Diphtheria vaccination: schedule and revaccination

Diphtheria is an acute bacterial infection, the danger of which is determined by the diphtheria toxin: it damages the heart, peripheral nerves, and adrenal glands, while the dense film in the pharynx can block the airways. In recent decades, widespread vaccination has made the classic respiratory form rare in countries with high coverage, but sporadic cases and outbreaks of the infection continue. Outbreaks of cutaneous diphtheria have been reported in groups with low vaccination coverage and difficult living conditions. [1]

Vaccination remains a key preventative measure. Modern vaccines contain detoxified Corynebacterium diphtheriae toxin adsorbed on aluminum adjuvants, which is safe and promotes the development of antitoxic immunity. Preparations for children under 10 years of age use a "full" dose of toxoid, while those for adolescents and adults use a "reduced" dose with lower reactogenicity while maintaining protection. [2]

International recommendations converge: children receive a primary series in infancy, followed by boosters in preschool and adolescence. Adults receive maintenance boosters every 10 years after a single dose of a combination vaccine with a pertussis component in older adults. This strategy helps maintain herd immunity and reduce the risk of severe outcomes. [3]

In Europe and Spain, the schedule is updated as data accumulates. Spain uses a "lifelong schedule": hexa-vaccines are administered in infancy, followed by boosters at age 6 and, in adolescence, a reduced-dose diphtheria and pertussis antigen. Regions may specify the age of boosters, but the principles are the same. [4]

Briefly about the pathogen and epidemiology

The disease is caused by toxigenic strains of Corynebacterium diphtheriae and Corynebacterium ulcerans. The incubation period is usually 2-10 days. Transmission occurs through airborne droplets and contact with contaminated secretions and objects, and, in the cutaneous form, through broken skin. In unvaccinated individuals, the disease is more severe, with a risk of myocarditis and neuritis. [5]

In the European Union, the infection remains rare, but periodic clusters, including cutaneous forms, are reported in vulnerable groups and travelers from endemic regions. In 2024–2025, the European Centre for Disease Prevention and Control published risk assessments for individual genetic lineages of the pathogen, emphasizing the importance of contact tracing, timely antibiotic prophylaxis, and vaccination of the unvaccinated. [6]

Serological surveys of the population in some countries show that the proportion of people with "complete" antitoxic protection decreases with age, so booster doses in adults remain necessary even with long-standing primary immunization. This explains the universal recommendation for revaccination every 10 years. [7]

Travel to regions with ongoing circulation of toxigenic strains and migration flows maintain the risk of introduction. High vaccination coverage and the readiness of services to promptly manage cases and contacts are the main barriers to spread. [8]

Vaccines: composition, types and age of application

All available diphtheria vaccines are inactivated. The antigen is diphtheria toxoid adsorbed onto aluminum salts. Vaccines are produced only as combination preparations with tetanus toxoid, often with a pertussis component, and often with polio, Haemophilus influenzae, and hepatitis B components. There are no single-component diphtheria vaccines in European practice. [9]

For children under 10 years of age, a "high-dose" diphtheria component is used, such as in childhood hexa-vaccines. For adolescents and adults, a "reduced" dose of diphtheria toxoid is used, which reduces the likelihood of local reactions while maintaining sufficient immunogenicity. The specific choice depends on age and the catch-up immunization situation. [10]

In the United States and several countries, uniform designations are in effect: the childhood vaccine with diphtheria, tetanus, and acellular pertussis is designated as DTaP, the adolescent-adult vaccine as Tdap, and the combination without pertussis as Td. Clinical guidelines allow the use of Tdap or Td for subsequent boosters in adults after a single dose of Tdap. [11]

Hexa-vaccines and combination drugs simplify administration during infancy, while a reduced-antigen load dose for adolescents closes the risk window into adulthood. In routine practice, all vaccines are stored at 2 to 8 degrees Celsius, protected from light, and do not contain live microorganisms. [12]

Table 1. Types of vaccines and where they are used

Type	Composition and purpose	Age groups	Notes
DTaP and hexa vaccines	Full dose diphtheria toxoid, acellular pertussis, tetanus and other antigens	Up to 10 years	The main series in infancy
Tdap	Reduced dose diphtheria toxoid and acellular pertussis plus tetanus	Teenagers and adults	Once in adolescence, then boosters
Td	Reduced dose of diphtheria and tetanus	Adults	Boosters every 10 years after Tdap
Source: Immunization guidelines. [13]

Who should get vaccinated and when?

Infants and children. Routine immunization begins in the first months of life with combination vaccines, followed by a booster in early childhood. The goal is to build antitoxic immunity before entering children's groups. In Spain, a "2 plus 1" schedule is used at 2, 4, and 11 months, using hexa-vaccines. [14]

Preschool and school age. A booster with a reduced antigen load is administered before school, and a second booster is administered at age 6, depending on the national calendar. This maintains high antibody levels against the backdrop of increased contact and seasonal respiratory infections. [15]

Adolescents. A single dose of the adolescent-adult vaccine with a pertussis component and a reduced dose of diphtheria is recommended for ages 10-12 years. This closes the "immune gap" and provides additional protection against whooping cough, which is important for protecting infants in the family. [16]

Adults. After a single dose of Tdap in older adults, diphtheria-tetanus boosters are given every 10 years with Td or Tdap. If a dose of Tdap has not been given in the past, one is given at the next visit, and then regular boosters are continued. [17]

Table 2. Basic schemes by age

Age	Scheme	Target
2, 4 and 11 months	Hexa-vaccines	Formation of primary immunity
6 years	Reduced dose antigen booster	Pre-school advocacy support
10-12 years	Single Tdap	Closing the risk window in adolescence
19 years and older	Booster every 10 years Td or Tdap	Long-term immune support
Source: national and international recommendations. [18]

Catch-up vaccination

If a series has been started but not completed, it is not restarted: the doses already administered are taken into account and the minimum intervals are observed. For children aged 4-6 and 7-18 years, there are tables of "catch-up" regimens with minimum intervals between doses. This approach saves time and reduces the number of visits. [19]

Adolescents and adults without a documented series are prescribed a course with minimal intervals, with the first adult dose preferably being Tdap, and subsequent boosters being Td or Tdap. If there is a long break between doses, the series is continued rather than restarted. [20]

Serological testing is permissible for individuals in risk groups and healthcare workers when indicated, but is not mandatory for routine catch-up immunization. The decision is made on an individual basis, based on calendar annotations and the epidemiological situation. [21]

Some Spanish autonomous regions are further clarifying the age of adolescent boosters and the use of Tdap instead of Td to enhance protection against whooping cough. These updates do not change the goal of maintaining antitoxin protection against diphtheria and regular boosters into adulthood. [22]

Table 3. Minimum intervals in “catch-up” schemes

Situation	Minimum intervals	Comments
Started in childhood, the series is not finished	Intervals according to tables for 4-6 and 7-18 years	Series are not reset
Adult without documented doses	First dose of Tdap, then intervals as noted	Then boosters every 10 years
Long break between doses	Continue taking into account the minimum intervals	No restart required
High risk and health workers	Spot seromonitoring is possible	According to individual indications
Source: schedules and notes. [23]

Special situations: pregnancy, immunodeficiencies, old age and travel

Pregnancy is indicated for one dose of Tdap in each gestational period, preferably in the second or third trimester, to protect the newborn against whooping cough. This dose also maintains maternal antitoxin protection against diphtheria. [24]

People with immunodeficiencies and the elderly may experience a more rapid decline in antibody levels, so it's important to not skip boosters every 10 years and to promptly receive catch-up vaccinations if there are any concerns about your vaccination status. Healthcare personnel are also included in this context. [25]

Travelers to regions with circulating toxigenic strains are advised to ensure they have received the adolescent Tdap vaccine and are current on the 10-year booster. For long trips and volunteer work in refugee camps, prevention options are discussed in advance. [26]

If the pertussis component is contraindicated in adults, a non-pertussis vaccine with a reduced dose of diphtheria toxoid is used. Individual decisions are made based on the patient's medical history and the instructions for specific medications. [27]

Table 4. Who should receive special attention?

Group	What to do now
Pregnant women	Introduce Tdap into current pregnancy
Healthcare workers	Check the status; if Tdap is missing, enter it once.
Elderly	Don't miss 10-year boosters
Travelers	Check that there is a teen Tdap and a current booster
Source: clinical guidelines. [28]

Contact management and post-exposure prophylaxis

If diphtheria is confirmed, health authorities identify close contacts, take nasal and throat swabs, observe them for 7-10 days, and prescribe antibacterial prophylaxis with erythromycin or penicillin. At the same time, they follow up with vaccinations for unvaccinated individuals and those whose status is unknown. [29]

European documents emphasize that even vaccinated contacts require bacteriological testing, as the vaccine prevents severe forms but does not always rule out asymptomatic carriage. During the observation period, contact restrictions may be imposed in accordance with local protocols. [30]

For cutaneous infections caused by non-toxigenic strains, measures are limited to clinical management and general infection control measures. Contact tracing is not required in this case; however, if a toxigenic strain is suspected, the algorithm is the same as for the respiratory form. [31]

After completion of antibiotic therapy, repeat cultures are performed in patients and close contacts to confirm eradication. During the recovery period, the initiated or age-appropriate vaccinations are continued. [32]

Table 5. Post-exposure prophylaxis

Contact	What to do	For what
Close contact with diphtheria erysipelas or a toxigenic strain	Nasal and throat swabs, prophylactic antibiotics, and assessment of vaccination status	Reduce the risk of disease and interrupt transmission
Vaccinated, but the last booster was more than 10 years ago.	Administer a booster as indicated	Restore antibody levels
Unvaccinated or status unknown	Launch catch-up vaccination	Quickly form a defense
Contact with a non-toxigenic strain	Local measures without contact tracing	There is no risk of toxic disease
Source: clinical guidelines. [33]

Safety, tolerability and contraindications

Inactivated diphtheria vaccines are safe. Most commonly reported are mild local reactions at the injection site and short-term malaise. Serious adverse events are extremely rare and are not comparable to the risks of diphtheria itself. The vaccines do not contain live pathogens and are not capable of causing infection. [34]

An absolute contraindication is anaphylaxis to a previous dose or a confirmed allergy to a vaccine component. If adults have previously developed a severe reaction to the pertussis component, a vaccine without the pertussis component is used for maintenance boosters. The doctor makes this decision. [35]

Pregnancy is not a contraindication to the administration of the adolescent-adult combination dose. In fact, administration at each gestational period is the standard for protecting infants from whooping cough while simultaneously maintaining maternal antitoxin protection. [36]

Storage of all medications at a temperature of 2 to 8 degrees Celsius and protection from light are essential to maintain efficacy. Freezing is unacceptable due to the risk of loss of potency and increased reactogenicity. [37]

Table 6. Common reactions and what to do

Reaction	How often	Tactics
Pain, redness, and swelling at the injection site	Often	Symptomatic therapy if necessary
Short-term malaise, subfebrile temperature	Sometimes	Observation, antipyretic if necessary
Allergic reaction	Rarely	Emergency care, further vaccine without the problematic component
In pregnant women	The data is favorable	Vaccination is recommended during every pregnancy.
Source: manuals and reviews. [38]

Practical answers to frequently asked questions

Is testing required before vaccination? No testing is required for routine vaccination. Exceptions are possible for individuals with special conditions, as determined by a physician. In areas of infection, swabs are mandatory from contacts. [39]

What if doses are missed? The series is continued with the minimum intervals. A restart is not necessary, regardless of the length of the break. [40]

How often should adults receive a booster? After a single dose for adolescents and adults, maintenance boosters are administered every 10 years with a reduced-dose diphtheria toxoid. If there is no history of Tdap, it is administered once at the next visit. [41]

Can they be combined with other vaccines? Yes, inactivated vaccines can be administered simultaneously at different sites. Combining is a common practice in pediatrics and simplifies schedule adherence. [42]

Table 7. Storage and administration technique

Parameter	Requirement
Storage temperature	From 2 to 8 degrees Celsius
Protection from light	Required
Shake the suspension before administration	Necessarily
Compatibility with other inactivated vaccines	Allowed for administration to different areas
Source: instructions and chapters of reference books. [43]

Brief conclusions

1. Diphtheria remains controllable with high vaccination coverage, but spread and cutaneous forms are possible, so up-to-date doses and proper contact management are important. [44]
2. Children receive a primary series in infancy and boosters in preschool and adolescence, while adults receive boosters every 10 years after a single dose of Tdap. [45]
3. In Spain, a "lifelong calendar" approach is in place with hexa-vaccines in infancy and a booster in adolescence; autonomies can specify the age of administration. [46]
4. In infection foci, contacts are subject to observation, smears and antibiotic prophylaxis, and unvaccinated individuals are subject to urgent vaccination. [47]