Enteroaggregative E. coli and Childhood Diarrhea

ABSTRACT & COMMENTARY

Synopsis: Enteroaggregative E. coli was the third most common bacterial pathogen detected in children with diarrhea, often persistent, in Germany.

Source: Huppert HI, et al. Acute and chronic diarrhea and abdominal colic associated with enteroaggregative Escherichia coli in young children living in western Europe. Lancet 1997;349:1660-1662.

Huppert and colleagues enrolled all 798 children less than 16 years of age admitted with diarrhea to either of two hospitals in Wurzburg, Germany, in order to assess the role of enteroaggregative Escherichia coli (EAggEC) as a cause of diarrhea in this setting. "Standard" stool cultures revealed a bacterial pathogen in 169 (21.2%), including Salmonella spp. in 107 (13.4% of those enrolled), verocytoxin-producing E. coli in 25 (3.1%), Campylobacter jejuni in 15 (1.9%), and Yersinia in six (0.8%).

Screening colonies from stool culture by PCR for a fragment of plasmid pCVD423 ("EAggEC probe") found that 16 (2.0%) children were infected with EAggEC. The results were confirmed by demonstrating that all isolates positive by the probe demonstrated an aggregative adherence pattern on HEp-2 cells. Only one stool specimen positive for EAggEC yielded a second pathogen (Salmonella stanleyville). EAggEC was not identified in any of the stool samples obtained from 580 children without diarrhea. Four-fifths of EAggEC identifications were made in the summer months. Four of the infections were apparently acquired in developing countries, the remainder in western Europe.

Four of the children with EAggEC infection had chronic diarrhea, which lasted for three weeks to as long as five months. Another five children had abdominal colic that lasted for 2-4 weeks, although their diarrhea lasted only 1-6 days.

COMMENT BY STAN DERESINSKI, MD, FACP

E. coli has acquired multiple mechanisms by which it can cause diarrhea in humans. The table lists the types of E. coli, their names indicating characteristics associated with a diarrheogenic phenotype. EAggEC (also frequently abbreviated as EAEC) bind to small intestinal cells but do not invade or cause an obvious histological changes in those cells. In contrast to ETEC, they form small aggregates on the cell surface, appearing as clumps of bacteria.

Table

E. coli that cause diarrhea

Enterotoxigenic ETEC

Enteroinvasive EIEC

Enterohemmorhagic EHEC

Enteropathogenic* EPEC

Diffuse adherence DAEC

Enteroaggregative EAggEC

*localized pattern of adherence

Thus, EAggEC were originally defined by the "stacked bricks" appearance resulting from the adherence to HEp-2 cells. The "bundle-forming" fimbriae that account for this adherence are encoded by a large plasmid which also encodes a toxin believed by many investigators to be the cause of the associated diarrhea.

Diarrhea caused by EAggEC appears to be the result of its production of a low molecular weight, plasmid-encoded, heat-stable enterotoxin, which has been called EAggEC heat-stable enterotoxin 1 (EAST1). EAST1 has significant homology with the enterotoxic domain of the heat-stable enterotoxin of enterotoxigenic E. coli (Savarino SJ, et al. Proc Natl Acad Sci U S A 1993; 90:3093-3097). EAggEC also produce a second type of toxin that resembles the well-known hemolysin produced by some strains of E. coli.

While EAggEC has been demonstrated to be a common cause of diarrhea, including persistent diarrhea in young children living in developing countries, its role as a cause of diarrhea in developed countries has remained undefined. In the prospective study reviewed here, EAggEC (EAEC), most often locally acquired, was the third most frequently isolated bacterial pathogen in Wurzburg, Germany. The diarrhea, which was watery, was of greater than two weeks duration in one-fourth the children affected. There was also an association with prolonged abdominal colic, which at times was present before the appearance of diarrhea or which persisted after the diarrhea resolved.