Advertisement

Current HIV/AIDS Reports

, Volume 9, Issue 3, pp 267–277 | Cite as

New Insights in the Prevention, Diagnosis, and Treatment of Cryptococcal Meningitis

  • Arthur Jackson
  • Charles van der Horst
Co-infections (C Benson, Section Editor)

Abstract

Cryptococcal meningitis (CM) remains a major cause of morbidity and mortality among immunocompromised patients, especially in areas of high HIV prevalence, although it can also cause disease in the apparently immunocompetent. Improving the management of HIV-associated CM is important to ensure that patients can survive to benefit from increasing access to ART. In this review we focus on recent advances in prevention, diagnosis, and treatment of CM.

Keywords

Cryptococcus Cryptococcal meningitis Meningitis HIV Immunocompromised Prevention Diagnosis Treatment 

Notes

Disclosure

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

References

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

  1. 1.
    Okongo M, Morgan D, Mayanja B, Ross A, Whitworth J. 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. Epub 1998/10/03.PubMedCrossRefGoogle Scholar
  2. 2.
    French N, Gray K, Watera C, Nakiyingi J, Lugada E, Moore M, et al. Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS. 2002;16(7):1031–8.PubMedCrossRefGoogle Scholar
  3. 3.
    • Park B, Wannemuehler K, Marston B, Govender N, Pappas P, Chiller T. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS. 2009;23(4):525–30. This article highlights the devastating effect of this underappreciated disease in resource-limited areas. PubMedCrossRefGoogle Scholar
  4. 4.
    Kiertiburanakul S, Watcharatipagorn S, Chongtrakool P, Santanirand P. Epidemiology of bloodstream infections and predictive factors of mortality among HIV-infected adult patients in Thailand in the era of highly active antiretroviral therapy. Jpn J Infect Dis. 2012;65(1):28–32. Epub 2012/01/26.PubMedGoogle Scholar
  5. 5.
    Scarborough M, Gordon SB, Whitty CJ, French N, Njalale Y, Chitani A, et al. Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. N Engl J Med. 2007;357(24):2441–50.PubMedCrossRefGoogle Scholar
  6. 6.
    Ellis DH, Pfeiffer TJ. Ecology, life cycle, and infectious propagule of Cryptococcus neoformans. Lancet. 1990;336(8720):923–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Bartlett KH, Cheng PY, Duncan C, Galanis E, Hoang L, Kidd S, et al. A decade of experience: Cryptococcus gattii in British Columbia. Mycopathologia. 2012;173(5–6):311–9Google Scholar
  8. 8.
    Harris JR, Lockhart SR, Debess E, Marsden-Haug N, Goldoft M, Wohrle R, et al. Cryptococcus gattii in the United States: clinical aspects of infection with an emerging pathogen. Clin Infect Dis. 2011;53(12):1188–95.PubMedCrossRefGoogle Scholar
  9. 9.
    Patel M, Beckerman KP, Reznik S, Madan RP, Goldman DL. Transplacental transmission of Cryptococcus neoformans to an HIV-exposed premature neonate. J Perinatol. 2012;32(3):235–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Baddley JW, Schain DC, Gupte AA, Lodhi SA, Kayler LK, Frade JP, et al. Transmission of Cryptococcus neoformans by Organ Transplantation. Clin Infect Dis. 2011;52(4):e94–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Sun HY, Alexander BD, Lortholary O, Dromer F, Forrest GN, Lyon GM, et al. Unrecognized pretransplant and donor-derived cryptococcal disease in organ transplant recipients. Clin Infect Dis. 2010;51(9):1062–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Goldman DL, Khine H, Abadi J, Lindenberg DJ, Pirofski L, Niang R, et al. Serologic evidence for Cryptococcus neoformans infection in early childhood. Pediatrics. 2001;107(5):E66.PubMedCrossRefGoogle Scholar
  13. 13.
    Davis J, Zheng WY, Glatman-Freedman A, Ng JA, Pagcatipunan MR, Lessin H, et al. Serologic evidence for regional differences in pediatric cryptococcal infection. Pediatr Infect Dis J. 2007;26(6):549–51.PubMedCrossRefGoogle Scholar
  14. 14.
    van der Horst CM, Saag MS, Cloud GA, Hamill RJ, Graybill JR, Sobel JD, et al. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group. N Engl J Med. 1997;337(1):15–21.PubMedCrossRefGoogle Scholar
  15. 15.
    Pappas PG, Perfect JR, Cloud GA, Larsen RA, Pankey GA, Lancaster DJ, et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis. 2001;33(5):690–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Shih CC, Chen YC, Chang SC, Luh KT, Hsieh WC. Cryptococcal meningitis in non-HIV-infected patients. QJM. 2000;93(4):245–51.PubMedCrossRefGoogle Scholar
  17. 17.
    Blevins LB, Fenn J, Segal H, Newcomb-Gayman P, Carroll KC. False-positive cryptococcal antigen latex agglutination caused by disinfectants and soaps. J Clin Microbiol. 1995;33(6):1674–5.PubMedGoogle Scholar
  18. 18.
    Wilson DA, Sholtis M, Parshall S, Hall GS, Procop GW. False-positive cryptococcal antigen test associated with use of BBL Port-a-Cul transport vials. J Clin Microbiol. 2011;49(2):702–3.PubMedCrossRefGoogle Scholar
  19. 19.
    • Lindsley MD, Mekha N, Baggett HC, Surinthong Y, Autthateinchai R, Sawatwong P, et al. Evaluation of a newly developed lateral flow immunoassay for the diagnosis of cryptococcosis. Clin Infect Dis. 2011;53(4):321–5. A study that validates the use of a newer, simpler, cheaper test for the diagnosis of CM. PubMedCrossRefGoogle Scholar
  20. 20.
    Jarvis JN, Percival A, Bauman S, Pelfrey J, Meintjes G, Williams GN, 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.PubMedCrossRefGoogle Scholar
  21. 21.
    Saha DC, Xess I, Biswas A, Bhowmik DM, Padma MV. Detection of Cryptococcus by conventional, serological and molecular methods. J Med Microbiol. 2009;58(Pt 8):1098–105.PubMedCrossRefGoogle Scholar
  22. 22.
    Jurado R, Walker H. In: Walker H, Hall W, Hurst J, editors. Cerebrospinal fluid. 3rd ed. Butterworths; 1990.Google Scholar
  23. 23.
    Yan Y, He Y, Maier T, Quinn C, Shi G, Li H, et al. Improved identification of yeast species directly from positive blood culture media by combining Sepsityper specimen processing and Microflex analysis with the matrix-assisted laser desorption ionization Biotyper system. J Clin Microbiol. 2011;49(7):2528–32.PubMedCrossRefGoogle Scholar
  24. 24.
    Pinto A, Halliday C, Zahra M, van Hal S, Olma T, Maszewska K, et al. Matrix-assisted laser desorption ionization-time of flight mass spectrometry identification of yeasts is contingent on robust reference spectra. PLoS One. 2011;6(10):e25712.PubMedCrossRefGoogle Scholar
  25. 25.
    Qishui O, Ling J, Ni L, Bin Y, Wen L. Comparison of real-time florescence quantitative PCR measurements of VAD1 mRNA with three conventional methods in diagnosis and follow-up treatment of Cryptococcus neoformans infection. Mycoses. 2011.Google Scholar
  26. 26.
    Anekthananon T, Manosuthi W, Chetchotisakd P, Kiertiburanakul S, Supparatpinyo K, Ratanasuwan W, et al. Predictors of poor clinical outcome of cryptococcal meningitis in HIV-infected patients. Int J STD AIDS. 2011;22(11):665–70.PubMedCrossRefGoogle Scholar
  27. 27.
    Brouwer A, Rajanuwong A, Chierakul W, Griffin G, Larsen R, White N, et al. Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial. Lancet. 2004;363(9423):1764–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Graybill JR, Sobel J, Saag M, van Der Horst C, Powderly W, Cloud G, et al. Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. The NIAID Mycoses Study Group and AIDS Cooperative Treatment Groups. Clin Infect Dis. 2000;30(1):47–54.PubMedCrossRefGoogle Scholar
  29. 29.
    •• Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, 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. Updated guidelines from IDSA on management of cryptococcosis, including CM. PubMedCrossRefGoogle Scholar
  30. 30.
    • WHO. Rapid advice: diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children. 2011. Updated guidelines with practical advice on aspects of management of cryptococcal disease. Google Scholar
  31. 31.
    Maher D, Mwandumba H. Cryptococcal meningitis in Lilongwe and Blantyre, Malawi. J Infect. 1994;28(1):59–64.PubMedCrossRefGoogle Scholar
  32. 32.
    • Bicanic T, Muzoora C, Brouwer A, Meintjes G, Longley N, Taseera K, et al. Independent association between rate of clearance of infection and clinical outcome of HIV-associated cryptococcal meningitis: analysis of a combined cohort of 262 patients. Clin Infect Dis. 2009;49(5):702–9. This article validates early fungicidal activity (EFA) as a useful tool for assessing efficacy of anticryptococcal regimens. PubMedCrossRefGoogle Scholar
  33. 33.
    Robinson PA, Bauer M, Leal MA, Evans SG, Holtom PD, Diamond DA, et al. Early mycological treatment failure in AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1999;28(1):82–92.PubMedCrossRefGoogle Scholar
  34. 34.
    Hamill RJ, Sobel JD, El-Sadr W, Johnson PC, Graybill JR, Javaly K, et al. Comparison of 2 doses of liposomal amphotericin B and conventional amphotericin B deoxycholate for treatment of AIDS-associated acute cryptococcal meningitis: a randomized, double-blind clinical trial of efficacy and safety. Clin Infect Dis. 2010;51(2):225–32.PubMedCrossRefGoogle Scholar
  35. 35.
    • Nussbaum J, Jackson A, Namarika D, Phulusa J, Kenala J, Kanyemba C, et al. Combination flucytosine and high-dose fluconazole compared with fluconazole monotherapy for the treatment of cryptococcal meningitis: a randomized trial in Malawi. Clin Infect Dis. 2010;50(3):338–44. This article shows the most effective oral regimen for CM to date, with EFA of fluconazole 1200 mg/day plus 5FC approaching that of AmB alone. It lends weight to the call for 5FC to be made available in resource-limited settings. PubMedCrossRefGoogle Scholar
  36. 36.
    Dromer F, Mathoulin-Pelissier S, Launay O, Lortholary O. Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study. PLoS Med. 2007;4(2):e21.PubMedCrossRefGoogle Scholar
  37. 37.
    Bicanic T, Meintjes G, Wood R, Hayes M, Rebe K, Bekker L, et al. Fungal burden, early fungicidal activity, and outcome in cryptococcal meningitis in antiretroviral-naive or antiretroviral-experienced patients treated with amphotericin B or fluconazole. Clin Infect Dis. 2007;45(1):76–80.PubMedCrossRefGoogle Scholar
  38. 38.
    Mwaba P, Mwansa J, Chintu C, Pobee J, Scarborough M, Portsmouth S, 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
  39. 39.
    Bicanic T, Harrison T, Niepieklo A, Dyakopu N, Meintjes G. Symptomatic relapse of HIV-associated cryptococcal meningitis after initial fluconazole monotherapy: the role of fluconazole resistance and immune reconstitution. Clin Infect Dis. 2006;43(8):1069–73.PubMedCrossRefGoogle Scholar
  40. 40.
    Mdodo R, Moser SA, Jaoko W, Baddley J, Pappas P, Kempf MC, et al. Antifungal susceptibilities of Cryptococcus neoformans cerebrospinal fluid isolates from AIDS patients in Kenya. Mycoses. 2011;54(5):e438–42.PubMedCrossRefGoogle Scholar
  41. 41.
    Govender NP, Patel J, van Wyk M, Chiller TM, Lockhart SR, Group for Enteric RaMDSiSA. Trends in antifungal drug susceptibility of Cryptococcus neoformans isolates obtained through population-based surveillance in South Africa in 2002–2003 and 2007–2008. Antimicrob Agents Chemother. 2011;55(6):2606–11.PubMedCrossRefGoogle Scholar
  42. 42.
    Longley N, Muzoora C, Taseera K, Mwesigye J, Rwebembera J, Chakera A, et al. Dose response effect of high-dose fluconazole for HIV-associated cryptococcal meningitis in southwestern Uganda. Clin Infect Dis. 2008;47(12):1556–61.PubMedCrossRefGoogle Scholar
  43. 43.
    Muzoora CK, Kabanda T, Ortu G, Ssentamu J, Hearn P, Mwesigye J, et al. Short course amphotericin B with high dose fluconazole for HIV-associated cryptococcal meningitis. J Infect. 2012;64(1):76–81.PubMedCrossRefGoogle Scholar
  44. 44.
    • Jackson A, Phulusa J, Namarika D, Chikasema M, Kanyemba C, Nussbaum J, et al., editors. A randomized controlled trial studying the effect of oral flucytosine on short course amphotericin B plus fluconazole for the treatment of Cryptococcal meningitis in Malawi—a role for triple therapy? Abstract 1506. Infectious Diseases Society of America 48th Annual Meeting; 2010; Vancouver, Canada. This study demonstrates the safe and effective use of shortened-course AmB for CM, and contributes to the evidence supporting the use of 5FC in developing world settings. Google Scholar
  45. 45.
    • Pappas P, Chetchotisakd P, Larsen R, Manosuthi W, Morris M, Anekthananon T, et al. A phase II randomized trial of amphotericin B alone or combined with fluconazole in the treatment of HIV-associated cryptococcal meningitis. Clin Infect Dis. 2009;48(12):1775–83. This study suggests improved efficacy in the treatment of CM when using 14 days of AmB with fluconazole 800 mg compared to AmB alone. PubMedCrossRefGoogle Scholar
  46. 46.
    Bennett JE, Dismukes WE, Duma RJ, Medoff G, Sande MA, Gallis H, et al. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis. N Engl J Med. 1979;301(3):126–31.PubMedCrossRefGoogle Scholar
  47. 47.
    Dismukes WE, Cloud G, Gallis HA, Kerkering TM, Medoff G, Craven PC, et al. Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N Engl J Med. 1987;317(6):334–41.PubMedCrossRefGoogle Scholar
  48. 48.
    Apseloff G, Hilligoss DM, Gardner MJ, Henry EB, Inskeep PB, Gerber N, et al. Induction of fluconazole metabolism by rifampin: in vivo study in humans. J Clin Pharmacol. 1991;31(4):358–61.PubMedGoogle Scholar
  49. 49.
    Bozzette SA, Larsen RA, Chiu J, Leal MA, Jacobsen J, Rothman P, et al. A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med. 1991;324(9):580–4.PubMedCrossRefGoogle Scholar
  50. 50.
    Powderly WG, Saag MS, Cloud GA, Robinson P, Meyer RD, Jacobson JM, et al. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group. N Engl J Med. 1992;326(12):793–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Saag M, Cloud G, Graybill J, Sobel J, Tuazon C, Johnson P, et al. A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis. 1999;28(2):291–6.PubMedCrossRefGoogle Scholar
  52. 52.
    Vibhagool A, Sungkanuparph S, Mootsikapun P, Chetchotisakd P, Tansuphaswaswadikul S, Bowonwatanuwong C, et al. Discontinuation of secondary prophylaxis for cryptococcal meningitis in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy: a prospective, multicenter, randomized study. Clin Infect Dis. 2003;36(10):1329–31.PubMedCrossRefGoogle Scholar
  53. 53.
    Aberg JA, Price RW, Heeren DM, Bredt B. A pilot study of the discontinuation of antifungal therapy for disseminated cryptococcal disease in patients with acquired immunodeficiency syndrome, following immunologic response to antiretroviral therapy. J Infect Dis. 2002;185(8):1179–82.PubMedCrossRefGoogle Scholar
  54. 54.
    12Brouwer A, Siddiqui A, Kester M, Sigaloff K, Rajanuwong A, Wannapasni S, et al. Immune dysfunction in HIV-seronegative, Cryptococcus gattii meningitis. J Infect. 2007;54(3):e165–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Netea MG, Brouwer AE, Hoogendoorn EH, Van der Meer JW, Koolen M, Verweij PE, et al. Two patients with cryptococcal meningitis and idiopathic CD4 lymphopenia: defective cytokine production and reversal by recombinant interferon- gamma therapy. Clin Infect Dis. 2004;39(9):e83–7.PubMedCrossRefGoogle Scholar
  56. 56.
    • Jarvis JN, Meintjes G, Rebe K, Williams GN, Bicanic T, Williams A, et al. Adjunctive interferon-gamma immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial. AIDS. 2012;26(9):1105–1113. This study using a novel adjunct demonstrates a regimen with the highest recorded EFA. Google Scholar
  57. 57.
    Bicanic T, Harrison T, Niepieklo A, Dyakopu N, Meintjes G. Symptomatic relapse of HIV-associated cryptococcal meningitis after initial fluconazole monotherapy: the role of fluconazole resistance and immune reconstitution. Clin Infect Dis. 2006;43(8):1069–73.PubMedCrossRefGoogle Scholar
  58. 58.
    Perfect JR, Cox GM, Dodge RK, Schell WA. In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans. Antimicrob Agents Chemother. 1996;40(8):1910–3.PubMedGoogle Scholar
  59. 59.
    Pfaller MA, Zhang J, Messer SA, Brandt ME, Hajjeh RA, Jessup CJ, et al. In vitro activities of voriconazole, fluconazole, and itraconazole against 566 clinical isolates of Cryptococcus neoformans from the United States and Africa. Antimicrob Agents Chemother. 1999;43(1):169–71.PubMedCrossRefGoogle Scholar
  60. 60.
    Barchiesi F, Spreghini E, Schimizzi AM, Maracci M, Giannini D, Carle F, et al. Posaconazole and amphotericin B combination therapy against Cryptococcus neoformans infection. Antimicrob Agents Chemother. 2004;48(9):3312–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Serena C, Pastor FJ, Marine M, Rodriguez MM, Guarro J. Efficacy of voriconazole in a murine model of cryptococcal central nervous system infection. J Antimicrob Chemother. 2007;60(1):162–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Sabbatani S, Manfredi R, Pavoni M, Consales A, Chiodo F. Voriconazole proves effective in long-term treatment of a cerebral cryptococcoma in a chronic nephropathic HIV-negative patient, after fluconazole failure. Mycopathologia. 2004;158(2):165–71.PubMedCrossRefGoogle Scholar
  63. 63.
    Pitisuttithum P, Negroni R, Graybill JR, Bustamante B, Pappas P, Chapman S, et al. Activity of posaconazole in the treatment of central nervous system fungal infections. J Antimicrob Chemother. 2005;56(4):745–55.PubMedCrossRefGoogle Scholar
  64. 64.
    Perfect JR, Marr KA, Walsh TJ, Greenberg RN, DuPont B, de la Torre-Cisneros J, et al. Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis. 2003;36(9):1122–31.PubMedCrossRefGoogle Scholar
  65. 65.
    Lutsar I, Roffey S, Troke P. Voriconazole concentrations in the cerebrospinal fluid and brain tissue of guinea pigs and immunocompromised patients. Clin Infect Dis. 2003;37(5):728–32.PubMedCrossRefGoogle Scholar
  66. 66.
    Sionov E, Chang YC, Garraffo HM, Dolan MA, Ghannoum MA, Kwon-Chung KJ. Identification of a Cryptococcus neoformans cytochrome P450 lanosterol 14alpha-demethylase (Erg11) residue critical for differential susceptibility between fluconazole/voriconazole and itraconazole/posaconazole. Antimicrob Agents Chemother. 2012;56(3):1162–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Loyse A, Wilson D, Meintjes G, Jarvis JN, Bicanic T, Bishop L, et al. Comparison of the early fungicidal activity of high-dose fluconazole, voriconazole, and flucytosine as second-line drugs given in combination with amphotericin B for the treatment of HIV-associated cryptococcal meningitis. Clin Infect Dis. 2012;54(1):121–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Bryan RA, Guimaraes AJ, Hopcraft S, Jiang Z, Bonilla K, Morgenstern A, et al. Toward developing a universal treatment for fungal disease using radioimmunotherapy targeting common fungal antigens. Mycopathologia. 2012;173(5–6):463–71Google Scholar
  69. 69.
    Jiang Z, Bryan RA, Morgenstern A, Bruchertseifer F, Casadevall A, Dadachova E. Treatment of early and established Cryptococcus neoformans infection with radiolabeled antibodies in immunocompetent mice. Antimicrob Agents Chemother. 2012;56(1):552–4.PubMedCrossRefGoogle Scholar
  70. 70.
    Bryan RA, Jiang Z, Howell RC, Morgenstern A, Bruchertseifer F, Casadevall A, et al. Radioimmunotherapy is more effective than antifungal treatment in experimental cryptococcal infection. J Infect Dis. 2010;202(4):633–7.PubMedCrossRefGoogle Scholar
  71. 71.
    • Bicanic T, Brouwer A, Meintjes G, Rebe K, Limmathurotsakul D, Chierakul W, et al. Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures. AIDS. 2009;23(6):701–6. This study highlights the importance of measuring and treating CSF pressure in patients with CM. PubMedGoogle Scholar
  72. 72.
    Loyse A, Wainwright H, Jarvis JN, Bicanic T, Rebe K, Meintjes G, et al. Histopathology of the arachnoid granulations and brain in HIV-associated cryptococcal meningitis: correlation with cerebrospinal fluid pressure. AIDS. 2010;24(3):405–10.PubMedCrossRefGoogle Scholar
  73. 73.
    Fessler R, Sobel J, Guyot L, Crane L, Vazquez J, Szuba M, et al. Management of elevated intracranial pressure in patients with Cryptococcal meningitis. J Acquir Immune Defic Syndr Hum Retrovirol. 1998;17(2):137–42.PubMedCrossRefGoogle Scholar
  74. 74.
    Manosuthi W, Sungkanuparph S, Chottanapund S, Tansuphaswadikul S, Chimsuntorn S, Limpanadusadee P, et al. Temporary external lumbar drainage for reducing elevated intracranial pressure in HIV-infected patients with cryptococcal meningitis. Int J STD AIDS. 2008;19(4):268–71.PubMedCrossRefGoogle Scholar
  75. 75.
    Park MK, Hospenthal DR, Bennett JE. Treatment of hydrocephalus secondary to cryptococcal meningitis by use of shunting. Clin Infect Dis. 1999;28(3):629–33.PubMedCrossRefGoogle Scholar
  76. 76.
    Newton PN, Thai le H, Tip NQ, Short JM, Chierakul W, Rajanuwong A, et al. A randomized, double-blind, placebo-controlled trial of acetazolamide for the treatment of elevated intracranial pressure in cryptococcal meningitis. Clin Infect Dis. 2002;35(6):769–72.PubMedCrossRefGoogle Scholar
  77. 77.
    Bicanic T, Meintjes G, Rebe K, Williams A, Loyse A, Wood R, et al. Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study. J Acquir Immune Defic Syndr. 2009;51(2):130–4.PubMedCrossRefGoogle Scholar
  78. 78.
    Muller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(4):251–61.PubMedCrossRefGoogle Scholar
  79. 79.
    Bisson G, Nthobatsong R, Thakur R, Lesetedi G, Vinekar K, Tebas P, et al. The use of HAART is associated with decreased risk of death during initial treatment of cryptococcal meningitis in adults in Botswana. J Acquir Immune Defic Syndr. 2008;49(2):227–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Haddow L, Colebunders R, Meintjes G, Lawn S, Elliott J, Manabe Y, et al. Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: literature review and proposed clinical case definitions. Lancet Infect Dis. 2010;10(11):791–802.PubMedCrossRefGoogle Scholar
  81. 81.
    Lortholary O, Fontanet A, Memain N, Martin A, Sitbon K, Dromer F. Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France. AIDS. 2005;19(10):1043–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Sitapati A, Kao C, Cachay E, Masoumi H, Wallis R, Mathews W. Treatment of HIV-related inflammatory cerebral cryptococcoma with adalimumab. Clin Infect Dis. 2010;50(2):e7–10.PubMedCrossRefGoogle Scholar
  83. 83.
    Zolopa A, Andersen J, Powderly W, Sanchez A, Sanne I, Suckow C, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS One. 2009;4(5):e5575.PubMedCrossRefGoogle Scholar
  84. 84.
    Makadzange AT, Ndhlovu CE, Takarinda K, Reid M, Kurangwa M, Gona P, et al. Early versus delayed initiation of antiretroviral therapy for concurrent HIV infection and cryptococcal meningitis in sub-saharan Africa. Clin Infect Dis. 2010;50(11):1532–8.PubMedCrossRefGoogle Scholar
  85. 85.
    NIH press release. May 2012. Available at: http://www.niaid.nih.gov/news/newsreleases/2012/Pages/COAT.aspx
  86. 86.
    McCarthy K, Meintjes G. Guidelines for the prevention, diagnosis and management of cryptococcal meningitis and disseminated cryptococcosis in HIV-infected patients. The Southern African Journal of HIV Medicine. 2007; Spring 25–35.Google Scholar
  87. 87.
    Chang C, Dorasamy A, Elliott J, Naranbhai V, Gosnell B, Mahabeer Y, et al. HIV+ patients with CM who attain CSF sterility pre-cART commencement experience improved outcomes in the first 24 weeks. Poster 955. 19th Conference on Retroviruses and Opportunistic Infections; 2012; Seattle, USA.Google Scholar
  88. 88.
    Powderly W, Finkelstein D, Feinberg J, Frame P, He W, van der Horst C, et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med. 1995;332(11):700–5.PubMedCrossRefGoogle Scholar
  89. 89.
    Chariyalertsak S, Supparatpinyo K, Sirisanthana T, Nelson K. A controlled trial of itraconazole as primary prophylaxis for systemic fungal infections in patients with advanced human immunodeficiency virus infection in Thailand. Clin Infect Dis. 2002;34(2):277–84.PubMedCrossRefGoogle Scholar
  90. 90.
    WHO. Essential prevention and careinterventions for adults and adolescents living with HIV in resource-limited settings. 2008.Google Scholar
  91. 91.
    • Parkes-Ratanshi R, Wakeham K, Levin J, Namusoke D, Whitworth J, Coutinho A, et al. Primary prophylaxis of cryptococcal disease with fluconazole in HIV-positive Ugandan adults: a double-blind, randomised, placebo-controlled trial. Lancet Infect Dis. 2011;11(12):933–41. This study shows that the risk of cryptococcal meningitis can be reduced in advanced HIV by using fluconazole prophylaxis, supporting its use in those patients for whom ART must be deferred. PubMedCrossRefGoogle Scholar
  92. 92.
    Liechty C, Solberg P, Were W, Ekwaru J, Ransom R, Weidle 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
  93. 93.
    Pongsai P, Atamasirikul K, Sungkanuparph S. 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
  94. 94.
    •• Jarvis J, Lawn S, Vogt M, Bangani N, Wood R, Harrison T. Screening for cryptococcal antigenemia in patients accessing an antiretroviral treatment program in South Africa. Clin Infect Dis. 2009;48(7):856–62. This study suggests an approach to reduce the incidence of clinical CM in resource-limited settings by screening for CrAg in at-risk individuals. PubMedCrossRefGoogle Scholar
  95. 95.
    • Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, Kambugu A, 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 study shows the cost-benefit implications of a CrAg screening approach in resource-limited settings. It is shown to be a cost-effective method. PubMedCrossRefGoogle Scholar
  96. 96.
    Lawn SD, Wood R. Point-of-care urine antigen screening tests for tuberculosis and cryptococcosis: potential for mortality reduction in antiretroviral treatment programs in Africa. Clin Infect Dis. 2012;54(5):739–40.PubMedCrossRefGoogle Scholar
  97. 97.
    Wozniak KL, Young ML, Wormley Jr FL. Protective immunity against experimental pulmonary cryptococcosis in T cell-depleted mice. Clin Vaccine Immunol. 2011;18(5):717–23.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Center for Infectious DiseasesChapel HillUSA

Personalised recommendations