Spread of artemisinin resistance in Plasmodium falciparum malaria.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS: Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS: The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS: Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.).

Level of utilization and provider-related barriers to the use of hydroxyurea in the treatment of sickle cell disease patients in Jos, North-Central Nigeria.

BACKGROUND: Hydroxyurea is underutilized by sickle cell health-care providers in Nigeria despite available evidence of its effectiveness in reducing the manifestations and complications of sickle cell disease (SCD). OBJECTIVES: To assess the level of utilization and provider-related barriers to the use of hydroxyurea in SCD therapy in Jos, Nigeria. METHODS: A cross-sectional study conducted among 132 medical doctors providing care for SCD patients. Data on sociodemographics, utilization and barriers to hydroxyurea use were obtained. The barriers were fed cumulatively into the logistic regression model as predictors of utilization. RESULTS: Of the 132 care providers, 88 (67%) had been in medical practice for ≥6years. The level of utilization of hydroxyurea was 24.2%. The significant barriers that predicted the non-utilization of hydroxyurea included lack of expertise (OR=5.1; 95% CI=2.65-9.05), lack of clinical guidelines (OR=3.84; 95% CI=2.37-14.33), fear of side-effects (OR=0.50; 95% CI=0.22-0.68) and doubt about its effectiveness (OR=0.30; 95% CI=0.20-0.90). CONCLUSION: The level of utilization of hydroxyurea in the treatment of SCD among the care providers is sub-optimal with the lack of expertise in its use identified as the most prominent barrier. There is an urgent need for the training of sickle cell care-providers and the development of clinical guidelines on hydroxyurea use.