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Singh, Jasjit M.D.

Section Editor(s): AZIMI, PARVIN H. M.D.; GROSSMAN, MOSES M.D.

The Pediatric Infectious Disease Journal: September 1999 - Volume 18 - Issue 9 - p 842, 847-848
Your Diagnosis, Please

Accepted for publication April 15, 1999.

Division of Infectious Diseases; Children's Hospital of Orange County; Orange, CA

A 6-year-old Caucasian male was referred to a children's hospital in Southern California by his pediatrician for evaluation of fever of unknown origin. He had been in good health until 5 weeks previously, when he was seen for fever. Otitis media was diagnosed and amoxicillin was prescribed. Fever continued as high as 40.3°C with chills and vomiting. He was admitted to a local hospital and treated with intravenous ampicillin. The parents described a 6-h period during which his neurologic status seemed to be depressed; this resolved without specific therapy. There was no history of seizure activity. He defervesced after the first day and remained afebrile and neurologically normal during the ensuing 3 days of hospitalization. However, during this period he did develop an erythematous maculopapular rash over the extensor surfaces of the large joints for ∼3 days. He was discharged to home with no medications.

The patient did well until 19 days later when he again had fever as high as 39.7°C. He was seen by his physician. A complete blood count revealed a white blood cell count of 8400/μl with 71% neutrophils, 19% lymphocytes and 7% eosinophils. Hemoglobin was 10.7 g/dl and platelets 78 000/μl. A chest radiograph was normal. He defervesced after 3 days and again felt well. Six days later fever to a maximum of 39.5°C began again, this time lasting for 2 days. A repeat complete blood count showed a white blood cell count of 11 600/μl with 76% segmented neutrophils, 15% lymphocytes and 16% monocytes. Hemoglobin was 11.6 g/dl, and platelets had normalized to 201 000/ul. The sedimentation rate was 50 mm/h. One week later, while the patient was afebrile, these laboratory studies were essentially unchanged. He developed fever 9 days after his last febrile episode. Sinus radiographs done by his pediatrician were negative and he was referred for admission.

His parents stated that when he was febrile, the child would complain of headaches. He had several episodes of vomiting but no diarrhea. There were no upper respiratory symptoms. His past medical history was unremarkable. The family had traveled to Big Bear, CA, stayed in a cabin and went hiking 4 to 5 days before the onset of his first febrile episode. There was exposure to dogs and cats, but no known bites or scratches. There were no known tick or insect bites. The patient's parents and two siblings were healthy.

On physical examination temperature was 40.4°C, pulse 135, respiratory rate 26 and blood pressure 93/65 mm Hg. His weight was 20.9 kg (50th percentile for age). He had chills but no meningismus, conjunctivitis, rash, hepatosplenomegaly or significant lymphadenopathy. The remainder of the examination was normal. Laboratory studies revealed a white blood cell count of 9400/μl with 75% neutrophils, 14% lymphocytes, 10% monocytes and 1% basophils. A sedimentation rate was 80 mm/hr. Serum chemistries and urinalysis were normal. Headache and nausea persisted. A computed tomography scan of the head was normal. The patient was scheduled for a lumbar puncture when a diagnostic report was received.

Jasjit Singh, M.D.

Division of Infectious Diseases; Children's Hospital of Orange County; Orange, CA

For denouement see p. 847.

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The report received was a peripheral blood smear sent to the microbiology laboratory to look for evidence of spirochetes. Giemsa staining revealed the loosely coiled spirochete responsible for relapsing fever (Fig. 1). The patient was treated with an oral dose of penicillin which he tolerated well. He was sent home afebrile to complete a 10-day course of erythromycin. At follow-up 3 weeks later he was normal with no intermittent fevers. A repeat sedimentation rate was 19 mm/h.

Fig. 1

Fig. 1

Relapsing fever is caused by spirochetes of the genus Borrelia. Borrelia recurrentis causes louse-borne (epidemic) relapsing fever. Most tick-borne relapsing fever in the US is caused by Borellia hermsii.1 Infection typically results from tick exposures in rodent-infested cabins in western mountainous areas, including state and national parks. In well-studied outbreaks,2 including one in 1989 at Big Bear Lake, CA,3 cabins were found to contain large rodent nests, from which infected ticks were recovered. In 1997 there were no other cases reported from Big Bear, and in 1998 there was also only one case reported (E Trevino, San Bernadino County Public Health Department, personal communication). Ticks become infected by feeding on rodents and transmit infection via saliva when they take subsequent blood meals. The ticks are soft-bodied, feed briefly at night and have painless bites; patients are often unaware that they have been bitten. The incubation period is 4 to 18 days.

Clinically relapsing fever is characterized by acute onset of high fever, chills, sweats, headache and myalgia. A transient macular rash can sometimes occur. Initially a febrile period of 3 to 7 days terminates spontaneously by crisis, often with an accompanying Jarisch-Herxheimer reaction. The initial febrile episode is followed by an afebrile period of several days to weeks, then by one or more relapses. Relapses become shorter and milder and are thought to occur because of the ability of the spirochete to alter outer surface proteins and evade the host's immune response. Complications can include hepatosplenomegaly, jaundice, pleuritis, pneumonitis, meningitis and myocarditis. Infection in pregnancy can be severe and result in fetal loss.4

Borrelia species causing relapsing fever are unique in that they can be identified on blood smear because of their loose-coiled morphology and ready staining by Wright or Giemsa stains, particularly during febrile episodes. This is not true of other pathogenic spirochetes such as Leptospira, Treponema or Borellia burgdorferi. Therefore diagnosis depends on a high index of suspicion, usually based on a careful history. The organism can sometimes be cultured from blood by using complex media or by intraperitoneal inoculation of immature laboratory mice. A positive convalescent test for serum agglutinins directed against Proteus Ox-K (Weil-Felix) supports the diagnosis. Serum antibodies to Borrelia can be measured by enzyme immunoassay. However, the tests are not standardized, and antigenic variations between species and strains can occur.1

Treatment with tetracyclines, erythromycin and chloramphenicol is effective in clearing spirochetemia and eliminating symptoms. The use of penicillin may delay the clearance of spirochetes and attenuate the accompanying Jarisch-Herxheimer reaction, caused by release of inflammatory mediators after bacterial lysis, which can manifest as transient hypotension and cardiac failure. Therefore febrile patients should receive an oral or intravenous dose of penicillin for initial therapy and should be monitored closely in the first 12 h of treatment. Thereafter a 10-day course of oral tetracycline or erythromycin (for patients <8 years) will eradicate tissue spirochetes and prevent relapse.4 Oral ampicillin results in relapse rates as high as 30%.5 This may explain why our patient continued to have symptoms despite two short courses (<4 days) of oral amoxicillin and intravenous ampicillin. With current therapy case fatality rates from relapsing fever are <5%.4

1. American Academy of Pediatrics. Borrelia (relapsing fever). In: Peter G, ed. 1997 Red Book: report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997:155-7.
2. Lakin A, Wurgler J, Brickley C, et al. Outbreak of relapsing fever: Grand Canyon National Park, Arizona, 1990. MMWR 1991;40:296-7.
3. Koonce WC, Abbott S, Hosea S, et al. Common source outbreak of relapsing fever: California. MMWR 1990;39:579-86.
4. Boyer, K. Borrelia (relapsing fever). In: Feigin RD, Cherry JD, eds. Textbook of pediatric infectious diseases. 4th ed. Philadelphia: Saunders, 1998:1517-21.
5. Lovett MA, Goldstein EJC, Fleischmann J. Fever in a couple vacationing in the mountains of Southern California. Clin Infect Dis 1992;14:1254-8.

Borreliosis; tick-borne disease; fever of unknown origin; recurrent fever

© 1999 Lippincott Williams & Wilkins, Inc.