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Group A Streptococcal Infections

Updated: Nov 03, 2016
Author: Zartash Zafar Khan, MD, FACP; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS,
MD more...

OVERVIEW

Background
Infection with Streptococcus pyogenes, a beta-hemolytic bacterium that belongs to Lancefield
serogroup A, also known as the group A streptococci (GAS), causes a wide variety of diseases
in humans. A ubiquitous organism, S pyogenes is the most common bacterial cause of acute
pharyngitis, accounting for 15-30% of cases in children and 5-10% of cases in adults. [1] During
the winter and spring in temperate climates, up to 20% of asymptomatic school-aged children
may be group A streptococcus carriers. (See Pathophysiology, Etiology, and Epidemiology.) [2, 3]

An understanding of the diverse nature of infectious disease complications attributable to this

organism is an important cornerstone of pediatric medicine. In addition to infections of the upper
respiratory tract and the skin, S pyogenes can cause a wide variety of invasive systemic
infections. Along with Staphylococcus aureus, group A streptococcus is one of the most
common pathogens responsible for cellulitis. Infection with this pathogen is also causally linked
to 2 potentially serious nonsuppurative complications: acute rheumatic fever (ARF) and acute
glomerulonephritis. In addition, infection with S pyogenes has reemerged as an important cause
of toxic shock syndrome (TSS) and of life-threatening skin and soft-tissue infections, especially
necrotizing fasciitis (see the image below). (See Pathophysiology, Etiology, Presentation,
Workup, Treatment, and Medication.)

Invasive soft tissue infection due to Streptococcus pyogenes. This child developed fever and soft-tissue
swelling on the fifth day of a varicella-zoster infection. Leading edge aspirate of cellulitis grew S pyogenes.
Although the patient responded to intravenous penicillin and clindamycin, operative dbridement was
necessary because of clinical suspicion of early necrotizing fasciitis.

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Lancefield classification scheme

As originally described by Lancefield, beta-hemolytic streptococci can be divided into many

groups based on the antigenic differences in group-specific polysaccharides located in the
bacterial cell wall. More than 20 serologic groups have been identified and designated by letters
(eg, A, B, C). Of the nongroup A streptococci, group B is the most important human pathogen
(the most common cause of neonatal sepsis and bacteremia), although other groups
(particularly group G) have occasionally been implicated as causes of pharyngitis. (See
Pathophysiology.)

The emm classification scheme

The traditional Lancefield classification system, which is based on serotyping, has been
replaced by emm typing, which has been used to characterize and measure the genetic
diversity among isolates of S pyogenes. This system is based on a sequence at the 5' end of a
locus (emm) that is present in all isolates. The targeted region of emm displays the highest level
of sequence polymorphism known for an S pyogenes gene; more than 150 emm types have
been described to date. [4] The emm gene encodes the M protein.

There are 4 major subfamilies of emm genes, which are defined by sequence differences within
the 3' end, encoding the peptidoglycan-spanning domain. The chromosomal arrangement of
emm subfamily genes reveals 5 major emm patterns, designated as emm patterns A through E.
An example of the usefulness of emm typing is described by McGregor et al. [5]

Identification of GAS

Although serologic grouping by the Lancefield method is the criterion standard for differentiation
of pathogenic streptococcal species, group A organisms can be identified more cost effectively
by numerous latex agglutination, coagglutination, or enzyme immunoassay procedures. (See
Workup.)

Group A strains can also be distinguished from other groups by their sensitivity to bacitracin. A
disc that contains 0.04U of bacitracin inhibits the growth of more than 95% of group A strains,
whereas 80-90% of nongroup A strains are resistant to this antibiotic. The bacitracin disc test
is simple to perform and interpret in an office-based laboratory and is sufficiently accurate for
presumptive identification of GAS.

Presumptive identification of a strain as a group A streptococcus can also be made on the basis
of production of the enzyme L-pyrrolidonyl-beta-naphthylamide (PYRase). Among the
beta-hemolytic streptococci isolated from throat culture, only group A isolates produce PYRase,
which can be identified on the basis of the characteristic color change (red) after inoculation of a
disk on an agar plate followed by overnight incubation.

When cultured on blood agar plates, the production of a characteristic zone of complete
hemolysis (beta hemolysis) is another important clue to the classification of S pyogenes (see
the image below). (For example, Streptococcus pneumoniae generates a zone of only partial
hemolysis [alpha hemolysis].)

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Streptococcus group A infections. Beta hemolysis is demonstrated on blood agar media.

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Spectrum of diseases caused by group A streptococcal infections

In the preantibiotic era, streptococci frequently caused significant morbidity and were associated
with significant mortality rates. However, in the postantibiotic period, diseases due to
streptococcal infections are well-controlled and uncommonly cause death. GAS can cause a
diverse variety of suppurative diseases and nonsuppurative postinfectious sequelae. (See
Pathophysiology, Etiology, Prognosis, and Treatment.)

The suppurative spectrum of GAS diseases includes the following:

Pharyngitis - With or without tonsillopharyngeal cellulitis or abscess

Impetigo - Purulent, honey-colored, crusted skin lesions
Pneumonia
Necrotizing fasciitis
Cellulitis
Streptococcal bacteremia
Osteomyelitis
Otitis media
Sinusitis
Meningitis or brain abscess (a rare complication resulting from direct extension of an ear
or sinus infection or from hematogenous spread)

The nonsuppurative sequelae of GAS infections include the following:

ARF - Defined by Jones criteria

Rheumatic heart disease - Chronic valvular damage, predominantly the mitral valve
Acute glomerulonephritis

A superantigen-mediated immune response may result in the development of scarlet fever or

streptococcal TSS. Scarlet fever is characterized by an upper-body rash, generally following
pharyngitis.

Streptococcal TSS is characterized by systemic shock with multiorgan failure, with

manifestations that include respiratory failure, acute renal failure, hepatic failure, neurologic
symptoms, hematologic abnormalities, and skin findings, among others. This is predominantly
associated with M types 1 and 3 that produce pyrogenic exotoxin A, exotoxin B, or both. [6]

Pathophysiology

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Streptococci are a large group of gram-positive, nonmotile, nonspore-forming cocci about

0.5-1.2m in size. They often grow in pairs or chains and are negative for oxidase and catalase.

S pyogenes tends to colonize the upper respiratory tract and is highly virulent as it overcomes
the host defense system. The most common forms of S pyogenes disease include respiratory
and skin infections, with different strains usually responsible for each form.

The cell wall of S pyogenes is very complex and chemically diverse. The antigenic components
of the cell are the virulence factors. The extracellular components responsible for the disease
process include invasins and exotoxins. The outermost capsule is composed of hyaluronic acid,
which has a chemical structure resembling host connective tissue, allowing the bacterium to
escape recognition by the host as an offending agent. Thus, the bacterium escapes
phagocytosis by neutrophils or macrophages, allowing it to colonize. Lipoteichoic acid and M
proteins located on the cell membrane traverse through the cell wall and project outside the
capsule.

Epithelial cell invasion

A characteristic of S pyogenes is the organisms ability to invade epithelial cells. Failure of

penicillin to eradicate S pyogenes from the throats of patients, especially those who are carriers
of S pyogenes, has been increasingly reported. The results of one study strongly suggested that
if the carrier state results from intraepithelial cell streptococci survival, the failure of penicillin to
kill ingested S pyogenes may be related to a lack of effective penicillin entry into epithelial cells.
[7] These observations may have clinical implications for understanding carriers and managing S
pyogenes infection.

Bacterial virulence factors

The cell wall antigens include capsular polysaccharide (C-substance), peptidoglycan and
lipoteichoic acid (LTA), R and T proteins, and various surface proteins, including M protein,
fimbrial proteins, fibronectin-binding proteins (eg, protein F), and cell-bound streptokinase.

The C-substance is composed of a branched polymer of L-rhamnose and N -acetyl-

D-glucosamine. It may have a role in increased invasive capacity. The R and T proteins are
used as epidemiologic markers and have no known role in virulence. [8]

Another virulence factor, C5A peptidase, destroys the chemotactic signals by cleaving the
complement component of C5A.

M protein, the major virulence factor, is a macromolecule incorporated in fimbriae present on the
cell membrane projecting on the bacterial cell wall. It is the primary cause of antigenic shift and
antigenic drift among GAS. (See the image below.) [9, 10]

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Streptococcus group A infections. M protein.

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M protein binds the host fibrinogen and blocks the binding of complement to the underlying
peptidoglycan. This allows survival of the organism by inhibiting phagocytosis. Strains that
contain an abundance of M protein resist phagocytosis, multiply rapidly in human tissues, and
initiate the disease process. After an acute infection, type-specific antibodies develop against M
protein activity in some cases.

However, although such antibodies protect against infection by a homologous M protein type,
they confer no immunity against other M types. This observation is one of the factors
representing a major theoretical obstacle to the S pyogenes vaccine design, because more than
80 M serotypes have been described to date.

Community-based outbreaks of particular streptococcal diseases tend to be associated with

certain M types; therefore, M serotyping has been very valuable for epidemiologic studies.

Bacterial adherence factors

At least 11 different surface components of GAS have been suggested to play a role in
adhesion. In 1997, Hasty and Courtney proposed that GAS express different arrays of adhesins
in various environmental niches. Based on their review, M protein mediates adhesion to HEp-2
cells, but not to buccal cells, in humans, whereas FBP54 mediates adhesion to buccal cells, but
not to HEp-2 cells. Protein F mediates adhesion to Langerhans cells, but not to keratinocytes.

One of the theories proposed with regard to the process of adhesion is a 2-step model. The
initial step in overcoming the electrostatic repulsion of the bacteria from the host is mediated by
LTA, which provides weak, reversible adhesion. The second step takes the form of firm,
irreversible adhesion mediated by tissue-specific M protein, protein F, or FBP54, among others.
Once adherence has occurred, the streptococci resist phagocytosis, proliferate, and begin to
invade the local tissues. [11]

GAS show enormous and evolving molecular diversity, driven by horizontal transmission among
various strains. This is also true when they are compared with other streptococci. Acquisition of
prophages accounts for much of the diversity, conferring not only virulence via phage-
associated virulence factors but also increased bacterial survival against host defenses.

Extracellular products and toxins

Various extracellular growth products and toxins produced by GAS are responsible for host cell
damage and inflammatory response.

Hemolysins

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S pyogenes elaborates 2 distinct hemolysins. These proteins are responsible for the zone of
hemolysis observed on blood agar plates and are also important in the pathogenesis of tissue
damage in the infected host. Streptolysin O is toxic to a wide variety of cell types, including
myocardium, and is highly immunogenic. The determination of the antibody responses to this
protein (antistreptolysin O [ASO] titer) is often useful in the serodiagnosis of recent infection.

Streptolysin S is another virulence factor capable of damaging polymorphonuclear leukocytes

and subcellular organelles. However, in contrast to streptolysin O, it does not appear to be
immunogenic.

Pyrogenic exotoxins

The family of streptococcal pyrogenic exotoxins (SPEs) includes SPEs A, B, C, and F. These
toxins are responsible for the rash of scarlet fever. Other pathogenic effects caused by these
substances include pyrogenicity, cytotoxicity, and enhancement of susceptibility to endotoxin.
SPE B is a precursor of a cysteine protease, another determinant of virulence. [12]

Group A streptococcal isolates associated with streptococcal TSS encode certain SPEs (ie, A,
C, F) capable of functioning as superantigens. These antigens induce a marked febrile
response, induce proliferation of T lymphocytes, and induce synthesis and release of multiple
cytokines, including tumor necrosis factor, interleukin-1 beta, and interleukin-6. This activity is
attributed to the ability of the superantigen to simultaneously bind to the V-beta region of the
T-cell receptor and to class II major histocompatibility antigens of antigen-presenting
mononuclear cells, resulting in widespread, nonspecific T-cell proliferation and increased
production of interleukin-2.

Nucleases

Four antigenically distinct nucleases (A, B, C, D) assist in the liquefaction of pus and help to
generate substrate for growth.

Other products

Other extracellular products include NADase (leukotoxic), hyaluronidase (which digests host
connective tissue, hyaluronic acid, and the organism's own capsule), streptokinases
(proteolytic), and streptodornase A-D (deoxyribonuclease activity). [13]

Proteinase, amylase, and esterase are additional streptococcal virulence factors, although the
role of these proteins in pathogenesis is not fully understood.

Suppurative disease spectrum

Streptococcal pharyngitis

S pyogenes causes up to 15-30% of cases of acute pharyngitis. [14] Frank disease occurs based
on the degree of bacterial virulence after colonization of the upper respiratory tract. Accurate
diagnosis is essential for appropriate antibiotic selection.

Impetigo

Pyoderma is the most common form of skin infection caused by GAS. Also referred to as
streptococcal impetigo or impetigo contagiosa, it occurs most commonly in tropical climates but
can be highly prevalent in northern climates as well, particularly in the summer months. Risk
factors that predispose to this infection include low socioeconomic status; low level of overall

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hygiene; and local injury to skin caused by insect bites, scabies, atopic dermatitis, and minor
trauma. Colonization of unbroken skin precedes the development of pyoderma by approximately
10 days.

Streptococcal pyoderma may occur in children belonging to certain population groups and in
overcrowded institutions. The modes of transmission are direct contact, environmental
contamination, and houseflies. The strains of streptococci that cause pyoderma differ from those
that cause exudative tonsillitis.

The bacterial toxins cause proteolysis of epidermal and subepidermal layers, allowing the
bacteria to spread quickly along the skin layers and thereby cause blisters or purulent lesions.
The other common cause of impetigo is Staphylococcus aureus.

Pneumonia

Invasive GAS can cause pulmonary infection, often with rapid progression to necrotizing
pneumonia.

Necrotizing fasciitis

Necrotizing fasciitis is caused by bacterial invasion into the subcutaneous tissue, with
subsequent spread through superficial and deep fascial planes. The spread of GAS is aided by
bacterial toxins and enzymes (eg, lipase, hyaluronidase, collagenase, streptokinase),
interactions among organisms (synergistic infections), local tissue factors (eg, decreased blood
and oxygen supply), and general host factors (eg, immunocompromised state, chronic illness,
surgery).

As the infection spreads deep along the fascial planes, vascular occlusion, tissue ischemia, and
necrosis occur. [15] Although GAS is often isolated in cases of necrotizing fasciitis, this disease
state is frequently polymicrobial.

Otitis media and sinusitis

These are common suppurative complications of streptococcal tonsillopharyngitis. They are

caused by the spread of organisms via the eustachian tube (otitis media) or by direct spread to
the sinuses (sinusitis).

Nonsuppurative disease spectrum

Acute rheumatic fever

ARF is a delayed, nonsuppurative sequela of GAS tonsillopharyngitis. Following the pharyngitis,

a latent period of 2-3 weeks passes before the signs or symptoms of ARF appear. The disease
presents with various clinical manifestations, including arthritis, carditis, chorea, subcutaneous
nodules, and erythema marginatum.

Rheumatic fever may be the result of host genetic predisposition. The disease gene may be
transmitted either in an autosomal-dominant fashion or in an autosomal-recessive fashion, with
limited penetrance. However, the disease gene has not yet been identified.

Considerable evidence supports the link between group A streptococcal infections of the upper
respiratory tract and ARF, although only certain M-group serotypes (ie, 1, 3, 5, 6, 18, 24) are
associated with this complication. Very mucoid strains, particularly strains of M type 18, have
appeared in numerous communities prior to the appearance of rheumatic fever. Rheumatic

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fever is most frequently observed in children aged 5-15 years (the age group most susceptible
to GAS infections).

The attack rate following upper respiratory tract infection is approximately 3% for individuals
with untreated or inadequately treated infection. The latent period between the GAS infection
and the onset of rheumatic fever varies from 2-4 weeks. In contrast to poststreptococcal
glomerulonephritis (PSGN), which may follow either pharyngitis or streptococcal pyoderma,
rheumatic fever can occur only after an infection of the upper respiratory tract.

Despite the depth of knowledge that has been accumulated about the molecular microbiology of
Streptococcus pyogenes, the pathogenesis of ARF remains unknown. A direct effect of a
streptococcal extracellular toxin, in particular streptolysin O, may be responsible for the
pathogenesis of ARF, according to some hypotheses. Observations that streptolysin O is
cardiotoxic in animal models support this hypothesis, but linking this toxicity to the valvular
damage observed in ARF has been difficult.

A more popular hypothesis is that an abnormal host immune response to some component of
the group A Streptococcus is responsible. The M protein of GAS shares certain amino acid
sequences with some human tissues, and this has been proposed as a source of cross-
reactivity between the organism and human host that could lead to an immunopathologic
immune response. Also, antigenic similarity between the group-specific polysaccharide of S
pyogenes and glycoproteins found in human and bovine cardiac valves has been recognized,
and patients with ARF have prolonged persistence of these antibodies compared with controls
with uncomplicated pharyngitis. Other GAS antigens appear to cross-react with cardiac
sarcolemma membranes. [16]

During the course of the host's immune response to the GAS, the host's antigens may, as a
result of this molecular mimicry, be mistaken as foreign; this leads to an inflammatory cascade
with resultant tissue damage. In patients with ARF with Sydenham chorea, common antibodies
to antigens found in the S pyogenes cell membrane and the caudate nucleus of the brain are
present, further supporting the concept of an aberrant autoimmune response in the
development of ARF.

Interest in whether such autoimmune responses play a role in the pathogenesis of the
syndrome known as pediatric autoimmune neuropsychiatric disorders associated with
streptococcal infections (PANDAS) has been considerable, although further work is necessary
to establish the link between streptococcal infections and these syndromes.

Poststreptococcal glomerulonephritis

Glomerulonephritis can follow group A streptococcal infections of either the pharynx or the skin,
and incidence varies with the prevalence of so-called nephritogenic strains of group A
streptococci in the community. Type 12 is the most frequent M serotype that causes PSGN after
pharyngitis, and M type 49 is the serotype most commonly related to pyoderma-associated
nephritis. The latent period between GAS infection and the onset of glomerulonephritis varies
from 1-2 weeks.

Pathogenesis appears to be immunologically mediated. Immunoglobulins, complement

components, and antigens that react with streptococcal antisera are present in the glomerulus
early in the course of the disease, and antibodies elicited by nephritogenic streptococci are
postulated to react with renal tissue in such a way as to promote glomerular injury. In contrast to
acute rheumatic fever, recurrences of PSGN are rare. Diagnosis of PSGN is based on clinical
history, physical examination findings, and confirmatory evidence of recent streptococcal
infection.

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Toxic shock syndrome

Severe GAS infections associated with shock and organ failure have been reported with
increasing frequency, predominantly in North America and Europe.

Considerable overlap occurs between streptococcal TSS and streptococcal necrotizing fasciitis,
insofar as most cases occur in association with soft-tissue infections. However, streptococcal
TSS may also occur in association with other focal streptococcal infections, including
pharyngeal infection.

The pathogenesis of streptococcal TSS appears to be related in part to the ability of certain (ie,
A, C, F) streptococcal pyogenic exotoxins (SPEs) to function as superantigens.

Scarlet fever

When a fine, diffuse, erythematous rash is present in the setting of acute streptococcal
pharyngitis, the illness is called scarlet fever. The rash of scarlet fever is caused by the
pyrogenic exotoxins (ie, SPE A, B, C, and F). The rash highly depends on toxin expression;
preexisting humoral immunity to the specific SPE toxin prevents the clinical manifestations of
scarlet fever.

Scarlet fever has apparently become less common and less virulent than in past decades;
however, incidence is cyclic, depending on the prevalence of toxin-producing strains and the
immune status of the population. Modes of transmission, age distribution of cases, and other
epidemiologic features are similar to those for streptococcal pharyngitis.

Central nervous system diseases

The primary evidence for poststreptococcal autoimmune central nervous system (CNS) disease
is provided by studies of Sydenham chorea, the neurologic manifestation of rheumatic fever.
Reports of obsessive-compulsive disorder (OCD), tic disorders, and other neuropsychiatric
symptoms occurring in association with group A beta-hemolytic streptococcal infections suggest
that various CNS sequelae may be triggered by poststreptococcal autoimmunity. [17]

Etiology
S pyogenes is highly communicable and can cause disease in healthy people of all ages who
do not have type-specific immunity against the specific serotype responsible for infection. The
streptococcus can be present on healthy skin for at least a week before lesions appear.

S pyogenes is primarily spread through person-to-person transmission, although foodborne and

waterborne outbreaks have been documented. Neither spread of organisms by fomites nor
transmission from animals (eg, family pets) appears to play a significant role in contagion.

Respiratory droplet spread is the major route for transmission of strains associated with upper
respiratory tract infection, although skin-to-skin spread is known to occur with strains associated
with streptococcal pyoderma. Impetigo serotypes may colonize the throat.

Children with untreated acute infections spread organisms by airborne salivary droplet and
nasal discharge. The incubation period for pharyngitis is 2-5 days. Children are usually not
infectious within 24 hours after appropriate antibiotic therapy has been started, an observation
that has important implications for return to the daycare or school environment.

Individuals who are streptococcal carriers (chronic asymptomatic pharyngeal and

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nasopharyngeal colonization) are not usually at risk of spreading disease to others because of
the generally small reservoir of often-avirulent organisms.

Fingernails and the perianal region can harbor streptococci and can play a role in disseminating
impetigo.

Multiple streptococcal infections in the same family are common. Impetigo and pharyngitis are
more likely to occur among children living in crowded homes and in suboptimal hygienic
conditions.

Epidemiology
Occurrence in the United States

According to a report from the Centers for Disease Control and Prevention (CDC),
approximately 9,000-11,500 cases of invasive GAS disease (3.2-3.9 per 100,000 population)
occur each year in the United States. Streptococcal TSS and necrotizing fasciitis each
accounted for approximately 6-7% of cases. More than 10 million noninvasive GAS infections
(primarily throat and superficial skin infections) occur annually. [18, 19]

Upper respiratory tract infection is most common in the northern regions of the United States,
especially during winter and early spring. By contrast, streptococcal skin infections occur most
frequently during the summer (or year-round in warm climates), when the skin is exposed and
abrasions and insect bites are more likely to occur. Interestingly, unique strains characterized by
Erdem and colleagues appear to be predominant in Hawaii, [20] and novel emm types are
associated with invasive disease and streptococcal-related sequelae.

Evidence suggests that the frequency of severe, invasive group A streptococcal infections is
increasing and that strains of streptococci with increased pathogenic potential are appearing. An
increasing number of patients are being identified who have various soft-tissue infections that
are unusually severe and that are associated with marked systemic toxicity, bacteremia, and
shock. Factors responsible for the emergence of these more virulent strains of S pyogenes are
not clearly defined, although many of these outbreaks appear to be clonal in nature.

Acute rheumatic fever

During the 1960s and 1970s, ARF nearly disappeared in the United States, although it
continued unabated in developing countries. This decline in disease was largely attributed to
careful disease surveillance and initiation of prompt aggressive antibiotic therapy in primary care
practice. However, in 1985, several multifocal outbreaks of rheumatic fever occurred in several
parts of the United States.

In contrast with earlier outbreaks in this country, most of the patients were white, middle-class
children from rural and suburban communities who had good access to health care. This
unexplained resurgence in acute rheumatic fever underscores the point that a great deal
remains to be learned about the pathogenesis of this disease.

International occurrence

The resurgence of GAS as a cause of serious human infections in the United States, Europe,
and elsewhere in the 1980s and into the 1990s was thoroughly documented and heightened
public awareness about this organism. Disease resurgence, coupled with the lack of a licensed
GAS vaccine and ongoing concern about the acquisition of penicillin resistance, remains a

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major concern.

In Denmark, the incidence of rheumatic fever decreased from 250 cases per 100,000 population
to 100 cases per 100,000 population from 1862-1962. By 1980, the incidence ranged from
0.23-1.88 cases per 100,000 population.

The incidence of PSGN ranges from 9.5-28.5 new cases per 100,000 individuals per year.
PSGN accounted for 2.6% to 3.7% of all primary glomerulopathies from 1987-1992, but only 9
cases were reported between 1992 and 1994.

In China and Singapore, the incidence of PSGN has decreased in the past 40 years. In Chile,
the disease had virtually disappeared by 1999, while in Maracaibo, Venezuela, the incidence of
sporadic PSGN decreased from 90-110 cases per year from 1980-1985 to 15 cases per year
from 2001-2005. In Guadalajara, Mexico, the combined data from 2 hospitals showed a
reduction in cases of PSGN from 27 in 1992 to only 6 in 2003. [21]

The Strep-EURO program, which analyzed data gathered from 11 participating countries,
investigated the epidemiology of severe S pyogenes disease in Europe during the 2000s. A
crude rate of 2.46 cases per 100,000 population was reported in Finland; 2.58 per 100,000
population, in Denmark; 3.1 per 100,000 population, in Sweden; and 3.31 per 100,000
population in the United Kingdom.

In contrast, the rates reported in more central and southern countriesthe Czech Republic,
Romania, Cyprus, and Italywere substantially lower (0.3-1.5 per 100,000 population),
although this was attributed to poor microbiologic investigative methods in these countries.

The prevalence of streptococcal pyoderma is higher in regions near the tropics. Aside from this
observation, no geographic barriers to infection with this ubiquitous organism are recognized.

Race- and sex-related demographics

GAS infections are observed worldwide. Streptococcal pyoderma is a more common

complication closer to tropical regions of the world. Otherwise, no racial or ethnic
predispositions to infection with this organism are recognized.

GAS infections have no sex predilection, although rheumatic mitral stenosis is more common in
females.

Age-related demographics

GAS infections may be observed in people of any age, although the prevalence of infection is
higher in children, presumably because of the combination of multiple exposures (in school or
daycare) and little immunity. Group A streptococcal pharyngitis is particularly common in
school-aged children. Strep throat is more common in school-aged children and teens.

Disease in neonates is uncommon, probably in part because of the effect of protective,

transplacentally acquired antibody. Prevalence of pharyngeal infection is highest in children
older than 3 years. Indeed, group A streptococcal pharyngitis has been described as a hazard in
school-aged children. [22] S pyogenes also has the potential to produce outbreaks of disease in
younger children in daycare.

Rheumatic fever is most frequently observed in the age group most susceptible to group A
streptococcal infections (ie, children aged 5-15 y). The attack rate following upper respiratory
tract infection is approximately 3% in individuals with untreated or inadequately treated infection.

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ARF is commonly seen in young adults or children aged 4-9 years, while PSGN is more
common in persons older than 60 years and in children younger than 15 years.

Prognosis
Acute proliferative PSGN carries a good prognosis, as more than 95% of patients recover
spontaneously within 3-4 weeks with no long-term sequelae. With appropriate treatment,
pharyngitis and skin infections also have a good prognosis.

As reported by the CDC in April 2008, invasive GAS infections carry an overall mortality rate of
10-15%, with streptococcal TSS and necrotizing fasciitis carrying fatality rates of over 35% and
approximately 25%, respectively.

Complications
Suppurative complications from the spread of streptococci to adjacent structures were very
common in the preantibiotic era. Cervical adenitis, peritonsillar abscess, retropharyngeal
abscess, otitis media, mastoiditis, and sinusitis still occur in children in whom the primary illness
has gone unnoticed or in whom treatment of the pharyngitis has been inadequate because of
noncompliance. [23]

Acute hematogenous osteomyelitis is an important complication of streptococcal infection.

Isolated bacteremia, meningitis, and endocarditis are described but appear to be rare
manifestations of acute infection. [24]

Streptococcal TSS may cause organ system failure (including renal impairment in approximately
80% of patients, and hepatic dysfunction in 65% of patients), while necrotizing fasciitis may
result in amputation. [18]

Puerperal sepsis follows abortion or delivery when streptococci that colonize the genital tract
invade the endometrium and enter the bloodstream. Pelvic cellulitis, septic pelvic
thrombophlebitis, pelvic abscess, and septicemia can occur. Peripartum genital tract infections
with group B streptococci are relatively more common, but fatal peripartum GAS infections have
been reported. [25]

Empyema develops in 30-40% of pneumonia cases. Other complications of pneumonia include

mediastinitis, pericarditis, pneumothorax, and bronchiectasis.

The nonsuppurative complications of GAS tonsillopharyngitis include ARF, rheumatic heart

disease, and acute glomerulonephritis.

Patient Education
For patient education resources, see the Infections Center, the Women's Health Center, and the
Ear, Nose, and Throat Center, as well as Sore Throat, Toxic Shock Syndrome, and Strep
Throat.

Clinical Presentation

References

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Group A Streptococcal Infections: Background, Pathophysiology, Etiology http://emedicine.medscape.com/article/228936-overview

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Media Gallery

Invasive soft tissue infection due to Streptococcus pyogenes. This child developed fever
and soft-tissue swelling on the fifth day of a varicella-zoster infection. Leading edge
aspirate of cellulitis grew S pyogenes. Although the patient responded to intravenous
penicillin and clindamycin, operative dbridement was necessary because of clinical
suspicion of early necrotizing fasciitis.
Streptococcus group A infections. Beta hemolysis is demonstrated on blood agar media.
Streptococcus group A infections. M protein.
Streptococcus group A infections. Erysipelas is a group A streptococcal infection of skin
and subcutaneous tissue.

15 dari 19 20/12/2016 7:58

Group A Streptococcal Infections: Background, Pathophysiology, Etiology http://emedicine.medscape.com/article/228936-overview

Streptococcus group A infections. White strawberry tongue observed in streptococcal

pharyngitis. Image courtesy of J. Bashera.
Streptococcus group A infections. Streptococcal rash. Image courtesy of J. Bashera.
Group A Streptococcus on Gram stain of blood isolated from a patient who developed
toxic shock syndrome.
Streptococcus group A infections. Necrotizing fasciitis of the left hand in a patient who had
severe pain in the affected area.
Streptococcus group A infections. Patient who had had necrotizing fasciitis of the left hand
and severe pain in the affected area (from Image 8). This photo was taken at a later date,
and the wound is healing. The patient required skin grafting.
Streptococcus group A infections. Gangrenous streptococcal cellulitis in a patient with
diabetes.
Erythema secondary to group A streptococcal cellulitis.
Invasive soft tissue infection due to Streptococcus pyogenes. This child developed fever
and soft-tissue swelling on the fifth day of a varicella-zoster infection. Leading edge
aspirate of cellulitis grew S pyogenes. Although the patient responded to intravenous
penicillin and clindamycin, operative dbridement was necessary because of clinical
suspicion of early necrotizing fasciitis.
Streptococcus group A infections. Necrotizing fasciitis rapidly progresses from erythema to
bullae formation and necrosis of skin and subcutaneous tissue.

Throat swab. Video courtesy of Therese Canares, MD; Marleny Franco, MD; and
Jonathan Valente, MD (Rhode Island Hospital, Brown University).

of 14

Tables

Back to List

Contributor Information and Disclosures

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Group A Streptococcal Infections: Background, Pathophysiology, Etiology http://emedicine.medscape.com/article/228936-overview

Author

Zartash Zafar Khan, MD, FACP Infectious Disease Consultant

Zartash Zafar Khan, MD, FACP is a member of the following medical societies: American
College of Physicians, Infectious Diseases Society of America, International Society for
Infectious Diseases

Disclosure: Nothing to disclose.

Coauthor(s)

Michelle R Salvaggio, MD, FACP Assistant Professor, Department of Internal Medicine,

Section of Infectious Diseases, University of Oklahoma College of Medicine; Medical Director of
Infectious Diseases Institute, Director, Clinical Trials Unit, Director, Ryan White Programs,
Department of Medicine, University of Oklahoma Health Sciences Center; Attending Physician,
Infectious Diseases Consultation Service, Infectious Diseases Institute, OU Medical Center

Michelle R Salvaggio, MD, FACP is a member of the following medical societies: American
College of Physicians, Infectious Diseases Society of America

Disclosure: Received honoraria from Merck for speaking and teaching.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease,

Program Director of Infectious Disease Fellowship, Department of Internal Medicine, Wayne
State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies:

American College of Physicians, American Society for Microbiology, International
Immunocompromised Host Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Acknowledgements

John L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School;
Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health
Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of
Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Godfrey Harding, MD, FRCP(C) Program Director of Medical Microbiology, Professor,

Department of Medicine, Section of Infectious Diseases and Microbiology, St Boniface Hospital,
University of Manitoba, Canada

Godfrey Harding, MD, FRCP(C) is a member of the following medical societies: American
College of Physicians, American Society for Microbiology, Canadian Infectious Disease Society,
Canadian Medical Association, Infectious Diseases Society of America, and Royal College of
Physicians and Surgeons of Canada

17 dari 19 20/12/2016 7:58

Group A Streptococcal Infections: Background, Pathophysiology, Etiology http://emedicine.medscape.com/article/228936-overview

Disclosure: Nothing to disclose.

Larry I Lutwick, MD Professor of Medicine, State University of New York Downstate Medical
School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System,
Brooklyn Campus

Larry I Lutwick, MD is a member of the following medical societies: American College of

Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Jos Rafael Romero, MD Director of Pediatric Infectious Diseases Fellowship Program,

Associate Professor, Department of Pediatrics, Combined Division of Pediatric Infectious
Diseases, Creighton University/University of Nebraska Medical Center

Jos Rafael Romero, MD is a member of the following medical societies: American Academy of
Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, New
York Academy of Sciences, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Mark R Schleiss, MD American Legion Chair of Pediatrics, Professor of Pediatrics, Division

Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University
of Minnesota Medical School

Mark R Schleiss, MD is a member of the following medical societies: American Pediatric

Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and
Society for Pediatric Research

Disclosure: Nothing to disclose.

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of
Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface
General Hospital

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of
Sleep Medicine, American College of Chest Physicians, American College of Physicians-
American Society of Internal Medicine, American Thoracic Society, Canadian Medical
Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine,
Society of Critical Care Medicine, and World Medical Association

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's

Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of
Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of

Pediatrics, American Association of Immunologists, American Pediatric Society, American
Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical
Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern
Medical Association

Disclosure: Nothing to disclose.

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Group A Streptococcal Infections: Background, Pathophysiology, Etiology http://emedicine.medscape.com/article/228936-overview

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska

Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center
College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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