Chapter 20 : Cryptococcosis in Africa

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This chapter reviews the epidemiology, diagnosis, clinical manifestations, treatment, and prognosis of cryptococcosis in Africa and the ecology and population genetics of African isolates of . In the pre-highly active antiretroviral therapy (HAART) era in sub-Saharan Africa, cryptococcosis was often a sentinel opportunistic infection among HIV-infected adults, heralding the diagnosis of AIDS in more than 88% of cryptococcal cases. The initial diagnosis of cryptococcal meningitis in HAART naive, HIV-infected patients is relatively straightforward and involves microscopy and culture of clinical specimens, as well as serology. Maintenance therapy with fluconazole is usually prescribed for those patients who survive their initial episode of disease. The diagnosis of cryptococcal disease in HAART-treated patients with paradoxical immune reconstitution inflammatory syndrome (IRIS) is slightly more difficult. The formidable challenges of cryptococcosis in sub-Saharan Africa involve significant problems with diagnosis, management, and prevention. In sub-Saharan Africa, cases of cryptococcosis due to far exceed the number of infections caused by . Sub-Saharan Africa is the global epicenter of cryptococcosis and the HIV/AIDS pandemic. It is possible to elucidate the evolutionary relationships among African strains of and their global ancestors.

Citation: Govender N, Mitchell T, Litvintseva A, Miglia K. 2011. Cryptococcosis in Africa, p 269-285. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch20
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Summary of studies conducted in sub-Saharan Africa between 1983 and 2003 that reported the percentage of laboratory-confirmed meningitis caused by species ( ). Data are overlaid on a choropleth map of Africa, which illustrates estimated HIV seroprevalence in the general population, by country, 1999 to 2001. For each study, boxes denote the country, date(s) of study, and percentage of people with confirmed cryptococcal meningitis. Most fractions denote the number with cryptococcal meningitis divided by the number with laboratory-confirmed meningitis (i.e., any abnormal CSF parameters with or without detection of a pathogen). Exceptions: Denominator included: , people with clinically suspected meningitis; , people with elevated leukocytes in the CSF; or , people whose CSF specimens were examined with India ink.

Citation: Govender N, Mitchell T, Litvintseva A, Miglia K. 2011. Cryptococcosis in Africa, p 269-285. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch20
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Image of FIGURE 2

Published incidence rates for cryptococcosis from studies conducted in antiretroviral treatment-naive, HIV-infected, adult populations in sub-Saharan Africa ( ).

Citation: Govender N, Mitchell T, Litvintseva A, Miglia K. 2011. Cryptococcosis in Africa, p 269-285. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch20
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Distribution of molecular types in Africa as determined by MLST, amplified fragment length polymorphisms, and PCR fingerprinting ( ).

Citation: Govender N, Mitchell T, Litvintseva A, Miglia K. 2011. Cryptococcosis in Africa, p 269-285. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch20
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Strains of endemic to sub-Saharan Africa possess ancestral haplotypes of all MLST loci that have been analyzed, and these strains are associated with native African trees, including the mopane and baobab. This model suggests that a small number of strains emerged from Africa, established a new ecological niche in the excreta of (rock pigeon), and then disseminated around the world.

Citation: Govender N, Mitchell T, Litvintseva A, Miglia K. 2011. Cryptococcosis in Africa, p 269-285. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch20
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Pediatric isolates from the Republic of South Africa (RSA) were analyzed using Bayesian concordance analysis ( ). The nuclear DNA sequence data were obtained from 10 unlinked loci: , and , which total 6,259 base pairs, consisting of exons, introns, and an intragenic spacer region. Each strain in the Bayesian tree has a different sequence. The branch lengths for each genotype are presented as equal in length for aesthetic purposes only. The subpopulations were identified as follows: VNII by inclusion of the reference strain (WM626) and five other global VNII strains; VNI by RSA6420, which has the same genotype as the VNI reference strain (WM148); and VNB genotypes were identified from a separate Bayesian phylogeny of each locus that included several VNB reference strains (bt34, bt63, bt85, bt88, bt89, and bt131) ( ). The outgroup is the sequenced VNIV strain of serotype D (JEC21).

Citation: Govender N, Mitchell T, Litvintseva A, Miglia K. 2011. Cryptococcosis in Africa, p 269-285. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch20
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Nomenclature of the subpopulations of and

Citation: Govender N, Mitchell T, Litvintseva A, Miglia K. 2011. Cryptococcosis in Africa, p 269-285. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch20
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Environmental isolations of species from Africa

Citation: Govender N, Mitchell T, Litvintseva A, Miglia K. 2011. Cryptococcosis in Africa, p 269-285. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch20
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Clinical isolates of species from Africa

Citation: Govender N, Mitchell T, Litvintseva A, Miglia K. 2011. Cryptococcosis in Africa, p 269-285. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch20
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Comparison of clinical isolates of from adult and pediatric patients with cryptococcosis in South Africa

Citation: Govender N, Mitchell T, Litvintseva A, Miglia K. 2011. Cryptococcosis in Africa, p 269-285. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch20

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