The rainforests of Central Africa are the cradle of many of the large viral outbreaks that the world has witnessed in the past decades. Western East Africa borders on these large and relatively isolated jungles. Improved accessibility and rising population numbers put an increasing number of East Africans at risk of infection. This may in turn affect transmission dynamics and accelerate the geographic spread of viral pathogens. Spatio-temporal monitoring of viral prevalence along the Western border of East Africa is therefore of great importance to public health. In addition, its proximity to the apparent origin of multiple global viral outbreaks positions the region as a valuable sentinel in global surveillance.
Next generation metagenomic sequencing has been demonstrated to be a cost-effective and relatively uncomplicated solution for large scale surveillance of bacterial pathogens [ref the DTU sewage project]. Viral metagenomics is not quite as straightforward, for the main reason that viral genetic material makes up only a fraction of any organismal or environmental sample. However, if we restrict our attention to RNA viruses, then the elimination of DNA prior to sequencing considerably improves the signal-to-noise ratio in the collected data. Studies have shown next generation sequencing to be a viable approach to metagenomic viral characterisation of pooled samples, and as having the potential to uncover hitherto undetected or novel viruses.
We propose to perform viral metagenomics on pooled samples of mosquitoes collected at multiple points in time, at multiple locations in Tanzania, including the Western border area. Though this restricts findings to mosquito-borne viruses, it has the advantages of being non-human-invasive and, practically, of benefiting from the sample collection infrastructure already in place for malaria surveillance. Also, arboviruses are a significant group in terms of human morbidity. This notwithstanding, it would evidently be desirable to complement this study with metagenomic analyses of (pooled) human samples, both to widen the targeted range of viruses, and to establish prevalence at the human endpoint rather than the vector. This could conceivably be done noninvasively by sampling blood at regional blood banks.
It will need to be determined whether it is feasible to perform both mosquito and human analyses in the time frame and budget of a (single) GeMVi research fellowship.
Objectives and Deliverables
The primary goal of the study is to establish a proof of concept demonstrating the feasibility and potential value of viral surveillance using metagenomic NGS on mosquitoes in Tanzania. To this end, the study must assess data quantity and quality, sensitivity characteristics, and limitations of the approach. In practical terms, the project will deliver a laboratory protocol and automated computational pipeline that can be used “off-the-shelf” for subsequent surveillance, as well as the initial baseline map of viral prevalence detected across the sampling locations.