MICR 201 Microbiology for Health Related Sciences

1. MICR 201 Microbiology for Health Related Sciences Microbiology- a clinical approach by Anthony Strelkauskas et al. 2010 Chapter 22: Infections of the digestive system

2. Why is this chapter important? • The digestive system is the second leading portal of entry into the body. As a health care professional you will see many patients with infections of the digestive system.

3. Map for chapter 22

4. Anatomy of the digestive system

5. Overview • The digestive system is a major portal of entry. • Many pathogens enter the body when we ingest water and food. • Defenses of the digestive system are very strong. • Lysozyme, low gastric pH, bile salts • Paneth cells in small intestine • GALT • IgA • Normal microbiota • Keep many infections from ever happening. • Digestive infections and food poisoning are a major cause of morbidity and mortality. • Cause the death of millions of children • Immune system is not mature.

6. Clinical symptoms of gastrointestinal infections and food poisoning • Most common symptoms are: • Abdominal pain • Diarrhea • Vomiting • Fever • Food poisoning • Preformed toxins, act rather as neurotoxins • Nausea and vomiting may be main symptoms • Rapid onset is rapid and short duration • Typically without fever • Infection • Bacteria have to colonize, establish infection before toxins are produced and can act • Onset several days after uptake and ~ 1 week duration • Two major types of toxins • Enterotoxin: watery diarrhea • Cytotoxin: fever, bloody diarrhea

7. Food poisoning • Usually connected to one meal • Single source of contamination • Typically involves multiple patients • Almost always involves improper food handling • Has increased with the popularity of fast food • Main sources for toxin • Staphylococcus aureusenterotoxin (superantigen) • Salads containing mayonnaise, custards • Bacillus cereus enterotoxin • Undercooked rice

8. Clinical symptoms of gastrointestinal infections • The central feature in all cases is diarrhea. • The nature of the diarrhea is used to classify gastrointestinal infections into three categories: • Watery diarrhea: enterotoxin mediated such as in ETEC in traveler's diarrhea or in cholera • Dysentery: cytotoxin mediated such as in Shigella dysentery • Enteric fever: translocation of pathogen from intestinal lumen into circulation and systemic spreading; diarrhea less prominent; such as in typhoid fever caused by Salmonella typhi

9. Epidemiology of gastrointestinal infections • Transmitted via food and water • Fecal-oral cycle can be broken by: • Proper sewage disposal • Disinfection of drinking water • Proper food preparation and storage

10. Nosocomial gastrointestinal infections • Acquired in a hospital and usually traced to: • Clostridiun difficileaccounts for 90% of infections. • Symptoms range from mild diarrhea to fulminant pseudomembranous colitis. • Colitis arises either during or after treatment with antibiotics.

11. Treatment of food poisoning and gastrointestinal infections • Mainly supportive care with liquid replacement and rest • Substantial liquid loss requires intravenous replacement. • Infection with E. coli O157:H7 can result in renal failure. • Requires dialysis or transplant. • If bacteria spread from the intestine antibiotics are given.

12. Dental and periodontal infections • Most commonly seen infections in the mouth are: • Dental caries. • Infections of the gum tissue. • In both cases, the major source of infection is plaque. • Forms as a result of bacterial colonization on surface of teeth originating from normal microbiota

13. Formation of dental plaque • Tooth surface is normally covered by pellicle (lipids, protein) • Bacteria adhere to the pellicle. • Facilitated by bacterial adhesion molecules • Initial adherent is usually Streptococcus mutans • Additional species are recruited • Biofilm develops

14. Formation of dental plaque

15. Dental caries • Organisms that produce acid can cause dental caries. • Streptococcus mutansis the major cause. • Other organisms contribute. • Carbohydrates easily enter the plaque and are readily metabolized. • Acid damages tooth enamel. • Repeated snacking on sugar keeps acid level high. • This continues demineralization of the tooth. • Chewing sugar free gum reduces caries

16. Gingivitis and periodontitis • There are two forms of plaque-induced periodontal disease. • Gingivitis • Inflammatory condition limited to the surfaces of the gingiva • Does not involve loss of bone • Can be corrected • Will continue as long as dental plaque remains • Periodontitis • Infection of the gingiva • Results in loss of supportive bone and ligaments • Responsible for most tooth loss in adults

17. Which of the following statements regarding caries is incorrect? • S. mutans is solely responsible for caries development. • In caries acids damage the enamel. • Caries is considered an infectious disease because microbes are the ones converting sugars into the damaging acid. • Caries involves biofilm formation on the teeth. • All statements are correct.

18. In contrast to periodontitis, gingivitis________. • Is a disease between the teeth. • Is not an infectious disease. • Does not involve bone loss. • All are correct. • None of the above is correct.

19. Bacterial infections of the digestive system • Helicobacter pylori • Enterobacteriaceae • Escherichia coli • Salmonella • Shigella • Yersinia • Campylobacter spec. • Vibrio cholerae

20. Helicobacter pylori • Gram-negative curved rod • Microaerophilic • Polar flagella • Produces urease • Generates ammonia • Allows it to survive in very acidic environments • Vacuolating cytotoxin • Causes apoptosis in eukaryotic cells

21. Helicobacter pylori • Helicobacter pyloriinfection causes ulcers. • Treat with antibiotics (tetracycline plus clarithromycin ) • Found in 30-50% of all adults in developed countries • Practically 100% of adults in developing countries • Mode of transmission is not known. • Presumed to be person-to-person by the fecal-oral route • Can develop into gastric cancer

22. Enterobacteriaceae • Diverse family of Gram-negative rod-shaped bacteria • Facultative anaerobic • Some are part of the indigenous microflora in the intestine: Escherichia coli • Some are human primary pathogens: Salmonella, Shigella, Yersinia • May produce various virulence factors • Enterotoxin, cytotoxin (shiga toxin), type III secretion apparatus • Identification biochemically and serologically • Antigens: LPS, flagellin, capsule • Many serotypes (Salmonella over 2000)

23. E. coli • Over 150 different serogroups of E. coli • Classified according to O, K, and H antigens • Many use fimbriae and pili to attach to host cells. • E. coli can be divided into the following: • Enterotoxigenic E. coli (ETEC): watery diarrhea • Enteropathogenic E. coli (EPEC): often in newborns • Enteroinvasive E. coli (EIEC): dysentery • Enteroaggregative E. coli (EAEC) • Enterohemorrhagic E. coli (EHEC): bloody diarrhea

24. EnterohemorrhagicE. coli (EHEC) • E. coli O157:H7 is a well known enterohemorrhagic E. coli. • Low ID50 (around 103) • Causes bloody diarrhea • Associated with ground meat and unpasteurized juices (vegetable and fruit) • Person-to-person transmission can occur. • Infection is more common in developed industrialized countries.

25. EnterohemorrhagicE. coli (EHEC): Pathogenesis • Distinguishing clinical factors are: • Production of shiga-like toxin. • Effacement of intestinal microvilli. • Attack the colon by adhering through attachment proteins • Use the secretion infection system to deliver proteins into target cells • These proteins alter cytoskeletal components.

26. EnterohemorrhagicE. coli (EHEC)Pathogenesis • Certain strains produce shiga like toxin • Toxin is resorbed and enters circulation • Bacteria remain in the intestine on top of the cells, not inside • Toxin is transported to small vessel • Microvascular endothelial cell damage • Inhibition of protein synthesis • Apoptosis • Platelet activation

27. Kidney damage in hemolytic uremic syndrome Normal Diseased

28. Shigella • Shigella species cause severe dysentery. • Spread from person to person in unsanitary conditions • Shigella species are closely related to E. coli but: • Cannot ferment lactose. • Lack flagella. • All species produce Shiga toxin, a cytotoxin.

29. Shigella: Epidemiology • ID50 is fewer than 200 organisms. • It is easily transmissible. • 40% of patients get infection from family member.

30. Shigellosis • Shigella is acid-resistant. • Survives passage through the stomach • Invade the cells of the colonic mucosa • Intense acute inflammatory response, leukocytes in feces • Causes mucosal ulcerations and abscess formation

31. Salmonella • All types of Salmonella infecting humans are now classified as one species, enterica. • Salmonella entericais divided into serotypes based on its antigens. • O antigens identify the serogroup. • K and H antigens are used for further subdivision. • Can also distinguish Salmonella by host range • Some are strictly adapted to humans. • Many colonize various animals

32. Salmonella invasion

33. Salmonellosis • Ingested • Requires large dose (105) • Sources include chicken and reptiles like turtles • Salmonella enterica serovars such as S. enterica Typhimurium • Affects small intestine • Mortality (<1%) due to septic shock caused by endotoxin • Systemic in immunocompromised

34. Typhoid Fever • Salmonella enterica Typhi • Human adapted • Low infectious dose (~1000) • Enter through small intestine • Bacteria routinely spread throughout body in phagocytes • High fever, continued headaches • Diarrhea only during 2.. and 3. week when fever declines • 1-3% recovered patients become chronic carriers, harboring Salmonella in their gallbladder

35. Yersiniagastroenteritis • Can reproduce at 4°C • Usually transmitted in meat and milk • Associated with arthritis

36. Campylobactergastroenteritis • Microaerophilic gram negative rods (not a member of Enterobacteriacea) • Usually transmitted in cow's milk • Linked to Guillian-Barre syndrome, an autoimmune neurological disorder with temporary paralysis http://en.wikipedia.org/wiki/Campylobacter

37. Vibrio • Gram-negative, non spore-forming, and rod-shaped • Not a member of the family of Enterobacteriaceae • Commonly found in salt water • Have a unique morphology • Form S shapes and half spirals • Highly motile by means of a single polar flagella

38. Vibrio • Low tolerance for acidic conditions • Grow well in mildly alkaline environments • Vibrio choleraeproduces an enterotoxin. • Acts on enterocytes • Causes a devastating fluid loss without actually damaging the enterocytes

39. Cholera • Cholera has a rapid onset characterized by: • Abdominal fullness. • Discomfort. • Rushes of peristalsis. • Loose stools. • Stools quickly become watery, voluminous, and almost odorless. • Can progress to rice stool containing mucus • No fever • No blood in stool • Treatment: liquid replacement

40. Cholera bed

41. Turtles have been found to serve as reservoir for which pathogen? • Yersinia • EHEC • Shigella • Campylobacter • Salmonella

42. Viral diseases of the digestive system • Mumps • Gastroenteritis • Hepatitis

43. Mumps • Mumps virus • Enters through respiratory tract • Infects parotid glands and leads to painful swelling and fever • May cause orchitis (infection of the testis that may lead to infertility), even less frequently meningitis, inflammation of ovaries, and pancreatitis • Prevented with MMR vaccine

44. Viral gastroenteritis • Digestive system is an important portal of entry for viruses. • For some it is only an entry point • Disease occurs somewhere else. • Most common sign of enteric viral infection is diarrhea. • Fecal -oral transmission • Rapid onset – within hours • Vomiting along with diarrhea • Lasts for less than three weeks • Abundant excretion of virions in the stool • 108 per gram of stool

45. Viral infections of the digestive system • Several groups of viruses cause gastrointestinal infections • Rotavirus • Enterovirus

46. Rotavirus • Not discovered until 1973 • Now found around the world • Believed to account for 40 - 60% of cases of acute gastroenteritis • Watery stools, low grade fever • Can undergo genetic re-assortment • Difficult to deal with immunologically • Outbreaks of rotavirus infections common in infants and children under 2 and often causing death in underdeveloped countries. • Adults are usually only minimally affected. • Can affect the elderly or institutionalized

47. Hepatitis viruses • Hepatitis describes any disease that affects the hepatocytes of the liver. • Diseases can be caused by a variety of agents: • Bacteria • Protozoans • Viruses • Toxins • Drugs • At least 6 different viruses cause hepatitis • They are distinctly different from one another. • Therapy is mainly symptomatic • Interferon-alpha therapy for HCV • Vaccines available for HAV and HBV • HBV required for all healthcare workers

48. Hepatitis viruses

49. Liver cirrhosis as complication of hepatitis

50. Hepatitis C virus • Belongs to Flaviviridae • + ssRNA, enveloped, entirely cytoplasmic replication • Transmitted mainly by transfusion (including needle sharing and hemodialysis, also sexual • Is considered persistent (infects mainly hepatocytes, but also documented for peripheral blood mononuclear cells) • CTL escape mutations • Interfere with interferon regulatory factor • Usually mild hepatitis or asymptomatic • 80% of the infected become chronically infected and of these up to 20% develop cirrhosis and of these up to 5% hepatocellular carcinoma.