WHAT IS SALMONELLA?

It has long been said that, in 1885, pioneering American veterinary scientist, Daniel E. Salmon, discovered the first strain of Salmonella. Actually, though, Theobald Smith, research-assistant to Dr. Salmon, discovered the first strain of SalmonellaSalmonella cholerae suis. But, being in charge, Dr. Salmon received all of the credit. Today, the number of known serotypes of Salmonella bacteria totals over two thousand. Concerns have been raised in recent years, as particular strains of Salmonella have become resistant to traditional antibiotics.

The term Salmonella refers to a group or family of bacteria that variously cause illness in humans. The taxonomy and nomenclature of Salmonella have changed over the years and are still evolving. Currently, the Centers for Disease Control and Prevention (CDC) recognizes two species of Salmonella, which are divided into seven subspecies. These subspecies are divided into over 50 serogroups based on somatic (O) antigens present. The most common Salmonella serogroups are A, B, C, D, E, F, and G. Serogroups are further divided into over 2,500 serotypes, and are typically identified through a series of tests of antigenic formulas listed in a document called the Kauffmann-White Scheme, which is published by the World Health Organization Collaborating Centre for Reference and Research on Salmonella.[1]

Three Salmonella serotypes—Enteritidis, Typhimurium, and Newport—have persisted as the serotypes most often isolated in patients and reported to the CDC over the last decade. In 2009, these three serotypes accounted for 42% of all reported cases of Salmonella.[2]

Where Does Salmonella Come From?

Salmonella is an enteric bacterium, which means that it lives in the intestinal tracts of humans and other animals. Salmonella bacteria are usually transmitted to humans by eating foods contaminated with animal feces, or foods that have been handled by infected food service workers who have practiced poor personal hygiene. Contaminated foods usually look and smell normal and are often of animal origin, such as beef, poultry, milk, or eggs. But all foods, including vegetables, may become contaminated. Many raw foods of animal origin are frequently contaminated, but thorough cooking kills Salmonella. Though, the food handler who neglects to thoroughly wash his or her hands with soap and warm water after using the bathroom may contaminate foods that have otherwise been properly prepared.

What are the Symptoms of Salmonellosis?

Once in the lumen of the small intestine, the bacteria penetrate the epithelium, multiply, and enter the blood within 24 to 72 hours. Variables such as the health and age of the host, and virulence differences among the serotypes, affect the nature of the diagnosis. Infants, the elderly, individuals hospitalized, and the immune-suppressed are the populations that are most susceptible to Salmonellosis and suffer the most severe symptoms.

“The majority of persons infected with Salmonella have diarrhea, fever, and abdominal cramps 12-72 hours after exposure. The illness usually lasts 4-7 days, and the majority of persons recover without treatment.” MMWR Weekly, supra at 684. However, much longer incubation periods of 120 hours to 31 days have been documented in previous Salmonella outbreaks.[3]

The acute symptoms of Salmonella gastroenteritis include the sudden onset of nausea, abdominal cramping, and bloody diarrhea with mucous. As already noted, there is no real cure for a Salmonella infection; treatment, therefore, tends to be palliative – although prescription of antibiotics is common, even if usually contraindicated.

Medical treatment is acutely important, though, if the patient becomes severely dehydrated or if the infection spreads from the intestines. Persons with severe diarrhea often require re-hydration, usually with intravenous (IV) fluids. But antibiotics are not necessary or indicated unless the infection spreads from the intestines, at which time the infection can be treated with ampicillin, gentamicin, trimethoprim/sulfamethoxazole, or ciprofloxacin. Unfortunately, though, some Salmonella bacteria have become resistant to antibiotics, largely as a result of the use of antibiotics to promote the growth of feed animals.

MEDICAL COMPLICATIONS

Reactive Arthritis

The term reactive arthritis refers to an inflammation of one or more joints, following an infection localized at a site distant from the affected joints. The predominant site of the infection is the gastrointestinal tract. And reactive arthritis can be post infection, meaning that the infection may not be active when diagnosed. Several bacteria, including Salmonella, can reactive arthritis.[4]  And although the resulting joint pain and inflammation can resolve completely over time, permanent joint damage can occur.[5]

Reiter’s syndrome, a form of reactive arthritis, is an uncommon but debilitating syndrome caused by gastrointestinal or genitourinary infections. The reactive arthritis associated with Reiter’s may develop after a person eats food that has been tainted with bacteria. In a small number of persons, the joint inflammation is accompanied by conjunctivitis (inflammation of the eyes), and uveitis (painful urination). Id. This triad of symptoms is called Reiter’s Syndrome.[6]    Salmonella is one of the most common gastrointestinal bacteria involved with Reiter’s Syndrome. And although Reiter’s syndrome is characterized by a triad of arthritis, conjunctivitis, and urethritis, not all three symptoms occur in all affected individuals.[7]

Even though the initial infection may not be recognized, reactive arthritis can still occur. Reactive arthritis typically involves inflammation of one joint (monoarthritis), or four or fewer joints (oligoarthritis), preferentially affecting those of the lower extremities; the pattern of joint involvement is usually asymmetric. Inflammation is common at the places where ligaments and tendons attach to bone (enthuses), especially the knee and the ankle.

Salmonella has been the most frequently studied bacteria associated with reactive arthritis. Overall, studies have found rates of Salmonella-associated reactive arthritis to vary between six and thirty percent.[8] The frequency of post-infectious Reiter’s Syndrome, however, has not been well described. In a Washington State study, while twenty-nine percent of research participants developed arthritis, only three percent developed the triad of symptoms associated with Reiter’s syndrome.[9] In addition, individuals of Caucasian descent were found to be potentially more likely than those of Asian descent to develop reactive arthritis,[10] and children potentially less susceptible than adults to reactive arthritis following infection with Salmonella.[11]

A clear association has been made between reactive arthritis and a genetic factor called the human leukocyte antigen (HLA) B27 genotype. HLA is the major histocompatibility complex in humans; these are proteins present on the surface of all body cells that contain a nucleus, and are in especially high concentrations in white blood cells (leukocytes). It is thought that HLA-B27 may affect the elimination of the infecting bacteria or an individual’s immune response.[12]  HLA-B27 has been shown to be a predisposing factor in one-half to over two-thirds of individuals with reactive arthritis.[13] While HLA-B27 does not appear to predispose to the initial infection itself, it increases the risk of developing arthritis that is more likely to be severe and prolonged. This risk may be slightly greater for Salmonella and Yersinia-associated arthritis than with Campylobacter, but more research is required to clarify this.[14]

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a chronic disorder characterized by alternating bouts of constipation and diarrhea, both of which are generally accompanied by abdominal cramping and pain.[15] In one recent study, over one-third of IBS sufferers had lived with IBS for more than ten years, and their symptoms remained fairly constant over time.[16] The study found that IBS sufferers typically experienced symptoms for an average of 8.1 days per month.[17]

Another recently-published study—The Walkerton Health Study (WHS)—surveyed the extant scientific literature and noted that post-infectious irritable bowel syndrome (PI-IBS) is a common clinical phenomenon first-described over five decades ago.[18] The WHS further notes that between five and thirty percent of patients who suffer an acute episode of infectious gastroenteritis develop chronic gastrointestinal symptoms, despite clearance of the inciting pathogens.[19] In terms of its own data, the WHS “confirm[ed] a strong and significant relationship between acute enteric infection and subsequent IBS symptoms.”[20] The WHS also identified risk-factors for subsequent IBS including: younger age; female sex; and four features of the acute enteric illness—diarrhea for > 7days, presence of blood in stools, abdominal cramps, and weight loss of at least ten pounds.[21]

As would be expected from a chronic disorder with symptoms of such persistence, IBS sufferers were found to require more time off work, spend more days in bed, and to more often cut down on usual activities, when compared with non-IBS sufferers.[22] And even when able to work, a significant majority (67%) of IBS sufferers felt less productive at work because of their symptoms.[23] IBS symptoms also have a significantly deleterious impact on social well-being and daily social activities, such as undertaking a long drive, going to a restaurant, or taking a vacation.[24] And finally, although a patient’s psychological state may influence the way in which he or she copes with illness and responds to treatment, there is no evidence to supports the theory that psychological disturbances in fact cause IBS or its symptoms.[25]

[1]     Grimont, PAD, Weill, F.  Antigenic formulae of the Salmonella serovars, 2007, 9th Edition. WHO Collaborating Centre for Reference and Research on Salmonella. Paris: Pasteur Institute.  http://www.pasteur.fr/ip/portal/action/WebdriveActionEvent/oid/01S-000036-089.

[2]     http://www.cdc.gov/ncezid/dfwed/PDFs/SalmonellaAnnualSummaryTables2009.pdf, Table 1.

[3]     O’ Mahony, et al.  An outbreak of Salmonella Heidelberg infection associated with a long incubation period.  J. Public Health (1990) 12 (1): 19-21;  Abe, et al.  Prolonged Incubation Period of Salmonellosis Associated with Low Bacterial Doses.  J. Food Protection (2004) Vol. 67, No. 12; 2735-2740.

[4]     See Reactive Arthritis. “Questions and Answers About.” N.p., n.d. Web. 12 Nov. 2015.

[5]     Id.

[6]     IdSee also, Dworkin, et al.  “Reactive Arthritis and Reiter’s Syndrome following an outbreak of gastroenteritis caused by Salmonella enteritidis,” Clin. Infect. Dis., 2001 Oct. 1;33(7): 1010-4; Barth, W. and Segal, K.  “Reactive Arthritis (Reiter’s Syndrome),” American Family Physician, Aug. 1999, online at www.aafp.org/afp/990800ap/499.html.

[7]     Hill Gaston JS, Lillicrap MS.  (2003).  Arthritis associated with enteric infection.  Best Practices & Research Clinical Rheumatology.  17(2):219-239.

[8]     Id.

[9]     Dworkin MS, Shoemaker PC, Goldoft MJ, Kobayashi JM.  “Reactive arthritis and Reiter’s syndrome following an outbreak of gastroenteritis caused by Salmonella enteritidis.”  Clin. Infect. Dis. 33(7):1010-1014.

[10]    McColl GJ, Diviney MB, Holdsworth RF, McNair PD, Carnie J, Hart W, McCluskey J.  “HLA-B27 expression and reactive arthritis susceptibility in two patient cohorts infected with Salmonella Typhimurium,” Australian and New Zealand Journal of Medicine.  30(1):28-32 (2001).

[11]    Rudwaleit M, Richter S, Braun J, Sieper J.  “Low incidence of reactive arthritis in children following a Salmonella outbreak,” Annals of the Rheumatic Diseases, 60(11):1055-1057 (2001).

[12]    Hill Gaston and Lillicrap, supra Note 7.

[13]    Id.; Barth WF, Segal K., “Reactive arthritis (Reiter’s syndrome).” American Family Physician, 60(2):499-503, 507 (1999).

[14]    Hill Gaston and Lillicrap, supra Note 7.

[15]    A.P.S. Hungin, et al.  Irritable Bowel Syndrome in the United States: Prevalence, Symptom Patterns and Impact, Aliment Pharmacol. Ther., 2005:21 (11); 1365-75.

[16]    Id. at 1367.

[17]    Id.

[18]    J. Marshall, et al.  Incidence and Epidemiology of Irritable Bowel Syndrome After a Large Waterborne Outbreak of Bacterial Dysentery, Gastro., 2006; 131;445-50 (hereinafter “Walkerton Health Study” or “WHS”).  The WHS followed one of the largest E. coli O157:H7 outbreaks in the history of North America.  Contaminated drinking water caused over 2,300 people to be infected with E. coli O157:H7, resulting in 27 recognized cases of HUS, and 7 deaths.  Id. at 445.  The WHS followed 2,069 eligible study participants.  Id.  For Salmonella specific references, see Smith, J.L., Bayles, D.O., Post-Infectious Irritable Bowel Syndrome: A Long Term Consequence of Bacterial Gastroenteritis.  Journal of Food Protection, 2007:70(7);1762-1769.

[19]    Id. at 445 (citing multiple sources).

[20]    WHS, supra note 34, at 449.

[21]    Id. at 447.

[22]    Id. at 1368.

[23]    Id.

[24]    Id.

[25]    Amy Foxx-Orenstein, DO, FACG, FACP.  IBS—Review and What’s New.  General Medicine, 2006:8(3) (Medscape 2006) (collecting and citing studies).  Indeed, PI-IBS has been found to be characterized by more diarrhea but less psychiatric illness with regard to its pathogenesis.  See Nicholas J. Talley, MD, PhD.  Irritable Bowel Syndrome: From Epidemiology to Treatment, from American College of Gastroenterology 68th Annual Scientific Meeting and Postgraduate Course (Medscape 2003).