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BACKGROUND AND OBJECTIVES Infant influenza and pertussis disease causes considerable morbidity and mortality worldwide. We examined the effectiveness of maternal influenza and pertussis vaccines in preventing these diseases in infants. METHODS This inception cohort study comprised women whose pregnancies ended between September 1, 2015, and December 31, 2017, in Victoria, Australia. Maternal vaccination status was sourced from the Victorian Perinatal Data Collection and linked to 5 data sets to ascertain infant outcomes and vaccination. The primary outcome of interest was laboratory-confirmed influenza or pertussis disease in infants aged RESULTS Among 186 962 pregnant women, 85 830 (45.9%) and 128 060 (68.5%) were vaccinated against influenza and pertussis, respectively. There were 175 and 51 infants with laboratory-confirmed influenza and pertussis disease, respectively. Influenza VE was 56.1% (95% CI, 23.3% to 74.9%) for infants aged CONCLUSIONS Our study provides evidence of the direct effectiveness of maternal influenza and pertussis vaccination in preventing these diseases in infants aged

BACKGROUND AND OBJECTIVES: Maternal immunization with tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is routinely recommended in many countries as a strategy to protect young infants against severe pertussis infection; few studies have assessed whether prenatal exposure to the vaccine is associated with any longer-term adverse health effects in children. We evaluated the long-term safety of exposure to Tdap vaccination during pregnancy. METHODS: Population-based retrospective cohort study conducted in Ontario, Canada using multiple linked province-wide health administrative databases. All live births between April 2012 and March 2017 were included, and children were followed for up to 6 years to ascertain study outcomes. Children exposed to prenatal Tdap were propensity score matched to unexposed children at a 1:5 ratio. Tdap vaccination during pregnancy was ascertained by using vaccine-specific fee codes. Immune-related (infectious diseases, asthma) and nonimmune-related (neoplasm, sensory disorders) outcomes and a nonspecific morbidity outcome (urgent or inpatient health service use) were evaluated from birth to end of follow-up. RESULTS: Of 625 643 live births, 12 045 (1.9%) were exposed to Tdap in utero. There were no significant increased risks of adverse childhood outcomes and prenatal Tdap exposure; however, we observed inverse associations (adjusted incidence rate ratio [95% confidence interval]) with upper respiratory infections (0.94 [0.90–0.99]), gastrointestinal infections (0.85 [0.79–0.91]), and urgent and inpatient health service use (0.93 [0.91–0.96]). CONCLUSIONS: Exposure to Tdap vaccination in pregnancy was not associated with any increased risk of adverse health outcomes in early childhood, supporting the long-term safety of Tdap administration in pregnancy.

* Abbreviations: aP — : acellular pertussis DTaP — : diphtheria-tetanus-acellular pertussis DTwP — : diphtheria, tetanus, and whole-cell pertussis HIC — : high-income country LMICs — : low- and middle-income countries WHO — : World Health Organization Pertussis is a major public health concern. In 2014, 24 million cases and 160 000 deaths from pertussis in children

BACKGROUND: Mandatory vaccination has been effective in maintaining high vaccination coverage in countries such as the United States. However, there are no peer-reviewed analyses of the association between mandates and both coverage and subsequent incidence of vaccine-preventable disease in Europe. METHODS: Using data from the European Centre for Disease Prevention and Control and the World Health Organization, we evaluated the relationship between country-level mandatory vaccination policies and (1) measles and pertussis vaccine coverage and (2) the annual incidence of these diseases in 29 European countries. Multivariate negative binomial and linear regression models were used to quantify these associations. RESULTS: Mandatory vaccination was associated with a 3.71 (95% confidence interval [CI]: 1.68 to 5.74) percentage point higher prevalence of measles vaccination and a 2.14 (95% CI: 0.13 to 4.15) percentage point higher prevalence of pertussis vaccination when compared with countries that did not have mandatory vaccination. Mandatory vaccination was only associated with decreased measles incidence for countries without nonmedical exemptions (adjusted incidence rate ratio = 0.14; 95% CI: 0.05 to 0.36). We did not find a significant association between mandatory vaccination and pertussis incidence. CONCLUSIONS: Mandatory vaccination and the magnitude of fines were associated with higher vaccination coverage. Moreover, mandatory vaccination was associated with lower measles incidence for countries with mandatory vaccination without nonmedical exemptions. These findings can inform legislative policies aimed at increasing vaccination coverage.

* Abbreviations: DTaP — : diphtheria-tetanus-acellular pertussis DTwP — : diphtheria, tetanus toxoids, and whole-cell pertussis KPNC — : Kaiser Permanente Northern California In this issue of Pediatrics , the vaccine research group at Kaiser Permanente Northern California (KPNC) contributed another important article outlining the challenges of pertussis control in a highly vaccinated population.1 Nearly one-half million children born between 1999 and 2016 and managed at KPNC from 2006 to 2017 were evaluated. Of those immunized children, all had received only diphtheria-tetanus-acellular pertussis (DTaP) vaccine. In total, 738 polymerase chain reaction–confirmed pertussis cases were diagnosed. Pertussis risk was 13 times higher among unvaccinated and nearly 2 times higher among undervaccinated children when compared with those who were fully vaccinated. However, >80% of the total pertussis cases were seen in children who had received all their recommended DTaP vaccine doses. Pertussis risk increased with increasing time since vaccination, clearly demonstrating waning immunity, which the KPNC group and others had previously reported.2,3 Those individuals who began their medical career after 1997, when DTaP totally replaced the conventional diphtheria, tetanus toxoids, and whole-cell pertussis (DTwP) vaccines, may question why DTaP replaced DTwP in the first place. When I began my academic career at Vanderbilt University School of Medicine in 1980, pertussis disease appeared to be well controlled.4 Rarely would cases present to the medical center, and generally … Address correspondence to Kathryn M. Edwards, MD, Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University School of Medicine, 1161 21st Ave South, D-7227 Medical Center North, Nashville, TN 37232. E-mail: kathryn.edwards{at}vumc.org

BACKGROUND: Rotavirus remains an important cause of gastroenteritis and has been associated with the hospitalization of 34 to 53 per 10 000 children METHODS: The National Immunization Survey is a random-digit–dial, population-based survey including US children 19 to 35 months of age. Children fully vaccinated for rotavirus were those who received 3 doses of the pentavalent rotavirus vaccine, 2 doses of the monovalent rotavirus vaccine, or ≥3 doses of either vaccine type. Doses of the diphtheria-tetanus-acellular pertussis vaccine received from 6 weeks through 8 months and 0 days of age when the rotavirus vaccine was not received were considered missed opportunities for rotavirus vaccination according to Advisory Committee on Immunization Practices (ACIP) guidelines, and doses of the diphtheria-tetanus-acellular pertussis vaccine or measles-mumps-rubella vaccine from 6 weeks through 24 months and 0 days of age were considered missed opportunities according to World Health Organization recommendations. RESULTS: Of the 14 571 children included in the 2014 National Immunization Survey, 71% were fully vaccinated for rotavirus. Lower socioeconomic status increased the likelihood of being unvaccinated for rotavirus. Among the 14% of children who received no doses of the rotavirus vaccine, 72% had ≥1 ACIP-defined missed opportunities, and 83% had ≥1 World Health Organization–defined missed opportunities. Higher socioeconomic status increased the likelihood of having missed opportunities. Complete rotavirus vaccine coverage could be improved to 81% if all missed opportunities within the ACIP-recommended schedule were addressed. CONCLUSIONS: Addressing missed opportunities for rotavirus vaccination is essential to achieving the 80% rotavirus vaccine coverage target outlined by Healthy People 2020.

[Figure: see text] OBJECTIVES: To determine pertussis risk by diphtheria-tetanus-acellular pertussis (DTaP) vaccination status and time since last DTaP dose. METHODS: Children born at Kaiser Permanente Northern California between 1999 and 2016 were followed from 3 months of age until they tested positive for pertussis; disenrolled from Kaiser Permanente Northern California; received the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed vaccine; turned 11 years of age, or the end of the study period. DTaP vaccination status was categorized on the basis of the number of doses received in relation to the number of doses expected according to the Advisory Committee on Immunization Practice–recommended ages. RESULTS: Among 469 982 children ages 3 months to 11 years, we identified 738 pertussis cases. A total of 99 cases were unvaccinated, 36 were undervaccinated, 515 were fully vaccinated, and 88 were fully vaccinated plus 1 dose. Pertussis risk was 13 times higher among unvaccinated (adjusted hazard ratio [aHR] = 13.53; 95% confidence interval [CI] 10.64–17.21) compared with fully vaccinated children and 1.9 times higher (aHR = 1.86; 95% CI 1.32–2.63) among undervaccinated children. Among vaccinated children ages 19 to

EB Walter, NP Klein, AP Wodi. Pediatrics . 2020;145(3):e20191909 To determine if administration of the quadrivalent inactivated influenza vaccine (IIV4) at a separate visit from the 13-valent pneumococcal conjugate vaccine (PCV13) and diphtheria–tetanus–acellular pertussis vaccine (DTaP) would affect the occurrence of postvaccination fever. The study included 221 children aged 12 to 16 months (median age 14.6 months) who were fully up-to-date on vaccinations as per the Advisory Committee on Immunization Practices (ACIP). 93.2% of patients were receiving either their first or only dose of influenza vaccine for the season, …

BACKGROUND: Increasing vaccination of pregnant women makes it important to assess safety events potentially linked to prenatal vaccination. This study investigates the association between prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination and autism spectrum disorder (ASD) risk in offspring. METHODS: This is a retrospective cohort study of mother-child pairs with deliveries January 1, 2011 to December 31, 2014 at Kaiser Permanente Southern California hospitals. Maternal Tdap vaccination from pregnancy start to delivery date was obtained from electronic medical records. A diagnosis of ASD was obtained by using International Classification of Diseases, Ninth and Tenth Revision codes. Children were managed from birth to first ASD diagnosis, end of membership, or end of follow-up (June 30, 2017). Cox proportional hazards models estimated the unadjusted and adjusted hazard ratios (HRs) for the association between maternal Tdap vaccination and ASD, with inverse probability of treatment weighting to adjust for confounding. RESULTS: Women vaccinated were more likely to be Asian American or Pacific Islander, be nulliparous, have a higher education, receive influenza vaccination prenatally, and give birth at term. ASD was diagnosed in 1341 (1.6%) children, and the incidence rate was 3.78 per 1000 person years in the Tdap exposed and 4.05 per 1000 person years in the unexposed group (HR: 0.98, 95% confidence interval: 0.88–1.09). The inverse probability of treatment weighting–adjusted analyses revealed that prenatal Tdap vaccination was not associated with an increased ASD risk (HR: 0.85, 95% confidence interval: 0.77–0.95). CONCLUSIONS: Prenatal Tdap vaccination was not associated with an increased ASD risk. We support recommendations to vaccinate pregnant women to protect infants, who are at highest risk of death after pertussis infection.

* Abbreviations: DTaP — : diphtheria, tetanus, and acellular pertussis DTwP — : diphtheria, tetanus, whole-cell pertussis VAERS — : Vaccine Adverse Event Reporting System The decision to replace effective whole-cell vaccines for pertussis with less reactogenic but potentially less efficacious acellular vaccines for the primary immunization of children in the United States in the 1990s was carefully considered.1 The performance of the heat- or formalin-inactivated Bordetella pertussis whole-cell vaccine combined with diphtheria and tetanus toxoids (diphtheria, tetanus, whole-cell pertussis [DTwP]) licensed in the 1940s had resulted in a dramatic decrease in the number of cases of pertussis to a nadir in the mid-1970s.2 However, parallel to this success, the occurrence of rare but potentially serious adverse events associated with DTwP administration became unacceptable. Particularly concerning was the occurrence of high fever, febrile seizures, prolonged crying, and acute encephalopathy that sometimes followed whole-cell pertussis vaccination in some young infants. The development and licensure of diphtheria, tetanus, and acellular pertussis (DTaP) vaccines in the United States in the 1990s was an anticipated event for pediatric providers and parents who feared the reactogenicity associated with the administration of DTwP vaccines in infants and toddlers. … Address correspondence to Flor M. Munoz, MD, Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, Texas Children’s Hospital, Feigin Tower, 1102 Bates, Houston, TX 77030. E-mail: florm{at}bcm.edu

BACKGROUND: In 2010, 9120 cases of pertussis were reported in California, more than any year since 1947. Although this resurgence has been widely attributed to waning immunity of the acellular vaccine, the role of vaccine refusal has not been explored in the published literature. Many factors likely contributed to the outbreak, including the cyclical nature of pertussis, improved diagnosis, and waning immunity; however, it is important to understand if clustering of unvaccinated individuals also played a role. METHODS: We analyzed nonmedical exemptions (NMEs) for children entering kindergarten from 2005 through 2010 and pertussis cases with onset in 2010 in California to determine if NMEs increased in that period, if children obtaining NMEs clustered spatially, if pertussis cases clustered spatially and temporally, and if there was statistically significant overlap between clusters of NMEs and cases. RESULTS: Kulldorff’s scan statistics identified 39 statistically significant clusters of high NME rates and 2 statistically significant clusters of pertussis cases in this time period. Census tracts within an exemptions cluster were 2.5 times more likely to be in a pertussis cluster (odds ratio = 2.47, 95% confidence interval: 2.22–2.75). More cases occurred within as compared with outside exemptions clusters (incident rate ratios = 1.20, 95% confidence interval: 1.10–1.30). The association remained significant after adjustment for demographic factors. NMEs clustered spatially and were associated with clusters of pertussis cases. CONCLUSIONS: Our data suggest clustering of NMEs may have been 1 of several factors in the 2010 California pertussis resurgence.

BACKGROUND:In the United States, the proportion of Bordetella pertussis isolates lacking pertactin, a component of acellular pertussis vaccines, increased from 14% in 2010 to 85% in 2012. The impact on vaccine effectiveness (VE) is unknown.METHODS:We conducted 2 matched case-control evaluations in Vermont to assess VE of the 5-dose diphtheria, tetanus, and acellular pertussis vaccine (DTaP) series among 4- to 10-year-olds, and tetanus, diphtheria, and acellular pertussis vaccine (Tdap) among 11- to 19-year-olds. Cases reported during 2011 to 2013 were included. Three controls were matched to each case by medical home, and additionally by birth year for the Tdap evaluation. Vaccination history was obtained from medical records and parent interviews. Odds ratios (OR) were calculated by using conditional logistic regression; VE was estimated as (1-OR) × 100%. Pertactin status was determined for cases with available isolates.RESULTS:Overall DTaP VE was 84% (95% confidence interval [CI] 58%–94%). VE within 12 months of dose 5 was 90% (95% CI 71%–97%), declining to 68% (95% CI 10%–88%) by 5–7 years post-vaccination. Overall Tdap VE was 70% (95% CI 54%–81%). Within 12 months of Tdap vaccination, VE was 76% (95% CI 60%–85%), declining to 56% (95% CI 16%–77%) by 2–4 years post-vaccination. Of cases with available isolates, >90% were pertactin-deficient.CONCLUSIONS:Our DTaP and Tdap VE estimates remain similar to those found in other settings, despite high prevalence of pertactin deficiency in Vermont, suggesting these vaccines continue to be protective against reported pertussis disease.

BACKGROUND AND OBJECTIVES: We investigated a pertussis outbreak characterized by atypical cases, confirmed by polymerase chain reaction (PCR) alone at a single laboratory, which persisted despite high vaccine coverage and routine control measures. We aimed to determine whether Bordetella pertussis was the causative agent and advise on control interventions. METHODS: We conducted case ascertainment, confirmatory testing for pertussis and other pathogens, and an assessment for possible sources of specimen contamination, including a survey of clinic practices, sampling clinics for B pertussis DNA, and review of laboratory quality indicators. RESULTS: Between November 28, 2008, and September 4, 2009, 125 cases were reported, of which 92 (74%) were PCR positive. Cases occurring after April 2009 (n = 79; 63%) had fewer classic pertussis symptoms (63% vs 98%; P < .01), smaller amounts of B pertussis DNA (mean PCR cycle threshold value: 40.9 vs 33.1; P < .01), and a greater proportion of PCR-positive results (34% vs 6%; P < .01). Cultures and serology for B pertussis were negative. Other common respiratory pathogens were detected. We identified factors that likely resulted in specimen contamination at the point of collection: environmentally present B pertussis DNA in clinics from vaccine, clinic standard specimen collection practices, use of liquid transport medium, and lack of clinically relevant PCR cutoffs. CONCLUSIONS: A summer pertussis pseudo-outbreak, multifactorial in cause, likely occurred. Recommendations beyond standard practice were made to providers on specimen collection and environmental cleaning, and to laboratories on standardizing PCR protocols and reporting results, to minimize false-positive results from contaminated clinical specimens.

OBJECTIVE:To determine the frequency of parents' requests for alternative childhood immunization schedules (ACISs) and pediatricians' comfort with and willingness to use ACISs.METHODS:Washington State primary care pediatricians were asked to complete an Internet-based survey on ACISs. The main outcome measures were the frequency of parents' requests for ACISs, pediatricians' comfort with their use, and pediatricians' willingness to use ACISs for individual vaccines. In addition, respondents were asked to characterize their practices and to provide demographic information.RESULTS:Of the 311 respondents (response rate: 65%), 209 met inclusion criteria and were included in analyses. Overall, 77% of eligible respondents reported that parents sometimes or frequently requested ACISs, and 61% were comfortable using an ACIS if requested by a parent. Pediatricians were least willing to consider using ACISs for diphtheria-tetanus toxoids-acellular pertussis vaccine, Haemophilus influenzae type b vaccine, and pneumococcal conjugate vaccine. Pediatricians who practiced in a neighborhood or community clinic were less comfortable using ACISs than were those in a 1- or 2-physician practice (odds ratio: 0.10).CONCLUSIONS:Washington State pediatricians are regularly being asked to use ACISs, and most of them are comfortable using them if requested. Pediatricians are least willing to delay H influenzae type b vaccine, diphtheria-tetanus toxoids-acellular pertussis vaccine, and pneumococcal conjugate vaccine, which suggests prioritization of immunizations that protect against potentially devastating bacterial infections of infancy and early childhood.

* Abbreviations: MMR — : measles-mumps-rubella NME — : nonmedical exemption VPD — : vaccine-preventable disease Previously controlled vaccine preventable diseases (VPDs) are in resurgence.1,2 To date, there have been 477 confirmed measles cases in the United States in 2014, the most in 18 years.3 In 2013 there were ∼25 000 pertussis cases in the United States. Vaccine refusal has been associated with outbreaks of invasive Haemophilus influenzae type b disease,4 varicella,5 pneumococcal disease,6 measles,7 and pertussis.8–12 Even while national and statewide immunization coverage remain high, rates of parents who refuse vaccines via nonmedical exemptions (NMEs) to school immunization requirements have been increasing.13,14 Furthermore, NMEs cluster geographically,9,10 leading to critical reductions in herd immunity and a perfect storm for sustained transmission, outbreaks, and increased risk of VPDs to both unvaccinated and vaccinated individuals.7,9,10,15,16 Beyond active refusal, many parents are delaying vaccines and using “alternative immunization schedules” to spread out the number of vaccines given per visit or in infancy.17 Seventy-seven percent of parents of young children report concerns about vaccines, such as the number of vaccines or doses given simultaneously or before age two, what ingredients are contained in vaccines, or if there are associations with adverse outcomes such as autism and other chronic diseases.18 Some have gone so far as to identify a “vaccine crisis in confidence.”19–21 Parental vaccine … Address correspondence to Jessica Atwell, MPH, 615 North Wolfe St, Baltimore, MD 21205. E-mail: jatwell5{at}jhu.edu

OBJECTIVE: In clinical trials, the pentavalent rotavirus vaccine (RV5) was efficacious in preventing severe rotavirus gastroenteritis (RGE) and related health care encounters. We assessed the vaccine effectiveness (VE) of RV5 among US infants during the first 2 rotavirus seasons after vaccine licensure. METHODS: Using a large, national, health insurance claim database, we monitored 2 cohorts of infants (infants who received 3 doses of RV5 and a concurrent group of infants who received 3 doses of diphtheria-tetanus-acellular pertussis vaccine but did not receive RV5) through the 2007 and 2008 rotavirus seasons (January 1 to May 31), to identify cases of RGE and all-cause acute gastroenteritis (AGE) resulting in medical care encounters. We estimated the VE in reducing hospitalizations, emergency department (ED) and physician office visits, and health care resource utilization, as measured by days and costs of hospitalizations and ED visits. RESULTS: A total of 33 140 RV5-vaccinated infants and 26 167 infants in the concurrent diphtheria-tetanus-acellular pertussis vaccine cohort were included in the analysis. The VE against RGE (hospitalization and ED) was 100% (95% confidence interval [CI]: 87%–100%), whereas the VE against AGE was 59% (95% CI: 47%–68%). In the outpatient setting, the VE against RGE and AGE was 96% (95% CI: 76%–100%) and 28% (95% CI: 22%–33%), respectively. There was a complete (100%) reduction in RGE hospitalization and ED visit days and a 100% reduction in costs. RV5 was associated with a 66% decrease in AGE-related hospitalization and ED visit days and a 74% reduction in costs. CONCLUSIONS: In this first nationwide study evaluating VE under conditions of routine use, RV5 was highly effective in preventing RGE and AGE and in reducing health care resource utilization. Further research is needed to assess VE with an incomplete rotavirus vaccination regimen.

OBJECTIVE. The objective of this study was to determine if children who contracted pertussis infection were more likely to have parents who refused pertussis vaccinations than a similar group of children who did not develop pertussis infection. METHODS. We conducted a case-control study of children enrolled in the Kaiser Permanente of Colorado health plan between 1996 and 2007. Each pertussis case was matched to 4 randomly selected controls. Pertussis case status and vaccination status were ascertained by medical chart review. RESULTS. We identified 156 laboratory-confirmed pertussis cases and 595 matched controls. There were 18 (12%) pertussis vaccine refusers among the cases and 3 (0.5%) pertussis vaccine refusers among the controls. Children of parents who refused pertussis immunizations were at an increased risk for pertussis compared with children of parents who accepted vaccinations. In a secondary case-control analysis of children continuously enrolled in Kaiser Permanente of Colorado from 2 to 20 months of age, vaccine refusal was associated with a similarly increased risk of pertussis. In the entire Kaiser Permanente of Colorado pediatric population, 11% of all pertussis cases were attributed to parental vaccine refusal. CONCLUSIONS. Children of parents who refuse pertussis immunizations are at high risk for pertussis infection relative to vaccinated children. Herd immunity does not seem to completely protect unvaccinated children from pertussis. These findings stress the need to further understand why parents refuse immunizations and to develop strategies for conveying the risks and benefits of immunizations to parents more effectively.

OBJECTIVE. This study estimates the potential impact, on rates of pertussis infections, hospitalizations, and deaths among infants in the United States, of administering the first dose of diphtheria and tetanus toxoids and acellular pertussis vaccine at 6 weeks rather than 2 months of age.METHODS. We used existing data to estimate current US rates of pertussis infections, hospitalizations, and deaths according to age and infant population in 2004. We then estimated the potential impact of accelerating the administration of the first dose of diphtheria and tetanus toxoids and acellular pertussis vaccine from 2 months to 6 weeks of age, an alternative schedule consistent with current vaccination guidelines. We used Poisson distribution analysis to determine 95% confidence intervals for projected rates of pertussis disease.RESULTS. Acceleration of administration of the first dose of diphtheria and tetanus toxoids and acellular pertussis vaccine from 2 months to 6 weeks of age is expected to prevent 1236 cases of pertussis, 898 hospitalizations, and 7 deaths attributable to pertussis per year in the United States. These decreases represent 9% reduction in cases, 9% reduction in hospitalizations, and 6% reduction in deaths attributable to pertussis among infants CONCLUSION. Acceleration of administration of diphtheria and tetanus toxoids and acellular pertussis vaccine from 2 months to 6 weeks should reduce the burden of pertussis among young infants.

OBJECTIVE. Tetanus, diphtheria, and acellular pertussis vaccination is recommended for adults who are in contact with infants who are younger than 12 months and in the NICU. The objective of this study was to determine the feasibility of tetanus, diphtheria, and acellular pertussis vaccine administration to parents in a tertiary care, level III NICU and to measure its effect on vaccination rates among parents of this high-risk population.METHODS. For a 4-month period from July to October 2007, all parents of admitted patients were informed of the risks and benefits of tetanus, diphtheria, and acellular pertussis vaccine by placing an information letter at their infant's bedside. All staff were educated about the dangers of pertussis infection and instructed to reinforce the need to obtain vaccination. Immunization was available for 20 hours per day at no cost. Student's t tests were used for data analysis.RESULTS. During the study period, 352 children (598 eligible parents) were admitted to the NICU at gestational ages ranging from 23 to 42 weeks, and 495 (82.8%) parents were offered the vaccine. Overall vaccination rate was 86.9% (430 parents) of the screened population. Fifty-five (11.1%) parents in the screened cohort refused vaccination, predominately citing pertussis as an insignificant health threat or disbelief in vaccination. There were no differences in vaccination rate on the basis of parental age. No allergic reactions to vaccination were observed. The 54 infants whose parents were not offered vaccine had a significantly shorter length of stay, higher birth weight, and higher gestational age than parents who were offered vaccine.CONCLUSIONS. Administration of tetanus, diphtheria, and acellular pertussis vaccine in the NICU is an effective means of increasing vaccination rates of parents of this population. Logistic barriers persist when implementing this program for infants with a short (

OBJECTIVE. The American Academy of Pediatrics recommends immunization of preterm infants at 2 months' chronological age with diphtheria-tetanus-acellular pertussis vaccine, regardless of birth weight and gestational age. Several investigators have reported an increased incidence of cardiorespiratory events in preterm infants after immunization. Consequently, many primary care providers do not adhere to American Academy of Pediatrics guidelines. The purpose of this study was to reexamine the relationship between diphtheria-tetanus-acellular pertussis and cardiorespiratory events in preterm infants by using a random control study design and an objective assessment of cardiorespiratory events. METHODS. Ten hospitals enrolled 191 infants who were born at RESULTS. In the diphtheria-tetanus-acellular pertussis group, 16.1% experienced at least 1 episode of prolonged apnea compared with 20.4% of control infants. One or more prolonged bradycardia events occurred in 58.1% of immunized infants and 56.1% of the control infants. The frequency of episodes was not significantly different between groups. The immunization group and the control group each had an average of 0.5 episodes of prolonged apnea. The mean number of prolonged bradycardia episodes was 2.6 in the immunization group and 2.7 in the control group. CONCLUSIONS. Preterm infants who received diphtheria-tetanus-acellular pertussis at 2 months after birth were no more likely to experience prolonged apnea and bradycardia than were control infants. This study supports the American Academy of Pediatrics recommendation regarding diphtheria-tetanus-acellular pertussis immunization at 2 months of age for preterm infants.

OBJECTIVE. The goal was to determine whether disparities in childhood immunization coverage exist between American Indian/Alaska Native children and non-Hispanic white children. METHODS. We compared immunization coverage with the 4 diphtheria-tetanus-pertussis, 3 poliovirus, 1 measles-mumps-rubella, 3 Haemophilus influenza type b, and 3 hepatitis B(4:3:1:3:3) series and its individual vaccine components (≥4 doses of diphtheria, tetanus, and pertussis vaccine; ≥3 doses of oral or inactivated polio vaccine; ≥1 dose of measles, mumps, and rubella vaccine; ≥3 doses of Haemophilus influenzae type b vaccine; and ≥3 doses of hepatitis B vaccine) between American Indian/Alaska Native children and non-Hispanic white children from 2000 to 2005, using data from the National Immunization Survey. RESULTS. Although immunization coverage increased for both populations from 2001 to 2004, American Indian/Alaska Native children had significantly lower immunization coverage, compared with non-Hispanic white children, over that time period. In 2005, coverage continued to increase for American Indian/Alaska Native children but decreased for non-Hispanic white children, and no statistically significant disparity in 4:3:1:3:3 coverage was evident in that year. CONCLUSIONS. Disparities in immunization coverage for American Indian/Alaska Native children have been present, but unrecognized, since 2001. The absence of a disparity in coverage in 2005 is encouraging but is tempered by the fact that coverage for non-Hispanic white children decreased in that year.

Adolescents in the United States now have the opportunity to receive new vaccines that prevent invasive meningococcal infections, pertussis (whooping cough), and cervical cancer. Except for their potential to cause serious illness, these infections could not be more different. Their incidence ranges from extremely low to quite high. Early clinical manifestations of infection range from none to life-threatening illness. Two of the vaccines are similar to those already in use, whereas 1 is completely new. In conjunction with the 4 vaccines previously recommended for adolescents (the tetanus and diphtheria booster, hepatitis B, measles-mumps-rubella, and varicella), the 3 new vaccines (meningococcal, human papillomavirus, and the tetanus-diphtheria-pertussis booster [which replaced the tetanus-diphtheria booster]) bring the number recommended for adolescents to 6. In this article, we describe key characteristics of the 3 new vaccines and infections they were designed to prevent. We also briefly discuss other vaccines recommended for all adolescents who have not already received them and new vaccines that are still under development.

OBJECTIVE. Our goal was to evaluate the immunogenicity and safety of pertussis booster vaccination in children infected with HIV on highly active antiretroviral therapy (HAART). PATIENTS AND METHODS. HIV-infected children on stable HAART for ≥3 months with plasma HIV-RNA concentrations of RESULTS. Ninety-two subjects received DTaP vaccine and met criteria for analysis. Antibody concentrations were low at entry: pertussis toxin geometric mean concentration at 4.8 enzyme-linked immunosorbent assay units (EU) per mL and filamentous hemagglutinin geometric mean concentration at 4.1 EU/mL. Pertussis toxin and filamentous hemagglutinin geometric mean concentrations rose to 22.3 and 77.0 EU/mL, respectively, 8 weeks after the study DTaP vaccine. Antibody concentrations fell by 24 weeks after vaccination but remained higher than before vaccination. Predictors of response 8 weeks after DTaP vaccine included the concentration of homologous antibody, lower HIV-RNA level, and higher CD4 percentage at entry. One vaccinated subject experienced erythema and induration of ≥25 mm. CONCLUSIONS. A DTaP vaccine booster was well tolerated by children on HAART and induced increases in antibodies. Antibody concentrations after vaccination were lower than those reported in populations uninfected by HIV. Although comparison among studies must be made with caution, these data suggest that children infected with HIV may be deficient in immunologic memory from previous DTP-containing vaccination and/or that immune reconstitution with HAART may be incomplete for pertussis antigens.

BACKGROUND. The possible link between immunization and atopic diseases has been under intense debate in the last decade. OBJECTIVE. The aim of this study was to systematically review the available evidence on the association of whole-cell pertussis and BCG vaccination with the risk of asthma in childhood and adolescence. METHODS. The major medical electronic databases (Medline, National Library of Medicine Gateway, and Cochrane Library) were searched, and reference lists of the relevant publications were reviewed for relevant birth-cohort studies and randomized, controlled trials from 1966 to March 2006. Only studies that directly compared vaccinated and unvaccinated children, validated vaccination status by medical charts, and used preset criteria to define asthma were included. Data were abstracted by using a standardized protocol and computerized report form. Results were analyzed by applying a fixed-effect or random-effect model, according to the heterogeneity of the studies. Sensitivity analyses by scoring criteria were performed. RESULTS. Seven studies of pertussis vaccination (with a total of 186663 patients) and 5 studies of BCG vaccination (with a total of 41479 patients) met our inclusion criteria. No statistically significant association was detected between either whole-cell pertussis or BCG vaccination and incidence rates of asthma during childhood and adolescence. This lack of a significant association proved to be robust on sensitivity analyses for BCG but not for pertussis vaccine. CONCLUSIONS. Currently available data, based on observational studies, do not support an association, provocative or protective, between receipt of the BCG or whole-cell pertussis vaccine and risk of asthma in childhood and adolescence.

BACKGROUND: This study in 11- to 15-year-old boys and girls compared the immunogenicity and safety of GARDASIL 9 (9-valent human papillomavirus [9vHPV] vaccine) administered either concomitantly or nonconcomitantly with 2 vaccines routinely administered in this age group (Menactra [MCV4; Neisseria meningitidis serotypes A/C/Y/W-135] or Adacel [Tdap; diphtheria/tetanus/acellular pertussis]). METHODS: Participants received 9vHPV vaccine at day 1 and months 2 and 6; the concomitant group (n = 621) received MCV4/Tdap concomitantly with 9vHPV vaccine at day 1; the nonconcomitant group (n = 620) received MCV4/Tdap at month 1. Antibodies to HPV-, MCV4-, and Tdap-relevant antigens were determined. Injection-site and systemic adverse events (AEs) were monitored for 15 days after any vaccination; serious AEs were monitored throughout the study. RESULTS: The geometric mean titers for all HPV types in 9vHPV vaccine 4 weeks after dose 3, proportion of subjects with a fourfold rise or greater in titers for 4 N meningitidis serotypes 4 weeks after injection with MCV4, proportion of subjects with antibody titers to diphtheria and tetanus ≥0.1 IU/mL, and geometric mean titers for pertussis antigens 4 weeks after injection with Tdap were all noninferior in the concomitant group compared with the nonconcomitant group. Injection-site swelling occurred more frequently in the concomitant group. There were no vaccine-related serious AEs. CONCLUSIONS: Concomitant administration of 9vHPV vaccine with MCV4/Tdap was generally well tolerated and did not interfere with the antibody response to any of these vaccines. This strategy would minimize the number of visits required to deliver each vaccine individually.

American infants are at highest risk of severe pertussis and death. We investigated the role of ≥1 pertussis vaccinations in preventing pertussis-related deaths and risk markers for death among infants aged42 days.We analyzed characteristics of fatal and nonfatal infant pertussis cases reported nationally during 1991-2008. Infants were categorized into 2 age groups on the basis of eligibility to receive a first pertussis vaccine dose at age 6 weeks; dose 1 was considered valid if given ≥14 days before illness onset. Multivariable logistic regression was used to estimate the effect of ≥1 pertussis vaccine doses on outcome and risk markers.Pertussis-related deaths occurred among 258 of 45 404 cases. Fatal and nonfatal cases were confirmed by culture (54% vs 49%) and polymerase chain reaction (31% vs 27%). All deaths occurred before age 34 weeks at illness onset; 64% occurred before age 6 weeks. Among infants aged ≥42 days, receiving ≥1 doses of vaccine protected against death (adjusted odds ratio [aOR]: 0.28; 95% confidence interval [CI]: 0.11-0.74), hospitalization (aOR: 0.69; 95% CI: 0.63-0.77), and pneumonia (aOR: 0.80; 95% CI: 0.68-0.95). Risk was elevated for Hispanic ethnicity (aOR: 2.28; 95% CI: 1.36-3.83) and American Indian/Alaska Native race (aOR: 5.15; 95% CI: 2.37-11.2) and lower for recommended antibiotic treatment (aOR: 0.28; 95% CI: 0.16-0.47). Among infants aged42 days, risk was elevated for Hispanic ethnicity and lower with recommended antibiotic use.The first pertussis vaccine dose and antibiotic treatment protect against death, hospitalization, and pneumonia.

The Global Pertussis Initiative (GPI) is an expert scientific forum addressing the worldwide burden of pertussis, which remains a serious health issue, especially in infants. This age cohort is at risk for developing pertussis by transmission from those in close proximity. Risk is increased in infants aged 0 to 6 weeks, as they are too young to be vaccinated. Older infants are at risk when their vaccination schedules are incomplete. Infants also bear the greatest disease burden owing to their high risk for pertussis-related complications and death; therefore, protecting them is a high priority. Two vaccine strategies have been proposed to protect infants. The first involves vaccinating pregnant women, which directly protects through the passive transfer of pertussis antibodies. The second strategy, cocooning, involves vaccinating parents, caregivers, and other close contacts, which indirectly protects infants from transmission by preventing disease in those in close proximity. The goal of this review was to present and discuss evidence on these 2 strategies. Based on available data, the GPI recommends vaccination during pregnancy as the primary strategy, given its efficacy, safety, and logistic advantages over a cocoon approach. If vaccination during pregnancy is not feasible, then all individuals having close contact with infants

OBJECTIVES. The purpose of this work was to evaluate the long-term effectiveness of vaccination with acellular pertussis vaccines at 3, 5, and 12 months of age. METHODS. Clinical follow-up of reported culture- and polymerase chain reaction–confirmed cases of pertussis was initiated during October 1997 in most of Sweden (except Gothenburg and environs). The study population included 90% of Swedish children born during 1996 or later (ie, who received diphtheria-tetanus-acellular pertussis vaccines at 3, 5, and 12 months of age) and children who had participated in a large pertussis vaccine trial in 1993–1996. Age-specific incidences were estimated using reported culture- or polymerase chain reaction–confirmed pertussis from October 1997 to September 2004 in areas covered by enhanced surveillance. In addition, annual overall and age-specific incidences of pertussis throughout Sweden before and after introduction of acellular pertussis vaccines were estimated. RESULTS. The overall incidence of notified culture- and polymerase chain reaction–confirmed pertussis dropped from 113 to 150 per 100 000 during 1992–1995 to 11 to 16 per 100 000 during 2001–2004. In areas of enhanced surveillance, the incidence of pertussis was 31 per 100 000 person-years after 2 doses and 19 per 100 000 person-years after the third dose at 12 months of age. The age-specific incidence remained low for ∼5 years after the third dose but increased in children aged 6 to 8 years, becoming 32 and 48 per 100 000 person-years, respectively. The highest incidence occurred among infants who were unvaccinated or had received only 1 dose of diphtheria-tetanus-acellular pertussis vaccine. CONCLUSIONS. The increased incidence among 7- to 8-year-olds (ie, mainly acellular pertussis vaccine–vaccinated children) suggests waning of vaccine-induced protection from pertussis. Along with a concomitant increase in incidence among infants, most likely infected by older siblings, these data suggest a booster dose of acellular pertussis vaccine is warranted from 5 to 7 years of age.

Background. Despite the dramatic pertussis decrease since the licensure of whole-cell pertussis (diphtheria-tetanus toxoids-pertussis [DTP]) vaccines in the middle 1940s, pertussis remains endemic in the United States and can cause illness among persons at any age; >11000 pertussis cases were reported in 2003. Since July 1996, in addition to 2 DTP vaccines already in use, 5 acellular pertussis (diphtheria-tetanus toxoids-acellular pertussis [DTaP]) vaccines were licensed for use among infants; 3 DTaP vaccines were distributed widely during the study period. Because of the availability of 3 DTaP and 2 DTP vaccines and the likelihood of the vaccines being used interchangeably to vaccinate children with the recommended 5-dose schedule, measuring the effectiveness of the pertussis vaccines was a high priority. Objective. To measure the pertussis vaccine effectiveness (VE) among US children 6 to 59 months of age. Design. We conducted a case-control study in the Cincinnati, Ohio, metropolitan area, Colorado, Idaho, and Minnesota. Participants. Confirmed pertussis cases among children 6 to 59 months of age at the time of disease onset, with onset in 1998–2001, were included. For each case subject, 5 control children were matched from birth certificate records, according to the date of birth and residence. Outcome Measures. A standardized questionnaire was used to obtain vaccination data from parents and providers. Parents/guardians were asked about demographic characteristics, child care attendance, the number of household members who stayed at the same home as the enrolled child for ≥2 nights per week, and cough illness of ≥2-week duration among these household members in the month before the case patient's cough onset. Pertussis vaccine doses among case children were counted as valid if they were received ≥14 days before the cough onset date (“valid period”). The age of the case patient (in days) at the end of the valid period was determined, and doses of vaccine for the matched control subjects were counted as valid if they were received by that age. Conditional logistic regression models were used to estimate the matched odds ratios (ORs) for pertussis according to the number of pertussis vaccine doses. The VE was calculated with the following formula: (1 − OR) × 100. Because the pertussis antigen components or amounts differed according to vaccine, the VE of 3 or 4 doses of DTP and/or DTaP was estimated according to the recorded vaccine manufacturer and vaccine type. Results. All enrolled children (184 case subjects and 893 control subjects) had their vaccine history verified. The proportions of children who received 0, 1 or 2, 3, and ≥4 pertussis (DTP and/or DTaP) vaccine doses among case subjects were 26%, 14%, 26%, and 34% and among control subjects were 2%, 8%, 33%, and 57%, respectively. Compared with 0 doses, the unadjusted VE estimate for 1 or 2 pertussis doses was 83.6% (95% confidence interval [CI]: 61.1–93.1%), that for 3 doses was 95.6% (95% CI: 89.7–98.0%), and for ≥4 doses was 97.7% (95% CI: 94.7–99.0%). Among children who received 4 pertussis vaccinations, the risk of pertussis was slightly higher among those who received only 1 type of vaccine (either 4 DTP doses or 4 DTaP doses), compared with those who received a combination of DTP for doses 1 to 3 and DTaP for dose 4 (OR: 2.4; 95% CI: 1.1–5.2). Among children who received 3 or 4 DTaP vaccine doses, the risk of pertussis was slightly higher among those who received a DTaP vaccine with 4 pertussis antigen components (a vaccine no longer available), compared with those who received the DTaP vaccine with 2 pertussis antigen components (OR: 2.5; 95% CI: 1.1–5.8). Among children who received 4 doses, the risk of pertussis was 2.7 times higher for children who received dose 4 early (age of ≤13 months), compared with children who received dose 4 at an older age (age of ≥14 months) (95% CI: 1.1–6.8). For children 6 to 23 months of age, features of household structure were significant risk factors for pertussis. In a multivariate model, compared with living with an older parent (≥25 years of age), not living with an “other” household member (a relative other than a parent or sibling or a nonrelated person), and not living with a sibling 6 to 11 years of age, the risk of pertussis for children 6 to 23 months of age was 6.8 times higher if they lived with a young parent (≤24 years of age) (95% CI: 3.1–15.0), 2.5 times higher if they lived with an “other” household member (95% CI: 1.2–5.4), and 2.2 times higher if they lived with a sibling 6 to 11 years of age (95% CI: 1.2–4.3). Adjusting for these risk factors did not change the VE. Compared with control children, case children were significantly more likely to live with a household member (representing all age groups and relationships) who reported a recent cough illness with duration of ≥2 weeks (87 [52%] of 168 case subjects, compared with 79 [8%] of 860 control subjects). Conclusions. Any combination of ≥3 DTP/DTaP vaccine doses for children 6 to 59 months of age was highly protective against pertussis. However, there were differences according to vaccine type (DTaP or DTP) and DTaP manufacturer. Among children who received 4 pertussis vaccine doses, a combination of 3 DTP doses followed by 1 DTaP dose had a slightly higher VE than other combinations; among children who received 3 or 4 DTaP vaccine doses, 1 DTaP vaccine performed less well. The finding that pertussis dose 4 was more effective when given to children at ≥14 months of age might be confounded if health care providers were more likely to vaccinate children at 12 months of age because of a perceived risk of undervaccination and if these same children were also at higher risk for pertussis. Household members of any age group and relationship could have been the source of pertussis, and household structure was associated with risk for pertussis for children 6 to 23 months of age. In contrast to control children in the study, 26% of case children had never been vaccinated against pertussis. Unvaccinated children are at risk for pertussis and, in a community with other unvaccinated children, can lead to community-wide pertussis outbreaks. Parents need to be educated about the morbidity and mortality risks associated with Bordetella pertussis infection, and they need to be encouraged to vaccinate their children against pertussis on time and with the recommended number of vaccine doses for optimal protection.

Background. The Vaccines for Children (VFC) program is designed to reduce the cost of vaccines for vulnerable children, including Medicaid-eligible children, American Indian/Alaska Native children, uninsured children, and underinsured children whose health insurance does not cover the cost of vaccinations. A desired consequence of the program is to promote comprehensive continuous medical care within a medical home for these children.Objectives. To explore how having a medical home is associated with vaccination coverage among children eligible for the program.Participants. A total of 24514 children 19 to 35 months of age sampled by the National Immunization Survey.Design. VFC eligibility was evaluated for 24514 children 19 to 35 months of age who were sampled by the National Immunization Survey. Children were considered to have a medical home if they had a doctor, nurse, or physician's assistant who provided them with ongoing routine care, including well-child care, preventive care, and sick care, according to their parents. Sampled children were determined to be 4:3:1:3:3 up-to-date (UTD) if their vaccination providers reported administering ≥4 doses of diphtheria-tetanus toxoids-acellular pertussis vaccine, ≥3 doses of polio vaccine, ≥1 dose of measles-mumps-rubella vaccine, ≥3 doses of Haemophilus influenzae type b vaccine, and ≥3 doses of hepatitis B vaccine.Results. Nationally, 44.9% of all children were VFC eligible and 93.0% of the VFC-eligible children received all vaccine doses at a provider enrolled in the VFC program. Compared with children who were not VFC eligible, VFC-eligible children were less likely to be UTD (70.8% vs 77.7%) and less likely to have a medical home (82.1% vs 95.0%). However, among VFC-eligible children, children who had a medical home were significantly more likely to be UTD, compared with children who did not have a medical home (72.3% vs 63.5%). Also, among VFC-eligible children who had a medical home, children who used their medical home consistently to receive all of their vaccination doses were significantly more likely to be UTD, compared with children who did not receive all of their doses from their medical home (75.3% vs 65.7%). Finally, the 4:3:1:3:3 vaccination coverage rate among VFC-eligible children who received all of their vaccination doses from their medical home was not significantly different from that among non-VFC-eligible children, after controlling for significant differences in sociodemographic factors between these groups (adjusted difference: 2.8%; 95% confidence interval: −0.1% to 5.7%).Conclusions. Although the vaccination coverage rate among VFC-eligible children who had a medical home and received all vaccine doses from their medical home was essentially equivalent to that of non-VFC-eligible children, substantial percentages of VFC-eligible children either did not have a medical home or did not use their medical home to receive all of their recommended vaccinations. The vaccination coverage rate among these children was significantly lower. This suggests that there may be opportunities to increase vaccination coverage by removing barriers that prevent the adoption and consistent use of a medical home among these children.

Objective. This was a prospective, controlled, multicenter study to investigate the relationship between Bordetella pertussis infections and sudden unexpected deaths among German infants.Design. Between 1995 and 1997, all infants who died at 7 to 365 days of age and for whom autopsies were performed in 1 of 8 participating institutes of legal medicine were enrolled. During a standardized autopsy, nasopharyngeal specimens (NPSs) and tracheal specimens were obtained for polymerase chain reaction (PCR) assays to detect B pertussis. The oligonucleotide primers PTp1 and PTp2, which specifically amplify a 191-base pair DNA fragment of the pertussis toxin operon of B pertussis, were used. Two control subjects (matched according to residence, age, gender, and nationality) were enrolled for each case subject, via a network of pediatricians in private practice, and NPSs were obtained from those infants. Parents of case subjects and control subjects were asked to provide specific information on respiratory illnesses of the child, contact with a known case of pertussis, or close contact with a person with a cough illness during the 4 weeks before death or enrollment, as well as the child's pertussis immunization status. The pathologists performing the autopsies were unaware of the PCR results.Results. Enrolled were 254 infants (66% male) with sudden unexpected deaths and 441 matched control subjects. Autopsies according to protocol were performed for 234 of the case subjects (92%); a diagnosis of sudden infant death syndrome (SIDS) was made for 76%. For the remaining subjects, causes of death were respiratory or other infections (14%), congenital anomalies or organ failures (4%), aspiration (2%), or accidents or traumatic events (4%). PCR results were positive for B pertussis for 12 case subjects (5.1%) (all with SIDS or respiratory infections) and 5.3% of control subjects. Of the 12 case subjects with positive PCR results, 10 (83%) were male. Questionnaires had been returned by the parents of 5 of the 12 infants. Three had experienced a respiratory illness (all with cough), beginning 7, 14, and 19 days before death. None had a known contact with a case of pertussis. Four of 15 control infants (27%) with positive PCR findings for B pertussis had a cough illness, indicating possible pertussis, and 2 of those 4 developed typical symptoms (whooping). Background information was received from 116 parents (46%) of case subjects and from parents of all control subjects. Upper respiratory tract infections within 4 weeks before death were reported for 53% of case subjects and 38% of control subjects. Also, fewer case subjects (33%) than control subjects (68%) had received age-adequate numbers of pertussis vaccine doses.Conclusions. The concept of infection as a factor in SIDS is supported by a number of observations, including the seasonal distribution of the occurrence of SIDS; the high incidence of concurrent upper respiratory tract infections among infants dying as a result of SIDS; the peak age at 3 to 4 months; nicotine use in a child's household, which predisposes children to respiratory infections such as otitis media; and the protective role of breastfeeding. A prominent role might be suspected for B pertussis, for several reasons. 1) B pertussis infections in infancy are frequently associated with apneic spells, which are occasionally life-threatening and, if leading to death, might be reported as SIDS. 2) Epidemiologic evidence from the United Kingdom, Sweden, and Norway indicates that SIDS is associated with B pertussis infection. 3) In a previously published study, we detected B pertussis DNA in the nasopharynx of 9 of 51 consecutive infants (18%) with sudden unexpected deaths. This is the first prospective, controlled study to investigate the possible etiologic role of B pertussis in SIDS. Clinically unrecognized B pertussis infections were relatively frequent (5.3%) among control infants during the course of our study. The rate of infection was similar or perhaps greater for control subjects, compared with case subjects (1.7%), when only NPS results were compared. This may seem surprising but is supported by other studies, in which asymptomatic infections or mild respiratory illnesses were observed among infants exposed to B pertussis. Careful autopsies, including histologic evaluations of organ specimens and use of PCR to detect B pertussis in NPSs and tracheal specimens, represented a strength of this study. Our general findings were as expected. The majority of cases were classified as SIDS. The second largest group included infants for whom respiratory infections were found. The findings of various other diagnoses, which in several instances would have been undiscovered otherwise, emphasize the need for autopsies after unexpected infant deaths. What is the significance of the identified B pertussis infections in 12 cases? Several pieces of evidence support the plausibility of a cause-and-effect relationship. Eight of the 12 case subjects died before 6 months of age, the typical age for death attributable to pertussis. In autopsies, 9 of the subjects were found to have signs of respiratory infections; for 2 infants, the autopsies suggested that death was attributable to a respiratory infection. One additional infant (data not shown) had brain edema (which could have been attributable to hypoxemia during pertussis). Lower rates of completed primary series or age-adequate numbers of pertussis vaccine doses among case subjects than among control subjects may indicate that immunization against pertussis protects children from death attributable to unrecognized B pertussis infection. Moreover, a recent study indicated that immunization with diphtheria-tetanus-pertussis vaccine induces antibodies that cross-react with pyrogenic staphylococcal toxins, which have been implicated in several cases of SIDS. Other microorganisms may be involved in the sudden death of infants, as suggested in this study by the higher rate of a history of concurrent upper respiratory tract infections among case subjects, compared with control subjects. Similarly, in a Scandinavian study, 48% of 244 SIDS case subjects, compared with 31% of 869 control subjects, exhibited symptoms of upper airway infection during the last week before death or interview, respectively. Because SIDS is a diagnosis of exclusion, every attempt should be made to identify a cause of death during autopsy. This should include the search for pathogenic microorganisms in the respiratory tract with the use of PCR and other sensitive tests. In conclusion, B pertussis infection was found for 12 of 234 infants (5.1%) with unexpected deaths, and the infections might have contributed to the deaths.

Background. Acellular pertussis (aP)-containing vaccines cause fewer adverse events than whole-cell versions for primary doses. Booster doses, however, may be followed by extensive injection-site reactions. This study compares the frequency, severity, and impact of local reactions among children receiving 5 consecutive doses of an aP combination vaccine (including inactivated polio virus, conjugated Haemophilus influenzae type b antigen, and diphtheria and tetanus toxoids) to children receiving a mixed series of whole-cell and aP combination vaccines. Methods. Participants were parents or guardians of children 4 to 6 years old immunized at public health clinics across British Columbia, Canada. This included 398 children receiving the fifth consecutive dose of an aP combination vaccine and 402 receiving the fifth dose in a mixed series consisting of at least 1 prior dose of whole-cell pertussis combination vaccine with the remainder as aP combination vaccine. A cross-sectional telephone survey evaluated the extent of local reactions 48 to 96 hours after immunization by asking participants to compare the size of redness and swelling with familiar household items such as Oreo cookies or coins. Associated discomfort and impact on recreational activities, health care utilization, parental time off work, and attitudes toward immunization were also assessed. Results. Children who received the fifth consecutive dose of an aP combination vaccine more often experienced redness (24%) or swelling (16%) the size of an Oreo cookie or larger (≥46 mm) than children given a mixed series (10% and 9%, respectively) but less often experienced tenderness or limitation of movement at the injection site. Related health care utilization was low. There was no discernible effect on participation in recreational activities or parental attitudes toward vaccine; 90% would recommend the same vaccine to others with children of the same age. Conclusions. We conclude that injection-site reactions are more extensive after the fifth consecutive dose of an aP combination vaccine compared with the fifth dose in a mixed series of whole-cell and aP combination vaccines. These reactions are unlikely to affect parental acceptance of immunization recommendations or health care utilization.

* Abbreviations: DTaP — : pediatric diphtheria and tetanus toxoids and acellular pertussis vaccine DTP — : pediatric diphtheria and tetanus toxoids and whole-cell pertussis vaccine FHA — : filamentous hemagglutinin FIM — : fimbriae PCR — : polymerase chain reaction PRN — : pertactin PT — : pertussis toxin WHO — : World Health Organization During the 2010 pertussis epidemic in California, there was considerable concern in the press and in public health communications about the possible contribution of vaccine failures to the problem.1,2 In this commentary, I examine why pertussis vaccines fail and Table 1 lists 8 possible reasons. View this table: TABLE 1 Possible Reasons Why DTP, DTaP, and Adolescent- and Adult-Formulated Tetanus and Diphtheria Toxoids and Acellular Pertussis Vaccines Fail The first reason, and perhaps the most important one, is that our estimates of vaccine efficacy have been inflated because of case definition.3–11 At the time of the pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine efficacy trials in the early 1990s, it was hoped that a universal case definition could be developed so that the results of the various trials could be compared. To this end, the World Health Organization (WHO) case definition was developed.3 The primary case definition required laboratory confirmation and ≥21 days of paroxysmal cough. I was a member of the WHO committee and disagreed with the primary case definition because it was clear at that time that this definition would eliminate a substantial number of cases and therefore inflate reported efficacy values.4–11 Nevertheless, the Center for Biologics Evaluation and Research of the Food and Drug Administration accepted this definition, and package inserts of the US-licensed DTaP vaccines reflect this. For example, Infanrix (containing 25 μg pertussis toxin [PT], 25 μg filamentous hemagglutinin [FHA], and 8 μg pertactin [PRN]) and Daptacel (containing 10 μg PT, 5 μg FHA, 5 μg fimbriae [FIM]-2/3, and 3 μg … Address correspondence to James D. Cherry, MD, MSc, Department of Pediatrics, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, MDCC 22-442, Los Angeles, CA 90095-1752. E-mail: jcherry{at}mednet.ucla.edu

CONTEXT: Reimmunizing patients who had an adverse event following immunization (AEFI) is sometimes a challenge because there are limited data on the risk and severity of AEFI recurrence. OBJECTIVE: To summarize the literature on the risk of AEFI recurrence. DATA SOURCES: PubMed, Embase, and Cochrane library. STUDY SELECTION: We included articles in English or French published before September 30, 2016. Articles were selected if they estimated the risk of AEFI recurrence in at least 5 individuals. Studies with experimental vaccines were excluded. DATA EXTRACTION: Data on study design, setting, population, vaccines, and AEFI recurrence were extracted. RESULTS: Twenty-nine articles were included. Among patients with a history of hypotonic hyporesponsive episode ( n = 398), anaphylaxis ( n = 133), or seizures ( n = 60) who were reimmunized, events recurred in 0% to 0.8%. Allergic-like events recurred in 30 of 594 reimmunized patients. Fever recurred in 0% to 84% of 836 reimmunized patients, depending on the vaccine and dose number. Among children with extensive limb swelling after the fourth dose of diphtheria-tetanus-acellular pertussis vaccine, recurrence was higher when the fifth dose was given withthe full-antigen formulation (78%) compared with the reduced-antigen formulation (53%, P = .02) LIMITATIONS: Many studies, included few patients, and those with severe AEFIs were often not reimmunized. CONCLUSIONS: Despite vaccines being administered to millions of people annually, there are few studies in which researchers evaluated AEFI recurrence. Published studies suggest that reimmunization is usually safe. However in these studies, severe cases were often not reimmunized.

BACKGROUND AND OBJECTIVES: Washington State experienced a pertussis epidemic from October 2011 to December 2012. There was wide variation in incidence by county. The objectives of this study were to determine how the pertussis epidemic affected infant vaccination in Washington State and whether the incidence in counties modified this effect. METHODS: We conducted an ecologic before–after study to compare the proportion of infants up to date (UTD) with a pertussis-containing vaccine at time points before (September 30, 2011), during (September 30, 2012), and after (September 30, 2013) the epidemic. Children aged 3 to 8 months enrolled in the Washington State Immunization Information System with documented county of residence were included. UTD status was determined as ≥1, ≥2, or ≥3 doses of a pertussis-containing vaccine at ages 3, 5, and 7 months, respectively. Generalized linear models with extension to the binomial family and clustered robust standard errors were used to examine differences in the proportion of UTD infants between preepidemic and either epidemic or postepidemic points. The potential modifying effect of pertussis incidence by county was examined. RESULTS: We found no significant difference in statewide UTD status with a pertussis-containing vaccine between preepidemic and either epidemic (absolute difference 2.1%; 95% confidence interval, −1.6 to 5.9) or postepidemic (absolute difference 0.2%; 95% confidence interval, −4.0 to 4.5) time points. There was no significant modification by county pertussis incidence. There was wide variation in the absolute difference in UTD status across counties. CONCLUSIONS: A statewide pertussis epidemic does not appear to have significantly changed the proportion of infants who were UTD with a pertussis-containing vaccine.

OBJECTIVE: Data on the effectiveness of the diphtheria–tetanus–acellular pertussis (DTaP) vaccine in the first 4 years of life are sparse. We evaluated the vaccine effectiveness (VE) of 1 and 2 doses of DTaP before 6 months of age and of 3 doses from 6 months of age in Australia, where, since 2003, a fourth dose is not given until 4 years. METHODS: We matched reported pertussis cases aged 2 to 47 months between January 2005 and December 2009 to controls from a population-based immunization register by date of birth and region of residence. VE by number of doses and age group was calculated as (1 – odds ratio) × 100%. RESULTS: VE against hospitalization increased from 55.3% (95% confidence interval [CI], 42.7%–65.1%) for 1 dose before 4 months of age to 83.0% (95% CI, 70.2%–90.3%) for 2 doses before 6 months. The VE of 3 doses of DTaP against all reported pertussis was 83.5% (95% CI, 79.1%–87.8%) between 6 and 11 months, declining to 70.7% (95% CI, 64.5%–75.8%) between 2 and 3 years of age and 59.2% (95% CI, 51.0%–66.0%) between 3 and 4 years of age. CONCLUSIONS: DTaP provided good protection against pertussis in the first year of life from the first dose. Without a booster dose, the effectiveness of 3 doses waned more rapidly from 2 to 4 years of age than previously documented for children >6 years of age who had received 5 doses.

Objective.Immunologic interference particular to the Haemophilus influenzae type b (Hib) response has been observed with previous acellular pertussis-Hib combination vaccines. To test this hypothesis a clinical trial to assess the safety and immunogenicity of a five-component (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], and fimbriae 2 and 3 [FIM]), pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP) when given simultaneously with a lyophilized Hib-tetanus toxoid conjugate vaccine (PRP-T) in infants at 2, 4, 6, and 18 months of age was conducted. The study compared two methods of administration: both vaccines combined in a single syringe and administered as a single injection, or both vaccines administered concurrently but at separate sites of injection.Methods.Healthy 2-month-old infants were enrolled at the National Taiwan University Hospital. DTaP, PRP-T, and oral poliomyelitis vaccine (OPV) were given at 2, 4, 6, and 18 months. Reaction information was collected by telephone 2 days after each vaccination. Serum was collected at 2, 6, 7, 18, and 19 months of age.Results.One hundred thirty-five healthy infants were enrolled in Taiwan, of which 127 (94%) completed the 18-month booster: 68 received the combined vaccine and 67 the separate vaccines. All vaccines were well tolerated. No differences in rates of local and systemic reactions were seen between the two methods of administration. No serious adverse events were reported. Serologic responses were comparable between the groups. Pertussis responses (enzyme-liked immunoabsorbant assay units [EU]/mL) at 7 months were, for combined versus separate, PT (131 vs 105), FHA (116 vs 116), PRN (100 vs 77), and FIM (922 vs 702). At 19 months, pertussis results were, for combined versus separate, PT (216 vs 182), FHA (203 vs 200), PRN (263 vs 197), and FIM (892 vs 732). Only the 7-month PT response in the combined group was significantly higher (combined 131 EU/mL vs separate 105 EU/mL). After the third dose (age 6 months), all subjects achieved serologic serum antibody levels indicative of protection against Hib, diphtheria, tetanus, and poliovirus types 1, 2, and 3. In fact, 96% of children had anti-PRP levels indicative of protection (≥0.15 μg/mL) against Hib after only two doses. At 7 months, anti-PRP geometric mean titer values were 11.8 μg/mL in the combined group compared with 13.0 μg/mL in the separate group. The anti-PRP geometric mean titers after the 18-month booster were 58.5 μg/mL in the combined group versus 55.3 μg/mL in the separate group.Conclusion.The five-component DTaP vaccine may be combined with PRP-T vaccine without clinically significant immunologic interaction when given in a 2-, 4-, 6-, and 18-month schedule.

Background. In the course of a large pertussis vaccine efficacy trial we realized that investigator compliance could have a major impact on calculated vaccine efficacy. Design. In our pertussis vaccine efficacy trial, the study investigators were to monitor illness in study families by telephone every 2 weeks. If a cough illness of ≥7 days duration was noted, the study child was to be evaluated. If the cough illness persisted for ≥14 days, the child was to be referred to a central investigator. For this report we analyzed study physician evaluation rates and rates of referral to the central investigators. Physician practices were separated into three compliance categories: high, intermediate, and low. We analyzed vaccine efficacy of an acellular pertussis component DTP vaccine (DTaP) and a whole cell pertussis component DTP vaccine (DTP) by compliance category. Bordetella pertussisinfection was documented by culture of the organism in the study child or in a household contact or by a significant antibody response to pertussis toxin determined by enzyme-linked immunosorbent assay. Results. Using a clinical case definition that included both mild and typical pertussis (cough illness ≥7 days duration) efficacy of DTaP vaccine was 40% (95% confidence interval [CI] = −3–65) in the high compliance category and 78% (95% CI = 65–86) and 75% (95% CI = 53–87) in the intermediate and low compliance groups, respectively. Similar, but less marked, differences in efficacy were noted with DTP vaccine recipients. Using a clinical case definition that required ≥21 days of cough with paroxysms, whoop, or vomiting (typical pertussis) the efficacy of DTaP vaccine was 69% (95% CI = 41–83) in the high compliance category and 86% (95% CI = 76–92) and 84% (95% CI = 64–93) in the intermediate and low compliance groups, respectively. In contrast, the efficacy of DTP vaccine did not vary by compliance category using this case definition. The attack rate in children vaccinated with diphtheria and tetanus toxoids vaccine (DT) was twofold less in low compliance physician practices when compared with the rates in high and intermediate groups. The DT/DTaP and DT/DTP fold-change differences were less in the high compliance group compared with the intermediate and low compliance groups. Conclusions. Our data suggest that observer compliance (observer bias), can significantly inflate calculated vaccine efficacy. It is likely that all recently completed efficacy trials have been effected by this type of observer bias and all vaccines have considerably less efficacy against mild disease than published data suggest.

Background. A household contact substudy was performed as part of a prospective, cohort pertussis vaccine efficacy trial in Germany. Design. Infants received four doses of either the Lederle/Takeda acellular pertussis component diphtheria-tetanus toxoids (DTP) vaccine (DTaP) or Lederle whole-cell component DTP vaccine at 3, 4.5, 6, and 15 to 18 months of age (Wyeth-Lederle Vaccines and Pediatrics, Pearl River, NY). An open control group received three doses of diphtheria and tetanus toxoids vaccine (DT) at 3, 4.5, and 15 to 18 months of age. Vaccine efficacy rates were calculated using a number of principal and ancillary case definitions for primary, secondary, and noncases by analyzing secondary attack rates in study infants after exposure to pertussis in the household using 7- to 28- and 7- to 42-day postexposure observation periods and the inclusion and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period. Results. During a 3.5-year study period, 10 271 infants (DTP or DTaP, n = 8532; DT, n = 1739) were enrolled and actively followed along with all household members for cough illnesses. Depending on the case definition, 160 to 519 household exposures to pertussis were identified. In general, secondary attack rates in DT recipients were low and this was primarily because of the frequent use of antimicrobial prophylaxis. Using the principal case definitions and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period and the 7- to 42-day observation period, the efficacy of DTP against cough illness of ≥7 days duration caused by Bordetella pertussis was 84% (95% confidence interval [CI] = 65–93) and that of DTaP was 58% (95% CI = 30–75). Using similar criteria, the efficacy against typical pertussis (≥21 days of cough with either paroxysms, whoop, or posttussive vomiting) was 94% (95% CI = 77–99) and 86% (95% CI = 62–95) for DTP and DTaP, respectively. The efficacy against any cough illness (with or without) laboratory confirmation was 54% (95% CI = 32–69) and 38% (95% CI = 13–56) for DTP and DTaP, respectively. Conclusion. This household contact substudy within our cohort study, with active investigator-generated surveillance, was a severe test of vaccine efficacy. Both vaccines (DTP and DTaP) are better at preventing typical pertussis than mild illness. When case definitions similar to those in other recent trials are used, the Lederle/Takeda vaccine has an efficacy similar to other multicomponent DTaP vaccines.

Objective. Our earlier research found that the strongest predictor of not being up to date on the full series of immunizations by 24 months is failure to receive the first diphtheria vaccine and tetanus toxoid and pertussis vaccine (DTP1) on time. To learn more about the relationship between successful vaccination during the DTP1 age-appropriate (DTP1-AA) period (between 42 and 92 days of life, inclusive) and an infant's early visit to the physician (before 42 days of life), we quantified children's progression through a sequence of provider visits and outcomes. Design. This study analyzed data from 426 children living in the 57 poorest census tracts in Baltimore. For each DTP1-AA visit, we calculated the percentage of times a DTP1-AA vaccination, provider missed opportunity, or deferral for a valid contraindication occurred. Relative and attributable risks were computed to assess associations between DTP1-AA vaccination and early visits and missed opportunities. Results. We found the following: 1) Children who made a visit before 42 days of life were more than twice as likely to receive a DTP1-AA vaccination; 2) the missed opportunity rate for children who did not make an early visit was approximately twice that of the early-visit group; and 3) well visits were more likely to result in DTP1-AA immunization than sick visits. Attributable risk calculations show that DTP1-AA vaccination rates could be increased in this population by one third if all infants had an early visit. Conclusions. Early in-office visits seem to make DTP1-AA vaccination more likely. These rates may be amenable to intervention by increasing early visits and reducing DTP1-AA missed opportunities. Introduction of the hepatitis B vaccine to the recommended series may place more emphasis on early visits and result in increased DTP1-AA rates and, ultimately, higher vaccination coverage rates.

BACKGROUND:During the 1990s, the United States switched from combined diphtheria, tetanus toxoids, whole-cell pertussis (DTwP) vaccines to combined acellular pertussis (DTaP) vaccines because of safety concerns. After a 2010–2011 pertussis outbreak, we sought to evaluate whether disease risk in 10 to 17 year olds differed between those who previously received DTwP from those who received DTaP.METHODS:A case-control study among individuals born from 1994 to 1999 who received 4 pertussis-containing vaccines during the first 2 years of life at Kaiser Permanente Northern California (KPNC). We separately compared pertussis polymerase chain reaction (PCR)-positive cases with PCR-negative and KPNC-matched controls. We assessed risk of pertussis relative to vaccine type in early childhood (4 DTwPs, mixed DTwP/DTaP, or 4 DTaPs) by using conditional logistic regression stratified for calendar time and adjusted for gender, race, medical clinic, and receipt of reduced antigen content acellular pertussis (Tdap) vaccine.RESULTS:We compared 138 PCR-positive cases with 899 PCR-negative and 54 339 KPNC-matched controls. Teenagers who had received 4 DTwPs were much less likely to be pertussis PCR-positive than those who had received 4 DTaPs (odds ratio 5.63, 95% confidence interval 2.55–12.46) or mixed DTwP/DTaP vaccines (odds ratio 3.77, 95% confidence interval 1.57–9.07). Decreasing number of DTwP doses was significantly associated with increased pertussis risk (P < .0001).CONCLUSIONS:Teenagers who received DTwP vaccines in childhood were more protected during a pertussis outbreak than were those who received DTaP vaccines.

Objective. To characterize pertussis deaths and to identify possible risk factors and prevention strategies. Methods. A retrospective review of all deaths attributed to pertussis with disease onset during 1992 and 1993 reported to the Centers for Disease Control and Prevention. Hospital discharge summaries and autopsy reports were reviewed, and additional clinical information was provided by physicians involved in the care of the children. Results. During 1992 and 1993, 23 deaths attributed to pertussis were reported to the Centers for Disease Control and Prevention. Cultures for Bordetella pertussis were positive in 18 (90%) of the 20 cases in which it was performed. Twenty (87%) of the 23 children who died were younger than 1 year of age, and 18 (78%) of the children had received no doses of pertussis vaccine. Among 20 children for whom gestational ages were known, 12 (60%) were born at 36 weeks' gestation or earlier; in contrast, 10.7% of live births in the United States in 1992 were at 36 weeks' gestation or earlier. The median age of mothers whose children had fatal pertussis was 20 (range, 14 to 37) years in the 15 cases in which ages were known, compared with the national median age of 26.3 years in 1992. Pneumonia was a complication in all but 1 (96%) of the cases. Seizures occurred in 4 cases (17%), and acute encephalopathy occurred in 3 cases (13%). Conclusions. Pertussis continues to cause serious illness and death in the United States, particularly among infants who are not vaccinated. Preterm delivery and young maternal age may place infants at increased risk of death because of pertussis. Under the current pertussis vaccination schedule, three fourths of the infants who died were too young to have received three doses of pertussis vaccine, the minimum number of doses considered necessary for adequate protection against clinical pertussis. Additional strategies to prevent deaths caused by pertussis in young infants, such as starting infant vaccination at an earlier age and booster doses to adolescents and adults, need to be evaluated.

Objective. To determine whether gender, race (black or white), or level of parental education influenced serologic responses or reporting of clinical reactions after immunization with acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. Methods. Healthy infants were prospectively randomized to receive one of 13 DTaP, Lederle DTP, or another DTP. Parents recorded the occurrence of adverse reactions for 2 weeks after each inoculation. Sera obtained before the first immunization and 1 month after the third immunization were analyzed for antibody to pertussis toxin, filamentous hemagglutinin, fimbriae, and pertactin (PRN). Chinese hamster ovary cell pertussis toxin neutralization assays were performed, and levels of agglutinating antibodies determined. Results. Prevaccination antibody levels did not differ by race, gender, or parental education. Postimmunization geometric mean titers (GMTs) were strongly and consistently associated with race. For both DTaP and DTP and for every included antigen, postimmunization GMTs were about twice as high for black as for white infants. Among DTaP recipients, these differences were significant for pertussis toxin, Chinese hamster ovary cell pertussis toxin neutralization assay, filamentous hemagglutinin, PRN, and agglutinins ; among the much smaller sample of WCL recipients, the differences achieved or approached statistical significance for agglutinins, PRN, and fimbriae. These findings were confirmed by regression analyses that controlled for gender, parental education, study site, and preimmunization antibody level. Reported reactions were not correlated with parental education level and showed no material correlation with gender. Black infants were reported to have had more pain than white infants after receiving WCL and DTaP and were reported to be more fussy after receiving WCL. Conclusions. The consistently higher postimmunization GMTs among black infants seems to be a real finding for which we have no explanation ; the infants did not significantly differ by race in vaccine assignment, preimmunization antibody levels, age at immunization, or interval from immunization to phlebotomy. These observations should be confirmed and further evaluated in future pertussis vaccine trials. Reported differences by race in pain and fussiness after receiving WCL might reflect chance, differences by race in the occurrence of reactions, or differences by race in the reporting of reactions. Pediatrics 1995 ;96 :584-587 ; acellular, antibody, diphtheria-tetanus-pertussis, vaccine, whole-cell, whooping cough.

Objective. To compare the immunogenicity and reactogenicity of a diphtheria and tetanus toxoids and three-component acellular pertussis vaccine (DTaP) with a diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTwP) when administered as a booster dose to infants 15 through 20 months of age. Design. Randomized, double-blind, comparative study. Setting. Three pediatric practices (two private; one hospital-based). Participants. One hundred and sixty-five healthy 15-through 20-month old infants. Selection procedures and interventions. Infants were randomly assigned in a 2:1 ratio to receive vaccine from a single lot of DTaP or from commercially available DTwP. DTaP contained 25 µg of pertussis toxoid, 25 µg of filamentous hemagglutinin, 8 µg of pertactin (69-kilodalton outer membrane protein), 25 flocculating units of diphtheria toxoid, and 10 flocculating units of tetanus toxoid per 0.5-mL dose. DTwP contained one half the concentrations of diphtheria and tetanus toxoids compared with DTaP and a pertussis component with a potency of 4 U/0.5-mL dose. Serum samples were obtained on the day of immunization and 4 weeks later. Adverse reactions were recorded by parents for 7 days after immunization. An interval history was obtained 4 weeks after immunization. Measurements and results. IgG antibody to pertussis toxoid, filamentous hemagglutinin, pertactin, diphtheria toxoid, and tetanus toxoid was measured by an indirect enzyme-linked immunosorbent assay (ELISA) method. One month after immunization, the geometric mean antibody levels after DTaP compared with DTwP were: pertussis toxoid, 70.6 vs 28 ELISA U/mL (P = .003); filamentous hemagglutinin, 183.4 vs 43 ELISA U/mL (P < .001); pertactin, 216 vs 49.9 ELISA U/mL (P < .001); diphtheria, 14.1 vs 14.9 IU/mL (P = .74); and tetanus, 11.9 vs 14.8 IU/mL (P = .089). After immunization with DTaP, most local and systemic adverse experiences were significantly fewer compared with DTwP (P < .05). Conclusions. This three-component DTaP vaccine demonstrates significantly greater immune responses to pertussis toxoid, filamentous hemagglutinin, and pertactin, equivalent immune responses to diphtheria and tetanus toxoids, and significantly less reactogenicity compared with a licensed DTwP.

Objective. To compare the safety and immunogenicity of a variety of acellular (AC) and whole-cell (WC) pertussis vaccines combined with diphtheria and tetanus toxoids. Methods. Standard enrollment and reaction forms were used at five sites, and serologic evaluation was performed at a single site. Nine AC (Massachusetts Public Health Laboratories, Biocine Sclavo recombinant pertussis toxoid [PT], Connaught/BIKEN, Lederle three-component, Biocine Sclavo recombinant three-component, SmithKline Beecham three-component, Porton three-component, Takeda-Wyeth, and Connaught multicomponent), and three WC (Connaught Laboratoties, Lederle Laboratories, and Massachusetts Public Health Laboratories) were studied. All AC contained varying concentrations of PT; some vaccines also contamed filamentous hemagglutinin (FHA), pertactin, and/or agglutinogens. Results. Two hundred forty children, aged 16 to 21 months and 4 to 6 years, were enrolled at five sites. Significantly less fever, redness, swelling, pain, limp, and use of pain medication were noted following AC compared with WC. Significant increases in antibody to PT were seen following all vaccines. Significant rises in FHA antibody were seen following all WC and the seven AC that contained FHA. Postbooster PT antibody levels were similar among the AC groups, regardless of the amount of PT administered (between 3.5 and 25 µg per dose). The dose of FHA did not affect PT antibody response. Infants primed with WC who were boosted with a monocomponent PT vaccine did not manifest a significant antibody response to FHA. Conclusion. The rate of adverse reactions was not a function of the number of antigens or the antigen quantity in the acellular vaccines, and antibody responses following AC were similar or better than antibody responses following WC. These results support the further evaluation of these vaccines in a larger National Institute of Allergy and Infectious Diseases-sponsored study in infants.