Nature of Causative Organism
Streptococcus pyogenes, a group A streptococci, is a gram-positive, non-spore forming bacteria that can be seen as oval cocci chain forming shapes less than 2 micrometers in diameter under the microscope. It is a facultative anaerobe that can use fermentation for its metabolism. It needs a blood containing medium to grow and exhibits beta-hemolysis. It is a non-motile, nonspore forming bacterium. S. pyogenes has a number of virulence factors that work in its favor including a hyaluronic acid capsule. Hyaluronic acid is the ground substance in connective tissue so having a capsule made of this tissue cement gives it a good disguise that helps prevent phagocytosis. The M protein on its cell also helps prevent phagocytosis by deactivating a C3 convertase enzyme. Although, plasma B cells can still generate antibodies against the M protein to opsonize the cell and allow the macrophages and neutrophils to digest the bacteria.
Attachment to a human host is of primary importance to a bacterium. Protein F is a fibronectinbinding protein that helps it adhere to host epithelial cells. Lipoteichoic acid also helps bind to fibronectin. M protein positions the lipoteichoic acid so that the lipid moiety on the cell surface can bind effectively to the fibronectin on the epithelial cells. Once bound to the host, S. pyogenes has enzymes that go to work breaking down the tissues. Streptokinase binds and activates human plasminogen which breaks down blood plasma proteins including fibrin clots.
Streptodornase prevents the bacterium from being swallowed up in the neutrophil extracellular traps by digesting the DNA web and the neutrophil serine proteases that can kill the bacteria. The neutrophil extracellular traps work to bind pathogens and secrete antimicrobials that kill them and then engulf the microbes. Hyaluronidase enzymes catalyze, through hydrolysis, the connective tissue in the extracellular matrix making it less viscous and increasing permeability.
S. pyogenes employs streptolysin O in beta-hemolysis. Streptolysin is an oxygen changing toxin that binds to cholesterol on the membrane of a cell and makes circular arc damage that is large enough for molecules 15 nm in size to pass through. The fever inducing erythrogenic toxin causes T cells to rapidly increase and produces the scarlet fever rash. Lastly in its arsenal of toxicants is stretococcal erythrogenic toxin B. This noxious substance activates interleukin 1 beta causing an inflammatory response, deteriorates glycoproteins in the extra cellular matrix by triggering human vitronectin, cleaves fibronectin, induces apoptosis, and releases active kinins that cause vasodilation and contraction of smooth muscle.
The earliest mention of Streptococcus pyogenes, may be in the writings of Hippocrates around 400 BCE. He describes a patient with sore throat and skin ulcers. A 1553 medical book by Giovanni Filippo Ingrassia, De tumoribus praeter Naturam, describes the scarlet fever rash as rossalia or rosania. A book published in Paris in 1578 gives a clear description of scarlet fever, by Joannes Coyttarus entitled, De febre purpura epidemiale et contagiosa libri duo (Rolleston, 1928). Streptococci were demonstrated in cases of erysipelas and wound infections by Billroth in 1874 and in the blood of a patient with puerperal sepsis by Pasteur in 1879.
Fehleisen, in 1883, isolated chain-forming organisms in pure culture from erysipelas lesions and then demonstrated that these organisms could induce typical erysipelas in humans. Rosenbach applied the designation (Mandell, 1990). In 1928, Rebecca Lancefield studied the cell wall of S. pyogenes. She serologically isolated eighteen group-specific antigens now called Lancefield groups in 1946 (Todar, 2012). In past centuries, this bacterium was the cause of many deaths. Notably from puerperal fever after childbirth. Poor hygeine and contaminated delivery methods caused genital tract sepsis and usually affected women in the first 3 days after childbirth. Prior to antibiotics, scarlet fever was a prevalent complication of streptococcal infections. Today streptococcal pharyngitis is the most common infection but is cleared with antibiotic drugs. Infections of the integumentary system are impetigo which only involves the most superficial layers of the skin and cellulitis, infecting deeper layers of skin.
More severe forms of infections present themselves when the bacteria gets into blood or organs as necrotizing fasciitis, pneumonia, bacteremia, and toxic shock syndrome. If left untreated, acute rheumatic fever and poststreptococcal glomerulonephritis can develop. Streptococcus pyogenes is host specific to humans. A group of scientists at the College of Veterinary Medicine at Cornell University tracked the evolution of S. pyongenes by looking at sister species from the pyogenic group.
They were able to identify through reconciliation analysis 113 genes that were gained on the lineage leading to S. pyogenes and almost half (46%) of these gained genes were phage associated and 14 showed significant matches to experimentally verified bacteria virulence factors. Subsequent to the origin of S. pyogenes, over half of the phage associated genes were involved in 90 different lateral gene transfer events, mostly involving different strains of S. pyogenes, but with a high proportion involving the horse specific pathogen S. equi subsp. equi, with the directionality almost exclusively (86%) in the S. pyogenes to S. equi direction (Lefebure, 2012).
Lefebure and his associates concluded that S. pyogenes adapted to a human host primarily through virulence factors and by building new regulation networks. By studying the history of S. pyogenes genomic features, they hope to be able to develop better medical strategies for dealing with infection by this bacterium.
Current Clinical Picture
Streptococcus pyogenes is one of the most widespread pathogens for humans. There are estimations that about 15-20% of school age children are carriers of S. pyogenes in their respiratory tract (Masci, 1995). The burden of invasive GAS diseases is unexpectedly high, with at least 663 000 new cases and 163 000 deaths each year worldwide (Carapetis, 2005). Group A is more prevalent in countries with limited resources. An unexplained resurgence of group A streptococcal infections has been observed since the mid-1980s. The first indication that infections due to S. pyogenes were on the rise was an outbreak of rheumatic fever which affected approximately 200 children during a 5-year period. From the mid-1980s to the 1990s, eight rheumatic fever outbreaks were documented in the United States, with the largest in Salt Lake City, Utah. Outbreaks were reported in Pennsylvania, Ohio, Tennessee, and West Virginia and at the Naval Training Center in San Diego, Calif. A decline in rheumatic fever with a milder disease pattern had been observed in the previous decade (Cunningham, 2000).
Streptococcus pyogenes can present itself in a number of different ways. As a pharyngeal infection, there exists a swelling and irritation of the throat, cervical lymph nodes are swollen, and fever and/or white patches on the tonsils may or may not accompany these symptoms. Scarlet fever occurs as a result of a pharyngitis and is evidenced by purple or red spots that are caused by breakage in blood vessels and are especially prevalent in the creases of the neck and elbows as well as the chest. The rash has a rough texture. Muscle aches, pain in the abdomen and a swollen red tongue are also symptoms of scarlet fever. Inflammation in the joints and heart valve damage can be caused by rheumatic fever. Inflammation of the kidneys and impaired kidney function are caused by glomerulonephritis.
Necrotizing fasciitis deemed the flesh-eating bacteria is not really from the bacteria eating the flesh but rather from virulence toxins breaking down the tissue. Signs of necrotizing fasciitis are inflammation, fever, and tachycardia. The disease progresses rapidly with tissue becoming swollen, discolored, and blistered often within hours. Mortality rates are very high if not treated expeditiously. Cellulitis is an infection of the superficial layers of the skin and results in an area that is hot, red, and painful with red streaks running up the infected appendage. Toxic shock syndrome caused by S. pyogenes occurs in people with pre-existing skin infections and presents itself with extreme pain in the infected area followed by a high fever, low blood pressure, a feeling of malaise and confusion which can develop into stupor, coma, and organ failure.
Risk factors that enhance transmission of the disease involve host and environmental issues. Most streptococcal infections are introduced to a household by a child. As stated earlier, 15-20% of children are carriers alone. Individuals that have a compromised immune system due to cancer, diabetes, HIV, or cardiac disease are much more prone to infection. Since S. pyogenes is so pervasive and there is no vaccine methods for controlling it are limited. Skin infections can be avoided by taking proper hygiene measure
s. Infected individuals should start antibiotics as soon as possible and finish the entire course. People with skin infections or infectious wounds should not work in are engage in food preparation in kitchens or restaurants. This bacteria is susceptible to 1% sodium hypochlorite, 4% formaldehyde, 2% glutaraldehyde, 70% ethanol, 70% propanol, 2% peracetic acid, 3-6% hydrogen peroxide and 0,16% iodine (Wright, 1983). Streptococcus pyogenes can live on a dry surface for 3 days to 6 months (Kramer, 2006).
Diagnosis and Treatment
Diagnosis of infection can be established with a swab taken and sent for laboratory testing. A Gram stain can be done to show Gram positive cocci in strands. The bacterium can be cultured on blood agar to show beta-hemolytic capabilities. A bacitracin antibiotic disc can show a zone of inhibition to the antibiotic. Serological identification of the organism involves testing for the presence of group A specific polysaccharide in the bacterium’s cell wall using the Phadebact test (Burdash, 1982). Group A strains are sensitive to bactitracin, whereas non-group A strains are more resistant to this antibiotic. Treatment for S. pyogenes is provided by a 10 day dose of penicillin. If the patient has an allergy to penicillin; erythromycin, clarithromycin, and azithromycin can be used.
Due to the pervasiveness of Streptococcus pyogenes, there is much research in pursuit of a vaccine but none are available yet. Advances in molecular biology, including the cloning and sequencing of the genomes of several prevalent GAS serotypes and genotypes, have shed new light on the pathogenesis of GAS infections and have identified a number of virulence factors as potential vaccine targets (Bisno, 2005). Although S. pyogenes remains susceptible to penicillin, much time and money are spent each year treating infections and rheumatic heart-disease requires costly cardiac surgeries. The need for a vaccination is of great importance to decrease the morbidity and mortality of this bacterium.
Bisno, A. L., Rubin, F. A., Cleary, P. P., & Dale, J. B. (2005). Prospects for a Group A Streptococcal Vaccine: Rationale, Feasibility, and Obstacles–Report of a National Institute of Allergy and Infectious Diseases Workshop. Clinical Infectious Diseases, 41(8), 1150-1156. doi: 10.1086/444505
Burdash, N. M., & West, M. E. (1982). Identification of Streptococcus pneumoniae by the Phadebact coagglutination test. Journal of Clinical Microbiology, 15(3), 391-394. Retrieved March 16, 2014, from www.ncbi.nlm.nih.gov/pmc/articles/PMC272105/. Carapetis, J. R., Steer, A. C., Mulholland, E. K., & Weber, M. (2005). The global burden of group A streptococcal diseases. The Lancet Infectious Diseases, 5(11), 685-694. doi: 10.1016/S1473-3099(05)70267-X
Cunningham, M. W. (2000, July 01). Pathogenesis of Group A Streptococcal Infections. Clinical Microbiology Reviews, 13(3), 470-511. doi: 10.1128/CMR.13.3.470-511.2000 Kramer, A., Schwebke, I., & Kampf, G. (2006, August 16). How long do nosocomial pathogens persist on inanimate surfaces. Retrieved March 17, 2014, from http:// www.ncbi.nlm.nih.gov/pmc/articles/PMC1564025/#!po=22.9167
Lefebure, T., Richards, V. P., Lang, P., Pavinski-Bitar, P., & Stanhope, M. J. (n.d.). Gene Repertoire Evolution of Streptococcus pyogenes Inferred from Phylogenomic Analysis with Streptococcus canis and Streptococcus dysgalactiae. doi: 10.1371/journal.pone. 0037607
Mandell, G. L., Douglas, R. G., & Bennett, J. E. (1990). Principles and practice of infectious diseases (7th ed., Vol. 2). New York: Churchill Livingstone. Masci, J. R. (1995). Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 6th Edition:Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 6th Edition (G. L. Mandell, J. E. Bennett, & R. Dolin, Eds.). Clinical Infectious Diseases, 2(2), 1786-1799. doi: 10.1086/431218
Rolleston, J. D. (1928, November 24). The history of scarlet fever. Retrieved March 17, 2014, from http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles
Todar, K., PhD. (2012). Streptococcus pyogenes and Streptococcal Disease. Retrieved March 5, 2014, from www.textbookofbacteriology.net
Wright, A. E. (1983). Laboratory-acquired infections: By C. H. Collins. 1983. The Butterworth Group, Sevenoaks, Kent. Pp. xi and 277. 21.00. Journal of Medical Microbiology, 16(4), 504-504. doi: 10.1099/00222615-16-4-504