Despite the availability of safe and effective vaccines, pertussis remains a significant public health problem. An epidemic of pertussis in California this year, which

has claimed the lives of at least 8 infants, is a vivid reminder that Bordetella pertussis continues to circulate in the United States. As of the end of August, the rate of reported pertussis among infants younger than 6 months of age in California was 1.68 per 1000, according to state health officials; most of these cases occurred in infants less than 3 months of age. Treatment with antibiotics early in the course of illness and chemoprophylaxis of close contacts can reduce transmission of B pertussis, especially to vulnerable infants, but may not prevent the morbidity associated with the disease (see part 2 of Pertussis 2010: Recognition, Diagnosis, Treatment … Prevention). Treatment and postexposure prophylaxis, though vital, don’t get at the heart of the problem: the need to prevent pertussis through immunization. Timely immunization of children and adults is key to reduc-ing the incidence of disease and protecting those most at risk. Although overall childhood vaccination rates are high, significant gaps remain, and booster immunization among adolescents and adults falls well short of needed coverage. The challenge is a large one, but practical strategies are available to help meet it.

AVAILABLE PERTUSSIS VACCINESAll pertussis vaccines used in the United States today are acellular vaccines comprised of purified, inactivated antigenic components of B pertussis cells combined with tetanus and diphtheria toxoids (Td). Diphtheria, tetanus, and acellular pertussis (DTaP) vaccine is licensed for infants and children 6 weeks through 6 years of age; tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is licensed for adolescents and adults 10 or 11 years of age (depend-ing on the product) through 64 years of age.

Different pertussis vaccines contain different combinations of pertussis antigens. DTaP and Tdap formulations contain 2 or more of the following antigens considered instrumental in producing clinical immunity by triggering antibody formation against B pertus-sis: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertac-tin (PRN), and fimbriae serotypes 2 (FIM-2) and 3 (FIM-3).1

Acellular pertussis vaccines cause significantly fewer adverse reac-tions compared to the older, whole-cell formulation, which has not been available in the US since 2002. The most common side effects of DTaP are local reactions such as pain, redness, and swell-ing. Mild systemic reactions (drowsiness, fretfulness, low-grade fever) also may occur. More severe reactions—high fever, febrile seizures, crying for 3 hours or longer, hypotonic-hyporesponsive episodes—are rare (fewer than 1 in 10,000 doses).1

No serious side effects have been attributed to Tdap, according to the Centers for Disease Control and Prevention (CDC).1 The most frequent adverse reactions are pain, redness, or swelling at the injection site. The rate of adverse reactions to Tdap is comparable to that of Td vaccine.1

Vaccines that combine DTaP with one or more components intended to prevent other diseases—inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib), and hepatitis B (HepB)—are also available (Table 1). The CDC’s Advisory Committee on Immunization Practices (ACIP) recommends administering com-bination vaccines whenever feasible: “The use of a combina-tion vaccine generally is preferred over separate injections of its equivalent component vaccines.” 2 In choosing among vaccines, the ACIP says that providers should take into consideration their own assessment findings, patient preferences, and the potential for adverse effects.2

Data from Canada, which has a childhood immunization sched-ule similar to that of the US, demonstrate that pertussis-containing combination vaccines are safe and efficacious. For more than a decade, DTaP-IPV/Hib vaccine was given exclusively as a 4-dose series throughout Canada to children at 2, 4, 6, and 18 months of age, followed by a combination DTaP-IPV vaccine at 4-6 years of age. More than 14.5 million doses of DTaP-IPV/Hib have been administered,3 and reports of serious adverse events have been extremely rare.4 Over the past 10 years, pertussis has declined sig-nificantly among older infants and school-age children throughout Canada, and the cyclical peaks characteristic of the disease have

Faculty ReviewersTina Q. Tan, MDProfessor of PediatricsFeinberg School of MedicineNorthwestern UniversityChicago, Illinois

Audrey Stevenson, PhD, MPH, FNP-BCDirector, Family Health Services DivisionSalt Lake Valley Health DepartmentSalt Lake City, Utah

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been blunted or eliminated. At the same time, invasive Hib disease in children younger than 5 years of age has remained well con-trolled at a rate of <1 case per 100,000 children per year.5

THE PROBLEM OF UNdERIMMUNIzATIONCompliance with the ACIP recommendations for routine pertus-sis immunization (Table 2) is high in terms of overall coverage for the first 3 doses of DTaP but falls short when it comes to timeli-ness of immunization and completion of the full pertussis series. Data for July 2008-June 2009 show that by 24 months of age, 96% of children had received the third (6-month) dose of DTaP but only 81% had received the fourth (15-18-month) dose.6 Moreover, coverage rates for 4 or more doses of pertussis vaccine vary greatly from state to state, ranging from 68% in Montana to 89% in Massachusetts.6

Timeliness is a concern for childhood vaccines in general. The CDC’s National Immunization Survey (NIS) for 2003 found that only 26% of children between 24 and 35 months of age had been vaccinated on time with 6 routinely recommend-ed vaccines, including DTaP.7 The remaining children were undervaccinated for a mean of 172 days, and 21% were “severely” undervaccinated—behind by longer than 6 months and for at least 4 vaccines. Some 30% of children were undervaccinated for DTaP for at least 3 months of their first 24 months of life.7 NIS data for 2006-2007 show that 20% of children fell behind in immunizations between 7 months and 16 months of age, mostly because of missed opportunities for simultaneous vaccination and not from a lack of access to care.8

Data such as these suggest that children who are fully vaccinated by 2 years of age may nevertheless be undervaccinated for significant periods within those 2 years, when they’re most susceptible to vaccine-preventable diseases. Failure to institute an aggressive catch-up schedule can lead to a domino effect that lengthens the period of risk.9

Studies make clear that delayed and missed vaccine doses increase the likelihood of infection for infants and young children. In one study, 54% of children between 6 and 11 months of age and 20%

of children between 1 and 4 years of age with available vaccination histories who were diagnosed with pertussis in 2005-2006 had not received 3 doses of pertussis vaccine.10

VACCINE REFUSAL INCREASES RISK OF dISEASEParents may delay or refuse vaccinations for their child for a variety of reasons, including religious or other personal beliefs; concerns about vaccine safety, side effects, or effectiveness; acute illness in the child; belief that the child’s susceptibility to disease or the severity of disease is low; or a conviction that children get too many vaccines.11,12

While all states allow medical exemptions to state-mandated immunization requirements, 48 states also permit religious exemp-tions, and 20 of those states allow broader personal belief exemp-tions—religious, philosophical, and other, unspecified nonmedical exemptions (Figure).13 Rates of nonmedical exemptions have risen in recent years, especially in states with personal belief exemptions.11

Vaccination refusal increases the risk of pertussis to individuals and the community. A case-control study of children enrolled in Kaiser Permanente of Colorado between 1996 and 2007 found a 23-fold greater risk of pertussis among children whose parents had refused vaccination than among vaccinated children. Eleven percent of all pertussis cases in the Kaiser Permanente of Colorado population were attributed to vaccine refusal.14

An earlier Colorado study found that children whose parents refused vaccination were almost 6 times more likely than vaccinat-ed children to contract pertussis. Schools that experienced pertussis outbreaks had almost 3 times as many vaccine-exempted children as schools without outbreaks.15

IMMUNIzATION OF AdOLESCENTS ANd AdULTS Progress has been made in immunizing adolescents with a booster dose of Tdap since the vaccine was licensed in 2005. In 2009, 56% of adolescents 13-17 years of age had received the vaccine. Nevertheless, close to half of teenagers remain unprotected.16 Far fewer adults 18-64 years of age have been immunized with Tdap—only 6% had reported receiving the vaccine as of 2008.17

Immunizing adults and adolescents in accordance with the ACIP recommendations on Tdap vaccine, especially those in close contact with young infants, is key to reducing the burden of disease and protecting the vulnerable infant population. Adults and adolescents are an important source of pertussis infection for infants, the age group at greatest risk of severe disease and death. Vaccination can reduce morbidity and mortality by breaking the cycle of transmission.18

Health-care workers comprise an important, and sometimes overlooked, group in need of vaccination because they’re much more likely than the general population to contract and transmit pertussis. Nosocomial spread has been documented, especially in pediatric facilities, endangering vulnerable patients and exacting a high toll in missed work and the cost of controlling even small outbreaks. The CDC recommends a dose of Tdap for all health-care personnel in a hospital or clinic setting who have direct patient contact and have not received Tdap previously.18

STRATEGIES TO IMPROVE COVERAGEImproving immunization rates and timeliness can seem like daunting challenges, but some practical steps will help achieve progress. They include:

Table 1. PerTussis-ConTaining VaCCines24

Vaccine use in pertussis immunizationschedule

Components

DTaP All childhood doses

Diphtheria and tetanus toxoids, acellular pertussis

DTaP + Hib Fourth dose only Diphtheria and tetanus toxoids, acellular pertussis, lyophilized Haemophilus influenzae type b (Hib)

DTaP + IPV + HepB First 3 doses of series

Diphtheria and tetanus toxoids, inactivated poliovirus, hepatitis B surface antigen

DTaP + IPV + Hib 4-dose series Diphtheria and tetanus toxoids, inactivated poliovirus, lyophilized Hib

DTaP + IPV Booster dose at 4-6 yr of age

Diphtheria and tetanus toxoids, acellular pertussis, inactivated poliovirus

Tdap 1-time booster for adolescents and adults

Tetanus and reduced diphtheria toxoids, acellular pertussis

Maximize opportunities to vaccinate. Because missed opportu-nities have been shown to be a key reason for undervaccination, it’s critical that providers use every patient visit—minor injury or illness, school or camp physical, precollege visit—to assess immu-nization status and vaccinate if necessary. Give all indicated immu-nizations at a single visit, and avoid deferring vaccination for mild acute illness.1 The fourth dose of DTaP vaccine or DTaP-IPV/Hib vaccine can be given as early as 12 months of age if 6 months have elapsed since the previous dose and the clinician believes that the opportunity to vaccinate may be missed later.2

The CDC advocates using standing orders to take advantage of immunization opportunities, including incorporating Tdap into postpartum discharge orders and into wound management protocols (instead of Td).18,19 Sample standing orders are available from the Immunization Action Coalition at www.immunize.org/standingorders.

Establish a reminder-recall system for every patient. A comput-erized immunization registry (immunization information system) can help keep track of patients’ vaccination histories. Registries consolidate scattered records, identify patients who need vaccina-tions, provide automated reminder and recall, help manage vaccine supplies, and generate vaccination records for parents and schools.

Maximize opportunities to educate parents and patients about timely, thorough vaccination. Parent education should begin at early infant visits—even at a prenatal visit if the parent visits your office during that time. Include CDC Vaccine Information Statements (www.cdc.gov/vaccines/Pubs/vis/default.htm) in new-born visit packets and hand them out, as required by federal law, when you give each dose of a recommended vaccine.

In waiting areas and exam rooms, display vaccine brochures and reminders encouraging adults to get vaccinated; include vaccine

information on your practice’s Web site and in newsletters and billing statements. (See the resources box on the next page.)

Parents with doubts about immunization merit special attention and counseling. One study found that such parents who ultimately changed their minds about delaying or refusing vaccination most often cited “information or assurances from health-care provider” as the primary reason.12

Inform patients and anxious parents about strategies to manage injection pain and anxiety. For babies, strategies include coddling and distraction (such as bubble blowing); for teenagers, listening to music through headphones may be helpful. Explain that vapocool-ant spray can minimize pain from the needlestick, and acetamino-phen can relieve subsequent soreness at the injection site.

Use combination vaccines to enhance compliance. Combination vaccines have the potential to improve vaccine coverage and timeliness. Giving more vaccines at once means fewer injections and fewer office visits, less patient discomfort and parent anxiety, fewer vaccine doses to store, and fewer opportunities for admin-istration errors.20

Combination vaccines are effective and well-tolerated with no clinically important safety or immunologic differences from separately administered vaccines. Studies in the US and abroad have demonstrated that giving combination vaccines instead of monovalent vaccines improves coverage rates and timeliness of vaccination.21-23 A study of Georgia Medicaid patients, for example, found better on-time vaccination rates for 3 doses of DTaP in chil-dren who received DTaP-HepB-IPV vaccine (66.3% compared with 60.8% for controls) and fewer cumulative days undervacci-nated (29.5 compared with 70.4).21 In a study in Germany, on-time immunization rates rose significantly with successive switches to a higher-valent combination vaccine (DTaP-Hib, DTaP-IPV-Hib, DTaP-IPV-Hib-HepB).23

Make sure parents get immunized. The ACIP recommends a “cocoon” strategy to protect unimmunized or incompletely immu-nized infants by vaccinating parents and other key contacts against pertussis.18 The strategy calls for giving Tdap to all adults who are, or expect to be, in close contact with an infant <12 months of age, including parents, grandparents <65 years of age, child-care providers, and health-care personnel. Adults should receive Tdap at least 2 weeks before coming in contact with the infant; an interval as short as 2 years from the last dose of Td is acceptable.18 A com-prehensive cocooning strategy includes vaccinating key contacts of all ages, including siblings, with age-appropriate vaccines.

Pediatricians can incorporate parental immunization screening into the office routine: Have the receptionist ask about parental Figure. Exemptions from childhood immunization requirements.

Image courtesy of the Institute for Vaccine Safety, www.vaccinesafety.edu. Map current as of April 2009.

48 states allow religious exemptions from state-mandated immunizationrequirements; 20 of them allow broader “personal belief” exemptions

Allow personalbelief exemptions, including religious

Allow religiousexemptions (but notother personalbelief exemptions)

Allow medicalexemptions only

Table 2. rouTine PerTussis/TeTanus/DiPHTHeria immunizaTion sCHeDule2,25,a

2 mo 4 mo 6 mo 15-18 mob 4-6 yr 11-12 yrc 13-18 yr 19-64 yr c,d,e ≥65 yr

DTaP DTaP DTaP DTaP (if fourth dose not given at 12 mo)

DTaP Tdap Tdap catch-up dose

Tdap; substitute 1 dose for Td booster in adults who haven’t received Tdap previously, then boost with Td every 10 yr

Td booster every 10 yr

a Children who have recovered from documented pertussis do not need additional doses of pediatric pertussis vaccine. Tdap vaccine is recommended when the child becomes age eligible. When confirmation of pertussis diagnosis is lacking, vaccination with pediatric pertussis vaccine should be completed.1

b Fourth dose of DTaP can be given as early as 12 months of age if at least 6 months have elapsed since third dose. c Adolescents and adults whose primary vaccination history with tetanus and diphtheria toxoid-containing vaccines is uncertain or incomplete should begin or complete a primary vaccination series; Tdap can replace any 1 of the Td doses in the 3-dose primary series.

d An interval as short as 2 years, or less, from the last Td dose may be used in wound management and high-risk transmission situations such as outbreaks and contact with an infant. All close contacts of infants <12 months of age who haven’t received Tdap should do so. e Pregnant women who received Td vaccine ≥10 years previously should be given Td during the second or third trimester. Women whose latest Td vaccination was <10 years previously should receive Tdap immediately postpartum.

Tdap vaccination status at the newborn and 1-month visits, and have the nurse ask when checking the baby’s height and weight. Incorporate immunization status into paper and electronic check-lists such as the newborn and medical history checklists. Use stickers on the infant’s chart or notations in the electronic medical record to track parents’ immunizations.

Some pediatric practices now immunize adult parents with Tdap vaccine. If you don’t choose to offer this service in your office, you can coordinate immunization with the parent’s primary care physi-cian. Be sure to immunize yourself and your office staff to protect your patients. An approach that considers all age groups—timely and complete immunization of infants and young children and booster immunization of adolescents and adults—is the most effective way to help prevent pertussis and its potentially life-threatening complications.

REFERENCES1. Centers for Disease Control and Prevention (CDC). Pertussis. In: Atkinson W, Wolfe S, Hamborsky J, et al (eds): Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 11th ed.:199-216. Washington, DC: Public Health Foundation, 2009.2. CDC. Recommended immunization schedules for persons aged 0 through 18 years— United States, 2010. MMWR. 2009;58(51&52):Q1-Q4.3. Sanofi Pasteur Inc. Data on file (Pentacel Doses Sold). March 27, 2008. MKT15262.4. Food and Drug Administration. Pentacel clinical safety review. June 13, 2008. http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm125895.pdf. Accessed June 28, 2010.5. Greenberg DP, Doemland M, Bettinger JA, et al. Epidemiology of pertussis and Haemophilus influenzae type b disease in Canada with exclusive use of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b pediatric combination vaccine and adolescent-adult tetanus-diphtheria-acellular pertussis vaccine. Implications for

disease prevention in the United States. Pediatr Infect Dis J. 2009;28(6):521-528. 6. CDC. Estimated vaccination coverage with individual vaccines and selected vaccination series before 24 months of age by state and local area US, National Immunization Survey, Q3/2008-Q2/2009. http://www.cdc.gov/vaccines/stats-surv/nis/data/tables_0809.htm. Accessed July 1, 2010.7. Luman ET, Barker LE, Shaw KM, et al. Timeliness of childhood vaccinations in the United States: days undervaccinated and number of vaccines delayed. JAMA. 2005;293(10):1204-1211.8. Luman ET, Chu SY. When and why children fall behind with vaccinations: missed visits and missed opportunities at milestone ages. Am J Prev Med. 2009;36(2):105-111.9. Guerra FA. Delays in immunization have potentially serious health consequences. Paediatr Drugs. 2007;9(3):143-148.10. Guerra FA, Blatter MM, Greenberg DP, et al, on behalf of the Pentacel Study Group. Safety and immunogenicity of a pentavalent vaccine compared with separate administra-tion of licensed equivalent vaccines in US infants and toddlers and persistence of antibodies before a preschool booster dose: a randomized clinical trial. Pediatrics. 2009;123(1):301-312.11. Omer SB, Salmon DA, Orenstein WA, et al. Vaccine refusal, mandatory immuniza-tion, and the risks of vaccine-preventable diseases. N Engl J Med. 2009;360(19):1981-1988.12. Gust DA, Darling N, Kennedy A, et al. Parents with doubts about vaccines: which vaccines and reasons why. Pediatrics. 2008;122(4):718-725.13. Institute for Vaccine Safety. Vaccine exemptions. http://www.vaccinesafety.edu/ cc-exem.htm. Accessed June 1, 2010. 14. Glanz JM, McClure DL, Magid DI, et al. Parental refusal of pertussis vaccination is associ-ated with an increased risk of pertussis infection in children. Pediatrics. 2009;123(6):1446-1451.15. Feiken DR, Lezotte DC, Hamman RF, et al. Individual community risks of measles and pertussis associated with personal exemptions to immunization. JAMA. 2000;284(24):3145-3150.16. CDC. National, state, and local area vaccination coverage among adolescents aged 13-17 years—United States, 2009. MMWR. 2010;59(32):1018-1023.17. Miller B, Kretsinger K, Ahmed F, et al. Coverage with tetanus toxoid-containing vac-cination (TTCV), including tetanus, diphtheria, acellular pertussis (Tdap) vaccine, among U.S. adults. Presented at: National Immunization Conference, April 21, 2010, Atlanta, Georgia. http://cdc.confex.com/cdc/nic2010/webprogram/Session10726.html. Accessed June 17, 2010.18. CDC. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus tox-oid, reduced diphtheria toxoid and acellular pertussis vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among healthcare personnel. MMWR. 2006;55(RR-17):1-37.19. CDC. Use of standing orders programs to increase adult immunization rates: recommendations of the Advisory Committee on Immunization Practices. MMWR. 2000;49(RR-1):15-26. 20. CDC. Combination vaccines for childhood immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP). MMWR. 1999;48(RR-5):1-15. 21. Happe LE, Lunacsek OE, Kruzikas DT, Marshall GS. Impact of a pentavalent combi-nation vaccine on immunization timeliness in a state Medicaid population. Pediatr Infect Dis J. 2009;28(2):98-101. 22. Marshall GS, Happe LE, Lunacsek OE, et al. Use of combination vaccines is associated with improved coverage rates. Pediatr Infect Dis J. 2007;26(6):496-500.23. Kalies H, Grote V, Verstraeten T, et al. The use of combination vaccines has improved timeliness of vaccination in children. Pediatr Infect Dis J. 2006;25(6):507-512.24. Brown K, Cassiday P, Tondella ML, et al. Pertussis. In: Manual for the Surveillance of Vaccine-Preventable Diseases. 4th ed. 2008. http://www.cdc.gov/vaccines/Pubs/surv-manual/chpt10-pertussis.htm. Accessed August 20, 2010.25. CDC. Recommended adult immunization schedule—United States, 2010. MMWR. 2010;59(1):1-4.

american academy of Pediatrics www.aap.org/immunization

Centers for Disease Control and Prevention www.cdc.gov/vaccines

Children’s Hospital of Philadelphia www.vaccine.chop.edu

every Child by Two www.ecbt.org

immunization action Coalition www.immunize.org

HelPFul resourCes on immunizaTion For PraCTiTioners anD PaTienTs

national association of Pediatric nurse Practitioners www.napnap.org/pertussis.aspxnational Healthy mothers, Healthy Babies Coalition www.hmhb.orgnational network for immunization information www.immunizationinfo.orgParents of Kids with infectious Diseases (PKiDs) www.pkids.orgVoices for Vaccines www.voicesforvaccines.org

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