Hermy Lior

Growing concerns and recent outbreaks involving non-O157:H7 serotypes of verotoxigenic Escherichia coli

Verocytotoxin-producing E. coli (VTEC) of serotype O157:H7 have been shown to be important agents of foodborne disease in humans worldwide. While the majority of research effort has been targeted on this serotype it is becoming more evident that other serotypes of VTEC can also be associated with human disease. An increasing number of these non-O157:H7 VTEC have been isolated from humans suffering from HUS and diarrhea. Recently a number of foodborne outbreaks in the USA, Australia, and other countries have been attributed to non-O157:H7 VTEC serotypes. Surveys of animal populations in a variety of countries have shown that the cattle reservoir contains more than 100 serotypes of VTEC, many of which are similar to those isolated from humans. The diversity and complexity of the VTEC family requires that laboratories and public health surveillance systems have the ability to detect and monitor all serotypes of VTEC.

An outbreak of diarrhea due to verotoxin-producing Escherichia coli in the Canadian Northwest Territories.

In the summer of 1991 a large outbreak of Escherichia coli O157:H7 associated diarrhea occurred in 6 Inuit communities in the Canadian Northwest Territories. The total population of these communities is 5,292. Of the 521 individuals who developed diarrhea, 152 (29%) were positive for E. coli O157:H7 on stool culture or positive by verotoxin analysis. Median age was 6 years. The attack rate for children < 1 year was 43% in the major affected community of Arviat. Hemolytic-uremic syndrome (HUS) developed in 22 cases, and 2 patients died. Asymptomatic stool carriage of verotoxin-producing E. coli (VTEC) 2-5 weeks after diarrheal illness was noted in 4/28 persons followed prospectively. Epidemic curves, case-control studies and phage type testing suggested person-to-person transmission. The original source of infection was not identified, though a food source was suspected. VTEC were detected in 6 food samples (minced beef and caribou) taken from retail outlets and homes. Primary prevention of infection through health education and promotion activities, as well as long-term follow-up of HUS survivors, are indicated in this population.

Epidemic Escherichia coli O157:H7 gastroenteritis and hemolytic-uremic syndrome in a Canadian Inuit community: Intestinal illness in family members as a risk factor

Abstract Objective : To evaluate risk factors for childhood hemolytic-uremic syndrome (HUS) and gastroenteritis during an epidemic of Escherichia coli O157:H7 infection. Design : Case-control study. Setting : Remote Inuit community of Arviat in northern Canada. Participants : Of the 565 Arviat residents less than 15 years of age, 19 had HUS and 65 more had E. coli O157:H7 gastroenteritis. The 19 children with HUS were compared with 19 age- and gender-matched children with uncomplicated E. coli O157:H7 gastroenteritis, and both HUS and gastroenteritis patients were compared with 19 healthy control subjects. Interventions : Questionnaire administered face-to-face to parents of participants in the home. Main outcome measures : Rates of exposure to foods, travel, sources of water, and gastrointestinal illness in family members. Results : Patients with HUS and those with uncomplicated E. coli O157:H7 gastroenteritis differed only on measures of clinical severity. In the 7 days before the onset of gastrointestinal symptoms, children with HUS and those with uncomplicated gastroenteritis were more likely to have been exposed to a family member with diarrhea than were the healthy control subjects (odds ratio=9 for HUS vs healthy control subjects; 95% confidence interval 2 to 43; p E. coli O157:H7 infection. Conclusions : These findings emphasize the potential for extensive intrafamilial transmission of verotoxin-producing E. coli once infection is introduced into certain communities. (J PEDIATR 1994;124:21-6)

A PHASE II RANDOMIZED CONTROLLED TRIAL OF SYNSORB-PK FOR THE PREVENTION OF HEMOLYTIC UREMIC SYNDROME IN CHILDREN WITH VEROTOXIN-PRODUCING E. COLI (VTEC) GASTROENTERITIS. † 1684

A PHASE II RANDOMIZED CONTROLLED TRIAL OF SYNSORB-PK FOR THE PREVENTION OF HEMOLYTIC UREMIC SYNDROME IN CHILDREN WITH VEROTOXIN-PRODUCING E. COLI (VTEC) GASTROENTERITIS. † 1684

Epidemic Escherichia coli 0157: H7 gastroenteritis and hemolytic-uremic syndrome in a Canadian Inuit community: Intestinal illnes in family members as a risk factor

OBJECTIVE To evaluate risk factors for childhood hemolytic-uremic syndrome (HUS) and gastroenteritis during an epidemic of Escherichia coli O157:H7 infection. DESIGN Case-control study. SETTING Remote Inuit community of Arviat in northern Canada. PARTICIPANTS Of the 565 Arviat residents less than 15 years of age, 19 had HUS and 65 more had E. coli O157:H7 gastroenteritis. The 19 children with HUS were compared with 19 age- and gender-matched children with uncomplicated E. coli O157:H7 gastroenteritis, and both HUS and gastroenteritis patients were compared with 19 healthy control subjects. INTERVENTIONS Questionnaire administered face-to-face to parents of participants in the home. MAIN OUTCOME MEASURES Rates of exposure to foods, travel, sources of water, and gastrointestinal illness in family members. RESULTS Patients with HUS and those with uncomplicated E. coli O157:H7 gastroenteritis differed only on measures of clinical severity. In the 7 days before the onset of gastrointestinal symptoms, children with HUS and those with uncomplicated gastroenteritis were more likely to have been exposed to a family member with diarrhea than were the healthy control subjects (odds ratio = 9 for HUS vs healthy control subjects; 95% confidence interval 2 to 43; p < 0.01). Undercooked ground meat and foods traditionally consumed by the Inuit were not implicated as risk factors in E. coli O157:H7 infection. CONCLUSIONS These findings emphasize the potential for extensive intrafamilial transmission of verotoxin-producing E. coli once infection is introduced into certain communities.

AN IDIOTYPIC NATURAL AUTOANTIBODY NETWORK IN HEMOLYTIC UREMIC SYNDROME (HUS).|[dagger]| 1020

Introduction: We hypothesized that immune-mediated events rather than direct toxin injury might be involved in the pathogenesis of HUS associated with shiga-like toxin (SLT) producing E. coli.Purposes: Our objectives were to learn whether antibodies (AB) exist to the SLT glycolipid receptor Gb3, to define the occurrence and relationship between such anti-Gb3 ABs (α-Gb3) and anti-idiotypic ABs to them (α-α-Gb3), and to evaluate children infected with E. coli O157:H7 for these ABs.Methods: ELISAs were used for detecting α-Gb3 orα-α-Gb3 in sera from normal adults [n=15] and from children with E. coli O157:H7 associated with [n=24] or without [n=38] development of HUS. Results: Normals have both α-Gb3 and α-α-Gb3; levels of these ABs are correlated [r=0.9654]. The relationship between these antibodies in E. coli O157:H7 infection is shown below: Table Conclusions:(1) Autoantibodies to Gb3 are normally found. (2) α-Gb3 exists in balance with α-α-Gb3. (3) Children with HUS during the acute phase have significantly decreased levels of these ABs. We hypothesize that these ABs are low because α-α-Gb3 binds to SLT leaving α-Gb3 available to bind to Gb3 of endothelial cells and induce vascular injury. [Supported in part by NIH-PO1 HD-13021]

RISK OF HEMOLYTIC UREMIC SYNDROME FOLLOWING SPORADIC E. COLI O157 INFECTION: RESULTS OF A CANADIAN COLLABORATIVE STUDY |[dagger]| 760

The risk of hemolytic uremic syndrome (HUS) following E. coli O157 gastroenteritis has been estimated to range widely (from 3-26%), and has been reported as a summary estimate for all ages. The objective of this study was to better estimate the age-specific risk of HUS and hemolytic anemia (HA) following O157 infection among a representative cohort of children from the Province of Alberta, and to compare this to children presenting to tertiary centers in the rest of Canada. Children with HUS or E. coli O157 gastroenteritis were eligible if they were less than 15 years old and stool samples had been submitted to one of 18 participating hospital labs or to one of the two Provincial Health Laboratories (PHL) in Alberta. Samples from the PHL allowed identification of an almost complete cohort of non-referred Alberta children with O157 gastroenteritis. Hemoglobin, blood smear, urinalysis, and serum creatinine were obtained 8-10 days after the onset of diarrhea; subjects were followed for 1 month. Compliance with blood specimens was 92% in Alberta and 90% in the rest of Canada. O157 infection was considered present in those with HUS if the stool culture grew O157 or if the acute or convalescent anti-O157 lipopolysaccharide antibody titer was ≥ 1:500. From June, 1991 to March, 1994 HUS was diagnosed in 205 Canadian children. Of these, 77% (26 in Alberta and 131 in other provinces) had evidence of O157 infection. In addition 586 children had O157 gastroenteritis but no HUS; 4 of these in Alberta and 14 elsewhere had HA. The risk of HUS following O157 infection in Alberta was 26/322, or 8.1% (95% CI, 5.3-11.6); if those with HA are included, the risk increases to 9.3%. In the rest of Canada, the risk of HUS following O157 infection was 31.1%, reflecting referral bias. In Alberta children, the highest age-specific risk of HUS/HA was 13% in those younger than 5 years (95% CI, 7.6-18.5%). These data help guide clinical care and provide a basis for sample size estimates for prevention trials. More than 90% of HUS patients across Canada had been seen by a physician in the two weeks before diagnosis, identifying the potential for intervention at an early phase of the illness.