e patient was a previously healthy 11-year-old female who came to the emergency
ID: 3166460 • Letter: E
Question
e patient was a previously healthy 11-year-old female who came to the emergency department (ED) in mid-September with a 2-day history of bloody diarrhea. Three days previously she had the onset of fever, headache, and lower abdominal pain. Her diarrhea began as watery and became increasingly bloody. She denied any recent travel but reported that her brother also had bloody diarrhea. In her history, she said she had eaten a hamburger at a school picnic prior to the onset of disease, as well as having consumed spinach. There was no family history Th of inflammatory bowel disease or bloody stools. On physical examination, the patient's vital signs were normal and the physi- cal findings were unremarkable except for severe abdominal pain. Her stool was hemoccult positive and showed 2+ white blood cells (WBCs). A complete blood count was within normal limits except for a WBC of 14,900/pl, with an absolutse neutrophil count of 13,500/ul. She was given morphine in the ED for her abdom- inal pain. An abdominal ultrasound ruled out acute appendicitis but revealed thickened bowel loops consistent with colitis. During the first week of her hospital course she continued to have bloody diarrhea and severe abdominal pain. Her final stool submitted to the laboratory on hospital day 7 was consistent with a blood clot. During her hospital course she developed low urine output and hematuria, with a serum creatinine of 2.1 mg/d on hospital day 5. Her renal symptoms were treated with fluids and her renal function was closely monitored. In addition, on hospital day 6 she had a platelet count of 16,000/pl and a hemoglobin level of 7.2 mg/dl. She received a unit of packed red blood cells on the 6th, 7th, and 11th hospital days. By discharge on the 13th hospital day her serum creatinine, blood urea nitrogen, and platelet count had returned to normal and her hemoglobin had stabilized at 10.2 mg/dl. Culture of her stool on sorbitol MacConkey agar is seen in Fig. 30.1. i. What organism 2. What two virulence factors does is infecting this patient? this organism produce, and what are their roles in the gastrointes- tinal disease seen in this patient? Explain why multiple serotypes of this organism can produce these virulence factors. 3. Was the clinical course of her illness consistent with infec- tion caused by this organism? Figure 30.1Explanation / Answer
Q1) The causative microorganism in this case is enterohemorrhagic E coli (EHEC).
Q2) The two virulance factors this organism produces are i ) Endotoxin and ii) shiga toxin.
EHEC is a gram negative bacteria, outer membrane of EHEC has an outer facing leaflet of lipopolysaccharide (LPS). LPS contains lipid A, core polysaccharide, and O-Antigen, having 40-80 repeating subunits of 4 sugars that in the case of E. coli O157:H7 is unique to the O157 serogroup, having N-acetyl-d-perosamine, l-fucose, d-glucose, and N-acetyl-d-galactose. The core polysaccharide is conserved in all E. coli ecotypes.
Lipid A is the toxic component of LPS, also known as endotoxin,it is a heat-stable toxin. Lipid A consists of a phosphorylated disaccharide of glucosamine linked by a beta-1,6 linkage and modified by fatty acids, in addition to the first ketodeoxyoctanoate of the core polysaccharide. Endotoxin is released by cell lysis . Endotoxin is less potent and less specific than exotoxins. It can cause fever, hemorrhagic shock, and diarrhea.
ii) Shiga toxins (Stxs) are the major virulence factors of EHEC in the pathogenesis of HUS. It is found that after intestinal infection with EHEC, Stxs cross the intestinal barrier and bind to endothelial cells. here they injure the host cell by inhibiting protein synthesis, by stimulation of prothrombotic messages, or by induction of apoptosis. Shiga-like toxins (Shiga-toxins or verotoxins), SLT1 (Stx1, VT1) and SLT2 (Stx2, VT2).This toxin produced by lysogenization with one or more toxin-converting phages. Toxins consist of one A subunit and B subunit. SLT1 and SLT2 bind to Gb3, the globotriaosyl ceramide membrane receptor. after binding to cells the A subunit is internalized, and is cleaved, and then blocks protein synthesis by interfering with tRNA delivery of amino acids to ribosomes. The B subunit of Stx binds to the membrane receptor globotriaosylceramide (Gb3). Gb3 helps in endocytosis and intracellular trafficking of the toxin. The Stx A subunit hydrolyzes a specific adenine residue of the 60S ribosomal subunit of mammalian cells.as a result, Stx stops the protein machinery of the susceptible cell.
Stx receptors are found on intestinal endothelial cells and also on the glomerular endothelial cells. Death of colonic cells and lesions in small blood vessels causes bloody diarrhea. In the kidney, Stx damages glomerular endothelial cells by binding to globotrioacyl ceramide.Due to glomerular endothelial cell damage, there is a loss of glomerular barrier function which allows the passage of red blood cells and proteins into the urinary space. Thus, Stx causes glomerular endothelial cell dysfunction, inflammation, and microvascular thrombosis. resulting inhibition of blood supply to kidney leading to loss of kidney function.
Q3) Yes the clinical course of her illness was consistent with infection caused by the organism.
The renal findings were consistent with infection with this organism, as her renal symptoms were treated with fluids , and renal functions were closely monitored , it helped in preventing renal sequlae of this disease.
Shiga toxin causes bloody diarrhea and in approximately 5-10% of cases hemolytic uremic syndrome (HUS), which can lead to complete kidney failure. Patients with bloody diarrhea usually recover within ten days and those who develop HUS usually recover within a few weeks, but in cases of kidney failure the patient may die. While people of any age are susceptible, the young and elder people are usually more affected. Treatment of EHEC is typically done by rehydration process without administrating antibiotics , hospitalization in severe cases, especially in HUS is done. EHEC infection is prevented by maintaining hygiene, by proper cooking of food, not swallowing water while swimming, and avoiding unpasteurized milk .
E coli enteric infections requires fluid replacement with solutions having electrolytes. (Antimicrobials like doxycycline, trimethoprim/sulfamethoxazole (TMP/SMZ), fluoroquinolones, and rifaximin are useful in cases of traveler's diarrhea . They shorten the duration of diarrhea by 24-36 hr). But here the child, has not travelled, so it is not travellers diarrohea, so not given any of these drugs and antibiotics are also not useful in enterohemorrhagic E coli (EHEC) infection and may lead to development of HUS. Research shows that it is harmful to use antibiotics in EHEC, as they release more toxins. It is studied that the risk for HUS after antibiotic treatment is higher in children.so they are not administered.
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