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Relapsing Fever

  • Author: Kauser Akhter, MD; Chief Editor: Michael Stuart Bronze, MD  more...
 
Updated: Dec 10, 2014
 

Background

Relapsing fever, as the name implies, is characterized by recurrent acute episodes of fever. These are followed by periods of defervescence of increasing duration. The infection is caused by various spirochete species of the Borrelia genus. Spirochetes are a unique species of bacteria that also cause syphilis, Lyme disease, and leptospirosis.[1] The fever relapses result from spirochetal antigenic variation. Relapsing fever, if untreated, may be fatal.

Relapsing fever is an arthropod-borne infection spread by lice (Pediculus humanus) and ticks (Ornithodoros species). Two main forms of this infection exist: tick-borne relapsing fever (TBRF) and louse-borne relapsing fever (LBRF).

TBRF is caused by 8 or more Borrelia species (eg, Borrelia hermsii, Borrelia turicatae, Borrelia parkeri,Borrelia duttonii), while LBRF is caused solely by Borrelia recurrentis.[1]

TBRF and LBRF vary significantly in terms of epidemiology. A soft-bodied tick (Ornithodoros) transmits multiple Borrelia species that cause endemic relapsing fever, whereas the human body louse transmits B recurrentis, which causes an epidemic form of relapsing fever. Unlike hard ticks, Ornithodoros adult ticks are able to live for many years, feed repeatedly on blood meals, lay eggs, and perpetuate their life cycle.[2] In addition, Ornithodoros ticks may survive long periods in a fasting state. In fact, Ornithodoros turicata ticks have been known to transmit spirochetes in the laboratory setting after 7 years without a blood meal.[2]

Humans are the sole host of B recurrentis, while mammals (eg, cattle, pigs, prairie dogs, ground and tree squirrels, chipmunks) and reptiles (lizards, snakes, gopher tortoises) may serve as a reservoir for tick-borne Borrelia species.[2]

The first reported case of TBRF in the United States was identified in 1905 in New York. The patient had previously traveled to Texas.[3] In the United States, where fewer than 30 cases of TBRF are diagnosed each year,[4] B hermsii and B turicatae cause most outbreaks. A recently discovered Borrelia species, Borrelia miyamotoi, has been found in hard-bodies ticks in regions where Lyme disease is endemic.

TBRF is reported worldwide, except Antarctica, Australia, and the Pacific Southwest.

LBRF is uncommon in the United States but is occasionally observed in travelers returning from endemic regions (see International). The last reported outbreak of LBRF in the United States occurred in 1871.[5]

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Pathophysiology

Spirochetes are wavy filamentous bacteria with one or more flagellae at each end.[1] Most borrelial spirochetes measure 10-30 µm long X 0.2 µm wide. In TBRF, the spirochetes are transmitted via the bite of an infected tick, whereas, in LBRF, contact with hemolymph from the human body louse (eg, from scratching-induced louse crushing) is the mode of spirochete transfer.

Most Ornithodoros tick bites occur at night and go unnoticed in most individuals.[6] Other described modes of transmission in the literature include blood transfusions, a laboratory worker who was bitten by an infected monkey with gingival bleeding, and intravenous drug use.[2] In rare cases, transplacental transmission has been reported.[7] The spirochete is not transmitted via aerosol, saliva, urine, feces, or semen.

The recently discovered B miyamotoi species is transmitted by tick bite and may be transmissible via blood transfusion.[8] Recent data demonstrate that this species resists human complement-mediated killing.[9]

Spirochetes enter breaks in the skin or mucous membranes, gain access to the vasculature, and disseminate to the spleen, bone marrow, liver, lungs, kidneys, and CNS. All it takes is a single spirochete to initiate the infectious process.

Borrelia species are able to induce cycles of disease by varying antigen expression and by displaying new outer-surface proteins during the disease course. The antigenic variants are referred to as serotypes. The proteins are named either variable small proteins or variable large proteins and are encoded within plasmid DNA. Alteration of these proteins prevents elimination of the spirochetes by the immune system, leading to recurrent febrile episodes.[2] In 2008, Thein et al identified and described the first porin of relapsing fever, Oms38, which is present in the outer membranes of B hermsii, B turicatae, B duttonii, and B recurrentis.[10]

Recent experiments in mice have shown that interleukin-10 (IL-10) may play a protective role in down-regulating inflammation and spirochete load.[11, 12] Extraordinarily high serum IL-10 levels have been found in patients with LBRF in whom the disease course is relatively mild.[12] Hemorrhage and thrombosis were more commonly observed in IL-10–deficient mice.[12]

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Epidemiology

Frequency

United States

TBRF has been reported in 14 states west of the Mississippi river, including Arizona, California, Colorado, Idaho, Kansas, Montana, Nevada, New Mexico, Oklahoma, Oregon, Texas, Utah, Washington, and Wyoming.[13] It has also been reported in Ohio. TBRF usually occurs during the summer in people who are on vacation and/or who are traveling to mountainous regions (elevation >8000 ft).[13] Cases of TBRF have been reported in persons inhabiting seasonally occupied lake areas and cabins infested with rodents and/or their ticks. During winter, the ticks are attracted to heat and carbon dioxide generated from indoor fires.[13]

International

TBRF is endemic in Canada (southern portion of British Columbia), Mexico, Central and South America, central Asia, Africa, the Mediterranean region, and Russia.[14]

LBRF is endemic in Ethiopia and Sudan, especially during the rainy season. The disease typically occurs in areas of war, famine, mass migrations, or overcrowding.[4] Homeless people in crowded shelters are also at risk of LBRF. In a study of 930 homeless people in Marseilles, France, body lice were found in 22%, and immunoglobulin G (IgG) to B recurrentis was found in 15 individuals.[15]

Mortality/Morbidity

In the United States, TBRF carries a low mortality rate. Overall, TBRF carries a mortality rate of less than 2% (in treated patients) to 4-10% (in untreated individuals).[16] LBRF carries a higher mortality rate, with a case-fatality rate of 4% (in treated patients) to 40% (in untreated individuals).[17] Two species of Borrelia associated with a relatively high rate of relapsing fever–related fatality include B recurrentis (causes LBRF; found in Africa, South America, Europe, and Asia) and B duttoni (causes TBRF; found in East Africa and transmitted by the soft tick Ornithodoros moubata).[2]

Poor prognostic indicators include coma on admission, bleeding, myocarditis, hepatic failure, bronchopneumonia, or co-infection with malaria,[18, 19] typhus, or typhoid fever.[20]

Natives of areas with LBRF endemicity usually experience a milder form of the disease than visitors.

Antibiotic treatment of relapsing fever commonly results in Jarisch-Herxheimer reaction (JHR; see Complications). This reaction tends to be more severe in patients with LBRF treated with penicillin. Pretreatment with steroids does not seem to alter this reaction.

TBRF has been linked to complications during pregnancy, resulting in neonatal death (up to 50%), spontaneous abortion, and premature birth (see Complications).[21]

Race

Relapsing fever has no racial predilection.

Sex

Relapsing fever has no sexual predilection.

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Contributor Information and Disclosures
Author

Kauser Akhter, MD Assistant Professor, Department of Internal Medicine, Florida State University College of Medicine; Associate Program Director, Infectious Diseases Fellowship Program, Orlando Health

Disclosure: Nothing to disclose.

Coauthor(s)

Pierre A Dorsainvil, MD Medical Director, HIV Specialist, Palm Beach County Main Detention Center; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Lake Ida Medical Center

Disclosure: Nothing to disclose.

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Joseph F John, Jr, MD, FACP, FIDSA, FSHEA Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina College of Medicine; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center

Joseph F John, Jr, MD, FACP, FIDSA, FSHEA is a member of the following medical societies: Charleston County Medical Association, Infectious Diseases Society of America, South Carolina Infectious Diseases Society

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

John M Leedom, MD Professor Emeritus of Medicine, Keck School of Medicine of the University of Southern California

John M Leedom, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, Phi Beta Kappa

Disclosure: Nothing to disclose.

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Peripheral blood smear in relapsing fever. (Image originally printed in Blevins SM, Greenfield RA, Bronze MS. Blood smear analysis in babesiosis, ehrlichiosis, relapsing fever, malaria, and Chagas disease. Cleve Clin J Med. Jul 2008;75(7):521-30. Reprinted with permission from the Cleveland Clinic.)
 
 
 
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