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PATHOGEN DESCRIPTION

Salmonella typhi, an obligate intracellular pathogen, is the cause of typhoid fever. The organism is a gram-negative, nonsporing bacillus, actively motile with numerous long peritrichous flagellae. Other salmonellae, S.paratyphi A and B, cause paratyphoid fever, which is similar to typhoid fever but usually a milder disease clinically. These organisms can be differentiated based on their cultural characteristics. S. typhi and S. paratyphi have a strong host specificity for man and do not naturally infect animals. In most countries in which these diseases have been studied, the ratio of disease caused by S. typhi to that caused by S. paratyphi is about 10 to 1. (For further information on S.typhi, see Hornick, 1982, 1985.)

HOST IMMUNE RESPONSE

Infection with S. typhi confers some immunity, but second illnesses can occur following reexposure. It appears that immunity can be overwhelmed by the ingestion of a large number of S. typhi, as was suggested by studies in which volunteers with previously documented typhoid fever ingested 105S. typhi and had a clinical attack rate similar to that of a control group.

Several specific antibody responses have been demonstrated after typhoid fever. However, there is no evidence that these responses to O, H, and Vi antigens are protective against infection or illness. It is likely that secretory IgA is also produced in the small intestine, but this has not been well documented.

Animal models indicate that the cellular immune response probably is of primary importance in the protection against typhoid fever. Host defense relies on macrophage microbicidal mechanisms to kill phagocytosed bacteria. Enhancement of macrophage function is directed by specifically committed activated T-lymphocytes and controlled by a family of effector and regulatory T-cells. Current knowledge about immunity to S. typhi in humans does not permit more than general speculation about the way in which cell-mediated immunity is stimulated by either prior disease or a vaccine to prevent acute typhoid fever and its complications, or the development of the chronic carrier state (Germanier, 1984; Hornick, 1982, 1985; Levine et al., 1983).

DISTRIBUTION OF DISEASE

Geographic Distribution

Typhoid fever has worldwide distribution, but is especially prevalent in less-developed countries. Areas with environmental conditions conducive to the spread of the disease or with populations with a high prevalence of biliary tract disease and chronic carriage of S. typhi have higher rates of the disease (Germanier, 1984).



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