Pooled Multicenter Analysis of Cardiovascular Safety and Population Pharmacokinetic Properties of Piperaquine in African Patients with Uncomplicated Falciparum Malaria.

Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicenter trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90-ms mean QTc prolongation per 100-ng/ml increase in piperaquine concentration. The effect of piperaquine on absolute QTc interval estimated a mean maximum QTc interval of 456?ms (50% effective concentration of 209 ng/ml). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98 to 2.46% risk of having QTc prolongation?of >60 ms in all treatment settings. Although piperaquine administration resulted in QTc prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern. (This study has been registered at ClinicalTrials.gov under identifier NCT02199951.)

Epidemiology of Underweight among Infants in Rural Burkina Faso.

Infant undernutrition is thought to contribute to growth failure and mortality. We evaluated the patterns in underweight in a population-based sample of children aged 1-11 months in rural northwestern Burkina Faso. Data were collected during the baseline assessment of a community-randomized trial evaluating mass azithromycin distribution in Nouna District, Burkina Faso. A door-to-door census was undertaken for all households in all communities. Infants aged 1-11 months were weighed for weight-based dosing in the trial and their weights were used to calculate weight-for-age Z-scores (WAZ). Underweight was defined as WAZ ≤ 2. We evaluated the age patterns in WAZ and underweight by demographic, seasonal, and geographic characteristics. Of 7,109 infants, 6,077 had accurate weight and global positioning system (GPS) coordinate data (85.5%). Infants were a median of 6 months old (interquartile range [IQR] 3-8) and 48.4% were female. Mean WAZ was -0.68 (SD 1.6) and 19.0% were underweight. The WAZ decreased with increasing age, and the prevalence of underweight increased from 2.5% among 1-month-olds to 27.6% among 11-month-olds. Underweight was more common among boys than girls (22.1% among boys versus 15.6% among girls). Improved latrine use by the household was associated with increased WAZ, and this effect was stronger in male compared with female infants. Given the large burden of underweight among infants, interventions addressing undernutrition should specifically include infants