Current Fungal Infection Reports

, Volume 6, Issue 1, pp 35–40 | Cite as

Diagnosis and Management of Cryptococcal Disease in Resource-Limited Settings

  • Michelle Vanselow
  • Mary E. Brandt
  • Benjamin J. ParkEmail author
Current Management of Fungal Infections (L Ostrosky-Zeichner, Section Editor)


Cryptococcal meningitis is one of the most important fungal infections in the developing world, where deaths related to this disease are numerous. In resource-limited settings, mortality is high in large part because of difficulties in the diagnosis and management of this infection. This paper outlines many of the realities in many resource-limited settings, and describes priorities for public health action and research.


Cryptococcus Cryptococcosis Cryptococcal meningitis Diagnosis Management HIV/AIDS Resource-limited settings Amphotericin Fluconazole Lateral flow assay Cryptococcal antigen Latex agglutination 



The findings and conclusions in this presentation/report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.


No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Ellis DH, Pfeiffer TJ. Ecology, life cycle, and infectious propagule of Cryptococcus neoformans. Lancet. 1990;336(8720):923–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Mitchell TG, Perfect JR. Cryptococcosis in the era of AIDS—100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev. 1995;8(4):515–48.PubMedGoogle Scholar
  3. 3.
    •• Park BJ, Wannemuehler KA, et al. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS. 2009;23(4):525–30. This paper demonstrated the disparity in the burden of cryptococcal disease; it showed that the vast majority of cases were occurring in resource-limited settings. PubMedCrossRefGoogle Scholar
  4. 4.
    Kaplan JE, Hanson D, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis. 2000;30 Suppl 1:S5–S14.PubMedCrossRefGoogle Scholar
  5. 5.
    van Elden LJ, Walenkamp AM, et al. Declining number of patients with cryptococcosis in the Netherlands in the era of highly active antiretroviral therapy. AIDS. 2000;14(17):2787–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Chen SC. Cryptococcosis in Australasia and the treatment of cryptococcal and other fungal infections with liposomal amphotericin B. J Antimicrob Chemother. 2002;49 Suppl 1:57–61.PubMedCrossRefGoogle Scholar
  7. 7.
    Mirza SA, Phelan M, et al. The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992–2000. Clin Infect Dis. 2003;36(6):789–94.PubMedCrossRefGoogle Scholar
  8. 8.
    Dromer F, Mathoulin-Pelissier S, et al. Epidemiology of HIV-associated cryptococcosis in France (1985–2001): comparison of the pre- and post-HAART eras. AIDS. 2004;18(3):555–62.PubMedCrossRefGoogle Scholar
  9. 9.
    Okongo M, Morgan D, et al. Causes of death in a rural, population-based human immunodeficiency virus type 1 (HIV-1) natural history cohort in Uganda. Int J Epidemiol. 1998;27(4):698–702.PubMedCrossRefGoogle Scholar
  10. 10.
    Bogaerts J, Rouvroy D, et al. AIDS-associated cryptococcal meningitis in Rwanda (1983–1992): epidemiologic and diagnostic features. J Infect. 1999;39(1):32–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Hakim JG, Gangaidzo IT, et al. Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients. AIDS. 2000;14(10):1401–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Mwaba P, Mwansa J, et al. 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. 2001;77(914):769–73.PubMedCrossRefGoogle Scholar
  13. 13.
    French N, Gray K, et al. Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS. 2002;16(7):1031–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Helbok R, Pongpakdee S, et al. Chronic meningitis in Thailand. Clinical characteristics, laboratory data and outcome in patients with specific reference to tuberculosis and cryptococcosis. Neuroepidemiology. 2006;26(1):37–44.PubMedCrossRefGoogle Scholar
  15. 15.
    Lortholary O, Poizat G, et al. Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy. AIDS. 2006;20(17):2183–91.PubMedCrossRefGoogle Scholar
  16. 16.
    Perfect JR, Dismukes WE, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(3):291–322.PubMedCrossRefGoogle Scholar
  17. 17.
    McCarthy KM, Morgan J, et al. Population-based surveillance for cryptococcosis in an antiretroviral-naive South African province with a high HIV seroprevalence. AIDS. 2006;20(17):2199–206.PubMedCrossRefGoogle Scholar
  18. 18.
    Saha DC, Xess I, et al. Evaluation of conventional & serological methods for rapid diagnosis of cryptococcosis. Indian J Med Res. 2008;127(5):483–8.PubMedGoogle Scholar
  19. 19.
    Mundy C, Ngwira M, et al. Evaluation of microscope condition in Malawi. Trans R Soc Trop Med Hyg. 2000;94(5):583–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Bates I, Bekoe V, et al. Improving the accuracy of malaria-related laboratory tests in Ghana. Malar J. 2004;3:38.PubMedCrossRefGoogle Scholar
  21. 21.
    Perry L, Malkin R. Effectiveness of medical equipment donations to improve health systems: how much medical equipment is broken in the developing world? Med Biol Eng Comput. 2011;49(7):719–22.PubMedCrossRefGoogle Scholar
  22. 22.
    Bimenya GS, Nzarubara GR, et al. The accuracy of self monitoring blood glucose meter systems in Kampala, Uganda. Afr Health Sci. 2003;3(1):23–32.PubMedGoogle Scholar
  23. 23.
    Harries AD, Michongwe J, et al. Using a bus service for transporting sputum specimens to the Central Reference Laboratory: effect on the routine TB culture service in Malawi. Int J Tuberc Lung Dis. 2004;8(2):204–10.PubMedGoogle Scholar
  24. 24.
    Frank UK, Nishimura SL, et al. Evaluation of an enzyme immunoassay for detection of cryptococcal capsular polysaccharide antigen in serum and cerebrospinal fluid. J Clin Microbiol. 1993;31(1):97–101.PubMedGoogle Scholar
  25. 25.
    Tanner DC, Weinstein MP, et al. Comparison of commercial kits for detection of cryptococcal antigen. J Clin Microbiol. 1994;32(7):1680–4.PubMedGoogle Scholar
  26. 26.
    Feldmesser M, Harris C, et al. Serum cryptococcal antigen in patients with AIDS. Clin Infect Dis. 1996;23(4):827–30.PubMedCrossRefGoogle Scholar
  27. 27.
    •• Meya DB, Manabe YC, et al. Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings. Clin Infect Dis. 2010;51(4):448–55. This paper is one of the first to demonstrate the effectiveness of early diagnosis and treatment of cryptococcal disease. PubMedCrossRefGoogle Scholar
  28. 28.
    Petti CA, Polage CR, et al. Laboratory medicine in Africa: a barrier to effective health care. Clin Infect Dis. 2006;42(3):377–82.PubMedCrossRefGoogle Scholar
  29. 29.
    •• Jarvis JN, Percival A, et al. Evaluation of a novel point-of-care cryptococcal antigen test on serum, plasma, and urine from patients with HIV-associated cryptococcal meningitis. Clin Infect Dis. 2011;53(10):1019–23. This paper demonstrates the utility of a point-of-care test, the lateral flow assay, in the diagnosis of cryptococcal disease. PubMedCrossRefGoogle Scholar
  30. 30.
    •• Lindsley MD, Mekha N, et al. Evaluation of a newly developed lateral flow immunoassay for the diagnosis of cryptococcosis. Clin Infect Dis. 2011;53(4):321–5. This paper demonstrates the utility of a point-of-care test, the lateral flow assay, in the diagnosis of cryptococcal disease. PubMedCrossRefGoogle Scholar
  31. 31.
    Urdea M, Penny LA, et al. Requirements for high impact diagnostics in the developing world. Nature. 2006;444 Suppl 1:73–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Mock C, Nguyen S, et al. Evaluation of trauma care capabilities in four countries using the WHO-IATSIC Guidelines for Essential Trauma Care. World J Surg. 2006;30(6):946–56.PubMedCrossRefGoogle Scholar
  33. 33.
    Grimes CE, Bowman KG, et al. Systematic review of barriers to surgical care in low-income and middle-income countries. World J Surg. 2011;35(5):941–50.PubMedCrossRefGoogle Scholar
  34. 34.
    • Jackson A, Hosseinipour MC. Management of cryptococcal meningitis in sub-Saharan Africa. Curr HIV/AIDS Rep. 2010;7(3):134–42. This paper summarizes the approach to cryptococcal management in many resource-limited settings. PubMedCrossRefGoogle Scholar
  35. 35.
    Liechty CA, Solberg P, et al. Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda. Trop Med Int Health. 2007;12(8):929–35.PubMedCrossRefGoogle Scholar
  36. 36.
    Micol R, Lortholary O, et al. Prevalence, determinants of positivity, and clinical utility of cryptococcal antigenemia in Cambodian HIV-infected patients. J Acquir Immune Defic Syndr. 2007;45(5):555–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Jarvis JN, Lawn SD, et al. Screening for cryptococcal antigenemia in patients accessing an antiretroviral treatment program in South Africa. Clin Infect Dis. 2009;48(7):856–62.PubMedCrossRefGoogle Scholar
  38. 38.
    Pongsai P, Atamasirikul K, et al. The role of serum cryptococcal antigen screening for the early diagnosis of cryptococcosis in HIV-infected patients with different ranges of CD4 cell counts. J Infect. 2010;60(6):474–7.PubMedCrossRefGoogle Scholar
  39. 39.
    •• Micol R, Tajahmady A, et al. Cost-effectiveness of primary prophylaxis of AIDS associated cryptococcosis in Cambodia. PLoS One. 2010;5(11):e13856. This paper compares public health strategies to reduce the burden of cryptococcal disease in Cambodia. PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2012

Authors and Affiliations

  • Michelle Vanselow
    • 1
  • Mary E. Brandt
    • 1
  • Benjamin J. Park
    • 1
    Email author
  1. 1.Mycotic Diseases Branch, Centers for Disease Control and PreventionAtlantaUSA

Personalised recommendations