Travellers’ diarrhoea is one of the most predictable miseries of international travel, striking between 30 and 70 percent of visitors to high-risk regions and derailing military deployments, holidays and business trips alike. For decades, scientists have chased a reliable preventive measure, and for decades the candidates have disappointed. Now one of the most commercially successful of those candidates, an over-the-counter supplement derived from the colostrum of immunised cows, has been put through its most rigorous real-world test yet, and it has failed to deliver. A large randomised, double-blind, placebo-controlled trial published in eClinicalMedicine found that enterotoxigenic Escherichia coli hyperimmune bovine colostrum, marketed in the United States, Australia and Canada under the name Travelan, did not significantly reduce the incidence of travellers’ diarrhoea among military personnel and civilian travellers heading to some of the world’s highest-risk destinations.

The logic behind hyperimmune bovine colostrum is elegant. Cows are immunised with thirteen strains of enterotoxigenic E. coli, or ETEC, the leading bacterial cause of travellers’ diarrhoea worldwide. Their colostrum, the antibody-rich first milk produced after calving, then contains polyclonal antibodies directed against key ETEC virulence factors, including the O6 and O78 polysaccharides, colonisation factor antigens CFA/I and CFA/II, the coli surface antigens CS3, CS4 and CS6, and the heat-labile enterotoxin. When a traveller swallows the powder, these antibodies are meant to bind matching pathogens in the gut, blocking their ability to colonise the intestinal wall and secrete their toxins. Unlike probiotics or prebiotics, which act through diffuse effects on the microbiome, passive immunoprophylaxis is a precision weapon: pathogen-specific antibodies neutralising specific molecular targets.

Earlier laboratory evidence had been striking. In controlled human infection models, in which volunteers deliberately swallow a known dose of a single bacterial strain under close medical supervision, ETEC-targeting colostrum products achieved protective efficacy estimates ranging from roughly 77 to more than 90 percent. One study of an O78-targeting formulation reported protection between 76.7 and 90.9 percent after oral challenge, while a preparation aimed at the CFA/I colonisation factor shielded 90 percent of volunteers from a matching strain. Those numbers, generated under idealised conditions with a single homologous challenge strain, directly observed dosing and intensive monitoring, fuelled both commercial enthusiasm and scientific optimism. What they could not answer was whether the same protection would survive contact with the messy reality of travel.

The new trial, conducted between June 2022 and April 2025 by investigators from the Uniformed Services University of the Health Sciences and collaborators in the United Kingdom, was designed to answer exactly that question. The team enrolled 975 participants and randomised 850 to receive either ETEC hyperimmune bovine colostrum or a visually identical maltodextrin placebo. Participants were US and UK military personnel and civilian travellers aged 18 to 70, planning trips of at least ten consecutive days to regions with substantial diarrhoea risk, including South and Southeast Asia, Africa, Central and South America, the Middle East and parts of Eastern Europe. Most were young men, with a median age of 29, and nearly nine in ten were travelling for military purposes. Roughly half were prescribed doxycycline for malaria prophylaxis, a detail that would prove unexpectedly consequential.

Participants were given powdered study product in masked sachets, dosed at 600 milligrams twice daily before meals, beginning two days before arrival in a risk region and continuing for up to 20 days. The twice-daily schedule was a pragmatic modification of the manufacturer’s recommended three-times-daily caplet regimen, chosen to reduce pill burden and improve adherence during deployments with unpredictable meal times. Each participant kept a daily travel diary recording gastrointestinal symptoms and medication use, and self-collected stool samples on filter-paper cards before and after prophylaxis and during any diarrhoeal episodes. Those samples were shipped to a central laboratory and tested with a customised TaqMan Array Card, a multiplex polymerase chain reaction platform capable of detecting a broad panel of enteric pathogens simultaneously.

The primary outcome, registered prospectively as gut health disruption and corresponding to the standard clinical definition of travellers’ diarrhoea, required either three or more unformed stools within 24 hours, or two or more unformed stools accompanied by symptoms such as cramps, nausea, vomiting, fever or blood in the stool, or self-reported antibiotic treatment for diarrhoea. In the modified intention-to-treat population of 640 participants who took at least one dose in the risk area, diarrhoea struck 22.7 percent of the colostrum group and 26.3 percent of the placebo group. That translates to a relative protective efficacy of just 13.7 percent, with a 95 percent confidence interval spanning from minus 13.4 to 34.3 percent, well below the prespecified 35 percent threshold for clinical relevance and statistically indistinguishable from no effect at all. Per-protocol and incidence-rate analyses told the same story, and Kaplan-Meier curves for remaining diarrhoea-free were essentially superimposable.

The molecular detective work revealed why a single-pathogen weapon struggles in the field. Of 157 diarrhoea cases, 96 submitted usable stool samples, and 65 of those yielded at least one pathogen. Diarrhoeagenic E. coli dominated the detections, accounting for 91 percent, but ETEC itself was attributable to only about 17 percent of cases once background carriage in asymptomatic controls was accounted for. More striking still, nearly half of the pathogen-positive samples contained multiple organisms, with enteroaggregative E. coli, enteropathogenic E. coli, Campylobacter, Plesiomonas shigelloides and others frequently co-detected. Breakthrough ETEC infections occurred in both trial arms and included strains expressing colonisation factors both covered by the product, such as CS3, CS6 and the heat-labile toxin, and not covered, such as CS20 and CS21. The antigenic diversity of real-world ETEC, combined with polymicrobial infections and variable inoculum exposure repeated over weeks, simply overwhelmed a formulation calibrated to a narrow set of targets.

One secondary finding may shape future prevention research more than the primary result. In multivariable analysis, participants taking doxycycline for malaria chemoprophylaxis had roughly 30 percent lower risk of travellers’ diarrhoea, with a relative risk of 0.70 and a p-value of 0.01. Doxycycline is not recommended for diarrhoea prophylaxis because of widespread tetracycline resistance, side effects and concerns about selecting resistant gut flora, and the authors caution that the association is exploratory and non-causal, since the drug was not randomised and adherence was not systematically captured. Yet the signal, consistent with earlier observational work, suggests that concurrent antimicrobial exposures can act as powerful confounders and effect modifiers in prevention trials, and the investigators flag it as a critical variable for future studies to measure and control.

The trial’s limitations are worth weighing. The population was dominated by young military personnel, with UK troops often deployed to controlled training environments where diarrhoea attack rates were dramatically lower, at 7 percent versus roughly 29 percent among US military and civilian travellers, introducing heterogeneity that may have diluted treatment effects. Attrition between randomisation and follow-up removed about a fifth of participants, and stool submission was incomplete, reducing precision for pathogen-specific analyses. Adherence was assessed only through self-reported diaries, and the modified dosing schedule may have differed from the manufacturer’s intended pharmacokinetics, which remain poorly characterised for orally administered immunoglobulins that must survive stomach acid and digestive enzymes to act at the mucosal surface.

Nevertheless, the verdict is clear and consequential. The product was safe and well tolerated, with only four mild adverse events across both arms, but the biological activity demonstrated in challenge studies did not translate into meaningful field protection. The authors conclude that routine use of ETEC hyperimmune bovine colostrum for preventing travellers’ diarrhoea cannot be recommended on current evidence, and that interventions targeting a single pathogen are unlikely to succeed in settings where multiple enteropathogens circulate simultaneously. Future strategies, they argue, should pursue broader antigenic coverage, multi-pathogen combinations and rigorous field evaluation using clinically meaningful, pathogen-attributed outcomes. For the millions of travellers who swallow supplements in the hope of a symptom-free trip, the message is sobering: the cow’s antibodies, however cleverly engineered, are no match for the microbial chaos of the road.

Subject of Research: Field efficacy of ETEC hyperimmune bovine colostrum for preventing travellers' diarrhoea

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

Article References: Lalani, T., Copeland, N. K., Barton, J. Q., Schofield, C., Colombo, R. E., Troth, T., Defres, S., Rizzo-Pelley, M., Joya, C. A., Cerroni, M., Kuo, H.-C., Jian, N., Griffith, T., Burns, D., Porter, C. K., Rimmer, J., & Tribble, D. R. (2026). Enterotoxigenic Escherichia coli hyperimmune bovine colostrum for preventing travellers’ diarrhoea (TD): a randomised, double-blind, placebo-controlled trial. eClinicalMedicine, 100, Article 104249. https://doi.org/10.1016/j.eclinm.2026.104249

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104249

Keywords: travellers' diarrhoea, enterotoxigenic E. coli, hyperimmune bovine colostrum, passive immunoprophylaxis, randomised controlled trial, Travelan, ETEC, doxycycline, military health, TaqMan Array Card, polymicrobial infection, travel medicine