63 research outputs found

    The Impact of Human Conflict on the Genetics of Mastomys natalensis and Lassa Virus in West Africa

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    Environmental changes have been shown to play an important role in the emergence of new human diseases of zoonotic origin. The contribution of social factors to their spread, especially conflicts followed by mass movement of populations, has not been extensively investigated. Here we reveal the effects of civil war on the phylogeography of a zoonotic emerging infectious disease by concomitantly studying the population structure, evolution and demography of Lassa virus and its natural reservoir, the rodent Mastomys natalensis, in Guinea, West Africa. Analysis of nucleoprotein gene sequences enabled us to reconstruct the evolutionary history of Lassa virus, which appeared 750 to 900 years ago in Nigeria and only recently spread across western Africa (170 years ago). Bayesian demographic inferences revealed that both the host and the virus populations have gone recently through severe genetic bottlenecks. The timing of these events matches civil war-related mass movements of refugees and accompanying environmental degradation. Forest and habitat destruction and human predation of the natural reservoir are likely explanations for the sharp decline observed in the rodent populations, the consequent virus population decline, and the coincident increased incidence of Lassa fever in these regions. Interestingly, we were also able to detect a similar pattern in Nigeria coinciding with the Biafra war. Our findings show that anthropogenic factors may profoundly impact the population genetics of a virus and its reservoir within the context of an emerging infectious disease

    Experimental confirmation of efficient island divertor operation and successful neoclassical transport optimization in Wendelstein 7-X

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    Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever

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    Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis

    Experimental confirmation of efficient island divertor operation and successful neoclassical transport optimization in Wendelstein 7-X

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    We present recent highlights from the most recent operation phases of Wendelstein 7-X, the most advanced stellarator in the world. Stable detachment with good particle exhaust, low impurity content, and energy confinement times exceeding 100 ms, have been maintained for tens of seconds. Pellet fueling allows for plasma phases with reduced ion-temperature-gradient turbulence, and during such phases, the overall confinement is so good (energy confinement times often exceeding 200 ms) that the attained density and temperature profiles would not have been possible in less optimized devices, since they would have had neoclassical transport losses exceeding the heating applied in W7-X. This provides proof that the reduction of neoclassical transport through magnetic field optimization is successful. W7-X plasmas generally show good impurity screening and high plasma purity, but there is evidence of longer impurity confinement times during turbulence-suppressed phases.EC/H2020/633053/EU/Implementation of activities described in the Roadmap to Fusion during Horizon 2020 through a Joint programme of the members of the EUROfusion consortium/ EUROfusio

    Estimating the proportion of clinically suspected cholera cases that are true Vibrio cholerae infections: A systematic review and meta-analysis.

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    BackgroundCholera surveillance relies on clinical diagnosis of acute watery diarrhea. Suspected cholera case definitions have high sensitivity but low specificity, challenging our ability to characterize cholera burden and epidemiology. Our objective was to estimate the proportion of clinically suspected cholera that are true Vibrio cholerae infections and identify factors that explain variation in positivity.Methods and findingsWe conducted a systematic review of studies that tested ≥10 suspected cholera cases for V. cholerae O1/O139 using culture, PCR, and/or a rapid diagnostic test. We searched PubMed, Embase, Scopus, and Google Scholar for studies that sampled at least one suspected case between January 1, 2000 and April 19, 2023, to reflect contemporary patterns in V. cholerae positivity. We estimated diagnostic test sensitivity and specificity using a latent class meta-analysis. We estimated V. cholerae positivity using a random-effects meta-analysis, adjusting for test performance. We included 119 studies from 30 countries. V. cholerae positivity was lower in studies with representative sampling and in studies that set minimum ages in suspected case definitions. After adjusting for test performance, on average, 52% (95% credible interval (CrI): 24%, 80%) of suspected cases represented true V. cholerae infections. After adjusting for test performance and study methodology, the odds of a suspected case having a true infection were 5.71 (odds ratio 95% CrI: 1.53, 15.43) times higher when surveillance was initiated in response to an outbreak than in non-outbreak settings. Variation across studies was high, and a limitation of our approach was that we were unable to explain all the heterogeneity with study-level attributes, including diagnostic test used, setting, and case definitions.ConclusionsIn this study, we found that burden estimates based on suspected cases alone may overestimate the incidence of medically attended cholera by 2-fold. However, accounting for cases missed by traditional clinical surveillance is key to unbiased cholera burden estimates. Given the substantial variability in positivity between settings, extrapolations from suspected to confirmed cases, which is necessary to estimate cholera incidence rates without exhaustive testing, should be based on local data
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