Relapsing Fever


Article Author:
Jessica Snowden


Article Editor:
Tony Oliver


Editors In Chief:
David Tauber


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
5/6/2019 12:27:44 AM

Introduction

Relapsing fever typically refers to malaria-like illnesses caused by various spirochetes belonging to Borrelia species, characterized by recurrent fevers, chills, and malaise. The causative organism and associated vector vary based on the geographic area of exposure.[1][2][3]

Etiology

The term relapsing fever refers to a variety of recurrent fever syndromes caused by the spirochete, Borrelia. Borrelia recurrentis is the cause of epidemic relapsing fever, which is reported most frequently in northern and eastern Africa. Tick-borne relapsing fever is reported the United States and can be caused by several species, including Borrelia hermsii, Borrelia turicatae, and Borrelia parkeri.[4]

Epidemiology

Borrelia recurrentis, or epidemic relapsing fever, is reported most commonly in areas of crowding and poor personal hygiene. It is transmitted via lice and has decreased in frequency substantially since the first half of the 20th century. However, it is still commonly reported in parts of Africa and among migrants from Africa to Europe in recent years. Other species causing relapsing fever in Africa include Borrelia duttonii, Borrelia hispanica, and Borrelia crocidurae. Humans are the only known host and reservoir of Borrelia recurrentis. In contrast, small rodents and other mammals may serve as a reservoir for tick-borne Borrelia species. Borrelia hermsii, or tick-borne relapsing fever, is reported in the United States in Colorado, near Lake Tahoe, and near the Grand Canyon. It is transmitted via the bite of soft-bodied, night feeding Ornithodoros ticks. Other species that cause tick-borne relapsing fever in the United States include Borrelia turicatae and Borrelia parkeri, also transmitted via tick bite. As the ticks feed at night, patients are often unaware of the bite. Borrelia miyamotoi is a relapsing fever, similar to Lyme disease, transmitted by the Ixodes tick. It is reported in the northeastern United States, Japan, and Russia, with slight variations in presentation depending on geography.[5]

Pathophysiology

Relapsing fever is caused by Borrelia species, which are fastidious spirochetes. These spirochetes 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.

Borrelia recurrentis infection typically occurs after the bite of an infected human body louse Pediculosis humanus corporis. However, the infection may also occur through intact skin and mucosal surfaces. Borrelia hermsii, Borrelia parkeri and Borrelia turicatae are transmitted via the bite of soft-bodied Ornithodoros ticks rather than through intact skin or mucosa. Borrelia miyamotoi is transmitted via the Ixodes tick, similar to Lyme disease.

The clinical manifestations of relapsing fever, including fever, myalgias, chills, and arthralgias, are caused by an endotoxin-like substance produced by the spirochete. The initial febrile episode in relapsing fever resolves due to the development of antibodies directed at surface proteins of the organism. However, a reservoir of organisms in reticuloendothelial organs undergo genetic reassortment to alter the expression of surface proteins. This allows for escape from immune clearance and re-emergence of spirochetemia and clinical symptoms. The typical recurrence pattern of Borrelia symptoms in relapsing fever is due to repeated cycles of reassortment of surface proteins followed by antibody-mediated suppression of infection. Both the Borrelia organism and the saliva of the infected tick are thought Infection is not associated with long-term immunity and patients may be reinfected as soon as six months after initial infection.

History and Physical

The incubation period is typically four to 18 days following exposure to Borrelia. The symptoms of relapsing fevers are characterized by the abrupt onset of fever and chills, often accompanied by malaise, arthralgias, and myalgias. Hemorrhagic and non-hemorrhagic rashes, nausea, vomiting, jaundice, and neurologic issues like paraplegia, mononeuritis multiplex may also occur. After the resolution of the first episode, which typically lasts one week, patients will experience several recurrences of fever that are shorter and less severe. Episodes occur every five to ten days and may persist for several cycles before resolution. In an epidemic, or louse-borne, relapsing fever, there are typically only one or two episodes of fever. However, in endemic, tick-borne relapsing fever, three to seven recurrences may occur before the resolution of symptoms. Hepatic tenderness is the most common sign and 40 % can have signs of meningism.[3]

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 leukopenia or leukocytosis, as well as thrombocytopenia.

Diagnosis is confirmed by detection of Borrelia in Giemsa-stained blood films, serologic analysis or via PCR detection of the organism. These organisms are not identifiable in routine laboratory cultures. 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. Between episodes and in later recurrences, the spirochetes may not be visible at all. Serology may also be used to diagnose tick-borne relapsing fever, particularly in situations in which diagnosis is suspected later in the course of illness. In that case, repeated testing with a rise in Immunoglobulin G (IgG) is suggestive of recent infection. However, these serologic tests cross-react with other spirochetes such as Leptospirosis and syphilis and must be interpreted in the setting of clinical symptoms.[3][6]  

Treatment / Management

Relapsing fever is treated with doxycycline 100 mg twice a day for seven to ten days. In children under eight years of age, penicillin or erythromycin are the preferred agents due to the concern of dental staining with doxycycline use. It is important to observe patients for several hours after initiation of antibiotic therapy, as Jarisch-Herxheimer reaction is common. Jarisch-Herxheimer reaction is a sepsis-like response to the release of inflammatory contents from within the bacteria after lysis by antibiotics. It is rarely fatal and managed with supportive care. This reaction is more common in adolescents than in younger children. Borrelia infections may also be self-limited and resolve without treatment in some cases.[7][8][9]

Differential Diagnosis

Malaria

Leptospirosis

Trench fever

Viral hepatitis

Prognosis

With antibiotic treatment, the mortality of epidemic relapsing fever decreases from 10% to 40% to 2% to 4%. Fatalities are rare in tick-borne relapsing fever. Mortality is attributed to myocarditis

Complications

Meningitis

Mono Neuropathy Multiplex

Hyper pyrexia

Acute Respiratory Distress Syndrome ( ARDS)

Acute Pulmonary Edema

Gastrointestinal Bleed

Splenic Rupture

Disseminated Intravascular Coagulation ( DIC)

Consultations

Internal medicine

Infectious Disease

Deterrence and Patient Education

Improved personal hygiene

Sterilization of the patient's clothes and bedding

Pearls and Other Issues

There is currently no vaccine available for any of the Borrelia species associated with relapsing fever. Avoidance of louse and tick exposure through 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, but other isolation is not required other than eradication of body lice.

Enhancing Healthcare Team Outcomes

The diagnosis of relapsing fever can be challenging and is best managed by a multidisciplinary team that includes the emergency department physician, nurse practitioner, infectious disease expert, and a laboratory specialist. Once the diagnosis is made, the treatment is straightforward and most patients have no sequelae. There is currently no vaccine available for any of the Borrelia species associated with relapsing fever. Avoidance of louse and tick exposure through 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, but other isolation is not required other than eradication of body lice.[10]


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Relapsing Fever - Questions

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Which of the following organisms cause relapsing fever and is transmitted by lice or ticks?



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A patient presents with tick borne relapsing fever after a family vacation to Colorado. After initiating treatment, the patient should be monitored closely for what complication to treatment?



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A 5-year-old girl presents to clinic with a history of recurrent fever. The episodes are getting shorter and milder, but have now occurred five times in the last six weeks. With her second episode of fever, evaluation in the emergency department identified thrombocytopenia. Her only other associated symptoms are joint and body aches during the fever. Which of the following is likely true in this case?



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A 5-year-old boy presents with episodes of recurrent fever that have occurred over the last six weeks. The episodes started after a family vacation to Colorado. Relapsing fever is suspected. Which of these tests would not help diagnose this illness?



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A 12-year-old patient with recurrent fever and a history of travel to Colorado presents with suspected tick-borne relapsing fever. What is the drug of choice for treating this infection?



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Relapsing Fever - References

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;     [PubMed]
Pukhovskaya NM,Morozova OV,Vysochina NP,Belozerova NB,Ivanov LI, Prevalence of {i}Borrelia burgdorferi{/i} sensu lato and {i}Borrelia miyamotoi{/i} in ixodid ticks in the Far East of Russia. International journal for parasitology. Parasites and wildlife. 2019 Apr;     [PubMed]
Warrell DA, Louse-borne relapsing fever (Borrelia recurrentis infection). Epidemiology and infection. 2019 Jan;     [PubMed]
Margos G,Gofton A,Wibberg D,Dangel A,Marosevic D,Loh SM,Oskam C,Fingerle V, The genus Borrelia reloaded. PloS one. 2018;     [PubMed]
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. 2018 Nov 13;     [PubMed]
Middelveen MJ,Shah JS,Fesler MC,Stricker RB, Relapsing fever {i}Borrelia{/i} in California: a pilot serological study. International journal of general medicine. 2018;     [PubMed]
Sathiamoorthi S,Smith WM, The eye and tick-borne disease in the United States. Current opinion in ophthalmology. 2016 Nov;     [PubMed]
Choi E,Pyzocha NJ,Maurer DM, Tick-Borne Illnesses. Current sports medicine reports. 2016 Mar-Apr;     [PubMed]
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;     [PubMed]
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;     [PubMed]

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