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Shigellosis
 
Shigellosis is an infectious disease caused by various species of Shigella. People infected with Shigella develop diarrhea, fever and stomach cramps starting a day or two after they are exposed to the bacterium. The diarrhea is often bloody. Shigellosis usually resolves in 5 to 7 days, but in some persons, especially young children and the elderly, the diarrhea can be so severe that the patient needs to be hospitalized. A severe infection with high fever may also be associated with seizures in children less than 2 years old. Some persons who are infected may have no symptoms at all, but may still transmit the bacteria to others.

Shigella were discovered over 100 years ago by the Japanese microbiologist, Shiga, for whom the genus is named. There are four species of Shigella: S. boydii, S. dysenteriae, S. flexneri, and S. sonnei. Shigella sonnei, also known as Group D Shigella, accounts for over two-thirds of the shigellosis in the United States. Shigella flexneri, or Group B Shigella, accounts for almost all of the rest. Other types of Shigella are rare in this country, although they are important causes of disease in the developing world. One type, Shigella dysenteriae type 1, causes deadly epidemics in many developing regions and nations.

Diagnosis
Determining that Shigella is the cause of the illness depends on laboratory tests that identify the bacteria in the stool of an infected person. Some of the tests may not be performed routinely, so the bacteriology laboratory should be instructed to look for the organism. The laboratory can also do tests to determine which type of Shigella is involved, and which antibiotics, if any, would be best for treatment.

Figure 1. Several media have been designed to selectively grow enteric bacteria and allow differentiation of Salmonella and Shigella from E. coli. The primary plating media shown here are eosin methylene blue (EMB) agar, MacConkey agar, ENDO agar, Hektoen enteric (HE) agar and Salmonella-Shigella (SS) agar.

Treatment
Shigellosis can usually be treated with antibiotics. The antibiotics commonly used are ampicillin, trimethoprim/sulfamethoxazole (also known as Bactrim or Septra), nalidixic acid and the fluoroquinolone, ciprofloxacin. Appropriate treatment kills the bacteria present in the gastrointestinal tract and shortens the course of the illness.

Some Shigella have become resistant to antibiotics and inappropriate use of antibiotics to treat shigellosis can make the organisms more resistant in the future. Persons with mild infections will usually recover quickly without antibiotic treatment. Therefore, when many persons in a community are affected by shigellosis, antibiotics are sometimes used selectively to treat only the more severe cases. Antidiarrheal agents such as loperamide (Imodium) or diphenoxylate with atropine (Lomotil) are likely to make the illness worse and should be avoided.

Reiter's syndrome
Persons with diarrhea usually recover completely, although it may be several months before their bowel habits are entirely normal. About 3% of persons who are infected with Shigella flexneri  may subsequently develop pains in their joints, irritation of the eyes, and painful urination. This condition is called Reiter's syndrome. It can last for months or years, and can lead to chronic arthritis which is difficult to treat. Reiter's syndrome is a late complication of S. flexneri infection, especially in persons with a certain genetic predisposition, namely HLA-B27. [Human Leukocyte Antigen B27 (HLA-B27) is a class I surface antigen in the major histocompatibility complex (MHC) on chromosome 6 and presents microbial antigens to T-cells. HLA-B27  has been strongly associated with a certain set of autoimmune diseases referred to as the "seronegative spondyloarthropathies".]

Hemolytic Uremic Syndrome (HUS)
Hemolytic uremic syndrome (HUS) can occur after S. dysenteriae type 1 infection. Convulsions may occur in children; the mechanism may be related to a rapid rate of temperature elevation or metabolic alterations, and is associated with the production of the Shiga toxin, which is discussed below.

Transmission

Shigella is transmitted from an infected person to another usually by a fecal-oral route. Shigella are present in the diarrheal stools of infected persons while they are ill and for a week or two afterwards. Most Shigella infections are the result of the bacterium passing from stools or soiled fingers of one person to the mouth of another person. This happens when basic hygiene and handwashing habits are inadequate. It is particularly likely to occur among toddlers who are not fully toilet-trained. Family members and playmates of such children are at high risk of becoming infected. The spread of Shigella from an infected person to other persons can be stopped by frequent and careful handwashing with soap, practiced by all age groups.

Part of the reason for the efficiency of transmission is because a very small inoculum (10 to 200 organisms) is sufficient to cause infection. As a result, spread can occur easily by the fecal-oral route and readily occurs in settings where hygiene is poor.

Epidemics may be foodborne or waterborne. Shigella infections may be acquired from eating food that has become contaminated by infected food handlers. Vegetables can become contaminated if they are harvested from a field with contaminated sewage or wherein infected field workers defecate. Shigella can also be transmitted by flies. Flies can breed in infected feces and then contaminate food. Shigella infections can be acquired by drinking or swimming in contaminated water. Water may become contaminated if sewage runs into it, or even if someone with shigellosis swims or bathes or, worse, defecates, in it.

Immunity and Vaccines

Once someone has had shigellosis, they are not likely to get infected with that specific type again for at least several years. However, they can still get infected with other types of Shigella. Presumably, this immunity is due to secretory IgA. Circulating antibodies can also be detected in immune individuals. Although CMI may not be ruled out, the cellular immune response is ineffective against Shigella in animal models, and Shigella-specific cytotoxic T lymphocytes have not been isolated from convalescent individuals.

In addition, factors that permit the bacterium to optimize its lifestyle in the human colon may also have been acquired by means of horizontal gene transmission from other enteric bacteria in the colon after acquisition of the prototypic virulence plasmid. An example of this is the acquisition by horizontal transfer of O-antigen genes, such as those present on the virulence plasmid of S. sonnei, and subsequent inactivation of native O-antigen genes (30). Serotypic diversity due to the variations in O antigen is seen among Shigella strains. Such diversity likely facilitates evasion of the host humoral immune response.

Studies are underway around the world to develop a vaccine to prevent shigellosis. Since the virulence of Shigella is well-understood, and considering the present art of vaccine development, it seems that vaccination should be feasible. The need of the vaccine is based on the burden of disease globally: there are 160 million cases of shigellosis in the world each year, resulting in about 1.5 million deaths. Three approaches to shigella vaccine development that are under active investigation are: 1) parenteral O-specific polysaccharide conjugate vaccines; 2) nasal proteosomes delivering Shigella LPS; and 3) live, attenuated invasive shigella deletion mutants that are administered orally.

Several live attenuated Shigella vaccines of different serotypes have been shown to be safe, immunogenic, and in one case, effective against challenge with virulent strains. The ability to invade epithelial cells remains critical for the success of these vaccine candidates. Live, orally administered Shigella vaccine derivatives are also being evaluated as multivalent mucosal vaccines able to deliver bacterial antigens to the gut associated lymphoid tissues (GALT).

Incidence and Risk of Infection

In the United States, there are approximately 14,000 laboratory-confirmed cases of shigellosis and an estimated 448,240 total cases (85% due to S. sonnei) that occur  each year, according to CDC. Groups at increased risk of shigellosis include children in child-care centers and persons in custodial institutions, where personal hygiene is difficult to maintain.

In the developing world, S. flexneri predominates. Epidemics of S. dysenteriae type 1 have occurred in Africa and Central America with case fatality rates of 5-15%.