By Mohammad Abo El.MagdEndemic and infectious diseases Unit

Over view on Enteric Infections

OverviewThird most common syndrome seen in

general practice in the USOn the global scale, diarrheal diseases are

the leading cause of childhood deathThe frequency, type, and severity of these

infections depend on:Who you are (host factors)Where you are (Endemic areas)When you are there (times of outbreaks wet

seasons and winter)

Host factorsAge: (EPEC and rotovirus tend you affect young

children)Personal hygiene : (fecooral)Gastric acidity, physical barriersIntestinal motility (expel the pathogens.

Antimotility assoc with prolonged fever shedding shigella, complication c diff, HUS in ETEC)

Enteric microflora ( c.diffcile )Specific immunity: phagocytes, B-cell, T-

cell

Infectious doses of enteric pathogen

Shigella: 101-2

Giardia lamblia: 101-2

Entamoeba histolytica: 101-2 Campylobacter jejuni:102-6

Salmonella: 105

E. coli: 108

Vibrio cholerae: 108

Pathophysiology 1- Toxin production

Neurotoxins (preformed toxin): Bacillus cereus, Clostridium perfringens, Staphylococcus aureus

Enterotoxin: Aeromonas species, enterotoxigenic E. coli, Vibrio cholerae

Cytotoxin: Clostridium difficile, E. coli 0157:H7

Pathophysiology 2- Enteroadherence

Cryptosporidiosis (Cryptosporidium parvum)

Cyclospora species (?)Enteroadherent and enteropathogenic E.

coliHelminths :D .Latum,StrongloydesGiardiasis (Giardia lamblia)

Pathophysiology 3- Mucosal invasion

Minimal invasion: Norwalk virus, Rotavirus, other viruses

Variable invasion: Aeromonas sp., Campylobacter sp., Salmonella sp., Vibrio parahemolyticus

Severe invasion: Entamoeba histolytica, enteroinvasive E. coli, Shigella species

Clinical presentation Low-versus high-volume

diarrheaLow volume (low water): colonicHigh volume (high water): small bowel

OSMOTIC DIARRHEA: high-volume diarrhea in which the measured fecal osmolality is less than 2 [Na + K]

SECRETORY DIARRHEA: high-volume diarrhea in which the measured fecal osmolality equals 2 [Na + K]

Clinical presentation Small- versus large-bowel

diarrheaSmall bowel: large volume, watery, less

frequent, painless stools. Blood and WBCs are rare. Proctoscopy is normal. Pain is mid-abdominal.

Large bowel: small volume, often mucoid, more frequent, painful stools. Blood and WBCs are common. Proctoscopy is abnormal. Pain is lower-abdominal (left lower quadrant)

Clinical presentation Noninflammatory vs

inflammatoryNon inflammatory diarrhea: pathogens act

primarily on small intestine to induce fluid secretionsVoluminous watery diarrhea, nausea,

vomiting, abdominal cramps, low grade fever.

Inflammatory diarrhea: induce inflammation by invasion or cytotoxinsStools of small volume, fever, blood and

mucus, tenesmus, abdominal cramping.

Overview of Infectious diarrheaACUTE (symptoms 14 days)

Community-acquired: gram-negative bacterial pathogensViral pathogens

Norovirus: family clusters, winter outbreaksRotovirus: children, seasonal peak in winter

Protozoal pathogensEntamoeba Histolytica: acute colitis with

fever and dysentryNosocomial ( > 3 days after hospitalization)

Clostridium difficileTravelers:

ETEC

Overview of Infectious diarrheaPERSISTENT (symptoms > 14 days)

Parasitic: Girdia lamblia, Cryptosporidium parvum, Cyclospora, Isospora belli

Immunocompromised host: also consider microsporidium, Mycobacterium-avium complex, and cytomegalovirus

FoodNet Data, CDC 2007Incidence of Various Pathogens per

100,000 Population in U.S.Salmonella 14.92Campylobacter 12.79Shigella 6.26Cryptosporidium 2.67

(EHEC )O157:H7 1.20Yersinia 0.36Listeria 0.27Vibrio 0.24

Gram-negative Bacteria Associated with Diarrhea

Campylobacter SalmonellaShigellaEscherichia coliYersinia enterocolicaVibrio Aeromonas

Campylobacter jejuniCurved gram-negative rodsZoonotic infection and carried in GI tract of

animalsPoulty common source of infectionDisease caused by ingestion of

contaminated food or waterIncubation period 1-7 daysTwo-thirds present with fever, headache,

myalgias followed by abdominal pain and bloody diarrhea

Campylobacter jejuni

Fecal leukocytesAntibiotic therapy reserved for

immunocompromised and those with severe symptoms

Reactive arthritis 1% of patients. 1-2 weeks after diarrhea

Associated with Guillain-Barre, usually 1-3 weeks after diarrhea. 20-40% GBS cases are attributable to antecedent C. jejuni infection

Salmonella gastroenteritis Non-lactose fermenting gram-negative bacilliNon-typhoidal strains seen in the US (S.

enterica) serovars S. typhimurium, S. enteritidis, etc

Found in GI tracts of mammals, birds, reptilesAcquired from ingestion of contaminated

poultry, eggs, meat and exposure to pet reptiles

Fever, abdominal cramping, nausea, vomiting, diarrhea with fecal leukocytes

Untreated diarrhea lasts 4-10 days

Other syndromes of Salmonella

Enteric feverBacteremia with or without metastatic

diseaseAsymptomatic carrier state

Bacteremia in salmonellosisUsually transient and inconsequentialSickle cell disease: osteomyelitisAtherosclerosis: mycotic aneurysmUnderlying heart disease: endocarditisYoung children: ? meningitis

Salmonella carrier state

3% of cases of typhoid fever .0.2% to 0.6% of symptomatic non typhoidal

infections (relevant especially to food handlers)

High association with biliary tract disease and gallstones

ShigellosisNon-lactose fermenting gram-negative rodFour species:

S. dysenteriaeS. flexneriS. boydiS. sonnei

Highly infectious: infectious dose < 200 Incubation period 1-7 daysSymptoms can develop 12 hours after

ingestion

ShigellosisPresents as fever, abdominal pain, tenesmus,

bloody diarrheaBacteremia 4% of patientsReactive arthritis 1-2%, 1-2 weeks (S. flexneri)S. dysenteriae can be associated with HUSAntimotility drugs have been associated with

toxic megacolonself-limited but treatment recommended to

prevent secondary spread to contacts

E. coli gastroenteritisEnterotoxigenic: watery diarrhea

(travelers diarrhea)Enteropathogenic: diarrhea in infants

common in developing countriesEnteroinvasive: dysentery with blood

and mucusEnterohemorrhagic (E coli 0157:H7):

copious bloody diarrhea sometimes with the hemolytic-uremic syndrome

Enteroaggregative

Enterohemorrhagic E. coli(0157:H7)

Most common strain in developed countries Usually transmitted by beef, but many other

foods transmit. Associated with petting zoo Low infectious dose (as few as 100 bacteria) Shiga-toxin Crampy abdominal pain, often disproportionate

to physical findings along with bloody diarrhea with little or no fever

Complications include hemolytic-uremic syndrome in children, thrombotic thrombocytopenic purpura in adults

Clostridium difficile1970s: Found to be the cause of

enterocolitis related to the antibiotic clindamycin

Pseudomembranous colitis with yellow-white plaques; can progress to toxic megacolon

At least two toxins (A and B) cause necrosis of epithelium

Nosocomial transmission

Clostridium difficileColonization rate is 2% to 3% in healthy

adults; 20% to 40% in hospitalized patientsWidespread contamination of hospital

environmentsInfection control measures including hand

washing and gloves have been shown to reduce infection rates

Endoscopic view of multiple scattered, yellowish plaques consistent with pseudomembranous colitis. (From Iseman DT, Hamza SH, Eloubeidi MA. Pseudomembranous [Clostridium difficile] colitis. Gastrointest Endosc. 2002;56:907.)

Abdominal radiograph demonstrating markedly dilated colon, wall edema, and loss of haustration in a patient with Clostridium difficile-associated pseudomembranous colitis complicated by toxic megacolon. (From Agnifili A, Gola P, Manno M, et al. The role and timing of surgery in the treatment of pseudomembranous colitis: A case complicated by toxic megacolon. Hepatogastroenterology. 1994;41:394-396.)

Yersinia enterocoliticaCarried in GI tract of pigs, cattle, rodents,

sheep, dogs and catsInfection acquired by inadequately

cooked pork, unnpasteurized milk, contaminated water

Diarrhea, fever, abdominal painMesenteric adenitis/terminal ileitis:

fever, RLQ pain, leukocytosisReactive polyarthritis, often with

erythema nodosum Septicemia especially in children

Entamoeba histolytica (amebiasis)

Affects 10% of world’s populationIn the United States, affects up to 4%Order of involvement: ceacum, ascending

colon, rectum, sigmoidFlask-shaped ulcersLiver abscesses in up to 10%

Giardia lamblia (giardiasis)WaterborneRocky Mountains; Leningrad; but also

widespreadCan cause diarrhea by several mechanismsWeight loss (62%), cramps (61%),

steatorrhea (57%), flatulence (35%), vomiting (29%), belching (26%), fever (17%)

Cryptosporidium parvumFormerly best known as an animal

pathogen infecting numerous speciesSeverity and duration of human infection

vary directly with immunocompetenceHealthy adults: self-limited diarrhea,

usually lasting 10 to 14 daysAIDS patients: severe intractable diarrhea

Rotavirus diarrheaUsually sporadic but

can cause epidemics in institutions, including nursing homes

Winter months in temperate climates: usually infants and young children

fecal-oral transmissions

DNA virus with at least 2 sterotypes; can be demonstrated with ELISA

Norovirus diarrheaTypically epidemic, often traced to a

common sourceThroughout the yearUsually adults and school-aged childrenOften traced to contaminated food or waterAt least 3 serotypes; can be demonstrated

by immune electron microscopy or radioimmunoassay

Traveler’s diarrheaBacterial:

Enterotoxigenic E. coli (ETEC)ShigellaSalmonellaCampylobacter

Protozoa:Giardia, Entamoeba, Cryptosporidium

Virus:Norwalk, rotavirus, enterovirus

Staphylococcal food poisoningCommon food borne illnessInfections originate from asymptomatic carriers

of staphylococcus aureusCan contaminate processed meats, potato

salad, ice-creamPreformed toxin (enterotoxin) in food rather

than from direct effect of organismIncubation period about 4 hours. Symptoms last < 24 hours (no new toxin

produced by ingested bacteria)Severe nausea and vomiting along with

abdominal pain and diarrhea. No fever

Helicobacter pylori70-90% of population

in developing countries. Almost 45% in developed countries

Associated with gastritis, duodenal ulcer, gastric ulcer, gastric adenocarcinoma, MALT lymphomas

Fecal-oral transmission