Safety and pharmacokinetic properties of a new formulation of parenteral artesunate in healthy Thai volunteers.

Background: Parenteral artesunate is the first-line therapy for severe malaria. Artesunate, in its current formulation, must be prepared immediately before administration by first dissolving in sodium bicarbonate solution and then diluting in saline. A novel solvent for rapid and stable single step reconstitution of artesunate was recently developed showing improved solubility and stability.

A randomised trial of malaria vaccine R21/Matrix-M™ with and without antimalarial drugs in Thai adults.

In preparation for mass vaccinations with R21/Matrix-M™ combined with mass administrations of dihydroartemisinin, piperaquine, and a single low dose primaquine we assessed the tolerability, safety, and potential interactions of this combination affecting immunogenicity or pharmacokinetics. 120 healthy Thai volunteers were randomised to receive either antimalarials combined with vaccinations (n = 50), vaccinations alone (n = 50), or antimalarials only (n = 20). Three rounds of vaccines and antimalarials were administered one month apart.

Primaquine in glucose-6-phosphate dehydrogenase deficiency: an adaptive pharmacometric assessment of ascending dose regimens in healthy volunteers.

Background: Primaquine is an 8-aminoquinoline antimalarial. It is the only widely available treatment to prevent relapses of malaria. The 8-aminoquinolines cause dose-dependent haemolysis in glucose-6-phosphate dehydrogenase deficiency (G6PDd).

Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial.

Unlabelled: In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance.

Background: Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive.

Efficacy of household larval control practices in a peri-urban township, Yangon, Myanmar: Implication for entomological surveillance.

Dengue is a major public health concern in Myanmar. We carried out a cross-sectional study to investigate the efficacy of larval control practices in household water containers, such as the use of the larvicide, temephos, covering the containers with lids and weekly cleaning. We surveyed 300 households in Kaw Hmu Township, a peri-urban community in the Yangon region.

Clinical Antiviral Efficacy of Remdesivir in Coronavirus Disease 2019: An Open-Label, Randomized Controlled Adaptive Platform Trial (PLATCOV).

Background: Uncertainty over the therapeutic benefit of parenteral remdesivir in coronavirus disease 2019 (COVID-19) has resulted in varying treatment guidelines.

Methods: In a multicenter open-label, controlled, adaptive, pharmacometric platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to 1 of 8 treatment arms including intravenous remdesivir (200 mg followed by 100 mg daily for 5 days) or no study drug. The primary outcome was the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance (estimated under a linear model fit to the daily log10 viral densities, days 0-7) in standardized duplicate oropharyngeal swab eluates, in a modified intention-to-treat population.

Effectiveness of dengue training programmes on prevention and control among high school students in the Yangon region, Myanmar.

Background: Dengue is one of the health problems in Myanmar. Thus, health promotion in schools is considered a key approach for reducing risk-taking behaviours related to dengue.

Objectives: The study aimed to evaluate a dengue training programme for high school students to measure changes in knowledge, attitude and practices (KAP) towards dengue; evaluate the effectiveness of the programme in improving prevention and control practices among families and determining changes in larval indices in their dwelling places.

Ivermectin metabolites reduce Anopheles survival.

Ivermectin mass drug administration to humans or livestock is a potential vector control tool for malaria elimination. The mosquito-lethal effect of ivermectin in clinical trials exceeds that predicted from in vitro laboratory experiments, suggesting that ivermectin metabolites have mosquito-lethal effect. The three primary ivermectin metabolites in humans (i.

Born too soon in a resource-limited setting: A 10-year mixed methods review of a special care baby unit for refugees and migrants on the Myanmar-Thailand border.

Background: Preterm birth is a major public health concern with the largest burden of morbidity and mortality falling within low- and middle-income countries (LMIC).

Materials And Methods: This sequential explanatory mixed methods study was conducted in special care baby units (SCBUs) serving migrants and refugees along the Myanmar-Thailand border. It included a retrospective medical records review, qualitative interviews with mothers receiving care within SCBUs, and focus group discussions with health workers.

Pharmacometrics of high-dose ivermectin in early COVID-19 from an open label, randomized, controlled adaptive platform trial (PLATCOV).

Background: There is no generally accepted methodology for in vivo assessment of antiviral activity in SARS-CoV-2 infections. Ivermectin has been recommended widely as a treatment of COVID-19, but whether it has clinically significant antiviral activity in vivo is uncertain.

Methods: In a multicentre open label, randomized, controlled adaptive platform trial, adult patients with early symptomatic COVID-19 were randomized to one of six treatment arms including high-dose oral ivermectin (600 µg/kg daily for 7 days), the monoclonal antibodies casirivimab and imdevimab (600 mg/600 mg), and no study drug.

Correction: A systematic review and an individual patient data meta-analysis of ivermectin use in children weighing less than fifteen kilograms: Is it time to reconsider the current contraindication?

[This corrects the article DOI: 10.1371/journal.pntd.

Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response.

The emergence and spread of artemisinin-resistant Plasmodium falciparum, first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria elimination ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS between 2016-2018.

Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination.

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.

Prevention of mother-to-child transmission of hepatitis B virus: protocol for a one-arm, open-label intervention study to estimate the optimal timing of tenofovir in pregnancy.

Introduction: Hepatitis B virus (HBV) remains a public health threat and the main route of transmission is from mother to child (MTCT). Tenofovir disoproxil fumarate (TDF) treatment can reduce MTCT of HBV although the optimal timing to attain undetectable HBV DNA concentrations at delivery is unknown. This protocol describes the procedures following early initiation of maternal TDF prior to 20 weeks gestation to determine efficacy, safety and feasibility of this approach in a limited-resource setting.

Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial.

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.

Safety, Pharmacokinetics, and Mosquito-Lethal Effects of Ivermectin in Combination With Dihydroartemisinin-Piperaquine and Primaquine in Healthy Adult Thai Subjects.

Mass administration of antimalarial drugs and ivermectin are being considered as potential accelerators of malaria elimination. The safety, tolerability, pharmacokinetics, and mosquito-lethal effects of combinations of ivermectin, dihydroartemisinin-piperaquine, and primaquine were evaluated. Coadministration of ivermectin and dihydroartemisinin-piperaquine resulted in increased ivermectin concentrations with corresponding increases in mosquito-lethal effect across all subjects.

Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study.

Background: The emergence and spread of resistance in Plasmodium falciparum malaria to artemisinin combination therapies in the Greater Mekong subregion poses a major threat to malaria control and elimination. The current study is part of a multi-country, open-label, randomised clinical trial (TRACII, 2015-18) evaluating the efficacy, safety, and tolerability of triple artemisinin combination therapies. A very high rate of treatment failure after treatment with dihydroartemisinin-piperaquine was observed in Thailand, Cambodia, and Vietnam.

Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study.

Background: A multidrug-resistant co-lineage of Plasmodium falciparum malaria, named KEL1/PLA1, spread across Cambodia in 2008-13, causing high rates of treatment failure with the frontline combination therapy dihydroartemisinin-piperaquine. Here, we report on the evolution and spread of KEL1/PLA1 in subsequent years.

Methods: For this genomic epidemiology study, we analysed whole genome sequencing data from P falciparum clinical samples collected from patients with malaria between 2007 and 2018 from Cambodia, Laos, northeastern Thailand, and Vietnam, through the MalariaGEN P falciparum Community Project.

Combining antimalarial drugs and vaccine for malaria elimination campaigns: a randomized safety and immunogenicity trial of RTS,S/AS01 administered with dihydroartemisinin, piperaquine, and primaquine in healthy Thai adult volunteers.

: RTS,S/AS01 is currently the most advanced malaria vaccine but provides incomplete, short-term protection. It was developed for use within the expanded program on immunizations (EPI) for African children. Another use could be adding mass RTS,S/AS01 vaccination to the integrated malaria elimination strategy in the Greater Mekong Subregion (GMS), where multidrug-resistant strains have emerged and spread.