Skip to main content
Top
Published in: Journal of the International AIDS Society 1/2011

Open Access 01-12-2011 | Research

Universal screening of Tanzanian HIV-infected adult inpatients with the serum cryptococcal antigen to improve diagnosis and reduce mortality: an operational study

Authors: Bahati MK Wajanga, Samuel Kalluvya, Jennifer A Downs, Warren D Johnson, Daniel W Fitzgerald, Robert N Peck

Published in: Journal of the International AIDS Society | Issue 1/2011

Login to get access

Abstract

Background

Cryptococcal meningitis is a leading cause of death among HIV-infected individuals in sub-Saharan Africa. Recent developments include the availability of intravenous fluconazole, cryptococcal antigen assays and new data to support fluconazole pre-emptive treatment. In this study, we describe the impact of screening HIV-positive adult inpatients with serum cryptococcal antigen (CRAG) at a Tanzanian referral hospital.

Methods

All adults admitted to the medical ward of Bugando Medical Centre are counseled and tested for HIV. In this prospective cohort study, we consecutively enrolled HIV-positive patients admitted between September 2009 and January 2010. All patients were interviewed, examined and screened with serum CRAG. Patients with positive serum CRAG or signs of meningitis underwent lumbar puncture. Patients were managed according to standard World Health Organization treatment guidelines. Discharge diagnoses and in-hospital mortality were recorded.

Results

Of 333 HIV-infected adults enrolled in our study, 15 (4.4%) had confirmed cryptococcal meningitis and 10 of these 15 (66%) died. All patients with cryptococcal meningitis had at least two of four classic symptoms and signs of meningitis: fever, headache, neck stiffness and altered mental status. Cryptococcal meningitis accounted for a quarter of all in-hospital deaths.

Conclusions

Despite screening of all HIV-positive adult inpatients with the serum CRAG at the time of admission and prompt treatment with high-dose intravenous fluconazole in those with confirmed cryptococcal meningitis, the in-hospital mortality rate remained unacceptably high. Improved strategies for earlier diagnosis and treatment of HIV, implementation of fluconazole pre-emptive treatment for high-risk patients and acquisition of better resources for treatment of cryptococcal meningitis are needed.
Literature
1.
go back to reference Holmes CB, Losina E, Walensky RP, Yazdanpanah Y, Freedberg KA: Review of human immunodeficiency virus type 1-related opportunistic infections in sub-Saharan Africa. Clin Infect Dis 2003,36(5):652–662.PubMedCrossRef Holmes CB, Losina E, Walensky RP, Yazdanpanah Y, Freedberg KA: Review of human immunodeficiency virus type 1-related opportunistic infections in sub-Saharan Africa. Clin Infect Dis 2003,36(5):652–662.PubMedCrossRef
2.
go back to reference Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM: Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 2009,23(4):525–530.PubMedCrossRef Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM: Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 2009,23(4):525–530.PubMedCrossRef
3.
go back to reference French N, Gray K, Watera C, Nakiyingi J, Lugada E, Moore M, Lalloo D, Whitworth JA, Gilks CF: Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS 2002,16(7):1031–1038.PubMedCrossRef French N, Gray K, Watera C, Nakiyingi J, Lugada E, Moore M, Lalloo D, Whitworth JA, Gilks CF: Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS 2002,16(7):1031–1038.PubMedCrossRef
4.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
5.
go back to reference Churchyard GJ, Kleinschmidt I, Corbett EL, Murray J, Smit J, De Cock KM: Factors associated with an increased case-fatality rate in HIV-infected and non-infected South African gold miners with pulmonary tuberculosis. Int J Tuberc Lung Dis 2000,4(8):705–712.PubMed Churchyard GJ, Kleinschmidt I, Corbett EL, Murray J, Smit J, De Cock KM: Factors associated with an increased case-fatality rate in HIV-infected and non-infected South African gold miners with pulmonary tuberculosis. Int J Tuberc Lung Dis 2000,4(8):705–712.PubMed
6.
go back to reference Jarvis JN, Boulle A, Loyse A, Bicanic T, Rebe K, Williams A, Harrison TS, Meintjes G: High ongoing burden of cryptococcal disease in Africa despite antiretroviral roll out. AIDS 2009,23(9):1182–1183.PubMedCrossRef Jarvis JN, Boulle A, Loyse A, Bicanic T, Rebe K, Williams A, Harrison TS, Meintjes G: High ongoing burden of cryptococcal disease in Africa despite antiretroviral roll out. AIDS 2009,23(9):1182–1183.PubMedCrossRef
7.
go back to reference Leimann BC, Koifman RJ: Cryptococcal meningitis in Rio de Janeiro State, Brazil, 1994–2004. Cad Saude Publica 2008,24(11):2582–2592.PubMedCrossRef Leimann BC, Koifman RJ: Cryptococcal meningitis in Rio de Janeiro State, Brazil, 1994–2004. Cad Saude Publica 2008,24(11):2582–2592.PubMedCrossRef
8.
go back to reference Sloan DJ, Dedicoat MJ, Lalloo DG: Treatment of cryptococcal meningitis in resource limited settings. Curr Opin Infect Dis 2009,22(5):455–463.PubMedCrossRef Sloan DJ, Dedicoat MJ, Lalloo DG: Treatment of cryptococcal meningitis in resource limited settings. Curr Opin Infect Dis 2009,22(5):455–463.PubMedCrossRef
9.
go back to reference Sloan D, Dlamini S, Paul N, Dedicoat M: Treatment of acute cryptococcal meningitis in HIV infected adults, with an emphasis on resource-limited settings. Cochrane Database Syst Rev 2008, (4):CD005647. Sloan D, Dlamini S, Paul N, Dedicoat M: Treatment of acute cryptococcal meningitis in HIV infected adults, with an emphasis on resource-limited settings. Cochrane Database Syst Rev 2008, (4):CD005647.
10.
go back to reference Longley N, Muzoora C, Taseera K, Mwesigye J, Rwebembera J, Chakera A, Wall E, Andia I, Jaffar S, Harrison TS: Dose response effect of high-dose fluconazole for HIV-associated cryptococcal meningitis in southwestern Uganda. Clin Infect Dis 2008,47(12):1556–1561.PubMedCrossRef Longley N, Muzoora C, Taseera K, Mwesigye J, Rwebembera J, Chakera A, Wall E, Andia I, Jaffar S, Harrison TS: Dose response effect of high-dose fluconazole for HIV-associated cryptococcal meningitis in southwestern Uganda. Clin Infect Dis 2008,47(12):1556–1561.PubMedCrossRef
11.
go back to reference Bicanic T, Meintjes G, Wood R, Hayes M, Rebe K, Bekker LG, Harrison T: 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.PubMedCrossRef Bicanic T, Meintjes G, Wood R, Hayes M, Rebe K, Bekker LG, Harrison T: 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.PubMedCrossRef
12.
go back to reference Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, 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.PubMedCrossRef Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, 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.PubMedCrossRef
13.
go back to reference Jarvis JN, Lawn SD, Vogt M, Bangani N, Wood R, Harrison TS: Screening for cryptococcal antigenemia in patients accessing an antiretroviral treatment program in South Africa. Clin Infect Dis 2009,48(7):856–862.PubMedCrossRef Jarvis JN, Lawn SD, Vogt M, Bangani N, Wood R, Harrison TS: Screening for cryptococcal antigenemia in patients accessing an antiretroviral treatment program in South Africa. Clin Infect Dis 2009,48(7):856–862.PubMedCrossRef
14.
go back to reference Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, Kambugu A, Kamya MR, Bohjanen PR, Boulware DR: 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):448–455.PubMedCrossRef Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, Kambugu A, Kamya MR, Bohjanen PR, Boulware DR: 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):448–455.PubMedCrossRef
18.
go back to reference Tanner DC, Weinstein MP, Fedorciw B, Joho KL, Thorpe JJ, Reller L: Comparison of commercial kits for detection of cryptococcal antigen. J Clin Microbiol 1994,32(7):1680–1684.PubMed Tanner DC, Weinstein MP, Fedorciw B, Joho KL, Thorpe JJ, Reller L: Comparison of commercial kits for detection of cryptococcal antigen. J Clin Microbiol 1994,32(7):1680–1684.PubMed
19.
go back to reference Kisenge PR, Hawkins AT, Maro VP, McHele JP, Swai NS, Mueller A, Houpt ER: Low CD4 count plus coma predicts cryptococcal meningitis in Tanzania. BMC Infect Dis 2007, 7:39.PubMedCrossRef Kisenge PR, Hawkins AT, Maro VP, McHele JP, Swai NS, Mueller A, Houpt ER: Low CD4 count plus coma predicts cryptococcal meningitis in Tanzania. BMC Infect Dis 2007, 7:39.PubMedCrossRef
20.
go back to reference Bogaerts J, Rouvroy D, Taelman H, Kagame A, Aziz MA, Swinne D, Verhaegen J: AIDS-associated cryptococcal meningitis in Rwanda (1983–1992): epidemiologic and diagnostic features. J Infect 1999,39(1):32–37.PubMedCrossRef Bogaerts J, Rouvroy D, Taelman H, Kagame A, Aziz MA, Swinne D, Verhaegen J: AIDS-associated cryptococcal meningitis in Rwanda (1983–1992): epidemiologic and diagnostic features. J Infect 1999,39(1):32–37.PubMedCrossRef
22.
go back to reference Graybill JR, Sobel J, Saag M, van Der Horst C, Powderly W, Cloud G, Riser L, Hamill R, Dismukes W: 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.PubMedCrossRef Graybill JR, Sobel J, Saag M, van Der Horst C, Powderly W, Cloud G, Riser L, Hamill R, Dismukes W: 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.PubMedCrossRef
23.
go back to reference Bicanic T, Brouwer AE, Meintjes G, Rebe K, Limmathurotsakul D, Chierakul W, Teparrakkul P, Loyse A, White NJ, Wood R, et al.: Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures. AIDS 2009,23(6):701–706.PubMed Bicanic T, Brouwer AE, Meintjes G, Rebe K, Limmathurotsakul D, Chierakul W, Teparrakkul P, Loyse A, White NJ, Wood R, et al.: Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures. AIDS 2009,23(6):701–706.PubMed
24.
go back to reference Kigozi IM, Dobkin LM, Martin JN, Geng EH, Muyindike W, Emenyonu NI, Bangsberg DR, Hahn JA: Late-disease stage at presentation to an HIV clinic in the era of free antiretroviral therapy in Sub-Saharan Africa. J Acquir Immune Defic Syndr 2009,52(2):280–289.PubMedCrossRef Kigozi IM, Dobkin LM, Martin JN, Geng EH, Muyindike W, Emenyonu NI, Bangsberg DR, Hahn JA: Late-disease stage at presentation to an HIV clinic in the era of free antiretroviral therapy in Sub-Saharan Africa. J Acquir Immune Defic Syndr 2009,52(2):280–289.PubMedCrossRef
25.
go back to reference Lawn SD, Harries AD, Wood R: Strategies to reduce early morbidity and mortality in adults receiving antiretroviral therapy in resource-limited settings. Curr Opin HIV AIDS 2010,5(1):18–26.PubMedCrossRef Lawn SD, Harries AD, Wood R: Strategies to reduce early morbidity and mortality in adults receiving antiretroviral therapy in resource-limited settings. Curr Opin HIV AIDS 2010,5(1):18–26.PubMedCrossRef
26.
go back to reference Micol R, Lortholary O, Sar B, Laureillard D, Ngeth C, Dousset JP, Chanroeun H, Ferradini L, Guerin PJ, Dromer F, 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):555–559.PubMedCrossRef Micol R, Lortholary O, Sar B, Laureillard D, Ngeth C, Dousset JP, Chanroeun H, Ferradini L, Guerin PJ, Dromer F, 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):555–559.PubMedCrossRef
27.
go back to reference Liechty CA, Solberg P, Were W, Ekwaru JP, Ransom RL, Weidle PJ, Downing R, Coutinho A, Mermin J: Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda. Trop Med Int Health 2007,12(8):929–935.PubMedCrossRef Liechty CA, Solberg P, Were W, Ekwaru JP, Ransom RL, Weidle PJ, Downing R, Coutinho A, Mermin J: Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda. Trop Med Int Health 2007,12(8):929–935.PubMedCrossRef
28.
go back to reference Micol R, Tajahmady A, Lortholary O, Balkan S, Quillet C, Dousset JP, Chanroeun H, Madec Y, Fontanet A, Yazdanpanah Y: Cost-effectiveness of primary prophylaxis of AIDS associated cryptococcosis in Cambodia. PLoS One 2010,5(11):e13856.PubMedCrossRef Micol R, Tajahmady A, Lortholary O, Balkan S, Quillet C, Dousset JP, Chanroeun H, Madec Y, Fontanet A, Yazdanpanah Y: Cost-effectiveness of primary prophylaxis of AIDS associated cryptococcosis in Cambodia. PLoS One 2010,5(11):e13856.PubMedCrossRef
29.
go back to reference Haddow LJ, Colebunders R, Meintjes G, Lawn SD, Elliott JH, Manabe YC, Bohjanen PR, Sungkanuparph S, Easterbrook PJ, French MA, et al.: Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: proposed clinical case definitions. Lancet Infect Dis 2010,10(11):791–802.PubMedCrossRef Haddow LJ, Colebunders R, Meintjes G, Lawn SD, Elliott JH, Manabe YC, Bohjanen PR, Sungkanuparph S, Easterbrook PJ, French MA, et al.: Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: proposed clinical case definitions. Lancet Infect Dis 2010,10(11):791–802.PubMedCrossRef
Metadata
Title
Universal screening of Tanzanian HIV-infected adult inpatients with the serum cryptococcal antigen to improve diagnosis and reduce mortality: an operational study
Authors
Bahati MK Wajanga
Samuel Kalluvya
Jennifer A Downs
Warren D Johnson
Daniel W Fitzgerald
Robert N Peck
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of the International AIDS Society / Issue 1/2011
Electronic ISSN: 1758-2652
DOI
https://doi.org/10.1186/1758-2652-14-48

Other articles of this Issue 1/2011

Journal of the International AIDS Society 1/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.