Streptococcus Group A

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Streptococcus Group A Binding From [Dr. Richard Gallo's Dermatology Lab at University California San Diego]

Introduction

Group A Streptococcus (GAS), also known as Streptococcus pyogenes, is a bacterium that is generally found in the inner throat and on various parts of the skin. (5) The letter "A" corresponds to a classification of bacteria in the genus Streptococcus according to the structure of the organism's cell wall. This Gram Positive bacterium can cause infections that range from mild to life threatening. It tends to cause relatively mild illnesses, such as streptococcal sore throat (strep throat) and streptococcal skin infections (impetigo). (1) Group A strep can also cause more severe illnesses such as scarlet fever, rheumatic fever, postpartum fever, wound infections, and pneumonia. Signs and symptoms depend on the type of illness caused by the bacterium. These symptoms can usually be seen from one to three days upon infection. Most infections can be treated with antibiotics. This bacterium can be spread by direct person-to-person contact that can be found worldwide. Scarlet fever (known as scarlatina in literature references dating before 1869) is one serious infection resulting from Group A Streptococcus and is considered an exotoxin-mediated disease. (13) In essence, scarlet fever is a more severe case of strep throat with the additional symptom of a rash. The toxins (poison) released from Group A Streptococcus can cause the scarlet-colored rash from which this illness gets its name. (13)

Description of scarlet fever

An Infected Mouse with a rash From [Dr. Richard Gallo's Dermatology Lab at University California San Diego]

Scarlet fever typically evolves from tonsillar or pharyngeal GAS infection ("strep throat"), but can also develop from wound infection; slightly less than 10% of untreated strep throat cases will turn into scarlet fever. It is most prevalent in temperate climates and urban areas, where the population density expedites transmission--hence the epidemics in Europe after the industrial revolution. Children are the primary victims of the epidemic because of their lack of antibodies to the microbe's exotoxin (infants are protected by the lingering presence of maternal antibodies.) Most infections occur during the colder months of the year.

Symptoms of scarlet fever typically show within 48 hours of the strep symptoms, although onset can occur faster. During the 19th century epidemic, there were cases of death within 48 hours of the first signs of infection. Symptoms include sore throat, rapid pulse, the characteristic dry, scarlet rash, and swelling of the neck glands. Severe cases exhibit septicemia, vomiting, and toxic shock syndrome. The most striking characteristic of the fever is the rash, which first appears on the neck and head and can later spread to the rest of the body. It looks like a bad sunburn with dry bumps covering the skin and is caused by the erythrogenic exotoxin released by GAS. (10)

Scarlet fever was a severe epidemic during the 19th and early 20th century and a major cause of death, especially among children. Fatalities due to the disease have alleviated since the advent of penicillin and subsequent antibiotics, which are an effective cure. However, cases still occur in temperate climates throughout the world and it is still a threat in countries where antibiotics are unavailable.

Description of the microbe

Streptococcus Group A From [Dr. Richard Gallo's Dermatology Lab at University California San Diego]

Streptococcus Group A, a gram-positive bacteria, is nonmotile and does not form spores. (13) It's cells typically range from 0.6 to 1.0 micrometers in diameter, which is a fairly small size for a bacteria. These cells are usually found in groups and are seldom seen alone. Rather than using aerobic or anaerobic respiration, Group A Streptococcus uses a metabolic pathway of lesser efficiency, fermentation. This makes the cells grow much slower with a lower chance of survival than those bacteria that use aerobic or anaerobic respiration since fermentation is a pathway which does not use the highly effective Electron Transport Chain (ETC). Nutrient-enriched blood is usually required for Group A Streptococcus to grow and they "typically have a capsule composed of hyaluronic acid and exhibit beta (clear) hemolysis on blood agar." (13)

Proven to be an efficient method of classifying this bacteria is the hemolytic reaction that occurs on the blood agar. There is an alpha-hemolysis, a beta-hemolysis and a gamma-hemolysis. Alpha-hemolysis is a partial ("green") hemolysis associated with the reduction of red cell hemoglobin, while beta-hemolysis is associated with the complete lysing of those red cells that surround the colony and gamma-hemolysis is the term used for non-hemolytic colonies. (13) Knowing this information, one can classify Streptococcus Group A bacteria since it is almost always beta-hemolytic. Although this method is not perfectly accurate, it is still very widely used.

Transmission of disease

"Scarlet fever transmission typically occurs through direct contact with throat mucus, nasal discharge, and saliva of an infected person." (8) The microbe can quickly be spread by droplets being released from a sneeze, cough, or by nasal and oral fluids. It can also be transferred by direct skin to skin contact. (9) The microbe displays great tenacity for life since it seems to cling to any object it encounters. (6) The microbe is very driven since it can live outside of an individual for some time making it very difficult to avoid without the right precautions. It can cling to dishes, cups, toys, and any other accessible surfaces. "If you touch your mouth, nose, or eyes after touching something that has these fluids on them, you may become ill." (7) "Numerous epidemics spread by milk have been reported." (6) One of the biggest problems with the transmission of the microbe is that some individuals are the so-called walking or unrecognized cases which show minimal evidence such as merely a sore throat. (6) These individuals are carriers for the disease without knowing it and without many of the symptoms of an infected individual making the spread of the microbe very easy among the rest of the healthy, unsuspecting population.

Prevention

Preventative strategies effective against scarlet fever are the same generally used to avoid bacterial infection. All wounds should be checked for signs of infection, and wound dressings should be replaced regularly. It is important to clean one's hands and to avoid contact with anyone known to carry the infection. Anything touched by that person, particularly eating utensils or any object that could be contaminated by mucous membranes from the infected individual, should be cleaned with a disinfectant after use. A vaccine was developed for scarlet fever in the 1920s but fell out of use after the invention of penicillin. (4) Avoiding contact with an infected person and with the areas they could have contaminated is the best way to avoid infections of the Streptococcus Group A bacterium. (5)

Why is this disease a problem in Europe

Scarlet fever has to be regarded as one of the most fearsome diseases of any person’s childhood. Not only can an attack be so severe as to cause death in a brief time or cause severe complications, but because the hope of recovery, even in the mildest cases, is very rare. In the eighteenth century, epidemics of scarlet fever were very common especially in Europe. One major contribution to Europe’s large number of cases is its cold climate. This disease is quite frequent among temperate climates. This temperate environment causes the average temperature to be roughly around 65 degrees; meaning it is on the cooler side of the spectrum, and thus making individuals who live in Europe more susceptible to scarlet fever. Since scarlet fever is an infection that is highly infectious and extremely contagious, it can cause numerous problems in cities that are majorly urbanized. Urbanization is another reason Europe is a big target because scarlet fever tends to be more common among cities than rural areas. This then creates difficulties within the schooling system causing many students to easily become infected. (10)

Additionally, Europe is responsible for having many traces of streptococcus in the milk supply. Milk is capable of containing the infective material and giving the disease to many susceptible people. The cows from where the milk was taken suffered from a vesicular infection of the udder. This vesicular infection had streptococcus very similar to that obtained from the infected cows/infected milk to the scarlet fever patients. While it is unlikely that the spread of the infection can be pinpointed to just the infected milk supply, it is safe to assume that a good portion of the population could have likely been infected via milk in Europe. (3)

Another common reason Europe suffered so greatly with this epidemic was common practical sanitation knowledge. Some simple medical practices such as wearing gloves, washing hands, and staying clean were barely beginning to emerge. (10) The lack of these habits might have fueled the scarlet fever epidemic further because of the high rate infectivity and how easily it can be contracted from person to person.

Past measures taken against scarlet fever

Government Issued Quarantined Warning From [The United States Department of Health and Human Services]

Because the cause of the disease was largely mysterious in the 19th century, the typical procedure was to quarantine patients in a sterile environment; actual treatments were dietary palliative. This approach was the only method available to the doctors of the time period and showed little efficacy in curtailing fatalities by the disease until the 1880s, when the methods of sterilization, antisepsis, and quarantine were refined.

In the period between the 1840s and 1880s when scarlet fever ran rampant in Great Britain's urban districts, fear sometimes led to extreme countermeasures. To prevent transmission, health officials would sometimes burn all the possessions of quarantine patients. During this time the government funded quarantine facilities, such as the Metropolitan Asylums Board, were somewhat controversial due to the limited efficacy they showed in preventing disease spread. Criticism was also turned to the dairy industry, whose workers were blamed for infecting the milk supply with the then-unknown agent of the disease. Streptococcal ulcers were found on the utters of dairy cows, which dairy workers admitted sometimes bled into the milk pails.(3) Schoolchildren were heavily monitored for symptoms of the disease and were removed from school when symptoms showed.

Before the development of an anti-toxin in the 1920s, the only medical recourses against the disease were sterilization and antisepsis. Streptococcus's tenacity of life outside the host posed a great challenge to the sterile procedures of the day. The sickroom of a patient with scarlet fever would be emptied of all objects that were unnecessary for the treatment. Bedclothes used by the patient were soaked in a tub of disinfectant solution, such as 5% carbolic acid or 2% creosol. Wipes used for the patient's mucous discharge would be burned. No articles used by the patient would leave the room unless soaked in disinfectant or boiled for 20 minutes. Patients usually remained in this environment for approximately a month, or until the desquamation (peeling of the rash) was complete, although the disease happens to not be contagious during this period.(6)

The first major medical recourse against scarlet fever was an anti-toxin developed by George Frederick Dick in the 1920s. Dr. Dick, working with his wife Dr. Gladys Henry Dick, isolated the exotoxin that caused the rash in scarlet fever patients and developed an anti-toxin that could be used as a vaccination against the disease. They also discovered that susceptibility to the disease could be determined via inoculation with the exotoxin, a process that became known as the Dick Test. Their anti-toxin was used until it became obsolete after the development of Penicillin in the 1940s.(4)

What else could be done to address this problem

Are there solutions that could be successful but haven't been implemented due to political or economic reasons? Are there successful efforts in other countries? Are there reasons why these efforts may or may not be successful in the country you've focused on? etc. etc.

To analyze the the symptoms and diagnose the disease of an individual, the doctor uses a cotton swab to rub the back of the throat and uses the swab for rapid antigen test or throat culture to check for Streptococcus Group A infection. (7) If test shows positive results for Group A Streptococcus, the doctor will initially prescribe an antibiotic as the main treatment for scarlet fever. The most common antibiotics used include penicillin, cephalexin, and amoxicillin. These antibiotics should be taken as recommended by the doctor and consumption should not cease until indicated by the prescription.

The main symptoms of scarlet fever are body aches, fever, and moderate to severe sore throat. The doctor will recommend over-the-counter drugs such as acetominophen (which is commonly referred to as Tylenol and Datril) or Ibuprofen (which is marketed as Advil, Motrin, and Nuprin). Patients under the age of 20 should not take aspirin unless indicated by the doctor. (8) Sponge baths are also used along with the drugs to help combat high fevers. If skin is itching and burning, best remedies available are vaseline and oil or prescription of cream or lotion. (6) To treat a sore throat doctors recommend cold drinks, frozen desserts, or warm liquids such as soups. "Gargling with saltwater (about half a teaspoon salt to 8 ounces of warm water) and sucking on throat lozenges" (8) can be used to treat this symptom. Parents are also advised to purchase a cool mist humidifier to prevent the air and the throat from becoming too dry and causing more severe soreness. It is also highly recommended that a patient obtains plenty of rest and abstain from strenuous activities.

Current research on Group A Streptococcus focuses on the production of its unique proteins. There are over 120 different strains that cause a specific group of diseases. "With the support of the National Institute of Allergy and Infectious Disease (NIAID), scientists have determined the genetic sequence, or DNA code, for five different strains of the Group A Streptococcus organism." (11) Through studying a certain organism's genes, scientists were able to understand the function of specific proteins which are responsible for virulence of the disease. This information is very valuable and is the basis of the development of the Group A Streptococcus vaccines. These vaccines target specific proteins at different stages of the diseases' development. Doctors and researchers claim that effective vaccines will not only prevent specific symptoms but will also help fight the most serious post-infectious complication. (11) Currently research includes studies of determining the spread of the disease across different countries in an effort to characterize the disease.

Summary

This gram-positive bacteria can cause several diseases of different severity. One fatal form it has taken is scarlet fever, which has existed for over five centuries. This disease was prevalent in Europe during the seventeenth century and was thought to have been introduced into North America in the year 1735. (1) Although this disease has the dangerous characteristic of being asymptomatic for a long period of time, the main symptoms associated with it are sore throat, fever and rash. This disease strongly impacted Europe due to its urbanization, its cold climate, its contaminated supply of milk and poor sanitary habits. These conditions allowed the microbe to flourish since it's transferred by oral and nasal fluids and can live outside of an individual for a long time infecting inanimate objects. During the scarlet fever epidemics of the 1800s, due to the nonexistence of antibiotics, efforts to contain the disease amounted to a mad rush to quarantine those who showed symptoms and disinfect everything they touched. This approach took some time to tailor to the GAS transmission mechanism, but once refined was moderately successful. Currently doctors treat scarlet fever with an amalgam of antibiotics and over-the-counter drugs. Also, several prescription and non-prescription creams are used to treat the resulting rash. Current and future research primarily focus on creating a new vaccine that will help fight and even prevent future outbreaks of the disease.

References

Edited by David Audish, Sean Blum, Mark Habib, and Michael Mitry, students of Rachel Larsen

1.Balentine, Jerry. "Scarlet Fever". Trip Database. 24 August

2.Clemow, Frank. The Geography of disease. London: macmillan, 1903.

3.Creighton, Charles. A History of Epidemics in Britain. London: CJ Clay and Sons, 1894.

4."George Frederick Dick," Microsoft® Encarta® Online Encyclopedia 2009 © 1997-2009 Microsoft Corporation.

5.“Group A Streptococcus.”Health Promotion of Education. 24 August, 2009.

6.“Scarlet Fever.” Albert D. Kaiser The American Journal of Nursing, Vol. 15, No. 9 (Jun., 1915), pp. 717-722. Published by: Lippincott Williams & Wilkins.

7."Scarlet Fever." Center for Disease Control and Prevention.13 April, 2008.24 August, 2009.

8."Scarlet Fever."E MedTV.03 December, 2006. 24 August, 2009.

9."Scarlet Fever."SFGA. November,2007. 24 August, 2009.

10.“Scarlet Fever.”Patient UK.1988. 24 August, 2009.

11."Streptococcus Infections." Medicine NET.16 November,2007. 24 August, 2009.

12.Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, Pestonjamasp V, Piraino J, Huttner K, Gallo RL. "Innate antimicrobial peptide protects the skin from invasive bacterial infection."Nature. 1 October 2001. 24 August 2009.

13.Todar, Kenneth. "Streptococcus pyogenes and Streptococcal Disease".Todar's Online Textbook of Bacteriology. August 22, 2009.