Lower Alimentary Tract Infections

Learning Objectives

  • Identify the dominating genus of bacteria that constitute the normal flora in the gastrointestinal tract.

  • Differentiate between intoxications and infections with emphasis on individual organisms.

  • Differentiate between dysentery and gastroenteritis.

  • Describe the major causes of intoxications and gastroenteritis by identifying the endotoxins and exotoxins.

  • Identify common sources of gastrointestinal infections.

  • Describe some clinical features of viral intestinal infections including norovirus, rotavirus, and Hepatitis A, B, C, D, and E.

Transmission of Infections/Intoxications

  • Most gastrointestinal infections are transmitted via the fecal-oral route.

  • Breaking the chain of transmission involves:

    • Proper disposal and treatment of sewage.

    • Disinfection of drinking water.

    • Proper food preparation and handling.

  • Consideration of feasibility in Canada versus other countries.

Predominant Flora of the Intestine

  • The gastrointestinal tract is primarily populated by Gram-negative bacteria, including both anaerobes and aerobes.

  • The dominating species include Bacteroides, with over 500 different bacteria expected to be present, many of which are unidentified.

Types of Diseases of the GI Tract

Infections
  • Pathogen multiplies in the mucosa or disseminates to other systemic organs.

  • Characterized by symptoms such as:

    • Fever

    • Release of endotoxin (lipopolysaccharide, LPS).

Intoxications
  • Involves the ingestion of preformed toxins, leading to:

    • Sudden onset of symptoms without fever or systemic symptoms.

  • Common result of both types includes diarrhea, a major cause of infant mortality due to dehydration.

Main Pathogenic Mechanisms of Lower Alimentary Tract Pathogens

  • Attachment: Bacteria attach to intestinal cells.

  • Cell Invasion: Some pathogens may invade host cells.

  • Loss of Microvilli: Damage to intestinal microvilli occurs, affecting absorption.

  • Exotoxin Production:

    1. Increases secretion of water and electrolytes (e.g. Vibrio cholerae enterotoxin).

    2. Inhibits protein synthesis and causes cell death (e.g. Clostridium difficile cytotoxin).

  • Many GI pathogens are Gram-negative and possess both endotoxins and exotoxins.

Dysentery vs Gastroenteritis

Dysentery
  • Defined as severe diarrhea containing blood, often pus, and/or mucus.

    • Examples include Entamoeba histolytica and Shigella dysenteriae.

Gastroenteritis
  • Inflammation of the stomach and intestinal mucosa without pus.

    • Examples include Vibrio cholerae and Cryptosporidium.

  • Common symptoms include:

    • Diarrhea

    • Vomiting

    • Abdominal cramps

    • Nausea

Food Intoxications Overview

Cause

% of Cases

Time to Onset

Main Clinical Symptoms

Characteristic Foods

Staphylococcus aureus

5-25%

2-4 hr

Vomiting

Meats, custards, salads

Bacillus cereus

1-2%

1-6 hr

Vomiting, diarrhea

Rice, meat, vegetables

Clostridium botulinum

5-15%

12-72 hr

Neuromuscular paralysis

Improperly preserved vegetables

Staphylococcal Food Poisoning

  • In Canada, the economic cost of food recalls due to S. aureus is estimated at 3.2 million CAD/year.

  • S. aureus produces heat-stable enterotoxins, that can survive boiling for up to 30 minutes and are resistant to enzymatic destruction in the GI tract.

  • Factors for growth include:

    • Salt tolerance

    • Osmotic stability due to the cell wall

    • Resistance to heat (up to 60°C for 30 minutes).

  • Common foods include custards, gravy, cream pie, and ham; adequate refrigeration can help prevent growth.

Staphylococcal Enterotoxin

  • Triggers the vomiting reflex.

  • Causes abdominal cramps.

  • Symptoms typically appear 2-4 hours after ingestion.

  • Recovery is usually complete within 24 hours with no lasting side effects.

Bacillus cereus

  • Associated with Bacillus cereus tainted bean curd.

  • Can present in two forms:

    1. Diarrhea due to enterotoxin produced in the gut (8-16 hr - infection).

    2. Vomiting due to ingestion of the enterotoxin in food (1-6 hr - intoxication).

  • Gram-positive, aerobic, spore-forming bacilli.

  • Heating may not kill spores; prevalent in rice dishes.

  • Considered a self-limiting disease.

Common Infections of the GI Tract

  • Most common causes include:

    • Salmonella

    • Shigella

    • Campylobacter

    • E. coli (e.g. ETEC, EIEC, EPEC, EHEC)

    • Clostridium perfringens

    • Bacillus cereus (both intoxication and infection)

    • Vibrio cholerae

    • E. histolytica, Giardia, Cryptosporidium

    • Rotavirus, norovirus, sapovirus

    • Hepatitis A.

Salmonellosis (Salmonella Gastroenteritis)

  • Caused by Gram-negative, non-spore-forming, motile bacilli.

  • Two main types of Salmonella infections:

    • Gastroenteritis

    • Typhoid fever

  • Salmonella enterica enterica and Salmonella enterica typhi are common serotypes.

Incidence and Economic Impact of Salmonellosis

  • Approximately 1 in 6 people (about 48 million) get sick each year from contaminated food in the U.S.

  • Salmonella infections account for an estimated 365 million CAD in direct medical costs each year.

Specific Features of Salmonella Gastroenteritis

  • There are over 2000 serotypes responsible for human diseases (zoonotic).

  • Symptoms typically take 12-36 hours post-exposure to develop.

  • Bacteria are sensitive to gastric acid; a high bacterial load is required for infection.

  • Common sources include meat products, eggs, poultry, and reptile skin; S. enteritidis can infect chickens leading to bacteria inside the eggs.

  • Treatment usually does not involve antibiotics due to the risk of prolonging bacterial shedding.

  • Currently, there is no vaccine available.

Typhoid Fever

  • Caused specifically by S. typhi.

  • Characterized by different pathogenesis and transmitted only from human to human.

  • Main symptoms include:

    • High fever (≥ 40°C)

    • Headaches

    • Diarrhea beginning in the second or third week, not the primary symptom.

  • Results in sepsis (enteric fever); bacteria multiply in phagocytic cells, rapidly disseminating to the bloodstream.

    • Chronic carriers can emerge post-recovery, as seen in cases like Typhoid Mary.

  • Treatment involves antibiotics such as ceftriaxone.

Shigellosis

  • This is an infection caused by Gram-negative bacilli, which are non-motile.

  • The four primary species are:

    • Shigella dysenteriae (A)

    • Shigella boydii (B)

    • Shigella flexneri (C)

    • Shigella sonnei (D)

  • Severity varies by the infecting strain; more virulent strains may have plasmids essential for attachment and entry into cells.

  • Transmission occurs from person-to-person, lacking an animal reservoir.

  • The bacteria produce Shiga toxin, a key virulence factor responsible for their cytotoxic effects.

Campylobacter Gastroenteritis

  • A facultatively anaerobic, Gram-negative, spiral-shaped bacillus.

  • It is the leading cause of foodborne bacterial illness in the U.S. and Canada, with an estimated 4 million cases in Canada annually.

  • Common in poultry and cattle as commensals; the disease is typically self-limiting.

  • Preventative measures include hygienic practices related to the handling of poultry and monitoring water sources.

  • Complications may include Irritable Bowel Syndrome (IBS) and Guillain-Barré Syndrome.

  • Currently, there is no vaccine available.

Escherichia coli Gastroenteritis

  • Most strains are harmless and normal residents of the GI tract, but pathogenic strains may have specialized fimbriae enabling attachment and produce toxins.

  • Pathogenic strains include:

    • Enterotoxigenic E. coli (ETEC)

    • Enteroinvasive E. coli (EIEC)

    • Enteroadhesive E. coli (EAEC)

    • Enteropathogenic E. coli (EPEC)

    • Enterohemorrhagic E. coli (EHEC)

Enterohemorrhagic E. coli (EHEC)

  • This strain is increasingly recognized in developed nations and is known for causing “Hamburger Disease.”

  • The associated healthcare costs in Canada are around 240 million CAD.

  • The strain O157:H7 is well known for producing Shiga-like toxins, leading to hemorrhagic colitis and hemolytic uremic syndrome (HUS).

HUS Complications

  • Hemolytic uremic syndrome may result in kidney failure.

  • Estimated that 5-10% of small children infected with EHEC develop HUS, with a mortality rate of 5%.

  • Common sources include poorly handled meat, poultry, raw alfalfa sprouts, and contaminated water.

  • Most cases are self-limiting in adults, but children and the elderly are at higher risk for complications.

  • Treatment generally focuses on rehydration and supportive care without a vaccine available.

Clostridium Gastroenteritis

  • Clostridium perfringens (Gram-positive, spore-forming, anaerobic bacilli) can proliferate in the intestinal tract, producing an exotoxin that leads to abdominal pain and diarrhea.

  • Most cases are mild, presenting 8-12 hours post-ingestion.

  • Severe cases may occur in individuals lacking trypsin or consuming diets rich in trypsin inhibitors (such as soybeans), potentially resulting in Pigbel (gangrene of intestines).

  • Associated with meat dishes (stews) and generally not treated with antibiotics; there is no vaccine.

Vibrio cholerae

  • A facultatively anaerobic, Gram-negative 'vibrio' (comma-shaped) bacterium.

  • Capable of causing over 20 liters of fluid loss per day, presenting as “rice water stool.”

  • Prevalent in fecally contaminated water and a major source for infection.

  • Known for causing global pandemics, including the 2010 Haiti outbreak that saw 650,000 infections and over 8,000 deaths.

  • Key virulence factors include the cholera enterotoxin (heat-labile) and TCP (toxin co-regulated pili).

  • A vaccine exists with 40-60% effectiveness (oral vaccine Dukoral), and treatment primarily involves rehydration with glucose and electrolytes.

Viral Gastroenteritis

  • Clinical infections are noted globally, with severe implications in developing countries as a leading cause of death in children.

  • Distinctions from other gastroenteritis causes are typically non-specific clinically.

  • Predominant pathogens include rotavirus and norovirus, both transmitted via fecal-oral routes.

Rotavirus Gastroenteritis

  • RNA virus, wheel-shaped, and non-enveloped.

  • Primarily affects children, with most cases occurring in those under 2 years of age.

  • Incubation period is 2-3 days with symptoms including low-grade fever, diarrhea, and vomiting for about a week.

  • There are new vaccines available, e.g., Rotorix® and Rotateq®.

Norovirus Gastroenteritis

  • RNA, small round, non-enveloped virus.

  • Major contributor to epidemics of viral gastroenteritis, responsible for 2/3 of food poisoning cases.

  • Has a 2-day incubation period and symptoms similar to rotavirus with sudden onset, typically self-limiting and lasts 1-3 days.

Protozoan Diseases

  • Commonly associated with diarrhea:

    • Giardia lamblia

    • Cryptosporidium

    • Entamoeba histolytica

Helminthic Diseases

  • Typically present without diarrhea:

    • Tapeworms (cestodes)

    • Roundworms (nematodes)

Hepatitis Overview

  • Infections can lead to inflammation of the liver caused by various viruses:

    • Hepatitis A

    • Hepatitis B

    • Hepatitis C

    • Hepatitis D

    • Hepatitis E

  • CMV and EBV can also cause infectious hepatitis.

Hepatitis A (HAV)

  • RNA, non-enveloped virus, transmitted fecal-orally via contaminated water and mollusks.

  • The virus is resistant to chlorine and has an incubation period of 2-4 weeks.

  • Pathogenesis involves multiplication in intestinal epithelial cells, followed by infection of the liver and excretion in feces.

  • Symptoms include nausea, fever, anorexia, vomiting, and jaundice, often with sudden onset.

  • Generally self-limiting with no chronic form; 50% of infections are subclinical.

  • Diagnosis is made by detecting HAV IgM antibodies in serum, and lifelong immunity exists after infection, for which a vaccine is available.

Hepatitis B (HBV)

  • Enveloped DNA virus from the Hepadnaviridae family.

  • Transmitted via sexual contact or as a bloodborne disease; capable of causing both acute and chronic diseases:

    • Acute: liver inflammation, vomiting, jaundice.

    • Chronic: cirrhosis and hepatocellular carcinoma (liver cancer).

  • A vaccine is available, and treatments include antivirals such as lamivudine, Harvoni, and Sovaldi (costly lifetime treatments averaging 50,000-94,500 CAD).

Hepatitis C (HCV)

  • Enveloped RNA virus with bloodborne transmission.

  • Like HBV, it can induce both acute and chronic disease, with 80% of acute cases leading to chronic infection.

  • Chronic manifestations are similar to those of HBV, including cirrhosis and liver cancer.

  • There is no vaccine available; however, new antivirals have been approved since 2011.

Hepatitis D Virus (HDV)

  • Enveloped RNA virus that acts as a satellite virus, relying on HBV for its replication.

  • Transmission parallels that of HBV and disease can only occur in the presence of HBV.

Hepatitis E Virus (HEV)

  • Non-enveloped RNA virus within the Caliciviridae family, transmitted via the fecal-oral route, similar to HAV.

  • Endemic in areas with poor sanitation, particularly in India and Southeast Asia; does not cause chronic disease but poses a significant risk to pregnant women (up to 20% mortality).

Summary of Hepatitis Viruses

Virus Description

Type

Transmission

Chronic Infection

Prevention

HAV

Non-enveloped RNA virus

Fecal-oral

No

Hygiene, Vaccine available

HBV

Enveloped DNA virus

Bloodborne, STI

Yes

Vaccine available

HCV

Enveloped RNA virus

Bloodborne

Yes

Behaviour modification, new antivirals

HDV

Enveloped RNA virus

Bloodborne, requires HBV

Yes

Behaviour modification

HEV

Non-enveloped RNA virus

Fecal-oral

No

Hygiene, Vaccine in development