Streptococcal Infections

Streptococcal infections are caused by the bacteria called Streptococci, a very diverse group (genus). Many species of Streptococcus are encountered every day and do not cause any disease or problem. Some species, often under certain conditions, can cause streptococcal infections. Often these are mild, but sometimes are severe. The most common streptocococcal infection is strep throat.

Other Names

• Strep

Among the most commonly-encountered terms referring to certain types of Streptococcus are:

• Strep. pneumo or pneumococcus or S. pneumoniae
• Viridans strep or Strep. viridans
• Group A beta-hemolytic streptococcus, also called Strep pyogenes, group A strep, GABHS, or GAS
• Group B strep, also called GBS

Types

Streptococcal (strep) infections can range from a mild skin infection or a sore throat to severe, life-threatening conditions. Most people are familiar with strep throat, which along with minor skin infections like impetigo is the most common form of the disease. The CDC estimates that more than 10 million mild throat and skin infections occur every year. Most of these resolve by themselves without treatment.

Strep infections include:

• Strep Throat
• Impetigo
• Cellulitis
• Erysipelas
• Scarlet fever
• Pneumonia

They also include severe, life-threatening strep infections such as

• Sepsis (bacteria in the blood)
• Puerperal fever
• Toxic shock syndrome
• Necrotizing fasciitis (commonly called flesh-eating disease)
• Myositis
• Meningitis
• Endocarditis

Streptococcal (pneumococcal) Pneumonia

Streptococcus species are a primary cause of pneumonia, especially Group A strep like Streptococcus pneumoniae. Until 2000, S. pneumoniae infections caused 100,000-135,000 hospitalizations for pneumonia, 6 million cases of otitis media, and 60,000 cases of severe invasive disease, including 3300 cases of meningitis. After the pneumococcal conjugate vaccine was introduced in 2002, the rate of severe disease dropped to 13 cases per 100,000 in the United States.^[1] Strep-caused pneumonia is a common bacterial complication of influenza and measles.

Severe strep infections

Some Streptococcus cause more severe infections. The severity of the illness depends on both the strain or species of Streptococcus and on the health status of the patient. Patients whose immune system is weakened are more likely to be more susceptible to infections than those who are not.

Most severe strep infections are caused by Group A β-hemolytic strep. In 2006, 4,587 cases of severe group A streptococcal disease were reported to the Centers for Disease Control and Prevention (CDC).

However, group B strep in the right setting can also lead to worrisome illnesses; including:

• Sepsis or bacteremia, an infection of the bloodstream
• Pneumonia
• Meningitis, an infection of protective layering of the brain
• Necrotizing fasciitis, one of the most severe of strep infections and may occur with or without toxic shock-like syndrome)

Newborn babies are the most at risk for Group B strep infections. Newborn strep infections can lead to sepsis and meningitis. Mothers with Group B strep in their genital tract can transmit the bacteria to the baby during delivery. Infants usually present with an infection during the first week. This is early-onset disease. If the infant presents after one week, the infection is caused from other sources. To prevent these complications of neonatal sepsis and meningitis, the mothers are tested in the third trimester for Group B strep infections.

Symptoms

Depending on the specific infection, symptoms can include

• Fever
• Severe pain and swelling
• Redness at the site of a wound
• Rash over large areas of the body
• Dizziness
• Confusion

Cause

Streptocococcal infections are caused by bacteria of the genus Streptococcus. There are many kinds (or species) of Streptococcus, and they can infect both humans and animals. Recently the emergence of antibiotic resistant strep (especially multi-resistant strep) has caused a number of disease outbreaks and, in general, raised their importance.

Streptococci have several distinct characteristics. They are non-motile, meaning they cannot move on their own. They are Gram-positive (meaning they look blue under the microscope after being stained with the Gram stain. They do not, unlike some bacteria, form environmentally resistant forms called spores. They are characteristically round or oval in shape, and live in pairs or chains of varying length.

In human infections, the four most important types of strep are:

1. α-hemolytic streptococci:

a. Streptococcus pneumoniae, a single species, also known as the pneumococcus

b. Streptococcus Viridans group, a group of species that behave similarly

2. β-hemolytic streptococci:

a. Group A strep (GAS or GABHS), for the most part a single species called Streptococcus pyogenes

b. Group B strep (GBS), for the most part a single species called Streptococcus agalactiae

Pneumococcus

Streptococcus pneumoniae, or the pneumococcus, causes pneumonia, otitis media, and meningitis.

Viridans group strep

Viridans group strep is found normally in the oral cavity, upper respiratory tract, and the bowel. However, when it enters the bloodstream, those with damaged heart valves can develop endocarditis. It usually occurs after certain procedures such as dental extraction. This is why patients with heart valve problems or artificial valves are asked to let their dentists know, so they can take preventive antibiotics. Viridans strep is the most common cause of endocarditis.

Group A strep

The most commonly encountered group A Streptococcus is Streptococcus pyogenes. Often S. pyogenes and related bacteria are classified as group A beta-hemolytic streptococcus or GABHS. People may carry group A streptococci in the throat or on the skin and have no symptoms of illness.

The most common infections caused by GABHS are strep throat and impetigo, a skin infection. It can also cause cellulitis and erysipelas as well as scarlet fever. GABHS is also notorious for producing a number of complications, particularly rheumatic fever and post-streptococcal glomerulonephritis.

Group A strep (S. pyogenes) colonies showing beta-hemolysis. Source: CDC

Group A streptococci also are one cause of a serious invasive infection called necrotizing fasciitis.

Group B strep

Group B Streptococcus (GBS) are primarily in the species Streptococcus agalactiae. These can cause pneumonia, sepsis and meningitis; especially in newborns and the elderly. They can also colonize the intestines and the female reproductive tract, increasing the risk for premature rupture of membranes and transmission to the infant. The American College of Obstetricians and Gynecologists, American Academy of Pediatrics and the Centers for Disease Control recommend all pregnant women between 35 and 37 weeks gestation should be tested for GBS. Women who test positive should be given prophylactic antibiotics during labor, which will usually prevent transmission to the infant.^[2]

Diagnosis

Streptococcal infection diagnosis depends on the site of infection and the nature of the symptoms. Options include culture, the ASO titer (a type of blood test), and, for strep throat, the rapid strep test.

Treatment

If the laboratory has confirmed streptococcal infection, then the most appropriate antibiotic is usually penicillin. Most streptococci are very sensitive to penicillin. Those patients with penicillin allergy may be given erythromycin or a cephalosporin (eg. ceftriaxone), which are effective against most streptococci although some erythromycin resistance is emerging. In very severe S. pyogenes infections such as necrotising fasciitis, clindamycin may be added to penicillin as very large numbers of bacteria may overwhelm penicillin's mechanism of action.

Skin infections

It can be difficult to distinguish clinically between skin infection caused by streptococci and other bacteria such as Staphylococcus aureus. Antibiotics should therefore be chosen to cover the most likely organisms. Flucloxacillin is more appropriate than simple [penicillin]] as it treats both Streptococcus and Staphylococcus. In an age when MRSA is becoming increasingly common, it is usually a good idea for a patient to be prescribed an antibiotic that kills MRSA as well as a penicillin for strep, since it isn't always possible to tell if a skin infection is from MRSA or strep.

Streptococcal skin infections are generally treated with penicillin but low levels of resistance have recently been reported. In more serious infections ceftriaxone or vancomycin may be more appropriate.

Pneumonia

Pneumococcal disease is treated primarily with penicillin. In recent years, pneumococcal strains resistant to one or more of these commonly used antibiotics have emerged. This resistance makes treatment difficult and may result in longer hospitalizations and more expensive alternative therapy. The emergence of resistant strains places further emphasis on the need for preventing pneumococcal disease through vaccination.

Prevention

The best way to protect against respiratory streptococcal (aka pneumococcal) disease is through vaccination. There are two types of pneumococcal vaccine currently available: a polysaccharide vaccine and a conjugate vaccine. The polysaccharide vaccine is used in adults and the conjugate vaccine is used in children. The polysaccharide has been available in the United States for more than 20 years. Yet in 2000, only 53 percent of those 65 years of age and older reported ever receiving the pneumococcal vaccine.^[3]

Vaccination with pneumococcal polysaccharide vaccine is recommended for:

• Everyone two years of age and older with chronic medical conditions such as diabetes, chronic lung (except asthma), heart, kidney or liver disease, or alcoholism (see ACIP recommendations for children 24 to 59 months of age).
• Those whose immune systems have been weakened by such conditions as cancer or HIV infection.
• People without a functioning spleen and those with sickle cell disease.
• Residents of chronic care or long-term care facilities.

The polysaccharide vaccine is not recommended for infants and young children under two years of age, as this age group does not respond well to polysaccharide vaccines. Children under age two fall into the highest general risk group for invasive pneumococcal infections. Pneumococcal conjugate vaccine is recommended for all children 2 to 23 months of age. Other children at increased risk include those with sickle cell disease, HIV infection, and other immunocompromising or chronic medical conditions; these children should receive pneumococcal conjugate vaccine and pneumococcal polysaccharide vaccine. ^[2]

In adults, pneumococcal vaccination with the polysaccharide vaccine, which is reimbursable by Medicare Part B, is appropriate at any time of the year. It can be administered at the same time as the influenza vaccine. In infants aged 2 to 23 months, the conjugate vaccine has been incorporated into the childhood immunization schedule.

Pneumococcal vaccines are considered clinically effective and safe. Pneumococcal vaccination of adults with the polysaccharide vaccine has been shown to be effective in the prevention of invasive pneumococcal disease, offering protection against 23 of the most prevalent pneumococcal types. Serotypes contained in the vaccine account for nearly 90 percent of pneumococcal disease.

In infants and children, studies have shown that the conjugate vaccine reduces the incidence of invasive pneumococcal disease, pneumococcal pneumonia, and otitis media.

The vaccine may cause some local reaction or soreness around the site of the injection; however, these reactions are usually minor and subside within a few days. In children, the conjugate vaccine may cause mild fever, fussiness, and decreased appetite.

In infants and children aged 11 months or younger, three or four doses of conjugate vaccine are required, depending upon the age the first dose is given. Children 12 to 23 months of age require two doses. Healthy children 24 to 59 months of age require one dose of conjugate vaccine, and those with certain chronic diseases require two doses.

Individuals who have had a previous allergic reaction (e.g., hives, difficulty breathing) to the pneumococcal vaccine should avoid vaccination. The vaccine should also be avoided during radiation therapy or chemotherapy.

Chances of Developing Streptococcal Infections

Risk factors

Children under 2 and adults over 65 years are at increased risk for pneumococcal infection. Persons who have certain underlying medical conditions also are at increased risk for developing pneumococcal infection or experiencing severe disease and complications. Adults at increased risk include those who are generally immunocompetent but who have chronic cardiovascular diseases (e.g., congestive heart failure or cardiomyopathy), chronic pulmonary diseases (e.g., chronic obstructive pulmonary disease {COPD} or emphysema), or chronic liver diseases (e.g., cirrhosis). Diabetes mellitus often is associated with cardiovascular or renal dysfunction, which increases the risk for severe pneumococcal illness. The incidence of pneumococcal infection is increased for persons who have liver disease as a result of alcohol abuse ^[4]. Asthma has not been associated with an increased risk for pneumococcal disease, unless it occurs with chronic bronchitis, emphysema, or long-term use of systemic corticosteroids.

People without a functioning spleen (e.g., sickle cell disease) are at highest risk for Streptococcus infection, because this condition leads to reduced clearance of encapsulated bacteria from the bloodstream. Children who have sickle cell disease or have had a splenectomy are at increased risk for pneumococcal sepsis associated with high mortality. Before the widespread use of penicillin chemoprophylaxis for these patients, children with sickle cell disease were 600-fold more likely than children without this disease to develop Streptococcus meningitis ^[5]

The risk for Streptococcus infection is high for people with immunosuppressive conditions. For example:

• congenital immunodeficiency
• human immunodeficiency virus {HIV} infection
• leukemia
• lymphoma
• multiple myeloma
• Hodgkins disease
• organ or bone marrow transplantation

Also people undergoing therapy with alkylating agents, antimetabolites, or systemic corticosteroids and those with chronic renal failure or nephrotic syndrome. S. pneumoniae is the most commonly identified bacterial pathogen that causes pneumonia in people with AIDS. In children, invasive pneumococcal disease is often the first clinical manifestation of HIV infection. As many as 91% of adults who have invasive pneumococcal infection have at least one of the previously mentioned underlying medical conditions, including age greater than or equal to 65 years.^[6]

A case-control study conducted in Finland identified day care center attendance among children aged less than 2 years as a major risk factor for invasive pneumococcal disease .^[7]. Although the risk for invasive pneumococcal infection associated with day care center attendance was significantly higher (i.e., 36-fold) among children aged less than 2 years compared with those who did not attend day care, the risk among children aged greater than or equal to 2 years (the age group in which pneumococcal polysaccharide vaccine could potentially prevent disease) was not significantly different from that for those who did not attend day care. Studies conducted in the United States also have indicated that children aged less than 2 years who attend day care are at higher risk for infection than are those who do not (35). In addition, clusters of invasive pneumococcal disease have been reported among children who attend day care.^[6]

Related Problems

Complications

Untreated group A strep infections can result in rheumatic fever and post-streptococcal glomerulonephritis (PSGN).

Rheumatic fever can develop about 18 days after a bout of strep throat and causes heart disease with or without joint pain. It can be followed months later by Sydenham chorea, a disorder in which the muscles of the torso, arms, and legs move involuntarily in a dancing and jerky manner.

Post-streptococcal glomerulonephritis (PSGN) is an inflammation of the kidneys that may follow an untreated strep throat but more often comes after a strep skin infection.

Both disorders are rarely seen in the United States because of prompt and effective treatment of most cases of strep throat.

Research

Through research, health experts have learned that there are more than 120 different strains of group A streptococci bacteria, each producing its own unique proteins. Some of these proteins are responsible for specific group A streptococcal diseases.

With the support of NIAID, scientists have determined the genetic sequence, or DNA code, for five strains of the group A streptococcus bacterium.

By studying its genes, scientists can learn which proteins are responsible for virulence,”crucial information that will lead to new and improved drugs and vaccines.

NIAID supports research to develop a group A streptococcus vaccine. Several candidate vaccines are in various phases of development. While some scientists are conducting animal model studies to obtain data to pursue clinical trials in humans, other scientists are close to evaluating group A streptococcus vaccine candidates in Phase I clinical trials.

As a result of NIAID-supported research, the first group A streptococcus vaccine clinical trial in 30 years was started. The vaccine was well tolerated by patients and has led to further clinical evaluation of a similar vaccine candidate.

An effective vaccine will prevent not only strep throat and impetigo but also more serious invasive disease and post-infectious complications like rheumatic fever.

Vaccine development efforts include NIAID-supported epidemiological studies:

• To determine the extent of group A streptococcal disease
• To characterize group A streptococcal strains causing illness in the United States and developing countries

NIAID, in collaboration with the Centers for Disease Control and Prevention and the World Health Organization, has developed standard definitions and methods for surveillance of group A streptococcal diseases.This was accomplished by meetings with experts in the group A streptococcal research community that included research scientists, academic investigators, clinicians, and public health officials.

References

1. ↑ Centers for Disease Control and Prevention. Streptococcus pneumonia disease fact sheet. National Center for Immunization and Respiratory Diseases: Division of Bacterial Diseases. Available here
2. ↑ ^{2.0 2.1} Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Recomm Rep 51 (RR-11):1–22. (2002). Abstract Full Text
3. ↑ Centers for Disease Control and Prevention, Health, United States 2002. National Center for Health Statistics, CDC. available here
4. ↑ CDC . Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immunoglobulins in persons with altered immunocompetence.MMWR 1993;42(No. RR-4):1-18.Full Text
5. ↑ Mufson MA, Oley G, Hughey D. Pneumococcal disease in a medium-sized community in the United States. JAMA 1982;248:1486-9. Abstract
6. ↑ ^{6.0 6.1} Robinson KA, Baughman W, Rothrock G, et al. Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995-1998: Opportunities for prevention in the conjugate vaccine era. JAMA. Apr 4 2001;285(13):1729-35. Abstract | Full Text
7. ↑ Takala AK, Jero J, Kela E, Reenberg P-R, Koskenniemi E, Eskola J. Risk factors for primary invasive pneumococcal disease among children in Finland. JAMA 1995;273:859-64. Abstract

External Links

Group A Streptococcal Infections - National Institute of Allergy and Infectious Diseases

Medical college of Wisconsin: Strep Throat

CDC: Group A Streptococcal Disease

KidsHealth: Cellulitis

Family Practice: Cellulitis