372 HIV-1-infected adults, enrolled and followed up between October 1995 and January 1999 at two community clinics in Entebbe, Uganda.
Systematic and standardized assessment of illness episodes to describe cryptococcal disease and death rates.
Cryptococcal disease was diagnosed in 77 individuals (rate 40.4/1000 person-years) and was associated with 17% of all deaths (77 out of 444) in the cohort. Risk of infection was strongly associated with CD4 T cell counts < 200 x 10(6) cells/l(75 patients) and World Health Organization (WHO) clinical stage 3 and 4 (68 patients). Meningism was present infrequently on presentation (18%). Clinical findings had limited discriminatory diagnostic value. Serum cryptococcal antigen testing was the most sensitive and robust diagnostic test. Cryptococcal antigenaemia preceded symptoms by a median of 22 days (> 100 days in 11% of patients). Survival following diagnosis was poor (median survival 26 days; range 0-138).
Cryptococcal infection is an important contributor to mortality and suffering in HIV-infected Ugandans. Improvements in access to effective therapy of established disease are necessary. In addition, prevention strategies, in particular chemoprophylaxis, should be evaluated while awaiting the outcome of initiatives to make antiretroviral therapy more widely available.

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Available from: Jessica Nakiyingi-Miiro, Aug 10, 2015
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    • "In sub-Saharan Africa and South-East Asia, invasive cryptococcal disease is the second most common life-threatening HIV-associated opportunistic infection after tuberculosis and results in up to 20% of deaths (Tansuphasawadikul et al. 1999; Chariyalertsak et al. 2001; French et al. 2002; Lawn et al. 2008). A recent study estimates that cryptococcal meningitis may even be surpassing tuberculosis as the leading cause of death among individuals with HIV infection in sub-Saharan Africa (Park et al. 2009). "
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    ABSTRACT: OBJECTIVES: To test the hypothesis that a screening and treatment intervention for early cryptococcal infection would improve survival among HIV-infected individuals with low CD4 cell counts. METHODS: Newly enrolled patients at Family AIDS Care and Education Services (FACES) in Kenya with CD4 ≤ 100 cells/μl were tested for serum cryptococcal antigen (sCrAg). Individuals with sCrAg titre ≥ 1:2 were treated with high-dose fluconazole. Cox proportional hazard models of Kaplan-Meier curves were used to compare survival among individuals with CD4 ≤ 100 cells/μl in the intervention and historical control groups. RESULTS: The median age was 34 years [IQR: 29,41], 54% were female, and median CD4 was 43 cells/μl [IQR: 18,71]. Follow-up time was 1224 person-years. In the intervention group, 66% (514/782) were tested for sCrAg; of whom, 11% (59/514) were sCrAg positive. Mortality was 25% (196/782) in the intervention group and 25% (191/771) in the control group. There was no significant difference between the intervention and control group in overall survival [hazard ratio (HR): 1.1 (95%CI:0.9,1.3)] or three-month survival [HR: 1.0 (95%CI:0.8,1.3)]. Within the intervention group, sCrAg-positive individuals had significantly lower survival rates than sCrAg-negative individuals [HR:1.8 (95%CI: 1.0, 3.0)]. CONCLUSIONS: A screening and treatment intervention to identify sCrAg-positive individuals and treat them with high-dose fluconazole did not significantly improve overall survival among HIV-infected individuals with CD4 counts ≤ 100 cells/μl compared to a historical control, perhaps due to intervention uptake rates or poor efficacy of high-dose oral fluconazole.
    Tropical Medicine & International Health 02/2013; 18(4). DOI:10.1111/tmi.12067 · 2.30 Impact Factor
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    • "Country Population CRAG + outcomes Comments French 2002 Uganda 1372 HIV+, No ART Average survival 26 days Serum CRAG was a sensitive test. Detectable a median of 22 days before symptoms (100 days in 11%). "
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    ABSTRACT: Cryptococcal meningitis is a leading cause of death in AIDS patients in sub-Saharan Africa. Cryptococcal antigen (CRAG) can be detected weeks before onset of symptoms, and those who are asymptomatic but CRAG positive have a high risk of subsequent cryptococcal meningitis and mortality. A new CRAG point of care immunochromatographic test is available that is remarkably easy to administer without laboratory infrastructure or expertise and has excellent sensitivity and specificity. We review the benefits of targeted CRAG screening, developments in CRAG diagnostics, and evidence regarding treatment options that can be implemented into routine HIV care in areas of high cryptococcal burden. Based on published CRAG+ prevalence rates of 2%-12%, the cost to save one life is between $20 to $140 in sub-Saharan Africa. We provide recommendations for implementation, pre-emptive treatment, and identify the gaps in our current knowledge.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2012; 59(5):e85-91. DOI:10.1097/QAI.0b013e31824c837e · 4.39 Impact Factor
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    • "Current trends indicate that, most cases of cyptococcal meningitis found in Africa are among HIV-infected people with <100 cells/µl CD4 T cell count. Based on reported figures it is known that cyptococcal meningitis causes between 10-20 % deaths in Africa (French, 2002; Okongo, 1998; Park, 2009). Recently, a study in Malawi found cyptococcal meningitis to be the most common cause of meningitis disease with 40 % of cases from HIV-infected people. "
    Pathogenesis of Encephalitis, Edited by Daisuke Hayasaka, 12/2011: chapter 13: pages 195-208; InTech., ISBN: 978-953-307-741-3
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