Mr Michelo Simuyandi, Research Fellow
Centre for Infectious Disease Research in Zambia (Zambia)
Dr Subhra Chakraborty, Johns Hopkins University (USA)
Professor Gordon Dougan, The Sanger Institute (UK)
Enterotoxigenic Escherichia coli (ETEC) are among the most important pathogens associated with moderate-to-severe diarrhoea (MSD) in children less than 5 years old living in low and middle income countries (LMICs). Estimated deaths associated with ETEC are 42,000 among children under-5 and 74,100 deaths among all ages. ETEC is also estimated to cause 12 million episodes of travellers’ diarrhoea each year; although these estimates are likely underreported due to insufficient surveillance structures in endemic areas. Repeated bouts of diarrhoeal disease can result in cognitive and developmental impairment, life-long disability and reduced life expectancy. There are limited data on country and region-specific incidences of ETEC, especially in developing countries, which bear the highest burden of diarrhoea-associated morbidity and mortality. A major constraint is the complexity of the diagnostic methods currently used to detect ETEC infections, which are both insufficiently sensitive and/or not feasible in most resource-poor settings.
We propose exploratory work to fill this critical gap in the availability of appropriately sensitive and cost-effective rapid diagnostic test (RDT) for ETEC and to characterise the circulating ETEC strains in Zambia with the goal of improving diagnosis, contributing to the generation of accurate burden data, and accelerating vaccine development in Africa.
The aim of this research proposal is to evaluate and validate a novel ETEC RDT based on a loop-mediated isothermal amplification (LAMP) technique developed by our collaborator at the Johns Hopkins University (JHU). The ETEC RDT is simple, rapid, sensitive, specific, equipment is electricity free, comparatively inexpensive, easy to scale up and use in resource-poor settings. The LAMP assay uses an innovative sample preparation directly from stool without isolating DNA, and targets the ETEC toxin genes. The performance of the ETEC RDT will be evaluated and validated against culture and the quantitative polymerase chain reaction (QPCR) methods in Zambia.