Summary Background Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalarial drug resistance. Methods In this multicentre, open-label, randomised trial, we recruited patients with uncomplicated P falciparum malaria at 18 hospitals and health clinics in eight countries. Eligible patients were aged 2–65 years, with acute, uncomplicated P falciparum malaria alone or mixed with non- falciparum species, and a temperature of 37·5°C or higher, or a history of fever in the past 24 h. Patients were randomly assigned (1:1) to one of two treatments using block randomisation, depending on their location: in Thailand, Cambodia, Vietnam, and Myanmar patients were assigned to either dihydroartemisinin–piperaquine or dihydroartemisinin–piperaquine plus mefloquine; at three sites in Cambodia they were assigned to either artesunate–mefloquine or dihydroartemisinin–piperaquine plus mefloquine; and in Laos, Myanmar, Bangladesh, India, and the Democratic Republic of the Congo they were assigned to either artemether–lumefantrine or artemether–lumefantrine plus amodiaquine. All drugs were administered orally and doses varied by drug combination and site. Patients were followed-up weekly for 42 days. The primary endpoint was efficacy, defined by 42-day PCR-corrected adequate clinical and parasitological response. Primary analysis was by intention to treat. A detailed assessment of safety and tolerability of the study drugs was done in all patients randomly assigned to treatment. This study is registered at ClinicalTrials.gov , NCT02453308 , and is complete. Findings Between Aug 7, 2015, and Feb 8, 2018, 1100 patients were given either dihydroartemisinin–piperaquine (183 [17%]), dihydroartemisinin–piperaquine plus mefloquine (269 [24%]), artesunate–mefloquine (73 [7%]), artemether–lumefantrine (289 [26%]), or artemether–lumefantrine plus amodiaquine (286 [26%]). The median age was 23 years (IQR 13 to 34) and 854 (78%) of 1100 patients were male. In Cambodia, Thailand, and Vietnam the 42-day PCR-corrected efficacy after dihydroartemisinin–piperaquine plus mefloquine was 98% (149 of 152; 95% CI 94 to 100) and after dihydroartemisinin–piperaquine was 48% (67 of 141; 95% CI 39 to 56; risk difference 51%, 95% CI 42 to 59; p<0·0001). Efficacy of dihydroartemisinin–piperaquine plus mefloquine in the three sites in Myanmar was 91% (42 of 46; 95% CI 79 to 98) versus 100% (42 of 42; 95% CI 92 to 100) after dihydroartemisinin–piperaquine (risk difference 9%, 95% CI 1 to 17; p=0·12). The 42-day PCR corrected efficacy of dihydr...

Background:National Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures.Methods:Samples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs.Results:GenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs.Conclusions:GenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community.Funding:The GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of samples were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the National Institute of Allergy and Infectious Diseases.

BACKGROUND Recent studies have suggested that antiemetic therapy with a triple combination of the neurokinin‐1 receptor antagonist MK‐869, a serotonin (5‐HT3) antagonist, and dexamethasone provides enhanced control of cisplatin‐induced emesis compared with standard therapy regimens. The authors compared the antiemetic activity of a dual combination of MK‐869 and dexamethasone with that of a standard dual combination of ondansetron and dexamethasone to characterize further the efficacy and tolerability profile of MK‐869. METHODS This was a multicenter, double‐blind, randomized, active agent‐controlled study of 177 cisplatin‐naïve patients with malignant disease. On Day 1, MK‐869 was given intravenously as its water‐soluble prodrug, L‐758,298. Patients were randomized to one of three groups as follows. Group I received L‐758,298 100 mg intravenously (i.v.), then dexamethasone 20 mg i.v., and cisplatin ≥ 70 mg/m2 on Day 1 followed by 300 mg MK‐869 (tablet) orally on Days 2–5; Group II received L‐758,298 100 mg i.v., then dexamethasone 20 mg i.v., and cisplatin ≥ 70 mg/m2 on Day 1 followed by placebo on Days 2–5; and Group III received ondansetron 32 mg i.v., then dexamethasone 20 mg i.v., and cisplatin ≥ 70 mg/m2 on Day 1 followed by placebo on Days 2–5. Emesis was recorded over Days 1–5 in a diary. Nausea was assessed every 24 hours by visual analog scale. Additional medication was available for emesis or nausea at any time. The primary efficacy parameters of interest were the proportion of patients without emesis and the proportion without emesis or rescue therapy on Day 1 (acute phase) and on Days 2–5 (delayed phase). RESULTS No serious adverse events were attributed to L‐758,298 or MK‐869. On Day 1, the proportions of patients with no emesis and no use of rescue medication were 44% of patients in Group I, 36% of patients in Group II, 40% of patients in Groups I and II combined, and 83% of patients in Group III (P < 0.001 for Group III vs. the combined Groups I and II). The proportions of patients with no emesis and no use of rescue medication on Days 2–5 were 59% of patients in Group I, 46% of patients in Group II, and 38% of patients in Group III (P < 0.05 for Group I vs. Group III). The proportions of patients who were without emesis on Day 1 were 49% of patients in Group I, 47% of patients in Group II, and 84% of patients in Group III (P < 0.01 for Group I or II vs. Group III). On Days 2‐5, however, the proportions of patients who were without emesis on Days 2–5 were 65% of patients in Group I, 61% of patients in Group II, and 41% of patients in Group III (P < 0.05 for Group I or II vs. Group III). Nausea scores in the acute phase were lower for Group III than for Group I, Group II, or Groups I and II combined (P < 0.05), although there was no significant difference among groups either for the delayed phase or overall for Days 1–5. CONCLUSIONS Although the L‐758,298 and dexamethasone combination reduced acute (Day 1) emesis compared with historic rates, dual therapy with ondansetron and dexamethasone...

A method of assessing body condition of Asian elephants (Elephas maximus)is presented. The method uses visual assessment to assign numerical scores to six different regions of the body, which are totaled to give a numerical index ranging from 0-11. The relationship between the index and morphometric variables is compared for a sample of 119 juvenile and young adult elephants from southern India, Nepal, and Myanmar. Mean ages of males and females were similar. Mean index of body condition (with standard error [SE]) was 7.3 + 0.2 points. No significant correlation was found between index of body condition and age over both sexes (r = 0.01, n = 50). Results were equivalent when sexes were treated separately (females: i-= 0.03, « = 24; males: i-= 0.01, n = 26). Sexes did not differ in height of the shoulder or body condition in our sample, but there was significant sexual dimorphism in breadth of the zygomatic arch and three measures of subcutaneous fat: girth of neck, thickness of cervical fold, and thickness of anal flap. These three measures were also significantly correlated with each other. Our assessment method should prove a practical tool for écologie studies, but the relationship of the index to V. Krishnamurthy is deceased. percentage of body fat should be determined using heavy water dilution methodology.