Diphtheria: Causes, Pathophysiology, Symptoms, Risk Factors, Complications, Diagnosis and Treatment

It is a disease caused by an infection with the bacteria Corynebacterium diphtheriae.

These bacteria infect and multiply in the respiratory tract, releasing a dangerous toxin that can cause damage to the main organs of the body.

Diphtheria is a dangerous condition and can be fatal in about 5-10% of cases.

An effective diphtheria vaccine has dramatically reduced infection and mortality rates from the disease since its introduction, making diphtheria a rare disease in many countries.


Diphtheria is caused by infection with the bacteria Corynebacterium diphtheriae, which is spread through millions of tiny droplets, which contain many bacteria, when an infected person sneezes or coughs in the air.

If a drop gets into someone else’s nose or mouth, they can become infected with the bacteria.

The bacteria infect the respiratory tract and multiply there, forming a gray membrane that grows from the tonsils to the throat, and sometimes reaches the nose.

Bacteria also release a dangerous toxin.

La bacteria Corynebacterium diphtheriae

Corynebacterium diphtheriae is responsible for both endemic and epidemic diseases.

Diphtheria manifests as a skin infection of the upper respiratory tract and is caused by this gram-positive aerobic bacteria.

The infection usually occurs in the spring or winter months.

It is transmissible for 2 to 6 weeks without antibiotic treatment.

Corynebacterium diphtheriae is a gram-positive, non-encapsulated bacillus, and it is not motile.

The pathogenic strains can cause localized upper respiratory infection, localized skin infections, and, rarely, systemic infection.

Exotoxins are associated with invasive, localized, and systemic forms of this disease.

Exotoxins are encoded in viral bacteriophages, which are transmitted from bacteria to bacteria.

The 3 isolated strains of Corynebacterium diphtheriae include gravis, intermedius, and mitis.

Intermediate is thought to be responsible for the systemic development of the disease, as it is often associated with exotoxin. However, all 3 strains are capable of producing toxins.

Corynebacterium ulcerans is a relatively rare species, most commonly causing cutaneous diphtheria, however this species can rarely cause respiratory symptoms.

The severity of the disease depends on the production of exotoxin.

Corynebacterium ulcerans has also been linked to zoonotic transmission to humans and has been seen more frequently in agricultural communities associated with livestock.


Overcrowding, poor health, poor living conditions, incomplete immunization, and immunocompromised organisms facilitate susceptibility to diphtheria and are risk factors associated with the transmission of this disease.

Human carriers are the main reservoir of infection, however case reports have linked the disease to livestock.

Infected patients and asymptomatic carriers can transmit diphtheria through respiratory droplets, nasopharyngeal secretions, and, rarely, fomites.

In the case of skin disease, contact with wound exudates can cause transmission of the disease to the skin and respiratory tract.

Immunity from exposure or vaccination decreases with time.

An inappropriate increase in previously vaccinated people can increase the risk of contracting the disease from a carrier, even if they had already been adequately immunized previously.

Furthermore, since the advent of widespread vaccination, cases of non-toxigenic strains causing invasive diseases have increased.

Diphtheria adheres to mucosal epithelial cells where exotoxin, released by endosomes, causes a local inflammatory reaction followed by tissue destruction and necrosis. The toxin is made up of two proteins linked together.

Fragment B binds to a receptor on the surface of the susceptible host cell, which proteolytically hides the lipid layer of the membrane allowing segment A.

Molecularly, it has been suggested that cellular susceptibility is also due to the modification of diphtamide, which depends on the type of human leukocyte antigen that predisposes to a more serious infection.

The diptamide molecule is present in all eukaryotic organisms and is localized to a histidine residue of translation elongation factor 2.

This is responsible for the modification of this histidine residue and is the target of diphtheria toxin.

Fragment A inhibits the transfer of amino acids from the RNA translocase to the ribosomal amino acid chain, thus inhibiting protein synthesis is required for normal host cell function.

Diphtheria toxin causes catalytic transfer of NAD to diptamide, which inactivates elongation factor, resulting in inactivation of translation elongation factor 2, resulting in blocking of protein synthesis and subsequent cell death .

When the toxin destroys local tissue, it is transported lymphatically and hematologically to other parts of the body.

Diphtheria toxin can affect organs such as the heart, kidneys, and nervous system.

Nontoxigenic strains tend to produce less severe infections, however, since widespread vaccination, cases of nontoxigenic strains of Corynebacterium diphtheriae causing invasive disease have been documented.

Signs and symptoms

Some people show little or no symptoms after being infected.

When diphtheria symptoms do appear, they usually begin after the incubation period (the period of time that separates the time of infection and the onset of clinical symptoms) and is usually 2 to 6 days after infection.

The symptoms of diphtheria can resemble other medical conditions.

It is necessary to go to the doctor for the diagnosis. The severity of symptoms depends on the location of the inflammation:

General symptoms: vomiting, swollen lymph nodes, altered general condition, agitation, loss of appetite.

  • Nasal diphtheria: nasal discharge of pus with blood (often in babies). It can also be characterized by the presence of serous, unilateral nasal discharge that forms crusts around the external nostrils.
  • Diphtheria of the pharynx: It is the most common type of diphtheria and is associated with the highest toxicity. It is characterized by marked tonsillar and pharyngeal inflammation and the presence of a pseudo-membrane, as well as a sweet smell in the mouth and fever. This tough, yellowish-gray membrane is made up of fibrin, bacteria, epithelial cells, mononuclear and polymorphic cells and adheres firmly to the underlying tissue.
  • Laryngeal diphtheria: wheezing, tightness and choking, hoarseness, causes a hoarse voice, subsequent dyspnea and cyanosis due to respiratory obstruction. Breathing difficulty can go as far as suffocation.
  • Toxic Diphtheria: It is the most serious form of diphtheria that can cause cardiovascular problems, bleeding problems, kidney and liver damage, inflammation of the nerves called neuritis, and a weak heart muscle known as myocarditis that can cause heart rhythm disorders.
  • Cutaneous Diphtheria: Diphtheria bacteria can also infect the skin. This type of diphtheria has milder symptoms and lesions such as impetigo may appear with yellow spots or red and inflamed sores on the skin with grayish patches around it. It is usually associated with burns and poor personal hygiene.

Diphtheria usually attacks the airways, but it can affect any mucous membrane or skin wound.

It is spread by respiratory secretions. Although diphtheria is considered a childhood disease, it increasingly affects adults due to lack of immunization in childhood.

Local manifestations are due to a pseudo-membrane, while systemic manifestations are due to exotoxin formation.

However, the presence of a pseudo-membrane is not essential for diagnosis.

The exotoxin produced by the body is responsible for myocarditis and neuropathy.

Other symptoms such as:

  • Neurological manifestations.
  • Palatal and pharyngeal wall paralysis.
  • Cranial nerve palsy.
  • Paraesthesia
  • Polyneuropathy
  • Rarely encephalitis.
  • Fever and chills
  • Bluish color of the skin.
  • Babeo.

Risk factor’s

People with the highest risk factors are those who are not immunized, children, people who live in or travel to a country where diphtheria is found, including Eastern Europe, Russia, and Southeast Asia.

People living in crowded or other highly unsanitary conditions.

People who suffer from a condition that weakens the immune system , in addition to being in contact with a carrier or sick individual.

A carrier is someone whose cultures are positive for the diphtheria species but who has no signs or symptoms.

Studies show that as the number of asymptomatic carriers decreases, the number of diphtheria cases decreases.


The course of the disease depends on the general condition of the patient and the time of initiation of the appropriate treatment.

The main complications of diphtheria are inflammation of the heart muscle (myocarditis) and the gray membrane in the throat that grows and blocks the airways, both of which can be fatal.

Brain damage from diphtheria toxin has also been observed.

Other complications of diphtheria can include:

  • Inflammation of the lungs ( pneumonia ).
  • Neurological disorders such as mainly diverse paralysis manifested by difficulty swallowing and respiratory depression.
  • Inflammation of the liver
  • Limitation of kidney function.

Methods for diagnosis

Your doctor will make an initial diagnosis of diphtheria based on your symptoms.

They will also take samples from your nose or throat (swab sample) or any skin lesions you may have, and send them to laboratory tests.

The diagnosis is confirmed by the isolation of the pathogen in the collected secretions.

In the early stages, diphtheria can be easily confused with other diseases such as strep throat, infectious mononucleosis, Vincent’s angina, and mycosis.

Diphtheria treatment

Treatment for diphtheria should be immediate.

Because diphtheria toxin can cause damage quickly, treatment will often begin before a final diagnosis is made.

Complete isolation of the patient, bed rest

Due to the altered general condition, hospitalization is often necessary, with bed rest and control of cardiovascular parameters.

The recovery period is usually very long.

Especially after myocarditis, the patient must rest for many weeks.

People suspected of having diphtheria are also placed in isolation for a few weeks until there is no danger of them infecting other people.

Antitoxin to neutralize diphtheria toxin

When your doctor suspects diphtheria, you will be given an injection of antitoxin, a substance that can neutralize diphtheria toxin and make it harmless.

The antitoxin is prepared from horse serum for all cases when diphtheria is suspected.

It should be administered early to avoid further binding of the toxin to tissue receptors, since the fixed toxin is not neutralized by the antitoxin.

Supportive treatment

To help your body recover and keep it out of harm’s way, you may receive supportive treatment that may include:

  • Removal of the gray membrane of the throat by direct laryngoscopy or bronchoscopy: This procedure may be necessary to prevent or relieve airway obstruction.
  • Intubation: insertion of a breathing tube to avoid airway blockage.
  • Electrocardiography of the heart: to detect any irregularities in the function of the heart.
Use of antibiotics

Patients should receive 500 mg of erythromycin every 6 hours for 14 days. Clarithromycin or azithromycin can be used.


Diphtheria can be a mild disease, but it can also become severe.

Death can occur in one in five untreated cases and in up to one in 10 treated cases.



There is an effective vaccine against diphtheria, which is part of the regular vaccination program in many countries.

Vaccination is the best protection against infection.

It can be done from two months of age, in combination with vaccination against pertussis, tetanus and polio.

In their first year of life, children are given this triple vaccine and then several booster doses are given in infancy.

The first 3 vaccines are given at 2, 4, and 6 months of age.

Between 15 and 18 months of age, the fourth injection and a fifth injection are given when a child enters school between 4 and 6 years of age.

With regular checkups for 11- or 12-year-olds, a preteen should receive a dose of the vaccine.

If an adult did not get the vaccine as a preteen or teen, then they should get a dose.

There is no final immunity against the disease, having contracted the disease, as it does not protect against reinfection.

For the prevention of diphtheria in adults, the individual must be immunized with the administration of the toxoid.

Adults over the age of 60 are advised to receive another dose to increase the lowered immunity to the disease.

A booster shot should be done every ten years, and after age 60, the booster should be done every five years.

Because diphtheria is still prevalent in underdeveloped countries, the vaccine is still required in case of exposure to a carrier (a person with diphtheria) who is visiting from another country or if a person travels to an area where diphtheria exists.

Preventive antibiotics

People who have been exposed to a person infected with diphtheria can be treated with antibiotics to prevent infection.

Contact with infected people should be avoided and general hygiene measures (hand washing, mouth protection) must be respected.