[Significance Of Toxoids In Active Immunity Pdf Download
Ainoha Sistek
This document discusses the significance of toxoids in active immunity. It defines key terms like vaccines, toxoids, live vaccines, attenuated live vaccines, inactivated vaccines, polysaccharide vaccines, and surface antigen vaccines. It explains that toxoids create immunity to the toxins produced by pathogens rather than the pathogens themselves. Various routes of administration are outlined including subcutaneous, intramuscular, oral, intradermal, and intranasal. Vaccination schedules for primary vaccination and booster doses are also summarized.Read less
C. diphtheriae is an aerobic, gram-positive bacillus. Toxin production (toxigenicity) occurs only when the bacillus is itself infected (lysogenized) by specific viruses (corynebacteriophages) carrying the genetic information for the toxin (tox gene). Diphtheria toxin causes the local and systemic manifestations of diphtheria.
C. diphtheriae has four biotypes: gravis, intermedius, mitis, and belfanti. All biotypes can become toxigenic and cause severe disease. All isolates of C. diphtheriae should be tested for toxigenicity.
Susceptible persons may acquire toxigenic diphtheria bacilli in the nasopharynx. The organism produces a toxin that inhibits cellular protein synthesis and is responsible for local tissue destruction and formation of the pseudomembrane that is characteristic of this disease. The toxin produced at the site of the membrane is absorbed into the bloodstream and then distributed to the tissues of the body. The toxin is responsible for major complications such as myocarditis, polyneuropathies, and nephritis, and can also cause thrombocytopenia.
Non-toxin-producing C. diphtheriae strains can cause mild to severe exudative pharyngitis. Severe cases with pseudomembranes caused by such strains have been reported rarely; it is possible that these infections were caused by toxigenic strains that were not detected because of inadequate culture sampling. Other manifestations of nontoxigenic C. diphtheriae infection include cutaneous lesions, endocarditis, bacteremia, and septic arthritis.
The incubation period for diphtheria is 2 to 5 days, with a range of 1 to 10 days. Disease can involve almost any mucous membrane. In untreated people, organisms can be present in discharges and lesions 2 to 6 weeks after infection. For clinical purposes, it is convenient to classify diphtheria by anatomic site: respiratory (pharyngeal, tonsillar, laryngeal, nasal) and non-respiratory (cutaneous and other mucus membranes) disease.
The most common sites of diphtheria infection are the pharynx and the tonsils. Infection at these sites is usually associated with substantial systemic absorption of toxin. The onset of pharyngitis is gradual. Early symptoms include malaise, sore throat, anorexia, and low-grade fever (less than 101F). Within 2 to 3 days, a bluish-white membrane forms and extends, varying in size from covering a small patch on the tonsils to covering most of the soft palate. Often by the time a physician is contacted the membrane is greyish-green or, if bleeding has occurred, black. There is a minimal amount of mucosal erythema surrounding the membrane. The membrane is firmly adherent to the tissue, and forcible attempts to remove it cause bleeding. Extensive membrane formation may result in respiratory obstruction.
Laryngeal diphtheria can be either an extension of the pharyngeal form or can involve only this site. Symptoms include fever, hoarseness, and a barking cough. The membrane can lead to airway obstruction, coma, and death.
The onset of anterior nasal diphtheria looks much like the common cold and is usually characterized by a mucopurulent nasal discharge that may become blood-tinged. A white membrane usually forms on the nasal septum. The disease is usually fairly mild because of apparent poor systemic absorption of toxin from this location, and it can be terminated rapidly by diphtheria antitoxin and antibiotic therapy.
Skin infections may be manifested by a scaling rash or by ulcers with clearly demarcated edges and an overlying membrane, but any chronic skin lesion may harbor C. diphtheriae along with other organisms. Cutaneous diphtheria is quite common in the tropics and is probably responsible for the high levels of natural immunity found in these populations. Infection with toxigenic strains appears to result less frequently in systemic complications with cutaneous compared to other forms of diphtheria. C. diphtheriae isolated from cutaneous cases in the United States typically has been nontoxigenic, although recently a number of imported toxigenic cutaneous cases have been identified.
Most complications of diphtheria, including death, are caused by effects of the toxin. The severity of the disease and complications are generally related to the extent of local disease. The toxin, when absorbed, affects organs and tissues distant from the site of invasion. The most frequent complications of diphtheria are myocarditis and neuritis.
Neuritis most often affects motor nerves and usually resolves completely. Paralysis of the soft palate is most frequent during the third week of illness. Paralysis of eye muscles, limbs, and the diaphragm can occur after the fifth week. Secondary pneumonia and respiratory failure may result from diaphragmatic paralysis.
Diagnosis of respiratory diphtheria is usually made based on clinical presentation because it is imperative to begin presumptive therapy quickly. Non-respiratory diphtheria, such as cutaneous diphtheria, may not be clinically suspected and therefore diagnosis is typically based on the laboratory finding.
If antibiotic therapy was started prior to specimen collection from a suspected diphtheria case, and culture was negative for C. diphtheriae, two sources of evidence can help support presumptive diagnosis:
Diphtheria antitoxin, produced in horses, has been used for treatment of respiratory diphtheria in the United States since the 1890s. It typically is not administered in cases of non-respiratory diphtheria and it is not indicated for prophylaxis of diphtheria patient contacts. Diphtheria antitoxin is available only from CDC, through an Investigational New Drug (IND) protocol. Diphtheria antitoxin does not neutralize toxin that is already fixed to tissues, but it will neutralize circulating toxin and prevent progression of disease.
In addition to diphtheria antitoxin, patients with respiratory diphtheria should also be treated with antibiotics. The disease is usually no longer contagious 48 hours after antibiotics have been given. Elimination of the organism should be documented by two consecutive negative cultures taken 24 hours apart, with the first specimen collected 24 hours after therapy is completed.
Diphtheria disease might not confer immunity. Unvaccinated or incompletely vaccinated persons recovering from diphtheria should begin or complete active immunization with diphtheria toxoid during convalescence.
Vaccination history of close contacts of diphtheria patients should also be assessed: if vaccination history is incomplete or unknown, the contact should receive a dose of diphtheria toxoid-containing vaccine immediately, and the vaccination series should be completed according recommendations from the Advisory Committee on Immunization Practices (ACIP). If the contact is up-to-date according to ACIP recommendations but the last dose was more than 5 years ago, a diphtheria toxoid-containing vaccine should be immediately administered. In addition, close contacts should receive a single intramuscular dose of benzathine penicillin G or a 7- to 10-day course of oral erythromycin. Benzathine penicillin G should be given to contacts for whom surveillance cannot be maintained for 7 to 10 days. Contacts should be closely monitored and begin diphtheria antitoxin treatment at the first signs of illness.
Diphtheria occurs worldwide, particularly in countries with suboptimal vaccination coverage. Diphtheria is rare in industrialized countries, including the United States. Because it is a rare disease, seasonal and geographic distribution patterns are no longer observed.
From 1996 through 2018, 14 cases of diphtheria were reported in the United States, an average of less than 1 per year. One fatal case occurred in a 63-year-old male returning to the United States from a country with endemic diphtheria disease.
Diphtheria toxoid is combined with tetanus toxoid as diphtheria and tetanus toxoid (DT) vaccine or tetanus and diphtheria toxoid (Td [Tenivac and Tdvax]) vaccine. Diphtheria toxoid is also combined with both tetanus toxoid and acellular pertussis vaccine as DTaP (Infanrix and Daptacel) or Tdap (Boostrix and Adacel) vaccines. Td contains reduced amounts of diphtheria toxoid compared with DT. DTaP and Tdap contain the same pertussis components, but Tdap contains a reduced quantity of some pertussis antigens and diphtheria toxoid. Boostrix contains a reduced quantity of tetanus toxoid compared to Infanrix.
Children younger than age 7 years should receive DTaP vaccine or DT vaccine (in instances where the pertussis vaccine component is contraindicated or where the physician decides that pertussis vaccine is not to be administered). Persons age 7 years or older should receive the Td vaccine or Tdap vaccine, even if they have not completed a series of DTaP or DT (Tdap would be off-label for children age 7 through 9 years but is still recommended by ACIP). Tdap (Boostrix) is approved for persons age 10 years or older; Tdap (Adacel) is approved for persons age 10 through 64 years. DTP vaccines are combined diphtheria and tetanus toxoids and whole cell pertussis vaccine, but none are currently licensed in the United States.
There are five combination vaccines that contain DTaP vaccine. DTaP-HepB-IPV (Pediarix) is licensed for the first 3 doses of the DTaP series among children age 6 weeks through 6 years. DTaP-IPV/Hib (Pentacel) is licensed for the first 4 doses of the component vaccines among children age 6 weeks through 4 years. DTaP-IPV (Kinrix) is licensed only for the fifth dose of DTaP and fourth dose of IPV among children age 4 through 6 years. DTaP-IPV (Quadracel) is licensed only for the fifth dose of DTaP and fourth or fifth dose of IPV among children age 4 through 6 years. DTaP-IPV-Hib-HepB (Vaxelis) is licensed for use in children age 6 weeks through 4 years.
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