Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV).

Background: The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity , and observational and clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended in therapeutic guidelines and their antiviral activity has not been characterised.

Methods: PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos.

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.

Non-invasive detection of bilirubin concentrations during the first week of life in a low-resource setting along the Thailand-Myanmar border.

Background: Neonatal hyperbilirubinaemia (NH) is a common problem worldwide and is a cause of morbidity and mortality especially in low-resource settings.

Methods: A study was carried out at Shoklo Malaria Research Unit (SMRU) clinics along the Thailand-Myanmar border to evaluate a non-invasive test for diagnosis of NH in a low-resource setting. Performance of a transcutaneous bilirubinometer Dräger Jaundice Meter JM-105 was assessed against routine capillary serum bilirubin testing (with BR-501 microbilirubinometer) before phototherapy during neonatal care in the first week of life.

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.

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.

Activity of Ivermectin and Its Metabolites against Asexual Blood Stage Plasmodium falciparum and Its Interactions with Antimalarial Drugs.

Ivermectin is an endectocide used widely to treat a variety of internal and external parasites. Field trials of ivermectin mass drug administration for malaria transmission control have demonstrated a reduction of mosquito survival and human malaria incidence. Ivermectin will mostly be deployed together with artemisinin-based combination therapies (ACT), the first-line treatment of falciparum malaria.

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.

Culturally responsive research ethics: How the socio-ethical norms of Arr-nar/Kreng-jai inform research participation at the Thai-Myanmar border.

Despite advances, international research ethics guidelines still tend to consist of high-level ethical principles reflecting residual influence from North American and European traditions of ethics. Local ethics committees and community advisory boards can offer more culturally-sensitive approaches to training but most institutions lack substantive practical ethics guidance to engage rich moral understandings in day-to-day research practice in diverse cultural contexts. To address this gap, we conducted an international series of qualitative research ethics case studies, linked prospectively to active research programs in diverse settings.

Clinical Characteristics of Acute Kidney Injury Associated with Tropical Acute Febrile Illness.

Tropical acute febrile illness (TAFI) is one of the most frequent causes of acute kidney injury (AKI). The prevalence of AKI varies worldwide because there are limited reports available and different definitions are used. This retrospective study aimed to determine the prevalence, clinical characteristics, and outcomes of AKI associated with TAFI among patients.

Good participatory practice for coronavirus disease 2019 (COVID-19) research: the case of a COVID-19 prevention study.

The COPCOV study (chloroquine/ hydroxychloroquine prevention of coronavirus disease), which started recruitment in April 2020, is a multi-country double-blind, randomised, placebo-controlled trial which is being conducted in healthcare facilities involved in COVID-19 case management. Participants are staff employed in facilities managing people with proven or suspected COVID-19. As part of the study, we conducted a series of engagement sessions.

High-Dose Primaquine Induces Proximal Tubular Degeneration and Ventricular Cardiomyopathy Linked to Host Cells Mitochondrial Dysregulation.

Primaquine (PQ) is the only antimalarial medication used to eradicate many species of gametocytes and prevent relapse in vivax and ovale malarias. PQ metabolites induce oxidative stress and impair parasitic mitochondria, leading to protozoal growth retardation and death. Collateral damage is also presented in mammalian host cells, particularly erythrocytes, resulting in hemolysis and tissue destruction.

Severity of COVID-19 in Patients with Diarrhoea: A Systematic Review and Meta-Analysis.

COVID-19 patients occasionally present with diarrhoea. Our objective was to estimate the risk of developing the severe disease in COVID-19 patients with and without diarrhoea and to provide a more precise estimate of the prevalence of COVID-19-associated digestive symptoms. A total of 88 studies (n = 67,794) on patients with a COVID-19 infection published between 1 January 2020 and 20 October 2022 were included in this meta-analysis.

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.

Technical evaluation and usability of a quantitative G6PD POC test in cord blood: a mixed-methods study in a low-resource setting.

Objectives: New point-of-care (POC) quantitative G6PD testing devices developed to provide safe radical cure for malaria may be used to diagnose G6PD deficiency in newborns at risk of severe neonatal hyperbilirubinaemia, improving clinical care, and preventing related morbidity and mortality.

Methods: We conducted a mixed-methods study analysing technical performance and usability of the 'STANDARD G6PD' Biosensor when used by trained midwives on cord blood samples at two rural clinics on the Thailand-Myanmar border.

Results: In 307 cord blood samples, the Biosensor had a sensitivity of 1.

Performance of the onstructural 1 Antigen Rapid Test for detecting all four DENV serotypes in clinical specimens from Bangkok, Thailand.

Background: Dengue is an arboviral disease that has a large effect on public health in subtropical and tropical countries. Rapid and accurate detection of dengue infection is necessary for diagnosis and disease management. We previously developed highly sensitive immunochromatographic devices, the TKK 1 and TKK 2 kits, based on dengue virus (DENV) nonstructural protein 1 detection.

Cardiovascular concentration-effect relationships of amodiaquine and its metabolite desethylamodiaquine: Clinical and preclinical studies.

Aims: Amodiaquine is a 4-aminoquinoline used extensively for the treatment and prevention of malaria. Orally administered amodiaquine is largely converted to the active metabolite desethylamodiaquine. Amodiaquine can cause bradycardia, hypotension, and electrocardiograph QT interval prolongation, but the relationship of these changes to drug concentrations is not well characterized.