Pathogenic strains of salmonella

Medical illustration of non-typhoidal Salmonella

Serotypes are groups within a single species of microorganisms, such as bacteria or viruses, which share distinctive surface structures. For instance, Salmonella bacteria look alike under the microscope but can be separated into many serotypes based on two structures on their surface:

• The outermost portion of the bacteria’s surface covering, called the O antigen; and
• A slender threadlike structure, called the H antigen, that is part of the flagella.

The O antigens are distinguished by their different chemical make-up. The H antigens are distinguished by the protein content of the flagella. Each O and H antigen has a unique code number. Scientists determine the serotype based on the distinct combination of O and H antigens.

Salmonella have many different serotypes. Some serotypes are only found in one kind of animal or in a single place. Others are found in many different animals and all over the world. Some can cause especially severe illnesses when they infect people; while others cause milder illnesses.

• The bacteria’s surface are covered with lipopolysaccharide (LPS). The outermost portion of the LPS is the O antigen.
• Flagella are whip-like tails that bacteria use to move around. Flagella is the whole structure, while the slender threadlike portion of the flagella is called the H antigen.

New technology is transforming how we detect and investigate outbreaks. Watch the video to learn more.

Some groups of people, such as older adults, people with weakened immune systems, and children under five years old have a higher risk for Salmonella infection. Infections in these groups can be more severe, resulting in long-term health consequences or death. 1

More than 2,500 serotypes have been described for Salmonella; but, because they are rare, scientists know very little about most of them. Less than 100 serotypes account for most human infections. What we learn about the more common serotypes can help us better understand illness and the natural history of all the Salmonella strains.

Serotyping is a subtyping test based on differences in microbial (e.g., viral or bacterial) surfaces. Serology refers to the antibodies that form because of a viral or bacterial infection. Serotyping is sometimes referred to as serology, but this is technically inaccurate.

Since the 1960s, public health scientists in the US have used serotyping to help find Salmonella outbreaks and track them to their sources. Laboratory experts serotype the Salmonella from infected people. When cases with one serotype increase, they suspect an outbreak and disease detectives start their investigation.

Serotyping has been the core of public health monitoring of Salmonella infections for over 50 years. Now, scientists use DNA testing to further divide each serotype into more subtypes and to detect more outbreaks. With the next generation of sequencing technology, advancements continue as the laboratory can find information about the species, serovar, and subtype of bacteria in just one test. Currently, at least two scientists must generate these three important pieces of information using three separate tests or more. 2

Resistance to two clinically important drugs, ceftriaxone (a cephem) and ciprofloxacin (a quinolone), has climbed in non-typhoidal Salmonella since 1996. In 2011, about 5% of Salmonella tested by CDC were resistant to five or more types of drugs. 3

CDC has posted a series of interactive graphs that allow users to see the percentage of Salmonella human isolates resistant to various antibiotics tracked, by year, through the National Antimicrobial Resistance Monitoring System (NARMS). This graph includes the option to view all Salmonella isolates or any one of five common serotypes with resistance to antibiotics used to treat Salmonella infections: Enteritidis, Typhimurium, Newport, Heidelberg, and I 4,[5],12:i: -.

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 ]

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.