Department of Infectious Diseases and Hepatology Nicolaus Copernicus University

1. Edyta Grąbczewska Acute infectious diarrheal diseases and bacterial food poisoning Department of InfectiousDiseases and Hepatology Nicolaus Copernicus University Ludwik Rydygier Collegium Medicum in Bydgoszcz

2. Etiological factors of infectious diarrhea and food poisoning Bacilli Gram negative Bacilli Other Salmonella Campylobacter jejuni, coli Yersinia entorocolitica, pseudotuberculosis Shigella Vibrio cholerae Escherichia coli Staphylococcus aureus Aerobe Bacillus anthracis Bacillus cereus Virus Rotavirus Norwalk virus Anaerobe Clostridium perfringens A, C Clostridium botulinum Clostridium difficile Gram positive Bacilli Listeria monocytogenes

3. Mechanisms causing acute diarrhea

4. Host defenses The normal host canprotectitselfagainstdisease • normal flora: the largenumbers of bacteriathatnormallyinhabit the intestineact as animportant host defense by preventingcolonizaton by potentialentericpathogen • gastricacidpH of the stomachisanimportantbarrier to entericpathogen • intestinalmotility: normalperistalsisis the major mechanism for clearence of bacteria from the proximal small intestine • immunity: bothcellularimmuneresponses and antibodyproductionplayimportanatroles in protection from entericinfections. • geneticdeterminants

5. Host defense

6. Clinical symptoms • stomach ache • nausea, vomiting, loose bowel movements • fever • shivery • sings of dehydration: • mild dehydration: thirst, dry mouth, decreased axillary sweat, decreasesd urine output, slight weight loss, • moderate dehydration: orthostatic fall in blood pressure, tenting of skin, sunken eyes • severe dehydration: lethargy, obtundation, feeble pulse, hypotension, shock • disturbances of electrolytes and acid-base balance • weakness • myalgia and myasthenia

7. Infectious diarrhea - definition • ≥3 looseorliquidbowelmovements per day • can be blood, pusormucus in stool

8. Time of diarrhea • acute diarrhea is an episode of diarrhea of <14 days in duration • persistent diarrhea is an episode of diarrhea >14 days in duration • chronic diarrhea is diarrhea that lasts for >28 days

9. Physical examination • vital signs • blood pressure, pulse, temperature, the number of breathes • general assessment • precise physical examination • ultrasound scan of abdomen • evaluation of peristalsis • digital rectal examination • blood, pus, mucus

10. Diagnostic approach • many cases of noniflammatory diarrhea are selflimited or require symptomatic treatment. There is no need to determine a specific etiology • routine culture should be done. All patients with fever, evidence of inflammatory process, disease acquired outside the hospital (Salmonella, Shigella, Campylobacter), epidemiological factors

11. Diagnostic approach • evaluation of nosocomialdiarrheashouldinitiallyfocus on C.difficile • rapidenzymeimmunoassys and latexagglutination test • PCR test • if the clinicalpresentationsuggests the posibility of intestinalamebiasis, stoolshould be examined by the rapidantigendetectionassay • diagnoseviralinfection of digestive system • enzymeimmunoassays ELISA ( viralantigen) or by techniques for detectingViral RNA

12. Clinical algorithm for the approach to patients with community-aquired infectious diarrheal diseases and bacterial food poisoning Diarrhea, Nausea, orVomiting Resolution Yes Symptomatictherapy Oralrehydrationtherapy No Continuedilliness Obtainhistory: duration, feverappearence of stool, frequency of bowelmovement, abdominalpain, vomiting, antibioticuse, travel, commonsource, tenesmus Obtainstool to be examined for WBC and parasites

13. Clinical algorithm for the approach to patients with community-aquired infectious diarrhea and bacterial food poisoning Noninflammatory No WBC Inflammatory WBC Examinestool for parasites Continuesymptomatictherapyfurtherevaluationif no resolution Culture for Shigella, Salmonella, C.jejuni, ConsiderC.difficile Specificantiparasitictherapy ConsiderEmpricalantimicrobialtherapy

14. Treatment - mainly symptomatic • compensation of the water-electrolyte disorders, hydration, • analgesic medicines (Metamizolum natricum, Paracetamol) • relaxant medicines (No-Spa, Papaverine, Spasmophen) • medicines blocking diarrhea (Carbo medicinalis, Smecta, Tanalbina) • loperamid must not be used!!!! • in cases of poisoning with enterotoxine do not inhibit vomiting • in cases of poisoning with Salmonella rods, antibiotics are not administered when there are no complications (prolonging of the period of discharge with excrements)

15. Treatment - antibiotic therapy - in exeptional cases • patients with immunity deficits,elderly patients • in the typhoid form (symptoms of sepsis), • administrative indications (professional contact with food, with children) • cephalosporin, quinolone, ampicillin, trimetoprim-sulphamethoxazol

16. Clinical course: poisoning with Salmonella spp • incubation period: 12 – 36 hours, • in the history: consumption of eggs (raw egg yolk with sugar…) • sudden onest • most often gets a form of acute gastroenteritis • stomachache • intensivediarrhea - sometimes with addition of mucus and blood (particularlycommon in infections with Salmonella enteritidis), • nausea and vomitingseldomoccur

17. Clinical course: Salmonella spp poisoning • fever up to 38-40oC • chills • weakeness • headache • muscles pain • symptoms of dehydration: feeling of dryness in the mouth cavity, thirst, anuria

18. Clinical course: physical examination • furred, dry tongue and mucosa, • live peristalsis, • decreased RR, • increased heart rate, • in cases of poisoning with S. enteritidis the symptoms suggesting acute abdomen accompanied by peritoneal symptoms can occur

19. Clinical course Dysenteric form: • strongerstomachache, oftensimilar to colicpain, • visibleadmixture of freshblood in the stool Typhoid form: • breaking the intestinalbarrier by Salmonella, high fever for 7-10 days, strongheadaches, ill-being (occasionallyenlarged spleen, slowrecovery)

20. Clinical course: Staphylococcalpoisoning • fever over 38ºC (occurs at the beginning of the illness and recedes normally when vomiting stops), • diarrhea is not characteristic, occurs slightly later and lasts for a short time, • the symptoms of vascularcollapsemayoccur (lowering of RR, paleness of skin integument, abnormalconsciousness), • the diseaseusuallylasts for severalhours

21. Bacterial dysentery (Dysenteria bacterica)- definition • infectious and contagiousdisease, • caused by variousspecies of rods SHIGELLA, • similarsymptomsmay be caused by: • proteusvulgaris, • escherichia coli • pseudomonasaeruginosa • somerods of Salmonella, • in children - infections with someviruses, • dysenterysyndrome

22. Epidemiology • worldwide occurrence, • the highest level of incidence in the countries with warm climate, • reservoir of the germ is a sick person or a carrier, • infection through the alimentary way (fecal-oral), • it spreads directly (through the contact with the sick person) and indirectly through food products infected with stools (vegetables, fruit, milk), objects, rarely by contaminated by excrements water or mechanically by flies

23. Differential diagnosis • acute surgical diseases of the peritoneum („acute abdomen”) • typhoid fever • extrauterine pregnancy complications • abdominal form of the cardiac infarct • mesenteric infarct • exacerbation of chronic colitis • diarrhea related to antibiotic use

24. Differential diagnosis • bacterial enteritis (enterohaemorrhagic and enteroinvasive E.coli, Campylobacter jejuni, Salmonella enteritidis, Clostridium difficile) • parasites – Entamoeba histolytica • ulcerative colitis , Leśniowski-Crohn’s disease • sigmoid and rectum tumour • colon diverticulitis • subacute poisoning with heavy metal salts • uraemia • haemorrhoidal nodules • appendicitis

25. Prevention Avoid: • not fresh products • unproperlystored food • food coming from uncertainsources • raweggs • tapwater, rawmilk etc.

26. Botulism Botulinumtoxin – is the most toxicsubstanceknown Etiology 1895 – van Ermengem – firstisolation of bacterium Clostridium botulinum – anaearobic gram-positiveorganismsthat form subterminalspores. The hardy sporescansurviveenviromentalcondition and ordinarycookingprocedure Botulinumtoxin – 7 types : A, B, C, D, E, F, G C. botulinum = 1 typeneurotoxin Toxinserotypes A, B, E causehumandisease Botulinumtoxinisactive in the anaerobiccondition and temeraturecan be from 30ºC to 2ºC, but sensitive for high temperature100ºC about 10min

27. Mechanism Inhibition of acetylocholine realease by any seven toxin serotypes results in characteristc flaccid paralysis. Recovery follows sprouting of new nerves terminals. Toxin binding is irreversible

28. Epidemiology • Food-borne botulismiscaused by consumption of food contaminated with botulismtoxin. All of the eventscaused by homemadefoods • Woundbotulismiscaused by contamination of wounds with C.botulinumspores. Exclusivelyithasoccured in injectiondruguseres. • Infant botulismresults from absorption of toxinproduced in situ by toxogenicClostridiacolonizing the intestine of children ≥ 1 yearold Colonizationisbelieved to occurbecause the normalbowel flora is not yetfullyestablish.

29. Clinical manifestations The incubation period from ingestion of food containingbotulinumtoxin to onsetsymptomsisusually 18 –36 h, canrange from fewhours to severaldays. Symptoms: • Prodromalsymptoms: weakness, nausea, vomiting, stomachache • Inability to suck and swallow, dysarthria, weakendvoice, ptosis, floppyneck, flaccidity, respiratory compromised • Constipation • Retention of urine, anuria Symetriccranialnervepalsies, symetricdescendingflaccidparalysisthatmayprogress to respiratory arrest and death. • Extraocularmuscleparalysis, diplopia, blurredvision, inabilityto acomodate • Facialparalysis, ptosis, strabismus

30. Clinical manifestations Remember ! • No sensory disturbances • No disorders of consciousness • Temperatureisnormalexceptcomplications (infection of urinarytract, aspiration pneumonia

31. Diagnosis and treatment • Botulism in a symptomatic patient can be confirmed in the laboratory by demonstration of toxin in clinical specimens (serum, stool, sterile water or saline enema, gastric aspirates, wound material • The treatment for botulism are meticulous intensive care with frequent monitoring of vital capacity and mechanical ventilation if required and immidiate administration of botulinum antitoxin (equine antitoxin).

32. Cholera – definition and etiology Cholera isanacutediarrhealdiseasethatcan in a matter of hours, result in profoundrapidly progressive dehydration and death. 3mln cases of cholera occuryearly (of whichonly 200000 arereported to the WHO, resulting in 100000 deathsannually (of which 5000 arereported to the WHO

33. Cholera – definition and etiology Bacteria of Vibrio kind, Pathogenic for a human: V. cholerae,V. parahaemolyticus, V. mimicis,V. fluvialis. V. cholerae : serologic group 01 or 0139,therearegroups with epidemicpotentialTo be reported to sanitary authoritiesToxins: Enterotoxins, neuraminidase, genes (ctxAB, zot, ace, cep)Typical symptom: painlesswatery, intensive diarrhoea, epidemic spread

34. Epidemiology • The disease takes epidemic or pandemic form, mainly in poor, developing countries, in the tropical and subtropical climate in Asia, Africa and South America • The infection spreads through alimentary tract, the infectious dose must be high – over a billion of bacterial cells . It ismarkedlyreduced in hypochlorhydriac person, in thoseusingantacids, whengastricacidityisbufffered by a meal • Source of infection – water contaminated with human excrements (much less frequently consumption of the infected dishes), germ reservoir – a sick person or carrier, • Mortality approx 1% (in extreme cases up to do 20%) when treated properly and 50% without the treatment

37. Clinical course • Incubation period 1-2 days (in extreme cases - several hours), sudden onset of the disease, lack of fever, vomiting, • Intensifying rapidly diarrhoea – to a few or even over a dozen litres a day (without rectal tenesmus and abdominal pains) • The stool reminds of water after the rinsing of rice, “the rice-like stool” – completely fluid, with scarce amount of mucus, colourless, grey, without admixture of blood, with slightly sweet smell, • Spasmodic muscle pains (electrolyte disorders – can lead to damaging or necrosis of renal tubule) • Thirst, dryness in the mouth cavity, hoarseness, sueaky voice (vox cholerica), wrinkled skin, not flexible,Facies cholerica (hollowed eyes, sharpened face features)In the more serious cases orientation disorders, coma, death,

38. Laboratory examinations: Laboratory examinations: high Ht, RBC (normal or higher),in the smear test, shift towards the left, higher urea and creatinine (extrarenal uraemia) diselectrolytemia disorders of acid-basebalance

39. Therapy 1. Symptomatic treatment: immediate compensation of water-electrolyte disorders, Administration of liquids orally ( WHOORS – recommended by WHO solution for oral watering – NaCl, KCl, sodium citrate, glucose) and also intravenous infusions 2. Casual treatment: Supportive, not necessary, Shortens diarrhea period, limits the period of liquids administration, necessity to examine resistance of local strains against antibacterial medicines Adults may choose: tetracycline, alternatively: doxycycline, ciprofloxacin, erythromycin, children may choose: tetracycline, alternatively: sulfamethoxazolum

40. Prevention The most crucial – supply people with clean water, use of boiled water for drinking purposes, Protection against contamination of food resources, Treating of asymptomatic carriers, Vaccines from killed vibrio give very little protection, during epidemic they can cause more harm than benefit (large general reaction, that may shorten the incubation period and cause more serious course of illness if administered to an infected person), Certain hope for live vaccines, attenuated…

41. Clostridium difficile • anaerobic, Gram-positive, spore-forming bacillus • opportunisticpatogen • Clostridium difficileinfectionis a uniquecolonicdiseasethatisaquiredassociated with antimicrobialuse and the consequentdisruption of the normalcolonic flora • the most commonlydiagnoseddiarrheal illinessaquired in the hospital

42. Highly virulant strain of C.difficile NAP1/027 • epidemicorganismisability to produce 18-23 timeshigherlevel of toxinproduction (toxin A and B) • newtoxin - binary toxin • produce much morespores • 3-fold mortalityratethan less virulantstrains • easiertransmission in 2001 typehiperviralentrepresented 0,23% of allisolates but currentlythistype of bacteriarepresents 84% in Quebec High-levelresistance to allfluoroquinolone

43. Clinical manifestations of infection C.difficile • MILD: Postantibiotic diarrhea • MODERATE: Postantibiotic colitis • SEVERE: Pseudomembranous enterocolitis

44. Pseudomembranous enterocolitis • Enterocolitis with toxin-producing C. difficile • severe clinical manifestation • there are about 20-25% infection of C. difficile • characteristic clinical syndrome • endoscopic image of pseudomembranous colitis with yellow pseudomembrances seen of the wall of the sigmoid colon.

45. Nosocomial infection C.difficille

46. Reservoirs of toxigenic C.difficile • asymptomatic fecal carriage: • neonates: first 6 months of live 15-75% • healthy adults: 1-3% - healthcare workers: ≈ 20% • hospitalized patients: 10-20% • sick patients (C.difficile Infection) • indirect infection • Envionmental surfaces (medical equipment, electronic rectal thermometers, floor, toilet + hands of hospital personnel) • contaminated food

47. Risk of factors C.difficile • advanceage > 65 y • diseases and procedures • antibioticuse (cephalospoins, clindamycin and fluoroquinolones) • inflammatoryboweldiseases(C.ulcerosa; Ch.L.Crohna) • chemotherapy/transplantation • chronickidneydisease • HIV • blood-borne infection (sepsis, endocarditis) • antiacidtherapy : proton pump inhibitor (PPI) • hospitalizationorresidence in nursing homes orrehbilitation • contact with children ↓ 2 y.o

48. Clinical manifestation • diarrhea > 3 do >30 loosebowelmovements with a characteristicodor • abdominalpain, fever, dehydration, lethargy • hypoalbuminemia, oedema (enteropathy) • complications life-threatening: • fulminant colitis • ileus • megacolontoxic • perforatio • SIRS (SystemicInflammatoryResponseSyndrome)

49. Hallmarks of severe Clostridium difficile colitis • age >70 • leucocytosis > 20 000/mL • creatinine level >2mg% • ileus • enterocolitis in imagining CT

50. Diagnostic approach CDI • clinical manifestation • laboratory tests • stool culture • enzyme immunoassay for toxin A or B in stool • enzyme immunoassay for C.difficile commonantigen in stool • PCR for C.difficile toxin A and B gene in stool • colonoscopy or sigmoidoscopy • CT abdomen • USG abdomen (megacolon toxicum!)