Heterogeneity of Rift Valley fever virus transmission potential across livestock hosts, quantified through a model-based analysis of host viral load and vector infection

Abstract

Quantifying the variation of pathogens’ life history traits in multiple host systems is crucial to understand their transmission dynamics. It is particularly important for arthropod-borne viruses (arboviruses), which are prone to infecting several species of vertebrate hosts. Here, we focus on how host-pathogen interactions determine the ability of host species to transmit a virus to susceptible vectors upon a potentially infectious contact. Rift Valley fever (RVF) is a viral, vector-borne, zoonotic disease, chosen as a case study. The relative contributions of livestock species to RVFV transmission has not been previously quantified. To estimate their potential to transmit the virus over the course of their infection, we 1) fitted a within-host model to viral RNA and infectious virus measures, obtained daily from infected lambs, calves, and young goats, 2) estimated the relationship between vertebrate host infectious titers and probability to infect mosquitoes, and 3) estimated the net infectiousness of each host species over the duration of their infectious periods, taking into account different survival outcomes for lambs. Our results indicate that the efficiency of viral replication, along with the lifespan of infectious particles, could be sources of heterogeneity between hosts. Given available data on RVFV competent vectors, we found that, for similar infectious titers, infection rates in the Aedes genus were on average higher than in the Culex genus. Consequently, for Aedes-mediated infections, we estimated the net infectiousness of lambs to be 2.93 (median) and 3.65 times higher than that of calves and goats, respectively. In lambs, we estimated the overall infectiousness to be 1.93 times higher in individuals which eventually died from the infection than in those recovering. Beyond infectiousness, the relative contributions of host species to transmission depend on local ecological factors, including relative abundances and vector host-feeding preferences. Quantifying these contributions will ultimately help design efficient, targeted, surveillance and vaccination strategies.

Author summary

Viruses spread by mosquitoes present a major threat to animal and public health worldwide. When these pathogenic viruses can infect multiple species, controlling their spread becomes difficult. Rift Valley fever virus (RVFV) is such a virus. It spreads predominantly among ruminant livestock but can also spill over and cause severe disease in humans. Understanding which of these ruminant species are most important for the transmission of RVFV can help for effective control. One piece of this puzzle is to assess how effective infected animals are at transmitting RVFV to mosquitoes. To answer this question, we combine mathematical models with observations from experimental infections in cattle, sheep, and goats, and model changes in viremia over time within individuals. We then quantify the relationship between hosts’ viremia and the probability to infect mosquitoes. In combining these two analyses, we estimate the overall transmission potential of sheep, when in contact with mosquitoes, to be 3 to 5 times higher than that of goats and cattle. Further, sheep that experience a lethal infection have an even larger overall transmission potential. Once applied at the level of populations, with setting-specific herd composition and exposure to mosquitoes, these results will help unravel species’ role in RVF outbreaks.