1887

Abstract

HIV and cryptococcal meningitis co-infection is a major public health problem in most developing countries. 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 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 meningitis in this cohort were males (=33/55; 60.0 %). The predominant genotype among the Zimbabwean isolates was genotype AFLP1/VNI (=40; 72.7 %), followed by AFLP1A/VNB/VNII (=8; 14.6 %), and AFLP1B/VNII was the least isolated (=7; 12.7 %). Most of the isolates were mating-type α (=51; 92.7 %), and only four (7.3 %) were mating-type . Overall in-hospital mortality was 55.6 % (=30), and no difference between infecting genotype and clinical outcome of patient (=0.73) or CD4 counts (=0.79) was observed. Zimbabwean 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 in Zimbabwe has a high level of genetic diversity when compared to other regional isolates.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000354
2016-11-16
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jmm/65/11/1281.html?itemId=/content/journal/jmm/10.1099/jmm.0.000354&mimeType=html&fmt=ahah

References

  1. Agapow P.-M., Burt A. 2001; Indices of multilocus linkage disequilibrium. Mol Ecol Notes 1:101–102 [View Article]
    [Google Scholar]
  2. Arsic Arsenijevic V., Pekmezovic M. G., Meis J. F., Hagen F. 2014; Molecular epidemiology and antifungal susceptibility of Serbian Cryptococcus neoformans isolates. Mycoses 57:380–387 [View Article][PubMed]
    [Google Scholar]
  3. Beale M. A., Sabiiti W., Robertson E. J., Fuentes-Cabrejo K. M., O'Hanlon S. J., Jarvis J. N., Loyse A., Meintjes G., Harrison T. S. et al. 2015; Genotypic diversity is associated with clinical outcome and phenotype in cryptococcal meningitis across Southern Africa. PLoS Negl Trop Dis 9:e0003847 [View Article][PubMed]
    [Google Scholar]
  4. Beardsley J., Wolbers M., Kibengo F. M., Ggayi A. B., Kamali A., Cuc N. T., Binh T. Q., Chau N. V., Farrar J. et al. 2016; Adjunctive dexamethasone in HIV-associated cryptococcal meningitis. N Engl J Med 374:542–554 [View Article][PubMed]
    [Google Scholar]
  5. Boekhout T., Theelen B., Diaz M., Fell J. W., Hop W. C., Abeln E. C., Dromer F., Meyer W. 2001; Hybrid genotypes in the pathogenic yeast Cryptococcus neoformans . Microbiology 147:891–907 [View Article][PubMed]
    [Google Scholar]
  6. Bogaerts J., Rouvroy D., Taelman H., Kagame A., Aziz M. A., Swinne D., Verhaegen J. 1999; AIDS-associated cryptococcal meningitis in Rwanda (1983–1992): epidemiologic and diagnostic features. J Infect 39:32–37 [View Article][PubMed]
    [Google Scholar]
  7. Boulware D. R., Meya D. B., Muzoora C., Rolfes M. A., Huppler Hullsiek K., Musubire A., Taseera K., Nabeta H. W., Schutz C. et al. 2014; Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med 370:2487–2498 [View Article][PubMed]
    [Google Scholar]
  8. Chaskes S., Frases S., Cammer M., Gerfen G., Casadevall A. 2008; Growth and pigment production on D-tryptophan medium by Cryptococcus gattii, Cryptococcus neoformans, and Candida albicans . J Clin Microbiol 46:255–264 [View Article][PubMed]
    [Google Scholar]
  9. Chen Y., Litvintseva A. P., Frazzitta A. E., Haverkamp M. R., Wang L., Fang C., Muthoga C., Mitchell T. G., Perfect J. R. 2015; Comparative analyses of clinical and environmental populations of Cryptococcus neoformans in Botswana. Mol Ecol 24:3559–3571 [View Article][PubMed]
    [Google Scholar]
  10. Cogliati M. 2013; Global molecular epidemiology of Cryptococcus neoformans and Cryptococcus gattii: an atlas of the molecular types. Scientifica 2013:1–23 [View Article]
    [Google Scholar]
  11. Day J. N. 2004; Cryptococcal meningitis. Pract Neurol 5:274–285
    [Google Scholar]
  12. Fonseca A., Boekhout T., Fell J. W. 2011; Cryptococcus. In The Yeast: A Taxonomic Study , pp. 1661–17347 Edited by Kurtzman C. P., Fell J. W., Boekhout T. Elsevier Science; [CrossRef]
    [Google Scholar]
  13. Hagen F., Illnait-Zaragozí M. T., Meis J. F., Chew W. H., Curfs-Breuker I., Mouton J. W., Hoepelman A. I., Spanjaard L., Verweij P. E. et al. 2012; Extensive genetic diversity within the Dutch clinical Cryptococcus neoformans population. J Clin Microbiol 50:1918–1926 [View Article][PubMed]
    [Google Scholar]
  14. Hagen F., Khayhan K., Theelen B., Kolecka A., Polacheck I., Sionov E., Falk R., Parnmen S., Lumbsch H. T., Boekhout T. 2015; Recognition of seven species in the Cryptococcus gattii/Cryptococcus neoformans species complex. Fungal Genet Biol 78:16–48 [View Article][PubMed]
    [Google Scholar]
  15. Hakim J. G., Gangaidzo I. T., Heyderman R. S., Mielke J., Mushangi E., Taziwa A., Robertson V. J., Musvaire P., Mason P. R. 2000; Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients. AIDS 14:1401–1407 [View Article][PubMed]
    [Google Scholar]
  16. Heyderman R. S., Gangaidzo I. T., Hakim J. G., Mielke J., Taziwa A., Musvaire P., Robertson V. J., Mason P. R. 1998; Cryptococcal meningitis in human immunodeficiency virus-infected patients in Harare, Zimbabwe. Clin Infect Dis 26:284–289 [View Article][PubMed]
    [Google Scholar]
  17. Hiremath S. S., Chowdhary A., Kowshik T., Randhawa H. S., Sun S., Xu J. 2008; Long-distance dispersal and recombination in environmental populations of Cryptococcus neoformans var. grubii from India. Microbiology 154:1513–1524 [View Article][PubMed]
    [Google Scholar]
  18. Illnait-Zaragozi M. T., Martínez-Machín G. F., Fernández-Andreu C. M., Boekhout T., Meis J. F., Klaassen C. H. 2010; Microsatellite typing of clinical and environmental Cryptococcus neoformans var. grubii isolates from Cuba shows multiple genetic lineages. PLoS One 5:e9124 [View Article][PubMed]
    [Google Scholar]
  19. Irokanulo E. A., Akueshi C. O., Makinde A. A. 1994; Differentiation of Cryptococcus neoformans serotypes A and D using creatinine dextrose bromothymol blue thymine medium. Br J Biomed Sci 51:100–103[PubMed]
    [Google Scholar]
  20. Jarvis J. N., Meintjes G., Williams A., Brown Y., Crede T., Harrison T. S. 2010; Adult meningitis in a setting of high HIV and TB prevalence: findings from 4961 suspected cases. BMC Infect Dis 10: [View Article][PubMed]
    [Google Scholar]
  21. Kambugu A., Meya D. B., Rhein J., O'Brien M., Janoff E. N., Ronald A. R., Kamya M. R., Mayanja-Kizza H., Sande M. A. et al. 2008; Outcomes of cryptococcal meningitis in Uganda before and after the availability of highly active antiretroviral therapy. Clin Infect Dis 46:1694–1701 [View Article][PubMed]
    [Google Scholar]
  22. Kangogo M., Bader O., Boga H., Wanyoike W., Folba C., Worasilchai N., Weig M., Groß U., Bii C. C. 2015; Molecular types of Cryptococcus gattii/Cryptococcus neoformans species complex from clinical and environmental sources in Nairobi, Kenya. Mycoses 58:665–670 [View Article][PubMed]
    [Google Scholar]
  23. Kwon-Chung K. J., Polacheck I., Bennett J. E. 1982; Improved diagnostic medium for separation of Cryptococcus neoformans var. neoformans (serotypes A and D) and Cryptococcus neoformans var. gattii (serotypes B and C). J Clin Microbiol 15:535–537[PubMed]
    [Google Scholar]
  24. Lessells R. J., Mutevedzi P. C., Heller T., Newell M. L. 2011; Poor long-term outcomes for cryptococcal meningitis in rural South Africa. S Afr Med J 101:251–252 [View Article][PubMed]
    [Google Scholar]
  25. Litvintseva A. P., Marra R. E., Nielsen K., Heitman J., Vilgalys R., Mitchell T. G., Mitchell T. G. 2003; Evidence of sexual recombination among Cryptococcus neoformans serotype A isolates in sub-Saharan Africa. Eukaryot Cell 2:1162–1168 [View Article][PubMed]
    [Google Scholar]
  26. Litvintseva A. P., Thakur R., Reller L. B., Mitchell T. G. 2005; Prevalence of clinical isolates of Cryptococcus gattii serotype C among patients with AIDS in sub-Saharan Africa. J Infect Dis 192:888–892 [View Article][PubMed]
    [Google Scholar]
  27. Liu X.-Z., Wang Q.-M., Göker M., Groenewald M., Kachalkin A. V., Lumbsch H. T., Millanes A. M., Wedin M., Yurkov A. M. et al. 2015a; Towards an integrated phylogenetic classification of the Tremellomycetes. Studies in Mycol 81:85–147 [View Article]
    [Google Scholar]
  28. Liu X. Z., Wang Q. M., Theelen B., Groenewald M., Bai F. Y., Boekhout T. 2015b; Phylogeny of tremellomycetous yeasts and related dimorphic and filamentous basidiomycetes reconstructed from multiple gene sequence analyses. Stud Mycol 81:1–26 [View Article]
    [Google Scholar]
  29. Makadzange A. T., Ndhlovu C. E., Takarinda K., Reid M., Kurangwa M., Gona P., Hakim J. G. 2010; Early versus delayed initiation of antiretroviral therapy for concurrent HIV infection and cryptococcal meningitis in sub-Saharan Africa. Clin Infect Dis 50:1532–1538 [View Article][PubMed]
    [Google Scholar]
  30. McCarthy K. M., Morgan J., Wannemuehler K. A., Mirza S. A., Gould S. M., Mhlongo N., Moeng P., Maloba B. R., Crewe-Brown H. H. et al. 2006; Population-based surveillance for cryptococcosis in an antiretroviral-naive South African province with a high HIV seroprevalence. AIDS 20:2199–2206 [View Article][PubMed]
    [Google Scholar]
  31. McClelland E. E., Hobbs L. M., Rivera J., Casadevall A., Potts W. K., Smith J. M., Ory J. J. 2013; The role of host gender in the pathogenesis of Cryptococcus neoformans infections. PLoS One 8:e63632 [View Article][PubMed]
    [Google Scholar]
  32. Mitchell T. G., Perfect J. R. 1995; Cryptococcosis in the era of AIDS-100 years after the discovery of Cryptococcus neoformans . Clin Microbiol Rev 8:515–548[PubMed]
    [Google Scholar]
  33. Mwaba P., Mwansa J., Chintu C., Pobee J., Scarborough M., Portsmouth S., Zumla A. 2001; Clinical presentation, natural history, and cumulative death rates of 230 adults with primary cryptococcal meningitis in Zambian AIDS patients treated under local conditions. Postgrad Med J 77:769–773 [View Article][PubMed]
    [Google Scholar]
  34. Nyazika T. K., Hagen F., Meis J. F., Robertson V. J. 2016a; Cryptococcus tetragattii as a major cause of cryptococcal meningitis among HIV-infected individuals in Harare, Zimbabwe. J Infect 72:745–752 [View Article]
    [Google Scholar]
  35. Nyazika T. K., Robertson V. J., Nherera B., Mapondera P., Meis J. F., Hagen F. 2016b; Comparison of biotyping methods as alternative identification tools to molecular typing of pathogenic Cryptococcus species in sub-Saharan Africa. Mycoses 59:151–156 [CrossRef]
    [Google Scholar]
  36. Park B. J., Wannemuehler K. A., Marston B. J., Govender N., Pappas P. G., Chiller T. M. 2009; Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23:525–530 [View Article][PubMed]
    [Google Scholar]
  37. Sogbanmu O. O., John M.-A. A., Lalloo U. 2014; Management of cryptococcal meningitis in adults at Mthatha Hospital Complex, Eastern Cape, South Africa. South Afr J HIV Med 15:104 [View Article]
    [Google Scholar]
  38. Swinne D., Nkurikiyinfura J. B., Muyembe T. L. 1986; Clinical isolates of Cryptococcus neoformans from Zaire. Eur J Clin Microbiol 5:50–51 [View Article][PubMed]
    [Google Scholar]
  39. Swinne D., Deppner M., Laroche R., Floch J. J., Kadende P. 1989; Isolation of Cryptococcus neoformans from houses of AIDS-associated cryptococcosis patients in Bujumbura (Burundi). AIDS 3:389–390 [View Article][PubMed]
    [Google Scholar]
  40. Swinne D., Deppner M., Maniratunga S., Laroche R., Floch J. J., Kadende P. 1991; AIDS-associated cryptococcosis in Bujumbura, Burundi: an epidemiological study. J Med Vet Mycol 29:25–30 [View Article][PubMed]
    [Google Scholar]
  41. Van Wyk M., Govender N. P., Mitchell T. G., Litvintseva A. P. GERMS-SA 2014; Multilocus sequence typing of serially collected isolates of Cryptococcus from HIV-infected patients in South Africa. J Clin Microbiol 52:1921–1931 [View Article][PubMed]
    [Google Scholar]
  42. Wiesner D. L., Moskalenko O., Corcoran J. M., McDonald T., Rolfes M. A., Meya D. B., Kajumbula H., Kambugu A., Bohjanen P. R. et al. 2012; Cryptococcal genotype influences immunologic response and human clinical outcome after meningitis. MBio 3: e00196-12 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000354
Loading
/content/journal/jmm/10.1099/jmm.0.000354
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error