Microbiology, virology, immunology with the course of infectious diseases department, UzhNU

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1 Diarrheal syndrome Gastrointestinal infections Dr. Karabinyosh S.O. Microbiology, virology, immunology with the course of infectious diseases department, UzhNU

2 Definitions Diarrhea - is the condition of having at least three loose or liquid bowel movements each day, due to the reversal of the normal net absorptive status of water and electrolyte absorption to secretion. Associated symptoms can include abdominal cramps fever, nausea, vomiting, fatigue and urgency. Chronic diarrhea can be accompanied by weight loss, malnutrition, abdominal pain or other symptoms of the underling illness. Clues for organic disease are weight loss, diarrhea that wakes you up at night, or blood in the stools.

3 Clinical types Acute watery diarrhea lasts several hours or days, and includes cholera; Acute bloody diarrhea also called dysentery; Persistent diarrhea lasts 14 days or longer.

4 Pathophysiology Diarrhea is the reversal of the normal net absorptive status of water and electrolyte absorption to secretion. Such a derangement can be the result of either an osmotic force that acts in the lumen to drive water into the gut or the result of an active secre tory state induced in the enterocytes. In the former case, diarrhea is osmolar in nature, as is observed after the ingestion of non-absorbable sugars such as lactulose or lactose in lactose malabsorbers. Instead, in the typical active secretory state, enhanced anion secretion (mostly by the crypt cell compartment) is best exemplified by enterotoxin- induced diarrhea.

5 Major classification osmotic secretory increased mucosal permeability abnormal motility

6 WHO classification osmotic secretory exudative inflammatory dysentery

7 Invasive Diarrhea Invasion of the bowel mucosal surface Symptoms o Fecal leukocytes o RBCs o Sometimes fever Organisms o Salmonella spp. o Campylobacter spp. o Shigella spp. o E. coli o E. histolitica

8 Differential stool classification Stool Characteristics Small Bowel Large Bowel Appearance Watery Mucoid and/or bloody Volume Large Small Frequency Increased Highly increased Blood Possibly positive but never Commonly grossly gross blood bloody ph Possibly < 5.5 >5.5 Reducing substances Possibly positive Negative WBCs < 5/high power field Commonly >10/high power field Serum WBCs Normal Possible leukocytosis, bandemia

9 Stool Characteristics Small Bowel Large Bowel Invasive bacteria Organisms Viral Rotavirus Adenovirus Calicivirus Astrovirus Norovirus Enterotoxigenic bacteria Escherichia Coli (enteroinvasive, enterohemorrhagic) Shigella species Salmonella species Campylobacter species Yersinia species Aeromonas species Plesiomonas species E coli Klebsiella Clostridium perfringens Cholera species Vibrio species Parasites Giardia species Toxic bacteria Clostridium difficile Parasites

10 Organisms and Frequency of Symptoms Organism Incubation Duration Vomiting Fever Abdominal Pain Rotavirus 1-7 d 4-8 d Yes Low No Adenovirus 8-10 d 5-12 d Delayed Low No Norovirus 1-2 d 2 d Yes No No Astrovirus 1-2 d 4-8 d +/- +/- No Calicivirus 1-4 d 4-8 d Yes +/- No Aeromonas species None 0-2 wk +/- +/- No Campylobacter species 2-4 d 5-7 d No Yes Yes C difficile Variable Variable No Few Few C perfringens Minimal 1 d Mild No Yes Enterohemorrhagic E coli 1-8 d 3-6 d No +/- Yes Enterotoxigenic E coli 1-3 d 3-5 d Yes Low Yes Plesiomonas species None 0-2 wk +/- +/- +/- Salmonella species 0-3 d 2-7 d Yes Yes Yes Shigella species 0-2 d 2-5 d No High Yes Vibrio species 0-1 d 5-7 d Yes No Yes Y enterocolitica None 1-46 d Yes Yes Yes Giardia species 2 wk 1+ wk No No Yes Cryptosporidium species 5-21 d Months No Low Yes Entamoeba species 5-7 d 1-2+ wk No Yes No

11 Risk Factors Number of Ingested Organisms o Median infectious dose (ID 50 ) The number of ingested organisms that must be ingested to cause a diarrheal illness in 50% of exposed individuals Achlorhydria o Inadequate stomach acidity Reduction in normal flora o Use of antibiotics

12 Dehydration The most severe threat posed by diarrhoea is dehydration. During a diarrhoeal episode, water and electrolytes (sodium, chloride, potassium and bicarbonate) are lost through liquid stools, vomit, sweat, urine and breathing. Dehydration occurs when these losses are not replaced. Lethargy, depressed consciousness, sunken anterior fontanel, dry mucous membranes, sunken eyes, lack of tears, poor skin turgor, and delayed capillary refill are obvious and important signs of dehydration. Hydration 0-5% Dehydration (Mild) 5-10% Dehydration (Moderate) 10% or More (Severe) General Well Restless Lethargic Eyes Normal Sunken Very sunken Tears Present Absent Absent Mouth Moist Dry Very dry Thirst Drinks normally Thirsty Drinks poorly Skin Pinch retracts immediately Pinch retracts slowly Pinch stays folded

13 Gastroenteritis Diarrhea, vomiting, cramping o Increased fluid output, more than 4-5, watery bowel movements per day Acute diarrhea symptoms for less than 2 weeks o Exception: C. difficile can last longer

14 Pathophysiology Viruses damage the small intestinal villi, decreasing intestinal surface area and unmasking ongoing fluid secretion by enteric crypts Rotavirus produces an enterotoxin that induces secretion and contributes to the watery diarrhea

15 Pathophysiology Invasive bacteria cause mucosal ulceration and abscess formation with an inflammatory response (WBCs in stool) Bacterial toxins may influence enteric and extraenteric cellular processes (HUS, etc) Other noninvasive bacteria and protozoa adhere to the gut wall, causing inflammation

16 Patient Evaluation Duration of symptoms Quantity (frequency of stools) Quality (watery) Fever Hematochezia visible blood in stool S/S of dehydration Other sx: N/V, abd pain, tenesmus, anorexia Recent travel, recent abx use, hepatitis risk Other family members sick? Ability to take PO fluids

17 Physical Exam Jaundice Hydration status check for signs of dehydration Stool Guaiac occult blood Abdominal tenderness, bowel sounds Mental status

18 Oral Rehydration Replace water, salt, sugars lost due to diarrhea, vomiting In mildly dehydrated patient, it is first line therapy before IV rehydration. Formulas are based on patient weight, degree of dehydration 75 ml/kg over 4 hrs every 2 min

19 Enteric Illness, categories Non-specific gastroenteritis Gastroenteritis with bloody diarrhea Extraintestinal illness Non-infectious causes of GI symptoms

20 Nonspecific Gastroenteritis Diarrhea without high fever or bloody stool May have: cramps, low grade fever, headache, malaise, dehydration, N/V Etiology: Viral (Norwalk-like viruses, Rotavirus), protozoal (giardia, crypto), foodborne toxins (S. aureus), traveller s diarrhea, noninfectious causes.

21 Gastroenteritis with bloody diarrhea Bloody stools with fever, +/- vomiting: Consider Salmonella, Shigella, Campylobacter (bacterial) Bloody stools without fever: Could be above or E. coli 0157:H7.

22 GI illness with Extraintestinal Disease Jaundice: Hepatitis A (we ll get there in a little bit) Meningitis: Listeria, salmonella Arthritis: Campylobacter, salmonella Flaccid paralysis and cranial neuropathies: C. botulinum (Botulism) HUS: E. coli 0157:H7

23 Noninfectious causes of GI sx Otitis media, Group A Streptococcal infection, irritable bowel syndrome, inflammatory colitis, stress, medications, gallbladder disease, peptic ulcer disease

24 Diagnosing Cause of Diarrhea Physical Exam o Dehydration o Toxic megacolon o Increase in heart rate or decrease in blood pressure after standing upright Laboratory Diagnosis o CBC o Fecal WBC o Stool Culture o O &P o Electrolyte panel

25 Enterotoxin-Mediated Diarrhea Symptoms o Rapid onset of diarrhea Less than 12 hours o Lack fever o Absence of blood or pus Point to enterotoxin mediated illness o Large number of watery stools Sometimes >20 per day

26 Enterotoxin-Mediated Pathogens o ETEC o V. cholerae o S. aureus o C. perfringens o B. cereus Diarrhea Other types o Viral and parasitic can be similar but symptoms longer lasting

27 Staphylococcal Food Toxin S/S: Vomiting, severe cramping, low grade fever, diarrhea (no blood in stool) Incubation: VERY short 30 minutes to a few hours. Complications: None, spontaneous recovery Diagnosis: No specific test available. Clinical dx.

28 Staphylococcal Food Toxin Treatment: Supportive rest, hydration, compazine or other antiemetic for persistent vomiting Origin: Toxin producing S. aureus strains, usually from human skin, inoculate food, multiply at room temp. Toxins not destroyed by reheating. Other toxin producing bacteria: Clostridium perfringens, Bacillus cereus.

29 Staphylococcal Food Toxin Prevention o Decrease food handling odo not allow foods to sit at room temp. for long periods oglove use by food handlers oexclude persons from food handling when obvious skin infections are present.

30 Salmonella Agent: Multiple subtypes of Salmonella species (S. enteritidis, S. typhimurium are most common) Reservoir: Birds (chickens, turkeys), reptiles, others Occurrence: Common Transmission: Undercooked meat/eggs, cross contamination by meat juices, unpasteurized milk, handling reptiles

31 Salmonella Incubation: 6-72 hours (usually 10-12) Diagnosis: Stool culture Clinical: Diarrhea, often bloody, fever, cramps, vomiting Complications (elderly, immunocomp.): Arthritis, meningitis, sepsis. Treatment: Usually supportive. Quinolones if severe or if immunocompromised.

32 Salmonella

33 Campylobacter Agent: C. jejuni Reservoir: Poultry, cattle, others Occurrence: Common Transmission: Undercooked poultry, cross contamination, unpasteurized milk Incubation: 3-5 days Diagnosis: Stool culture

34 Campylobacter Clinical manifestation: Diarrhea (often bloody), severe cramps, fever, +/- vomiting Complications: Arthritis, cholecystitis Treatment: Quinolones or erythromycin Prevention: Adequate cooking, kitchen hygiene, pasteurization

35 Campylobacter jejuni: Fast facts Grows best at 42 degrees C Microaerophilic conditions Capnophilic conditions Campy plate Gram-negative curved rods, seagull wings

36 E. Coli 0157:H7 Agent: Escherichia coli O157:H7 Reservoir: Cattle (and foods contaminated with cow feces) Occurrence: Less common than Salmonella and Campy, but increasing Transmission: Ingestion of undercooked beef, cross contamination, unwashed contaminated fruits & veggies, person to person, water contamination. HIGHLY transmissible.

37 E. Coli 0157:H7 The principal groups of this organism responsible for enteric disease include: enteropathogenic (EPEC), enterotoxigenic (ETEC), enteroinvasive (EIEC), enterohemorrhagic (EHEC), enteroaggregative (EAEC) strains.

38 E. Coli 0157:H7 Incubation: 2-7 days Clinical manifestation: Watery diarrhea progressing to bloody diarrhea after a few days. Fever usually absent. Cramps, vomiting. Complications: 5-10% of kids younger than 5 will develop HUS, a life threatening multisystem disease. Can occur in adults.

39 E. Coli 0157:H7 Diagnosis: Stool culture, toxin assay Treatment: Supportive. Antibiotics usually avoided (can increase HUS) Prevention: Thorough cooking of ground beef, avoid cross contamination with beef juices, wash fruits/veggies, pasteurization. Early diagnosis will prevent person to person transmission.

40 E. coli O157:H7 on MAC and SMAC

41 Shigella Agent: S. sonnei, S. flexneri, others Reservoir: Humans Transmission: Person to person, foodborne, flies. Clinical manifestation: Fever, bloody diarrhea, cramps, vomiting. Patients often appear toxic. Diagnosis: Stool culture

42 Shigella Complications: Sepsis, meningitis Treatment: Quinolones, hydration Communicability: Extremely high Prevention: Early diagnosis and isolation, hand washing, food and water hygiene Occurrence: Rare locally, high in third world countries.

43 Shigella

44 Clostridium difficile Most common antibiotic associated diarrhea- due to changes in colonic bacterial fermentation of carbohydrates Colitis associated with toxin produced by C. diff. Hospitalized, immunocompromised are most susceptible

45 Clostridium difficile Antibiotics disrupt the normal flora, C. diff. flourishes (carried asymptomatically by 3-8% healthy adults). Any abx can trigger, but most common are: cephalosporins, penicillins, clindamycin, flouroquinolones Sx start during or after abx therapy, may be delayed 8 weeks Easily transmitted in hospital setting

46 Clostridium difficile Toxins (A- enterotoxin & B-cytotoxin) have effect on colon- secretes fluid, develops pseudomembranes (discrete yellow-white plaques), easily dislodged. Diagnosed by C. diff toxins in stool. EIA rapid toxin A & B. Treat with Metronidazole 500 mg po tid x10-14 d. D/c other abx if possible. Infection control measures to reduce spread in hospital settings.

47 Clostridium difficle

48 Viral Gastroenteritis Most common cause of infectious diarrhea in US Infect epithelium of small intestine Diarrhea is watery WBC s and visible blood are rare 4 categories: Rotavirus, Claicivirus (norovirus), Astroviurs, Enteric and Adenovirus.

49 Rotavirus Most common cause of diarrhea in young children Highly contagious: fecal-oral. Incubation 1-3 days, lasts 4-8 days Dehydration and hospitalization common in young children Diagnose by EIA antigen in stool Treat with oral rehydration or IV Oral vaccine now available (controversial)

50 Calcivirus Infect older children and adults Nonspecific, self-limiting Large water-borne and food-borne outbreaks occur, fecal-oral Incubation hrs, lasts hrs No commercial tests to diagnose Treatment supportive (oral rehydration)

51 Giardiasis Agent: Giardia lamblia Reservoir: Human and animal stool Occurrence: Very common Transmission: fecal-oral, contaminated water or food Incubation: 3-10 days

52 Giardiasis Clinical manifestation: Persistent or recurring diarrhea, bloating, cramps, steatorrhea (frothy fatty stool), weight loss. No blood in stool. Diagnosis: Ova and parasite slide or direct antigen test. Treatment: Metronidazole or other antiparasitic Prevention: Water filtration, avoid drinking untreated surface water.

53 Balantidiasis Agent: Balantidium coli Reservoir: Human and animal stool Occurrence: Very common Transmission: fecal-oral, contaminated water or food Incubation: 3-10 days

54 Balantidiasis Clinical manifestation: Symptoms can be local due to involvement of the intestinal mucosa, or systemic in nature and include either diarrhea or constipation. Persistent or recurring diarrhea, bloating, cramps. Diagnosis: history of current exposure to amebiasis through travel, contact with infected persons, or anal intercourse, microscopic examination of stool or tissue samples. Treatment: can be treated with tetracycline, carbarsone, metronidazole, or diiodohydroxyquin Prevention: Water filtration, avoid drinking

55 Thank you for your attention!