Diphtheria and its complications are vaccine preventable.

Diphtheria and its complications are vaccine preventable.



Diphtheria and its complications are vaccine preventable.
Diphtheria and its complications are vaccine preventable.

Diphtheria is a highly infectious disease affecting mainly children who are not immunized but may affect adults also. It was a major cause of death in under 5 year age children. Since launch of national immunization schedule across many  countries the incidence of diphtheria has decreased over the years and is continued on decreasing trend. But still in developing countries where vaccination coverage is inadequate and no herd immunity in those regions it a health concern. Diphtheria was indeed a major cause of death few decades back and still continues to be so in part of world where people are uneducated and ignorant about health and vaccination.

​Diphtheria is caused by toxin produced by Corynebacterium diphtheriae. It is also known as the Klebs-Löffler bacillus, because it was discovered in 1884 by German bacteriologists Edwin Klebs and Friedrich Löffler. Four subspecies are recognized: mitis, intermedius, gravis, and belfanti They are classified according to their colonial morphology and biochemical properties. Biochemical properties here mean the ability to use certain nutrients. They can produce toxin causing diphtheria or not toxigenic.

C. diphtheriae is seen as Gram-positive organism on gram stain. It is pleomorphic organisms that means does not occur in particular arrangement. Albert’s stain and Ponder's stain are used to see the bacterium. They demonstrate the metachromatic granules formed in the polar regions in turn identification process. The metachromatic granules are also known by names polar granules, Babes Ernst granules, volutin, etc. Growth on An enrichment medium, such as Löffler's medium, followed by a differential plate known as tellurite agar, allows all Corynebacteria (including C. diphtheriae) to reduce tellurite to metallic tellurium. When tellurite is reduced it turns to brown colour giving that brown colour to colonies for most Cornyebacteria species. It may form a halo coloured black around the C. diphtheriae colonies.

In history diphtheria was known as "strangling angel of children,". When vaccinations were not available diphtheria was common cause of death among children. Klebs got a break through in 1884. He was the first to identify the bacterium causing diphtheria. Loeffler successfully cultivated the bacterium a year later. Roux and Yersin purified the toxin in 1889, and the antitoxin was invented shortly afterwards. In the 1920s, the toxoid was developed.

Other diphtheroids (eg, coryneform bacteria) are found everywhere in nature. They are ubiquitus. C diphtheriae is exclusively infects and stays in human. It mainly infects mucous membranes and skin. It spreads from one person to other by airborne respiratory droplets, direct contact with respiratory secretions of symptomatic individuals, or contact with exudate from infected skin lesions. Also asymptomatic persons who are infected that is carriers can spread the bacterium when they cough or sneezing.

How does diphtheria affects children?

  • ​Diphtheria spreads as droplet infection. After entering respiratory tract of children it infects superficial layer of mucosal wall. Also if the skin comes in contact with exudate it infects the superficial layer of the skin, sometimes causing ulcer. It may infect already ulcerated wound also. 
  • It derives its nutrition by damaging these surfaces. It affects the protein forming ability of cells it infects so that those cells die forming a dead slough on the surface. When this slough is removed bleeding is found underneath the layer.
  • Diphtheria produces diphtheriae toxin. This toxin is particularly produced by strains of C diphtheriae which are able to produce toxin and they are called toxigenic strains. This toxin is protein in nature and is made up of a single polypeptide. Toxigenic strains of C diphtheriae carry the tox structural gene. This gene makes them able to produce the toxin. Toxin producing strains cause the disease in infected host.
  • Strains that can produce large amount of toxin have multiple tox genes. Generally 2 or 3 tox + genes are found inserted into the genome. Expression of these is controlled by bacterium and in turn this toxin causes the disease and its complications. This bacterium with tox gene low concentration of iron to enhance the production of toxin. Toxin comes out of bacterium and it forms 2 chains. Namely chain A and chain B. When the toxin concentration is increased locally it gets absorbed in to the blood. It spreads through circulation to all other organs. Though it can affect any organ of the body it mainly affects the myocardium and peripheral especially the cranial nerves.
  • In first few days of infection the infected site undergoes necrosis. The dead cells, clot and fibrin material gets accumulates at the local site. These all materials form the thick crust at the local area. If it occurs in pharynx it may block the airway. Additional to this crust there is also large amount of inflammation causing local swelling of mucosa and neck. Child typically seen having bull neck. Toxin which have got absorbed in blood cause low platelet count. Toxin can damage kidneys by causing necrosis of kidney tubules. Toxin also damages the heart muscles adversely affecting the pumping function of the heart. This myocardiopathy can cause death also. Additionally toxin can affect the peripheral nerves. The outer layer of peripheral nerves called myelin is totally damaged to cause demyelination of the nerves. These complication usually occurs 2-10 weeks later of initial episode.
  • Majority of children who have diphtheria the most common infected area is tonsils. A few percentage is affected as infection of the ulcer. 


What are the symptoms of diphtheria?

The infection can cause the symptoms ranging from asymptomatic to sever. Many factors affect the severity of disease. Namely these factors are

  • Site of infection
  • Whether the child has received vaccination or not.
  • Formation and distribution of toxin in to the circulation.​
  • Age of the patient.
  • Availability and affordability of antitoxin available for early administration.
  • Availability of treatment of complications.

Tonsils and pharynx:

  • Diphtheria most commonly affects tonsils and pharynx. Patients initially complains of difficulty and pain while swallowing. Initially usually systemic symptoms are very mild or may even absent. Mild grade fever with sometimes headache may be present.
  • For patient who were not vaccinated adequately the infection spreads locally affecting tonsils, pharynx, soft palate and uvula. Eventually larynx and trachea gets involves forming a thick layer with edema. This may obstruct the airway and affects the breathing. It may even lead to death by suffocation.
  • Also externally there is swelling at local site. Neck is swollen to a large extent. This swelling affects and chokes the airway by external pressure. Child tries to relieve this pressure. Child bends the neck backwards to do so. Typically it is describes as bull neck.
  • The toxin is produced locally by the bacteria. This toxin is absorbed into the blood. It needs to be neutralized by as early as possible by the antitoxin. Or it spreads to the other organs affecting heart, nerves and kidneys.

      Larynx: 

  • ​In a minority of patients, the infection may start from larynx. If larynx is the organ affected initially it presents like laryngotracheobronchitis. These cases present with hoarseness of voice or alteration of voice. If infection prohresses further it may obstruct the airway causing suffocation and death. In infants diphtheria may affect nose initially.

       Skin: 

  • The variety of diphtheria where skin is affected is called as cutaneous diphtheria.  Mainly already wounded or bruised sites may get affected by this infection. When the diphtheria affects local wound there is pain, tenderness, and redness and minimal swelling at local site. This leads to local necrosis and lysis of the affected tissue leading to formation of the ulcer. The ulcer is of typical character. The ulcer has sharp borders. It may have a membrane coloured brownish green. This ulcer generally remains for prolonged time. It may take some months to heal.

         Septicaemial:

  • Septicaemia is infection of blood by the bacterium. This condition occurs in minority of patient.
  • When it occurs nothing can save the patient. 
  • Universally all patients getting diphtheria septicaemia die. 



What are complications of diphtheria?

  • Heart disease : though the disease does not directly infect heart the toxin produced by the bacterium reaches heart through circulation. It affects the myocardium by mechanism yet not known.
    • It may lead to various heart conditions.
    • 50% of those who got local infection get heart disease.
    • May cause arrhythmia and death.
    • If patient survives of initial episode the recovery may be complete.​
  • Nerve damage : Diphtheria generally damages the outer layer of the nerves by unknown mechanism.
    • ​The nerve sheaths are destroyed.
    • 50% of all who got disease get nerve palsies.
    • It affects the signal carrying capacities of nerves.
    • This may cause the nerve palsies.
    • Especially cranial nerve palsies.
    • Patient is not able to swallow and this may lead to death if nutrition is not given properly.
    • The recovery is usually complete but minimal residual weakness may remain.
    • It takes months to recover and a lot of expenditure.
  • Kidney damage : The toxin also attacks kidneys by some unknown mechanism.
    • ​Generally kidney tubules are affected.
    • It may lead to tubular necrosis.

How is diphtheria treated?

  • Rather than treating disease it is better to prevent the infection.
  • It can be easily prevented by the vaccine.
  • Even after treatment of disease the complication may occur.
  • It is treated by antibiotics.
  • Also the antitoxin is important to neutralize the already formed toxin.
  • The airway should be managed with priority as it may be fatal.
  • The proper nutrition should be provided as child affected by diphtheria also have the inability to swallow.
  • This surely means patient may need admission for prolonged periods even for months.
  • Contacts should be given preventable care.
  • All the contacts should be vaccinated.
  • Also chemical prophylaxis in form of antibiotics is given.

How to prevent diphtheria and its complications?

  • Diphtheria is vaccine preventable illness.
  • Vaccine is very effective, cheap and universally available
  • generally included in national immunization schedule of all countries.
  • Vaccine has caused very great reduction in incidence of disease and its complications.
  • Generally vaccine is provided as triple in form of DPT or pentavac and hexavalent vaccine variety.
  • All are equally effective.
  • Thus Diphtheria and its complications are vaccine preventable.​

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