Bacterial Diseases of the Digestive System

Bacterial Gastroenteritis

Gastroenteritis is characterized by inflammation of the gastrointestinal tract that involves both the stomach and the small intestine.

Learning Objectives

Describe the cause and effect of bacterial gastroenteritis

Key Takeaways

Key Points

  • Gastroenteritis typically involves both diarrhea and vomiting, or less commonly, presents with only one or the other.
  • Transmission rates are also related to poor hygiene, especially among children, in crowded households, and in those with pre-existing poor nutritional status.
  • A supply of easily accessible uncontaminated water and good sanitation practices are important for reducing rates of infection and clinically significant gastroenteritis.

Key Terms

  • inflammation: A condition of any part of the body, consisting in congestion of the blood vessels, with obstruction of the blood current, and growth of morbid tissue. It is manifested outwardly by redness and swelling, attended with heat and pain.
  • gastroenteritis: Inflammation of the mucous membranes of the stomach and intestine; often caused by an infection.

Gastroenteritis is a medical condition characterized by inflammation (“-itis”) of the gastrointestinal tract that involves both the stomach (“gastro”-) and the small intestine (“entero”-), resulting in some combination of diarrhea, vomiting, and abdominal pain and cramping. Although unrelated to influenza, it has also been called ‘stomach flu’ and ‘gastric flu’.

Globally, most cases in children are caused by rotavirus. Less common causes include other bacteria (or their toxins) and parasites. Transmission may occur due to consumption of improperly prepared foods, contaminated water, or via close contact with individuals who are infectious. The foundation of management for this illness is adequate hydration. For mild or moderate cases, this can typically be achieved via oral rehydration solution. For more severe cases, intravenous fluids may be needed. Gastroenteritis primarily affects children and those in the developing world. Gastroenteritis typically involves both diarrhea and vomiting, or less commonly, presents with only one or the other. Abdominal cramping may also be present.

Signs and symptoms usually begin 12–72 hours after contracting the infectious agent. Some bacterial infections may be associated with severe abdominal pain and may persist for several weeks. In the developed world, Campylobacter jejuni is the primary cause of bacterial gastroenteritis, with half of these cases associated with exposure to poultry. In children, bacteria are the cause in about 15% of cases, with the most common types being Escherichia coli, Salmonella, Shigella, and Campylobacter species. If food becomes contaminated with bacteria and remains at room temperature for a period of several hours, the bacteria multiply and increase the risk of infection in those who consume the food. Toxigenic Clostridium difficile is an important cause of diarrhea that occurs more often in the elderly. Infants can carry these bacteria without developing symptoms. It is a common cause of diarrhea in those who are hospitalized and is frequently associated with antibiotic use. Staphylococcus aureus infectious diarrhea may also occur in those who have used antibiotics. “Traveler’s diarrhea” is usually a type of bacterial gastroenteritis. Acid-suppressing medication appears to increase the risk of significant infection after exposure to a number of organisms, including Clostridium difficile, Salmonella, and Campylobacter species.

image

Salmonella Typhimurium: Salmonella enterica serovar Typhimurium as seen with a microscope at 1000 fold magnification and following Gram staining. Salmonella is a common cause of gastroenteritis in children.

Transmission rates are also related to poor hygiene, especially among children, in crowded households, and in those with pre-existing poor nutritional status. After developing tolerance, adults may carry certain organisms without exhibiting signs or symptoms, and thus act as natural reservoirs of contagion. While some agents (such as Shigella) only occur in primates, others may occur in a wide variety of animals (such as Giardia).

Gastroenteritis is typically diagnosed clinically, based on a person’s signs and symptoms. Determining the exact cause is usually not needed as it does not alter management of the condition. However, stool cultures should be performed in those with blood in the stool, those who might have been exposed to food poisoning, and those who have recently traveled to the developing world. Electrolytes and kidney function should also be checked when there is a concern about severe dehydration.

A supply of easily accessible uncontaminated water and good sanitation practices are important for reducing rates of infection and clinically significant gastroenteritis. Personal measures (such as hand washing) have been found to decrease incidence and prevalence rates of gastroenteritis in both the developing and developed world by as much as 30%.

Staphylococcal Food Poisoning

Staphylococcal toxins are a common cause of food poisoning, as they can be produced in improperly-stored food.

Learning Objectives

Recognize the causes of staphylococcal food poisoning

Key Takeaways

Key Points

  • Staphylococcus is a Gram-positive bacteria which includes several species that can cause a wide variety of infections in humans and other animals through infection or the production of toxins.
  • Foodborne illness usually arises from improper handling, preparation, or storage of food.
  • Good hygiene practices before, during, and after food preparation can reduce the chances of contracting an illness.

Key Terms

  • toxin: A toxic or poisonous substance produced by the biological processes of biological organisms.
  • norovirus: The genus of a number of species of virus, family Caliciviridae, causing human gastroenteritis, of which Norwalk virus is the prototype.

Staphylococcus is a Gram-positive bacteria which includes several species that can cause a wide variety of infections in humans and other animals through infection or the production of toxins. Staphylococcal toxins are a common cause of food poisoning, as they can be produced in improperly-stored food. The main coagulase-positive staphylococcus is Staphylococcus aureus. These bacteria can survive on dry surfaces, increasing the chance of transmission.

image

Staphylococcus aureus: Staphylococcus is a Gram-positive bacteria which includes several species that can cause a wide variety of infections in humans and other animals through infection or the production of toxins.

Any S. aureus infection can cause the staphylococcal scalded skin syndrome, a cutaneous reaction to exotoxin absorbed into the bloodstream. It can also cause a type of septicaemia called pyaemia. The infection can be life-threatening. Problematically, Methicillin-resistant Staphylococcus aureus (MRSA) has become a major cause of hospital-acquired infections and is being recognized with increasing frequency in community-acquired infections.

Foodborne illness usually arises from improper handling, preparation, or food storage. Good hygiene practices before, during, and after food preparation can reduce the chances of contracting an illness. There is a consensus in the public health community that regular hand-washing is one of the most effective defenses against the spread of foodborne illness. The action of monitoring food to ensure that it will not cause foodborne illness is known as food safety.

Foodborne disease can also be caused by a large variety of toxins that affect the environment, such as pesticides or medicines in food, and naturally toxic substances such as poisonous mushrooms or reef fish. In the past, bacterial infections were thought to be more prevalent because few places had the capability to test for norovirus and no active surveillance was being done for this particular agent. Toxins for bacterial infections are delayed because the bacteria need time to multiply. Their symptoms are usually not seen until 12–72 hours or more after eating contaminated food.

Salmonellosis

Salmonellosis is an infection by the Salmonella bacteria that results in diarrhea, fever, vomiting, and abdominal cramps.

Learning Objectives

Distinguish between nontyphoidal and typhoidal Salmonella

Key Takeaways

Key Points

  • In severe cases, the Salmonella infection may spread from the intestines to the bloodstream, and then to other body sites, and can cause death unless the person is treated with antibiotics.
  • The type of Salmonella usually associated with infections in humans, nontyphoidal Salmonella, is often contracted from contaminated food or reptiles.
  • The Salmonella bacterium induces responses in the animal it is infecting, and this is what typically causes the symptoms, rather than any direct toxin that is produced.

Key Terms

  • typhoid fever: An illness caused by the bacterium Salmonella typhi. Not to be confused with typhus.
  • endotoxin: Any toxin secreted by a microorganism and released into the surrounding environment only when it dies.
  • arthritis: Inflammation of a joint or joints causing pain and/or disability, swelling, and stiffness; and due to various causes such as infection, trauma, degenerative changes, or metabolic disorders.

Salmonellosis is an infection with the Salmonella bacteria. Most people infected with Salmonella develop diarrhea, fever, vomiting, and abdominal cramps 12 to 72 hours after infection. In most cases, the illness lasts four to seven days, and most people recover without treatment. However, in some cases the diarrhea may be so severe that the patient becomes dangerously dehydrated and must be taken to a hospital. At the hospital, the patient may receive intravenous fluids to treat the dehydration, and may be given medications to relieve symptoms, such as fever reducers. In severe cases, the Salmonella infection may spread from the intestines to the bloodstream, and then to other body sites, and can cause death unless the person is promptly treated with antibiotics. The elderly, infants, and those with impaired immune systems are more likely to develop severe illness. Some people afflicted with Salmonellosis later experience reactive arthritis, which can have long-lasting, disabling effects.

image

Salmonella: Salmonella is a genus of rod-shaped, gram-negative, non-spore-forming, predominantly motile enterobacteria (shown here in red).

Different Kinds of Salmonella

The different kinds of Salmonella include S. bongori and S. enterica. The type of Salmonella usually associated with infections in humans, nontyphoidal Salmonella, is usually contracted from: poultry, pork, and beef when the meat is prepared incorrectly or is infected with the bacteria after preparation; infected eggs, egg products, and milk when not prepared, handled, or refrigerated properly; reptiles (such as turtles, lizards, and snakes) which can carry the bacteria in their intestines; and tainted fruits and vegetables.

The typhoidal form of Salmonella can lead to typhoid fever. Typhoid fever is a life-threatening illness, and about four hundred cases are reported in the United States each year, with 75% of those acquired while traveling out of the country. It is carried only by humans and is usually contracted through direct contact with the fecal matter of an infected person. Typhoidal Salmonella is more commonly found in poorer countries, where unsanitary conditions are more likely to occur, and can affect as many as 21.5 million people a year.

Salmonella Infection

The Salmonella bacterium induces responses in the animal it is infecting, and this is what typically causes the symptoms rather than any direct toxin that is produced. Symptoms are usually gastrointestinal, including nausea, vomiting, abdominal cramps, and bloody diarrhea with mucus. Headache, fatigue, and rose spots are also possible. These symptoms can be severe, especially in young children and the elderly. Symptoms last generally up to a week, and can appear 12 to 72 hours after ingesting the bacterium. After bacterial infections, reactive arthritis (Reiter’s syndrome) can develop.

An infectious process can only begin after living salmonellae (not only their toxins) reach the gastrointestinal tract. Some of the microorganisms are killed in the stomach, while the surviving salmonellae enter the small intestine and multiply in tissues (this is the localized form). By the end of the incubation period, the macro-organisms are poisoned by endotoxins that are released from the dead salmonellae. The local response to the endotoxins is enteritis and gastrointestinal disorder. In the generalized form of the disease, salmonellae pass through the lymphatic system of the intestine into the blood of the patients (typhoid form) and are carried to various organs (liver, spleen, kidneys) to form secondary foci (septic form).

Endotoxins first act on affected organs’ vascular and nervous systems, manifested by: increased permeability and decreased tone of the vessels, upset thermal regulation, vomiting, and diarrhea. In severe forms of the disease, enough liquid and electrolytes are lost to upset the body’s metabolism of water and salt, decreasing the circulating blood volume and arterial pressure to enough of a degree to cause hypovolemic shock. Septic shock may also develop. Shock of mixed character (with signs of both hypovolemic and septic shock) is more common in severe salmonellosis. Oliguria and azotemia develop in severe cases as a result of kidney involvement due to hypoxia and bacteremia.

Typhoid Fever

Typhoid fever is a common, worldwide bacterial disease transmitted by Salmonella typhi, serotype Typhi.

Learning Objectives

Summarize the four stages of untreated typhoid fever and methods of preventing it

Key Takeaways

Key Points

  • The impact of Typhoid fever fell sharply with the improved sanitation techniques of the 20th century.
  • Classically, the course of untreated typhoid fever is divided into four individual stages, each lasting approximately one week.
  • Diagnosis is made by any blood, bone marrow or stool cultures and with the Widal test (demonstration of salmonella antibodies against antigens O-somatic and H-flagellar).

Key Terms

  • dicrotic: A type of pulse associated with low systemic vascular resistance and a compliant aorta, e.g sepsis
  • Peyer’s patch: Peyer’s patches (or aggregated lymphoid nodules) are usually found in the lowest portion of the small intestine, the ileum, in humans.
  • Widal test: The agglutination test for typhoid fever.
  • eosinopenia: Eosinopenia is a form of agranulocytosis where the number of eosinophil granulocyte is lower than expected; usually a predictor of bacterial infection.
  • lymphocytosis: An increase in the number or proportion of lymphocytes in the blood.

Typhoid Fever

Typhoid fever, also known as typhoid, is a common, worldwide bacterial disease. It is transmitted by the ingestion of food or water that has been contaminated with the feces of a person infected by the bacterium Salmonella typhi, serotype Typhi.

The disease has been known by many names, such as gastric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever or pythogenic (originating from filth or putrefaction) fever. The name “typhoid” means “resembling typhus” and comes from the neuropsychiatric symptoms common to typhoid and typhus. The term “enteric fever” is a collective term that refers to typhoid and paratyphoid.

The impact of this disease fell sharply with the improved sanitation techniques of the 20th century.

STAGES

Classically, the course of untreated typhoid fever is divided into four individual stages, each lasting approximately one week.

First stage: the temperature rises slowly and fever fluctuations are seen with relative bradycardia (slow pulse), malaise, headache and cough. Nose bleeds (epistaxis) are seen in 25% of cases and abdominal pain can occur. There is leukopenia (a decrease in the number of circulating white blood cells), with eosinopenia and relative lymphocytosis. The classic Widal test is negative in the first week.

Second stage: the patient lies prostrate with high fever in plateau around 40 °C (104 °F) and bradycardia, classically with a dicrotic pulse wave. Delirium is frequent; patients may be calm, but sometimes agitated. This delirium gives typhoid its nickname of “nervous fever”. Rose spots appear on the lower chest and abdomen in around a third of patients. The Widal test is strongly positive with antiO and antiH antibodies. Blood cultures may be still positive at this stage. (The major symptom of typhoid is that the fever usually rises in the afternoon in the first and second stages. )

image

Typhoid Fever: Rose spots on the chest of a patient with typhoid fever due to the bacterium Salmonella typhi

Third stage: a number of complications can occur: intestinal hemorrhage due to bleeding in congested Peyer’s patches and intestinal perforation in the distal ileum.

Fourth stage: by the end of the third week the fever starts subsiding (defervescence). This carries on into the fourth and final week.

PREVENTION

The bacteria which cause typhoid fever may be spread through poor hygiene habits and public sanitation conditions and, sometimes, also by flying insects feeding on infected feces. Public education campaigns encouraging people to wash their hands after defecating and before handling food are an important component in controlling the spread of the disease. A person may become an asymptomatic carrier of typhoid fever, suffering no symptoms, but capable of infecting others.

DIAGNOSIS

Diagnosis is made by any blood, bone marrow or stool cultures and with the Widal test (demonstration of salmonella antibodies against antigens O-somatic and H-flagellar). In epidemics and less wealthy countries, after excluding malaria, dysentery or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of the Widal test, and cultures of the blood and stool. The Widal test is time-consuming and often, when a diagnosis is reached, it is too late to start an antibiotic regimen.

VACCINATION

There are two vaccines licensed for use for the prevention of typhoid: the live, oral Ty21a vaccine (sold as Vivotif Berna) and the injectable Typhoid polysaccharide vaccine (sold as Typhim Vi by Sanofi Pasteur and Typherix by GlaxoSmithKline).

TREATMENT

The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general.

Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime. Cefixime is a suitable oral alternative. Typhoid fever in most cases is not fatal. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin and ciprofloxacin have been commonly used to treat typhoid fever.

Cholera

Cholera is an infection in the small intestine caused by the bacterium Vibrio cholerae.

Learning Objectives

Describe the mode of transmission for Vibrio cholerae and the steps that can be taken to prevent this

Key Takeaways

Key Points

  • The primary symptoms of cholera are profuse, painless diarrhea and vomiting of clear fluid.
  • V. cholerae bacteria that survive the gastric juices produce the hollow cylindrical protein flagellin to make flagella, the cork-screw helical fibers they rotate to propel themselves through the mucus of the small intestine.
  • A number of safe and effective oral vaccines for cholera are available.

Key Terms

  • flagella: A flagellum is a lash-like appendage that protrudes from the cell body of certain prokaryotic and eukaryotic cells.
  • electrolyte: any of the various ions (such as sodium or chloride) that regulate the electric charge on cells and the flow of water across their membranes

Vibrio Cholerae

Cholera is an infection in the small intestine caused by the bacterium Vibrio cholerae. The primary symptoms of cholera are profuse, painless diarrhea and vomiting of clear fluid. These symptoms usually start suddenly, one to five days after ingestion of the bacteria. The diarrhea is frequently described as “rice water” in nature and may have a fishy odor. If the severe diarrhea is not treated with intravenous rehydration, it can result in life-threatening dehydration and electrolyte imbalances.

image

Adult cholera patient: A person with severe dehydration due to cholera – note the sunken eyes and decreased skin turgor which produces wrinkled hands.

Transmission

Cholera is typically transmitted by either contaminated food or water. In the developed world, seafood is the usual cause, while in the developing world it is more often water. Cholera is rarely spread directly from person to person. Both toxic and nontoxic strains exist.

Most V. cholerae bacteria, when consumed, do not survive the acidic conditions of the human stomach. The few surviving bacteria conserve their energy and stored nutrients during the passage through the stomach by shutting down much protein production. When the surviving bacteria exit the stomach and reach the small intestine, they need to propel themselves through the thick mucus that lines the small intestine to get to the intestinal walls, where they can thrive. V. cholerae bacteria begin production of the hollow cylindrical protein flagellin to make flagella. These flagella are cork-screw helical fibers that rotate to propel the bacteria through the mucus of the small intestine.

Once the cholera bacteria reach the intestinal wall, they no longer need the flagella to move. The bacteria stop producing the protein flagellin, again conserving energy and nutrients by changing the mix of proteins they manufacture in response to the changed chemical surroundings. The V. cholerae start producing the toxic proteins that give the infected person a watery diarrhea.

The diarrhea carries new generations of V. cholerae bacteria out into the drinking water of the next host if proper sanitation measures are not in place. A rapid dip-stick test is available to determine the presence of V. cholerae in a water supply. Samples that test positive should be further tested to determine antibiotic resistance. In epidemic situations, a clinical diagnosis may be made by taking a patient history and doing a brief examination. Treatment is usually started without or before confirmation by laboratory analysis. Although cholera may be life-threatening, prevention of the disease is normally straightforward if proper sanitation practices are followed. In developed countries, due to nearly universal advanced water treatment and sanitation practices, cholera is no longer a major health threat.

Breaking the Transmission Path

Effective sanitation practices, if instituted and adhered to in time, are usually sufficient to stop an epidemic. There are several points along the cholera transmission path at which its spread may be halted.

  • Sterilization or proper disposal and treatment of infected fecal waste water produced by cholera victims and all contaminated materials (e.g. clothing, bedding, etc.) is essential. All materials that come in contact with cholera patients should be sanitized by washing in hot water, using chlorine bleach if possible. Hands that touch cholera patients or their clothing, bedding, etc., should be thoroughly cleaned and disinfected with chlorinated water or other effective antimicrobial agents.
  • Antibacterial treatment of general sewage by chlorine, ozone, ultraviolet light or other effective treatment before it enters the waterways or underground water supplies helps prevent undiagnosed patients from inadvertently spreading the disease.
  • Warnings about possible cholera contamination should be posted around contaminated water sources with directions on how to decontaminate the water (boiling, chlorination etc.) for possible use.
  • All water used for drinking, washing, or cooking should be sterilized by either boiling, chlorination, ozone water treatment, ultraviolet light sterilization (e.g. by solar water disinfection), or antimicrobial filtration in any area where cholera may be present.
  • Public health education and adherence to appropriate sanitation practices are of primary importance to help prevent and control transmission of cholera and other diseases.

Prevention and Treatment

A number of safe and effective oral vaccines for cholera are available. In most cases, cholera can be successfully treated with oral rehydration therapy (ORT), which is effective, safe, and simple to administer. Rice-based solutions are more efficient than glucose-based ones. In cases of severe dehydration, intravenous rehydration may be necessary. Antibiotic treatments for one to three days shorten the course of the disease and reduce the symptoms. People will recover without them, however, if sufficient hydration is maintained. Doxycycline is typically used first line, although some strains of V. cholerae have shown resistance. Testing for resistance during an outbreak can help determine appropriate future choices. Other antibiotics proven to be effective include cotrimoxazole, erythromycin, tetracycline, chloramphenicol, and furazolidone. Fluoroquinolones, such as norfloxacin, also may be used, but resistance has been reported.

Noncholera Vibrios

Vibrio is a Gram-negative bacteria possessing a curved rod shape (comma shape), several species of which can cause foodborne infection.

Learning Objectives

Discuss the difference between cholera and noncholera causing Vibrios

Key Takeaways

Key Points

  • Vibrio species are prevalent in estuarine and marine environments. Seven species can cause food borne infections associated with seafood.
  • Patients with noncholera Vibrio wound infection or septicemia are much more ill and frequently have other medical conditions.
  • Early medical intervention is paramount and consists of antimicrobial therapy, intensive medical therapy for disease symptoms, and surgical removal of infected tissues if necessary.

Key Terms

  • necrotizing fasciitis: Necrotizing fasciitis, commonly known as flesh-eating disease or flesh-eating bacteria syndrome, is a rare infection of the deeper layers of skin and subcutaneous tissues, that easily spreads across the fascial plane within the subcutaneous tissue.
  • hemolysin: any substance that damages the membranes of red blood cells and thus releases hemoglobin
  • septicemia: A disease caused by the presence of pathogenic organisms, especially bacteria or their toxins in the bloodstream, characterized by chills and fever.
  • vibrio: Any of several bacteria, of the genus Vibrio, shaped like a curved rod.

Vibrio is a genus of Gram-negative bacteria possessing a curved rod shape (comma shape). Several species of Vibro can cause food borne infection, usually associated with eating undercooked seafood. Vibrio species are prevalent in estuarine and marine environments. Seven species can cause food borne infections associated with seafood. Vibrio cholerae O1 and O139 serovtypes produce cholera toxin and are agents of cholera. Vibrio species are facultative anaerobes that test positive for oxidase and do not form spores. All members of the genus are motile and have polar flagella with sheaths.

image

Vibrio Cholerae: Flagellar stain of V. cholerae

Patients with noncholera Vibrio wound infection or septicemia are much more ill and frequently have other medical conditions. Medical therapy consists of the following: prompt initiation of effective antibiotic therapy (doxycycline or a quinolone), intensive medical therapy with aggressive fluid replacement, vasopressors for hypotension and septic shock, early fasciotomy within 24 hours after development of clinical symptoms in patients with necrotizing fasciitis, early debridement of the infected wound, expeditious and serial surgical evaluation and intervention to prevent rapid deterioration, especially in patients with necrotizing fasciitis or compartment syndrome. Reconstructive surgery, such as skin graft, is indicated in the recovery phase.

Fecal-oral route infections in the terrestrial environment are responsible for epidemic cholera. Most strains cause gastroenteritis such as V. cholerae non-O1/O139 strains and Vibrio parahaemolytitcus strains capable of producing thermostable direct hemolysin (TDH) and/or TDH-related hemolysin. Vibrio vulnificus is responsible for seafood borne primary septicemia. Its infectivity depends primarily on the risk factors of the host. V. vulnificus infection has the highest fatality rate (50%) of any food borne pathogen. Four other species (V. mimicus, V. hollisae, V. fluvialis, and V. furnissii) can cause gastroenteritis. Some strains of these species produce known toxins, but the pathogenic mechanism is largely not understood.

Pathogenic Escherichia coli

Most E. coli strains are harmless, but some serotypes are pathogenic and can cause serious food poisoning in humans and other species.

Learning Objectives

Distinguish between the different types of pathogenic E. coli in regards to classification and mode of transmission

Key Takeaways

Key Points

  • Pathogenic E. coli strains can be categorized based on elements that can elicit an immune response in animals. The different categories are: O antigen, K antigen, H antigen, and F antigen in the lipopolysaccharide.
  • In humans and in domestic animals, virulent strains of E. coli can cause gastroenteritis, urinary tract infections, and neonatal meningitis.
  • Bacterial infections are usually treated with antibiotics.

Key Terms

  • bacteraemia: The medical condition of having bacteria in the bloodstream.
  • lipopolysaccharide: any of a large class of lipids conjugated with polysaccharides
  • flora: the microorganisms that inhabit some part of the body, such as intestinal flora
  • enterohemorrhagic E. coli: strains of the bacterium Escherichia coli that, when infecting humans, have been linked with the severe complication hemolytic-uremic syndrome

Escherichia coli (E. coli) is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms (endotherms). Most E. coli strains are harmless, but some serotypes are pathogenic and can cause serious food poisoning in humans and other species. The harmless strains are part of the normal flora of the gut, and can benefit their hosts by producing vitamin K2, and by preventing the establishment of pathogenic bacteria within the intestine.

Pathogenic E. coli

Pathogenic E. coli strains can be categorized based on elements that can elicit an immune response in animals, namely: O antigen, K antigen, H antigen, and F antigen in the lipopolysaccharide (LPS) molecules found in the outer membrane of the E. coli cell. The O antigen is a polymer of immunogenic repeating oligosaccharides which is used for serotyping E.coli. It should be noted though that antibodies towards several O antigens cross-react with other O antigens and partially to K antigens not only from E. coli, but also from other Escherichia species and Enterobacteriaceae species. There are two separate groups of K-antigen groups, named group I and group II (while a small in-between subset (K3, K10, and K54/K96) has been classified as group III). Group I consists of 100 kDa (large) capsular polysaccharides, while those in Group II, associated with extraintestinal diseases, are under 50 kDa in size.

image

Lipopolysaccharide: Structure of a lipopolysaccharide showing the O antigen, core region and lipid A.

In humans and in domestic animals, virulent strains of E. coli can cause various diseases. In humans, gastroenteritis, urinary tract infections, and neonatal meningitis can occur. In rarer cases, virulent strains are also responsible for haemolytic-uremic syndrome, peritonitis, mastitis, septicemia, and Gram-negative pneumonia. Certain strains of E. coli produce potentially lethal toxins. Food poisoning caused by E. coli can result from eating unwashed vegetables or undercooked meat. If E. coli bacteria escape the intestinal tract through a perforation (for example from an ulcer, a ruptured appendix, or due to a surgical error) and enter the abdomen, they usually cause peritonitis that can be fatal without prompt treatment.

Transmission of pathogenic E. coli often occurs via fecal–oral transmission. Common routes of transmission include unhygienic food preparation, farm contamination due to manure fertilization, irrigation of crops with contaminated greywater or raw sewage, feral pigs on cropland, or direct consumption of sewage-contaminated water. According to the U.S. Food and Drug Administration, the fecal-oral cycle of transmission can be disrupted by cooking food properly, preventing cross-contamination, instituting barriers such as gloves for food workers, instituting health care policies so food industry employees seek treatment when they are ill, pasteurization of juice or dairy products and proper hand washing requirements.

Uropathogenic E. coli

Uropathogenic E. coli (UPEC) is responsible for approximately 90% of urinary tract infections (UTI) seen in individuals with ordinary anatomy. In ascending infections, fecal bacteria colonize the urethra and spread up the urinary tract to the bladder, as well as to the kidneys (causing pyelonephritis), or the prostate in males. Because women have a shorter urethra than men, they are 14 times more likely to suffer from an ascending UTI. Uropathogenic E. coli use P fimbriae (pyelonephritis-associated pili) to bind urinary tract endothelial cells and colonize the bladder. UPEC can evade the body’s innate immune defences (e.g. the complement system) by invading superficial umbrella cells to form intracellular bacterial communities (IBCs). They also have the ability to form K antigen, capsular polysaccharides that contribute to biofilm formation. Descending infections in turn, though relatively rare, occur when E. coli cells enter the upper urinary tract organs (kidneys, bladder or ureters) from the blood stream.

E. coli and Meningitis

Neonatal meningitis is produced by a serotype of E. coli that contains a capsular antigen called K1. The colonization of the newborn’s intestines with these stems, that are present in the mother’s vagina, lead to bacteraemia, which leads to meningitis. Severe meningitis in the neonates are caused because of the absence of the IgM antibodies from the mother (these do not cross the placenta because FcRn only mediates the transfer of IgG), plus the fact that the body recognizes as self the K1 antigen, as it resembles the cerebral glicopeptides. In stool samples, microscopy will show Gram-negative rods, with no particular cell arrangement.

Treating E. coli

Bacterial infections are usually treated with antibiotics. However, the antibiotic sensitivities of different strains of E. coli vary widely. As Gram-negative organisms, E. coli are resistant to many antibiotics that are effective against Gram-positive organisms. Antibiotics which may be used to treat E. coli infection include amoxicillin, as well as other semisynthetic penicillins, many cephalosporins, carbapenems, aztreonam, trimethoprim-sulfamethoxazole, ciprofloxacin, nitrofurantoin, and the aminoglycosides. Researchers have actively been working to develop safe, effective vaccines to lower the worldwide incidence of E. coli infection.

Campylobacter

Campylobacter (meaning ‘twisted bacteria’) is a genus of bacteria that are Gram-negative, spiral, and microaerophilic.

Learning Objectives

Discuss the method of transmission for Campylobacter

Key Takeaways

Key Points

  • Campylobacter jejuni is now recognized as one of the main causes of bacterial foodborne disease in many developed countries.
  • The common routes of transmission are fecal-oral, ingestion of contaminated food or water, and the eating of raw meat.
  • It produces an inflammatory, sometimes bloody, diarrhea, periodontitis or dysentery syndrome, mostly including cramps, fever and pain.

Key Terms

  • microaerophilic: living and thriving in an environment low in oxygen
  • enteritis: Inflammation of the intestines, generally the small intestine, that may lead to diarrhea.
  • flagella: A flagellum is a lash-like appendage that protrudes from the cell body of certain prokaryotic and eukaryotic cells.

Description of Campylobacter Bacteria

Campylobacter is a genus of bacteria that are Gram-negative, spiral, and microaerophilic. The name means “twisted bacteria” because of the spiral formation; motile, with either unipolar or bipolar flagella, the organisms have a characteristic spiral/corkscrew appearance and are oxidase-positive.

image

Epsilonproteobacteria: Campylobacter bacteria are the number-one cause of food-related gastrointestinal illness in the United States. To learn more about this pathogen, ARS scientists are sequencing multiple Campylobacter genomes. This scanning electron microscope image shows the characteristic spiral, or corkscrew, shape of C. jejuni cells and related structures.

Campylobacter jejuni is now recognized as one of the main causes of bacterial foodborne disease in many developed countries. At least a dozen species of Campylobacter have been implicated in human disease, with C. jejuni and C. coli the most common. C. fetus is a cause of spontaneous abortions in cattle and sheep, as well as an opportunistic pathogen in humans.

Campylobacter species contain two flagellin genes in tandem for motility: flaA and flaB. These genes undergo intergenic recombination, further contributing to their virulence. Nonmotile mutants do not colonize.

Methods of Transmission and Treatment

The common routes of transmission are fecal-oral; the bacteria are introducted through ingestion of contaminated food or water and by the eating of raw meat. Infection produces an inflammatory, sometimes bloody diarrhea, periodontitis, or dysentery syndrome, mostly including cramps, fever and pain. The infection is usually self-limiting. In most cases symptomatic treatment by liquid and electrolyte replacement is enough in human infections. The use of antibiotics, on the other hand, is controversial.

Diagnosis

Symptoms typically last for five to seven days. The sites of tissue injury include the jejunum, the ileum, and the colon. Most strains of C. jejuni produce a toxin (cytolethal distending toxin) that hinders the cells from dividing and activating the immune system. This symptom helps the bacteria evade the immune system and survive for a limited time in the cells. A cholera-like enterotoxin was also once thought to be made, but this appears not to be the case. The organism produces diffuse, bloody, edematous, and exudative enteritis. Although rarely has the infection been considered a cause of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, no unequivocal case reports exist. In some cases, a Campylobacter infection can be the underlying cause of Guillain-Barré syndrome. Gastrointestinal perforation is a rare complication of ileal infection.

Diagnosis of the illness is made by testing a specimen of faeces (bowel motion). Standard treatment is now azithromycin and, on occassion, terbinafine. Quinolone antibiotics such as ciprofloxacin or levofloxacin are no longer as effective due to resistance. Dehydrated children may require intravenous (by vein) fluid treatment in a hospital. The illness is contagious, and children must be kept at home until they have been clear of symptoms for at least two days. Good hygiene is important to avoid contracting the illness or spreading it to others.

Peptic Ulcer Disease

A peptic ulcer, also known as peptic ulcer disease, is an erosion in the wall of the stomach, duodenum, or esophagus.

Learning Objectives

List the causes of and treatments for peptic ulcer disease

Key Takeaways

Key Points

  • 70–90% of peptic ulcers are associated with Helicobacter pylori, a spiral-shaped bacterium that lives in the acidic environment of the stomach.
  • Diagnosis is mainly established based on the characteristic symptoms. Stomach pain is usually the first signal of a peptic ulcer.
  • Treatment of H. pylori usually leads to clearing of infection, relief of symptoms, and eventual healing of ulcers.
  • Gas in the peritoneal cavity, shown on an erect chest x-ray or supine lateral abdominal x-ray, is an omen of perforated peptic ulcer disease, which requires emergency surgery.
  • Gastrointestinal bleeding is the most common complication. Sudden large bleeding can be life-threatening. It occurs when the ulcer erodes one of the blood vessels, such as the gastroduodenal artery.
  • Most bleeding ulcers require endoscopy urgently to stop bleeding with cautery, injection, or clipping.
  • During the active phase, the base of the ulcer shows 4 zones: inflammatory exudate, fibrinoid necrosis, granulation tissue and fibrous tissue.
  • A gastric peptic ulcer is a mucosal defect which penetrates the muscularis mucosae and muscularis propria, produced by acid-pepsin aggression.
  • Ulcers are not purely an infectious disease and that psychological factors do play a significant role.
  • Diagnosis is mainly established based on the characteristic symptoms. Stomach pain is usually the first signal of a peptic ulcer.
  • Gastric ulcers are most often localized on the lesser curvature of the stomach.
  • Gas in the peritoneal cavity, shown on an erect chest X-ray or supine lateral abdominal X-ray, is an omen of perforated peptic ulcer disease.
  • Gastrointestinal bleeding is the most common complication. Sudden large bleeding can be life-threatening. It occurs when the ulcer erodes one of the blood vessels, such as the gastroduodenal artery.
  • Burning or gnawing feeling in the stomach area lasting between 30 minutes and 3 hours commonly accompanies ulcers.
  • Typical ulcers tend to heal and recur and as a result the pain may occur for few days and weeks and then wane or disappear.

Key Terms

  • prostaglandin: Any of a group of naturally occurring lipids derived from the C20 acid prostanoic acid; they have a number of physiological functions and may be considered to be hormones.
  • NSAID: Any drug of the non-steroidal anti-inflammatory class used as a pain reliever.
  • gastrin: A hormone that stimulates the production of gastric acid in the stomach.
  • gastritis: Inflammation of the lining of the stomach, characterized by nausea, loss of appetite, and upper abdominal discomfort or pain.

A peptic ulcer, also known as peptic ulcer disease, is an erosion in the wall of the stomach, duodenum, or esophagus. As many as 70–90% of such ulcers are associated with Helicobacter pylori, a spiral-shaped bacterium that lives in the acidic environment of the stomach. Ulcers can also be caused or worsened by drugs such as aspirin, ibuprofen, and other NSAIDs.

image

Deep gastric ulcer: This image, acquired via endoscope, shows a deep gastric ulcer.

Symptoms

Symptoms of a peptic ulcer include abdominal pain, classically near the stomach with severity relating to mealtimes, about three hours after eating a meal; bloating and abdominal fullness; nausea; copious vomiting; loss of appetite and weight loss; vomiting of blood; and melena, which are tarry, foul-smelling feces due to oxidized iron from hemoglobin. Rarely, an ulcer can lead to a gastric or duodenal perforation, which leads to acute peritonitis. This is extremely serious and requires immediate surgery.

Causes

A major causative factor of ulcers is chronic inflammation due to Helicobacter pylori that colonizes the mucosa. The immune system is unable to clear the infection, despite the appearance of antibodies. Thus, the bacterium can cause a chronic active gastritis, resulting in a defect in the regulation of gastrin production by that part of the stomach. Gastrin secretion can either be increased, or as in most cases, decreased, resulting in a too basic or too acidic stomach environment, respectively. A decrease in acid can promote H. pylori growth and an increase in acid can contribute to the erosion of the mucosa and therefore ulcer formation.

Another major cause is the use of NSAIDs. The gastric mucosa protects itself from gastric acid with a layer of mucus, the secretion of which is stimulated by certain prostaglandins. NSAIDs block the function of cyclooxygenase 1 (cox-1), which is essential for the production of these prostaglandins.

Researchers also continue to look at stress as a possible cause, or at least complication, in the development of ulcers. There is debate as to whether psychological stress can influence the development of peptic ulcers. Burns and head trauma, however, can lead to physiologic stress ulcers, which are reported in many patients who are on mechanical ventilation.

Diagnosis

The diagnosis is mainly established based on the characteristic symptoms. Stomach pain is usually the first signal of a peptic ulcer. In some cases, doctors may treat ulcers without diagnosing them with specific tests and observe whether the symptoms resolve, this indicating that their primary diagnosis was accurate.

image

Gastric ulcer: This endoscopic image shows a gastric ulcer, which upon biopsy was shown to be gastric cancer.

Confirmation of the diagnosis is made with the help of tests such as endoscopies or barium contrast x-rays. The tests are typically ordered if the symptoms do not resolve after a few weeks of treatment. Tests are also given when first appear in a person who is over age 45 or who has other symptoms such as weight loss, because stomach cancer can cause similar symptoms. Also, when severe ulcers resist treatment, particularly if a person has several ulcers or the ulcers are in unusual places, a doctor may suspect an underlying condition that causes the stomach to overproduce acid.

An esophagogastroduodenoscopy (EGD), a form of endoscopy, also known as a gastroscopy, is carried out on patients in whom a peptic ulcer is suspected. By direct visual identification, the location and severity of an ulcer can be described. Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis.

If a peptic ulcer perforates, air will leak from the inside of the gastrointestinal tract (which always contains some air) to the peritoneal cavity (which normally never contains air). This leads to “free gas” within the peritoneal cavity. If the patient stands erect, as when having a chest x-ray, the gas will float to a position underneath the diaphragm. Therefore, gas in the peritoneal cavity, shown on an erect chest x-ray or supine lateral abdominal x-ray, is an omen of perforated peptic ulcer disease.

Treatment

image

Benign gastric ulcer: This gastric ulcer was found in tissue removed during a gastrectomy.

Younger patients with ulcer-like symptoms are often treated with antacids. The ability of antacids to neutralize acidity by increasing the pH or blocking the secretion of acid by gastric cells is critical in reducing acidity in the stomach. Patients who are taking NSAIDs may also be prescribed a prostaglandin analogue in order to help prevent peptic ulcers by replacing the prostaglandins whose formation is blocked by NSAID use.

When H. pylori infection is present, the most effective treatments are combinations of two antibiotics, such as Clarithromycin, Amoxicillin, Tetracycline, and Metronidazole; and one proton pump inhibitor, sometimes in combination with antacids. In complicated, treatment-resistant cases, three antibiotics may be used together with a proton pump inhibitor. Treatment of H. pylori usually leads to clearing of infection, relief of symptoms and eventual healing of ulcers. Recurrence of infection can occur and retreatment may be required, if necessary with other antibiotics.

Perforated peptic ulcer is a surgical emergency and requires surgical repair of the perforation. Most bleeding ulcers require endoscopy urgently to stop bleeding with cautery, injection, or clipping.

Listeriosis

Listeriosis is a bacterial infection caused by a Gram-positive, motile bacterium called Listeria monocytogenes.

Learning Objectives

Discuss the mechanism of action for listeriosis

Key Takeaways

Key Points

  • Listeriosis has a low incidence in humans and occurs in pregnant women, newborn infants, elderly patients, and patients who are immunocompromised.
  • Listeria can invade through unusually tough barriers in humans: the blood-brain barrier and the feto-placental barrier, which contain high levels of cadherin protein on their membrane.
  • The main route of acquisition of Listeria is through the ingestion of contaminated food products.

Key Terms

  • incidence: a measure of the risk that a person develops a new condition within a specified period of time, usually a year
  • listeriosis: An infectious disease of humans and animals caused by the bacteria Listeria monocytogenes and Listeria ivanovii, often through contaminated food.
  • meningitis: Inflammation of the meninges, characterized by headache, neck stiffness and photophobia and also fever, chills, vomiting, and myalgia.
  • cadherin: Any of a class of transmembrane proteins important in maintaining tissue structure.
  • blood-brain barrier: a structure in the central nervous system (CNS) that keeps various substances found in the bloodstream out of the brain while allowing in the substances essential to metabolic function

Listeriosis is a bacterial infection caused by a Gram-positive, motile bacterium, Listeria monocytogenes. Listeriosis has a low incidence in humans and occurs in pregnant women, newborn infants, elderly patients, and patients who are immunocompromised. Pregnant women are the most susceptible and infection can lead to early delivery, infection of the newborn, and death of the baby.

image

Listeria monocytogenes: A bacterial infection caused by a Gram-positive, motile bacterium, Listeria monocytogenes which is shown here on a blood agar plate.

The symptoms of listeriosis usually last 7–10 days, with the most common symptoms being fever, muscle aches, and vomiting. Diarrhea is another symptom, but less common. If the infection spreads to the nervous system it can cause meningitis, an infection of the covering of the brain and spinal cord.

Listeria originally evolved to invade membranes of the intestines, as an intracellular infection, and developed a chemical mechanism to do so. This involves a bacterial protein “internalin” which attaches to a protein on the intestinal cell membrane “cadherin. ” These adhesion molecules are also to be found in two other unusually tough barriers in humans – the blood-brain barrier and the feto-placental barrier, and this may explain the apparent affinity that Listeria has for causing meningitis and affecting babies in-utero. Particular strains of a food-borne bacteria are able to invade the heart, leading to serious and difficult-to-treat heart infections.

Listeria monocytogenes is ubiquitous in the environment. The main route of acquisition is by the ingestion of contaminated food products. Listeria has been isolated from raw meat, dairy products, vegetables, fruit and seafood. Soft cheeses, unpasteurized milk and unpasteurised pâté are potential dangers too. The main prevention is through the promotion of safe handling, cooking and consumption of food. This includes washing raw vegetables and cooking raw food thoroughly, as well as reheating leftover or ready-to-eat foods, like hot dogs, until steaming hot. Another preventative measure is to advise high-risk groups such as pregnant women and immunocompromised patients to avoid unpasteurized pâtés and foods such as soft cheeses.

In the advent of listeriosis, bacteremia should be treated for two weeks, meningitis for three weeks, and brain abscess for at least six weeks. Ampicillin generally is considered the antibiotic of choice and gentamicin is added frequently for its synergistic effects. About 10 percent of serious listeria infections involve cardiac infections that are difficult to treat, with more than one-third proving fatal.