Intestinal immunoglobulin a response to naturally acquired enterotoxigenic Escherichia coli in US travelers to an endemic area of Mexico.

BACKGROUND: Simple methods for detecting secretory immunoglobulin A (sIgA) immune responses following natural enteric infection and oral immunization are needed. METHODS: Fourteen students from the United States acquiring enterotoxigenic Escherichia coli (ETEC) diarrhea in Mexico were studied for fecal immunoglobulin A (IgA) response to their homologous infecting ETEC and to heat-labile (LT) toxin of ETEC using Dot-Blot microfiltration and enzyme-linked immunosorbent assay (ELISA) methods. Paired stool samples were collected on the day of presentation and 5 days later. RESULTS: Twelve of 14 (86%) patients with ETEC diarrhea (5 heat-stable [ST]/LT positive, 4 LT-only, and 5 ST-only) developed sIgA antibodies directed against their homologous ETEC and 6 (66%) of the 9 patients harboring ST/LT or LT-only strains developed sIgA LT-antibody responses. Single fecal samples from 9 healthy controls were negative for ETEC specific antibodies. CONCLUSIONS: Patients with diarrhea due to noninvasive ST/LT ETEC and LT ETEC commonly produce a specific sIgA antibody response early in the illness. We feel that the methods employed will be useful to detect antibodies during natural infection by enteric pathogens and following oral enteric vaccine administration.

Rifaximin versus ciprofloxacin for the treatment of traveler's diarrhea: a randomized, double-blind clinical trial.

Rifaximin is a poorly absorbed rifamycin derivative under investigation for treatment of infectious diarrhea. Adult students from the United States in Mexico and international tourists in Jamaica were randomized to receive either rifaximin (400 mg twice per day) or ciprofloxacin (500 mg twice per day) for 3 days, following a double-blinded model, from June 1997 to September 1998. A total of 187 subjects with diarrhea were studied. Time from initiation of therapy to passage of last unformed stool was comparable for those receiving rifaximin or ciprofloxacin (median, 25.7 hours versus 25.0 hours, respectively). There was no significant difference in the proportion of subjects in the 2 groups with respect to clinical improvement during the first 24 hours (P=.199), failure to respond to treatment (P=.411), or microbiological cure (P=.222). The incidence of adverse events was low and similar in each group. Rifaximin is a safe and effective alternative to ciprofloxacin in the treatment of traveler's diarrhea.

Enteroaggregative Escherichia coli as a major etiologic agent in traveler's diarrhea in 3 regions of the world.

Enteroaggregative Escherichia coli (EAEC) has been reported to cause traveler's diarrhea and persistent diarrhea in children in developing countries and in immunocompromised patients. To clarify the prevalence of EAEC in traveler's diarrhea, we studied 636 US, Canadian, or European travelers with diarrhea: 218 in Guadalajara, Mexico (June--August 1997 and 1998), 125 in Ocho Rios, Jamaica (September 1997--May 1998), and 293 in Goa, India (January 1997--April 1997 and October 1997--February 1998). Stool samples were tested for conventional enteropathogens. EAEC strains were identified by use of the HEp-2 assay. EAEC was isolated in 26% of cases of traveler's diarrhea (ranging from 19% in Goa to 33% in Guadalajara) and was second only to enterotoxigenic E. coli as the most common enteropathogen in all areas. Identification of EAEC reduced the number of cases for which the pathogen was unknown from 327 (51%) to 237 (37%) and explained 28% of cases with unknown etiology. EAEC was a major cause of traveler's diarrhea in 3 geographically distinct study areas.

Risk and aetiology of diarrhoea at various tourist destinations.

Almost two of three tourists developed traveller's diarrhoea during 2-week stays at high-risk destinations. Large differences in infection rates between hotels were seen. Patients with milder forms of diarrhoea show a similar chronology to those more severely affected. Although enterotoxigenic Escherichia coil was the most frequent cause, viral pathogens were detected more often than in other studies.

Intestinal secretory immunoglobulin A response to enteroaggregative Escherichia coli in travelers with diarrhea.

We examined stool samples from travelers for secretory immunoglobulin A (sIgA) to enteroaggregative Escherichia coli (EAEC) during episodes of acute diarrhea. Ten paired samples from 10 patients with diarrhea caused by EAEC were examined for the presence of specific sIgA by dot blot and Western blot immunoassays. Five samples were positive by dot blotting, and two samples were positive by Western blotting.

Characterization of enterotoxigenic Escherichia coli strains in patients with travelers' diarrhea acquired in Guadalajara, Mexico, 1992-1997.

The relationship between enterotoxigenic Escherichia coli (ETEC) and travelers' diarrhea was examined in a high-risk area in 1992-1997. Toxin patterns, colonization-factor antigens (CFAs), and in vitro antimicrobial susceptibility were determined. In total, 928 US students with diarrhea acquired in Guadalajara, Mexico, were screened for enteric pathogens. Diagnosis of ETEC infection was done with oligonucleotide probes. ETEC was isolated in 19.9% of the travelers with diarrhea. CFAs were identified in 51% of the ETEC strains. The highest CFA frequency was observed among heat-stable isolates. Ampicillin, furazolidone, and sulfisoxazole resistance of ETEC increased during the study period. ETEC isolation rates and CFA patterns varied little during the 6 years of the study, which has implications for immunoprophylactic strategies. The finding that differences in the results of ribotyping and plasmid analysis change over time suggests that multiple strains of ETEC were responsible for the illness in the region studied.

Etiology of travelers' diarrhea on a Caribbean island.

BACKGROUND: Between December 6, 1994 and March 10, 1996, a study of the etiology of diarrhea was carried out among 332 travelers to five all-inclusive hotels in Negril, Jamaica. METHODS: Stool specimens were collected and sent to Montego Bay for laboratory analysis. Escherichia coli strains isolated at the Jamaican laboratory were sent to Houston for toxin testing. RESULTS: A recognized enteropathogen was found in 118 of the 332 (35.5%) cases. Enterotoxigenic E. coli (ETEC) were the most commonly identified pathogen (87/332; 26.2%) followed by Salmonella (4.2%) and Shigella (4.2%). Clustering of etiologically defined cases was studied at each hotel. A cluster was defined as 2 or more cases with the same pathogen identified in the same hotel within 7 days. In the 3 hotels with the highest number of cases of diarrhea, enteropathogens were part of a cluster in 65 of 99 cases (65.7%) of diarrhea of which an etiologic agent was identified. In the other 2 hotels, only 4 of 20 cases (20%) occurred in clusters. CONCLUSIONS: A total of 25 clusters of travelers' diarrhea cases was detected at the five hotels during the study period. Seventeen of 25 (68%) ETEC isolations occurred as part of a clustering of diarrhea cases. The largest outbreak of pathogen-identified diarrhea consisted of 7 cases of ETEC producing both heat-stable and heat-labile enterotoxins. In the Jamaican hotels with all inclusive meal packages most diarrhea cases occurred as small clusters, presumably as the result of foodborne outbreaks.

Serum antibody response induced in mice after oral administration of three different antigens of enterotoxigenic Escherichia coli in enteric coated microparticles.

BACKGROUND: Gastric digestion of these antigens plays an important role, decreasing the ability to deliver antigens to the gut-associated lymphoid tissue. To overcome this obstacle, microencapsulated antigens from enterotoxigenic Escherichia coli (ETEC) were evaluated for oral immunization of mice. METHODS: Four groups of 10 each received 3 series of 3 doses each of (1) B subunit of cholera toxin (CTB), similar to heat-labile toxin of ETEC, (2) formalin-killed whole cell ETEC H10407 (FK-ETEC), (3) crude preparation of colonization factor antigen I (CFA/I), or (4) placebo. Serum antibody was measured on day 0 and 60 by ELISA. RESULTS: In group 1 a CTB antibody response was induced in all mice, 3 with 1:105 titer and 7 with 1:106. These antibodies neutralized cholera toxin-induced steriodogenesis of Y-1 adrenal cells. In group 2, 8 mice developed a whole H10407 bacteria antibody titer of 1:100, one 1:200 and one showed no immune response. In the same group, an anti-CFA/I response was observed in 6 mice and anti-LPS in 4 mice as determined by Western blot. All mice in group 3 showed > 1:104 anti-CFA/I antibody titer. Group 4 mice did not develop an immune response to any ETEC antigens. CONCLUSIONS: Microencapsulation appears to be a suitable approach for oral vaccination against ETEC and Vibrio cholerae.

Markers of enteric inflammation in enteroaggregative Escherichia coli diarrhea in travelers.

As part of a traveler's diarrhea study carried out in Guadalajara, Mexico, and Goa, India, we conducted a case control study to evaluate fecal markers of enteric inflammation in three groups. Forty-five cases of enteroaggregative Escherichia coli (EAEC) diarrhea were compared to 56 controls with enterotoxigenic E. coli (ETEC) diarrhea, and 126 controls with diarrhea without identifiable pathogens. For EAEC cases we found fecal leukocytes, occult blood, and lactoferrin in 13 (28.9%), 14 (31.1%), and 27 (60.0%) patients, respectively; for ETEC controls they were 15 (26.8%), 16 (28.6%), and 15 (26.8%) respectively; and for patients without identifiable pathogens 19 (15.1%), 34 (27.0%) and 27 (21.4%) were seen for the presence of a positive fecal lactoferrin test in EAEC cases was statistically significant compared to both control groups. The study provides evidence that EAEC infection is associated with an intestinal inflammatory response.

Improved detection of enterotoxigenic Escherichia coli among patients with travelers' diarrhea, by use of the polymerase chain reaction technique.

This study sought to determine whether a specific polymerase chain reaction (PCR) for enterotoxigenic Escherichia coli (ETEC) toxins after chaotropic extraction of DNA from stool would increase the detection of ETEC over that of conventional oligonucleotide probe hybridization of 5 E. coli colonies per stool sample (a standard method). By DNA hybridization, 29 (21%) of 140 patients were positive for ETEC, and 59 (42%) of 140 were positive for ETEC when PCR was used. Sensitivity of the PCR assay was confirmed through spiked stool experiments to be approximately 100-1000 ETEC colonies per sample. Specificity of the assay was determined by showing an absence of ETEC by the PCR technique in a subgroup of 48 subjects and by confirming the presence of ETEC DNA of positive samples by dot blot procedure. PCR technique detected significantly more ETEC infections in these subjects than did the hybridization method (P<.0001).

Enteroaggregative Escherichia coli as a cause of traveler's diarrhea: clinical response to ciprofloxacin.

The purpose of this study was to determine the role of enteroaggregative Escherichia coli (EAEC) in the development of traveler's diarrhea and the clinical response of patients with EAEC diarrhea following treatment with ciprofloxacin. Sixty-four travelers with diarrhea and no other recognized enteropathogen were enrolled in treatment studies in Jamaica and Mexico from July 1997 to July 1998. EAEC was isolated from 29 travelers (45.3%). There was a significant reduction in the duration of posttreatment diarrhea in the 16 patients treated with ciprofloxacin, as compared with that in the 13 patients who received placebo (mean of 35.3 versus 55.5 hours; P = .049). There was a nonsignificant reduction in the mean number of unformed stools passed during the 72 hours after enrollment in the ciprofloxacin-treated group (5.6), as compared with that in the placebo group (7.5) (P = .128). This study provides additional evidence that EAEC should be considered as a cause of antibiotic-responsive traveler's diarrhea.

Epidemiology, etiology, and impact of traveler's diarrhea in Jamaica.

CONTEXT: Traveler's diarrhea (TD) can incapacitate travelers. Characteristics of TD could be helpful in identifying individuals who might benefit from a vaccine against TD. OBJECTIVE: To determine epidemiology, etiology, and impact of TD in Jamaica. Design Two-armed, cross-sectional survey conducted between March 1996 and May 1997. SETTING: Sangster International Airport and 10 hotels in Montego Bay area, Jamaica. SUBJECTS: To investigate epidemiology and impact, 30369 short-term visitors completed a questionnaire just before boarding their homebound aircrafts. To investigate etiology, 322 patients (hotel guests) with TD provided stool samples. MAIN OUTCOME MEASURES: Attack and incidence rates of reported diarrhea and of classically defined TD (> or =3 unformed stool samples in 24 hours and > or =1 accompanying symptom), incapacity, risk factors, and etiology. RESULTS: The attack rate for diarrhea was 23.6% overall, with 11.7% having classically defined TD. For a mean duration of stay of 4 to 7 days, the incidence rate was 20.9% (all TD) and 10.0% (classic TD). Among airport respondents, the incapacity lasted a mean of 11.6 hours. Less than 3% of all travelers avoided potentially high-risk food and beverages. The most frequently detected pathogens were enterotoxigenic Escherichia coli, Rotavirus, and Salmonella species. CONCLUSIONS: A realistic plan for reducing TD is needed. Preventive measures such as the improvement of hygienic conditions at the destination, and/or the development of vaccines against the most frequent pathogens associated with TD may contribute toward achieving this goal.

Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States.

BACKGROUND: Few data have been published recently on the etiology of outpatient pediatric diarrhea in the US. METHODS: We determined the etiology of acute, nondysenteric diarrhea among 147 children between 2 and 11 years old presenting to 9 outpatient clinics in various regions of the US between August, 1991, and August, 1993. Enteropathogens were sought by conventional laboratory methods. The various diarrheagenic Escherichia coli were sought. RESULTS: A recognized etiologic agent was detected in the stools of 89 (60.5%) children and 15 (10) patients had multiple agents detected. Rotavirus was found in 43 (29.3%) of the children, with a spring and winter peak in occurrence. Giardia lamblia was identified in 22 (15%) cases with a spring peak. HEp-2 cell-adherent E. coli were found in 15 (10.2%). Other agents found included: enteric adenovirus in 7 (4.8%); Salmonella in 5 (3.4%); enterohemorrhagic E. coli in 5 (3.4%); enteropathogenic E. coli in 2 (1.4%); enterotoxigenic E. coli in 2 (1.4%); Entamoeba histolytica in 1 (0.70%); and Campylobacter jejuni in 1 (0.7%). CONCLUSIONS: In addition to the presence of conventional enteropathogens, diarrheagenic E. coli (HEp-2 cell-adherent E. coli, enterohemorrhagic E. coli, enteropathogenic E. coli and enterotoxigenic E. coli) were associated with endemic pediatric diarrhea in the US.

HIV-1 seroprevalence in Zambian patients with acute diarrhea: a community-based study.

The seroprevalence of HIV-1 in sub-Saharan African patients with diarrhea in the community remains largely unknown. We present the findings of a 2-month study that we undertook to ascertain the seroprevalence of HIV-1 in Zambian patients presenting with acute diarrhea in a community-based health center. A total of 256 patients with diarrhea and 140 apparently healthy controls was seen. Of the patients with diarrhea, 161 were < 16 years old and 95 were adults. Most children with diarrhea were < 6 years old (147 of 161; 91%). Overall, 81 of 256 (32%) patients with diarrhea were HIV-1-seropositive. When results from children < 18 months old and possibly having maternal anti-HIV-1 antibodies were excluded, 64 of 172 (37%) patients with diarrhea were HIV-seropositive. Rates of HIV-1 seropositivity for patients with diarrhea were significantly higher than were rates for diarrhea-free controls (p < .001 for both the total population; odds ratio [OR], 95% confidence interval [CI], 1.42 < 2.48 < 4.35) and population > 18 months old (OR, 95% CI, 1.54 < 2.90 < 5.49). Among children between 18 months and 5 years old, 14 of 63 (22%) were HIV-1-seropositive compared with 8 of 62 (13%) without diarrhea (p > .05, not significant). Moreover, 49 of 95 (52%) adults with acute diarrhea were HIV-1-seropositive compared with 10 of 44 (23%) healthy adult controls (p < .003; OR, 95% CI, 1.51 < 3.62 < 8.87). No significant differences were found in HIV-1 seroprevalence rates between males and females in all age groups. These data show a close association between acute diarrhea and HIV seropositivity in Zambian adults in the community.

PIP: Chronic diarrhea is a common clinical presentation of HIV infection worldwide and a major cause of mortality in cohorts of HIV-infected African children. Findings are presented from a study of HIV-1 seroprevalence among Zambian patients presenting to George Health Center, a community-based health center northwest of center Lusaka, with acute diarrhea during March-April 1994. 256 patients with diarrhea and 140 apparently healthy controls participated in the study. Of the patients with diarrhea, 161 were under 16 years old and 95 were adults. 147 (91%) of the children with diarrhea were under age 6 years. Overall, 81 of the 256 (32%) patients with diarrhea were HIV-1-seropositive. Excluding results from infants under age 18 months who may have had maternal anti-HIV-1 antibodies, 64 of 172 (37%) patients with diarrhea were HIV-seropositive. Among children aged 18 months to 5 years, 14 of 63 (22%) were HIV-1-seropositive compared with 8 of 62 (13%) without diarrhea. 49 of 95 adults with acute diarrhea were HIV-1-seropositive compared with 10 of 44 healthy adult controls. No significant differences were found in HIV-1 seroprevalence rates between males and females in all age groups. These data point to a close association between acute diarrhea and HIV seropositivity in this research setting.

Rifaximin: a nonabsorbed antimicrobial in the therapy of travelers' diarrhea.

BACKGROUND/AIMS: Bacterial enteropathogens, the major cause of travelers' diarrhea, are customarily treated with antibacterial drugs. Rifaximin, a nonabsorbed antimicrobial was examined as treatment for travelers' diarrhea. METHODS: A randomized, prospective, double-blind clinical trial was carried out in 72 US adults in Mexico. Patients with acute diarrhea received one of three doses of rifaximin (200, 400 and 600 mg t.i.d.) or trimethoprim/sulfamethoxazole (TMP/SMX, 160 mg/800 mg b.i.d.) for 5 days. Results were compared with data from 2 placebo-treated historical control populations. RESULTS: The shortest duration of treated diarrhea was seen in the group receiving 200 mg rifaximin t. i.d (NS). Clinical failure to respond to treatment occurred in 6 of 55 (11%) rifaximin-treated subjects versus 5 of 17 (29%) of TMP/SMX-treated subjects (NS). Sixteen of twenty (80%) of the enteropathogens isolated from the rifaximin-treated subjects and 7 of 7 (100%) from the TMP/SMX group were eradicated by treatment (NS). Sixteen of twenty-four (67%) enteropathogens identified were susceptible to TMP and all 24 were inhibited by

HEp-2 cell-adherent Escherichia coli and intestinal secretory immune response to human immunodeficiency virus (HIV) in outpatients with HIV-associated diarrhea.

HEp-2 cell-adherent Escherichia coli and the human immunodeficiency virus (HIV) itself have recently been incriminated as causes of chronic HIV-associated diarrhea. This study sought to determine the prevalence of these two agents among HIV-infected patients with diarrhea in an outpatient setting in the United States and to compare their prevalence to that of other commonly recognized enteropathogens known to be present in this population. HEp-2 cell-adherent E. coli was found in 20 of 83 (24.1%) patients with diarrhea. A diffuse pattern of adherence was the most common, found in 14 of 20 (70%) patients, followed by a localized adherence pattern (6 of 20; 30%). An intestinal secretory immune response against the p24 antigen of HIV was found in 9 of 34 (27.5%) patients with HIV-associated diarrhea. The following pathogens or products were also detected in lower frequencies: Cryptosporidium spp. (10.8%), Clostridium difficile toxin (8.8%), microsporidia (6%), Isospora belli (3.6%), Blastocystis hominis (2.4%), Giardia spp. (1.2%), Salmonella spp. (1.2%), and Mycobacterium spp. (1.2%). The role of HEp-2 cell-adherent E. coli and HIV enteric infections in patients with HIV-associated diarrhea deserves further study.