Travel to developing countries is increasing annually with travelers diarrhea (TD) the most common health problem and Enterotoxigenic E. coli (ETEC) the most common pathogen encountered by travelers from developed countries during such trips.MoreTravel to developing countries is increasing annually with travelers diarrhea (TD) the most common health problem and Enterotoxigenic E. coli (ETEC) the most common pathogen encountered by travelers from developed countries during such trips. Objectives here were to study TD natural history in Guatemala (GU) and Mexico (MX), develop clinically important incapacitating illness definitions, and reanalyze a Phase III oral killed ETEC vaccine (OKV) trial.
Methods. Rates and odds of TD in Antigua, GU and Cuernavaca, MX were calculated, etiology under active and passive surveillance compared, tools to evaluate candidate vaccines developed and evaluated, and protective efficacy of an OKV against moderate and severe TD definitions determined. Results. TD was temporally stable, with higher rates in rainy versus dry seasons and in travelers to GU versus MX.
ETEC was the most common pathogen isolated with a high proportion of those infected experiencing TD. Heat-Stable Toxin (ST) and Heat-Labile(LT)+ST Toxin expressing ETEC were more virulent compared to LT ETEC. ST ETEC expressing coli surface antigen CS6 was the most common ETEC strain isolated. No difference in etiology was found under passive versus active surveillance. Key features of incapacitating ETEC TD were ≥6 loose stools in 24 hours along with moderate to severe abdominal pain and nausea. Volunteer challenge model (VCM) infection produced illness comparable to natural infection.
Vaccine recipients who developed cholera toxin B-subunit (CTB) antibody titer at or above the vaccine group median titer at arrival had reduced odds of moderate-severe TD due to ETEC with antigens homologous to the OKV.
These subjects also had reduced odds of campylobacter infection versus placebo recipients. Conclusions. Universal ETEC vaccines should include multiple Colonization Factor Antigens. CTB Antibody titer correlating with protection from infection by pathogens expressing cross-reacting antigens should continue to be evaluated. Use of VCM in evaluation and selection of candidate ETEC vaccines should continue. CTB antibody titer post-vaccination may serve as a marker for vaccine field efficacy.
And finally, based on safety and performance under moderate to severe TD definitions further development of the OKV is warranted.