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Diphtheria | causes, symptoms, complications and treatment

Diphtheria is caused by Corynebacterium species, mostly by toxin-producing Corynebacterium diphtheriae and rarely by toxin-producing strains of C. ulcerans and C. pseudotuberculosisThe most common type of diphtheria is classic respiratory diphtheria, whereby the exotoxin produced characteristically causes the formation of a pseudomembrane in the upper respiratory tract and damages other organs, usually the myocardium and peripheral nerves. 
Diphtheria is caused by Corynebacterium species



Acute respiratory obstruction, acute systemic toxicity, myocarditis and neurologic complications are the usual causes of death. The infection can also affect the skin (cutaneous diphtheria). More rarely, it can affect mucous membranes at other non-respiratory sites, such as genitalia and conjunctiva.




Reservoir: Infected humans are the only reservoir.
Incubation period: The incubation period is usually 2–5 days (range 1–10 days).

Description of illness

Classic diphtheria is an upper-respiratory tract illness characterized by sore throat, low-grade fever, and an adherent pseudomembrane of the tonsil(s), pharynx, and/or nose. However, disease can involve almost any mucous membrane. Complications of diphtheria include myocarditis, neuritis, airway obstruction, and death. The fatality rate for diphtheria is approximately 10%. For clinical purposes, diphtheria can be classified according to the site of the infection:

1. Anterior nasal diphtheria
Anterior nasal diphtheria usually presents with mucopurulent discharge from the nose which may be bloody and a white pseudomembrane on the nasal septum.

2. Pharyngeal and tonsillar diphtheria
Pharyngeal and tonsillar diphtheria, the most common type of infection, initially presents with malaise, sore throat, anorexia, and low-grade fever. Within a few days, a bluish-white pseudomembrane forms on one or both tonsils which can extend to the tonsillar pillars, uvula, soft palate, pharynx and nasopharynx. Over time, the pseudomembrane evolves into a dirty gray color with areas of green or black necrosis surrounded by a minimal amount of erythema. Attempts to remove the pseudomembrane cause bleeding. 

Progressive extension of the membrane can cause respiratory obstruction. With severe disease, patients can develop edema of the anterior neck giving a characteristic “bullneck” appearance. If a significant amount of toxin is absorbed into the blood stream, patients may develop pallor, rapid pulse, coma and death.

The differential diagnosis of diphtheria includes streptococcal pharyngitis, viral pharyngitis, Vincent's angina, infectious mononucleosis, oral syphilis and candidiasis.

3. Laryngeal diphtheria
If the infection involves the larynx, the patient can present with fever, hoarseness and a barking cough. Airway obstruction can result in coma and death.

4. Cutaneous (skin) diphtheria
Cutaneous diphtheria may present as a scaling rash or as clearly demarcated ulcers. Peripheral effects of the toxin are usually not evident. Since 1980, cutaneous diphtheria caused by either toxigenic or non-toxigenic strains of C. diphtheriae has not been reportable to the National Notifiable Disease Surveillance System (NNDSS) in the United States. Nevertheless, all C. diphtheriae isolates should be submitted for testing to determine whether the tox gene is present.

5. Other possible sites of infection include the conjunctiva, vulvovaginal area and external auditory canal.  Rarely, other Corynebacterium species (C. ulcerans and C. pseudotuberculosis) may produce diphtheria toxin and cause classic respiratory diphtheria-like illness.

Modes of transmission

Diphtheria is transmitted from person to person through respiratory droplets or less commonly, through contact with discharge from skin lesions. Rarely, raw milk and fomites have served as vehicles.


Diphtheria Antitoxin

Diphtheria antitoxin, produced in horses, was used for treatment of diphtheria in the United States since the 1890s. It is not indicated for prophylaxis of contacts of diphtheria patients. Since 1997, diphtheria antitoxin has been available only from CDC, through an Investigational New Drug (IND) protocol. Diphtheria antitoxin does not neutralize toxin that is already fixed to tissues, but it will neutralize circulating (unbound) toxin and prevent progression of disease. The patient must be tested for sensitivity before antitoxin is given. Consultation on the use of diphtheria antitoxin is available through the duty officer at the CDC through CDC’s Emergency Operations Center.

After a provisional clinical diagnosis is made, appropriate specimens should be obtained for culture and the patient placed in isolation. Persons with suspected diphtheria should be given diphtheria antitoxin and antibiotics in adequate dosage. Respiratory support and airway maintenance should also be administered as needed.

Immunity

Since lifelong immunity may not be acquired after disease or inapparent infection, confirmed diphtheria patients should begin or complete an age appropriate diphtheria toxoid containing vaccination series during convalescence. Immunization with diphtheria toxoid produces prolonged but not lifelong immunity and persons should receive booster vaccination every ten years thereafter. Serosurveys in the United States indicate that more than 40% of adults lack protective levels of circulating antitoxin. However, many of these older adults may have immunologic memory and would have some protection against disease if exposed.

Antibiotics

Treatment with erythromycin orally or by injection (40 mg/kg/day; maximum, 2 gm/day) for 14 days, or procaine penicillin G daily, intramuscularly (300,000 U/day for those weighing 10 kg or less, and 600,000 U/day for those weighing more than 10 kg) for 14 days. The disease is usually not contagious 48 hours after antibiotics are instituted. Elimination of the organism should be documented by two consecutive negative cultures after therapy is completed.

A person in close contact with someone who has diphtheria should receive treatment as well. Close contacts should be quickly identified and monitored for symptoms of diphtheria. Contacts should be tested for diphtheria, given antibiotics, and an age-appropriate dose of diphtheria containing vaccine. 

Close contacts may include:
• Persons who live in the same house;
• Persons who have contact with mouth or nose secretions, such as through a cough, sneeze, kissing, or sexual contact. This also includes people who share food and eating utensils;
• Persons who have done medical treatments such as mouth-to-mouth resuscitation or intubation; or
• Close contacts in child and daycare settings or schools.




Reference
https://www.cdc.gov/diphtheria/index.html
https://www.mayoclinic.org/diseases-conditions/diphtheria/symptoms-causes/syc-20351897
https://www.who.int/immunization/diseases/diphtheria/en/
https://www.healthline.com/health/diphtheria
https://www.medicalnewstoday.com/articles/159534
https://emedicine.medscape.com/article/782051-overview
https://www.nhs.uk/conditions/diphtheria/
https://www.msdmanuals.com/professional/infectious-diseases/gram-positive-bacilli/diphtheria

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