Dennis L. Murray
Relapsing fever is a vector-borne, remittent febrile illness, transmitted by lice and ticks, which is caused by several species of spirochetes of the genus Borrelia.
EPIDEMIOLOGY
Louse-borne (epidemic) relapsing fever is caused by B recurrentis. The body louse, Pediculus humanus, becomes infected by ingesting blood from infected humans, and the disease is transmitted when the louse is crushed and the spirochetes (Borrelia) penetrate human skin of a new host.1 Epidemic Borrelia infection has disappeared from the United States, along with louse-borne typhus. The disease does occur in other areas of the world, particularly Africa, where epidemics occur, especially among the homeless and refugee populations. Endemic relapsing fever is transmitted by soft-bodied Ornithodoros ticks. They are distributed worldwide and have painless bites. Most tick-borne relapsing fever in the United States occurs in the western states4 and is caused by B hermsii.1 Exposure to rodent-infested cabins or caves is important to human infection with Borrelia associated with tick-borne disease.1,2,5-7
Borrelia do not infect blood cells directly, but the concentration of the spirochetes in the blood correlates directly with severity. Repeated episodes of spirochetemia, each involving a different predominate antigenic variant, account for the cyclic nature of the disease.3,7-9 IgM antibodies help clear the more common variant each time, but other variants proliferate between episodes.10 Organisms can be sequestered in the liver, spleen, central nervous system, and/or bone marrow.10,11 Periodic relapses continue to occur until the number of antigenic variations are eliminated or the patient receives effective treatment.
CLINICAL MANIFESTATIONS
After a variable incubation period (4–18 days, mean of 7 days), the illness starts abruptly with fever, chills, headache, myalgia, and arthralgia. Conjunctivitis, petechiae, and hepatosplenomegaly with tenderness may be present. This first phase of illness typically lasts 3 to 6 days and subsides spontaneously.10 During the next 5 to 7 days, the infected patient experiences extreme fatigue and may have a diffuse maculopapular rash, but the patient is afebrile or has only a low-grade fever.
Return of fever and chills after 4 to 14 days signals the relapse phase of the disease.11 Several such relapses can occur (up to 10 in tick-related cases; a lesser number in louse-borne disease),9 although the duration of relapses typically becomes shorter and milder over time. Relapsing fever may resolve even among untreated patients with tick-borne disease. Myocarditis is prominent in fatal cases of tick-borne disease.
Vertical transmission of infection can occur, resulting in abortion or severe infection of the neonate. Children and pregnant women tend to have a more prolonged disease course.4
DIAGNOSIS
Relapsing fever may be suspected, along with typhus, when body lice (not head lice or crab lice) are prevalent, particularly with crowded and unsanitary conditions.1,13 With the endemic form, the disease should be suspected in patients with appropriate symptoms who have had exposure to environments where Ornithodoros ticks are located.1,6,10,14 In developing countries, malaria, typhoid fever, and rickettsial diseases may show clinical findings similar to those of epidemic relapsing fever. For the initial presentation of endemic relapsing fever, influenza, enterovirus, Colorado tick fever, Lyme borreliosis, Rickettsia, and Ehrlichia deserve consideration as a cause of illness.9,10 The periodic fever disorders, such as PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis), may resemble relapsing fever, but PFAPA is milder and the intervals between febrile episodes are longer.9
A definitive diagnosis is made by demonstrating the Borrelia on a blood smear.1,2,9 Spirochetes can be observed by dark-field microscopy, and in Wright, Giemsa, or acridine orange–stained preparations of either thick or thin blood smears. Culture is an insensitive method for confirming the diagnosis. Immunofluorescence testing and polymerase chain reaction primers and probes have been developed but may not be commercially available.15,16 Serologic tests are not well standardized; cross-reactions occur with other spirochetes, including the infectious agent of Lyme disease, B burgdorferi.2,17
TREATMENT
Treatment with penicillin, tetracyclines, or erythromycin is effective. A macrolide antibiotic is considered the drug of choice for children younger than 8 years of age.1 Intravenous penicillin is an effective drug for the initial illness, especially when central nervous system involvement is suspected. Ceftriaxone may also be effective. Doxycycline and erythromycin have been used as single-dose treatment for louse-borne disease in Ethiopia.9 Sudden killing of many spirochetes and release of bacterial products may produce a life-threatening Jarisch-Herxheimer reaction, especially in louse-borne disease.18 A Jarisch-Herxheimer reaction is caused by massive cytokine release (tumor necrosis factor-α and other cytokines3), and usually manifests as fever, tachycardia, diaphoresis, rigors, and hypotension.2 For that reason, the patient needs very careful monitoring and may need intensive management, especially for low blood pressure, in the first 6 to 8 hours after the initial antimicrobial dose. Jarisch-Herxheimer reactions in children are generally milder than those in adults.1 For the febrile patient, it is safer to give as a first antimicrobial a low-dose oral penicillin (7.5 mg/kg of phenoxymethyl penicillin in a single dose) or intravenous aqueous penicillin G (10,000 U/kg by infusion over 30 minutes).9 Following this first dose, gradual clearing of spirochetes and defervescence should occur. The patient should then receive either erythromycin or tetracycline for 7 to 10 days to prevent relapse. For the afebrile child between relapses, oral erythromycin or tetracycline alone can be given.1,9
With appropriate therapy, case fatality rates are less than 5% in tick-borne disease.12 Mortality rates are higher in untreated louse-borne relapsing fever.1,9
PREVENTION
Environmental use of insecticides on interior walls of primitive buildings and dwellings has reduced the frequency of disease caused by ticks.1,10 Good personal hygiene and prompt treatment of louse infestation with effective pediculocides can aid in controlling this vector. Use of permethrin or lindine on clothing is an essential adjunct to prevention of tickborne disease.1 Tick-borne disease is reportable to the state health department in some US states,9and louse-borne disease is reportable to the World Health Organization.9