TICK-BORNE RELAPSING FEVER CAUSED BY BORRELIA TURICATAE

Tick-borne relapsing fever manifests as relapsing episodes of fever with significant morbidity and mortality. We report a case of Borrelia turicatae disease in a 13-year-old male youth with outdoor exposures in Texas. After multiple clinic visits the diagnosis was made, and treatment was initiated. The patient did well without long term sequelae. Summer time activities and family travel bring children in contact with unique, often geographically distinct vector-borne diseases. Tick-borne relapsing fever is caused by a group of closely related Borrelia species and is characterized by the abrupt onset of fever, rigors, malaise and abdominal complaints. A high index of suspicion is required to make this diagnosis. Case report. A 13-year-old previously healthy male Caucasian youth from Hawaii visited Texas during summer vacation and was referred to the Pediatric Infectious Disease Clinic at the San Antonio Military Pediatric Center (SAMPC) with a 2-week history of fever. He had arrived in Texas on May 29, 1999, 26 days before presentation at SAMPC. He had attended a camp along the Frio River for the next 13 days. While at the camp he swam in a freshwater stream, explored a cave and had extensive exposure to mosquitoes, chiggers and ticks. Thirteen days before presentation at SAMPC, he developed a fever to 40°C, nausea, vomiting and rigors, which continued for 2 days. Eleven days before presentation he was seen in an emergency department and received 5 liters of intravenous fluid for volume depletion. Laboratory studies at that time included a white blood cell count of 11.5 × 103/mm3 with 84% neutrophils, 5% lymphocytes, and 11% monocytes and 117 × 103 platelets/mm3. He was discharged from the emergency department with the diagnosis of viral syndrome. The next day his symptoms resolved. Throughout the next week he continued to have low grade fevers, mild malaise and fatigue and a transient erythematous maculopapular rash located on his arms and legs, sparing his palms and soles. Three days before presentation, 10 days after the initial symptoms, he again was febrile to 40°C, without rigors. He denied vomiting, diarrhea, cough, congestion, headache, photophobia or arthralgia. He was seen at a pediatric clinic and was described as mildly ill-appearing with no focus of infection. He had no lymphadenopathy, hepatosplenomegaly or rash. Laboratory studies included a white blood cell count of 9.3 × 103/mm3 with 67% neutrophils, 16% lymphocytes and 16% monocytes; 417 × 103 platelets/mm3; normal aspartate aminotransferase; negative Monospot; negative cytomegalovirus by serology; and negative serology for hepatitis A, B and C. Fever continued for 2 more days. He was referred to the Pediatric Infectious Disease clinic at SAMPC on June 24, 1999. At that time he was afebrile and had mild malaise. He appeared well and had a normal physical examination. Laboratory studies revealed a white blood cell count of 6.9 × 103/mm3 with 40% neutrophils, 5% band forms, 31% lymphocytes, 21% monocytes and 2% atypical lymphocytes; hematocrit 35%; 332 × 103 platelets/mm3; erythrocyte sedimentation rate, 88 mm/h; sodium, 131 mmol/l; normal aspartate aminotransferase; and normal urinalysis. Cultures and serology for leptospirosis and serology for Borrelia species were sent to Centers for Disease Control and Prevention. The patient developed bilateral conjunctivitis that was treated by his parents with an over-the-counter medication. One week after presentation in our clinic, he returned with malaise and chills without fever. His blood smear was negative for spirochetes with acridine orange stain and was also negative for malaria parasites. He was presumptively started on doxycycline for suspected tick-borne relapsing fever. His first dose of doxycycline was given in the hospital, and he was discharged to complete a 10-day course as an outpatient. He returned to Hawaii 5 days after initiating therapy. Twenty-six days after presentation at our clinic, he developed bilateral conjunctivitis and photophobia and was examined in Hawaii by an ophthalmologist. A diagnosis of iritis was made. He was treated successfully with topical prednisolone 1% ophthalmic suspension for 23 days, with return of visual acuity to 20/20 bilaterally. Serology for Borrelia burgdorferi and Borrelia turicatae were positive. The Texas State Department of Health investigated the cave he had explored at summer camp. Thirty ticks of the Ornithodoros turicata species were collected, all of which revealed the presence of spirochetes, later identified as B. turicatae. The patient’s culture and serology for leptospirosis were negative. Discussion. Relapsing fever is an acute borrelial disease characterized by recurrent episodes of fever and spirochetemia separated by afebrile periods. Epidemic relapsing fever is caused by Borrelia recurrentis and is transmitted by lice. It is virtually unknown in the United States. Endemic relapsing fever is caused by a group of closely related Borrelia species, transmitted by ticks of the genus Ornithodoros, and occurs worldwide. 1 Different species of Ornithodoros have distinct geographic distribution and unique tick-spirochete specificity. In the southwest United States, including Texas, B. turicatae is transmitted by O. turicata. Tick speciation has been used to identify the infecting Borrelia species in cases of tick-borne relapsing fever. 1–3 Soft shelled Ornithodoros ticks act as both vectors and reservoirs for Borrelia species. Transovarial transmission allows all developmental stages to be infective. The natural reservoir includes rodents and small animals. Ornithodoros ticks prefer warm, humid environments such as caves, particularly those with guano on the cave floor, decaying wood, rodent burrows and animal shelters. However, many human cases have been reported among persons staying in mountain cabins in the western United States. Because Ornithodoros ticks generally feed at night, have a painless bite and take short blood meals lasting 5 to 20 min, they are often unrecognized. 1 Therefore tick bites are often not reported by the patient. The onset of illness with tick-borne relapsing fever typically occurs after an incubation period of 7 days. Disease is characterized by the abrupt onset of high fever and could include rigors, headache, myalgia, arthralgia, abdominal pain, nausea and vomiting. Other manifestations include pruritic eschar, splenomegaly in 40%, hepatomegaly in 18%, rash in 25 to 30% and neurologic involvement in <10%. 4 Febrile periods usually last for 3 days and are followed by a 6- to 7-day afebrile period. During the acute febrile period spirochetes are present in the blood, but they disappear during the afebrile period, when they are sequestered in internal organs. With each relapse they reemerge, antigenically modified. 5 An average of three relapses occurs, with each succeeding relapse being less severe. 1 Tick-borne relapsing fever is generally self-limited, but some features may be severe and prolonged, such as visual defects from an immunologically mediated iritis or iridocyclitis, which occurs in as many as 15% of cases. Severe depression from neurologic complications may occur in <10% of patients. 4 Other complications are uncommon and include hemorrhage, pneumonia, acute respiratory distress syndrome and myocarditis. Death is rare, except in infants, in whom mortality may be as high as 20%. 6 In addition to the poor outcome in infancy, relapsing fever in pregnancy may cause spontaneous abortion. 4 Fetal death is probably caused by direct placental invasion of spirochetes. 7 Infection in the neonatal period usually occurs by placental transmission and presents as overwhelming sepsis with a very high case fatality rate. 6 Diagnosis can be difficult and requires a high index of suspicion. Routine laboratory studies are of little help in the diagnosis of tick-borne relapsing fever. The white blood cell count may be elevated or decreased, but is usually normal. 4 Thrombocytopenia and an elevated erythrocyte sedimentation rate are common but nonspecific. 1 Definitive diagnosis can be made by specific serology or by visualizing spirochetes on wet blood smears by dark field microscopy or in Giemsa- or Wright-stained thick and thin smears. 1, 4 Smears made during febrile episodes are positive in 70% of patients. 4 The diagnostic yield can be increased by obtaining thick and thin smears stained with acridine orange. 8 The most specific serologic test is a Western blot for B. turicatae and is available through the Centers for Disease Control and Prevention. Patients with tick-borne relapsing fever will have false positive indirect fluorescent antibody test and enzyme immunoassay for other tick-borne spirochetes such as B. burgdorferi.9 Therefore Lyme serology, which is widely available, may lead to a false diagnosis of Lyme disease if the possibility of tick-borne relapsing fever is not considered. Standard treatment consists of a 10-day course of tetracycline, doxycycline or erythromycin. 1, 4 Because the Jarisch-Herxheimer reaction has been reported during treatment, close monitoring during the initial therapy is warranted. 9 The differential diagnosis of nonfocal, recurrent or relapsing febrile illness must include leptospirosis and malaria. Leptospirosis occurs in tropical and temperate areas and is acquired from soil or freshwater that are contaminated with infected animal urine. Malaria is rare in the United States. It is most often seen in returning travelers but has been reported along the Texas-Mexico border. Rocky Mountain spotted fever and ehrlichiosis should also be considered; however, these diseases would have a progressive course rather than a relapsing pattern and are uncommon agents in Texas. In summary, tick-borne relapsing fever is a regional and seasonal vector-borne disease that requires a high index of suspicion for diagnosis. It should be considered in the differential diagnosis of relapsing fever with systemic symptoms in endemic areas to prevent rare but serious sequelae.