Diphtheria: Videos & Practice Problems

Diphtheria, caused by the gram-positive, non-endospore-forming rod Corynebacterium diphtheriae, is an upper respiratory infection transmitted via respiratory droplets. The bacteria produce a potent exotoxin encoded by a lysogenic bacteriophage, inhibiting protein synthesis and causing tissue damage, including a characteristic pseudomembrane that can obstruct airways. Diagnosis involves bacterial culture and immunoassays like the ELIC test or PCR for the exotoxin gene. Treatment combines antibiotics such as erythromycin or penicillin with antitoxins to neutralize the exotoxin. Immunity is provided by the DTaP toxoid vaccine, targeting the exotoxin to prevent severe systemic effects and complications.

Diptheria

Diphtheria is a serious upper respiratory tract infection caused by the bacterium Corynebacterium diphtheriae, which is a gram-positive, non-endospore-forming rod-shaped bacterium often described as club-shaped due to its thicker ends. The pathogenicity of C. diphtheriae arises from an exotoxin it produces, but only when the bacterium is lysogenized by a bacteriophage—a virus that infects bacteria. This phage carries the gene encoding the exotoxin, meaning the bacteria alone are not harmful unless infected by the phage.

The exotoxin is a potent protein composed of two parts: one facilitates entry into host cells, and the other enzymatically inhibits protein synthesis by inactivating elongation factor-2 (EF-2). This inhibition leads to cell death and can cause severe complications such as heart, kidney, and nerve damage, potentially resulting in fatality. While C. diphtheriae can also cause skin infections, these are less dangerous because the exotoxin is poorly absorbed through the skin.

Diphtheria spreads primarily through respiratory droplets during close contact, but transmission can also occur via contact with contaminated objects. The hallmark symptom is the formation of a pseudomembrane in the throat, a thick layer of fibrin and dead cells that can obstruct the airway and cause suffocation. This pseudomembrane adheres tightly to the underlying tissue, making removal difficult and potentially harmful. Other symptoms include a sore throat, fever, weakness, and a characteristic swollen neck known as "bull neck."

Diagnosis involves confirming the presence of C. diphtheriae and its exotoxin. This is achieved through bacterial culture on selective and differential media, immunoassays such as the enzyme-linked immunosorbent assay (ELISA) to detect the exotoxin, and molecular techniques like polymerase chain reaction (PCR) to identify the toxin gene.

Treatment combines antibiotics, such as erythromycin or penicillin, to eliminate the bacteria, with administration of diphtheria antitoxin to neutralize circulating exotoxin. The antitoxin is crucial because the toxin irreversibly inhibits protein synthesis within host cells, and antibiotics alone cannot reverse this damage.

Prevention is effectively managed through vaccination with the DTaP vaccine, which includes a diphtheria toxoid component. This toxoid vaccine stimulates immunity against the exotoxin rather than the bacteria itself, providing protection against the most dangerous effects of the disease. Booster vaccines such as Tdap and Td maintain immunity in older children and adults, differing slightly in formulation but continuing to protect against diphtheria and tetanus.

Diphtheria Example 1

Diphtheria is a serious bacterial infection caused by Corynebacterium diphtheriae, which produces a harmful exotoxin responsible for the disease's dangerous effects. Proper treatment of diphtheria requires both antibiotics and an antitoxin. Antibiotics target and kill the bacteria, while the antitoxin neutralizes the exotoxin already present in the body, preventing further cellular damage. It is important to note that antiviral medications are not used in treating diphtheria, as the infection is bacterial, not viral.

Diphtheria can manifest as a skin infection, but these cases are generally less severe than respiratory diphtheria. The respiratory form is more dangerous due to the production of exotoxin and the formation of a pseudomembrane—a layer of dead cells and fibrin—that can block the airway and cause suffocation.

The disease can be fatal through multiple mechanisms. The pseudomembrane can physically obstruct the airway, leading to suffocation. Additionally, the exotoxin can spread systemically, causing nerve, heart, and other cellular damage by inhibiting protein synthesis within cells. This occurs because the exotoxin blocks translation, preventing cells from producing essential proteins, which can result in cell death and organ failure.

The diphtheria vaccine is a toxoid vaccine, meaning it does not prevent infection by Corynebacterium diphtheriae itself but protects against the harmful effects of the exotoxin. By stimulating immunity to the exotoxin, the vaccine prevents the severe symptoms and complications of diphtheria, even if the bacteria are present. This distinction is crucial for understanding how vaccination reduces disease severity rather than bacterial colonization.

Which of the following microscope slides shows C. diphtheriae?

• A. Slide 1
  
• B. Slide 2
  
• C. Slide 3
  
• D. Slide 4
  

Answer: (B)

Not all Corynebacterium diphtheriae cause diphtheria. What is different about the bacteria that do?

• A. They contain cord factor as part of the mycolic acid component of their cell wall.
• B. They have been infected with a phage that codes for an exotoxin.
• C. They infect the alveoli rather than being sequestered to the upper respiratory tract.
• D. They are part of a pseudomembrane, which allows them to become established in the airway more easily.

Answer: (B)

To prevent the spread of diphtheria, which vaccination is given to children starting at 2 months old?

• A. BCG vaccine.
• B. MMR vaccine.
• C. Tdap vaccine.
• D. DTaP vaccine.

Answer: (D)

Here’s what students ask on this topic:

What causes diphtheria and how does the bacterium produce its toxin?

Diphtheria is caused by the bacterium Corynebacterium diphtheriae, a gram-positive, non-endospore-forming rod. The bacterium itself is not harmful unless it is infected by a lysogenic bacteriophage (a virus that infects bacteria). This phage carries the gene for an exotoxin, which the bacterium produces only when lysogenized. The exotoxin is a protein with two parts: one part allows it to enter host cells, and the other inhibits protein synthesis by inactivating elongation factor-2, effectively shutting down protein production. This toxin causes cell death and tissue damage, leading to severe symptoms such as the formation of a pseudomembrane in the respiratory tract and systemic effects like heart, kidney, and nerve damage.

How is diphtheria transmitted and what are its main symptoms?

Diphtheria is primarily transmitted through respiratory droplets during close contact with an infected person. It can also spread via contact with contaminated objects. The main symptoms result from the exotoxin's effects and include a sore throat, fever, and the formation of a characteristic pseudomembrane—a thick layer of dead cells and fibrin that can block the airway. Another notable symptom is a swollen neck, often called "bull neck." As the toxin spreads, it can cause weakness and damage to the heart, kidneys, and nerves, potentially leading to severe complications or death if untreated.

How is diphtheria diagnosed in the laboratory?

Diagnosing diphtheria involves confirming the presence of Corynebacterium diphtheriae and verifying that it produces the exotoxin. This is done by culturing the bacteria on selective and differential media. Additionally, specialized tests like the Elek test, an immunoprecipitation assay, detect the exotoxin production by using antibodies. Modern molecular methods such as PCR can identify the gene encoding the exotoxin. Both bacterial presence and toxin production must be confirmed for an accurate diagnosis, as the bacteria alone are not harmful without the toxin.

What treatments are used for diphtheria and why is antitoxin important?

Treatment of diphtheria includes antibiotics such as erythromycin or penicillin to kill the Corynebacterium diphtheriae bacteria. However, because the exotoxin causes the most severe damage, an antitoxin is also administered to neutralize circulating toxin molecules. The antitoxin binds to the toxin, preventing it from entering cells and inhibiting protein synthesis. This combination of antibiotics and antitoxin is critical to reduce both bacterial infection and toxin-mediated tissue damage, improving patient outcomes and preventing complications like airway obstruction and organ damage.

How does the diphtheria vaccine work and what types are available?

The diphtheria vaccine is a toxoid vaccine, meaning it contains an inactivated form of the exotoxin that stimulates the immune system to produce antibodies against the toxin, not the bacteria itself. This immunity protects against the harmful effects of the toxin. The vaccine is commonly given as part of the DTaP vaccine, which also protects against tetanus and acellular pertussis, starting at two months of age. Booster vaccines like Tdap or Td are given later in life to maintain immunity. These vaccines differ slightly in formulation but all include protection against diphtheria toxin.