Expanding pharmacist–patient care services to include vaccine promotion and administration within ambulatory clinics is an example of the expanding role of pharmacists and their contribution to primary care practice.
Seasonal influenza virus is associated with considerable morbidity and mortality each year in the United States.1 Most people recover from influenza illness without requiring medical attention; however, among those who are immunocompromised, influenza can cause severe illness, complications, and death. Patients who are immunocompromised experience greater morbidity and mortality from vaccine-preventable illnesses, including influenza, due to an insufficient immune response.2-4 Because of these risks, influenza vaccination is a critical strategy to prevent infection in this patient population.4,5
An immunocompromised state can result from HIV infection, solid organ transplant, hematopoietic malignancies, radiation, chemotherapy, or immunosuppressive or biologic therapy used to treat inflammatory disorders (eg, psoriasis, rheumatoid arthritis, ulcerative colitis, multiple sclerosis).6,7 The degree to which immunosuppressive drugs are associated with clinically significant immunodeficiencies is generally doserelated, and it varies according to the pharmacologic agent used.6
Vaccination is the most effective way to prevent influenza, pneumonia, meningitis, and hepatitis B in the immunocompromised population. Results from several studies, however, have demonstrated that influenza vaccination rates are suboptimal in this population.8,9 Pharmacists can address these gaps in influenza vaccinations in clinical practice and promote higher vaccination rates among vulnerable populations by providing informed recommendations.10 This review discusses considerations for use of influenza vaccines in patients who are immunocompromised and potential pharmacy interventions that can improve vaccination management in the ambulatory care setting.
Considerations for Patients Who Are Immunocompromised
The CDC’s Advisory Committee on Immunization Practices (ACIP) recommends that a single injection of a standard-dose influenza vaccine be given to all individuals 6 months and older every influenza season, with few exceptions.11 For persons 6 months and older who are immunocompromised, the Infectious Disease Society of America (IDSA) recommends use of an annual inactivated influenza vaccination, except in those who are very unlikely to respond (eg, those undergoing intensive chemotherapy or those receiving antibodies that target B cells within 6 months). Inactivated vaccines should be administered at least 2 weeks prior to immunosuppression. Live vaccines should not be administered to patients with immune deficiencies, as they may transmit the live virus to the immunodeficient person.6
Patients receiving biologic and nonbiologic immunosuppressants may have an insufficient response to influenza vaccination.7 Individuals who are immunocompromised may have lower or nonprotective responses to a standard dose of influenza vaccine, thereby increasing the risk of severe influenza and influenzarelated complications. Therefore, the degree of immunocompetence in a patient should be assessed by a physician to determine whether an immune response to vaccination is likely.12 Clinical laboratory measurements such as a complete blood count with differential (B- and T-lymphocyte counts), immunoglobulin levels, and more can be used to demonstrate the status of immunity.
In addition, household members and other close contacts of persons with altered immunocompetence should receive the influenza vaccination.6,12 Unless the individual who is immunocompromised needs a protective environment (ie, a specialized care area with increased air ventilation and filtration), their close contacts and healthy members of their household can be given the live attenuated influenza vaccine.12 ACIP and IDSA guidelines can provide additional insight on immunocompromised patients who are candidates for influenza vaccination.6,12
Strategies to improve the immunogenicity of influenza vaccines in immunocompromised persons are currently being studied. These include the use of adjuvanted vaccines, high-dose vaccines, booster doses, and intradermal vaccination and the temporary discontinuation of immunosuppressant regimens.7,13 However, results of larger, randomized controlled trials are necessary to further elucidate the impact of these strategies.7 These options have not yet been endorsed by national and global health authorities; until then, the use of existing vaccines should be encouraged for immunocompromised individuals and those who are in close contact with them.7 Ambulatory care pharmacists should assess patients’ vaccination status to improve vaccination rates and patient outcomes in immunocompromised populations.
Identifying Candidates for Vaccination
Vaccination rates tend to rise when the pharmacist joins other health care providers in providing vaccination education, facilitation, and administration.14 However, screening rates for vaccinations by ambulatory care pharmacists are low, indicating that ambulatory care pharmacists have an opportunity to become more involved in their practice site’s vaccination efforts.15,16
The CDC recommends that people receive an influenza vaccination by the end of October.11 Therefore, ambulatory care pharmacists should increase their efforts before influenza season to target all patients and especially those who are immunocompromised. Ambulatory care pharmacists will likely need to collaborate with both clinical and nonclinical staff to implement interventions. They can independently review patient records and immunization histories of those seen at clinics and use the ACIP recommendations to identify individuals who are at high risk of influenza and eligible for a seasonal influenza vaccination. Ambulatory care pharmacists also can perform chart reviews to target patients who are at high risk for influenza infection but who have no documentation of vaccination from the previous influenza season.
To maximize the impact of these chart reviews, ambulatory care pharmacists can target specific providers or departments within their clinic with a high volume of patients who are immunocompromised. These departments may include oncology, rheumatology, gastroenterology, dermatology, transplantation, infectious diseases, and neurology, where patients with cancer, rheumatoid arthritis, ulcerative colitis, psoriasis, history of transplant, HIV/AIDS, and multiple sclerosis, respectively, are seen. Efforts also can be focused on other health care providers who use therapies that may alter the immune response. A list of common immunosuppressants is listed in the Table.17
During chart review and prior to influenza vaccination, ambulatory care pharmacists should screen patients for any potential contraindications and precautions, including an allergy or a history of a serious reaction to an influenza vaccine. The development of a new screening tool may be necessary to identify candidates for influenza vaccination who are immunocompromised. Efforts should target all those who are immunocompromised and followed in the clinic or via telehealth appointments.
Incorporating Screenings Into Clinical Workflow
Both clinical and nonclinical staff in ambulatory clinics may assist with the screening, identification, and follow-up of patients who are immunocompromised and who need to receive an influenza vaccine. Pharmacists can provide annual training to staff in their ambulatory clinics regarding available influenza vaccine products. They can also educate clinical team members about considerations for immunizing patients and the importance of effective communication with patients about the influenza vaccine. A variety of strategies can be used to incorporate screening and identification into the workflow; these include staff education and provider and system-based interventions.
All staff in ambulatory clinics can play a role in promoting vaccination among individuals who are immunocompromised. Vaccine availability should be promoted by spreading information via letters to patients and their families and announcements on social media platforms or the clinic website. Front desk staff can share vaccine information sheets via email or during visit check-ins, whereas medical assistants and nurses can encourage vaccination before the patient is seen by the provider. If a patient declines vaccination, a pharmacist or provider can be asked to ease specific concerns, educate patients on the risk of influenza-related complications, and discuss common misconceptions about influenza vaccination. Nurses, pharmacists, and providers can administer vaccines to ease the workflow.
Clinicians should develop a checklist to use when screening patients to determine current vaccination status and medical eligibility. In addition, any potential barriers to vaccination (eg, vaccine hesitancy, safety or efficacy concerns, health literacy, transportation to clinic, cost) should be identified and addressed. This checklist for clinicians can be incorporated into the electronic health record (EHR) to increase influenza vaccination rates among patients who are immunocompromised. Pharmacists also can use wellness visits or sick visits to identify those patients who are due for influenza vaccination.
System-based interventions and technology can improve vaccination coverage. Technology-based interventions include reminder/recall, clinical decision support for providers in the EHR, and the use of social media. Reminder/recall can be used to notify patients through mail, telephone, text messages, and email that they are eligible or overdue for vaccinations.18 Some EHRs also offer text message reminders.
The use of clinical decision support delivered through the EHR is effective for providing alerts to facilitate clinical decision-making and improve patient care.18 Vaccine decision support and EHR-based clinical alert systems that target health care providers have proven effective in reducing missed opportunities and improving vaccination rates.18-20 A best practice alert (BPA) initiates a patientspecific warning when certain criteria are met and informs the health care provider of specific health recommendations that can be addressed during an encounter. For vaccinations, BPAs can help to identify appropriate patients, update their vaccination history in the EHR if it is unavailable, and record reasons why a patient declined vaccination.19
Pharmacists can work with providers to review influenza vaccination recommendations and create algorithms in the EHR to deliver accurate vaccine guidance. A sample BPA workflow is included in the Figure.20 In addition, the use of EHR-based provider order entry can facilitate workflow by transmitting vaccine orders and automatically documenting vaccine receipt.18
Staff also can generate reports using the EHR or insurance claims data to identify patients who have not been vaccinated. Pharmacists can work with clinical staff to determine a routine for regularly producing and reviewing reports that can identify patients who are due for annual influenza vaccination. Clinical staff can generate regular reports for patients taking immunosuppressants to ensure that they are vaccinated, ideally at least 2 weeks before they start therapy, and are counseled on the importance of receiving vaccination. Reports can be created by searching for several patient characteristics, such as specific chronic conditions and active chemotherapy or immunosuppressive regimens.
How to Track Patients
Gap reports can be leveraged to identify gaps in vaccinations among patients who are immunocompromised and those who are immunocompetent. These reports can be used to recognize the clinic’s vaccination coverage among these patients and identify potential opportunities to further increase vaccination rates. These reports can be generated on a regular basis; a member of the staff can be assigned to assess performance and reach out to eligible patients via phone call, mail, or other communication methods, as appropriate.
A patient population database can replace a spreadsheet to track vaccination status, analyze data, and report vaccination rates. Providers should receive reminders that identify patients who are unvaccinated to ensure implementation of the vaccination. These reminders should be sent on a recurring schedule as well as just prior to a patient’s upcoming visit.
Patients who are immunocompromised and who already received a vaccination may experience a reduced immune response. These patients should be closely monitored for signs and symptoms of influenza infection and told about when they should reach out to their provider.
Increasing Access to Care
Quality improvement initiatives should be reviewed and discussed each influenza season to promote influenza vaccinations for all patients and ensure proper follow-up. Staff should analyze the primary reasons for missed vaccinations and identify drivers necessary to achieve the desired goal. All clinical staff should be trained to check immunization status.
To increase access to care, patients who are at the highest risk of infection should be the priority, and any required follow-up should be scheduled before they leave the office. Public health campaigns using the internet and social media may increase awareness and vaccine uptake. In addition, vaccination-only, drive-up, and weekend or evening appointments can be offered to patients who are not available during normal clinic hours. Access to a seasonal flu clinic should be considered so patients can be vaccinated conveniently. Influenza vaccinations for siblings or for the entire family should be offered and administered during scheduled clinic visits, sick visits, or acute care visits.
To address potential barriers, influenza vaccinations should be offered at low or no cost, patient access to transportation should be considered, and translators for patients whose first language is not English should be available.
Pharmacists are well-equipped to promote and actively administer vaccines in all practice settings, including ambulatory care. Expanding pharmacist–patient care services to include vaccine promotion and administration within ambulatory clinics is an example of the expanding role of pharmacists and their contribution to primary care practice. Because patients who are immunocompromised are at greater risk of experiencing complications and dying from influenza, higher immunization rates involving this patient group should be a target for pharmacists in the ambulatory care setting. Pharmacist promotion of vaccination, use of clinical staff for support, and technological interventions may be useful in improving influenza vaccination rates among the immunocompromised population.
About the Author
Andrea Bush, PharmD, AAHIVP, is an ambulatory care pharmacy resident (postgraduate year 2) at Nova Southeastern University College of Pharmacy in Fort Lauderdale, Florida.
1. Disease burden of flu. CDC. October 4, 2022. Accessed April 25, 2023. https://www.cdc.gov/flu/about/burden/index.html
2. Memoli MJ, Athota R, Reed S, et al. The natural history of influenza infection in the severely immunocompromised vs nonimmunocompromised hosts. Clin Infect Dis. 2014;58(2):214-224. doi:10.1093/cid/cit725
3. Kunisaki KM, Janoff EN. Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses. Lancet Infect Dis. 2009;9(8):493-504. doi:10.1016/S1473-3099(09)70175-6
4. Bosaeed M, Kumar D. Seasonal influenza vaccine in immunocompromised persons. Hum Vaccin Immunother. 2018;14(6):1311-1322. doi:10.1080/21645515.2018.1445446
5. Zbinden D, Manuel O. Influenza vaccination in immunocompromised patients: efficacy and safety. Immunotherapy. 2014;6(2):131-139. doi:10.2217/imt.13.171
6. Rubin L, Levin M, Ljungman P, et al; Infectious Disease Society of America. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):e44-e100. doi:10.1093/cid/cit684
7. Caldera F, Mercer M, Samson SI, Pitt JM, Hayney MS. Influenza vaccination in immunocompromised populations: strategies to improve immunogenicity. Vaccine. 2021;39(suppl 1):A15-A23. doi:10.1016/j.vaccine.2020.11.037
8. Loubet P, Kernéis S, Groh M, et al. Attitude, knowledge and factors associated with influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency. Vaccine. 2015;33(31):3703-3708. doi:10.1016/j.vaccine.2015.06.012
9. Shapiro Ben David S, Goren I, Mourad V, Cahan A. Vaccination coverage among immunocompromised patients in a large health maintenance organization: findings from a novel computerized registry. Vaccines (Basel). 2022;10(10):1654. doi:10.3390/vaccines10101654
10. Langer R, Thanner M. Pharmacists’ seasonal influenza vaccine recommendations. Pharmacy (Basel). 2022;10(3):51. doi:10.3390/ pharmacy10030051
11. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices — United States, 2022-23 influenza season. CDC. August 25, 2022. Accessed May 18, 2023. https://www.cdc.gov/mmwr/volumes/71/rr/rr7101a1.htm
12. Altered immunocompetence. CDC. February 10, 2023. Accessed May 18, 2023. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html
13. Leibovici Weissman Y, Cooper L, Sternbach N, Ashkenazi-Hoffnung L, Yahav D. Clinical efficacy and safety of high dose trivalent influenza vaccine in adults and immunosuppressed populations - a systematic review and meta-analysis. J Infect. 2021;83(4):444-451. doi:10.1016/j.jinf.2021.08.028
14. Isenor JE, Edwards NT, Alia TA, et al. Impact of pharmacists as immunizers on vaccination rates: a systematic review and meta-analysis. Vaccine. 2016;34(47):5708-5723. doi:10.1016/j.vaccine.2016.08.085
15. Knapp KK, Blalock SJ, Black BL. ASHP survey of ambulatory care responsibilities of pharmacists in managed care and integrated health systems--2001. Am J Health Syst Pharm. 2001;58(22):2151-2166. doi:10.1093/ajhp/58.22.2151
16. Knapp KK, Okamoto MP, Black BL. ASHP survey of ambulatory care pharmacy practice in health systems—2004. Am J Health Syst Pharm. 2005;62(3):274-284. doi:10.1093/ajhp/62.3.274
17. Immunocompromised travelers. Yellow book 2024. CDC. May 1, 2023. Accessed May 16, 2023. https://wwwnc.cdc.gov/travel/yellowbook/2024/additional-considerations/immunocompromised-travelers
18. Stockwell MS, Fiks AG. Utilizing health information technology to improve vaccine communication and coverage. Hum Vaccin Immunother. 2013;9(8):1802-1811. doi:10.4161/hv.25031
19. McAdam-Marx C, Tak C, Petigara T, et al. Impact of a guideline-based best practice alert on pneumococcal vaccination rates in adults in a primary care setting. BMC Health Serv Res. 2019;19(1):474. doi:10.1186/s12913-019-4263-2
20. Ledwich LJ, Harrington TM, Ayoub WT, Sartorius JA, Newman ED. Improved influenza and pneumococcal vaccination in rheumatology patients taking immunosuppressants using an electronic health record best practice alert. Arthritis Rheum. 2009;61(11):1505-1510. doi:10.1002/art.24873