ARTICULO MEDICO: SALMONELOSIS. EPIDEMIOLOGIA Y MICROBIOLOGIA

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Microbiology and epidemiology of salmonellosis

Author
Elizabeth L Hohmann, MD

Section Editor
Stephen B Calderwood, MD

Deputy Editor
Elinor L Baron, MD, DTMH

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jan 2013. | This topic last updated: ene 2, 2013.

INTRODUCTION — Salmonellae are motile gram-negative bacilli that infect or colonize a wide range of mammalian hosts. They cause a number of characteristic clinical infections in humans, including:

• Gastroenteritis
• Enteric fever (systemic illness with fever and abdominal symptoms)
• Bacteremia and endovascular infection
• Focal metastatic infections such as osteomyelitis or abscess
• An asymptomatic chronic carrier state

The bacteriology, epidemiology, and trends in antimicrobial resistance of these organisms will be reviewed here. The pathogenesis, clinical description, and treatment of specific Salmonella syndromes are discussed separately.

BACTERIOLOGY — The genus Salmonella consists of two species, Salmonella enterica and Salmonella bongori; the former is further divided into six different subspecies. Based upon high levels of DNA similarity, most clinically important Salmonellae are formally classified within a single subspecies, Salmonella enterica, subspecies enterica [1]. Familiar organisms such as Salmonella typhi, Salmonella choleraesuis, and Salmonella enteritidis, previously believed to represent separate species based upon antigenic structures, host range, and biochemical characteristics, are now individual serotypes of this single subspecies. Many laboratories will continue to report names recognizable to clinicians such as: Salmonella Typhimurium or Salmonella enterica serovar Typhi. Serotype and serovar are synonymous.

Salmonella are relatively easy to identify in the clinical microbiology laboratory [2]. Salmonellae grow under both aerobic and anaerobic conditions. Salmonella are oxidase negative and virtually all are lactose negative (white on MacConkey agar plates); most Salmonellae produce hydrogen sulfide, which is easily detected on selective indicator plates such as Hektoen, or Salmonella-Shigella agar, which are used for plating stool specimens.

Most laboratories identify Salmonellae by a combination of antigenic and biochemical reactions. Suspicious colonies are agglutinated using antisera directed against specific O (lipopolysaccharide) and H (flagellar) antigens that allow identification of the serogroup. Only S. typhi, S. paratyphi C, and some strains of Salmonella dublin and Citrobacter freundii possess the Vi capsular polysaccharide antigen [3], which can be rapidly detected by slide agglutination studies.

Although serogrouping may provide a clue as to the specific organism (table 1), this may not always be useful clinically. As an example, both S. enteritidis (which most frequently causes gastroenteritis) and S. typhi (which causes enteric fever) belong to group D; S. enteritidis may occasionally cause a systemic "typhoidal" illness with bacteremia. Formal serotyping is more specific than serogrouping and usually is only performed at state or reference laboratories.

Some have advocated the use of typing techniques such as pulsed-field gel electrophoresis on strains of S. enterica serotype typhimurium to detect outbreaks that might otherwise be missed. The Minnesota Department of Health adopted such an approach and identified 16 outbreaks accounting for 154 of 958 isolates between 1994 and 1998 [4]. Twenty-seven percent of isolates were resistant to at least five antibiotics when sensitivity testing was performed; the multidrug resistant strains all had unique pulsed-field gel electrophoresis patterns.

EPIDEMIOLOGY — Typhoidal and nontyphoidal Salmonella infections are quite different in their epidemiology. The former are usually acquired abroad whereas the latter are most often domestically acquired.

Salmonella typhi and Salmonella paratyphi — These organisms, which cause typhoid fever, have a high host specificity for humans. Infection virtually always implies contact with an acutely infected individual, a chronic carrier, or contaminated food and water.

Typhoid fever remains a global health problem, with an estimated 21.6 million illnesses and 216,500 deaths worldwide in 2000 [5]. The incidence was high (>100 cases per 100,000 population per year) in south-central Asia, Southeast Asia, and southern Africa; medium (10 to 100 cases per 100,000) in the rest of Asia, Africa, Latin America, and Oceania, except for Australia and New Zealand; and low in the other parts of the world (<10 100="" cases="" o:p="" per="">

Paratyphoid fever was estimated to have caused 5.4 million illnesses in 2000 [5]. The proportion of cases due to S. paratyphi is increasing in some areas, including Nepal (34 percent of isolates from 1999 to 2003, up from 23 percent in the mid-1990s) [6].

Improvements in food handling, waste management, and water treatment are clearly the most important means of controlling typhoid fever and other enteric pathogens.

In the United States, typhoid fever has become less prevalent and is now primarily a disease of travelers and immigrants:

• In a review of laboratory-confirmed cases reported to the Centers for Disease Control and Prevention (CDC) between 1999 and 2006, there were about 1900 cases of S. typhi infection [7]. Nearly 80 percent were associated with travel, and only 5 percent of those reporting immunizations had received a typhoid fever vaccine. Four countries accounted for most travel-associated cases: India (47 percent), Pakistan, Bangladesh, and Mexico.
• The risk of travel to the Indian subcontinent (estimated rate >100 cases per million travelers), or Southeast Asia and Africa (estimated 5 to 14 cases per million travelers) is significantly higher [8,9]. Travelers to these and other high-risk endemic areas should be vaccinated with either the live oral attenuated vaccine Ty21a or the Vi capsular polysaccharide vaccine.

In the United States, domestically acquired typhoid fever may be related to chronic carriers, but the source of sporadic cases frequently remains enigmatic [9]. Outbreaks have been described related to contaminated water supplies [10], specific foods consumed at social gatherings [11,12], unappreciated chronic carriers working in the food service industry [13], and close personal contact in a psychiatric institution.

Nontyphoidal Salmonellae — Unlike infection with typhoidal Salmonellae, nontyphoidal salmonellosis increased steadily in the United States from World War II through the 1980s (figure 1). A substantial decline in nontyphoidal salmonellosis began in the mid-1990s, but cases increased again in the late 2000s [15]. S. enteritidis, S. newport, and S. typhimurium are now the serotypes most frequently isolated in the United States [16]. During 2003, a total of 43,657 cases of salmonellosis were reported in the United States, of which 40 percent occurred among children aged <15 span="" years="">17]. These numbers represent a fraction of the true incidence, as many cases are not diagnosed. There are an estimated 39 cases of undocumented salmonellosis for each culture-confirmed case [18]. The global burden of nontyphoidal Salmonella gastroenteritis has been estimated at about 94 million cases (mostly foodborne) and 155,000 deaths [19].

Foodborne infection — Nontyphoidal Salmonellae are associated with animal reservoirs and therefore with agricultural products, especially eggs and poultry [20-22]. Among 6647 outbreaks of foodborne disease reported to the CDC between 1998 and 2002, S. enteritidis accounted for the largest number of outbreaks and outbreak-related cases [23]. The majority of S. enteritidis outbreaks were related to eggs.

Salmonellae can be passed transovarially from chickens to intact shell eggs [24]. Thus, single, intact, normal-appearing eggs can transmit infection. The frequency of S. enteritidis-contaminated eggs is difficult to estimate because the rate varies depending upon the level of colonization among hens in a flock and the timing of egg production with respect to acquisition of infection in the hen [21]. On average, in the United States, the frequency of contamination is one in 20,000 eggs [25].

Pooling of large numbers of eggs can result in contamination of food products that may be distributed nationally and potentially transmit infection to thousands. As an example, a nationwide outbreak of 224,000 cases of S. enteritidis infection resulted from ice cream manufactured in one state and distributed widely [26]. The putative source of contamination was tankers, which transported ice cream base but previously had been used to carry liquid eggs.

Peanut butter containing products contaminated with S. typhimurium were implicated in 2008-2009 as the cause of illness in 529 persons from 43 states [27,28]. The contamination was traced to a Georgia plant and many products were recalled.

Nontyphoidal Salmonellae have also been associated with fresh produce, meat (including ground beef as well as dog food), milk, spices, and other foods (table 2) [29-41]. Contamination can occur at many points along the food processing pathway, which, in developed countries, has become increasingly industrialized, centralized, and global in scope.

Patients with foodborne salmonellosis may have more severe disease than with other foodborne infections. This was suggested in a registry-based study from Denmark that included 52,121 patients with foodborne bacterial gastroenteritis: 18 percent had infection due to nontyphoidal Salmonella spp, and 14 percent were hospitalized within 90 days of a microbiologic diagnosis [42]. The risk of invasive illness was more than sixfold higher in patients with infection due to nontyphoidal Salmonella compared with other bacterial causes of gastroenteritis.

Surveillance — FoodNet is a collaborative active surveillance program involving 10 state public health departments, the CDC, FDA, and Department of Agriculture, which now surveys approximately 15 percent of the United States population for foodborne illnesses. FoodNet began in 1996; the following observations since that time have been noted:

• Conservative estimates indicated that there were about 1.4 million Salmonella infections in the United States, which resulted in about 15,000 hospitalizations and approximately 400 deaths per year [18].
• Nontyphoidal Salmonella infections proportionally cause the greatest percentage of hospitalizations and deaths due to foodborne pathogens [43].
• Salmonellosis is most problematic in people over 60 and infants. Most deaths occurred in older patients with comorbid illnesses. Seventy-one percent of patients with invasive salmonellosis were hospitalized and approximately 5 percent died [44].
• Case control studies in infants strongly suggested that breast feeding protects against acquisition of Salmonella infection in infancy [45,46]. Other independent studies show that risks for salmonellosis in infants include riding in a shopping cart with meat or poultry placed next to them and ingestion of concentrated liquid infant formula, perhaps related to the storage and handling of opened cans of concentrated formula [46]; outbreaks of salmonellosis also have been linked to consumption of powdered infant formula [47,48].
• Chicken consumption (not just egg consumption) appeared to be a new risk factor for development of Salmonella enteritidis infection [49,50].
• Salmonellosis rates differed by region. A decrease in rate was seen and in some areas may have been due to on-farm control measures, better refrigeration, consumer education, and better food handling in restaurants and homes [51]. However, not all sites had lower rates.

From 1996 to 1999, overall cases of salmonellosis decreased in FoodNet sites (including Minnesota, Oregon, California, Connecticut and Georgia). The decline in salmonellosis continued through 2003 (13.5 versus 14.5 cases per 100,000 in 1996-1998) [52], and was due to a reduction in S. typhimurium infection [52,53]. However, rates of salmonellosis, driven partly by increases in infections with S. enteritidis and S. newport, subsequently rebounded to 17.6 cases per 100,000 persons in 2010 [15,54]. Salmonella remains the most common isolated pathogen of those evaluated in the FoodNet survey, accounting for 43 percent of cases in 2010 [15]. Salmonella outbreaks due to multiple serotypes may occur more frequently than recognized [55]. Because certain serotypes are known to be likely associated with particular food types or animal sources, evaluating for the presence of multiple serotypes (if resources permit) can help focus the investigation on potential outbreak sources.

Other methods of transmission — In addition to foodborne outbreaks, transmission of Salmonella can occur in day care settings from pet reptiles and amphibians (eg, snakes, lizards, turtles, iguanas, frogs) in infants and preschool-aged children [46,56-60], from live poultry including chicks and ducklings [61,62], from pet rodents (hamsters, mice, and rats) [63,64], from cats and dogs [65], contaminated marijuana [66], and pet foods [67,68].

A case-control study conducted in 1996 and 1997 in five states in the United States estimated that reptiles and amphibians accounted for 6 percent of all human, laboratory-confirmed sporadic Salmonella infections, and 21 percent in individuals under age 21 [69]. In a subsequent report from Michigan, reptile-associated salmonellosis accounted for 12 percent of cases of Salmonella infection in children ≤5 years of age between January 2001 and June 2003 [57]. Turtles were considered the probable source of many of these infections. However, since nontyphoidal Salmonella infections are common and usually sporadic, the association with turtle exposure may not be detected [56].

The Centers for Disease Control (CDC) in the United States recommends that children under five years of age and immunocompromised patients avoid contact with reptiles [58,70,71]. Although there is a federal law prohibiting the sale of small turtles, turtle sales continue to occur. The risk of Salmonella infection after reptile exposure can be reduced by washing hands with soap and water after handling reptiles and keeping the reptiles away from food-preparation areas [59]. CDC recommendations for turtles as pets are available at: http://www.cdc.gov/healthypets/spotlight_an_turtles.htm

Live poultry are a source of Salmonella infection that is relatively under-recognized by the general public. Between 2004 and 2011, 316 illnesses caused by a particular strain of S. montevideo were reported from multiple states across the United States [62]. The majority of patients were children younger than five years old, and most reported contact with live young poultry, many of which had been purchased as pets, in the week prior to the illness. Of those interviewed, only 21 percent were aware of the risk of Salmonella with the handling of live poultry, and only 7 percent were apprised of this risk on acquisition of the bird. Investigation traced the outbreak to a mail-order hatchery, which subsequently instituted control measures that decreased but did not eliminate the number of cases caused by this strain of S. montevideo in subsequent years. Smaller outbreaks of different Salmonella species have been also been linked to handling of live poultry purchased as pets or for backyard flocks [61,72]. The potential impact of this risk is quite large, as approximately 50 million live poultry are sold through mail-order hatcheries in the United States annually. The Centers for Disease Control and Prevention (CDC) in the United States recommends that live poultry should not be kept inside the house, particularly in areas where food or drink is prepared or served. Hands should be washed with soap and water after touching live poultry or their environment, and children under five years of age and immunocompromised patients should avoid handling live poultry, including chicks and ducks.

Although other pets are rarely confirmed as the source of human salmonellosis, zoonotic transmission of gastrointestinal illnesses from sick pets may occur [63-65]. Raw pet foods and treats for companion animals may also be a hidden reservoir of Salmonella in the home [73,74].

In addition to infection from pets, there have been multiple outbreaks of enteric disease associated with animal exposure in public settings, such as county fairs, farms, and petting zoos. In a review of 55 such outbreaks, Salmonella species accounted for 22 percent [75].

An outbreak of fluoroquinolone-resistant salmonellosis, in which the presumed mechanism of spread was person-to-person or via contact with contaminated surfaces, has also been described [76].

ANTIMICROBIAL RESISTANCE — The National Antimicrobial Resistance Monitoring Systems (NARMS): Enteric Bacteria is a collaboration among the CDC, United States Food and Drug Administration (FDA), and United States Department of Agriculture (USDA) that monitors antimicrobial resistance in enteric bacteria, including Salmonella spp [77]. The website has the most currently available information on resistance reports in the United States (www.cdc.gov/narms/).

Salmonella typhi — Since 1989, Salmonella typhi resistant to chloramphenicol, ampicillin, trimethoprim, and sulfonamides (ie, multidrug-resistant or MDR strains) have become a worldwide problem [78], necessitating the use of newer antimicrobials such as the fluoroquinolones and third generation cephalosporins for therapy of typhoid fever. However, the appearance of fluoroquinolone-resistant strains of S. typhi in Thailand [79] and India [80,81] represents a new obstacle for clinicians in endemic areas in which rapidly effective oral agents are needed for the treatment of typhoid fever. Nalidixic acid resistance among S. typhi isolates in Asia increased from 5 to 50 percent between 1993 and 2004 [82].

In 2007, 62 percent of all US isolates were resistant to nalidixic acid [77]. Approximately 88 percent of US cases imported from India between 1999 and 2006 were nalidixic acid resistant [7]. Another report from central India noted that 98 percent of isolates were nalidixic acid resistant [83]. Full resistance to fluoroquinolones (MIC >1 mcg/mL) in both S. typhi and S. paratyphi is less common but increasing worldwide. A compilation of studies showed rates of fully quinolone-resistant organisms ranged from 0 to 13 percent [84]. Ceftriaxone-resistant S. typhi or S. paratyphi does not yet appear to have emerged, but routine use of this drug in resource poor areas is limited by cost.

Nontyphoidal Salmonella — Antimicrobial resistance is a global problem with nontyphoidal Salmonellae [85,86]. There is significant geographic variability, and epidemics of specific problematic strains occur worldwide. In the United States, data on nontyphoidal Salmonella isolates collected by the CDC showed that the prevalence of S. typhimurium isolates with resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline increased between 1979 and 1996 from 0.6 to 34 percent [87]. Many isolates with this resistance pattern were Salmonella typhimurium definitive phage type 104 (DT104), a virulent epidemic strain had become widespread in the United Kingdom earlier [88], though a report from the European Enter-net International Surveillance network notes the decline of DT104 [89]. Clinically important trends include:

• About 2.2 percent of nontyphoidal strains in the United States are nalidixic acid resistant [77]; in Europe this number is 14 percent [90].
• In the United States about 3.3 percent of nontyphoidal strains were resistant to ceftiofur, a veterinary third generation cephalosporin; resistance to this agent often correlates with decreased susceptibility toceftriaxone. Europe reports 0.7 percent resistance to cefotaxime.

Extended-spectrum beta-lactamase (ESBL) genes are emerging in Salmonellae in all areas, and certain serotypes may be more likely to support specific plasmids or resistance-encoding genetic elements [91,92]. The Clinical and Laboratory Standards Institute has altered break points that define susceptibility of Enterobacteriaceae (including Salmonellae) to third generation cephalosporins, in part to simplify recognition of strains potentially bearing beta-lactamase resistance elements by non-reference laboratories that do not routinely perform more sophisticated testing directed at identifying these enzymes [93]. The revised breakpoints eliminate the need to perform ESBL screen and confirmatory tests for treatment decisions. Laboratories are implementing these changes slowly, so reports may have varying definitions of resistance to these important clinical agents.

Several reports highlight the transmission of antibiotic-resistant strains of Salmonella from food animals.

• A study from Denmark linked transmission of S. typhimurium DT104 infections in 25 patients to a Danish swine herd [94]. Eleven patients were hospitalized, two died, and the organism had reduced susceptibility to fluoroquinolones. Other reports confirm emergence of fluoroquinolone resistance among nontyphoidal isolates [95,96].
• A report from Canada described a strong correlation between ceftiofur resistance in Salmonella Heidelberg isolated from retail chicken and the incidence of ceftiofur resistance in clinical isolates from across Canada [97].

These data highlight the need for judicious use of antimicrobial agents in both clinical practice and animal husbandry, as well as the need for ongoing surveillance of antimicrobial resistance patterns of important foodborne pathogens.

REFERENCES