II. Gastrointestinal Infections

Sanitation is Key for preventing most gastrointestinal infections.

GI Tract Defenses

• Supports large and diverse microflora populations that compete with pathogens.

• Saliva contains lysozyme and lactoferrin.

• The stomach has a low pH.

• A mucus layer is present throughout the entire GI tract.

• Gut-associated lymphoid tissue provides immune function.

Bacterial Toxins

• Exotoxin: A toxin secreted by bacteria, typically protein in nature. Can cause damage to the host by destroying cells or disrupting normal cellular metabolism.

  • Enterotoxin: A type of exotoxin that specifically targets the intestine, usually causing diarrhea and vomiting.

• Endotoxin: A toxic substance bound to the bacterial cell wall and released when the bacterium ruptures or disintegrates. Endotoxins consist of lipopolysaccharide and lipoprotein complexes. An endotoxin that targets the intestines is also called an enterotoxin.

Helicobacter pylori

• Causes Gastric ulcers. High levels are often found in individuals with stomach cancer.

• A gram-negative bacterium.

• Discovered by Robin Warren and Barry Marshall (won the 2005 Nobel Prize). Marshall famously ingested H. pylori to demonstrate its role.

• Adapted to survive in the stomach by secreting urease, which converts urea to CO2 and basic ammonia, neutralizing the stomach acid around the bacteria.

• Invades and digests the mucus layer, allowing stomach acid to leak and cause ulcers.

• Common in healthy people.

• Humans are the major, if not only, reservoir.

• Transmitted person-to-person via fecal-oral or oral-oral routes.

• Stress and diet may trigger disease development.

• Could potentially have beneficial roles, such as acid control and influencing appetite.

Vibrio cholerae

• Causes Cholera.

• A gram-negative, comma-shaped bacterium.

• First isolated by Koch.

• Invades the small intestine.

• Produces an Enterotoxin (Cholera toxin, an exotoxin with A and B factors).

• The toxin causes massive loss of ions and fluids by preventing intestinal absorption.

• A large infectious dose (10^6-10^8 cells) is needed.

• Death can result if fluids are not replaced; most people die from dehydration. Rehydration therapy is important and the most common treatment.

• Transmitted almost exclusively through contaminated water supplies, occasionally shellfish.

• Not a major problem in countries with good sanitation and public health.

• Causes 3-5 million cases and 100,000 deaths yearly worldwide.

• The gene for the cholera toxin is acquired and expressed via lysogenic conversion: a lysogenic phage (CTX phage) genome integrated into the bacterial cell genome expresses gene products (cholera toxin) that affect the phenotype of the host bacterium.

• Treatment includes salt solution, intravenous fluids, and antibiotics may be used. Hydration therapy is most common.

• The Haiti outbreak in October 2010, following the January 2010 earthquake, was caused by the collapse of the country's water, sanitation, and health systems. It resulted in >386,000 cases and 5,885 deaths by July 2011.

• John Snow, an English doctor, conducted a classic epidemiological study in 1854, determining that contaminated water (specifically the Broad Street Well) was the source of a cholera outbreak by mapping cases and shutting off the well.

E. coli

• Causes Gastroenteritis.

• Most E. coli are harmless members of the normal intestinal flora.

• Pathogenic strains cause mild to very severe diarrhea and cramps.

• Transmission is fecal-oral, usually through contaminated food or drink (can include ruminants as sources).

• Antibiotics may make things worse for certain strains by causing the release of toxins.

• Rehydration therapy is important.

• Types of pathogenic E. coli:

  • Enterohemorrhagic E. coli O157:H7 (STEC): First described in 1982. O and H refer to antigen numbers. Causes severe, bloody diarrhea. Hemolytic uremic syndrome (kidney failure) can develop. Shiga Toxin genes are carried on a phage via lysogenic conversion. A 1993 outbreak in Washington state was traced to undercooked hamburgers. Recent outbreaks have been linked to contaminated produce.

  • Enterotoxigenic E. coli: Makes two types of toxin. The cause of "Traveler’s diarrhea". Can be life-threatening in infants.

  • Enteroinvasive E. coli: Invades mucosal cells of the large intestine.

  • Enteropathogenic E. coli: Similar to STEC but does not produce toxin. Causes significant infant mortality in developing countries.

Salmonella

• S. enterica affects the stomach and GI tract (Salmonellosis).

• S. typhi (associated with Typhoid Mary) can enter all the body’s cells.

• Prevention is best achieved by proper handling and cooking of food.

• Very common, with possibly 2 million cases yearly in the U.S..

• Rehydration therapy is important.

• Some strains cause typhoid fever: they multiply in macrophages and are carried throughout the bloodstream. Humans are the source for these strains.

• Most cases originate from non-human sources.

• Produces an Enterotoxin that targets the intestines.

• Pet reptiles can pose a risk, as Salmonella is part of the normal microflora of most reptiles. The CDC recommends that households with children under 5 years old do not keep reptiles as pets. Careful hand washing and hygiene are essential. A ban on the sale of small turtles in the U.S. was enacted in 1975.

Campylobacter jejuni

• A gram-negative, rod-shaped, motile bacterium.

• One of the most common causes of diarrhea in the U.S..

• Very low infectious dose, less than 500 bacteria.

• Common in domestic animals, especially poultry feces.

• Spread is food or waterborne; person-to-person transmission is very rare. It is considered a zoonosis.

• Intestinal infection can last over two weeks.

• Produces an Enterotoxin derived from exotoxins.

• Causes diarrhea, fever, nausea, and vomiting.

• Most individuals recover without treatment.

• Prevention includes proper cooking, pasteurization, and sanitation.

Clostridium difficile (antibiotic diarrhea)

• A gram-positive, endospore-forming, rod-shaped bacterium.

• Found in normal intestinal flora.

• Disease often follows antibiotic therapy that eliminates competing microbes.

• Can cause severe inflammation and sloughing off of layers of cells.

• Often leads to chronic infections.

• Very painful and can result in death.

• Transmission is fecal-oral, especially common in nursing homes and other healthcare settings.

• Can also live in soil and water and persist as endospores.

• Treatment involves appropriate antibiotics (sometimes) or a fecal transplant.

• Antibiotic resistance is a particular problem.

Viral Gastroenteritis

• Caused by Rotavirus and Norwalk virus (Norovirus).

• Both are spread by the fecal-oral route.

• Have a very low infectious dose.

• Infect small intestine epithelial cells.

• Cause nausea, vomiting, and diarrhea.

• Lasts a few days to a week.

• Prevention by hand-washing and sanitation.

• Rotavirus: Causes the death of millions of children every year in developing countries. Common in livestock, with high morbidity and mortality; genetic exchange occurs.

• Norwalk virus: Causes the majority of food poisoning outbreaks on cruise ships. Humans are the only known reservoir.

Porcine Epidemic Diarrhea Virus (PEDV)

• A coronavirus.

• Fecal-oral transmission.

• Causes a high mortality rate in baby pigs (> 90%).

• Pigs are the only host.

• Now widespread in the U.S..

Food Poisoning (distinct from gastrointestinal infections)

• Caused by pre-formed toxins, meaning bacterial growth is not required in the host.

• Results in vomiting and severe diarrhea.

• Has a short incubation period, typically just a few hours.

• Staphylococcus aureus is an important cause. It makes heat-stable toxins that bind receptors in the bowels, stimulating the medullary centers and causing vomiting.

• May also be caused by toxins of non-microbial origin, such as arsenic, fertilizer, pesticides, or mercury.