1975;56;606 Pediatrics

A. R. Colon, D. R. Gross and M. A. Tamer

Typhoid Fever in Children

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606 TYPHOID FEVER IN CHILDREN
which corrected without specific therapy. Cerebral spinal
fluid obtained during a pneumoencephalogram contained 18
lymphocytes per cubic millimeter and protein level was 49
mg/l00 ml. Etiology of the pleocytosis was not certain, but
may have been due to the irritation of the meninges during
the pneumoencephalogram .Electroencephalogram, radioac-
tive brain scan, carotid and vertebral arteriography, and
pneumoencephalography were within normal limits.
The diagnostic impression was cerebellar dysfunction
secondary to some toxic factor in the paint. There was
subjective improvement in general well-being and no
progression of the cerebellar signs 2#{189} months after her initial
visit. Neurologic examination five months after discon-
tinuing paint-sniffing indicated objective improvement.
Finger-to-nose and heel-to-shin testing revealed less ataxia.
The right side was worse than the left. She could now
perform Romberg testing without any sway or falling, but
still exhibited abnonnal tandem gait.
DISCUSSION
Since the patient purchased particular brands
and colors because of tastes and odor and did
not actually select them because of content, a
survey of labels of her preferred brands was
conducted. This indicated that there was a
common ingredient, toluene, in all the brands
that she sniffed. Toluene (toluol, methylbenzene)
is a common ingredient of paint thinners and
glues. It is the volatile substance most frequently
associated with illicit sniffing abuse.2 Previous
reports have documented sudden death,3 addic-
tive-like behavior,4 renal abnormalities,5 and
suggested possible hepatic and hematologic ill
effects. Neurologic symptoms, including acute
brain syndrome, electroencephalographic
changes, visual hallucinations, confusion, seizures,
and erratic behavior,275 are the most frequently
cited effects. These appear to be transient for the
most part. Only one previous instance of irrever-
sible cerebellar damage from toluene inhalation9
could be found. This patient was a 21-year-old
male aircraft worker who apparently was quite
careful about obtaining only pure toluene to
inhale, but who had a long-enduring habit and a
chronic neurologic picture distinctly similar to
the present patient.
SUMMARY AND CONCLUSIONS
This is the second reported case of cerebellar
impairment attributed to chronic toluene inhala-
tion. Sniffing of substances containing this solvent
is not uncommon. M inimal cases might be
detected if careful neurological observation is
employed. Prevention of further damage by absti-
nence from the habit seems possible as judged by
the course of the present patient. M ore impor-
tantly, potential abusers might be prevented from
starting this pernicious practice with the know!-
edge that definite, persistent neurologic abnor-
malities can result.
COL THOM AS W . KELLY, M C, USA
Chief, Neurology Service
Box 332
Tripler Army M edical Center
APO San FrancLico, California 96438
REFERENCES
1. Gleason M N, Gosselin RE, Hodge HC, Sm ith RP:
Clinical Toxicology of Commercial Products, ed 3.
Baltimore, W illiams & W ilkins, 1969, section 2, p
144.
2. Press E, Done AK: Solvent sniffing. Pediatrics 39:451,
1967.
3. Bass M : Sudden sniffing death. JAM A 212:2075, 1970.
4. Nylander I: Thinner addiction in children and adoles-
cents. Acta Paedopsychiatr 29:273, 1962.
5. Taher SM , Anderson RJ, M cCartney R, Popvtzer M M ,
Schrier RW : Renal tubular acidosis associated with
toluene sniffing. N Engl J M ed 290:765, 1974.
6. Jacobziner H, Raybin HW : Lead poisoning and glue
sniffing intoxication. NY State J M ed 63:2846,
1963.
7. M assengale ON, Glaser HH, LeLievre RE, Dodds JB,
Kiock M E: Physical and psychologic factors in glue
sniffing. N Engl J M ed 269: 1340, 1963.
8. Brozovsky M , W inkler EG: Glue sniffing in children and
adolescents, NY State J M ed 65: 1984, 1965.
9. Grabski DA: Toluene sniffing producing cerebellar
degeneration. Am J Psychiatry 118:461, 1961.
Typhoid Fever in Children
An epidemic of typhoid fever occurred in a
migrant labor camp some 15 miles south of
M iami, Florida in February 1973. It was the
largest reported outbreak of typhoid fever in the
United States in the last 30 years. Epidemiolog-
ical data revealed that an 1 1-year-old retarded
girl was the index case, and that her disease was
contracted from a carrier living next door. Spread
occurred via a faulty well, chlorinator, and
sewerage system in the camp. During a period of
approximately three weeks, over 300 patients
were hospitalized with suspected typhoid. Of this
number, 147 were children under 13 years of age.
A portion of the pediatric ward at Jackson M emo-
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PRESENT I NG SI GNS A ND SY M PT OM S I N 94 CH I L DREN
W I T H T Y PH OI D FEV ER COM PA RED T O DA T A FOR A DUL T S
M EA N L A BORA T ORY RESUL T S I N 94 CH I L DREN W I T H
TYPHOID FEVER
#{ 176} Fr omH uck st ep.3
TABLE I TABLE II
E X P E R IE N C E A N D R E A S O N 607
Signs and Symptoms
Children
(%)
Adults
(%)
T emper at ur e over 37.8 C 84.6 6
Di ar r hea 50.3 30
Vomiting 46.2 25
Abdominal pain 38.8 61
Anorexia 22.4 90
Nausea 18.3 -
Cough 12.2 22
Headache 7.5 75
Lethargy 52.0 29
Hepatomegaly 23.7 -
Splenomegaly 12.6 14
Rash 5
rial Hospital (JM H) in M iami was modified to
care for all suspected typhoid cases and all
children entered an established protocol.
Salmonella typhi, phage type E infection was
confirmed in 94 children, either by positive blood
or stool culture and/or a four-fold increase in
W idal titers. Another 14 children had shigellosis
and 5 had urinary tract infections. The remaining
34 children had nontyphoid febrile illnesses of
short duration and varied etiologies.
All suspected cases entered a protocol requir-
ing clinical observations with vital signs every
four hours. Laboratory work included complete
blood cell count, reticulocyte count, urinanalysis,
electrolytes, glucose, blood urea nitrogen, SM A-
12, Australia antigen, W idal titer, and blood,
stool, and urine cultures. Urine cultures were
collected by clean midstream catch or catheteri-
zation and accepted as positive if only a single
organism grew more than 100,000 colonies per
milliliter. No attempt was made to identify the
organism in cultures growing less than 100,000
colonies per milliliter. The W idal titers were
repeated ten days after admission in 27 patients
who had strong clinical or bacteriologic evidence
for typhoid fever yet had insignificant titers at
admission. Blood cultures were performed three
times in the first 24 hours after admission while
stools were cultured twice in the first 48 hours.
Children admitted directly to JM H were
started on orally administered chloramphenicol
(50 mg/kg day for three days), followed by 25
mg/kg day for ten days. Those patients trans-
Measure Mean Range
Hemoglobin (gm/100 ml ) 11.7 5.2 t o 14.3
Hematocrit (% ) 33.6 17.0 to 42.7
W BC (per cu mm) 8.5#{176} 2.1 to 18.5
Reticulocytes (% ) 1.2 0.2 to 7.8
Sodium (mEg/liter) 131.8 127 to 148
Potassium (mEg/liter) 4.0 2.7 to 6.7
Chloride (mEg/liter) 98.0 88 to 116
CO2 (vol% ) 21.0 11 to 28
Gl ucose (mg/100 ml ) 98.5 55 t o 150
Australia antigen (% ) 0.0 -
Calcium (mg/l00 ml) 9.1 7.5 to 10.2
Phosphorus (mg/100 ml) 4.5 1.7 to 6.5
Cholesterol (mg/100 ml) 146.0 105 to 235
Uric acid (mg/100 ml) 4.7 1.8 to 9.2
BUN (mg/l00 ml) 10.8 3 to 32
L DH (mg/l00 ml) 400.0 180 to 600
SCOT (lU/mI) 104.5 20 t o 300
Alkaline phosphatase (lU/mi) 175.4 25 to 330
Biliruhin (mg/100 ml) 0.51t
-
Creatinine (mg/100 ml) 0.58 0.3 to 1.2
#{176}Five patients had < 4/cu mm.
tEight patients had > 1 mg/100 ml.
ferred to JM H from a neighboring hospital who
had already initiated treatment with orally
administered ampicillin were continued with the
same agent in a dose of 200 mg/kg.
During and after hospitalization, those on
chioramphenicol were monitored for blood
dyscrasias. Following treatment, stool cultures
were repeated and follow-up examinations were
scheduled for neighboring clinics.
Tables I and II itemize the presenting signs,
symptoms, and laboratory data in our series.
The mean age was 6.7 years with a range of 8
months to 13 years of age. The mean admission
temperature was 39 C. It should be noted that
two children presented with normal temperatures
which never rose above 38.2 C; one had a positive
blood culture while the other had a positive stool
culture. No significant temperature-pulse disso-
ciation was noted in any of the patients. Deferves-
cence occurred on an average of 3.9 days
following the initiation of therapy. Hospital stay
averaged 13.9 days. Both defervescence and dura-
tion of illness averaged the same for ampicillin
and chloramphenicol.
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TA BL E I I I
608 TYPHOID FEVER IN CHILDREN
W EI DA L TI TER (0 A NTI GEN) CHA NGES I N 53 CHI L DREN A FTER T R E AT M E NT
Total
No.
Presenting
Titers
Titer s Ten Days After Treatment
Negative 1:20 1:40 1:80 1:160 1:320 1:640 1:2,560
12 Negati ve 7 3 - 2 - - - -
3 1:20 2 1 - - - - - -
7 1:40 3 1 - 3 - - - -
13 1:80 - 3 1 4 3 - 1 1
10 1: 160 3 1 - 3 2 - - 1
5 1:320 1 1 - 1 2 - - -
2 1:640 - - - - - - 2 -
1 1: 2,560 - - - - - 1 - -
Hepatomegal y was noted i n 52%, spl enomegal y
i n 23.7%, and rash i n 12.6%. These pati ents had
nonspeci f i ed macul ar-papul ar erupti ons. Onl y
two chi l dren had rose spots. A l l chi l dren were
A ustral i a anti gen-negati ve. Serum L DH and
SGOT l evel s were el evated. L DH l evel s averaged
400 uni ts/mi and SGOT 105 uni ts/mi . M ean total
bi l i rubi n, however, was .51 mg/ 100 ml wi th onl y
9% of the chi l dren havi ng bi l i rubi ns greater than
1.0 mg/100 ml total .
There was no hypogl ycemi a and no evi dence of
renal i mpai rment as measured by BUN and crea-
ti ni ne. Of pati ents who had posi ti ve bl ood
cul tures f or Salmonella, 9.5% had negati ve or
i nsi gni f i cant W i dal ti ters i ni ti al l y and when
repeated ten days l ater. Ti ters of 1:80 or hi gher
were present i n 90.5% of the chi l dren. Y et, bl ood
cul tures were posi ti ve i n onl y 65 chi l dren and
stool cul tures posi ti ve i n 57 chi l dren. Tabl e I I I
shows ti ter changes af ter treatment i n 53 chi l -
dren.
Of i nterest was the presence of concommi tant
uri nary tract i nf ecti on i n 13% of the chi l dren wi th
a predomi nance of E. coli.
Ei ghty of the 94 pati ents were treated wi th
chi orampheni col and the remai nder wi th ampi ci l -
un. Fi ve of the chi orampheni col -treated pati ents
rel apsed. None of 14 pati ents treated wi th ampi -
ci l l i n rel apsed (Fi sher exact test, F> .8). There
were no deaths and no seri ous morbi di ty. W e
encountered no hemorrhage, perf orati on, phl ebi -
ti s, hepati ti s, bronchopneumoni a, osteomyel i ti s,
arthri ti s, or meni ngi ti s. There were no compl i ca-
ti ons secondary to chl orampheni col therapy.
D IS C U S S IO N
I n thei r studi es of i nf ected adul t vol unteers,
Horni ck et al.2 noted that f ever was the f i rst
symptom, ascendi ng over a two- to three-day
peri od, f ol l owed by headache, abdomi nal pai n,
anorexi a, and myal gi a. These observati ons
matched those reported by Huckstep i n hi s
anal ysi s of nearl y 1,000 mostl y adul t pati ents wi th
typhoi d.
The cl i ni cal pi cture, however, i s al tered i n
chi l dren, and the di sease tends to be l ess severe.
Fever, di arrhea, and vomi ti ng are more common
i n chi l dren. The di sease presents more acutel y
wi th f ever of one day s durati on, i ni ti ati ng
gastroi ntesti nal si gns, and l i ttl e of the l ethargy
whi ch i s f requentl y seen i n adul ts.
The headache, myal gi a, anorexi a, nausea,
thrombocytopeni a, and l eukopeni a attri buted to
S . typhosa endotoxi n4 was not the rul e i n the
chi l dren we report. Onl y f i ve had l eukopeni a l ess
than 4,000/cu mm and two had thrombocytope-
ma. M eni ngi smus was i nf requent.
The f i ndi ngs of concommi tant nontyphoi d
uri nary tract i nf ecti on i n 13% of the pati ents was
of i nterest and not readi l y expl ai nabl e. Studi es by
K uni n 6 i ndi cate that up to 2% of the school gi rl s
i n the Uni ted States may have asymptomati c
bacteruri a. Theref ore, 13% was a si gni f i cant
number surpassi ng the i ndi ces of K uni n. I n addi -
l i on, three of these pati ents were boys. I n a
mi grant l abor camp the natural i nci dence of
asymptomati c bacteruri a may be hi gher, but thi s
i nf ormati on was not avai l abl e. No S. typhi organ-
i sms were i sol ated f rom uri ne cul tures, most l i kel y
because our l aboratory f ai l ed to i denti f y cul tures
growi ng l ess than 1,000 col oni es per mi l l i l i ter.
The rel apse rate wi th chl orampheni col was
nearl y 6.2%. The S. typhi strai n was not rel ated to
the recentl y reported V i etnam or M exi can
strai ns resi stant to chl orampheni col . None of the
14 pati ents treated wi th ampi ci l l i n had rel apse.
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EXPERIENCE AND REASON 609
This epidemic served to emphasize the clinical
manifestations of typhoid in children as compared
to adults, that concommitant nontyphoid urinary
tract infections are common in typhoid, that
W idal titers may not rise with early therapy, that
hyponatremia is common, and that relapses are
common and, in this study, none occurred with
ampicillin therapy.
M iam i, Florida
A. R. COL ON, M .D.
D. R. GROSS, M .D.
M . A. T AM ER, M .D.
Department of Pediatrics,
School of M edicine,
University of M iami
Supported in part by grant PE 00 106-08-5676808 from
the National Institutes of Health.
Read before the Southern Society for Pediatric Research,
New Orleans, January 26, 1974.
ADDRESS FOR REPRINTS: (A.R.C.) Department of
Pediatrics, School of M edicine, Georgetown University,
W ashington, D.C.
REFERENCES
1. Nitzkin JL: Typhoid Fever, South Dade County Labor
Camp. Dade County Public Health Report, 1973.
2. Hornick RB, et al: Typhoid fever: Pathogenesis and
immunologic control. N EngI J M ed 282:686,
1970.
3. Huckstep RL: Typhoid Fever. Edinburgh, E Livingston
Ltd. 1962.
4. Hornick RB, et a!: Tyhpoid fever: Pathogenesis and
immunologic control. N Engi J M ed 282:739,
1970.
5. Kunin CM : Natural history of recurrent bacteruria in
schoolgirls. N Engi J M ed 282: 1443, 1970.
6. Kunin CM : Ten-year study of bacteruria in schoolgirls. J
Infect Dis 122:382, 1970.
7. Butler T, et al: Chloramphenicol-resistant typhoid fever
in Vietnam associated with R. factor. Lancet 2:983,
1974.
8. Gonzales-Cortes A, et al: W ater-borne transmission of
chloramphenicol-resistant Salm onella typhi in M ex-
ico. Lancet 2:605, 1973.
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1975;56;606 Pediatrics
A. R. Colon, D. R. Gross and M. A. Tamer
Typhoid Fever in Children

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Online ISSN: 1098-4275.
Copyright 1975 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005.
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007.
has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the
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