BACKGROUND Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed “radical cure”). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax . METHODS This multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial was conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. We enrolled 522 patients with microscopically confirmed P. vivax infection (>100 to <100,000 parasites per microliter) and normal glucose-6-phosphate dehydrogenase (G6PD) activity (with normal activity defined as ≥70% of the median value determined at each trial site among 36 healthy male volunteers who were otherwise not involved in the trial). All patients received a 3-day course of chloroquine (total dose of 1500 mg). In addition, patients were assigned to receive a single 300-mg dose of tafenoquine on day 1 or 2 (260 patients), placebo (133 patients), or a 15-mg dose of prima-quine once daily for 14 days (129 patients). The primary outcome was the Kaplan– Meier estimated percentage of patients who were free from recurrence at 6 months, defined as P. vivax clearance without recurrent parasitemia. RESULTS In the intention-to-treat population, the percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P<0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P<0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention. CONCLUSIONS Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity. (Funded by GlaxoSmith-Kline and Medicines for Malaria Venture; DETECTIVE ClinicalTrials.gov number, NCT01376167.)

CL was found to be complicated and difficult to treat. MCL was common, and patients presented after long delays. There is an urgent need to look for better treatment options for CL and improve access to care.

Background Cutaneous leishmaniasis is one of the neglected tropical diseases in the Ethiopian highlands and studies on assessment of knowledge, attitude and practice of the community in endemic areas are scanty. The study aimed to assess the knowledge, attitude towards cutaneous leishmaniasis and treatment seeking practices in people living in the endemic highlands areas in the Northwest, Ethiopia and to provide evidence-based information to guide development of appropriate interventions to reduce the impact of cutaneous leishmaniasis on communities. Methods Quantitative cross-sectional study was conducted in cutaneous leishmaniasis endemic districts (woredas) using a semi structured questionnaire. Households were randomly selected according to probability proportional to size of households in each enumeration area. Systematic random sampling of eligible households was based on the number of households recorded during listing of households. Descriptive statistics was used to describe numerical data, organise and summarise the data in a manner that gave meaning to the numerical form. Frequency tables were used to show descriptive analysis and regression analysis was used to determine correlation between variables. Results Majority of respondents 321(78.7%) lived in rural areas, age ranged between 18 and 85 years and most were farmers. Illiteracy was high (47.6%) among respondents and majority 358(87.8%) had seen patients with CL. Less than quarter (21.6%) had heard about sand flies and knowledge on the peak transmission period was low (46.3%). About 192 (47.1%) of the respondents indicated disfiguring lesions were the major clinical presentations, less than half 55(27.5%) of urban residents believed CL was treatable compared to 145(72.5%) of rural residents (P < 0.001). Traditional medicines were indicated as best treatment option by 209(51.2%) compared to 114(27.9%) for modern treatment. Major factors influencing treatment options included accessibility to treatment facilities, distance and short duration of treatment. Participants expressed negative experiential attitude and perceived control towards modern treatment because of inaccessibility and distance from where modern treatment is provided. Conclusion Priority should be given to primary prevention and appropriate awareness campaigns on lesion recognition. Information on modern treatment should be intensified.

BackgroundAntimonials are still being used for visceral leishmaniasis (VL) treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B. Besides tolerability, emergence of resistance to antimonials is a major concern.ObjectivesThis study was aimed at assessing the clinical outcome of VL-HIV co-infected patients when treated with sodium stibogluconate (SSG).MethodsRetrospective patient record analysis of VL-HIV co-infected patients treated at a clinical trial site in north-west Ethiopia was done. Patients with parasitologically confirmed VL and HIV co-infection treated with SSG were included. The dose of SSG used was 20 mg Sb5 (pentavalent antimony)/kg and maximum of 850 mg Sb5 for 30 days. The clinical outcomes were defined based on the tissue aspiration results as cure or failure, and additionally the safety and mortality rates were computed.ResultsThe study included 57 patients treated with SSG and by the end of treatment only 43.9% of patients were cured. The parasitological treatment failure and the case fatality rate were 31.6% and 14.0% respectively. SSG was discontinued temporarily or permanently for 12 (21.1%) cases due to safety issues. High baseline parasite load (graded more than 4+) was significantly associated with treatment failure (odds ratio = 8.9, 95% confidence interval = .5-51.7).ConclusionSSG is not only unsafe, but also has low effectiveness for VL-HIV patients. Safe and effective alternative medications are very urgently needed. Drug sensitivity surveillance should be introduced in the region.

This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr, dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination.