Description
The diphtheria toxoid is produced by the pathogenic agent of diphtheria, corynebacterium diphteriae, which is an aerobic, immobile, gram-positive, non-sporogenic bacterium of the Actinomycetales family The cause of diphtheria, an infectious disease which is often accompanied by life-threatening complications and late effects, is not the corynebacterium diphtheria itself but the diphtheria toxoid synthesised by it. The toxoid interrupts protein biosynthesis by inhibiting the elongation factor, thus affecting the stability of the cell membrane and damaging or even destroying the infected cells.
Diphtheria can be found worldwide, more frequently in temperate climatic zones in autumn and winter. Humans are the only reservoir for the pathogen. The disease has been successfully controlled by active immunisation (toxoid vaccine) but not eradicated completely. During the fifties, as many as 4300 people still died of diphtheria in Germany. At present, 60% of Germans between the ages of 30 and 40 have insufficient protection against the disease. Due to these vaccination gaps, diphtheria continues to occur in limited areas. The success of vaccination in western industrial countries is clearly shown by figures: in 1920, the U.S. recorded around 150,000 cases of diphtheria per year, 15,000 of which were fatal. Between 1980 and 1986, only 24 cases, two of them fatal, occurred. In the territory of the former Soviet Union a strong increase in diphtheria cases was found during the first half of the nineties, with for example 50,000 infections and around 2,000 fatalities in each of the years 1994 and 1995.
Since diphtheria still occurs in many developing and some east European countries, the danger of introducing the virus is omnipresent, especially in the U.S., France and Germany.
The disease is transmitted from person to person by aerosols and smear infection, skin diphtheria also by direct contact, but rarely via contaminated objects. People who already suffer from diphtheria carry a higher risk of transmitting the pathogen than individuals who are infected but not yet ill. Contagiousness exists as long as the pathogen is present in secretions and wounds. When treated, diphtheria is only contagious for two to four days. In untreated cases the period of contagiosity is two to four weeks.
The incubation period is on average two to five days, in rare cases eight days. The disease mainly starts with a general feeling of illness, fever (up to 39°C), a sore throat, stomachache and joint pains. Symptoms of pharyngeal and laryngeal diphtheria include pharyngitis and tonsillitis with a grey-white coating (pseudomembrane), which often extends from the tonsils to the palate and the uvula, in rare cases even to the larynx, trachea and bronchi, leading to local tissue necrosis. A sweetish breath, which can be perceived from some distance, is a particular characteristic of the disease. Nasal diphtheria, which mainly occurs in infants and small children, manifests as nasal discharge. Skin diphtheria is predominantly a tropical disease. In western countries, it mainly affects risk groups, such as homeless persons, or alcohol or drug addicts. The symptoms are similar to those of other bacterial skin infections. The pathogen enters the body via skin wounds. Conjunctival diphtheria is characterised by bloody watery secretion and membrane formation at the conjunctiva. Often the cornea is also affected.
During the course of the disease, barking cough with stridor, hoarseness, paralysis of the soft palate, vomiting and lymph node swelling may develop. The toxic effect of the exotoxin secreted by the pathogen (diphtheria toxoid) causes the dreaded life-threatening toxic courses with myocarditis, paralysis of the motoric cerebral nerves and liver and kidney disorders.
An initial diagnosis of diphtheria can often be made from clinical symptoms, enabling treatment to be started immediately. For confirmation of acute diphtheria, direct detection with cultivation of the bacteria is possible, but takes several days. Microscopic diagnosis is insufficient. The identification of corynebacteria types expressing the diphtheria toxoid via detection of the toxoid-encoding gene and the 16S rRNA sequence using PCR is restricted to specialised laboratories.
The determination of human antibodies against diphtheria toxoid is relevant in evaluating an unclear immune status, serologically clarifying the anti-diphtheria toxoid immunity status and monitoring the immune response in certain basic diseases (e.g. malignoma, AIDS, haematological diseases) or therapeutic regimes (e.g. immunosuppression, cytostatic drugs, radiation treatment). Detection of the pathogen, suspected cases of diphtheria, diphtheria infections and fatal cases have been notifiable in Germany since 1st January 2001.
The most important therapeutic measure is the administration of diphtheria antitoxin, a horse immune serum. The antitoxin only neutralises the freely circulating toxin in the blood. The second measure is an antibiotic therapy to prevent the bacteria from spreading. Depending on the complications, intensive medical treatment may be necessary, e.g. timely intubation or operative removal of the pseudomembranes blocking the respiratory tract.
Although the frequency of the disease has been significantly reduced by passive immunisation using serum introduced by the physician and Nobel prize winner Emil von Behring and by active immunisation using diphtheria toxoid introduced by Gaston Ramon, diphtheria has not been eliminated, unlike e.g. smallpox. Therefore, active immunisation remains the main prophylaxis with respect to diphtheria. Only vaccination provides sufficient protection from the disease. Country-specific recommendations for vaccination should be consulted for advice about the recommended time frame and coverage of basic immunisation, booster shots and catch-up vaccinations (for example, in Germany: Standing Vaccination Committee (STIKO) at the Robert-Koch Institute). Almost 90% of children in Germany are protected from diphtheria by vaccination, whereas only a quarter of adults have protection. This also applies for the US. Adults should therefore consider a booster shot when their last vaccination against diphtheria dates back more than ten years. It must be taken into account that even immunity after recovery from the disease does not persist for life