Relapsing fever is a type of fever caused by various spirochete bacteria where the infection results in recurrent episodes of fever with an intermittent period of remission.
This characteristic pattern of remission and relapse gives relapsing fever its name and allows it to differentiate from other causes of fever.
Other diseases caused by spirochetes include syphilis, Lyme disease, and leptospirosis. They belong to the Borrelia genus, Borrelia recurrentis being the commonly known agent.
These bacteria can escape the immune system by antigenic variation and lead to relapse of the fever.
Types of Relapsing Fever
Relapsing fever is of two types depending on the vector of transmission involved. Even the infectious agents are different in both types.
Tick-borne fever is reported worldwide, except Antarctica, Australia, and the Pacific Southwest.
Louse-borne fever occurs in areas of war, famine, mass migrations, or overcrowding like refugee camps. Louse-borne relapsing fever epidemics were common in Europe during the 20th century. Now, these are found in Ethiopia and Sudan, especially during the rainy season.
The louse-borne relapsing fever is more lethal and mortality rate reported is 30-70% without treatment during epidemics and about 5% with treatment.
Tick-borne relapsing fever has less than 1% mortality.
Antibiotic treatment of relapsing fever commonly results in Jarisch-Herxheimer reaction. This reaction tends to be more severe in patients with louse-borne fever treated with penicillin.
Relapsing fever has no racial or gender predilection. However, Tick-borne occurs more often in males [probably due to greater exposure to ticks] whereas louse-borne has slight female preponderance.
Both relapsing fevers are more common in children.
Louse-borne relapsing fever is caused is B recurrentis, which is transmitted from human to human via the body louse.
These organisms multiply in the gut of the louse and are transferred to humans when they come in contact with hemolymph due to scratching-induced louse crushing.
Soft tick Ornithodoros hermsii is responsible for tick-borne relapsing fever. The spirochetes are transmitted via the bite of an infected Ornithodoros tick which often bites in the night.
Spirochetes gain access to the vessels through broken skin or mucous membrane and spread to the organs [spleen, bone marrow, liver, lungs, kidneys, and CNS].
Relapse of the fever occurs because borrelia can vary in antigen expression or serotypes.
Quiescent period in between two fevers occurs because new variant takes time to multiply.
The switch in antigenic expression helps the bacteriae to escape the host immunity.
Both types of relapsing fevers have a similar clinical picture.
The hallmark is
- Two or more episodes of high fever (usually > 39-degree Celsius)
After the transmission, the incubation period is about 7 days [4-18 days]. The first episode occurs in conjunction with spirochetemia.
The first episode of fever lasts about 3-5 days and there is a period of 7-9 days between the relapse. Generally, the tick-borne fever has a shorter span and a shorter interval between two relapses.
The first fever episode usually ends with crisis which consists of
It lasts for 15-30 minutes and is followed by profuse sweating. falling temperature and hypotension which lasts for a few hours.
Louse-borne relapsing fever normally produces fewer relapses (usually one relapse). Tick-borne relapsing fever produces an average of 3 relapses but sometimes can lead to more than 10 relapses.
The patient feels well between episodes.
Other non-specific symptoms during fever are
- Joint pains
- Muscle pains
- Abdominal pain
- Neural symptoms [given below]
- Nonproductive cough [more with louse borne]
- Diarrhea, dizziness, headache, neck stiffness, photophobia, rash, and dysuria
Adult respiratory distress syndrome may occur during tick-borne fever crises.
Louse-borne relapsing is associated with a higher incidence of jaundice, petechiae, hemoptysis, epistaxis, and CNS involvement.
Tick-borne relapsing fever has a greater number of relapses [3 or more] than louse-borne which usually has one relapse on average.
Neurologic findings are more common in tick-borne and result from direct spirochetal CNS invasion.
In louse-borne fever, CNS symptoms result from spirochetemia rather than direct spirochetal invasion.
- Focal neurologic symptoms [more often in tick borne]
- Facial paralysis
- B miyamotoi infection in immunocompromised individuals
Physical examination may reveal many finding which are non-specific
- Rash [tick borne]
- Abdominal tenderness
- Petechiae, ecchymosis (more common in louse-borne fever)
- Epistaxis (common in louse-borne fever)
- Rales, rhonchi in the lung
- Nuchal rigidity (more common in louse-borne fever)
- Iritis and iridocyclitis
- Myocarditis [gallops on examination]
- Neurologic findings as described above
Because the presentation and findings are non-specific, any infectious fever pattern needs to be considered in the diagnosis.
- Typhoid Fever
- Rat bite fever
- Viral hemorrhagic fever like dengue, yellow fever
- Viral Hepatitis
- Viral Meningitis
These include normal to mildly increased leukocyte counts, anemia, thrombocytopenia, increased liver enzyme levels, and prolonged coagulation parameters.
Chemistry panel can show increased liver function test and elevated bilirubin levels.
ECG may show a prolonged QTc interval.
Direct observation of the spirochete in the film helps to confirm the organism.
Smears should be made when the patient is having fever because the smears prepared during relapse does not demonstrate the bacteria.
A peripheral blood smear is more sensitive in tick-borne relapsing fever.
Serial testing of blood smears can reveal the clearance of spirochetes from the blood and effectiveness of therapy. Patients usually have undetectable spirochetes within 8 hours of the first dose of antibiotics.
Other techniques for visualizing the bacteria are
- Direct or immunofluorescence staining
- Dark-field microscopy
- Peripheral blood wet mounts
Cerebrospinal fluid Examination
This is indicated with patients having neurological involvement. It may show
- Mononuclear pleocytosis [cell count]
- Mildly elevated protein level
- Borrelia on Smear
- Quantitative buffy coat examination
- Bacterial Culture
- Polymerase chain reaction for Borrelia species
- Antibodies to Borrelia using enzyme immunoassays
Microscopic findings are
- Endothelial cell edema
- Microvascular leakage
- Perivascular mononuclear infiltrates
The organs affected are heart, liver, spleen, brain, eyes and kidney.
For spirochetes detection in tissues, silver stains or immunofluorescence antibodies are used.
No special imaging is required in relapsing fever. Imaging is performed only to evaluate suspected intracranial hemorrhage or other complications.
Chest radiography may reveal pulmonary edema.
Imaging studies are not routinely useful, although chest radiography and hepatobiliary ultrasonography might be indicated in isolated cases in which pulmonary or hepatic manifestations predominate.
CT scanning of the brain may be indicated in cases with predominant central nervous system (CNS) manifestations.
Antibiotics are used to kill spirochetes.
Penicillins and tetracyclines have been used since long.
Borrelia species is also vulnerable to cephalosporins, macrolides, and chloramphenicol in vitro.
In louse-borne relapsing fever, the drugs used can be single dose of tetracycline 500 mg or doxycycline 200 mg.
Erythromycin 500 mg can be used when tetracyclines are contraindicated.
In tick-borne fever, the treatment should last for 7-10 days.
Treatment of tick-borne relapsing fever consists of same drugs and duration is 7-10 days as the relapses have been reported after single dose treatment.
The schedule varies with the drug
- Tetracycline 500 mg every 6 hours
- Doxycycline 100 mg 12 hourly
- Erythromycin 500 mg every 6 hours
If the patient cannot tolerate oral therapy, intravenous therapy using the same drugs should be considered.
Procaine penicillin G is another option when intravenous therapy is considered. It is given in a single dose of 600,000 in louse-borne or 600,000 IU daily in patients with tick-borne fever.
For tick-borne relapsing fever with neurologic involvement, the following drugs are given.
- Penicillin G 3 million units IV every 4 hours or
- Ceftriaxone 2 g IV daily
In children younger than 8 years and in pregnant or nursing women, erythromycin [12.5 mg/kg] is a preferred drug.
For older children tetracycline 12.5 mg/kg, oral doxycycline 5 mg/kg, or intramuscular penicillin G procaine 200,000-400,000 units can be given.
Antibiotic therapy can trigger a Jarisch-Herxheimer reaction. The reaction is more common in louse-borne relapsing fever.
The prevention of exposure to vectors is the mainstay as no vaccine is available for either type of relapsing fever.
Avoiding sleeping in rodent-infested buildings and using insect repellents to prevent tick bite are the precautions one can take in endemic areas. If there is an exposure, postexposure treatment with doxycycline can be used.
Special care must be taken in places where crowding occurs. Better hygienic practices would decrease the risk of exposure.
Chemical delousing may be required in epidemic situations.
For louse-borne relapsing fever, maintaining personal hygiene to avoid lice prevents the disease.
Prognosis & Complications
Untreated relapsing fever is quite fatal. The mortality rate of untreated louse-borne fever has been reported between 10-70% while that of untreated tick-borne fever is 4%-10%.
With treatment, however, the mortality rate comes down significantly.
Known complications of relapsing fever are
- Spontaneous bleeding
- Jarisch-Herxheimer reaction
- Acute Respiratory Distress Syndrome (ARDS)
In pregnant women following complications may occur
- Premature labor
- Spontaneous abortion
- Transplacental spread with neonatal death
Features associated with poor prognosis are
- Stupor or coma on admission
- Diffuse bleeding
- Poor liver function
- Lung infection
- Coinfection with malaria, typhoid, or typhus
- Dworkin MS, Schwan TG, Anderson DE Jr, Borchardt SM. Tick-borne relapsing fever. Infect Dis Clin North Am. 2008 Sep. 22(3):449-68, viii.
- Wilting KR, Stienstra Y, Sinha B, Braks M, Cornish D, Grundmann H. Louse-borne relapsing fever (Borrelia recurrentis) in asylum seekers from Eritrea, the Netherlands, July 2015. Euro Surveill. 2015 Jul 30. 20 (30)
- Hovius JW, de Wever B, Sohne M, Brouwer MC, Coumou J, Wagemakers A, et al. A case of meningoencephalitis by the relapsing fever spirochaete Borrelia miyamotoi in Europe. Lancet. 2013 Aug 17. 382(9892):658.
- Guerrier G, Doherty T. Comparison of antibiotic regimens for treating louse-borne relapsing fever: a meta-analysis. Trans R Soc Trop Med Hyg. 2011 Sep. 105(9):483-90.
- Hasin T, Davidovitch N, Cohen R, Dagan T, Romem A, Orr N, et al. Postexposure treatment with doxycycline for the prevention of tick-borne relapsing fever. N Engl J Med. 2006 Jul 13. 355(2):148-55.