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  • EVI

Anti-Toxin Responses to Natural ETEC Infection in Adults and Children in Bangladesh

12 December 2023

Enterotoxigenic Escherichia coli (ETEC) infection is an important cause of diarrhoea in children in low- and middle-income countries (LMIC) and is also one of the main causes of traveller’s diarrhoea (TD). ETEC-induced diarrhoea is mainly attributed to the effects of the heat labile toxin (LT) and heat-stable toxin (ST). The antibodies neutralising these ETEC toxins can be considered protective, although it is not known what levels of such antibodies are sufficient. Adults living in endemic regions acquire protective immunity due to repeated exposure, while young children are the most susceptible. Assessing the toxin-neutralizing potency of plasma from the acute infection phase and convalescence is expected to guide vaccine efforts and approaches against ETEC infection.

The SHIGETECVAX project, led by EVI and funded by the European Commission, conducted a study in Dhaka, Bangladesh, from January 2020 to February 2021. The goal was to understand how adults and children in Bangladesh respond to ETEC infection. The study focused on analysing the anti-toxin antibody profiles in plasma samples from infected individuals, as Bangladesh is known for being prone to ETEC infections. A total of 617 adults and 480 paediatric diarrhoeal patients were screened, and 43 adults and 46 children (below 5 years of age) with an acute ETEC infection completed the study. Blood samples from patients were collected at enrolment (day 2/3 after onset of diarrhoea), and follow-up visits at day 7 ± 1 and day 30 ± 4 and once from healthy adult participants. The plasma samples were analysed for antibody responses against the ETEC.

In the study, ST positive ETEC was found as the main cause of ETEC infection in adults, unlike in children in an endemic setting. 42% of the enrolled children were infected with an LT-only containing ETEC strain. In contrast, only 14% of the adults were infected with an ETEC strain that expressed only LT (LT+ST−). A very low levels of anti-ST antibodies were detected, and no ST-neutralising activity. However, infection with ETEC strains expressing the LT induced systemic antibody responses was found in less than 25% of subjects. The antibody levels against LTA and LTB, as well as cholera toxin (CT), correlated well. The anti-LT antibodies were shown to have LT- and CT- neutralising activity. The antibody reactivity against linear LT epitopes did not correlate with toxin-neutralising activity. Unlike LT, ST is a poor antigen and even adults have low anti-ST antibody levels that do not allow for the detection of toxin-neutralising activity.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 815568.

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