Tick-Borne Relapsing Fever—North American Style
abstract & commentary
Synopsis: Tick-borne relapsing fever is a geographically widespread desease that often goes undiagnosed and unreported.
Source: Dworkin MS, et al. Tick-borne relapsing fever in the Northwestern United States and Southwestern Canada. Clin Infect Dis 1998;26:122-131.
Dworkin and colleagues reviewed 182 cases of tick-borne relapsing fever (TBRF) identified in the states of Washington, Oregon, and Idaho, as well as the province of British Colombia over an approximately 15-year period. One hundred thirty-three of the cases were confirmed by visualization of the organism in a peripheral blood smear, while 49 cases were classified as probable (compatible clinical history together with either an exposure associated with a confirmed case or a positive Western blot).
Patients ranged in age from birth to 81 years (median, 33 years). The youngest was a neonate born to one of four women infected during pregnancy. Cases occurred throughout the year but most commonly during the summer months. Known or presumed tick exposure usually occurred in rural habitats. Three-fourths of the patients noted rodents (mice, squirrels, chipmunks, or rats) at the exposure site. The median elevation of the sites of exposure was 2131 feet (range, 100-6436 feet).
The median maximum recorded body temperature was 40°C, and the WBC was greater than 14,000/mm3 in most; thrombocytopenia was common. Proteinuria and microscopic hematuria were frequently detected. Only one-fifth of patients were diagnosed before they had at least one relapse; 31% had three relapses. Consistent with this observation, the diagnosis was frequently missed. At one hospital, seven (44%) of 16 patients had been discharged with a diagnosis of Lyme disease.
Blood cultured in Barbour-Stoenner-Kelly (BSK) II medium was positive within 48 hours in all 10 subjects who had not received antibiotics in whom this was attempted. While antibody tests for infection with Borrelia hermsii, the etiologic agent of TBRF, were usually positive, there was evidence of frequent method-independent cross-reactivity with Borrelia burgdorferi. However, while there was frequent cross-reactivity for a number of bands on western blot, careful analysis could differentiate the two.
Thirty-three (54.1%) of 61 patients, for whom relevant clinical information was available, had an apparent Jarisch-Herxheimer reaction within two hours of antibiotic administration. At least one was admitted to an ICU as a result.
Comment by Stan Deresinski, MD, FACP
Relapsing fever comes in two flavors: louse-borne and tick-borne. Louse-borne (epidemic) relapsing fever is caused by Borrelia recurrentis. The countries with the highest incidence of infection are Ethiopia and Sudan, but this infection has also occurred in other areas of Africa and Asia, as well as areas of the Andean highlands and in Guatemala. Its epidemiology is largely that of the body louse, Pediculus humanus, and, thus, it presents a danger in circumstances of crowding and poor hygiene, as occurs with migration of large numbers of refugees.
TBRF, also called endemic relapsing fever, is transmitted by the bite of soft-bodied ticks of the genus Ornithodoros, and the various species of Borrelia causing TBRF are often named after the species of tick that serves as its vector. The tick exposure often goes unnoticed since Ornithodorus usually cause painless bites and drop off after feeding for only 30-60 minutes.
TBRF occurs in areas of North and South America, Africa, Europe, and Asia. At least nine tick-borne Borrelia species are reported to be pathogenic in man, each endemic within a particular geographic area (Barbour A, Hayes S. Microbiol Rev 1986;50:381-400). Borrelia turicatae, transmitted by Ornithodorus turicatae, is found in the southwestern U.S. and northern Mexico, while B. hermsii, transmitted by Ornithodorus hermsii, is endemic in the western U.S. and southern British Colombia. Patients often are exposed while in and around inadequately rodent-proofed dwellings.
In either form of relapsing fever, patients abruptly develop high fever, rigors, and headache. Febrile episodes last 1-3 days, with intervening afebrile intervals of 3-10 days. In untreated louse-borne relapsing fever, there is usually only one relapse that is less severe and shorter than the initial episode. Nonetheless, this infection is, in contrast to TBRF, associated with a high mortality rate. Relapses of TBRF, of which an average of three occur in untreated disease, tend to be less severe than the initial episode.
The diagnosis is usually made by observation of the spirochete on a routine, Wright-stained, peripheral blood smear; dark filed examination of unstained blood allows detection of the organism’s characteristic pattern of motility. Smears are best obtained at or near the peak of fever. Organisms usually cannot be visualized during the inter-febrile intervals. Both B. hermsii and B. turicatae may be readily recovered in culture in BSK II medium.
The first effective drug in the treatment of relapsing fever, penicillin, was reported in 1945 (Taft W, Pike J. JAMA 1945;129:1002-1005). However, the current drug of choice for treatment of both forms of relapsing fever is tetracycline because the relapse rate after penicillin therapy may be high. An alternative, although poorly documented, choice is erythromycin. Central nervous system involvement may occur, especially with B. turicatae infection, and it has been recommended that when this is the case, consideration should be given to prolonged high-dose parenteral therapy with penicillin, cefotaxime, or ceftriaxone (Cadavid D, Barbour AG. Clin Infect Dis 1998;26:151-164).
As in the series discussed here, the frequency of Jarisch-Herxheimer reaction is remarkably high. A recent study has demonstrated that pretreatment with sheep polyclonal Fab antibody against TNF-a prior to penicillin administration suppresses the Jarisch-Herxheimer reaction in patients with louse-borne relapsing fever (Fekade D, et al. N Engl J Med 1996;335:311-315). Meptazinol, an opiate antagonist, has also been demonstrated to provide benefit, while both corticosteroids and pentoxifylline do not (Teklu B, et al. Lancet 1983;1:835-839; J Infect Dis 1996;174:627-630).
TBRF is an underdiagnosed and under-reported infection. The authors point out that only 11 serologically confirmed cases of Lyme disease were reported in Washington state between 1991 and 1994, a period during which 24 cases of TBRF had been reported. Since, as described above, there is significant serological cross-reactivity between B. hermsii and B. burgdorferi, the serological diagnosis of Lyme disease, already problematic, is fraught with even greater difficulty in areas in which TBRF occurs. This is true not only in the areas reported on by Dworkin and colleagues. For instance, there were 195 cases of TBRF reported in California between 1970 and 1992 (Calif Morb August 21, 1992; #33/#34).
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