All about salmonella bacteria

Key facts

• Salmonella is 1 of 4 key global causes of diarrhoeal diseases.
• Most cases of salmonellosis are mild; however, sometimes it can be life-threatening. The severity of the disease depends on host factors and the serotype of Salmonella.
• Antimicrobial resistance is a global public health concern and Salmonella is one of the microorganisms in which some resistant serotypes have emerged, affecting the food chain.
• Basic food hygiene practices, such as "cook thoroughly", are recommended as a preventive measure against salmonellosis.

Salmonella is a gram negative rods genus belonging to the Enterobacteriaceae family. Within 2 species, Salmonella bongori and Samonella enterica, over 2500 different serotypes or serovars have been identified to date. Salmonella is a ubiquitous and hardy bacteria that can survive several weeks in a dry environment and several months in water.

While all serotypes can cause disease in humans, a few are host-specific and can reside in only one or a few animal species: for example, Salmonella enterica serotype Dublin in cattle and Salmonella enterica serotype Choleraesuis in pigs. When these particular serotypes cause disease in humans, it is often invasive and can be life-threatening. Most serotypes, however, are present in a wide range of hosts. Typically, such serotypes cause gastroenteritis, which is often uncomplicated and does not need treatment, but disease can be severe in the young, the elderly, and patients with weakened immunity. This group features Salmonella enterica serotype Enteritidis and Salmonella enterica serotype Typhimurium, the two most important serotypes of Salmonella transmitted from animals to humans in most parts of the world.

The disease

Salmonellosis is a disease caused by the bacteria Salmonella. It is usually characterized by acute onset of fever, abdominal pain, diarrhoea, nausea and sometimes vomiting.

The onset of disease symptoms occurs 6–72 hours (usually 12–36 hours) after ingestion of Salmonella, and illness lasts 2–7 days.

Symptoms of salmonellosis are relatively mild and patients will make a recovery without specific treatment in most cases. However, in some cases, particularly in children and elderly patients, the associated dehydration can become severe and life-threatening.

Although large Salmonella outbreaks usually attract media attention, 60–80% of all salmonellosis cases are not recognized as part of a known outbreak and are classified as sporadic cases, or are not diagnosed as such at all.

Sources and transmission

• Salmonella bacteria are widely distributed in domestic and wild animals. They are prevalent in food animals such as poultry, pigs, and cattle; and in pets, including cats, dogs, birds, and reptiles such as turtles.
• Salmonella can pass through the entire food chain from animal feed, primary production, and all the way to households or food-service establishments and institutions.
• Salmonellosis in humans is generally contracted through the consumption of contaminated food of animal origin (mainly eggs, meat, poultry, and milk), although other foods, including green vegetables contaminated by manure, have been implicated in its transmission.
• Person-to-person transmission can also occur through the faecal-oral route.
• Human cases also occur where individuals have contact with infected animals, including pets. These infected animals often do not show signs of disease.

Treatment

Treatment in severe cases is electrolyte replacement (to provide electrolytes, such as sodium, potassium and chloride ions, lost through vomiting and diarrhoea) and rehydration.

Routine antimicrobial therapy is not recommended for mild or moderate cases in healthy individuals. This is because antimicrobials may not completely eliminate the bacteria and may select for resistant strains, which subsequently can lead to the drug becoming ineffective. However, health risk groups such as infants, the elderly, and immunocompromised patients may need to receive antimicrobial therapy. Antimicrobials are also administered if the infection spreads from the intestine to other body parts. Because of the global increase of antimicrobial resistance, treatment guidelines should be reviewed on a regular basis taking into account the resistance pattern of the bacteria based on the local surveillance system.

Prevention methods

Prevention requires control measures at all stages of the food chain, from agricultural production, to processing, manufacturing and preparation of foods in both commercial establishments and at home.

Preventive measures for Salmonella in the home are similar to those used against other foodborne bacterial diseases (see recommendations for food handlers below).

The contact between infants/young children and pet animals that may be carrying Salmonella (such as cats, dogs, and turtles) needs careful supervision.

National and regional surveillance systems on foodborne diseases are important means to know and follow the situation of these diseases and also to detect and respond to salmonellosis and other enteric infections in early stages, and thus to prevent them from further spreading.

Recommendations for the public and travellers

The following recommendations will help ensure safety while travelling:

• Ensure food is properly cooked and still hot when served.
• Avoid raw milk and products made from raw milk. Drink only pasteurized or boiled milk.
• Avoid ice unless it is made from safe water.
• When the safety of drinking water is questionable, boil it or if this is not possible, disinfect it with a reliable, slow-release disinfectant agent (usually available at pharmacies).
• Wash hands thoroughly and frequently using soap, in particular after contact with pets or farm animals, or after having been to the toilet.
• Wash fruits and vegetables carefully, particularly if they are eaten raw. If possible, vegetables and fruits should be peeled.

• A guide on safe food for travellers

Recommendations for food handlers

WHO provides the following guidance for people handling food:

• Both professional and domestic food handlers should be vigilant while preparing food and should observe hygienic rules of food preparation.
• Professional food handlers who suffer from fever, diarrhoea, vomiting or visible infected skin lesions should report to their employer immediately.
• The WHO Five keys to safer food serve as the basis for educational programmes to train food handlers and educate consumers. They are especially important in preventing food poisoning. The five keys to Safer Food are:
  • keep clean
  • separate raw and cooked
  • cook thoroughly
  • keep food at safe temperatures
  • use safe water and raw materials.

• Five keys to safer food

Recommendations for producers of fruits, vegetables and fish

The WHO Five keys to growing safer fruits and vegetables: promoting health by decreasing microbial contamination and the Five keys to safer aquaculture products to protect public health provide rural workers, including small farmers who grow fresh fruits and vegetables and fish for themselves, their families and for sale in local market with key practices to prevent microbial contamination.

The Five keys to growing safer fruits and vegetables are:

• Practice good personal hygiene.
• Protect fields from animal faecal contamination.
• Use treated faecal waste.
• Evaluate and manage risks from irrigation water.
• Keep harvest and storage equipment clean and dry.

• Five keys to growing safer fruits and vegetables

The Five keys to safer aquaculture products to protect public health are:

• Practice good personal hygiene.
• Clean the pond site.
• Manage water quality.
• Keep fish healthy.
• Use clean harvest equipment and containers.

• Five keys to safer aquaculture products to protect public health

WHO response

In partnership with other stakeholders, WHO is strongly advocating the importance of food safety as an essential element in ensuring access to safe and nutritious diets. WHO is providing policies and recommendations that cover the entire food chain from production to consumption, making use of different types of expertise across different sectors.

WHO is working towards the strengthening of food safety systems in an increasingly globalized world. Setting international food safety standards, enhancing disease surveillance, educating consumers and training food handlers in safe food handling are amongst the most critical interventions in the prevention of foodborne illnesses.

WHO is strengthening the capacities of national and regional laboratories in the surveillance of foodborne pathogens, such as Campylobacter and Salmonella.

WHO is also promoting the integrated surveillance of antimicrobial resistance of pathogens in the food chain, collecting samples from humans, food and animals and analysing data across the sectors.

WHO, jointly with FAO, is assisting Member States by coordinating international efforts for early detection and response to foodborne disease outbreaks through the network of national authorities in Member States.

WHO also provides scientific assessments as basis for international food standards, guidelines and recommendations developed by the FAO/WHO Codex Alimentarius Commission to prevent foodborne diseases.

• Salmonella bacteria live in the intestinal tract of humans and animals and are excreted in feces. Poultry, beef, milk, and eggs all can contain Salmonella bacteria.
• Salmonella infection is a foodborne illness that occurs from consumption of raw meats and eggs, contaminated dairy foods such as unpasteurized (raw) milk, or fruits and vegetables contaminated by food handlers.
• A Salmonella bacterial infection causes gastrointestinal symptoms, including
  • diarrhea,
  • abdominal pain,
  • nausea, and
  • vomiting.
• Symptoms develop within 12-72 hours and typically last four to seven days.
• The two most common types in the U.S. are S. typhimurium and S. enteritidis. Some types of Salmonella bacteria cause the illness known as typhoid fever.
• In most cases, no specific treatment is needed other than adequate hydration.
• Most cases of salmonellosis are not life-threatening and resolve on their own without complications.
• People at risk for complications or those with particularly severe illness or a weakened immune system may need antibiotic therapy.
• There is no vaccine to prevent Salmonella infection.
• Salmonella may infect reptiles, rodents, and birds. Contact with these animals increases the likelihood of getting the infection.
• People may prevent infection by following established food safety practices, including attention to hygiene during food preparation and handling of animals.

Many of the members of the bacterial genus Salmonella are contagious. The organisms can be transferred from person to person, by both direct (via saliva, fecal/oral spread, kissing) and indirect contact (for example, using contaminated eating utensils). In addition, a number of Salmonella species can be transmitted from animals (snakes, turtles, chickens, hamsters, cats, and dogs) to humans, usually by direct contact.

Salmonella infection, or salmonellosis, is another name for Salmonella food poisoning. Salmonella are a type of bacteria known to cause food-borne illness for over 125 years. The organism is named for a scientist named Daniel Elmer Salmon, who discovered the bacteria. Salmonellosis is a food-borne infection typically caused by consumption of contaminated foods. Salmonella causes an estimated 1 million food-borne illnesses every year in the U.S. and about 19,000 hospitalizations.

Different types (called serotypes or serovars) of the Salmonella bacteria can cause the illness. The two most common serotypes in the U.S. are S. typhimurium and S. enteritidis. Specific strains of the bacteria can be responsible for outbreaks of the disease. For example, an outbreak in 2013-2014 was linked to multidrug-resistant serotype Salmonella Heidelberg. This strain and some other strains have become resistant to many drugs traditionally used to treat the infection, posing a risk to public health.

Some types of Salmonella bacteria (S. typhi) cause typhoid fever, a serious illness that occurs most often in nonindustrialized areas of the world.

Salmonella illness causes an inflammation of the gastrointestinal tract; this is known as gastroenteritis.

• Symptoms of Salmonella poisoning usually begin 12-72 hours after infection.
• Diarrhea, abdominal cramping, and fever are common symptoms.
• The diarrhea is typically loose and not bloody.
• Nausea
• Vomiting
• Headache
• Muscle aches

The symptoms usually go away on their own after four to seven days.

Poultry, beef, milk, and eggs may contain Salmonella bacteria, since the bacteria live in the intestines of humans and animals. Thorough cooking of these foods destroys the bacteria.

Foods, including vegetables and fruits, may also be contaminated during handling or processing of the food, and this is another common source of outbreaks. For example, food may be contaminated by the feces of infected people or animals or from the unwashed hands of a person handling or preparing the food.

Small rodents such as hamsters, as well as baby chicks and ducklings, may also carry the bacteria, and contamination of food after handling these animals may also result in salmonellosis. Reptiles may also harbor Salmonella bacteria. In the 1970s, outbreaks were associated with baby turtles kept as pets. Further, the infection may be spread by contaminated surfaces (such as cutting boards) that have had contact with contaminated foods.

Contaminated foods usually look and smell normal. Over the past years, outbreaks of salmonellosis have been associated with a number of different foods, including chicken, cucumbers, alfalfa sprouts, bean sprouts, ground beef, mangoes, peanut butter, and cantaloupe. These are just a few examples. An outbreak in February 2016 caused by the strain Salmonella muenchen was linked to contaminated alfalfa sprouts. In 2017, an outbreak was linked to papayas from Mexico. A breakfast cereal known as Honey Smacks caused an outbreak in 2018.

Since foods contaminated with Salmonella are not obvious, anyone may consume contaminated foods. Owning pets such as small rodents, chicks, ducklings, small turtles and some other reptiles, and some birds may increase the risk of coming in contact with Salmonella bacteria. People who are exposed to many people, such as those living in group housing, may have an increased risk. Young children (under 5 years of age) have the highest reported incidence of infection.

People with medical conditions that lead to immune suppression are at risk for a more severe illness when they do become infected.

By Rachel Ross 07 November 2018

Salmonella is a group of bacteria that commonly cause a foodborne illness called salmonellosis. Every year, about 1.2 million people are infected with Salmonella, with 23,000 individuals hospitalized due to the infection and 450 dying from it, according to the U.S. Centers for Disease Control and Prevention (CDC). Most people who get infected with Salmonella get the bacteria from contaminated food or water.

There are more than 2,300 types of bacteria in the Salmonella genus, according to the U.S. Department of Agriculture (USDA). Salmonella Enteritidis and Salmonella Typhimurium are the most common strains of Salmonella in the U.S. and are responsible for at least half of all infections.

Contamination typically happens after infected feces comes into contact with animals, crops or water and people then consume or touch those items and don't wash their hands.

Humans and animals typically have some Salmonella bacteria in their stomach and intestines, but stomach acid and intestinal bacteria generally kill the Salmonella before it has the opportunity to invade cells and replicate. Or, the Salmonella simply exit the digestive tract before it causes problems, according to Medical Microbiology (4th Ed., University of Texas Medical Branch at Galveston, 1996).

Causes

Salmonella can be found in many food sources, including raw meat, undercooked or improperly stored poultry and seafood, raw eggs, fresh produce, and even spices, nuts and supplements, according to the Mayo Clinic.

"We should thoroughly wash fruits and vegetables to remove any contaminating microorganisms," said Sarah Fankhauser, an assistant professor of biology at Oxford College of Emory University in Georgia. "However, washing will never get rid of 100 percent of bacteria on a fruit or vegetable, and this is problematic if the fruit/vegetable has been contaminated by particularly dangerous bacteria, such as Salmonella."

A cantaloupe, for example, has a rough and porous surface, which can make it difficult to wash all the bacteria away, Fankhauser told Live Science.

Contaminated ingredients can also find their way into baked goods, such as cereals and crackers.

Food can also become contaminated when people improperly handle it, by failing to thoroughly wash their hands after using the toilet, changing a diaper or touching a contaminated surface. Contamination can also happen if you prep produce on a surface where there was raw meat.

The temperature of the water you use when washing your hands can also make a difference. "Our bodies are 98 degrees F (37 degrees C), which is an optimal temperature for Salmonella, so 'warm' water will not kill Salmonella," Fankhauser said. For that reason, it's best to wash your hands with soap and the hottest water you can handle.

People at an increased risk of developing a Salmonella infection include young children, older adults, pregnant women, and people who have compromised immune systems or diseases of the intestinal tract, such as inflammatory bowel disease, according to the Mayo Clinic.

Healthy adults can also become more susceptible to a Salmonella infection by taking antacids, which lower the stomach's acidity, or antibiotics, which reduce the number of Salmonella-killing bacteria in the intestines.

Cases of Salmonella peak in mid-September, Fankhauser said, because warmer summer temperatures create ideal conditions for Salmonella, as well as many other bacteria.

Symptoms

Some people with a Salmonella infection have no symptoms, according to the Mayo Clinic. Others experience symptoms beginning within 8 to 72 hours after eating something that was contaminated.

Symptoms include diarrhea, nausea, vomiting, abdominal cramps, fever, chills, headache and blood in the stool. Some strains of Salmonella may result in typhoid fever, which is rare in the U.S. and primarily occurs in developing countries.

Most healthy people recover from their symptoms within two to seven days without receiving any specific treatment.

Diagnosis and treatment

Salmonellosis can be diagnosed via a stool sample; however, for many people, the symptoms dissipate by the time the test results return from the lab. A blood sample may be taken to determine if the Salmonella infected the bloodstream, according to the Mayo Clinic.

The primary treatments for a salmonella infection include keeping hydrated, getting rest and replacing electrolytes (by drinking things like Gatorade or other sports drinks, Pedialyte or other electrolyte solution, or even coconut water). If diarrhea or vomiting make it difficult to stay hydrated, a hospital stay may be needed so that fluids can be administered intravenously.

If someone does come down with a Salmonella infection, it's important that all of the person's dirty clothes, bedding and towels get washed in a washing machine using the hottest water setting, Medical News Today reported. In addition, all surfaces that the infected person may have touched should be thoroughly disinfected; that includes handles on cabinets and doors.

Antibiotics aren't typically used to treat Salmonella, unless the infection may have spread to the bloodstream. But there is also evidence that taking antibiotics to treat Salmonella may prolong the infection.

"Salmonella is an intracellular bacterial pathogen, meaning these bacteria enter and survive inside our cells," Fankhauser said. "Many antibiotics work on extracellular bacteria and cannot get into our cells to kill the Salmonella."

If Salmonella gets into the bloodstream (typically through the immune cells that line the intestinal system, according to Fankhauser), additional complications can occur in tissue in and around the brain, spinal cord, heart and blood vessels. The bacteria can even work their way into bones and bone marrow. Reactive arthritis, another complication that can result from Salmonella entering the bloodstream, causes joint pain, eye irritation and painful urination.

Prevention

Many precautions can help prevent salmonellosis, according to the U.S. government's Food Safety site:

• Avoid eating raw or undercooked poultry, eggs or meat.
• Avoid consuming unpasteurized milk, dairy products or juice.
• Keep food refrigerated below 40 degrees Fahrenheit (4 degrees Celsius) before and after cooking.
• Defrost food in the refrigerator or microwave.
• Cook meats and eggs to a safe internal temperature and check with a food thermometer.
• Thoroughly wash hands with soap and hot water before handling food and after having contact with animals (especially reptiles) and their food or living environments.
• Clean all surfaces thoroughly before and after preparing food on them.
• Separate cooked and raw food, including using separate utensils, dishes and surfaces for prepping cooked and raw food.

It is also important to use proper cleaning materials when cleaning surfaces.

"A warm, soapy sponge could just spread the Salmonella and not kill it," Fankhauser pointed out. "I personally use a disinfectant on my counters after handling raw meat."

Be sure to use hot and soapy water — or, ideally, a dishwasher — for washing potentially contaminated dishes.

Around the world, Salmonella is one of the main causes of diarrhea. Other common symptoms of a Salmonella infection include abdominal cramps and vomiting.

There are many types of Salmonella bacteria, and they can cause a range of illnesses, including typhoid fever and gastroenteritis.

Most people with Salmonella infections have mild symptoms and recover without treatment. However, some require care in a hospital setting.

People often develop this type of infection after coming into contact with contaminated food or water.

In 2019, 13 people from eight states became sick after eating ground beef that contained a strain of Salmonella. The Centers for Disease Control and Prevention (CDC) issued a safety alert but declared the outbreak over by the end of the year.

Pet reptiles and amphibians can also transmit Salmonella. In 2017, an outbreak linked to pet turtles affected at least 76 people in 19 states, according to the CDC.

Share on Pinterest Washing raw fruits and vegetables before eating them may help prevent a Salmonella infection.

Salmonella is a type of bacteria that can cause diarrheal illness in humans.

There are over 2,500 subtypes, including animal and human strains. Some are present in animals but can also affect humans. Fewer than 100 strains of Salmonella bacteria are likely to infect people.

In the United States, Salmonella is a major cause of bacterial infection. According to the CDC, it causes around 1.35 million infections, leading to 26,500 hospitalizations and 420 deaths, every year.

Symptoms usually appear between 6 hours and 6 days after the initial infection and last 4–7 days, according to the CDC.

• diarrhea
• stomach cramps and abdominal pain
• a sudden fever
• nausea
• vomiting, in some cases

Some strains of Salmonella can infect the urine, blood, bones, joints, and the nervous system, including the spinal fluid and brain. Severe complications can result.

Some people with Salmonella infections experience joint pain, known as reactive arthritis. It can last for months or years, and it can become chronic arthritis.

Salmonella bacteria live in the intestines of birds, animals, and humans. Most infections in humans develop after eating food or drinking water that has been contaminated by feces.

Uncooked meat, seafood, and poultry

Contamination can occur during processing. For example, harvesting seafood in contaminated waters is a common cause of Salmonella infection.

Also, the infection can spread if a person handles contaminated raw meat, then touches other food without washing their hands.

Uncooked eggs

Eggs from a bird with a Salmonella infection can contain the bacteria.

The Food and Drug Administration (FDA) estimate that every year, 79,000 cases of foodborne illness occur in the U.S. due to eggs containing Salmonella.

Cooking the eggs can reduce the risk. However, some popular sauces, such as mayonnaise, can contain raw eggs.

Fruits and vegetables

Watering fruit or vegetable plants with contaminated water, or washing the produce in this water, can lead to Salmonella infection.

Lack of hygiene

Contamination and infection can occur if people do not keep kitchen surfaces clean and do not wash their hands during food preparation, after using the bathroom, and after changing a baby’s diapers.

When a person has the bacteria on their hands, they can spread it by touching other people or by touching frequently used objects and surfaces.

Pet reptiles or amphibians

Most reptiles and amphibians carry Salmonella in their guts without becoming ill. They shed the bacteria in their droppings.

The bacteria can then quickly spread to their skin and anything that they come into contact with, including cages, toys, clothes, furniture, and household surfaces.

People should not keep pet reptiles indoors if there are children under 5 years of age, pregnant women, older people, or people with weakened immune systems in the household.

Since 1975, the FDA have banned the sale and distribution of small turtles because of the risk of Salmonella infection.

Salmonella infections are more common in summer than in winter.

Overall, people with the highest risks of infection are:

• children
• older people
• people with weakened immune systems
• pregnant women

Because of the risk of infection, caregivers should not allow young children to handle reptiles or chicks and young birds.

If a woman develops a Salmonella infection during pregnancy, there can be additional risks. Dehydration and a lack of nutrients that result from the infection can harm the mother and baby.

In around 4% of Salmonella infections during pregnancy, the bacteria spread to the blood. This can lead to intrauterine sepsis, a potentially life threatening condition.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996.

Medical Microbiology. 4th edition.

Ralph A. Giannella .

General Concepts

Salmonellosis ranges clinically from the common Salmonella gastroenteritis (diarrhea, abdominal cramps, and fever) to enteric fevers (including typhoid fever) which are life-threatening febrile systemic illness requiring prompt antibiotic therapy. Focal infections and an asymptomatic carrier state occur. The most common form of salmonellosis is a self-limited, uncomplicated gastroenteritis.

Salmonella species are Gram-negative, flagellated facultatively anaerobic bacilli characterized by O, H, and Vi antigens. There are over 1800 known serovars which current classification considers to be separate species.

Pathogenic salmonellae ingested in food survive passage through the gastric acid barrier and invade the mucosa of the small and large intestine and produce toxins. Invasion of epithelial cells stimulates the release of proinflammatory cytokines which induce an inflammatory reaction. The acute inflammatory response causes diarrhea and may lead to ulceration and destruction of the mucosa. The bacteria can disseminate from the intestines to cause systemic disease.

Both nonspecific and specific host defenses are active. Non-specific defenses consist of gastric acidity, intestinal mucus, intestinal motility (peristalsis), lactoferrin, and lysozyme. Specific defenses consist of mucosal and systemic antibodies and genetic resistance to invasion. Various factors affect susceptibility.

Non-typhoidal salmonellosis is a worldwide disease of humans and animals. Animals are the main reservoir, and the disease is usually food borne, although it can be spread from person to person. The salmonellae that cause Typhoid fever and other enteric fevers spread mainly from person-to-person via the fecal-oral route and have no significant animal reservoirs. Asymptomatic human carriers (“typhoid Marys”) may spread the disease.

Salmonellosis should be considered in any acute diarrheal or febrile illness without obvious cause. The diagnosis is confirmed by isolating the organisms from clinical specimens (stool or blood).

Effective vaccines exist for typhoid fever but not for non-typhoidal salmonellosis. Those diseases are controlled by hygienic slaughtering practices and thorough cooking and refrigeration of food.

Introduction

Salmonellae are ubiquitous human and animal pathogens, and salmonellosis, a disease that affects an estimated 2 million Americans each year, is common throughout the world. Salmonellosis in humans usually takes the form of a self-limiting food poisoning (gastroenteritis), but occasionally manifests as a serious systemic infection (enteric fever) which requires prompt antibiotic treatment. In addition, salmonellosis causes substantial losses of livestock.

Clinical Manifestations

Some infectious disease texts recognize three clinical forms of salmonellosis: (1) gastroenteritis, (2) septicemia, and (3) enteric fevers. This chapter focuses on the two extremes of the clinical spectrum—gastroenteritis and enteric fever. The septicemic form of salmonella infection can be an intermediate stage of infection in which the patient is not experiencing intestinal symptoms and the bacteria cannot be isolated from fecal specimens. The severity of the infection and whether it remains localized in the intestine or disseminates to the bloodstream may depend on the resistance of the patient and the virulence of the Salmonella isolate.

The incubation period for Salmonella gastroenteritis (food poisoning) depends on the dose of bacteria. Symptoms usually begin 6 to 48 hours after ingestion of contaminated food or water and usually take the form of nausea, vomiting, diarrhea, and abdominal pain. Myalgia and headache are common; however, the cardinal manifestation is diarrhea. Fever (38°C to 39°C) and chills are also common. At least two-thirds of patients complain of abdominal cramps. The duration of fever and diarrhea varies, but is usually 2 to 7 days.

Enteric fevers are severe systemic forms of salmonellosis. The best studied enteric fever is typhoid fever, the form caused by S typhi, but any species of Salmonella may cause this type of disease. The symptoms begin after an incubation period of 10 to 14 days. Enteric fevers may be preceded by gastroenteritis, which usually resolves before the onset of systemic disease. The symptoms of enteric fevers are nonspecific and include fever, anorexia, headache, myalgias, and constipation. Enteric fevers are severe infections and may be fatal if antibiotics are not promptly administered.

Structure, Classification, and Antigenic Types

Salmonellae are Gram-negative, flagellated, facultatively anaerobic bacilli possessing three major antigens: H or flagellar antigen; O or somatic antigen; and Vi antigen (possessed by only a few serovars). H antigen may occur in either or both of two forms, called phase 1 and phase 2. The organisms tend to change from one phase to the other. O antigens occur on the surface of the outer membrane and are determined by specific sugar sequences on the cell surface. Vi antigen is a superficial antigen overlying the O antigen; it is present in a few serovars, the most important being S typhi.

Antigenic analysis of salmonellae by using specific antisera offers clinical and epidemiological advantages. Determination of antigenic structure permits one to identify the organisms clinically and assign them to one of nine serogroups (A-I), each containing many serovars (Table 1). H antigen also provides a useful epidemiologic tool with which to determine the source of infection and its mode of spread.

Ecologic Classification of Salmonellae.

As with other Gram-negative bacilli, the cell envelope of salmonellae contains a complex lipopolysaccharide (LPS) structure that is liberated on lysis of the cell and, to some extent, during culture. The lipopolysaccharide moiety may function as an endotoxin, and may be important in determining virulence of the organisms. This macromolecular endotoxin complex consists of three components, an outer O-polysaccharide coat, a middle portion (the R core), and an inner lipid A coat. Lipopolysaccharide structure is important for several reasons. First, the nature of the repeating sugar units in the outer O-polysaccharide chains is responsible for O antigen specificity; it may also help determine the virulence of the organism. Salmonellae lacking the complete sequence of O-sugar repeat units are called rough because of the rough appearance of the colonies; they are usually avirulent or less virulent than the smooth strains which possess a full complement of O-sugar repeat units. Second, antibodies directed against the R core (common enterobacterial antigen) may protect against infection by a wide variety of Gram-negative bacteria sharing a common core structure or may moderate their lethal effects. Third, the endotoxin component of the cell wall may play an important role in the pathogenesis of many clinical manifestations of Gram-negative infections. Endotoxins evoke fever, activate the serum complement, kinin, and clotting systems, depress myocardial function, and alter lymphocyte function. Circulating endotoxin may be responsible in part for many of the manifestations of septic shock that can occur in systemic infections.

Pathogenesis

Salmonellosis includes several syndromes (gastroenteritis, enteric fevers, septicemia, focal infections, and an asymptomatic carrier state) (Fig. 1). Particular serovars show a strong propensity to produce a particular syndrome (S typhi, S paratyphi-A, and S schottmuelleri produce enteric fever; S choleraesuis produces septicemia or focal infections; S typhimurium and S enteritidis produce gastroenteritis); however, on occasion, any serotype can produce any of the syndromes. In general, more serious infections occur in infants, in adults over the age of 50, and in subjects with debilitating illnesses.

Pathogenesis of salmonellosis.

Most non-typhoidal salmonellae enter the body when contaminated food is ingested (Fig. 2). Person-to-person spread of salmonellae also occurs. To be fully pathogenic, salmonellae must possess a variety of attributes called virulence factors. These include (1) the ability to invade cells, (2) a complete lipopolysaccharide coat, (3) the ability to replicate intracellularly, and (4) possibly the elaboration of toxin(s). After ingestion, the organisms colonize the ileum and colon, invade the intestinal epithelium, and proliferate within the epithelium and lymphoid follicles. The mechanism by which salmonellae invade the epithelium is partially understood and involves an initial binding to specific receptors on the epithelial cell surface followed by invasion. Invasion occurs by the organism inducing the enterocyte membrane to undergo “ruffling” and thereby to stimulate pinocytosis of the organisms (Fig. 3). Invasion is dependent on rearrangement of the cell cytoskeleton and probably involves increases in cellular inositol phosphate and calcium. Attachment and invasion are under distinct genetic control and involve multiple genes in both chromosomes and plasmids.

Scheme of the Pathogenesis of Salmonella enterocolitis and diarrhea.

Invasion of intestinal mucosa by Salmonella.

After invading the epithelium, the organisms multiply intracellularly and then spread to mesenteric lymph nodes and throughout the body via the systemic circulation; they are taken up by the reticuloendothelial cells. The reticuloendothelial system confines and controls spread of the organism. However, depending on the serotype and the effectiveness of the host defenses against that serotype, some organisms may infect the liver, spleen, gallbladder, bones, meninges, and other organs (Fig. 1). Fortunately, most serovars are killed promptly in extraintestinal sites, and the most common human Salmonella infection, gastroenteritis, remains confined to the intestine.

After invading the intestine, most salmonellae induce an acute inflammatory response, which can cause ulceration. They may elaborate cytotoxins that inhibit protein synthesis. Whether these cytotoxins contribute to the inflammatory response or to ulceration is not known. However, invasion of the mucosa causes the epithelial cells to synthesize and release various proinflammatory cytokines, including: IL-1, IL-6, IL-8, TNF-2, IFN-U, MCP-1, and GM-CSF. These evoke an acute inflammatory response and may also be responsible for damage to the intestine. Because of the intestinal inflammatory reaction, symptoms of inflammation such as fever, chills, abdominal pain, leukocytosis, and diarrhea are common. The stools may contain polymorphonuclear leukocytes, blood, and mucus.

Much is now known about the mechanisms of Salmonella gastroenteritis and diarrhea. Figures 2 and 3 summarize the pathogenesis of Salmonella enterocolitis and diarrhea. Only strains that penetrate the intestinal mucosa are associated with the appearance of an acute inflammatory reaction and diarrhea (Fig. 4); the diarrhea is due to secretion of fluid and electrolytes by the small and large intestines. The mechanisms of secretion are unclear, but the secretion is not merely a manifestation of tissue destruction and ulceration. Salmonella penetrate the intestinal epithelial cells but, unlike Shigella and invasive E. coli, do not escape the phagosome. Thus, the extent of intercellular spread and ulceration of the epithelium is minimal. Salmonella escape from the basal side of epithelial cells into the lamina propria. Systemic spread of the organisms can occur, giving rise to enteric fever. Invasion of the intestinal mucosa is followed by activation of mucosal adenylate cyclase; the resultant increase in cyclic AMP induces secretion. The mechanism by which adenylate cyclase is stimulated is not understood; it may involve local production of prostaglandins or other components of the inflammatory reaction. In addition, Salmonella strains elaborate one or more enterotoxin-like substances which may stimulate intestinal secretion. However, the precise role of these toxins in the pathogenesis of Salmonella enterocolitis and diarrhea has not been established.

Electron photomicrograph demonstrating invasion of guinea pig ileal epithelial cells by Salmonella typhimurium. Arrows point to invading Salmonella organisms. (Courtesy Akio Takeuchi, Walter Reed Army Institute of Research, Washington, D.C.).

Host Defenses

Various host defenses are important in resisting intestinal colonization and invasion by Salmonella (Table 2). Normal gastric acidity (pH N Engl J Med. 1960; 262 :811, 864, 921. [PubMed : 13801166 ]