The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for malaria elimination. To characterise the genetic diversity of this parasite within individual infections and across the population, we performed deep genome sequencing of >200 clinical samples collected across the Asia-Pacific region, and analysed data on >300,000 SNPs and 9 regions of the genome with large copy number variations. Individual infections showed complex patterns of genetic structure, with variation not only in the number of dominant clones but also in their level of relatedness and inbreeding. At the population level, we observed strong signals of recent evolutionary selection both in known drug resistance genes and at novel loci, and these varied markedly between geographical locations. These findings reveal a dynamic landscape of local evolutionary adaptation in P. vivax populations, and provide a foundation for genomic surveillance to guide effective strategies for control and elimination.

Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection.

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Progress made in malaria control during the past decade has prompted increasing global dialogue on malaria elimination and eradication. The product development pipeline for malaria has never been stronger, with promising new tools to detect, treat, and prevent malaria, including innovative diagnostics, medicines, vaccines, vector control products, and improved mechanisms for surveillance and response. There are at least 25 projects in the global malaria vaccine pipeline, as well as 47 medicines and 13 vector control products. In addition, there are several next-generation diagnostic tools and reference methods currently in development, with many expected to be introduced in the next decade. The development and adoption of these tools, bolstered by strategies that ensure rapid uptake in target populations, intensified mechanisms for information management, surveillance, and response, and continued financial and political commitment are all essential to achieving global eradication.

17The emergence of a novel coronavirus, SARS-CoV-2, resulted in a pandemic. Here, we used X-ray 18 structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from 19 SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, 20 and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins 21 known to serve or not serve as receptor allows to define residues important for binding. From the 20 22 amino acids in ACE2 that contact S up to seven can be replaced and ACE2 can still function as the SARS-23CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery 24 of the binding site, while changes of the invariable residues prevent S-binding or infection of the 25 respective animal. Some ACE2 proteins even tolerate the loss or the acquisition of N-glycosylation sites 26 located near the S-interface. Of note, Pigs and dogs, which are not or not effectively infected and have 27 only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. 28Comparison of the RBD of S of SARS-CoV-2 with viruses from Bat-CoV-RaTG13 and Pangolin-CoV 29 revealed that the latter contains only one substitution, whereas the Bat-CoV-RaTG13 exhibits five. 30However, ACE2 of pangolin exhibit seven changes relative to human ACE2, a similar number of 31 substitutions is present in ACE2 of bats, raccoon, and civet suggesting that SARS-CoV-2 may not 32 especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new 33 insight into the receptor usage and animal source/origin of SARS-CoV-2. 34 IMPORTANCE 35 SARS-CoV-2 is threatening people worldwide and there are no drugs or vaccines available to mitigate 36 its spread. The origin of the virus is still unclear and whether pets and livestock can be infected and 37 transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host 38 receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis 39 provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from 40 species known to support SARS-CoV-2 infection tolerate many amino acid changes indicating that the 41 species barrier might be low. An exception are dogs and especially pigs, which, however, revealed 42

Qi Gao and colleagues describe China's 1-3-7 strategy for eliminating malaria: reporting of malaria cases within one day, their confirmation and investigation within three days, and the appropriate public health response to prevent further transmission within seven days.

In areas of low malaria transmission, it is currently recommended that a single dose of primaquine (0.75 mg base/kg; 45 mg adult dose) be added to artemisinin combination treatment (ACT) in acute falciparum malaria to block malaria transmission. Review of studies of transmission-blocking activity based on the infectivity of patients or volunteers to anopheline mosquitoes, and of haemolytic toxicity in glucose 6-dehydrogenase (G6PD) deficient subjects, suggests that a lower primaquine dose (0.25 mg base/kg) would be safer and equally effective. This lower dose could be deployed together with ACTs without G6PD testing wherever use of a specific gametocytocide is indicated.

BackgroundLoop-mediated isothermal amplification (LAMP) is a high performance method for detecting DNA and holds promise for use in the molecular detection of infectious pathogens, including Plasmodium spp. However, in most malaria-endemic areas, which are often resource-limited, current LAMP methods are not feasible for diagnosis due to difficulties in accurately interpreting results with problems of sensitive visualization of amplified products, and the risk of contamination resulting from the high quantity of amplified DNA produced. In this study, we establish a novel visualized LAMP method in a closed-tube system, and validate it for the diagnosis of malaria under simulated field conditions.MethodsA visualized LAMP method was established by the addition of a microcrystalline wax-dye capsule containing the highly sensitive DNA fluorescence dye SYBR Green I to a normal LAMP reaction prior to the initiation of the reaction. A total of 89 blood samples were collected on filter paper and processed using a simple boiling method for DNA extraction, and then tested by the visualized LAMP method for Plasmodium vivax infection.ResultsThe wax capsule remained intact during isothermal amplification, and released the DNA dye to the reaction mixture only when the temperature was raised to the melting point following amplification. Soon after cooling down, the solidified wax sealed the reaction mix at the bottom of the tube, thus minimizing the risk of aerosol contamination. Compared to microscopy, the sensitivity and specificity of LAMP were 98.3% (95% confidence interval (CI): 91.1-99.7%) and 100% (95% CI: 88.3-100%), and were in close agreement with a nested polymerase chain reaction method.ConclusionsThis novel, cheap and quick visualized LAMP method is feasible for malaria diagnosis in resource-limited field settings.