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Published in: BMC Infectious Diseases 1/2020

01-12-2020 | Fluconazole | Research article

Prevalence and mortality of cryptococcal disease in adults with advanced HIV in an urban tertiary hospital in Sierra Leone: a prospective study

Authors: Sulaiman Lakoh, Hannah Rickman, Momodu Sesay, Sartie Kenneh, Rachael Burke, Mamadu Baldeh, Darlinda F. Jiba, Yusuf S. Tejan, Sonia Boyle, Comfort Koroma, Gibrilla F. Deen, Fenella Beynon

Published in: BMC Infectious Diseases | Issue 1/2020

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Abstract

Background

The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count < 100/μl. As there is no previous published study on the burden and impact of cryptococcal disease in Sierra Leone, research is needed to inform public health policies. We aimed to establish the seroprevalence and mortality of cryptococcal disease in adults with advanced HIV attending an urban tertiary hospital in Sierra Leone.

Methods

A prospective cohort study design was used to screen consecutive adult (18 years or older) HIV patients at Connaught Hospital in Freetown, Sierra Leone with CD4 count below 100 cells/mm3 from January to April 2018. Participants received a blood CrAg lateral flow assay (IMMY, Oklahoma, USA). All participants with a positive serum CrAg had lumbar puncture and cerebrospinal fluid (CSF) CrAg assay, and those with cryptococcal diseases had fluconazole monotherapy with 8 weeks followed up. Data were entered into Excel and analysed in Stata version 13.0. Proportions, median and interquartile ranges were used to summarise the data. Fisher’s exact test was used to compare categorical variables.

Results

A total of 170 patients, with median age of 36 (IQR 30–43) and median CD4 count of 45 cells/mm3 (IQR 23–63) were screened. At the time of enrolment, 54% were inpatients, 51% were newly diagnosed with HIV, and 56% were either ART-naïve or newly initiated (≤ 30 days). Eight participants had a positive blood CrAg, giving a prevalence of 4.7% (95% CI: 2.4–9.2%). Of those with a positive CrAg, CSF CrAg was positive in five (62.5%). Five (62.5%) CrAg-positive participants died within the first month, while the remaining three were alive and established on ART at 8 weeks.

Conclusion

A substantial prevalence of cryptococcal antigenaemia and poor outcome of cryptococcal disease were demonstrated in our study. The high mortality suggests a need for the HIV programme to formulate and implement policies on screening and pre-emptive fluconazole therapy for all adults with advanced HIV in Sierra Leone, and advocate for affordable access to effective antifungal therapies.
Literature
1.
go back to reference Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP, Chiller TM, et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis. 2017;17(8):873–81.CrossRef Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP, Chiller TM, et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis. 2017;17(8):873–81.CrossRef
3.
go back to reference Meya DB, Manabe YC, Castelnuovo B, Cook BA, Ali M, Kambugu A, et al. Serum Cryptococcal antigen (CRAG) screening is a cost- effective method to prevent death in HIV- infected persons with CD4 <100/uL starting HIV therapy in resource-limited settings. Clin Infect Dis. 2010;51(4):448–55.CrossRef Meya DB, Manabe YC, Castelnuovo B, Cook BA, Ali M, Kambugu A, et al. Serum Cryptococcal antigen (CRAG) screening is a cost- effective method to prevent death in HIV- infected persons with CD4 <100/uL starting HIV therapy in resource-limited settings. Clin Infect Dis. 2010;51(4):448–55.CrossRef
4.
go back to reference Jarvis JN, Harrison TS, Lawn SD, Meintjes G, Wood R, Cleary S. Cost effectiveness of Cryptococcal antigen screening as a strategy to prevent HIV-associated Cryptococcal meningitis in South Africa. PLoS One. 2013;8(7):1–10.CrossRef Jarvis JN, Harrison TS, Lawn SD, Meintjes G, Wood R, Cleary S. Cost effectiveness of Cryptococcal antigen screening as a strategy to prevent HIV-associated Cryptococcal meningitis in South Africa. PLoS One. 2013;8(7):1–10.CrossRef
5.
go back to reference Hakim J, Musiime V, Szubert AJ, Mallewa J, Siika A, Agutu C, et al. Enhanced prophylaxis plus antiretroviral therapy for advanced HIV infection in Africa. N Engl J Med. 2017 Jul;377(3):233–45.CrossRef Hakim J, Musiime V, Szubert AJ, Mallewa J, Siika A, Agutu C, et al. Enhanced prophylaxis plus antiretroviral therapy for advanced HIV infection in Africa. N Engl J Med. 2017 Jul;377(3):233–45.CrossRef
6.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference Gaskell KM, Rothe C, Gnanadurai R, Goodson P, Jassi C, Heyderman RS, et al. A Prospective Study of Mortality from Cryptococcal Meningitis following Treatment Induction with 1200mg Oral Fluconazole in Blantyre, Malawi. Filler SG, editor. PLoS One. 2014;9(11):e110285.CrossRef Gaskell KM, Rothe C, Gnanadurai R, Goodson P, Jassi C, Heyderman RS, et al. A Prospective Study of Mortality from Cryptococcal Meningitis following Treatment Induction with 1200mg Oral Fluconazole in Blantyre, Malawi. Filler SG, editor. PLoS One. 2014;9(11):e110285.CrossRef
10.
go back to reference Boyles TH, Gatley E, Wasserman S, Meintjes G. Brief report. JAIDS J Acquir Immune Defic Syndr. 2017;74(3):e64–6.CrossRef Boyles TH, Gatley E, Wasserman S, Meintjes G. Brief report. JAIDS J Acquir Immune Defic Syndr. 2017;74(3):e64–6.CrossRef
11.
go back to reference Molyneux E. Where there is no laboratory, a urine patch test helps diagnose meningitis. J Neurosci Rural Pract. 2013 Apr;4(2):117–8.CrossRef Molyneux E. Where there is no laboratory, a urine patch test helps diagnose meningitis. J Neurosci Rural Pract. 2013 Apr;4(2):117–8.CrossRef
12.
go back to reference World Health Organization. Sierra Leone Sierra Leone. Time. 2016, 2003;(January):–4. World Health Organization. Sierra Leone Sierra Leone. Time. 2016, 2003;(January):–4.
14.
go back to reference Thomsen D, Hviid CJ, Hønge BL, Medina C, da Silva Té D, Correira FG, et al. Increased mortality among HIV infected patients with cryptococcal antigenemia in Guinea-Bissau. Pan Afr Med J. 2018. Thomsen D, Hviid CJ, Hønge BL, Medina C, da Silva Té D, Correira FG, et al. Increased mortality among HIV infected patients with cryptococcal antigenemia in Guinea-Bissau. Pan Afr Med J. 2018.
15.
go back to reference Osazuwa F, Dirisu JO, Okuonghae PE, Ugbebor O. Screening for cryptococcal antigenemia in anti-retroviral naïve AIDS patients in Benin City, Nigeria. Oman Med J. 2012;27(3):228–31.CrossRef Osazuwa F, Dirisu JO, Okuonghae PE, Ugbebor O. Screening for cryptococcal antigenemia in anti-retroviral naïve AIDS patients in Benin City, Nigeria. Oman Med J. 2012;27(3):228–31.CrossRef
16.
go back to reference Oladele RO, Akanmu AS, Nwosu AO, Ogunsola FT, Richardson MD, Denning DW. Cryptococcal antigenemia in Nigerian patients with advanced human immunodeficiency virus: Influence of antiretroviral therapy adherence. Open Forum Infect Dis. 2016;3(2):ofw055.CrossRef Oladele RO, Akanmu AS, Nwosu AO, Ogunsola FT, Richardson MD, Denning DW. Cryptococcal antigenemia in Nigerian patients with advanced human immunodeficiency virus: Influence of antiretroviral therapy adherence. Open Forum Infect Dis. 2016;3(2):ofw055.CrossRef
17.
go back to reference Ezeanolue EE, Nwizu C, Greene GS, Amusu O, Chukwuka C, Ndembi N, et al. Brief report: geographical variation in prevalence of Cryptococcal Antigenemia among HIV-infected, treatment-naive patients in Nigeria: a multicenter cross-sectional study. J Acquir Immune Defic Syndr. 2016;73(1):117–21.CrossRef Ezeanolue EE, Nwizu C, Greene GS, Amusu O, Chukwuka C, Ndembi N, et al. Brief report: geographical variation in prevalence of Cryptococcal Antigenemia among HIV-infected, treatment-naive patients in Nigeria: a multicenter cross-sectional study. J Acquir Immune Defic Syndr. 2016;73(1):117–21.CrossRef
18.
go back to reference Mamoojee Y, Shakoor S, Gorton RL, Sarfo S, Appiah LT, Norman B, et al. Short communication: low seroprevalence of cryptococcal antigenaemia in patients with advanced HIV infection enrolling in an antiretroviral programme in Ghana. Tropical Med Int Health. 2011;16(1):53–6.CrossRef Mamoojee Y, Shakoor S, Gorton RL, Sarfo S, Appiah LT, Norman B, et al. Short communication: low seroprevalence of cryptococcal antigenaemia in patients with advanced HIV infection enrolling in an antiretroviral programme in Ghana. Tropical Med Int Health. 2011;16(1):53–6.CrossRef
19.
go back to reference Meya D, Rajasingham R, Nalintya E, Tenforde M, Jarvis JN. Preventing Cryptococcosis—shifting the paradigm in the era of highly active antiretroviral therapy. Curr Trop Med Reports. 2015;2(2):81–9.CrossRef Meya D, Rajasingham R, Nalintya E, Tenforde M, Jarvis JN. Preventing Cryptococcosis—shifting the paradigm in the era of highly active antiretroviral therapy. Curr Trop Med Reports. 2015;2(2):81–9.CrossRef
25.
go back to reference Ousley J, Niyibizi AA, Wanjala S, Vandenbulcke A, Kirubi B, Omwoyo W, et al. High proportions of patients with advanced HIV are antiretroviral therapy experienced: hospitalization outcomes from 2 sub-Saharan African sites. Clin Infect Dis. 2018;66(August):S126–32.CrossRef Ousley J, Niyibizi AA, Wanjala S, Vandenbulcke A, Kirubi B, Omwoyo W, et al. High proportions of patients with advanced HIV are antiretroviral therapy experienced: hospitalization outcomes from 2 sub-Saharan African sites. Clin Infect Dis. 2018;66(August):S126–32.CrossRef
Metadata
Title
Prevalence and mortality of cryptococcal disease in adults with advanced HIV in an urban tertiary hospital in Sierra Leone: a prospective study
Authors
Sulaiman Lakoh
Hannah Rickman
Momodu Sesay
Sartie Kenneh
Rachael Burke
Mamadu Baldeh
Darlinda F. Jiba
Yusuf S. Tejan
Sonia Boyle
Comfort Koroma
Gibrilla F. Deen
Fenella Beynon
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2020
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-020-4862-x

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