Pablo C. Okhuysen

Post-Diarrhea Chronic Intestinal Symptoms and Irritable Bowel Syndrome in North American Travelers to Mexico

OBJECTIVES:Irritable bowel syndrome (IBS) has been reported to complicate bacterial diarrhea. Because of the frequency of international travel and the common occurrence of bacterial diarrhea, we studied the occurrence of chronic gastrointestinal complaints and post-diarrhea IBS in North U.S. travelers to Mexico.METHODS:One hundred and sixty-nine healthy students were followed prospectively for 5 wk for the occurrence and etiology of diarrhea while studying for 5 wk in Mexico. Subjects recorded their symptoms during travel and completed a gastrointestinal symptom questionnaire 6 months after returning to the United States to determine the presence of IBS using the Rome II criteria.RESULTS:Ninety-seven (57%) subjects returned a completed questionnaire. Sixty-one (63%) developed diarrhea while in Mexico, mostly due to enterotoxigenic and enteroaggregative Escherichia coli. Six months after travel the following chronic symptoms were reported: loose stools, abdominal pain, and fecal urgency in 17 (18%), 17 (18%), and 9 (9%) respectively. Of the 60 patients surveyed who had acquired diarrhea in Mexico, 7 (11%) met the criteria for IBS 6 months later of which 6 (10%) were newly diagnosed. No identified pathogen in the initial illness was associated with the development of IBS.CONCLUSIONS:Chronic gastrointestinal complaints including IBS are common in returning travelers having experienced diarrhea. Postinfectious complications of travelers diarrhea require further study for etiology and strategy for prevention.

Genetic Susceptibility to Enteroaggregative Escherichia coli Diarrhea: Polymorphism in the Interleukin-8 Promotor Region

Enteroaggregative Escherichia coli (EAEC) infection can be identified in 26% of travelers with diarrhea and is associated with fecal interleukin (IL)-8 production. We hypothesized that single-nucleotide polymorphisms (SNPs) in the IL-8 gene are associated with EAEC-related symptoms. Fecal IL-8 production and IL-8 SNPs at 5 loci were identified in 69 US students who remained in Mexico for 5 weeks; 23 subjects had EAEC-associated diarrhea, 7 were asymptomatic EAEC carriers, 22 had nonspecific diarrhea, and 17 were asymptomatic without an enteropathogen. The chances of having EAEC-associated diarrhea were significantly increased among those with the AA genotype at the -251 position (odds ratio [OR], 208.51; 95% confidence interval [CI], 28.5-1525.36) and among those with AT genotype (OR, 14.3; 95% CI, 1.98-105.74), compared with those with the TT genotype at the -251 position. Among subjects with EAEC-associated diarrhea, the AA genotype at the -251 position produced greater concentrations of fecal IL-8 than those with the AT or TT genotype (P=.0053). In the present study, the AA genotype at the -251 position was associated with the occurrence of EAEC-associated diarrhea and increased levels of fecal IL-8.

Traveler's Diarrhea Due to Intestinal Protozoa

Intestinal protozoa account for a minority of cases of acute travelers diarrhea, but they are common pathogens in travelers who experience protracted diarrhea during or after travel. Evaluation of the traveler with chronic diarrhea should include a careful examination for typical infecting organisms, such as Giardia and Entamoeba species, as well as for emerging parasites, such as Cryptosporidium species, Cyclospora species, and microsporidia. The microbiology, epidemiology, clinical presentation, and treatment of the most common intestinal parasites found in travelers are presented in this minireview.

The Antibody Response to 27-, 17-, and 15-kDa Cryptosporidium Antigens following Experimental Infection in Humans

Previous studies have suggested that persons infected with Cryptosporidium parvum develop antibody responses to 27-, 17-, and 15-kDa C. parvum antigens. Studies of volunteers infected with Cryptosporidium species provided an opportunity to evaluate the relationship between antibody reactivity to these antigens and infection outcome. As monitored by immunoblot, increases in specific antibody reactivity were more prevalent among volunteers who developed signs and symptoms of cryptosporidiosis (n = 11) than among asymptomatic infected (n = 7; P = .05) or oocyst-negative volunteers (n = 11; P = .02). Volunteers with preexisting IgG antibody to the 27-kDa antigen excreted fewer oocysts than volunteers without this antibody (P = .003). IgG reactivity to the 17-kDa antigens and IgM reactivity to the 27-kDa antigens were higher at day 0 for asymptomatic infected persons than for those who developed symptoms (P = .03 and P = .04, respectively). These results suggest that characteristic antibody responses develop following C. parvum infection and that persons with preexisting antibodies may be less likely to develop illness.

Enteroaggregative Escherichia coli Is a Cause of Acute Diarrheal Illness: A Meta-Analysis

BACKGROUND Conflicting studies exist regarding the role of enteroaggregative Escherichia coli (EAEC) as a cause of acute diarrheal illness. The objective of this meta-analysis was to determine whether identification of EAEC in stool samples is associated with acute diarrheal illness among different subpopulations, by geographic area. METHODS A comprehensive search of electronic bibliographic databases (Medline and PubMed) from August 1985 to January 2006, as well as a search of conference proceedings, references of articles, and contacts with investigators of EAEC, yielded 354 studies. RESULTS Forty-one studies (12%) that met the selection criteria (i.e., that examined the association between acute diarrheal illness and the excretion of EAEC among different subpopulations) were included. In this meta-analysis, presence of EAEC identified with the HEp-2 cell adherence assay was found to be significantly associated with acute diarrheal illness among children residing in developing regions (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.36-1.83) and industrialized regions (OR, 1.23; 95% CI, 1.03-1.48), adults with human immunodeficiency virus infection residing in developing regions (OR, 6.43; 95% CI, 2.91-14.16), adults residing in developing regions (OR, 7.15; 95% CI, 1.96-26.04), and international travelers to developing regions (OR, 6.72; 95% CI, 2.62-17.20). A limited number of studies were available that examined the role of EAEC identified by its virulence genes by a DNA probe. CONCLUSIONS On the basis of this meta-analysis, we conclude that EAEC is a cause of acute diarrheal illness among many different subpopulations in both developing and industrialized regions, that EAEC strains are very heterogeneous and that additional studies that examine the role of EAEC in acute diarrheal illness are needed.

Enteroaggregative Escherichia coli: An Emerging Enteric Pathogen

Enteroaggregative Escherichiacoli (EAEC) represents an emerging pathogen that causes enteric and food-borne infectious diseases. Subgroups in many populations throughout the world are susceptible to EAEC infection. EAEC pathogenesis involves adherence to the intestinal mucosa; increased production and deposition of a mucus biofilm; and mucosal toxicity due to inflammation and cytokine release. Due to the heterogeneity of EAEC strains and differing host immune responses, not all EAEC infections are symptomatic. Recent data suggest that individuals with a homozygous genotype –251 AA single nucleotide polymorphism (SNP), in the IL-8 promoter region, are more susceptible to EAEC diarrhea. The HEp-2 cell adherent assay allows identification of EAECs characteristic aggregative or “stacked brick” adherence pattern. Antimicrobial treatment of individuals who develop EAEC diarrhea should be individually based. Ciprofloxacin and rifaximin, compared to placebo, have been shown to significantly shorten the course of diarrhea in patients who developed EAEC infection. The objective of this review is to increase awareness of this important emerging pathogen and to discuss the epidemiology, pathogenesis, and host-pathogen factors associated with EAEC infection.

Cryptosporidium dose response studies: variation between isolates.

The infectivity of three different isolates of the waterborne protozoan parasite Cryptosporidium parvum has been tested in human feeding studies. These three isolates (Iowa, TAMU, and UCP) have different ID50s, indicating substantial variation in their infectivity for humans. This finding is of great importance for quantitative risk assessment as it provides strong evidence for heterogeneity in infectivity among isolates of the same species.

Prophylactic Effect of Bovine Anti-Cryptosporidium Hyperimmune Colostrum Immunoglobulin in Healthy Volunteers Challenged with Cryptosporidium parvum

Bovine hyperimmune anti-Cryptosporidium colostrum immunoglobulin (BACI) decreases the intensity of Cryptosporidium parvum infection in vitro. We investigated the prophylactic effect of BACI in healthy adults challenged with C. parvum. After we established an oocyst dose that resulted in 100% infection in four volunteers (baseline group), 16 volunteers were randomized to receive (1) BACI prior to C. parvum challenge (BACI group) and a nonfat milk placebo 30 minutes later, (2) BACI prior to and 30 minutes after challenge (reinforced BACI group), or (3) nonfat milk placebo prior to and 30 minutes after challenge. Subjects received BACI (10 g) or nonfat milk placebo three times a day for a total of 5 days and were followed for clinical symptoms and oocyst excretion for 30 days. A trend toward less diarrhea (P = .08) was observed for subjects receiving BACI in comparison with occurrences in placebo recipients. Subjects receiving BACI or nonfat milk placebo had a 100-fold reduction in oocyst excretion as compared with excretion in the baseline group.

Infectivity of a Cryptosporidium parvum isolate of cervine origin for healthy adults and interferon-γ knockout mice

The infectivity of a Cryptosporidium parvum isolate of cervine origin (type 2, Moredun) propagated in calves was investigated simultaneously in healthy adult human volunteers and in interferon-gamma knockout (GKO) mice. After exposure to 100-3000 oocysts, 16 volunteers recorded, for a duration of 6 weeks, the number and form of stools that they passed and any symptoms that they experienced. Oocyst excretion was assessed by enzyme-linked immunosorbent assay and direct immunofluorescence assay. Eleven subjects (69%) became ill, and 8 subjects (50%) shed oocysts in stool. The median duration of illness was 169 h, and the median number of unformed stools passed was 24. The duration and intensity of symptoms were more severe than were those associated with previously studied isolates. The median infectious dose was estimated to be 300 oocysts for humans and 1 oocyst for the GKO mouse model. The Moredun isolate was more pathogenic than the reference GCH-1 isolate. The GKO mouse model of cryptosporidiosis is useful for discerning isolate-specific differences in pathogenicity.

A Functional Collagen Adhesin Gene, acm, in Clinical Isolates of Enterococcus faecium Correlates with the Recent Success of This Emerging Nosocomial Pathogen

ABSTRACT Enterococcus faecium recently evolved from a generally avirulent commensal into a multidrug-resistant health care-associated pathogen causing difficult-to-treat infections, but little is known about the factors responsible for this change. We previously showed that some E. faecium strains express a cell wall-anchored collagen adhesin, Acm. Here we analyzed 90 E. faecium isolates (99% acm+) and found that the Acm protein was detected predominantly in clinically derived isolates, while the acm gene was present as a transposon-interrupted pseudogene in 12 of 47 isolates of nonclinical origin. A highly significant association between clinical (versus fecal or food) origin and collagen adherence (P ≤ 0.0003) was also demonstrated, and levels of adherence were highly correlated (r = 0.879) with the amount of cell surface Acm detected by whole-cell enzyme-linked immunosorbent assay and flow cytometry. Thirty-seven of 41 sera from patients with E. faecium infections showed reactivity with recombinant Acm, while only 4 of 30 community and hospitalized patient control group sera reacted (P ≤ 0.0003); importantly, antibodies to Acm were present in all 14 E. faecium endocarditis patient sera. Although pulsed-field gel electrophoresis indicated that multiple strains expressed collagen adherence, multilocus sequence typing demonstrated that the majority of collagen-adhering isolates, as well as 16 of 17 endocarditis isolates, are part of the hospital-associated E. faecium genogroup referred to as clonal complex 17 (CC17), which has emerged globally. Taken together, our findings support the hypothesis that Acm has contributed to the emergence of E. faecium and CC17 in nosocomial infections.