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Relapsing fever is caused by infection with any of several species of Borrelia spirochetes. Physicians in ancient Greece distinguished relapsing fever from other febrile disorders by its characteristic clinical presentation: two or more fever episodes separated by varying periods of well-being. In the nineteenth century, relapsing fever was one of the first diseases to be associated with a specific microbe by virtue of its characteristic laboratory finding: the presence of large numbers of spirochetes of the genus Borrelia in the blood.

The host responds with systemic inflammation that results in an illness ranging from a flulike syndrome to sepsis. Other manifestations are the consequences of central nervous system (CNS) involvement and coagulopathy. Antigenic variation of the spirochetes’ surface proteins accounts for the infection’s relapsing course. Acquired immunity follows the serial development of antibodies to each of the several variants appearing during an infection. Treatment with antibiotics results in rapid cure but at the risk of a moderate to severe Jarisch-Herxheimer reaction.

image Louse-borne relapsing fever caused large epidemics well into the twentieth century and currently occurs in northeastern Africa. At present, however, most cases of relapsing fever are tick-borne in origin. Sporadic cases and small outbreaks are focally distributed on most continents, with Africa most affected. In North America, the majority of reports of relapsing fever have been from the western United States and Canada. Nevertheless, the recent discovery that another species in the relapsing fever group causes human disease in the same geographic distribution as Lyme disease (Chap. 82) confounds epidemiologic distinctions between the two major types of Borrelia infection.


Coiled, thin microscopic filaments that swim in one direction and then coil up before heading in another were first observed in the blood of patients with relapsing fever in the 1880s ( These microbes were categorized as spirochetes and grouped as several species in the genus Borrelia. It was not until the 1960s that the organisms were isolated in pure culture. The breakthrough cultivation medium and its derivatives are rich in their ingredients, ranging from simple (e.g., amino acids and N-acetylglucosamine) to more complex (e.g., serum and protein hydrolysates). The limited biosynthetic capacity of Borrelia cells is accounted for by a genome content one-quarter that of Escherichia coli.

Like other spirochetes, the helix-shaped Borrelia cells have two membranes, the outer of which is more loosely secured than in other double-membrane bacteria, such as E. coli. As a consequence, fixed organisms with damaged membranes can assume a variety of morphologies in smears and histologic preparations. The flagella of spirochetes run between the two membranes and are not on the cell surface. Although technically gram-negative in their staining properties, the 10- to 20-μm-long Borrelia cells, with a diameter of 0.1–0.2 μm, are too narrow to be seen by bright-field microscopy of Gram-stained specimens.

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