Bayesian estimation of Lassa virus epidemiological parameters: implications for spillover prevention using wildlife vaccination

Abstract

32Lassa virus is a significant burden on human health throughout its endemic region in 33 West Africa, with most human infections the result of spillover from the primary rodent 34 reservoir of the virus, the natal multimammate mouse, M. natalensis. Here we develop a 35 Bayesian methodology for estimating epidemiological parameters of Lassa virus within its 36 rodent reservoir and for generating probabilistic predictions for the efficacy of rodent 37 vaccination programs. Our approach uses Approximate Bayesian Computation (ABC) to 38 integrate mechanistic mathematical models, remotely-sensed precipitation data, and Lassa 39 virus surveillance data from rodent populations. Using simulated data, we show that our 40 method accurately estimates key model parameters, even when surveillance data are available 41 from only a relatively small number of points in space and time. Applying our method to 42 previously published data from two villages in Guinea estimates the time-averaged of Lassa 0 43 virus to be 1.658 and 1.453 for rodent populations in the villages of Bantou and Tanganya, 44 respectively. Using the posterior distribution for model parameters derived from these 45 Guinean populations, we evaluate the likely efficacy of vaccination programs relying on 46 distribution of vaccine-laced baits. Our results demonstrate that effective and durable 47 reductions in the risk of Lassa virus spillover into the human population will require repeated 48 distribution of large quantities of vaccine. 49 3 50 Author Summary 51 Lassa virus is a chronic source of illness throughout West Africa, and is considered to be a threat 52 for widespread emergence. Because most human infections result from contact with infected 53 rodents, interventions that reduce the number of rodents infected with Lassa virus represent 54 promising opportunities for reducing the public health burden of this disease. Evaluating how 55 well alternative interventions are likely to perform is complicated by our relatively poor 56 understanding of viral epidemiology within the reservoir population. Here we develop a novel 57 statistical approach that couples mathematical models and viral surveillance data from rodent 58 populations to robustly estimate key epidemiological parameters. Applying our method to 59 existing data from Guinea yields well-resolved parameter estimates and allows us to simulate a 60 variety of rodent vaccination programs. Together, our results demonstrate that rodent 61 vaccination alone is unlikely to be an effective tool for reducing that public health burden of 62 Lassa fever within West Africa. 63 65 Lassa virus is a zoonotic pathogen endemic to West Africa where it poses a significant 66 burden on human health (Buckley et al. 1970). Although only a relatively small proportion of 67 human cases result in severe symptoms and mortality, human infection is common, with 8-52% 68 of the human population within Sierra Leone seropositive (McCormick et al. 1987; Bausch et al. 69 2001; Dan-Nwafor et al. 2019), indicative of past...

Quantifying the effectiveness of betaherpesvirus-vectored transmissible vaccines

“…The greater resistance to the vaccine exhibited by LCMV is mostly due to its increased infectious period which we have assumed is, on average, lifelong. In contrast, the infectious period for LASV has been estimated to be 22 d, on average (22,23). These results highlight that pathogens that generate acute, short-term infections and have relatively low R0 are most readily controlled using MCMV-vectored transmissible vaccines.…”

“…Although the primary reservoir of LASV, the multimammate rat Mastomys natalensis, is only distantly related to the domestic mouse, both LASV and LCMV do infect species within the genus Mus (21). Using published estimates for the seroprevalence and infectious period of these pathogens (22,23) we developed models describing their response to an MCMV-vectored transmissible vaccine. These models were used to simulate the introduction of a transmissible vaccine into a reservoir population where the target pathogen was endemic.…”

HHi-FiVe: A high-fidelity genetic engineering pipeline for construction of herpesvirus-based vaccines

“…However, most highly pathogenic emerging viruses spill over into human populations from inaccessible wild animal populations 36 , which poses a considerable limitation on the use of directly administered vaccines. The features of CMVs thus motivate the development of CMV-based vectors as a transmissible vaccine platform to achieve high immune coverage in such situations 6,13,14 . Our study has provided the means and experience whereby the e cient production of precision-made, genetically validated herpesvirus-based vectors can contribute to the further development of this platform.…”

“…The vaccines are also amenable to reuse, as prior vector-speci c immunity does not prevent reinfection 3,5,11,12 . These features, combined with high host species restriction and the ability to spread among individuals, have motivated the development of transmissible herpesvirus-based vaccines for targeting emerging zoonotic pathogens in the inaccessible wildlife animal populations from which they frequently arise 13,14 . Advances in bacterial arti cial chromosome (BAC)-based genetic engineering have played a large part in the development of technology for manipulating the vectors 15 .…”

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

“…Temporal fluctuations in population density, due to seasonal rainfall, would provide another important insight into the seasonal burden of human LF cases [11]. Understanding this ecological connection is important because distributing vaccines at seasonal population lows in wildlife demographic cycles can, in theory, substantially increase the probability of pathogen elimination [58, 59]. Incorporating these temporal layers will become more feasible as more time-series data on population density in the focal reservoir species become available.…”