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Pediatr Infect Dis J. Author manuscript; available in PMC 2016 May 01.
Published in final edited form as:
Pediatr Infect Dis J. 2015 May ; 34(5): 463–468. doi:10.1097/INF.0000000000000608.
Streptococcal Pharyngitis in Schoolchildren in Bamako, Mali
Milagritos D. Tapia, MD1, Samba O. Sow, MD, MS2, Boubou Tamboura, Pharm D2,
Mahamadou M. Keita, MD2, Abdoulaye Berthe, MD2, Mariam Samake, Pharm D2, James P.
Nataro, MD, PhD, MBA3, Uma O. Onwuchekwa2, Thomas A. Penfound, PhD4, William
Blackwelder, PhD5, James B. Dale, MD4, and Karen L. Kotloff, MD1,5
1Division
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of Infectious Disease and Tropical Pediatrics, Department of Pediatrics, University of
Maryland School of Medicine, Baltimore, MD, USA
2Centre
pour le Développement des Vaccins – Mali, Bamako, Mali
3Department
of Pediatrics, University of Virginia, Charlottesville, VA, USA
4University
of Tennessee Health Science Center and Veterans Affairs Medical Center Research
Service, Memphis, TN, USA
5Division
of Geographic Medicine, Department of Medicine, Center for Vaccine Development,
University of Maryland School of Medicine, Baltimore, MD, USA
Abstract
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Background—Group A streptococcus (GAS) pharyngitis is associated with high rates of
rheumatic heart disease (RHD) in developing countries. We sought to identify guidelines for
empiric treatment of pharyngitis in low resource settings. To inform the design of GAS vaccines,
we determined the emm types associated with pharyngitis among African schoolchildren.
Methods—Surveillance for pharyngitis was conducted among children 5 to 16 years of age
attending schools in Bamako, Mali. Students were encouraged to visit a study clinician when they
had a sore throat. Enrollees underwent evaluation and throat swab for isolation of GAS. Strains
were emm typed by standard methods.
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Results—GAS was isolated from 449 (25.5%) of the 1,759 sore throat episodes. Painful cervical
adenopathy identified 403 children (89.8%) with GAS infection and was absent in 369 uninfected
children (28.2%). Emm type was determined in 396 (88.2%) of the 449 culture-positive children;
70 types were represented and 14 types accounted for 49% of isolates. Based on the proportion of
the 449 isolates bearing emm types included in the 30-valent vaccine (31.0%) plus non-vaccine
types previously shown to react to vaccine-induced bactericidal antibodies (44.1%), the vaccine
could protect against almost 75% of GAS infections among Bamako schoolchildren.
Conclusions—Two promising strategies could reduce RHD in low resource settings.
Administering antibiotics to children with sore throat and tender cervical adenopathy could treat
Corresponding Author: Milagritos Tapia, MD, University of Maryland School of Medicine, Center for Vaccine Development, 685
W. Baltimore St., Rm 480, Baltimore, MD 21201, mtapia@medicine.umaryland.edu, Phone: 410 – 706 – 5328, Fax: 410 – 706 –
6205.
Conflicts of interest
The remaining authors have no conflicts of interest to declare.
Tapia et al.
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most GAS-positive children while reducing use of unnecessary antibiotics for uninfected children.
Broad coverage against M types associated with pharyngitis in Bamako schoolchildren might be
achieved with the 30-valent GAS vaccine under development.
Keywords
Group A Streptococcus; Streptococcal pharyngitis; emm; Mali
INTRODUCTION
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Left untreated, pharyngitis due to Streptococcus pyogenes, or group A streptococcus (GAS),
can lead to suppurative complications and acute rheumatic fever (ARF). Whereas ARF and
its sequela, rheumatic heart disease (RHD), were important causes of morbidity and
mortality in the U.S. and other high income countries in the late 1800s,1, 2 a combination of
factors including economic development and specific antibiotic therapy for overt GAS
pharyngitis have been credited with subsequent reductions in cases to the point of nearelimination, even in the face of a stable incidence in GAS pharyngitis.3
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In stark contrast, RHD afflicts an estimated 1.9 million children aged 5 to 14 years residing
in developing countries.4 Many of these children live in conditions with crowding and poor
sanitation. In addition, effective prevention of ARF in developing countries is impeded by
the poor availability of public education to teach parents when to seek medical care for a
child with sore throat, diagnostic tests to guide the practitioners’ decisions regarding
initiation of antibiotic treatment, and skills in cardiac auscultation and syndrome recognition
that enable a clinician to detect persons with RHD in need of antibiotic prophylaxis.
Whereas many studies have been performed to construct clinical algorithms for
identification of GAS pharyngitis in developed countries,5–9 there is a need for data to guide
clinicians in developing countries, in particular those in sub-Saharan Africa, as the relative
risks and benefits of empiric treatment are quite different in these settings with high ARF
incidence. Ultimately, development of a safe and effective GAS vaccine that could reduce or
supplant the need for primary and secondary antibiotic prophylaxis for RHD offers many
advantages. The candidate most advanced in clinical development includes the N-terminal
regions of 30 GAS M proteins, designed to evoke type-specific opsonizing antibodies, a
correlate of protective immunity.10 The composition of this vaccine was designed based on
data from North America and Europe. However, the predicted efficacy for the prevention of
RHD will depend on the vaccine’s ability to prevent infections with emm types that cause
pharyngitis in developing regions of the world.
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We describe herein a prospective cohort study of the epidemiology of GAS pharyngitis
among schoolchildren living in Bamako, Mali. This study was conducted to address two
aims: 1) to identify clinical features associated with sore throat that are capable of
identifying children in this population with GAS infection while minimizing unnecessary
treatment of uninfected children, and 2) to characterize the emm types of GAS associated
with pharyngitis in this African setting to inform the development of M protein-based
vaccines.
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METHODS
Sampling Frame and Recruitment Activities
The study was conducted at four public schools in Djikoroni-para and Sébénikoro, two
adjacent quartiers (neighborhoods) in Commune IV of Bamako, Mali. Between 1,600 and
5,000 students were enrolled in each school. Children at two of the schools attended either a
morning or afternoon session to alleviate over-crowding. Medical care was available at each
school for children who became ill during the school day; three schools maintained an onsite infirmary while the fourth utilized a neighboring health center. Study clinicians manned
all four facilities to enroll eligible children on weekdays year round.
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The study was introduced at the start of each school year by inviting the community to an
informational session. Thereafter, study personnel visited the classrooms at least once per
week and encouraged students to seek care from study personnel if they developed a sore
throat. The school year ran from October to May, with a 3-week break. When school was
not in session, local criers visited the quartiers several times per week chanting reminders to
parents and children via loudspeaker that the study was ongoing.
Ethical Approvals and Informed Consent
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The study was approved by the institutional review boards at the Faculté de Médecine,
Pharmacie et Odontostomatologie in Bamako, Mali, the University of Maryland, Baltimore,
University of Tennessee Health Science Center and the Memphis Veterans Affair Medical
Center. Prior to beginning study activities, the investigators met with the local school and
community authorities and obtained community consent. Parental consent was obtained for
all participants either at the beginning of the school year or at the time of a pharyngitis
episode. In addition, written assent was obtained from all participants 13 to 16 years of age.
Detection and management of pharyngitis cases and sampling
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Students aged 5 to 16 years who presented to study personnel at the school infirmary or
school-associated health center complaining of sore throat were invited to participate.
Enrolled children provided clinical information solicited using a standardized interview to
determine the presence of headache, rhinorrhea, chills, cough, difficulty swallowing,
hoarseness, nausea, vomiting, malaise, abdominal pain, diarrhea, or a history of
feverishness. Thereafter, a study clinician systematically measured the child’s oral
temperature, examined the conjunctiva, mouth, pharynx, tonsils, palate, uvula, cervical
lymph nodes, and skin, and recorded the findings on a standardized case report form. A
swab of the posterior pharynx and tonsillar fossae was collected, placed in Amies charcoal
media (CultureSwab™, Becton Dickinson) and transported to the laboratory at ambient
temperature for plating within 6 hours of collection.
All participants were given a 3-day supply of acetaminophen at weight-appropriate dosages
free of charge. If GAS was isolated, they were given a 10-day supply of penicillin VK and
encouraged to complete the treatment course. At the end of the treatment period, a field
worker visited the home to recover and record any remaining doses.
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Microbiology and emm typing
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Throat swabs were used to inoculate 5% sheep’s blood agar media by isolation streaking. A
bacitracin disk (0.04 U) was placed in the area of the primary inoculum and the plate was
incubated at 35–37°C. Each plate was checked for growth at 24 and 48 hours. Betahemolytic, catalase-negative, bacitracin-sensitive, Gram positive cocci in pairs and chains
that tested positive for GAS antigen agglutination (Remel, Lenexa) were designated as GAS.
Isolates were stored at −80°C in trypticase soy broth with 15% glycerol.
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DNA from the GAS isolates was extracted and the emm gene was amplified using standard
methodology (Centers for Disease Control (CDC), Atlanta, GA).11 The amplified DNA
product was sent to the University of Maryland Biopolymer Laboratory for 5’ sequencing.
Trimmed emm sequences containing 150 nucleotide bases encoding the mature protein were
aligned with the CDC database of defined emm-types (downloaded September 27, 2012)
using FASTA 36.3.5d.12 Each sequence was assigned an emm-type based on parameters as
described (http://www.cdc.gov/ncidod/biotech/strep/assigning.htm).
Data analysis
Data were collected on case report forms (Teleform version 8.2.0) that were scanned and
used to populate an Access database (Microsoft). Data were analyzed using EpiInfo (CDC,
Atlanta GA), NCSS (Number Cruncher Statistical Systems, Kaysville, Utah), and SAS
version 9.3 (SAS Institute Inc., Cary NC). Associations between symptoms and GAS were
assessed by logistic regression models, allowing for within-individual correlation due to
multiple episodes of pharyngitis in an individual participant. A two-sided p-value < 0.05 was
considered statistically significant.
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RESULTS
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From May 2006 to September 2009, 1,418 students at the participating schools contributed
1,759 episodes of pharyngitis (Table 1). There were 244 students who experienced more
than 1 episode of pharyngitis; of these, 19 students had 4 or more episodes, 50 had 3
episodes and 175 had 2 episodes. GAS was isolated in 449 episodes (25.5%) experienced by
421 (29.7%) students. GAS was isolated 3 times from 5 students and twice from 18 students.
GAS was more commonly isolated from girls with pharyngitis than boys (290/1042 vs
159/717; odds ratio 1.4 (95% CI 1.1–1.7), p = 0.008). There was no evidence of an
association between age and GAS isolation (p = 0.88). Pill counts taken at the follow-up
visits suggested that a total of 429 (95.5%) children with GAS pharyngitis took all doses of
penicillin prescribed; no medication-related adverse events were observed. The percentage
of cases positive for GAS was similar from season to season (26.8% in the cold season,
23.6% in the hot season and 25.3% in the rainy season).
The relative frequency of clinical findings was similar among GAS-positive and GASnegative children, although there were differences in the absolute proportions (Figure 1).
The most frequent findings among GAS-positive and GAS-negative patients, respectively,
were tender cervical lymph nodes (89.8% vs 71.8%) and tonsillar erythema (89.3% vs
86.4%). No suppurative or non-suppurative complications of GAS were identified. In
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multiple logistic regression analysis, the presence of tender cervical lymph nodes, tonsillar
exudate, chills, tonsillar hypertrophy, and uvular erythema were positively associated with
the isolation of GAS whereas complaints of cough, malaise, and hoarseness were negatively
associated, i.e., the absence of these symptoms was significantly more common when GAS
was present (Table 2). We evaluated the predictive value of these eight signs and symptoms,
when present alone or in combination, for GAS isolation (Table 3). Tender cervical lymph
nodes alone conferred a sensitivity of 89.8%. Inclusion of additional signs increased the
sensitivity to a maximum of 96.4%. The maximum specificity associated with a sensitivity
of 89.8% or higher was seen with tender cervical lymph nodes alone; using this single
parameter, 30.0% of episodes classified as GAS are truly infected, and 88.9% of episodes
without this sign are truly uninfected, and unnecessary antibiotics could be avoided for
28.2% of truly uninfected children who lack this finding.
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All 449 GAS strains isolated during the surveillance period were subjected to emm typing.
An emm type was identified in 396 (88.2%) of the isolates. The sequences did not yield an
interpretable result in the remaining 53 isolates. Although 70 emm types were represented,
49% of isolates belonged to 14 emm types (Figure 1). The most common emm type, emm65,
accounted for 5.6% of isolates. Twelve emm types were represented only once. Only one of
the students who had more than one episode of GAS positive pharyngitis had the same emm
type isolated twice (emm 75.1) and these episodes occurred greater than 9 months apart.
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We examined the proportion of emm types that are represented in the 30-valent GAS
vaccine currently under development (Figures 2 and 3).10 A total of 139 isolates (31.0%)
belonged to 19 of the emm types included in the vaccine. An additional 198 isolates
(44.1%), representing 30 emm types, were non-vaccine type isolates but have been shown to
exhibit more than 50% bactericidal killing in the presence of rabbit antisera generated after
vaccination with the 30-valent vaccine. The most commonly isolated emm type (emm65)
was among these. The vaccine did not induce bactericidal activity against 5 non-vaccine
types (6.7%), and there were insufficient data to assess whether the vaccine induced crossreactive bactericidal antibodies for the remaining 15 types (6.5%) isolated. The most
commonly isolated type not covered by the vaccine was emm55, of which there were 17
isolates (3.8% of the total). The proportion of isolates that might be covered either directly
or by cross-reactive antibodies induced by vaccination varied from year to year (81.5% in
2006, 65.3% in 2007, 75.4% in 2008 and 93.1% in 2009, chi-square, p=0.022).
DISCUSSION
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To our knowledge, this is the first study to systematically quantify the frequency and clinical
presentation of GAS pharyngitis among school-aged children in a country designated by the
United Nations as least developed. We found that approximately 25% of sore throat
episodes among children 5 to 16 years of age attending school in Bamako, Mali were
positive for GAS, which is similar to that observed in upper and middle income
countries.13–16 Several clinical scoring systems have been developed for use in low resource
settings in an attempt to reduce unnecessary antibiotic treatment of the 75% of children with
sore throat who are not infected with GAS. The goal is to identify a subset of children who
are likely to be GAS positive for microbiologic confirmation, or if unavailable, for empiric
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treatment. These scoring systems, which generally include multiple clinical parameters, have
been evaluated in middle income countries such as Brazil,13, 14, 17, Egypt,13, Latvia and
Croatia,15 but it is not known whether they are applicable, feasible, or practical for use in the
less developed countries of sub-Saharan Africa where overall implementation of
recommended guidelines for clinical care is known to be inadequate.18, 19 After searching
for a simplified approach, we found that a single finding, tender cervical lymph nodes, could
identify 89.8% of GAS-positive children with sore throat and when absent could avoid
unnecessary antibiotics administration in 28.2% of GAS-negative children. Cervical
adenopathy (variously defined as enlargement and/or tenderness) has improved the
sensitivity of most decision rules (although not to the extent that we observed) and has been
incorporated into numerous models.20 Our findings suggest that if Bamako schoolchildren
with sore throat were screened for cervical tenderness, then 2.3 GAS-negative children
would be treated for every GAS-positive child treated, compared to a treatment ratio of 3.5:1
associated with the standard practice of treating all children with sore throat in our
population.
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Use of clinical algorithms is driven by the belief that antibiotic cost, toxicity, and treatmentinduced antibiotic resistance outweigh the benefits of empiric treatment of all episodes of
pharyngitis, and that the 9–16% of GAS-positive children who do not meet criteria have
more subtle symptoms and are likely carriers who are at low risk for ARF. However, data
are insufficient to draw the same conclusion for low income countries such as Mali. Even if
future studies validate the feasibility and performance characteristics of our clinical rule in
Mali and other low income settings, the benefits of administering antibiotics to all children
with sore throat might still prevail when one considers factors such as the high prevalence of
RHD, the difficulty implementing secondary prophylaxis to reduce the risk of chronic
valvular damage,21 the absence of penicillin resistance despite widespread utilization, the
relatively low cost and low risk of penicillin, and the high cost of RHD, both direct (medical
costs) and indirect (loss of productivity).
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Based on over 3 years of surveillance among Bamako schoolchildren with sore throat, our
findings support and extend observations that considerable emm type diversity occurs in
numerous low and middle income countries such as India,22 Brazil,23 and Fiji;24 in these
settings, many emm types were identified, but each accounted for a relatively small
proportion of the total infections. We found that 25 emm types accounted for 70.2% of the
70 types identified, which is similar to a recent report from Africa where 25 emm types
accounted for 62.5% of the 90 types identified.25 By comparison, in high income countries
25 emm types accounted for the vast majority (90.3%) of the 171 types found.25 There are
also substantial geographic differences in the relative frequency of the emm types that occur
most commonly. Whereas in high income countries the most common emm types are emm1,
emm12, emm28, emm3 and emm4, accounting for about half of strains isolated,25 in Bamako
these represented only 14 (3.5%) of the 396 typed isolates. The emm type diversity observed
in the regions most in need of a vaccine to prevent RHD has driven the development of
polyvalent type-specific vaccines, as well as the search for vaccine components that contain
conserved regions of the M protein or other highly conserved GAS antigens that might
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provide protection against a large proportion of the >200 emm types that have been
identified.10, 26–29
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Several GAS vaccines are undergoing preclinical development and two have previously
been evaluated in early-stage clinical trials.26, 27 The latter vaccines incorporate fusion
proteins containing peptides of the N-terminal region of M proteins which have been shown
to elicit type-specific opsonic antibodies that Lancefield originally associated with
protective immunity.30 In addition, there is evidence that these vaccines may provide crossprotection which is thought to be based upon bactericidal antibodies that recognize shared
epitopes in the N-terminal region of various emm types.10, 31 Type-specific vaccines
containing 6 and 26 M types have been well-tolerated and immunogenic when administered
intramuscularly with alum adjuvant in clinical trials.26, 27 A 30-valent vaccine has now been
constructed that contains emm types responsible for more than 90% of GAS infections
occurring in North America and Europe but has far less homology with the broad spectrum
of emm types seen in many developing countries.10 Consequently, an important finding in
our study is that bactericidal activity against 44.1% of the non-vaccine emm types
circulating in Bamako in addition to 31.0% coverage by vaccine types could translate into
nearly 75% protective efficacy by the 30-valent vaccine for Malian children.10, 31 Since we
conducted surveillance over a 3-year period, we were able to observe the emm type
distribution prospectively and found that significant variations occurred from year-to-year
and had a minimum coverage of 65.3%.
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A limitation of our study is that asymptomatic children were not included for comparison, so
it is difficult to ascertain whether certain emm types were more strongly associated with
pharyngitis. Moreover, we cannot determine whether the strain identified in an individual
child represents clinical infection and therefore poses a risk for ARF, or asymptomatic
colonization, which does not. Therefore, we must infer with caution that the distribution of
emm types identified among children with sore throat resemble those associated with ARF in
our population. Of note, emm3 and emm18, which accounted for 4.8% of our isolates, have
been previously isolated in cases of ARF.32–39 In addition, our data may not be
generalizable to children in the same neighborhoods who do not attend school or in less
densely populated areas of Mali and where more heterogeneous populations may live.23
From local demographic surveillance data collected over the study period, we know that
only 70% of the children living in Djikoroni, one of the study quartiers, attended school.
ACKNOWLEDGMENTS
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The authors acknowledge the contributions of the student bodies at the participating schools, school administrators,
parent-teacher organizations and health care personnel. We thank Joshua Orvis for his assistance in emm typing of
GAS isolates. We also offer special thanks to Fran Rubin, PhD and Robin Mason for their dedication to this project
and their invaluable guidance and support.
Source of Funding
Dr. Dale is the inventor of certain technologies related to the development of group A streptococcal vaccines, which
have been licensed by the University of Tennessee Research Foundation to Vaxent, LLC. Dr. Dale serves as the
Chief Scientific Officer of Vaxent and is a member.
Source of Support: National Institutes of Health, UO1AI060592 awarded to JB Dale.
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34. Smoot JC, Korgenski EK, Daly JA, Veasy LG, Musser JM. Molecular analysis of group A
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35. Veasy LG, Tani LY, Daly JA, et al. Temporal association of the appearance of mucoid strains of
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38. Shulman ST, Stollerman G, Beall B, Dale JB, Tanz RR. Temporal changes in streptococcal M
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Pediatr Infect Dis J. Author manuscript; available in PMC 2016 May 01.
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Figure 1.
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The number of patients with and without various clinical findings, alone or in combination,
according to the presence of group A streptococcus (GAS) by throat culture. *5 findings
denotes: tender cervical lymph nodes, tonsillar exudate, tonsillar hypertrophy, chills, or
uvular erythema; **3 findings denotes: tender cervical lymph nodes, tonsillar exudate, or
tonsillar hypertrophy; ‡2 findings denotes: tender cervical lymph nodes or tonsillar exudate.
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Figure 2.
The frequency of each emm type among the 396 isolates for which typing data was
available. The first 14 types represent 49% of the isolates.
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Figure 3.
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Of the 449 GAS isolates, 31% (indicated as VT or vaccine type) are included in the 30valent vaccine presently under development. Based on data indicating that cross-coverage of
certain emm types has been observed in-vitro (indicated as non-vaccine type killed, NVTK), this vaccine could cover almost 75% of the Mali isolates. The vaccine does not cover
6.7% of isolates and there is no information regarding potential coverage of the remaining
18.3% (indicated as no data or no emm type).
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Figure 4.
Of the 70 emm types observed in Malian school children with pharyngitis, 19 types (VT)
were among those covered by the 30-valent vaccine under development. Based on in vitro
data, the 30-valent vaccine could induce cross-coverage of an additional 30 non-vaccine
types (NVT-K). Six types (NVT-NK) would not be covered; there is no data on the coverage
of the remaining 15 types observed.
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Table 1
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Frequency of group A streptococcal pharyngitis among Bamako schoolchildren.
Age Group
Number of cases
of sore throat
GAS positive cases
N
%
5 to 7 years old
160
45
28.1
8 to 10 years old
517
120
23.2
11 to 13 years old
817
220
26.9
14 to 16 years old
265
64
24.1
Total
1759
449
100.0
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Table 2
Pediatr Infect Dis J. Author manuscript; available in PMC 2016 May 01.
Number (%)
with symptom
who have GAS
Number (%)
without
symptom
who have
GAS
Multivaria
te Odds
Ratio
95%
Confiden
ce Limit
p-value
in
multiple
regressi
on
Tender cervical lymph nodes
403 (30.0)
96 (20.6)
3.06
2.17–4.33
<0.0001
Tonsillar exudate
152 (47.1)
347 (23.4)
2.69
2.04–3.54
<0.0001
Tonsillar hypertrophy
334 (30.4)
165 (23.2)
1.49
1.16–1.93
0.002
Chills
129 (27.9)
370 (27.5)
1.37
1.03–1.81
0.030
Uvular erythema
159 (30.5)
340 (26.4)
1.32
1.02–1.70
0.034
Cough
177 (21.7)
322 (32.5)
0.72
0.57–0.91
0.005
Malaise
168 (23.5)
331(30.2)
0.67
0.52–0.87
0.003
Hoarseness
103 (21.5)
396 (29.8)
0.65
0.48–0.87
0.003
Tapia et al.
Multiple logistic regression model to determine the signs and symptoms which were positively or negatively (i.e. odds ratio <1) associated with the
isolation of group A streptococcus (GAS) from Bamako schoolchildren with sore throat.
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Table 3
Clinical Finding
Sensitivity
Specificity
Positive
predictive
value
Negative
predictive
value
Treatment
ratio‡
Tender cervical lymph nodes (LN)
89.8
28.2
30.0
88.9
3.0
Tonsillar hypertrophy
74.4
41.7
30.4
82.6
2.8
Uvular erythema
35.4
72.3
30.5
76.6
3.3
Tonsillar exudate
33.9
86.9
47.1
79.3
3.2
Chills
28.7
86.9
27.9
75.3
3.6
Cough
39.4
51.1
21.7
71.1
2.6
Malaise
37.4
58.3
23.5
73.1
2.3
Hoarseness
22.9
71.4
21.5
73.0
2.6
Either tender cervical LN or tonsillar exudate
92.9
26.8
30.3
91.6
2.3
≥1 of 3 findings*
95.5
17.2
28.3
91.8
2.5
≥1 of 5 findings**
96.4
10.8
27.0
89.8
2.7
≥2 of 5 findings**
84.0
35.7
30.9
86.7
2.2
Tapia et al.
Calculated sensitivity, specificity and positive and negative predictive values for individual signs and symptoms significantly associated with isolation of
group A streptococcus (GAS) in multivariate logistic regression, when considered alone or in combination.
Individual signs
Pediatr Infect Dis J. Author manuscript; available in PMC 2016 May 01.
Combinations of signs
Either tender cervical LN or tonsillar exudate, and either cough, hoarseness, or malaise
65.3
56.4
33.9
82.6
2.5
≥1 of 3 findings* and ≤2 of: cough, hoarseness, malaise
67.5
48.1
30.8
81.2
2.4
≥1 of 3 findings* and no cough
88.2
28.0
29.6
87.4
2.0
≥1 of 3 findings* and no hoarseness
58.4
59.1
32.8
80.5
2.3
≥1 of 3 findings* and no malaise
73.1
42.3
30.3
82.1
2.3
*
3 findings denotes: tender cervical LN, tonsillar exudate, or tonsillar hypertrophy
**
5 findings denotes: tender cervical LN, tonsillar exudate, tonsillar hypertrophy, chills, or uvular erythema
‡
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Based on the presence of the clinical finding, the number of GAS-negative episodes that would be treated for every GAS-positive episode treated