SummaryBackgroundChloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria.MethodsWe did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per μL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 μL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for AQ-13 and the upper limit of the 95% CI was less than the non-inferiority margin of 15%. This trial is registered at ClinicalTrials.gov, number NCT01614964.FindingsBetween Aug 6 and Nov 18, 2013, and between Sept 18 and Nov 20, 2015, 66 Malian men with uncomplicated malaria were enrolled. 33 participants were randomly assigned to each group. There were no serious adverse events (grade 2–4) and asexual parasites were cleared by day 7 in both groups. 453 less-severe adverse events (≤grade 1) were reported: 214 in the combination group and 239 in the AQ-13 group. Two participants withdrew from the AQ-13 group after parasite clearance and three were lost to follow-up. In the artemether plus lumefantrine group, two participants had late treatment failures (same markers as original isolates). On the basis of the per-protocol analysis, the AQ-13 and artemether plus lumefantrine groups had similar proportions cured (28 [100%] of 28 vs 31 [93·9%] of 33; p=0·50) and AQ-13 was not inferior to artemether plus lumefantrine (difference −6·1%, 95% CI −...

The geographic and evolutionary origins of the SARS-CoV-2 Omicron variant (BA.1), which was first detected mid-November 2021 in Southern Africa, remain unknown. We tested 13,097 COVID-19 patients sampled between mid-2021 to early 2022 from 22 African countries for BA.1 by real-time RT-PCR. By November-December 2021, BA.1 had replaced the Delta variant in all African sub-regions following a South-North gradient, with a peak Rt of 4.1. Polymerase chain reaction and near-full genome sequencing data revealed genetically diverse Omicron ancestors already existed across Africa by August 2021. Mutations, altering viral tropism, replication and immune escape, gradually accumulated in the spike gene. Omicron ancestors were therefore present in several African countries months before Omicron dominated transmission. These data also indicate that travel bans are ineffective in the face of undetected and widespread infection.

Background The current first-line treatments for uncomplicated malaria recommended by the National Malaria Control Programme in Mali are artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ). From 2015 to 2016, an in vivo study was carried out to assess the clinical and parasitological responses to AL and ASAQ in Sélingué, Mali. Methods Children between 6 and 59 months of age with uncomplicated Plasmodium falciparum infection and 2000–200,000 asexual parasites/μL of blood were enrolled, randomly assigned to either AL or ASAQ, and followed up for 42 days. Uncorrected and PCR-corrected efficacy results at days 28 and 42. were calculated. Known markers of resistance in the Pfk13, Pfmdr1, and Pfcrt genes were assessed using Sanger sequencing. Results A total of 449 patients were enrolled: 225 in the AL group and 224 in the ASAQ group. Uncorrected efficacy at day 28 was 83.4% (95% CI 78.5–88.4%) in the AL arm and 93.1% (95% CI 89.7–96.5%) in the ASAQ arm. The per protocol PCR-corrected efficacy at day 28 was 91.0% (86.0–95.9%) in the AL arm and 97.1% (93.6–100%) in the ASAQ arm. ASAQ was significantly (p < 0.05) better than AL for each of the aforementioned efficacy outcomes. No mutations associated with artemisinin resistance were identified in the Pfk13 gene. Overall, for Pfmdr1, the N86 allele and the NFD haplotype were the most common. The NFD haplotype was significantly more prevalent in the post-treatment than in the pre-treatment isolates in the AL arm (p < 0.01) but not in the ASAQ arm. For Pfcrt, the CVIET haplotype was the most common. Conclusions The findings indicate that both AL and ASAQ remain effective for the treatment of uncomplicated malaria in Sélingué, Mali.

Background The current first-line treatments for uncomplicated malaria recommended by the National Malaria Control Program in Mali are artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ). From 2015–2016, we conducted an in vivo study to assess the clinical and parasitological responses to AL and ASAQ in Sélingué, Mali. Methods Children between 6 and 59 months of age with uncomplicated Plasmodium falciparum infection and 2,000–200,000 asexual parasites/µL of blood were enrolled, randomly assigned to either AL or ASAQ, and followed up for 42 days. Uncorrected and PCR-corrected efficacy results at days 28 and 42 were calculated. Known markers of resistance in the Pfk13, Pfmdr1, and Pfcrt genes were assessed using Sanger sequencing. Results A total of 449 patients were enrolled: 225 in the AL group and 224 in the ASAQ group. Uncorrected efficacy at day 28 was 83.4% (95% CI: 78.5–88.4%) in the AL arm and 93.1% (95% CI: 89.7–96.5%) in the ASAQ arm. The per protocol PCR-corrected efficacy at day 28 was 91.0% (86.0–95.9%) in the AL arm and 97.1% (93.6–100%) in the ASAQ arm. ASAQ was significantly (p < 0.05) better than AL for each of the aforementioned efficacy outcomes. No mutations associated with artemisinin resistance were identified in the Pfk13 gene. Overall, for Pfmdr1, the N86 allele and the NFD haplotype were the most common. The NFD haplotype was significantly more prevalent in the post-treatment than in the pre-treatment isolates in the AL arm (p < 0.01) but not in the ASAQ arm. For Pfcrt, the CVIET haplotype was the most common. Conclusions Our findings indicate that both AL and ASAQ remain effective for the treatment of uncomplicated malaria in Sélingué, Mali.

In Sub-Saharan Africa, Genotype-Environment interaction plays a key role in formulating strategies for crop improvement. Multi-location trials have created enabling structure to determine varieties yield performance and stability. Crop modeling led to prediction of long-term and spatial effects of climate variability. Three improved varieties were compared to three landraces. Optimum cultivation areas minimizing the risk of crop failure were delineated by comparing predicted flowering dates and end of rainy seasons. Agronomic values were determined in trials from three climatically different zones in 27 farms. Yield stability was determined using linear regression depending on each environmental mean and the AMMI model. Photoperiod sensitive varieties have wider optimal cultivation areas whereas early-maturing varieties (photoperiod insensitive) are subjected to strong constraints on sowing date. In low productivity conditions, landraces and improved varieties are not distinct. As the environmental cropping conditions increase, improved lines become significantly superior to landraces. Photoperiod insensitive landrace is subservient to climate conditions of its area of origin and its productivity drops sharply when moved to a wetter area. Varieties studied combined productivity and stability traits. These findings are important steps toward breeding climate resilient varieties for meeting the challenges of climate smart agriculture and sustainable intensification.