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Shingles vaccine deemed effective in people with autoimmune disease
The herpes zoster vaccine reduces the risk of shingles in older adults with autoimmune disease, even if they are taking immunosuppressants for their condition, but the protection begins to wane after about 5 years, a recent retrospective study found.
“There has been some concern that patients with autoimmune conditions might have a lower immunogenic response to herpes zoster vaccination, especially when treated with immunosuppressive medications such as glucocorticoids,” wrote Huifeng Yun, PhD, of the University of Alabama at Birmingham, and her colleagues.
The researchers used 2006-2013 Medicare data to calculate the risk of shingles among Medicare recipients who had an autoimmune disease and either did or did not receive the herpes zoster vaccine. All the patients had been enrolled in Medicare for at least 12 continuous months and had a diagnosis of ankylosing spondylitis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis.
The researchers matched 59,627 patients who received the herpes zoster vaccine with 119,254 unvaccinated patients, based on age, sex, race, calendar year, autoimmune disease type, and use of autoimmune drugs (biologics, disease-modifying antirheumatic drugs, and glucocorticoids). During a follow-up of up to 7 years, the researchers additionally accounted for comorbid medical conditions and concurrent medications each year.
The cohort, with an average age of 73.5 years in both groups, included 53.1% of adults with rheumatoid arthritis, 31.6% with psoriasis, 20.9% with inflammatory bowel disease, 4.7% with psoriatic arthritis, and 1.4% with ankylosing spondylitis.
Those who received the vaccine had a rate of 0.75 herpes zoster cases per 100 people during the first year, which rose to 1.25 cases per 100 people per year at the seventh year after vaccination. The rate among unvaccinated individuals stayed steady at approximately 1.3-1.7 cases per 100 people per year throughout the study period. These rates, as expected, were approximately 50% higher than in the general population over age 70 without autoimmune disease.
Compared with unvaccinated individuals, vaccinated individuals had a reduced relative risk for shingles of 0.74-0.77 after adjustment for confounders, but the risk reduction only remained statistically significant for the first 5 years after vaccination.
The waning seen with the vaccine’s effectiveness “raises the possibility that patients might benefit from a booster vaccine at some point after initial vaccination, although no recommendation currently exists that would support such a practice,” the authors wrote.
Dr. Yun has received research funding from Amgen. Other authors disclosed ties to Amgen, AstraZeneca, Bristol-Myers Squibb, Crescendo Bioscience, Janssen, and Pfizer. One author has received research support and consulting fees from Corrona. The study did not note an external source of funding.
The herpes zoster vaccine reduces the risk of shingles in older adults with autoimmune disease, even if they are taking immunosuppressants for their condition, but the protection begins to wane after about 5 years, a recent retrospective study found.
“There has been some concern that patients with autoimmune conditions might have a lower immunogenic response to herpes zoster vaccination, especially when treated with immunosuppressive medications such as glucocorticoids,” wrote Huifeng Yun, PhD, of the University of Alabama at Birmingham, and her colleagues.
The researchers used 2006-2013 Medicare data to calculate the risk of shingles among Medicare recipients who had an autoimmune disease and either did or did not receive the herpes zoster vaccine. All the patients had been enrolled in Medicare for at least 12 continuous months and had a diagnosis of ankylosing spondylitis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis.
The researchers matched 59,627 patients who received the herpes zoster vaccine with 119,254 unvaccinated patients, based on age, sex, race, calendar year, autoimmune disease type, and use of autoimmune drugs (biologics, disease-modifying antirheumatic drugs, and glucocorticoids). During a follow-up of up to 7 years, the researchers additionally accounted for comorbid medical conditions and concurrent medications each year.
The cohort, with an average age of 73.5 years in both groups, included 53.1% of adults with rheumatoid arthritis, 31.6% with psoriasis, 20.9% with inflammatory bowel disease, 4.7% with psoriatic arthritis, and 1.4% with ankylosing spondylitis.
Those who received the vaccine had a rate of 0.75 herpes zoster cases per 100 people during the first year, which rose to 1.25 cases per 100 people per year at the seventh year after vaccination. The rate among unvaccinated individuals stayed steady at approximately 1.3-1.7 cases per 100 people per year throughout the study period. These rates, as expected, were approximately 50% higher than in the general population over age 70 without autoimmune disease.
Compared with unvaccinated individuals, vaccinated individuals had a reduced relative risk for shingles of 0.74-0.77 after adjustment for confounders, but the risk reduction only remained statistically significant for the first 5 years after vaccination.
The waning seen with the vaccine’s effectiveness “raises the possibility that patients might benefit from a booster vaccine at some point after initial vaccination, although no recommendation currently exists that would support such a practice,” the authors wrote.
Dr. Yun has received research funding from Amgen. Other authors disclosed ties to Amgen, AstraZeneca, Bristol-Myers Squibb, Crescendo Bioscience, Janssen, and Pfizer. One author has received research support and consulting fees from Corrona. The study did not note an external source of funding.
The herpes zoster vaccine reduces the risk of shingles in older adults with autoimmune disease, even if they are taking immunosuppressants for their condition, but the protection begins to wane after about 5 years, a recent retrospective study found.
“There has been some concern that patients with autoimmune conditions might have a lower immunogenic response to herpes zoster vaccination, especially when treated with immunosuppressive medications such as glucocorticoids,” wrote Huifeng Yun, PhD, of the University of Alabama at Birmingham, and her colleagues.
The researchers used 2006-2013 Medicare data to calculate the risk of shingles among Medicare recipients who had an autoimmune disease and either did or did not receive the herpes zoster vaccine. All the patients had been enrolled in Medicare for at least 12 continuous months and had a diagnosis of ankylosing spondylitis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis.
The researchers matched 59,627 patients who received the herpes zoster vaccine with 119,254 unvaccinated patients, based on age, sex, race, calendar year, autoimmune disease type, and use of autoimmune drugs (biologics, disease-modifying antirheumatic drugs, and glucocorticoids). During a follow-up of up to 7 years, the researchers additionally accounted for comorbid medical conditions and concurrent medications each year.
The cohort, with an average age of 73.5 years in both groups, included 53.1% of adults with rheumatoid arthritis, 31.6% with psoriasis, 20.9% with inflammatory bowel disease, 4.7% with psoriatic arthritis, and 1.4% with ankylosing spondylitis.
Those who received the vaccine had a rate of 0.75 herpes zoster cases per 100 people during the first year, which rose to 1.25 cases per 100 people per year at the seventh year after vaccination. The rate among unvaccinated individuals stayed steady at approximately 1.3-1.7 cases per 100 people per year throughout the study period. These rates, as expected, were approximately 50% higher than in the general population over age 70 without autoimmune disease.
Compared with unvaccinated individuals, vaccinated individuals had a reduced relative risk for shingles of 0.74-0.77 after adjustment for confounders, but the risk reduction only remained statistically significant for the first 5 years after vaccination.
The waning seen with the vaccine’s effectiveness “raises the possibility that patients might benefit from a booster vaccine at some point after initial vaccination, although no recommendation currently exists that would support such a practice,” the authors wrote.
Dr. Yun has received research funding from Amgen. Other authors disclosed ties to Amgen, AstraZeneca, Bristol-Myers Squibb, Crescendo Bioscience, Janssen, and Pfizer. One author has received research support and consulting fees from Corrona. The study did not note an external source of funding.
Key clinical point:
Major finding: Medicare patients with autoimmune disease had a 23%-26% reduced risk of shingles for 5 years after receiving the herpes zoster vaccine.
Data source: The findings are based on analysis of 2006-2013 Medicare data on 59,627 patients who received the herpes zoster vaccine and 119,254 patients who didn’t.
Disclosures: Dr. Yun has received research funding from Amgen. Other authors disclosed ties to Amgen, AstraZeneca, Bristol-Myers Squibb, Crescendo Bioscience, Janssen, and Pfizer. One author has received research support and consulting fees from Corrona. The study did not note an external source of funding.
HIV vaccine could prevent 30 million cases by 2035
Global cases of HIV from 2015 to 2035 would be reduced by over 50% if the Joint United Nations Program on HIV/AIDS 95/95/95 target is met and a moderately effective HIV vaccine is introduced by 2020, according to new research published in Proceedings of the National Academy of Sciences.
A custom model based on current rates of diagnosis and treatment in 127 countries predicts that a total of 49 million new cases of HIV would occur globally from 2015 to 2035, investigators said. Achieving the UNAIDS goal of 95% disease diagnosis, 95% antiretroviral coverage, and 95% viral suppression by 2030 would avert 25 million cases by 2035. Achieving the more modest 90/90/90 target would avert 22 million cases within the same time period.
“Recent results from the HVTN 100 vaccine trial have bolstered optimism for the development and deployment of an HIV vaccine in the near term,” the investigators said. “HIV vaccination would enable a strategic shift from reactive to proactive control, as suggested by our finding that an HIV vaccine with even moderate efficacy rolled out in 2020 could avert 17 million new infections by 2035 relative to expectations under status quo interventions.”
Find the full study in PNAS (doi: 10.1073/pnas.1620788114)
lfranki@frontlinemedcom.com
On Twitter @IDPractitioner
Global cases of HIV from 2015 to 2035 would be reduced by over 50% if the Joint United Nations Program on HIV/AIDS 95/95/95 target is met and a moderately effective HIV vaccine is introduced by 2020, according to new research published in Proceedings of the National Academy of Sciences.
A custom model based on current rates of diagnosis and treatment in 127 countries predicts that a total of 49 million new cases of HIV would occur globally from 2015 to 2035, investigators said. Achieving the UNAIDS goal of 95% disease diagnosis, 95% antiretroviral coverage, and 95% viral suppression by 2030 would avert 25 million cases by 2035. Achieving the more modest 90/90/90 target would avert 22 million cases within the same time period.
“Recent results from the HVTN 100 vaccine trial have bolstered optimism for the development and deployment of an HIV vaccine in the near term,” the investigators said. “HIV vaccination would enable a strategic shift from reactive to proactive control, as suggested by our finding that an HIV vaccine with even moderate efficacy rolled out in 2020 could avert 17 million new infections by 2035 relative to expectations under status quo interventions.”
Find the full study in PNAS (doi: 10.1073/pnas.1620788114)
lfranki@frontlinemedcom.com
On Twitter @IDPractitioner
Global cases of HIV from 2015 to 2035 would be reduced by over 50% if the Joint United Nations Program on HIV/AIDS 95/95/95 target is met and a moderately effective HIV vaccine is introduced by 2020, according to new research published in Proceedings of the National Academy of Sciences.
A custom model based on current rates of diagnosis and treatment in 127 countries predicts that a total of 49 million new cases of HIV would occur globally from 2015 to 2035, investigators said. Achieving the UNAIDS goal of 95% disease diagnosis, 95% antiretroviral coverage, and 95% viral suppression by 2030 would avert 25 million cases by 2035. Achieving the more modest 90/90/90 target would avert 22 million cases within the same time period.
“Recent results from the HVTN 100 vaccine trial have bolstered optimism for the development and deployment of an HIV vaccine in the near term,” the investigators said. “HIV vaccination would enable a strategic shift from reactive to proactive control, as suggested by our finding that an HIV vaccine with even moderate efficacy rolled out in 2020 could avert 17 million new infections by 2035 relative to expectations under status quo interventions.”
Find the full study in PNAS (doi: 10.1073/pnas.1620788114)
lfranki@frontlinemedcom.com
On Twitter @IDPractitioner
Influenza vaccine is underused in children with heart disease
The influenza vaccine is underused in children with heart disease; approximately one-third were vaccinated in a prospective study of 186 children in September and October 2012.
“Annual influenza vaccination is the most effective and safe means of preventing the disease,” and children with chronic diseases including heart conditions are at increased risk for complications that would require hospitalization, wrote Gilat Livni, MD, of Tel Aviv University and colleagues.
Overall, 59% of parents reported that their primary pediatrician recommended flu vaccination, and 53% of these parents complied. By contrast, only 13% of children whose pediatricians had not recommended vaccination received it.
“The failure of parents to receive information or advice from a physician regarding vaccination was strongly inversely related to vaccination of the child,” the researchers wrote. Parents’ misconceptions included the belief that the vaccine would cause flu (66%, of whom 30% had their child vaccinated); the belief that the vaccine would cause severe side effects (55%, of whom 26% had their child vaccinated), and the belief that the vaccine was unsafe (47%, 21% of whom had their child vaccinated).
“Our results emphasize the need to raise awareness among physicians and other medical health care personnel dealing with children with heart disease of the importance of properly counseling parents regarding influenza vaccination,” the researchers said. “Recommending the vaccine should be made part of routine patient visits in fall and winter.”
The researchers had no financial conflicts to disclose. The findings were published online ahead of print in the Pediatric Infectious Disease Journal (Ped Infect Dis J. 2017. doi: 10.1097/INF.0000000000001579).
The influenza vaccine is underused in children with heart disease; approximately one-third were vaccinated in a prospective study of 186 children in September and October 2012.
“Annual influenza vaccination is the most effective and safe means of preventing the disease,” and children with chronic diseases including heart conditions are at increased risk for complications that would require hospitalization, wrote Gilat Livni, MD, of Tel Aviv University and colleagues.
Overall, 59% of parents reported that their primary pediatrician recommended flu vaccination, and 53% of these parents complied. By contrast, only 13% of children whose pediatricians had not recommended vaccination received it.
“The failure of parents to receive information or advice from a physician regarding vaccination was strongly inversely related to vaccination of the child,” the researchers wrote. Parents’ misconceptions included the belief that the vaccine would cause flu (66%, of whom 30% had their child vaccinated); the belief that the vaccine would cause severe side effects (55%, of whom 26% had their child vaccinated), and the belief that the vaccine was unsafe (47%, 21% of whom had their child vaccinated).
“Our results emphasize the need to raise awareness among physicians and other medical health care personnel dealing with children with heart disease of the importance of properly counseling parents regarding influenza vaccination,” the researchers said. “Recommending the vaccine should be made part of routine patient visits in fall and winter.”
The researchers had no financial conflicts to disclose. The findings were published online ahead of print in the Pediatric Infectious Disease Journal (Ped Infect Dis J. 2017. doi: 10.1097/INF.0000000000001579).
The influenza vaccine is underused in children with heart disease; approximately one-third were vaccinated in a prospective study of 186 children in September and October 2012.
“Annual influenza vaccination is the most effective and safe means of preventing the disease,” and children with chronic diseases including heart conditions are at increased risk for complications that would require hospitalization, wrote Gilat Livni, MD, of Tel Aviv University and colleagues.
Overall, 59% of parents reported that their primary pediatrician recommended flu vaccination, and 53% of these parents complied. By contrast, only 13% of children whose pediatricians had not recommended vaccination received it.
“The failure of parents to receive information or advice from a physician regarding vaccination was strongly inversely related to vaccination of the child,” the researchers wrote. Parents’ misconceptions included the belief that the vaccine would cause flu (66%, of whom 30% had their child vaccinated); the belief that the vaccine would cause severe side effects (55%, of whom 26% had their child vaccinated), and the belief that the vaccine was unsafe (47%, 21% of whom had their child vaccinated).
“Our results emphasize the need to raise awareness among physicians and other medical health care personnel dealing with children with heart disease of the importance of properly counseling parents regarding influenza vaccination,” the researchers said. “Recommending the vaccine should be made part of routine patient visits in fall and winter.”
The researchers had no financial conflicts to disclose. The findings were published online ahead of print in the Pediatric Infectious Disease Journal (Ped Infect Dis J. 2017. doi: 10.1097/INF.0000000000001579).
FROM THE JOURNAL OF PEDIATRICS
Generalized Vaccinia After Smallpox Vaccination With Concomitant Primary Epstein Barr Virus Infection
Generalized vaccinia (GV) is a rare, self-limiting complication of the smallpox vaccination that is caused by the systemic spread of the virus from the inoculation site. The incidence of GV became rare after routine vaccination was discontinued in the U.S. in 1971 and globally in the 1980s after the disease was eradicated.1,2 However in 2002, heightened concerns for the deliberate release of the smallpox virus as a bioweapon led the U.S. military to restart its smallpox vaccination program for soldiers and public health workers.3,4 Here, the authors describe a patient with concomitant GV and mononucleosis.
Case Report
A 19-year-old active-duty marine presented to his battalion aid station with concern for a spreading vesicular rash 9 days after a primary inoculation with the smallpox vaccine. The rash was limited to the inoculation site on his left shoulder (Figure 1). He had no medical history of eczema, atopic dermatitis, or other rashes and reported no systemic symptoms. His vitals also were within normal limits. A clinical diagnosis of inadvertent inoculation (also termed accidental infection) with satellite lesions was made, and he was discharged with counseling on wound care and close follow-up. Two days later, on postvaccination day 11, he presented with new symptoms of a headache, fever, chills, diffuse myalgia, sore throat, and spreading erythematous macules, papules, and vesicles on his arms, chest, abdomen, back, legs, and face (Figures 2A-2D). His vital signs were remarkable for tachycardia with heart rate of 100 bpm and a fever of 103º F (39.4º C). He was sent to the emergency department with a presumed GV diagnosis.
A complete blood count, liver function tests, and basic metabolic panel were unremarkable. Given his symptom of pharyngitis, a rapid strep test was performed. The test was negative, and a throat culture showed no growth. A mononucleosis screen also was performed and was positive. The patient was diagnosed with mononucleosis and GV. His condition improved, and his vital signs stabilized with conservative treatment without the need for vaccine immune globulin (VIG). He convalesced for 72 hours and was referred to dermatology on the following day. Quarantining him in a single occupancy barracks room until all lesions crusted over addressed the concern for spread of the virus to nonimmunized marines or family members. 
On postvaccination day 12, the patient continued to be clinically well, and he remained afebrile. The dermatologist obtained a skin biopsy from a lesion on the patient’s right shin. The biopsy demonstrated marked epidermal necrosis with peripheral keratinocytes showing ballooning degeneration and viral cytopathic changes consistent with GV. Antibody titers showing high levels of Epstein-Barr virus (EBV) capsid IgM and IgG present confirmed mononucleosis infection within the past 6 months. The patient remained clinically well and was released from quarantine on postvaccination day 22 when all lesions crusted over (Figures 3A-3D).
Discussion
The CDC current definition for GV is “the spread of lesions to other parts of the body that are benign in appearance and occur as a result of viremia.”5 Although the exact mechanisms of viral spread are unknown, it may be due to a subtle immunologic defect, specifically in the B-cell line.6,7 Epstein-Barr virus affects the B-cell line, and concurrent infection may depress humoral immunity and allow for systemic spread of the virus.8,9
This case illustrates the potential for a severe reaction after smallpox vaccination in a patient with a concomitant EBV infection. Service members primarily receive the smallpox vaccination early in their career when the risk of mononucleosis is at its highest incidence among young adults, 11 to 48 per 1,000.10-13 Although the potential for disseminated vaccinia following vaccination is rare, clinicians need to remain cognizant of the risk, which may be enhanced by recent or subsequent infection with EBV. However, regular screening for EBV would be of questionable value given the large number of tests needed to prevent a single case of GV.
Generalized vaccinia is a rare complication after smallpox vaccination. Despite its dire appearance, GV typically resolves spontaneously with limited adverse effects (AEs).14 The pre-eradication reported incidence was 17.7 per 1,000,000 recipients in a national survey.15 Posteradication the incidence of GV was 3 times as high with 2 reported cases in 2003 after administration of 38,440 vaccinations.16 Inflammatory reactions can be common; however, these reactions are not due to systemic viral spread.5 When dealing with a vaccinia-specific AE, it is important to distinguish the benign inadvertent inoculations and GV from the more serious reactions of eczema vaccinatum (EV) or progressive vaccinia (PV). 5
Inadvertent inoculations and GV are usually benign and self-limited—requiring only prevention of secondary transmission and nosocomial infection. Eczema vaccinatum occurs among persons with atopic dermatitis or eczema.5 The
Conclusion
The smallpox vaccination is unique among vaccinations. It is the only vaccine that is administered via inoculation with a bifurcated needle, requires regular follow-up care, and can be spread to casual contacts.5
It is important for any practitioner administering the smallpox vaccine to be aware of associated AEs. A greater knowledge of the unique challenges with the smallpox vaccine allows for better patient selection that eliminates those with conditions that impair their immune system and improves patient education.
1. Centers for Disease Control and prevention. Public Health Service recommendation on smallpox vaccination. MMWR Recomm Rep. 1971;20:339
2. The global eradication of smallpox. World Health Organization Web site. http://apps.who.int/iris/bitstream/10665/39253/1/a41438.pdf. Accessed February 8, 2017.
3. Belongia EA, Naleway A. Smallpox vaccine: the good, the bad and the ugly. Clin Med Res. 2003;1(2):87-92.
4. Wharton M, Strikas RA, Harpaz R, et al. Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 2003;52(RR-7):1-16.
5. Cono J, Casey CG, Bell DM. Smallpox vaccination and adverse reactions. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5204a1.htm. Updated February 10, 2003. Accessed February 2, 2017.
6. Chahroudi A, Chavan R, Kozyr N, Waller EK, Silvestri G, Feinberg MB. Vaccinia virus tropism for primary hematolymphoid cells is determined by restricted expression of a unique virus receptor. J Virol. 2005;79(16):10397-10407.
7. , , Blasco R. of different leukocyte cell types to Vaccinia virus infection. Virol J. 2004;1(1):10.
8. Küppers R. B cells under influence: transformation of B cells by Epstein-Barr virus. Nat Rev Immunol. 2003;3(10):801-812.
9. Nemerow G, Cooper N. Infection of B lymphocytes by a human herpesvirus, Epstein-Barr virus, is blocked by calmodulin antagonists. Proc Natl Acad Sci U S A. 1984;81(15):4955-4959.
10. Hallee TJ, Evans AS, Niederman JC, Brooks CM, Voegtly JH. Infectious Mononucleosis at the United States Military Academy. A prospective study of a single class over four years. Yale J Biol Med. 1974;47(3):182-195.
11. Evans AS, Robinton ED. An epidemiological study of infectious mononucleosis. N Engl J Med. 1950;242:492-496.
12. Niederman JC, Evans AS, Subrahmanyan L, McCollum RW. Prevalence, incidence and persistence of EB virus antibody in young adults. N Engl J Med. 1970;282(7):361-365.
13. Sawyer RN, Evans AS, Niederman JC, McCollum RW. Prospective studies of a group of Yale University freshmen. I. Occurrence of infectious mononucleosis. J Infect Dis. 1971;123(3):263-270.
14. Henderson DA, Borio LL, Lane MJ. Smallpox and vaccinia. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 4th ed. Philadelphia, PA: Elsevier; 2004:123-153.
15. Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968—national surveillance in the United States. N Engl J Med. 1969;281(22):1201-1208.
16. Vellozzi C, Lane JM, Averhoff F, et al. Generalized vaccinia, progressive vaccinia and eczema vaccinatum are rare following smallpox (vaccinia) vaccination: United States surveillance, 2003. Clin Infect Dis. 2005;41(5):689-697.
17. Reed J, Scott D. Bray M. Eczema Vaccinatum. Clin Infect Dis. 2012;54(6):832-840.
18. Bray M, Wright ME. Progressive vaccinia. Clin Infect Dis. 2003;36(6):766-774.
19. Fulginiti V, Kempe C, Hathaway W, et al. Progressive vaccinia in immunologically deficient individuals. Birth Defects Orig Artic Ser. 1968;4:129-145.
Generalized vaccinia (GV) is a rare, self-limiting complication of the smallpox vaccination that is caused by the systemic spread of the virus from the inoculation site. The incidence of GV became rare after routine vaccination was discontinued in the U.S. in 1971 and globally in the 1980s after the disease was eradicated.1,2 However in 2002, heightened concerns for the deliberate release of the smallpox virus as a bioweapon led the U.S. military to restart its smallpox vaccination program for soldiers and public health workers.3,4 Here, the authors describe a patient with concomitant GV and mononucleosis.
Case Report
A 19-year-old active-duty marine presented to his battalion aid station with concern for a spreading vesicular rash 9 days after a primary inoculation with the smallpox vaccine. The rash was limited to the inoculation site on his left shoulder (Figure 1). He had no medical history of eczema, atopic dermatitis, or other rashes and reported no systemic symptoms. His vitals also were within normal limits. A clinical diagnosis of inadvertent inoculation (also termed accidental infection) with satellite lesions was made, and he was discharged with counseling on wound care and close follow-up. Two days later, on postvaccination day 11, he presented with new symptoms of a headache, fever, chills, diffuse myalgia, sore throat, and spreading erythematous macules, papules, and vesicles on his arms, chest, abdomen, back, legs, and face (Figures 2A-2D). His vital signs were remarkable for tachycardia with heart rate of 100 bpm and a fever of 103º F (39.4º C). He was sent to the emergency department with a presumed GV diagnosis.
A complete blood count, liver function tests, and basic metabolic panel were unremarkable. Given his symptom of pharyngitis, a rapid strep test was performed. The test was negative, and a throat culture showed no growth. A mononucleosis screen also was performed and was positive. The patient was diagnosed with mononucleosis and GV. His condition improved, and his vital signs stabilized with conservative treatment without the need for vaccine immune globulin (VIG). He convalesced for 72 hours and was referred to dermatology on the following day. Quarantining him in a single occupancy barracks room until all lesions crusted over addressed the concern for spread of the virus to nonimmunized marines or family members.
On postvaccination day 12, the patient continued to be clinically well, and he remained afebrile. The dermatologist obtained a skin biopsy from a lesion on the patient’s right shin. The biopsy demonstrated marked epidermal necrosis with peripheral keratinocytes showing ballooning degeneration and viral cytopathic changes consistent with GV. Antibody titers showing high levels of Epstein-Barr virus (EBV) capsid IgM and IgG present confirmed mononucleosis infection within the past 6 months. The patient remained clinically well and was released from quarantine on postvaccination day 22 when all lesions crusted over (Figures 3A-3D).
Discussion
The CDC current definition for GV is “the spread of lesions to other parts of the body that are benign in appearance and occur as a result of viremia.”5 Although the exact mechanisms of viral spread are unknown, it may be due to a subtle immunologic defect, specifically in the B-cell line.6,7 Epstein-Barr virus affects the B-cell line, and concurrent infection may depress humoral immunity and allow for systemic spread of the virus.8,9
This case illustrates the potential for a severe reaction after smallpox vaccination in a patient with a concomitant EBV infection. Service members primarily receive the smallpox vaccination early in their career when the risk of mononucleosis is at its highest incidence among young adults, 11 to 48 per 1,000.10-13 Although the potential for disseminated vaccinia following vaccination is rare, clinicians need to remain cognizant of the risk, which may be enhanced by recent or subsequent infection with EBV. However, regular screening for EBV would be of questionable value given the large number of tests needed to prevent a single case of GV.
Generalized vaccinia is a rare complication after smallpox vaccination. Despite its dire appearance, GV typically resolves spontaneously with limited adverse effects (AEs).14 The pre-eradication reported incidence was 17.7 per 1,000,000 recipients in a national survey.15 Posteradication the incidence of GV was 3 times as high with 2 reported cases in 2003 after administration of 38,440 vaccinations.16 Inflammatory reactions can be common; however, these reactions are not due to systemic viral spread.5 When dealing with a vaccinia-specific AE, it is important to distinguish the benign inadvertent inoculations and GV from the more serious reactions of eczema vaccinatum (EV) or progressive vaccinia (PV). 5
Inadvertent inoculations and GV are usually benign and self-limited—requiring only prevention of secondary transmission and nosocomial infection. Eczema vaccinatum occurs among persons with atopic dermatitis or eczema.5 The
Conclusion
The smallpox vaccination is unique among vaccinations. It is the only vaccine that is administered via inoculation with a bifurcated needle, requires regular follow-up care, and can be spread to casual contacts.5
It is important for any practitioner administering the smallpox vaccine to be aware of associated AEs. A greater knowledge of the unique challenges with the smallpox vaccine allows for better patient selection that eliminates those with conditions that impair their immune system and improves patient education.
Generalized vaccinia (GV) is a rare, self-limiting complication of the smallpox vaccination that is caused by the systemic spread of the virus from the inoculation site. The incidence of GV became rare after routine vaccination was discontinued in the U.S. in 1971 and globally in the 1980s after the disease was eradicated.1,2 However in 2002, heightened concerns for the deliberate release of the smallpox virus as a bioweapon led the U.S. military to restart its smallpox vaccination program for soldiers and public health workers.3,4 Here, the authors describe a patient with concomitant GV and mononucleosis.
Case Report
A 19-year-old active-duty marine presented to his battalion aid station with concern for a spreading vesicular rash 9 days after a primary inoculation with the smallpox vaccine. The rash was limited to the inoculation site on his left shoulder (Figure 1). He had no medical history of eczema, atopic dermatitis, or other rashes and reported no systemic symptoms. His vitals also were within normal limits. A clinical diagnosis of inadvertent inoculation (also termed accidental infection) with satellite lesions was made, and he was discharged with counseling on wound care and close follow-up. Two days later, on postvaccination day 11, he presented with new symptoms of a headache, fever, chills, diffuse myalgia, sore throat, and spreading erythematous macules, papules, and vesicles on his arms, chest, abdomen, back, legs, and face (Figures 2A-2D). His vital signs were remarkable for tachycardia with heart rate of 100 bpm and a fever of 103º F (39.4º C). He was sent to the emergency department with a presumed GV diagnosis.
A complete blood count, liver function tests, and basic metabolic panel were unremarkable. Given his symptom of pharyngitis, a rapid strep test was performed. The test was negative, and a throat culture showed no growth. A mononucleosis screen also was performed and was positive. The patient was diagnosed with mononucleosis and GV. His condition improved, and his vital signs stabilized with conservative treatment without the need for vaccine immune globulin (VIG). He convalesced for 72 hours and was referred to dermatology on the following day. Quarantining him in a single occupancy barracks room until all lesions crusted over addressed the concern for spread of the virus to nonimmunized marines or family members.
On postvaccination day 12, the patient continued to be clinically well, and he remained afebrile. The dermatologist obtained a skin biopsy from a lesion on the patient’s right shin. The biopsy demonstrated marked epidermal necrosis with peripheral keratinocytes showing ballooning degeneration and viral cytopathic changes consistent with GV. Antibody titers showing high levels of Epstein-Barr virus (EBV) capsid IgM and IgG present confirmed mononucleosis infection within the past 6 months. The patient remained clinically well and was released from quarantine on postvaccination day 22 when all lesions crusted over (Figures 3A-3D).
Discussion
The CDC current definition for GV is “the spread of lesions to other parts of the body that are benign in appearance and occur as a result of viremia.”5 Although the exact mechanisms of viral spread are unknown, it may be due to a subtle immunologic defect, specifically in the B-cell line.6,7 Epstein-Barr virus affects the B-cell line, and concurrent infection may depress humoral immunity and allow for systemic spread of the virus.8,9
This case illustrates the potential for a severe reaction after smallpox vaccination in a patient with a concomitant EBV infection. Service members primarily receive the smallpox vaccination early in their career when the risk of mononucleosis is at its highest incidence among young adults, 11 to 48 per 1,000.10-13 Although the potential for disseminated vaccinia following vaccination is rare, clinicians need to remain cognizant of the risk, which may be enhanced by recent or subsequent infection with EBV. However, regular screening for EBV would be of questionable value given the large number of tests needed to prevent a single case of GV.
Generalized vaccinia is a rare complication after smallpox vaccination. Despite its dire appearance, GV typically resolves spontaneously with limited adverse effects (AEs).14 The pre-eradication reported incidence was 17.7 per 1,000,000 recipients in a national survey.15 Posteradication the incidence of GV was 3 times as high with 2 reported cases in 2003 after administration of 38,440 vaccinations.16 Inflammatory reactions can be common; however, these reactions are not due to systemic viral spread.5 When dealing with a vaccinia-specific AE, it is important to distinguish the benign inadvertent inoculations and GV from the more serious reactions of eczema vaccinatum (EV) or progressive vaccinia (PV). 5
Inadvertent inoculations and GV are usually benign and self-limited—requiring only prevention of secondary transmission and nosocomial infection. Eczema vaccinatum occurs among persons with atopic dermatitis or eczema.5 The
Conclusion
The smallpox vaccination is unique among vaccinations. It is the only vaccine that is administered via inoculation with a bifurcated needle, requires regular follow-up care, and can be spread to casual contacts.5
It is important for any practitioner administering the smallpox vaccine to be aware of associated AEs. A greater knowledge of the unique challenges with the smallpox vaccine allows for better patient selection that eliminates those with conditions that impair their immune system and improves patient education.
1. Centers for Disease Control and prevention. Public Health Service recommendation on smallpox vaccination. MMWR Recomm Rep. 1971;20:339
2. The global eradication of smallpox. World Health Organization Web site. http://apps.who.int/iris/bitstream/10665/39253/1/a41438.pdf. Accessed February 8, 2017.
3. Belongia EA, Naleway A. Smallpox vaccine: the good, the bad and the ugly. Clin Med Res. 2003;1(2):87-92.
4. Wharton M, Strikas RA, Harpaz R, et al. Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 2003;52(RR-7):1-16.
5. Cono J, Casey CG, Bell DM. Smallpox vaccination and adverse reactions. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5204a1.htm. Updated February 10, 2003. Accessed February 2, 2017.
6. Chahroudi A, Chavan R, Kozyr N, Waller EK, Silvestri G, Feinberg MB. Vaccinia virus tropism for primary hematolymphoid cells is determined by restricted expression of a unique virus receptor. J Virol. 2005;79(16):10397-10407.
7. , , Blasco R. of different leukocyte cell types to Vaccinia virus infection. Virol J. 2004;1(1):10.
8. Küppers R. B cells under influence: transformation of B cells by Epstein-Barr virus. Nat Rev Immunol. 2003;3(10):801-812.
9. Nemerow G, Cooper N. Infection of B lymphocytes by a human herpesvirus, Epstein-Barr virus, is blocked by calmodulin antagonists. Proc Natl Acad Sci U S A. 1984;81(15):4955-4959.
10. Hallee TJ, Evans AS, Niederman JC, Brooks CM, Voegtly JH. Infectious Mononucleosis at the United States Military Academy. A prospective study of a single class over four years. Yale J Biol Med. 1974;47(3):182-195.
11. Evans AS, Robinton ED. An epidemiological study of infectious mononucleosis. N Engl J Med. 1950;242:492-496.
12. Niederman JC, Evans AS, Subrahmanyan L, McCollum RW. Prevalence, incidence and persistence of EB virus antibody in young adults. N Engl J Med. 1970;282(7):361-365.
13. Sawyer RN, Evans AS, Niederman JC, McCollum RW. Prospective studies of a group of Yale University freshmen. I. Occurrence of infectious mononucleosis. J Infect Dis. 1971;123(3):263-270.
14. Henderson DA, Borio LL, Lane MJ. Smallpox and vaccinia. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 4th ed. Philadelphia, PA: Elsevier; 2004:123-153.
15. Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968—national surveillance in the United States. N Engl J Med. 1969;281(22):1201-1208.
16. Vellozzi C, Lane JM, Averhoff F, et al. Generalized vaccinia, progressive vaccinia and eczema vaccinatum are rare following smallpox (vaccinia) vaccination: United States surveillance, 2003. Clin Infect Dis. 2005;41(5):689-697.
17. Reed J, Scott D. Bray M. Eczema Vaccinatum. Clin Infect Dis. 2012;54(6):832-840.
18. Bray M, Wright ME. Progressive vaccinia. Clin Infect Dis. 2003;36(6):766-774.
19. Fulginiti V, Kempe C, Hathaway W, et al. Progressive vaccinia in immunologically deficient individuals. Birth Defects Orig Artic Ser. 1968;4:129-145.
1. Centers for Disease Control and prevention. Public Health Service recommendation on smallpox vaccination. MMWR Recomm Rep. 1971;20:339
2. The global eradication of smallpox. World Health Organization Web site. http://apps.who.int/iris/bitstream/10665/39253/1/a41438.pdf. Accessed February 8, 2017.
3. Belongia EA, Naleway A. Smallpox vaccine: the good, the bad and the ugly. Clin Med Res. 2003;1(2):87-92.
4. Wharton M, Strikas RA, Harpaz R, et al. Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 2003;52(RR-7):1-16.
5. Cono J, Casey CG, Bell DM. Smallpox vaccination and adverse reactions. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5204a1.htm. Updated February 10, 2003. Accessed February 2, 2017.
6. Chahroudi A, Chavan R, Kozyr N, Waller EK, Silvestri G, Feinberg MB. Vaccinia virus tropism for primary hematolymphoid cells is determined by restricted expression of a unique virus receptor. J Virol. 2005;79(16):10397-10407.
7. , , Blasco R. of different leukocyte cell types to Vaccinia virus infection. Virol J. 2004;1(1):10.
8. Küppers R. B cells under influence: transformation of B cells by Epstein-Barr virus. Nat Rev Immunol. 2003;3(10):801-812.
9. Nemerow G, Cooper N. Infection of B lymphocytes by a human herpesvirus, Epstein-Barr virus, is blocked by calmodulin antagonists. Proc Natl Acad Sci U S A. 1984;81(15):4955-4959.
10. Hallee TJ, Evans AS, Niederman JC, Brooks CM, Voegtly JH. Infectious Mononucleosis at the United States Military Academy. A prospective study of a single class over four years. Yale J Biol Med. 1974;47(3):182-195.
11. Evans AS, Robinton ED. An epidemiological study of infectious mononucleosis. N Engl J Med. 1950;242:492-496.
12. Niederman JC, Evans AS, Subrahmanyan L, McCollum RW. Prevalence, incidence and persistence of EB virus antibody in young adults. N Engl J Med. 1970;282(7):361-365.
13. Sawyer RN, Evans AS, Niederman JC, McCollum RW. Prospective studies of a group of Yale University freshmen. I. Occurrence of infectious mononucleosis. J Infect Dis. 1971;123(3):263-270.
14. Henderson DA, Borio LL, Lane MJ. Smallpox and vaccinia. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 4th ed. Philadelphia, PA: Elsevier; 2004:123-153.
15. Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968—national surveillance in the United States. N Engl J Med. 1969;281(22):1201-1208.
16. Vellozzi C, Lane JM, Averhoff F, et al. Generalized vaccinia, progressive vaccinia and eczema vaccinatum are rare following smallpox (vaccinia) vaccination: United States surveillance, 2003. Clin Infect Dis. 2005;41(5):689-697.
17. Reed J, Scott D. Bray M. Eczema Vaccinatum. Clin Infect Dis. 2012;54(6):832-840.
18. Bray M, Wright ME. Progressive vaccinia. Clin Infect Dis. 2003;36(6):766-774.
19. Fulginiti V, Kempe C, Hathaway W, et al. Progressive vaccinia in immunologically deficient individuals. Birth Defects Orig Artic Ser. 1968;4:129-145.
Parental reasons for HPV nonvaccination are shifting
NATIONAL HARBOR, MD. – Parents are now less concerned about whether their daughters are sexually active when weighing whether to vaccinate against human papillomavirus (HPV), compared with just a few years ago.
This shift in parental attitudes can inform physician guidance and shift the HPV vaccination discussion, Anna Beavis, MD, a clinical fellow in gynecologic oncology at Johns Hopkins Medicine, Baltimore, said at the annual meeting of the Society of Gynecologic Oncology.
About 90% of cervical cancer is preventable with the HPV vaccine, but “U.S. vaccination rates are still suboptimal,” putting the United States far behind many other developed countries, Dr. Beavis said.
It’s been shown that the physician recommendation is one of the strongest predictors of whether an adolescent will be immunized against HPV, yet many providers remain reluctant to raise the issue, she said. Discomfort about discussing adolescent sexuality with the teen and with parents has been cited by physicians as a primary barrier.
To evaluate why parents of adolescent girls would opt out of HPV vaccination and to identify whether the reasons had changed over time, Dr. Beavis and her colleagues formulated a study that compared parent responses to a nationwide survey about HPV vaccination given in 2014 to those in 2010.
The study drew from the National Immunization Survey–Teen, a random digit-dialing survey administered by the Centers for Disease Control and Prevention. Only data pertaining to girls aged 13-17 years was included in the analysis, and for the sake of accuracy, only provider-verified responses were used.
Of the 49,345 responses that could be provider verified during the period from 2010 to 2014, 54% had received at least one HPV vaccination. Of the remaining responses, 55% of the parents said they had no intention of vaccinating their daughters.
During this period, vaccination rates have climbed slowly, from a little less than half in 2010 to about 60% in 2014 (test of trend, P less than .001), according to Dr. Beavis.
However, the reasons parents gave for declining vaccination has shifted over time, she said. The primary reason given in 2010 was concern about safety or side effects, followed by the sense that the vaccine was not necessary. These remained the top two reasons in 2014, though they had swapped places.
In 2010, the third most common reason parents gave for declining the HPV vaccination was that their daughters were not sexually active. By 2014, this reason had slid to the bottom of the top five reasons, and now was given by fewer than 10% of parents (test of trend, P less than .01).
This is important information for physicians, Dr. Beavis said in a video interview. If a physician has been reluctant to start the HPV discussion for fear of stepping into awkward territory with parents of teen girls, they should know that it’s significantly less likely that issues of sexuality will be on the parental radar when talking about HPV vaccination.
Looking deeper into the data, the investigators found that white race, younger patient age, and living above the poverty level were risk factors for nonvaccination. This means, Dr. Beavis said, that physicians should consider “developing a targeted HPV message” for families at higher risk of nonvaccination.
“This vaccine message should focus on cancer prevention, necessity, and the safety of the HPV vaccine,” Dr. Beavis said.
She reported having no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
koakes@frontlinemedcom.com
On Twitter @karioakes
NATIONAL HARBOR, MD. – Parents are now less concerned about whether their daughters are sexually active when weighing whether to vaccinate against human papillomavirus (HPV), compared with just a few years ago.
This shift in parental attitudes can inform physician guidance and shift the HPV vaccination discussion, Anna Beavis, MD, a clinical fellow in gynecologic oncology at Johns Hopkins Medicine, Baltimore, said at the annual meeting of the Society of Gynecologic Oncology.
About 90% of cervical cancer is preventable with the HPV vaccine, but “U.S. vaccination rates are still suboptimal,” putting the United States far behind many other developed countries, Dr. Beavis said.
It’s been shown that the physician recommendation is one of the strongest predictors of whether an adolescent will be immunized against HPV, yet many providers remain reluctant to raise the issue, she said. Discomfort about discussing adolescent sexuality with the teen and with parents has been cited by physicians as a primary barrier.
To evaluate why parents of adolescent girls would opt out of HPV vaccination and to identify whether the reasons had changed over time, Dr. Beavis and her colleagues formulated a study that compared parent responses to a nationwide survey about HPV vaccination given in 2014 to those in 2010.
The study drew from the National Immunization Survey–Teen, a random digit-dialing survey administered by the Centers for Disease Control and Prevention. Only data pertaining to girls aged 13-17 years was included in the analysis, and for the sake of accuracy, only provider-verified responses were used.
Of the 49,345 responses that could be provider verified during the period from 2010 to 2014, 54% had received at least one HPV vaccination. Of the remaining responses, 55% of the parents said they had no intention of vaccinating their daughters.
During this period, vaccination rates have climbed slowly, from a little less than half in 2010 to about 60% in 2014 (test of trend, P less than .001), according to Dr. Beavis.
However, the reasons parents gave for declining vaccination has shifted over time, she said. The primary reason given in 2010 was concern about safety or side effects, followed by the sense that the vaccine was not necessary. These remained the top two reasons in 2014, though they had swapped places.
In 2010, the third most common reason parents gave for declining the HPV vaccination was that their daughters were not sexually active. By 2014, this reason had slid to the bottom of the top five reasons, and now was given by fewer than 10% of parents (test of trend, P less than .01).
This is important information for physicians, Dr. Beavis said in a video interview. If a physician has been reluctant to start the HPV discussion for fear of stepping into awkward territory with parents of teen girls, they should know that it’s significantly less likely that issues of sexuality will be on the parental radar when talking about HPV vaccination.
Looking deeper into the data, the investigators found that white race, younger patient age, and living above the poverty level were risk factors for nonvaccination. This means, Dr. Beavis said, that physicians should consider “developing a targeted HPV message” for families at higher risk of nonvaccination.
“This vaccine message should focus on cancer prevention, necessity, and the safety of the HPV vaccine,” Dr. Beavis said.
She reported having no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
koakes@frontlinemedcom.com
On Twitter @karioakes
NATIONAL HARBOR, MD. – Parents are now less concerned about whether their daughters are sexually active when weighing whether to vaccinate against human papillomavirus (HPV), compared with just a few years ago.
This shift in parental attitudes can inform physician guidance and shift the HPV vaccination discussion, Anna Beavis, MD, a clinical fellow in gynecologic oncology at Johns Hopkins Medicine, Baltimore, said at the annual meeting of the Society of Gynecologic Oncology.
About 90% of cervical cancer is preventable with the HPV vaccine, but “U.S. vaccination rates are still suboptimal,” putting the United States far behind many other developed countries, Dr. Beavis said.
It’s been shown that the physician recommendation is one of the strongest predictors of whether an adolescent will be immunized against HPV, yet many providers remain reluctant to raise the issue, she said. Discomfort about discussing adolescent sexuality with the teen and with parents has been cited by physicians as a primary barrier.
To evaluate why parents of adolescent girls would opt out of HPV vaccination and to identify whether the reasons had changed over time, Dr. Beavis and her colleagues formulated a study that compared parent responses to a nationwide survey about HPV vaccination given in 2014 to those in 2010.
The study drew from the National Immunization Survey–Teen, a random digit-dialing survey administered by the Centers for Disease Control and Prevention. Only data pertaining to girls aged 13-17 years was included in the analysis, and for the sake of accuracy, only provider-verified responses were used.
Of the 49,345 responses that could be provider verified during the period from 2010 to 2014, 54% had received at least one HPV vaccination. Of the remaining responses, 55% of the parents said they had no intention of vaccinating their daughters.
During this period, vaccination rates have climbed slowly, from a little less than half in 2010 to about 60% in 2014 (test of trend, P less than .001), according to Dr. Beavis.
However, the reasons parents gave for declining vaccination has shifted over time, she said. The primary reason given in 2010 was concern about safety or side effects, followed by the sense that the vaccine was not necessary. These remained the top two reasons in 2014, though they had swapped places.
In 2010, the third most common reason parents gave for declining the HPV vaccination was that their daughters were not sexually active. By 2014, this reason had slid to the bottom of the top five reasons, and now was given by fewer than 10% of parents (test of trend, P less than .01).
This is important information for physicians, Dr. Beavis said in a video interview. If a physician has been reluctant to start the HPV discussion for fear of stepping into awkward territory with parents of teen girls, they should know that it’s significantly less likely that issues of sexuality will be on the parental radar when talking about HPV vaccination.
Looking deeper into the data, the investigators found that white race, younger patient age, and living above the poverty level were risk factors for nonvaccination. This means, Dr. Beavis said, that physicians should consider “developing a targeted HPV message” for families at higher risk of nonvaccination.
“This vaccine message should focus on cancer prevention, necessity, and the safety of the HPV vaccine,” Dr. Beavis said.
She reported having no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
koakes@frontlinemedcom.com
On Twitter @karioakes
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Infant hepatitis B vaccine protection lingers into adolescence
Adolescents who received hepatitis B virus (HBV) vaccinations as infants still showed protection despite little evidence of residual antibodies, a study showed.
This finding was based on data from a prospective study of 137 children, aged 10-11 years, and 213 children, aged 15-16 years, with no history of HBV infection who were vaccinated at 2, 4, and 6 months of age. Michelle Pinto, MD, of the Vaccine Evaluation Center in Vancouver and her colleagues measured residual immunity to determine whether HBV boosters might be needed in adolescents vaccinated as infants to prolong immunity and reduce disease transmission in adulthood.
Overall, 97% of the younger age group and 91% of the older age group showed reactions to an HBV vaccine challenge. An additional 3 (2%) younger children and 12 (6%) older children responded to a second vaccine challenge after failing to respond to the first.
Limitations of the study included a “limited ability of the challenge vaccine procedure to accurately identify immune memory and anamnestic responses” and the differences between the findings and those from long-term outcome data in similar studies in other countries, Dr. Pinto and her associates wrote.
However, “the fact that substantial differences exist in measures of residual protection among teenagers after infant or adolescent HBV vaccinations warrants close ongoing scrutiny of whether important differences will emerge in long-term protection, with or without booster vaccination,” they said (Pediatr Infect Dis J. 2017. doi: 10.1097/INF.0000000000001543).
Adolescents who received hepatitis B virus (HBV) vaccinations as infants still showed protection despite little evidence of residual antibodies, a study showed.
This finding was based on data from a prospective study of 137 children, aged 10-11 years, and 213 children, aged 15-16 years, with no history of HBV infection who were vaccinated at 2, 4, and 6 months of age. Michelle Pinto, MD, of the Vaccine Evaluation Center in Vancouver and her colleagues measured residual immunity to determine whether HBV boosters might be needed in adolescents vaccinated as infants to prolong immunity and reduce disease transmission in adulthood.
Overall, 97% of the younger age group and 91% of the older age group showed reactions to an HBV vaccine challenge. An additional 3 (2%) younger children and 12 (6%) older children responded to a second vaccine challenge after failing to respond to the first.
Limitations of the study included a “limited ability of the challenge vaccine procedure to accurately identify immune memory and anamnestic responses” and the differences between the findings and those from long-term outcome data in similar studies in other countries, Dr. Pinto and her associates wrote.
However, “the fact that substantial differences exist in measures of residual protection among teenagers after infant or adolescent HBV vaccinations warrants close ongoing scrutiny of whether important differences will emerge in long-term protection, with or without booster vaccination,” they said (Pediatr Infect Dis J. 2017. doi: 10.1097/INF.0000000000001543).
Adolescents who received hepatitis B virus (HBV) vaccinations as infants still showed protection despite little evidence of residual antibodies, a study showed.
This finding was based on data from a prospective study of 137 children, aged 10-11 years, and 213 children, aged 15-16 years, with no history of HBV infection who were vaccinated at 2, 4, and 6 months of age. Michelle Pinto, MD, of the Vaccine Evaluation Center in Vancouver and her colleagues measured residual immunity to determine whether HBV boosters might be needed in adolescents vaccinated as infants to prolong immunity and reduce disease transmission in adulthood.
Overall, 97% of the younger age group and 91% of the older age group showed reactions to an HBV vaccine challenge. An additional 3 (2%) younger children and 12 (6%) older children responded to a second vaccine challenge after failing to respond to the first.
Limitations of the study included a “limited ability of the challenge vaccine procedure to accurately identify immune memory and anamnestic responses” and the differences between the findings and those from long-term outcome data in similar studies in other countries, Dr. Pinto and her associates wrote.
However, “the fact that substantial differences exist in measures of residual protection among teenagers after infant or adolescent HBV vaccinations warrants close ongoing scrutiny of whether important differences will emerge in long-term protection, with or without booster vaccination,” they said (Pediatr Infect Dis J. 2017. doi: 10.1097/INF.0000000000001543).
FROM THE PEDIATRIC INFECTIOUS DISEASE JOURNAL
Pneumococcal conjugate vaccine beats Streptococcus pneumoniae bacteremia
Routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) reduced the incidence of Streptococcus pneumoniae bacteremia by 95% from a time period before to a time period after the vaccine was implemented, based on a review of more than 57,000 blood cultures from children aged 3-36 months.
Kaiser Permanente implemented universal immunization with PCV13 in June 2010. “Initial trends through 2012 demonstrated continued decline in pneumococcal infections, with the biggest impact in children less than 5 years old,” wrote Tara Greenhow, MD, of Kaiser Permanente Northern California, San Francisco, and her colleagues.
Overall, the incidence of S. pneumoniae bacteremia declined from 74.5 per 100,000 children during the period before PCV7 (1998-1999) to 3.5 per 100,000 children during a period after routine use of PCV13 (2013-2014). The annual number of bacteremia cases from any cause dropped by 78% between these two time periods.
As bacteremia caused by pneumococci decreased, 77% of cases in the post-PCV13 time period were caused by Escherichia coli, Salmonella spp., and Staphylococcus aureus. “A total of 76% of bacteremia occurred with a source, including 34% urinary tract infections, 17% gastroenteritis, 8% pneumonias, 8% osteomyelitis, 6% skin and soft tissue infections, and 3% other,” Dr. Greenhow and her associates reported.
The large population of the Kaiser Permanente system supports the accuracy of the now rare incidence of bacteremia in young children, the researchers noted. However, “because bacteremia in the post-PCV13 era is more likely to occur with a source, a focused examination should be performed and appropriate studies should be obtained at the time of a blood culture collection,” they said.
Routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) reduced the incidence of Streptococcus pneumoniae bacteremia by 95% from a time period before to a time period after the vaccine was implemented, based on a review of more than 57,000 blood cultures from children aged 3-36 months.
Kaiser Permanente implemented universal immunization with PCV13 in June 2010. “Initial trends through 2012 demonstrated continued decline in pneumococcal infections, with the biggest impact in children less than 5 years old,” wrote Tara Greenhow, MD, of Kaiser Permanente Northern California, San Francisco, and her colleagues.
Overall, the incidence of S. pneumoniae bacteremia declined from 74.5 per 100,000 children during the period before PCV7 (1998-1999) to 3.5 per 100,000 children during a period after routine use of PCV13 (2013-2014). The annual number of bacteremia cases from any cause dropped by 78% between these two time periods.
As bacteremia caused by pneumococci decreased, 77% of cases in the post-PCV13 time period were caused by Escherichia coli, Salmonella spp., and Staphylococcus aureus. “A total of 76% of bacteremia occurred with a source, including 34% urinary tract infections, 17% gastroenteritis, 8% pneumonias, 8% osteomyelitis, 6% skin and soft tissue infections, and 3% other,” Dr. Greenhow and her associates reported.
The large population of the Kaiser Permanente system supports the accuracy of the now rare incidence of bacteremia in young children, the researchers noted. However, “because bacteremia in the post-PCV13 era is more likely to occur with a source, a focused examination should be performed and appropriate studies should be obtained at the time of a blood culture collection,” they said.
Routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) reduced the incidence of Streptococcus pneumoniae bacteremia by 95% from a time period before to a time period after the vaccine was implemented, based on a review of more than 57,000 blood cultures from children aged 3-36 months.
Kaiser Permanente implemented universal immunization with PCV13 in June 2010. “Initial trends through 2012 demonstrated continued decline in pneumococcal infections, with the biggest impact in children less than 5 years old,” wrote Tara Greenhow, MD, of Kaiser Permanente Northern California, San Francisco, and her colleagues.
Overall, the incidence of S. pneumoniae bacteremia declined from 74.5 per 100,000 children during the period before PCV7 (1998-1999) to 3.5 per 100,000 children during a period after routine use of PCV13 (2013-2014). The annual number of bacteremia cases from any cause dropped by 78% between these two time periods.
As bacteremia caused by pneumococci decreased, 77% of cases in the post-PCV13 time period were caused by Escherichia coli, Salmonella spp., and Staphylococcus aureus. “A total of 76% of bacteremia occurred with a source, including 34% urinary tract infections, 17% gastroenteritis, 8% pneumonias, 8% osteomyelitis, 6% skin and soft tissue infections, and 3% other,” Dr. Greenhow and her associates reported.
The large population of the Kaiser Permanente system supports the accuracy of the now rare incidence of bacteremia in young children, the researchers noted. However, “because bacteremia in the post-PCV13 era is more likely to occur with a source, a focused examination should be performed and appropriate studies should be obtained at the time of a blood culture collection,” they said.
FROM PEDIATRICS
FDA committee approves strains for 2017-2018 flu shot
ROCKVILLE, MD. – A committee of Food and Drug Administration advisers backed the World Health Organization’s influenza vaccine recommendations for the 2017-2018 season at a meeting March 9.
In a unanimous vote, members of the Vaccines and Related Biological Products Advisory Committee recommended that trivalent vaccines for the 2017-2018 season should contain the following vaccine strains: A/Michigan/45/2015(H1N1)pdm09-like, A/Hong Kong/4801/2014(H3N2)-like, and B/Brisbane/60/2008-like.
These recommendations echo those from the 2016-2017 season, with the exception of a slight update to the H1N1 strain, which had previously been A/California/7/2009(H1N1)pdm09-like virus.
Regarding vaccine efficacy, the cell propagated A/Hong Kong strain was the strongest candidate, covering 93% of A(H3N2) viruses seen in the 2016-2017 season, according to Jacqueline Katz, PhD, director of the WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza at the Centers for Disease Control and Prevention. In comparison, the egg propagated version of the A/Hong Kong virus covered 59%.
For the influenza B virus, the Yamagata lineage and Victoria lineage strain cycled monthly as the predominant strain in the 2016-2017 season, with a split of “around 50/50,” leaning toward Yamagata in North America, Europe, and Oceana, Dr. Katz explained. The Victoria lineage, in some cases, accounted for nearly 75% of B viruses in Africa and South America.
Committee members expressed concern over the difference between strain prevalence in the United States and abroad and considered recommending a strain that did not coincide with the WHO recommendation, something that has not happened in the history of the advisory committee.
“I’m very aware of influenza vaccinations being a global enterprise, and companies manufacture vaccines for use in multiple countries,” said Committee Chair Kathryn Edwards, MD, professor of pediatrics at Vanderbilt University, Nashville, Tenn. “If we to select a B strain that differed from the WHO recommendation, would that adversely impact vaccine production for the U.S. market?”
Despite these questions, the committee continued to back the WHO recommendations.
Historically, the advisory committee has recommended flu vaccine strains earlier in the year, according to Beverly Taylor, PhD, head of influenza scientific affairs and pandemic readiness at Seqirus Vaccines. Dr. Taylor presented the vaccine manufacturers’ perspective. The delay has put added pressure on manufacturers.
“We haven’t seen impacts yet on start of vaccination dates,” said Dr. Taylor. “But the very clear message from manufacturers is if you keep squashing that manufacturing window, then there will reach a point where we are concerned we will see an impact on vaccine supply time.”
None of the committee members presented waivers of conflict of interest. While the FDA is not obligated to follow the recommendations of the advisory committee, it generally does.
ezimmerman@frontlinemedcom.com
On Twitter @EAZTweets
ROCKVILLE, MD. – A committee of Food and Drug Administration advisers backed the World Health Organization’s influenza vaccine recommendations for the 2017-2018 season at a meeting March 9.
In a unanimous vote, members of the Vaccines and Related Biological Products Advisory Committee recommended that trivalent vaccines for the 2017-2018 season should contain the following vaccine strains: A/Michigan/45/2015(H1N1)pdm09-like, A/Hong Kong/4801/2014(H3N2)-like, and B/Brisbane/60/2008-like.
These recommendations echo those from the 2016-2017 season, with the exception of a slight update to the H1N1 strain, which had previously been A/California/7/2009(H1N1)pdm09-like virus.
Regarding vaccine efficacy, the cell propagated A/Hong Kong strain was the strongest candidate, covering 93% of A(H3N2) viruses seen in the 2016-2017 season, according to Jacqueline Katz, PhD, director of the WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza at the Centers for Disease Control and Prevention. In comparison, the egg propagated version of the A/Hong Kong virus covered 59%.
For the influenza B virus, the Yamagata lineage and Victoria lineage strain cycled monthly as the predominant strain in the 2016-2017 season, with a split of “around 50/50,” leaning toward Yamagata in North America, Europe, and Oceana, Dr. Katz explained. The Victoria lineage, in some cases, accounted for nearly 75% of B viruses in Africa and South America.
Committee members expressed concern over the difference between strain prevalence in the United States and abroad and considered recommending a strain that did not coincide with the WHO recommendation, something that has not happened in the history of the advisory committee.
“I’m very aware of influenza vaccinations being a global enterprise, and companies manufacture vaccines for use in multiple countries,” said Committee Chair Kathryn Edwards, MD, professor of pediatrics at Vanderbilt University, Nashville, Tenn. “If we to select a B strain that differed from the WHO recommendation, would that adversely impact vaccine production for the U.S. market?”
Despite these questions, the committee continued to back the WHO recommendations.
Historically, the advisory committee has recommended flu vaccine strains earlier in the year, according to Beverly Taylor, PhD, head of influenza scientific affairs and pandemic readiness at Seqirus Vaccines. Dr. Taylor presented the vaccine manufacturers’ perspective. The delay has put added pressure on manufacturers.
“We haven’t seen impacts yet on start of vaccination dates,” said Dr. Taylor. “But the very clear message from manufacturers is if you keep squashing that manufacturing window, then there will reach a point where we are concerned we will see an impact on vaccine supply time.”
None of the committee members presented waivers of conflict of interest. While the FDA is not obligated to follow the recommendations of the advisory committee, it generally does.
ezimmerman@frontlinemedcom.com
On Twitter @EAZTweets
ROCKVILLE, MD. – A committee of Food and Drug Administration advisers backed the World Health Organization’s influenza vaccine recommendations for the 2017-2018 season at a meeting March 9.
In a unanimous vote, members of the Vaccines and Related Biological Products Advisory Committee recommended that trivalent vaccines for the 2017-2018 season should contain the following vaccine strains: A/Michigan/45/2015(H1N1)pdm09-like, A/Hong Kong/4801/2014(H3N2)-like, and B/Brisbane/60/2008-like.
These recommendations echo those from the 2016-2017 season, with the exception of a slight update to the H1N1 strain, which had previously been A/California/7/2009(H1N1)pdm09-like virus.
Regarding vaccine efficacy, the cell propagated A/Hong Kong strain was the strongest candidate, covering 93% of A(H3N2) viruses seen in the 2016-2017 season, according to Jacqueline Katz, PhD, director of the WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza at the Centers for Disease Control and Prevention. In comparison, the egg propagated version of the A/Hong Kong virus covered 59%.
For the influenza B virus, the Yamagata lineage and Victoria lineage strain cycled monthly as the predominant strain in the 2016-2017 season, with a split of “around 50/50,” leaning toward Yamagata in North America, Europe, and Oceana, Dr. Katz explained. The Victoria lineage, in some cases, accounted for nearly 75% of B viruses in Africa and South America.
Committee members expressed concern over the difference between strain prevalence in the United States and abroad and considered recommending a strain that did not coincide with the WHO recommendation, something that has not happened in the history of the advisory committee.
“I’m very aware of influenza vaccinations being a global enterprise, and companies manufacture vaccines for use in multiple countries,” said Committee Chair Kathryn Edwards, MD, professor of pediatrics at Vanderbilt University, Nashville, Tenn. “If we to select a B strain that differed from the WHO recommendation, would that adversely impact vaccine production for the U.S. market?”
Despite these questions, the committee continued to back the WHO recommendations.
Historically, the advisory committee has recommended flu vaccine strains earlier in the year, according to Beverly Taylor, PhD, head of influenza scientific affairs and pandemic readiness at Seqirus Vaccines. Dr. Taylor presented the vaccine manufacturers’ perspective. The delay has put added pressure on manufacturers.
“We haven’t seen impacts yet on start of vaccination dates,” said Dr. Taylor. “But the very clear message from manufacturers is if you keep squashing that manufacturing window, then there will reach a point where we are concerned we will see an impact on vaccine supply time.”
None of the committee members presented waivers of conflict of interest. While the FDA is not obligated to follow the recommendations of the advisory committee, it generally does.
ezimmerman@frontlinemedcom.com
On Twitter @EAZTweets
AT AN FDA ADVISORY COMMITTEE MEETING
Communicating with Families About HPV Vaccines
From the University of Colorado Denver, Aurora, CO.
Abstract
- Objective: To provide evidence-based guidance on strategies that are likely or unlikely to be successful in navigating HPV vaccine conversations with patients and parents.
- Methods: Nonsystematic review of the literature.
- Results: This review highlights some of the most recent innovations in provider HPV vaccine communication and describes provider communication strategies that have been found to improve adolescent vaccination rates in rigorous scientific studies. Promising strategies for which additional research is needed and strategies that probably do not work are also described.
- Conclusion: By understanding what works, what may work, and what not to do when it comes to communicating with families about HPV vaccines, providers can be better prepared for maximizing the impact they can have on adolescent HPV vaccination rates.
Key words: human papillomavirus; vaccine hesitancy; health communication; parents; immunization.
In the United States, more than 14 million people newly acquire genital human papillomavirus (HPV) annually, and 75 million Americans are infected at any given time [1]. As the most common sexually transmitted disease, more than 80% of sexually active U.S. adults are estimated to be infected with HPV by the age of 50 [1,2]. Although the majority of infections are “silent” and resolve without clinical sequelae, a proportion of infected individuals will go on to develop HPV-related diseases. In women, these include cervical cancer and pre-cancer (ie, abnormal Pap smears); cancers of the vagina, vulva, anus, and oropharynx; and genital warts [3]. Males also bear a high burden of HPV-related disease in the form of penile, anal, and oropharyngeal cancers, as well as genital warts [3]. While once thought of as primarily a “woman’s disease” [4], recent research demonstrates men are also significantly impacted by HPV—particularly in the form of oropharyngeal cancers, which are 2 to 3 times more common in men than in women [5]. In fact, it is estimated by the year 2020 more men will die of HPV-related oropharyngeal cancer than women will die of cervical cancer [6,7]. The combined cost of HPV-associated cancers and other conditions is estimated to be $8 billion per year in the United States [8–11].
HPV Vaccines
Effective HPV vaccines have been available for females aged 9 to 26 years since 2006 (bivalent and quadrivalent vaccines) and for males aged 9 to 26 since 2010 (quadrivalent vaccine only) [12]. These vaccines have been shown in clinical trials to be highly efficacious in preventing HPV infection, cervical pre-cancer, and anal, vaginal, penile, and vulvar cancers caused by the HPV types covered in the vaccine [2]. Although their effectiveness against head and neck cancer has not been studied in clinical trials, most experts believe that these vaccines will also provide protection against at least a proportion of these cancers [13,14]. In 2015 the U.S. Food and Drug Administration approved licensure of a 9-valent HPV vaccine that will soon replace the quadrivalent vaccine in the U.S. market [15]. The 9-valent vaccine is licensed for both males and females aged 9 to 26 and is expected to prevent an even higher proportion of HPV-related cancers than earlier HPV vaccines due to the protection against 5 additional oncogenic HPV types [15].
Despite the potential of HPV vaccines to drastically reduce the incidence of HPV-related cancers and other diseases, these vaccines are not being as widely used in the United States as was hoped. The most recent national data from 2015 demonstrates that only 41.9% of girls and 28.1% of boys have received all 3 doses recommended in the HPV vaccine series [16]. This level of vaccine utilization is significantly lower than the Healthy People 2020 goal of 80% coverage [17], and also significantly lower than that of other developed countries such as Australia and the United Kingdom, which have achieved vaccination levels of ~70% among their target adolescent populations [18,19]. In the future, these low vaccination levels will likely be mitigated somewhat by the recent approval from the FDA and recent recommendation from the Advisory Committee on Immunization Practices (ACIP) for only 2 doses of the 9-valent HPV vaccine (spaced 6 to 12 months apart) for adolescents less than 15 years of age [20,21]. Three doses are still recommended for those aged 15 to 26 years.
Provider Communication About HPV Vaccines
How providers communicate with parents and patients about HPV vaccines is a key influential factor driving current U.S. adolescent HPV vaccination levels [22,23]. Numerous studies demonstrate that a provider’s recommendation generally has the largest impact on whether or not an adolescent receives the vaccine, even above that of parent factors such as attitudes and beliefs about the vaccine and patient characteristics such as age and insurance status [23–31]. Moreover, parents consistently cite their adolescent’s provider as one of the most trusted and impactful resources for obtaining vaccine information [22,32].
Unfortunately, research also shows that providers often fail to adequately recommend the HPV vaccine for their patients, especially for 11 to 12 year olds for whom the vaccine is preferentially recommended [33,34]. For example, in a national study of parents done in 2013, not being recommended by a provider was one of the top 5 reasons parents of males and of females aged 11 to 17 gave for not getting their adolescent vaccinated against HPV [35]. Supporting this also is a 2014 study of 776 pediatricians and family medicine providers nationally, in which Gilkey and colleagues found that more than 1 out of 4 providers did not highly endorse the HPV vaccine for 11 to 12 year olds despite this having been the recommended practice from ACIP for the prior 8 years for girls and 4 years for boys. This is in comparison to the other adolescents vaccines that were reported in the same study as being endorsed highly by these providers > 95% of the time [36].
Recognizing that providers’ HPV vaccine recommendations are often suboptimal, researchers have begun to define what components comprise “high-quality” HPV vaccine recommendations. This has been operationalized by one research group as (1) timeliness—routinely recommending the vaccine starting when the patient is ≤ 12 years; (2) consistency—recommending the vaccine for all eligible adolescents as opposed to an approach based on providers’ perception of their patients’ risk for HPV infection; (3) urgency—recommending that the vaccine be given on the same day the vaccine is being discussed, rather than offering the option of getting it at a future visit; and (4) strength—using language that clearly conveys that the provider believes the vaccine is very important for the adolescent to receive. A national study of primary care providers done in 2014 examined how frequently these quality components were implemented [37]. The results were startling and discouraging. Nearly half of providers (49%) reported they usually recommended that 11 to 12 year olds get the vaccine at a later visit, 41% used a risk-based approach for deciding when to recommend the vaccine, 27% did not tell the parents the vaccine was “very or extremely important,” and a large proportion did not start routinely recommending the vaccine before the age of 13 (39% for male patients and 25% for females) [37].
Much research has now accumulated to explain the underlying reasons why providers may not give consistent and high-quality HPV vaccine recommendations to all eligible adolescents [22]. Issues such as providers’ own knowledge about HPV-related diseases, personal beliefs about the vaccine’s safety and necessity, concern that a discussion about the vaccine will necessitate a discussion about adolescent sexuality with the parent, belief that parents will not want their child vaccinated if asked, perceptions that a provider can adequately select those patients most “in need” of HPV vaccination, and concern that raising the vaccine discussion with vaccine-hesitant parents will result in prolonged discussions have been shown to impact whether and how providers communicate about HPV vaccination during clinical visits [22,36–45]. Now that these barriers have been defined and described, there is a great need to use this knowledge to develop and evaluate interventions that help to mitigate these barriers and improve providers’ vaccine communication abilities. Such interventions are needed not only for HPV, but for all vaccines [46,47].
Possible Strategies for Helping Providers Communicate About HPV Vaccines
Before discussing these interventions, it is worth noting that several of the passive and active strategies have been shown in clinical trials to improve adolescent HPV vaccination rates. Although these are beyond the scope of this article, inclusion of these strategies should certainly be considered by any practice as a mechanism to increase vaccination levels, especially given that the most successful interventions to improve vaccination levels consist of multiple components [48]. Also useful is a recently described “taxonomy of vaccine communication interventions” that provides additional perspective on the scope and complexity of interventions to improve vaccine delivery [49]. There are several well-written review articles that describe interventions that focus on passive and active strategies at the practice or community level [50–52].
Interpersonal Communication Strategies Shown to Increase HPV Vaccination
Presumptive Communication
One of the first studies to examine the specific “way” in which providers communicate about vaccines focused not on HPV but rather on young childhood vaccines. In 2013 Opel and colleagues performed a study in which they taped clinical encounters between a pediatrician and a parent of a child aged 1 to 19 months [53]. Of the 111 encounters recorded, 50% of parents were classified as vaccine hesitant. Parents were aware they were being taped but not aware that the overall purpose of the study was to examine providers’ communication related to vaccination. The researchers found that providers generally used one of 2 communication styles to introduce the vaccine discussion. The first, called the “presumptive” style, assumed that parents would agree to vaccination and presented the vaccines as routine (ie, “We have to do some shots today”). The second style, called “participatory,” was more parent-oriented and used language suggesting shared decision-making (ie, “So what do you want to do about shots today?”). The study showed that the odds of resisting the provider’s vaccine recommendations were significantly higher when providers used a participatory approach than a presumptive one, suggesting that even small changes in language can have a major impact on the likelihood of vaccination. However, given the study design, causality between providers’ recommendation style and parents vaccination decisions could not be delineated.
In 2015 Moss and colleagues performed a study that examined the use of these 2 communication styles with regard to HPV vaccination [54]. This study used data from the 2010 National Immunization Survey–Teen, a national survey on childhood vaccination that includes provider verification of vaccines given [16]. Researchers categorized provider vaccine communication styles into “provider-driven,” which was similar to the presumptive style described Opel, and “patient-driven,” which was similar to Opel’s permissive style. Parents who received a more provider-driven style of HPV vaccine recommendation were far more likely to have allowed their adolescent to be vaccinated than those receiving patient-driven recommendations [54]. Further supporting this communication approach are results from a qualitative study done by Hughes and colleagues in which triads of mothers, adolescents, and providers were interviewed after a preventive care visit to assess the communication that occurred regarding HPV vaccination [39]. Providers’ communication style was categorized into 1 of 3 groups: paternalistic (clinician makes the vaccination decision and communicates this to the family); informed (patient and family gathers information from the clinician and other sources to reach a vaccination decision); and shared (medical and personal information is exchanged between the provider and family and then a decision is reached jointly). Providers who typically adopted the paternalistic approach perceived that they had the highest success in convincing parents to vaccinate—a perception that was confirmed in quantitative assessments of vaccination status among adolescents in the study sample [39]. Our own research demonstrates that learning and implementing a presumptive/paternalistic HPV vaccine recommendation style is easy for primary care providers to do and is perceived as often shortening the time taken during clinical visits to discuss the vaccine [55,56]. Thus, providers should consider opening the HPV vaccine conversation using this approach, and then turning to some of the other communication techniques described below when met with parental resistance or questions.
Motivational Interviewing
A second communication technique that seems effective for promoting HPV vaccination, especially for vaccine hesitant parents, is motivational interviewing. Motivational interviewing describes a communication technique in which the provider leverages a parents’ or patients’ intrinsic motivation to engage in a preferred health behavior [57]. Motivational interviewing was originally developed to combat substance abuse [58,59] but has subsequently been successfully applied to a number of other health issues [60–64]. There is growing interest from public health and medical providers in using this technique for increasing vaccination [39,65–68]. Our research group performed a large, cluster-randomized controlled trial of 16 pediatric and family medicine clinics to examine the impact of a provider communication “toolkit” on adolescent HPV vaccine series initiation and completion [50,69]. The toolkit consisted of motivational interviewing training for providers related to HPV vaccination and training on 3 tangible resources providers could also use with parents—an HPV fact sheet, an HPV vaccine decision aid, and an educational website. Results from the study demonstrated that motivational interviewing was the toolkit component most widely utilized by providers and was also perceived as being the most useful. More importantly, HPV vaccine series initiation levels were significantly higher among adolescents in practices receiving the toolkit than in control practices. There was no impact on HPV vaccine series completion (unpublished results). The usefulness of motivational interviewing for vaccination is further supported by a small study in which community pharmacists receiving motivational interviewing training for adult vaccination reported significantly higher patient readiness to receive vaccines following their interaction with the pharmacist than those who did not receive the training [70]. Finally, Perkins et al performed a cluster randomized controlled trial that evaluated the impact of a provider-focused intervention on adolescent HPV vaccination rates. The intervention included frequent provider support meetings, education on HPV infection and vaccination, feedback on providers’ individual HPV vaccination rates, provider incentives, and “basic motivational interviewing principles with vaccine-hesitant parents.” HPV vaccination series initiation and completion rates were significantly higher in intervention practices than controls, and this effect was sustained for at least 6 months after the active intervention period was over [67]. However, it was unknown how much the motivational interviewing contributed to these results. Based on the above information, and the long history of success of motivational interviewing for improving patient compliance with other recommended health behaviors, this technique appears to have a reasonable evidence base and should be considered for communicating with families that express resistance to HPV vaccination.
Personalized Communication
Parents’ reasons for not having their adolescent vaccinated against HPV are often complex and multifactorial [71,72]. Personalized approaches are needed to account for each parent’s unique informational needs, beliefs, and prior experiences [65]. Unfortunately, given the short amount of time allotted for clinical visits, it is often difficult to provide adequate information to parents during these encounters [73–75]. Indeed, concern about prolonged HPV vaccine discussions has been identified as an important barrier for providers that cause some to forgo recommending the vaccine [36,75].
One potential solution to this issue is to leverage technology in the form of web-based interventions that use software to tailor materials to each individual’s unique informational needs. Feasibility for this idea comes from the knowledge that many parents already use the web to research health issues related to their children [76], and that doctors’ offices are increasingly using patient portals and other web-based resources to help parents prepare for upcoming visits, especially those focused on health maintenance [77,78]. Tailored messaging interventions have been shown across populations and health issues to generally result in superior adherence with health behaviors when compared to untailored controls [79–82]. Several researchers have thus begun exploring whether such a personalized communication strategy may be similarly effective for adolescent HPV vaccination [50,83–85]. As an example, Maertens and colleagues used community-based participatory research techniques to develop a web-based tailored messaging intervention for Latinos regarding HPV vaccination [86]. A subsequent randomized controlled trial of the intervention in over 1200 parents of adolescents and young adults demonstrated that the intervention improved participants’ intentions to vaccinate compared to usual care [87], and among adolescents, higher HPV vaccine series initiation levels (unpublished data). Although additional work is needed to understand the feasibility of implementing such an intervention more broadly, additional support for the usefulness of a tailored messaging approach comes from a study of female university students that demonstrated higher HPV vaccination intentions after exposure to tailored information compared to untailored information. However, the impact on actual HPV vaccine utilization was not measured in the study [84]. Contrasting results were found in a different study of university students where researchers failed to find an impact of message tailoring on HPV vaccination utilization. However, this study was limited by a low response rate (~50%) to the follow up survey where vaccination status was assessed, and also by overall low levels of HPV vaccine initiation among the entire study sample (8%) [85]. Given the low number of studies in this area, and some conflicting data, additional research is needed to better understand the impact of personalized communication on HPV vaccination levels. However, results from these studies suggest that a modest benefit may be achieved with this approach, especially if coupled with other, evidence-based, clinic-level interventions to promote vaccination (eg, vaccine reminders, extended office hours), as is suggested by the Task Force on Community Preventive Services [48].
Focusing Communication on Cancer Prevention
HPV vaccines are unique in that they are only 1 of 2 vaccines for cancer prevention (the other being hepatitis B). Provider and parent surveys suggest that while most providers do mention cancer prevention when discussing HPV vaccines [40,88,89], this may be more commonly done with female patients than males [22]. Focusing on cancer prevention rather than sexual transmissibility is a communication technique suggested by the Centers for Disease Control and Prevention (CDC) as many parents cite this aspect of the vaccine as one of the most compelling reasons for vaccinating [45,90]. CDC’s “You are the Key” program [91] uses cancer prevention as a central theme in their physician and patient communication materials, based on significant prior market research on the acceptability and impact of such messages among parents and providers. In 2016 Malo and colleagues tested the potential impact of brief messages related to HPV vaccination, including cancer prevention messages, among a national sample of 776 medical providers and 1504 parents of adolescents [92]. In addition to their potential to motivate parents to vaccination, associations between parental endorsement of each message and their adolescent’s vaccination status were also examined. The cancer prevention messages were among those most highly endorsed by both parents and providers as being motivating for parents to get their adolescent vaccinated. More importantly, among parents these endorsements were associated with a significantly higher likelihood of the adolescent having been vaccinated against HPV. Interestingly, one of the briefest messages in the study, “I [the physician] strongly believe in the importance of this cancer preventing vaccine for [child’s name],” was perceived as the most persuasive message by parents.
Further support for the positive impact of framing HPV vaccines primarily as cancer prevention comes from another national study of 1495 parents of 11 to 17 year olds that examined 3 measures of quality of their adolescent provider’s HPV vaccine recommendation, and the relationship between recommendation quality and likelihood of adolescent HPV vaccination [40]. The 3 quality indicators assessed included providing information about cancer prevention, encouraging the vaccine “strongly,” and recommending it be given on the same day as it was being discussed. While 49% of parents reported receiving no HPV vaccine recommendation from their adolescents’ provider, of those that did, 86% received a cancer prevention message. Parents who had been given high quality recommendations that included either 2 or 3 of the quality indicator measures had over 9 times the odds of vaccine series initiation and 3 times the odds of vaccine series follow through than those who had not received any recommendation, and also significantly higher odds of vaccination than parents who had received low quality recommendations (ie, included only 1 indicator). Taken together, these results suggest that focusing discussions about HPV vaccines on their ability to prevent cancer is likely to be persuasive for some parents.
Strategies That Are Promising But Not Thoroughly Tested
Helping Parents Create Vaccination Plans
A recent commentary suggested that instead of focusing on changing beliefs or “educating” parents and patients about the need for a given vaccine, perhaps a better way to craft interventions for increasing vaccination is to focus on structuring the environment to make vaccination “easy” [93,94]. Examples of this include strategies such as extended office hours and making the vaccine available in other locations such as schools and pharmacies, both of which have been shown in some populations and settings to improve vaccine utilization [48,95]. One aspect of structuring a vaccine-conducive environment that relates to provider communication is helping parents create “implementation intentions” for future vaccination visits. In its most obvious form, this would mean providers provide office resources that facilitate making an appointment for the next dose in the HPV vaccine series during a clinic visit where the first dose was provided. But such an approach could also potentially extend to parents who are on the fence about the vaccine—to make an appointment before the parent leaves the office with an unvaccinated child to either re-discuss the vaccine in the future or to actually start the vaccine series. Support for such a strategy comes primarily from the social sciences, which suggest that implementation intentions work by increasing attention to specific cues to action, making it more likely that that the cue will be acted upon [96–98]. Creating implementation intentions has been shown to be helpful for improving adherence with a variety of health behaviors [99–105], and there is a growing evidence base related to how implementation intentions may facilitate vaccination specifically. For example Vet and colleagues performed a randomized controlled trial among 616 men who have sex with men with either strong or weak intentions to receive the hepatitis B vaccine [106]. Half of the participants were asked to create an implementation intention plan where they described when, where and how they would obtain the vaccine. Those in the control arm were not given this prompt. Regardless of whether their initial vaccination intention was weak or strong, those who had been asked to create an implementation plan had more than double the likelihood of actually getting the vaccine than participants who did not receive the implementation plan prompt. Similarly, a study of influenza vaccination rates among corporate employees found that those who were asked to write down the day and time they planned to go to employee health to get the free vaccine were somewhat more likely (4% higher) to be vaccinated than those who did not receive this prompt [107]. In addition, a study of elderly individuals found that influenza vaccination rates were significantly higher among those who had received “action instructions” on how, when and where to get the vaccine than those who did not [108]. These studies suggest that helping parents craft a definitive follow-up plan regarding vaccination could have a significant impact on vaccination rates—particularly for vaccines like HPV that require multiple doses.
Treating all Adolescent Vaccines the Same
Prior research has demonstrated that providers often communicate differently about HPV vaccines than other adolescent vaccines such as the tetanus-diphtheria-pertussis (Tdap) and meningococcal (MCV) vaccines [22,36]. Providers often tend to discuss the HPV vaccine last among these 3 vaccines, provide weaker endorsements of the vaccine, and pre-emptively give much more detail about the HPV compared to the other vaccines, even in the absence of a parent’s request for additional information [36,39,41]. The CDC and the American Academy of Pediatrics now suggest putting HPV at the beginning or middle of the list of vaccines recommended to the adolescent (ie, “HPV, Tdap and MCV”), and treating all recommended vaccines equivalently in terms of the level of detail provided to parents in the absence of a parent’s request for more information [109,110]. Through these suggestions have face validity, their specific impact on HPV vaccination rates, and on patient and provider satisfaction with the visit have yet to be evaluated.
Strategies that Probably Don’t Work
Presenting Myths and Facts
Research related to promoting other vaccines provides insight into communication activities that probably would not work well for promoting HPV vaccination. A 2012 study by Nyhan and colleagues examined the impact of 2 different messages related to influenza vaccines on participants’ beliefs about the vaccine’s safety and intentions to get vaccinated [111]. One group received information to correct the commonly held belief that influenza vaccine can cause the flu while the other received information about the risks associated with contracting an influenza infection. While the correction of myths did improve participants’ perceptions of the vaccine’s safety, information about influenza dangers did not. Neither message impacted intentions to vaccinate in the study subjects overall. However, in sub-analyses the correction of myths actually decreased intentions to vaccinate among those with high baseline levels of concern about the vaccine’s side effects—that is, among those most concerned that the flu vaccine can give someone the flu, correcting this myth actually decreased the likelihood that they would receive the vaccine. Similar findings have been reported in other studies related to vaccination [112–114], and suggest that the “threat” generated by providing information opposing a person’s beliefs may actually entrench these beliefs further as part of the threat response—a phenomenon known as attitude polarization [115]. These results also are consistent with the concept of negativity bias, which posits that negative information influences people’s risk perceptions more than positive information, and that the more strongly a risk is attempted to be negated, the lower the effectiveness and perceived trust of the information [116].
Using Fear Appeals
One tactic that has been suggested by some as a way to promote vaccination is to provide graphic depictions of the possible sequelae of vaccine-preventable diseases. The thought behind this idea is that because vaccination is so successful, most parents will have never experienced significant impacts from vaccine preventable diseases that, in the past, had been a major motivator for parents to vaccinate. Thus, in order to counter beliefs about “controversial” issues like vaccination, highly emotionally compelling and engaging information may be especially useful. This is a common tactic used by anti-vaccination groups to spread their own messages [117]. However, several studies suggested that using “fear appeals” (aka scare tactics) such as this to promote vaccination can actually have a negative effect on vaccination intentions. For example, in a 2011 study of a nationally representative sample of parents of children < 18 years, 4 different message formats were tested for their impact on parental intentions to vaccinate a future child with the measles-mumps-rubella vaccine (MMR) [113]. Message formats included correcting the misinformation that MMR causes autism, presenting information on MMR-related disease risk, providing a dramatic narrative about a child endangered by measles, and showing pictures of infants affected by these diseases. Counter to the study’s hypotheses, the dramatic narrative message actually increased parents’ perceptions that MMR vaccines had serious side effects, and the pictures increased parents’ belief that the MMR vaccine could cause autism. These counter-intuitive results are consistent with other studies that have examined the impact of message framing on adults’ vaccination intentions for HPV and influenza [108,118,119]. Taken together, fear appeals seem unlikely to sway many hesitant parents towards HPV vaccination.
Looking Into the Future
Moving forward, additional interventions to improve providers’ ability to communicate with families about HPV vaccination will undoubtedly be developed. A major area of interest in this regard is leveraging the power of technology and the internet, including using social media, mobile technologies, and online interventions to augment the provider/parent interaction that occurs during the clinical visit [50,120]. Web-based approaches have the benefit of generally being low cost and easy to disseminate to large populations. Such interventions have already been developed for a number of other health issues, some of which have proven effective [121,122]. However, use of the internet to promote healthy behaviors in general, and vaccination specifically, is still in its infancy. There is still much to be learned about how to create effective web-based tools, how to engage patients with them, and how to assess their impact on health outcomes [123].
Another interesting area for future research is identifying psychological “levers” to motivate parents’ vaccination intentions [94]. One example is focusing on using parents’ values (ie, protecting my child from harm) as an intervention target rather than beliefs or attitudes. This is because values tend to be inherent and static over time, compared to beliefs and attitudes, which are subject to change depending on the context [124]. Prior research has shown that interventions that leverage values rather than facts can be an effective way to overcome beliefs that are highly emotional or controversial, and that individuals are more likely to trust sources and individuals with shared values than those without [125], suggesting that this may be a useful way to motivate parents toward vaccinating their children. Self-affirmation is another example of a psychological lever that has a significant evidence base from the social science literature as a helpful tool for moving patients towards a desired health behavior [126,127], but it has not been extensively applied to the field of vaccination. Researchers in the field of vaccine delivery are increasingly recognizing the potential value of these unique intervention approaches [101,128–134], and it may be fruitful in the future to more closely examine the efficacy of interventions that target things like values, self-affirmation or other psychological levers to change parents’ HPV vaccination behaviors.
A final notable area for intervention research related to HPV vaccination is the use of video games. Although not likely to be used directly during patient visits, this strategy could be conceptualized as a potential way to augment the information conveyed to a parent by a provider directly during a clinical encounter. A meta-analysis from 2016 identified 16 different “serious” video games that were used to train and educate users about specific vaccine preventable diseases (usually influenza, none for HPV) and the need for vaccination [135]. In many of them, the objective of the game was to protect a virtual community from a vaccine preventable disease and/or manage outbreaks. Only 2 of the games evaluated outcomes in the short term (ie, at the time the game was being played). None have evaluated longer-term impacts such as vaccination intention or utilization. In the era of “plugged in” parents and adolescents, video games represent a unique but understudied mechanism for helping providers “communicate,” albeit indirectly, with families about the need for vaccination. Imagine providing a prescription to an HPV-vaccine hesitant family to “go play Zombie Wars HPV!” One would expect the curiosity factor alone would result in significant engagement with this intervention tool.
Conclusion
With persistently lagging HPV vaccination rates among U.S. adolescents, there is a growing need for effective interventions to improve adolescent HPV vaccine utilization. How providers communicate with families is one of the most influential factors in parents’ vaccination decisions. Emerging research is beginning to delineate potentially effective communication techniques such as presumptive approaches to making the vaccine recommendation, framing the vaccine as cancer preventing, and using motivational interviewing and personalized messaging when met with parental vaccine resistance. Moving forward the list of evidence-based interventions to improve providers’ HPV vaccine communication is likely to grow, and to increasingly leverage technology based solutions. However, given the complexities of the vaccination decision [136] and the ever growing spread of vaccine hesitancy [137], it is unlikely that a single intervention approach will be effective for getting adolescent HPV vaccine levels up to the national goal of 80% coverage. As has been recognized in the past, the most effective interventions for HPV vaccination in the future are likely to be multicomponent, including not only provider communication strategies but also clinic-, community-, and parent-level interventions [48].
Corresponding author: Amanda Dempsey, MD, PhD, MPH, 13199 East Montview Blvd, Suite 300, Aurora, CO 80045, amanda.dempsey@ucdenver.edu.
Financial disclosures: None reported.
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From the University of Colorado Denver, Aurora, CO.
Abstract
- Objective: To provide evidence-based guidance on strategies that are likely or unlikely to be successful in navigating HPV vaccine conversations with patients and parents.
- Methods: Nonsystematic review of the literature.
- Results: This review highlights some of the most recent innovations in provider HPV vaccine communication and describes provider communication strategies that have been found to improve adolescent vaccination rates in rigorous scientific studies. Promising strategies for which additional research is needed and strategies that probably do not work are also described.
- Conclusion: By understanding what works, what may work, and what not to do when it comes to communicating with families about HPV vaccines, providers can be better prepared for maximizing the impact they can have on adolescent HPV vaccination rates.
Key words: human papillomavirus; vaccine hesitancy; health communication; parents; immunization.
In the United States, more than 14 million people newly acquire genital human papillomavirus (HPV) annually, and 75 million Americans are infected at any given time [1]. As the most common sexually transmitted disease, more than 80% of sexually active U.S. adults are estimated to be infected with HPV by the age of 50 [1,2]. Although the majority of infections are “silent” and resolve without clinical sequelae, a proportion of infected individuals will go on to develop HPV-related diseases. In women, these include cervical cancer and pre-cancer (ie, abnormal Pap smears); cancers of the vagina, vulva, anus, and oropharynx; and genital warts [3]. Males also bear a high burden of HPV-related disease in the form of penile, anal, and oropharyngeal cancers, as well as genital warts [3]. While once thought of as primarily a “woman’s disease” [4], recent research demonstrates men are also significantly impacted by HPV—particularly in the form of oropharyngeal cancers, which are 2 to 3 times more common in men than in women [5]. In fact, it is estimated by the year 2020 more men will die of HPV-related oropharyngeal cancer than women will die of cervical cancer [6,7]. The combined cost of HPV-associated cancers and other conditions is estimated to be $8 billion per year in the United States [8–11].
HPV Vaccines
Effective HPV vaccines have been available for females aged 9 to 26 years since 2006 (bivalent and quadrivalent vaccines) and for males aged 9 to 26 since 2010 (quadrivalent vaccine only) [12]. These vaccines have been shown in clinical trials to be highly efficacious in preventing HPV infection, cervical pre-cancer, and anal, vaginal, penile, and vulvar cancers caused by the HPV types covered in the vaccine [2]. Although their effectiveness against head and neck cancer has not been studied in clinical trials, most experts believe that these vaccines will also provide protection against at least a proportion of these cancers [13,14]. In 2015 the U.S. Food and Drug Administration approved licensure of a 9-valent HPV vaccine that will soon replace the quadrivalent vaccine in the U.S. market [15]. The 9-valent vaccine is licensed for both males and females aged 9 to 26 and is expected to prevent an even higher proportion of HPV-related cancers than earlier HPV vaccines due to the protection against 5 additional oncogenic HPV types [15].
Despite the potential of HPV vaccines to drastically reduce the incidence of HPV-related cancers and other diseases, these vaccines are not being as widely used in the United States as was hoped. The most recent national data from 2015 demonstrates that only 41.9% of girls and 28.1% of boys have received all 3 doses recommended in the HPV vaccine series [16]. This level of vaccine utilization is significantly lower than the Healthy People 2020 goal of 80% coverage [17], and also significantly lower than that of other developed countries such as Australia and the United Kingdom, which have achieved vaccination levels of ~70% among their target adolescent populations [18,19]. In the future, these low vaccination levels will likely be mitigated somewhat by the recent approval from the FDA and recent recommendation from the Advisory Committee on Immunization Practices (ACIP) for only 2 doses of the 9-valent HPV vaccine (spaced 6 to 12 months apart) for adolescents less than 15 years of age [20,21]. Three doses are still recommended for those aged 15 to 26 years.
Provider Communication About HPV Vaccines
How providers communicate with parents and patients about HPV vaccines is a key influential factor driving current U.S. adolescent HPV vaccination levels [22,23]. Numerous studies demonstrate that a provider’s recommendation generally has the largest impact on whether or not an adolescent receives the vaccine, even above that of parent factors such as attitudes and beliefs about the vaccine and patient characteristics such as age and insurance status [23–31]. Moreover, parents consistently cite their adolescent’s provider as one of the most trusted and impactful resources for obtaining vaccine information [22,32].
Unfortunately, research also shows that providers often fail to adequately recommend the HPV vaccine for their patients, especially for 11 to 12 year olds for whom the vaccine is preferentially recommended [33,34]. For example, in a national study of parents done in 2013, not being recommended by a provider was one of the top 5 reasons parents of males and of females aged 11 to 17 gave for not getting their adolescent vaccinated against HPV [35]. Supporting this also is a 2014 study of 776 pediatricians and family medicine providers nationally, in which Gilkey and colleagues found that more than 1 out of 4 providers did not highly endorse the HPV vaccine for 11 to 12 year olds despite this having been the recommended practice from ACIP for the prior 8 years for girls and 4 years for boys. This is in comparison to the other adolescents vaccines that were reported in the same study as being endorsed highly by these providers > 95% of the time [36].
Recognizing that providers’ HPV vaccine recommendations are often suboptimal, researchers have begun to define what components comprise “high-quality” HPV vaccine recommendations. This has been operationalized by one research group as (1) timeliness—routinely recommending the vaccine starting when the patient is ≤ 12 years; (2) consistency—recommending the vaccine for all eligible adolescents as opposed to an approach based on providers’ perception of their patients’ risk for HPV infection; (3) urgency—recommending that the vaccine be given on the same day the vaccine is being discussed, rather than offering the option of getting it at a future visit; and (4) strength—using language that clearly conveys that the provider believes the vaccine is very important for the adolescent to receive. A national study of primary care providers done in 2014 examined how frequently these quality components were implemented [37]. The results were startling and discouraging. Nearly half of providers (49%) reported they usually recommended that 11 to 12 year olds get the vaccine at a later visit, 41% used a risk-based approach for deciding when to recommend the vaccine, 27% did not tell the parents the vaccine was “very or extremely important,” and a large proportion did not start routinely recommending the vaccine before the age of 13 (39% for male patients and 25% for females) [37].
Much research has now accumulated to explain the underlying reasons why providers may not give consistent and high-quality HPV vaccine recommendations to all eligible adolescents [22]. Issues such as providers’ own knowledge about HPV-related diseases, personal beliefs about the vaccine’s safety and necessity, concern that a discussion about the vaccine will necessitate a discussion about adolescent sexuality with the parent, belief that parents will not want their child vaccinated if asked, perceptions that a provider can adequately select those patients most “in need” of HPV vaccination, and concern that raising the vaccine discussion with vaccine-hesitant parents will result in prolonged discussions have been shown to impact whether and how providers communicate about HPV vaccination during clinical visits [22,36–45]. Now that these barriers have been defined and described, there is a great need to use this knowledge to develop and evaluate interventions that help to mitigate these barriers and improve providers’ vaccine communication abilities. Such interventions are needed not only for HPV, but for all vaccines [46,47].
Possible Strategies for Helping Providers Communicate About HPV Vaccines
Before discussing these interventions, it is worth noting that several of the passive and active strategies have been shown in clinical trials to improve adolescent HPV vaccination rates. Although these are beyond the scope of this article, inclusion of these strategies should certainly be considered by any practice as a mechanism to increase vaccination levels, especially given that the most successful interventions to improve vaccination levels consist of multiple components [48]. Also useful is a recently described “taxonomy of vaccine communication interventions” that provides additional perspective on the scope and complexity of interventions to improve vaccine delivery [49]. There are several well-written review articles that describe interventions that focus on passive and active strategies at the practice or community level [50–52].
Interpersonal Communication Strategies Shown to Increase HPV Vaccination
Presumptive Communication
One of the first studies to examine the specific “way” in which providers communicate about vaccines focused not on HPV but rather on young childhood vaccines. In 2013 Opel and colleagues performed a study in which they taped clinical encounters between a pediatrician and a parent of a child aged 1 to 19 months [53]. Of the 111 encounters recorded, 50% of parents were classified as vaccine hesitant. Parents were aware they were being taped but not aware that the overall purpose of the study was to examine providers’ communication related to vaccination. The researchers found that providers generally used one of 2 communication styles to introduce the vaccine discussion. The first, called the “presumptive” style, assumed that parents would agree to vaccination and presented the vaccines as routine (ie, “We have to do some shots today”). The second style, called “participatory,” was more parent-oriented and used language suggesting shared decision-making (ie, “So what do you want to do about shots today?”). The study showed that the odds of resisting the provider’s vaccine recommendations were significantly higher when providers used a participatory approach than a presumptive one, suggesting that even small changes in language can have a major impact on the likelihood of vaccination. However, given the study design, causality between providers’ recommendation style and parents vaccination decisions could not be delineated.
In 2015 Moss and colleagues performed a study that examined the use of these 2 communication styles with regard to HPV vaccination [54]. This study used data from the 2010 National Immunization Survey–Teen, a national survey on childhood vaccination that includes provider verification of vaccines given [16]. Researchers categorized provider vaccine communication styles into “provider-driven,” which was similar to the presumptive style described Opel, and “patient-driven,” which was similar to Opel’s permissive style. Parents who received a more provider-driven style of HPV vaccine recommendation were far more likely to have allowed their adolescent to be vaccinated than those receiving patient-driven recommendations [54]. Further supporting this communication approach are results from a qualitative study done by Hughes and colleagues in which triads of mothers, adolescents, and providers were interviewed after a preventive care visit to assess the communication that occurred regarding HPV vaccination [39]. Providers’ communication style was categorized into 1 of 3 groups: paternalistic (clinician makes the vaccination decision and communicates this to the family); informed (patient and family gathers information from the clinician and other sources to reach a vaccination decision); and shared (medical and personal information is exchanged between the provider and family and then a decision is reached jointly). Providers who typically adopted the paternalistic approach perceived that they had the highest success in convincing parents to vaccinate—a perception that was confirmed in quantitative assessments of vaccination status among adolescents in the study sample [39]. Our own research demonstrates that learning and implementing a presumptive/paternalistic HPV vaccine recommendation style is easy for primary care providers to do and is perceived as often shortening the time taken during clinical visits to discuss the vaccine [55,56]. Thus, providers should consider opening the HPV vaccine conversation using this approach, and then turning to some of the other communication techniques described below when met with parental resistance or questions.
Motivational Interviewing
A second communication technique that seems effective for promoting HPV vaccination, especially for vaccine hesitant parents, is motivational interviewing. Motivational interviewing describes a communication technique in which the provider leverages a parents’ or patients’ intrinsic motivation to engage in a preferred health behavior [57]. Motivational interviewing was originally developed to combat substance abuse [58,59] but has subsequently been successfully applied to a number of other health issues [60–64]. There is growing interest from public health and medical providers in using this technique for increasing vaccination [39,65–68]. Our research group performed a large, cluster-randomized controlled trial of 16 pediatric and family medicine clinics to examine the impact of a provider communication “toolkit” on adolescent HPV vaccine series initiation and completion [50,69]. The toolkit consisted of motivational interviewing training for providers related to HPV vaccination and training on 3 tangible resources providers could also use with parents—an HPV fact sheet, an HPV vaccine decision aid, and an educational website. Results from the study demonstrated that motivational interviewing was the toolkit component most widely utilized by providers and was also perceived as being the most useful. More importantly, HPV vaccine series initiation levels were significantly higher among adolescents in practices receiving the toolkit than in control practices. There was no impact on HPV vaccine series completion (unpublished results). The usefulness of motivational interviewing for vaccination is further supported by a small study in which community pharmacists receiving motivational interviewing training for adult vaccination reported significantly higher patient readiness to receive vaccines following their interaction with the pharmacist than those who did not receive the training [70]. Finally, Perkins et al performed a cluster randomized controlled trial that evaluated the impact of a provider-focused intervention on adolescent HPV vaccination rates. The intervention included frequent provider support meetings, education on HPV infection and vaccination, feedback on providers’ individual HPV vaccination rates, provider incentives, and “basic motivational interviewing principles with vaccine-hesitant parents.” HPV vaccination series initiation and completion rates were significantly higher in intervention practices than controls, and this effect was sustained for at least 6 months after the active intervention period was over [67]. However, it was unknown how much the motivational interviewing contributed to these results. Based on the above information, and the long history of success of motivational interviewing for improving patient compliance with other recommended health behaviors, this technique appears to have a reasonable evidence base and should be considered for communicating with families that express resistance to HPV vaccination.
Personalized Communication
Parents’ reasons for not having their adolescent vaccinated against HPV are often complex and multifactorial [71,72]. Personalized approaches are needed to account for each parent’s unique informational needs, beliefs, and prior experiences [65]. Unfortunately, given the short amount of time allotted for clinical visits, it is often difficult to provide adequate information to parents during these encounters [73–75]. Indeed, concern about prolonged HPV vaccine discussions has been identified as an important barrier for providers that cause some to forgo recommending the vaccine [36,75].
One potential solution to this issue is to leverage technology in the form of web-based interventions that use software to tailor materials to each individual’s unique informational needs. Feasibility for this idea comes from the knowledge that many parents already use the web to research health issues related to their children [76], and that doctors’ offices are increasingly using patient portals and other web-based resources to help parents prepare for upcoming visits, especially those focused on health maintenance [77,78]. Tailored messaging interventions have been shown across populations and health issues to generally result in superior adherence with health behaviors when compared to untailored controls [79–82]. Several researchers have thus begun exploring whether such a personalized communication strategy may be similarly effective for adolescent HPV vaccination [50,83–85]. As an example, Maertens and colleagues used community-based participatory research techniques to develop a web-based tailored messaging intervention for Latinos regarding HPV vaccination [86]. A subsequent randomized controlled trial of the intervention in over 1200 parents of adolescents and young adults demonstrated that the intervention improved participants’ intentions to vaccinate compared to usual care [87], and among adolescents, higher HPV vaccine series initiation levels (unpublished data). Although additional work is needed to understand the feasibility of implementing such an intervention more broadly, additional support for the usefulness of a tailored messaging approach comes from a study of female university students that demonstrated higher HPV vaccination intentions after exposure to tailored information compared to untailored information. However, the impact on actual HPV vaccine utilization was not measured in the study [84]. Contrasting results were found in a different study of university students where researchers failed to find an impact of message tailoring on HPV vaccination utilization. However, this study was limited by a low response rate (~50%) to the follow up survey where vaccination status was assessed, and also by overall low levels of HPV vaccine initiation among the entire study sample (8%) [85]. Given the low number of studies in this area, and some conflicting data, additional research is needed to better understand the impact of personalized communication on HPV vaccination levels. However, results from these studies suggest that a modest benefit may be achieved with this approach, especially if coupled with other, evidence-based, clinic-level interventions to promote vaccination (eg, vaccine reminders, extended office hours), as is suggested by the Task Force on Community Preventive Services [48].
Focusing Communication on Cancer Prevention
HPV vaccines are unique in that they are only 1 of 2 vaccines for cancer prevention (the other being hepatitis B). Provider and parent surveys suggest that while most providers do mention cancer prevention when discussing HPV vaccines [40,88,89], this may be more commonly done with female patients than males [22]. Focusing on cancer prevention rather than sexual transmissibility is a communication technique suggested by the Centers for Disease Control and Prevention (CDC) as many parents cite this aspect of the vaccine as one of the most compelling reasons for vaccinating [45,90]. CDC’s “You are the Key” program [91] uses cancer prevention as a central theme in their physician and patient communication materials, based on significant prior market research on the acceptability and impact of such messages among parents and providers. In 2016 Malo and colleagues tested the potential impact of brief messages related to HPV vaccination, including cancer prevention messages, among a national sample of 776 medical providers and 1504 parents of adolescents [92]. In addition to their potential to motivate parents to vaccination, associations between parental endorsement of each message and their adolescent’s vaccination status were also examined. The cancer prevention messages were among those most highly endorsed by both parents and providers as being motivating for parents to get their adolescent vaccinated. More importantly, among parents these endorsements were associated with a significantly higher likelihood of the adolescent having been vaccinated against HPV. Interestingly, one of the briefest messages in the study, “I [the physician] strongly believe in the importance of this cancer preventing vaccine for [child’s name],” was perceived as the most persuasive message by parents.
Further support for the positive impact of framing HPV vaccines primarily as cancer prevention comes from another national study of 1495 parents of 11 to 17 year olds that examined 3 measures of quality of their adolescent provider’s HPV vaccine recommendation, and the relationship between recommendation quality and likelihood of adolescent HPV vaccination [40]. The 3 quality indicators assessed included providing information about cancer prevention, encouraging the vaccine “strongly,” and recommending it be given on the same day as it was being discussed. While 49% of parents reported receiving no HPV vaccine recommendation from their adolescents’ provider, of those that did, 86% received a cancer prevention message. Parents who had been given high quality recommendations that included either 2 or 3 of the quality indicator measures had over 9 times the odds of vaccine series initiation and 3 times the odds of vaccine series follow through than those who had not received any recommendation, and also significantly higher odds of vaccination than parents who had received low quality recommendations (ie, included only 1 indicator). Taken together, these results suggest that focusing discussions about HPV vaccines on their ability to prevent cancer is likely to be persuasive for some parents.
Strategies That Are Promising But Not Thoroughly Tested
Helping Parents Create Vaccination Plans
A recent commentary suggested that instead of focusing on changing beliefs or “educating” parents and patients about the need for a given vaccine, perhaps a better way to craft interventions for increasing vaccination is to focus on structuring the environment to make vaccination “easy” [93,94]. Examples of this include strategies such as extended office hours and making the vaccine available in other locations such as schools and pharmacies, both of which have been shown in some populations and settings to improve vaccine utilization [48,95]. One aspect of structuring a vaccine-conducive environment that relates to provider communication is helping parents create “implementation intentions” for future vaccination visits. In its most obvious form, this would mean providers provide office resources that facilitate making an appointment for the next dose in the HPV vaccine series during a clinic visit where the first dose was provided. But such an approach could also potentially extend to parents who are on the fence about the vaccine—to make an appointment before the parent leaves the office with an unvaccinated child to either re-discuss the vaccine in the future or to actually start the vaccine series. Support for such a strategy comes primarily from the social sciences, which suggest that implementation intentions work by increasing attention to specific cues to action, making it more likely that that the cue will be acted upon [96–98]. Creating implementation intentions has been shown to be helpful for improving adherence with a variety of health behaviors [99–105], and there is a growing evidence base related to how implementation intentions may facilitate vaccination specifically. For example Vet and colleagues performed a randomized controlled trial among 616 men who have sex with men with either strong or weak intentions to receive the hepatitis B vaccine [106]. Half of the participants were asked to create an implementation intention plan where they described when, where and how they would obtain the vaccine. Those in the control arm were not given this prompt. Regardless of whether their initial vaccination intention was weak or strong, those who had been asked to create an implementation plan had more than double the likelihood of actually getting the vaccine than participants who did not receive the implementation plan prompt. Similarly, a study of influenza vaccination rates among corporate employees found that those who were asked to write down the day and time they planned to go to employee health to get the free vaccine were somewhat more likely (4% higher) to be vaccinated than those who did not receive this prompt [107]. In addition, a study of elderly individuals found that influenza vaccination rates were significantly higher among those who had received “action instructions” on how, when and where to get the vaccine than those who did not [108]. These studies suggest that helping parents craft a definitive follow-up plan regarding vaccination could have a significant impact on vaccination rates—particularly for vaccines like HPV that require multiple doses.
Treating all Adolescent Vaccines the Same
Prior research has demonstrated that providers often communicate differently about HPV vaccines than other adolescent vaccines such as the tetanus-diphtheria-pertussis (Tdap) and meningococcal (MCV) vaccines [22,36]. Providers often tend to discuss the HPV vaccine last among these 3 vaccines, provide weaker endorsements of the vaccine, and pre-emptively give much more detail about the HPV compared to the other vaccines, even in the absence of a parent’s request for additional information [36,39,41]. The CDC and the American Academy of Pediatrics now suggest putting HPV at the beginning or middle of the list of vaccines recommended to the adolescent (ie, “HPV, Tdap and MCV”), and treating all recommended vaccines equivalently in terms of the level of detail provided to parents in the absence of a parent’s request for more information [109,110]. Through these suggestions have face validity, their specific impact on HPV vaccination rates, and on patient and provider satisfaction with the visit have yet to be evaluated.
Strategies that Probably Don’t Work
Presenting Myths and Facts
Research related to promoting other vaccines provides insight into communication activities that probably would not work well for promoting HPV vaccination. A 2012 study by Nyhan and colleagues examined the impact of 2 different messages related to influenza vaccines on participants’ beliefs about the vaccine’s safety and intentions to get vaccinated [111]. One group received information to correct the commonly held belief that influenza vaccine can cause the flu while the other received information about the risks associated with contracting an influenza infection. While the correction of myths did improve participants’ perceptions of the vaccine’s safety, information about influenza dangers did not. Neither message impacted intentions to vaccinate in the study subjects overall. However, in sub-analyses the correction of myths actually decreased intentions to vaccinate among those with high baseline levels of concern about the vaccine’s side effects—that is, among those most concerned that the flu vaccine can give someone the flu, correcting this myth actually decreased the likelihood that they would receive the vaccine. Similar findings have been reported in other studies related to vaccination [112–114], and suggest that the “threat” generated by providing information opposing a person’s beliefs may actually entrench these beliefs further as part of the threat response—a phenomenon known as attitude polarization [115]. These results also are consistent with the concept of negativity bias, which posits that negative information influences people’s risk perceptions more than positive information, and that the more strongly a risk is attempted to be negated, the lower the effectiveness and perceived trust of the information [116].
Using Fear Appeals
One tactic that has been suggested by some as a way to promote vaccination is to provide graphic depictions of the possible sequelae of vaccine-preventable diseases. The thought behind this idea is that because vaccination is so successful, most parents will have never experienced significant impacts from vaccine preventable diseases that, in the past, had been a major motivator for parents to vaccinate. Thus, in order to counter beliefs about “controversial” issues like vaccination, highly emotionally compelling and engaging information may be especially useful. This is a common tactic used by anti-vaccination groups to spread their own messages [117]. However, several studies suggested that using “fear appeals” (aka scare tactics) such as this to promote vaccination can actually have a negative effect on vaccination intentions. For example, in a 2011 study of a nationally representative sample of parents of children < 18 years, 4 different message formats were tested for their impact on parental intentions to vaccinate a future child with the measles-mumps-rubella vaccine (MMR) [113]. Message formats included correcting the misinformation that MMR causes autism, presenting information on MMR-related disease risk, providing a dramatic narrative about a child endangered by measles, and showing pictures of infants affected by these diseases. Counter to the study’s hypotheses, the dramatic narrative message actually increased parents’ perceptions that MMR vaccines had serious side effects, and the pictures increased parents’ belief that the MMR vaccine could cause autism. These counter-intuitive results are consistent with other studies that have examined the impact of message framing on adults’ vaccination intentions for HPV and influenza [108,118,119]. Taken together, fear appeals seem unlikely to sway many hesitant parents towards HPV vaccination.
Looking Into the Future
Moving forward, additional interventions to improve providers’ ability to communicate with families about HPV vaccination will undoubtedly be developed. A major area of interest in this regard is leveraging the power of technology and the internet, including using social media, mobile technologies, and online interventions to augment the provider/parent interaction that occurs during the clinical visit [50,120]. Web-based approaches have the benefit of generally being low cost and easy to disseminate to large populations. Such interventions have already been developed for a number of other health issues, some of which have proven effective [121,122]. However, use of the internet to promote healthy behaviors in general, and vaccination specifically, is still in its infancy. There is still much to be learned about how to create effective web-based tools, how to engage patients with them, and how to assess their impact on health outcomes [123].
Another interesting area for future research is identifying psychological “levers” to motivate parents’ vaccination intentions [94]. One example is focusing on using parents’ values (ie, protecting my child from harm) as an intervention target rather than beliefs or attitudes. This is because values tend to be inherent and static over time, compared to beliefs and attitudes, which are subject to change depending on the context [124]. Prior research has shown that interventions that leverage values rather than facts can be an effective way to overcome beliefs that are highly emotional or controversial, and that individuals are more likely to trust sources and individuals with shared values than those without [125], suggesting that this may be a useful way to motivate parents toward vaccinating their children. Self-affirmation is another example of a psychological lever that has a significant evidence base from the social science literature as a helpful tool for moving patients towards a desired health behavior [126,127], but it has not been extensively applied to the field of vaccination. Researchers in the field of vaccine delivery are increasingly recognizing the potential value of these unique intervention approaches [101,128–134], and it may be fruitful in the future to more closely examine the efficacy of interventions that target things like values, self-affirmation or other psychological levers to change parents’ HPV vaccination behaviors.
A final notable area for intervention research related to HPV vaccination is the use of video games. Although not likely to be used directly during patient visits, this strategy could be conceptualized as a potential way to augment the information conveyed to a parent by a provider directly during a clinical encounter. A meta-analysis from 2016 identified 16 different “serious” video games that were used to train and educate users about specific vaccine preventable diseases (usually influenza, none for HPV) and the need for vaccination [135]. In many of them, the objective of the game was to protect a virtual community from a vaccine preventable disease and/or manage outbreaks. Only 2 of the games evaluated outcomes in the short term (ie, at the time the game was being played). None have evaluated longer-term impacts such as vaccination intention or utilization. In the era of “plugged in” parents and adolescents, video games represent a unique but understudied mechanism for helping providers “communicate,” albeit indirectly, with families about the need for vaccination. Imagine providing a prescription to an HPV-vaccine hesitant family to “go play Zombie Wars HPV!” One would expect the curiosity factor alone would result in significant engagement with this intervention tool.
Conclusion
With persistently lagging HPV vaccination rates among U.S. adolescents, there is a growing need for effective interventions to improve adolescent HPV vaccine utilization. How providers communicate with families is one of the most influential factors in parents’ vaccination decisions. Emerging research is beginning to delineate potentially effective communication techniques such as presumptive approaches to making the vaccine recommendation, framing the vaccine as cancer preventing, and using motivational interviewing and personalized messaging when met with parental vaccine resistance. Moving forward the list of evidence-based interventions to improve providers’ HPV vaccine communication is likely to grow, and to increasingly leverage technology based solutions. However, given the complexities of the vaccination decision [136] and the ever growing spread of vaccine hesitancy [137], it is unlikely that a single intervention approach will be effective for getting adolescent HPV vaccine levels up to the national goal of 80% coverage. As has been recognized in the past, the most effective interventions for HPV vaccination in the future are likely to be multicomponent, including not only provider communication strategies but also clinic-, community-, and parent-level interventions [48].
Corresponding author: Amanda Dempsey, MD, PhD, MPH, 13199 East Montview Blvd, Suite 300, Aurora, CO 80045, amanda.dempsey@ucdenver.edu.
Financial disclosures: None reported.
From the University of Colorado Denver, Aurora, CO.
Abstract
- Objective: To provide evidence-based guidance on strategies that are likely or unlikely to be successful in navigating HPV vaccine conversations with patients and parents.
- Methods: Nonsystematic review of the literature.
- Results: This review highlights some of the most recent innovations in provider HPV vaccine communication and describes provider communication strategies that have been found to improve adolescent vaccination rates in rigorous scientific studies. Promising strategies for which additional research is needed and strategies that probably do not work are also described.
- Conclusion: By understanding what works, what may work, and what not to do when it comes to communicating with families about HPV vaccines, providers can be better prepared for maximizing the impact they can have on adolescent HPV vaccination rates.
Key words: human papillomavirus; vaccine hesitancy; health communication; parents; immunization.
In the United States, more than 14 million people newly acquire genital human papillomavirus (HPV) annually, and 75 million Americans are infected at any given time [1]. As the most common sexually transmitted disease, more than 80% of sexually active U.S. adults are estimated to be infected with HPV by the age of 50 [1,2]. Although the majority of infections are “silent” and resolve without clinical sequelae, a proportion of infected individuals will go on to develop HPV-related diseases. In women, these include cervical cancer and pre-cancer (ie, abnormal Pap smears); cancers of the vagina, vulva, anus, and oropharynx; and genital warts [3]. Males also bear a high burden of HPV-related disease in the form of penile, anal, and oropharyngeal cancers, as well as genital warts [3]. While once thought of as primarily a “woman’s disease” [4], recent research demonstrates men are also significantly impacted by HPV—particularly in the form of oropharyngeal cancers, which are 2 to 3 times more common in men than in women [5]. In fact, it is estimated by the year 2020 more men will die of HPV-related oropharyngeal cancer than women will die of cervical cancer [6,7]. The combined cost of HPV-associated cancers and other conditions is estimated to be $8 billion per year in the United States [8–11].
HPV Vaccines
Effective HPV vaccines have been available for females aged 9 to 26 years since 2006 (bivalent and quadrivalent vaccines) and for males aged 9 to 26 since 2010 (quadrivalent vaccine only) [12]. These vaccines have been shown in clinical trials to be highly efficacious in preventing HPV infection, cervical pre-cancer, and anal, vaginal, penile, and vulvar cancers caused by the HPV types covered in the vaccine [2]. Although their effectiveness against head and neck cancer has not been studied in clinical trials, most experts believe that these vaccines will also provide protection against at least a proportion of these cancers [13,14]. In 2015 the U.S. Food and Drug Administration approved licensure of a 9-valent HPV vaccine that will soon replace the quadrivalent vaccine in the U.S. market [15]. The 9-valent vaccine is licensed for both males and females aged 9 to 26 and is expected to prevent an even higher proportion of HPV-related cancers than earlier HPV vaccines due to the protection against 5 additional oncogenic HPV types [15].
Despite the potential of HPV vaccines to drastically reduce the incidence of HPV-related cancers and other diseases, these vaccines are not being as widely used in the United States as was hoped. The most recent national data from 2015 demonstrates that only 41.9% of girls and 28.1% of boys have received all 3 doses recommended in the HPV vaccine series [16]. This level of vaccine utilization is significantly lower than the Healthy People 2020 goal of 80% coverage [17], and also significantly lower than that of other developed countries such as Australia and the United Kingdom, which have achieved vaccination levels of ~70% among their target adolescent populations [18,19]. In the future, these low vaccination levels will likely be mitigated somewhat by the recent approval from the FDA and recent recommendation from the Advisory Committee on Immunization Practices (ACIP) for only 2 doses of the 9-valent HPV vaccine (spaced 6 to 12 months apart) for adolescents less than 15 years of age [20,21]. Three doses are still recommended for those aged 15 to 26 years.
Provider Communication About HPV Vaccines
How providers communicate with parents and patients about HPV vaccines is a key influential factor driving current U.S. adolescent HPV vaccination levels [22,23]. Numerous studies demonstrate that a provider’s recommendation generally has the largest impact on whether or not an adolescent receives the vaccine, even above that of parent factors such as attitudes and beliefs about the vaccine and patient characteristics such as age and insurance status [23–31]. Moreover, parents consistently cite their adolescent’s provider as one of the most trusted and impactful resources for obtaining vaccine information [22,32].
Unfortunately, research also shows that providers often fail to adequately recommend the HPV vaccine for their patients, especially for 11 to 12 year olds for whom the vaccine is preferentially recommended [33,34]. For example, in a national study of parents done in 2013, not being recommended by a provider was one of the top 5 reasons parents of males and of females aged 11 to 17 gave for not getting their adolescent vaccinated against HPV [35]. Supporting this also is a 2014 study of 776 pediatricians and family medicine providers nationally, in which Gilkey and colleagues found that more than 1 out of 4 providers did not highly endorse the HPV vaccine for 11 to 12 year olds despite this having been the recommended practice from ACIP for the prior 8 years for girls and 4 years for boys. This is in comparison to the other adolescents vaccines that were reported in the same study as being endorsed highly by these providers > 95% of the time [36].
Recognizing that providers’ HPV vaccine recommendations are often suboptimal, researchers have begun to define what components comprise “high-quality” HPV vaccine recommendations. This has been operationalized by one research group as (1) timeliness—routinely recommending the vaccine starting when the patient is ≤ 12 years; (2) consistency—recommending the vaccine for all eligible adolescents as opposed to an approach based on providers’ perception of their patients’ risk for HPV infection; (3) urgency—recommending that the vaccine be given on the same day the vaccine is being discussed, rather than offering the option of getting it at a future visit; and (4) strength—using language that clearly conveys that the provider believes the vaccine is very important for the adolescent to receive. A national study of primary care providers done in 2014 examined how frequently these quality components were implemented [37]. The results were startling and discouraging. Nearly half of providers (49%) reported they usually recommended that 11 to 12 year olds get the vaccine at a later visit, 41% used a risk-based approach for deciding when to recommend the vaccine, 27% did not tell the parents the vaccine was “very or extremely important,” and a large proportion did not start routinely recommending the vaccine before the age of 13 (39% for male patients and 25% for females) [37].
Much research has now accumulated to explain the underlying reasons why providers may not give consistent and high-quality HPV vaccine recommendations to all eligible adolescents [22]. Issues such as providers’ own knowledge about HPV-related diseases, personal beliefs about the vaccine’s safety and necessity, concern that a discussion about the vaccine will necessitate a discussion about adolescent sexuality with the parent, belief that parents will not want their child vaccinated if asked, perceptions that a provider can adequately select those patients most “in need” of HPV vaccination, and concern that raising the vaccine discussion with vaccine-hesitant parents will result in prolonged discussions have been shown to impact whether and how providers communicate about HPV vaccination during clinical visits [22,36–45]. Now that these barriers have been defined and described, there is a great need to use this knowledge to develop and evaluate interventions that help to mitigate these barriers and improve providers’ vaccine communication abilities. Such interventions are needed not only for HPV, but for all vaccines [46,47].
Possible Strategies for Helping Providers Communicate About HPV Vaccines
Before discussing these interventions, it is worth noting that several of the passive and active strategies have been shown in clinical trials to improve adolescent HPV vaccination rates. Although these are beyond the scope of this article, inclusion of these strategies should certainly be considered by any practice as a mechanism to increase vaccination levels, especially given that the most successful interventions to improve vaccination levels consist of multiple components [48]. Also useful is a recently described “taxonomy of vaccine communication interventions” that provides additional perspective on the scope and complexity of interventions to improve vaccine delivery [49]. There are several well-written review articles that describe interventions that focus on passive and active strategies at the practice or community level [50–52].
Interpersonal Communication Strategies Shown to Increase HPV Vaccination
Presumptive Communication
One of the first studies to examine the specific “way” in which providers communicate about vaccines focused not on HPV but rather on young childhood vaccines. In 2013 Opel and colleagues performed a study in which they taped clinical encounters between a pediatrician and a parent of a child aged 1 to 19 months [53]. Of the 111 encounters recorded, 50% of parents were classified as vaccine hesitant. Parents were aware they were being taped but not aware that the overall purpose of the study was to examine providers’ communication related to vaccination. The researchers found that providers generally used one of 2 communication styles to introduce the vaccine discussion. The first, called the “presumptive” style, assumed that parents would agree to vaccination and presented the vaccines as routine (ie, “We have to do some shots today”). The second style, called “participatory,” was more parent-oriented and used language suggesting shared decision-making (ie, “So what do you want to do about shots today?”). The study showed that the odds of resisting the provider’s vaccine recommendations were significantly higher when providers used a participatory approach than a presumptive one, suggesting that even small changes in language can have a major impact on the likelihood of vaccination. However, given the study design, causality between providers’ recommendation style and parents vaccination decisions could not be delineated.
In 2015 Moss and colleagues performed a study that examined the use of these 2 communication styles with regard to HPV vaccination [54]. This study used data from the 2010 National Immunization Survey–Teen, a national survey on childhood vaccination that includes provider verification of vaccines given [16]. Researchers categorized provider vaccine communication styles into “provider-driven,” which was similar to the presumptive style described Opel, and “patient-driven,” which was similar to Opel’s permissive style. Parents who received a more provider-driven style of HPV vaccine recommendation were far more likely to have allowed their adolescent to be vaccinated than those receiving patient-driven recommendations [54]. Further supporting this communication approach are results from a qualitative study done by Hughes and colleagues in which triads of mothers, adolescents, and providers were interviewed after a preventive care visit to assess the communication that occurred regarding HPV vaccination [39]. Providers’ communication style was categorized into 1 of 3 groups: paternalistic (clinician makes the vaccination decision and communicates this to the family); informed (patient and family gathers information from the clinician and other sources to reach a vaccination decision); and shared (medical and personal information is exchanged between the provider and family and then a decision is reached jointly). Providers who typically adopted the paternalistic approach perceived that they had the highest success in convincing parents to vaccinate—a perception that was confirmed in quantitative assessments of vaccination status among adolescents in the study sample [39]. Our own research demonstrates that learning and implementing a presumptive/paternalistic HPV vaccine recommendation style is easy for primary care providers to do and is perceived as often shortening the time taken during clinical visits to discuss the vaccine [55,56]. Thus, providers should consider opening the HPV vaccine conversation using this approach, and then turning to some of the other communication techniques described below when met with parental resistance or questions.
Motivational Interviewing
A second communication technique that seems effective for promoting HPV vaccination, especially for vaccine hesitant parents, is motivational interviewing. Motivational interviewing describes a communication technique in which the provider leverages a parents’ or patients’ intrinsic motivation to engage in a preferred health behavior [57]. Motivational interviewing was originally developed to combat substance abuse [58,59] but has subsequently been successfully applied to a number of other health issues [60–64]. There is growing interest from public health and medical providers in using this technique for increasing vaccination [39,65–68]. Our research group performed a large, cluster-randomized controlled trial of 16 pediatric and family medicine clinics to examine the impact of a provider communication “toolkit” on adolescent HPV vaccine series initiation and completion [50,69]. The toolkit consisted of motivational interviewing training for providers related to HPV vaccination and training on 3 tangible resources providers could also use with parents—an HPV fact sheet, an HPV vaccine decision aid, and an educational website. Results from the study demonstrated that motivational interviewing was the toolkit component most widely utilized by providers and was also perceived as being the most useful. More importantly, HPV vaccine series initiation levels were significantly higher among adolescents in practices receiving the toolkit than in control practices. There was no impact on HPV vaccine series completion (unpublished results). The usefulness of motivational interviewing for vaccination is further supported by a small study in which community pharmacists receiving motivational interviewing training for adult vaccination reported significantly higher patient readiness to receive vaccines following their interaction with the pharmacist than those who did not receive the training [70]. Finally, Perkins et al performed a cluster randomized controlled trial that evaluated the impact of a provider-focused intervention on adolescent HPV vaccination rates. The intervention included frequent provider support meetings, education on HPV infection and vaccination, feedback on providers’ individual HPV vaccination rates, provider incentives, and “basic motivational interviewing principles with vaccine-hesitant parents.” HPV vaccination series initiation and completion rates were significantly higher in intervention practices than controls, and this effect was sustained for at least 6 months after the active intervention period was over [67]. However, it was unknown how much the motivational interviewing contributed to these results. Based on the above information, and the long history of success of motivational interviewing for improving patient compliance with other recommended health behaviors, this technique appears to have a reasonable evidence base and should be considered for communicating with families that express resistance to HPV vaccination.
Personalized Communication
Parents’ reasons for not having their adolescent vaccinated against HPV are often complex and multifactorial [71,72]. Personalized approaches are needed to account for each parent’s unique informational needs, beliefs, and prior experiences [65]. Unfortunately, given the short amount of time allotted for clinical visits, it is often difficult to provide adequate information to parents during these encounters [73–75]. Indeed, concern about prolonged HPV vaccine discussions has been identified as an important barrier for providers that cause some to forgo recommending the vaccine [36,75].
One potential solution to this issue is to leverage technology in the form of web-based interventions that use software to tailor materials to each individual’s unique informational needs. Feasibility for this idea comes from the knowledge that many parents already use the web to research health issues related to their children [76], and that doctors’ offices are increasingly using patient portals and other web-based resources to help parents prepare for upcoming visits, especially those focused on health maintenance [77,78]. Tailored messaging interventions have been shown across populations and health issues to generally result in superior adherence with health behaviors when compared to untailored controls [79–82]. Several researchers have thus begun exploring whether such a personalized communication strategy may be similarly effective for adolescent HPV vaccination [50,83–85]. As an example, Maertens and colleagues used community-based participatory research techniques to develop a web-based tailored messaging intervention for Latinos regarding HPV vaccination [86]. A subsequent randomized controlled trial of the intervention in over 1200 parents of adolescents and young adults demonstrated that the intervention improved participants’ intentions to vaccinate compared to usual care [87], and among adolescents, higher HPV vaccine series initiation levels (unpublished data). Although additional work is needed to understand the feasibility of implementing such an intervention more broadly, additional support for the usefulness of a tailored messaging approach comes from a study of female university students that demonstrated higher HPV vaccination intentions after exposure to tailored information compared to untailored information. However, the impact on actual HPV vaccine utilization was not measured in the study [84]. Contrasting results were found in a different study of university students where researchers failed to find an impact of message tailoring on HPV vaccination utilization. However, this study was limited by a low response rate (~50%) to the follow up survey where vaccination status was assessed, and also by overall low levels of HPV vaccine initiation among the entire study sample (8%) [85]. Given the low number of studies in this area, and some conflicting data, additional research is needed to better understand the impact of personalized communication on HPV vaccination levels. However, results from these studies suggest that a modest benefit may be achieved with this approach, especially if coupled with other, evidence-based, clinic-level interventions to promote vaccination (eg, vaccine reminders, extended office hours), as is suggested by the Task Force on Community Preventive Services [48].
Focusing Communication on Cancer Prevention
HPV vaccines are unique in that they are only 1 of 2 vaccines for cancer prevention (the other being hepatitis B). Provider and parent surveys suggest that while most providers do mention cancer prevention when discussing HPV vaccines [40,88,89], this may be more commonly done with female patients than males [22]. Focusing on cancer prevention rather than sexual transmissibility is a communication technique suggested by the Centers for Disease Control and Prevention (CDC) as many parents cite this aspect of the vaccine as one of the most compelling reasons for vaccinating [45,90]. CDC’s “You are the Key” program [91] uses cancer prevention as a central theme in their physician and patient communication materials, based on significant prior market research on the acceptability and impact of such messages among parents and providers. In 2016 Malo and colleagues tested the potential impact of brief messages related to HPV vaccination, including cancer prevention messages, among a national sample of 776 medical providers and 1504 parents of adolescents [92]. In addition to their potential to motivate parents to vaccination, associations between parental endorsement of each message and their adolescent’s vaccination status were also examined. The cancer prevention messages were among those most highly endorsed by both parents and providers as being motivating for parents to get their adolescent vaccinated. More importantly, among parents these endorsements were associated with a significantly higher likelihood of the adolescent having been vaccinated against HPV. Interestingly, one of the briefest messages in the study, “I [the physician] strongly believe in the importance of this cancer preventing vaccine for [child’s name],” was perceived as the most persuasive message by parents.
Further support for the positive impact of framing HPV vaccines primarily as cancer prevention comes from another national study of 1495 parents of 11 to 17 year olds that examined 3 measures of quality of their adolescent provider’s HPV vaccine recommendation, and the relationship between recommendation quality and likelihood of adolescent HPV vaccination [40]. The 3 quality indicators assessed included providing information about cancer prevention, encouraging the vaccine “strongly,” and recommending it be given on the same day as it was being discussed. While 49% of parents reported receiving no HPV vaccine recommendation from their adolescents’ provider, of those that did, 86% received a cancer prevention message. Parents who had been given high quality recommendations that included either 2 or 3 of the quality indicator measures had over 9 times the odds of vaccine series initiation and 3 times the odds of vaccine series follow through than those who had not received any recommendation, and also significantly higher odds of vaccination than parents who had received low quality recommendations (ie, included only 1 indicator). Taken together, these results suggest that focusing discussions about HPV vaccines on their ability to prevent cancer is likely to be persuasive for some parents.
Strategies That Are Promising But Not Thoroughly Tested
Helping Parents Create Vaccination Plans
A recent commentary suggested that instead of focusing on changing beliefs or “educating” parents and patients about the need for a given vaccine, perhaps a better way to craft interventions for increasing vaccination is to focus on structuring the environment to make vaccination “easy” [93,94]. Examples of this include strategies such as extended office hours and making the vaccine available in other locations such as schools and pharmacies, both of which have been shown in some populations and settings to improve vaccine utilization [48,95]. One aspect of structuring a vaccine-conducive environment that relates to provider communication is helping parents create “implementation intentions” for future vaccination visits. In its most obvious form, this would mean providers provide office resources that facilitate making an appointment for the next dose in the HPV vaccine series during a clinic visit where the first dose was provided. But such an approach could also potentially extend to parents who are on the fence about the vaccine—to make an appointment before the parent leaves the office with an unvaccinated child to either re-discuss the vaccine in the future or to actually start the vaccine series. Support for such a strategy comes primarily from the social sciences, which suggest that implementation intentions work by increasing attention to specific cues to action, making it more likely that that the cue will be acted upon [96–98]. Creating implementation intentions has been shown to be helpful for improving adherence with a variety of health behaviors [99–105], and there is a growing evidence base related to how implementation intentions may facilitate vaccination specifically. For example Vet and colleagues performed a randomized controlled trial among 616 men who have sex with men with either strong or weak intentions to receive the hepatitis B vaccine [106]. Half of the participants were asked to create an implementation intention plan where they described when, where and how they would obtain the vaccine. Those in the control arm were not given this prompt. Regardless of whether their initial vaccination intention was weak or strong, those who had been asked to create an implementation plan had more than double the likelihood of actually getting the vaccine than participants who did not receive the implementation plan prompt. Similarly, a study of influenza vaccination rates among corporate employees found that those who were asked to write down the day and time they planned to go to employee health to get the free vaccine were somewhat more likely (4% higher) to be vaccinated than those who did not receive this prompt [107]. In addition, a study of elderly individuals found that influenza vaccination rates were significantly higher among those who had received “action instructions” on how, when and where to get the vaccine than those who did not [108]. These studies suggest that helping parents craft a definitive follow-up plan regarding vaccination could have a significant impact on vaccination rates—particularly for vaccines like HPV that require multiple doses.
Treating all Adolescent Vaccines the Same
Prior research has demonstrated that providers often communicate differently about HPV vaccines than other adolescent vaccines such as the tetanus-diphtheria-pertussis (Tdap) and meningococcal (MCV) vaccines [22,36]. Providers often tend to discuss the HPV vaccine last among these 3 vaccines, provide weaker endorsements of the vaccine, and pre-emptively give much more detail about the HPV compared to the other vaccines, even in the absence of a parent’s request for additional information [36,39,41]. The CDC and the American Academy of Pediatrics now suggest putting HPV at the beginning or middle of the list of vaccines recommended to the adolescent (ie, “HPV, Tdap and MCV”), and treating all recommended vaccines equivalently in terms of the level of detail provided to parents in the absence of a parent’s request for more information [109,110]. Through these suggestions have face validity, their specific impact on HPV vaccination rates, and on patient and provider satisfaction with the visit have yet to be evaluated.
Strategies that Probably Don’t Work
Presenting Myths and Facts
Research related to promoting other vaccines provides insight into communication activities that probably would not work well for promoting HPV vaccination. A 2012 study by Nyhan and colleagues examined the impact of 2 different messages related to influenza vaccines on participants’ beliefs about the vaccine’s safety and intentions to get vaccinated [111]. One group received information to correct the commonly held belief that influenza vaccine can cause the flu while the other received information about the risks associated with contracting an influenza infection. While the correction of myths did improve participants’ perceptions of the vaccine’s safety, information about influenza dangers did not. Neither message impacted intentions to vaccinate in the study subjects overall. However, in sub-analyses the correction of myths actually decreased intentions to vaccinate among those with high baseline levels of concern about the vaccine’s side effects—that is, among those most concerned that the flu vaccine can give someone the flu, correcting this myth actually decreased the likelihood that they would receive the vaccine. Similar findings have been reported in other studies related to vaccination [112–114], and suggest that the “threat” generated by providing information opposing a person’s beliefs may actually entrench these beliefs further as part of the threat response—a phenomenon known as attitude polarization [115]. These results also are consistent with the concept of negativity bias, which posits that negative information influences people’s risk perceptions more than positive information, and that the more strongly a risk is attempted to be negated, the lower the effectiveness and perceived trust of the information [116].
Using Fear Appeals
One tactic that has been suggested by some as a way to promote vaccination is to provide graphic depictions of the possible sequelae of vaccine-preventable diseases. The thought behind this idea is that because vaccination is so successful, most parents will have never experienced significant impacts from vaccine preventable diseases that, in the past, had been a major motivator for parents to vaccinate. Thus, in order to counter beliefs about “controversial” issues like vaccination, highly emotionally compelling and engaging information may be especially useful. This is a common tactic used by anti-vaccination groups to spread their own messages [117]. However, several studies suggested that using “fear appeals” (aka scare tactics) such as this to promote vaccination can actually have a negative effect on vaccination intentions. For example, in a 2011 study of a nationally representative sample of parents of children < 18 years, 4 different message formats were tested for their impact on parental intentions to vaccinate a future child with the measles-mumps-rubella vaccine (MMR) [113]. Message formats included correcting the misinformation that MMR causes autism, presenting information on MMR-related disease risk, providing a dramatic narrative about a child endangered by measles, and showing pictures of infants affected by these diseases. Counter to the study’s hypotheses, the dramatic narrative message actually increased parents’ perceptions that MMR vaccines had serious side effects, and the pictures increased parents’ belief that the MMR vaccine could cause autism. These counter-intuitive results are consistent with other studies that have examined the impact of message framing on adults’ vaccination intentions for HPV and influenza [108,118,119]. Taken together, fear appeals seem unlikely to sway many hesitant parents towards HPV vaccination.
Looking Into the Future
Moving forward, additional interventions to improve providers’ ability to communicate with families about HPV vaccination will undoubtedly be developed. A major area of interest in this regard is leveraging the power of technology and the internet, including using social media, mobile technologies, and online interventions to augment the provider/parent interaction that occurs during the clinical visit [50,120]. Web-based approaches have the benefit of generally being low cost and easy to disseminate to large populations. Such interventions have already been developed for a number of other health issues, some of which have proven effective [121,122]. However, use of the internet to promote healthy behaviors in general, and vaccination specifically, is still in its infancy. There is still much to be learned about how to create effective web-based tools, how to engage patients with them, and how to assess their impact on health outcomes [123].
Another interesting area for future research is identifying psychological “levers” to motivate parents’ vaccination intentions [94]. One example is focusing on using parents’ values (ie, protecting my child from harm) as an intervention target rather than beliefs or attitudes. This is because values tend to be inherent and static over time, compared to beliefs and attitudes, which are subject to change depending on the context [124]. Prior research has shown that interventions that leverage values rather than facts can be an effective way to overcome beliefs that are highly emotional or controversial, and that individuals are more likely to trust sources and individuals with shared values than those without [125], suggesting that this may be a useful way to motivate parents toward vaccinating their children. Self-affirmation is another example of a psychological lever that has a significant evidence base from the social science literature as a helpful tool for moving patients towards a desired health behavior [126,127], but it has not been extensively applied to the field of vaccination. Researchers in the field of vaccine delivery are increasingly recognizing the potential value of these unique intervention approaches [101,128–134], and it may be fruitful in the future to more closely examine the efficacy of interventions that target things like values, self-affirmation or other psychological levers to change parents’ HPV vaccination behaviors.
A final notable area for intervention research related to HPV vaccination is the use of video games. Although not likely to be used directly during patient visits, this strategy could be conceptualized as a potential way to augment the information conveyed to a parent by a provider directly during a clinical encounter. A meta-analysis from 2016 identified 16 different “serious” video games that were used to train and educate users about specific vaccine preventable diseases (usually influenza, none for HPV) and the need for vaccination [135]. In many of them, the objective of the game was to protect a virtual community from a vaccine preventable disease and/or manage outbreaks. Only 2 of the games evaluated outcomes in the short term (ie, at the time the game was being played). None have evaluated longer-term impacts such as vaccination intention or utilization. In the era of “plugged in” parents and adolescents, video games represent a unique but understudied mechanism for helping providers “communicate,” albeit indirectly, with families about the need for vaccination. Imagine providing a prescription to an HPV-vaccine hesitant family to “go play Zombie Wars HPV!” One would expect the curiosity factor alone would result in significant engagement with this intervention tool.
Conclusion
With persistently lagging HPV vaccination rates among U.S. adolescents, there is a growing need for effective interventions to improve adolescent HPV vaccine utilization. How providers communicate with families is one of the most influential factors in parents’ vaccination decisions. Emerging research is beginning to delineate potentially effective communication techniques such as presumptive approaches to making the vaccine recommendation, framing the vaccine as cancer preventing, and using motivational interviewing and personalized messaging when met with parental vaccine resistance. Moving forward the list of evidence-based interventions to improve providers’ HPV vaccine communication is likely to grow, and to increasingly leverage technology based solutions. However, given the complexities of the vaccination decision [136] and the ever growing spread of vaccine hesitancy [137], it is unlikely that a single intervention approach will be effective for getting adolescent HPV vaccine levels up to the national goal of 80% coverage. As has been recognized in the past, the most effective interventions for HPV vaccination in the future are likely to be multicomponent, including not only provider communication strategies but also clinic-, community-, and parent-level interventions [48].
Corresponding author: Amanda Dempsey, MD, PhD, MPH, 13199 East Montview Blvd, Suite 300, Aurora, CO 80045, amanda.dempsey@ucdenver.edu.
Financial disclosures: None reported.
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DTaP5-IPV noninferior to DTaP5 plus IPV for fifth dose
The stand-alone diphtheria, tetanus, acellular, pertussis and inactivated poliovirus combination vaccine – DTaP5-IPV – is equivalent as a fifth dose to the separate DTaP5 plus IPV vaccines in children aged 4-6 years, according to a noninferiority study.
In a phase III, controlled, open-label study, 3,372 children who had completed the 4-dose infant/toddler vaccination were randomized to DTaP5-IPV plus MMR and varicella virus (VZV) vaccines, DTaP5+IPV with MMR and VZV, DTaP5-IPV with/without MMR/VZV, or DTaP5+IPV with/without MMR/VZV.
Michael J. Smith, MD, MSCE, of the University of Louisville (Ky.) and coauthors saw significantly higher pertussis antibody levels for all antigens in the group who received the DTaP5-IPV plus MMR and VZV vaccines than in the group who received the DTaP5+IPV with MMR and VZV. Twenty-eight days after the vaccine was given, booster responses ranged from 95% to 97% for the DTaP5-IPV group and from 87% to 93% in the DTaP5+IPV group.
Similarly, the DTaP5-IPV vaccine showed noninferiority in the booster response for antitetanus, antidiphtheria, and antipoliovirus antibody levels (Pediatr Infect Dis J. 2017 Mar;36[3]:319-25).
“Overall, the levels of immune responses described in both treatment groups in the current study are above the levels described in the Swedish infant efficacy study, which demonstrated 85% protective efficacy against World Health Organization–defined pertussis disease,” the authors wrote. “Thus, it is reasonable to conclude that protective efficacy against pertussis will be achieved when either DTaP5-IPV or DTaP5+IPV is given as a booster dose to children 4-6 years of age.”
The two vaccines showed a similar safety profile. The rate of immediate, unsolicited, adverse systemic events was 0.9% in the DTaP5-IPV group and 1% in the DTaP5+IPV group, while the rate of immediate, unsolicited, adverse reactions was 0.1% in the DTaP5-IPV group and 0.2% in the DTaP5+IPV group.
Solicited reactions also were similar between the two groups: 93% of participants who received DTaP5-IPV and 92% of those who received DTaP5+IPV reported reactions such as myalgia, malaise, pain, erythema, and change in limb circumference.
“This is consistent with the established safety profile of DTaP5+IPV vaccine, based on 16 years of postmarketing surveillance and more than 7 million doses distributed,” the authors wrote.
There were also three serious adverse events in the DTaP5-IPV group within 28 days of the vaccination – lobular pneumonia, asthma, and new-onset type 1 diabetes mellitus – but the investigator decided these were unrelated to vaccination.
The study was sponsored by Sanofi Pasteur, which manufactures both vaccines. Three authors were employees of Sanofi Pasteur, and one author declared funding from Sanofi Pasteur to present the study results at a meeting.
The stand-alone diphtheria, tetanus, acellular, pertussis and inactivated poliovirus combination vaccine – DTaP5-IPV – is equivalent as a fifth dose to the separate DTaP5 plus IPV vaccines in children aged 4-6 years, according to a noninferiority study.
In a phase III, controlled, open-label study, 3,372 children who had completed the 4-dose infant/toddler vaccination were randomized to DTaP5-IPV plus MMR and varicella virus (VZV) vaccines, DTaP5+IPV with MMR and VZV, DTaP5-IPV with/without MMR/VZV, or DTaP5+IPV with/without MMR/VZV.
Michael J. Smith, MD, MSCE, of the University of Louisville (Ky.) and coauthors saw significantly higher pertussis antibody levels for all antigens in the group who received the DTaP5-IPV plus MMR and VZV vaccines than in the group who received the DTaP5+IPV with MMR and VZV. Twenty-eight days after the vaccine was given, booster responses ranged from 95% to 97% for the DTaP5-IPV group and from 87% to 93% in the DTaP5+IPV group.
Similarly, the DTaP5-IPV vaccine showed noninferiority in the booster response for antitetanus, antidiphtheria, and antipoliovirus antibody levels (Pediatr Infect Dis J. 2017 Mar;36[3]:319-25).
“Overall, the levels of immune responses described in both treatment groups in the current study are above the levels described in the Swedish infant efficacy study, which demonstrated 85% protective efficacy against World Health Organization–defined pertussis disease,” the authors wrote. “Thus, it is reasonable to conclude that protective efficacy against pertussis will be achieved when either DTaP5-IPV or DTaP5+IPV is given as a booster dose to children 4-6 years of age.”
The two vaccines showed a similar safety profile. The rate of immediate, unsolicited, adverse systemic events was 0.9% in the DTaP5-IPV group and 1% in the DTaP5+IPV group, while the rate of immediate, unsolicited, adverse reactions was 0.1% in the DTaP5-IPV group and 0.2% in the DTaP5+IPV group.
Solicited reactions also were similar between the two groups: 93% of participants who received DTaP5-IPV and 92% of those who received DTaP5+IPV reported reactions such as myalgia, malaise, pain, erythema, and change in limb circumference.
“This is consistent with the established safety profile of DTaP5+IPV vaccine, based on 16 years of postmarketing surveillance and more than 7 million doses distributed,” the authors wrote.
There were also three serious adverse events in the DTaP5-IPV group within 28 days of the vaccination – lobular pneumonia, asthma, and new-onset type 1 diabetes mellitus – but the investigator decided these were unrelated to vaccination.
The study was sponsored by Sanofi Pasteur, which manufactures both vaccines. Three authors were employees of Sanofi Pasteur, and one author declared funding from Sanofi Pasteur to present the study results at a meeting.
The stand-alone diphtheria, tetanus, acellular, pertussis and inactivated poliovirus combination vaccine – DTaP5-IPV – is equivalent as a fifth dose to the separate DTaP5 plus IPV vaccines in children aged 4-6 years, according to a noninferiority study.
In a phase III, controlled, open-label study, 3,372 children who had completed the 4-dose infant/toddler vaccination were randomized to DTaP5-IPV plus MMR and varicella virus (VZV) vaccines, DTaP5+IPV with MMR and VZV, DTaP5-IPV with/without MMR/VZV, or DTaP5+IPV with/without MMR/VZV.
Michael J. Smith, MD, MSCE, of the University of Louisville (Ky.) and coauthors saw significantly higher pertussis antibody levels for all antigens in the group who received the DTaP5-IPV plus MMR and VZV vaccines than in the group who received the DTaP5+IPV with MMR and VZV. Twenty-eight days after the vaccine was given, booster responses ranged from 95% to 97% for the DTaP5-IPV group and from 87% to 93% in the DTaP5+IPV group.
Similarly, the DTaP5-IPV vaccine showed noninferiority in the booster response for antitetanus, antidiphtheria, and antipoliovirus antibody levels (Pediatr Infect Dis J. 2017 Mar;36[3]:319-25).
“Overall, the levels of immune responses described in both treatment groups in the current study are above the levels described in the Swedish infant efficacy study, which demonstrated 85% protective efficacy against World Health Organization–defined pertussis disease,” the authors wrote. “Thus, it is reasonable to conclude that protective efficacy against pertussis will be achieved when either DTaP5-IPV or DTaP5+IPV is given as a booster dose to children 4-6 years of age.”
The two vaccines showed a similar safety profile. The rate of immediate, unsolicited, adverse systemic events was 0.9% in the DTaP5-IPV group and 1% in the DTaP5+IPV group, while the rate of immediate, unsolicited, adverse reactions was 0.1% in the DTaP5-IPV group and 0.2% in the DTaP5+IPV group.
Solicited reactions also were similar between the two groups: 93% of participants who received DTaP5-IPV and 92% of those who received DTaP5+IPV reported reactions such as myalgia, malaise, pain, erythema, and change in limb circumference.
“This is consistent with the established safety profile of DTaP5+IPV vaccine, based on 16 years of postmarketing surveillance and more than 7 million doses distributed,” the authors wrote.
There were also three serious adverse events in the DTaP5-IPV group within 28 days of the vaccination – lobular pneumonia, asthma, and new-onset type 1 diabetes mellitus – but the investigator decided these were unrelated to vaccination.
The study was sponsored by Sanofi Pasteur, which manufactures both vaccines. Three authors were employees of Sanofi Pasteur, and one author declared funding from Sanofi Pasteur to present the study results at a meeting.
Key clinical point: The stand-alone DTaP5-IPV combination vaccine is equivalent as a fifth dose to the separate DTaP5 plus IPV vaccines in children aged 4-6 years.
Major finding:
Data source: A phase III, controlled, randomized open-label study in 3,372 children.
Disclosures: The study was sponsored by Sanofi Pasteur, which manufactures both vaccines. Three authors were employees of Sanofi Pasteur, and one author declared funding from Sanofi Pasteur to present the study results at a meeting.