Adverse Events After Administration of Tetanus‐Diphtheria‐Acellular Pertussis Vaccine toHealthcare Workers • Author(s): Thomas J. Sandora, MD, MPH; Elizabeth Pfoh, BA; Grace M. Lee, MD, MPHSource: Infection Control and Hospital Epidemiology, Vol. 30, No. 4 (April 2009), pp. 389-391Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiologyof AmericaStable URL: http://www.jstor.org/stable/10.1086/596201 .

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infection control and hospital epidemiology april 2009, vol. 30, no. 4

c o n c i s e c o m m u n i c a t i o n

Adverse Events After Administrationof Tetanus-Diphtheria-AcellularPertussis Vaccine to Healthcare Workers

Thomas J. Sandora, MD, MPH; Elizabeth Pfoh, BA;Grace M. Lee, MD, MPH

Healthcare workers who received the tetanus-diphtheria–acellularpertussis (Tdap) vaccine were surveyed about adverse events. Localadverse events were more common among women and among thosewho received the Tdap vaccine less than 5 years after they hadreceived the tetanus-diphtheria vaccine. Systemic adverse events weremore common among healthcare workers aged less than 30 years.These findings provide guidance for counseling of healthcare work-ers who receive Tdap vaccine.

Infect Control Hosp Epidemiol 2009; 30:389-391

In recognition of the impact of transmission of pertussis inthe healthcare setting, the Advisory Committee on Immuni-zation Practices has recommended tetanus-diphtheria–acellu-lar pertussis (Tdap) booster vaccination for healthcare workers(HCWs) and that healthcare institutions establish Tdap vac-cination campaigns for HCWs.1 Although general prelicensuresafety data about Tdap are available, no data have been pub-lished about adverse event rates among HCWs, who may re-ceive vaccines at shorter intervals (as little as 2 years sincereceipt of their prior tetanus booster).1 Data from a Canadianstudy suggest that the vaccine is likely to be safe if given afterthis shorter interval,2 but there are concerns that severe injec-tion site reactions, including Arthus-type reactions, may occurwith shorter intervals between administration.3,4 The impactof the shorter interval on adverse event rates among HCWs isunknown.

We conducted a prospective study to assess adverse eventrates after Tdap vaccination in a cohort of HCWs at a pe-diatric hospital. Our objectives were (1) to describe local andsystemic adverse event rates and (2) to understand risk factorsassociated with local and systemic adverse events, includingtime since prior administration of tetanus-diphtheria (Td)vaccine.

methods

HCWs were recruited during the period July–September 2006at the time that they received the Tdap vaccine. The studywas approved by our institutional review board. To be eligible,participants were required to be a hospital employee, to havereceived Tdap vaccine in the hospital, and to be able to readEnglish. At the time of enrollment, participants were askedto provide the number of years since they had received theirprevious Td booster (less than 2 years, 2 to less than 5 years,

5 years to less than 10 years, and 10 or more years; becauseof small numbers, the first 2 categories were combined forall analyses). Estimated dates of Td vaccination were validatedusing electronic records from our Occupational Health Ser-vice or written documentation from outside providers, ifavailable. If documented dates of Td administration wereavailable, the exact Td date was used.

Enrolled participants received a link to a confidential Web-based survey 2 weeks after vaccination. E-mail reminders weresent within 1–2 weeks for nonrespondents. The survey con-tained questions about local adverse events (ie, pain, redness,and swelling) and systemic adverse events (ie, fever, headache,and fatigue), as well as entire limb swelling. We also askedrespondents to report unsolicited adverse events that occurredafter Tdap vaccination. Specific severity categories were notprovided on the survey.

Bivariate and multivariable logistic regression models werebuilt to identify risk factors for any local adverse event (ie,pain, redness, or swelling) or for any systemic adverse event(ie, fever, headache, or fatigue). Potential risk factors includedage (less than 30 years vs 30 or more years), sex, and timesince receipt of the previous Td booster (less than 5 years, 5to less than 10 years, and 10 or more years). Statistical analyseswere performed using SAS software, version 9.1 (SAS). Pvalues of less than .05 were considered to be statisticallysignificant.

results

Study population. Two hundred sixty-eight eligible subjectswere recruited for the study; 17 declined to participate, and251 (94%) provided consent to participate. Of these, 207(82%) completed the adverse events survey. The median du-ration from receipt of the survey to completion was 3 days,and 75% of respondents completed the survey within 7 daysafter they had received it (ie, within 21 days after vaccination).The ages of the participants were as follows: less than 30years, 53 (26%) of 207 persons; 30–39 years, 53 persons(26%); 40–49 years, 50 persons (24%); and 50 or more years,51 persons (25%). Seventy-two percent of subjects were fe-male. The exact date of Td administration was known for 43(21%) of the respondents, and the remaining 164 (79%) pro-vided an estimated range for receipt of the most recent Tdbooster (Table 1). For subjects who provided exact dates ofTd vaccination, the median interval since receipt of the pre-vious Td vaccine was 6.6 years (range, 2.1–31.1 years).

Frequency and severity of vaccine adverse events. In total,167 participants (81%) experienced at least 1 adverse event(Table 2). One participant (0.5%) reported that vaccine-related adverse events (ie, fever, headache, and fatigue) were

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390 infection control and hospital epidemiology april 2009, vol. 30, no. 4

table 1. Interval Since Most Recent Tetanus-Diphtheria (Td) Booster, July–September 2006

No. of years since receipt ofprevious Td booster

No. (%) of subjects

Respondents with estimatedTd booster date

(n p 164)

Respondents with exact Tdbooster date

(n p 43)All respondents

(n p 207)

Less than 5 Years 50 (30) 15 (35) 65 (31)From 5 to less than 10 years 57 (35) 21 (49) 78 (38)At least 10 years 57 (35) 7 (16) 64 (31)

note. Exact dates of Td administration were determined by a review of the electronic hospital vaccine registry.

table 2. Vaccine-Related Adverse Events in Healthcare Workers, July–Sep-tember 2006

Adverse eventNo. (%) of subjects

(n p 207)Duration, days, median

(range)

Solicited local reactionsRedness at site 15 (7) 3 (1–14)Pain at site 159 (77) 3 (1–16)Swelling at site 22 (11) 3 (1–13)

Solicited systemic reactionsFever 10 (5) 1 (1–7)Headache 19 (9) 2 (1–14)Fatigue 29 (14) 2 (1–14)

Swelling of the entire limb 0 (0) …

note. Other unsolicited adverse events included bruising (1%) and pruritus (0.5%)at the injection site; myalgias, arthralgias, “flu-like symptoms,” and/or muscle weakness(10%); chills (1%); dizziness (0.5%); swollen lymph nodes (1%); nausea and/or vomiting(1%); cough (0.5%); and radial nerve palsy and/or tingling sensation of upper extremity(1%).

severe enough to result in missed work. Adverse events weresevere enough to interfere with nonwork activities for 12participants (6%); in all cases, pain was the reason cited fordisruption of activities.

Risk factors for any local adverse event. The proportion ofparticipants who reported experiencing local adverse eventsdecreased from 86% for those with intervals of less than 5years to 66% for those with intervals of 10 or more years. Inmultivariate analyses, HCWs who received the Tdap vaccineat an interval of less than 5 years after receipt of Td vaccinewere significantly more likely to experience local adverseevents, compared with those who reported an interval of 10or more years (odds ratio, 3.06 [95% confidence interval,1.25–7.52]). Female sex was also an independent predictorof local adverse events after Tdap vaccination (odds ratio,3.06 [95% confidence interval, 1.51–6.23]).

Risk factors for any systemic adverse event. Multivariateanalyses revealed that an age of less than 30 years was sig-nificantly associated with higher rates of systemic adverseevents (odds ratio, 4.15 [95% confidence interval, 1.94–8.86]). Neither sex nor interval since most recent Td vacci-nation was significantly associated with the development ofsystemic adverse events after receipt of Tdap.

discussion

In prelicensure studies, serious adverse events after admin-istration of Tdap were uncommon.5-9 In one randomized trial,4,480 adolescents and adults received either Tdap or Td vac-cine, and data regarding adverse events after vaccination wererecorded for 14 days.6 The rates of local and systemic adverseevents were similar between the groups. Among adults, themost common events after Tdap vaccination were pain(64%), increase in the injection limb circumference of 1 ormore cm (30%), erythema at the injection site (23%), head-ache (23%), injection site swelling (20%), fatigue (19%), andgeneralized body ache or muscle weakness (17%). Our studyfound that a slightly higher proportion of HCWs (77%) re-ported pain, and fewer reported erythema, swelling, or fa-tigue. No reports of increased limb circumference were notedin our study.

In a study from Canada, slightly increased rates of rednessand swelling were observed in several cohorts with intervalsof less than 10 years since receipt of the previous Td booster;however, these differences were not significant.2 In our study,pain became significantly less common as the number of yearsafter Td administration increased. Our finding supports con-cerns about reactogenicity associated with repeated exposure

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tdap adverse events in hcws 391

to vaccine antigens, including extensive limb swelling afterreceipt of pertussis-containing vaccines.3,10

In our study, female HCWs were 3 times as likely as maleHCWs to experience local adverse events after Tdap admin-istration. This trend was also noted in a prelicensure studyof Tdap, although specific details were not provided; a similartrend was also noted in the Td comparison group.6

Our study has several limitations. The survey was con-ducted at a single institution. We did not have a placebo orTd comparison group, so reported adverse events may notbe attributable to the pertussis component of the Tdap vac-cine. We chose to administer the survey 14 days after vac-cination to minimize recall bias (because most adverse eventsoccur within 2 weeks), but we may have missed late-occurringevents. A minority of participants provided a documentedexact date of Td administration; however, we attempted tominimize misclassification by offering response options thatcovered wide intervals. Finally, despite our high response rateof 82%, the reported adverse event rates may be exaggeratedif nonrespondents were less likely to experience events.

We found that, among HCWs who received Tdap at apediatric hospital, 77% reported pain after vaccination. Painwas significant enough to interfere with nonwork activitiesfor 6% of recipients. Female sex and shorter interval aftermost recent Td vaccination were associated with an increasedrisk of local adverse events after Tdap vaccination, and youn-ger age was associated with increased risk of systemic adverseevents. Targeted counseling for HCWs with the outlined riskfactors will help inform the expectations of vaccine recipients.

acknowledgments

Potential conflicts of interest. All authors report no conflict of interest rel-evant to this article.

From the Division of Infectious Diseases (T.J.S., G.M.L) and the Depart-ment of Laboratory Medicine (T.J.S., G.M.L.), Children’s Hospital Boston,and the Department of Ambulatory Care and Prevention, Harvard Medi-cal School and Harvard Pilgrim Health Care (E.P., G.M.L.), Boston,Massachusetts

Address reprints request to Thomas J. Sandora, MD, MPH, Division ofInfectious Diseases, 333 Longwood Avenue, Children’s Hospital Boston, Bos-ton, MA 02115 (thomas.sandora@childrens.harvard.edu).

Received August 11, 2008; accepted November 10, 2008; electronicallypublished February 24, 2009.� 2009 by The Society for Healthcare Epidemiology of America. All rightsreserved. 0899-823X/2009/3004-0014$15.00. DOI: 10.1086/596201

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