Basics
Description
- Tick-borne relapsing fever (TBRF) and Colorado tick fever (CTF) will be discussed in this chapter.
- TBRF is a vector-borne infection characterized by recurrent fevers caused by several species of spirochetes of the genus Borrelia. In the United States, the vector for TBRF is the soft-bodied tick of the genus Ornithodoros.
- CTF is a febrile, usually benign, systemic illness caused by coltivirus in the family Reoviridae and transmitted by a tick bite. Although the primary reservoir for infection is the Dermacentor andersoni tick (wood tick), the causative organism has been isolated from many other ticks.
Epidemiology
- TBRF
- Reported in almost all western states up to and including Texas
- Sites of high exposure include limestone caves and forested areas.
- Most cases present during June through September; ’ Ό450 cases were reported in the United States between 1977 and 2000.
- CTF
- Human infections typically occur in areas where D. andersoni is found: Western United States and southwestern Canada at elevations of 4,000 " 10,000 feet
- Cases usually occur between May and June when adult ticks are most active.
- There are only a very small number of cases reported annually the United States.
- Infection is more common in males and the median age of those infected is 43 years, but 25% of cases occur in those younger than 20 years.
- Transfusion-related and laboratory-associated infection are rare but have been reported.
General Prevention
- Both of these infections can be prevented by avoidance or protection from the tick vector.
- Light-colored, long-sleeved shirts and pants should be worn when tick-infested areas cannot be avoided.
- Permethrin should be applied to clothing and diethyltoluamide (DEET) and picaridin applied to exposed skin to help repel ticks.
- Persons who enter endemic areas should inspect themselves and each other frequently for adherent ticks.
- Avoid rodent-infested homes in endemic areas. If necessary, rodent-nesting materials should be removed with protective gloves.
- Confirmed cases should be reported to health authorities so that control measures can be instituted.
Pathophysiology
- TBRF
- Ornithodoros ticks typically feed at night and for short periods.
- When an Ornithodoros tick feeds on a natural host (e.g., squirrels, chipmunks, and rodents), Borrelia subsequently invade all tissues of the tick including the salivary glands. Ticks in the larval stage are unlikely to be infectious.
- Borrelia is transmitted to humans when the tick takes a blood meal and then detaches itself. Transmission is possible within minutes of the start of a blood meal. After transmission, spirochetemia develops, resulting in systemic symptoms.
- Between episodes of spirochetemia, organisms likely persist in the CNS, bone marrow, liver, and spleen.
- Pathologic findings in humans include petechial hemorrhages on visceral surfaces, hepatosplenomegaly, and a histiocytic myocarditis.
- CTF
- Ticks are infected during their larval stage when they feed on viremic, intermediate hosts such as chipmunks, ground squirrels, and porcupines.
- Once infected, ticks remain infected for life (as long as 3 years).
- Human infection typically takes place when the adult D. andersoni wood tick attaches and ingests a blood meal from an incidental human host.
- CTF virus is thought to infect hematopoietic cells, causing leukopenia and prolonged viremia for up to 3 " 4 months.
Etiology
- TBRF is caused by several species of spirochetes in the genus Borrelia. Borrelia hermsii, Borrelia turicatae and Borreliaparkeri are the most common species found in the United States.
- CTF is caused by CTF virus, a double-stranded RNA coltivirus in the family Reoviridae.
Diagnosis
History
- Both TBRF and CTF most commonly present with high fever, headache, myalgias, and chills. A thorough history documenting recent travel and a description of the fever curve are necessary to help direct the clinician to either diagnosis.
- TBRF
- Fevers present after a mean incubation period of 5 " 7 days (range 4 " 18 days). Symptoms resolve after 3 " 6 days but then recur within 7 days. Relapses may be less severe than the initial episode with prolonged asymptomatic intervals. Average number of relapses is 3 " 5 in untreated patients.
- Patients commonly complain of headache, myalgia, nausea, vomiting, arthralgias, and abdominal pain. Less commonly, patients are symptomatic with confusion, dry cough, diarrhea, photophobia, rash, dysuria, or hepatosplenomegaly.
- Patients rarely are aware of a recent tick bite.
- CTF
- CTF has a usual incubation period of 3 " 4 days (range 0 " 14 days):
- In ’ Ό50% of patients, fever will present in a "saddleback " pattern. The fever persists for 2 " 3 days with resolution for 2 " 3 days. Fever then recurs and lasts for another 2 " 3 days. Some patients will have a 3rd febrile period.
- Patients may complain of lethargy, photophobia, retro-orbital pain, and conjunctival injection.
- Less commonly, patients will have gastrointestinal symptoms, pharyngitis, nuchal rigidity, and a rash.
- Unlike TBRF, 90% of patients presenting with CTF will have a previous history of tick exposure.
Physical Exam
The presentation for TBRF and CTF are varied. High fevers (39 " 41 °C) are common to both. Additional findings for each may include the following:
- TBRF
- Elevated pulse and BP are common.
- Tender hepatosplenomegaly with jaundice
- Nuchal rigidity suggesting meningitis.
- Gallop on cardiac auscultation suggesting underlying myocarditis
- A macular rash starting on the trunk that becomes generalized and or petechial in nature
- Neurologic deficits are less common but can include delirium, cranial nerve deficits (7th or 8th nerve palsy), and visual impairment from iridocyclitis.
- CTF
- A small, red painless papule may be seen.
- A maculopapular rash with petechial lesions has been reported in ’ Ό10% of cases.
- Pharyngitis is reported in 20% of cases.
- Hepatosplenomegaly has been found in some patients.
- Nuchal rigidity and delirium are rare but, if present, suggest meningitis or encephalitis.
Diagnostic Tests & Interpretation
- TBRF
- The diagnosis can be readily made by identification of loosely coiled spirochetes on thick and thin smears of the peripheral blood. Blood samples taken at the time of fever have the highest yield.
- Increased sensitivity can be obtained by examining acridine orange " stained preparations of dehemoglobinized thick smears or buffy coat preparations.
- The organism can only be cultured on special culture medium. Intraperitoneal inoculation of mice with the patient 's blood can lead to spirochetemia in the mice.
- Multiple serologic antibody studies exist, including direct and indirect immunofluorescence, ELISA, and immunoblot analysis:
- A 4-fold rise in titers between acute and convalescent studies is considered confirmatory.
- These studies may have false-positive reactions in patients with prior spirochete infections such as Lyme disease.
- Polymerase chain reaction (PCR) analysis can be useful in identifying the causative organism but is not readily available.
- Other nonspecific laboratory findings may include leukocytosis, anemia, thrombocytopenia, unconjugated hyperbilirubinemia, elevated hepatic transaminases, and proteinuria.
- If myocarditis is present, an electrocardiogram can reveal abnormalities such as a prolonged corrected QT interval.
- In cases complicated by meningitis, the CSF will typically have moderately elevated protein and a mononuclear pleocytosis.
- CTF
- Leukopenia is a hallmark of this illness.
- Direct immunofluorescent examination of blood smears for intraerythrocytic viral antigen is a rapid approach to the diagnosis.
- PCR testing and viral cultures are available in certain laboratories. PCR testing is the most sensitive and timely approach for diagnosing acute infection.
- Various techniques (e.g., complement fixation, indirect immunofluorescence, EIA, and Western blot) have been used to establish a serologic diagnosis:
- Serologic testing for antibody presence is not diagnostic in the acute phase because antibodies are slow to rise. Presence of a 4-fold rise in neutralizing antibody titers at >2 weeks after onset can be confirmatory.
- Associated laboratory findings include leukopenia and thrombocytopenia.
- In patients with meningitis or encephalitis, CSF studies may also reveal elevated protein and a lymphocytic pleocytosis.
Differential Diagnosis
- TBRF and CTF are similar clinically. The presence of biphasic or relapsing fever along with a history of travel to an area where appropriate vectors are found are helpful clues in diagnosing either disease. Leukopenia and a history of a tick bite may differentiate CTF from TBRF. TBRF and CTF may be misdiagnosed as influenza or enteroviral infections, especially with the 1st febrile episode.
- Other infectious illnesses that may present with recurrent fevers include yellow fever, dengue fever, lymphocytic choriomeningitis, brucellosis, malaria, leptospirosis, rat bite fever, and chronic meningococcemia. The patient 's travel history and animal exposure should help differentiate among some of these diagnoses.
Treatment
Medication
- TBRF
- The treatment of choice is oral tetracycline/doxycycline for 7 " 10 days. Children <8 years of age and pregnant women should receive erythromycin or penicillin.
- Newer macrolides may be effective but are not routinely recommended.
- In >50% of cases, treatment results in a Jarisch-Herxheimer reaction (severe fevers, rigors, diaphoresis, and hypotension) related to rapid clearing of the spirochetemia. Close observation, IV fluids, and good supportive care are important in treating possible reactions.
- Some experts support the use of an initial single dose of oral penicillin V potassium (7.5 mg/kg) or IV penicillin G (10,000 U/kg given over 30 minutes) in patients presenting with systemic symptoms. It is thought that this initial dose of penicillin leads to gradual clearance of spirochetes, decreasing the risk of the Jarisch-Herxheimer reaction. These patients should then receive a 10-day course of tetracycline or erythromycin because penicillin has been associated with an increased rate of relapse.
- Single-dose tetracycline or erythromycin has been successful for the treatment of louse-borne epidemic relapsing fever in Ethiopia.
- CTF
- There is no specific therapy for patients with CTF, as the treatment is primarily supportive.
Ongoing Care
Prognosis
- TBRF
- Generally responds rapidly to appropriate antibiotic therapy
- Mortality in patients treated appropriately is thought to be ’ Ό1%.
- CTF
- Usually a self-limiting illness without sequelae
- Death is rare but has been reported in children with generalized bleeding likely secondary to thrombocytopenia; thus, thrombocytopenia should be monitored closely.
- Prolonged weakness may persist for ≥3 weeks and is more likely in those patients >30 years old.
Complications
- TBRF
- May be associated with splenic rupture, diffuse histiocytic interstitial myocarditis, hepatitis, pneumonia, ARDS, and iridocyclitis
- CNS complications include meningitis, meningoencephalitis, and focal deficits such as cranial nerve palsy.
- In utero infection may result in fetal loss or severe neonatal infection.
- CTF
- Complications are rare but most commonly occur in children.
- May lead to aseptic meningitis, encephalitis, myocarditis, pneumonitis, hepatitis, hemorrhage, and epididymo-orchitis
Additional Reading
- Badger MS. Tick talk: unusually severe case of tick-borne relapsing fever with acute respiratory distress syndrome " case report and review of the literature. Wilderness Environ Med. 2008;19(4):280 " 286. [View Abstract]
- Brackney MM, Marfin AA, Staples JE, et al. Epidemiology of Colorado tick fever in Montana, Utah, and Wyoming, 1995 " 2003. Vector Borne Zoonotic Dis. 2010;10(4):381 " 385. [View Abstract]
- Cutler SJ. Relapsing fever " a forgotten disease revealed. J Appl Microbiol. 2010;108(4):1115 " 1122. [View Abstract]
- Dworkin MS, Schwan TG, Anderson DE Jr, et al. Tick-borne relapsing fever. Infect Dis Clin N Am. 2008;22(3):449 " 468. [View Abstract]
- Larsson C, Andersson M, Bergstrom S. Current issues in relapsing fever. Curr Opin Infect Dis. 2009;22(5):443 " 449. [View Abstract]
- Romero JR, Simonsen KA. Powassan encephalitis and Colorado tick fever. Infect Dis Clin North Am. 2008;22(3):545 " 559. [View Abstract]
- Roscoe C, Epperly T. Tick-borne relapsing fever. Am Fam Physician. 2005;72(10):2039 " 2044. [View Abstract]
Codes
ICD09
- 087.1 Relapsing fever, tick-borne
- 066.1 Tick-borne fever
ICD10
- A68.1 Tick-borne relapsing fever
- A93.2 Colorado tick fever
SNOMED
- 10301003 Tick-borne relapsing fever
- 6452009 Colorado tick fever (disorder)
FAQ
- Q: When should a clinician suspect tick fever?
- A: A history of recurring or relapsing fever in the appropriate epidemiologic setting (such as travel history to the western parts of the United States, summertime illness, history of tick exposure) should raise the possibility of a tick fever.