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.

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.

Improving the diagnosis of severe malaria in African children using platelet counts and plasma HRP2 concentrations.

Severe malaria caused by is difficult to diagnose accurately in children in high-transmission settings. Using data from 2649 pediatric and adult patients enrolled in four studies of severe illness in three countries (Bangladesh, Kenya, and Uganda), we fitted Bayesian latent class models using two diagnostic markers: the platelet count and the plasma concentration of histidine-rich protein 2 (HRP2). In severely ill patients with clinical features consistent with severe malaria, the combination of a platelet count of ≤150,000/μl and a plasma HRP2 concentration of ≥1000 ng/ml had an estimated sensitivity of 74% and specificity of 93% in identifying severe falciparum malaria.

Protective effect of Mediterranean-type glucose-6-phosphate dehydrogenase deficiency against malaria.

X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The severe Mediterranean variant (G6PD Med) found across Europe and Asia is thought to confer protection against malaria, but its effect is unclear. We fitted a Bayesian statistical model to observed G6PD Med allele frequencies in 999 Pashtun patients presenting with acute malaria and 1408 population controls.

Case Report: Application of hepatitis B virus (HBV) deep sequencing to distinguish between acute and chronic infection.

Deep sequencing of the full-length hepatitis B virus (HBV) genome provides the opportunity to determine the extent to which viral diversity, genotype, polymorphisms, insertions and deletions may influence presentation and outcomes of disease. Increasing experience with analysis of HBV genomic data opens up the potential for using these data to inform insights into pathophysiology of infection and to underpin decision making in clinical practice. We here set out to undertake whole genome HBV sequencing from an adult who presented acutely unwell with a new diagnosis of HBV infection, and tested positive for both HBV anti-core IgM and IgG, possibly representing either acute hepatitis B infection (AHB) or chronic hepatitis B with an acute reactivation (CHB-AR).

Pharmacokinetic Study of Rectal Artesunate in Children with Severe Malaria in Africa.

When severe malaria is suspected in children, the WHO recommends pretreatment with a single rectal dose of artesunate before referral to an appropriate facility. This was an individually randomized, open-label, 2-arm, crossover clinical trial in 82 Congolese children with severe malaria to characterize the pharmacokinetics of rectal artesunate. At admission, children received a single dose of rectal artesunate (10 mg/kg of body weight) followed 12 h later by intravenous artesunate (2.

Plasma Plasmodium falciparum Histidine-rich Protein 2 Concentrations in Children With Malaria Infections of Differing Severity in Kilifi, Kenya.

Background: Most previous studies support a direct link between total parasite load and the clinical severity of Plasmodium falciparum malaria infections.

Methods: We estimated P. falciparum parasite loads in 3 groups of children with malaria infections of differing severity: (1) children with World Health Organization-defined severe malaria (n = 1544), (2) children admitted with malaria but without features of severity (n = 200), and (3) children in the community with asymptomatic parasitemia (n = 33).

K13-Mediated Reduced Susceptibility to Artemisinin in Plasmodium falciparum Is Overlaid on a Trait of Enhanced DNA Damage Repair.

Southeast Asia has been the hotbed for the development of drug-resistant malaria parasites, including those with resistance to artemisinin combination therapy. While mutations in the kelch propeller domain (K13 mutations) are associated with artemisinin resistance, a range of evidence suggests that other factors are critical for the establishment and subsequent transmission of resistance in the field. Here, we perform a quantitative analysis of DNA damage and repair in the malaria parasite Plasmodium falciparum and find a strong link between enhanced DNA damage repair and artemisinin resistance.

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.

Delayed diagnosis of T3 supplementation in a bodybuilder presenting with tachycardia and features of sepsis.

A 25-year-old man presented generally unwell to the emergency department. Initial assessment identified systemic inflammatory response syndrome markers with an insect bite as a potential source of infection and he was treated for presumed sepsis. Tachycardia persisted and baseline thyroid function testing showed undetectable free thyroxine and thyroid-stimulating hormone (TSH), prompting further endocrine investigation.

HRP2: Transforming Malaria Diagnosis, but with Caveats.

The major growth in point-of-care malaria diagnosis over the past decade has been based on immunochromatographic malaria rapid diagnostic tests (mRDTs), which generally detect Plasmodium falciparum via its abundant histidine-rich protein 2 (HRP2). Here, we review the discovery and biology of HRP2, as well as the strengths and weaknesses of HRP2-based diagnosis compared with alternative antigens. We highlight recent studies describing HRP2 deletion in Latin America, Eritrea, and possibly other regions, and the methodological challenges of confirming deletion of the pfhrp2 gene.

Isolated leptomeningeal carcinomatosis and possible fungal meningitis as late sequelae of oesophageal adenocarcinoma.

We describe a case of a 67-year-old man with known chronic obstructive pulmonary disease, type 2 diabetes mellitus, hypertension, osteoarthritis, previous history of excess alcohol intake, and oesophagectomy 3 years earlier for T3N0 adenocarcinoma, referred by his general practitioner with confusion, weight loss and several recent falls. CT of the chest, abdomen and pelvis revealed a right middle-lobe pulmonary embolism, while CT of the head revealed a communicating hydrocephalus. Lumbar puncture was performed, and empirical treatment for tuberculous and fungal meningitis was commenced.

The efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine with and without primaquine on Plasmodium vivax recurrence: A systematic review and individual patient data meta-analysis.

Background: Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax.

The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

Background: Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax.

Methods: A systematic review identified P.

Artemisinin Resistance and Stage Dependency of Parasite Clearance in Falciparum Malaria.

Background: Artemisinin resistance in falciparum malaria is associated with kelch13 propeller mutations, reduced ring stage parasite killing, and, consequently, slow parasite clearance. We assessed how parasite age affects parasite clearance in artemisinin resistance.

Methods: Developmental stages of Plasmodium falciparum parasites on blood films performed at hospital admission and their kelch13 genotypes were assessed for 816 patients enrolled in a multinational clinical trial of artemisinin combination therapy.

Correction to: Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration.

Following publication of the original article [1], one of the authors has highlighted an xml-related discrepancy concerning the author group titled 'Additional Tracking Resistance to Artemisinin Collaboration authors (TRAC Group Authorship)', listed under the Acknowledgements section.

The effect of chloroquine dose and primaquine on Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient pooled meta-analysis.

Background: Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings.

Methods: A systematic review done in MEDLINE, Web of Science, Embase, and Cochrane Database of Systematic Reviews identified P vivax clinical trials published between Jan 1, 2000, and March 22, 2017.

Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum.

Multidrug resistant Plasmodium falciparum in Southeast Asia endangers regional malaria elimination and threatens to spread to other malaria endemic areas. Understanding mechanisms of piperaquine (PPQ) resistance is crucial for tracking its emergence and spread, and to develop effective strategies for overcoming it. Here we analyze a mechanism of PPQ resistance in Cambodian parasites.

Malaria.

Following unsuccessful eradication attempts there was a resurgence of malaria towards the end of the 20th century. Renewed control efforts using a range of improved tools, such as long-lasting insecticide-treated bednets and artemisinin-based combination therapies, have more than halved the global burden of disease, but it remains high with 445 000 deaths and more than 200 million cases in 2016. Pitfalls in individual patient management are delayed diagnosis and overzealous fluid resuscitation in severe malaria.

Disease Severity and Effective Parasite Multiplication Rate in Falciparum Malaria.

Patients presenting with severe falciparum malaria in a Bangladeshi tertiary hospital had higher total parasite burden, estimated by parasitemia and plasma PfHRP2, than uncomplicated malaria patients despite shorter fever duration. This suggests that higher parasite multiplication rates (PMR) contribute to causing the higher biomass found in severe disease. Compared with patients without a history of previous malaria, patients with previous malaria carried a lower parasite biomass with similar fever duration at presentation, suggesting that host immunity reduces the PMR.

Chloroquine-Primaquine versus Chloroquine Alone to Treat Vivax Malaria in Afghanistan: An Open Randomized Superiority Trial.

Afghanistan's national guidelines recommend primaquine (PQ) for radical treatment of malaria, but this is rarely implemented because of concerns over potential hemolysis in patients who have G6PD deficiency. Between August 2009 and February 2014, we conducted an open-label, randomized controlled trial of chloroquine (CQ) alone versus chloroquine plus primaquine (0.25 mg base/kg/day for 14 days) (CQ+PQ) in patients aged 6 months and older with microscopy confirmed infection.

Plasmodium vivax genetic diversity and heterozygosity in blood samples and resulting oocysts at the Thai-Myanmar border.

Background: Polyclonal blood-stage infections of Plasmodium vivax are frequent even in low transmission settings, allowing meiotic recombination between heterologous parasites. Empirical data on meiotic products are however lacking. This study examined microsatellites in oocysts derived by membrane feeding of mosquitoes from blood-stage P.