DPT vaccine

For other uses, see DTP (disambiguation).
TDAP redirects here. For the trade organisation in Pakistan, see Trade Development Authority (Pakistan).
DPT vaccine
Combination of
Diphtheria vaccine Vaccine
Pertussis vaccine Vaccine
Tetanus vaccine Vaccine
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DPT (also DTP and DTwP) refers to a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus. The vaccine components include diphtheria and tetanus toxoids and killed whole cells of the organism that causes pertussis (wP).

DTaP and Tdap refer to similar combination vaccines in which the component with lower case 'a' is acellular.

Also available is the DT or TD vaccine, which lacks the pertussis component. The Tdap vaccine is currently recommended by the CDC and covers tetanus, diphtheria and pertussis (CDC Vaccines, 2013).

In the United Kingdom, the Netherlands and France, the abbreviation DTP refers to a combination vaccine against diphtheria, tetanus, and poliomyelitis. In the Netherlands, pertussis is known as kinkhoest and DKTP refers to a combination vaccine against diphtheria, pertussis/kinkhoest, tetanus, and polio.

The usual course of childhood immunization in the USA is five doses between 2 months and 15 years. For adults, separate combination (booster) vaccines are used that adjust the relative concentrations of their components.

In the latter 20th century, vaccinations helped to comprehensively reduce the incidence of childhood pertussis in the United States. Despite this, reported instances of the disease increased twenty-fold in the early 21st century, resulting in numerous fatalities.[1] Over this time, many parents declined to vaccinate their children against the disease for fear of side effects.[1] In 2009, Pediatrics concluded the largest risk among unvaccinated children was not the contraction of side effects, but rather the disease that the vaccination aims to protect against.[1]

DTP was licensed in 1949.[2]

Combination vaccines with acellular pertussis

DTap and Tdap are both combined vaccines against diphtheria, tetanus, and pertussis. The difference is in the dosage, with the upper case letters meaning higher quantity.[3] The names are easy to confuse, and the Institute for Safe Medication Practices reports hundreds of cases of accidental mix-ups.[4]

DTaP

DTaP (also DTPa and TDaP) is a combined vaccine against diphtheria, tetanus, and pertussis, in which the component with lower case 'a' is acellular. This is in contrast to whole-cell, inactivated DTP (aka DTwP). The acellular vaccine uses selected antigens of the pertussis pathogen to induce immunity. Because it uses fewer antigens than the whole cell vaccines, it is considered safer, but it is also more expensive. Recent research suggests that the DTP vaccine is more effective than DTaP in conferring immunity; this is because DTaP's narrower antigen base is less effective against current pathogen strains.[5]

The acellular vaccine is safer to administer in that it causes substantially fewer side-effects (estimated at 90% fewer), which commonly include local pain and redness, or fever.

DTaP was developed in Japan in 1981.

Recent research in non human primates has shown that while DTaP does confer immunity, it does not prevent transmission because it does not prevent Pertussis from colonizing the airways of vaccinated individuals. Thus non human primates who have received DTaP can infect unvaccinated or immunocompromised non human primates.[6] Other recent research has shown that DTaP confers less immunity than whole cell DTP (aka DTwP).[7]

Tdap

The lower case "d" and "p" indicated smaller concentrations of diphtheria pertussis toxoids, and "a" in "ap" indicates that the pertussis toxoids are acellular. Two Tdap vaccines are available in the U.S. Adacel, manufactured by Sanofi Pasteur, is licensed for use in adults ages 11 to 64. Boostrix, manufactured by GlaxoSmithKline, is licensed for use in adolescents and adults ages 10 to 64. The U.S.'s Advisory Committee on Immunization Practices (ACIP) has recommended its use in adults of all ages, including those age 65 and above. After the 2010 passage of Assembly Bill 354, the State of California requires all students entering grades 7-12 provide proof of Tdap vaccination as a condition of enrollment in both public and private schools.[8][9][10]

The U.S.'s Advisory Committee on Immunization Practices (ACIP) and Canada's National Advisory Committee on Immunization (NACI) recommended that both adolescents and adults receive Tdap in place of their next Td booster (recommended to be given every 10 years).[11][12][13][14] Tdap can be used as prophylaxis for tetanus in wound management. People who will be in contact with young infants are encouraged to get Tdap even if it has been less than 5 years since Td or TT to reduce the risk of infants being exposed to pertussis. The ACIP statement on Tdap use in adolescents encourages 5 years between Td and Tdap to reduce this risk; however, both suggest that shorter intervals may be appropriate in some circumstances, such as for protection in pertussis outbreaks. NACI suggests intervals shorter than 5 years can be used for catch-up programs and other instances where programmatic concerns make 5-year intervals difficult.

Thiomersal

Thiomersal (INN), commonly known in the US as thimerosal, is an organomercury compound used as a preservative in certain vaccines. Out of the eight manufactured DPT vaccines, only three ever contained thiomersal. Currently, seven out of the eight DPT vaccines on the market do not use thiomersal, and the product that does (Tripedia) contains trace levels, less than 0.3 micrograms per dose.[15] The World Health Organization has concluded that there is no evidence of toxicity from thiomersal in vaccines.[16] however, following a review of mercury-containing food and drugs mandated in 1999, the Centers for Disease Control (CDC) and the American Academy of Pediatrics asked vaccine manufacturers to remove thiomersal from vaccines as a purely precautionary measure, and it was rapidly phased out of most U.S. and European vaccines.[17][18]

Medication errors

In August 2006, the non-profit patient safety organization Institute for Safe Medication Practices described medication errors from the confusion between the two different formulations.[19]

There were several mix-ups between DAPTACEL and ADACEL. Daptacel is for active immunization in infants and children 6 weeks to 6 years old. Adacel is indicated for active booster immunization as a single dose in persons 11 to 64 years old and is the first vaccine approved as a pertussis booster for adults. The component antigens in Adacel and Daptacel are the same, but the relative amounts are much greater with the infant vaccination. As such, these are easy to confuse.

In one clinic, 13 adults were vaccinated with Daptacel in error. At another clinic, seven adults received Daptacel instead of Adacel. None of the patients appeared to have experienced any unusual vaccine reactions despite the fact that the pediatric formulation contains greater amounts of the detoxified pertussis toxin and diphtheria toxoid. The similarities of the brand names, generic designations, and vaccine abbreviations (Tdap and DTaP) were felt to have contributed to the confusion.

The World Health Organization recommends a pentavalent vaccine, combining the DTP vaccine with vaccines against Haemophilus influenzae type B and hepatitis B. There is not yet sufficient evidence on how effective this pentavalent vaccine is in relation to the individual vaccines.[20]

In pregnancy

Guidelines on prenatal care in the United States state that, if an urgent need for tetanus protection occurs during pregnancy, Td vaccine should be administered.[21] If no urgent need arises and the woman has previously received tetanus vaccine, Td vaccination should be delayed until the postpartum period.[21] All postpartum women who have not received Td or Tdap vaccine in the last two years are recommended to receive Tdap prior to discharge after delivery.[21] It is recommended for pregnant women who have never received tetanus vaccine (i.e., have never received DTP, DTaP or DT as child or Td or TT as adult) to receive a series of three Td vaccinations starting during pregnancy to ensure protection against maternal and neonatal tetanus.[21] In such cases, administration of Tdap is recommended after 20 weeks' gestation,[22] and in earlier pregnancy a single dose of Tdap can be substituted for one dose of Td, and then the series completed with Td.[21] The United States Center for Disease Control (CDC) Advisory Committee on Immunization Practices (ACIP) voted to recommend that health-care personnel should administer a dose of Tdap during each pregnancy at 27 through 36 weeks gestation irrespective of the patient's prior history of receiving Tdap.[23]

Non-specific effects

DTP vaccine seem to have negative non-specific effects other than the beneficial effect against the targeted disease.[24] The negative effects are seen as long as DTP vaccine is the most recent vaccine. BCG or measles vaccine given after DTP reverses the negative effects of DTP.[24] The negative effects are seen mostly in females.[24]

The negative effects are found in several observational studies. However, six WHO-commissioned studies concluded that there were strong beneficial effects of DTP on overall mortality.[25][26][27][28][29][30] However, controversy ensued as to the design of these studies that had important methodological shortcomings.[31][32] Among others, the WHO-commissioned studies had counted “no information about vaccination” as “unvaccinated”, and they had retrospectively updated vaccine information from surviving children, while no similar update could be made for dead children, creating a so-called “survival bias” which will always produce highly beneficial effect estimates for the most recent vaccine.[33]

As all the studies of the overall mortality effect of DTP vaccine are observational studies, they are probably prone to selection bias, but this selection bias would tend to work in favor of vaccinated children, and therefore the consistent observation of negative effects in studies without survival bias is worrying.

References

  1. 1 2 3 "Is Vaccine Refusal Worth The Risk?". NPR. 2009-05-26. Retrieved 2009-06-19.
  2. "Vaccine Timeline: Historic Dates and Events Related to Vaccines and Immunization". Immunization Action Coalition. 2013-05-17. Retrieved 2014-06-25.
  3. "The difference between Tdap and DTaP; dabigatran versus warfarin". JAAPA. Retrieved 2014-06-25.
  4. "DTaP-Tdap mix-ups now affecting hundreds of patients". Ismp.org. Retrieved 2014-06-25.
  5. Higgs, Higgins, Ross and Mills 2012 'Immunity to the respiratory pathogen Bordatella pertussis' Mucosal Immunol 5(5):485-500
  6. Jason M. Warfel, Lindsey I. Zimmerman, and Tod J. Merkel1. "Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model". Pnas.org. Retrieved 2014-06-25.
  7. "Comparative Effectiveness of Acellular Versus Whole-Cell Pertussis Vaccines in Teenagers". Pediatrics.aappublications.org. Retrieved 2014-06-25.
  8. "Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010". MMWR Morb. Mortal. Wkly. Rep. 60 (1): 13–5. January 2011. PMID 21228763.
  9. Staff Reports (May 15, 2012). "No shot, no school reminder issued to parents". Freedom Communications. Retrieved 2012-06-09.
  10. California State Legislature (September 29, 2010). "AB 354 Assembly Bill". Legislative Counsel of California. Retrieved 2012-06-09.
  11. Broder KR, Cortese MM, Iskander JK, et al. (Mar 2006). "Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep 55 (RR–3): 1–34. PMID 16557217., page 18.
  12. "ACIP Votes to Recommend Use of Combined Tetanus, Diphtheria and Pertussis (Tdap) Vaccine for Adults" (PDF).
  13. "Interval Between Administration of Vaccines Against Diphtheria, Tetanus, and Pertussis".
  14. Kretsinger K, Broder KR, Cortese MM, et al. (December 2006). "Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel". MMWR Recomm Rep 55 (RR–17): 1–37. PMID 17167397.
  15. United States Food and Drug Administration. "Thiomersal in Vaccines".
  16. Global Advisory Committee on Vaccine Safety (2006-07-14). "Thiomersal and vaccines". World Health Organization. Retrieved 2007-11-20.
  17. Baker JP (2008). "Mercury, Vaccines, and Autism: One Controversy, Three Histories". Am J Public Health 98 (2): 244–53. doi:10.2105/AJPH.2007.113159. PMC 2376879. PMID 18172138.
  18. "Thimerosal in vaccines: frequently asked questions (FAQs)". Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. 2007-06-07. Retrieved 2008-07-22.
  19. "Adacel (Tdap) and Daptacel (DTaP) confusion". ISMP Medication Safety Alert!. Institute for Safe Medication Practices. August 24, 2006.
  20. Bar-On ES, Goldberg E, Hellmann S, Leibovici L (2012). "Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB)". Cochrane Database Syst Rev 4 (4): CD005530. doi:10.1002/14651858.CD005530.pub3. PMID 22513932.
  21. 1 2 3 4 5 Health Care Guideline: Routine Prenatal Care. Fourteenth Edition. By the Institute for Clinical Systems Improvement. July 2010.
  22. Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine (Tdap) in Pregnant Women and Persons Who Have or Anticipate Having Close Contact with an Infant Aged <12 Months, 2011 - section "Safety of Tdap in Pregnant Women". By the Advisory Committee on Immunization Practices (ACIP), at Centers for Disease Control and Prevention.
  23. Archived January 23, 2013 at the Wayback Machine
  24. 1 2 3 Aaby, P; Benn, C; Nielsen, J; Lisse, IM; Rodrigues, A; Ravn, H (2012). "Testing the hypothesis that diphtheria-tetanus-pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries". BMJ Open 2 (3): e000707. doi:10.1136/bmjopen-2011-000707. PMID 22619263.
  25. Nyarko, P; Pence, B; Debpuur, C (2001). "Immunization status and child survival in rural Ghana.". Population council. Working papers no. 147.
  26. Lehmann, D; Vail, J; Firth, MJ; de Klerk, NH; Alpers, MP (Feb 2005). "Benefits of routine immunizations on childhood survival in Tari, Southern Highlands Province, Papua New Guinea". Int J Epidemiol 34 (1): 138–48. doi:10.1093/ije/dyh262. PMID 15561755.
  27. Elguero, E; Simondon, KB; Vaugelade, J; Marra, A; Simondon, F (October 2010). "Non-specific effects of vaccination on child survival? A prospective study in Senegal.". Trop Med Int Health 10 (10): 956–60. doi:10.1111/j.1365-3156.2005.01479.x. PMID 16185229.
  28. Vaugelade, J; Pinchinat, S; Guiella, G; Elguero, E; Simondon, F (4 December 2004). "Non-specific effects of vaccination on child survival: prospective cohort study in Burkina Faso". BMJ 329 (7478): 1309. doi:10.1136/bmj.38261.496366.82. PMID 15550402.
  29. Moulton, LH; Rahmathullah, L; Halsey, NA; Thulasiraj, RD; Katz, J; Tielsch, JM (October 2005). "Evaluation of non-specific effects of infant immunizations on early infant mortality in a southern Indian population". Trop Med Int Health 10 (10): 947–55. doi:10.1111/j.1365-3156.2005.01434.x. PMID 16185228.
  30. Breiman, RF; Streatfield, PK; Phelan, M; Shifa, N; Rashid, M; Yunus, M (December 2004). "Effect of infant immunisation on childhood mortality in rural Bangladesh: analysis of health and demographic surveillance data". Lancet 364 (9452): 2204–11. doi:10.1016/s0140-6736(04)17593-4. PMID 15610807.
  31. Aaby, P; Benn, CS; Nielsen, J; Lisse, IM; Rodrigues, A; Jensen, H (Jan 2007). "DTP vaccination and child survival in observational studies with incomplete vaccination data". Trop Med Int Health 12 (1): 15–24. doi:10.1111/j.1365-3156.2006.01774.x. PMID 17207144.
  32. Fine, PEM; Smith, PG (2007). "Editorial: ‘Non-specific effects of vaccines’- an important analytical insight, and call for a workshop". Trop Med Int Health 12 (1): 1–4. doi:10.1111/j.1365-3156.2006.01794.x. PMID 17207142.
  33. Jensen, H; Benn, CS; Lisse, IM; Rodrigues, A; Andersen, PK; Aaby, P (Jan 2007). "Survival bias in observational studies of the impact of routine immunizations on childhood survival". Trop Med Int Health 12 (1): 5–14. doi:10.1111/j.1365-3156.2006.01773.x. PMID 17207143.

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