FS-034-035-044 Bacterial GI Infections.pptx

Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions CC BY NC 2.5 https://xkcd.com/1471 FS3-034, FS3-035, FS3-044 Bacterial Infections of the Gastrointestinal Tract Michael Carruthers, Ph.D. Associate Professor Department of Microbiology & Immunology [email protected] | 281 Ryan Hall 1 Bacterial GI Infections Background Objectives Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 1.Differentiate between bacterial GI tract pathogens based upon disease presentation and abnormal clinical findings. 2.Differentiate between bacterial GI tract pathogens based upon results of laboratory findings and/or diagnostic tests. 3.Describe epidemiology associated with and risk factors for developing each bacterial GI tract disease. 4.Explain the pathogenic process of each bacterial GI tract pathogen, including virulence factor mechanisms of action. 5.Describe the laboratory methods appropriate for diagnosis of disease caused by GI tract pathogens. 6.Compare and contrast treatment and/or prevention strategies for diseases caused by GI tract pathogens. 2 Bacterial GI Infections Background In 1976 it was estimated… Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 3 Bacterial GI Infections Background Flow Charts: Use Them Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions M.D. Carruthers. 2023. CC BY-NC-SA 4.0 4 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Diarrhea (WHO Facts and estimates) ORIGIN Greek diarrhoia, from diarrhein ‘flow through,’ from dia ‘through’ + rhein ‘to flow.’ Passage of 3 or more loose or liquid stools per day Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Diarrheal illness kills ~525,000 kids under 5 each year Inflammatory-ish Listeria monocytogenes Leading cause of malnutrition in children under 5 Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 1.7 billion cases of childhood diarrhea each year >2 billion people drink from fecally contaminated water sources 2.4 million lack access to basic sanitation facilities 5 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Definitions Gastritis- inflammation of the stomach I am not going to test you over the definition of these terms Gastroenteritis- inflammation of the stomach & intestines Enteritis- inflammation of the small intestine Enterocolitis- inflammation of the small & large intestine Colitis- inflammation of the large intestine Dysentery – Inflammatory disorder of the GI tract often associated: Diarrhea with blood and pus in the feces Pain, fever, abdominal cramps Usually resulting from disease of the large intestine Supportive therapy – Fluid, electrolyte, and nutritional management 6 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus GI Tract Infections Various etiologies: bacteria, viruses, and parasites Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Fecal-oral transmission most common – Human or animal feces – Any way feces can get to the mouth fingers, feet, forks, fluids (e.g., water, milk), food, etc. Lack of sanitation, hygiene and safe water sources 7 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Foodborne Disease Surveillance in the US Ran by the CDC or FDA or Both Foodborne Disease Active Surveillance Network (FoodNet) – 15% of the US population – Seven bacterial agents and 2 parasitic agents – Active investigation with detailed reporting involving dedicated public health officials at local, state, and federal levels National Electronic Norovirus Outbreak Network (CaliciNet) Foodborne Disease Outbreak Surveillance System (FDOSS) National Molecular Subtyping Network for Foodborne Disease Surveillance (PulseNet) National Notifiable Diseases Surveillance System (NNDSS) National Environmental Assessment Reporting System (NEARS) National Outbreak Reporting System (NORS) Take away: Surveillance is complicated and messy. Don’t memorize these, just know surveillance mechanisms exist. 8 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus CDC US Foodborne Illness Estimates I am not going to test you over these statistics 1 in 6 Americans get sick from foodborne illness (48 million) – 128,000 hospitalizations with 3,000 deaths Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 80% of foodborne illnesses (US) due to unspecified agents Pathogen Norovirus Cases Hospitalizat Death ions s 20,796,079 14,663 149 Nontyphoidal Salmonella 1,095,079 19,336 378 Campylobacter spp. 1,058,387 8,463 76 Clostridium perfringens 966,120 2,138 26 Staphylococcus aureus 241,188 1,064 6 Toxoplasma gondii 173,415 4,428 Scallan et. al. Foodborne Illness Acquired in the United States - Major Pathogens, Emerging Infectious Diseases www.cdc.gov/eid Vol. 17, No. 1, January 2011 Listeria 1,607 1,455 327 9 255 Bacterial GI Infections Background COVID-19 Pandemic Affect on GI diseases- FoodNet Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions I am not going to test you over these statistics 10 Bacterial GI Infections Background COVID-19 Pandemic Affect on GI diseases- FoodNet Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions I am not going to test you over these statistics 11 Bacterial GI Infections Background Bacterial Food Poisoning Normal GI Microbiota Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Mims’s Medical Microbiology, 5h Edition, © 2013 Saunders 12 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli GI Host Defenses I will not test over GI Host Defenses Mouth Mucus Low pH (stomach) Peristalsis Shedding of epithelium Bile Secretory IgA Normal microbiota Esophagus Stomach Small intestine Large intestine Summary & Questions 13 Bacterial GI Infections Diarrhea: Background Watery vs. Bloody Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Ranges from: watery  sometimes bloody  often bloody – EHEC, Campylobacter jejuni, EIEC, Shigella spp., Yersinia enterocolitica, Clostridioides difficile, Salmonella spp., Vibrio parahaemolyticus Watery, rarely bloody – all types of bacterial food-poisoning, EPEC, ETEC, Bacillus cereus, Vibrio cholerae, Listeria monocytogenes 14 Bacterial GI Infections Background Bacterial GI Tract Disease Manifestations by Time Bacterial Food Poisoning Timing is significant Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions (times are approximate, not hard rules) Time After Ingestio n Type of Pathogene sis Bacterial Agents 1–8 hours Preformed Toxin Staphylococcus aureus Bacillus cereus (emetic) Clostridium botulinum 8 – 16 hours Toxin produced in vivo Bacillus cereus (diarrheal) Clostridium perfringens Clostridium botulinum 16+ hours Attachment, growth, and virulence factor production Shigella spp. Salmonella spp. (6h-2days) Listeria monocytogenes Escherichia coli (EPEC, EHEC, ETEC, EIEC) Campylobacter spp. 15 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Bacterial Food Poisoning Ingestion of preformed toxin is an intoxication Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Ingestion of spores/organism that produce toxin (depending on the resource) is an intoxication, toxico-infection, or infection Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Clinical presentation – Diarrhea, vomiting or both, NO FEVER! Four bacterial causes: – Staphylococcus aureus, Clostridium botulinum, Clostridium perfringens, Bacillus cereus 16 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Bacterial Food Poisoning Types Ingestion of: 1. Preformed toxins- toxins produced by bacteria in food before the food is consumed Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli 2. Ingestion of spores- Large numbers of spores ingested, spores germinate in intestine and vegetative bacteria produce toxins 3. Ingestion of organisms that produce toxins Summary & Questions 17 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Staphylococcus aureus Characteristics- you should know by now Clinical manifestation – Severe vomiting, diarrhea & abdominal pain within 1-8 hours post consumption, resolves in ~24 hrs. Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Pathogenesis – Ingestions of preformed staphylococcal enterotoxins Enterotoxin A to Z (enterotoxin A most common) All are heat-stable toxins (survive cooking/reheating) Don’t need to know mechanism of action Treatment – Supportive therapy Epidemiology – Growth of S. aureus and production toxins in food before or after cooking 18 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Clostridium botulinum Characteristics – Gram-positive, rod – Obligate anaerobe – Spore forming Different flavors of botulism – Foodborne – Infant – Wound – Iatrogenic – Adult intestinal colonization – Bioterrorism associated 19 Bacterial GI Infections Background Clostridium botulinum Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Epidemiology – Often seen in home-canning (improperly canned food items) – Can occur at any age, even in infants 20 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Clostridium botulinum Clinical Manifestation of foodborne botulism – < 8 h of toxin or 16 h of spore ingestion diarrhea, abdominal pain, sometimes vomiting Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – ~ 1-3 days Cranial nerve deficits present first: double or blurred vision, bilateral ptosis, mydriasis, ophthalmoplegia, diminished/loss of pupillary construction to light dizziness, constipation, thick-feeling tongue, slurred speech, bilateral descending weakness  flaccid paralysis – Death may occur; usually due to respiratory arrest – If patient survives: lingering weakness & dyspnea up to 1 year or more after primary disease Toxin binds irreversibly; affected nerve endings must regrow 21 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Clostridium botulinum Pathogenesis – Mediated by botulism toxin – Ingestion of either: Preformed toxin Large number of spores  germinate in intestine  produce toxin – Botulism toxin = flaccid paralysis Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Murray, Medical Microbiology, 8th Edition, © 2016 Saunders 22 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Clostridium botulinum Botulism Case (real life event) College student buys frozen hash browns in a airtight shrink wrapped container, and thinking it safe, stores them in a pantry. He cooked the hash browns, took one bite and spat it out. Soon after he started vomiting, then lost the ability to swallow. Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions After calling 911 and being admitted to a hospital, he was totally paralyzed for two weeks (couldn’t even open his eyes). He was in intensive care for 3 months, with 2 of those months on a respirator. During a large portion of this time he couldn’t express pain. After 6 months, he was discharged from the hospital. He attended physical therapy several times a week and was projected to take an additional 6 months to fully recover. 23 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Clostridium botulinum Treatment – Supportive therapy (IV fluids, etc.) – Ventilation if needed – IV anti-toxin administration ASAP; Cannot reverse existing paralysis, only stop progression Not normally stocked, must call local/state public health departments or CDC Prevention – Impossible to prevent food contamination by spores – Maintain food at acidic pH’s – Storing food at < 4˚C – Destroy toxin in food (80˚C for 30 min) DO NOT COOK FOODS THAT ARE KNOWN OR SUSPECTED TO CONTAIN BOTULISM TOXIN TO “DETOXIFY” THEM! – Proper canning Goals: destroy spores, prevent germination/inhibit growth or kill bacteria from spores that have just germinated CDC Home Canning and Botulism 24 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Clostridium botulinum Infant botulism (floppy baby syndrome) – Occurs between birth – 6 months (up to 1 year) After 6 months permeability of the intestinal mucosa changes Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish – Most common form of botulism in the United states – Ingestion of small amounts of spores from honey, contaminated formula Germination of C. botulinum spores in intestines  growth  toxin production Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli – Clinical manifestation Often milder and lower mortality than adult botulism Constipation, weak cry, “failure to thrive” --> flaccid paralysis (< 2% are fatal) – Treatment Same as botulism Summary & Questions 25 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Botulism FAQ Questions – Can infants get botulism? – What is the difference between botulism (in an infant) and infant botulism (floppy baby syndrome)? Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Answers – Large amounts of toxin or spores that affect adults will affect infants often more severely – Small or very small amounts of spores that do not elicit symptoms in adults can affect infants, causing floppy baby syndrome 26 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Clostridium perfringens Characteristics – Gram-positive, rod – Spore forming Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Clinical Manifestation – Onset of diarrhea and abdominal cramps 8-16 h post-ingestion and lasts for ~24 h – Mediated by C. perfringens enterotoxin Epidemiology – Associated with meat products/ gravies held at below recommended temperatures Pathogenesis Spores survive cooking of food and germinate Bacteria grow in food (not kept heated properly) Ingestion of organisms Organisms sporulate in the intestine Sporulation leads to enterotoxin production Toxin alters enterocyte membrane permeability Treatment – Supportive therapy Diarrhea 27 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Bacterial Food Poisoning Overall Prevention One of the most common causes of foodborne illness When in doubt, throw it out! Beware of the temperature danger zone Summary & Questions https://www.fsis.usda.gov/food-safety 28 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Bacillus cereus Characteristics – Gram-positive, Spore forming Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Disease and Pathogenesis Emetic Form Diarrheal Form Food Reheated rice Meat, vegetables Cause Ingestion of preformed heat-stable toxin Onset 15 min - 8 h Vomiting, nausea, abdominal cramps Spores germinate in intestine  Heat-liable toxin 8-16 h Diarrhea, nausea, abdominal cramps Symptoms Treatment Supportive Therapy Treatment – Supportive therapy 29 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Helicobacter pylori Characteristics – Gram-negative flagellated, curved rod – Microaerophilic (5% oxygen) – Exclusive to humans Epidemiology – Percentage of population with H. pylori stomach carriage: 30-50% in developed countries ~100% in developing countries – Transmission unknown (fecaloral, vomit-oral?) Worku et al. 1999. Microbiology. 145(10) 28032811 30 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Helicobacter pylori Clinical Manifestations – Gastritis Feeling of fullness, upset stomach, nausea, vomiting Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – Ulcers Ulcers in ~10-15% of chronic gastritis cases Dull stomach pain, heart burn, nausea / vomiting, sometimes with stomach bleeding that presents as black or tarry stools – Stomach cancer ( 90% of gastric ulcers they tested Fed up with animal experiments to satisfy Koch’s postulates – Marshall ingested a culture of H. pylori and developed severe gastritis – Treated himself with antibiotic Killed the dogma that ulcers were caused by stress, smoking and spicy foods – Ended the use of surgery to remove ulcers Won the Nobel prize in 1995 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Helicobacter pylori Pathogenesis – Contact with the gastric mucosa Uses flagella-based motility to penetrate gastric mucosa and adhere to epithelium Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – Damage to and death of gastric epithelial cells Secretes a powerful urease enzyme (converts urea to ammonia and CO2) – Ammonia increases to toxic levels – Decreasing stomach acidity Vacuolating toxin A (VacA) = accumulation of vacuoles CagA (oncogenic protein), injected by type 4 secretion system = targets multiple cell physiologic processes – Ulcer formation Ulcers form due to cellular damage/death, severe inflammation, loss of stomach epithelium Exposure of ulcer to stomach acid = further ulceration and pain Ulcers can bleed 33 Bacterial GI Infections Background Helicobacter pylori Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Lippencott’s Illustrated Reviews: Microbiology Summary & Questions 34 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Helicobacter pylori Diagnosis – Urea breath test Maiga et al. 2012. Ind. J. Med. Res. 135(5)731-736 Ingestion of 13C-urea, H. pylori urease degrades into 13CO2 + NH3, detection of 13CO2 via gas chromatography – Biopsy Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Treatment – Only after a positive test for H. pylori – Antibiotics and proton pump inhibitor or antacid (control acid/further mucosal damage) 35 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Bacterial GI Infections Non No inflammatory major intestinal damage or marked inflammation – Bacteria: passing through the intestine producing toxins adherent to the intestinal epithelium inducing pathologic change EPEC, ETEC, Vibrio cholerae Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Inflammatory Listeria monocytogenes ish Some resources consider it inflammatory/others do not Inflammatory Intestinal inflammation and damage – Bacteria adherent to intestinal epithelium Invasion and/or cytotoxins killing cells More likely to see: –Fecal occult or visible blood –Fecal leukocytes EHEC, Salmonella spp., Campylobacter, Shigella spp. C. difficile (moderate to severe cases), Vibrio parahaemolyticus, Yersinia enterocolitica 36 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Culture/ID of Gram-negatives in Diagnostic Lab Selective and differential media to ID an organism – MacConkey agar Lactose fermentation + - – Positive = red colonies /agar » E. coli and a few others – Negative = white and/or translucent colonies, no agar color change » Salmonella, Shigella and others – Indole test Test for indole production – Positive = red color change » Escherichia coli, Vibrio spp. and others – Negative = no color change » Salmonella 37 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Culture/ID of Gram-negatives in Diagnostic Lab – Hydrogen sulfite (H2S) production Used to diff. between: – Salmonella  Black colonies = H2S producer – Shigella  Non-black= does not produce H2S Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes A variety of media can test for this: – Hektoen agar or SS agar Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 38 Bacterial GI Infections Background Grouping of Pathogenic E. coli Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus ETEC EPEC Gastritis/Ulcers Helicobacter pylori Non-inflammatory IPEC Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions EAEC EIEC Inflammatory-ish Listeria monocytogenes STEC E. coli AIEC ExPE C UPEC NME C SEPE C APEC EHEC Othe rs IPEC: Intestinal pathogenic E. coli (causes intestinal disease) – – – – – – ETEC: Enterotoxigenic E. coli EPEC: Enteropathogenic E. coli STEC: Shiga Toxin Producing E. coli EHEC: Enterohemorrhagic E. coli EAEC: Enteroaggregative E. coli EIEC: Enteroinvasive E. coli AIEC: Adherent-Invasive E. coli ExPEC: Extraintestinal pathogenic E. coli (normal microbiota in intestines, causes disease outside of the intestines) – – – – UPEC: Uropathogenic E. coli NMEC: Neonatal Meningitis E. coli SEPEC: Sepsis Associated E. coli APEC: Avian Pathogenic E. coli 39 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Virotypes of Pathogenic E. coli E. coli Virotype Enterotoxigenic (ETEC) Pathogenesis LT and ST = fluid and electrolyte loss Enteropathogenic (EPEC) Enterohemorrhagic (EHEC) A/E lesions, loss of microvilli A/E lesions, Stx production Small Enteroinvasive (EIEC) Cell invasion, intracellular motility Aggregative adherence Large Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Intestinal Site Small Enteroaggregative (EAggEC) Large Small Disease /Epidem. Travelers, infant, watery diarrhea Infant diarrhea Bloody diarrhea, HUS sequelae Dysentery Bacterial GI Infections Background Bacterial Food Poisoning Virotypes of Pathogenic E. coli Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 41 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Enteropathogenic E. coli (EPEC) Characteristics – Gram-negative – Facultative anaerobe Epidemiology – Fecal-oral, generally human to human – Infant diarrhea and pediatric diarrhea in developing countries ~5-10% of pediatric diarrhea ~20% of diarrhea cases < 1-year-old Clinical Manifestation – Watery diarrhea to severe watery diarrhea 42 Bacterial GI Infections Background Enteropathogenic E. coli (EPEC) Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Pathogenesis – Adhesins Schaechter’s Mechanisms of Microbial Disease, 4 th ed. BfpA (bundle forming pilus) Intimin on bacterial surface Type III secretion system injects Tir into host cell Tir – Intimin interaction = adherence – Actin polymerization on Tir = attaching and effacing lesion Loss of microvilli = malabsorption diarrhea No toxins 43 Bacterial GI Infections Background Enteropathogenic E. coli (EPEC) Bacterial Food Poisoning “Attaching and Effacing” Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory EPEC Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Microvilli Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions A/E lesion Modified from: Mims’s Medical Microbiology, 5h Edition, © 2013 Saunders 44 Bacterial GI Infections Background Enteropathogenic E. coli (EPEC) Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Diagnosis – Culture not informative – PCR to identify virulence genes in fecal samples Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Treatment Supportive therapy Summary & Questions 45 Bacterial GI Infections Background Enterotoxigenic E. coli (ETEC) Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Characteristics – Same as EPEC Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Clinical manifestation – Watery diarrhea, sometimes vomiting Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Epidemiology – Travelers’ diarrhea = travel to developing countries and consumption of contaminated water or ice – Leading bacterial cause of diarrhea in children in the developing world – ~200 million cases of diarrhea and 380,000 deaths per year worldwide, mostly in children in developing countries. 46 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Enterotoxigenic E. coli (ETEC) Bacterial GI Infections Background Enterotoxigenic E. coli (ETEC) Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Pathogenesis – Adheres to epithelium via pili LT Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – Produces plasmid encoded toxins LT- heat liable toxin – AB toxin –  cAMP – Liable in the Air ST- heat stable toxin – Non-AB toxin, does not enter cell –  cGMP – Stable on the Ground – Not invasive, non-inflammatory, no overt toxicity to the epithelium Modified from Microbiology: An evolving science © W.W. Norton and Company, Inc. 48 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Enterotoxigenic E. coli (ETEC) Diagnosis – Clinical history – NAAT (PCR) to detect LT and ST encoding genes in clinical samples and cultures Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Treatment – Supportive therapy Summary & Questions 49 Bacterial GI Infections Background Vibrio spp. Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Disease causing Vibrio spp. Mims’s Medical Microbiology, 5h Edition, © 2013 Saunders – Vibrio cholerae (gastroenteritis) – Vibrio parahaemolyticus (gastroenteritis, bacteremia, wound infection) – Vibrio vulnificus (bacteremia, wound infection) Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Characteristics – Gram-negative, facultative anaerobes – Comma (curved) shaped – Free-living in water – Growth Broad temperature and pH range (susceptible to stomach acid, high infectious dose ~109) Halophilic = thrives in salt water 50 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Vibrio cholerae Clinical Manifestation of cholera – Asymptomatic to severe watery diarrhea – 2-3 day incubation, up to 7-day duration – 5-25% of infected individuals develop severe watery diarrhea Mims’s Medical Microbiology, 5h Edition, © 2013 Saunders Abrupt onset ~250 ml/kg body weight/day – 150 lb person = 17 liters or 4.5 gallons “Rice water” stool Can kill within hours via dehydration 51 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Vibrio cholerae Epidemiology – Spread easily through contaminated water Broad street pump, 1854, London Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae – Important cause of diarrheal disease in the developing world WHO: 1.3-4 million cases and 21,000-143,000 deaths globally each year Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli – Infection = long term immunity (appears to be O antigen specific) – Associated with epidemics and pandemics Natural disaster, population displacement, poor sanitary conditions There have been 7 documented cholera pandemics (currently in #7) Summary & Questions 52 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Vibrio cholerae Pathogenesis – Adherence to enterocytes via Toxin co-regulated pilus (Tcp) Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli – Massive fluid efflux caused by cholera toxin AB toxin Activation of adenylate cyclase  increase cAMP  massive efflux of Cl-, other ions, water follows = watery secretions No significant cell damage Very similar to ETEC LT toxin Encoded on CTXϕ (prophage) Summary & Questions Ramamurthy T, Nandy RK, Mukhopadhyay AK, Dutta S, Mutreja A, Okamoto K, Miyoshi S-I, Nair GB and Ghosh A (2020) Virulence Regulation and Innate Host Response in the Pathogenicity of Vibrio cholerae. Front. Cell. Infect. Microbiol. 10:572096. doi: 10.3389/fcimb.2020.572096 53 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Vibrio cholerae Diagnosis – Culture- in places where cholera is not endemic Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Treatment and Prevention – Rehydration therapy- IV and oral ~90% mortality in severe cases Without rehydration therapy – Prevent transmission Clean water & proper sanitation – Oral vaccines are available with mixed efficacy Recommended for people that plan to work with displaced populations in endemic areas WHO recommends use in endemic areas, especially during an outbreak investigation 54 Bacterial GI Infections Background Vibrio cholerae Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions © Aurelie Lachant/MSF 55 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Listeria monocytogenes Characteristics – Gram positive, facultative anaerobic – Short rods, sometimes occur in pairs – Intracellular pathogen – Key survival traits: Wide growth range (1˚C - 45˚C) Resistant high salt concentrations Wide pH range Summary & Questions 56 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Listeria monocytogenes Epidemiology – ~800 cases per year in the U.S. – Animal reservoirs (mammals, birds, fish) Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – Primary Source = Ready to eat meats, raw vegetables Sporadic cases to large outbreaks – High risk of infection Young, elderly, immunocompromised individuals (pregnant women) – Human to human transmission possible Primarily from mother to fetus 57 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Listeria monocytogenes Clinical manifestation – Healthy adults Usually asymptomatic, but may have fever, nausea and/or diarrhea – Immunocompromised adults Bacteremia – Fever, malaise and chills with no obvious focus Meningitis and encephalitis – Symptoms not distinct from other causes » Fever, persistent headache, stiff neck, vomiting and or confusion – 20-50% mortality rate, significant neurologic sequelae in survivors 58 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Listeria monocytogenes Clinical Manifestation continued… – Infections in pregnant women May develop nausea, fever, and/or diarrhea Fever with no obvious infection = blood culture Risk of disease transmission to the neonate Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae – Fetal/Neonatal Listeriosis (see table below) Inflammatory-ish Early-onset listeriosis Late-onset listeriosis Baby Usually premature Usually full-term and healthy Mother Recent flu-like illness before delivery No signs of illness before delivery Source of infection In utero; L. monocytogenes bacteria cross the placenta from mother to baby Unclear; baby contact with the mother’s birth canal, GI tract (maternal feces), or post-birth from the environment Develops 0 to 7 days after birth (1.5 day mean) 5 to 30 days after birth (14 day mean) Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Presentati Blood infection, pneumonia, & on meningitis Blood infection and meningitis 59 Bacterial GI Infections Background Listeria monocytogenes Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Pathogenesis – Internalin-A (IntA) mediates adherence, induced uptake Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – Listeriolysin O (LLO) disrupts vacuole membrane to allow for escape to the cytosol – Replication in host cell cytosol – ActA mediated actin polymerization (intracellular motility = spread to neighboring cells and/or blood stream – Disseminated infection Liver, spleen, CNS Modified from: Sherris, Medical Microbiology, 6 th Edition, © 2014 McGraw HIll 60 Bacterial GI Infections Background Listeria monocytogenes Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Juliet Theriot and Dan Portnoy 61 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Listeria monocytogenes Diagnosis – Culture of normally sterile sites (cerebral spinal fluid, blood) Cold enrichment selection Weak β-hemolysis on blood agar Motility test ASM MicrobeLibrary.org © Buxton - + – NAAT of CSF ASM MicrobeLibrary.org © Gini 62 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Listeria monocytogenes Treatment – Antibiotics Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Prevention – Properly cook animal products including ready-to-eat meats, wash raw vegetables Especially if immuno-compromised or pregnant Summary & Questions 63 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Enterohemorrhagic E. coli (EHEC) Characteristics – Gram-negative, facultative anaerobe – Also known as STEC (Shiga toxin E. coli) – Several serotypes O157:H7 (a lot of news coverage) causes 50% of severe disease in US – Animal reservoirs = cattle or other ruminants – Generally non-invasive Epidemiology – Sporadic cases and outbreaks mainly in the developed world associated with contaminated: ground beef (hamburger) raw vegetables or fruit (spinach, sprouts, lettuce, melons, etc. washed with water from rivers/streams) 64 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Enterohemorrhagic E. coli (EHEC) Clinical Manifestation – Hemorrhagic colitis = Bloody diarrhea – Generally little to no fever, – Marked abdominal tenderness – Sequelae- hemolytic uremic syndrome (HUS) Anemia and kidney failure Summary & Questions 65 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Enterohemorrhagic E. coli (EHEC) Pathogenesis – Attaching and Effacing lesion like EPEC – Shiga toxin (AB toxin) Inhibits protein synthesis by cleaving part of the 60S subunit of the ribosome = cell death Causes localized damage to the intestine = blood in diarrhea Travels in blood Hemolytic Uremic Syndrome – Glomeruli rich in toxin glycolipid receptor Gb3  kidney damage (kidney cell death & ischemic damage from thrombi)  kidney failure Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 66 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Enterohemorrhagic E. coli (EHEC) Diagnosis – Presumptive  bloody diarrhea WITHOUT fever – Culture E. coli O157:H7 is does NOT ferment sorbitol (rare for an E. coli) – MacConkey's with sorbitol instead of lactose » Most E. coli will ferment sorbitol = red/pink colonies » E. coli O157:H7 = colorless colonies – PCR (NAAT) Detection of stx gene that encodes toxin Treatment – Supportive therapy – Antibiotic therapy not beneficial and may be harmful Antibiotic use  bacterial cell damage  lysogenic phage (Stx)  lytic cycle  increased toxin production  increase in HUS rate Prevention – Properly cook hamburger, cook raw vegetables 67 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Salmonella spp. Nomenclature is problematic Salmonella enterica subspecies enterica serovar _______ – Over 2500 serotypes – S. Typhi Salmonella enterica subspecies enterica serovar Typhi – Non-typhoidal Salmonella Salmonella enterica subspecies enterica serovar Choleraesuis Salmonella enterica subspecies enterica serovar Enteritidis Salmonella enterica subspecies enterica serovar Typhimurium 68 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Salmonella Typhi Characteristics – Gram negative, facultative anaerobe – Motile rods, flagellated (H antigen) – Intracellular pathogen – Highly adapted to humans Epidemiology – Humans are the only reservoir – 400 - 500 cases per year in US (80% associated with travel to endemic areas) – Endemic in developing areas of: Africa, the Americas, South-East Asia and the Western Pacific regions – 11-20 million cases per year, with ~150,000 deaths worldwide – Fecal - oral transmission Contaminated food/water from infected person – Infectious dose 105 - 106 bacteria 69 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Salmonella Typhi Clinical Manifestation – ~13 day incubation Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – Symptom Progression Fever with headache Rising fever over 3 days Typhoid (enteric) fever = Prolonged fever (~ 4 weeks) Infection of the gall bladder  reinfection of the intestine  diarrhea Potentially, chronic colonization of the gall bladder – Shedding of S. Typhi in stool 70 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Salmonella Typhi Clinical Manifestation Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 71 Bacterial GI Infections Background Salmonella Typhi Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Pathogenesis – Adherence to Mcells and enterocytes – M-cells sample and present intestinal contents to immune cells Associated with Peyer’s patches in the ileum Modified from: Murray, Medical Microbiology, 8 th Edition, © 2016 Saunders 72 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Salmonella Typhi Scanning electron micrograph of mouse intestine during Salmonella infection  Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions M-cell in the center – Salmonella-induced of apical membrane (membrane ruffling) M-cell in upper-left M. Jepson and M. Clark. The role of M cells in Salmonella infection. 2001. Microbes and infection. 3:1183-1190. – Typical uninfected M-cell 73 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Salmonella Typhi Pathogenesis – Type III Secretion system (T3SS) mediated uptake into M-cell T3SS = molecular syringe Injection of SspsSalmonella-secreted invasion proteins Membrane ruffling  endocytic uptake Modified from: Sherris, Medical Microbiology, 6 th Edition, © 2014 McGraw HIll 74 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Salmonella Typhi Pathogenesis – Salmonella traffics to the basal surface of M-cell Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae – Selective phagocytosis into macrophage Vi-antigen polysaccharide capsule prevents neutrophil phagocytosis Inflammatory-ish Listeria monocytogenes – Macrophage transit to draining lymph nodes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – Vi-antigen polysaccharide capsule promotes extended intracellular replication – Bacteremia Fever from septicemia (LPS aka. endotoxin) Modified from: Murray, Medical Microbiology, 8 th Edition, © 2016 Saunders 75 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Salmonella Typhi Diagnosis – Culture of stool and blood samples Non-lactose fermenting (white on MacConkey's) Produces H2S on SS or Hektoen agar= black precipitate Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Treatment – Antibiotic therapy based of susceptibility profile Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Prevention – Avoid potential sources of infection Drink only bottled water in endemic areas, no ice, thoroughly cooked food, avoid raw fruits and vegetables – Vaccination for travelers to endemic areas Ty21A- capsule by mouth, 4 doses ViCPS- injection, 1 dose 76 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Salmonella Typhi Mary Mallon: born September 23, 1869 Cookstown, Ireland. Emigrated to the U.S. around the age of 15. From 1900 to 1907, – Worked at 7 jobs in which 22 people had become ill with Typhoid fever, including one young girl who died. Quarantined - 3 years, Riverside Hospital, North Brother Island, NY. In 1910, a new health commissioner decided that Mallon could go free as long as she agreed never to work as a cook again. In 1915 the Sloane Maternity Hospital in Manhattan suffered a typhoid fever outbreak. – Twenty-five people became ill and two of them died. – Mary Mallon was working in the hospital as a cook. Again sent to North Brother Island, died there in 1938. Forty-seven illnesses and 3 deaths were attributed to Typhoid Mary. 77 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Nontyphoidal Salmonella Nomenclature – Non-typhoidal Salmonella (Enteric) Salmonella enterica subspecies enterica serovar Choleraesuis Salmonella enterica subspecies enterica serovar Enteritidis Salmonella enterica subspecies enterica serovar Salmonella enterica serovar Typhimurium Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Characteristics – Gram negative, facultative anaerobe – Motile rods, flagellated (H antigen) – Intracellular pathogens Same as S. Typhi except it is not as human adapted. 78 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Nontyphoidal Salmonella Epidemiology – ~50,000 cases per year in US (low estimate) – Disease of industrialized countries – Higher incidence in young children/elderly – Source of infection Numerous animal reservoirs (turtles, chickens, pigs, etc…) Contaminated food (poultry, eggs, dairy products, peanut butter) Human to human transmission unlikely – Infectious dose is 106 – 108 bacteria Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 79 Mims’s Medical Microbiology, 5 h Edition, © 2013 Saunders Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Nontyphoidal Salmonella Clinical manifestations – Occur between 6 - 48 h post-ingestion Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – Nausea & vomiting with/followed by abdominal cramps – Diarrhea = Loose stool ➜ pus/blood (severe dysentery-like diarrhea) – Persistent diarrhea for 3-4 days, can last 1-2 weeks – Spontaneous resolution within ~7 day – 50% of cases present with fever 80 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Nontyphoidal Salmonella Pathogenesis – Initial pathogenesis like S. Typhi (entry and movement through enterocyte) Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – Once nontyphoidal Salmonella are in macrophage: Rapid killing of macrophage via multiple mechanisms – Massive inflammatory response that: » Confines the infection » Damages intestine resulting in diarrhea Immunocompromised or severe cases = Salmonella dissemination around the body – Systemic dissemination, bacteremia – Focal infections- arthritis, osteomyelitis, endocarditis, etc… Modified from: Sherris, Medical Microbiology, 6 th Edition, © 2014 McGraw Hill 81 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Nontyphoidal Salmonella Diagnosis – Culture from blood and stool Does NOT ferment lactose (white on MacConkey's) Produces H2S on SS, TSI, Hektoen agar= black precipitate Treatment – Gastroenteritis Supportive therapy Antibiotic therapy not recommended – Enhances carrier state (asymptomatic shedding for up to 1 year) – Severe cases or systemic infection Antibiotic therapy depending on resistance profile Prevention = food safety 82 Bacterial GI Infections Background Bacterial Food Poisoning S. Typhi vs. S. Typhimurium (all other non-typhoidal Salmonella Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Early stages of pathogenesis (uptake and movement through enterocyte) for S. Typhi and non-typhoidal Salmonella are very similar Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Vi-antigen polysaccharide capsule of S. Typhi responsible major difference between typhoidal and non-typhoidal pathogenesis – Prevents phagocytosis by neutrophils – Promotes extended survival in macrophage 83 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Campylobacter jejuni Characteristics – Gram-negative rod, curved or “sea-gull” shaped – Motile via flagella – Microaerophilic, 42˚C growth Clinical Manifestation Mims' Medical Microbiology 5th Ed. © 2013 Saunders – Long incubation time (2-11 days) – Lower abdominal pain, fever, diarrhea = watery  pus/blood – Most cases spontaneously revolve < 1 week – Complications Sepsis Sequelae = Guillain-Barre syndrome 84 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Campylobacter jejuni Epidemiology – Was not recognized as a pathogen until 1973 (needed proper culturing techniques) – Source often contaminated food or pets Undercooked poultry Raw Milk Many animal reservoirs (turkeys, sheep, cattle ,chickens, birds, dogs) – #1 cause of GI infection in developed countries – Low infectious dose ~100 organisms Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Pathogenesis – Flagella mediated adherence to intestinal epithelium – Production of toxins – Intestinal pathology Acute inflammation, crypt abscesses, occasional entry into bloodstream 85 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Campylobacter jejuni Guillain-Barre syndrome (GBS) – Heterogeneous syndrome of acute immune-mediated polyneuropathy – Progressive, symmetric muscle weakness accompanied by absent or depressed deep tendon reflexes – Symptoms vary difficulty walking  nearly complete paralysis (extremity, facial respiratory and bulbar muscles) ~30-40% of GBS is attributable to Campylobacter infection – Type II hypersensitivity= antibodies against C. jejuni LOS (LPS but shorter) cross reaction with host peripheral nerve myelin gangliosides 86 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Campylobacter jejuni Diagnosis – Stool culture (done routinely) Culture at 42˚C Selective media in a microaerophilic environment Observation of a gram-negative, curved rod Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Treatment – Uncomplicated cases Supportive therapy – Complicated cases = severe disease, bacteremia, etc.. Antibiotic Therapy 87 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Vibrio parahaemolyticus Characteristics – See Vibrio slide just before V. cholerae Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Epidemiology – Associated with consumption of raw shellfish – Leading cause of seafood-borne enteritis world-wide Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Clinical manifestation – 4-hour to 4-day incubation, lasting ~3 days (< 1 week) – Two distinct presentations: Most common - watery diarrhea, nausea, vomiting, abdominal cramps, ¼ of patients have fever and chills Least common – dysentery (severe abdominal cramps, nausea, vomiting, bloody and/or mucoid stools) 88 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Vibrio parahaemolyticus Pathogenesis – Currently being elucidated – Two major hemolysin toxins (thermostable direct hemolysin Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Treatment and Prevention – Supportive therapy – Proper cooking of shellfish Summary & Questions 89 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Yersinia enterocolitica Characteristics – Just like Y. pestis – Gram-negative coccobacilli – Bi-polar staining with Giemsa stain (safety pin appearance) – Causes a disease called yersiniosis Summary & Questions 90 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Yersinia enterocolitica Clinical Manifestation – Can affect any age, most often in young children – 4-7 day incubation – 1-3 weeks or more of fever, abdominal pain and cramps, watery  bloody diarrhea – Acute mesenteric lymphadenitis Pain may be so severe it is confused with acute appendicitis – Lasts 1 - 2 weeks 91 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Yersinia enterocolitica Epidemiology – Widespread in nature and animals Most isolates are avirulent – Transmission Raw/undercooked pork = most common source (e.g., improperly cured/cooked/prepared pork sausage, cross contamination while preparing chitlins Others: unpasteurized milk/milk products, untreated water, etc. Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 92 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Yersinia enterocolitica Pathogenesis – A lot is known, not high yield Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Diagnosis – GI NAAT/CIDT Panel, positive followed by culture – Culture of stool, blood, bile, wound, throat swab, mesenteric lymph node biopsy, CSF, or peritoneal fluid in suspected cases. Must notify the clinical lab. Treatment – Supportive therapy in most cases as the disease is usually self limiting. – Antibiotics for severe cases. 93 Bacterial GI Infections Background Clostridioides difficile Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus C. diff Pseudomembrane colitis – (old name Clostridium difficile) Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Characteristics – Gram-positive anaerobe – Spore forming – Emerging nosocomial pathogen Wikimedia Clinical Manifestation – Symptoms vary Asymptomatic carriage  CDAD  pseudomembrane colitis  fulminant colitis with toxic megacolon 94 Bacterial GI Infections Background Clinical Variants: C. diff. infection Diarrhea Other Symptom s Physical Exam Sigmoidosc opic Examinatio n Asymptomatic carriage Absent Absent Normal Normal C. difficileassociated diarrhea CDAD Watery diarrhea Fecal Leukocytes Occult blood sometimes seen Nausea, anorexia, fever, malaise, dehydration, leukocytosis with left shift Abdominal distention, tenderness Diffuse or patchy nonspecific colitis Pseudomembrane colitis Profuse watery diarrhea Fecal Leukocytes Occult blood sometimes seen Same as CDAD but more severe Marked abdominal distention, tenderness Adherent yellow plaques (pseudomembrane) Fulminant colitis Diarrhea may be severe or diminished Surgical consult required Lethargy, fever, tachycardia, may observe dilated colon on abdominal film May present as acute abdomen (sudden, severe abdominal pain) Procedure contraindicated Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Type of Infection Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 95 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Clostridioides difficile Pathogenesis Antibiotics alter normal intestinal microbiota Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish C. difficile survive, germinate and thrive (increased numbers, less competition) Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Toxin A and toxin B produced in significant quantities Mucosal cell injury and inflammation Diarrhea; possibly more severe symptoms 96 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Clostridioides difficile Risk Factors for Developing C. diff Disease – Recent antibiotic use = 7-10x more likely to develop C. diff disease – Extended stays in healthcare settings – ≥ 65 yr – Weakened immune system – Previous C. diff infection – Known C. diff exposure 97 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Clostridioides difficile Diagnosis – Test for C. diff in patients with ≥ 3 loose stools in 24 hrs with risk factors – Many Diagnostic Testing Algorithms Most suggest at least 2 testing modalities – Tests EIA test for toxin A, toxin B, or both in stool – Less sensitive but rapid and cheap – Side note: 2 hrs at room temp = loss of detectable toxin C. diff glutamate dehydrogenase (GDH) detection in stool – Cannot distinguish between toxin & non-toxin producing strains NAAT (PCR) test for toxin B gene – High sensitivity – Issues with overdiagnosis, cannot distinguish infection from asymptomatic carriage Culture (not common) 98 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Clostridioides difficile Treatment- based on occurrence – Initial infection, 1st recurrence Antibiotics: vancomycin, fidaxomicin, or metronidazole – > 2nd recurrence and/or antibiotic resistance Antibiotics (vancomycin, fidaxomicin, or metronidazole) or Fecal Microbiota Transplant (FMT) Summary & Questions 99 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Clostridioides difficile Prevention & Special Precautions – C.diff patients must be isolated – Specific contact precautions (gown and glove) – Hand hygiene = hand washing (hand sanitizer does not kill spores) – Environmental cleaning and disinfection with sporicidal agents Summary & Questions 100 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Shigella spp. Characteristics – Gram negative rods, facultative anaerobe – Intracellular pathogens Epidemiology – ~150 million cases, 600,000 deaths per year worldwide – Humans are the only reservoir – Transmission through the fecal oral route – Extremely low infectious dose, < 10 organisms – Incidence directly related to hygiene Poor sanitary infrastructure, crowded healthcare systems Day care centers – Global species distribution: S. sonnei- developed countries S. flexneri- developing countries S. dysenteriae- underdeveloped tropical areas – Most severe infections due to high Shiga toxin production 101 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Shigella spp. Iowa Department of Public Health Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions 102 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Shigella spp. Clinical Manifestations of Shigellosis – 1-3 days post-ingestion Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – Disease usually self-limiting, 2 to 5 days post manifestation – Generally, strain-specific S. sonnei – Fever, malaise, and watery diarrhea S. flexerni and S. dysenteriae – Bacillary dysentery » Fever, malaise, abdominal cramps, watery diarrhea, tenesmus (frequently feeling need to defecate) frequent bloody and pusfilled stools – S. dysenteriae- potential for hemolytic uremic syndrome (HUS) 103 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Shigella spp. Pathogenesis – T3SS mediated uptake into M-Cells – Release from M-Cells – Phagocytosed by macrophages – Rapid escape from phagosome and induction of macrophage apoptosis (programmed cell death) Image adapted from: Schroeder et al. 2008 Clin. Microbiol. Rev. 104 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Shigella spp. Pathogenesis – Interact with baso-lateral face of enterocytes Gastritis/Ulcers Helicobacter pylori – Induce uptake via T3SS Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Image adapted from: Schroeder et al. 2008 Clin. Microbiol. Rev. – Escape from endocytic vacuole – Spread to neighboring cells via actin polymerization – Enterocyte escape/invasion leads to cell death Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions – Ulcers form in infected areas – Diarrhea primarily from severe inflammation – Shiga toxin production (Stx) Same as EHEC Shiga-like toxin 105 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Shigella spp. Diagnosis – Stool culture using selective media Does not ferment lactose, does not produce H2S White/clear colonies on MacConkey’s and Hektoen or SS-agar Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Treatment – Rehydration therapy – Antibiotic therapy Shorten duration of illness and/or limit disease severity Antibiotic choice dependent on susceptibility profile Prevention – Improved sanitation and personal hygiene – Infection does not confer immunity! 106 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Helicobacter pylori Enteroinvasive E. coli Characteristics – Gram-negative, facultative anaerobe Epidemiology – Not common Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Clinical Manifestation – Generally milder form of shigellosis symptoms (dysentery) Pathogenesis Nature Reviews Microbiology – Same as Shigella infection EXCEPT no Shiga-toxin Appears E. coli obtained pathogenicity island from Shigella spp. via horizontal gene transfer 107 Bacterial GI Infections Background Bacterial Food Poisoning Staphylococcus aureus Clostridium botulinum Clostridium perfringens Bacillus cereus Gastritis/Ulcers Treatment of Infectious Diarrhea or Bacterial Food Poisoning No specific diagnosis in most cases Helicobacter pylori Non-inflammatory Enteropathogenic E. coli Enterotoxigenic E. coli Vibrio cholerae Inflammatory-ish Listeria monocytogenes Inflammatory Enterohemorrhagic E. coli Salmonella Typhi Nontyphoidal Salmonella Campylobacter jejuni Vibrio parahaemolyticus Yersinia enterocolitica Clostridioides difficile Shigella spp. Enteroinvasive E. coli Summary & Questions Clinical diagnosis made via history, physical, stool examination, and dehydration severity Supportive therapy in most cases – Rehydration, nutritional supplementation, etc. Antibiotic therapy can shorten duration and lessen severity in some cases of infectious diarrhea – Often reserved for complicated cases, cases in age extremes, immune compromised, severe cases, etc. – Contraindicated in certain cases (EHEC, salmonellosis) 108 Bacterial GI Infections Organism Background Diarrhea Type EPEC Bacterial Food E

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