BackgroundArtemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children.Methodology/Principal FindingsThe non-inferiority of DHA-PQP versus artemether-lumefantrine (AL) in children 6–59 months old with uncomplicated P. falciparum malaria was tested in five African countries (Burkina Faso, Kenya, Mozambique, Uganda and Zambia). Patients were randomised (2∶1) to receive either DHA-PQP or AL. Non-inferiority was assessed using a margin of −5% for the lower limit of the one-sided 97.5% confidence interval on the treatment difference (DHA-PQP vs. AL) of the day 28 polymerase chain reaction (PCR) corrected cure rate. Efficacy analysis was performed in several populations, and two of them are presented here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 1553 children were randomised, 1039 receiving DHA-PQP and 514 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% (ePP) in the AL group. The lower limits of the one-sided 97.5% CI of the difference between the two treatments were −2.80% and −2.96%, in the ITT and ePP populations, respectively. In the ITT population, the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55% (95% CI: 11.35%–15.76%) for DHA-PQP vs 24.00% (95% CI: 20.11%–27.88%) for AL (p<0.0001).Conclusions/SignificanceDHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity settings, and shows a comparable safety profile. The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group, indicating a longer post-treatment prophylactic effect.Trial RegistrationControlled-trials.com ISRCTN16263443

The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.

Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-treatment prophylaxis, whereas dihydroartemisinin-piperaquine had the best efficacy and an acceptable safety profile. (Funded by the European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.).

Objectives To characterize antiretroviral therapy (ART) adherence across different programmes and examine the relationship between individual and programme characteristics and incomplete adherence among ART clients in sub-Saharan Africa. Design A cross-sectional study. Methods Systematically selected ART clients (≥18 years; on ART ≥6 months) attending 18 facilities in three countries (250 clients/facility) were interviewed. Client self-reports (3-day, 30-day, Case Index ≥48 consecutive hours of missed ART), healthcare provider estimates and the pharmacy medication possession ratio (MPR) were used to estimate ART adherence. Participants from two facilities per country underwent HIV RNA testing. Optimal adherence measures were selected on the basis of degree of association with concurrent HIV RNA dichotomized at less than or greater/equal to 1000 copies/ml. Multivariate regression analysis, adjusted for site-level clustering, assessed associations between incomplete adherence and individual and programme factors. Results A total of 4489 participants were included, of whom 1498 underwent HIV RNA testing. Nonadherence ranged from 3.2% missing at least 48 consecutive hours to 40.1% having an MPR of less than 90%. The percentage with HIV RNA at least 1000 copies/ml ranged from 7.2 to 17.2% across study sites (mean = 9.9%). Having at least 48 consecutive hours of missed ART was the adherence measure most strongly related to virologic failure. Factors significantly related to incomplete adherence included visiting a traditional healer, screening positive for alcohol abuse, experiencing more HIV symptoms, having an ART regimen without nevirapine and greater levels of internalized stigma. Conclusion Results support more in-depth investigations of the role of traditional healers, and the development of interventions to address alcohol abuse and internalized stigma among treatment-experienced adult ART patients.

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