A double blind, randomized, controlled Phase 2 clinical trial was conducted to assess the safety, immunogenicity, and biologic impact of the vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1), adjuvanted with Alhydrogel ® . Participants were healthy children 2-3 years old living in or near the village of Bancoumana, Mali. A total of 300 children received either the study vaccine or the comparator. No impact of vaccination was seen on the primary endpoint, the frequency of parasitemia measured as episodes >3000 per μL per day at risk. There was a negative impact of vaccination on the hemoglobin level during clinical malaria, and mean incidence of hemoglobin <8.5 g/dL, in the direction of lower hemoglobin in the children who received AMA1-C1, although these differences were not significant after correction for multiple tests. These differences were not seen in the second year of transmission.

Background: Recent studies have shown that intermittent preventive malaria treatment (IPT) in infants in areas of stable malaria transmission reduces malaria and severe anaemia incidence. However in most areas malaria morbidity and mortality remain high in older children.

Division of Intramural Research, National Institute of Allergy and Infectious Diseases.

The choice of appropriate artemisin-based combination therapy depends on several factors (cost, efficacy, safety, reinfection rate, and simplicity of administration). In this study, we tested the hypothesis that artesunatemefloquine (Artequin™) is as efficacious as artemether-lumefantrine (Coartem) in treatment of uncomplicated Plasmodium falciparum malaria. The study was carried out from August 2004 through February 2005 in Kambila, Mali. Subjects with weights Ն 10 kg and uncomplicated malaria were enrolled. Artesunate-mefloquine was given once a day for three days and artemether/lumefantrine twice a day for three days. A total of 470 (235 in each arm) patients were enrolled. The unadjusted 28-day cure rate was higher in artesunate-mefloquine arm than in the artemether-lumefantrine arm (79.7% versus 67.8%; P < 0.004). After correction for reinfection, the 28-day cure rates were similar in the two groups (96.04% versus 96.93%). Artesunate-mefloquine is well-tolerated and is as effective as artemether-lumefantrine for the treatment of P. falciparum malaria. Artesunate-mefloquine also prevented more new infections.

SummaryBackground-Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malariaendemic settings.Methods-We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 Findings-We included 61 studies done between Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose).Interpretation-The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups.Funding-Bill & Melinda Gates Foundation. IntroductionArtemisinin-based combination therapies are the first-line treatment for uncomplicated Plasmodium falciparum malaria in most malaria-endemic countries, 1 and they have been advocated to counter the threat of antimalarial drug resistance by delaying its emergence and spread. 2 As such, artemisinin-based combination therapies are a key component of malaria elimination efforts. 3The combination of artemether and lumefantrine was originally introduced as a four-dose regimen that proved to be efficacious in studies done in China, 4 Africa, 5 and India; 6 however, after detailed pharmacokinetic-pharmacodynamic assess...

Background The extent of SARS-CoV-2 exposure and transmission in Mali and the surrounding region is not well understood. We aimed to estimate the cumulative incidence of SARS-CoV-2 in three communities, and understand factors associated with infection. Methods Between July 2020 and January 2021, we collected blood samples and demographic, social, medical, and self-reported symptoms information from residents aged 6 months and older over two study visits. SARS-CoV-2 antibodies were measured using a highly specific two-antigen ELISA optimized for use in Mali. We calculated cumulative adjusted seroprevalence for each community and evaluated factors associated with serostatus at each visit by univariate and multivariate analysis. Results Overall, 94.8% (2533/2672) of participants completed both study visits. A total of 31.3% (837/2672) were aged &lt;10 years, 27.6% (737/2672) were aged 10-17 years, and 41.1% (1098/2572) were aged ≥18 years. The cumulative SARS-CoV-2 exposure rate was 58.5% (95% CI: 47.5 to 69.4). This varied between sites and was 73.4% in the urban community of Sotuba, 53.2% in the rural town of Bancoumana, and 37.1% in the rural village of Donéguébougou. Study site and increased age were associated with serostatus at both study visits. There was minimal difference in reported symptoms based on serostatus. Conclusion The true extent of SARS-CoV-2 exposure in Mali is greater than previously reported and may now approach hypothetical ‘herd immunity’ in urban areas. The epidemiology of the pandemic in the region may be primarily subclinical and within background illness rates.

The choice of artemisinin-based combination that is being adopted for malaria treatment in sub-Saharan Africa may depend on several factors, including cost, efficacy, side effects, and simplicity of administration. We tested the hypothesis that artesunate-sulfamethoxypyrazine-pyrimethamine is as efficacious as the four-dose regimen of artemether-lumefantrine for treatment of Plasmodium falciparum malaria. The study was carried out during two transmission seasons (2003 and 2004) in Sotuba, Mali. Participants at least 6 months of age with uncomplicated P. falciparum malaria were randomly assigned to receive artesunate-sulfamethoxypyrazine-pyrimethamine or artemether-lumefantrine. Treatment efficacy was assessed using the World Health Organization 28-day protocol. A total of 606 (303 in each arm) patients were enrolled. The cure rate was higher for artesunate-sulfamethoxypyrazine-pyrimethamine than for artemether-lumefantrine (98.7% versus 89.6%; P < 0.0001). After correction for cases of re-infection, the cure rates were 100% and 99.0%, respectively (P = 0.08). No serious adverse events occurred. Artesunate-sulfamethoxypyrazine-pyrimethamine is well-tolerated and effective against P. falciparum malaria. It showed an additional benefit of preventing new infections.

Initial responses to questionnaires used to assess participants' understanding of informed consent for malaria vaccine trials conducted in the United States and Mali were tallied. Total scores were analyzed by age, sex, literacy (if known), and location. Ninety-two percent (92%) of answers by United States participants and 85% of answers by Malian participants were correct. Questions more likely to be answered incorrectly in Mali related to risk, and to the type of vaccine. For adult participants, independent predictors of higher scores were younger age and female sex in the United States, and male sex in Mali. Scores in the United States were higher than in Mali ( P = 0.005). Despite this difference participants at both sites were well informed overall. Although interpretation must be qualified because questionnaires were not intended as research tools and were not standardized among sites, these results do not support concerns about systematic low understanding among research participants in developing versus developed countries