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DPT vaccine

The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus.[7] The vaccine components include diphtheria and tetanus toxoids and either killed whole cells of the bacterium that causes pertussis or pertussis antigens. The term toxoid refers to vaccines which use an inactivated toxin produced by the pathogen which they are targeted against in order to generate an immune response. In this way, the toxoid vaccine generates an immune response which is targeted against the toxin which is produced by the pathogen and causes disease, rather than a vaccine which is targeted against the pathogen itself.[8] The whole cells or antigens will be depicted as either "DTwP" or "DTaP", where the lower-case "w" indicates whole-cell inactivated pertussis and the lower-case "a" stands for "acellular".[9] In comparison to alternative vaccine types, such as live attenuated vaccines, the DTP vaccine does not contain the pathogen itself, but rather uses inactivated toxoid to generate an immune response; therefore, there is not a risk of use in populations that are immune compromised since there is not any known risk of causing the disease itself. As a result, the DTP vaccine is considered a safe vaccine to use in anyone and it generates a much more targeted immune response specific for the pathogen of interest.[10] However, booster doses are recommended every ten years to maintain immune protection against these pathogens.

DPT vaccine
Global vaccination coverage- diphtheria-tetanus-pertussis (DTP3) immunization[1]
Combination of
Diphtheria vaccineVaccine
Pertussis vaccineVaccine
Tetanus vaccineVaccine
Clinical data
Trade namesAdacel, Boostrix, Revaxis, others
AHFS/Drugs.comUK Drug Information
Routes of
administration
Intramuscular injection
Legal status
Legal status
Identifiers
CAS Number
  • 863488-19-1 Y
ChemSpider
  • none
 NY (what is this?)  (verify)

In the United States, the DPT vaccine was administered as part of the childhood vaccines recommended by the Centers for Disease Control and Prevention (CDC) until 1996 when the acellular DTaP vaccine was licensed for use.[11]

History

In the 20th century, the advancements in vaccinations helped to reduce the incidence of childhood pertussis and had a dramatically positive effect on the health of populations in the United States.[12] However, in the early 21st century, reported instances of the disease increased 20-fold due to a downturn in the number of immunizations received and resulted in numerous fatalities.[13] During the 21st century, many parents declined to vaccinate their children against pertussis for fear of perceived side effects despite scientific evidence showing vaccines to be highly effective and safe.[13] In 2009, the journal 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.[13]

Diphtheria and tetanus toxoids and pertussis (DTP) vaccination was licensed in 1949.[14] Since the introduction of the combination vaccine, there has been an extensive decline in the incidence of pertussis, or whooping cough, the disease which the vaccine protects against. Additionally, the rates of disease have continued to decline as more extensive immunization strategies have been implemented, including booster doses and increased emphasis on increasing health literacy.[15]

Vaccination Rates

In 2016, the CDC reported that 80.4% of children in the US have received four or more DTaP vaccinations by 2 years of life.[16] Vaccination rates for children aged 13–17 with one or more TDaP shots was 90.2% in 2019.[16] Only 43.6% of adults (older than 18) have received a TDaP shot in the last 10 years.[16] The CDC aims to increase vaccination rate among 2-year-olds from 80.4% to 90.0%[17]

Combination vaccines with acellular pertussis

DTaP and Tdap are both combination vaccines against diphtheria, tetanus, and pertussis. The lower-case "d" and "p" indicate smaller concentrations of diphtheria toxoids and pertussis antigens, and "a" in "ap/aP" indicates that the pertussis toxoids are acellular.[18]

DTaP

DTaP (also DTPa and TDaP) is a combination vaccine against diphtheria, tetanus, and pertussis, in which the pertussis component is acellular.[19] This is in contrast to whole-cell, inactivated DTP (DTwP).[20] The acellular vaccine uses selected antigens of the pertussis pathogen to induce immunity.[21] Because it uses fewer antigens than the whole-cell vaccines, it is considered to cause fewer side effects, but it is also more expensive.[21] Research suggests that the DTP vaccine is more effective than DTaP in conferring immunity, because DTaP's narrower antigen base is less effective against current pathogen strains.[22]

Tdap

Tdap, (also dTpa), is a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine. It was licensed in the United States for use in adults and adolescents on 10 June 2005.[23] Two Tdap vaccines are available in the US. In January 2011, the US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommended the use of Tdap in adults of all ages, including those age 65 and above.[24] In October 2011, in an effort to reduce the burden of pertussis in infants, the ACIP recommended that unvaccinated pregnant women receive a dose of Tdap. On 24 October 2012, the ACIP voted to recommend the use of Tdap during every pregnancy.[25][26]

The 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 ten years).[27][28][29][23] Tdap and Td 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 five years since Td or TT to reduce the risk of infants being exposed to pertussis. NACI suggests intervals shorter than five years can be used for catch-up programs and other instances where programmatic concerns make five-year intervals difficult.[30]

The World Health Organization (WHO) recommends a pentavalent vaccine, combining the DTP vaccine with vaccines against Haemophilus influenzae type B and hepatitis B. Evidence on how effective this pentavalent vaccine is compared to the individual vaccines has not yet been determined.[31]

A 2019 study in the American Economic Journal found that state requirements mandating the use of the Tdap vaccine "increased Tdap vaccine take-up and reduced pertussis (whooping cough) incidence by about 32 percent."[32]

Related combination vaccines

Excluding pertussis

DT and Td vaccines lack the pertussis component.[33][34][35] The Td vaccine is administered to children over the age of seven as well as to adults. It is most commonly administered as a booster shot every 10 years.[33] The Td booster shot may also be administered as protection from a severe burn or dirty wound.[33] The DT vaccine is given to children under the age of seven, who are unable to receive the pertussis antigen in the DTaP vaccine due to a contraindication.[36]

Including polio

In the United States, a combined vaccine inactivated polio vaccine (IPV), DTaP, and hepatitis B vaccine is available for children.[37][38] In the UK, all babies born on or after 1 August 2017 are offered a hexavalent vaccine: DTaP, IPV, Haemophilus influenzae, and hepatitis B.[39]

Contraindications

The DPT vaccine should be avoided in persons who experienced a severe allergic reaction, such as anaphylaxis, to a past vaccine containing tetanus, diphtheria, or pertussis. It should also be avoided in persons with a known severe allergy to an ingredient in the vaccine. If the reaction was caused by tetanus toxoids, the CDC recommends considering a passive immunization with tetanus immune globulin (TIG) if a person has a large or unclean wound.[40] The DPT vaccine should also be avoided if a person developed encephalopathy (seizures, coma, declined consciousness) within seven days of receiving any pertussis-containing vaccine and the encephalopathy cannot be traced to another cause.[41] A DT vaccine is available for children under the ages of seven who have contraindications or precautions to pertussis-containing vaccines.[42]

Side effects

DTaP

Common side effects include soreness where the shot was given, fever, irritability, tenderness, loss of appetite, and vomiting.[19] Most side effects are mild to moderate and may last from one to three days.[19] More serious but rare reactions after a DTaP vaccination may include seizures, lowered consciousness, or a high fever over 105 °F (41 °C).[7] Allergic reactions are uncommon, but are medical emergencies. Signs of an allergic reaction include hives, dyspnea, wheezing, swelling of face and throat, syncope, and tachycardia and the child should be rushed to the nearest hospital.[43]

Tdap

Common side effects include pain or swelling where the shot was given, mild fever, headache, tiredness, nausea, vomiting, diarrhea, and stomach ache.[19] Allergic reactions are possible and have the same presentation and indications as described above for allergic reactions in DTaP. Any individual who has experienced a life-threatening allergic reaction after receiving a previous dose of diphtheria, tetanus, or pertussis containing vaccine should not receive the Tdap vaccination.[19]

In pregnant women, research suggests that Tdap administration may be associated with an increased risk of chorioamnionitis, a placental infection.[44] Increased incidence of fever is also noted in pregnant women.[44] Despite the observed increase in incidence of chorioamnionitis in pregnant women following Tdap administration, there has been no observed increase in the incidence of preterm birth, for which chorioamnionitis is a risk factor.[44][45] Research has not discerned an association between Tdap administration during pregnancy and other serious pregnancy complications such as neonatal death and stillbirth.[44][45] An association between Tdap administration during pregnancy and pregnancy-related hypertensive disorders (such as pre-eclampsia) has not been identified.[45]

Immunization schedules and requirements

France

In France, DTP refers to a diphtheria, tetanus and polio vaccine. It is mandatory and given at 2 months (first dose) and 4 months (second dose) with a booster at 11 months. Subsequent boosters are recommended at ages 6, 11–13, 25, 45, 65, then every ten years.[46]

Netherlands

In the Netherlands, pertussis is known as kinkhoest and DKTP refers to the DTaP-IPV combination vaccine against diphtheria, kinkhoest, tetanus, and polio. DTP is given as part of the National Immunisation Programme.[47]

United Kingdom

In the United Kingdom, DTP is called the "3-in-1 teenage booster" and protects against tetanus, diphtheria and polio. It is given by the NHS to all teenagers aged 14 (the hexavalent vaccine is given to infants and provides the first stage of protection against diphtheria, tetanus, and polio, as well as pertussis, Haemophilus influenzae type B and hepatitis B). Subsequent boosters are recommended for foreign travellers where more than 10 years has passed since their last booster.[48] This is provided on the NHS free of charge due to the significant risk that an imported case of polio could pose to public health in Britain.[49]

United States

The standard immunization regimen for children within the United States is five doses of DTaP between the ages of two months and fifteen years. To be considered fully vaccinated, the Center for Disease Control and Prevention (CDC) typically requires five doses of Tdap.[50] The CDC recommends that children receive their first dose at two months, the second dose at four months, the third dose at six months, the fourth dose between 15 and 18 months, and the fifth dose between 4–6 years. If the fourth dose of the DTaP immunization regimen falls on or subsequent to the recipient's fourth birthday, the CDC states that only four doses are required to be fully vaccinated.[50] In the instance that an individual under 18 has not received the DTaP vaccine, individuals should be vaccinated on the schedule in accordance with the vaccination "catch up schedule" provided by the CDC.[50]

Infants younger than 12 months of age, specifically less than three months of age, are at highest risk of acquiring pertussis.[51] In U.S, there is no current tetanus-diphtheria-pertussis vaccination (whooping cough) recommended or licensed for new born infants.[51] As a result, in their first few months of life, unprotected infants are at highest risk of life-threatening complications and infections from pertussis. Infants should not receive pertussis vaccination younger than six weeks of age.[52] Ideally, Infants should receive DTaP (name of whooping cough vaccine for children from age 2 months through 6 years) at 2, 4, 6 months of age and they are not protected until the full series is completed.[51] To protect infants younger than twelve months of age not vaccinated with Tdap against pertussis, ACIP also recommends adults (e.g., parents, siblings, grandparents, childcare providers, and healthcare personnel) and children to receive Tdap at least two weeks before being in contact with the infant.[41]

The CDC recommends that adults who have received their childhood DTP series receive a Td or Tdap booster every ten years.[53][54] For adults that have not received the DTP series, the CDC recommends a three-part vaccine series followed by a Td or Tdap booster every ten years.[53]

In pregnancy

According to the CDC's Advisory Committee on Immunization Practices (ACIP) guidelines, one dose of Tdap is recommended during each pregnancy to ensure protection against pertussis in newborn infants.[55] Optimal timing to administer a dose of Tdap during each pregnancy is between 27 through 36 weeks gestation.[55] If Tdap is administered early in pregnancy, it is not recommended to administer again during the 27 through 36 weeks gestation period as only one dose is recommended during pregnancy.[56] In October 2022, Boostrix (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed [Tdap]) was approved for immunization during the third trimester of pregnancy to prevent pertussis, commonly known as whooping cough, in infants younger than two months of age.[57]

Pregnant women who have not previously vaccinated with Tdap (i.e., have never received DTP, DTaP, or DT as child or Td or TT as an adult) are recommended to receive a series of three Td vaccinations starting during pregnancy to ensure protection against maternal and neonatal tetanus.[58] In such cases, administration of Tdap is recommended after 20 weeks' gestation,[59][26] and in earlier pregnancy a single dose of Tdap can be substituted for one dose of Td, and then the series completed with Td.[58][26] For pregnant women not previously vaccinated with Tdap, if Tdap is not administered during pregnancy, it should be administered immediately postpartum.[41] Postpartum administration of TDaP is not equivalent to administration of the vaccination during pregnancy.[60] Because the vaccine is administered postpartum, the mother is unable to develop antibodies that can be transferred to the infant in utero, consequently, leaving the infant vulnerable to the diseases preventable by the Tdap Vaccine.[60] Postpartum administration of the TdaP vaccine to the mother seeks to reduce the likelihood that the mother will contract disease that can be subsequently passed on the infant, albeit there will still be a two week period prior to the protective effects of the vaccine setting in.[60] Postpartum administration is an extension of the concept of "cocooning", a term that refers to the full vaccination of all individuals that may come into direct contact with the infant.[60] Cocooning, like postpartum Tdap aministration, is not recommended by the CDC.[60] Cocooning depends on ensuring full vaccination of all individuals that the infant may come into contact with, and there may be financial, administrative or personal barriers that preclude full and timely vaccination of all individuals within the "cocoon".[60]

Brand names

Australia

TDaP Vaccines in Australia
Trade name Approval date Comments
Adacel[61] 2005[62] Adacel is indicated for active immunisation against tetanus, diphtheria and pertussis in persons aged ten years and over as a booster following primary immunisation [62] and is informally known as 'triple antigen' in Australia.[63]
Adacel Polio[64] 2006[65] Adacel Polio is indicated for active immunization against diphtheria, tetanus, pertussis and poliomyelitis in adults, adolescents and children aged four years and older as a booster following primary immunization.[65]

United Kingdom

Brand names in the United Kingdom include Revaxis (Sanofi Pasteur).[66]

United States

As of January 2020, there are six DTaP vaccines and two Tdap vaccines licensed and available for use in the United States.[67][68] All of them are indicated as childhood vaccinations with the schedules as follows:

DTaP Vaccines in the US
Trade name Approval date Comments Contraindications
Daptacel[69] 2002[70] For use in ages six weeks through six years as a five-dose series at 2, 4, and 6 months (6–8 weeks apart) and at 15–20 months of age and at 4–6 years.[69]
  • Severe allergic reaction (anaphylaxis) after a previous dose of Daptacel or tetanus, diphtheria, or pertussis containing vaccine.
  • Encephalopathy (coma, prolonged seizures, and decreased level of consciousness) within seven days of a previous dose of a pertussis containing vaccine.
  • Progressive neurologic disorder (spasms, epilepsy, progressive encephalopathy)[69]
Infanrix[71] 1997[72] For use in ages six weeks through six years (before the seventh birthday) as a five-dose series as: a three-dose course at 2, 5, and 6 months (4–8 weeks apart), followed by a two booster doses at 15–20 months of age and 4–6 years of age.[71]
  • Severe allergic reaction (anaphylaxis) after a previous dose of Infanrix or tetanus, diphtheria, or pertussis-containing vaccine.
  • Encephalopathy (coma, prolonged seizures, and decreased level of consciousness) within seven days of a previous dose of a pertussis containing vaccine.
  • Progressive neurologic disorder (spasms, epilepsy, progressive encephalopathy)[71]
Kinrix[73] 2008[74] DTaP-IPV vaccine; also immunizes against poliomyelitis. Kinrix can be utilized for the fifth (last) dose in the DTaP immunization series and the fourth dose in the IPV immunization series in children 4–6 years old (before the seventh birthday) whose previous DTaP vaccine doses have been with Infanrix and/or Pediarix for the first three doses and Infanrix for the fourth dose.[73]
  • Severe allergic reaction (anaphylaxis) after a previous dose of any vaccine containing diphtheria, tetanus, pertussis or poliovirus
  • Severe allergic reaction (anaphylaxis) to any ingredient in any of Kinrix's vaccines
  • Encephalopathy (declining level of consciousness, coma, seizure) within seven days of receiving any pertussis-containing vaccine
  • Progressive neurologic disorders (spasms, epilepsy)[73]
Pediarix[75] 2002[76] DTaP-IPV-HepB vaccine; also immunizes against hepatitis B and poliomyelitis as a three-dose series in infants two, four, and six months (4–8 weeks apart).[75]
  • Severe allergic reaction (anaphylaxis) after a previous dose of Pediarix, any type of ingredient of Pediarix, or any other diphtheria toxoid, tetanus toxoid, pertussis-containing vaccine, inactivated poliovirus vaccine or H. influenzae type b vaccine.
  • Encephalopathy within seven days of pertussis-containing vaccine.
  • Progressive neurologic disorder of spasms, epilepsy until the condition has stabilized.[75]
Pentacel[77] 2008[78] DTaP-IPV/Hib vaccine; also immunizes against invasive Haemophilus influenza type b and poliomyelitis. It is a four-dose series given at: 2, 4, and 6 months, and at 15–18 months of age.[77]
  • Severe allergic reaction (anaphylaxis) after a previous dose of Pentacel, any type of ingredient of Pentacel, or any other diphtheria toxoid, tetanus toxoid, pertussis-containing vaccine, inactivated poliovirus vaccine or H. influenzae type b vaccine.
  • Encephalopathy within seven days of pertussis-containing vaccine.
  • Progressive neurologic disorder of spasms, epilepsy until the condition has stabilized.[77]
Quadracel[79] 2015[80] DTaP-IPV vaccine; also immunizes against poliomyelitis. It is approved for use as a fifth dose for children aged 4–6 years old in the DTaP vaccination series and as a fourth or fifth dose in the inactivated polio (IPV) series.[79]
  • Severe allergic reaction (anaphylaxis) after a previous dose of Quadracel, any type of ingredient of Quadracel, or any other diphtheria toxoid, tetanus toxoid, pertussis-containing vaccine, inactivated poliovirus vaccine or H. influenzae type b vaccine.
  • Encephalopathy within seven days of pertussis-containing vaccine.
  • Progressive neurologic disorder of spasms, epilepsy until the condition has stabilized.[79]
TDaP Vaccines in the US
Trade name Approval date Comments Contraindications
Adacel[81] 2005[82] For use in ages 10 through 64 as an active booster immunization against tetanus, diphtheria, and pertussis. It may also be administered as prophylaxis for wound management.[81] It has not been shown to be safe or effective as a primary immunization or to complete the series.
  • Hypersensitivity reaction (anaphylaxis) after a previous dose of Adacel, any type of ingredient of Adacel, or any other diphtheria toxoid, tetanus toxoid, pertussis-containing vaccine, inactivated poliovirus vaccine or H. influenzae type b vaccine.
  • Encephalopathy (coma, seizure, loss of consciousness) within seven days of pertussis-containing vaccine.
  • Progressive neurologic disorder of spasms, epilepsy until the condition has stabilized.[81]
Boostrix[83] 2005[84] For use in ages ten and older as a single intramuscular injection into the deltoid as a booster immunization against tetanus, diphtheria, and pertussis. It may also be administered as prophylaxis for wound management.[83]
  • Hypersensitivity reaction (anaphylaxis) after previously receiving a vaccine containing any form of tetanus toxoid, diphtheria toxoid, or pertussis-containing antigen.
  • Hypersensitivity reaction (anaphylaxis) to any ingredient within a previously administered Boostrix vaccine.
  • Encephalopathy (coma, seizure, loss of consciousness) progression within seven days of receiving a vaccine with antigens from pertussis.[83]

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Diphtheria

  • World Health Organization (2009). The immunological basis for immunization : module 2: diphtheria - update 2009. World Health Organization (WHO). hdl:10665/44094. ISBN 9789241597869.
  • Ramsay M, ed. (2013). "Chapter 15: Diphtheria". Immunisation against infectious disease. Public Health England.
  • Roush SW, Baldy LM, Hall MA, eds. (March 2019). Manual for the surveillance of vaccine-preventable diseases. Atlanta GA: U.S. Centers for Disease Control and Prevention (CDC).

Pertussis

  • World Health Organization (2017). The immunological basis for immunization series: module 4: pertussis, update 2017. World Health Organization (WHO). hdl:10665/259388. ISBN 9789241513173.
  • Ramsay M, ed. (2013). "Chapter 24: Pertussis". Immunisation against infectious disease. Public Health England.
  • Hamborsky J, Kroger A, Wolfe S, eds. (2015). "Chapter 16: Pertussis". Epidemiology and Prevention of Vaccine-Preventable Diseases (13th ed.). Washington D.C.: U.S. Centers for Disease Control and Prevention (CDC). ISBN 978-0990449119.
  • Roush SW, Baldy LM, Hall MA, eds. (March 2019). "Chapter 10: Pertussis". Manual for the surveillance of vaccine-preventable diseases. Atlanta GA: U.S. Centers for Disease Control and Prevention (CDC).

Tetanus

External links

vaccine, other, uses, disambiguation, tdap, redirects, here, other, uses, tdap, disambiguation, vaccine, class, combination, vaccines, against, three, infectious, diseases, humans, diphtheria, pertussis, whooping, cough, tetanus, vaccine, components, include, . For other uses see DPT disambiguation TDAP redirects here For other uses see TDAP disambiguation The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans diphtheria pertussis whooping cough and tetanus 7 The vaccine components include diphtheria and tetanus toxoids and either killed whole cells of the bacterium that causes pertussis or pertussis antigens The term toxoid refers to vaccines which use an inactivated toxin produced by the pathogen which they are targeted against in order to generate an immune response In this way the toxoid vaccine generates an immune response which is targeted against the toxin which is produced by the pathogen and causes disease rather than a vaccine which is targeted against the pathogen itself 8 The whole cells or antigens will be depicted as either DTwP or DTaP where the lower case w indicates whole cell inactivated pertussis and the lower case a stands for acellular 9 In comparison to alternative vaccine types such as live attenuated vaccines the DTP vaccine does not contain the pathogen itself but rather uses inactivated toxoid to generate an immune response therefore there is not a risk of use in populations that are immune compromised since there is not any known risk of causing the disease itself As a result the DTP vaccine is considered a safe vaccine to use in anyone and it generates a much more targeted immune response specific for the pathogen of interest 10 However booster doses are recommended every ten years to maintain immune protection against these pathogens DPT vaccineGlobal vaccination coverage diphtheria tetanus pertussis DTP3 immunization 1 Combination ofDiphtheria vaccineVaccinePertussis vaccineVaccineTetanus vaccineVaccineClinical dataTrade namesAdacel Boostrix Revaxis othersAHFS Drugs comUK Drug InformationRoutes ofadministrationIntramuscular injectionLegal statusLegal statusAU S4 Prescription only US only with standing order 2 3 4 5 EU Rx only 6 In general Prescription only IdentifiersCAS Number863488 19 1 YChemSpidernone N Y what is this verify In the United States the DPT vaccine was administered as part of the childhood vaccines recommended by the Centers for Disease Control and Prevention CDC until 1996 when the acellular DTaP vaccine was licensed for use 11 Contents 1 History 1 1 Vaccination Rates 2 Combination vaccines with acellular pertussis 2 1 DTaP 2 2 Tdap 3 Related combination vaccines 3 1 Excluding pertussis 3 2 Including polio 4 Contraindications 5 Side effects 5 1 DTaP 5 2 Tdap 6 Immunization schedules and requirements 6 1 France 6 2 Netherlands 6 3 United Kingdom 6 4 United States 6 4 1 In pregnancy 7 Brand names 7 1 Australia 7 2 United Kingdom 7 3 United States 8 References 8 1 Diphtheria 8 2 Pertussis 8 3 Tetanus 9 External linksHistory EditIn the 20th century the advancements in vaccinations helped to reduce the incidence of childhood pertussis and had a dramatically positive effect on the health of populations in the United States 12 However in the early 21st century reported instances of the disease increased 20 fold due to a downturn in the number of immunizations received and resulted in numerous fatalities 13 During the 21st century many parents declined to vaccinate their children against pertussis for fear of perceived side effects despite scientific evidence showing vaccines to be highly effective and safe 13 In 2009 the journal 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 13 Diphtheria and tetanus toxoids and pertussis DTP vaccination was licensed in 1949 14 Since the introduction of the combination vaccine there has been an extensive decline in the incidence of pertussis or whooping cough the disease which the vaccine protects against Additionally the rates of disease have continued to decline as more extensive immunization strategies have been implemented including booster doses and increased emphasis on increasing health literacy 15 Vaccination Rates Edit In 2016 the CDC reported that 80 4 of children in the US have received four or more DTaP vaccinations by 2 years of life 16 Vaccination rates for children aged 13 17 with one or more TDaP shots was 90 2 in 2019 16 Only 43 6 of adults older than 18 have received a TDaP shot in the last 10 years 16 The CDC aims to increase vaccination rate among 2 year olds from 80 4 to 90 0 17 Combination vaccines with acellular pertussis EditDTaP and Tdap are both combination vaccines against diphtheria tetanus and pertussis The lower case d and p indicate smaller concentrations of diphtheria toxoids and pertussis antigens and a in ap aP indicates that the pertussis toxoids are acellular 18 DTaP Edit DTaP also DTPa and TDaP is a combination vaccine against diphtheria tetanus and pertussis in which the pertussis component is acellular 19 This is in contrast to whole cell inactivated DTP DTwP 20 The acellular vaccine uses selected antigens of the pertussis pathogen to induce immunity 21 Because it uses fewer antigens than the whole cell vaccines it is considered to cause fewer side effects but it is also more expensive 21 Research suggests that the DTP vaccine is more effective than DTaP in conferring immunity because DTaP s narrower antigen base is less effective against current pathogen strains 22 Tdap Edit Tdap also dTpa is a tetanus toxoid reduced diphtheria toxoid and acellular pertussis vaccine It was licensed in the United States for use in adults and adolescents on 10 June 2005 23 Two Tdap vaccines are available in the US In January 2011 the US Centers for Disease Control and Prevention CDC Advisory Committee on Immunization Practices ACIP recommended the use of Tdap in adults of all ages including those age 65 and above 24 In October 2011 in an effort to reduce the burden of pertussis in infants the ACIP recommended that unvaccinated pregnant women receive a dose of Tdap On 24 October 2012 the ACIP voted to recommend the use of Tdap during every pregnancy 25 26 The 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 ten years 27 28 29 23 Tdap and Td 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 five years since Td or TT to reduce the risk of infants being exposed to pertussis NACI suggests intervals shorter than five years can be used for catch up programs and other instances where programmatic concerns make five year intervals difficult 30 The World Health Organization WHO recommends a pentavalent vaccine combining the DTP vaccine with vaccines against Haemophilus influenzae type B and hepatitis B Evidence on how effective this pentavalent vaccine is compared to the individual vaccines has not yet been determined 31 A 2019 study in the American Economic Journal found that state requirements mandating the use of the Tdap vaccine increased Tdap vaccine take up and reduced pertussis whooping cough incidence by about 32 percent 32 Related combination vaccines EditExcluding pertussis Edit DT and Td vaccines lack the pertussis component 33 34 35 The Td vaccine is administered to children over the age of seven as well as to adults It is most commonly administered as a booster shot every 10 years 33 The Td booster shot may also be administered as protection from a severe burn or dirty wound 33 The DT vaccine is given to children under the age of seven who are unable to receive the pertussis antigen in the DTaP vaccine due to a contraindication 36 Including polio Edit Main articles DTaP IPV vaccine and Hexavalent vaccine In the United States a combined vaccine inactivated polio vaccine IPV DTaP and hepatitis B vaccine is available for children 37 38 In the UK all babies born on or after 1 August 2017 are offered a hexavalent vaccine DTaP IPV Haemophilus influenzae and hepatitis B 39 Contraindications EditThe DPT vaccine should be avoided in persons who experienced a severe allergic reaction such as anaphylaxis to a past vaccine containing tetanus diphtheria or pertussis It should also be avoided in persons with a known severe allergy to an ingredient in the vaccine If the reaction was caused by tetanus toxoids the CDC recommends considering a passive immunization with tetanus immune globulin TIG if a person has a large or unclean wound 40 The DPT vaccine should also be avoided if a person developed encephalopathy seizures coma declined consciousness within seven days of receiving any pertussis containing vaccine and the encephalopathy cannot be traced to another cause 41 A DT vaccine is available for children under the ages of seven who have contraindications or precautions to pertussis containing vaccines 42 Side effects EditDTaP Edit Common side effects include soreness where the shot was given fever irritability tenderness loss of appetite and vomiting 19 Most side effects are mild to moderate and may last from one to three days 19 More serious but rare reactions after a DTaP vaccination may include seizures lowered consciousness or a high fever over 105 F 41 C 7 Allergic reactions are uncommon but are medical emergencies Signs of an allergic reaction include hives dyspnea wheezing swelling of face and throat syncope and tachycardia and the child should be rushed to the nearest hospital 43 Tdap Edit Common side effects include pain or swelling where the shot was given mild fever headache tiredness nausea vomiting diarrhea and stomach ache 19 Allergic reactions are possible and have the same presentation and indications as described above for allergic reactions in DTaP Any individual who has experienced a life threatening allergic reaction after receiving a previous dose of diphtheria tetanus or pertussis containing vaccine should not receive the Tdap vaccination 19 In pregnant women research suggests that Tdap administration may be associated with an increased risk of chorioamnionitis a placental infection 44 Increased incidence of fever is also noted in pregnant women 44 Despite the observed increase in incidence of chorioamnionitis in pregnant women following Tdap administration there has been no observed increase in the incidence of preterm birth for which chorioamnionitis is a risk factor 44 45 Research has not discerned an association between Tdap administration during pregnancy and other serious pregnancy complications such as neonatal death and stillbirth 44 45 An association between Tdap administration during pregnancy and pregnancy related hypertensive disorders such as pre eclampsia has not been identified 45 Immunization schedules and requirements EditFrance Edit In France DTP refers to a diphtheria tetanus and polio vaccine It is mandatory and given at 2 months first dose and 4 months second dose with a booster at 11 months Subsequent boosters are recommended at ages 6 11 13 25 45 65 then every ten years 46 Netherlands Edit In the Netherlands pertussis is known as kinkhoest and DKTP refers to the DTaP IPV combination vaccine against diphtheria kinkhoest tetanus and polio DTP is given as part of the National Immunisation Programme 47 United Kingdom Edit In the United Kingdom DTP is called the 3 in 1 teenage booster and protects against tetanus diphtheria and polio It is given by the NHS to all teenagers aged 14 the hexavalent vaccine is given to infants and provides the first stage of protection against diphtheria tetanus and polio as well as pertussis Haemophilus influenzae type B and hepatitis B Subsequent boosters are recommended for foreign travellers where more than 10 years has passed since their last booster 48 This is provided on the NHS free of charge due to the significant risk that an imported case of polio could pose to public health in Britain 49 United States Edit The standard immunization regimen for children within the United States is five doses of DTaP between the ages of two months and fifteen years To be considered fully vaccinated the Center for Disease Control and Prevention CDC typically requires five doses of Tdap 50 The CDC recommends that children receive their first dose at two months the second dose at four months the third dose at six months the fourth dose between 15 and 18 months and the fifth dose between 4 6 years If the fourth dose of the DTaP immunization regimen falls on or subsequent to the recipient s fourth birthday the CDC states that only four doses are required to be fully vaccinated 50 In the instance that an individual under 18 has not received the DTaP vaccine individuals should be vaccinated on the schedule in accordance with the vaccination catch up schedule provided by the CDC 50 Infants younger than 12 months of age specifically less than three months of age are at highest risk of acquiring pertussis 51 In U S there is no current tetanus diphtheria pertussis vaccination whooping cough recommended or licensed for new born infants 51 As a result in their first few months of life unprotected infants are at highest risk of life threatening complications and infections from pertussis Infants should not receive pertussis vaccination younger than six weeks of age 52 Ideally Infants should receive DTaP name of whooping cough vaccine for children from age 2 months through 6 years at 2 4 6 months of age and they are not protected until the full series is completed 51 To protect infants younger than twelve months of age not vaccinated with Tdap against pertussis ACIP also recommends adults e g parents siblings grandparents childcare providers and healthcare personnel and children to receive Tdap at least two weeks before being in contact with the infant 41 The CDC recommends that adults who have received their childhood DTP series receive a Td or Tdap booster every ten years 53 54 For adults that have not received the DTP series the CDC recommends a three part vaccine series followed by a Td or Tdap booster every ten years 53 In pregnancy Edit According to the CDC s Advisory Committee on Immunization Practices ACIP guidelines one dose of Tdap is recommended during each pregnancy to ensure protection against pertussis in newborn infants 55 Optimal timing to administer a dose of Tdap during each pregnancy is between 27 through 36 weeks gestation 55 If Tdap is administered early in pregnancy it is not recommended to administer again during the 27 through 36 weeks gestation period as only one dose is recommended during pregnancy 56 In October 2022 Boostrix Tetanus Toxoid Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Tdap was approved for immunization during the third trimester of pregnancy to prevent pertussis commonly known as whooping cough in infants younger than two months of age 57 Pregnant women who have not previously vaccinated with Tdap i e have never received DTP DTaP or DT as child or Td or TT as an adult are recommended to receive a series of three Td vaccinations starting during pregnancy to ensure protection against maternal and neonatal tetanus 58 In such cases administration of Tdap is recommended after 20 weeks gestation 59 26 and in earlier pregnancy a single dose of Tdap can be substituted for one dose of Td and then the series completed with Td 58 26 For pregnant women not previously vaccinated with Tdap if Tdap is not administered during pregnancy it should be administered immediately postpartum 41 Postpartum administration of TDaP is not equivalent to administration of the vaccination during pregnancy 60 Because the vaccine is administered postpartum the mother is unable to develop antibodies that can be transferred to the infant in utero consequently leaving the infant vulnerable to the diseases preventable by the Tdap Vaccine 60 Postpartum administration of the TdaP vaccine to the mother seeks to reduce the likelihood that the mother will contract disease that can be subsequently passed on the infant albeit there will still be a two week period prior to the protective effects of the vaccine setting in 60 Postpartum administration is an extension of the concept of cocooning a term that refers to the full vaccination of all individuals that may come into direct contact with the infant 60 Cocooning like postpartum Tdap aministration is not recommended by the CDC 60 Cocooning depends on ensuring full vaccination of all individuals that the infant may come into contact with and there may be financial administrative or personal barriers that preclude full and timely vaccination of all individuals within the cocoon 60 Brand names EditAustralia Edit TDaP Vaccines in Australia Trade name Approval date CommentsAdacel 61 2005 62 Adacel is indicated for active immunisation against tetanus diphtheria and pertussis in persons aged ten years and over as a booster following primary immunisation 62 and is informally known as triple antigen in Australia 63 Adacel Polio 64 2006 65 Adacel Polio is indicated for active immunization against diphtheria tetanus pertussis and poliomyelitis in adults adolescents and children aged four years and older as a booster following primary immunization 65 United Kingdom Edit Brand names in the United Kingdom include Revaxis Sanofi Pasteur 66 United States Edit As of January 2020 update there are six DTaP vaccines and two Tdap vaccines licensed and available for use in the United States 67 68 All of them are indicated as childhood vaccinations with the schedules as follows DTaP Vaccines in the US Trade name Approval date Comments ContraindicationsDaptacel 69 2002 70 For use in ages six weeks through six years as a five dose series at 2 4 and 6 months 6 8 weeks apart and at 15 20 months of age and at 4 6 years 69 Severe allergic reaction anaphylaxis after a previous dose of Daptacel or tetanus diphtheria or pertussis containing vaccine Encephalopathy coma prolonged seizures and decreased level of consciousness within seven days of a previous dose of a pertussis containing vaccine Progressive neurologic disorder spasms epilepsy progressive encephalopathy 69 Infanrix 71 1997 72 For use in ages six weeks through six years before the seventh birthday as a five dose series as a three dose course at 2 5 and 6 months 4 8 weeks apart followed by a two booster doses at 15 20 months of age and 4 6 years of age 71 Severe allergic reaction anaphylaxis after a previous dose of Infanrix or tetanus diphtheria or pertussis containing vaccine Encephalopathy coma prolonged seizures and decreased level of consciousness within seven days of a previous dose of a pertussis containing vaccine Progressive neurologic disorder spasms epilepsy progressive encephalopathy 71 Kinrix 73 2008 74 DTaP IPV vaccine also immunizes against poliomyelitis Kinrix can be utilized for the fifth last dose in the DTaP immunization series and the fourth dose in the IPV immunization series in children 4 6 years old before the seventh birthday whose previous DTaP vaccine doses have been with Infanrix and or Pediarix for the first three doses and Infanrix for the fourth dose 73 Severe allergic reaction anaphylaxis after a previous dose of any vaccine containing diphtheria tetanus pertussis or poliovirus Severe allergic reaction anaphylaxis to any ingredient in any of Kinrix s vaccines Encephalopathy declining level of consciousness coma seizure within seven days of receiving any pertussis containing vaccine Progressive neurologic disorders spasms epilepsy 73 Pediarix 75 2002 76 DTaP IPV HepB vaccine also immunizes against hepatitis B and poliomyelitis as a three dose series in infants two four and six months 4 8 weeks apart 75 Severe allergic reaction anaphylaxis after a previous dose of Pediarix any type of ingredient of Pediarix or any other diphtheria toxoid tetanus toxoid pertussis containing vaccine inactivated poliovirus vaccine or H influenzae type b vaccine Encephalopathy within seven days of pertussis containing vaccine Progressive neurologic disorder of spasms epilepsy until the condition has stabilized 75 Pentacel 77 2008 78 DTaP IPV Hib vaccine also immunizes against invasive Haemophilus influenza type b and poliomyelitis It is a four dose series given at 2 4 and 6 months and at 15 18 months of age 77 Severe allergic reaction anaphylaxis after a previous dose of Pentacel any type of ingredient of Pentacel or any other diphtheria toxoid tetanus toxoid pertussis containing vaccine inactivated poliovirus vaccine or H influenzae type b vaccine Encephalopathy within seven days of pertussis containing vaccine Progressive neurologic disorder of spasms epilepsy until the condition has stabilized 77 Quadracel 79 2015 80 DTaP IPV vaccine also immunizes against poliomyelitis It is approved for use as a fifth dose for children aged 4 6 years old in the DTaP vaccination series and as a fourth or fifth dose in the inactivated polio IPV series 79 Severe allergic reaction anaphylaxis after a previous dose of Quadracel any type of ingredient of Quadracel or any other diphtheria toxoid tetanus toxoid pertussis containing vaccine inactivated poliovirus vaccine or H influenzae type b vaccine Encephalopathy within seven days of pertussis containing vaccine Progressive neurologic disorder of spasms epilepsy until the condition has stabilized 79 TDaP Vaccines in the US Trade name Approval date Comments ContraindicationsAdacel 81 2005 82 For use in ages 10 through 64 as an active booster immunization against tetanus diphtheria and pertussis It may also be administered as prophylaxis for wound management 81 It has not been shown to be safe or effective as a primary immunization or to complete the series Hypersensitivity reaction anaphylaxis after a previous dose of Adacel any type of ingredient of Adacel or any other diphtheria toxoid tetanus toxoid pertussis containing vaccine inactivated poliovirus vaccine or H influenzae type b vaccine Encephalopathy coma seizure loss of consciousness within seven days of pertussis containing vaccine Progressive neurologic disorder of spasms epilepsy until the condition has stabilized 81 Boostrix 83 2005 84 For use in ages ten and older as a single intramuscular injection into the deltoid as a booster immunization against tetanus diphtheria and pertussis It may also be administered as prophylaxis for wound management 83 Hypersensitivity reaction anaphylaxis after previously receiving a vaccine containing any form of tetanus toxoid diphtheria toxoid or pertussis containing antigen Hypersensitivity reaction anaphylaxis to any ingredient within a previously administered Boostrix vaccine Encephalopathy coma seizure loss of consciousness progression within seven days of receiving a vaccine with antigens from pertussis 83 References Edit Global vaccination coverage Diphtheria tetanus pertussis DTP3 immunization Our World in Data Archived from the original on 21 April 2020 Retrieved 5 March 2020 http www immunize org catg d p3073 pdf bare URL PDF http www immunize org catg d p3078a pdf bare URL PDF http www immunize org catg d p3078 pdf bare URL PDF http www immunize org catg d p3078b pdf bare URL PDF https www ema europa eu documents psusa diphtheria tetanus pertussis acellular component vaccine adsorbed diphtheria tetanus pertussis acellular component vaccine adsorbed reduced antigens contents list nationally authorised en pdf a b DTaP Diphtheria Tetanus Pertussis Vaccine Information Statement U S Centers for Disease Control and Prevention CDC 1 April 2020 Retrieved 27 July 2020 This article incorporates text from this source which is in the public domain Vaccine Types HHS 26 April 2021 Retrieved 19 September 2022 Liang JL Tiwari T Moro P Messonnier NE Reingold A Sawyer M Clark TA April 2018 Prevention of Pertussis Tetanus and Diphtheria with Vaccines in the United States Recommendations of the Advisory Committee on Immunization Practices ACIP MMWR Recommendations and Reports 67 2 1 44 doi 10 15585 mmwr rr6702a1 PMC 5919600 PMID 29702631 This article incorporates text from this source which is in the public domain Understanding Six Types of Vaccine Technologies Pfizer www pfizer com Retrieved 19 September 2022 Birth 18 Years Immunization Schedule U S Centers for Disease Control and Prevention CDC 2020 Retrieved 30 July 2020 Hebert CJ Hall CM Odoms LN May 2012 Lessons learned and applied what the 20th century vaccine experience can teach us about vaccines in the 21st century Human Vaccines amp Immunotherapeutics 8 5 560 568 doi 10 4161 hv 19204 PMC 3495718 PMID 22617834 a b c Is Vaccine Refusal Worth The Risk NPR 26 May 2009 Retrieved 19 June 2009 Vaccine Timeline Historic Dates and Events Related to Vaccines and Immunization Immunization Action Coalition 17 May 2013 Retrieved 25 June 2014 Kuchar E Karlikowska Skwarnik M Han S Nitsch Osuch A 2016 Pertussis History of the Disease and Current Prevention Failure Advances in Experimental Medicine and Biology 934 77 82 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About Diphtheria Tetanus and Pertussis Vaccination Centers for Disease Control and Prevention CDC 22 January 2020 Retrieved 16 July 2020 Licensed Biological Products with Supporting Documents U S Food and Drug Administration FDA 7 July 2020 Retrieved 17 July 2020 a b c Daptacel corynebacterium diphtheriae toxoid antigen formaldehyde inactivated clostridium tetani toxoid antigen formaldehyde inactivated bordetella pertussis toxoid antigen glutaraldehyde inactivated bordetella pertussis filamentous hemagglutinin antigen formaldehyde inactivated bordetella pertussis pertactin antigen and bordetella pertussis fimbriae 2 3 antigen injection suspension DailyMed Sanofi Pasteur Inc 14 May 2020 Retrieved 17 July 2020 Daptacel U S Food and Drug Administration FDA 22 July 2017 Archived from the original on 22 July 2017 Retrieved 17 July 2020 a b c Infanrix diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed suspension DailyMed GlaxoSmithKline Biologicals SA 6 November 2019 Retrieved 17 July 2020 Infanrix U S Food and Drug Administration FDA 22 July 2017 Archived from the original on 22 July 2017 Retrieved 17 July 2020 a b c Kinrix diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine injection suspension DailyMed GlaxoSmithKline Biologicals SA 6 November 2019 Retrieved 17 July 2020 Kinrix U S Food and Drug Administration FDA 22 July 2017 Archived from the original on 22 July 2017 Retrieved 17 July 2020 a b c Pediarix diphtheria and tetanus toxoids and acellular pertussis adsorbed hepatitis b recombinant and inactivated poliovirus vaccine combined injection suspension DailyMed GlaxoSmithKline Biologicals SA 6 November 2019 Retrieved 17 July 2020 Pediarix U S Food and Drug Administration FDA 23 July 2017 Archived from the original on 23 July 2017 Retrieved 17 July 2020 a b c Pentacel diphtheria and tetanus toxoids and acellular pertussis adsorbed inactivated poliovirus and haemophilus b conjugate tetanus toxoid conjugate vaccine kit DailyMed Sanofi Pasteur Inc 5 June 2020 Retrieved 17 July 2020 Pentacel U S Food and Drug Administration FDA 22 July 2017 Archived from the original on 22 July 2017 Retrieved 17 July 2020 a b c Quadracel diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine injection suspension DailyMed Sanofi Pasteur Inc 20 April 2020 Retrieved 17 July 2020 Quadracel U S Food and Drug Administration FDA 22 July 2017 Archived from the original on 22 July 2017 Retrieved 17 July 2020 a b c Adacel Tdap clostridium tetani toxoid antigen formaldehyde inactivated corynebacterium diphtheriae toxoid antigen formaldehyde inactivated bordetella pertussis toxoid antigen glutaraldehyde inactivated bordetella pertussis filamentous hemagglutinin antigen formaldehyde inactivated bordetella pertussis pertactin antigen and bordetella pertussis fimbriae 2 3 antigen injection suspension DailyMed 26 March 2020 Retrieved 29 July 2020 Adacel Food and Drug Administration Archived from the original on 23 July 2017 a b c Boostrix tetanus toxoid reduced diphtheria toxoid and acellular pertussis vaccine adsorbed suspension DailyMed 25 April 2019 Retrieved 29 July 2020 Boostrix Food and Drug Administration Archived from the original on 22 July 2017 Diphtheria Edit World Health Organization 2009 The immunological basis for immunization module 2 diphtheria update 2009 World Health Organization WHO hdl 10665 44094 ISBN 9789241597869 Ramsay M ed 2013 Chapter 15 Diphtheria Immunisation against infectious disease Public Health England Roush SW Baldy LM Hall MA eds March 2019 Manual for the surveillance of vaccine preventable diseases Atlanta GA U S Centers for Disease Control and Prevention CDC Pertussis Edit World Health Organization 2017 The immunological basis for immunization series module 4 pertussis update 2017 World Health Organization WHO hdl 10665 259388 ISBN 9789241513173 Ramsay M ed 2013 Chapter 24 Pertussis Immunisation against infectious disease Public Health England Hamborsky J Kroger A Wolfe S eds 2015 Chapter 16 Pertussis Epidemiology and Prevention of Vaccine Preventable Diseases 13th ed Washington D C U S Centers for Disease Control and Prevention CDC ISBN 978 0990449119 Roush SW Baldy LM Hall MA eds March 2019 Chapter 10 Pertussis Manual for the surveillance of vaccine preventable diseases Atlanta GA U S Centers for Disease Control and Prevention CDC Tetanus Edit World Health Organization 2018 The immunological basis for immunization series module 3 tetanus update 2018 World Health Organization WHO hdl 10665 275340 ISBN 9789241513616 Ramsay M ed 2013 Chapter 30 Tetanus Immunisation against infectious disease Public Health England Hamborsky J Kroger A Wolfe S eds 2015 Chapter 21 Tetanus Epidemiology and Prevention of Vaccine Preventable Diseases 13th ed Washington D C U S Centers for Disease Control and Prevention CDC ISBN 978 0990449119 Roush SW Baldy LM Hall MA eds March 2019 Chapter 16 Tetanus Manual for the surveillance of vaccine preventable diseases Atlanta GA U S Centers for Disease Control and Prevention CDC External links Edit Tdap Tetanus Diphtheria Pertussis Vaccine Information Statement U S Centers for Disease Control and Prevention CDC August 2021 DTaP Diphtheria Tetanus Pertussis Vaccine Information Statement U S Centers for Disease Control and Prevention CDC August 2021 DTaP Tdap Td ACIP Vaccine Recommendations U S Centers for Disease Control and Prevention CDC 28 January 2020 Tetanus Toxoid at the U S National Library of Medicine Medical Subject Headings MeSH Diphtheria Tetanus Vaccine at the U S National Library of Medicine Medical Subject Headings MeSH Diphtheria Tetanus Pertussis Vaccine at the U S National Library of Medicine Medical Subject Headings MeSH Diphtheria Tetanus acellular Pertussis Vaccines at the U S National Library of Medicine Medical Subject Headings MeSH Portals Medicine Viruses Retrieved from https en wikipedia org w index php title DPT vaccine 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