TABLE I
SYMvrosts IN 47 CIIILD1tEN LESS ‘l’IIAN 3 XEARS
OF AGI WITh EXUDATIVE TONSII.l.ITIS
Symptoms ( 81 79 72 7i 68 64 26
EXPERIENCE AND REASON-BRIEFLY RECORDED
Failure
to
Isolate
Streptococci
from
Children
under
the Age
of 3 Years
with
Exudative
Tonsillitis
Tonsillar exudate is traditionally associated
with the diagnosis of streptococcal infection
even though several agents are known to
pro-duce this clinical finding.’ Ii children less
than 3 years of age, exudative tonsillitis
caused by streptococci is less common than in
older children, but the actual frequency with
which streptococci are isolated when exudate
is present in these young children has not been
determined. This study was undertaken to
evaluate the clinical impression that throat
cultures from such patients rarel’ yield beta
llemolytic streptococci.
PLAN OF STUDY
Forty-seven patients less than 3 years of
age with exudative tonsillitis were studied
dur-ing the 8-month period from January through
August 1964. These patients were seen in the
Emergency Clinic of the Children’s Hospital Medical Center. This clinic, which has been described previously,#{176} is utilized largely by
medically indigent urban families who live
within a 5-mile radius of the hospital.
All patients were examined initially b’ a
resident physician who notified the
investi-gators when exudative tonsillitis was found in
a child less than 3 years of age. Each was seen
at that time by at least one of the investigators
and questioned about symptoms, exposure,
family and social history, and prior therapy.
Any patient who had received antimicrobial
drugs during the 30 days prior to this illness
was excluded from the study.
A complete physical examination was
per-formed and the presence of exudate was
con-firmed. The extent of tonsillar exudate was
scaled as 1+ (less than 10% of the available
surface or minimal involvement); 2+ (10% to
50%, or moderate involvement); 3+ (greater
than 50, or extensive). The exudate was
further described as being pinpoint or cheesy,
if these terms applied, and whether white or
yellow in color. Specimens for bacteriologic
and viral studies were obtained. Patients were
reexamined 2 weeks later.
BACTERIOLOGIC AND VIRAL STUDIES
Every patient had one nasopharyngeal and
tvo throat swabs, each of which was
immedi-ately inoculated in duplicate onto sheep and
Temperature oer 10#{176}F
Irritability
Anorexia
Coryza
Fever duration less titan ‘2 (lays
Vomiting or diarrhea
Dysphagia
horse blood agar plates. Tilese were examined in the hospital bacteriology laboratory’ for
pos-sible bacterial pathogens. Hemolytic
strepto-cocci, if found, were grouped by the Bacitracin
disc method.
A third throat swab for virus isolation was
collected from the first 27 patients in the study
and inoculated into KB, priniarv green monkey
kidney, WI-38, and either primary human
amnion or secondary human kidney tissue
cul-tures. Specimens from all but seven of the cases
were inoculated into one or more of the four
tissue cultures within 3 hours of collection. The
remaining tests were performed with material
which had been stored at -70#{176}C. The monkey
kidney cultures were tested for hemabsorption
of guinea pig red cells 7 to 14 days after
inocu-lation. Titers of neutralizing antibody for
res-piratory svncytial virus and complement-fixing
antibody for adenoviruses were determined on
paired sera obtained at a 2-week interval. ASO
titers were also determined on these paired
sera. All tests vere performed by standard
methods.7
RESULTS
The median age of the 47 patients with
exu-dative tonsillitis was 22 months (range 5 to 35).
There were 28 males and 19 females. The
presenting symptoms in the 47 children are
sum-marizd in Table I. A rectal temperature greater
than 102#{176}Fwas found in 81%, and fever had
been present for less than 2 days in 68%.
Lethargy or irritability, upper respiratory
symp-toms, and gastrointestinal symptoms were noted
in most patients; but local symptoms, such as
dysphagia, occurred in only one fourth of the patients. Seventy percent of the children had
been exposed to a respiratory illness, usually in
siblings.
* Two of tin-se j)lttieltts llit(l significant increase in
respiratory Sytl(’ytial Ililtihody 1)Ht no virus was
isolated.
664 TONSILLITIS
TABLE II
PHYSICAl. FINDINGS IN 47 CIIILDHEN LESS THAN 3
\EAItS 01’ AGI VlTll iXt’DAT1yF: ‘I’ONSILLITIS
Sly,is
l’.XU(latt I-1- (1-2
+
3+ 6
(l(lIOI)at liv
Ruiiiiorrht.a 49
Otitis llR(lja 34
lOXi(itv 6
Risii
and 3+ in 6 (Table II). Tonsillar or pharyngeal injection was found in 95%, adenopathy in 55%,
rllinorrhea ill 49%, and an abnormality of the
ear cirunis (ranging from hypermia to frank
suppuration aiid bulging) in 34%. Only three
(6%) appeared severely ill. One had a typical scarlet fever exanthem.
Group A beta hemolytic streptococci were
isolated from only 7 (14.6%) of the 47 patients
(Table III). Hemophilus influenza was found in
10 Patients anti pneumococcus in 3. There was
more than one possible bacterial pathogen
cul-tured from two of these patients (pneumococcus
-hemophilus influenza,
ptleumococcus-strep-tococcus). The use of duplicate throat cultures
and nasopharvngeal swabs did not increase the
yield of possible pathogens.
Evidence of a virus infection was found in 6
(22%) of the 27 patients studied. Four
adeno-viruses were isolated two were type 1, one was
type 2, and one was type 5). Only one of these
four patients had a fourfold or greater increase
in adenovirus antibody titer. Two patients had
serologic evidence of infection with respiratory
‘FABLE III
ISOLATIONS F1IOM CIIILunEN LESS I’IIAN 3 \EARS
OF’ AG : WITH EXUDATI yE TONSI LUTIs
. .\u,nber _Vuinber
Organism . . . .
Stu(lled Positi,’e Positire
Streptococcus 47 7 14.6
Ileutophilus ilifitleliza 47 10 23.7
Pnell,Iloco.(.lls 47 3 (1 . 4
Viruses ?7 6* 22 .0
svncytial virus, but no virus was isolated from
the throat of either. One of these patients also
had an increasing titer for adenovirus. A mixed
infection with a possible bacterial pathogen
and a virus (hemophilus alld adenovirus) was
found ill oiil’ one child. Poliomvelitis viruses, types 1 itid 2, were isolated from one
addi-tional patient who had been given oral
polio-myelitis vaccine 6 days before the onset of his
respiratory illness.
The 27 patients studied for virus also had
ASO titers determined Ofl the paired sera. Only
one patiellt, who also cultured streptococcus, demonstrated a rise in titer (less than 100 to
1,250). Three t)ther patients in this group
cul-tured streptococcus but, like the other patients,
showed 110 rise in titer.
The small size of the streptococcal group
fllakes meaningful comparison with the
11011-streptococcal group difficult. There were no
ob-vious differences other than a typical scarlet
fever rash ill one patient from the streptococcal
group. Streptococci were found in only one of
the three patients who were severely ill and in
none of the three patients with 3+ exudate.
There was no relationship between the color
and character of the exudate and the isolation of the streptococcus.
Thirty-six (76%) of the patients were reex-amined 2 weeks after the initial visit. Eigilty-three percent of these had no fever within 48 hours of being seen in the emergency clinic.
Two patients had developed a rash consistent
with roseola. Eleven patients were treated with antibiotics. Five patients were given penicillin for streptococcal infection and six were treated for otitis media. There was no apparent effect of
antibiotics on duration of fever, but these
numbers are small.
At the conclusion of the study, records from
the medical emergency clinic of patients vith
throat cultures positive for streptococcus for the
8-month period of the study were reviewed as
well as the emergency clinic register sheet
which contained the diagnosis and age of the
patients. An additional 24 patients less than
age 3 with exudative tonsillitis were identified.
These patients had not been reported to the
re-search team by the emergency clinic staff. Seven
had been treated with antibiotics without
cul-tures being taken. Seventeen had throat cultures taken in the usual nianner, were treated with
antimicrobials, and none were found to have
EXPERIENCE AND REASON-BRIEFLY RECORDED
COMMENT
Powers5 Ilas pointed out that streptococcal infection in children less than 3 years of age is characterized by insidious onset, moderate fever, nasal discharge, and persistence of
symp-toms for 4 to 6 weeks when untreated. Exuda-tive tonsillitis is unusual in this age group. Of
1,237 streptococcal infections studied, only 378
vere ill children less than 3 years old, and only 34 of these had exudative tonsillitis.
Holzel alld others5 found that of 192
chil-dren admitted to a hospital with a diagnosis of
tonsillitis, 147 (85.9%) were less than 4 ‘ears old. Group A beta hemolytic streptococci were
isolated from only 10.9% and viruses from only
23% of those in this young age group. Similar
results were reported by Taylor.9
Carrier rates for streptococci range from 107 to 40%,bn depending upon the age of the children studied and the time of the year. In
the present study the carrier state was not
differentiated from active infection .
There-fore, the proportion of the 47 young children
who vere actually infected with streptococci
may have been less than 14.6%. The first 6
months of the study correspond to that time
of year when streptococcal infections are more
common. Thus, any bias would have been in
the direction of finding the streptococcus.
If not streptococcal, what is the etiology of
exudative tonsillitis in children less than 3
‘ears of age? Only 22% of the viral studies
were positive. In patients with presumed viral
upper-respiratory infections2 as well as in
those attending well-baby conferences,’ the
virus isolation rate is approximately 20%.
Al-though this study used techniques adequate to isolate most of the presently known respiratory
viruses, techniques for isolating viruses may
not be sufficiently well developed to recover a
majority of the viruses capable of producing
respiratory illness. Further investigation of a
viral etiology would require adequate control
subjects and both tvell children and children
Vitl1 pharngitis without exudate. Tile
signifi-cance of the hemophilus isolates is doubtful,
since carrier rates for hemophilus can be as high as 40%.12,13
Recent studies have suggested a pathogenic
role for rnycoplasma homenis in huniaii
res-piratory infections. This organism, previously
considered non-pathogenic, is capable of
pro-ducmg exudative tonsillitis.
Age is clearly an important factor in
de-termiflillg the value of exudate as a clinical sign in the diagnosis of streptococal infection.
In older children (that is, those over the age
of 4) Breese14 reports a diagnostic accuracy of 75% with a clinical picture of headache, ab-dominal pain, and exudative tonsillitis.
Stiller-man15 found streptococci in 64% of children with exudate in this age group in contrast to the 14.6% of the younger patients in the
pres-ellt study. It is apparent that streptococcal
in-fection in young children seldom produces a
tonsillar exudate.
SUMMARY
Forty-seven children less than 3 years of
age with exudative tonsillitis were studied and
only seven (14.6%) were found to have strep-tococci. Attempts to explain the etiology of this syndrome by virological study were
tin-successful, although 22% of 27 patients studied
did have evidence of virus infection.
Children with exudate in this age group do
ilot usually require antimicrobial therapy tin-less there is proof by culture of the presence of streptococci or unless there is other clinical
indication such as otitis media. The presence
of exudate is, in fact, a strong indication that
tile streptococcus is not the etiologic agent.
JOEL
J.
ALPERT, M.D.M. RUTH PICKERING, M.D.
ROBERT
J.
WARREN, M.D.Department of Pediatrics
Harvard Medical School and
Child Health Division of
The Children’s Hospital Medical Center
Boston, Massachusetts 02115
The authors wish to express their appreciation
to
Dr. Benedict Massell and Dr. J. Gabriel Michaelfor determining the ASO titers.
REFERENCES
1. Van der Veen, J., and Kirkman, J. H. :
Asso-ciations of type 21 adenovirus with acute
respiratory illness in military recruits. Amer.
J. Hg., 76:149, 1962.
2. Ginsberg, H. S., Gold, E., Jordan, W. S., Datz,
S., Badger, G. F., and Dingle, J. H. :
Rela-tion of the new respiratory agents to acute
respiratory diseases. Amer. J. Public Health,
45:915, 1965.
3. Evans, A. S., and Dick, E. C. : Acute
pharyn-gitis anti tonsillitis in University of
666 TONSILLITIS
Cate, T. R., Taylor-Robinson, D., Chanock,
R. M. : Exudative pharyngitis following ex-penmental mycoplasma hominis type 1
in-fection. J.A.M.A., 192:1146, 1965.
5. Powers, G. F., and Boisvert, P. L. : Age as a
factor in streptococcosis. J. Pediat., 24:481,
1944.
6. Bergman, A. B., and Haggerty, R. J.: The
emergency clinic: a study of its role in a
teaching hospital. Amer. J. Dis. Child., 104: 36, 1962.
7. Hamre, D. : Critique of methods for recovery
of respiratory viruses. Amer. Rev. Resp.
Dis., 88:306-312, (Part 2 of two parts),
1963. From conference on newer respiratory
disease viruses, Bethesda, Maryland,
Octo-l)er 3-5, 1962.
8. Holzel, A., Parker, L., Patterson, W. H.,
Cartnlel, D., White, L. L. R., Purdy, R.,
Thompson, K. M., and Tobin, J. O’H. : Virus
isolations from throats of children admitted
to hospital with respiratory and other
dis-eases. Manchester, 1962-64. Brit. Med. J.,
1:614, 1965.
9. Taylor, W. C., and Read, C. H. : A study of
acute respiratory disease in infancy. J.
Pediat., 50:679, 1957.
10. Cornfield, D., and Hubbard, J. P. : A
four-year study of the occurrence of
beta-hemo-.lytic streptococci in 64 school children. New Eng. J. Med., 264:211, 1961.
11. Moffet, H. L., and Cramblett, H. G. : Viral isolations and illnesses in young infants
at-tending a well-baby clinic. New Eng. J.
Med., 267:1213, 1962.
12. Masters, P. L., Brumfitt, W., Mendez, R. L.,
and Likar, M. : Bacterial flora of the upper
respiratory tract in Paddington families,
1952-54. Brit. Med. J., 1:1200, 1958.
13. Turk, D. C. : Nasopharyngeal carriage of
hemophilus influenza type B. Brit. J. Hyg.
61:247, 1963.
14. Breese, B. B., and Disney, F. A. : The accuracy
of diagnosis of beta streptococcal infections
on clinical grounds. J. Pediat., 44:670, 1954.
15. Stillerman, M., and Bernstein, S. :
Strepto-coccal pharyngitis. Evaluation of clinical syndrome in diagnosis. Amer. J. Dis. Child.,
