User:Haw11967/Corynebacterium diphtheriae

Lead

* all work on lead b/c the article one is really bad :') *

Diphtheria is caused by the adhesion and infiltration of the bacteria into the mucosal layers of the body, primarily affecting the respiratory tract and the subsequent release of an endotoxin. The pathogen has both, a localized effect in terms of skin lesions, as well as a metastatic, proteolytic effects on other organ systems in severe cases. Originally a major cause of childhood mortality, diphtheria has been almost entirely eradicated from the United States due to the vigorous administration of the diphtheria vaccination in the 1910s. Lack of public resources and the bacteria's specificity has lead to a diminished understanding of the pathogen as model animals such as mice are not susceptible.

Today, diphtheria is no longer being transmitted as frequently as before due to the development of the vaccine, DTaP. Although diphtheria outbreaks continue to occur, it is usually occurring in developing countries where the majority of the population is not vaccinated. Diphtheria is also common in places where the living conditions are crowded and/or unsanitary.

Classification of Pathogen

Ted L. Hadfield, Peter McEvoy, Yury Polotsky, Vsevolod A. Tzinserling, Alexey A. Yakovlev, The Pathology of Diphtheria, The Journal of Infectious Diseases, Volume 181, Issue Supplement_1, February 2000, Pages S116–S120, https://doi.org/10.1086/315551 - this article has a really good classification in the beginning if you'd like to see it - Ashi

History

Corynebacterium diphtheriae is now rarely seen because of vaccines. In the 19th century, vaccines were not well heard of and there was limited amounts of research on them, which is why diseases were easily spread. Corynebacterium diphtheriae is a bacterial disease that can infect the skin (skin or cutaneous diphtheria) or the throat (respiratory diphtheria).

Pathology

The mechanism of action for C. diphtheriae involves the bacteria establishing itself on a mucosal layer, typically within the respiratory tract, ulcerating it, and creating an inflammatory pseudomembrane which can then form lesions. This is the localized action of C. diphtheriae. It also has a metastatic component wherein the bacteria will release a potent toxin that enters the bloodstream and causes issues to the system at whole but notably the heart, lymph nodes, and brain.

The first step of C. diphtheriae infection involves the bacteria being introduced into the system and planting itself on a mucosal layer. In young children, this typically occurs in the upper respiratory tract mucosa. In adults, faucial diphtheria is more common wherein the primary site of infection is typically the posterior mouth or upper pharynx region. Some unusual sites of infection include the heart, larynx, trachea, bronchi, and anterior areas of the mouth including the buccal mucosa, the lips, the tongue, and the hard and soft palate. The bacteria has a number of virulence factors to help it localize on areas of the respiratory tract, many of which are yet to be properly researched as diphtheria does not affect many model hosts such as mice. One common virulence factor that has been researched extensively in vitro is DIP0733, a multi-functional protein that has shown to have a role in bacterial adhesion to host cells as well as fibrogen-binding qualities. In experiments creating a mutant strand of the Cor. diphtheriae, adhesion and epithelial infiltration decreased significantly. Furthermore, the ability to bind to extracellular matrix aids the bacteria in avoiding detection by the body's immune system.

Once the bacteria has localized in one area, it starts multiplying to create the inflammatory pseudomembrane. In patients with faucial diphtheria typically have the pseudomembrane grow over the tonsil and accessory structures, uvula, soft palate, and possibly also the nasopharyngeal area. In upper respiratory tract diphtheria, the pseudomembrane can grow on the pharynx, larynx, trachea, and bronchi/bronchioles. The pseudomembrane starts off white in color and then later becomes dirty-gray and tough due to the necrotic epithelium.

When respiratory tract diphtheria causes psuedomembrane formation on the trachea or bronchi will decrease efficiency of airflow. Over time, the diffusion rate in the alveoli decreases due to the lower airflow and decreases the partial pressure of oxygen in the systemic circulation which can cause cyanosis and suffocation.

Diphtheria toxin can be proteolytically cleaved into two fragments - an N-terminal fragment A (catalytic domain), and fragment B (transmembrane and receptor binding domain). Fragment A catalyzes the NAD+ -dependent ADP-ribosylation of elongation factor 2, thereby inhibiting protein synthesis in eukaryotic cells. Fragment B binds to the cell surface receptor and facilitates the delivery of fragment A to the cytosol.

Epidemiology

Mode of transmission is person-to-person contact via respiratory droplets (i.e., coughing or sneezing), and less commonly, by touching open sores or contaminated surfaces.

A vaccine, DTaP, effectively prevents the disease and is mandatory in the United States for participation in public education and some professions (exceptions apply).

The invention of the toxoid vaccine, which provides protection against Corynebacterium diphtheriae, caused a dramatic shift on the bacterium’s rate of infection in the United States. Even though the vaccine was first made in the early 1800s, it did not become widely available until the early 1910s. According to the National Health and Nutrition Examination Survey (NHANES), “80 percent of persons age 12 to 19 years were immune to diphtheria” due to the wide use of the vaccine in the United States. Diphtheria’s rate of infection has plummeted in populations that are highly vaccinated. However, occasionally the bacterium will cause spontaneous outbreaks despite countries with predominantly vaccinated individuals. A research article through the Journal of Clinical Microbiology states that regions where Diphtheria is common give rise to spontaneous outbreaks in other regions. Recent flare ups of Diphtheria is mainly seen in communities with a weak public health system and low rates of vaccinations.

Stain subtyping involves comparing species of bacteria and categorizing them into subspecies. Strain subtyping also helps with identifying the origin of a certain bacteria’s outbreak. However, when it comes to the subtyping of C. diphtheriae, there is not a lot of useful or accurate classification due to the lack of publicly available resources to identify strains and therefore finding the origin of outbreaks.

Diagnosis/Laboratory Testing

As previously discussed in epidemiology, this is primarily transmitted by the exchange of human droplets (i.e. coughing). C. diphtheria has the ability to colonize the skin and/or the upper respiratory tract. This is the area where it releases its toxins which is what causes the symptoms. This is where the lesions on the tonsils come into play.

Diagnosis of respiratory C. diphtheria is made based on presentation clinically, whereas non-respiratory diphtheria may not be clinically suspected therefore laboratory testing is more reliant. Culturing is the most accurate kind of testing that will confirm or deny the prevalence of diphtheria toxins. The testing must be done by swabbing the possibly infected area, as well as any lesions and sores. Doctors will take these swabs and culture them. The growing of the cultures could potentially take longer than desirable, so if you are suspected to have diphtheria, starting treatment right away is important even if results were not available yet. This is due to the complications that could occur from this sickness.

Treatment/Prevention

When Corynebacterium diphtheriae infects the human body, it releases toxins that can cause harm, especially to the throat. Antitoxins are prescribed by healthcare professionals in order to prevent any more harm done by the toxins. Antibiotics are also prescribed to fight the infection caused by the bacterium. Typical antibiotics that are used against diphtheria involve penicillin or erythromycin.

People infected with diphtheria must quarantine for at least 48 hours after being prescribed antibiotics. In order to confirm that the patient is no longer contagious, tests must be run to ensure that the bacteria is gone. Patients are then vaccinated to put a stop to any more transmission of the disease.

The wide-use of the diphtheria vaccine dramatically decreased the rate of infection and allows for primary prevention of the disease. Most people receive a 3-in-1 vaccine that consist of protection against diphtheria, tetanus and pertussis, which is commonly knowns as the DTaP or Tdap vaccine. DTaP vaccine is for children while the Tdap vaccine is known for adolescents and adults.

In the United States, doctors recommend the DTaP vaccine to parents of infants which typically involves a series of five shots. These shots are injected through the arm or thigh and are administered when the infant is 2 months, 4 months, 6 months, 15-18 months and then 4-6 years old.

Possible side events that are associated with the diphtheria vaccine include "mild fever, fussiness, drowsiness or tenderness at the injection site". Although it is rare, the DTaP vaccine may cause an allergic reaction that causes hives or a rash to breakout within minutes of administering the vaccine.

Genetics

The Corynebacterium diphtheriae genome is a single circular chromosome that has no plasmids. These chromosomes have a high G+C content which is what contributes to their high genetic diversity. The high content of guanine and cytosine is not constant across the entire genome of the bacteria. There is a terminus of replication around the ~740kb region that causes a decrease in the G+C content. In other bacteria, it is often seen that the G+C content gets smaller near the terminus, but C. diphtheriae is a considerably strongly genome that has this occurrence. Chromosomal replication is one of the ways this happens within this genome.

Bibliography

Ted L. Hadfield, Peter McEvoy, Yury Polotsky, Vsevolod A. Tzinserling, Alexey A. Yakovlev, The Pathology of Diphtheria, The Journal of Infectious Diseases, Volume 181, Issue Supplement_1, February 2000, Pages S116–S120, https://doi.org/10.1086/315551

-this is an oxford journal with a lot of information on the pathology of diphtheria as well as multiple pictures

Shaun A Truelove, Lindsay T Keegan, William J Moss, Lelia H Chaisson, Emilie Macher, Andrew S Azman, Justin Lessler, Clinical and Epidemiological Aspects of Diphtheria: A Systematic Review and Pooled Analysis, Clinical Infectious Diseases, Volume 71, Issue 1, 1 July 2020, Pages 89–97, https://doi.org/10.1093/cid/ciz808

Zhou, X. J., Chen, C. R., Wang, X. M., Wu, H., Huang, T., Wang, L. N., & Niu, L. (2022). Zhonghua yu fang yi xue za zhi Chinese journal of preventive medicine, 56(8), 1107–1111. https://doi.org/10.3760/cma.j.cn112150-20211111-01045

• This is a academic, peer-reviewed journal that focuses on a diabetic foot of a person who was diagnosed with Corynebacterium diphtheriae

Muttaiyah, S., Best, E. J., Freeman, J. T., Taylor, S. L., Morris, A. J., & Roberts, S. A. (2011). Corynebacterium diphtheriae endocarditis: a case series and review of the treatment approach. International Journal of Infectious Diseases, 15(9), e584–e588. https://doi.org/10.1016/j.ijid.2011.04.003

• This journal reviews cases of Corynebacterium diphtheriae and how to approach its treatment

https://publications.aap.org/pediatrics/article/76/1/1/79417/Diphtheria-and-Theories-of-Infectious-Disease - This is an article on the effect of diphtheria on the history of medicine if you want to use it Asher - Ashi

Peter C. English; Diphtheria and Theories of Infectious Disease: Centennial Appreciation of the Critical Role of Diphtheria in the History of Medicine. Pediatrics July 1985; 76 (1): 1–9. 10.1542/peds.76.1.1