Six hundred forty-two students were enrolled in the study over 2 years. Seventy-three subjects (11.4%) were lost to follow-up; 25 (3.9%) did not provide a departure blood sample, and 48 (7.5%) did not come back to the clinic for follow-up. Thus, a total of 569 participants completed the study. As shown in Table , 403 students were female (70.8%), 516 were Caucasian (90.6%), and 57 were of Hispanic ethnicity (10.1%); the mean age at arrival was 35 years (SD, 14.4), and the mean length of stay in Mexico was 20 days (SD, 8.3). Two hundred fifty-five (44.8%) participants developed diarrhea while in Mexico. There were no significant differences in rates of diarrhea related to gender, race, or ethnicity; however, participants who developed diarrhea were younger (33 versus 36 years; P, 0.01) and stayed longer in Mexico (21 versus 19 days; P, 0.02) than those who remained asymptomatic during their trip. Those individuals who developed diarrhea while in Mexico had lower LT antibody geometric mean titers on arrival, although the difference was not statistically significant (28.75 versus 20.55; P, 0.07). One hundred twenty-one (21%) participants had a fourfold increase in LT-specific titers after their stay in Mexico, and travelers who developed diarrhea were more likely to seroconvert than subjects who remained healthy during travel (29.4% versus 14.6%; P < 0.0001).
Demographic characteristics of U.S. students participating in a prospective study of the occurrence of diarrhea during short-term stay in Mexico
Among the 255 participants who developed diarrhea, 173 (67.8%) provided a stool sample for microbiological analysis when ill. As shown in Table , 119 (69%) samples were positive for diarrheagenic E. coli by means of PCR; ETEC (ST or LT) was identified in 60 (35%) cases, EAEC was identified in 68 (39%) cases, 12 (7%) cases were found to be positive for EIEC, 49 (28%) cases were positive for EPEC, and EHEC was found in 24 (14%) cases. Other bacterial pathogens found by means of stool culture included five (3%) cases with Salmonella sp. and one (1%) case with Plesiomonas sp. All samples were negative for Campylobacter or Shigella. Parasites were found by ELISA in 2.9% of the travelers; three (2%) had Cryptosporidium sp. and two (1%) had Giardia sp. None of the samples tested positive for Entamoeba histolytica.
Etiology of TD and seroconversion to ETEC LT in U.S. travelers to Mexico
In terms of seroconversion, we observed that ETEC was more likely to be identified in the stools of travelers who seroconverted (53% versus 27%; P, 0.001), particularly when ETEC LT (29% versus 10%; P, 0.003) or ETEC LT/ST (20% versus 10%; P, 0.056) was found in the stools.
We then analyzed the effect that SNPs in IL-10 alleles had on diarrhea among ETEC LT seroconverters. As shown in Table , the relative risk (RR) for the development of TD was significantly higher in subjects with any of the alleles associated with high levels of IL-10 production. Participants possessing the −1082 G allele had a 1.24-fold increased risk of developing TD compared to those with the allele associated with low IL-10 production (95% confidence interval [CI], 1.02 to 1.51; P, 0.03). Participants with the −819 C allele had a 1.53-fold increased risk of TD (95% CI, 1.19 to 1.97; P < 0.0001), and participants with the −592 C allele had a 1.44-fold increased risk for TD (95% CI, 1.12 to 1.84; P, 0.004).
Analysis of alleles of subjects with and without TD among subjects showing seroconversion to ETEC LT
An analysis of the effect that SNPs in IL-10 haplotypes had on the risk of acquiring symptomatic diarrhea in subjects who seroconverted to ETEC LT is shown in Table . Participants with the high-IL-10 GCC haplotype had a significant higher risk for developing TD (71 versus 57%, RR, 1.85; 95% CI, 1.08 to 3.17; P, 0.02) than those with the ATA haplotype.
Influence of host IL-10 haplotype on TD occurrence in U.S. travelers to Mexico
In order to determine the relative contribution of the SNPs to diarrhea in the seroconverter group and to exclude confounding variables, we performed a multiple logistic regression analysis. The independent variables included in the model consisted of factors known to influence susceptibility to TD, such as gender, ethnicity, race, age on arrival, length of stay, and the three SNPs of the haplotype associated with a high, intermediate, or low level of IL-10 production. In this model, TD was considered the dependent variable. In the results of this multivariate analysis, the odds of having TD were significantly higher for participants having one of the SNPs associated with high IL-10 production (−819 C/C) (odds ratio, 6.8; P, 0.009).