Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries
Open accessAbstract
In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.
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The majority of cryptococcal meningitis deaths are reported from resource-limited countries owing to a lack of access to drugs and the high cost of effective treatments.
“The majority of deaths are reported from resource-limited countries owing to a lack of access to drugs and the high cost of effective treatments, signifying the urgency in developing affordable therapeutics against these deadly fungal pathogens7.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [7]
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- Authors
- Loyse, A., Burry, J., Cohn, J., Ford, N., Chiller, T., Ribeiro, I., Koulla-Shiro, S., Mghamba, J., Ramadhani, A., Nyirenda, R., Aliyu, S. H., Wilson, D., Le, T., Oladele, R., Lesikari, S., Muzoora, C., Kalata, N., Temfack, E., Mapoure, Y., Sini, V., Chanda, D., Shimwela, M., Lakhi, S., Ngoma, J., Gondwe-Chunda, L., Perfect, C., Shroufi, A., Andrieux-Meyer, I., Chan, A., Schutz, C., Hosseinipour, M., Van der Horst, C., Klausner, J. D., Boulware, D. R., Heyderman, R., Lalloo, D., Day, J., Jarvis, J. N., Rodrigues, M., Jaffar, S., Denning, D., Migone, C., Doherty, M., Lortholary, O., Dromer, F., Stack, M., Molloy, S. F., Bicanic, T., van Oosterhout, J., Mwaba, P., Kanyama, C., Kouanfack, C., Mfinanga, S., Govender, N., & Harrison, T. S.
- Affiliations
- St George's, University of London (GB)
- Médecins Sans Frontières (CH)
- World Health Organization (CH)
- Centers for Disease Control and Prevention (US)
- Drugs for Neglected Diseases Initiative (CH)
- Ministry of Health, Community Development, Gender, Elderly and Children (TZ)
- Ministry of Health (MW)
- National Agency for the Control of AIDS (NG)
- Edendale Hospital (ZA)
- Duke University (US)
- University of Lagos (NG)
- Mbarara University of Science and Technology (UG)
- University of Malawi (MW)
- University of Douala (CM)
- Central Hospital of Yaoundé (CM)
- University Teaching Hospital (ZM)
- Kamuzu Central Hospital (MW)
- Médecins Sans Frontières (ZA)
- Sunnybrook Health Science Centre (CA)
- University of Cape Town (ZA)
- University of California, Los Angeles (US)
- University of Minnesota (US)
- University College London (GB)
- Liverpool School of Tropical Medicine (GB)
- University of Oxford (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Institut Pasteur (FR)
- Lusaka Apex Medical University (ZM)
- Université de Dschang (CM)
- National Institute for Medical Research (TZ)
- National Institute for Communicable Diseases (ZA)
- Corresponding author
- Loyse, Angela
- ORCID
- Loyse, Angela
- Burry, Jessica
- Ford, Nathan
- Chiller, Tom
- Ribeiro, Isabela
- Mghamba, Janneth
- Aliyu, Sani H
- Wilson, Douglas
- Le, Thuy
- Oladele, Rita
- Muzoora, Conrad
- Kalata, Newton
- Temfack, Elvis
- Chanda, Duncan
- Lakhi, Shabir
- Shroufi, Amir
- Chan, Adrienne
- Schutz, Charlotte
- Hosseinipour, Mina
- Klausner, Jeffrey D
- Boulware, David R
- Heyderman, Robert
- Lalloo, David
- Day, Jeremy
- Jarvis, Joseph N
- Jaffar, Shabbar
- Denning, David
- Doherty, Megan
- Lortholary, Olivier
- Dromer, Françoise
- Molloy, Síle F
- Bicanic, Tihana
- Mwaba, Peter
- Kanyama, Cecilia
- Kouanfack, Charles
- Mfinanga, Sayoki
- Govender, Nelesh
- Harrison, Thomas S
- Venue
- The Lancet Infectious Diseases
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 19
- Issue
- 4
- Pages
- e143-e147
- ISSN
- 1473-3099 (ISSN-L)
- OpenAlex
- W2897851454
- Cited by
- 90
- References
- 24
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 14 · 2023: 10 · 2022: 17 · 2021: 17 · 2020: 6 · 2019: 9 · 2018: 1
- FWCI
- 6.44
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- The Lancet Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Medecins Sans Frontieres Field Research (Medecins Sans Frontieres) (submittedVersion)
- UNC Libraries
- Funders
- World Health Organization
- Medical Research Council (MC_PC_MR/P006922/1)
- National Institute of Allergy and Infectious Diseases (P30AI064518)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Keywords
- cryptococcal meningitis, WHO treatment guidelines, cryptococcal antigen detection, people living with HIV, low- and middle-income countries, access to essential medicines, mortality
- MeSH terms
- Africa, Amphotericin B, Antifungal Agents, Cryptococcus neoformans, Developing Countries, Drug Administration Schedule, Drug Therapy, Combination, Flucytosine, Humans, Income, HIV Infections, Fluconazole, Survival Analysis, Meningitis, Cryptococcal, Guidelines as Topic, Disease Management, Coinfection
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