Age-dependent pathogenic profiles of enterotoxigenic Escherichia coli diarrhea in Bangladesh

Abstract

Background: Age plays a significant role in susceptibility to enterotoxigenic Escherichia coli (ETEC) infections, yet the distribution of ETEC virulence factors across age groups remains understudied. This study investigated the differential pathogenic profiles ETEC across various age groups, emphasizing the importance of selecting potential ETEC antigens tailored to infection patterns in infants and adults in Bangladesh.

Methods: This study utilized the icddr,b's 2% systematic hospital surveillance data of diarrheal patients (n = 14,515) from 2017 to 2022 to examine the age-specific pathogenesis and clinical manifestations of ETEC infections.

Results: In total ETEC was identified in 1,371 (9.4%) of surveillance samples. ETEC-associated diarrhea was higher in children aged 0-2 years and decreased significantly in the 3-17 years age group. Among all ETEC cases, 56% were adults (p = 0.0079) with severe dehydration. Distinct age-specific distribution of ETEC toxin types and colonization factors (CFs) were observed: heat labile toxin (LT)-associated ETEC infections decreased with age (p < 0.0001), while heat stable toxin (ST)-associated-ETEC was prevalent across all ages. Adults exhibited significantly higher rates of ETEC diarrhea with strains secreting both types of toxins. A high prevalence of antimicrobial resistance among ETEC strains, particularly in pediatric cases, with significant resistance observed against commonly used antibiotics such as azithromycin and in line with similar age specific toxin profiles. The most common CFs were CFA/I, CS3, CS5, CS6, and CS21. CFA/I positive ETEC infection was more common in children (p < 0.001), while CS5 and CS6 were more common in adults (p < 0.0001).

Conclusion: The findings provide valuable insights into ETEC epidemiology, pathogenesis, and clinical manifestations. These observations imply that age-related differences in host-pathogen interactions exist for ETEC infections and this may influence the development of targeted vaccines or therapeutics and use in specific populations.

Keywords: AMR; ETEC; age; colonization factors (CFs); diarrhea; toxins.

Figure 1

Enterotoxigenic Escherichia coli (ETEC) diarrhea and its distribution in different age groups. (A) Rate of ETEC diarrhea in different years (2017–2022) among diarrheal patients, (B) distribution of ETEC diarrhea in different age groups in different years and (C) comparison between the rate of ETEC diarrhea in different age groups. Bars indicate Mean + SEM of the percentage of ETEC in any age group among total ETEC cases in five different years. Statistical analysis was performed between 0 and 6 months versus other age groups using the Mann–Whitney U test. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001; ns, not significant; p > 0.05.

Figure 2

Distribution of ETEC enterotoxins in different years and age groups. (A) ETEC toxin (LT, ST, and LT + ST) profiles in different years. Statistical analysis was performed between LT vs. ST, LT vs. LT + ST and ST vs. LT + ST using the Chi-square test. (B) ETEC toxin (LT, ST, and LT + ST) profiles in different age groups. Statistical analysis was performed between 0 and 1 years versus other age groups using the Chi-square test. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001; ns, not significant; p > 0.05.

Figure 3

Enterotoxigenic Escherichia coli expressing different colonization factors (CFs) isolated from diarrheal patients. (A) Frequency of ETEC expressing 13 different colonization factors, (B) frequency of CF + ve and CF−ve ETEC across diarrheal age group patients and (C) distribution of prevalent CFs (CFA/I, CS3, CS5, CS6, and CS21) in different age group. Bars represent the frequency of CFs among all ETEC cases. Statistical analysis was performed between 0 and 1 years versus other age groups using the Chi-square test. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001; ns, not significant; p > 0.05.

Figure 4

Enterotoxigenic Escherichia coli (ETEC) colonization factors (CFs) and its relation to toxins. (A) Toxin profiles of CFs positive and negative ETEC and (B) Association of prevalent CFs (CFA/I, CS3, CS5, CS6, CS17 and CS21) with carrying three different toxin types.

Figure 5

Dehydration status of ETEC diarrheal patients in different age groups.

Figure 6

Antimicrobial resistant (AMR) profile of ETEC. (A) Resistance profile of ETEC strains to ampicillin (AMP), azithromycin (AZM), ciprofloxacin (CIP), ceftriaxone (CRO), doxycycline (DOX), erythromycin (ERY), mecillinam (MEL), nalidixic acid (NAL), norfloxacin (NOR), streptomycin (STR), sulfamethoxazole-trimethoprim (SXT) and tetracycline (TE), isolated from diarrheal patients in 2018 and 2022. (B) Comparison of ETEC AMR resistance profile in <5 years and ≥5 years old diarrheal patients. (C) Toxins profile of azithromycin resistant ETEC strains. (D) Differences in toxin profiles of azithromycin resistant ETEC isolated from <5 years and ≥5 years old diarrheal patients and (E) colonization factors profile of azithromycin resistant ETEC strains. Statistical analysis was performed between <5 years and ≥5 years using the Chi-square test. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001.