Primary prevention
Universal immunization with a diphtheria toxoid-containing vaccine is the only effective measure. The efficacy of this approach is strongly demonstrated by historical data; in the 1920s, 100,000-200,000 cases were reported each year in the US, but following the introduction of diphtheria toxoid-containing vaccines in the 1940s, the number of cases declined, and now an average of <1 case per year is reported in the US.[27] Decades of worldwide experience have confirmed diphtheria toxoid vaccines as safe and well tolerated.
Diphtheria vaccines are made from cell-free purified toxin, treated with formaldehyde, and adsorbed onto an adjuvant. They are produced in two strengths, according to the diphtheria toxoid content; the higher strength is abbreviated to "D" and the lower strength is abbreviated to "d". In general, vaccines containing the higher dose of toxoid (D) are used to achieve a satisfactory primary immune response in younger children. Vaccines containing the lower dose of toxoid (d) are used for older age groups and boosters, where they provide a satisfactory immune response with a lower risk of adverse reactions (e.g., pain, redness, and tenderness at the injection site).[32][33] Monovalent diphtheria vaccines are not available, so immunization can only be given as part of combined products.
In the US, diphtheria vaccination is usually given during infancy with DTaP, a vaccine that contains diphtheria toxoid in combination with tetanus toxoid and acellular pertussis vaccine. The Advisory Committee on Immunization Practices (ACIP) recommends that a series of 5 doses of DTaP vaccine are given at 2, 4, and 6 months, at 15-18 months, and at 4-6 years of age.[34] The fourth dose may be administered early, from age 12 months, if at least 6 months has passed since the third dose. If the fourth dose of DTaP vaccine is inadvertently administered early, ACIP recommends that it does not need to be repeated if it was administered at least 4 months after the third dose, and the child was 12 months of age or older.[34] The fifth dose of DTaP is not considered necessary if the fourth dose was administered at age 4 years or older and at least 6 months after the third dose.[34]
A hexavalent vaccine is also approved by the US Food and Drug Administration to prevent diphtheria, tetanus, pertussis, polio, Haemophilus influenzae b, and hepatitis B. The DTaP-IPV-Hib-HepB vaccine is licensed for use in children ages 6 weeks to 4 years and is indicated for the primary vaccination series in infants at ages 2, 4, and 6 months.[35]
Children ages 7 to 18 years who are not fully immunized with DTaP vaccine should receive Tdap vaccine as one dose (preferably the first) in the catch-up series; if additional doses are needed, Td or Tdap should be used. For children ages 7 to 9 years who receive a dose of Tdap as part of the catch-up series, an adolescent Tdap vaccine dose at age 11 to 12 years may be administered. Children age 10 years who receive a dose of Tdap vaccine as part of the catch-up series do not require the routine Tdap dose at age 11 to 12 years.[34]
Adolescents ages 11 to 12 years receive a single dose of Tdap vaccine for booster immunization if they have completed the recommended DTaP vaccination series.[32][34]
Thereafter, adults should receive a booster dose of Td or Tdap vaccine every 10 years (Td is a combination vaccine containing tetanus and diphtheria toxoids).[32][36] ACIP recommends administering one dose of Tdap vaccine to pregnant women during each pregnancy (preferably between 27 and 36 weeks' gestation) regardless of time since prior Td or Tdap vaccination.[36][37] Tdap vaccination during pregnancy is not associated with an increased risk of infant hospitalization or death in the first 6 months of life.[38]
Adolescents and adults with unknown or incomplete history of a 3-dose primary series should receive a primary series of 3 doses of Td-containing vaccine. The first two doses should be administered at least 4 weeks apart, and the third dose 6 to 12 months after the second dose. For added protection against pertussis, Tdap vaccine should be used for at least one of the doses in the three-dose primary series (preferably the first dose).[32][36]
For travelers to countries where diphtheria is still endemic, ensure completion of a proper immunization schedule, including administration of booster doses if indicated.[12]
Secondary prevention
People traveling to areas where diphtheria is endemic should have their vaccination status checked and updated.[12]
Close contacts and household members of patients should be followed throughout the incubation period for evidence of infection. Nasopharyngeal, oropharyngeal, and cutaneous lesion cultures should be taken.[42] Prophylactic antibiotics should be given, irrespective of the immunization status, although efficacy has not been proved.[42] Individuals who are not fully immunized (i.e., have received fewer than three doses of vaccine) or whose immunization status is unknown should be fully vaccinated.[42] Children who have not received their fourth dose of vaccine should be immunized. Previously immunized patients should receive a booster vaccine if they have not received one in the previous 5 years.
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