Streptococcus pyogenes (group A streptococcus) is a gram-positive coccus that produces clear (beta) hemolysis on blood agar. This bacteriologic feature aids in the recognition and differentiation of S. pyogenes from viridans (alpha) streptococci and from nonhemolytic (gamma) streptococci. Selected strains of group A streptococci hemolyze slowly and produce a greenish hemolysis on the surface of blood agar plates, similar to that produced by viridans streptococci. These strains can be identified by their ability to produce clear hemolysis under anaerobic conditions.

Group A hemolytic streptococci can be differentiated from other hemolytic streptococci by laboratory identification of their group-specific cell wall carbohydrate. A commonly used office laboratory identification technique takes advantage of the finding that 95% of group A streptococci are unable to grow in the presence of bacitracin. Definitive identification of group A streptococci is established by the use of techniques that use group-specific antisera.

More than 60 types of group A streptococci have been identified on the basis of their serologically distinct surface proteins (i.e., M proteins). The M protein plays a role in the pathogenesis of infection caused by the group A streptococcus because it renders this organism resistant to phagocytosis.

Protruding from the surface of the group A streptococcal cell and into a hyaluronic capsule layer are hairlike fimbriae that are responsible for adhering group A streptococci to epithelial cells. These fimbriae contain lipoteichoic acid. The M protein also is associated with these fimbriae. Other surface proteins that have been identified are the T and R proteins, which bind nonspecifically to the Fc fragment of gamma globulins, and serum opacity reaction proteins. The specific function and precise location of each of these proteins on the surface of the organism have not been identified. However, evaluation of these characteristics has proven useful in the course of epidemiologic studies of streptococcal infections.

The carbohydrate substance that is responsible for group specificity is found in the cell wall. The group A carbohydrate is a polymer of rhamnose units with side chains of N-acetylglucosamine, which is responsible for its group specificity. The cell membrane lies within the cell wall and is composed primarily of lipoprotein complexes or lipid and protein. This membrane is the outer surface of the protoplasts or L-forms of streptococci, which lack cell walls and are resistant to penicillin and other cell wall–inhibiting antibiotics.

The group A streptococci release many biologically active extracellular products into surrounding media (Box 176.1). Streptolysin O (i.e., oxygen-labile hemolysin) and streptolysin S (i.e., oxygen-stable hemolysin) can injure cell membranes.
Streptolysin O is antigenic, but streptolysin S is not. Three erythrogenic or pyrogenic toxins may be elaborated. These substances, identified as A, B, or C, are similar to endotoxin in their ability to exhibit primary toxicity or a secondary toxicity that results from the acquisition of host hypersensitivity. Individual reports and local outbreaks beginning in the late 1980s of a toxic shock–like syndrome caused by streptococci are thought to be associated with the reappearance of strains making pyrogenic exotoxin A. Strains with the M protein types M₁ and M₃ also appear to be associated disproportionately with the streptococcal toxic shock syndrome, and both the M protein type and the presence of pyrogenic exotoxin A may play some role in the virulence of the strains involved.

Other extracellular products of group A streptococci include DNAases (i.e., A, B, C, D), the streptokinases, a hyaluronidase, an amylase, a proteinase, an nicotinamide adenine dinucleotidase (NADase), and an esterase. Several of these are antigenic (e.g., streptokinase, DNAase B, hyaluronidase, NADase), and measuring antibodies to these antigens has proven useful in documenting clinical infection.

Studies of patients with streptococcal pharyngitis suggest that airborne routes of spread and environmental contamination play little or no role in the spread of this form of streptococcal infection. Close contact is required for the spread of streptococcal pharyngitis; direct projection of large droplets or physical transfer of respiratory secretions containing the bacteria is necessary. The spread of group A streptococcal pharyngitis within families or in classrooms is common.

The period of greatest contagion for streptococcal pharyngitis or scarlet fever occurs during the acute stage of illness. Penicillin therapy rapidly suppresses the growth of group A streptococci and, if continued, usually eradicates the group A streptococcus from the upper respiratory tract. The patient can be considered much less contagious after 24 to 48 hours of antimicrobial therapy. If they are afebrile, children can return to school by that time with little risk of spread of the organism to close contacts.

Prolonged carriage (weeks to months) of group A streptococci may occur in the throat and has been reported in approximately 10% to 20% of school-aged children. Anal carriers of group A streptococci have been identified and have been proven to be the source of epidemic spread of the disease in hospitals. Rectal or anal carriage occurs more often than was suspected previously. Contaminated milk or food may result in outbreaks of streptococcal infection of the throat; more often, these outbreaks are caused by group C or group G streptococcus.

The production of streptococcal skin infections (i.e., pyoderma, impetigo) appears to require disruption of the cutaneous epithelium by trauma, preexisting skin disease, or insects. Group A streptococci often are found on normal skin, but they do not produce disease unless some means of access exists.

Group A streptococci are pathogenic for humans but are found infrequently in other species (Box 176.2). Streptococcal impetigo occurs with the greatest frequency in preschool children, but streptococcal pharyngitis is predominantly a disorder of school-aged children. Outbreaks of streptococcal respiratory tract infections have been observed in day-care centers. Streptococcal impetigo seems to be a recurrent disease in preschool and school-aged children.

Tonsillitis and pharyngitis caused by streptococci are particularly common in cold and temperate climates. Streptococcal impetigo and pyoderma occur with greater frequency in tropical climates. Streptococcal pharyngitis is more frequent during the winter and spring, and streptococcal impetigo generally is a disease of the summer months in temperate climates and appears with relatively equal frequency throughout the year in tropical countries.

The development of pharyngitis appears to depend on the attachment of group A streptococci to epithelial cells, which is accomplished by their fimbriae. The streptococci must compete with the other pharyngeal flora, which have the ability to interfere with colonization of group A streptococci in the throat.

Skin lipids are lethal for group A streptococci in vitro and may provide a barrier against the establishment of streptococcal infection of the skin under normal conditions. Invasion of tissues by group A streptococci is facilitated by various toxins and enzymes that attack hyaluronic acid and fibrin. The M protein is antiphagocytic and contains a substance that is cytotoxic in the presence of non–type-specific antibody. Type-specific antibody against M protein enhances phagocytosis, but usually this is not detectable until 6 to 8 weeks after the onset of infection. The primary role of type-specific antibody against M protein may be its prevention of reinfection by the same serologic type. Surface phagocytosis by monocytes and, subsequently, by polymorphonuclear leukocytes appears to be the primary mechanism for defense in the early stages of streptococcal infection.

The spread of streptococci to regional lymph nodes is common, particularly when infection occurs in the pharynx or tonsils. Bacteremia is uncommon in older children and adults, but it occurs more frequently in infants with streptococcal disease.

The rash of scarlet fever has been attributed to the elaboration of erythrogenic toxin. Streptococcal toxic shock syndrome may result from a direct influence of the pyrogenic exotoxins or the M protein acting as a “superantigen” to cause polyclonal stimulation of T cells that mediate the production of a variety of lymphokines (e.g., tumor necrosis factor-beta, interleukin-2, and interferon-gamma).

Streptococcal pharyngitis and tonsillitis are relatively brief illnesses, with incubation periods of several hours to 3 or 4 days. The infection varies in severity, from subclinical (i.e., no symptoms) to relatively extreme toxicity characterized by nausea, vomiting, high fever, and hypotension. The onset is acute and may be characterized by pharyngitis, headache, fever, and abdominal pain, particularly in children. The tonsils and pharynx may appear inflamed and are covered by an exudate in 50% to 80% of patients. The exudate usually appears by the second day of the disease, is characteristically whitish to yellow, and may become confluent. Swollen and tender anterior cervical lymphadenopathy affects 30% to 60% of the patients. Clinical manifestations of the disease subside in 3 to 5 days unless complications such as sinusitis or parapharyngeal, peritonsillar, or retropharyngeal abscess develop. Nonsuppurative complications such as acute nephritis (see Chapter 325) may be seen 10 days and rheumatic fever (see Chapter 285) an average of 18 days after the onset of group A streptococcal pharyngitis.

A form of streptococcal infection known as streptococcal fever or streptococcosis may occur in infants. This illness is characterized by a chronic low-grade fever, generalized lymphadenopathy, persistent mucoserous nasal discharge, and little evidence of localized pharyngeal inflammation.

Scarlet fever is unusual in infancy, possibly because of the transplacental transfer of maternal antibody to erythrogenic toxins. Apparently, hypersensitivity to these exotoxins must occur before a person can develop scarlet fever as a manifestation of streptococcal disease. The frequency of scarlet fever after infancy has increased since the late 1980s. It usually presents with fever, nausea, vomiting, and the appearance of the typical rash. Abdominal pain and vomiting may precede the development of the rash by 12 to 48 hours. Although sore throat usually is present, it may not be as troublesome as in patients with pharyngitis alone. The erythematous maculopapular rash usually begins on the trunk and spreads to cover the entire body within hours to days. The rash has the texture of sandpaper. The forehead and cheeks are flushed, and the area around the mouth is pallid (i.e., circumoral pallor). The rash generally fades on pressure and ultimately desquamates. Deep red, nonblanching, or petechial lesions may be seen in the folds of the joints (i.e., Pastia lines) or in other parts of the extremities. Early in the course of illness, the dorsum of the tongue has a white coat, through which edematous and red papillae project (i.e., white strawberry tongue). Several days later, the white covering desquamates, and the tongue becomes swollen, red, and mottled (i.e., red strawberry tongue).

A scarlatiniform rash may appear in patients with streptococcal wound infections or impetigo. An enanthema is characterized by bright red or hemorrhagic spots that appear on the interior pillars of the tonsil fossae and the soft palate. The cervical nodes are enlarged and tender, but the pharyngeal signs usually are minimal. The rash may desquamate over 7 to 21 days. Eosinophilia is common during the recovery phases from scarlet fever; the number of eosinophils may reach 30% of the differential leukocyte count in this disorder.

Streptococcal impetigo may develop up to several weeks after a strain of group A streptococci is detected on normal skin. The patient usually is afebrile, and the lesion is painless. The lesion appears initially as a superficial vesicle with little surrounding erythema and progresses to a pustule that becomes thick and yellow. The pustule may last for days to a week. A secondary staphylococcal infection occurs commonly in the pustular and subsequently crusted forms of this disease. Removal of the crust, which is a part of local therapy, reveals a moist or purulent undersurface early during the course of the disease. On healing, depigmentation may occur, but permanent scarring is uncommon because the infection does not involve the dermis.

Acute poststreptococcal nephritis (see Chapter 325) can follow impetigo or other forms of streptococcal skin infection or streptococcal pharyngitis. This disorder is produced by specific nephritogenic strains of streptococci. Rheumatic fever (see Chapter 285) has not been associated with streptococcal skin infections. The latent period for acute nephritis is longer after skin infection (average, 3 weeks) than after throat infection (average, 10 days). The serologic streptococcal types associated with nephritis after skin infection usually are different from those that produce nephritis after throat infection.