Cryptococcus neoformans population diversity and clinical outcomes of HIV-associated cryptococcal meningitis patients in Zimbabwe.

Abstract

HIV and cryptococcal meningitis co-infection is a major public health problem in most developing countries. Cryptococcus neoformans sensu stricto is responsible for the majority of HIV-associated cryptococcosis cases in sub-Saharan Africa. Despite the available information, little is known about cryptococcal population diversity and its association with clinical outcomes in patients with HIV-associated cryptococcal meningitis in sub-Saharan Africa. In a prospective cohort, we investigated the prevalence and clinical outcome of Cryptococcusneoformans sensu stricto meningitis among HIV-infected patients in Harare, Zimbabwe, and compared the genotypic diversity of the isolates with those collected from other parts of Africa. Molecular typing was done using amplified fragment length polymorphism genotyping and microsatellite typing. The majority of patients with HIV-associated Cryptococcusneoformans sensu stricto meningitis in this cohort were males (n=33/55; 60.0 %). The predominant Cryptococcus neoformans sensu stricto genotype among the Zimbabwean isolates was genotype AFLP1/VNI (n=40; 72.7 %), followed by AFLP1A/VNB/VNII (n=8; 14.6 %), and AFLP1B/VNII was the least isolated (n=7; 12.7 %). Most of the isolates were mating-type α (n=51; 92.7 %), and only four (7.3 %) were mating-type a. Overall in-hospital mortality was 55.6 % (n=30), and no difference between infecting genotype and clinical outcome of patient (P=0.73) or CD4+ counts (P=0.79) was observed. Zimbabwean Cryptococcusneoformans sensu stricto genotypes demonstrated a high level of genetic diversity by microsatellite typing, and 51 genotypes within the main molecular types AFLP1/VNI, AFLP1A/VNB/VNII and AFLP1B/VNII were identified. This study demonstrates that Cryptococcusneoformans sensu stricto in Zimbabwe has a high level of genetic diversity when compared to other regional isolates.