6 research outputs found

    The Potential Impact of Using Vaccination and Insect Repellent to Control the Spread of Yellow Fever

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    Yellow fever is a viral hemorrhagic fever transmitted by the Aedes aegypti mosquito. It has historically caused thousands of deaths throughout Africa, the Americas, Europe, and the Caribbean and continues to pose threats in Africa and Central and South America. The disease is most detrimental in densely populated areas with warmer climates where individuals have limited access to health care facilities. These conditions are exemplified by the yellow fever epidemic of 1878 in Memphis, Tennessee. The limited medical knowledge, warm climate, and densely populated urban areas greatly contributed to the magnitude of the epidemic that killed thousands. We developed an ordinary differential equations model to simulate the dynamics of human and mosquito populations during the Memphis 1878 yellow fever outbreak. Additionally, we examined the use of insect repellent and vaccination as methods to reduce the severity of the outbreak. We examine the conditions under which the disease-free equilibria are stable for the complete model. We use uncertainty and sensitivity analyses to quantify the reduction in cumulative infections and deaths due to the frequent use of insect repellent and vaccination among humans

    Stratified analyses refine association between TLR7 rare variants and severe COVID-19

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    Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway
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