Case 2 Answers
1. What enteropathogenic type of Escherichia coli is causing this infection?
Enterohemorrhagic E. coli. These organisms are usually of serotype 0157:H7 and the disease often occurs in outbreaks.
2. What complication of E. coli enteritis did this patient develop? Define the complication.
Hemolytic uremic syndrome (HUS).
HUS is a systemic disease characterized by microangiopathic hemolytic anemic, thrombocytopenia, and intra renal thrombosis resulting in hematuria, renal insufficiency, and central nervous system manifestations.
HUS developed in 6% of patients with EHEC from US outbreaks and the mortality was 1.2%.
3. List the virulence characteristics of E. coli that are responsible for this syndrome?
The major virulence factor is the production of one or more related shiga-like toxins, so called because they are biochemically, genetically and immunologically related to the Shiga toxin of Shigella dysenteriae.
The organisms also colonize the distal ileum, cecum and large bowel by means of a plasmid mediated factor, a pilus.
The organisms also have lipopolysaccharide, but its role in hemorrhagic colitis or HUS is not defined.
4. Describe the pathogenic process. In your response address how the infectious microorganism might be responsible for hemorrhage, anemia, and renal failure.
After ingestion, colonization of the ileum, cecum and colon occurs via pili. The attachment resembles the attachment and effacement lesion initially described for EPEC and presumably involves a plasmid encoded "bundle forming pilus". In EPEC, the interaction between the adherent organism and host cell involves an increase in calcium ions in host cell protein phosphorylation and cytoskeletal rearrangement with the formation of dense "pedestals" of filamentous actin under the site of attachment. The shiga-like toxin is an AB type in which the B subunit binds to cell membrane glycolipid. The A subunit is internalized by endocytosis into a membrane bound vesicle. It crosses the vacuolar membrane in the trans-Golgi network and enzymatically modifies the 28S ribosomal RNA of the 60s-ribosomal subunit by removing an adenine base. This prevents elongation-factor 1-dependent binding of amino acyl t-RNA to the ribosome blocking protein synthesis, leading to cell death.
Animal experiments with Shiga toxin
and shiga-like toxins disclose capillary thrombosis and associated
inflammation of the colonic mucosa leading to hemorrhagic colitis similar to
that seen in patients. It is postulated that some of the toxins gain access to
the circulation and cause endothelial damage in renal capillary beds, other
vascular beds, or that they alter platelet function. Alternatively, a recent
review of E. coli 0157:H7 and the
hemolytic uremic syndrome suggests that the colonic vascular damage allows Ips
and other inflammatory mediators to gain access to the circulation and initiate
HUS.
5. How is the infection acquired? Include in your answer an explanation of how the most common vehicle of transmission is likely to cause large outbreaks.
Infection is usually acquired by ingestion of undercooked ground beef.
Additionally more recent outbreaks have been associated with vegetables contaminated with tainted ground beef or other
cattle products and unpasteurized apple juice distributed from California.
Additionally several outbreaks associated with swimming, in fecally contaminated lakes or consumption of contaminated
municipal water supplies are reported.
Secondary cases occur in as many as 22% of contacts in households and day-care centers documenting person-to-person
transmission. These high secondary attack rates suggest that the inoculum required to cause infection is low.
One percent of healthy cattle are colonized with E. coli 0157:H7. The process of grinding beef may transfer the surface
pathogens to the interior which in turn protects the organisms from all but complete heating (cooking).
In addition, commercial ground beef includes meat from many carcasses allowing a small number of infected cattle to
contaminate a large supply of ground beef.
6. What are the other mechanisms by which E. coli is able to cause diarrhea?
B. EIEC - Enteroinvasive E. coli which causes clinical disease indistinguishable from that caused by invasive shigella (although less severe). C. EPEC - Enteropathogenic E. coli which produce the adherence and effacement lesions described above. They are associated with but not proven to cause self-limited diarrhea in adults and chronic watery diarrhea in infants.
D. EAEC - Enteroaggregative
E. coli are associated with watery
diarrhea in epidemiological and volunteer studies as well as chronic diarrhea
in certain developing countries. The poorly understood postulated mechanism is
similar to that described for EPEC, i.e. adherence and effacement.
7. Should the child be isolated in the hospital?
Yes. Given the
relatively high secondary attack rates, person-to-person spread is likely.
8. How does one diagnose the infection?
Most strains of E. coli 0157:H7 do not ferment sorbitol whereas other E. coli strains ferment sorbitol. Sorbitol-MacConkey agar can quickly identify sorbitol-negative strains. These strains can be confirmed with commercially available 0157 antisera. Reference laboratories canperform the H typing. The CDC recommends that clinical laboratories screen all stools for the organism. Many laboratories, including our own, have chosen to screen only bloody stools or on request of the physician, however many patients will not have grossly bloody stools. Given a conservatively estimated annual US incidence of 21,000 cases, and a greater frequency than shigella, screening is strongly encouraged. Tests for shiga-like toxin or for the toxin gene are being developed for use in the future.
9. Should antibiotics be used to treat the child? If so, which ones are used?
Trimethoprim/sulfamethoxazole (TMP-SMX) or quinolones should be used.