RESUMO
The medical humanitarian organization Médecins Sans Frontières (MSF) provides medical care in more than 70 countries and admits more than 7000 cases of snakebite in its facilities each year. We describe our activities against snakebite in three African countries: Central African Republic, South Sudan and Ethiopia, in which different models of care have been developed. A standard protocol using two different antivenoms depending on the patient's syndrome has been introduced, and a simple blood coagulation test is performed to detect venom-induced coagulopathy. Other services, including surgery for necrotizing wounds, are offered in the facilities where MSF admits a large number of snakebite patients. All services, including provision of antivenom, are offered free-of-charge in MSF-supported facilities. Community-based activities focusing on preventive measures and prompt transport to hospital have been developed in a few MSF projects. The provision of quality care and treatment, including effective antivenoms, without out-of-pocket payments by the patients, probably explains why MSF has admitted an increasing number of snakebite victims over the last years. This model requires significant resources and monitoring, including regular training of healthcare workers on treatment protocols and a considerable budget for antivenom procurement.
RESUMO
BACKGROUND: This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG/PM) for treatment of primary visceral leishmaniasis in eastern Africa. METHODS: An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg/kg sodium stibogluconate plus 15 mg/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months. RESULTS: Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM/MF and SSG/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], -6.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91.7% (155 of 169) in the PM/MF and SSG/PM arms (difference, -0.3%; 97.5% CI, -7.0 to 6.5), demonstrating noninferiority. Treatments were well tolerated. Four of 18 serious adverse events were study drug-related, and 1 death was SSG-related. Allometric dosing ensured similar MF exposure in children (<12 years) and adults. CONCLUSIONS: PM/MF and SSG/PM efficacies were similar, and adverse drug reactions were as expected given the drugs safety profiles. With 1 less injection each day, reduced treatment duration, and no risk of SSG-associated life-threatening cardiotoxicity, PM/MF is a more patient-friendly alternative for children and adults with primary visceral leishmaniasis in eastern Africa. CLINICAL TRIALS REGISTRATION: NCT03129646.
