Approximately 2 to 3 million deaths worldwide are avoided each year because of vaccinations.1 This has led to a 100% decrease in smallpox infections; a greater than 97% decrease in measles, mumps, and rubella (MMR) infection; and a 99% decrease in Haemophilus influenzae virus infections since the 20th century.2 Although vaccine distribution and availability have increased internationally, about 14% of children worldwide are not fully vaccinated for polio, diphtheria, tetanus, pertussis, and measles diseases.3 Approximately 1.5 million individuals die from vaccine preventable diseases each year, and, as frontline providers, pharmacists are well positioned to improve vaccination rates and educate individuals about the risks and benefits of immunizations.4

A total of 15 vaccinations are recommended and available for the pediatric population, administered in intervals from the time they are born to the age of 18.5 With the increasing rates of coronavirus disease 2019 (COVID-19) infections, protection against other infectious diseases is paramount.6 Despite the looming uncertainty of whether or not children will return to the classroom or remain educated at home, it is still important to remind parents that as the 2020-2021 school year begins, they should confirm their children are up-to-date on their vaccinations to ensure they are adequately protected.

VACCINE SAFETY
Questions regarding vaccine safety have arisen in recent decades, leading parents to consider the benefits and risks of vaccinating children.7 According to the results of a 2019 survey by Kempe and colleagues, approximately 1 in 15 US parents are hesitant about routine vaccination.8 Pharmacists can refer to the CDC website for patient pamphlets and resources that can help guide discussions regarding benefits of vaccination. The CDC’s Vaccinate With Confidence campaign provides educational materials for providers and families to ensure all individuals feel safe and confident in their decision to vaccinate.9

REGULATION AND MONITORING OF VACCINES
The safety and efficacy of vaccinations are regulated in the United States through the FDA’s Center for Biologics Evaluation and Research division.10 Vaccine development and testing follow similar guidance to that for the approval of drugs and biologics.11 Each new vaccine sponsor must go through extensive clinical trial testing and monitoring to ensure vaccines remain safe and effective both prior to distribution and while in clinical use.11

VACCINES AND AUTISM
Concerns regarding vaccines’ association with autism have led to controversy regarding the safety and efficacy of routine childhood vaccinations; however, current literature does not support a correlation between vaccines and the risk of developing autism spectrum disorders.7 Specific theories surrounding autism spectrum disorders and vaccines include the possible risk of an MMR vaccine potentiating the entrance of encephalopathic proteins into the body, the preservative thimerosal and its effect on the nervous system, and the idea that multiple vaccinations overload a child’s immune system, thereby rendering them immunocompromised.7,12 Evidence from epidemiologic studies does not support these hypotheses, and there are no current studies demonstrating a direct correlation between vaccines and autism spectrum disorders.13 Parents should be educated regarding the current literature and the recommendation to vaccinate children against vaccine preventable diseases.

VACCINES AND GUILLAIN-BARRÉ SYNDROME
Incidence of Guillain-Barré syndrome (GBS) following vaccination with influenza vaccines has led to controversy and concern from parents about vaccinating their children.14 Currently, there is a lack of adequate data showing a clear association between influenza vaccination and GBS that is greater than the idiopathic incidence of the syndrome in the normal population.14-16 Study results also have shown a potential increased risk of GBS following infection with the influenza virus itself.17

National guidelines are in favor of influenza vaccination in pediatric patients because the risk of GBS in this group is low, whereas the risk of influenza complications can be high.18 Expert opinion and national agencies such as the Advisory Committee on Immunization Practices (ACIP) and the CDC agree that the benefit of vaccination is greater than the potential risk, given a lack of strong evidence for an association between GBS and influenza vaccines.19 For parents who are concerned about GBS with the influenza vaccination, clinicians should discuss the current data and present both the benefits and potential risks of vaccination.

SAFETY OF MULTIPLE VACCINES IN PEDIATRIC PATIENTS
Safety concerns about the use of multiple vaccinations in children have increased in the last several decades, leading a minority of parents to question the benefit of immunizing their children repeatedly and with multiple vaccines at the same time.7 Evidence from several studies and reviews refutes the idea that infant and pediatric patients’ immune systems will be overwhelmed or weakened by multiple vaccinations.20 The American Academy of Pediatrics supports the immunization recommendations by the CDC and ACIP and recommends following guideline-directed immunization schedules to protect against vaccine preventable diseases.21 Pharmacists can refer to the CDC’s “Common Vaccine Safety Questions and Concerns” web page for additional information and educational material to give parents to ensure that all individuals are informed regarding the risks and benefits of immunizations.22

BACK-TO-SCHOOL VACCINATIONS TO CONSIDER
Back-to-school vaccinations provide protection for children against diseases such as chickenpox, hepatitis B, measles, mumps, rubella, tetanus, meningitis, influenza, and more.23 Ensuring children receive the appropriate immunizations and are up-to-date with their vaccination schedules is essential to conferring immunity. The COVID-19 pandemic has led to a decrease in outpatient pediatric visits and fewer vaccine doses being administered because of shelter-in-place orders.6,24 Health care providers must stay ahead of immunizations and ensure children do not miss their scheduled well visits.6,24 (For a complete list of vaccination schedules, refer to the “Recommended Child and Adult Immunization Schedules” on pages 34–35 in this issue.) The next section highlights routine vaccinations that parents should consider as the school year begins.

TETANUS
Tetanus is a serious and life-threatening disease that can result in significant morbidity and mortality if not treated immediately. Approximately 1 in 5 individuals die when infected with tetanus toxin, and those who survive may experience long-term sequelae of the disease.25 Tetanus toxin is found in soil, dust, and manure, and enters the body through breaks in the skin via cuts, punctures, burns, and bites.26 If left untreated, tetanus toxin can lead to debilitating muscle stiffness and can manifest as jaw cramping, difficulty breathing, seizures, fevers, paralysis, and death in severe circumstances.27

Immunization against tetanus is available through the scheduled diphtheria, tetanus, and pertussis (DTaP) vaccination and a booster tetanus, diphtheria, and pertussis (Tdap) vaccination for continued immunity.25 Both the DTaP and Tdap vaccines contain protection against diphtheria and pertussis (whooping cough).25 DTaP is provided in 5 scheduled doses, with the first dose given at 2 months of age and the fifth dose given between the ages of 4 and 6 years.25 A booster dose is administered between the ages of 11 and 12 years in the form of Tdap.25 Subsequent doses are given if potential exposure to the toxin occurs.28

The potential adverse events (AEs) that may occur following DTaP and Tdap vaccinations include injection-site reactions such as redness, swelling, and pain and, rarely, fever and vomiting post injection.25 Serious AEs are rare but should be monitored. If children are significantly febrile (≥105°F) and experience muscle jerking, twitching, and/or seizures, caregivers should seek emergency medical attention.25 Although these AEs are rare, providers should educate patients to monitor and act accordingly in the event they may occur.

MENINGITIS
Since the 1990s, infections of meningococcal disease have declined, with approximately 330 cases recorded in 2018.2,29 Vaccination against Neisseria meningitidis has been contributing to this decline since 2005, and eligible patients can be educated regarding the benefits of immunization. Populations at greater risk of meningococcal disease are pediatric patients younger than 1 year of age and adolescents and young adults between the ages of 16 and 23 years.2,29

There are currently 12 serogroups of N meningitidis in existence, with the A, B, C, W135, and Y groups having the highest incidence of infection in North America.2 Routine vaccination with the MenACWY vaccine—which protects against meningococcal disease caused by serogroups A, C, W, and Y—is recommended in a 2-dose schedule, with the first dose administered between the ages of 11 and 12 years and the second dose administered at age 16.30 The MenB vaccine provides protection against serogroup B of N meningitidis.30 Individuals between the ages of 16 and 18 years are encouraged to get the MenB vaccination.30

Both the MenACWY and MenB vaccines are safe, with minimal AEs such as injection-site reactions, malaise, and fever occurring in about 50% of recipients.31 The MenB vaccine may also cause headaches, muscle or joint pain, nausea, and diarrhea.31 Parents and guardians can be reassured that AEs resolve in 3 to 5 days and serious AEs rarely occur.30 Because of the risk of mortality with meningococcal infection, vaccination provides a substantial benefit.

INFLUENZA
The full impact of the influenza virus varies from year to year; however, it still causes considerable morbidity and mortality around the world. Between 2010 and 2018, there were an estimated 9.3 to 45 million positive influenza infections resulting in 140,000 to 810,000 hospitalizations and 12,000 to 61,000 deaths.32 Vaccination against influenza provides 1 mechanism of preventing infection and reducing morbidity and mortality from the disease.33 The influenza vaccine is administered annually, and its composition is modified to reflect the predicted strains of influenza that will most likely be prevalent during the influenza season (see “ACIP Updates Vaccine Recommendations for 2020: What Pharmacists Need to Know” on page 8 for strains included in the 2020-2021 influenza vaccine).33,34

The CDC, in consultation with ACIP, recommends that all individuals 6 months of age and older be vaccinated against influenza, unless there are contraindications, such as a severe allergy to a vaccine component or a severe allergic reaction to a previous dose of an influenza vaccine, that preclude vaccination.35,36 The influenza vaccine is available as both an inactivated vaccine and a live, attenuated vaccine.35 The live, attenuated vaccine should only be administered to healthy individuals between the ages of 2 and 49 years.37 The influenza vaccine’s efficacy is highly dependent on the prediction of virus strains in the upcoming influenza season.38 When the predicted strains are well matched to the strains circulating within the community during the high season, potentially millions of individuals can be protected from the virus and related complications. During the 2017-2018 season, for example, which was classified as being highly severe across all age groups and was the longest in recent years, with its influenzalike illness activity at or above the national baseline for 19 weeks, an estimated 6.7 million influenza infections, 91,000 influenza-associated hospitalizations, and 5700 influenza-associated deaths were prevented by influenza vaccinations.38,39

In pediatric populations, evidence from 2010 through 2014 showed a 51% reduction in influenza-related deaths in high-risk patients and a 65% reduction among healthy children because of influenza immunizations.40 Such evidence highlights the importance of vaccination against influenza in pediatric patients. Generally, current vaccines are most effective in preventing illness from influenza B and influenza A (H1N1) viruses.38 The vaccines are typically less efficacious against influenza A viruses of the H3N2 type.38 Variability in the efficacy of the influenza vaccine is due to some unpredictability regarding the circulating strains of influenza each season. 38 Health care providers can educate patients about the need for vaccination each year and explain the variation in prevention from 1 season to another to address any concerns regarding lack of effectiveness. If the influenza vaccine was not well matched in the prior season, this does not mean the current vaccine will be ineffective as it may still provide some protection.38

HEPATITIS B
Hepatitis B infections lead to approximately 780,000 deaths each year because of associated complications such as liver cirrhosis and liver cancer.41 Currently available hepatitis B vaccines have an average efficacy of 95% and provide immunity for approximately 20 years or longer.2,41 Hepatitis B vaccination is recommended in a 3-dose series starting at birth. For individuals who require catch-up vaccination, the 3-dose series should be initiated at intervals of 0, 1 to 2, and 6 months.42 For adolescents between the ages of 11 and 15 years who require catch-up vaccination, a 2-dose hepatitis B vaccine (Recombivax HB) may be administered 4 months apart.42 Adolescents aged 18 or older may receive either a 2-dose series with Heplisav-B, administered 4 weeks apart; a 3-dose series with Twinrix at 0, 1, and 6 months; or a 4-dose series with Twinrix at 0, 7, and 21 to 30 days followed by a fourth dose at 12 months.42 Vaccination against hepatitis B is safe and effective and associated with minimal AEs such as low-grade fever and injection-site pain.43

ADDITIONAL ACTIONS TO REDUCE THE RISK OF INFECTION
In addition to routine vaccination, maintaining good hygiene is essential in preventing respiratory infections that can be transmitted through droplet secretions.44 The CDC recommends frequent handwashing with soap and water for at least 20 seconds as a means to prevent contamination and the spread of both influenza and COVID-19.38,44 When soap and water are not available, providers can recommend that their patients use hand sanitizer containing at least 60% alcohol.44 Pharmacists also can caution their patients to avoid touching their eyes, nose, and mouth as much as possible. Additionally, they should advise individuals who present with signs or symptoms of infection to contact their health care providers and minimize contact with others to avoid community spread of disease.45

CONCLUSIONS
With the lack of immunization against COVID-19, it is of the utmost importance that communities remain as safe and healthy as possible. Pharmacists can aid in this effort by incorporating vaccine education into their daily practice to inform parents and guardians about the need to immunize their children in order to stay protected from vaccine-preventable diseases.
 
LUMA MUNJY, PHARMD, is an assistant professor of pharmacy practice at the Chapman University School of Pharmacy in Irvine, California. 


REFERENCES
  1. Immunization coverage. World Health Organization. July 15, 2020. Accessed August 6, 2020. https://www.who.int/news-room/fact-sheets/detail/ immunization-coverage
  2. Hamborsky J, Kroger A, Wolfe C, eds. Epidemiology and Prevention of Vaccine preventable Diseases. 13th ed. CDC; 2015.
  3. Peck M, Gacic-Dobo M, Diallo MS, Nedelec Y, Sodha SV, Wallace AS. Global routine vaccination coverage, 2018. MMWR Morb Mortal Wkly Rep. 2019;68(42):937-942. doi:10.15585/mmwr.mm6842a1
  4. Immunization. World Health Organization. December 5, 2019. Accessed August 6, 2020. https://www.who.int/news-room/facts-in-pictures/detail/immunization
  5. Table 1. Recommended child and adolescent immunization schedule for ages 18 years or younger, United States, 2020. CDC. Updated February 3, 2020. Accessed August 6, 2020. https://www.cdc.gov/vaccines/schedules/hcp/ imz/child-adolescent.html
  6. Information for pediatric health care providers. CDC. Updated July 17, 2020. Accessed August 6, 2020. https://www.cdc.gov/coronavirus/2019-ncov/hcp/pediatric-hcp.html
  7. DeStefano F, Bodenstab HM, Offit PA. Principal controversies in vaccine safety in the United States. Clin Infect Dis. 2019;69(4):726-731. doi:10.1093/ cid/ciz135
  8. Kempe A, Saville AW, Albertin C, et al. Parental hesitancy about routine childhood and influenza vaccinations: a national survey. Pediatrics. 2020;146(1):e20193852. doi:10.1542/peds.2019-3852
  9. Vaccinate with confidence. CDC. Updated October 30, 2019. Accessed August 6, 2020. https://www.cdc.gov/vaccines/partners/vaccinate-with-confidence.html
  10. Vaccines. FDA. Updated June 22, 2020. Accessed August 6, 2020. https:// www.fda.gov/vaccines-blood-biologics/vaccines
  11. Vaccine product approval process. FDA. Updated January 30, 2018. Accessed August 6, 2020. https://www.fda.gov/vaccines-blood-biologics/developmentapproval-process-cber/vaccine-product-approval-process
  12. DeStefano F, Shimabukuro TT. The MMR vaccine and autism. Annu Rev Virol. 2019;6(1):585-600. doi:10.1146/annurev-virology-092818-015515
  13. Vaccines do not cause autism. CDC. Updated March 26, 2020. Accessed August 6, 2020. https://www.cdc.gov/vaccinesafety/concerns/autism.html
  14. Haber P, Sejvar J, Mikaeloff Y, DeStefano F. Vaccines and Guillain-Barré syndrome. Drug Saf. 2009;32(4):309-323. doi:10.2165/00002018-200932040- 00005
  15. Haber P, DeStefano F, Angulo FJ, et al. Guillain-Barré syndrome following influenza vaccination. JAMA. 2004;292(20):2478-2481. doi:10.1001/ jama.292.20.2478
  16. Souayah N, Yacoub HA, Khan HM, et al. Guillain-Barré syndrome after influenza vaccination in the United States, a report from the CDC/FDA vaccine adverse event reporting system (1990-2009). J Clin Neuromuscul Dis. 2012;14(2):66-71. doi:10.1097/CND.0b013e31824db14e
  17. Vellozzi C, Iqbal S, Broder K. Guillain-Barre syndrome, influenza, and influenza vaccination: the epidemiologic evidence. Clin Infect Dis. 2014;58(8):1149- 1155. doi:10.1093/cid/ciu005
  18. Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2019–2020. Pediatrics. 2019;144(4):e20192478. doi:10.1542/peds.2019-2478
  19. Guillain-Barré Syndrome. CDC. Updated June 28, 2019. Accessed August 6, 2020. https://www.cdc.gov/vaccinesafety/concerns/guillain-barre-syndrome.html
  20. Multiple vaccines and the immune system. CDC. Updated October 1, 2018. Accessed August 6, 2020. https://www.cdc.gov/vaccinesafety/concerns/multiple-vaccines-immunity.html
  21. Committee on Infectious Diseases. Recommended childhood and adolescent immunization schedule: United States, 2020. Pediatrics. 2020;145(3):e20193995. doi:10.1542/peds.2019-3995
  22. Common vaccine safety questions and concerns. CDC. Updated June 7, 2016. Accessed August 6, 2020. https://www.cdc.gov/vaccinesafety/concerns/index. html
  23. Diseases & the vaccines that prevent them. CDC. Updated August 5, 2019. Accessed August 6, 2020. https://www.cdc.gov/vaccines/parents/diseases/index. html
  24. Santoli JM, Lindley MC, DeSilva MB, et al. Effects of the COVID-19 pandemic on routine pediatric vaccine ordering and administration—United States, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(19):591-593. doi:10.15585/ mmwr.mm6919e2
  25. Vaccine (shot) for tetanus. CDC. Updated August 2, 2019. Accessed August 6, 2020. https://www.cdc.gov/vaccines/parents/diseases/tetanus.html
  26. About tetanus. CDC. Updated February 28, 2019. Accessed August 6, 2020. https://www.cdc.gov/tetanus/about/index.html
  27. Symptoms & complications. CDC. Updated February 28, 2019. Accessed July 23, 2020. https://www.cdc.gov/tetanus/about/symptoms-complications.html
  28. Tdap (tetanus, diphtheria, pertussis) VIS. CDC. Updated April 1, 2020. Accessed August 6, 2020. https://www.cdc.gov/vaccines/hcp/vis/vis-statements/ tdap.html
  29. Surveillance. CDC. Updated May 31, 2019. Accessed August 6, 2020. https:// www.cdc.gov/meningococcal/surveillance/index.html
  30. Vaccine (shot) for meningococcal disease. CDC. Updated August 2, 2019. Accessed August 6, 2020. https://www.cdc.gov/vaccines/parents/diseases/mening. html
  31. Meningococcal vaccination. CDC. Updated April 8, 2020. Accessed August 6, 2020. https://www.cdc.gov/meningococcal/vaccine-info.html
  32. Disease burden of influenza. CDC. Updated April 17, 2020. Accessed August 6, 2020. https://www.cdc.gov/flu/about/burden/index.html
  33. FDA’s critical role in ensuring supply of influenza vaccine. FDA. Updated March 1, 2019. Accessed August 6, 2020. https://www.fda.gov/consumers/consumer-updates/fdas-critical-role-ensuring-supply-influenza-vaccine
  34. Influenza vaccines. World Health Organization. Accessed August 6, 2020. https://www.who.int/immunization/research/development/influenza/en/
  35. Prevention and control of seasonal influenza with vaccines, 2019-20. CDC. Updated October 3, 2019. Accessed August 6, 2020. https://www.cdc.gov/flu/ professionals/acip/
  36. Seasonal influenza vaccine safety: a summary for clinicians. CDC. Updated September 18, 2019. Accessed August 6, 2020. https://www.cdc.gov/flu/ professionals/vaccination/vaccine_safety.htm
  37. 2019-20 summary of recommendations. CDC. Updated August 9, 2019. Accessed August 6, 2020. https://www.cdc.gov/flu/professionals/acip/summary/ summary-recommendations.htm
  38. Vaccine effectiveness: how well do the flu vaccines work? CDC. Updated January 3, 2020. Accessed August 6, 2020. https://www.cdc.gov/flu/vaccines -work/vaccineeffect.htm
  39. Summary of the 2017-2018 influenza season. CDC. Updated September 5, 2019. Accessed August 6, 2020. https://www.cdc.gov/flu/about/season/fluseason-2017-2018.htm
  40. Flannery B, Reynolds SB, Blanton L, et al. Influenza vaccine effectiveness against pediatric deaths: 2010-2014. Pediatrics. 2017;139(5):e20164244. doi:10.1542/peds.2016-4244
  41. Hepatitis B. World Health Organization. Updated January 24, 2018. Accessed August 6, 2020. https://www.who.int/immunization/diseases/hepatitisB/en/
  42. Table 2. Catch-up immunization schedule for persons aged 4 months–18 years who start late or who are more than 1 month behind, United States, 2020. CDC. Updated February 3, 2020. Accessed August 6, 2020. https://www.cdc.gov/ vaccines/schedules/hcp/imz/catchup.html#table-catchup
  43. Hepatitis B vaccines. CDC. Updated July 9, 2020. Accessed August 6, 2020. https://www.cdc.gov/vaccinesafety/vaccines/hepatitis-b-vaccine.html #anchor_1584968266859
  44. How to protect yourself & others. CDC. Updated July 31, 2020. Accessed August 6, 2020. https://www.cdc.gov/coronavirus/2019-ncov/prevent-gettingsick/prevention.html
  45. \What to do if you are sick. CDC. May 8, 2020. Accessed August 6, 2020. https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/steps-when-sick.html