Primaquine is essential for malaria control and elimination since it is the only available drug preventing multiple clinical attacks by relapses of Plasmodium vivax. It is also the only therapy against the sexual stages of Plasmodium falciparum infectious to mosquitoes, and is thus useful in preventing malaria transmission. However, the difficulties of diagnosing glucose-6-phosphate dehydrogenase deficiency (G6PDd) greatly hinder primaquine’s widespread use, as this common genetic disorder makes patients susceptible to potentially severe and fatal primaquine-induced haemolysis. The risk of such an outcome varies widely among G6PD gene variants.

IgG fucosylation predicts dengue severity: Secondary infections with dengue virus (DENV) can produce life-threatening symptoms, including thrombocytopenia and hemorrhagic disease, when preexisting DENV-reactive immunoglobulin G1 (IgG1) antibodies promote the infection of immune cells. Although severe dengue symptoms are associated with increased levels of afucosylated IgG1 glycoforms, it is unclear whether this is simply a result of the infection or if it is a preexisting phenomenon that can dictate susceptibility to this disease. Bournazos et al. studied the Fab and Fc structures of anti-DENV antibodies from patients before and after infection and with variable disease outcomes (see the Perspective by de Alwis and Ooi). They found that DENV infection induced specific increases in IgG1 afucosylation, and levels of afucosylated IgG1 could indeed predict dengue disease severity, making IgG1 fucosylation status a potentially useful prognostic tool for the treatment of dengue patients. Science , abc7303, this issue p. 1102 ; see also abj0435, p. 1041

The most performing techniques enabling early diagnosis of infectious diseases rely on nucleic acid detection. Today, because of their high technicality and cost, nucleic acid amplification tests (NAAT) are of benefit only to a small fraction of developing countries population. By reducing costs, simplifying procedures and enabling multiplexing, paper microfluidics has the potential to considerably facilitate their accessibility. However, most of the studies performed in this area have not quit the lab. This letter brings NAAT on paper closer to the field, by using clinical samples and operating in a resource-limited setting. We first performed isothermal reverse transcription and Recombinase Polymerase Amplification (RT-RPA) of synthetic Ribonucleic Acid (RNA) of Ebola virus using paper microfluidics devices. We further applied this method in Guinea to detect the presence of Ebola virus in human sample RNA extracts, with minimal facilities (carry-on detection device and freeze-dried reagents on paper). RT-RPA results were available in few minutes and demonstrate a sensitivity of 90.0% compared to the gold-standard RT-PCR on a set of 43 patient samples. Furthermore, the realization of a nine-spot multilayered device achieving the parallel detection of three distinct RNA sequences opens a route toward the detection of multiple viral strains or pathogens.

Increased activation of adaptive immunity and proper feedback mechanisms can eliminate dengue viral infection without clinical symptoms.

Ethnic groups can display differential genetic susceptibility to infectious diseases. The arthropod-born viral dengue disease is one such disease, with empirical and limited genetic evidence showing that African ancestry may be protective against the haemorrhagic phenotype. Global ancestry analysis based on high-throughput genotyping in admixed populations can be used to test this hypothesis, while admixture mapping can map candidate protective genes. A Cuban dengue fever cohort was genotyped using a 2.5 million SNP chip. Global ancestry was ascertained through ADMIXTURE and used in a fine-matched corrected association study, while local ancestry was inferred by the RFMix algorithm. The expression of candidate genes was evaluated by RT-PCR in a Cuban dengue patient cohort and gene set enrichment analysis was performed in a Thai dengue transcriptome. OSBPL10 and RXRA candidate genes were identified, with most significant SNPs placed in inferred weak enhancers, promoters and lncRNAs. OSBPL10 had significantly lower expression in Africans than Europeans, while for RXRA several SNPs may differentially regulate its transcription between Africans and Europeans. Their expression was confirmed to change through dengue disease progression in Cuban patients and to vary with disease severity in a Thai transcriptome dataset. These genes interact in the LXR/RXR activation pathway that integrates lipid metabolism and immune functions, being a key player in dengue virus entrance into cells, its replication therein and in cytokine production. Knockdown of OSBPL10 expression in THP-1 cells by two shRNAs followed by DENV2 infection tests led to a significant reduction in DENV replication, being a direct functional proof that the lower OSBPL10 expression profile in Africans protects this ancestry against dengue disease. Dengue is a concern of worldwide health authorities given the increase on virus and vector dispersions. So far only one traditional GWAS survey has been performed in Vietnamese children. This disease is also epidemic in tropical and subtropical regions of the Americas, where most populations descend from a dynamic admixture between African, European and Native American backgrounds. Empirical evidence claimed that African descent was protective against dengue haemorrhagic phenotype in the Cuban population, and this study is the first to apply admixture mapping to identify candidate genes that confer African protection. We also present evidence that two candidate genes, OSBPL10 and RXRA, are differentially expressed along dengue disease progression in Cuban patients and in a Thai dengue transcriptome dataset, and directly show that knockdown of OSBPL10 gene expression leads to a significant reduction in DENV2 replication. A very important overall result of our work is that it provides a unifying framework for many genes that have been said to be protective in dengue. Our evidence places the LXR/RXR activation pathway at the center of natural dengue protection, and supports pursuing therapeutic techniques involving synthetic ligands of nuclear receptor genes or kinases inhibitors that interact with proteins involved in lipid metabolism.