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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Outcomes of flucytosine-containing combination treatment for cryptococcal meningitis in a South African national access programme: a cross-sectional observational study
The Lancet Infectious Diseases, Volume 22, No. 9, Year 2022
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Description
Background: Although flucytosine is a key component of WHO-recommended induction treatment for HIV-associated cryptococcal meningitis, this antifungal agent is not widely available in low-income and middle-income countries due to limited production and cost. In 2018, a national flucytosine access programme was initiated in South Africa. We aimed to determine the effectiveness of flucytosine-containing induction regimens in routine care to motivate for the urgent registration of flucytosine and its inclusion in treatment guidelines. Methods: In this cross-sectional study, we compared outcomes of adults aged 18 years and older with incident laboratory-confirmed cryptococcal meningitis treated with or without flucytosine-containing regimens at 19 sentinel hospitals in South Africa. A case of cryptococcosis was defined as illness in an adult with: (1) positive cerebrospinal fluid (CSF) India ink microscopy; (2) a positive CSF cryptococcal antigen test; or (3) culture of Cryptococcus neoformans or Cryptococcus gattii from CSF or any other specimen. We excluded patients without a case report form, those with an unknown or negative HIV serology result, those with a recurrent episode, and those who did not receive antifungal treatment in hospital. We assessed cumulative in-hospital mortality at 14 days and 30 days and calculated the overall crude in-hospital case-fatality ratio. We used random-effects logistic regression to examine the association between treatment group and in-hospital mortality. Findings: From July 1, 2018, to March 31, 2020, 10 668 individuals were diagnosed with laboratory-confirmed cryptococcal meningitis, 7787 cases diagnosed at non-enhanced surveillance sites and 567 cases from eight enhanced surveillance sites with no access to flucytosine were excluded. Of 2314 adults with a first episode of cryptococcosis diagnosed at 19 facilities with access to flucytosine, 1996 had a case report form and of these, 1539 received induction antifungal treatment and were confirmed HIV-seropositive first-episode cases. Of 1539 patients who received antifungal therapy, 596 (38·7%) individuals received a flucytosine-containing regimen and 943 (61·3%) received another regimen. The median age was 36 years (IQR 32–43) and 906 (58·9%) participants were male and 633 (41·1%) were female. The crude in-hospital case-fatality ratio was 23·9% (95% CI 20·0–27·0; 143 of 596) in those treated with flucytosine-containing regimens and 37·2% (95% CI 34·0–40·0; 351 of 943) in those treated with other regimens. Patients admitted to non-academic hospitals (adjusted odds ratio [aOR] 1·95 [95% CI 1·53–2·48]; p<0·0001) and those who were antiretroviral treatment-experienced (aOR 1·30 [1·02–1·67]; p=0·033) were more likely to receive flucytosine. After adjusting for relevant confounders, flucytosine treatment was associated with a 53% reduction in mortality (aOR 0·47 [95% CI 0·35–0·64]; p<0·0001). Among survivors, the median length of hospital admission in the flucytosine group was 11 days (IQR 8–15) versus 17 days (13–21) in the comparison group (p=0·0010). Interpretation: In-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit. Funding: National Institute for Communicable Diseases, a Division of the National Health Laboratory Service. Translation: For the Zulu translation of the abstract see Supplementary Materials section. © 2022 Elsevier Ltd
Authors & Co-Authors
Mashau, Rudzani C.
South Africa, Johannesburg
National Health Laboratory Service
Meiring, Susan T.
South Africa, Johannesburg
National Health Laboratory Service
South Africa, Johannesburg
University of the Witwatersrand Faculty of Health Sciences
Quan, Vanessa Cecilia
South Africa, Johannesburg
National Health Laboratory Service
Nel, Jeremy Stephen
South Africa, Johannesburg
University of the Witwatersrand
South Africa, Johannesburg
Helen Joseph Hospital
Greene, Greg S.
South Africa, Johannesburg
National Health Laboratory Service
Garcia, Andrea
United States, Boston
Clinton Health Access Initiative, Inc.
Menezes, Colin Nigel
South Africa, Johannesburg
University of the Witwatersrand
South Africa, Johannesburg
Chris Hani Baragwanath Hospital
Reddy, Denasha Lavanya
South Africa, Johannesburg
University of the Witwatersrand
South Africa, Johannesburg
Chris Hani Baragwanath Hospital
Venter, Michelle
South Africa, Johannesburg
University of the Witwatersrand
South Africa, Johannesburg
Chris Hani Baragwanath Hospital
Stacey, Sarah Lynn
South Africa, Johannesburg
University of the Witwatersrand
South Africa, Johannesburg
Charlotte Maxeke Johannesburg Academic Hospital
Madua, Matamela C.
South Africa, Mbombela
Rob Ferreira Hospital, Nelspruit
Boretti, Lia
South Africa, Port Elizabeth
Livingstone Hospital
Harrison, Thomas Stephen
United Kingdom, London
St George’s, University of London
United Kingdom, London
St George's University Hospitals Nhs Foundation Trust
United Kingdom, Exeter
University of Exeter
Meintjes, Graeme Ayton
South Africa, Cape Town
Wellcome Centre for Infectious Diseases Research in Africa
Shroufi, Amir
Switzerland, Geneva
Medecins Sans Frontieres
Triviño Durán, Laura
Switzerland, Geneva
Medecins Sans Frontieres
Black, John M.
South Africa, Port Elizabeth
Livingstone Hospital
Govender, Nelesh P.
South Africa, Johannesburg
National Health Laboratory Service
South Africa, Johannesburg
University of the Witwatersrand Faculty of Health Sciences
United Kingdom, London
St George’s, University of London
United Kingdom, Exeter
University of Exeter
South Africa, Cape Town
University of Cape Town
Abrahams, Shareef
Unknown Affiliation
Pearce, Vanessa
Unknown Affiliation
Moncho, Masego
Unknown Affiliation
Ntlemo, Motlatji Grace
Unknown Affiliation
Wadula, Jeannette
Unknown Affiliation
Richards, Lauren
Unknown Affiliation
Nchabeleng, Maphoshane J.
Unknown Affiliation
Tsitsi, Merika
Unknown Affiliation
Moshe, Mamokgethi
Unknown Affiliation
Said, Mohamed
Unknown Affiliation
Kolojane, Molebogeng
Unknown Affiliation
Mothibi, Lesego M.
Unknown Affiliation
Du Plessis, Nicolette Marie
Unknown Affiliation
Chomba, Rispah N.
Unknown Affiliation
Thomas, Teena S.M.
Unknown Affiliation
Avenant, T.
Unknown Affiliation
Nana, Trusha
Unknown Affiliation
Chibabhai, Vindana
Unknown Affiliation
Maharj, Adhil
Unknown Affiliation
Wilson, Douglas P.K.
Unknown Affiliation
Naby, Fathima
Unknown Affiliation
Dawood, Haiima
Unknown Affiliation
Swe Swe-Han, Khine Swe Swe
Unknown Affiliation
Sookan, Lisha
Unknown Affiliation
Dlamini, Nomonde Ritta
Unknown Affiliation
Ramajathan, Praksha
Unknown Affiliation
Mahabeer, Prasha
Unknown Affiliation
Bhola, Prathna
Unknown Affiliation
Naidoo, Romola
Unknown Affiliation
Haffejee, Sumayya
Unknown Affiliation
Sirkar, Surendra
Unknown Affiliation
Ramkillawan, Yeishna
Unknown Affiliation
Hamese, Ken
Unknown Affiliation
Sibiya, Ngoaka
Unknown Affiliation
Mangena, Phetho
Unknown Affiliation
Lekalakala, R. M.
Unknown Affiliation
Hoyland, Greta
Unknown Affiliation
Ntuli, Sindi
Unknown Affiliation
Variava, Ebrahim
Unknown Affiliation
Khantsi, Ignatius
Unknown Affiliation
Mekgoe, Omphile
Unknown Affiliation
Brink, Adrian John
Unknown Affiliation
Prentice, Elizabeth
Unknown Affiliation
Reddy, Kessendri
Unknown Affiliation
Whitelaw, Andrew C.
Unknown Affiliation
Hoosien, Ebrahim
Unknown Affiliation
Zietsman, Inge L.
Unknown Affiliation
Marshall, Terry
Unknown Affiliation
Poswa, Xoliswa
Unknown Affiliation
Govind, Chetna N.
Unknown Affiliation
Smit, Juanita
Unknown Affiliation
Pillay, Keshree
Unknown Affiliation
Seetharam, Sharona
Unknown Affiliation
Howell, Victoria
Unknown Affiliation
Samuel, Catherine Mary
Unknown Affiliation
Senekal, Marthinus
Unknown Affiliation
Bamford, Colleen M.
Unknown Affiliation
Dreyer, Andries William
Unknown Affiliation
Marcus, Louis
Unknown Affiliation
Lowman, Warren
Unknown Affiliation
von Gottberg, Anne M.
Unknown Affiliation
Smith, Anthony Marius
Unknown Affiliation
Mathunjwa, Azwifarwi
Unknown Affiliation
D'Abreu, Cecilia
Unknown Affiliation
Miller, Cecilia
Unknown Affiliation
Cohen, Cheryl D.
Unknown Affiliation
Ismail, Farzana
Unknown Affiliation
Moultrie, Harry
Unknown Affiliation
Ismail, Husna
Unknown Affiliation
Weyer, Jacqueline
Unknown Affiliation
Kleynhans, Jackie
Unknown Affiliation
Rossouw, Jenny
Unknown Affiliation
Frean, John Andrew
Unknown Affiliation
Ebonwu, Joy I.
Unknown Affiliation
Mwansa-Kambafwile, Judith R.M.
Unknown Affiliation
Thomas, Juno
Unknown Affiliation
Bishop, Kate
Unknown Affiliation
McCarthy, Kerrigan M.
Unknown Affiliation
Shuping, Liliwe L.
Unknown Affiliation
de Gouveia, Linda D.
Unknown Affiliation
Erasmus, Linda Kathleen
Unknown Affiliation
Puren, Adrian
Unknown Affiliation
Blumberg, Lucille Hellen
Unknown Affiliation
Smith, Marshagne
Unknown Affiliation
Makgoba, Martha
Unknown Affiliation
Groome, Michelle J.
Unknown Affiliation
Du Plessis, Mignon D.
Unknown Affiliation
Ngomane, Mimmy
Unknown Affiliation
Manaka, Mokupi
Unknown Affiliation
Moremi, Myra
Unknown Affiliation
Ismail, Nazir Ahmed
Unknown Affiliation
Legare, Neo
Unknown Affiliation
Page, Nicola A.
Unknown Affiliation
Hoho, Nombulelo
Unknown Affiliation
Perovic, Olga
Unknown Affiliation
Sekwadi, Phuti G.
Unknown Affiliation
Magobo, Rindidzani E.
Unknown Affiliation
Mpembe, Ruth S.
Unknown Affiliation
Walaza, Sibongile
Unknown Affiliation
Dlamini, Siyanda
Unknown Affiliation
Lebaka, Tiisetso
Unknown Affiliation
Ngubane, Wendy
Unknown Affiliation
Statistics
Citations: 9
Authors: 120
Affiliations: 15
Identifiers
Doi:
10.1016/S1473-3099(22)00234-1
ISSN:
14733099
Research Areas
Health System And Policy
Infectious Diseases
Study Design
Cross Sectional Study
Quasi Experimental Study
Case-Control Study
Study Approach
Quantitative
Study Locations
South Africa
Participants Gender
Male
Female