The Best Treatment for Cryptococcal Meningitis in Africa: Looks like Goldilocks got it right

Caring for cryptococcal meningitis in a resource limited setting can be a Scylla and Charybdis experience. Besides starting antiretrovirals and offering repeated lumbar punctures (if family will agree), the only treatment on offer to most patients is high dose oral fluconazole—cheap and available with limited toxicity, but not that great at clearing the infection. That is rock number one. Rock number 2 is the occasional patient who can afford amphotericin B. Not a fun drug to try and manage in the absence of the capacity to check and/or replenish electrolytes or evaluate renal function in a rapid and reliable fashion. So the recent clinical trial report in the NEJM provides incredibly valuable insights into optimal treatment for cryptococcal meningitis in the African setting.1 In their multi-country study, Molloy et al. found that 1 week of amphotericin plus flucytosine OR 2 weeks of high dose fluconazole plus flucytosine were both superior to 2 weeks of amphotericin B. Somewhere between the first and second week of ampho B is the tipping point for safety vs. efficacy in this fragile population. Two weeks of ampho B resulted in 8.8% of patients developing grade 3 or 4 elevated creatinines. Given that within the context of the study patients received preemptive electrolyte replacement (something not routinely available), the study may have under estimated the toxicity of ampho B in the ‘real work’ African setting. Thus my own preference for the fluconazole/ flucytosine option.

Key now is to see if the calls for generic, readily available flucytosine are successful.

  1. Molloy SF, Kanyama C, Heyderman RS, et al. Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa. N Engl J Med 2018; 378(11): 1004-17.


Gretchen L. Birbeck, MD, MPH

Gretchen L. Birbeck, MD, MPH

Gretchen Birbeck is a neurologist who divides her time between the US and Africa. Her US academic home is the University of Rochester where she is the Rykenboer Professor of Neurology and Research Director for the Strong Epilepsy Center with adjunct appointments in the Center for Human Experimental Therapeutics and the Department of Public Health. Her additional skills in epidemiology, health services research, and tropical medicine are brought to bear during the 6-months annually she spends in Africa where she serves as Director for the Chikankata Epilepsy Care Team in rural Mazabuka, Zambia, an Honorary Lecturer at the University of Zambia and a consultant for the Paediatric Research Ward at Queen Elizabeth Central Hospital in Blantyre, Malawi. Gretchen’s research programs are aimed at identifying opportunities to prevent or ameliorate the medical and social morbidities of common neurologic conditions in low-income, tropical settings with the ultimate goal of developing successful interventions feasible for scale up and broad implementation. She has been recognized as an Ambassador for Epilepsy by the International League against Epilepsy, a Global Health Research Ambassador by the US Paul Rogers Society, a National Outreach Scholar by the WK Kellogg Foundation and a Leader in Medicine by the American Medical Students Association.

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