Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania

The human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replicable associations with genome-wide levels of evidence including a newly implicated variant on chromosome 6. Jointly, these variants account for around one-tenth of the heritability of severe malaria, which we estimate as -23% using genome-wide genotypes. We interrogate available functional data and discover an erythroid-specific transcription start site underlying the known association in ATP2B4, but are unable to identify a likely causal mechanism at the chromosome 6 locus. Previously reported HLA associations do not replicate in these samples. This large dataset will provide a foundation for further research on thegenetic determinants of malaria resistance in diverse populations.Peer reviewe

Co-Pt nanoparticles encapsulated in carbon cages prepared by sonoelectrodeposition

Co–Pt nanoparticles encapsulated in carbon cages have been prepared by sonoelectrodeposition followed by annealing in a CO atmosphere. Sonoelectrodeposition is a useful technique to make metallic nanoparticles, using ultrasound during electrodeposition to remove nanoparticles as they grow on the cathode surface. We used an electrolyte containing chloroplatinic acid and cobalt chloride and found that the atomic ratio of Co:Pt in the as-formed materials varied from 0.2 to 0.8 as the deposition current density was changed from 15 to 35 mA cm−2. However, the as-deposited materials were inhomogeneous, comprising a mixture of Pt-rich and Co-rich nanoparticles. X-ray diffraction indicated that subsequent heat treatment (700 ◦C for 1 h) under CO gas created an ordered CoPt alloy phase that exhibited hard magnetic properties. Transmission electron microscopy showed many of the resulting nanoparticles to be encapsulated in carbon cages, which we ascribe to Co-catalyzed decomposition of CO during annealing. The thickness of the carbon cages was about ten layers, which may have helped reduce sintering during annealing. The size of the resultant nanoparticles was about 100 nm diameter, larger than the typical 5–10 nm diameter of as-deposited nanoparticles

Dengue-associated posterior reversible encephalopathy syndrome, Vietnam

10.3201/eid2402.171634Emerging Infectious Diseases242402-40

Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion: Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy

From free to forced adaptation: A political ecology of the ‘state‐society‐flood’ nexus in the Vietnamese Mekong Delta

10.1111/apv.12241Asia Pacific Viewpoin

Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: Double blind randomised controlled trial

10.1136/bmj.f3039BMJ (Online)3467911-BMJO