During October 2018–April 2023, a total of 512 participants who met the acute diarrhea or acute gastroenteritis case definitions were enrolled in the GTD study in Honduras (21%), Peru (3%), Egypt (3%), Djibouti (39%), Nepal (26%), and Georgia (8%) (Table 1). The average participant age was 34 (SD 12) Years. Among participants, 35% were female, 59% male, and 6% unidentified sex. Participants were primarily born in North America (45%) or Europe (22%); however, that did not necessarily imply country of origin before travel and enrollment in the study. Most participants were US military service members (58%) or tourists (20%) (Table 1).

Across all sites, 403 (79%) of 512 samples tested positive for >1 pathogens, identifying a total of 867 pathogens (Table 2). Of the 403 positive samples, 79.7% were single infections, 19.6% were double infections, and 0.7% were triple infections. No samples were positive for all 4 pathogen groups (Table 2).

Figure 2

Figure 2. Enteric pathogens detected in a study of etiology and epidemiology of travelers’ diarrhea among US military personnel and adult travelers, 2018–2023. The study included travelers from the following countries: A)...

E. coli was the most common pathogen identified in Peru (67%), Nepal (77%), Georgia (75%), Honduras (69%), Egypt (82%), and Djibouti (70%), whereas Salmonella was the least identified in all countries except Egypt (6%) and Djibouti (6%) (Figure 2). Coinfection analysis identified E. coli in a higher number of coinfections than any of the other 3 pathogen groups across all 6 countries (Appendix Figure 2).

ETEC colonization factors were identified from ETEC isolates recovered from samples collected in 3 countries: Honduras, Djibouti, and Nepal (Table 3). In total, 106 isolates were tested. The most identified ETEC colonization factors were CS3 (25%) and CS21 (25%), as well as CS2 (18%) and CS6 (15%) (Table 3). The least identified ETEC colonization factors were CS17/19 (1%) and CS14 (2%). Colonization factors CS5 and CS7 were not identified from any country (Table 3).

This study describes the etiology and epidemiology of TD among US military and adult civilian travelers across South and Central America, Northern and sub-Saharan Africa, Southern Asia, and Eastern Europe. We found E. coli was the leading (67%–82%) etiology of TD across global surveillance sites (Figure 2). ETEC was the most identified E. coli pathotype in 5 of 6 countries (Figure 2). Our investigation also identified Campylobacter, Salmonella, and norovirus as TD etiologies, although with lower proportions than observed for E. coli (Figure 2). Those data on TD disease etiology are consistent with the literature discussing both military and civilian populations throughout the globe, indicating bacterial pathogens are the leading causative agents of disease (4,12–15). Our study data suggest E. coli, specifically pathotypes ETEC, EAEC, and EPEC, are the leading causes of TD in Southern and Central Asia, Northern Africa, the Middle East, sub-Saharan Africa, and Central and South America (Figure 2), which is consistent with the GTD study data for all 6 surveillance countries (12).

The highest rates of Campylobacter and Salmonella associated with TD are found in Southeast and East Asia, and high rates are also found in Southern and Central Asia (12). The GTD study did not include a surveillance site in Southeast or East Asia, but among included countries, we identified the highest rates of Campylobacter in Peru (20%) and Nepal (16%) and the highest rates of Salmonella in Egypt (6%) and Djibouti (6%) (Figure 2).

Previous work by the GTD study found E. coli (including all pathotypes tested for) in 42% of the cases enrolled during 2013–2018 (n = 410) (4), which is lower than the cases enrolled during 2018–2023 (n = 512; 72%) (Figure 2). That increase may represent improved laboratory diagnostic methods for E. coli pathotypes; samples collected during 2013–2018 were analyzed by conventional PCR, whereas samples collected during 2018–2023 were analyzed by rPCR. Of note, case numbers of Salmonella and Campylobacter were similar across study periods despite updates to laboratory protocols (Figure 2) (4).

Vaccines used prophylactically to prevent TD have the potential to reduce disease incidence and severity; however, no vaccines for E. coli, Campylobacter, or Shigella are currently licensed by the US Food and Drug Administration. ETEC vaccine candidates currently under investigation are based on antitoxin or anticolonization factor immunity. Approximately 50%–80% of all colonization factor-positive clinical ETEC isolates found within the general population encode colonization factors A/I, CS3, CS5, and CS6 (16), making them potential vaccine targets (17,18). In this study, CS6, CS3, CS2, and CS21 were the most identified colonization factors across the geographic regions tested; however, colonization factor A/I was only identified in 3% of isolates and CS5 was not identified in any isolate (Table 3). Our results combined with the efforts of the Global Emerging Infections Surveillance network of global surveillance laboratories, including maintaining repositories of clinical samples collected throughout the world, may help guide future vaccine development and therapeutics for TD and other diseases of interest to the US military and global health.

One limitation of this study is that we considered the disease etiology proportions from Egypt (n = 17), Peru (n = 15), and Georgia (n = 40) unstable because of low enrollment; we recommend interpreting the results with caution. In addition, selection bias may have influenced results because of site accessibility and the potential that travelers with mild TD are less likely to seek care than are travelers with severe TD, which might have affected the pathogens observed.

Moving forward, we recommend the GTD study expand to include antimicrobial resistance (AMR) characterization of bacterial pathogens identified from TD cases by using antimicrobial susceptibility testing and next-generation sequencing technologies to identify genetic markers of AMR and virulence factors of enteric bacterial pathogens. Those combined efforts could provide insight on the effects of AMR across unique global regions, enhance antimicrobial stewardship to limit changes in drug resistance patterns in enteric pathogens, and improve military health readiness through targeted prevention and treatment interventions for TD.