eMedicine Specialties > Infectious Diseases > Bacterial Infections

Relapsing Fever

Author: Kauser Akhter, MD, Clinical Assistant Professor, Internal Medicine, Florida State University College of Medicine; Infectious Diseases Faculty Practice, Orlando Health
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; 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
Contributor Information and Disclosures

Updated: Apr 9, 2009

Introduction

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.

Relapsing fever is a vector-borne infection that is spread by lice (Pediculus humanus) and ticks (Ornithodoros species). The infection is caused by various spirochete species of the Borrelia genus. Spirochetes are a morphologically unique species of bacteria and also cause syphilis, Lyme disease, and leptospirosis.¹

Louse-borne relapsing fever (LBRF) is caused by Borrelia recurrentis, while tick-borne relapsing fever (TBRF) is caused by at least 15 different Borrelia species (eg, Borrelia hermsii, Borrelia turicatae, Borrelia parkeri, Borrelia duttonii).

LBRF and TBRF vary significantly in terms of epidemiology. The human body louse transmits B recurrentis, which causes an epidemic form of relapsing fever, while a soft-bodied tick (Ornithodoros) transmits multiple Borrelia species that cause endemic 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. TBRF is reported worldwide.

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

Pathophysiology

Spirochetes are wavy filamentous bacteria with one or more flagellae at each end.¹ Borrelial spirochetes measure 3-25 μm X 0.2-0.5 μm. 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.

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.

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 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.⁸

Recent experiments in mice have shown that interleukin-10 (IL-10) may play a protective role in down-regulating inflammation and spirochete load.^9,10 Extraordinarily high serum IL-10 levels have been found in patients with LBRF in whom the disease course is relatively mild.¹⁰ Hemorrhage and thrombosis were more commonly observed in IL-10–deficient mice.¹⁰

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.¹¹ 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).¹¹ 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.¹¹

Eleven states are currently required to report TBRF to their local state health departments: Arizona, California, Colorado, Idaho, Nevada, New Mexico, Oregon, Texas, Utah, Washington, and Wyoming.¹¹

International

• TBRF is endemic in Canada (southern portion of British Columbia), Mexico, Central and South America, central Asia, Africa, and the Mediterranean region.
• 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.¹²

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).¹³ LBRF carries a higher mortality rate, with a case-fatality rate of 4% (in treated patients) to 40% (in untreated individuals).¹⁴ 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
• 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).¹⁵

Race

Relapsing fever has no racial predilection.

Sex

Relapsing fever has no sexual predilection.

Clinical

History

• The hallmark of both louse-borne relapsing fever (LBRF) and tick-borne relapsing fever (TBRF) is two or more episodes of high fever (usually >39°C), headaches, and myalgias. The clinical manifestations are also similar. The mean incubation time is 7 days (range, 4-18 or more days).¹⁶
• Fever occurs in conjunction with spirochetemia. In TBRF, the initial febrile episode lasts an average of 3 days (range, 12 h to 17 d),¹⁵ with an average of 7 days between the initial episode and first relapse. In LBRF, the first febrile episode usually lasts longer, 5.5 days on average (range, 4-10 d), with an average of 9 days between the first episode and first relapse. Patients may feel well between episodes, but the febrile periods are characterized by crises marked by labile blood pressures and pulse. The risk of death is greatest during and immediately following the period of hypotension.⁴
• Other symptoms of relapsing fever include chills, arthralgias, nausea/vomiting, abdominal pain, mental status changes, nonproductive cough, diarrhea, dizziness, neck pain, photophobia, rash, and dysuria.
• LBRF is associated with a higher incidence of jaundice, petechiae, hemoptysis, epistaxis, and CNS involvement.¹⁵
• On average, individuals with TBRF experience 3 relapses, while those with LBRF experience only one.⁴ Fever tends to be milder with relapses, which result from antigenic variation of the spirochete's outer-surface proteins.²

Physical

Findings in patients with relapsing fever include mental status changes, petechiae, hepatosplenomegaly, abdominal tenderness, jaundice, eschars, abnormal lung function, possible neurologic deficits (cranial nerve palsies, focal deficits), conjunctival suffusion, and the ocular findings listed above.^4,14

• Petechiae and ecchymoses are more common in patients with LBRF than in those with TBRF.^17,18
• The organomegaly and lung and CNS abnormalities are more commonly associated with LBRF, secondary to direct invasion of spirochetes. Rash is reported more often in patients with TBRF.¹⁴

Causes

See Background.

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