Most streptococci that contain cell wall antigens of the Lancefield group A (Table 17-1) are known as Streptococcus pyogenes. Members of this species are almost always beta-hemolytic streptococci. S. pyogenes is the most common causative agent of pharyngitis and its resultant disorder, scarlet fever, and the skin infection, impetigo. The most common type of bacteria causing necrotizing fasciitis is S. pyogenes.

Table 17-1

Lancefield Streptococcus Classifications ^∗

Lancefield Group	Examples of Bacterial Species in the Group	Comments
A	Streptococcus pyogenes	Strains most pathogenic for human beings can cause strep throat, rheumatic fever, scarlet fever, acute glomerulonephritis, and necrotizing fasciitis.
B	Streptococcus mastitis Streptococcus agalactiae	Strains from mastitis in cows and from normal milk, including strains from the human throat and vagina Can cause pneumonia and meningitis in neonates and older adults, with occasional systemic bacteremia
C	Streptococcus equii Streptococcus dysgalactiae	Strains from various lower animals, including cattle, and from the human throat Can cause pharyngitis and other pyogenic infections similar to group A streptococci
D	Streptococcus faecalis (now Enterococcus faecalis) Other nonenterococcal group D strains include Streptococcus bovis and Streptococcus equinus.	Strains from cheese and humans Many former group D streptococci have been reclassified and placed in the genus Enterococcus.
E		Strains from certified milk
F	Streptococcus anginosus (Lancefield classification) or Streptococcus milleri group (European system)	Strains mainly from the human throat, associated with tonsillitis; minute hemolytic
G	Streptococcus canis is an example of a GBS Group B streptococcus (GBS) which is typically found in animals, but does not cause infection except in newborns at birth	Strains can cause infection in human beings (a few strains from monkeys and dogs). Note: This is not exclusively beta-hemolytic.
H, K, O		Nonpathogenic strains occasionally from normal human respiratory tracts

^∗This is a serologic classification of hemolytic streptococci, dividing them into groups based on antigenic serocharacteristics. It is based on precipitation tests depending on group-specific carbohydrate substances.

In terms of human morbidity and mortality worldwide, however, the role of S. pyogenes in the subsequent development of complications such as acute rheumatic fever and poststreptococcal glomerulonephritis is more important. Other S. pyogenes–associated infections include otitis media in children, sinusitis in adults, and osteomyelitis, septic arthritis, neonatal septicemia, and rare cases of pneumonia.

Necrotizing fasciitis is a rare infection that can destroy skin and soft tissues, including fat and the tissue-covering muscles (fascia). Because these tissues die rapidly, a person with necrotizing fasciitis is sometimes said to be infected with so-called flesh-eating bacteria. A highly invasive group A streptococcal infection is associated with toxic shock syndrome.

Morphologic Characteristics

S. pyogenes is a gram-positive coccus and the serotype most frequently associated with human infection. Lancefield divided these beta-hemolytic streptococci into serogroups A through O on the basis of the immunologic action of the cell wall carbohydrate (Fig. 17-1).

Figure 17-1 *S. pyogenes* contains many antigenic structural components and produces several antigenic enzymes, each of which may elicit a specific antibody response from the infected host. (Adapted from Forbes BA, Sahm DF, Weissfeld AS: Bailey and Scott’s diagnostic microbiology, ed 12, St Louis, 2007, Mosby.)

Structures called fimbriae arise near the plasma membrane and project through the cell wall and capsule. These processes contain important surface components of the streptococcus. Lipoteichoic acid on the fimbriae is important in the organism’s adherence to human epithelium and the initiation of infection. The M and R antigens, which are structurally similar but immunologically distinct, are also found on the fimbriae. R antigen has no known biological role.

M protein, a cell protein found in association with the hyaluronic capsule, is a major virulence factor of S. pyogenes. Strains of S. pyogenes that lack M protein cannot cause infection. M protein inhibits phagocytosis and antibody synthesized against M protein provides type-specific immunity to group A streptococci. In addition, M protein is the basis for a subclassification of group A streptococci into more than 60 M serotypes.

Extracellular Products

Extracellular products are important in the pathogenesis of disease and in the serologic diagnosis of streptococcal disease. Antibodies produced in response to these substances provide evidence of recent streptococcal infection. Two hemolysins, with the ability to damage human and animal erythrocytes, polymorphonuclear leukocytes (PMNs), and platelets, are produced by most group A strains, as follows:

• Streptolysin O (SLO), an oxygen-labile enzyme, binds to sterols in the red blood cell (RBC) membrane, causing stearic rearrangement. This rearrangement produces submicroscopic holes in the RBC membrane and hemoglobin diffuses from the cells. SLO is antigenic; the antibody response to it is the most frequently used serologic indicator of recent streptococcal infection.

• Streptolysin S, an oxygen-stable enzyme, is responsible for the beta (clear-appearing) hemolysis on the surface of a blood agar culture plate. Streptolysin S disrupts the selective permeability of the RBC membrane, causing osmotic lysis. It is not antigenic.

• Other substances produced by group A streptococci presumably facilitate rapid spread through subcutaneous or deeper soft tissues and include the following:

• Hyaluronidase, also called spreading factor, breaks down hyaluronic acid found in the host’s connective tissue.

• Four immunologically distinct deoxyribonucleases (DNases A, B, C, and D) degrade deoxyribonucleic acid (DNA).

• Streptokinase, an enzyme, dissolves clots by converting plasminogen to plasmin.

• Other extracellular products that can elicit an antibody response include NADase, proteinase, esterase, and amylase.

• Erythrogenic toxin is elaborated by scarlet fever–associated strains and is responsible for the characteristic rash.

Epidemiology

S. pyogenes is one of the most common and ubiquitous of human pathogens. It is found in the human respiratory tract and is always considered a potential pathogen. Upper respiratory infections caused by S. pyogenes occur most frequently in school-age children and are uncommon in children younger than 3 years. No gender or race predilection has been described.

Infection is spread by contact with large droplets produced in the upper respiratory tract. Although not as common, foodborne and milkborne epidemics do occur. Crowding enhances the spread of microorganisms.

A number of individuals, particularly school-age children, carry S. pyogenes without signs of illness. Carriers have positive cultures without serologic evidence of infection. If a person carries the organisms in the pharynx for prolonged periods after untreated infection, the number of organisms carried and their ability to produce M protein decline during carriage. This results in a progressive decline in the likelihood of spreading infection to others.

The incidence of a major complication of S. pyogenes, rheumatic fever, has decreased in the United States. It occurs primarily in the rural South and in areas of crowding and lower socioeconomic status. The incidence of rheumatic fever is 2% to 3% in epidemics and 0.1% to 1% after sporadic cases of streptococcal infection. The probability of developing rheumatic fever is age related, with younger patients more likely to develop carditis than older persons.

Rheumatic fever and resultant valvular heart disease, however, are syndromes of major importance among children in developing nations. Patients with a history of rheumatic heart disease resulting from rheumatic fever are at a significantly increased risk of developing cardiac malfunction and endocarditis later. The risk of recurrent rheumatic fever depends on factors such as the age of the patient at previous recurrences, length of time since the last recurrence, and presence of carditis. In addition, patients who develop streptococcal glomerulonephritis are at risk of later development of renal failure.

Signs and Symptoms

S. pyogenes causes a wide variety of infections, most often acute pharyngitis (strep throat) and upper respiratory infection, as well as impetigo (pyoderma). Other manifestations of infection with S. pyogenes include sinusitis, otitis, peritonsillar and retropharyngeal abscess, pneumonia, scarlet fever, erysipelas, cellulitis, puerperal sepsis, and gangrene. A concern still exists that group A streptococcus may be acquiring greater virulence.

Upper Respiratory Infection

The clinical manifestations of S. pyogenes–associated upper respiratory infection are age dependent. In an infant or young child, the infection is characterized by an insidious onset of rhinorrhea, coughing, fever, vomiting, and anorexia. Cervical adenopathy may also be present. Rhinorrhea is sometimes purulent. This syndrome is called streptococcosis.

The classic syndrome of streptococcal pharyngitis is seen in children older than 3 years. It begins with a sudden onset of sore throat and fever, which rapidly progress in severity. Pharyngeal erythema with purulent tonsillar exudate and petechiae may be observed on the palate, posterior pharynx, and tonsils. Younger children may have abdominal pain, nausea, and vomiting. Most patients, however, do not manifest the classic syndrome. It is more common for a child with S. pyogenes pharyngitis to have a fever, mild sore throat, and pharyngeal erythema without exudate.

Viral pharyngitis can produce many of the same symptoms and cannot be reliably differentiated from streptococcal pharyngitis on the basis of clinical examination alone.

Impetigo and Cellulitis

Impetigo is a skin infection that begins as a papule (Fig. 17-2). The lesion may itch and will eventually crust over and heal. Cellulitis caused by subcutaneous infection with group A streptococci is associated with a warm, red, tender area that may be mildly swollen. Erysipelas, a distinct cellulitis syndrome, usually involves the face and may be associated with pharyngitis. This syndrome is characterized by toxicity and a high fever. If left untreated, erysipelas can be fatal.