Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background.

The emergence of Plasmodium falciparum parasites resistant to artemisinins compromises the efficacy of Artemisinin Combination Therapies (ACTs), the global first-line malaria treatment. Artemisinin resistance is a complex genetic trait in which nonsynonymous SNPs in PfK13 cooperate with other genetic variations. Here, we present population genomic/transcriptomic analyses of P.

Data sharing and reuse in clinical research: Are we there yet? A cross-sectional study on progress, challenges and opportunities in LMICs.

Data sharing holds promise to accelerate innovative discoveries through artificial intelligence (AI) and traditional analytics. However, it remains unclear whether these prospects translate into tangible benefits in improving health care and scientific progress. In this cross-sectional study, we investigate current data reuse practices and explore ways to enhance the use of existing data in clinical research, focusing on low- and middle-income countries.

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.

Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial.

Background: Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use.

Methods And Findings: Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention.

Anti-infectivity efficacy and pharmacokinetics of WHO recommended single low-dose primaquine in children with acute Plasmodium falciparum in Burkina Faso: study protocol.

Background: Primaquine (PQ) has activity against mature P. falciparum gametocytes and proven transmission blocking efficacy (TBE) between humans and mosquitoes. WHO formerly recommended a single transmission blocking dose of 0.

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.

Bioequivalence of a new coated 15 mg primaquine formulation for malaria elimination.

Background: With only one 15 mg primaquine tablet registered by a stringent regulatory authority and marketed, more quality-assured primaquine is needed to meet the demands of malaria elimination.

Methods: A classic, two sequence, crossover study, with a 10-day wash out period, of 15 mg of IPCA-produced test primaquine tablets and 15 mg of Sanofi reference primaquine tablets was conducted. Healthy volunteers, aged 18-45 years, without glucose-6-phosphate dehydrogenase deficiency, a baseline haemoglobin ≥ 11 g/dL, creatinine clearance ≥ 70 mL/min/1.

Care seeking for childhood illnesses in rural Mtwara, south-east Tanzania: a mixed methods study.

Background: Care seeking was assessed in preparation for a study of the health impact of novel design houses in rural Mtwara, Tanzania.

Methods: A total of 578 residents of 60 villages participated in this mixed-methods study from April to August 2020. Among them, 550 participated in a healthcare-seeking survey, 17 in in-depth interviews and 28 in key informant interviews.

The relationship between viral clearance rates and disease progression in early symptomatic COVID-19: a systematic review and meta-regression analysis.

Background: Effective antiviral drugs accelerate viral clearance in acute COVID-19 infections; the relationship between accelerating viral clearance and reducing severe clinical outcomes is unclear.

Methods: A systematic review was conducted of randomized controlled trials (RCTs) of antiviral therapies in early symptomatic COVID-19, where viral clearance data were available. Treatment benefit was defined clinically as the relative risk of hospitalization/death during follow-up (≥14 days), and virologically as the SARS-CoV-2 viral clearance rate ratio (VCRR).

School and community driven dengue vector control and monitoring in Myanmar: Study protocol for a cluster randomized controlled trial.

Background: Dengue is the most common and widespread mosquito-borne arboviral disease globally estimated to cause >390 million infections and >20,000 deaths annually. There are no effective preventive drugs and the newly introduced vaccines are not yet available. Control of dengue transmission still relies primarily on mosquito vector control.

sensu stricto Giles (Diptera:Culicidae) bites after sunrise at two rural villages in northern Malawi and its implications for malaria vector control.

Introduction: Malawi has scaled up distribution and use of LLINs but their effectiveness depends on vector behaviour. This study reports information on where and when peak biting takes place by vectors at two study sites in northern Malawi.

Methods: The study was carried out at a single village each in Nkhata Bay and Karonga districts, northern Malawi.

Scrub typhus in Indonesia: A cross-sectional analysis of archived fever studies samples.

Background: Scrub typhus is an understudied vector-borne bacterial infection.

Methods: We tested archived fever samples for scrub typhus seropositivity to begin charting its geographic distribution in Indonesia. We analysed 1033 serum samples from three sites.

Mixed methods study protocol for combining stakeholder-led rapid evaluation with near real-time continuous registry data to facilitate evaluations of quality of care in intensive care units.

Background: Improved access to healthcare in low- and middle-income countries (LMICs) has not equated to improved health outcomes. Absence or unsustained quality of care is partly to blame. Improving outcomes in intensive care units (ICUs) requires delivery of complex interventions by multiple specialties working in concert, and the simultaneous prevention of avoidable harms associated with the illness and the treatment interventions.

Factors affecting haemoglobin dynamics in African children with acute uncomplicated Plasmodium falciparum malaria treated with single low-dose primaquine or placebo.

Background: Single low-dose primaquine (SLDPQ) effectively blocks the transmission of Plasmodium falciparum malaria, but anxiety remains regarding its haemolytic potential in patients with glucose-6-phopshate dehydrogenase (G6PD) deficiency. We, therefore, examined the independent effects of several factors on haemoglobin (Hb) dynamics in falciparum-infected children with a particular interest in SLDPQ and G6PD status.

Methods: This randomised, double-blind, placebo-controlled, safety trial was conducted in Congolese and Ugandan children aged 6 months-11 years with acute uncomplicated P.

Pharmacokinetics of single low dose primaquine in Ugandan and Congolese children with falciparum malaria.

Background: There are no pharmacokinetic data of single low dose primaquine (SLDPQ) as transmission blocking in African children with acute Plasmodium falciparum and glucose-6-phosphate dehydrogenase deficiency (G6PDd).

Methods: Primaquine pharmacokinetics of age-dosed SLDPQ (shown previously to be gametocytocidal with similar tolerability as placebo) were characterised in falciparum-infected Ugandan and Congolese children aged 6 months to 11 years, treated on admission with standard 3-day dihydroartemisinin-piperaquine or artemether-lumefantrine plus SLDPQ: 6 m-<1 y: 1.25 mg, 1-5 y: 2.

Short intravenous amphotericin B followed by oral posaconazole using a simple, stratified treatment approach for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis: a prospective cohort study.

Objectives: To evaluate the efficacy and safety of short-course intravenous amphotericin B followed by sustained release posaconazole tablets for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis.

Methods: This prospective, pragmatic study included adults with diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. Patients received short (7-14 days) or long (15-28 days) intravenous antifungal therapy (short intravenous antifungal treatment [SHIFT] or long intravenous antifungal treatment [LIFT], respectively) depending on the presence or absence of brain involvement.

Experiences, coping strategies and perspectives of people in Malaysia during the COVID-19 pandemic.

Background: A nationwide Movement Control Order (MCO) was enforced in Malaysia on 18 March 2020 in view of the global COVID-19 pandemic. Malaysia implemented various public health measures and later raced against time to administer COVID-19 vaccines when they became available. As a result of various public health measures to curb the spread of the virus, people in Malaysia faced unprecedented circumstances and new challenges.

Predicting adherence to postdischarge malaria chemoprevention in Malawian pre-school children: A prognostic multivariable analysis.

Chemoprevention with antimalarials is a key strategy for malaria control in sub-Saharan Africa. Three months of postdischarge malaria chemoprevention (PDMC) reduces malaria-related mortality and morbidity in pre-school children recently discharged from hospital following recovery from severe anemia. Research on adherence to preventive antimalarials in children is scarce.

Contribution of genetic factors to high rates of neonatal hyperbilirubinaemia on the Thailand-Myanmar border.

Very high unconjugated bilirubin plasma concentrations in neonates (neonatal hyperbilirubinaemia; NH) may cause neurologic damage (kernicterus). Both increased red blood cell turn-over and immaturity of hepatic glucuronidation contribute to neonatal hyperbilirubinaemia. The incidence of NH requiring phototherapy during the first week of life on the Thailand-Myanmar border is high (approximately 25%).

Investigating the Secondary Use of Clinical Research Data: Protocol for a Mixed Methods Study.

Background: The increasing emphasis to share patient data from clinical research has resulted in substantial investments in data repositories and infrastructure. However, it is unclear how shared data are used and whether anticipated benefits are being realized.

Objective: The purpose of our study is to examine the current utilization of shared clinical research data sets and assess the effects on both scientific research and public health outcomes.

Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

Background: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear.

Methods: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled.