All ETDs from UAB

Advisory Committee Chair

Pauline E Jolly

Advisory Committee Members

Walter Jaoko

Mirjam-Colette Kempf

Inmaculada B Aban

Peter G Pappas

John W Baddley

Document Type

Dissertation

Date of Award

2010

Degree Name by School

Doctor of Public Health (DrPH) School of Public Health

Abstract

Cryptococcal meningitis (CM) is a significant public health burden, and a leading cause of death among human immunodeficiency virus (HIV) positive patients in Kenya. The emergence of Cryptococcus neoformans resistance to fluconazole (FLC) was recently reported in Kenya but it is not known if this resistance is widespread. The objective of this dissertation was to determine the prevalence, risk factors and mortality associated with CM and antifungal drug susceptibilities of incident C. neoformans isolates from HIV positive patients presenting at two referral hospitals in Nairobi, Kenya. A cross-sectional study of confirmed HIV patients at Kenyatta National Hospital (KNH) and Mbagathi District Hospital (MDH) was conducted between August 2008 and February 2009. CM diagnosis was determined from cerebrospinal fluid (CSF) by Cryptococcus latex agglutination (CrAg) test. Data collected included demographic, clinical information and antifungal susceptibilities of C. neoformans. Of the 340 suspected CM patients 111 (33%) were confirmed positive for CM. Among the CM positive patients, in-hospital mortality was 36% (38/106), median age was 35 years (range, 19-60 years) and median CD4 count was 41 cells/µL (n=89, range 2-720 cells/µL). Clinical manifestations among CM patients were headache 103 (93%), neck stiffness 76 (69%) and weight loss 53 (48%). Factors independently associated with increased risk for CM in the multivariable model were male sex, headache, blurred vision and previous antifungal drug use. Night sweats and being on antiretroviral therapy were associated with reduced risk for CM. Previous or current ART and CD4 count <50 cells/ µL were independently associated with mortality. Six percent of the 67 isolates tested were identified as C. neoformans var. gattii serotype B or C and 94% as C. neoformans var. neoformans. All isolates were susceptible to AMB, VOR and RAV (100%), FLC (97%) and 5-FC (90%). Only 3% and 10% of the isolates' susceptibility to FLC and 5-FC respectively, was dose dependent or intermediate. Our findings show a high CM burden and mortality in HIV patients presenting at KNH and MDH despite aggressive treatment with antifungal drugs. Antifungal susceptibilities of incident C. neoformans isolates were high. This study demonstrates the need to address the existing inadequacies of CM management in Kenya.

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