Tick-Borne Relapsing Fever in Children

(1)

Tick-Borne

Relapsing

Fever

in Children

Chinh

T. Le, MD

From the Department of Pediatrics, Kaiser-Permanente Medical Center, Sacramento, California

ABSTRACT. Three cases of tick-borne fever diagnosed

during the summer of 1979 are reported and the eco-epidemiology, clinical manifestations, and treatment of this infection are reviewed. Although challenging, the diagnosis can be made easily if specific historical clues are sought and the patient’s blood smear is carefully exam-med. The diagnosis of this condition early in its course can save clinicians and patients the anxiety and cost of the work-up of a “fever of unknown origin.” Since vaca-tioning in the national parks and forests has become increasingly popular among many American families,

tick-borne relapsing fever should be considered in any

patient with an acute or recurrent fever of unknown

origin who exhibits nonspecific symptoms of an undiffer-entiated “viral illness,” and who gives a history of sleeping overnight in log cabins in the coniferous forests of the Western mountains of the United States. Pediatrics 66: 963-966, 1980.

Tick-borne relapsing fever is caused by the blood

spirochetes Borrelia and is transmitted to humans by the bite of an infected Ornithodoros soft-shelled

tick. This infection is considered uncommon in this

country: since the disease became reportable by law

in 1931 in California, only 462 cases have been

reported,’ including 16 cases in 1978 (the most since

1947). It may even appear to be an “exotic disease”

to many pediatricians, since it is not discussed in

several major pediatric textbooks, nor in the Report

of the Committee on Infectious Diseases of the

American Academy of Pediatrics.2

The following three cases of tick-borne relapsing

fever were diagnosed during the summer of 1979 at

the pediatric clinic of the Kaiser-Permanente

Med-ical Center, Sacramento, CA. Reported here are the

clinical features and treatment of this infectious

entity. Because vacationing in the national forests

of the Western mountains has become increasingly

Received for publication Nov 28, 1979; accepted March 3, 1980. Reprint requests to (C.T.L.) Dept of Pediatrics, Kaiser-Perma-nente Medical Center, 2015 Morse Aye, Sacramento, CA 95825. IEDIATRICS (ISSN 0031 4005). Copyright © 1980 by the American Academy of Pediatrics.

popular among many American families, clinicians should consider Borrelia infections in the

differen-tial diagnosis of acute or recurrent paroxysmal fever

when exposure in an endemic area is part of a patient’s medical history.

CASE REPORTS

Case I

A 15-month-old, previously well, white female infant was seen for recurrent febrile episodes. In late April 1979,

she developed fever up to 39.9 C and vomiting. The

results of a physical examination were normal except for a mildly inflamed pharynx. She was given symptomatic antipyretic therapy for a presumed viral infection. Over

the following month, the infant was seen for four more

acute febrile episodes, each lasting two to three days and

occurring seven to eight days apart (Fig 1). On each

occasion, symptoms were nonspecific, with fever, mild irritability, decreased appetite, and occasional vomiting. She behaved as though she had myalgia and photophobia. Repeated physical examinations revealed no significant

abnormalities. Symptomatic therapy was prescribed at

each visit. Between each febrile episode, she remained asymptomatic. The results of the following laboratory investigations were normal or within normal limits: mul-tiple urine, throat, and blood cultures; repeated urinalysis; liver function tests; stool examinations for enteric

bacte-rial pathogens and parasites; VDRL, antinuclear, and

rheumatoid factors; serology for toxoplasmosis,

coccidi-oidomycosis, typhoid, and paratyphoid A and B fevers;

skin tests for tuberculosis, and chest x-ray films. The infant’s family had always resided in the Sacra-mento area; the family denied traveling outside Califor-nia; there were no pets in the household, and no other family members were ill. However, by the fifth febrile episode of this infant, it was learned that the family had spent several weekends at their grandparents’ cabin at

North Lake Tahoe, CA. Squirrels were frequently fed

with nuts at the cabin doorstep. Although the family

denied any history or knowledge of tick or other animal bites, Borrelia infection was suspected. Dark-field

ex-amination and Wright stains of blood smears revealed

abundant spirochetes (Fig 2).

(2)

eryth-romycin estolate (60 mg/kg per day in four divided doses). Two hours after the first dose of antibiotics, her temper-ature rose to 40.3 C, but no other reactions or side effects

occurred and the temperature defervesced over the

fol-lowing three hours. She was discharged the next day to complete a seven-day course of erythromycin.

Repeated blood smears at 4, 8, 10, and 12 hours after

April

initiation of the erythromycin therapy did not reveal any

spirochetes. The infant remained asymptomatic with no

recurrence of the infection during four months of follow-up.

Case 2

20.22 27-28

42

4

40

39

38

37

In August 1979, a previously healthy 8-year-old girl was seen for a two-day history of fever and headache,

May June diffuse muscle aching, joint pains, and chills. She

ap-7-8 24-26 2-4 peared acutely ill but was not toxic-looking. Except for a

temperature of 40 C orally, the results of the physical examination were normal.

The child lived in Fairfield, CA, and was on her way

home with her family from a one-week camping trip near

Salmon Lake in the Sierra mountains, where the family Socromenfo ‘Hosp:toItzotson

WBC

(103/cu.mm)

PMN (%) Stab (%) ESR (mm/hr)

9.8 39

19

Erythromycin

17.4 65

3

had rented a log cabin. She saw many chipmunks but

denied any close animal contact and did not recall any

tick bites. No other family members were ill. Because she

had been in an endemic area, Borrelia infection was

immediately suspected.

The hemoglobin was 13.3 gm/100 ml. The WBC count

11.9 was 8,100/cu mm with 71% polymorphonuclear

leuko-47 cytes, 18% band cells, 8% lymphocytes, and 3%

mono-1 2 cytes. The platelet level was normal, and the erythrocyte

55 57 sedimentation rate was 35 mm/hr. Spirochetes were

found in the blood smears.

The child was observed in the clinic after a single oral Fig 1. Case 1: Temperature curve demonstrates

relaps-ing fever pattern.

Fig 2. Case 1: Peripheral blood smear shows Borrelia spirochete (Wright’s stain, original oil immersion; xl,000).

964 TICK-BORNE RELAPSING FEVER

U

0

4)

0

4) 0. E a)

at Viet Nam:AAP Sponsored on September 7, 2020

www.aappublications.org/news

(3)

dose of 500 mg of erythromycin estolate. Vital signs

remained stable, and the temperature gradually

defer-vesced. Four hours after the initial dose of erythromycin, a repeat blood smear contained no spirochetes. The child was discharged from the clinic taking 250 mg of erythro-mycin estolate four times daily for ten days. She did not

have any relapse of the infection during two months of

follow-up.

Case 3

A 2-year-old boy was seen in October 1979 for a tem-perature of 38.6 C rectally, the fourth recurrence of fever since the end of August 1979.

Typically, the febrile episodes began abruptly, with temperature peaks as high as 40.6 C rectally that lasted for 48 hours. Associated symptoms were mild vomiting, decreased appetite, and fussiness. Physical examination during the febrile episodes showed a non-toxic-looking child with normal findings except for fever and a mildly

infected pharynx. The WBC counts were normal on two

occasions except for a mild shift to the left. Routine blood, throat, and urine cultures and urinalysis were negative. On each occasion, symptomatic therapy was prescribed

for a presumed viral syndrome. The interval between

febrile relapses was ten to 14 days, during which the child remained asymptomatic.

By the fourth febrile attack, it was discovered that the family had stayed for five days in late September 1979 in

a log cabin in the Angeles National Forest, CA, where

squirrels and chipmunks abound. The parents recalled no tick bites, and no other family members were ill.

Borrelia infection was suspected, and spirochetes were found in Wright-stained blood smears. In the clinic, the child was given 150 mg of oral erythromycin estolate. One

hour after the first dose, his temperature rose to 40 C

rectally. Chills and prostration were noted, but the tem-perature gradually decreased to 37.9 C without antipy-retics. The child was sent home taking a seven-day course of erythromycin and remained free of febrile relapses. Microscopic examination revealed no spirochetes in blood samples taken four hours and seven days after the initial dose of erythromycin.

DISCUSSION

Two distinct but clinically similar forms of

re-lapsing fever are recognized, louse-borne (epidemic)

and tick-borne (endemic). Both are caused by

spi-rochetes of the genus Borrelia and are

character-ized by recurrent paroxysms of fever separated by

afebrile intervals. The louse-borne infection

re-quires a human reservoir. It has not been contracted

in the United States for many years but remains

common in many other parts of the world.

In North America, the reservoir for Borrelia con-sists of wild rodents and three species of Ornitho-doros argasid (soft) ticks found in endemic foci of

the Western mountain areas. These tick species, 0

turicata, 0 parkeri, and 0 hermsi, serve as vectors

for three Borrelia species (B turicata, B parkeri,

and B hermsi, respectively). The first two species

of soft ticks are found mainly in semiarid plains

regions (although a single case of B turicata was

reported in Ohio).3 Only 0 hermsi is known to occur

in the coniferous forest biome of the Western

United States.45 These ticks can live and remain

infected for years and can also transmit the

infec-tion transovarially. They live primarily in dead

trees, logs, woodpiles, rodent burrows, and nests.

They normally are parasites of rodents, especially

chipmunks and pine squirrels, but they also feed on

humans. Unlike the common wood tick

(Dermacen-tor), 0 hermsi ticks are night feeders and take blood meals lasting an average of 15 minutes, after which they detach themselves. Although it may produce a 2- to 3-mm pruritic eschar, the bite

characteristically is painless.6 Thus, few people who

acquire relapsing fever recall being bitten.7

The incidence of this endemic infection in the

United States is unknown. Because it is readily

treatable with oral antibiotics, cases may occur

unreported when physicians give a “therapeutic

trial of antibiotics” for an acute, undifferentiated

febrile illness. Some cases may be undiagnosed

be-cause of lack of relapses. Although the disease can

be contracted at any time of the year, most reported

cases occurred during the summer.

The clinical manifestations of tick-borne

relaps-ing fever are well described in standard infectious

disease textbooks8’9 and in an extensive review of

1,105 cases in the world literature reported by

Southern and Sanford.’#{176}

The reported incubation period was

approxi-mately seven days (range, four to > 18 days). As in

our patients, symptoms were all nonspecific and

could easily be interpreted as those of viral

infec-tions frequently encountered in the summer:

sud-den onset of fever, headache, myalgia, arthralgia,

photophobia, and vague abdominal distress.

How-ever, despite several relapses (our cases 1 and 3),

the physical findings of this condition can be

decep-tively normal in contrast to the frequent organ

involvement mentioned in the literature: jaundice,

hepatomegaly, splenomegaly, rash (morbilliform or

hemorrhagic) and various neurologic complications

including nm9’

Southern and Sanford reported a mortality of 2%

to 5% (20% below the age of 1 year) from cases in

the world literature.’0 The mortality in the United

States is probably significantly less: no fatalities have occurred in 462 cases reported in California

since 1931.’ However, to pregnant women, this

dis-ease may present a potential danger of abortion’#{176} and neonatal death by transplacental transmission of Borrelia.’2

(4)

practi-966

TICK-BORNE

RELAPSING

FEVER

cal aspects of this disease. First, the diagnosis can

be suspected and obtained only if the clinician

actively seeks a good medical history. Just as

ma-lana should be suspected in a patient with

parox-ysmal fever who may not volunteer a history of

travel to endemic parts of the world unless

specifi-cally asked, any patient with fever and nonspecific,

“flu-like” illness should be asked whether he or she

has slept overnight in a rustic log cabin during the

previous one to three weeks in a national park or

mountain area of the Western United States above

5,000-foot elevation. Interstate and even

interna-tional cases of relapsing fever have been traced to

common exposures in an endemic vacationing site.5

Second, the simplest diagnostic test for

tick-borne relapsing fever is the microscopic

examina-tion for spirochetes in blood smears during the

febrile episode. In approximately 70% of cases,

spi-rochetes are found in the initial blood smear and

the yield increases with multiple smears.’#{176} Often,

the diagnosis is made accidentally by laboratory

technicians who notice spirochetes while doing the

complete blood count and differential on the blood

smears.”3 However, in this “age of the computer,”

the use of the automated electronic scanning

hem-ogram for obtaining the white cell differential may

deny the physician this fortuitous help since blood

smears may no longer be routinely looked at by the

technician. Blood cultures will be negative but

an-imal inoculation (by intraperitoneal injection of the

patient’s blood clot into mice or rats and subsequent

examinations of the animal blood smear for

spiro-chetemia) is positive in 85% of the cases reported

by Southern and Sanford.’#{176} The Microbial Disease

Laboratory, Department of Health, Berkeley, CA,

indeed confirmed by animal inoculation the

diag-nosis of Borrelia infection in our patients. No spe-cific serologic tests are clinically useful.

Third, tetracycline and chloramphenicol are the

recommended drugs for treatment of Borrelia in-fections.’#{176} The potential adverse effects of these

two drugs in children are well known to

pediatri-cians. Penicillin is less effective. Linnemann and

associates3 reported tetracycline failure in a

6’/2-year-old boy with B turicatae. However, Butler and

co-workers’4 in Ethiopia recently showed that a

single dose of oral tetracycline or erythromycin is

effective in the treatment of louse-borne relapsing

fever. Spirochetes disappeared from the patient’s

blood three to four hours after a single oral dose.

However, the short duration of the follow-up

obser-vation (one week) in that study did not exclude the

possibility of relapse. Our three patients responded well to oral erythromycin estolate. The hyperpy-rexia and prostration seen in two infants (cases 1 and 3) following antibiotic administration may

rep-resent a mild degree ofJarisch-Herxheimer reaction

which was self-limiting. That blood smears were cleared of spirochetes by four hours after the initial dose suggests that the drug is extremely bactericidal

to the Borrelia spirochetes. However, since the oral

antibiotic therapy is relatively benign and the risk

of relapse with a single dose in unknown, we chose

to give our patients an empirical seven- to ten-day

course of erythromycin. No relapse occurred in any of the patients during the two- to four-month fol-low-up.

ACKNOWLEDGMENTS

I thank Drs R. Meagher and B. Coop for referring

cases 1 and 3, respectively. Della Mundy, MLS, assisted with preparation of the manuscript.

REFERENCES

1. Tick-borne relapsing fever. Calif Morbidity Weekly Rep,

Jan 19, 1979, p 1

2. Report of the Committee on Infectious Diseases, ed 18. Evanston, IL, American Academy of Pediatrics, 1977 3. Linnemann CC Jr, Barber LC, Dine MS, et al: Tick borne

relapsing fever in the Eastern United States. Am JDis Child

132:40, 1978

4. Felsenfeld 0: Borrelia: Strains, Vectors, Human and Ani-mal Borreliosis. St Louis, Warren Y Green, 1971, pp 30-37 5. Boyer KM, Munford RS, Maupin GO, et al: Tick-borne

relapsing fever: An interstate outbreak originating at Grand Canyon National Park. Am J Epidemiol 105:469, 1977 6. Longanecker DS: Laboratory and field studies on biology of

relapsing fever tick vector (Ornithodoros hermsi Wheeler) in high mountains of California. Am J Trop Med Hyg 31:373, 1951

7. Wynns HL: The epidemiology of relapsing fever, in Moulton FR (ed): A Symposium on Relapsing Fever in the Americas.

Washington, DC, American Association for the Advance-ment of Science, 1942, pp 100-105

8. Francis BJ, Thompson RS: Relapsing fever, in Hoeprich PD (ed): Infectious Diseases: A Modern Treatise of Infectious Processes, ed 2. Hagerstown, MD, Harper & Row, 1977, pp 1067-1071

9. Burgdorfer W: The relapsing fevers, in Hunter GW, Swartzwelder JC, Clyde DF (eds): Tropical Medicine, ed 5. Philadelphia, WB Saunders, 1976, pp 137-146

10. Southern PM Jr, Sanford JP: Relapsing fever. A clinical and microbiological review. Medicine 48:129, 1969

1 1. Taber LH, Feigin RD: Spirochetal infections. Pediatr Clin North Am 26:377, 1979

12. Fuchs PC, Oyama AA: Neonatal relapsing fever due to transplacental transmission ofBorrelia. JAMA 208:690, 1969 13. Malison MD: Relapsing fever. JAMA 241:2819, 1979 14. Butler T, Jones PK, Wallace CK: Borrelia recurrentis

infec-tion: Single dose antibiotic regimens and management of the Jarisch-Herxheimer reaction. J Infect Dis 137:573, 1978

(5)

1980;66;963

Pediatrics

Chinh T. Le