Bridging the gap: Using reservoir ecology and human serosurveys to estimate Lassa virus spillover in West Africa

Abstract

Forecasting the risk of pathogen spillover from reservoir populations of wild or domestic animals is essential for the effective deployment of interventions such as wildlife vaccination or culling. Due to the sporadic nature of spillover events and limited availability of data, developing and validating robust, spatially explicit, predictions is challenging. Recent efforts have begun to make progress in this direction by capitalizing on machine learning methodologies. An important weakness of existing approaches, however, is that they generally rely on combining human and reservoir infection data during the training process and thus conflate risk attributable to the prevalence of the pathogen in the reservoir population with the risk attributed to the realized rate of spillover into the human population. Because effective planning of interventions requires that these components of risk be disentangled, we developed a multi-layer machine learning framework that separates these processes. Our approach begins by training models to predict the geographic range of the primary reservoir and the subset of this range in which the pathogen occurs. The spillover risk predicted by the product of these reservoir specific models is then fit to data on realized patterns of historical spillover into the human population. The result is a geographically specific spillover risk forecast that can be easily decomposed and used to guide effective intervention. Applying our method to Lassa virus, a zoonotic pathogen that regularly spills over into the human population across West Africa, results in a model that explains a modest but statistically significant portion of geographic variation in historical patterns of spillover. When combined with a mechanistic mathematical model of infection dynamics, our spillover risk model predicts that 897,700 humans are infected by Lassa virus each year across West Africa, with Nigeria accounting for more than half of these human infections.

Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity

“…Instead, inhibitory peptide residues 1087-1099, as well as PB2-like segments 1759-1770 (lid), 1852-1860 and 1894-1896 (mid), 2077-2081 and 2089-2091 (link) pack against the back of the EN, stabilising it in its new location. For these two observed positions of the EN, the total buried surface area is comparable, 3005 Å 2 ( APO-ENDO , autoinhibited) and 2721 Å 2 ( MID-LINK , free), compatible with there being an equilibrium between the two states as observed in the two different apo-structures.…”

“…All movie frames were aligned and dose-weighted using MotionCor2 program (Supplementary Cryo-EM processing overview file EM-1, -3, -5, -7, -9). Thon rings from summed power spectra of every 4e-/Å 2 were used for contrast-transfer function parameter calculation with CTFFIND 4.1 45 . Particles were selected with WARP 46 .…”

“…It is a rodent-borne virus, endemic to West Africa and the causative agent of Lassa haemorrhagic fever, a febrile illness with increasing case numbers and a case fatality rate among hospitalized patients of ∼15% in Nigeria in 2018 1 . Recent studies applying computational modelling predict a total number of ∼900,000 human infections per year across West Africa 2 . The large (L) protein of LASV is a multi- domain molecular machine that binds the conserved 3’ and 5’ ends (the ‘promoter’) of each of the two viral RNA (vRNA) genome segments (denoted L and S) and plays a central role in the viral life cycle, which is entirely cytoplasmic.…”

“…Recent studies applying computational modelling predict a total number of ~900,000 human infections per year across West Africa 2 . The large (L) protein of LASV is a multi-domain molecular machine that binds the conserved 3' and 5' ends (the 'promoter') of each of the two viral RNA (vRNA) genome segments (denoted L and S) and plays a central role in the viral life cycle, which is entirely cytoplasmic.…”

Detection of Lassa virus in wild rodent feces: Implications for Lassa fever burden within households in the endemic region of Faranah, Guinea

“…Misdiagnosis of cases was exemplified in 2019 when a Guinean man died of LF after being mistakenly diagnosed with malaria, typhoid fever and Ebola [ 3 ]. Mathematical models estimate that 897,700 human infections occur annually [ 4 ]. LASV has a case-fatality rate as high as 50% during epidemics [ 5 ].…”