Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial.

Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce

Absolute Bioavailability of cis-Mirincamycin and trans-Mirincamycin in Healthy Rhesus Monkeys and Ex Vivo Antimalarial Activity against Plasmodium falciparum ▿

The pharmacokinetics, oral bioavailability, and ex vivo antimalarial activity of mirincamycin isomers in a healthy rhesus monkey model were assessed to support lead optimization of novel nonhemolytic drugs for radical cure and causal prophylaxis of malaria. Fourteen male rhesus monkeys were randomized to four groups, which included cis and trans isomers by the oral and intravenous routes, with vehicle-only controls for each dosing route. Concentration-time data were collected for 7 days and were analyzed by noncompartmental analysis. cis-Mirincamycin had an absolute oral bioavailability of 13.6%, which was slightly higher than that of trans-mirincamycin (11.7%), but this difference was not statistically significant. There was a statistically significant difference between the area under the concentration-time curve from zero to 48 h (AUC0–48) of cis-mirincamycin and that of trans-mirincamycin after oral dosing. When cultured in vitro with the W2 clone of Plasmodium falciparum, the 50% inhibitory concentrations for cis-mirincamycin, trans-mirincamycin, and dihydroartemisinin were 11,300, 12,300, and 2.30 nM, respectively. However, when dosed primate plasma was cultured ex vivo against the W2 clone, both isomers had much greater relative potencies than their in vitro activities relative to results for dihydroartemisinin, an increase of approximately 100-fold for the cis isomer and 150-fold for the trans isomer. Further, oral ex vivo activity was significantly higher than intravenous activity for both isomers, particularly during the first 90 min following dosing, suggesting the first-pass formation of one or more metabolites with blood-stage antimalarial activity. Identification of the metabolic pathways and metabolites may help to further delineate the properties of this class of drugs with previously demonstrated liver-stage antimalarial activity

Utilization of public or private health care providers by febrile children after user fee removal in Uganda

<p>Abstract</p> <p>Background</p> <p>Despite investments in providing free government health services in Uganda, many caretakers still seek treatment from the drug shops/private clinics. The study aimed to assess determinants for use of government facilities or drug shops/private clinics for febrile illnesses in children under five.</p> <p>Methods</p> <p>Structured questionnaires were administered to caretakers in 1078 randomly selected households in the Iganga – Mayuge Demographic Surveillance site. Those with children who had had fever in the previous two weeks and who had sought care from outside the home were interviewed on presenting symptoms and why they chose the provider they went to. Symptoms children presented with and reasons for seeking care from government facilities were compared with those of drug shops/private clinics.</p> <p>Results</p> <p>Of those who sought care outside the home, 62.7% (286/456) had first gone to drug shops/private clinics and 33.1% (151/456) first went to government facilities. Predictors of having gone to government facilities with a febrile child were child presenting with vomiting (OR 2.07; 95% CI 1.10 – 3.89) and perceiving that the health providers were qualified (OR 10.32; 95% CI 5.84 – 18.26) or experienced (OR 1.93; 95% CI 1.07 – 3.48). Those who took the febrile child to drug shops/private clinics did so because they were going there to get first aid (OR 0.20; 95% CI 0.08 – 0.52).</p> <p>Conclusion</p> <p>Private providers offer 'first aid' to caretakers with febrile children. Government financial assistance to health care providers should not stop at government facilities. Multi-faceted interventions in the private sector and implementation of community case management of febrile children through community medicine distributors could increase the proportion of children who access quality care promptly.</p