Tools
Relapsing Fever
Introduction
Relapsing fever typically refers to malaria-like illnesses characterized by recurrent fevers, chills, and malaise caused by various spirochetes belonging to Borrelia species. The syndrome is commonly referred to as either tick-borne relapsing fever (TBRF) or louse-borne relapsing fever (LBRF), which denotes their transmission vector. The causative organism and associated vector vary based on the geographic area of exposure.[1][2][3] Transmission is through the bite or crushing against the skin of an endemic arthropod, typically a tick or louse, that can transmit the pathogen.
In areas outside endemic transmission, imported cases may occur in returned travelers. The antigens on the spirochetes may interact with the host immune response to cause a constitutional and febrile response in the patient. The term "relapsing fever" was first coined in Edinburgh in the 1840s to describe the clinical manifestations of an outbreak affecting the city.[4] The syndrome's etiology was not identified for another 30 years, and the vectors driving transmission were not identified until the first half of the twentieth century.[5][6] However, relapsing fever (particularly LBRF) was typically implicated in outbreaks associated with warfare and poverty and was often found comorbid with trench fever, caused by Rickettsia quintana during World War I.[7]
Etiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
Borrelia recurrentis is the cause of epidemic relapsing fever, which is reported most frequently in northern and eastern Africa. Tick-borne relapsing fever, reported in the United States, can be caused by several species, including Borrelia hermsii, Borrelia mazzotti, Borrelia turicatae, and Borrelia parkeri.[8] Globally, other Borrelia species are linked with relapsing fever according to their geography.
In Africa, Borrelia duttonii, Borrelia hispanica, Borrelia crocidurae, Borrelia microti, Borrelia recurrentis, Borrelia merionesi, and Borrelia theileri may be transmitted by various Ornithodoros and Rhipcephalus ticks, while Borrelia persica, Borrelia latyschewii, and B. microti seen in Asia and the Middle East is transmitted via Ornithodorids.[6] B. hermsii, the primary cause of tick-borne relapsing fever, has been reported in the United States in Colorado, near Lake Tahoe and the Grand Canyon.[9] The latter has also been determined to be the most widely distributed Borrelia species across the Americas, with Borrelia venezuelensis found to a lesser extent.
Borrelia miyamotoi causes relapsing fever similar to Lyme disease and is reported in the northeastern United States, Japan, and Russia, with slight variations in presentation depending on geography.[10] Borrelia miyamotoi and B. turciatae, found in the United States, along with B. recurrentis, Borrelia lonestari, and Borrelia johnsonii, are also reported to have a worldwide distribution. Soft-bodied ticks can better carry Borrelia species associated with TBRF.[9] However, hard ticks such as Ixodes have been reported to have had cases of Borrelia, particularly north of 30° N, with Ambylomma appearing to a lesser extent.[11] Borrelia species are fastidious spirochetes. They are large with irregular spirals and readily stain with aniline dyes. Although Borrelia is technically gram-negative, they are most readily identified by Giemsa or Wright staining.[12]
Epidemiology
Borrelia recurrentis, or epidemic relapsing fever or LBRF, is reported most commonly in areas of overcrowding and poor personal hygiene. This pathogen generally causes epidemics and has previously been associated with war, poverty, and famines. Borrelia recurrentis is transmitted via lice and has decreased in frequency substantially since the first half of the 20th century. As a result, relapsing fever is generally recognized as a neglected tropical disease confined to neighboring countries of the Horn of Africa.[13]
Ethiopia and parts of Sudan are currently regarded as the only remaining countries where LBRF remains endemic.[14] Episodes of LBRF among people who emigrated from Africa to Europe in recent years reinforce this theory of endemicity from the Horn of Africa.[15] The louse species associated with spirochete transmission is Pediculus humanus humanus.[15] Unlike ticks, P. humanus is not associated with transovarial or transstadial transmission of Borrelia species, despite spirochetes being identified from louse feces.[16]
Tick-borne relapsing fever is associated with a wider variety of Borrelia species and is found worldwide, typically in areas of high tick endemicity, eg, in forests and woodland edges. The transmission of pathogenic spirochetes is generally caused by the bite of an infected tick or the crushed body of a feeding louse against the host’s body. Humans are the only known reservoir host for B. recurrentis.[17]
Humans and many other vertebrate species may be hosts for TBRF Borrelia species. Typical vectors include the Ornithodorids for humans, Argasidae for birds, and Rhipicephalus for ruminants (eg, bovine borreliosis). Rodents are the most common reservoir following vector transmission, but humans and other vertebrates can become infected. Tick vectors may also be considered reservoirs for Borrelia due to their transovarial and transstadial spirochete transmission through various generations of progeny.[18] Gravid ticks infected with Borrelia will lay multiple larvae, which progress and mature from nymphs to mating adults, which can propagate infection. In this way, Borrelia spirochetes may be epidemiologically dormant until their exposure to susceptible hosts following the next feed.
The incubation period from initial transmission to symptom onset is typically 4 to 18 days following exposure to Borrelia.[19] Following this incubation period, constitutional symptoms may develop, and pregnant women who become infected may be at risk of transplacental transmission.
Pathophysiology
Borrelia recurrentis is transmitted when an infected human body louse, Pediculosis humanus corporis, is crushed, and Borrelia recurrentis present in the hemocoel penetrate through intact skin and mucosal surfaces. Intact lice do not transmit epidemic-relapsing fever. A louse is infected when it feeds on a febrile patient with a relapsing fever. Humans are the only known host and reservoir of Borrelia recurrentis.
On the contrary, small rodents and other mammals (birds, bats) serve as a reservoir for tick-borne Borrelia species. Borrelia hermsii, Borrelia parkeri, and Borrelia turicatae are transmitted via the bite of soft-bodied night-feeding Ornithodoros ticks. As the ticks feed at night, patients are often unaware of the bite. Exposure to these ticks has been associated with sleeping in mountain cabins and spelunking. Borrelia miyamotoi is transmitted via the Ixodes tick, similar to Lyme disease. When affecting animals, eg, birds or ruminants, Borrelia miyamotoi can cause a periodic fever, but it is classically associated with relapsing fever among human hosts.
The clinical manifestations of relapsing fever, including fever, myalgias, chills, and arthralgias, are caused by an endotoxin-like substance produced by the spirochete. The severity of illness is associated with the level of spirochetemia with 5 spirochetes per immersion field in oil seen in blood smears of patients during the acute stage of febrile illness.[20] The initial febrile episode in relapsing fever resolves due to the development of antibodies directed at the surface proteins of the organism.
Following the acute phase of illness, the number of spirochetes declines substantially to as low as 1 spirochete per oil immersion field. However, a reservoir of organisms in reticuloendothelial organs and the central nervous system undergo genetic reassortment to alter the expression of surface proteins on their outer membranes (variable small proteins and variable large proteins).[12][21] This allows for an escape from immune clearance and reemergence of spirochetemia and clinical symptoms. The typical recurrence pattern of Borrelia symptoms in relapsing fever is due to repeated cycles of surface protein reassortment followed by antibody-mediated infection suppression. This characteristic variation of the outer-membrane lipoprotein is known as the relapse phenomenon. Infection is not associated with long-term immunity; patients may be reinfected as soon as 6 months after the initial infection.[3]
History and Physical
The symptoms of relapsing fevers are characterized by the abrupt onset of fever and chills, often accompanied by malaise, arthralgias, and myalgias. Other symptoms occurring early include anorexia, nausea, vomiting, and diarrhea. Additionally, patients frequently present with extreme exhaustion accompanied by confusion. A petechial rash on the skin and mucous membranes is often seen.[22]
Hepatic tenderness is the most common sign (60% of the patients), while 40% of patients can have signs of meningism.[23] Epistaxis and subconjunctival hemorrhage are more common compared to hemoptysis and retinal bleeds. Hepatic dysfunction and jaundice, enlargement of the spleen and liver may also occur. Left untreated, relapsing fever can also manifest with various complications, including cardiac, pulmonary, perinatal, and neurological. Pregnant women may experience a prolonged and severe illness.[19] Prompt recognition, particularly in high-endemic areas or travelers returning from such areas, is necessary to initiate prompt evaluation and empirical management.
After the resolution of the first episode, which typically lasts 1 week, patients will experience several recurrences of fever that are shorter and less severe. Episodes occur every 5 to 10 days and may persist for several cycles before resolution. Typically, only 1 or 2 episodes of fever occur during a louse-borne relapsing fever epidemic.[22] However, in endemic, tick-borne relapsing fever, 3 to 7 recurrences may occur before the resolution of symptoms.[5]
Evaluation
Diagnosis of relapsing fever requires a careful history with attention to travel history and other geographic information, living conditions, and the temporal pattern of the symptoms. Laboratory evaluation may include neutrophil leukocytosis and thrombocytopenia. Jarisch-Herxheimer reaction occurring in response to antibiotics is associated with leukopenia. Elevated liver function tests are seen with hepatic impairment. Additionally, mild renal dysfunction can occur. Cerebral involvement is associated with cerebrospinal fluid pleocytosis without the presence of spirochetes.
Diagnosis is confirmed by detecting Borrelia in Giemsa-stained blood films, serologic analysis, or polymerase chain reaction (PCR) detection of the organism. Of these, PCR has the highest level of evidence for diagnosis, followed by light microscopy identification of spirochetes and, to a lesser extent, indirect paired serology tests and clinical diagnosis based on pretest probability.[15]
Light microscopy of thin and thick smears may detect spirochetes using direct visualization of Giemsa or Wright stains (aniline dyes). This remains a gold standard method of diagnosis, particularly in low-resource settings.[15] However, the expertise of laboratory staff is required to recognize the spirochetes and perform the special stains. Traditional gram stains will only show weak gram-negative staining with Borrelia species and are better visualized using aniline dyes. Given their slow growth and requirements for specialized media, these organisms are not identifiable in routine laboratory cultures, often found in tertiary referral laboratories and research settings.[24] The diagnostic yield is highest with the earlier febrile episodes and decreases with each recurrence. Early in the course of illness, the number of spirochetes visible in the blood can reach 100,000/mm3. The spirochetes may not be visible between episodes and later recurrences.
Serology may also be used to diagnose tick-borne relapsing fever, particularly when diagnosis is suspected later in the course of illness. In that case, repeated testing with a rise in Immunoglobulin G (IgG) is suggestive of a recent infection. However, these serologic tests cross-react with other spirochetes (eg, leptospirosis and syphilis), and must be interpreted in the setting of clinical symptoms.[3][25] The decreased sensitivity for serology is due to the surface protein variation expressed by the spirochete, which may lead to proteins not being recognized by immunofluorescence and enzyme immunoassay tests.[12] However, serology tests may be used in more resource-poor settings, often due to the expense of PCR and the availability of wide-range primers. Serology tests may also be used in population serosurveys. However, serology testing does not differentiate acute from previous infections in endemic areas and does predict long-term sequelae or response to treatment.[24] Serology may first test positive 5 to 7 days after symptom onset, but empiric treatment may already need to be started, given the time needed for seroconversion.[26][27]
Treatment / Management
Relapsing Fever Management
Relapsing fever is treated with doxycycline 100 mg twice daily for 7 to 10 days. Doxycycline acts on the 30S ribosomal subunit to inhibit bacterial protein synthesis, resulting in bacteriostatic activity. In pregnant women and children younger than 8 years of age, penicillin or erythromycin are the preferred agents due to the concern of dental staining with doxycycline use, despite tooth staining being associated with doxycycline cumulative dose rather than as an idiosyncratic reaction. No discernible difference is observed in clinical outcomes in patients treated with >10 days of doxycycline compared with <10 days.[28]
Improving the patient's nutritional status can go a long way in improving patient outcomes. Borrelia infections may also be self-limited and resolve without treatment in some cases.[12][29][30][31](B3)
Jarisch-Herxheimer Reaction
Observing patients for several hours after initiating antibiotic therapy is essential due to the risk of the Jarisch-Herxheimer reaction, which is common. The Jarisch-Herxheimer reaction is a flu-like response mediated by the release of proinflammatory cytokines following the release of inflammatory contents from within the bacteria after lysis by antibiotics. Symptoms, including fever, chills, rigors, nausea and vomiting, headache, tachycardia, hypotension, hyperventilation, flushing, and myalgia characterize this reaction. It occurs in approximately 19% of patients treated with antibiotics.[24] The Jarisch-Herxheimer reaction is rarely fatal and should be managed with supportive care. This reaction is more common in adolescents than in younger children. The use of steroids or paracetamol does not appear to prevent the occurrence of Jarisch-Herxheimer reactions in LBRF.[32] Furthermore, the evidence does not show Jarisch-Herxheimer reactions can be prevented or ameliorated using slow-release penicillin.[33](A1)
Differential Diagnosis
All underlying etiologies of relapsing or periodic patterns of fevers should be considered, including malaria, typhoid, leptospirosis, brucellosis, yellow fever, dengue fever, trench fever, lymphocytic choriomeningitis, leptospirosis, melioidosis, and rat bite fever. The pattern may help differentiate the causative organism but their regularity and frequency.
Leptospirosis is characterized by an acute biphasic illness of an initial flu-like illness followed by jaundice, renal failure, and pulmonary edema. Leptospirosis can occasionally cause aseptic meningitis. Leptospirosis may be excluded through the absence of hematuria and jaundice. Louse-borne relapsing fever has a longer febrile period than trench fever and may be accompanied by jaundice, hepatomegaly, and albuminuria.[7] Typhoid may have associated gastrointestinal symptoms, relative bradycardia, and the presence of rose spots.[34]
Brucellosis was traditionally described as an undulant fever, intermittent and malignant, associated typically with infected milk from ruminants.[35] The clinical course of brucellosis may be marked by intermittent waves of fever of variable length compared to relapsing fever from tick or louse-borne disease. Malaria is a mosquito-borne illness common in parts of Africa where LBRF is endemic. However, it is characterized by cyclical fevers without the features of epistaxis and subconjunctival hemorrhage seen in LBRF.
Other differentials that should be considered in returned travelers or migrants include the following infectious and zoonotic diseases:
- Yellow fever
- Dengue fever
- Ehrlichiosis
- Anaplasmosis
- Rat-bite fever
- Ascending cholangitis
- Viral hemorrhagic fever
- Lymphocytic choriomeningitis
Prognosis
With appropriate antibiotic treatment, the mortality of relapsing fever decreases substantially. Fatalities are lower in tick-borne disease than in louse-borne disease, both with and without treatment. Untreated, LBRF has reported mortality rates ranging from 30% to 80% during epidemics, decreasing to <2% to 5.5% with treatment.[23][36] Mortality from TBRF ranges from 4% to 10% untreated to <2% treated.[5][37] Mortality with TBRF tends to be secondary to acute respiratory distress syndrome or associated neurological complications.[24]
Jarisch-Herxheimer reactions, known to be associated with relapsing fever, have not been observed to increase mortality rates when present. In pregnant women, up to 44% of TBRF patients experience adverse gestational outcomes, including intrauterine growth restriction, placental injury, maternal anemia, and impaired fetal circulation. Whereas in LBRF, adverse outcomes include premature labor, abortions in up to 71%, and high perinatal mortality.[24][38]
Relapse of clinical disease may occur with suboptimal treatment duration or dose, including penicillin.[23] Relapsing fever may be more severe in patients with immunodeficiency, eg, asplenia or B cell dysfunction.[39] Malnutrition, preexisting myocarditis, structural pulmonary disease, and hepatosplenic dysfunction may also present a poorer prognosis in patients with relapsing fever. Coinfections with malaria and typhoid fever where LBRF is endemic can also result in more severe clinical outcomes.[19][40][41] Children younger than 15 years tend to have less mortality than adults.[19]
Complications
Both LBRF and TBRF can manifest as multiorgan disease because of the interplay between the host immune response and the Borrelia spirochetes, including the Jarisch-Herxheimer reaction. The severity of the illness, correlated with the level of spirochetemia, is associated with the presence of complications in untreated patients, including:
- Hyperpyrexia [22]
- Epistaxis [22]
- Meningitis [42]
- Focal neurological deficits [43]
- Acute respiratory distress syndrome (ARDS) [44][45]
- Perivascular interstitial histiocytic myocarditis [46][47]
- Acute pulmonary edema from myocarditis [48]
- Hematemesis and hematochezia [49]
- Cerebral bleeding in LBRF [46][3]
- Splenic abscesses and rupture [22]
- Hepatic failure [3]
- Purpura [50]
- Disseminated intravascular coagulation (DIC) [50][51]
Neurological issues like limb paralysis, cranial nerve palsies, and mononeuritis multiplex can occur in both LBRF and TBRF, with focal convulsions comparatively more frequent in tick-borne disease.[43][52] An increased risk of mortality is attributed to cerebral hemorrhage and myocarditis, as well as bleeding complications.[46][48][50][53]
Deterrence and Patient Education
Given humans are the only hosts for LBRF, appropriate measures can be used to limit transmission from exposed and unexposed individuals by reducing the burden of the Pediculus humanus corporis, including:
- Improving personal hygiene (washing the hair of infested individuals with shampoo or soap does kill lice effectively)
- Immersing infested clothing in warm or cold water for at least 30 minutes with or without soap to clean the items of lice and eggs
- Treating clothes with either pyrethroids or DDT powder [54]
- Washing clothes set at 104 °F (40 °C) or more using a detergent for at least 7 days [Killing Clothes Lice]
- Bagging clothes away from an exposed individual for at least 7 days at 50 °F (10 °C) or at least 10 days at any temperature
- Sterilization of the patient's clothing and bedding to kill the lice by use of steel steaming drums [Disinfection Methods]
- Appropriate counseling of travelers to endemic regions is alsovitalt to highlight vigilance and precautions against exposure to lice and ticks.
- Promising observations that ivermectin for the treatment of body lice is sufficient for removal, administered at 7-day intervals require further validation [55]
Studies have demonstrated that bagging clothes away from an exposed individual for a prolonged period is sufficient to kill infected lice and their eggs.[Effect of Temperature on Lice Eggs] The mechanism is thought to be secondary to starvation of adult and nymphal lice and lower temperatures away from the warm environment of their hosts.
For TBRF, avoidance of habitats endemic with ticks that transmit TBRF is considered the best deterrence. When visiting potential tick habitats, using repellents and wide-brimmed hats and limiting exposure through long-sleeved shirts and long trousers or pants is recommended.[56] Permethrin-treated clothing may also effectively repel ticks. Appropriate education to at-risk individuals may include checks of themselves, their equipment, and any pets or children after potential exposure. Light-colored clothing may be useful in visualizing ticks. Postexposure prophylaxis with a single dose of doxycycline 100 mg up to 72 hours after tick exposure prevents disease.[57][58]
Pearls and Other Issues
Currently, no vaccine is available for any of the Borrelia species associated with relapsing fever. Avoidance of louse and tick exposure through proper hygiene, environmental cleaning to remove rodent nesting material, and insect repellant can decrease the risk of infection. As transmission is typically vector-borne, standard precautions are recommended, and isolation is not required other than eradicating body lice.[59] Because relapsing fever can mimic other periodic fever syndromes in endemic areas, ruling out relevant differential diagnoses of infectious and autoimmune conditions is essential based on the individual's risk factors and travel history.
Enhancing Healthcare Team Outcomes
Effective management of relapsing fever requires a coordinated interprofessional team approach to ensure timely diagnosis, appropriate treatment, and patient safety. Physicians and advanced practitioners play a key role in recognizing symptoms, obtaining detailed travel and exposure histories, and ordering the necessary laboratory tests, including microscopy, serology, and PCR for Borrelia detection. Emergency department physicians must promptly initiate treatment, balancing antibiotic therapy with the risk of a Jarisch-Herxheimer reaction. Nurses are essential in monitoring patients for adverse reactions, providing supportive care, and educating patients about the course of illness. Laboratory professionals contribute their expertise in identifying Borrelia species, which is critical for an accurate and timely diagnosis. Pharmacists ensure proper antibiotic selection and dosing, particularly when tailoring treatment for pediatric patients or those with contraindications.
In cases of severe disease with multiorgan involvement, effective communication and collaboration between specialists are essential to optimize patient outcomes. Critical care teams, including intensivists and ICU nurses, may be needed for patients experiencing severe Jarisch-Herxheimer reactions or organ dysfunction. Neurologists should be consulted for suspected meningitis or cerebral complications, while cardiologists play a role in evaluating potential myocarditis. Rehabilitation specialists, including physical and occupational therapists, support long-term recovery in cases of prolonged illness. Mental health professionals may also be involved in addressing psychological distress associated with the severe or prolonged disease. Seamless interprofessional communication and care coordination enhance patient safety, reduce complications, and improve overall team performance, ensuring patient-centered care at every stage of illness.
References
Eldin C, Jaulhac B, Mediannikov O, Arzouni JP, Raoult D. Values of diagnostic tests for the various species of spirochetes. Medecine et maladies infectieuses. 2019 Mar:49(2):102-111. doi: 10.1016/j.medmal.2019.01.009. Epub 2019 Feb 11 [PubMed PMID: 30765286]
Pukhovskaya NM, Morozova OV, Vysochina NP, Belozerova NB, Ivanov LI. Prevalence of Borrelia burgdorferi sensu lato and Borrelia miyamotoi in ixodid ticks in the Far East of Russia. International journal for parasitology. Parasites and wildlife. 2019 Apr:8():192-202. doi: 10.1016/j.ijppaw.2019.01.005. Epub 2019 Feb 6 [PubMed PMID: 30891399]
Warrell DA. Louse-borne relapsing fever (Borrelia recurrentis infection). Epidemiology and infection. 2019 Jan:147():e106. doi: 10.1017/S0950268819000116. Epub [PubMed PMID: 30869050]
Cutler SJ. Relapsing fever--a forgotten disease revealed. Journal of applied microbiology. 2010 Apr:108(4):1115-22. doi: 10.1111/j.1365-2672.2009.04598.x. Epub 2009 Oct 20 [PubMed PMID: 19886891]
Faccini-Martínez ÁA, Silva-Ramos CR, Santodomingo AM, Ramírez-Hernández A, Costa FB, Labruna MB, Muñoz-Leal S. Historical overview and update on relapsing fever group Borrelia in Latin America. Parasites & vectors. 2022 Jun 8:15(1):196. doi: 10.1186/s13071-022-05289-5. Epub 2022 Jun 8 [PubMed PMID: 35676728]
Level 3 (low-level) evidenceCutler SJ. Relapsing Fever Borreliae: A Global Review. Clinics in laboratory medicine. 2015 Dec:35(4):847-65. doi: 10.1016/j.cll.2015.07.001. Epub 2015 Aug 22 [PubMed PMID: 26593261]
Anstead GM. The centenary of the discovery of trench fever, an emerging infectious disease of World War 1. The Lancet. Infectious diseases. 2016 Aug:16(8):e164-72. doi: 10.1016/S1473-3099(16)30003-2. Epub 2016 Jun 30 [PubMed PMID: 27375211]
Margos G, Gofton A, Wibberg D, Dangel A, Marosevic D, Loh SM, Oskam C, Fingerle V. The genus Borrelia reloaded. PloS one. 2018:13(12):e0208432. doi: 10.1371/journal.pone.0208432. Epub 2018 Dec 26 [PubMed PMID: 30586413]
Tang T, Zhu Y, Zhang YY, Chen JJ, Tian JB, Xu Q, Jiang BG, Wang GL, Golding N, Mehlman ML, Lv CL, Hay SI, Fang LQ, Liu W. The global distribution and the risk prediction of relapsing fever group Borrelia: a data review with modelling analysis. The Lancet. Microbe. 2024 May:5(5):e442-e451. doi: 10.1016/S2666-5247(23)00396-8. Epub 2024 Mar 8 [PubMed PMID: 38467129]
Qiu Y, Nakao R, Hang'ombe BM, Sato K, Kajihara M, Kanchela S, Changula K, Eto Y, Ndebe J, Sasaki M, Thu MJ, Takada A, Sawa H, Sugimoto C, Kawabata H. Human Borreliosis Caused by a New World Relapsing Fever Borrelia-like Organism in the Old World. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019 Jun 18:69(1):107-112. doi: 10.1093/cid/ciy850. Epub [PubMed PMID: 30423022]
Level 2 (mid-level) evidenceVazquez Guillamet LJ, Marx GE, Benjamin W, Pappas P, Lieberman NAP, Bachiashvili K, Leal S, Lieberman JA. Relapsing Fever Caused by Borrelia lonestari after Tick Bite in Alabama, USA. Emerging infectious diseases. 2023 Feb:29(2):441-444. doi: 10.3201/eid2902.221281. Epub [PubMed PMID: 36692856]
Dworkin MS, Schwan TG, Anderson DE Jr, Borchardt SM. Tick-borne relapsing fever. Infectious disease clinics of North America. 2008 Sep:22(3):449-68, viii. doi: 10.1016/j.idc.2008.03.006. Epub [PubMed PMID: 18755384]
Level 3 (low-level) evidenceRaoult D, Roux V. The body louse as a vector of reemerging human diseases. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 1999 Oct:29(4):888-911 [PubMed PMID: 10589908]
Boutellis A, Mediannikov O, Bilcha KD, Ali J, Campelo D, Barker SC, Raoult D. Borrelia recurrentis in head lice, Ethiopia. Emerging infectious diseases. 2013 May:19(5):796-8. doi: 10.3201/eid1905.121480. Epub [PubMed PMID: 23648147]
Kahlig P, Paris DH, Neumayr A. Louse-borne relapsing fever-A systematic review and analysis of the literature: Part 1-Epidemiology and diagnostic aspects. PLoS neglected tropical diseases. 2021 Mar:15(3):e0008564. doi: 10.1371/journal.pntd.0008564. Epub 2021 Mar 11 [PubMed PMID: 33705384]
Level 1 (high-level) evidenceHouhamdi L, Raoult D. Excretion of living Borrelia recurrentis in feces of infected human body lice. The Journal of infectious diseases. 2005 Jun 1:191(11):1898-906 [PubMed PMID: 15871124]
Meri T, Cutler SJ, Blom AM, Meri S, Jokiranta TS. Relapsing fever spirochetes Borrelia recurrentis and B. duttonii acquire complement regulators C4b-binding protein and factor H. Infection and immunity. 2006 Jul:74(7):4157-63 [PubMed PMID: 16790790]
Schwan TG, Raffel SJ. Transovarial Transmission of Borrelia hermsii by Its Tick Vector and Reservoir Host Ornithodoros hermsi. Microorganisms. 2021 Sep 17:9(9):. doi: 10.3390/microorganisms9091978. Epub 2021 Sep 17 [PubMed PMID: 34576873]
Ramos JM, Malmierca E, Reyes F, Tesfamariam A. Louse-borne relapsing fever in Ethiopian children: experience of a rural hospital. Tropical doctor. 2009 Jan:39(1):34-6. doi: 10.1258/td.2008.080157. Epub [PubMed PMID: 19211422]
Dworkin MS, Anderson DE Jr, Schwan TG, Shoemaker PC, Banerjee SN, Kassen BO, Burgdorfer W. Tick-borne relapsing fever in the northwestern United States and southwestern Canada. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 1998 Jan:26(1):122-31 [PubMed PMID: 9455520]
Cadavid D, Londoño D. Understanding tropism and immunopathological mechanisms of relapsing fever spirochaetes. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2009 May:15(5):415-21. doi: 10.1111/j.1469-0691.2009.02785.x. Epub [PubMed PMID: 19489924]
Level 3 (low-level) evidenceSalih SY, Mustafa D, Abdel Wahab SM, Ahmed MA, Omer A. Louse-borne relapsing fever: I. A clinical and laboratory study of 363 cases in the Sudan. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1977:71(1):43-8 [PubMed PMID: 871032]
Level 3 (low-level) evidenceBryceson AD, Parry EH, Perine PL, Warrell DA, Vukotich D, Leithead CS. Louse-borne relapsing fever. The Quarterly journal of medicine. 1970 Jan:39(153):129-70 [PubMed PMID: 4913454]
Jakab Á, Kahlig P, Kuenzli E, Neumayr A. Tick borne relapsing fever - a systematic review and analysis of the literature. PLoS neglected tropical diseases. 2022 Feb:16(2):e0010212. doi: 10.1371/journal.pntd.0010212. Epub 2022 Feb 16 [PubMed PMID: 35171908]
Level 1 (high-level) evidenceMiddelveen MJ, Shah JS, Fesler MC, Stricker RB. Relapsing fever Borrelia in California: a pilot serological study. International journal of general medicine. 2018:11():373-382. doi: 10.2147/IJGM.S176493. Epub 2018 Sep 21 [PubMed PMID: 30288084]
Level 3 (low-level) evidenceLevett PN. Leptospirosis. Clinical microbiology reviews. 2001 Apr:14(2):296-326 [PubMed PMID: 11292640]
Bajani MD, Ashford DA, Bragg SL, Woods CW, Aye T, Spiegel RA, Plikaytis BD, Perkins BA, Phelan M, Levett PN, Weyant RS. Evaluation of four commercially available rapid serologic tests for diagnosis of leptospirosis. Journal of clinical microbiology. 2003 Feb:41(2):803-9 [PubMed PMID: 12574287]
Domínguez MC, Vergara S, Gómez MC, Roldán ME. Epidemiology of Tick-Borne Relapsing Fever in Endemic Area, Spain. Emerging infectious diseases. 2020 May:26(5):849-856. doi: 10.3201/eid2605.190745. Epub [PubMed PMID: 32308194]
Sathiamoorthi S, Smith WM. The eye and tick-borne disease in the United States. Current opinion in ophthalmology. 2016 Nov:27(6):530-537 [PubMed PMID: 27585218]
Level 3 (low-level) evidenceChoi E, Pyzocha NJ, Maurer DM. Tick-Borne Illnesses. Current sports medicine reports. 2016 Mar-Apr:15(2):98-104. doi: 10.1249/JSR.0000000000000238. Epub [PubMed PMID: 26963018]
Mafi N, Yaglom HD, Levy C, Taylor A, O'Grady C, Venkat H, Komatsu KK, Roller B, Seville MT, Kusne S, Po JL, Thorn S, Ampel NM. Tick-Borne Relapsing Fever in the White Mountains, Arizona, USA, 2013-2018. Emerging infectious diseases. 2019 Apr:25(4):649-653. doi: 10.3201/eid2504.181369. Epub [PubMed PMID: 30882304]
Butler T. The Jarisch-Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis. The American journal of tropical medicine and hygiene. 2017 Jan 11:96(1):46-52. doi: 10.4269/ajtmh.16-0434. Epub 2016 Oct 24 [PubMed PMID: 28077740]
Level 3 (low-level) evidenceWarrell DA, Perine PL, Krause DW, Bing DH, MacDougal SJ. Pathophysiology and immunology of the Jarisch-Herxheimer-like reaction in louse-borne relapsing fever: comparison of tetracycline and slow-release penicillin. The Journal of infectious diseases. 1983 May:147(5):898-909 [PubMed PMID: 6842024]
Hoffner RJ, Slaven E, Perez J, Magana RN, Henderson SO. Emergency department presentations of typhoid fever. The Journal of emergency medicine. 2000 Nov:19(4):317-21 [PubMed PMID: 11074322]
Huddleson IF, Johnson HW, Bates CP. Treatment of Undulant Fever. American journal of public health and the nation's health. 1936 Jul:26(7):730-1 [PubMed PMID: 18014466]
Steen R, Townsend RS. Relapsing Fever in Bulandshahr District. The Indian medical gazette. 1913 Sep:48(9):338-341 [PubMed PMID: 29005896]
Goubau PF. Relapsing fevers. A review. Annales de la Societe belge de medecine tropicale. 1984:64(4):335-64 [PubMed PMID: 6397148]
Kahlig P, Neumayr A, Paris DH. Louse-borne relapsing fever-A systematic review and analysis of the literature: Part 2-Mortality, Jarisch-Herxheimer reaction, impact on pregnancy. PLoS neglected tropical diseases. 2021 Mar:15(3):e0008656. doi: 10.1371/journal.pntd.0008656. Epub 2021 Mar 11 [PubMed PMID: 33705387]
Level 1 (high-level) evidenceMagnarelli LA, Meegan JM, Anderson JF, Chappell WA. Comparison of an indirect fluorescent-antibody test with an enzyme-linked immunosorbent assay for serological studies of Lyme disease. Journal of clinical microbiology. 1984 Aug:20(2):181-4 [PubMed PMID: 6386843]
Ramos JM, Reyes F, Tesfamariam A, Malmierca E. Louse-borne relapsing fever and malaria co-infection in Ethiopia. Tropical doctor. 2007 Apr:37(2):121-2 [PubMed PMID: 17540107]
ANDERSON TR, ZIMMERMAN LE. Relapsing fever in Korea; a clinicopathologic study of eleven fatal cases with special attention to association with Salmonella infections. The American journal of pathology. 1955 Nov-Dec:31(6):1083-109 [PubMed PMID: 13268613]
Level 3 (low-level) evidenceLarsson C, Andersson M, Pelkonen J, Guo BP, Nordstrand A, Bergström S. Persistent brain infection and disease reactivation in relapsing fever borreliosis. Microbes and infection. 2006 Jul:8(8):2213-9 [PubMed PMID: 16782384]
Castilla-Guerra L, Fernandez-Moreno MC, Vergara-Lopez S, Merino-Rumin M, Colmenero-Camacho MA. [Neurological complications of tick-borne relapsing fever]. Revista de neurologia. 2016 Sep 16:63(6):252-6 [PubMed PMID: 27600739]
Warrell DA, Pope HM, Parry EH, Perine PL, Bryceson AD. Cardiorespiratory disturbances associated with infective fever in man: studies of Ethiopian louse-borne relapsing fever. Clinical science. 1970 Jul:39(1):123-45 [PubMed PMID: 5448162]
Davis RD, Burke JP, Wright LJ. Relapsing fever associated with ARDS in a parturient woman. A case report and review of the literature. Chest. 1992 Aug:102(2):630-2 [PubMed PMID: 1643961]
Level 3 (low-level) evidenceSundnes KO, Haimanot AT. Epidemic of louse-borne relapsing fever in Ethiopia. Lancet (London, England). 1993 Nov 13:342(8881):1213-5 [PubMed PMID: 7901534]
Wengrower D, Knobler H, Gillis S, Chajek-Shaul T. Myocarditis in tick-borne relapsing fever. The Journal of infectious diseases. 1984 Jun:149(6):1033 [PubMed PMID: 6736677]
Parry EH, Warrell DA, Perine PL, Vukotich D, Bryceson AD. Some effects of louse-borne relapsing fever on the function of the heart. The American journal of medicine. 1970 Oct:49(4):472-9 [PubMed PMID: 4249048]
Zaidi SA, Singer C. Gastrointestinal and hepatic manifestations of tickborne diseases in the United States. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2002 May 1:34(9):1206-12 [PubMed PMID: 11941547]
Webster G, Schiffman JD, Dosanjh AS, Amieva MR, Gans HA, Sectish TC. Jarisch-Herxheimer reaction associated with ciprofloxacin administration for tick-borne relapsing fever. The Pediatric infectious disease journal. 2002 Jun:21(6):571-3 [PubMed PMID: 12182387]
Level 3 (low-level) evidencePerine PL, Parry EH, Vukotich D, Warrell DA, Bryceson AD. Bleeding in louse-borne relapsing fever. I. Clinical studies in 37 patients. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1971:65(6):776-81 [PubMed PMID: 5157439]
Liu H, Fitzgerald D, Gran B, Leong JM, Alugupalli KR. Induction of distinct neurologic disease manifestations during relapsing fever requires T lymphocytes. Journal of immunology (Baltimore, Md. : 1950). 2010 May 15:184(10):5859-64. doi: 10.4049/jimmunol.0902737. Epub 2010 Apr 9 [PubMed PMID: 20382883]
D'Ambrosio A, Patti G, Manzoli A, Sinagra G, Di Lenarda A, Silvestri F, Di Sciascio G. The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review. Heart (British Cardiac Society). 2001 May:85(5):499-504 [PubMed PMID: 11302994]
SOPER FL, DAVIS WA. Typhus fever in Italy, 1943-1945, and its control with louse powder. American journal of hygiene. 1947 May:45(3):305-34 [PubMed PMID: 20240018]
Foucault C, Ranque S, Badiaga S, Rovery C, Raoult D, Brouqui P. Oral ivermectin in the treatment of body lice. The Journal of infectious diseases. 2006 Feb 1:193(3):474-6 [PubMed PMID: 16388498]
Ogden NH, Lindsay LR, Schofield SW. Methods to Prevent Tick Bites and Lyme Disease. Clinics in laboratory medicine. 2015 Dec:35(4):883-99. doi: 10.1016/j.cll.2015.07.003. Epub 2015 Aug 28 [PubMed PMID: 26593263]
Hasin T, Davidovitch N, Cohen R, Dagan T, Romem A, Orr N, Klement E, Lubezky N, Kayouf R, Sela T, Keller N, Derazne E, Halperin T, Yavzori M, Grotto I, Cohen D. Postexposure treatment with doxycycline for the prevention of tick-borne relapsing fever. The New England journal of medicine. 2006 Jul 13:355(2):148-55 [PubMed PMID: 16837678]
Binenbaum Y, Ben-Ami R, Baneth G, Langford B, Negev Y, Friedlander E, Shasha D, Tau L, Paran Y. Single Dose of Doxycycline for the Prevention of Tick-borne Relapsing Fever. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020 Oct 23:71(7):1768-1771. doi: 10.1093/cid/ciaa034. Epub [PubMed PMID: 31955197]
Cochez C, Heyman P, Heylen D, Fonville M, Hengeveld P, Takken W, Simons L, Sprong H. The Presence of Borrelia miyamotoi, A Relapsing Fever Spirochaete, in Questing Ixodes ricinus in Belgium and in The Netherlands. Zoonoses and public health. 2015 Aug:62(5):331-3. doi: 10.1111/zph.12154. Epub 2014 Sep 12 [PubMed PMID: 25212814]
Level 3 (low-level) evidence