Salmonellas

The organism Salmonelleae belongs to the family Enterobacteriaceae and possesses a single genus, Salmonella, named after D.E Salmon, an American Microbiologist. The genus contains in excess of 2400 serotypes of a single species called Salmonella enterica. Salmonella enterica is further divided into various subspecies such as the following:

• indica 
• houtenae 
• enterica 
• arizonae 
• diarizonae

These subspecies are based on their somatic or (O), flagellar or (H), surface or (Vi) antigens and their habitats. Salmonellae are pathogenic to humans as well as animals and are responsible for economic loss in animal commerce. They are facultative anaerobic gram negative rods which are capable of fermenting glucose. They are customarily found in the animal intestine.

Pathogenesis

Salmonella enterica is an intracellular parasite. In order for infection to occur, a sufficient number of viable organisms must be present. Research has shown that the infective dose for different serotypes differs. For example, the infective dose for Salmonella typhi is 10⁶ to 10⁹ viable organisms. Numerous factors influence the quantity required for infection such as the following:

• Variation in strains influences pathogenicity which in turn affects the number of organisms needed to define infection.
• The vehicle of ingestion such as when the organisms are ingested with water or other liquids and are transported to the intestine more rapidly requires a smaller infective dose. 
• Gastric acid has adverse effects on the viability of the organism, therefore the administration of antacids or gastric resection reduces the size of the dose required for infection. Additionally, organisms ingested with foods escape the effect of gastric acids.

Salmonella are resistant to bile acids and compete with the commensal flora for colonization of the gut. Once adhered to the mucosal cells, the organisms invade the intestinal epithelial cells by a specific mechanism known as bacteria mediated endocytosis. Salmonellae preferentially adhere to the M cells which are located above the lymphoid tissue within the Peyer?s patches. After epithelial invasion, the organisms are phagocytosed by the macrophages present in the submucosa. The ability of Salmonellae to survive and replicate within the macrophages is responsible for systemic disease.

Cellular immunity plays a critical role in healing infection and prevention of re-infections. This is noted in the extreme susceptibility of patients suffering from HIV, organ transplant patients or patients suffering from lymphoproliferative disorders.

Epidemiology of typhoid fever

Salmonella typhi and Salmonella paratyphi only colonize the human gastrointestinal tract therefore human beings are the only reservoirs of infection. Bacteria are shed in the feces The feco-oral route is the primary mode of transmission. It can be transmitted either through fecally contaminated food or water. Fecal carriers have consistently been the most critical reservoir for the continuing chain of infection within the community. Direct person to person transmission is rare, but a few cases of anal ? oral transmission have been reported in literature. Occasionally a healthcare worker may also acquire infection from infected patients. This might be related to poor hand hygiene or inappropriate handling of specimens in the laboratory.

Each year, there are and estimated 16 million cases of typhoid fever and 6 lac deaths worldwide. The disease is endemic in developing countries. The use of over the counter drugs in these areas has been responsible for the development of drug resistant strains leading to multiple outbreaks. The 1970s saw epidemics of chloramphenicol resistant S.typhi in Mexico and the Indian subcontinent. In 1989, strains resistant to chloramphenicol, amipicillin and cotrimoxazole appeared in the Indian subcontinent, the Southeast Asia, the Middle East and Africa. Multiple outbreaks of these multi-drug resistant (MDR) strains led to increased morbidity and mortality. More recently, chromosomal and plasmid encoded resistance to ciprofloxacin has also developed. Resistance to third generation cephalosporins, though rare, has also been reported.

Nontyphoidal Salmonella

The incidence of nontyphoidal Salmonellosis has doubled in the last two decades with an estimated incidence rate of 17.7 per 1, 00,000 population. It is a significant causative agent of diarrhea among travelers and young children with disease mainly occurring during the rainy season. Outbreaks are associated with contaminated food, especially of animal origin, such as meat, poultry and eggs. Salmonellosis has also been associated with exotic pets, especially reptiles, who have a very high rate of carriage  (about 90%). In 1994, an estimated 24,000 people suffered from gastroenteritis with S.enteritidis after eating a nationally distributed ice cream in the United States. The source of the outbreak was the ice cream premix which was contaminated in transit in carriers previously used to transport eggs. Recent outbreaks due to consumption of contaminated fruits, vegetable and seeds have also been reported.

Salmonella typhimurium (DT104): The worldwide emergence of the Salmonella typhimurium strain (DT 104 ) alarming as it is resistant to at least 5 antimicrobials.  The following are the primary drugs involved:

• ampicillin 
• chloramphenicol 
• tetracycline 
• streptomycin
• sulphonamides.

This strain has been associated with increased morbidity and mortality when compared to susceptible strains of Salmonella typhimurium.

Immunization against typhoid fever

There are three typhoid vaccines approved for use in the United States. These vaccines are 50% to 80% effective and provide protection only for 3 to 5 years.  The vaccines are as follows:

• Oral live attenuated strain is prepared from the Ty21a strain of Salmonella typhi: The Ty21a strain is known to lack the UDP- galactose-4- epimerase enzyme (GalE mutation).The mutant is destroyed after four or five cell divisions therefore, it cannot induce clinical illness. The vaccine is an enteric coated capsule containing 10⁹ viable lyophilized mutant bacilli. It is administered as 4 capsules on alternate days one hour prior to meals with cold milk or water. A booster of 4 capsules is to be taken every 5 years.
• Parenteral thermally-killed, phenol preserved vaccine: The thermally killed vaccine consists of two 0.5 ml doses administered subcutaneously 4 to 6 weeks apart. Booster doses are recommended every three years. Therapeutic dosages are 0.5 ml for individuals older than 10 years, 0.25 ml for children between 6 months and 10 years and 0.1 ml intradermally for children older than 6 months. Adverse reactions are more likely to occur with the heat killed vaccine than the others.
• Parenteral capsular polysaccharide vaccine (ViCPS): The primary vaccination consists of 0.5 ml administered intramuscularly. A booster is recommended every 2 years. It is not recommended for use in children under 2 years of age. Recently, the Vi polysaccharide antigen fused with nontoxic recombinant P.aeruginosa exotoxin A (Vi - rEPA) has undergone clinical trails in Vietnam. A two dose regimen administered to children between 2 and 5 years of age was found to be highly immunogenic and approximately 91% effective in preventing disease. More studies in younger age groups will be required in order to assess the clinical usefulness of this new vaccine.