Enabling enterotoxigenic E. coli vaccine introduction in Malawi using pathogen whole genome sequencing

Summary

Childhood diarrhoea caused by bacteria is still a significant cause of death and disease in developing countries. Two kinds of intervention — vaccines and water, sanitation and hygiene (WaSH) improvements — will play essential roles in reducing the burden of diarrhoeal disease. Enterotoxigenic E. coli (ETEC) is a major bacterial cause of diarrhoea in Malawi. Vaccines are being developed that could stop people from becoming sick with ETEC infections, although these still require further proof of effectiveness. 

Before introducing a vaccine to a country, we need to know — do the bacteria targeted by the vaccine cause disease in that country? This question is particularly relevant for ETEC, as ETEC is a very diverse collection of different lineages of E. coli, with highly variable virulence profiles, and the vaccine does not protect against all ETEC variants. 

We want to contribute to the success of ETEC vaccines by looking at the DNA of ETEC from children with diarrhoea, enabling us to identify which lineages are present in Malawi. If the lineages responsible for most ETEC disease in Malawi are in the vaccine, Malawi could play a pivotal role in testing the ETEC vaccine. University of Malawi, College of Medicine (now known as Kamuzu University of Health Sciences, KUHeS) and Malawi-Liverpool-Wellcome Clinical Research Programme have been at the forefront of introducing vaccines against nationally and regionally important diseases, such as rotavirus and typhoid, and we are keen to build on this strength by laying the groundwork for ETEC vaccine trials.

Project outcomes

Whole genome sequencing, or the technique of looking at all of a bacteria’s DNA, can help us to design and target vaccines appropriately, by telling us whether available vaccines will help protect against the types of bacteria circulating in the community. We have isolated and characterised for the first time in Malawi,  a bacterium called Enterotoxigenic E. coli, a major cause of childhood diarrhoea in the country.  Although we were unfortunately only able to sequence two Enterotoxigenic E. coli isolates, they provide a first insight into the Malawian bacterial population.

This project, supported by BactiVac, increased the capacity for ETEC research at KUHeS and MLW and provided sufficient data for a poster at the Vaccines against Shigella and E. coli conference to be held in the USA in 2022.