Definition
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Definition.
Diphtheria is an acute, communicable disease that is caused by a bacterium which produces toxins that affects.
It is a serious bacterial infection affecting the mucous membranes of the nose and throat.
Causes.
It is caused by Corynebacterium diphtheria.
Mode of Transmission.
There are 2 modes of transmission
Airborne droplets:
When an infected person's sneeze or cough releases a mist of contaminated droplets, people nearby may inhale C. diphtheriae. Diphtheria spreads easily this way, especially in crowded conditions.
Contaminated fomites:
It can sometimes be contacted by handling infected things, like used tissues or hand towels that may be contaminated with the bacteria or by direct contact with an infected wound.
Epidemiology.
Diphtheria results in death among 5% to 10% of cases.
In children below the age of five and adults over the age of 40, the fatality rate may increase to as much as 20%. In 2013 3,300 death was recorded which is an improvement from 8,000 deaths recorded in 1990. The number of cases has metamorphosed over the last 20 years, specifically throughout developing countries. Improved standards of living, mass immunization, improved diagnosis, prompt treatment, and an effective health care have led to the decrease in the number of cases worldwide. Although outbreaks are rare, they still occur worldwide, even in developed nations such as Germany among children who were not vaccinated. “In Nazi Germany, contagious diseases such as diphtheria were among the leading causes of morbidity; they increased "after the mid-1920s, doubled again between 1932 and 1937, and reached extremely high levels during the war only to decline rapidly thereafter". Baten et al 2003.
“After the breakup of the former Soviet Union in the early 1990s, vaccination rates in its constituent countries fell so low that an explosion of diphtheria cases occurred. In 1991, 2,000 cases of diphtheria occurred in the USSR. Between 1991 and 1998 as many as 200,000 cases in the Commonwealth of Independent States were reported, with 5,000 deaths”. Laval 2006
Risk Factors.
People who are at increased risk of contracting diphtheria include:
· Children and adults who don't have up-to-date vaccinations
· People who live in crowded or unsanitary conditions
· People who travels to areas where diphtheria infections are prevalent.
Pathophysiology.
“Diphtheria toxin is produced by C. diphtheriae only when infected with a bacteriophage that integrates the toxin-encoding genetic elements into the bacteria”. Freeman 1951
Diphtheria toxin is a single, 60-kDa-molecular weight protein with two peptide chains, fragment A and fragment B which are held by a disulfide bond. Fragment B is a recognition subunit that allows the toxin access into the host cell by binding to the EGF-like domain of heparin-binding EGF-like growth factor on the surface of the cell. This signals the cell to internalize the toxin within an endosome via receptor-mediated endocytosis. Inside the endosome, the toxin is split by a trypsin-like protease into its individual A and B fragments. The acidity of the endosome causes fragment B to create pores in the endosome membrane, thereby catalyzing the release of fragment A into the cell's cytoplasm.
Fragment A inhibits the synthesis of new proteins in the affected cell by catalyzing ADP-ribosylation of elongation factor EF-2—a protein that is essential to the translation step of protein synthesis. This ADP-ribosylation involves the transfer of an ADP-ribose from NAD+ to a diphthamide (a modified histidine) residue within the EF-2 protein. Since EF-2 is needed for the moving of tRNA from the A-site to the P-site of the ribosome during protein translation, ADP-ribosylation of EF-2 prevents protein synthesis.
ADP-ribosylation of EF-2 is reversed by giving high doses of nicotinamide (a form of vitamin B3), since this is one of the reaction's end products, and high amounts drive the reaction in the opposite direction. Collier, 1975.
Signs and Symptoms.
The symptoms of diphtheria usually begin two to seven days after exposure to the bacteria:
· Fever of 38 °C (100.4 °F) or above
· Chills
· Fatigue
· Bluish skin coloration (cyanosis)
· Sore throat; hoarseness
· Brassy or barking cough
· Headache
· Difficulty swallowing and painful swallowing
· Difficulty with or rapid breathing
· Foul-smelling and bloodstained nasal discharge.
· Lymphadenopathy.
· Laryngeal diphtheria can present with a characteristic swollen neck and throat, or "bull neck“.
Within two to three days, diphtheria destroys healthy tissues in the respiratory system which then forms a thick, gray coating that accumulates in the throat or nose.
The thick gray coating is called a " pseudomembrane".
It gradually covers tissues in the nose, tonsils, voice box, and throat which makes it hard and nearly impossible to breathe and swallow.
Symptoms can also include
· Cardiac arrhythmias
· Myocarditis
· Cranial and peripheral nerve palsies.
· Diphtheria can also infect the skin and causes open sores or ulcers. Skin infections rarely result in any other severe disease.
Diagnosis.
· Make an appointment with a doctor immediately if you or your child has been exposed to a person diagnosed with diphtheria.
· Doctors assess individuals for diphtheria by assessing for common signs and symptoms.
· A swab of the back of the throat, nose or sore is taken and cultured for the causative organism of diphtheria. If the bacteria grow and produces a toxin the doctor is sure the patient has diphtheria and starts the appropriate treatment. However, it takes time to grow the bacteria, so it is pertinent to begin treatment immediately if diphtheria is suspected.
· Histopathologic diagnosis of diphtheria by Albert's stain
· Upper respiratory tract illness with sore throat
· Low-grade fever usually above 39 °C (102 °F) is rare
· An adherent, dense, grey pseudomembrane that covers the posterior aspect of the pharynx. In severe cases, it can extend to cover the entire tracheobronchial tree.
Treatment.
· Giving diphtheria antitoxin to stop the toxin produced by the bacteria from damaging the body’s cells and tissues. This is important for respiratory diphtheria infections, but it is rarely used for skin infections caused by the C. diphtheria.
· Prompt use of antibiotics to kill the bacteria. This is important for both infections in the respiratory system and the skin.
· Individuals with diphtheria are usually no longer able to infect others 48 hours after commencing antibiotics.
However, it is pertinent to complete the full course of prescribed antibiotics to ensure the bacteria is totally removed from the body.
· After the course of antibiotics is completed, further tests are run to ensure the bacteria is no longer in the system of the individual.
Prevention.
· Diphtheritic croup is extremely rare in countries where diphtheria vaccination is customary. So the term "croup" most often refers to an unrelated viral illness which produces a similar but milder respiratory symptom.
· Quinvaxem is a pentavalent vaccine, which is a combination of five vaccines in one that protect babies from diphtheria, among other common childhood diseases. Diphtheria vaccine is usually combined with tetanus vaccine (Td) and often with pertussis (DTP, DTaP, TdaP, Tdap) vaccines, as well.
Complications.
· Abnormal cardiac rhythms.
· Heart failure.
· Diphtheria can also cause paralysis in the eye, neck, throat, or respiratory muscles.
· Nerve damage.
