E.coli .mod.pdf

E.coli ILOs At the end of this session, the student will be able to: ▪ Demonstrate knowledge of the different strains and virulence factors of diarrheagenic e.coli ▪ Understand pathogenesis and pathology caused by e.coli infection ▪ Recognize enterotoxigenic e....

E.coli ILOs At the end of this session, the student will be able to: ▪ Demonstrate knowledge of the different strains and virulence factors of diarrheagenic e.coli ▪ Understand pathogenesis and pathology caused by e.coli infection ▪ Recognize enterotoxigenic e.coli as a cause of traveler’s diarrhea ▪ Recognize enterohemorrhagic e.coli as a cause of bloody diarrhea that may become complicated by hemolytic uremic syndrome ▪ Understand the role of stool culture in the diagnosis of e.coli Enterotoxigenic E. coli ETEC is a major cause of Traveler diarrhea. In most hospital-based studies, ETEC is the second to rotavirus as cause of gastroenteritis Infection occurs throughout the year but is most common in the wet season. Mode of Transmission Infected humans are the reservoir for ETEC strains that cause diarrhea. Transmission is feco-oral through contaminated food and less often by water. Transmission via contaminated weaning food is particularly important in infant’s infection. The infecting dose is high 109-1010 in the normal host. Pathogenesis Proximal small intestine is the principal site of host interaction. ETEC colonize the small intestine by means of protein spikes called fimbriae or pili and elaborates heat labile toxin (LT) or heat stable toxin (ST). These colonization factors of ETEC bind to specific receptors on the enterocyte surface and allow them to overcome the defense peristaltic mechanism of the small intestine. LT is a subunit toxin with a structure and mode of action similar to cholera toxin and has two subunits. Subunit B, Toxophore binds to GM ganglioside on the enterocyte surface to allow Subunit A to perform its action. Subunit A activates adenylate cyclase inside the enterocytes------ raised intracellular cyclic AMP-------- efflux of Cl, Na and water from villous crypt cells and produce an anti-absorptive effect on villous tips cells. The net effect is large fluid load enters the colon and a voluminous watery stool is produced. ST is a small molecular weight protein which activates guanylate cyclase which result in secretion of fluid and electrolyte into intestinal lumen. Clinical Presentation IP is short 1-2 days. Anorexia, vomiting and abdominal cramps. The diarrhea is explosive, voluminous, and watery up to 10 times daily. The illness is self-limited and usually lasts 1-5 days in well-nourished and up to 3 weeks in malnourished. Dehydration is a major complication. Diagnosis Culture of E. coli from feces Detection of pathogenicity genes (fimbrin, ST, LT) by DNA hybridization ELISA or bioassay for gene products (toxin) Treatment Assessment of dehydration and replacement of fluid and electrolytes Ciprofloxacin 750mg/twice daily for 5 days Enter invasive E.coli (EIEC) This is a small group of E coli that produces inflammatory diarrhea by invading and destroying colonic enterocytes. They resemble shigella in O antigens, non-motile and have similar pathogenetic genes on a large plasmid that encodes surface proteins mediating invasion into cells. Infection is less common than shigella. Trimethoprim/ sulphamethoxazole twice daily for 5 days Transmission Infected persons are the reservoir of infection. transmission is feco-oral through contaminated food. Pathogenensis The colonic mucosa is the preferred site for host interaction. The outer membrane proteins involved in the invasiveness, and EIEC enter enterocytes. After invasion, EIEC proliferate within the colonocytes leading to cell death. EIEC is characterized by intense polymorphonuclear leucocytes infiltration into the colonic mucosa. Clinical Presentation IP is short 10-18 hrs. Fever, severe abdominal cramps, and malaise. Watery diarrhea followed by dysentery of scanty stool with mucous and blood. Diagnosis Stool culture. Detection of pathogenicity genes by DNA hybridization. ELISA for gene products. Treatment Combination of Co-trimoxazole plus erythromycin. Enteropathogenic E.coli In developing countries, EPEC is a major cause of infantile diarrhea. EPEC were able to produce diarrhea without invasion and without elaboration of LT or ST. Mode of Transmission Infected individuals were the reservoir of EPEC infection. Transmission occurs through contaminated infant formula and weaning food. Pathogenesis The ingested EPEC adheres to the small intestinal mucosa using fimbria. They then penetrate between the microvilli of the brush border to become intimately attached to the enterocyte surface. The brush border is then lost by process of vesiculation. The above process is termed attaching effacement. The net effect is large areas for absorption of nutrients are lost. The levels of disaccharidase enzymes became markedly depressed as they were present in the microvillous membrane. So, sucrose, lactose and maltose in the diet cannot be cleaved to be absorbed and they pass to the colon causing a non- inflammatory osmotic diarrhea. Distinctive ultrastructural lesion in the small intestine. Clinical Presentation IP is short 9-12 hrs. Initially vomiting and fever. Diarrhea is severe, prolonged and may remit and relapse. Profuse watery diarrhea with mucous but no blood. Dehydration is present. High case fatality if severe and under 6ms of age. Diagnosis - Stool culture or duodenal aspirates for EPEC. - Detection of EPEC attaching effacement genes by DNA hybridization. Treatment - Rehydration. - Parenteral nutrition in severe and prolonged cases. - Antibiotics but resistance is observed. - Probiotics have been suggested to restore gut health. Enterohaemorrhagic E.coli EHEC was linked with hemorrhagic colitis and hemolytic uremic syndrome. Infections were caused by newly recognized serogroup E coli O157. Mode of Transmission Cattle and humans are the reservoir of infection. Transmission occurs by contaminated food, poorly cooked beef. Pathogenesis Terminal ileum and colon are preferred site. EHEC produces attaching effacement. EHEC produce one or both toxins Vero toxins (VT) 1 or 2 VT-1 is also called Shiga like toxin (cytotoxin, neurotoxin/ enterotoxin) These toxins inhibit protein synthesis, they are cytotoxin and in the colon they kill enterocytes leading to inflammatory hemorrhagic colitis. If they enter the systemic circulation, they can damage the epithelial cells and precipitated hemolytic uremic syndrome. Clinical Presentation IP 12-60 hrs. Hemorrhagic colitis: abdominal cramps and watery diarrhea followed by hemorrhagic discharge. Hemolytic uremic syndrome is the most common cause of acute renal failure in industrialized countries. Thrombocytopenia, coagulopathy and microangiopathic hemolytic anemia. Diagnosis - Detection of VT or its genes (DNA hybridization). - Detection of EHEC fimbrial adhesion factors. - Detection of serum antibody to VT. Treatment - Treatment of dehydration. - No role for antibiotics. - Hemolytic uremic syndrome: peritoneal dialysis. Enteroaggregative E.coli Recently discovered E coli. Mostly cause acute and persistent diarrhea with IP 20-48 hrs.