Enterotoxigenic Escherichia coli hyperimmune bovine colostrum for preventing travellers' diarrhoea (TD): a randomised, double-blind, placebo-controlled trial.

BACKGROUND

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of travellers' diarrhoea (TD). Hyperimmune bovine colostrum (HBC) containing ETEC specific antibodies has shown efficacy in controlled settings, but despite widespread use, real-world efficacy remains uncertain.

METHODS

In this randomised, double-blind, placebo-controlled superiority trial, US and UK military personnel and adult civilians (aged 18-70 years) travelling to TD-risk regions were randomised (1:1) to receive ETEC HBC (600 mg twice daily) or placebo, starting 2 days before arrival and continuing for 10-20 days while in the risk area. The primary outcome was TD, defined by standardised criteria. Stool smears collected during diarrhoeal episodes and at the end-of-prophylaxis were tested by PCR for pathogen attribution. ETEC-attributable TD was assessed as a secondary outcome. This trial is registered with ClinicalTrials.gov, NCT04605783 and is complete.

FINDINGS: Between June 2, 2022, and April 29, 2025, 975 participants were enrolled and 850 were randomised to ETEC HBC (n = 425) or placebo (n = 425). Of these, 317 ETEC HBC and 323 placebo recipients were included in the primary efficacy analysis. TD occurred in 22.7% of ETEC HBC and 26.3% of placebo recipients (relative protective efficacy [PE] 13.7 [95% CI -13.4 to 34.31]), below the protocol-specified efficacy threshold of ≥35%. ETEC accounted for 17% of attributable TD cases, with frequent multi-organism detections. The difference in ETEC attributable TD between the groups was not statistically significant (12.1 vs. 21.5%; PE: 43.8 [-28.5 to 75.4]). Adverse events were rare and mild (ETEC HBC 2/320 vs. placebo 2/325). Both events in the ETEC HBC group (frequent urination, hives) resolved spontaneously.

INTERPRETATION: ETEC HBC did not significantly reduce overall TD risk, with interpretation of ETEC-specific efficacy constrained by limited power. Further research is warranted to determine whether broader ETEC antigenic coverage or multi-pathogen approaches can overcome the pathogen diversity and polymicrobial infections observed in field settings.

FUNDING: Defense Health Agency.