Patient Presentation
A group of medical students were reviewing common vaccines with their preceptor. The students were confused by the vaccine names and why there were so many different ones. The preceptor noted that much of it had to do with history and vaccine improvement to increase their efficacy and decrease side effects. “For example, there are 4 current tetanus shots in the US and each has a different name,” she told the students. “You can tell what is in the vaccine by if the letter is capitalized or lower case. DTaP for example has a higher amount of diphtheria, and acellular pertussis which are written in upper case, but Tdap is written in lower case and those amounts are smaller. In general the higher amount is given to younger children to help induce better immunity and the lower amount is given to older kids, teenagers and adults to boost immunity. I’ve never seen diphtheria but it was one of those diseases that we still need to know about. I’ve seen other things that cause severe pharyngeal exudate and epiglottitis and those are horrible and really scary. I never want to think about what diphtheria would be like. This is why having a highly vaccinated public is so very important.”
Discussion
Diphtheria is caused by the toxin produced by Corynebacterium diphtheriae. Two other Corynebacterium species (C. ulcerans and C. pseudotuberculosis) may produce diphtheria toxin; both species are zoonotic. Diphtheria is spread by respiratory droplets and also contact with open ulcers or sores. Incubation period is 1-10 days with a usual period of 2-5 days. The bacteria attacks the respiratory tract mucosa causing cellular death which in turn causes a “pseudomembrane” of tissue to build up causing respiratory distress and possible death due to airway obstruction (5-10% for general population but up to 20% for those 40 years). Other problems include fever, sore throat, difficulty swallowing, loss of appetite, neck swelling due to lymphadenopathy, fatigue and weakness. Myocarditis, peripheral neuropathy and kidney damage can occur. Cutaneous diphtheria also appears as skin sores/ulcers and rash.
Diagnosis is suspected clinically with throat (under the membrane is best) or skin culture confirmation. Specific testing for toxin is by an immunodiffusion assay called the Elek test which is only performed by the CDC in the U.S.. Diphtheria is a reportable disease in the U.S.. Patients are treated with diphtheria anti-toxin to stop the anti-toxin effects and antibiotics (penicillin or erythromycin are recommended) to treat the bacteria. Immunization with appropriate vaccines and prophylactic antibiotics are also recommended for close contacts.
Differential diagnosis includes Group A streptococcus, Staphylococcus aureus, adenovirus, cytomegalovirus, Epstein-Barr virus, herpes virus and Candida albicans.
Non-toxin-producing strains of C. diphtheriae can also cause disease. It is generally less severe, potentially causing a mild sore throat and, rarely, a membranous pharyngitis. Invasive disease, including bacteremia and endocarditis, has been reported for non-toxin-producing strains of C. diphtheriae.
Learning Point
Diphtheria vaccine is one of the oldest produced vaccines, is safe and highly effective (90-100% depending on the study). It was first made in 1926, and first combined with pertussis and tetanus in 1943, and first registered for use in the US in 1948. There are 4 currently licensed vaccines to prevent diphtheria: DTaP, Tdap, DT, and Td. Infants and children < 7 years old should receive DTaP or DT. Those 7 years and older should receive Tdap or Td. Current US schedule is for the vaccine to be given at 2, 4, 6, and 15-18 months, 4-6 years with boosters at 11-12 years and every 10 years after that. Some people will give adult boosters at least on "0" birthdays, ie. 20 years, 30 years, 40 years etc.
Diphtheria is always in combination with tetanus (T) and may include pertussis (aP or acellular pertussis). A systemic review found that a 5-component vaccine TdaP vaccine was more efficacious than a single component vaccine; the component differences were in the pertussis component(s). These authors also noted that other good quality studies showed co-administration with other vaccines did not have any clinically relevance interference with efficacy. The potential side effects of the vaccine can be reviewed here. To also note, thimersol was taken out of childhood vaccines in 2001, and a review of current components of vaccines can be found here.
As noted diphtheria vaccine is highly effective but antibody levels decrease with time and boosters are needed. In populations it is important to maintain high antibody levels as there is only limited availability of diphtheria antitoxin. The rise of non-toxigenic strains has caused scientists to consider producing diphtheria vaccines with antigens for non-toxigenic strains. An initial study for such a vaccine was published in 2019. The vaccine may also be changing as the pertussis component may be moving to a nasal vaccine to improve pertussis’s immunogenicity.
Questions for Further Discussion
1. What other infectious diseases are toxin-mediated? A review can be found here
2. Why are pregnant women recommended to receive a Tdap vaccine during pregnancy?
3. What are recommendations for tetanus shot administration for wounds?
Related Cases
- Disease: Diphtheria | Immunization
- Symptom/Presentation: Health Maintenance and Disease Prevention
- Age: All
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for these topics: Diphtheria and Tetanus, Diphtheria and Pertussis Vaccines.
To view current news articles on this topic check Google News.
To view images related to this topic check Google Images.
To view videos related to this topic check YouTube Videos.
Squeri R, Genovese EC. Immunogenicity and antibody persistence of diphteria-tetanus-acellular pertussis vaccination in adolescents and adults: a systematic review of the literature showed different responses to the available vaccines. J Prev Med Hyg. 2021;61(4):E530-E541. doi:10.15167/2421-4248/jpmh2020.61.4.1832
Gidengil C, Goetz MB, Newberry S, et al. Safety of vaccines used for routine immunization in the United States: An updated systematic review and meta-analysis. Vaccine. 2021;39(28):3696-3716. doi:10.1016/j.vaccine.2021.03.079
Prygiel M. Mosiej E, Gorska P, Zasada AA. Diphtheria-tetanus-pertussis vaccine: past, current & future. Future Micobiol. 2021;17(3):185-97. doi:10.2217/fmb-2021-0167
Centers for Disease Control. Diphtheria. Published September 9, 2022. Accessed June 26, 2023. https://www.cdc.gov/diphtheria/index.html
Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa