DTAP
DTaP vaccines have been in used for more than 40 years.
- Diphtheria is caused by a bacteria, C. diphtheriae. A toxin is produced production only when the bacterium infected by a specific virus (bacteriophage) carrying the genetic information for the toxin (tox gene). Only toxigenic strains can cause severe disease.
- Tetanus is an acute infection caused by a toxin produced by the bacterium Clostridium tetani. Tetanus toxoid consists of a formaldehyde-treated toxin. Efficacy of the toxoid has never been studied in a vaccine trial. It has been inferred from protective antitoxin levels of 0.1 IU/mL are "protective" even though cases of tetanus have been reported with antibody levels much higher than this. It is a rare disease.
- Pertussis is an infection caused by the bacterium, Bordetella pertussis. Acellular pertussis vaccines are contain purified, inactivated components of B. pertussis cells. Several pertussis vaccines have been developed for different age groups; these contain different pertussis components in varying concentrations. Pertussis vaccines are available only as combinations with tetanus and diphtheria toxoids.
DTP vs. DTaP
Since the 1940s, whole cell pertussis vaccines were used to vaccinate infants. There were higher concentrations of the pertussis endotoxin in whole-cell DTP vaccines compared with DTaP. Because the high concentrations of endotoxin were correlated with a higher incidence of adverse events, the switch from whole-cell DTP to acellular DTaP for routine vaccinations in the US occurred in 2001. For more than 60 years, safer and less toxic pertussis vaccines were available but were not use. See The True Story of the Pertussis Vaccine, by Dr Mark Geier
DAPTACEL Package Insert (pdf)
INFANRIX package insert (pdf)
KINRIX package insert (pdf)
TRIPEDIA package insert (pdf) "In the German case-control study and US open-label safety study in which 14,971 infants received Tripedia vaccine, 13 deaths in Tripedia vaccine recipients were reported. Causes of deaths included seven SIDS, and one of each of the following: enteritis, Leigh Syndrome, adrenogenital syndrome, cardiac arrest, motor vehicle accident, and accidental drowning. All of these events occurred more than two weeks post immunization. The rate of SIDS observed in the German case-control study was 0.4/1,000 vaccinated infants. The rate of SIDS observed in the US open-label safety study was 0.8/1,000 vaccinated infants and the reported rate of SIDS in the US from 1985-1991 was 1.5/1,000 live births. By chance alone, some cases of SIDS can be expected to follow receipt of whole-cell pertussis DTP35 or DTaP vaccines.
June 8, 2015 -A Case of Necrotizing Epiglottitis Due to Nontoxigenic Corynebacterium diphtheriae "We report the first case of necrotizing epiglottitis secondary to nontoxigenic C diphtheriae. A fully vaccinated child developed fever, poor oral intake, and sore throat and was found to have necrotizing epiglottitis."
May 21, 2015 - Immunogenicity and reactogenicity of a decennial booster dose of a combined reduced-antigen-content diphtheria–tetanus–acellular pertussis and inactivated poliovirus booster vaccine (dTpa–IPV) in healthy adults (full text)"Pain was the most frequent solicited local adverse event (AE; ≥62.7% subjects) and fatigue the most frequent solicited general AE (≥18.5%). No serious AEs were reported during the study."..."This study was sponsored and funded by GlaxoSmithKline Biologicals SA. GlaxoSmithKline Biologicals SA was involved in all stages of the study conduct and analysis; and also took charge of all costs associated with developing and publishing the manuscript."
- Conflict of interest statement SK, KH and MK are employees of GSK
- and KH and MK declare having GSK stocks.
- NR was previously employed by GSK group of Companies.
- TFS has received honoraria from GSK as consultant, lecturer, member of advisory boards and for conducting clinical trials on behalf of his institution.
March 2015 -Immunogenicity, Safety, and Antibody Persistence at 3, 5, and 10 Years Postvaccination in Adolescents Randomized to Booster Immunization with a Combined Tetanus, Diphtheria, 5-Component Acellular Pertussis, and Inactivated Poliomyelitis Vaccine Administered with a Hepatitis B Virus Vaccine Concurrently or 1 Month Apart (pdf) "The study was powered to evaluate immunogenicity, and so rare AEs or SAEs may not have been detected. Safety was assessed for '14 days' after each vaccination (except for SAEs, which were collected at any time through 30 days after the last vaccination) but this information was not collected throughout the 10-year follow-up. Only 62.8% of the participants could be assessed at the 10-year follow-up, and not all participants could be assessed at all time points. The determination of prior exposure to pertussis disease or pertussis vaccination was based on participant recall only and was not verified from medical records."
- This study was funded by Sanofi Pasteur, which also contributed to the study design, data collection, analysis and interpretation, review and editing of the manuscript (by Robert Lersch), and the decision to publish.
- J. Embree and B. Law have no conflicts of interest to declare. T. Voloshen and A. Tomovici are employees of Sanofi Pasteur
'February 11, 2015 - Evaluation of invalid vaccine doses in 31 countries of the WHO African Region "Of the invalid DTP1 vaccinations, 7.4% and 5.5% were administered at child's age of less than one and two weeks, respectively. In 12 countries, the proportion of invalid DTP3 vaccinations administered with an interval of less than two weeks before the preceding dose varied between 30% and 50%. In 13 countries, the proportion of MCV doses administered at child's age of less than six months varied between 20% and 45%."
January 22, 2015 - Combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type B vaccine; Infanrix™ hexa: twelve years of experience in Italy. PubMed Commons by Jacob Puliyel "Further, the analysis in Table 2 of the linked article http://jacob.puliyel.
January 5, 2015 - Duration of Pertussis Immunity After DTaP Immunization: A Meta-analysis "Pertussis incidence is increasing, possibly due to the introduction of acellular vaccines, which may have decreased the durability of immune response. We sought to evaluate and compare the duration of protective immunity conferred by a childhood immunization series with 3 or 5 doses of diphtheria-tetanus-acellular pertussis (DTaP)."..."Disclosure: Fisman reports financial ties with GlaxoSmithKline, Merck, Novartis and Sanofi Pasteur.
December 2014 - Immunization for Streptococcus pneumoniae Infections in High-Risk Children "While previous reports documented a mixed Th1/Th2 or Th2-skewed response to DTaP vaccine in children, our data suggest that following the first DTaP booster, children aged 16 to 19 months have a cytokine profile consistent with a Th1 response, which is known to be essential for clearance of pertussis infection. To better define aP-induced immune responses following the booster vaccine, further studies are needed to assess cytokine responses pre- and postbooster in DTaP recipients"
October 29, 2014 - A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain (full text) "Almost all participants (97.3%) were observed for the full 30 min after vaccination. No AEs were observed during this period. A small number of participants (n = 25) self-reported AEs occurring 7 days after vaccination (2 in CTC, 23 in SCC, p < 0.000). These were characterized by a local reaction at the injection site with pain and swelling accompanied by fever in 13 cases and headache in 8. No AEs were reported by health centers."..."This study was financed by MSF and the project Optimize, a WHO-PATH collaboration funded by the Bill & Melinda Gates Foundation."
July 7, 2014 - Stool Microbiota and Vaccine Responses of Infants "Actinobacteria abundance was positively associated with T-cell responses to BCG, OPV, and TT; with the delayed-type hypersensitivity response; with immunoglobulin G responses; and with TI. B longum subspecies infantis correlated positively with TI and several vaccine responses. Bacterial diversity and abundance of Enterobacteriales, Pseudomonadales, and Clostridiales were associated with neutrophilia and lower vaccine responses."
July 2014 - Injection site abscess due to Mycobacterium tuberculosis following DPT vaccination. "Injection site abscesses are not so uncommon and usually bacterial in origin. Very occasionally, these are due to mycobacteria, particularly rapidly growing non-tuberculous mycobacteria."
June 24, 2014 - Whooping cough in school age children presenting with persistent cough in UK primary care after introduction of the preschool pertussis booster vaccination: prospective cohort study "The risk of pertussis was more than three times higher (21/53; 40%, 26% to 54%) in children who had received the preschool pertussis booster vaccination seven years or more previously than in those who had received it less than seven years previously (20/171; 12%, 7% to 17%). The risk of pertussis was similar between children who received five and three component preschool pertussis booster vaccines (risk ratio for five component vaccine 1.14, 0.64 to 2.03). Four of six children in whom cough frequency was measured coughed more than 400 times in 24 hours."
June 5, 2014 - Estimating the Effectiveness of Tdap Vaccine for Preventing Pertussis: Evidence of Rapidly Waning Immunity and Differences in Effectiveness by Tdap Brand "Our results demonstrate waning immunity following Tdap vaccination with either brand. Boostrix was more effective than Adacel in preventing pertussis among our cohort, but these findings may not be generalizable to adolescent cohorts that received different DTaP vaccines and should be further examined in studies that include childhood DTaP history."
May 19, 2014 - Immunogenicity and safety of one dose of diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine (Repevax®) followed by two doses of diphtheria, tetanus and poliomyelitis vaccine (Revaxis®) in adults aged ≥40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years "Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5–96.8); tetanus and poliomyelitis, 100% (CI: 98.8–100). Percentage of participants with an antibody titre ≥5 EU/mL against pertussis antigens was ≥95.8% for all five pertussis components." Comment: Add adults to the mix of combination vaccines. Sure will help pharma profits."
February 2014 - Prevalence and Molecular Characterization of Pertactin-Deficient Bordetella pertussis in the United States "Bordetella pertussis isolates lacking pertactin, a key antigen component of the acellular pertussis vaccine, have been observed, suggesting that B. pertussis is losing pertactin in response to vaccine immunity. Screening of 1,300 isolates from outbreak and surveillance studies (historical isolates collected from 1935 up to 2009, isolates from the 2010 California pertussis outbreak, U.S. isolates from routine surveillance between 2010-2012, and isolates from the 2012 Washington pertussis outbreak) by conventional PCR and later by Western blotting and prn sequencing analyses ultimately identified 306 pertactin-deficient isolates. Of these pertactin-deficient strains, 276 were identified as having an IS481 in the prn gene (prnIS481 positive)."
February 2014 - Antibody Responses to Bordetella pertussis Fim2 or Fim3 following Immunization with a Whole-Cell, Two-Component, or Five-Component Acellular Pertussis Vaccine and following Pertussis Disease in Children in Sweden in 1997 and 2007 "Those who received DTaP5 showed a large rise in anti-Fim2 IgG, reflecting the predominant Fim2 serotype at the time. In contrast, those who received DTwP showed an equal rise in anti-Fim2 and anti-Fim3 IgG concentrations, indicating that DTwP may provide a more efficient priming effect for a Fim3 response following contact with B. pertussis.
February 2014 - A Nonadjuvanted Transcutaneous Tetanus Patch Is Effective in Boosting Anti-Tetanus Toxoid Immune Responses "The study revealed significant rises in TTx IgG titers induced by the TTx patches after a low-dose subcutaneous (s.c.) prime with TTx adsorbed to aluminum hydroxide. The TTx patch can therefore be considered an effective alternative to a subcutaneous booster." Comment: Adsorbed to aluminum hydroxide, first needles, then nasal, patches, next foods, microchips...etc!
January 7, 2014 - Dynamic profiles of neutralizing antibody responses elicited in rhesus monkeys immunized with a combined tetravalent DTaP-Sabin IPV candidate vaccine "In this study, the immunogenicity of a combined tetravalent DTaP-sIPV candidate vaccine was investigated in primates by evaluating the neutralizing antibody responses it induced."..."This implies that protective immunogenic effects are conferred by this combined tetravalent formulation."
December 11, 2013 - A Non-adjuvanted Transcutaneous Tetanus Patch Is Effective In Boosting Anti-Tetanus Toxoid Immune Responses "The booster effects of the TTx patches were assessed in a guinea pig model. The study revealed significant rises in TTx IgG titers by the TTx patches after a low-dose s.c. prime with TTx adsorbed to aluminum hydroxide. The TTx patch can therefore be considered as an effective alternative to a subcutaneous booster."
December 9, 2013 - Evaluation of several approaches to immunize parents of neonates against B. pertussis "Offering dTap vaccine in the maternity ward is an effective approach to promote cocooning and increase vaccine uptake. The generalizability and cost effectiveness of this strategy should be investigated further."
November 14, 2013 - Motor palsies of cranial nerves (excluding VII) after vaccination: Reports to the US Vaccine Adverse Event Reporting System (full text) Cranial nerve palsies were reported after a wide variety of vaccines (Table 3). Most reports (43; 63%) listed a single vaccine. Among reports listing single vaccines, the most common vaccines were influenza vaccine seasonal trivalent inactivated, human papillomavirus vaccine quadrivalent, influenza H1N1 vaccine inactivated, and zoster vaccine live. Among reports listing multiple vaccines, the most common vaccines included hepatitis A vaccine; measles, mumps, and rubella vaccine live; diphtheria and tetanus toxoids and acellular pertussis vaccine; Hemophilus influenzae type b vaccine; and pneumococcal conjugate vaccine 7-valent. There was no conspicuous clustering of live or inactivated vaccines with palsies of particular cranial nerves.
November 11, 2013 - Vaccine-Preventable Disease Among Homeschooled Children: Two Cases of Tetanus in Oklahoma "In 2012, 2 cases of tetanus were reported in Oklahoma; both cases involved homeschooled children without documentation of diphtheria-tetanus-acellular pertussis vaccination. We describe the characteristics of both patients and outline innovative outreach measures with the potential to '''''increase vaccination access and coverage among homeschooled children."
October 17, 2013 - Respiratory Diphtheria "A 13-year-old girl with a history of incomplete childhood immunization (she had received only the first of three doses of the diphtheria–pertussis–tetanus vaccine)..."The throat culture was positive for Corynebacterium diphtheriae. The patient recovered without any major complication, with the bull neck disappearing within 1 week after the initiation of treatment."
August 15, 2013 - In the United States Court of Federal Claims OFFICE OF SPECIAL MASTERS H.H., by her parents, * STACEY HANSEN and GABRIEL HANSEN, Petitioners, v. SECRETARY OF HEALTH And Human Services, Respondent. No. 12-203V Special Master Christian J. Moran Filed: August 1, 2013 Reissued as Redacted: August 15, 2013 Stipulation; diphtheria-tetanus-acelluar pertussis (DTaP) vaccine; inactivated poliovirus (IPV) vaccine; encephalopathy (pdf) "B. A lump sum of $5,000.00, representing compensation for past unreimbursable expenses, in the form of a check payable jointly to petitioners, Stacey Hansen and Gabriel Hansen; and C. A lump sum of $52,429.49 in the form of a check payable to petitioners as guardians of the estate of H.H. This amount represents compensation for all remaining damages that would be available under 42 U.S.C. § 300aa-15(a).
June 2013 - Psoriasis triggered by tetanus-diphtheria vaccination "We report the case of a patient whose psoriasis was triggered by tetanus and diphtheria immunization (Td vaccine)."
February 15, 2013 - Importance of Timing of Maternal Combined Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Immunization and Protection of Young Infants "Infants of mothers immunized preconception or in early pregnancy have insufficient pertussis-specific antibodies to protect against infection. Maternal immunization during the third trimester, immunization of other infant contacts, and reimmunization during subsequent pregnancies may be necessary."
February 6, 2013 - Parent “cocoon” immunization to prevent pertussis-related hospitalization in infants: The case of Piemonte in Italy "We assessed the number needed to vaccinate (NNV) to prevent hospital admissions in infants (<12 months) and the potential cost-effectiveness of this strategy in Piemonte. The NNV for parental immunization was at least 5000 to prevent one infant hospitalization in the latest epidemic cycle (2005–2010) at the cost of >€100,000. The “cocoon” programme leads to net costs from a National Health Service (NHS) perspective (ROI < 1). In contexts of low incidence and without reliable data on a high parent-attributable infant risk, the parental “cocoon” programme is poorly efficient and very resource intensive in preventing pertussis in infants."
February 1, 2013 - Safety of a Tetanus-Diphtheria-Acellular Pertussis Vaccine When Used Off-Label in an Elderly Population "Although there is a small increased risk of medically attended inflammatory or allergic events in 1–6 days following Tdap compared to other time periods, it is no more common than that following Td. This study provides empirical safety data suggesting that immunizing adults aged ≥65 years with Tdap to reduce the risk of pertussis in the elderly and their contacts should not have untoward safety consequences."
January 4, 2013 - Adapting Group Sequential Methods to Observational Postlicensure Vaccine Safety Surveillance: Results of a Pentavalent Combination DTaP-IPV-Hib Vaccine Safety Study "In end-of-study prespecified subgroup analyses, risk of medically attended fever was elevated among 1- to 2-year-olds who received DTaP-IPV-Hib vaccine versus historical comparators (relative risk = 1.83, 95% confidence interval: 1.34, 2.50) but not among infants under 1 year old (relative risk = 0.83, 95% confidence interval: 0.73, 0.94)."..."Although lack of a controlled experiment presents numerous challenges, implementation of group sequential monitoring methods in observational safety surveillance studies is promising and warrants further investigation."
November 26, 2012 - Re-emergence of diphtheria and pertussis: Implications for Nigeria "The recent reported increases in the incidence of these two diseases in countries, which maintain high childhood vaccination coverage is a source of concern not only to these countries but also for developing countries with weak immunization programmes. Nigeria for example reported 11,281 cases of pertussis, the second highest number of cases worldwide in 2009."
November 26, 2012 - Improved protocols for histamine sensitization testing of acellular pertussis vaccines "The histamine sensitization test is a widely used method for measuring the residual toxicity of pertussis toxin in acellular pertussis vaccines Although it has been used as a routine assay for decades, the current protocols are difficult to standardize because the test results vary considerably and are based on several factors, including mouse strain, age and sex. In this study, we observed that mice of strains CD1, ddY and C57/BL6 were sufficiently sensitive to pertussis toxin among six mice strains tested and that aged male mice were more sensitive to pertussis toxin than younger or female mice."
November 8, 2012 - U.S. Postlicensure safety surveillance for adolescent and adult tetanus, diphtheria and acellular pertussis vaccines: 2005–2007 "A total of 2090 reports (7% were serious; 55% listed Tdap alone) involving Tdap vaccinees were submitted to VAERS May 2005–June 2007. The crude reporting rate was 10.2 per 100,000 vaccine doses distributed. The median age of vaccinees was 22 years, and the female to male ratio was about 2 to 1. The majority of reports described common local and systemic signs and symptoms, such as injection site reactions, fever, and headache. Rarely reported adverse events included myopericarditis, demyelinating diseases of the central nervous system, Guillain–Barré Syndrome, syncope, encephalopathy/encephalitis, seizure, Bell's palsy, anaphylaxis, and thrombocytopenia."
November 6, 2012 - Differences in avidity of IgG antibodies to pertussis toxin after acellular pertussis booster vaccination and natural infection "Although immunity after infection seems to persist longer than that after vaccination, the exact mechanism(s) is not known."..."Our results suggest that there may be difference in quality and quantity of antibodies to PT after vaccination and after infection. Furthermore, AI could be a help for vaccine studies."
November 1, 2012 - Evaluation of adult dTPaP vaccination coverage in France: experience in Lyon city, 2010--2011 "Comparison of reported data with confirmed data revealed a considerable percentage of subjects who wrongly believed their vaccinations to be up to date''''', particularly for pertussis. The percentage of people who thought they were vaccinated but who were not should prompt health authorities to develop VC monitoring programmes to prevent insufficient vaccination due to ignorance of individual status. The collection of vaccination coverage data needs to be improved and could be centred in the community and/or hospital and/or workplace. Investigations should evaluate the characteristics of individuals who incorrectly report their vaccine status. This issue was not explored because of limited sample size. Improving vaccination coverage involves adapting measurement tools, developing public information campaigns, training doctors and ensuring a better understanding on the part of the general public."
September 27, 2012 - Structural Basis for Gluten Intolerance in Celiac Sprue (pdf) "The primary sequence of the 33-mer gliadin peptide also had homologs among a few nongluten proteins. Among the strongest homologs were internal sequences from pertactin a highly immunogenic protein from Bordetella pertussis) and a mammalian protein tyrosine phosphatase of unknown function."
September 21, 2012 - A phase III, randomized controlled study to assess the safety and immunogenicity of a semi-synthetic diphtheria, tetanus and whole-cell pertussis vaccine in Indian infants "Reactions to DTwP vaccine are well known and are a matter of great concern, much for the development of next generation combination vaccines. To avoid such reactions which occur from foreign compounds, WHO suggested manufacture of DTwP vaccine using semi-synthetic medium."
September 13, 2012 -Waning Protection after Fifth Dose of Acellular Pertussis Vaccine in Children "after the fifth dose of DTaP, the odds of acquiring pertussis increased by an average of 42% per year."
June 15, 2012 - Unexpectedly Limited Durability of Immunity Following Acellular Pertussis Vaccination in Preadolescents in a North American Outbreak "The vaccination rate among PCR-positive preadolescents were approximately equal to that of controls. The vaccine effectiveness was 41%, 24%, and 79% for children aged 2–7 years, 8–12 years, 13–18 years, respectively."
June 7, 2012 - Diphtheria-Tetanus-Pertussis Vaccination Administered After Measles Vaccine: Increased Female Mortality? "We examined whether missing DTP vaccine at this time point was associated with sex-differential effects on mortality. In females, missing DTP was associated with 3.55 (95%CI=1.23-10.26) times higher risk of dying before 36 months, whereas it made no difference in males (0.97 (0.34-2.80)). The result supports that receiving DTP after measles vaccine affects females negatively."
February 27, 2012 - Clinical study of transcutaneous vaccination using a hydrogel patch for tetanus and diphtheria "This easy-to-use and safe TCI formulation enables mass treatment in an outbreak setting and increased vaccination rates in developing countries, and will greatly contribute to worldwide countermeasures against infectious diseases."
February 22, 2012 - Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b "DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of the first 2 vaccinations given at 3 and 5 months, although the absolute risk was small. Vaccination with DTaP-IPV-Hib was not associated with an increased risk of epilepsy."
February 13, 2012 - Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial "Two-thirds of the children had received DTP at 2 months and 50 deaths occurred between the 2-month and 6-month visits."
February 3, 2012 - Diphtheria, pertussis (whooping cough), and tetanus vaccine induced recurrent seizures and acute encephalopathy in a pediatric patient: Possibly due to pertussis fraction (full text) "The child was vaccinated for the first dose of DPT before 16 days. After 3 days of vaccination, the child developed seizures and admitted to the nearby community health center (CHC) for 9 days. The patient was discharged after the control of seizures and was at home for 3 days without any treatment. Treatment detail is not available on admission at CHC. Reappearance of seizures occurred at home. After that the patient was admitted and treated with phenytoin, methyl prednisolone, and levetiracetam in private hospital at Bhavnagar. Afterward the patient was transferred to our center for further management. There was no history of head injury, trauma, tuberculosis, febrile convulsion, and ear discharge. There was no previous history of seizure before DPT vaccination. Provisional diagnosis as postvaccination encephalopathy was made.
February 2012 - Safety and Immunogenicity of 2 Mixed Primary Infant Immunization Schedules of Pentavalent Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliomyelitis, and Haemophilus influenzae Type b Vaccines at 2, 4, and 6 Months of Age: A Randomized Controlled Trial "Mixed 2-, 4-, 6-month pentavalent infant vaccine schedules had different immunogenicity and reactogenicity, with a PPI schedule being more reactogenic, and less immunogenic for PRP and fimbriae 2 and 3 antigens at 7 months."
January 2012 - Combining vitamin A and vaccines: convenience or conflict? " We found that the two interventions were not independent. Vitamin A enhanced the antibody response to measles vaccine given at 9 months of age significantly, especially in boys. The effects were sustained over time; the children who had received vitamin A with their measles vaccine were more protected against measles at 6-8 years of age. Though vitamin A supplementation had a beneficial effect on the immune response to measles vaccine, it intrigued me that the effect of vitamin A supplementation on overall mortality was not always beneficial. While vitamin A was beneficial when given after 6 months of age, and two studies had shown a beneficial effect when given at birth, all studies testing the effect between 1-5 months of age had found no effect. These time windows are dominated by three different childhood vaccines: BCG vaccine given at birth, diphtheria-tetanus-pertussis (DTP) vaccine given between 1-5 months of age, and measles vaccine given at 9 months of age."..."The inactivated DTP vaccine worryingly has been associated with increased mortality from other infectious diseases. Both positive and negative effects are strongest for girls. I proposed the hypothesis that vitamin A amplifies not only the specific vaccine effects, as we saw for measles vaccine, but also the non-specific effects of vaccines on mortality from other infectious diseases."
January 2012 - Assessment of a Mandatory Tetanus, Diphtheria, and Pertussis Vaccination Requirement on Vaccine Uptake over Time "Beginning in April 2006, current employees were offered the Tdap vaccine. HCP (healthcare personnel) were informed of the r'equirements for vaccination via an employee newsletter and their supervisors, and they were given 2 years to become compliant with the policy."..."In March 2010, current employees were reminded via an employee newsletter that immunity [vaccination] to pertussis was required of all UNC employees. In September 2010, after an internal review of the policy, current HCP were informed (via supervisors and an employee newsletter) that any persons not providing evidence of a medical contraindication or proof of immunization by November 2, 2010, would be furloughed without pay."
January 2012 - A need for careful evaluation of endotoxin contents in acellular pertussis-based combination vaccines. "Three out of the four imported vaccine batches showed the levels of BWD toxicity even comparable to that of DT-whole cell pertussis vaccine."
November 3, 2011 - Neuropathology of vaccination in infants and children The Children's Hospital of Philadelphia, Department of Pathology - United States. Health Resources and Services Administration, National Vaccine Injury Compensation Program, United States. "Most commonly implicated vaccines were DTP/DTaP, followed by MMR and IPV/OPV, but almost all of the vaccines currently given to infants/children were alleged to be responsible for the illness/death."..."Conclusions There was no obvious relationship between type of vaccine (or vaccines simultaneously administered) to time of onset of symptoms, nature of symptoms or the lesions found."
February 2, 2011 - Tdap Vaccination Strategies for Adolescents and Adults, Including Health Care Personnel (pdf)
December 2010 - Thrombocytopenic Purpura Following Vaccination in Early Childhood: Experience of a Medical Center in the Past 2 Decades (pdf) "Six of the 12 post-vaccination cases had received combined-component vaccines, including 4 cases following DTaP-containing vaccine that occurred before 3.5 months of age, and 2 cases after MMR vaccine at 16 months of age. The other 6 cases received single component vaccines, including 5 cases after HBV vaccine at 1 month of age, and 1 case after varicella vaccine at 14 months of age.
Summer 2010 - Increase in localised symptoms in 4-year-olds following revaccination with DaPT-IPV. "In 2008, we received an increasing number of notifications of serious local reactions after the revaccination of 4-year-olds with acellular DPT-IPV (average 3 per 1000 vaccinated children) with a peak in October/November."
September 17, 2008 - Antibody decay after immunisation of health-care workers with an acellular pertussis vaccine
January 21, 2008 - Delay in diphtheria, pertussis, tetanus vaccination is associated with a reduced risk of childhood asthma "We found a negative association between delay in administration of the first dose of whole-cell DPT immunization in childhood and the development of asthma; the association was greater with delays in all of the first 3 doses. The mechanism for this phenomenon requires further research."
January 21, 2008 - Acute Hemolytic Anemia Related to Diphtheria-Pertussis-Tetanus Vaccination "Three infants developed severe hemolytic anemia following the second or third diphtheria-pertussis tetanus vaccination. Direct antiglobulin tests were positive, and the infant most severely affected also had reduced serum complement levels, indicating an immunological mechanism for the hemolysis."
January 2008 - Real-Time Polymerase Chain Reaction Detection of Bordetella pertussis DNA in Acellular Pertussis Vaccines
November 1, 2007 - Atypical Tetanus in a Completely Immunized 14-Year-Old Boy (full text) "However, as the clinical signs changed from flaccid paralysis to the tetanus-typical rigor, tetanus became clinically obvious despite the patient's history of appropriate tetanus vaccination."
March 8, 2007 - Lung pathology and immediate hypersensitivity in a mouse model after vaccination with pertussis vaccines and challenge with Bordetella pertussis.
January 4, 2007 - Modulation of the infant immune responses by the first pertussis vaccine administrations "However, Pa recipients also developed a strong Th2-type cytokine response to the B. pertussis antigens, as noted previously. In addition, they induced Th2-type cytokines to the co-administrated antigen tetanus toxoïd, as well as to the food antigen beta-lactoglobulin. Furthermore, the general cytokine profile of the Pa recipients was strongly Th2-skewed at 6 months, as indicated by the cytokines induced by the mitogen phytohaemagglutinin. These data demonstrate that the cytokine profile of 6-month-old infants is influenced by the type of formulation of the pertussis vaccine they received at 2, 3 and 4 months of life. Large prospective studies would be warranted to evaluate the possible long-term consequences of this early modulation of the cytokine responses in infants."
June 19, 2006 - Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants (full text)
February 2005 - Effects of lowering the aluminium content of a dTpa vaccine on its immunogenicity and reactogenicity when given as a booster to adolescents.
January 2005 - Reduced Immunogenicity of Diphtheria and Tetanus Toxoids When Combined With Pertussis Toxoid "Pertussis toxoid causes a small but significant reduction of the immunogenicity of diphtheria toxoid and tetanus toxoid."
September-October 2004 - Urinary tract diseases revealed after DTP vaccination in infants and young children: cytokine irregularities and down-regulation of cytochrome P-450 enzymes induced by the vaccine may uncover latent diseases in genetically predisposed subjects. "Also, interleukin genetic polymorphisms, especially the constellation of TNF-alpha and IL-6 genetic variants, might predispose some infants with infection to a more than usually intense inflammatory response in the kidneys after vaccination. It seems that the aforementioned pathomechanism may also be responsible for some cases of sudden infant death syndrome, which is often preceded by infection/inflammation."
February 2004 - Adverse events after immunisation with aluminium-containing DTP vaccines: systematic review of the evidence. "In older children, there was no association between exposure to aluminium-containing vaccines and onset of (local) induration, swelling, or a raised temperature, but there was an association with local pain lasting up to 14 days."
December 8, 2003 - Unexpectedly high incidence of persistent itching nodules and delayed hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer (pdf) "Persistent itching nodules and type IV hypersensitivity to aluminium was observed among children who received aluminium hydroxide adsorbed DT, DTaP and aP vaccines from SSI in a higher frequency than has ever been reported. Aluminium sensitization has also, for the first time, been demonstrated in children without any local reaction after vaccination."
June 19, 2002 - Transfusion support with RBCs from an Mk homozygote in a case of autoimmune hemolytic anemia following diphtheria-pertussis-tetanus vaccination "Several reports have identified the diphtheria-pertussis-tetanus (DPT) vaccination as a possible trigger for AIHA. Life-threatening AIHA was diagnosed in a 6-week-old infant 5 days after receiving a DPT vaccination. The patient required daily transfusion and/or exchange transfusion for 3 weeks."
May 2002 - Clinical implications of endotoxin concentrations in vaccines. "This analysis confirmed higher concentrations of endotoxin in whole-cell DTP vaccines compared with DTaP or DT vaccines. As high concentrations of endotoxin may be correlated with a higher incidence of adverse events, the switch from whole-cell DTP to DTaP for routine vaccinations in the US seems well justified."
April 24, 2002 - Vaccination-associated immune hemolytic anemia in two children "Two children in whom acute autoimmune hemolytic anemia (AIHA) developed after vaccination were studied. The children were a 20-month-old girl and a 21-month-old boy. The diagnosis of AIHA was made in accordance with established criteria (hemolysis, positive DAT, and lack of other reasons for the hemolysis). Serologic tests were performed according to standard technique."
September 14, 2001 - Assessment of injection site reactions to an acellular pertussis-based combination vaccine, including novel use of skin tests with vaccine antigens.
October 1, 2000 - Hypotonic–Hyporesponsive Episodes Reported to the Vaccine Adverse Event Reporting System (VAERS), 1996–1998 "The vast majority of children (93%) with HHE received a pertussis-containing vaccine, either diphtheria-tetanus-acellular pertussis (DTaP, 28%), DTwP (11%), or diphtheria-tetanus-pertussis-Haemophilus influenzae type b (DTwP-HIB, 61%)."
August 3, 2000 - Leslie Brown, as Legal Representative of her deceased daughter Lauren Brown, Petitioner, vs. Secretary of Department of Health and Human Services, Respondent. Curtis R. Webb, Twin Falls, Idaho, for petitioner. David L. Terzian, Washington, DC, for respondent. "In the article, the authors describe three children who received their second or third DPT and developed severe hemolytic anemia afterward. Direct antiglobulin tests were positive. The infant most severely affected also had reduced serum complement levels, indicative of an immunological mechanism for the hemolysis."..."Petitioner is entitled to $250,000.00. A check shall be made payable to petitioner for this sum."
February 2000 - Effects of diphtheria-tetanus-pertussis or tetanus vaccination on allergies and allergy-related respiratory symptoms among children and adolescents in the United States.
January 27, 2000 - Development of DTaP-based Hib conjugate combination vaccines: SmithKline Beecham (pdf) "In response to the continuing trend for an increase in the number of injections in national childhood immunization schedules, combination vaccines containing multiple antigens have been developed."
January 2000 - Safety and immunogenicity of six acellular pertussis vaccines and one whole-cell pertussis vaccine given as a fifth dose in four- to six-year-old children. "Significant increases in antibodies directed against the included antigens were observed for all DTaP vaccines in paired pre- and post-fifth dose sera. Post-fifth dose antibody concentrations differed significantly among the DTaP vaccines. Some children in the study showed an antibody response to an antigen not reported to be in the DTaP vaccine."
2000 - A severe adverse event after vaccine for diphtheria, tetanus, pertussis and poliomyelitis (DTP + polio) in a 4.5 month old infant "We report the case of neuroallergic reaction 5 days after receiving the second course of DTP + Polio vaccine in a 4.5 month old girl."
December 1999 - Local reactions and IgE antibodies to pertussis toxin after acellular diphtheria-tetanus-pertussis immunization. "Acellular pertussis immunization induces IgE antibodies to pertussis toxin, especially after booster vaccination. The higher median pre- and post-booster levels of pertussis toxin specific immunoglobulin E and post-booster levels of IgG to pertactin and diphtheria in children with local side-effects reflect a multifactorial immunological mechanism of such reactions."
September 1999 - Vaccination with pertussis toxin alters the antibody response to simultaneous respiratory syncytial virus challenge. "The ability of both chemically detoxified and purified PT to alter the immune response to coadministered inactivated antigens, as well as to simultaneously introduced live viral antigens, emphasizes that integration of numerous antigens into multivalent vaccines will require careful study of the immunomodulatory properties of each component. Further studies will clarify whether PT's ability to alter antibody isotype responses to live RSV infection also impacts other aspects of the RSV-specific immune response that could influence disease severity.
July 1999 - Severe apneas following immunization in premature infants. "Four premature infants developed apnoeas severe enough to warrant resuscitation after immunization with diphtheria, pertussis, and tetanus (DPT), and Haemophilus influenzae B (Hib). One required re-intubation and ventilation. Although apnoeas after immunisation are recognised, they are not well documented. It is time for further research to elucidate the best time to immunise such infants."
June 1999 - Approaches to the control of acellular pertussis vaccines. "The quality control of acellular pertussis vaccines presents particular problems related to the differences in composition and method of detoxification used in the various type of preparation. These vaccines are not amenable to potency assay by the active mouse protection test used for whole-cell pertussis vaccines and assurance of protective activity is problematic."
May 21, 1999 -Local reactions and IgE antibodies to pertussis toxin after acellular diphtheria-tetanus-pertussis immunization "The higher median pre- and post-booster levels of pertussis toxin specific immunoglobulin E and post-booster levels of IgG to pertactin and diphtheria in children with local side-effects reflect a multifactorial immunological mechanism of such reactions."
February 1999 - A clinical analysis of gelatin allergy and determination of its causal relationship to the previous administration of gelatin-containing acellular pertussis vaccine combined with diphtheria and tetanus toxoids "DTaP immunization histories suggest that the gelatin-containing DTaP vaccine may have a causal relationship to the development of this gelatin allergy."
November 1998 - Early childhood infection and atopic disorder. "Interpretation of the prediction of atopic disorders by immunisation with whole-cell pertussis vaccine and treatment with oral antibiotics needs to be very cautious because of the possibilities of confounding effects and reverse causation. However, plausible immune mechanisms are identifiable for the promotion of atopic disorders by both factors and further investigation of these associations is warranted."
November 1997 - Is infant immunization a risk factor for childhood asthma or allergy? "The Christchurch Health and Development Study comprises 1,265 children born in 1977. The 23 children who received no diphtheria/pertussis/tetanus (DPT) and polio immunizations had no recorded asthma episodes or consultations for asthma or other allergic illness before age 10 years; in the immunized children, 23.1% had asthma episodes, 22.5% asthma consultations, and 30.0% consultations for other allergic illness. Similar differences were observed at ages 5 and 16 years."
1997 - Are serological responses to acellular pertussis antigens sufficient criteria to ensure that new combination vaccines are effective for prevention of disease? "Thus, although diphtheria-tetanus-acellular pertussis (DTaP) vaccine has been considered a prime building block in the development of new combination vaccines, modifying DTaP by the addition of new vaccine components may decrease the ability of the vaccine to protect against pertussis without a change in serum antibody response."
August 3, 1995 - Effect of Inactivated Poliovirus Vaccine on the Antibody Response to Bordetella pertussis Antigens When Combined with Diphtheria-Pertussis-Tetanus Vaccine (full text) - "The interaction of antigens in combination vaccines is receiving increasing attention as recommendations for infant immunization change with the availability of new vaccines. This randomized study supports the conclusions of a previous nonrandomized study that found a diminished antibody response to B. pertussis antigens when poliovirus vaccine was administered with DTP."
April 1992 - Severe tetanus in immunized patients with high anti-tetanus titers. "Severe (grade III) tetanus occurred in three immunized patients who had high serum levels of anti-tetanus antibody. The disease was fatal in one patient. One patient had been hyperimmunized to produce commercial tetanus immune globulin. Two patients had received immunizations 1 year before presentation. Anti-tetanus antibody titers on admission were 25 IU/ml to 0.15 IU/ml by hemagglutination and ELISA assays; greater than 0.01 IU/ml is considered protective. Even though one patient had seemingly adequate anti-tetanus titers by in vitro measurement (0.20 IU), in vivo mouse protection bioassays showed a titer less than 0.01 IU/ml, implying that there may have been a hole in her immune repertoire to tetanus neurotoxin but not to toxoid."
March 1992 - Attributable risk of DTP (diphtheria and tetanus toxoids and pertussis vaccine) injection in provoking paralytic poliomyelitis during a large outbreak in Oman. "During a poliomyelitis outbreak investigation in Oman, vaccination records were reviewed for 70 children aged 5–24 months with poliomyelitis and from 692 matched control children. A significantly higher proportion of cases received a DTP (diphtheria and tetanus toxoids and pertussis vaccine) injection within 30 days before paralysis onset than did controls (42.9% vs. 28.3%; odds ratio, 2.4; 95% confidence interval, 1.3–4.2)."
October 1991 - Adverse reactions after injection of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine are not due only to pertussis organisms or pertussis components in the vaccine. "Due to the increasing concern about the toxicity of aluminium, other adjuvants like calcium phosphate may be evaluated as an alternative to aluminium adjuvants. To minimize reactions after immunization with DPT vaccine due to impurities in the toxoids, the use of toxoided purified toxins is suggested."
October 1988 - Infectious episodes following diphtheria-pertussis-tetanus vaccination. A preliminary observation in infants. "In addition to reactive fever during the first 3 days following DPT immunization, an increase in infectious episodes seems to occur in infants during the month following administration of this vaccine."
February 1, 1985 - Outbreaks of Group A Streptococcal Abscesses Following Diphtheria-Tetanus Toxoid-Pertussis Vaccination
1985 - Murine model for pertussis vaccine encephalopathy: role of the major histocompatibility complex; antibody to albumin and to Bordetella pertussis and pertussis toxin. "A mouse model for pertussis immunization encephalopathy has been described with features that closely resemble the severe adverse reactions occasionally seen after pertussis vaccine administration,m including seizures and a shock-like state leading to death. These reactions are produced with nearly one hundred percent efficiency provided that the mice immunized with Bordetella pertussis have 1) the appropriate major histocompatibility (H-2) genotype, 2) have been sensitized to bovine serum albumin (BSA), and 3) that the injected B. pertussis contained sufficient amounts of pertussis toxin."
May 1983 - The non-specific enhancement of allergy. I. In vivo effects of Bordetella pertussis vaccine on IgE synthesis. "Bordetella pertussis organisms, with or without a small dose of alumhydroxide, enhance in rats the production of IgE antibodies to an unrelated antigen, even if this antigen has been administered 6 weeks beforehand. This non-specific enhancement of IgE antibodies is accompanied by a substantial rise in total serum IgE and by the production of IgE antibodies to B. pertussis."
February 1979 - Increased Intracranial Pressure After Diphtheria, Tetanus, and Pertussis Immunization (full text) "There is a general tendency to under-report complications associated with immunizations. Part of the reason undoubtedly is related to the difficulty in proving cause and effect between the vaccine and the untoward response. However, if the complication occurs within 24 to 48 hours of administration of the vaccine in an otherwise well child, the association should arouse suspicion."
November 11, 1967 - Further experience of reactions, especially of a cerebral nature, in conjunction with triple vaccination: a study based on vaccinations in Sweden 1959-65. (full text) "Case 2.-This child was healthy and of normal development. There was no reaction after the first injection. The patient had a convulsive attack, and a temperature of 39.5' C. on the ninth day after the second injection at the age of 7 months. Next day there was a new attack-clonic on the right side-followed by paralysis. Lumbar puncture revealed albumin 34 mg./100 ml. and 2 cells. On the following day there were similar convulsions and paralysis, and complete loss of contact. E.E.G. showed incessant paroxysmal activity over the entire left hemisphere.