An attack of typhus confers long immunity. Many children in regions where typhus is frequent may contract subclinical or mild cases that protect them somewhat from a later, more severe infection. Because R. prowazekii persists in the tissues of its victims even after recovery from the disease, however, symptoms of the disease may reappear years later, especially under conditions of stress when a victim's immune system is depressed. This phenomenon was noted but not recognized in 1898, when New York physician Nathan Brill described a disease frequently diagnosed as typhoid but having symptoms more closely related to typhus. In 1910 Brill published an exhaustive study of 221 cases, and his thoroughness led to the designation of "Brill's disease" as a catchall for unknown, typhus-like symptoms. Two years later, U.S. Public Health Service investigators John F. Anderson and Joseph Goldberger demonstrated reciprocal cross-immunity in monkeys between Brill's disease and epidemic typhus.

For the next two decades, moreover, because of ignorance surrounding many other rickettsial diseases, illnesses exhibiting typhuslike symptoms anywhere in the world were often classified as Brill's disease. In 1934 Zinsser correctly hypothesized from epidemiological data that Brill's disease was a recrudescence of epidemic typhus in persons who had earlier suffered an attack of the classic disease. During the 1950s, laboratory investigations confirmed his hypothesis, and the disease was renamed Brill-Zinsser disease.

The first laboratory diagnostic test for typhus grew out of a chance observation in 1916 by Viennese physician Edmund Weil and his English colleague Arthur Felix that a strain of Bacillus proteus was agglutinated by the sera of typhus patients. Later studies revealed that the phenomenon was a chance antigenic "fit," but the Weil-Felix reaction, as it came to be called, provided a laboratory tool that became useful in several rickettsial diseases. In 1941 a more specific complement-fixation test was developed, and during the 1970s a variety of new techniques have improved the sensitivity and accuracy of laboratory diagnosis.

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