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Relapsing fever

Relapsing fever is an acute infectious disease caused by spirochetes of the genus Borrelia, primarily transmitted to humans through the bites of infected soft ticks, hard ticks, or body lice, and characterized by recurring episodes of high fever, chills, headache, myalgias, and arthralgias, typically lasting 3 to 6 days each and separated by 1 to 2 weeks of relative remission.^[1]^[2] The disease is classified into two main forms: tick-borne relapsing fever (TBRF), caused by multiple Borrelia species such as B. hermsii, B. turicatae, and B. miyamotoi—with B. hermsii and B. turicatae transmitted by soft-bodied ticks of the genus Ornithodoros and B. miyamotoi transmitted by hard ticks like Ixodes species—which is endemic in focal areas including the western United States, northeastern and midwestern United States, parts of Africa, Europe, Asia, and other tick-infested regions worldwide; and louse-borne relapsing fever (LBRF), caused exclusively by B. recurrentis and spread by the human body louse Pediculus humanus humanus, which remains a significant public health issue in endemic areas of East Africa, such as Ethiopia and Sudan, often exacerbated by poor sanitation and conflict.^[1]^[3]^[4] Clinically, the initial febrile episode often presents abruptly with temperatures exceeding 40°C (104°F), accompanied by nonspecific symptoms like fatigue, abdominal pain, and occasionally hepatosplenomegaly or rash, while subsequent relapses—up to 3 to 10 episodes—occur due to antigenic variation in the bacterial surface proteins, allowing evasion of the host immune response; untreated LBRF has a mortality rate of 30% to 70%, primarily from complications like bacterial endocarditis or central nervous system involvement, whereas TBRF is generally milder with untreated mortality around 5%.^[1]^[2]^[5] Diagnosis relies on demonstrating spirochetes in peripheral blood smears during febrile episodes, supplemented by polymerase chain reaction (PCR) assays for higher sensitivity or serologic testing, though cross-reactivity with other Borrelia species like those causing Lyme disease can complicate interpretation.^[1] Treatment involves antibiotics such as doxycycline (100 mg orally twice daily for 10 to 14 days) for adults or penicillin for pregnant women and children, with careful monitoring for the Jarisch-Herxheimer reaction—a potentially severe inflammatory response triggered by bacterial lysis occurring in up to 60% of cases—which can cause hypotension and requires supportive care.^[1]^[6] Prevention focuses on vector control: for TBRF, avoiding rodent-infested cabins in endemic areas, using permethrin-treated bedding, and applying insect repellents; for LBRF, maintaining personal hygiene, frequent clothing changes, and delousing measures in high-risk populations, as no human vaccine is currently available.^[7]^[1]^[3]

Epidemiology and Distribution

Global Incidence and Prevalence

Relapsing fever remains a neglected vector-borne disease with significant underreporting globally, complicating precise incidence estimates. Historical data indicate over 26,000 reported cases of infection by relapsing fever group Borrelia species from 1874 to 2022, but current annual figures are likely much higher due to limited surveillance in endemic areas. Louse-borne relapsing fever (LBRF), caused by Borrelia recurrentis, is primarily confined to sub-Saharan Africa, particularly the Horn of Africa, where it causes sporadic outbreaks and endemic transmission. In Ethiopia, an estimated 10,000 cases occur annually, predominantly among homeless individuals and those in crowded conditions, with a case fatality rate of 2–5% in treated patients and up to 40% in untreated cases, contributing to thousands of deaths each year in the region; recent outbreaks include over 170 cases in Addis Ababa hospitals from August to November 2023 and an outbreak in Jimma Zone in 2023.^[8]^[9]^[10]^[11] Tick-borne relapsing fever (TBRF), caused by various Borrelia species transmitted by soft or hard ticks, shows variable incidence by region. In the United States, 251 cases of soft tick relapsing fever were reported from 2012 to 2021 across 11 states, with a median of 24 cases annually; California accounted for 200 cases, while Washington reported 21, and annual counts ranged from 1 to 12 in affected states like these. No deaths occurred among these cases, though 55% of patients required hospitalization. In highly endemic foci such as Ethiopia, TBRF contributes hundreds to thousands of cases annually, often overlapping with LBRF in rural and highland areas.^[12]^[13]^[1] Demographic trends reveal that relapsing fever affects all age groups, but incidence is elevated among children under 15 years and adults over 50 in endemic settings, with bimodal age distributions observed in surveillance data—peaks in children aged 10–14 years and adults aged 40–44 years for TBRF in the US. Fatality risks are higher in infants, older adults, and those with comorbidities, particularly for LBRF. Recent reports from 2023–2024 highlight emerging cases in non-endemic areas, including a confirmed instance of TBRF caused by Borrelia lonestari in Alabama, USA, in 2023 in an immunocompromised patient following a tick bite. In Kazakhstan, surveys conducted in 2022–2023 and reported in 2024 detected B. miyamotoi and B. anserina in ticks from southern and southeastern regions, signaling potential expansion of TBRF risk beyond traditional foci.^[14]^[11]^[15]^[16]

Geographic Patterns and Risk Factors

Louse-borne relapsing fever (LBRF) is endemic in the Horn of Africa, particularly in Ethiopia and Sudan, where it remains a significant public health concern in highland regions during the rainy season.^[3] Outbreaks often occur in parts of East Africa, including Eritrea and Somalia, linked to seasonal environmental conditions that favor louse proliferation.^[1] Sporadic cases and epidemics of LBRF have been reported in Europe and Asia, typically during conflicts, famines, or refugee crises that disrupt sanitation and increase human displacement.^[17] Tick-borne relapsing fever (TBRF) exhibits a more fragmented global distribution, with foci in temperate and tropical regions where soft tick vectors thrive. In North America, TBRF is prominent in the western United States, including rustic cabins in California and Washington state, where Borrelia hermsii transmitted by Ornithodoros hermsi accounts for the majority of cases.^[18] Cases have also been documented in northwestern Canada, associated with similar rodent-infested environments.^[19] In South America, TBRF persists in Brazil's semiarid regions, such as the Caatinga biome, where Ornithodoros rudis serves as a vector for relapsing fever borreliae.^[20] Emerging foci are noted in southern Kazakhstan, with recent surveys detecting TBRF borreliae in tick populations amid expanding vector habitats.^[21] Key risk factors for LBRF include poverty, overcrowding, and poor sanitation, which facilitate body louse (Pediculus humanus humanus) transmission in congregate settings like refugee camps or urban slums.^[22] For TBRF, primary risks stem from exposure to rodent-infested cabins, caves, or rural dwellings harboring soft ticks such as Ornithodoros species, often during summer months in endemic areas.^[23] Climate change exacerbates TBRF transmission by expanding tick ranges northward and into higher elevations, as evidenced by the broadening distribution of Borrelia miyamotoi in Europe, North America, and Asia through increased habitat suitability driven by warmer temperatures.^[24] Vulnerable populations for relapsing fever encompass refugees and internally displaced persons in endemic zones, who face heightened exposure due to disrupted living conditions, as seen in outbreaks among East African migrants arriving in Europe.^[17] International travelers to rural or conflict-affected areas in Africa and Asia are at risk, particularly those staying in unmaintained accommodations.^[18] Immunocompromised individuals exhibit increased susceptibility to severe disease across both LBRF and TBRF forms.^[1] Recent 2024 global risk prediction models, incorporating vector habitat and climate data, underscore elevated threats in Africa and Central Asia, projecting up to 1.34 billion people at potential risk for B. miyamotoi-associated TBRF due to shifting ecological patterns.^[24]

Etiology and Pathogenesis

Causative Borrelia Species

Relapsing fever is caused by spirochetes belonging to the genus Borrelia within the family Borreliaceae, specifically those classified in the relapsing fever group (RFGB).^[2] These bacteria are distinguished from other borreliae, such as those causing Lyme disease, by their phylogenetic placement and phenotypic traits, with a 2015 taxonomic proposal suggesting the separation of RFGB spirochetes in the genus Borrelia (retaining the original name due to priority) while reclassifying Lyme disease agents under a new genus Borreliella, though this split has not been widely adopted.^[25] The RFGB encompasses species transmitted primarily by soft ticks of the genus Ornithodoros or lice, with key pathogens including B. recurrentis, the sole agent of louse-borne relapsing fever (LBRF), which is globally distributed but most prevalent in parts of Africa and Asia.^[26] For tick-borne relapsing fever (TBRF), prominent species in North America include B. hermsii, B. turicatae, and B. parkeri, which are vectored by soft ticks and associated with rodent reservoirs in western mountainous and cave environments.^[27] An emerging species, B. miyamotoi, represents a notable exception as it is transmitted by hard-bodied Ixodes ticks, similar to Lyme borreliae, and has been reported in temperate regions of North America, Europe, and Asia.^[28] Morphologically, RFGB spirochetes are helical, motile bacteria measuring approximately 10-40 μm in length and 0.2-0.5 μm in width, with irregular or regular coils and no hooked ends.^[29] They possess 7-11 periplasmic flagella attached subterminally at each end, enabling characteristic corkscrew motility essential for dissemination in the host bloodstream.^[30] Unlike many bacteria, RFGB cannot be routinely cultured on standard media; they require specialized conditions such as Barbour-Stoenner-Kelly (BSK) medium supplemented with rabbit serum to support growth in vitro. Genetically, RFGB exhibit a unique architecture among bacteria, featuring a linear chromosome of about 900-920 kb flanked by covalently closed hairpin telomeres, alongside multiple linear and circular plasmids that collectively comprise up to 40% of the genome.^[31] These plasmids harbor genes critical for infectivity and host adaptation, including those encoding variable major proteins (Vmps) central to immune evasion, contrasting with Lyme borreliae where outer surface protein C (OspC) plays a dominant role in early infection and transmission.^[32] In 2023, a novel RFGB species, provisionally named Candidatus Borrelia caatinga, was isolated from Ornithodoros cf. tabajara ticks collected in rodent burrows within the Brazilian Caatinga biome, marking the first such discovery in South America and highlighting the group's diversity in Neotropical soft ticks.^[33] This species shares phylogenetic affinities with Old World RFGB but was confirmed through multilocus sequencing and experimental transmission in guinea pigs, without inducing overt clinical signs in rodent models.^[33]

Mechanisms of Antigenic Variation and Relapse

Relapsing fever is characterized by recurrent episodes of fever due to the spirochete's ability to undergo antigenic variation, primarily through the expression of variable major proteins (Vmps), which include variable large proteins (Vlps, ~36 kDa) and variable small proteins (Vsps, ~20 kDa).^[34] These Vmps are encoded by genes on linear plasmids (28-53 kb in size), with a single active expression site on one plasmid and multiple silent vmp loci on others, allowing the bacterium to switch surface antigens rapidly.^[34] In species such as Borrelia hermsii, up to 60-70 distinct Vmp variants exist, divided into subfamilies (α, β, γ, δ), enabling diverse serotypes.^[34] The core mechanism of antigenic variation involves non-reciprocal gene conversion, where silent vmp genes are recombined into the active expression site via short homology regions: an upstream homology sequence (UHS, ≤62 nt) and a downstream homology sequence (DHS, ~214 nt repetitive elements).^[35] This recombination, often occurring at rates of 10⁻⁴ to 10⁻³ per generation, replaces the expressed Vmp with a new variant, altering the spirochete's outer membrane lipoproteins.^[35] Seminal work by Barbour and Stoenner (1982) first described this serotype switching in B. hermsii, while later studies by Dai et al. (2006) elucidated the recombination hotspots using upstream and downstream elements.^[36]^[37] Immune evasion arises as the host mounts a specific antibody response against the dominant Vmp serotype during a febrile episode, leading to clearance of that variant from the bloodstream and a temporary afebrile period.^[34] Surviving spirochetes then switch to a new Vmp through gene conversion, re-emerging in the blood as a different serotype and triggering relapse.^[34] This process can produce up to 10-13 relapse episodes, typically 3-10 cycles depending on the host and strain, as each switch evades the prior immunity, with the genetic repertoire of silent loci ensuring variant diversity.^[34] Molecular studies, including a 2023 in vitro analysis and a 2025 in vivo demonstration via serotype reisolations from infected mice, on Borrelia miyamotoi have confirmed this system's essentiality for relapses, showing Vmp switching (e.g., from Vsp1 to Vlp variants like vlpD4) under polyclonal antibody pressure via PCR and sequencing, highlighting its role even in spontaneous culture conditions.^[38]^[39] During relapses, high levels of spirochetemia—peaking at 10⁸ organisms per ml of blood—correlate with febrile episodes, as the new antigenic variant proliferates unchecked by existing antibodies.^[34] Vmps on the spirochete surface induce a cytokine storm, particularly tumor necrosis factor (TNF) production, which contributes to the systemic symptoms of fever, chills, and headache.^[34] This inflammatory response, driven by Vmp-lipoprotein interactions with host immune cells, underscores the pathogenic impact of antigenic switching.^[34] Relapse patterns follow a predictable cycle: the initial febrile episode lasts 3-7 days, followed by an afebrile interval of 7-10 days during which the immune response clears the current variant.^[34] Subsequent relapses decrease in duration and intensity, with febrile periods shortening and intervals lengthening, until immunity encompasses enough variants to halt further episodes, typically after 3-10 cycles depending on the host and strain.^[34]

Transmission and Vectors

Louse-Borne Transmission

Louse-borne relapsing fever (LBRF) is caused by the spirochete Borrelia recurrentis and is transmitted exclusively through the human body louse, Pediculus humanus humanus. The vector acquires the pathogen during blood meals from infected individuals, after which the spirochetes multiply in the louse's gut and hemocoel. Transmission to humans occurs when an infected louse is crushed during scratching or when louse feces containing the bacteria contaminate bite wounds or mucous membranes, allowing direct entry into the bloodstream. Nosocomial transmission via infected blood, such as through transfusions or needlestick injuries, is also possible.^[1]^[40] Unlike tick-borne forms, LBRF has no animal reservoir, with humans serving as the sole host and reservoir for B. recurrentis. The pathogen persists in human populations through asymptomatic or mild infections between outbreaks, facilitating epidemic resurgence. Transmission cycles amplify rapidly in conditions of overcrowding, poor sanitation, and social disruption, such as during wars, famines, or refugee crises, historically leading to massive epidemics in regions like the Horn of Africa.^[1]^[40] The incubation period typically ranges from 4 to 18 days, during which spirochetes disseminate systemically before clinical symptoms emerge.^[1]^[40]^[41] In recent years, LBRF has reemerged sporadically in Europe among migrants and refugees from East Africa and the Middle East, with cases reported as recently as 2015, highlighting ongoing risks in displaced populations traveling from endemic areas.^[1]^[40]^[42]

Tick-Borne Transmission

Tick-borne relapsing fever (TBRF) is predominantly transmitted by soft-bodied ticks of the genus Ornithodoros, which serve as the primary vectors for most relapsing fever group Borrelia (RFGB) species. These argasid ticks, including O. hermsi prevalent in the northwestern United States and O. turicata in the southwestern United States, are adapted to rapid feeding, typically completing engorgement in 15 to 30 minutes, often at night when hosts are asleep.^[43]^[44]^[45] This brief attachment period, combined with painless bites, frequently results in unnoticed infections. The spirochetes are acquired by ticks during feeding on infected hosts and are perpetuated within the tick population via transstadial transmission, where the pathogen passes through molting stages from larva to nymph to adult, and transovarial transmission, allowing infected females to pass Borrelia to their offspring through eggs.^[46]^[47]^[11] In contrast, a subset of TBRF is associated with hard-bodied ticks of the genus Ixodes, particularly I. scapularis and I. pacificus, which transmit Borrelia miyamotoi, the agent of hard tick relapsing fever. These ixodid ticks exhibit slower feeding behavior, with nymphs and adults attaching for 3 to 7 days to fully engorge, increasing the window for pathogen transmission during daytime or prolonged host contact.^[48]^[49] Unlike typical Lyme disease borreliae, B. miyamotoi supports transovarial transmission in Ixodes ticks, enabling vertical passage to larval progeny, though horizontal transmission via infected nymphs remains the dominant mode.^[50]^[51] This capability contributes to the pathogen's persistence in tick populations across the northern hemisphere. The enzootic cycle of TBRF is sustained primarily by rodent reservoirs, such as ground squirrels, tree squirrels, and chipmunks, which harbor RFGB spirochetes in their blood during bacteremic periods and provide blood meals to questing ticks in rodent nests or burrows.^[52]^[53] Humans act as incidental, dead-end hosts, typically acquiring infection during exposure in endemic areas like rustic cabins or caves where ticks and rodents cohabit.^[28] Recent discoveries highlight evolving understandings of TBRF transmission. In 2023, a novel RFGB spirochete was isolated from Ornithodoros ticks collected in rodent-inhabited rock formations of Brazil's Caatinga biome, expanding the known geographic range and genetic diversity of tick-borne relapsing fever agents in the Americas.^[54] Additionally, that same year, the first documented case of relapsing fever attributed to Borrelia lonestari—typically linked to southern tick-associated rash illness—was reported in an immunocompromised patient in Alabama, USA, following a lone star tick bite, underscoring potential opportunistic roles of this spirochete in vulnerable hosts.^[55]

Clinical Manifestations

Primary Signs and Symptoms

The primary signs and symptoms of relapsing fever manifest abruptly during the initial acute phase, typically 4 to 18 days after exposure, with a sudden onset of high fever, often reaching 39 to 41°C, accompanied by intense chills or rigors.^[1]^[40] Patients commonly experience severe headache, myalgias, and arthralgias, which contribute to profound fatigue and prostration; these musculoskeletal pains are particularly prominent in the back, knees, and elbows.^[40]^[5] The febrile episode generally lasts 2 to 7 days, averaging 3 days in tick-borne cases and 5 days in louse-borne cases, before resolving into a crisis characterized by diaphoresis and defervescence.^[5]^[40] Additional symptoms during the febrile phase include nausea, vomiting, and abdominal pain, which occur in over 70% of cases and may lead to dehydration if untreated.^[5] A petechial or erythematous rash appears on the trunk or extremities in up to 50% of louse-borne relapsing fever (LBRF) patients, though it is less common (around 18%) in tick-borne relapsing fever (TBRF); conjunctival suffusion and photophobia are also frequent.^[40] In LBRF, hepatomegaly with tenderness is noted in approximately 60% of cases, while splenomegaly occurs in about 50%, reflecting systemic inflammation; these findings are less common in TBRF (hepatomegaly ~10%, splenomegaly ~6%).^[40]^[1]^[5] Following the febrile phase, an afebrile interval ensues, lasting 4 to 10 days, during which patients are often asymptomatic or report only mild fatigue and malaise as spirochetes evade the immune response through antigenic variation.^[5] LBRF tends to present more severely, with higher fevers and greater risk of hemodynamic instability, whereas TBRF is often milder but associated with neurological symptoms, such as confusion or meningitis, in 10 to 40% of cases.^[1]^[5]

Relapse Patterns and Complications

Relapsing fever derives its name from the characteristic pattern of recurrent febrile episodes, which result from the pathogen's ability to undergo antigenic variation. In tick-borne relapsing fever (TBRF), patients typically experience 3-10 relapses following the initial episode, while louse-borne relapsing fever (LBRF) involves fewer, usually 1-3 episodes.^[56] Each subsequent relapse tends to be shorter in duration—often lasting 2-7 days compared to the initial 5-10 days—and less severe in intensity, with afebrile intervals of 2-10 days between episodes.^[1]^[57] This cyclic pattern is triggered by antigenic switching, where Borrelia species alter their variable major proteins (Vmps) through gene conversion and plasmid-mediated recombination, evading the host's adaptive immune response and allowing bacterial resurgence.^[56] In untreated cases, relapse rates can reach up to 70%, particularly in TBRF, though the infection eventually resolves spontaneously in most individuals after several cycles.^[56] Complications of relapsing fever can arise during acute episodes or following treatment initiation, with severity varying between TBRF and LBRF. The Jarisch-Herxheimer reaction, a systemic inflammatory response due to rapid bacterial lysis and cytokine release, occurs in 50-90% of treated cases, manifesting as worsening fever, chills, hypotension, and tachycardia within hours of antibiotic administration; it is more frequent and severe in LBRF (up to 56%) than in TBRF (around 19-54%).^[57]^[58] Neurological complications, including meningitis and cranial nerve palsies, affect 10-40% of TBRF patients but are less common in LBRF (though meningism occurs in up to 40% of LBRF cases), potentially leading to long-term sequelae if untreated.^[57]^[40] Cardiac involvement, such as myocarditis, and hepatic complications like failure or jaundice can occur in severe cases, contributing to multi-organ dysfunction.^[1]^[59] Case-fatality rates are low with prompt treatment—approximately 4% for treated LBRF and less than 2% for TBRF—but rise significantly in untreated LBRF (up to 70%).^[1] Long-term effects following relapsing fever are uncommon but may include prolonged fatigue and reactive arthritis in 5-10% of cases, with higher incidence in untreated or delayed-treatment scenarios due to persistent inflammation or immune-mediated damage.^[60] Recent reports highlight emerging complications in novel Borrelia species; for instance, a 2023 case (published in January 2023) of B. lonestari infection in Alabama, USA, presented with relapsing fevers and severe pancytopenia, underscoring potential hematologic risks in these atypical strains.^[61]

Diagnosis

Clinical Evaluation

Clinical evaluation of suspected relapsing fever begins with a detailed history-taking to identify risk factors and characteristic symptom patterns. Patients should be queried about recent travel to endemic regions, such as the Horn of Africa for louse-borne relapsing fever or western U.S. mountainous areas for tick-borne forms, as well as potential exposure to body lice or soft-bodied ticks (e.g., Ornithodoros species) through camping, hiking, or crowded living conditions.^[1] A history of recurrent episodes of high fever, often abrupt in onset and lasting 3-7 days, separated by afebrile intervals of 7-10 days, is highly suggestive, with subsequent relapses typically shorter and less severe.^[1] The incubation period following exposure is generally 4-18 days, averaging about 7 days.^[5] Physical examination during a febrile episode reveals key nonspecific signs that support the diagnosis when combined with history. High fever (often >40°C) and relative bradycardia or tachycardia are common, alongside a petechial or erythematous rash on the trunk and extremities in up to 50% of cases.^[1] Conjunctival suffusion or subconjunctival hemorrhage may be evident, reflecting vascular involvement, while hepatosplenomegaly occurs frequently, with splenomegaly noted in approximately 50% of patients.^[45] These findings, particularly in the context of recent exposure, heighten suspicion for relapsing fever. Differential diagnosis includes other causes of acute febrile illness with potential recurrence, such as malaria, dengue, leptospirosis, typhoid fever, brucellosis, and yellow fever.^[1] The relapsing pattern of fevers with intervening afebrile periods, often 3-5 relapses in untreated cases, helps distinguish relapsing fever from these mimics, where fever courses are typically continuous or biphasic without true remission.^[45] Neurological symptoms, such as severe headache, confusion, neck stiffness, or focal deficits indicating possible meningism (present in up to 40% of cases), represent red flags warranting urgent evaluation to rule out complications like meningitis or encephalitis.^[1]

Laboratory Confirmation

Laboratory confirmation of relapsing fever primarily involves direct microbiological visualization, serological assays, molecular detection, and, less commonly, culture-based methods, with samples ideally collected during febrile episodes when spirochete loads are highest.^[62] These approaches confirm infection by Borrelia species causing louse-borne or tick-borne relapsing fever, distinguishing it from similar illnesses like malaria or Lyme disease.^[1] Microscopy remains a cornerstone for rapid diagnosis, particularly through examination of peripheral blood smears obtained during peak fever. Thin and thick blood smears stained with Wright-Giemsa or Giemsa allow visualization of spirochetes under light microscopy, while dark-field microscopy enables direct observation of motile spirochetes without staining.^[6]^[1] This method detects spirochetes in approximately 70-80% of cases when performed early in untreated symptomatic patients, though sensitivity drops significantly during afebrile periods due to low bacteremia.^[63] Spirochetes appear as thin, irregularly coiled rods, often 5-20 per field in thick smears, confirming the diagnosis without need for species identification in most acute settings.^[64] Serological testing has limited utility for acute diagnosis due to delayed antibody responses and significant cross-reactivity with other spirochetes, such as those causing Lyme disease or syphilis. IgM and IgG enzyme-linked immunosorbent assays (ELISAs) targeting relapsing fever group Borrelia antigens, particularly the glycerophosphodiester phosphodiesterase (GlpQ) protein, offer improved specificity, as GlpQ is absent in Lyme disease agents.^[62]^[65] GlpQ-based IgM ELISA achieves sensitivities of up to 100% and specificities exceeding 96%, making it valuable for confirmation, particularly in convalescent sera.^[66] Cross-reactivity remains a challenge, necessitating confirmatory testing in endemic areas.^[67] Molecular methods, especially polymerase chain reaction (PCR), provide high sensitivity and specificity for detecting Borrelia DNA, particularly when microscopy is negative. Real-time PCR assays target conserved genes such as flaB (flagellin) or 16S rRNA, amplifying Borrelia-specific sequences from blood, cerebrospinal fluid, or tissue.^[68] For emerging species like B. miyamotoi, multiplex PCR panels detect multiple relapsing fever Borrelia (e.g., B. hermsii, B. miyamotoi, B. parkeri, B. turicatae) simultaneously, enabling species differentiation via probes for genes like glpQ.^[69] Recent advancements include semimultiplex real-time PCR assays that classify pathogens into relapsing fever groups with sensitivities far exceeding microscopy, and 2025 updates feature flaB-based profiling for rapid identification in vector samples or human cases.^[70]^[71] These assays are preferred for low-bacteremia cases, such as those involving B. miyamotoi, where PCR positivity rates approach 100% in acute blood samples.^[51] Culture of relapsing fever Borrelia is rarely successful in routine diagnostics due to fastidious growth requirements and low yields, limiting its use to research settings. Historical methods involved animal inoculation, such as intraperitoneal injection of patient blood into rats or mice, which could propagate spirochetes for subsequent visualization or PCR.^[72] Modern in vitro cultivation employs specialized media like Barbour-Stoenner-Kelly (BSK) at 33-37°C, but success rates remain low for clinical isolates, with recent protocols enabling continuous propagation of species like B. miyamotoi only under optimized anaerobic conditions.^[73]^[74] Due to these challenges, culture is considered outdated for confirmation and is superseded by PCR in contemporary practice.^[1]

Treatment and Management

Antimicrobial Therapy

Antimicrobial therapy for relapsing fever targets the causative Borrelia species and is highly effective when initiated promptly, with choices varying by transmission type, patient age, and pregnancy status.^[62] For tick-borne relapsing fever (TBRF), the first-line treatment in adults is doxycycline at 100 mg orally or intravenously twice daily for 10-14 days, particularly for severe cases to prevent relapse.^[62] In contrast, louse-borne relapsing fever (LBRF) is typically treated with a single dose of doxycycline 200 mg orally or tetracycline 500 mg orally in adults.^[6]^[75] For pregnant patients, alternatives to tetracyclines include penicillin G (e.g., 400,000-800,000 units intramuscularly as a single dose for LBRF or 4 million units intravenously every 6 hours for 10 days in TBRF) or erythromycin (500 mg orally four times daily for 10 days in TBRF).^[6]^[62] According to 2024 CDC guidelines, children with soft-tick TBRF should receive azithromycin at 10 mg/kg (maximum 500 mg) orally daily for 7-10 days, or amoxicillin for hard-tick relapsing fever (B. miyamotoi) at 50 mg/kg/day (maximum 500 mg) divided in three doses for 14 days; doxycycline is reserved for those over 8 years at 2.2 mg/kg (maximum 100 mg) twice daily, with LBRF typically using a single age-appropriate dose.^[6]^[62]^[76] For severe TBRF with neurologic involvement, a 10-14 day course of intravenous ceftriaxone (2 g daily in adults) or penicillin G is recommended.^[62] Treatment efficacy exceeds 95% cure rates across Borrelia species, with symptoms resolving within 24-72 hours in most cases.^[76]^[77] In LBRF, single-dose tetracycline or doxycycline reduces mortality from approximately 40% in untreated patients to 4-5% in treated ones.^[41] As of 2025, no antibiotic resistance has been reported in relapsing fever Borrelia species to standard treatments, though ongoing surveillance is recommended.^[78]^[79] Therapy may trigger a Jarisch-Herxheimer reaction, managed supportively as detailed elsewhere.^[62]

Management of Complications

The Jarisch-Herxheimer reaction (JHR) is a common complication occurring in 50-90% of relapsing fever patients shortly after initiation of antibiotic therapy, particularly in louse-borne cases where incidence exceeds 50%. This acute inflammatory response typically manifests within 2-4 hours of treatment and includes symptoms such as fever, chills, rigors, hypotension, tachycardia, myalgias, and headache, lasting up to 24 hours. Management focuses on supportive care, including close monitoring of vital signs for at least the first 4 hours post-antibiotics, administration of nonsteroidal anti-inflammatory drugs (NSAIDs) or antipyretics like acetaminophen for fever and pain, and intravenous fluids to address hypotension or dehydration. In severe cases, particularly those involving neurological symptoms or pregnancy, adjuvant corticosteroids may be considered, though evidence is limited to case reports and guidelines.^[6]^[80]^[81] Severe complications in relapsing fever, such as dehydration from vomiting and fever, seizures due to neurological involvement, and anemia, a common complication particularly hemolytic in nature and affecting up to 44% of pregnant cases, require prompt intervention to prevent morbidity. Dehydration is managed with intravenous crystalloid fluids to maintain hemodynamic stability, while seizures necessitate anticonvulsant therapy alongside evaluation for meningeal involvement. Anemia may warrant blood transfusions in cases of significant hemoglobin drop or hemodynamic compromise, especially in vulnerable populations like pregnant women or children. These measures emphasize multidisciplinary care, including infectious disease consultation for immunocompromised patients.^[1]^[80]^[81] Hospitalization is indicated for patients with neurological complications (e.g., seizures or meningitis), pregnancy, or extremes of age, as these increase the risk of severe JHR or sequelae; approximately 55% of tick-borne relapsing fever cases in the United States require admission for monitoring and supportive therapy. Outpatient management may suffice for mild, uncomplicated cases with close follow-up, but inpatient observation ensures timely response to deteriorations like acute respiratory distress syndrome or shock.^[62]^[1] Follow-up care involves monitoring for symptom recurrence, as relapses can occur in up to 20% of inadequately treated cases; if fever or other signs reemerge, polymerase chain reaction (PCR) testing of blood is recommended to confirm persistent borrelial infection and guide retreatment. Patients should be advised on symptom vigilance and prompt return to care, with serial clinical assessments to track resolution of anemia or other sequelae.^[1]^[81]

Prevention and Control

Vector Control Measures

Vector control measures for relapsing fever target the primary vectors—body lice for louse-borne relapsing fever (LBRF) and soft ticks (genus Ornithodoros) for tick-borne relapsing fever (TBRF)—to interrupt transmission cycles. These interventions emphasize site-specific and individual actions, such as insecticide application and environmental modifications, often integrated with professional pest management to address infested areas like dwellings or rodent habitats.^[3]^[82] For LBRF, control focuses on eliminating body lice (Pediculus humanus humanus) through improved personal hygiene and insecticide treatments. Regular clothing and bedding changes, combined with hot water showers, remove lice and nits, reducing infestation risks in crowded or unsanitary conditions.^[6] Topical insecticides, including 0.5% permethrin dust or liquid applied to clothing, provide effective louse elimination by disrupting their nervous systems; pyrethrins, malathion, or ivermectin serve as alternatives for resistant populations.^[83]^[6] In epidemic settings, delousing stations using heat treatment (e.g., steam at >60°C) or insecticide dusting on infested clothing have historically interrupted transmission, preventing further spread in affected communities.^[84]^[85] TBRF vector control prioritizes soft tick suppression in rodent-infested environments, where Ornithodoros species reside in burrows, nests, and structures. Acaricide applications, such as lambda-cyhalothrin spraying in cracks, crevices, and rodent burrows by licensed professionals, significantly reduce tick populations; one study in Tanzania demonstrated a near-elimination of ticks in treated homes, dropping TBRF cases from 29 to 1 among children under five in a monitored village.^[82]^[86] Structural modifications, including sealing cabins and buildings with metal sheeting, steel wool, or caulk around entry points (e.g., walls, roofs, pipes), prevent rodent and tick ingress, thereby limiting exposure in high-risk areas like vacation cabins.^[82]^[87] Permethrin-treated bedding and fumigation of infested structures further deter ticks, with permethrin retaining efficacy for weeks on fabrics.^[88]^[82] Personal protective measures complement environmental controls by minimizing direct vector contact. Applying DEET-based repellents (20-30% concentration) to exposed skin repels both lice and ticks, while permethrin (0.5%) treatment on clothing and gear provides prolonged protection against bites.^[89] Wearing long-sleeved shirts, long pants tucked into socks, and avoiding rodent habitats—particularly at night when soft ticks exhibit peak activity—further reduces risk, as bites often occur unnoticed during sleep.^[90]^[28]^[52] Integrated pest management (IPM) combining these strategies has proven effective in reducing TBRF transmission in U.S. high-risk sites, such as rodent-infested cabins in western states; protocols including habitat modification and targeted acaricide use have limited outbreaks, though national case surveillance from 2012-2021 reported 251 incidents, underscoring ongoing needs for vigilance.^[91]^[18]

Public Health Strategies

Public health strategies for relapsing fever emphasize robust surveillance systems to detect and monitor cases, particularly in endemic regions. In the United States, tick-borne relapsing fever is a notifiable condition in 12 states, including Arizona, California, Colorado, Idaho, Montana, Nevada, New Mexico, Oregon, Texas, Utah, Washington, and Wyoming (as of 2021), enabling early detection and response to sporadic outbreaks.^[92] The World Health Organization (WHO) supports surveillance for louse-borne relapsing fever in Africa through integrated communicable disease monitoring, focusing on high-burden areas in northern and eastern regions where epidemic forms predominate.^[1] Recent advancements include 2024 global risk models for relapsing fever group Borrelia, utilizing geographic information systems (GIS) and environmental data to predict high-risk zones, particularly in west Africa and southern Europe, aiding proactive resource allocation.^[24] Outbreak response protocols prioritize rapid intervention to curb transmission, especially for louse-borne relapsing fever epidemics. In affected communities, mass delousing campaigns target body lice vectors by treating infested clothing and bedding with heat or chemical methods, combined with distribution of single-dose antibiotics like doxycycline to symptomatic individuals suspected of infection.^[85]^[84] Contact tracing is often limited due to the primary role of vectors in transmission rather than direct human-to-human spread, shifting focus to environmental and hygiene interventions during crises like those in Ethiopia.^[10] Education initiatives form a cornerstone of prevention, targeting both travelers and endemic populations to reduce exposure risks. Traveler advisories from health authorities, such as the CDC, recommend precautions like avoiding tick-infested areas and using repellents in endemic zones, with counseling emphasizing prompt medical attention for recurrent fever symptoms post-travel.^[1] In high-burden communities in Africa and other regions, community awareness programs promote hygiene practices to prevent louse infestations, often integrated with broader malaria control efforts to leverage existing infrastructure for vector education and distribution of preventive resources.^[93] Persistent challenges hinder effective control, including significant underreporting in resource-poor settings where diagnostic access is limited, leading to underestimation of the true disease burden.^[94] Climate-driven changes, such as warmer temperatures expanding vector habitats, necessitate adaptive strategies like enhanced modeling and cross-sectoral collaboration to address emerging risks in previously unaffected areas.^[95]

History

Early Descriptions and Epidemics

Relapsing fever was first described in ancient medical texts as a condition characterized by periodic fevers. The earliest known account appears in the works of Hippocrates around 430 BCE, where he documented recurring febrile episodes among patients on the island of Thasos, noting the characteristic relapses and associated symptoms such as splenomegaly.^[96] This description aligned with the disease's hallmark pattern of intermittent high fevers interspersed with afebrile periods, though the etiology remained unknown for centuries.^[97] In the 19th century, relapsing fever emerged as a major epidemic threat in Europe, particularly amid industrialization, urbanization, and poor sanitation. Outbreaks ravaged cities like Edinburgh, Scotland, where two significant epidemics occurred in 1841 and 1843–1844, with the latter prompting the first clinical use of the term "relapsing fever" to describe the disease's distinctive course.^[98] In Ireland, the disease contributed substantially to mortality during the Great Famine of the 1840s, exacerbating deaths among the starving population and leading to thousands of cases across affected regions.^[96] Concurrently in Africa, explorers encountered severe outbreaks; British missionary David Livingstone linked the illness to tick bites during his 1857 travels in the Zambesi region, highlighting its endemic nature in tropical areas and resulting in numerous fatalities among European expeditions and local communities.^[96] Major epidemics intensified in the early 20th century, often coinciding with conflict and displacement. During World War I, a devastating outbreak struck Serbia in 1915, where relapsing fever co-occurred with typhus amid wartime overcrowding and malnutrition, contributing to the overall crisis that overwhelmed medical resources.^[99] In the Ethiopian highlands, recurrent outbreaks plagued the region from the 1940s through the 1960s, fueled by post-war instability and highland environmental factors favoring tick vectors, with reported cases surging beyond previous years (1947–1949) and straining local health systems.^[100] The disease's association with warfare persisted into the mid-20th century, earning louse-borne relapsing fever (LBRF) the moniker "war fever" due to its proliferation in conflict zones. During World War II, LBRF caused around one million cases across North Africa, particularly in areas of military activity and refugee movements, underscoring its role as a scourge in disrupted societies.^[3] In the United States, tick-borne relapsing fever (TBRF) affected rustic cabins and work sites in the Pacific Northwest from the 1920s to the 1940s, where workers in rodent-infested areas in states like Washington and Oregon faced repeated exposures to infected soft ticks, leading to localized outbreaks among laborers. Untreated relapsing fever epidemics historically carried high mortality rates, ranging from 30% to 70%, primarily due to complications like Jarisch-Herxheimer reactions, neurological involvement, and secondary infections in vulnerable populations.^[1] These rates were especially elevated in louse-borne forms during large-scale outbreaks, where lack of access to care amplified fatalities.^[11]

Key Scientific Discoveries

In 1873, Otto Obermeier, a German physician, made the groundbreaking observation of spirochetes in the blood smears of patients suffering from relapsing fever during an epidemic in Berlin, marking the first identification of a bacterial pathogen associated with the disease.^[97] This discovery shifted understanding from earlier humoral or miasmatic theories to a microbial etiology, although Obermeier could not initially cultivate the organism or prove transmissibility experimentally.^[79] Between 1905 and 1910, key advances established the arthropod vectors and formalized the taxonomy of the causative agents. Ronald Ross and A.E. Milne demonstrated in 1904–1905 that ticks, specifically Ornithodoros moubata, transmit the tick-borne form of relapsing fever in Africa, isolating spirochetes from infected ticks.^[96] Concurrently, researchers like Frederick P. Mackie confirmed louse transmission for the epidemic louse-borne variant in 1907, linking it to the human body louse Pediculus humanus humanus.^[40] In 1907, Dutch parasitologist N.H. Swellengrebel established the genus Borrelia and named the louse-borne species Borrelia recurrentis, distinguishing it from other spirochetes based on morphology and epidemiology.^[101] Throughout the 20th and into the 21st century, multiple tick-borne relapsing fever (TBRF) species were identified, expanding the known diversity of Borrelia pathogens. For instance, Borrelia hermsii was first associated with cases reported in California in 1922 and later from endemic foci in western states like Washington, formally described in 1942 as a distinct species causing North American TBRF transmitted by Ornithodoros hermsi ticks.^[5] Subsequent discoveries included other species like Borrelia turicatae and Borrelia parkeri, highlighting the role of soft-bodied ticks in maintaining enzootic cycles among rodents and small mammals. In the 1980s, molecular studies revealed the mechanism of antigenic variation enabling Borrelia persistence and relapse. Alan Barbour and colleagues demonstrated that Borrelia hermsii undergoes gene conversion events on linear plasmids, where silent variable major proteins (Vmps) are transposed to a single telomeric expression site, altering surface antigens to evade host immunity.^[102] This plasmid-mediated recombination, detailed in seminal works from 1985, explained the recurrent fevers and was confirmed across relapsing fever Borrelia species.^[103] Recent genetic analyses in 2023 have further validated antigenic variation's critical role in pathogen persistence. Studies on relapsing fever Borrelia, such as B. miyamotoi, showed that Vmp gene conversion not only drives serotype switching but also enhances spirochete survival in mammalian hosts by modulating immune recognition, with genomic sequencing revealing conserved recombination hotspots that facilitate chronic infection.^[104] These findings underscore the evolutionary adaptation of relapsing fever Borrelia for long-term transmission.

Current Research

Emerging Species and Diagnostics

Recent advancements in relapsing fever research have identified novel Borrelia strains, expanding the known diversity of pathogens within the relapsing fever group (RFGB). In 2023, researchers isolated a novel RFGB spirochete, designated Candidatus Borrelia caatinga, from Ornithodoros cf. tabajara ticks collected in rock formations of the Brazilian Caatinga biome. This strain was characterized through multilocus sequence analysis of 10 genetic loci and demonstrated vector competence in experimental infections of guinea pigs, though it caused no clinical illness in rodents. Similarly, in 2023, Borrelia lonestari was confirmed as the causative agent of relapsing fever in an immunocompromised patient in Alabama, USA, following an Amblyomma americanum tick bite; PCR and phylogenetic analysis of blood samples identified the pathogen with 100% sequence identity to known B. lonestari strains, marking the first documented human case. In 2025, a novel RFGB spirochete was isolated from Ornithodoros octodontus ticks in Chile and characterized through concatenated multilocus sequence typing (clpX, pepX, recG, rplB, uvrA), branching closely with Candidatus Borrelia caatinga; experimental transmission to rodents confirmed vector competence without causing clinical illness.^[105] Additionally, Borrelia miyamotoi, a hard tick-transmitted RFGB species, has shown geographic expansion in Europe and Asia since 2020, with suitable habitats shifting northward in northeastern Europe and northeast Asia due to climate influences on vector ticks like Ixodes persulcatus and Ixodes ricinus. Diagnostic innovations since 2020 have improved the detection of RFGB pathogens, particularly in distinguishing them from Lyme disease agents. A semimultiplex real-time PCR assay developed in 2021 enables simultaneous detection and grouping of clinically relevant RF Borrelia species—such as the B. hermsii group, B. miyamotoi, and B. recurrentis group—while differentiating them from Borrelia burgdorferi sensu lato, with an analytical sensitivity below 15 genome equivalents per reaction. More recent multiplex approaches, including high-definition PCR panels evaluated in 2023, have identified Borrelia species in pediatric Lyme disease cases, supporting their utility for RFGB versus Lyme differentiation. Point-of-care serological testing has advanced with customizable multiplex protein microarrays introduced in 2024, which detect antibodies against multiple tick-borne pathogens, including relapsing fever agents, achieving 95.2% sensitivity for B. burgdorferi IgG and high specificity adaptable for RFGB serology. Metagenomic sequencing has emerged as a tool for identifying unculturable or low-abundance RFGB strains; a 2024 study in Senegal used untargeted RNA metagenomics on plasma from febrile patients to detect relapsing fever Borrelia (primarily B. crocidurae) in 15.5% of cases, confirming infections via 16S rRNA phylogeny even in the absence of culture. In May 2025, ancient DNA analysis from historical samples revealed evolutionary insights into B. recurrentis, the agent of louse-borne relapsing fever, highlighting genetic adaptations over centuries.^[106] Despite these progresses, diagnostic challenges persist for relapsing fever. Cross-reactivity in serological assays between RFGB species, Lyme borreliosis agents, and other spirochetes like Treponema pallidum complicates interpretation, as no commercial RF-specific serology exists due to antigenic similarities and delayed seroconversion. Accurate detection also requires sampling during febrile episodes, as spirochetemia levels drop significantly during afebrile periods, reducing microscopy sensitivity to 70% overall and necessitating timed blood collection or PCR for optimal results. These emerging species and diagnostic tools have significant implications for public health surveillance, particularly amid climate-driven spread of RFGB vectors. Enhanced molecular methods enable better tracking in high-risk regions like west Africa, south Europe, and east Asia, where temperature shifts are projected to expand suitable habitats for species such as B. miyamotoi and B. crocidurae, facilitating proactive monitoring and outbreak prevention.

Therapeutic and Vaccine Developments

Recent studies have explored extended durations of doxycycline therapy for infections caused by Borrelia miyamotoi, the primary agent of hard tick relapsing fever (HTRF), recommending courses of 2 to 4 weeks to ensure complete clearance of persistent spirochetes and prevent relapses, particularly in immunocompromised patients.^[107] This approach builds on earlier evidence of doxycycline's efficacy against relapsing fever Borrelia, with 2025 guidelines emphasizing prolonged treatment to address the organism's potential for low-level persistence post-initial therapy.^[1] Combination antibiotic regimens have shown promise in mitigating the Jarisch-Herxheimer reaction (JHR), a common complication of relapsing fever treatment characterized by acute fever, chills, and hypotension due to rapid spirochete lysis. For louse-borne relapsing fever (LBRF), the U.S. Centers for Disease Control and Prevention (CDC) recommends an initial single dose of intramuscular procaine penicillin followed by a 7-day course of oral doxycycline (100 mg twice daily for adults), which reduces both relapse rates and JHR incidence compared to single-dose therapy alone.^[6] This strategy leverages penicillin's rapid bactericidal action with doxycycline's sustained coverage, minimizing inflammatory cytokine release associated with JHR.^[80] Vaccine development for relapsing fever remains in early experimental stages, with efforts centered on targeting variable major proteins (Vmps), the surface lipoproteins responsible for antigenic variation that enables immune evasion and disease relapses. Experimental vaccines based on Vmps, such as the variable tick protein (Vtp) from Borrelia hermsii, have demonstrated partial protective efficacy in mouse models by inducing antibodies that limit spirochetemia upon tick challenge, though challenges persist due to the high diversity of Vmp variants across Borrelia species.^[108] Antigenic variation, involving over 25 Vmp cassettes per strain, complicates broad-spectrum immunity, as relapsing fever Borrelia can switch expressions to evade host antibodies during infection.^[109] No licensed vaccines exist for any relapsing fever Borrelia species, highlighting significant research gaps in preventive strategies, particularly for emerging hard tick vectors like Ixodes species transmitting B. miyamotoi. Current focus prioritizes HTRF due to its increasing incidence in temperate regions, where soft tick vectors are less prevalent, but antigenic diversity and lack of human trial data impede progress. Ongoing preclinical studies aim to address these barriers through multi-epitope approaches targeting conserved Vmp regions, though no Phase I trials specific to relapsing fever have advanced in endemic African regions as of 2025.^[1]^[51]

References

[1]
Relapsing Fever - StatPearls - NCBI Bookshelf - NIH
May 4, 2025 · Relapsing fever typically refers to malaria-like illnesses characterized by recurrent fevers, chills, and malaise caused by various spirochetes ...
[2]
About Tick and Louse-borne Relapsing Fevers - CDC
May 15, 2024 · Relapsing fever is an illness characterized by one or more episodes of fever, headache, and muscle pain that lasts several days and is separated by roughly a ...
[3]
About Louse-borne Relapsing Fever (LBRF) - CDC
Jan 31, 2025 · Louse-borne relapsing fever (LBRF) is caused by Borrelia recurrentis bacteria and transmitted to people by the human body louse and, rarely, ...
[4]
Historical overview and update on relapsing fever group Borrelia in ...
Relapsing fever group Borrelia (RFGB) are motile spirochetes transmitted to mammalian or avian hosts through the bite of hematophagous arthropods, such as soft ...
[5]
Tick-Borne Relapsing Fever - PMC - PubMed Central
Relapsing fever is characterized by recurring episodes of fever and nonspecific symptoms (eg, headache, myalgia, arthralgia, shaking chills, and abdominal ...
[6]
Clinical Guidance for Louse-borne Relapsing Fever (LBRF) - CDC
May 15, 2024 · Regular changes of clothing and bedding and showers with hot water are the most important steps to treat a body louse infestation. Topical ...
[7]
About Soft Tick Relapsing Fever (STRF) - CDC
Jul 19, 2024 · Symptoms may appear 4 to 21 days after exposure and typically relapse, producing a recognizable pattern of fever that lasts around 3 days, ...
[8]
Louse-borne relapsing fever profile at Felegehiwot referral hospital ...
LBRF is now an important disease in the highlands of Ethiopia where an estimated 10,000 cases occur annually and affects mostly homeless people living in ...
[9]
A Forgotten, Yet Life-Threatening Infection | Global Health NOW
May 29, 2024 · Louse-borne relapsing fever is an ancient, yet neglected, infection caused by the Borrelia recurrentis bacteria and spread by body lice.Missing: sub- Saharan
[10]
Borrelia Infections Other Than Lyme Disease (Relapsing Fever)
Mortality rates are 10% to 70% in untreated louse-borne relapsing fever (possibly related to comorbidities and outbreaks associated with war, famine, and ...
[11]
Soft Tick Relapsing Fever - United States, 2012-2021 - PubMed
Jul 21, 2023 · During this period, 251 cases were identified in 11 states. The median annual case count was 24. Most patients with STRF (55%) were hospitalized ...
[12]
[PDF] Soft Tick Relapsing Fever — United States, 2012–2021 - CDC
Jul 21, 2023 · During this period, 251 cases were identified in 11 states. The median annual case count was 24. Most patients with STRF (55%) were hospitalized ...
[13]
Tickborne Relapsing Fever — United States, 1990–2011 - PMC - NIH
Jan 30, 2015 · Median age of patients was 38 years (range = 1–91 years). The age distribution was bimodal, with peaks among persons aged 10–14 years and 40–44 ...
[14]
Relapsing Fever Caused by Borrelia lonestari after Tick Bite in ... - NIH
We report an immunocompromised patient in Alabama, USA, 75 years of age, with relapsing fevers and pancytopenia who had spirochetemia after a tick bite.Missing: 2023-2025 Kazakhstan<|control11|><|separator|>
[15]
Survey of tick-borne relapsing fever borreliae in southern and ...
The data obtained provide strong evidence of the presence of B. miyamotoi and B. anserina in the southern and southeastern regions of Kazakhstan.
[16]
[PDF] louse-borne-relapsing-fever-in-eu-rapid-risk-assessment-17 ... - ECDC
Nov 17, 2015 · Louse-borne relapsing fever occurred among individuals coming from Somalia, Eritrea and Ethiopia. Most of them were travelling from the Horn of ...Missing: hotspots | Show results with:hotspots
[17]
Soft Tick Relapsing Fever — United States, 2012–2021 | MMWR
Jul 21, 2023 · A total of 251 STRF cases were identified in 11 of 12 states where infection is reportable; 55% of patients were hospitalized, and no deaths occurred.
[18]
[PDF] A case of tick-borne relapsing fever in pregnancy - Canada.ca
Oct 1, 2020 · Tick-borne relapsing fever (TBRF) is an infection caused by Borrelia spirochetes. In North. America, Borrelia hermsii is the most common ...Missing: Brazil Kazakhstan
[19]
Isolation and molecular characterization of a relapsing fever Borrelia ...
When bitten by infected ticks, humans can experience episodes of recurrent fever, which is a typical symptom of tick-borne relapsing fever, accompanied by ...
[20]
Survey of tick-borne relapsing fever borreliae in southern and ...
Sep 26, 2024 · Little is known about the prevalence of TBRFGB infections in ticks and humans in Kazakhstan. A total of 846 ticks belonging to ten species ...Missing: 2023-2025 Alabama
[21]
Louse-borne relapsing fever—A systematic review and analysis of ...
Mar 11, 2021 · Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding.Missing: Saharan | Show results with:Saharan
[22]
Tickborne Diseases: Diagnosis and Management - AAFP
May 1, 2020 · Unlike other ticks that live in tall brush and grass, the Ornithodoros tick species that spread tickborne relapsing fever live in rodent burrows ...
[23]
https://www.aafp.org/pubs/afp/issues/2020/0501/p530.html
[24]
Microbiological features distinguishing Lyme disease and relapsing ...
The recent proposal of splitting the genus Borrelia into two genera in the newly formed family of Borreliaceae, i. e. Borrelia and Borreliella has motivated ...Missing: morphology | Show results with:morphology
[25]
Microbiology, pathogenesis, and epidemiology of relapsing fever
Sep 18, 2024 · INTRODUCTION. Relapsing fever, which is caused by spirochetes of the genus Borrelia, is characterized by recurrent episodes of fever that ...
[26]
Historical overview and update on relapsing fever group Borrelia in ...
Jun 8, 2022 · In this review we summarize historical aspects of RFGB in Latin America and provide an update on the current scenario regarding these pathogens in the region.Soft Tick-Borne Relapsing... · Relapsing Fever In Mexico · Relapsing Fever In Venezuela
[27]
Relapsing Fever: Modern Lessons from an Ancient Disease
Jan 31, 2023 · More recently, a novel relapsing fever species, B. miyamotoi, was identified and shown to be transmitted by the same tick species that carry B.
[28]
[PDF] Borreliaceae - eScholarship.org
Cells are helical with regular or irregular coils. 0.2-0.3 µm in diameter and 10-40 µm in length. Cells do not have hooked ends. Motile.<|separator|>
[29]
Periplasmic Flagellar Export Apparatus Protein, FliH, Is Involved in ...
In the relapsing fever spirochete, Borrelia recurrentis, the number of periplasmic flagella is between 8 to10 [11]. To recognize, unfold and translocate ...
[30]
The Genome of Borrelia recurrentis, the Agent of Deadly Louse ...
Borreliae are unique among bacteria in that their genome is comprised of a linear chromosome and both linear and circular plasmids [14]. We sequenced the ...
[31]
The bdr Gene Families of the Lyme Disease and Relapsing Fever ...
The borrelial genome is unique among bacterial genomes in that it is composed of a linear chromosome and a series of linear and circular plasmids.
[32]
A Novel Relapsing Fever Group Borrelia Isolated from Ornithodoros ...
Feb 1, 2023 · This study investigated borrelial infection in Ornithodoros ticks collected in rodent-inhabited rock formations in the Brazilian semiarid region, within the ...
[33]
Immune Evasion Strategies of Relapsing Fever Spirochetes - PMC
Jul 23, 2020 · Antigenic Variation, a Powerful Mechanism of RFB to Escape Immune Avoidance. To evade clearance by the humoral immune response of the human ...Recruitment Of Complement... · Glossary · Abbreviations<|control11|><|separator|>
[34]
Antigenic variation by Borrelia hermsii occurs through recombination ...
The relapsing fever agent Borrelia hermsii undergoes multiphasic antigenic variation through gene conversion of a unique expression site on a linear plasmid.
[35]
https://pmc.ncbi.nlm.nih.gov/articles/PMC5614446/
[36]
https://doi.org/10.1084/jem.156.5.1312
[37]
Analysis of variable major protein antigenic variation in the relapsing ...
Feb 24, 2023 · Relapsing fever Borrelia undergo Vmp gene conversion at a single expression locus to generate new serotypes by antigenic switching which is the ...
[38]
Louse-borne relapsing fever (Borrelia recurrentis infection) - PMC
Mar 1, 2019 · Unlike most borreliae, transmission of B. recurrentis is restricted to one vector, the human body louse Pediculus humanus corporis, and, perhaps ...
[39]
Relapsing Fever - Infectious Diseases - Merck Manuals
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 (1).
[40]
The global distribution and the risk prediction of relapsing fever ...
Mar 8, 2024 · Most recent cases have been reported in European countries, and all were associated with refugees from east Africa and the Middle East.
[41]
Tick-borne Relapsing Fever | Washington State Department of Health
Tick-borne relapsing fever (TBRF) is an illness caused by certain species of Borrelia bacteria, which can be transmitted by some species of ticks.Missing: borreliae OspC
[42]
Assessment of the Geographic Distribution of Ornithodoros turicata ...
Feb 1, 2016 · Ornithodoros turicata is a veterinary and medically important argasid tick that is recognized as a vector of the relapsing fever spirochete Borrelia turicatae ...
[43]
Tick-Borne Relapsing Fever - AAFP
Nov 15, 2005 · Blood feeding by soft-bodied ticks takes less than one hour and usually occurs at night. Typical setting for transmission of tick-borne ...
[44]
https://pmc.ncbi.nlm.nih.gov/articles/PMC4734830/
[45]
Transovarial Transmission of Borrelia hermsii by Its Tick Vector and ...
Sep 17, 2021 · Ornithodoros hermsi is one of the smaller tick vectors of relapsing fever spirochetes [38,46] and females average only about 17 to 22 µL of ...
[46]
Tick Lifecycles - CDC
Oct 11, 2024 · The lifecycle of Ixodes scapularis ticks generally lasts two years. During this time, they go through four life stages: egg, larva, nymph, and adult.
[47]
Rearing Ixodes scapularis, the Black-legged Tick: Feeding Immature ...
May 8, 2017 · Larval ticks attach to their host for 3 - 5 days for feeding and drop off the host when fully engorged. This dependency on several different ...
[48]
Vertical transmission rates of Borrelia miyamotoi in Ixodes ...
Feb 26, 2019 · In contrast to Lyme borreliae, B. miyamotoi can be transmitted vertically from infected female ticks to their progeny.
[49]
Characteristics of Hard Tick Relapsing Fever Caused by Borrelia ...
Aug 18, 2023 · Of the 300 cases, 157 (52%) were in male and 143 (48%) among female patients; median age was 52 (range 1–86) years. Almost all cases were among ...
[50]
Tickborne Relapsing Fever — United States, 1990–2011 - CDC
Jan 30, 2015 · These soft ticks typically live in the nests of rodents such as ground squirrels, tree squirrels, and chipmunks in coniferous forests at ...
[51]
The ecology of tick-transmitted infections in the redwood chipmunk ...
Interestingly, chipmunks are an important reservoir for relapsing fever (RF) Borrelia spp. as well (Burgdorfer and Mavros, 1970). Most RF Borrelia spp. are ...
[52]
A Novel Relapsing Fever Group Borrelia Isolated from Ornithodoros ...
Feb 1, 2023 · This study investigated borrelial infection in Ornithodoros ticks collected in rodent-inhabited rock formations in the Brazilian semiarid region, within the ...Missing: RFGB | Show results with:RFGB
[53]
Relapsing Fever Caused by Borrelia lonestari after Tick Bite ... - CDC
We report an immunocompromised patient in Alabama, USA, 75 years of age, with relapsing fevers and pancytopenia who had spirochetemia after a tick bite. We ...Missing: Kazakhstan | Show results with:Kazakhstan
[54]
Pathogenesis of Relapsing Fever - PMC - PubMed Central - NIH
LBRF is caused by B. recurrentis, and TBRF is caused by several different Borrelia species. Many of the RF outbreaks described by Rutty and others in Northern ...
[55]
Tick borne relapsing fever - a systematic review and analysis of the ...
Feb 16, 2022 · The overall case fatality rate of TBRF (6.5%) and LBRF (4–10.2%) appears to not differ. Unlike LBRF, where perinatal fatalities are primarily ...
[56]
Tick-borne relapsing fever in the northwestern United ... - PubMed
Records from 182 cases of tick-borne relapsing fever (TBRF) were reviewed. In confirmed cases, there was febrile illness, and spirochetes were identified on ...Missing: Brazil Kazakhstan
[57]
Relapsing Fevers: Neglected Tick-Borne Diseases - PMC
Apr 4, 2018 · The disease occurs in temperate as well as tropical countries. Relapsing fever borreliae are spirochaetes, members of the Borreliaceae family ...
[58]
Borrelia miyamotoi: 43 Cases Diagnosed in France by Real-Time ...
Feb 28, 2020 · All patients complained about fatigue, joint pain and neuro-cognitive disorders. Some patients complained about respiratory problems (chest ...Missing: effects arthritis
[59]
Clinical Guidance for Soft Tick Relapsing Fever (STRF) - CDC
Jul 16, 2024 · Relapsing fever bacteria‎ Borrelia bacteria that cause relapsing fever have a unique process of DNA rearrangement. This process, called ...<|control11|><|separator|>
[60]
Relapsing fever borreliosis in Eurasia—forgotten, but certainly not ...
Thin and thick blood smears remain the most frequently used methods for laboratory diagnosis, with a sensitivity of 80%. PCR-based diagnosis is the most ...Review · The Vectors And The... · Taxonomy<|separator|>
[61]
Tick-borne relapsing fever - PMC - PubMed Central - NIH
Jul 16, 2020 · A peripheral blood smear demonstrating the presence of multiple ... positive for Borrelia hermsii, confirming the diagnosis of TBRF.
[62]
Serodiagnosis of Louse-Borne Relapsing Fever with ...
An ELISA using purified, recombinant His-tagged GlpQ as the antigen resulted in 21% of the acute-phase samples and 69% of the convalescent-phase samples ...
[63]
Novel approaches for the serodiagnosis of louse-borne relapsing fever
The GlpQ IgM ELISA achieved a sensitivity of 100% and a specificity of 99% (BD sera only) (Supplementary Figure 6A2) and 96.82% (including all control sera), ...
[64]
Cross-Reactivity in Serological Tests for Lyme Disease and Other ...
Strong cross-reactivity occurred when sera from individuals with Lymedisease, tick-borne relapsing fever, and louse-borne relapsing fever were tested against ...
[65]
Borrelia miyamotoi: A Comprehensive Review - MDPI
Borrelia miyamotoi is an emerging tick-borne pathogen in the Northern Hemisphere and is the causative agent of Borrelia miyamotoi disease (BMD).
[66]
Relapsing Fever Borrelia Species by PCR - ARUP Laboratories
This test is designed to detect but not differentiate the nucleic acid from B. hermsii, B. miyamotoi, B. parkeri, and B. turicatae.Missing: flaB 16S rRNA multiplex
[67]
Simultaneous Detection and Differentiation of Clinically Relevant ...
We developed a real-time semimultiplex PCR assay that detects multiple RF borreliae causing human illness and classifies them into one of three groups.
[68]
A Novel flaB Gene-Based Profiling Approach for the Rapid and ...
May 21, 2025 · In this study, we present a novel flaB gene-based profiling method for the detection and identification of Borrelia and Borreliella species in Ixodes ricinus ...
[69]
https://ltd.aruplab.com/Tests/Pub/3000010
[70]
Long-term in vitro cultivation of Borrelia miyamotoi - ScienceDirect.com
Here, we report a method for successful continuous in vitro cultivation of the emerging pathogen Borrelia miyamotoi.
[71]
(PDF) Cultivation Methods of Spirochetes from Borrelia burgdorferi ...
Aug 6, 2025 · Borrelia species are agents of relapsing fever (RF), caused by the RF Borrelia group, and Lyme disease, caused by the Lyme borreliosis (LB) ...
[72]
Relapsing Fever Treatment & Management - Medscape Reference
Dec 27, 2024 · In adults with louse-borne relapsing fever (LBRF), oral treatment consists of a single dose of tetracycline 500 mg, doxycycline 200 mg, or, when ...
[73]
Clinical Guidance for Hard Tick Relapsing Fever (HTRF) - CDC
May 15, 2024 · A 2-week course of oral doxycycline or amoxicillin has been found effective as treatment for most patients, including young children.
[74]
Efficacy and Safety of Antibiotics for the Treatment of Relapsing Fever
The mortality rate of relapsing fever can be reduced to less than 5% through antibiotic treatment. ... A clinical study involving 103 patients reported a case ...Results · Cure Rates · Discussion
[75]
[PDF] Tick & Louse-Borne Relapsing Fever - Disease Plan
Dec 15, 2016 · The mortality rates for untreated louse-borne relapsing fever (LBRF) and tick-borne relapsing fever (TBRF) are in the ranges of 10-70% and 4-10% ...
[76]
Tick borne relapsing fever - a systematic review and analysis of the ...
Feb 16, 2022 · Tick borne relapsing fever (TBRF) is a bacterial disease characterized by eponymous recurrent fever episodes. The disease is common on all continents except ...
[77]
Jarisch-Herxheimer Reaction - StatPearls - NCBI Bookshelf
Jul 7, 2025 · The Jarisch-Herxheimer reaction (JHR) is an acute, self-limited inflammatory response that develops within 24 hours of initiating antibiotic ...Continuing Education Activity · Introduction · Etiology · Treatment / Management
[78]
Louse-borne relapsing fever—A systematic review and analysis of ...
Mar 11, 2021 · Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding.
[79]
[PDF] Recommendations for Reducing Risk of Tick-Borne Relapsing Fever
Remove rodents and nests, stop rodents from reentering buildings, and reduce exposure to infected ticks. A fact sheet for pest control professionals ...
[80]
Louse-Borne Relapsing Fever (LBRF): What Is It? - WebMD
Jul 23, 2024 · ... insecticide like DDT or 0.5% permethrin dust. The Takeaway. Louse-born recovering fever can be fatal if left untreated. Talk to a doctor ...
[81]
[PDF] Delousing Procedures for Contingency Operations - Osd.mil
The purpose of this technical guide is to provide guidance on safe, effective and efficient procedures for controlling outbreaks of louse-borne disease ...
[82]
Louse-borne relapsing fever (Borrelia recurrentis infection)
Mar 1, 2019 · Breaking louse transmission is essential for the control of an epidemic. Infested clothing should be deloused using heat (>60 °C) or washing at ...Missing: efficacy | Show results with:efficacy
[83]
Spraying Tick-Infested Houses With Lambda-Cyhalothrin ... - PubMed
Spraying Tick-Infested Houses With Lambda-Cyhalothrin Reduces the Incidence of Tick-Borne Relapsing Fever in Children Under Five Years Old.
[84]
[PDF] Relapsing Fever | Washington State Department of Health
Soft tick-borne relapsing fever is most commonly caused by Borrelia hermsii, but can be caused by at least 14 other Borrelia species. Hard tick-borne relapsing ...
[85]
Tick-borne Relapsing Fever - American Lyme Disease Foundation
The bacteria are transmitted by the bite of soft tick Ornithodoros species. These ticks feed primarily at night. The bite of the tick is usually painless ...
[86]
https://pubmed.ncbi.nlm.nih.gov/9861389/
[87]
https://doh.wa.gov/sites/default/files/2025-08/420-075-Guideline-RelapsingFever.pdf
[88]
[PDF] Tick-Borne Disease Integrated Pest Management White Paper
Other methods of reducing exposure to ticks include landscape management, the use of area acaricides (including bait boxes and deer-4-poster devices), and other ...
[89]
[PDF] Soft Tick Relapsing Fever — United States, 2012–2021 - CDC
Jul 21, 2023 · * STRF was not consistently reportable in all 12 states during 2012–2021. In Texas, STRF was removed from the reportable diseases list in 2016 ...
[90]
Lesson From Response to Louse-Borne Relapsing Fever Outbreak ...
Nov 21, 2023 · In this article, we aimed to share lessons learnt from the public health response to the louse-borne relapsing fever (LBRF) outbreak coordinated ...
[91]
[PDF] Department of Communicable Disease Surveillance and Response
Control of the disease requires appropriate surveillance with universal case reporting. Health education of the population at risk and improvement of living ...
[92]
New concepts for the old challenge of African relapsing fever ...
The first epidemic, in West Africa, lasted from 1921 to 1929, and was responsible for 60 000 deaths [15]. During World War II, 400 000 cases were observed in ...
[93]
Vector-Borne Disease and Climate Change | IntechOpen
Nov 8, 2023 · Relapsing fever comes in three different forms: Relapsing tick-borne fever (TBRF), relapsing fever brought on by louses (LBRF), chronic ...
[94]
Relapsing Fever: A Two Thousand Year History | ASM.org
Relapsing fever has been known for over 2,000 years, with the first known description written by Hippocrates in 430 B.C. The disease has caused epidemics ...Missing: texts | Show results with:texts
[95]
Louse-borne relapsing fever—A systematic review and analysis of ...
Mar 11, 2021 · Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding.Missing: deaths | Show results with:deaths<|separator|>
[96]
Relapsing fever--a forgotten disease revealed - PubMed
Borrelial relapsing fever was once a major worldwide epidemic disease that made a significant impact on Livingstone during his epic travels through Africa ...
[97]
The Serbian Epidemics of Typhus and Relapsing Fever in 1915 - NIH
The Serbian Epidemics of Typhus and Relapsing Fever in 1915: Their Origin, Course, and Preventive Measures employed for their Arrest.
[98]
Relapsing Fever in Ethiopia and Scarlet Fever in Germany, 1950
In Ethiopia, reported cases of relapsing fever increased from late February and exceeded those of previous years (1947-1949). In Germany, a new surge of scarlet ...Missing: 1940s 1960s<|control11|><|separator|>
[99]
The genus Borrelia reloaded - PubMed
Dec 26, 2018 · The genus Borrelia, originally described by Swellengrebel in 1907, contains tick- or louse-transmitted spirochetes belonging to the relapsing ...
[100]
Tick-borne Relapsing Fever and Borrelia hermsii, Los Angeles ... - NIH
The primary cause of tick-borne relapsing fever in western North America is Borrelia hermsii, a rodent-associated spirochete transmitted by the fast-feeding ...Missing: symptoms | Show results with:symptoms
[101]
Transposition of structural genes to an expression sequence on a ...
Nov 21, 1985 · Transposition of structural genes to an expression sequence on a linear plasmid causes antigenic variation in the bacterium Borrelia hermsii.
[102]
Antigenic variation is associated with DNA rearrangements in a ...
Borrelia hermsii, an agent of relapsing fever, undergoes antigenic variation in its host. Surface-exposed proteins with differing primary structures ...
[103]
Analysis of variable major protein antigenic variation in the relapsing ...
Feb 24, 2023 · Relapsing fever Borrelia undergo Vmp gene conversion at a single expression locus to generate new serotypes by antigenic switching which is ...
[104]
Hard Tick Relapsing Fever | Vermont Department of Health
May 8, 2025 · Hard tick relapsing fever is treated with a 2 to 4 week course of doxycycline. Other antibiotics have also been used to treat this illness. How ...
[105]
Vaccination with the variable tick protein of the relapsing fever ... - NIH
Oct 21, 2015 · In western North America, most human cases of relapsing fever are caused by Borrelia hermsii, which cycles in nature between its tick vector ...
[106]
Host Immune Evasion by Lyme and Relapsing Fever Borreliae
To evade the humoral response, Borrelia utilize antigenic variation of either outer surface proteins (Osps) and the Vmp-like sequences (Vls) system (Lyme ...