Predicting the tripartite network of mosquito-borne disease

The potential for a pathogen to infect a host is mediated by traits of both the host and pathogen, as well as the complex interactions between them. Arthropod-borne viruses (arboviruses) require an intermediate vector, introducing an additional compatibility layer. Existing predictive models of host-virus networks rarely incorporate the unique aspects of vector transmission, instead treating vector biology as a hidden, unobserved layer. We explore two possible extensions to address this: first, we added vector traits into predictions of the bipartite host-virus network; and second, we used host, vector, and virus traits to predict the tripartite host-vector-virus network. We tested both approaches on mosquito-borne flaviviruses of mammals. Using host-virus models, we find that the inclusion of vector traits may improve inference in some cases, while viral traits proved to be the most important for model performance. Further, we found that it was possible, though quite difficult, to predict full tripartite (host-vector-virus) links. Both approaches are interesting avenues for further model development, but our results keenly underscore a need to collect more comprehensive datasets to characterize arbovirus ecology, across a wide and less biased geographic scope, especially outside of North America, and to better identify molecular traits that underpin host-vector-virus interactions.

A Survey of Potentially Pathogenic-Incriminated Arthropod Vectors of Health Concern in Botswana

Arthropod vectors play a crucial role in the transmission of many debilitating infections, causing significant morbidity and mortality globally. Despite the economic significance of arthropods to public health, public knowledge on vector biology, ecology and taxonomic status remains anecdotal and largely unexplored. The present study surveyed knowledge gaps regarding the biology and ecology of arthropod vectors in communities of Botswana, across all districts. Results showed that communities are largely aware of individual arthropod vectors; however, their ‘potential contribution’ in disease transmission in humans, livestock and wildlife could not be fully attested. As such, their knowledge was largely limited with regards to some aspects of vector biology, ecology and control. Communities were strongly concerned about the burden of mosquitoes, cockroaches, flies and ticks, with the least concerns about fleas, bedbugs and lice, although the same communities did not know of specific diseases potentially vectored by these arthropods. Knowledge on arthropod vector control was mainly limited to synthetic chemical pesticides for most respondents, regardless of their location. The limited knowledge on potentially pathogen-incriminated arthropod vectors reported here has large implications for bridging knowledge gaps on the bio-ecology of these vectors countrywide. This is potentially useful in reducing the local burden of associated diseases and preventing the risk of emerging and re-emerging infectious diseases under global change.

Marker-assisted mapping enables effective forward genetic analysis in the arboviral vector Aedes aegypti, a species with vast recombination deserts

Aedes aegypti is a major vector of arboviruses that cause dengue, chikungunya, yellow fever and Zika. Although recent success in reverse genetics has facilitated rapid progress in basic and applied research, integration of forward genetics with modern technologies remains challenging in this important species, as up-to-47% of its chromosome is refractory to genetic mapping due to extremely low rate of recombination. Here we report the development of a marker-assisted-mapping (MAM) strategy to readily screen for and genotype only the rare but informative recombinants, drastically increasing both the resolution and signal-to-noise ratio. Using MAM, we mapped a transgene that was inserted in a >100 Mb recombination desert and a sex-linked spontaneous red-eye (re) mutation just outside the region. We subsequently determined, by CRISPR/Cas9-mediated knockout, that cardinal is the causal gene of re, which is the first forward genetic identification of a causal gene in Ae. aegypti. This study provides the molecular foundation for using gene-editing to develop versatile and stable genetic sexing methods by improving upon the current re-based genetic sexing strains. MAM does not require densely populated markers and can be readily applied throughout the genome to facilitate the mapping of genes responsible for insecticide- and viral-resistance. By enabling effective forward genetic analysis, MAM bridges a significant gap in establishing Ae. aegypti as a model system for research in vector biology. As large regions of suppressed recombination are also common in other plant and animal species including those of economic significance, MAM will have broad applications beyond vector biology.