Pathology and Treatments of Streptococcal Pharyngitis

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Pathology and Treatments of Streptococcal Pharyngitis

A: Causative Agent

Streptococcal pharyngitis is the inflammation of the pharynx and presentation of white pus spots on the throat caused by the bacterium streptococcus pyogenes. Streptococcus pyogenes is a gram-positive cocci shaped bacterium that arranges in chains. Gram-positive cocci contain a thick peptidoglycan wall that encloses the inner plasma membrane and sits between the membrane and capsule.

Unlike gram-negative bacteria, gram-positive bacteria do not contain more than one cell membrane. Streptococcus pyogenes are facultative anaerobes, which allows the bacteria to grow in anaerobic conditions. Facultative anaerobes are able to use oxygen when present to grow rapidly, which explains how S. pyogenes grows so effectively in the throat where oxygen is readily available.

B: History

 The organism Streptococci was first founded in 1874 by Theodor Billroth. He discovered this organism through cases of wound infections and erysipelas. Louis Pasteur was the first to introduce this organism into history in 1879 through his discovery of isolating the microorganisms from the uterus and blood of women with puerperal fever.

Friedrich Rosenbach received credit for naming the organism Streptococcus Pyogenes in 1884. One of the treatments called Penicillin was not established to be an effective treatment until 1940. In 1928 Alexander Fleming was the first person to be credited with the discovery of Penicillin through his founding of Penicillium fungus.

However, Penicillin was not actually isolated to where it could be used as an effective treatment for diseases until 1939 by Howard Florey and Ernst Chain. Throughout decades this treatment continues to be the best option to treat streptococcal pharyngitis. With newer advances in technology led to more knowledge of the disease and the best treatment options to cure this disease.

C: Epidemiology

 Streptococcal pharyngitis is prevalent worldwide. Although, there are more cases of strep throat found in low income regions. There are thousands of people worldwide who are currently infected with strep throat. Colder temperatures can tend to influence the outbreak of the disease.

This is why strep throat is a very common disease to be infected with during this time of year. Based on the CDC there are 11,000 to 13,000 cases of streptococcal pharyngitis that arise every year in the United States alone (Centers for Disease Control and Prevention 2018). Each year 20-30% of strep throat cases are found in children and 5-15% of cases are found in adults (Centers for Disease Control and Prevention 2018).

There are more than 18 million cases of streptococcal pharyngitis found worldwide each year (World Health Organization 2009). According to the CDC the mortality rate for strep throat is approximately 1,100 to 1,600 people die each year in the U.S. (Centers for Disease Control and Prevention 2018). Globally the mortality rate is approximately 500,000 people die each year (World Health Organization 2009).

This disease is transmitted through direct contact with an infected person’s saliva or nasal fluids. These fluids are transmitted through airborne droplets by the infected person sneezing or coughing. It can also be transmitted by an infected person touching an item that will be touched by several people such as a doorknob.

A person will then be able to pick up the disease by touching the doorknob and transmitting it to either there mouth, nose, or eyes. Strep throat tends to spread more rapidly in crowded areas such as schools, dorms, daycare centers, military training facilities, and workplaces. Humans are the main reservoir of the disease. Asymptomatic Group A Streptococcus carriers are another reservoir of this disease. Children are most commonly infected with the disease.

D. Pathology

Streptococcus pyogenes can affect multiple systems, although in the case of pharyngitis S. pyogenes invades the epithelial cells of the pharynx and tonsils causing inflammation. Due to the body fighting off the infection, the tonsils and surrounding lymph nodes become swollen and white pus spots appear on the tonsils, back of the throat, and tongue. The accumulation of pus in the throat can cause a foul-smell to patients’ breath signaling there is an infection.

S. Pyogenes contains many virulence factors to aid in their invasion including: M proteins, exotoxins, hydrolytic enzymes, and a capsule around the cell wall. M proteins embedded in the cell wall aid the pathogen in adhering to host cells upon entry. Along with the M proteins, a hyaluronic capsule surrounds the microbe which also aids in adherence and prevents phagocytosis from the immune system.

The capsule appears sticky causing incoming macrophages be unable to properly engulf the bacteria. The major cause of damage occurs from enzymes and exotoxins released from the pathogen. Streptococcus pyogenes releases an exotoxin that degrades surrounding tissue and causes an excess release of cytokines from surrounding T cells. This excess of cytokines, or a superantigen, causes an increase in inflammation around the infected area. Hydrolytic enzymes are another mechanism that S. pyogenes uses to damage host cells.

These enzymes include C5a peptidase, streptolysin, and streptokinase. C5a peptidase is an enzyme that blocks the immune system’s complement cascade by cleaving C5 rendering it useless. Streptolysins O & S cause surrounding host cells and red blood cells to lyse and kill phagocytes. Lastly, the enzyme streptokinase is used to lyse blood clots which aid in the spread of bacteria to other tissue in the host.

When a host is infected with streptococcus pyogenes, the host will not exhibit symptoms for 2-5 days while the pathogen incubates. After 2 or so days, the rapid onset of a sore throat, swollen lymph nodes, fever, and malaise will set in. Vomiting in young children is common, although not as common in adults.

When showing signs of the infection, the patient should consult a doctor to start treatment and take proper precautions to prevent transmission to others. If the infection is treated, symptoms will resolve within 7-10 days. Although if left untreated, S. pyogenes can cause two major immune-mediated sequelae.

A sequelae is a condition that presents after a previous disease has subsided. Streptococcal pharyngitis, if untreated, can lead to acute rheumatic fever and scarlet fever. Acute rheumatic fever appears within 2-4 weeks after the initial sore throat and is caused by a cross-reaction between the pathogen’s M proteins and the host’s heart muscle.

This immunological cross-reaction causes the host to exhibit a fever, painful joints, and unregulated body movements. S. pyogenes’ other sequelae is scarlet fever. Scarlet fever occurs when streptococcus pyogenes has been infected with a phage. When a phage infects S. pyogenes, it begins to produce a erythrogenic toxin that causes a sandpaper-like rash to develop on the cheeks and chest along with a high fever.

E. Response and Treatment

The immune system takes action when fighting off strep throat. Inflammation of the throat and fever are key factors. CD4 T cells are directed against the M proteins of the streptococcus pyogenes bacteria. The body’s T cells secrete cytokines to guide that class switch recombination. Th17 cells protect against the GAS bacteria.

IgG1 and IgG3 are responsible for the body’s humoral response and are developed over time, therefore adults are much less susceptible to this infection than children. Once exposed to the GAS bacteria, the body produces antibodies which have a protective capacity against infection. The B memory cells developed within the body help to fight of future infection of the same strain of bacteria. Vaccine development is currently focusing on antibody development more than the T cell immunity to encompass more the one strain.

Treatment of the disease will shorten the duration of symptoms, reduce the chance of transmission between people in close contact, and prevent further complications. Clinicians should treat patients who test positive for streptococcus pyogenes (Strep Group A) through a throat culture test or rapid diagnostic throat test, in order to reduce the risk of serious sequelae.

Penicillin is the first choice of treatment for the bacteria, however cephalexin and vancomycin can be used if the patient is allergic to the penicillin family. Both of these antibiotics are taken for a span of 10 days to completely eradicate the bacteria. The body could potentially fight off the infection without treatment, however antibiotic treatment is important to prevent possible life-threatening sequelae.

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         In order to prevent the spread of the infection, proper hygiene and respiratory etiquette should be practiced. Washing hands after coughing or sneezing and before handling food will help stop the spread of bacteria.  Respiratory etiquette means covering your nose or mouth when coughing or sneezing and not coming into close-contact with sick individuals.

Normally, after twenty-four hours of antibiotic therapy, the individual is no longer at risk of transmitting the bacteria. They should stay at home for one entire day after starting the medication and until their fever is gone to further limit other’s exposure to possible illness.

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Infectious Disease Fact Sheet

Group Members: Kourtney Mathis, Savannah Ross, Hannah Stewart

Name of Disease	Streptococcal Pharyngitis
Name of Causative Agent	Streptococcus Pyogenes
Type of Microbe	Bacterium
If Bacterial:
Gram-reaction	Gram-positive
Cell Shape/Arrangement	cocci, chains
Epidemiology
Geographic Prevalence	Worldwide
Average Rates of Infection	11,000 to 13,000 cases each year in the U.S., 18 million cases worldwide, 20 – 30% in children, 5 – 15% in adults
Reservoir(s)	Humans (primarily children), (asymptomatic) Group A Streptococcus carriers
Mode(s) of Transmission	Respiratory dropletsDirect contactNasal or saliva droplets from an infected person
Pathology
Major Virulence Factors	Exotoxins (superantigens), M proteins, capsule, streptolysins O/S, streptokinase, hyaluronidase, C5a peptidase
Major tissues/organs affected	Epithelial cells in pharynx, tonsils
Major Signs/Symptoms	Pain, redness/inflammation of throat/lymph nodes, fever, vomiting in children
Sequelae?	Acute Rheumatic FeverScarlet Fever
Latency?	2-5 days
Main Treatment Methods
Pharmacological Treatments	Penicillin, Vancomycin, Cephalexin
Typical Length of Treatment	7-10 days
Prophylactic Measures	Avoid direct contact with sick individualsProper hygiene/hand washing and respiratory etiquette

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Works Cited

• Mortensen, Rasmus, et al. “Adaptive Immunity against Streptococcus Pyogenes in Adults Involves Increased IFN-γ and IgG3 Responses Compared with Children.” The Journal of Immunology, American Association of Immunologists, 15 Aug. 2015, www.jimmunol.org/content/195/4/1657.
• “Group A Streptococcal (GAS) Disease.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 1 Nov. 2018, https://www.cdc.gov/groupastrep/diseases-hcp/strep-throat.html.
• Costello, Anne Marie. “Group A Streptotoccus.” Austin Community College – Start Here. Get There., www.austincc.edu/microbio/2704y/gas.htm.
• Efstratiou, Androulla. “Epidemiology of Streptococcus Pyogenes.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, 3 Apr. 2017, www.ncbi.nlm.nih.gov/books/NBK343616/.
• “Strep Throat.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 28 Sept. 2018, www.mayoclinic.org/diseases-conditions/strep-throat/symptoms-causes/syc-20350338.
• Ferretti, Joseph. “History of Streptococcal Research.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, 10 Feb. 2016, www.ncbi.nlm.nih.gov/books/NBK333430/.

Related FAQs

1. What is Streptococcus pharyngitis?

Streptococcal pharyngitis, also known as strep throat, or Bacterial tonsillitis is an infection of the back of the throat including the tonsils caused by group A streptococcus (GAS). Common symptoms include fever, sore throat, red tonsils ( tonsilitis ), and enlarged lymph nodes in the neck.

2. When did penicillin become an effective treatment for streptococcal pharyngitis?

However, Penicillin was not actually isolated to where it could be used as an effective treatment for diseases until 1939 by Howard Florey and Ernst Chain. Throughout decades this treatment continues to be the best option to treat streptococcal pharyngitis.

3. What are the treatment options for acute streptococcal pharyngitis in children?

“Short-term late-generation antibiotics versus longer term penicillin for acute streptococcal pharyngitis in children”. Cochrane Database of Systematic Reviews (8): CD004872. doi: 10.1002/14651858.CD004872.pub3.

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4. What is the prognosis of untreated streptococcal pharyngitis?

Untreated streptococcal pharyngitis usually resolves within a few days. Treatment with antibiotics shortens the duration of the acute illness by about 16 hours. The primary reason for treatment with antibiotics is to reduce the risk of complications such as rheumatic fever and retropharyngeal abscesses.

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