Journal of the Pediatric Infectious Diseases Society Advance Access published October 30, 2014

Original Article

Management of Contacts of Patients With Severe

Invasive Group A Streptococcal Infection
Rosngela Stadnick Lauth de Almeida Torres,1,2 Talita Zajac dos Santos,3 Robson Antnio de Almeida Torres,2
Lygia Maria Coimbra de Manuel Petrini,4 Marion Burger,5,6 Andrew C. Steer,7,8 and Pierre R. Smeesters7,8,9
1
Laboratrio de Bacteriologia, Diviso de Laboratrios de Epidemiologia e Controle de Doenas, Laboratrio Central do Estado do
Paran, 2Universidade Positivo, Curitiba, 3Pontifcia Universidade Catlica do Paran, 4Hospital Vita, Curitiba, 5Secretaria
Municipal de Curitiba, 6Associao Hospitalar de Proteo a Infncia Dr Raul Carneiro, Curitiba, Paran, Brazil; 7Centre for
International Child Health, University of Melbourne; 8Group A Streptococcal Research Group, Murdoch Childrens Research
Institute, Parkville, Melbourne, Victoria, Australia; and 9Laboratory of Bacterial Genetics and Physiology, IBMM, Facult des
Sciences, Universit Libre de Bruxelles, Brussels, Belgium

Corresponding author: Rosngela Stadnick Lauth de Almeida Torres, MS, PhD, Laboratrio Central do Estado do Paran-Lacen-PR,
Rua: Sebastiana Santana Fraga, 1001, Bairro Guatup, CEP 83060-500, So Jos dos Pinhais, Paran, Brazil. E-mail: rslatorres@
gmail.com.
Received June 27, 2014; accepted October 5, 2014.

Background. Conicting recommendations regarding antibiotic prophylaxis for contacts of patients with
invasive group A streptococcal (GAS) infection exist. Close contacts of patients with such severe and rapidly
progressive disease often strongly appeal to the treating clinicians for antimicrobial treatment to prevent
additional cases. We aimed to use an approach based on pharyngeal culture testing of contacts and targeted
antibiotic prophylaxis.
Methods. A large throat swab survey including 105 contacts was undertaken after a fulminant and fatal case
of GAS necrotizing fasciitis. GAS strains were characterized by emm typing and antimicrobial susceptibility to
7 antibiotics. The presence of 30 virulence determinants was determined by polymerase chain reaction and
sequencing.
Results. The GAS isolate recovered from the index patient was an M1T1 GAS clone susceptible to all
antimicrobial agents tested. The same clone was present in the throat of 36% of close contacts who had exposure
to the index patient (family households and classroom contacts) for >24 hours/week, whereas the strain was
present in only 2% of the other contacts.
Conclusions. Although the study does not allow rm conclusions to be drawn as to whether antibiotic
prophylaxis is effective, we describe a practical approach, including an educational campaign and targeted
antibiotic treatment to close contacts who have been exposed to an index patient for > 24 hours/week before
the initial disease onset.
Key words. close contacts; group A streptococcus; necrotizing fasciitis; prevention; throat swab.

Invasive group A streptococcal (GAS) infections are of sig-
nicant concern worldwide [13], with a case fatality rate
of 15% to 30% and an all-ages incidence rate comparable
to that of meningococcal disease in nonepidemic regions in
the prevaccine era [4].
One of the key issues regarding invasive GAS infection is
the risk of infection in the close contacts of index patients
and the potential value of antibiotic prophylaxis to prevent
these infections. Only 3 published prospective studies, in
Canada, the United States, and, more recently, in
Australia, have quantied the risk of infection in close con-
tacts [57]. In these 3 studies combined, there were 2129
sporadic cases, and 8 of 3542 contacts developed invasive
GAS disease. The 1-year attack rate of invasive infection
was the highest in the Australian study, intermediate in
the Canadian study, and the lowest in the US study (449,
294, and 66 cases per 100 000, respectively). Similarly,
the incidence rate of invasive disease in household contacts
within 30 days of the onset of infection in the index patient
was, respectively, 2011, 1400, and 200 times higher than
that in the general reference population [57]. The US
Centers for Disease Control and Prevention (CDC) has rec-
ommended against routine antibiotic prophylaxis for
household contacts, preferring instead a strategy of

Journal of the Pediatric Infectious Diseases Society pp. 16, 2014. DOI:10.1093/jpids/piu107
The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society.
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2 de Almeida Torres et al

maintaining a heightened index of suspicion for subse-
quent disease in the 30 days after a severe GAS infection
[8]. Although antibiotic prophylaxis is not recommended
routinely by the CDC for household contacts, the recom-
mendations do allow for healthcare providers to choose
to offer antibiotic prophylaxis to household members
who are at increased risk for sporadic invasive GAS infec-
tion. For particularly severe invasive GAS infections, the
Ontario Group A Streptococcal Study Group has recom-
mended that antibiotic prophylaxis be offered to all house-
hold contacts who were in close contact with the index
patient in the week before the onset of illness [9]. Finally,
the authors of the Australian study strongly advocated
for routine antibiotic prophylaxis for household contacts
of patients with invasive GAS infection. The downsides
and limitations of such antibiotic prophylaxis are well
known, as previously reviewed, and include the lack of
data about the efcacy of antibiotics in preventing invasive
GAS infection, false reassurance to contacts, induction of
antibiotic resistance, and impact on the patients own
ora [10, 11].
The clinical reality is that family members and other
close contacts of patients with such severe and rapidly pro-
gressive disease often strongly appeal to the treating clini-
cians for chemoprophylaxis to prevent additional cases.
There have been numerous case reports of transmission
of invasive GAS strains to family contacts, schoolmates,
residents from care homes (recently reviewed [12]), and/
or healthcare workers [1346]. It should be noted that
the majority of these studies related some use of antibiotic
prophylaxis among the contacts of patients with invasive
GAS infection, and very few of them were undertaken out-
side North America or Europe (Supplementary Table 1).
We describe here our approach based on pharyngeal cul-
ture testing of contacts and targeted antibiotic prophylaxis
after a fulminant and fatal case of GAS necrotizing fasciitis
in Paran, Brazil.
CASE REPORT
In November 2011, a previously well 7-year-old girl pre-
sented with 5 days of fever associated with pain and swell-
ing of the right leg. She arrived at the hospital with
drowsiness, tachycardia (200 beats/minute), tachypnea
(32 breaths/minute), and an unrecordable blood pressure.
A necrotic lesion of her right thigh appeared on the rst day
of admission, and soft tissue necrosis quickly progressed
toward her abdomen and knee (Figure 1). Surgical debride-
ment could not be performed because of the hemodynamic
instability of the patient. Despite empirical intravenous an-
timicrobial therapy with ceftriaxone and amikacin, intra-
venous immunoglobulin, and intensive supportive care,
the disease rapidly progressed, and the patient developed
multiorgan failure and died on the second day of admission
of necrotizing fasciitis associated with toxic shock syn-
drome. Blood cultures performed after antibiotic treatment
were negative, but emm type 1 GAS was isolated from the
wound.
MATERIALS AND METHODS
Within 24 hours of the death of the patient, we started an
information campaign, throat culture survey, and contact
evaluation to investigate the number of contacts carrying
the same bacterial strain as the index patient. A single
throat swab was taken from each contact, and GAS was de-
tected by culture. Family, school, and healthcare worker
contacts were advised to seek medical attention if symp-
toms of GAS diseases occurred (sore throat, infected
wound, fever). One hundred ve contacts, including the
family household (mother, father, and 2 brothers [4 of 4

Figure 1. Necrotizing fasciitis. Clinical pictures of the girls lesion at admission (a) and 16 hours later (b).

were included]), casual family (relatives and neighbors [11
of 11]), school contacts (classroom of the index patient [18
of 21], classroom of the index patients brother [20 of 29],
and teachers and other employees of the daycare facility
[15 of 15]), and healthcare worker contacts (hospital A, in-
cluding 4 physicians, 3 nurses, and 9 nursing assistants [16
of 16], and hospital B, including 7 physicians, 5 nurses,
and 9 nursing assistants [21 of 21]), were included after
written and oral informed consents were obtained.
Throat swabs and data from all health professionals ( phy-
sicians, nurses, nursing assistants) who had some contact
(when examining and/or medicating) or those who were
on duty in the intensive care unit, independent of contact
duration, were collected. This study was approved by the
Ethics Committee of the Department of Health of
Paran-SESA/HT (approval number CAAE-02134412.
6.0000.5225).
Throat cultures were inoculated on blood agar plates
and incubated at 37C. GAS identication, emm typing
characterization and antimicrobial susceptibility prole
to 7 antibiotics ( penicillin, erythromycin, clindamycin, tet-
racycline, chloramphenicol, vancomycin, and tigecycline)
were performed as previously described [47]. Negative
throat cultures were not repeated. The presence of 30 viru-
lence genes, including 11 superantigens (speA, speC, speG,
speH, speJ, speI, speK, speL, speM, ssa, and smeZ), 12
adhesins (cpa, cpa-1, fba, fbp-54, pfbp, prtf-1, prtf-2,
prtf-15, sciA, sciB, sfb-2, and sfb), 6 streptodornases
(speF, sda, sdn, spd1, spd3, and spd4), and a phospholi-
pase (sla), were tested by polymerase chain reaction using
primers and protocols as previously described [4850]. The
presence of the speB gene was used as the internal control,
and the sequences of the speA and sda polymerase chain
reaction products were obtained to determine the allele
of each gene.
We searched the literature in PubMed using the key words
group A streptococcus, Streptococcus pyogenes, inva- 6 children, 2 others from this class harbored different emm
sive infections, outbreak, cluster, and prevention, types (12 and 77), which are associated with different viru-
restricted to the last 20 years. We excluded studies undertak-
en in care homes and long-term facilities, because they were
recently reviewed elsewhere [12], and studies involving mil-
itary camps. We nally included 30 different studies select-
ed on the basis of whether they provided information on
the decision to prescribe antibiotic prophylaxis, the con-
tacts of patients with invasive disease, and/or data about
carriage of the index strain among these contacts.
RESULTS
The GAS isolate from the wound of the index patient was a
highly mucoid GAS emm type 1 strain susceptible to all the
Secondary Streptococcal Infection 3
Figure 2. Number of contacts whose throat swabs tested positive for the M1T1
clone.
antimicrobial agents tested. Four superantigens (speA2,
speG, speJ, and smeZ), 4 adhesins (cpa-1, fba, fbp54,
and sciaB), and 3 streptodornases (speF, spd3, and sda1)
were detected; this prole is consistent with the so-called
M1T1 GAS clone, frequently associated with invasive in-
fection worldwide [5153].
The same clone was recovered from 2 of the 4 household
contacts (Figure 2). The 29-year-old mother and the
6-year-old brother of the index patient suffered from phar-
yngitis associated with a throat culture positive for this spe-
cic emm type 1 clone. The 5-year-old brother suffered
from pharyngitis and had commenced antibiotic treatment
when the throat swab was taken (culture negative). The fa-
ther was asymptomatic, and his throat swab was negative
for GAS. The 11 other family contacts (relatives and neigh-
bors), who did not live in the same house and only had ca-
sual contact with the index patient during the 2 weeks
before disease onset, were all asymptomatic and tested neg-
ative for GAS.
The emm type 1 GAS clone was also found on throat
swabs from 6 of the 18 children aged 7 to 8 years in the
same class as the index patient (33.3%). Apart from these
lence proles (Table 1). We also analyzed the throat swabs
from 20 schoolmates in the same classroom as the index pa-
tients 6-year-old brother. Three of these 20 children were
colonized with GAS, 2 with the emm type 1 clone and 1
with an unrelated emm type 4 (Table 1). The 15 teachers
and 37 healthcare professionals all tested negative for GAS.
The 13 contacts who had a throat swab positive for GAS
received treatment with oral amoxicillin for 10 days
(50 mg/kg per day three times daily for children and
1.5 g/day three times daily for adults). Of the 92 contacts
with a negative throat swab, none received antibiotics.
Follow-up was performed for 2 months, and no additional
cases of invasive GAS disease were detected.
4 de Almeida Torres et al

DISCUSSION

speA2 speC speG speH speI speJ speK speL speM smeZ Ssa cpa cpa-1 fba fbp54 pfbp prtf1 prtf2 prtf15 sciA sciaB sfb Sfb1 spd1 spd3 spd4 sda1 sdn SpeF sleA

+
The index patient suffered from GAS necrotizing fasciitis
caused by an M1T1 clone, previously well characterized

+
+
+
+
for its virulent potential [52]. Our throat culture survey
conrmed the presence of this clone in 10 of the 105 con-

+
tacts of the index patient. We do not know whether these
Streptodornases 10 contacts who had a throat swab test positive for M1T1
GAS actually acquired this strain from the index patient.
+

+
+
They could have been carrying this strain before the
index illness. Eight of the 10 contacts who harbored the
+

+ same M1T1 GAS clone were either living in the same

house as the index patient (mother and brother) or sharing
the same classroom at school, which means that they were
exposed to the index patient for a more prolonged and in-
+
+
+
+

tense period. It is also likely that the other sibling of the

index patient had GAS pharyngitis with the M1T1 clone.
A previous study reported that contacts exposed to an
index patient for <24 hours/week rarely (1.8%) became
colonized by invasive GAS, whereas those exposed to an
+

index patient for >24 hours/week were frequently colo-

nized (27%) [19]. Higher colonization rates among chil-
Table 1. Virulence Profiles From GAS Strains Recovered From Close Contacts of the Index Patient

dren than those among adults have been observed in

other studies [5, 19]. It should be noted that none of the
+

37 healthcare workers in our study was positive for the in-

vasive GAS strain, which is possibly related to both the
+

+
+

short duration of the hospitalization and the infection con-

+

+
+

trol and prevention measures used in the hospital setting.

Adhesins

Some practices to reduce the spread of invasive GAS

+

clusters in communities have been proposed. Among

them are the establishment of surveillance systems to detect
new cases more rapidly, educational programs at the pop-
ulation level to encourage early recognition of the signs and
+

+
+ indicate the presence of the specific gene. n stands for the number of isolates.

symptoms of GAS disease, characterization of the invasive

strain and swabbing of close contacts to determine whether
the strain is carried by these contacts, and antibiotic pro-
phylaxis for contacts to reduce the risk of spreading disease
[58, 54].
+

Our particular setting is characterized by high GAS dis-

+

ease burden, high mortality rates, and poor access to med-

+

ical care outside the major cities [47]. Therefore, our

internal process after severe invasive GAS infection associ-
+

ated with toxic shock syndrome includes (1) a heightened

index of suspicion for subsequent GAS disease among
+
+
+
+
Superantigens

healthcare workers and close contacts in the 30-day period

+

after contact with the index patient, including for those

with either negative swab results or those treated by antibi-
11 +

otics; (2) an educational campaign about the early signs

1
1
1
emm type n

and symptoms of GAS disease; (3) a throat swab survey

for close contacts who have had > 24 hours/week of expo-
sure to the index patient during the 2 weeks before disease
12
77
1

4

onset (with the addition of a skin swab if skin sores are pre-
sent) [19]; and (4) chemoprophylaxis with an oral antibiot-
ic (amoxicillin) for all close contacts with a GAS-positive
culture. Note that the choice of antibiotic regimen for treat-
ing such patients was recently reviewed elsewhere [4].
Our study does not allow rm conclusions to be drawn
as to whether antibiotic prophylaxis is effective. Ours was
an isolated study undertaken in a particular epidemiologi-
cal environment, and therefore caution should be taken
when comparing these results with those from other set-
tings. Indeed, one could argue that the data presented
here support a strategy of prescribing antibiotics to con-
tacts as much as not prescribing them. Additional data
are clearly needed to better dene the correct approach
to managing the contacts of patients with severe invasive
GAS disease. The additional value of rapid GAS testing,
rather than bacterial culture, for screening close contacts
and potentially decreasing the time before the initiation
of prophylaxis should be claried. However, the focus of
our report is to highlight that, when a decision to treat
the contact is made, both our data and the evidence in
the literature suggest that antibiotic prophylaxis should
be restricted to people in very close contact ( >24 hours/
week of exposure) [19].
Supplementary Data
Supplementary materials are available at the Journal of
The Pediatric Infectious Diseases Society online (http://
jpids.oxfordjournals.org). Supplementary materials con-
sist of data provided by the author that are published to
benet the reader. The posted materials are not copyedited.
The contents of all supplementary data are the sole respon-
sibility of the authors. Questions or messages regarding
errors should be addressed to the author.
Acknowledgements
Potential conicts of interest. All authors: No reported conicts.
All authors have submitted the ICMJE Form for Disclosure
of Potential Conicts of Interest. Conicts that the editors consider
relevant to the content of the manuscript have been disclosed.
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