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Background: The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13.Methods: We conducted prospective quinine efficacy studies in 2 villages, Kollé and Faladié, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites before versus after quinine treatment was determined by direct sequencing.Results: Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study, the prevalence of ms4760-1 was similar before and after treatment.Conclusions: This study supports a role for pfnhe-1 in decreased susceptibility of P. falciparum to quinine in the field. [ABSTRACT FROM AUTHOR]

Background: In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus-specific reverse transcription-polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis., Methods: To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome., Results: The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors., Conclusions: Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Trimethoprim-sulfamethoxazole (TS) prophylaxis is recommended for persons living with human immunodeficiency virus infection and acquired immunodeficiency syndrome in Africa. TS and the antimalarial combination sulfadoxine-pyrimethamine (SP) share mechanisms of action and resistance patterns, and concerns about the impact of TS resistance on SP efficacy have contributed to reluctance to implement TS prophylaxis in Africa., Methods: To determine whether TS prophylaxis impairs SP efficacy for treatment of uncomplicated falciparum malaria, we conducted a randomized, controlled, open-label study of TS prophylaxis. Two hundred and forty children 5-15 years old were randomized in a 2 : 1 fashion to receive either thrice-weekly TS for 12 weeks or no prophylaxis and were treated with SP for subsequent episodes of malaria. The incidence of malaria, SP efficacy, and the prevalence of parasite mutations that confer antifolate drug resistance were measured., Results: TS prophylaxis had a 99.5% protective efficacy against episodes of clinical malaria, with 97% efficacy against infection. Four SP treatment failures occurred in the control group, and none occurred in the TS group. No evidence was seen for selection by TS of antifolate resistance-conferring mutations in parasite dihydrofolate reductase or dihydropteroate synthase during subclinical infections., Conclusions: In this setting of low antifolate resistance, TS was highly effective in preventing falciparum malaria infection and disease and did not appear to select for SP-resistant parasites.