1. Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno Miroslav Votava Agents of digestive system infections – II Lecture for 3rd-year students 15th October, 2010

2. Digestive system – revision a microbiologist´s dreamlanda microbiologist´s dreamland a fruitful microbial gardena fruitful microbial garden its both ends are the „buggiest“ parts of the bodyits both ends are the „buggiest“ parts of the body in the colon: approx. 10 12 bacteria/gin the colon: approx. 10 12 bacteria/g normal colonic flora: 99 % anaerobes (Bacteroides, Fusobacterium, Clostridium, Peptostreptococcus), only 1 % enteric bacteria (mostly E. coli) & enterococcinormal colonic flora: 99 % anaerobes (Bacteroides, Fusobacterium, Clostridium, Peptostreptococcus), only 1 % enteric bacteria (mostly E. coli) & enterococci

3. Mouth cavity – revision I Normal flora: viridans (= α-haemolytic) streptococci (e.g. Streptococcus salivarius)viridans (= α-haemolytic) streptococci (e.g. Streptococcus salivarius) oral neisseriae (e.g. Neisseria subflava)oral neisseriae (e.g. Neisseria subflava) haemophili of very low pathogenicity (e.g. Haemophilus parainfluenzae)haemophili of very low pathogenicity (e.g. Haemophilus parainfluenzae) Dental plaque: adherent microbial layer at the tooth surface consisting of living and dead bacteria and their products together with components from the saliva In essence, dental plaque is a biofilm It cannot be washed off, only mechanically removed

4. Mouth cavity – revision II Dental caries: chronic infection caused by normal oral flora → localized destruction of tooth tissue Etiology: mouth microbes (mostly Strept. mutans) making acids from sucrose in food Thrush (in Latin soor): Candida albicans It occurs mostly in newborns Herpetic stomatitis: primary infection with HSV 1 Ludwig´s angina: polymicrobial anaerobic infection of sublingual and submandibular spaces (Porphyromonas, Prevotella etc.)

5. Oesophagus – revision Infections never occur in previously healthy individuals Only in severely immunocompromised persons (AIDS or after chemotherapy): Candida albicansCandida albicans Cytomegalovirus (CMV)Cytomegalovirus (CMV)

6. Stomach – revision Stomach = a sterilization chamber killing most of the swallowed microbes by means of HCl Exception: Helicobacter pylori It produces a potent urease and by splitting tissue urea it increases pH around itself (1 molecule of urea → 1 CO 2 + 2 NH 3 ) H. pylori causes chronic gastritischronic gastritis peptic ulcers (Warren & Marshall, Nobel price in 2005)peptic ulcers (Warren & Marshall, Nobel price in 2005)

7. Biliary tree & the liver – revision I Acute cholecystitis (colic, jaundice, fever): obstruction due to gallstones Etiology: intestinal bacteria (E. coli etc.) Complication: ascending cholangitis Chronic cholecystitis: the most dangerous agent is Salmonella Typhi (carriers of typhoid fever) Granulomatous hepatitis: in Q fever, tbc, brucellosis

8. Biliary tree & the liver – revision II Parasitic infections of the liver: Amoebiasis (Entamoeba histolytica: liver abscess) Malaria (the very first, clinically silent part of the life cycle of malaric plasmodia) Leishmaniasis (Leishmania donovani: kala-azar, L. infantum) Schistosomiasis (eggs of Schistosoma japonicum, less often S. mansoni)

9. Systemic infections which start in the digestive tract – revision Enteric fever (typhoid fever and paratyphoid fever): Salmonella Typhi, Salmonella Paratyphi A, B and C Listeriosis: Listeria monocytogenes Peritonitis: colonic flora (Bacteroides fragilis + other anaerobes + mixture of facultative anaerobes) Viral hepatitis: HAV, HBV, HCV, HDV, HEV

10. Small and large intestine - revision Bacterial overgrowth syndrome: After surgery, during depressed peristalsis or gastric achlorhydria bacteria may overgrow in the small intestine → steatorrhea, deficiency of vitamin B 12, diarrhea, malabsorption of vitamins A and D Diarrhea: increase in daily amount of stool water – common intestinal response to many agents Dysentery: acute inflammation of the colon → abdominal pain & small-volume stools with blood, pus and mucus

11. Etiology of diarrheal disease – revision Infectious etiology: Bacterial (most frequent)Bacterial (most frequent) ViralViral ParasiticParasitic MycoticMycotic Non-infectious etiology: Food poisoningFood poisoning

12. Bacterial agents of diarrhea and dysentery – I Escherichia coli Most E. coli strains are component (approx. 1 %) of normal intestinal flora - important - important - essential - essential - beneficial - beneficial - non-pathogenic in the intestine - non-pathogenic in the intestine Only some E. coli strains are pathogenic even in the intestine

13. Bacterial agents of diarrhea and dysentery – II Escherichia coli strains causing diarrheal disease: ETEC (enterotoxic E. coli): children in developing countries, traveller´s diarrhea; 2 enterotoxins (heat-labile and heat-stable)ETEC (enterotoxic E. coli): children in developing countries, traveller´s diarrhea; 2 enterotoxins (heat-labile and heat-stable) EPEC (enteropathogenic E. coli): O55, O111; small infants; disruption of microvillus structureEPEC (enteropathogenic E. coli): O55, O111; small infants; disruption of microvillus structure EIEC (enteroinvasive E. coli): similar to shigellae; invasion of colonic cellsEIEC (enteroinvasive E. coli): similar to shigellae; invasion of colonic cells EHEC (enterohaemorrhagic E. coli): O157:H7; 2 cytotoxic shigatoxins, destruction of microvilli; hemorrhagic colitis & hemolytic-uremic syndromeEHEC (enterohaemorrhagic E. coli): O157:H7; 2 cytotoxic shigatoxins, destruction of microvilli; hemorrhagic colitis & hemolytic-uremic syndrome

14. Bacterial agents of diarrhea and dysentery – III Salmonella Taxonomical remarks: There are >4.000 salmonella serotypes Official names of them are very inconvenient: 1.The most frequent salmonella: Salmonella enterica subspecies enterica serotype enteritidis 2.The most important salmonella: Salmonella enterica subspecies enterica serotype typhi Instead of them we can use more useful names: 1.Salmonella Enteritidis 2.Salmonella Typhi

15. Bacterial agents of diarrhea and dysentery – IV Two types of salmonella infections: 1)Systemic infections (enteric fever): S. Typhi, S. Paratyphi A – C 2)Gastroenteritis (salmonellosis): remaining >4.000 serotypes Pathogenesis of both starts with the invasion of intestinal epithelia In 1) invasion continues and infection becomes generalized → little or no diarrhea, but pronounced fever & other general symptoms In 2) infection is localized to ileocaecal region → diarrhea, nausea & vomiting, abdominal pain, temperature may be elevated

16. Bacterial agents of diarrhea and dysentery – V Diagnosis & treatment of salmonella infections: 1)Enteric fever (reservoir: human beings only): Detection of salmonellae in blood, urine and stool (on special media), later detection of antibodies (Widal reaction), in suspected carriers examination of duodenal fluid Treatment: antibiotics (chloramphenicol, fluorochinolones, ampicillin, cotrimoxazol) 2) Gastroenteritis (reservoir: poultry & animals): Examination of stool only Treatment: symptomatic only, no antibiotics

17. Bacterial agents of diarrhea and dysentery – VI Campylobacter jejuni As common as salmonella (or even more); invades jejunal epithelium ; reservoir: poultry Cultured on a special medium, in an atmosphere of reduced oxygen, at 42 °C Shigella sonnei, S.flexneri, S.boydii, S.dysenteriae Very low infectious dose → epidemic outbreaks Transmitted only among human beings Invasion of cells of colon and rectum The disease is called bacterial dysentery

18. Bacterial agents of diarrhea and dysentery – VII Yersinia enterocolitica gastroenteritis, in children also mesenterial lymphadenitis (mimicking acute appendicitis) gastroenteritis, in children also mesenterial lymphadenitis (mimicking acute appendicitis) vector: contaminated food vector: contaminated food the microbe multiplies in refrigerator even at 4 °C the microbe multiplies in refrigerator even at 4 °C Vibrio cholerae Cholera toxin activates adenylate cyclase → hypersecretion of water & electrolytes → death by dehydration and electrolyte abnormalities V. cholerae flourishes in water & causes epidemics Vibrio parahaemolyticus: from raw fish & shell-fish

19. Diarrhea during antibiotic therapy Common after tetracyclines; from excessively multiplied Staphylococcus aureus, Pseudomonas aeruginosa or Candida albicans (the example of diarrhea of mycotic origin) After lincomycin or clindamycin (but even after other ATB) → dangerous pseudomembranous colitis caused by Clostridium difficile Patients contaminate the hospital environment with resistant spores Colitis can be treated by metronidazol

20. Viral agents of diarrhea Generally: small, acid- and bile-resistant non- enveloped viruses Rotaviruses (Reoviridae family) serious diarrhea of young children, epidemics in winter Noroviruses and sapoviruses (formerly agents Norwalk and Sapporo, Caliciviridae family) epidemics in children and adults, too Astroviruses (star-shaped virions) Adenoviruses type 40 and 41 Small, round gastroenteritis viruses

21. Parasitic agents of diarrhea In previously healthy individuals: Entamoeba histolytica: amoebic dysentery Giardia lamblia: giardiasis Cryptosporidium parvum: cryptosporidiosis Cyclospora cayetanensis In AIDS also: Isospora belli (coccidium) Enterocytozoon bieneusi (microsporidium) Strongyloides stercoralis hyperinfection (helminth)

22. Other intestinal parasites (helminths) Small intestine: Ascaris lumbricoides (human roundworm) Ancylostoma duodenale (Old World hookworm) Necator americanus (New World hookworm) Strongyloides stercoralis (threadworm) Fasciolopsis buski (giant intestinal fluke) Taenia saginata (beef tapeworm) Taenia solium (pork tapeworm) Hymenolepis nana (dwarf tapeworm) Diphyllobothrium latum (fish tapeworm) Large intestine: Enterobius vermicularis (pinworm) Trichuris trichiura (whipworm)

23. Food poisoning 1. Intoxication due to a toxin preformed in the food Staphylococcus aureus: heat-stable enterotoxin Clostridium perfringens: heat-labile enterotoxin Bacillus cereus: heat-stable enterotoxin and vomiting toxin (mostly in rice) Clostridium botulinum: heat-labile neurotoxin 2. Intoxication due to invasive microorganisms Salmonella gastroenteritis ETEC and EHEC Listeria monocytogenes

24. Homework 3 – solution Paulus Peeter Rubens (1577-1640): Goddess of health Hygiene (1615)

25. Homework 3 – detail Paulus Peeter Rubens (1577-1640): Goddess of health Hygiene (1615)

26. Homework 3 Paulus Peeter Rubens (1577-1640): Goddess of health Hygiene (1615) Successful homework solvers Anna Malmström Filipp Fremming Chun-Chi Wang Initially at least partially successful solvers Klaus Asbjørn Vikeså Yulia Lindholm Ola Undrum Bergland Congratulations!

27. Homework 4 Who painted this picture and what is its name?

28. Answer and questions The solution of the homework and possible questions please mail to the address mvotava@med.muni.cz Thank you for your attention