Relapsing fever is a recurring febrile disease caused by several species of the spirochete Borrelia and transmitted by lice or ticks. Symptoms are recurrent febrile episodes with headache, myalgia, and vomiting lasting 3 to 5 days, separated by intervals of apparent recovery. Diagnosis is clinical, confirmed by staining of peripheral blood smears. Treatment is with a tetracycline, doxycycline, erythromycin, or procaine penicillin G.
Spirochetes are distinguished by the helical shape of the bacteria. Pathogenic spirochetes include Treponema, Leptospira, and Borrelia. Both Treponema and Leptospira are too thin to be seen using brightfield microscopy but are clearly seen using darkfield or phase microscopy. Borrelia are thicker and can also be stained and seen using brightfield microscopy.
The insect vector for relapsing fever may be the human body louse or certain ticks, depending on geographic location.
Louse-borne relapsing fever is rare in the US; it is endemic only in northeast Africa (Ethiopia, Sudan, Eritrea, Somalia) and was recently diagnosed in Europe in refugees from these African countries. Louse-borne relapsing fever tends to occur in epidemics, particularly in regions affected by war, and in refugee camps. The louse is infected by feeding on a febrile patient; humans are the only reservoir. The louse cannot excrete B. recurrentis in saliva or feces (1). If the louse is crushed on a new host, Borrelia recurrentis is released and can enter abraded skin or bites. B. recurrentis also is able to penetrate intact mucosa and skin. Intact lice do not transmit disease.
Tick-borne relapsing fever can be transmitted by soft-bodied ticks of the genus Ornithodoros or hard-bodied Ixodes scapularis ticks.
Tick-borne relapsing fever transmitted by soft-bodied ticks involves one of several Borrelia species and is endemic in the Americas, Africa, Asia, and Europe. In the US, the disease is generally confined to the western states, where occurrence is highest between May and September. Ticks acquire the spirochetes from rodent reservoirs. Humans are infected when spirochetes in the tick’s saliva or excreta enter the skin rapidly as the tick bites. Infection is more likely to be acquired by people sleeping in rodent-infested cabins in the mountains and has also been associated with spelunking.
The hard-bodied tick I. scapularis (which also transmits Lyme disease) can transmit Borrelia miyamotoi. Because I. scapularis is also the vector for Lyme disease, tick-borne relapsing fever transmitted by this tick occurs in the same places where Lyme disease occurs. Coinfection with other Borrelia diseases such as Lyme disease has also been reported.
Image courtesy of James Gathany via the Public Health Image Library of the Centers for Disease Control and Prevention.
Borrelia has also been rarely transmitted by blood transfusion.
Загальні джерела літератури
1. Raoult D, Roux V: The body louse as a vector of reemerging human diseases. Clin Infect Dis 29(4):888–911, 1999. doi: 10.1086/520454
Symptoms and Signs of Relapsing Fever
Because the soft ticks of the genus Ornithodoros feed transiently and painlessly at night and do not remain attached for a long time, most patients do not report a history of tick bite but may report an overnight exposure to caves or rustic dwellings.
When present, louse infestation is usually obvious.
The incubation period ranges from 3 to 11 days (median, 6 days).
The clinical manifestations of tick-borne and louse-borne relapsing fever are very similar. Symptoms correspond to the level of bacteremia and, after several days, resolve when Borrelia are cleared from the blood. Bacteremia and symptoms then return after a 1-week afebrile period. Symptoms are less severe with each subsequent return. A single relapse characterizes louse-borne relapsing fever, and up to 10 relapses may occur in tick-borne relapsing fever.
Sudden chills mark the onset, followed by high fever, tachycardia, severe headache, nausea, vomiting, muscle and joint pain, and often delirium. An eschar may be present at the site of the tick bite. An erythematous macular or purpuric rash may appear early over the trunk and extremities. Conjunctival, subcutaneous, or submucous hemorrhages may be present. Fever remains high for 3 to 5 days, then clears abruptly, indicating a turning point in the disease. The duration of illness ranges from 1 to 54 days (median, 18 days). Later in the several weeks’ course of the disease, jaundice, hepatomegaly, splenomegaly, myocarditis, and heart failure may occur, especially in louse-borne disease.
Other symptoms may include ophthalmitis, iridocyclitis, exacerbation of asthma, and erythema multiforme. Neurologic complications (eg, meningitis, meningoencephalitis, radiculomyelitis) may occur; they are more common in tick-borne relapsing fever. Spontaneous abortion can occur.
Patients are usually asymptomatic for several days to ≥ 1 week between the initial episode and the first relapse. Relapses, related to the cyclic development of the parasites, occur with a sudden return of fever and often arthralgia and all the former symptoms and signs. Jaundice is more common during relapse. The illness clears as before, but 2 to 10 similar episodes may follow at intervals of 1 to 2 weeks. The episodes become progressively less severe, and patients eventually recover as they develop immunity.
Diagnosis of Relapsing Fever
Darkfield or brightfield microscopy
The diagnosis of relapsing fever is suggested by recurrent fever and confirmed by visualization of spirochetes in the blood during a febrile episode. The spirochetes may be seen on darkfield or brightfield examination or Wright- or Giemsa-stained thick and thin blood smears. (Acridine orange stain for examining blood or tissue is more sensitive than Wright or Giemsa stain.)
Serologic tests are unreliable. Serologic tests for syphilis and Lyme disease may be falsely positive.
B. miyamotoi can also be diagnosed by polymerase chain reaction (PCR) tests.
Mild polymorphonuclear leukocytosis and thrombocythemia may occur.
Differential diagnosis includes Lyme arthritis, malaria, dengue, yellow fever, leptospirosis, typhus, influenza, and enteric fevers.
According to the Centers for Disease Control and Prevention (CDC), the causative Borrelia species is often inferred from the location of the patient’s exposure. For example, in the US in a western state at high elevation (1200 to 8000 feet), soft-bodied tick-borne relapsing fever is usually caused by B. hermsii, whereas in a southern state at low elevation, specifically Texas or Florida, it is usually caused by B. turicatae (1).
Довідковий матеріал щодо діагностики
1. Centers for Disease Control and Prevention (CDC): Tick-borne relapsing fever: Information for clinicians. Accessed 9/22/2022.
Prognosis for Relapsing Fever
The case fatality rate is generally < 5% with treatment but may be considerably higher in very young, pregnant, old, malnourished, or debilitated people or during epidemics of louse-borne fever.
For louse-borne relapsing fever, death occurs in 10 to 40% of untreated patients and in 2 to 5% of treated patients.
For tick-borne relapsing fever, the prognosis is better. The case fatality rate is < 10% for untreated patients and is < 2% for treated patients.
Treatment of Relapsing Fever
Tetracycline, doxycycline, erythromycin, or procaine penicillin G
In relapsing fever transmitted by ticks, tetracycline or erythromycin 500 mg orally every 6 hours or doxycycline 100 mg orally every 12 hours is given for 10 days.
For louse-transmitted relapsing fever, a single 500-mg oral dose of tetracycline or erythromycin, a single 200-mg oral dose of doxycycline, or a single dose of procaine penicillin G 400,000 to 800,000 units IM is effective. Children < 8 years of age are given erythromycin estolate 10 mg/kg orally 3 times a day.
When vomiting or severe disease precludes oral administration or when the central nervous system is affected, parenteral ceftriaxone 2 g once a day or 1 g every 12 hours for 10 to 14 days, doxycycline 1 to 2 mg/kg IV every 12 to 24 hours, or penicillin G 3 million units IV every 4 hours may be given to adults or children > 8 years of age. Children < 8 years are given penicillin G 25,000 units/kg IV every 6 hours.
Therapy should be started early during fever. A Jarisch-Herxheimer reaction may occur within 2 hours of starting therapy. Severity of the Jarisch-Herxheimer reaction may be lessened by giving acetaminophen 650 mg orally 2 hours before and 2 hours after the first dose of antibiotic therapy). This reaction tends to be more severe in patients with louse-borne relapsing fever treated with penicillin.
Dehydration and electrolyte imbalance should be corrected with parenteral fluids.
Acetaminophen with oxycodone or hydrocodone may be used for severe headache.
Nausea and vomiting should be treated with prochlorperazine 5 to 10 mg orally or IM once a day to 4 times a day.
If heart failure occurs, specific therapy is indicated.
Ключові моменти
Relapsing fever is caused by several Borrelia species and is transmitted by lice or ticks.
Patients have sudden chills, high fever, severe headache, nausea, vomiting, muscle and joint pain, and often delirium and/or a rash on the trunk and extremities; jaundice, hepatomegaly, splenomegaly, myocarditis, and heart failure may occur, especially in louse-borne disease.
Untreated patients have 2 to 10 relapses at 1- to 2-week intervals; relapses manifest with a sudden return of fever and often arthralgia and all the former symptoms and signs, although they may be less severe.
Diagnose using darkfield microscopy or Wright- or Giemsa-stained thick and thin blood smears; serologic tests are unreliable.
Treat with tetracycline, doxycycline, or erythromycin.
Додаткова інформація
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Centers for Disease Control and Prevention (CDC): Louse-Borne Relapsing Fever: Information for clinicians about distribution, transmission, and prevention of tick-borne relapsing fever and information about louse-borne relapsing fever and B. miyamotoi disease
