Pathogens within the Enteric tractShigella, Vibrio, Campylobacter, Helicobacter

Shigella:

Causes Enterocolitis.Enterocolitis with Shigella often called

Bacillary dysentery.Dysentery refers to bloody diarrhea.

Shigella are non-lactose fermentingGm neg. rodsDiffer from Salmonella in that they produce

no gas from fermentation of glucose, do not produce Hydrogen sulfide and are non motile.

All Shigella have O-antigens. Divided into A B C D groups.

• Pathogenesis:

• They are the most effective among enteric bacteria.

• A very low infectious dose required (100 orgs. unlike V.cholerae / salmonella of 100000 orgs.)

• Shigellosis is only a human disease.Transmission through Feco-oral route through fingers, flies, food and feces.

• No prolonged carrier state with Shigella infections.

• Shigella causes disease exclusively in the GI tract, by invading the cells of the mucosa of the distal ileum and colon, cause bloody diarrhea.

• Local inflammation with ulceration occurs, but org. rarely penetrate and enter blood stream, unlike Salmonella.

• Critical factor in pathogenesis is invasion as mutants without enterotoxin can still cause disease. Non invasive mutants are non pathogenic.

• Shiga toxins are encoded by lysogenic bacteriophages.

• Similar to toxins of O157:H7 strain of E.coli.

• Clinical findings:

• Incubation period of 1-4 days• Fever with abdominal cramps. Followed by diarrhea,

watery at first, the bloody with mucous.• Depending on the species and the age of the patient the

severity of the disease varies.• Young children and elderly most affected.• Sh.dysenteriae causes most severe wheras Sh.sonnei

causes mild disease.• Diarrhea resolves within 2-3 days. Antibiotics can shorten

course of symptoms.• Serum agglutinins appear after recovery but are not

protective as the org. does not enter blood stream.• Intestinal IgA may have a protective role.

• Lab diagnosis:

• Lactose non-fermenters on McConkeys and EMB agar.• On TSI show alkaline slant/acidic butt with no gas and

no hydrogen sulfide.• Confirmation and determination of group by slide

agglutination.• Important diagnosis is the Methylene blue staining of

Stool sample to determine presence of neutrophils.• Neutrophils, if present indicate an invasive infection,

caused by Shigella, Salmonella,or Campylobacter.• If not present, toxin producers like V.cholerae, E.coli

or Cl.perfringens are the causative agents.

• Treatment:

• Fluid and electrolyte replacement is main treatment.

• In severe cases : Fluoroquinolone like Ciprofloxacin is drug of choice.

• Antibiotic sensitivity tests may be required as multiple drug resistance conferred by plasmids, is very high.

• Trimethoprim-sulfamethoxazole is alternate choice.• Anti-peristaltic drugs contraindicated as they

prolong symptoms.

Prevention:

No vaccine nor prophylactic antibiotics recommended.

Proper sewage disposal, chlorination of water and personal hygiene, causing the interruption of fecal-oral route.

Vibrio

V. cholerae, major pathogen, causes Cholera.V.parahaemolyticus causes diarrhea

associated with undercooked sea food.V.vulnificus causes cellulitis and sepsis.

• Vibrios are curved, comma shaped gm. neg rods.• Divided into 2 groups based on O cell wall antigen.• O1 group causes epidemic disease, and Non O1

cause sporadic disease.• O1 have 2 biotypes (based on biochemical

differences, rather than antigenic differences as in serotypes). They are El Tor and cholerae.

• O1 have 3 serotypes. They are Ogawa, Inaba and Hikojima.

• V.parahaemolyticus and V.vulnificus are halophilic (require high salt conc. To grow) marine orgs.

• Pathogenesis:

• V.cholerae transmitted through fecal contamination of water.

• Human carriers present, either in their convalescent stage or incubation period, without symptoms.

• The pathogenesis is dependent on colonization of the small intestines and secretion of enterotoxin

• Large no. of orgs. required for colonization as orgs. Sensitive to stomach acids.

• Adherence to the cells of the gut is related to secretion of bacterial enzyme, mucinase, that dissolves the glycoprotein coating over the intestinal cells.

• After adhering, org. secretes an enterotoxin called Choleragen. Choleragen can produce symptoms in absence of orgs.

• Cholera toxin ADP-ribosylates the Gs protein, locks the protein on ON position with persistent stimulation of Adenylate cyclase.

• Watery stools contain no neutrophils nor red blood cells.

• Morbidity and death due to dehydration and electrolyte imbalance.

• Genes for Cholera toxin carried on a single stranded bacteriophage called CTX.

• Non O1 V.cholerae associated with undercooked contaminated shellfish, shrimps and oysters.

• Clinical findings:

• Rice-water, watery diarrhea in large volumes is the hallmark of infection.

• No abdominal cramps and other symptoms related to marked dehydration.

• Loss of fluid and electrolytes lead to cardiac and renal failure.

• Acidosis and hypokalemia due to loss of bicarbonate and potassium in stools.

• Mortality rate 40% without treatment.

• Lab. Diagnosis:

• Colorless colonies, lactose fermented very slowly on McConkey agar.

• Oxidase positive that differentiates from other enterobacteriaceae

• On TSI: acid slant/acid butt without hydrogen sulfide and without gas.

• Presumptive diagnosis based on slide agglutination with polyvalent O1 or Non O1 anti-serum.

• Treatment:

• Should be prompt, adequate replacement of water and electrolytes, either orally or intravenously.

• Glucose added to enhance uptake.• Antibiotics like tetracycline, not necessary,

but shorten duration of symptoms.• Prevention by public health measures to

ensure clean water and food supply.

Campylobacter• C.jejuni is frequent cause of enterocolitis,

especially in children.• Common atecedent of Guillian-Barre

syndrome.• Curved, gm neg, rods, either comma or S-

shaped.• Microareophillic (5% rather than 20% oxygen

present in atmosphere).• Grows well at 42 degrees centigrade,

whereas C.intesinalis do not.

• Pathogenesis:

• Fecal-oral route through food and water contaminated with domesticated (cattle, chickens, dogs) animal feces.

• Human to human less than animal to human transmission.

• Puppies with diarrhea common source for children getting infected.

• Inflammation of intestinal mucosa accompanied by blood in stools.

• Systemic infections occur in neonates or debilitated adults.

• Clinical findings:

• Enterocolitis, caused by C.jejuni begins as watery, foul smelling diarrhea followed by bloody stools, fever and severe abdominal pain.

• Systemic infection, most commonly bacteremia caused by C.intestinalis.

• GI infection with C.jejuni associated with Guillian Barre syndrome, the most common cause of neuromuscular paralysis. Antibodies against C.jejuni cross react with antigens on neurons.

• Infection with Campylobacter also associated with other Autoimmune disease like Arthritis and Reiters syndrome.

• Lab diagnosis:

• Cultured on antibiotic containing Skirrows agar to inhibit other fecal flora.

• Incubated at 42 degrees centigrade under microaerophillic conditions (5%oxygen and 10%carbon dioxide).

• Failure to grow at 25 degrees centigrade, oxidase positivity and sensitivity to Nalidixic acid are distinguishing features.

• C.intestinalis can grow at 25 degree centigrade and resistant to Nalidixic acid.

• Lactose fermentation not the criteria for identification.

Treatment:

Erythromycin or Ciprofloxacin for C.jejuni.Aminoglycoside for C.intestinalis bacteremia.Prevention is by personal hygiene and proper

sewage disposal.

Helicobacter• H.pylori causes gastritis and peptic ulcers.• It is a risk factor for gastric carcinoma and is

linked with mucosal-associated lymphoid tissue(MALT) lymphomas.

• They are curved, gm neg, comma or S-shaped rods like Campylobacter.

• They differ in biochemical and flagellar characteristics.

• They are strongly urease positive. Campylobacter are negative.

• Pathogenesis:

• H.pylori attaches to the mucus secreting cells of the gastric mucosa.• Production of large amounts of ammonia from urea coupled with an

inflammatory response, leads to the damage of the mucosa.• Loss of protective mucus predisposes to gastritis and peptic ulcer.• The ammonia neutralizes the stomach acid and allows the orgs. to survive.• Natural habitat of H.pylori is stomach acquired by ingestion. However, it

has not been isolated from food, water, stool or animals.• MALT lymphomas are B-cell tumors located typically in the stomach.

H.pylori is often found in MALT lesions and the chronic inflammation caused by the org. is believed to cause B-cell proliferation and eventually a B-cell lymphoma.

• Antibiotic treatment often causes the tumor to regress.

Clinical findings:

Gastritis and Peptic ulcer are characterized by recurrent pain in the upper abdomen, frequently accompanied by bleeding into the GI tract.

No bacteremia or dissemination occurs.

• Lab diagnosis:

• Gram stained biopsy specimens of gastric mucosa reveal orgs.

• In contrast to C.jejuni, H.pylori is Urease positive• Urea breath test: radiolabelled urea is ingested, If org. is

present will cleave the ingested urea and radiolabelled carbon dioxide evolved is detected as radioactivity in the breath.

• Agglutination testing for Helicobacter antigen in the stool can be used for diagnosis and confirmation of effective treatment eliminating the organism.

• Presence of IgG antibodies also indicative of infection.