SAARS: Salmonella spp. (epidemiology)

Although considered enteric pathogens in humans, Salmonella species may represent normal intestinal flora in birds and reptiles, as well as fish and birds. Cases of salmonellosis are most commonly associated with improperly cooked poultry products and, to a lesser degree, with exposure to reptiles and amphibians, including snakes, lizards, and turtles. The CDC estimates that 75% of S. enteritidis outbreaks are associated with the consumption of raw or inadequately cooked Grade A whole shell eggs. Some Salmonella species have been isolated from the outside of egg shells; S. enteritidis is also found inside the egg, in the yolk, strongly suggesting vertical transmission from an infected layer hen into the yolk prior to shell deposition (in Britian perhaps one in every 600 to 700 eggs carries Salmonella on the outer surface of its shell, and one in 7,000 has infected yolks). From two to four million cases of salmonellosis occur in the U.S. annually, and the incidence appears to be rising in industrialized nations. S. enteritidis isolations from humans have risen dramatically in the past decade. AIDS patients suffer salmonellosis with an estimated 20-fold higher frequency than the general population and suffer from recurrent episodes.

The largest outbreak of foodborne salmonellosis in the U.S. took place in 1985, involving 16,000 confirmed cases in six states (Centers for Disease Control, 1985). The outbreak was caused by low fat and whole milk from one Chicago dairy in which the pasteurization equipment had been modified to facilitate the running off of raw milk. Consequently, the pasteurized milk was contaminated with raw milk under certain conditions. Persons on antibiotic therapy were at increased risk to develop salmonellosis in this outbreak.

Despite more than 2200 described Salmonella serotypes three major categories of salmonellosis are well known: enteric fever, septicemia, and gastroenteritis:

• Gastroenteritis: Most common form of salmonellosis, can be caused by any serotype. Organisms penetrate from the GI lumen into the small intestinal epithelium where inflammation occurs. An enterotoxin may be produced, perhaps within the enterocyte. Patient becomes symptomatic (nausea, vomiting, abdominal cramps, headache, and diarrhea) 10 - 24 hours after ingestion of highly contaminated food. Symptoms may persist for two to seven days. Postenteritis reactive arthritis with a frequency of about 2% of culture-proven cases and Reiter's syndrome may occur after about three weeks.

• Septicemia: A fulminant, sometimes fatal disease independent of gastrointestinal disease. Some Salmonella species are particularly invasive of the intestinal mucosal epithelium where they seed the bloodstream; S. choleraesuis is isolated more commonly from the blood than from a gastroenteritis-associated stool culture. Unlike S. typhi (see below), S. choleraesuis does not survive phagocytosis by the reticuloendothelial system (RES). Nevertheless, septicemia can lead to focal infections throughout the body resulting in pneumonia, meningitis, and/or osteomyelitis, the latter especially in patients with sickle cell anemia. Septic arthritis occurring subsequently or coincident with septicemia can be difficult to treat.

• Enteric (Typhoid) Fever: Usually caused by S. typhi, or by S. enteritidis serotype paratyphi, and probably other serotypes as well, the causative organism penetrates the intestinal mucosa one to three weeks post-ingestion. Unlike S. choleraesuis, S. typhi is a facultative intracellular pathogen of macrophages, and the gallbladder may become a reservoir sustaining the organism. Consequently, regional lymphadenopathy follows initial invasion of the mucosa, with subsequent continuous seeding of the bloodstream which can lead to localized infections occurring anywhere in the body. (During the third week post-ingestion, the organism can be recovered from the urine of 25% of patients.) Symptoms of enteric fever are systemic: headache, loss of appetite, abdominal pain, weakness, continuous fever, and stupor are common, with diarrhea occurring only late in the disease after the gastrointestinal tract has been re-seeded from hematogenous spread. Splenomegaly is nearly universal and bacterial replication in the skin may cause the appearance of rose-colored spots. The fatality rate of typhoid fever is 10%, compared to less than 1% for other forms of salmonellosis.

Antibiotic treatment is vital in the patient with sepsis or enteric fever, but may only be required in the severest cases of gastroenteritis. Because of its biliary circulation, ampicillin may eliminate the carrier state.

Salmonella typhi, but not S. typhimurium, uses the cystic fibrosis transmembrane conductance regulator (CFTR) molecule as a receptor for translocating from the lumen of the GI tract into the submucosa. It is the CFTR molecule that is mutated in CF patients, producing deranged chloride ion secretion which in turn results in the disease. The mutant CFTR in the homozygous state results in the virtual cessation of S. typhi translocation into the submucosa. Mutant CFTR heterozygotes may be protected against typhoid fever, which may explain why mutant CFTR genes are maintained in some populations, just as sickle cell trait is protective against malaria (Pier, 1998).