Modeling the within-host dynamics of hypnozoite activation: An analysis of the SPf66 vaccine trial.

parasites can lie dormant in the liver as hypnozoites, activating weeks to months after sporozoite inoculation to cause relapsing malarial illness. It is not known what biological processes govern hypnozoite activation. We use longitudinal data from the most detailed cohort study ever conducted in an area where both and were endemic to fit a simple within-host mathematical model of hypnozoite activation.

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.

In-host modeling of dengue virus and non-structural protein 1 and the effects of ivermectin in patients with acute dengue fever.

The increased incidence of dengue poses a substantially global public health challenge. There are no approved antiviral drugs to treat dengue infections. Ivermectin, an old anti-parasitic drug, had no effect on dengue viremia, but reduced the dengue non-structural protein 1 (NS1) in a clinical trial.

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.

Lineage-informative microhaplotypes for recurrence classification and spatio-temporal surveillance of Plasmodium vivax malaria parasites.

Challenges in classifying recurrent Plasmodium vivax infections constrain surveillance of antimalarial efficacy and transmission. Recurrent infections may arise from activation of dormant liver stages (relapse), blood-stage treatment failure (recrudescence) or reinfection. Molecular inference of familial relatedness (identity-by-descent or IBD) can help resolve the probable origin of recurrences.

Transmission-blocking activities of artesunate, chloroquine, and methylene blue on gametocytes.

is now the main cause of malaria outside Africa. The gametocytocidal effects of antimalarial drugs are important to reduce malaria transmissibility, particularly in low-transmission settings, but they are not well characterized for . The transmission-blocking effects of chloroquine, artesunate, and methylene blue on gametocytes were assessed.

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.

Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar.

Background: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized.

Population pharmacokinetic modelling of primaquine exposures in lactating women and breastfed infants.

Current guidelines advise against primaquine treatment for breastfeeding mothers to avoid the potential for haemolysis in infants with G6PD deficiency. To predict the haemolytic risk, the amount of drug received from the breast milk and the resulting infant drug exposure need to be characterised. Here, we develop a pharmacokinetic model to describe the drug concentrations in breastfeeding women using venous, capillary, and breast milk data.

Comparison of WHO versus national COVID-19 therapeutic guidelines across the world: not exactly a perfect match.

Background: The COVID-19 pandemic affected all WHO member states. We compared and contrasted the COVID-19 treatment guidelines of each member state with the WHO COVID-19 therapeutic guidelines.

Methods: Ministries of Health or accessed National Infectious Disease websites and other relevant bodies and experts were contacted to obtain national guidelines (NGs) for COVID-19 treatment.

Comparison of lumefantrine, mefloquine, and piperaquine concentrations between capillary plasma and venous plasma samples in pregnant women with uncomplicated falciparum and vivax malaria.

Capillary samples offer practical benefits compared with venous samples for the measurement of drug concentrations, but the relationship between the two measures varies between different drugs. We measured the concentrations of lumefantrine, mefloquine, piperaquine in 270 pairs of venous plasma and concurrent capillary plasma samples collected from 270 pregnant women with uncomplicated falciparum or vivax malaria. The median and range of venous plasma concentrations included in this study were 447.

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).

Response to comment on 'The clinical pharmacology of tafenoquine in the radical cure of malaria: An individual patient data meta-analysis'.

In our recent paper on the clinical pharmacology of tafenoquine (Watson et al., 2022), we used all available individual patient pharmacometric data from the tafenoquine pre-registration clinical efficacy trials to characterise the determinants of anti-relapse efficacy in tropical vivax malaria. We concluded that the currently recommended dose of tafenoquine (300 mg in adults, average dose of 5 mg/kg) is insufficient for cure in all adults, and a 50% increase to 450 mg (7.

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.