Typhoid Fever in Children

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

Pediatrics 1975;56;606

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

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which corrected without specific therapy. Cerebral spinal SUMMARY AND CONCLUSIONS
fluid obtained during a pneumoencephalogram contained 18
lymphocytes per cubic millimeter and protein level was 49 This is the second reported case of cerebellar
mg/l00 ml. Etiology of the pleocytosis was not certain, but impairment attributed to chronic toluene inhala-
may have been due to the irritation of the meninges during tion. Sniffing of substances containing this solvent
the pneumoencephalogram .Electroencephalogram, radioac-
is not uncommon. Minimal cases might be
tive brain scan, carotid and vertebral arteriography, and
pneumoencephalography were within normal limits.
detected if careful neurological observation is
The diagnostic impression was cerebellar dysfunction employed. Prevention of further damage by absti-
secondary to some toxic factor in the paint. There was nence from the habit seems possible as judged by
subjective improvement in general well-being and no the course of the present patient. More impor-
progression of the cerebellar signs 2#{189} months after her initial
tantly, potential abusers might be prevented from
visit. Neurologic examination five months after discon-
tinuing paint-sniffing indicated objective improvement.
starting this pernicious practice with the know!-
Finger-to-nose and heel-to-shin testing revealed less ataxia. edge that definite, persistent neurologic abnor-
The right side was worse than the left. She could now malities can result.
perform Romberg testing without any sway or falling, but COL THOMAS W. KELLY, MC, USA
still exhibited abnonnal tandem gait.
Chief, Neurology Service
Box 332
DISCUSSION Tripler Army Medical Center
Since the patient purchased particular brands APO San FrancLico, California 96438
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)
REFERENCES
is a common ingredient of paint thinners and
1. Gleason MN, Gosselin RE, Hodge HC, Smith RP:
glues.’ It is the volatile substance most frequently Clinical Toxicology of Commercial Products, ed 3.
associated with illicit sniffing abuse.2 Previous Baltimore, Williams & Wilkins, 1969, section 2, p
reports have documented sudden death,3 addic- 144.
tive-like behavior,4 renal abnormalities,5 and 2. Press E, Done AK: Solvent sniffing. Pediatrics 39:451,
1967.
suggested possible hepatic” and hematologic’ ill
3. Bass M: Sudden sniffing death. JAMA 212:2075, 1970.
effects. Neurologic symptoms, including acute 4. Nylander I: “Thinner” addiction in children and adoles-
brain syndrome, electroencephalographic cents. Acta Paedopsychiatr 29:273, 1962.
changes, visual hallucinations, confusion, seizures, 5. Taher SM, Anderson RJ, McCartney R, Popvtzer MM,
and erratic behavior,275 are the most frequently Schrier RW: Renal tubular acidosis associated with
cited effects. These appear to be transient for the toluene sniffing. N Engl J Med 290:765, 1974.
6. Jacobziner H, Raybin HW: Lead poisoning and glue
most part. Only one previous instance of irrever- sniffing intoxication. NY State J Med 63:2846,
sible cerebellar damage from toluene inhalation9 1963.
could be found. This patient was a 21-year-old 7. Massengale ON, Glaser HH, LeLievre RE, Dodds JB,
male aircraft worker who apparently was quite Kiock ME: Physical and psychologic factors in glue
careful about obtaining only pure toluene to sniffing. N Engl J Med 269: 1340, 1963.
8. Brozovsky M, Winkler EG: Glue sniffing in children and
inhale, but who had a long-enduring habit and a
adolescents, NY State J Med 65: 1984, 1965.
chronic neurologic picture distinctly similar to 9. Grabski DA: Toluene sniffing producing cerebellar
the present patient. degeneration. Am J Psychiatry 118:461, 1961.

Typhoid Fever in Children girl was the index case, and that her disease was
contracted from a carrier living next door. Spread
An epidemic of typhoid fever occurred in a occurred via a faulty well, chlorinator, and
migrant labor camp some 15 miles south of sewerage system in the camp.’ During a period of
Miami, Florida in February 1973. It was the approximately three weeks, over 300 patients
largest reported outbreak of typhoid fever in the were hospitalized with suspected typhoid. Of this
United States in the last 30 years. Epidemiolog- number, 147 were children under 13 years of age.
ical data revealed that an 1 1-year-old retarded A portion of the pediatric ward at Jackson Memo-

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606 TYPHOID FEVER IN CHILDREN
 TABLE I TABLE II
PRESENTING SIGNS AND SYMPTOMS IN 94 CHILDREN MEAN LABORATORY RESULTS IN 94 CHILDREN WITH
WITH TYPHOID FEVER COMPARED TO DATA FOR ADULTS TYPHOID FEVER

Children Adults Measure Mean Range

Signs and Symptoms (%) (%)
Hemoglobin (gm/100 ml) 11.7 5.2 to 14.3
Temperature over 37.8 C 84.6 6 Hematocrit (%) 33.6 17.0 to 42.7
Diarrhea 50.3 30 WBC (per cu mm) 8.5#{176} 2.1 to 18.5
Vomiting 46.2 25 Reticulocytes (%) 1.2 0.2 to 7.8
Abdominal pain 38.8 61 Sodium (mEg/liter) 131.8 127 to 148
Anorexia 22.4 90 Potassium (mEg/liter) 4.0 2.7 to 6.7
Nausea 18.3 - Chloride (mEg/liter) 98.0 88 to 116
Cough 12.2 22 CO2 (vol%) 21.0 11 to 28
Headache 7.5 75 Glucose (mg/100 ml) 98.5 55 to 150
Lethargy 52.0 29 Australia antigen (%) 0.0 -
Hepatomegaly 23.7 -
Calcium (mg/l00 ml) 9.1 7.5 to 10.2
Splenomegaly 12.6 14 Phosphorus (mg/100 ml) 4.5 1.7 to 6.5
Rash 5 Cholesterol (mg/100 ml) 146.0 105 to 235
#{176}FromHuckstep.3 Uric acid (mg/100 ml) 4.7 1.8 to 9.2
BUN (mg/l00 ml) 10.8 3 to 32
LDH (mg/l00 ml) 400.0 180 to 600
rial Hospital (JMH) in Miami was modified to SCOT (lU/mI) 104.5 20 to 300
care for all suspected typhoid cases and all Alkaline phosphatase (lU/mi) 175.4 25 to 330
children entered an established protocol.
Biliruhin (mg/100 ml) 0.51t -
Salmonella typhi, phage type E infection was
Creatinine (mg/100 ml) 0.58 0.3 to 1.2
confirmed in 94 children, either by positive blood
#{176}Fivepatients had < 4/cu mm.
or stool culture and/or a four-fold increase in
tEight patients had > 1 mg/100 ml.
Widal 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. ferred to JMH from a neighboring hospital who
All suspected cases entered a protocol requir- had already initiated treatment with orally
ing clinical observations with vital signs every administered ampicillin were continued with the
four hours. Laboratory work included complete same agent in a dose of 200 mg/kg.
blood cell count, reticulocyte count, urinanalysis, During and after hospitalization, those on
electrolytes, glucose, blood urea nitrogen, SMA- chioramphenicol were monitored for blood
12, Australia antigen, Widal titer, and blood, dyscrasias. Following treatment, stool cultures
stool, and urine cultures. Urine cultures were were repeated and follow-up examinations were
collected by clean midstream catch or catheteri- scheduled for neighboring clinics.
zation and accepted as positive if only a single Tables I and II itemize the presenting signs,
organism grew more than 100,000 colonies per symptoms, and laboratory data in our series.
milliliter. No attempt was made to identify the The mean age was 6.7 years with a range of 8
organism in cultures growing less than 100,000 months to 13 years of age. The mean admission
colonies per milliliter. The Widal titers were temperature was 39 C. It should be noted that
repeated ten days after admission in 27 patients two children presented with normal temperatures
who had strong clinical or bacteriologic evidence which never rose above 38.2 C; one had a positive
for typhoid fever yet had insignificant titers at blood culture while the other had a positive stool
admission. Blood cultures were performed three culture. No significant temperature-pulse disso-
times in the first 24 hours after admission while ciation was noted in any of the patients. Deferves-
stools were cultured twice in the first 48 hours. cence occurred on an average of 3.9 days
Children admitted directly to JMH were following the initiation of therapy. Hospital stay
started on orally administered chloramphenicol averaged 13.9 days. Both defervescence and dura-
(50 mg/kg day for three days), followed by 25 tion of illness averaged the same for ampicillin
mg/kg day for ten days. Those patients trans- and chloramphenicol.

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EXPERIENCE January
AND 14, 2014
REASON 607
 TABLE III
WEIDAL TITER (0 ANTIGEN) CHANGES IN 53 CHILDREN AFTER TREATMENT

Titer s Ten Days After Treatment

Total Presenting
No. Titers Negative 1:20 1:40 1:80 1:160 1:320 1:640 1:2,560

12 Negative 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 - -

Hepatomegaly was noted in 52%, splenomegaly symptom, ascending over a two- to three-day
in 23.7%, and rash in 12.6%. These patients had period, followed by headache, abdominal pain,
nonspecified macular-papular eruptions. Only anorexia, and myalgia. These observations
two children had rose spots. All children were matched those reported by Huckstep’ in his
Australia antigen-negative. Serum LDH and analysis of nearly 1,000 mostly adult patients with
SGOT levels were elevated. LDH levels averaged typhoid.
400 units/mi and SGOT 105 units/mi. Mean total The clinical picture, however, is altered in
bilirubin, however, was .51 mg/ 100 ml with only children, and the disease tends to be less severe.
9% of the children having bilirubins greater than Fever, diarrhea, and vomiting are more common
1.0 mg/100 ml total. in children. The disease presents more acutely
There was no hypoglycemia and no evidence of with fever of one day’s duration, initiating
renal impairment as measured by BUN and crea- gastrointestinal signs, and little of the lethargy
tinine. Of patients who had positive blood which is frequently seen in adults.
cultures for Salmonella, 9.5% had negative or The headache, myalgia, anorexia, nausea,
insignificant Widal titers initially and when thrombocytopenia, and leukopenia attributed to
repeated ten days later. Titers of 1:80 or higher S. typhosa endotoxin4 was not the rule in the
were present in 90.5% of the children. Yet, blood children we report. Only five had leukopenia less
cultures were positive in only 65 children and than 4,000/cu mm and two had thrombocytope-
stool cultures positive in 57 children. Table III ma. Meningismus was infrequent.
shows titer changes after treatment in 53 chil- The findings of concommitant nontyphoid
dren. urinary tract infection in 13% of the patients was
Of interest was the presence of concommitant of interest and not readily explainable. Studies by
urinary tract infection in 13% of the children with Kunin”6 indicate that up to 2% of the schoolgirls
a predominance of E. coli. in the United States may have asymptomatic
Eighty of the 94 patients were treated with bacteruria. Therefore, 13% was a significant
chioramphenicol and the remainder with ampicil- number surpassing the indices of Kunin. In addi-
un. Five of the chioramphenicol-treated patients lion, three of these patients were boys. In a
relapsed. None of 14 patients treated with ampi- migrant labor camp the natural incidence of
cillin relapsed (Fisher exact test, F> .8). There asymptomatic bacteruria may be higher, but this
were no deaths and no serious morbidity. We information was not available. No S. typhi organ-
encountered no hemorrhage, perforation, phlebi- isms were isolated from urine cultures, most likely
tis, hepatitis, bronchopneumonia, osteomyelitis, because our laboratory failed to identify cultures
arthritis, or meningitis. There were no complica- growing less than 1,000 colonies per milliliter.
tions secondary to chloramphenicol therapy. The relapse rate with chloramphenicol was
nearly 6.2%. The S. typhi strain was not related to
DISCUSSION the recently reported Vietnam or Mexican’
In their studies of infected adult volunteers, strains resistant to chloramphenicol. None of the
Hornick et al.2 noted that fever was the first 14 patients treated with ampicillin had relapse.

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608 TYPHOID FEVER IN CHILDREN
 This epidemic served to emphasize the clinical ADDRESS FOR REPRINTS: (A.R.C.) Department of
Pediatrics, School of Medicine, Georgetown University,
manifestations of typhoid in children as compared
Washington, D.C.
to adults, that concommitant nontyphoid urinary
tract infections are common in typhoid, that REFERENCES
Widal titers may not rise with early therapy, that 1. Nitzkin JL: Typhoid Fever,
South Dade County Labor
hyponatremia is common, and that relapses are Camp. Dade CountyPublic Health Report, 1973.
common and, in this study, none occurred with 2. Hornick RB, et al: Typhoid fever: Pathogenesis and
immunologic control. N EngI J Med 282:686,
ampicillin therapy.
1970.
A. R. COLON, M.D. 3. Huckstep RL: Typhoid Fever. Edinburgh, E Livingston
D. R. GROSS, M.D. Ltd. 1962.
M. A. TAMER, M.D. 4. Hornick RB, et a!: Tyhpoid fever: Pathogenesis and
Department of Pediatrics, immunologic control. N Engi J Med 282:739,
1970.
School of Medicine,
5. Kunin CM: Natural history of recurrent bacteruria in
University of Miami schoolgirls. N Engi J Med 282: 1443, 1970.
Miami, Florida 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,
Supported in part by grant PE 00 106-08-5676808 from 1974.
the National Institutes of Health. 8. Gonzales-Cortes A, et al: Water-borne transmission of
Read before the Southern Society for Pediatric Research, chloramphenicol-resistant Salmonella typhi in Mex-
New Orleans, January 26, 1974. ico. Lancet 2:605, 1973.

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EXPERIENCE AND REASON 609
 Typhoid Fever in Children
A. R. Colon, D. R. Gross and M. A. Tamer
Pediatrics 1975;56;606
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007.
Copyright © 1975 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005.
Online ISSN: 1098-4275.

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on January 14, 2014