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Kenyan researcher investigates enteropathogen burden in the post-vaccine era


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About Agoti

Charles Agoti is a molecular epidemiologist based at the KEMRI-Wellcome Trust Programme (KWTRP) in Kenya. He is an IDeAL scheme Mid-career Research Fellow. His research focuses on the use of molecular tools and genomics to investigate epidemics of endemic viral respiratory and enteric pathogens in the continent. He holds a BSc degree from the University of Nairobi (Kenya), an MSc from the University of London (UK) and a PhD from the Open University (UK).

Agoti’s current research is on enteric pathogens of medical importance. He is leading a research program in coastal Kenya investigating aetiology, pathogenesis and genomic epidemiology of viral diarrhoea following the introduction of a vaccine against rotavirus, the leading global cause of life-threatening diarrhoea.

Kenyan researcher investigates enteropathogen burden in the post-vaccine era

For the first time, the full picture of enteropathogens in circulation in coastal Kenya is being painted using modern quantitative molecular techniques, according to results of a study conducted by Dr Charles Agoti, a molecular epidemiologist based at the KEMRI-Wellcome Trust Programme (KWTRP) in Kenya and an IDeAL scheme Mid-career Research Fellow. His study is among the few African studies describing enteropathogen burden in the post-vaccine era and how this has influence on rotavirus vaccine efficacy.  Agoti’s studies have provided evidence of high coinfection rates in children seeking medical attention following diarrhoea symptoms, an observation expected to influence the clinician perspective of diarrhoea treatment in the region. The observation that strains causing severe rotavirus infection in Kenyan children post-vaccine era are mostly newly introduced, offers novel insight on where to intensify control strategies. This highlights the importance of increasing the global rotavirus vaccine coverage otherwise non-vaccinating population/countries will continue to act as viral reservoirs that seed vaccine heterotypic viruses to vaccinating populations.

The effectiveness of rotavirus vaccines in low-income settings is only about 55% compared to >80% in high-income settings. Dr Agoti’s research aims to improve understanding on why rotavirus vaccines do not perform very well in low-income settings and quantify the burden and extent of coinfection with other enteric pathogens. This research endeavours to inform an improved vaccine and vaccination strategy against rotavirus and other leading infectious causes of diarrhoea in Africa.

IDeAL is one of the 12 programmes funded through the Developing Excellence in Leadership, Training and Science (DELTAS Africa) programme; a US$100 million programme of The African Academy of Sciences supporting the Africa-led development of world-class scientific leaders through health research support, training fellowships, mentorship, and investments in research infrastructure in 12 programmes spanning 21 countries.

Agoti’s research is embedded in ongoing hospital-based surveillance of severe diarrhoea in Kilifi County Hospital, located in the coastal region of Kenya. His studies involve whole genome sequencing of rotavirus positives detected in the surveillance (pre and post vaccine introduction) and also screening for 28 known enteropathogens using a quantitative PCR method. Preliminary results from the study show replacement of the previously dominant genotypes that were homotypic to the rotavirus vaccine (Rotarix®) with strains that are heterotypic to the vaccine strain in the post-introduction vaccine era. Following sequence analysis of >200 whole genomes, the study has noted that strains circulating in Kenya are majorly new introductions from other countries and these disappear from circulation after only 1-2 years. Compared to the pre-vaccine introduction period, the overall circulating rotavirus diversity has substantially reduced in the post-vaccine introduction period possibly reflecting an increasing immune population that rapidly extinguishes virus transmission chains. Further, screening for the full range of enteropathogens in the post-vaccine introduction samples has found a high level of enteropathogen coinfection including in samples testing positives for rotavirus. This has opened questions on the role of the co-infecting pathogens in severe rotavirus diarrhoea and reduced vaccine efficacy.

 In Africa, diarrhoea is the third leading cause of death among children under the age of five years.  In the year 2015 alone, diarrhoea was responsible for up to 330,000 deaths of African children and rotavirus infection estimated to be responsible for about half of them. Fortunately, effective rotavirus vaccines have become available in the last decade, and their increasing use has resulted in the rapid fall of rotavirus disease burden worldwide. However, these vaccines are reportedly having the lowest efficacy and effectiveness in sub-Saharan Africa where the disease burden is highest, hence most needed. There is an urgent need to elucidate and remove barriers to realising the full potential of the rotavirus vaccine for African children and that is what Dr Agoti’s research aims to achieve.

 In Kenya, ~ 25% of all hospitalised children under the age of five years have diarrhoea symptoms. Estimations indicate that ~6% of all deaths in Kenyan children result from severe diarrhoea related complications, including dehydration.  Rotavirus is a lead cause of life-threatening dehydrating diarrhoea and is estimated to cause ~9,000 child deaths in Kenya each year. In Kilifi County Hospital, we observed that approximately ~60% of the children presenting with diarrhoea symptoms have some dehydration or severe dehydration. Introducing the rotavirus vaccine in Kenya reduced the burden by almost half. Dr Agoti’s studies seek to discover how to realise the full potential of the rotavirus vaccines in the African continent.