Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries.
Loyse A., Burry J., Cohn J., Ford N., Chiller T., Ribeiro I., Koulla-Shiro S., Mghamba J., Ramadhani A., Nyirenda R., Aliyu SH., 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 JD., Boulware DR., Heyderman R., Lalloo D., Day J., Jarvis JN., Rodrigues M., Jaffar S., Denning D., Migone C., Doherty M., Lortholary O., Dromer F., Stack M., Molloy SF., Bicanic T., van Oosterhout J., Mwaba P., Kanyama C., Kouanfack C., Mfinanga S., Govender N., Harrison TS.
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.