Sage Journals: Discover world-class research

Abstract

Although influenza can lead to significant morbidity and mortality in solid organ transplant recipients, its vaccination rate among solid organ transplant recipients remains low. This study evaluates influenza vaccination among solid organ transplant recipients and compares rates before and after introducing a one-stop influenza vaccination service. In a prospective study on influenza vaccination among solid organ transplant recipients followed up from December 2014 to February 2015, 308 solid organ transplant recipients were surveyed, of which 25.0% received their annual influenza vaccination previously. Of those who have not, 60.6% were vaccinated after the education. We found most solid organ transplant recipients to be unaware of the importance of annual influenza vaccination (66.7%). Recipients with a shorter number of years post-transplant (odds ratio (OR) 0.95, 95% confidence interval (CI) 0.91–0.99) and a history of diabetes (OR 0.48, 95% CI 0.23–0.94) were more likely to receive vaccination. The incidence of influenza infection post-implementation was lower (4.9%, 2.6%; P=0.668). Solid organ transplant recipients who had had been vaccinated were associated with a lower incidence of influenza (OR 0.19, 95% CI 0.04–0.99). We conclude that the implementation of the one-stop influenza vaccination service had increased the vaccination uptake rate among solid organ transplant recipients by addressing the barriers and increasing accessibility.

Keywords

Influenza vaccination transplantation

Introduction

Influenza can lead to significant morbidity and mortality in solid organ transplant (SOT) recipients due to a greater risk of developing influenza-related complications compared to the general population.¹ Studies in SOT recipients have reported a rate of mortality associated with influenza infection ranging from 4% to 8% and severe complications in 12% to 20% of cases.^1,2 SOT recipients may have a greater viral burden and prolonged virus shedding as compared to the immunocompetent population.³ In addition to the usual complications of influenza, influenza infection has been associated with an increased risk of rejection in SOT recipients.⁴

As such the guideline of the American Society of Transplantation (AST) recommends annual trivalent inactivated influenza vaccination for all SOT recipients after transplantation.⁵ However, the reported rate of influenza vaccination among SOT recipients has been low at 52 % in three United States (US) health organisations between 1995 and 2005.⁶ Significant predictors of post-transplant vaccination identified included older age at transplant, receiving vaccination pre-transplant and year of transplant. However, the uptake rate of influenza vaccination in SOT recipients and the reasons for not vaccination remains unknown in the local population.

At Singapore General Hospital (SGH), SOT recipients are recommended to receive annual influenza vaccination in accordance with the recommendations from AST. Transplant coordinators would remind physicians on a written memo when the vaccination is due. If deemed fit for the vaccination, patients would then be referred to the community doctor to receive the vaccination. In December 2014, the SGH transplant centre introduced a one-stop influenza vaccination service. SOT recipients could receive the vaccination on the same day after their routine outpatient clinic visit. For those SOT recipients who did not wish to be vaccinated, pharmacists and nurses educated those using standardised educational materials from the Health Promotion Board, Singapore⁷ on the importance of annual influenza vaccination, potential side effects and management of side effects. Concerns raised by patients regarding influenza vaccination were also addressed.

As such, the vaccination rates are postulated to increase after implementation of the one-stop service. In addition, through identifying reasons for not receiving the vaccination, patient education can be tailored to increase the understanding of the importance of vaccination.

The primary objectives are to evaluate the rate of influenza vaccination among SOT recipients followed up at the SGH outpatient transplant centre at baseline in the past 12 months and to compare the rates of vaccination after patient education and implementation of the one-stop influenza vaccination service. The secondary objectives are to identify reasons for not receiving annual influenza vaccination among SOT recipients, to evaluate the incidence of influenza infection post-implementation and to identify factors that influence the rate of vaccination and the incidence of influenza infection.

Materials and methods

Study design

This is a single-centre prospective study on influenza vaccination among all SOT recipients followed up at SGH from December 2014 to February 2015. The study was approved by the Singhealth Centralised Institutional Review Board (CIRB).

A one-stop influenza vaccination service was implemented in the outpatient transplant centre where SOT recipients could receive the vaccination during their outpatient clinic visit. The influenza vaccine, which was available at the transplant centre, was then administered by nurses after the physician prescribed it at the same outpatient clinic visit. Survey forms were administered to collect data on the rate of influenza vaccination among SOT recipients before implementation of the one-stop service and the reasons for not receiving influenza vaccination annually. Pharmacists and nurses educated SOT recipients who refused the vaccination using standardised educational materials from the Health Promotion Board, Singapore.⁷

Patient selection

SOT recipients aged 21 years and older and followed up at SGH during the recruitment period were included in the study. SOT recipients were excluded from the study if they were ill or deemed unfit for the influenza vaccination by a physician, allergic or had hypersensitivity to any component of the formulation, or less than 6 months post-transplant.

Baseline data

SOT recipients’ demographics such as age, gender, type of SOT, year of SOT and comorbidities were collected from the electronic medical records.

Influenza vaccination status was determined in two ways. Records of vaccinations were accessed via the Prescription Manager (RxManager) to collect any data of vaccination administered prior to the clinic visit. SOT recipients were also asked in the survey form administered if they had received an influenza vaccine in the past year at a private general practitioner to capture data not reflected in RxManager. The number and types of immunosuppressant that the SOT recipients were receiving at the time of the clinic visit were also recorded.

Clinical endpoints

Influenza infection was defined as a positive influenza respiratory swab and/or initiation of treatment for influenza infection such as oseltamivir. The incidence of influenza infection was collected for the period from one year before to one year after the influenza vaccination at the clinic visit.

Statistical analysis

Statistical analysis of the data was performed with SPSS version 23.0 using descriptive statistics.

Comparisons of the rate of vaccination and incidence of influenza infection before and after implementation of patient education and the one-stop vaccination service were performed using the paired t-test. Logistic regression was utilised to determine the factors that affect influenza vaccination rates and the incidence of influenza infection among the SOT recipients. A P value of less than 0.05 was considered to be statistically significant.

Results

Study participants and baseline demographics

A total of 308 SOT recipients were surveyed for the period of December 2014 to February 2015. The demographics and baseline characteristics of the SOT recipients are shown in Table 1.

Table 1.

Baseline characteristics for SOT recipients.

Baseline variables (N=308)
Age, years (±SD)	55.3 ± 10.9
Male gender (%)	167 (54.2)
Chinese ethnicity (%)	251 (81.5)
Type of organ transplant (%)
Kidney (%)	269 (87.3)
Liver (%)	39 (12.7)
Time post-transplant, years (±SD)	10.8 ± 7.3
Comorbidities
Chronic heart disease (%)	50 (16.2)
Chronic kidney disease (%)	45 (14.6)
Chronic liver disease (%)	31 (10.1)
Chronic pulmonary disease (%)	7 (2.3)
Diabetes mellitus (%)	79 (25.6)
Influenza vaccination (%)	77 (25.0)
Influenza infection (%)	15 (4.9)

SOT: solid organ transplant.

The mean age of SOT recipients included in the study was 55 years old, with the majority being Chinese. The majority of the SOT recipients in the study received a kidney transplant. The mean number of years post-transplant among the SOT recipients surveyed was approximately 10 years.

Primary outcome

The primary outcome was to compare the vaccination rate before and after patient education and the one-stop vaccination service. Only 77(25.0%) SOT recipients received influenza vaccination in the previous year. Baseline influenza vaccination rates among SOT recipients in our transplant centre were lower than reported rates.⁶ After implementation of the service, 140 out of 231 SOT recipients (60.6%) who had not received influenza vaccination in the past year were vaccinated.

Secondary outcomes

Barriers to vaccination

The secondary objective was to identify potential barriers to annual vaccination. A survey was conducted to investigate the reasons why SOT recipients did not receive annual vaccination. The survey questions are listed in Table 2.

Table 2.

List of survey questions and SOT recipients’ response (n=231) in percentage (%).

Survey questions	Percentage of SOT recipients (%)	Potential barrier
I was not informed to receive the vaccination	66.7	Knowledge gap
I don’t think it is necessary to receive the vaccination	32.9
I am afraid that there will be side effects from the vaccination	8.7
I don’t know I can get the vaccination in the clinic	8.2	Accessibility
I find it is too troublesome to receive the vaccination	2.2	Accessibility
The cost of the vaccination is too expensive	4.3	Cost

SOT: solid organ transplant.

The majority of the SOT recipients reported that they were not informed to receive vaccination (66.7%), they did not think that the vaccination was necessary (32.9%) and they were concerned about the side effects of the vaccination (8.7%). This suggests that a high proportion of SOT recipients had knowledge gaps on the importance of influenza vaccination.

The other barriers identified included poor accessibility as some SOT recipients reported that they found it too troublesome to obtain the vaccination from their primary physician (2.2%) and they were not aware that the transplant centre provides a vaccination service (8.2%). The cost of vaccination was also a concern among SOT recipients (4.3%).

Logistic regression was utilised to determine the factors that affect influenza vaccination rates among the SOT recipients. The variables in Table 3 were included in the model. The number of years post-transplant and a history of diabetes were found to be significant factors that influenced the vaccination rate (P<0.05). The SOT recipients with a shorter post-transplant time were more likely to receive vaccination with an odds ratio (OR) of 0.95 (95% confidence interval (CI) 0.91–0.99). SOT recipients with a history of diabetes were more likely to be vaccinated (OR 0.48, 95% CI 0.23–0.94).

Table 3.

Logistics regression of factors that affect influenza vaccination rates.

Variables	Odds ratio	95% CI	P value
Type of organ transplant	1.16	0.34–3.90	0.816
Age	0.99	0.96–1.02	0.430
Gender	0.72	0.41–1.28	0.264
Post-transplant years	0.95	0.91–0.99	0.017*
Previous influenza infection	0.67	0.17–2.60	0.565
Number of immunosuppressants	1.05	0.63–1.77	0.850
Comorbidities
Chronic heart disease	1.79	0.80–3.99	0.156
Chronic kidney disease	1.39	0.63–3.05	0.413
Chronic liver disease	0.95	0.33–2.76	0.921
Chronic pulmonary disease	1.97	0.37–10.46	0.426
Diabetes mellitus	0.48	0.23–0.94	0.033*

CI: confidence interval.

P<0.05.

Influenza infection

The other secondary outcomes include comparing the incidence of influenza infection before and after the implementation of patient education and the one-stop vaccination service.

The number of SOT recipients who received treatment for influenza or had a positive influenza swab were 15(4.9%) and eight (2.6%) before and after the implementation of the service but the reduction was not statistically significant (P=0.668).

In addition, logistic regression was utilised to find factors that affect the incidence of influenza infection (Table 4) with adjustment for gender, age and type of organ transplant. SOT recipients who had previous vaccination have been associated with a lower incidence of influenza (OR 0.19, 95% CI 0.04–0.99).

Table 4.

Logistics regression of factors that affect incidence of influenza infection.

Variables	Odds ratio	95% CI	P value
Post-transplant years	1.03	0.91–1.17	0.625
Number of immunosuppressants	1.57	0.40–6.15	0.515
Previous influenza vaccination	0.19	0.04–0.99	0.049*
Comorbidities
Chronic kidney disease	1.26	0.16–9.92	0.825
Chronic liver disease	0.04	0.01–0.37	0.004*
Diabetes mellitus	0.37	0.06–2.16	0.266

CI: confidence interval.

P<0.05.

SOT recipients who had a background of chronic liver disease appeared to have a lowered influenza infection incidence (OR 0.04, 95% CI 0.01–0.37).

Discussion

Rate of influenza vaccination

Given the high morbidity and mortality associated with influenza infection, it is crucial for SOT recipients to receive annual influenza vaccination to avoid the complications associated with influenza infection.⁸ Yet, it has been found in studies that there is a low rate of influenza vaccination among SOT recipients.⁶ From our study, only 25.0% of SOT recipients received influenza vaccination prior to implementation of the one-stop vaccination service and patient education at the transplant centre. The rate of vaccination is lower than that reported in other studies. Possible reasons for the lower vaccination rates may be attributed to the knowledge gap on the importance and necessity of influenza vaccination, as reported in the survey results. This is also seen in a local study, in which only 18.6% of a group of diabetes patients had been vaccinated against influenza at least once a year.⁹ Knowledge deficit, whereby more than half of the participants thought that influenza vaccination is not necessary, was also observed in the study.

The one-stop vaccination service resulted in a significant improvement in the uptake of the influenza vaccination. After implementation of the service, 60.6% of SOT recipients who had not received an influenza vaccination last year were vaccinated.

Through identifying the potential barriers to influenza vaccination, a standardised patient education and vaccination service was implemented which aimed to address the identified barriers, including accessibility and cost. The importance of vaccination was re-emphasised through patient education and the one-stop vaccination service greatly improved the accessibility. Given that public reimbursement of influenza through either national or social health insurance was deemed important to improve the extent of influenza vaccine use,¹⁰ during the education session, the pharmacist also highlighted that the vaccine is payable via the medical expense account (Medisave), a national medical savings scheme.¹¹

It was found that SOT recipients with diabetes mellitus or with a shorter post-transplant time were more likely to receive vaccination. Studies have identified diabetes mellitus as a risk factor for influenza and related complications.^12,13 The US Centers for Disease Control and Prevention (CDC) and the Advisory Committee on Immunization Practices have recommended influenza vaccination for diabetes patients across all age groups.¹⁴ This could have prompted physicians to prescribe annual influenza vaccination in a timely manner as the SOT recipients have an extra risk factor for influenza infection.

Based on our study, SOT recipients with a shorter post-transplant time tend to be vaccinated. During the early post-transplant period, the risk of acute rejection and graft loss is at its peak.¹⁵ In addition, immunosuppression is most intense during this time. Physicians would be more concerned with the risk of infections including influenza. In addition, during the initial post-transplant period, SOT recipients are followed up more frequently.¹⁶ Through the closer follow-up with physicians, SOT recipients would be routinely reminded of the need for annual influenza vaccination.

Incidence of influenza infection

The improvement in the influenza vaccination rate also translated into a lower incidence of influenza infection. The percentage of SOT recipients who had influenza infection was reduced by 46.6% after the implementation of patient education and the one-stop vaccination service. Although it was not statistically significant, the absolute reduction in the incidence of influenza infection among SOT recipients may be clinically significant, given that the severity of influenza infection is higher in immunocompromised individuals.^1,2

From the study, SOT recipients with previous influenza vaccinations are associated with a reduced incidence of influenza infection. This is in line with the recommendations by the AST.⁵ It has also been shown in studies that vaccinations will lead to a lower rate and severity of infection.⁸

The other factor associated with a reduction in the incidence of influenza infection was the presence of liver disease. However, it is known that patients with a background of chronic liver disease are at high risk of developing complications with influenza infection.¹⁷ In fact, this group of patients is recommended to be vaccinated per CDC guidelines.¹⁴ Therefore, this seemed to be an anomaly result and a meaningful conclusion to this result cannot be drawn.

This is the first paper in a local population to look at influenza vaccination uptake rates among SOT recipients. In addition, the study had included approximately 30% of SOT recipients at SGH, which gives a good representation of the SOT recipients on long-term follow-up at the hospital. However, as mentioned, data for the incidence of influenza infection were collected from electronic medical records which only capture information from the public sector, as such records from the private sector may be missed. There could also be underreporting of influenza infection, when the disease is self-limiting and SOT recipients did not seek medical treatment.

Conclusion

From our study, influenza vaccination rates among SOT recipients who were not vaccinated previously increased to 60.6% post-implementation of patient education and the one-stop vaccination service. The main barrier to receiving influenza vaccination identified from the survey was the lack of knowledge of the need for influenza vaccination. SOT recipients who had received influenza vaccination in the previous year have been associated with a reduced incidence of influenza infection and SOT recipients with a shorter number of years post-transplant are more likely to receive influenza vaccination.

Footnotes

None.

Authors’ contributions

Conceived and designed the study: Lee PH,Fan P

Enrolled patients and performed the study: Yeo YT,Song JL,Ng E,Lee N,Fan P,Lee PH

Analysed the data: Song JL,Yeo YT,Lee PH

Wrote the first draft of the manuscript: Yeo YT

Wrote the paper: Yeo YT,Lee PH

Agree with manuscript results and conclusions: all authors.

Availability of data and materials

The datasets generated and/or analysed during the current study are available from Yeo YT.

Ethical approval

Ethical approval to report this case/these cases was obtained from Singhealth Centralised Institutional Review Board (CIRB). CIRB ref no. 2014/2026.

Informed consent

Written informed consent was obtained from all subjects before the study.

Conflict of interest

The author(s) declared no potential conflicts of interest with respect to the research,authorship,and/or publication of this article.

Funding

The author(s) received no financial support for the research,authorship,and/or publication of this article.

ORCID iDs

Yan Ting Yeo

Terence Yi Shern Kee

Chee Kiat Tan

References

Kumar

Michaels

Morris

, et al. Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study. Lancet Infect Dis 2010;10: 521–526.

Cordero

Pérez-Romero

Moreno

, et al. Pandemic influenza A (H1N1) virus infection is solid organ transplant recipients: impact of viral and non-viral co-infection. Clin Microbiol Infect 2012; 18: 67–73.

Klimov

Rocha

Hayden

, et al. Prolonged shedding of amantadine-resistant influenza A viruses by immunodeficient patients: detection by polymerase chain reaction restriction analysis. J Infect Dis 1995; 172: 1352–1355.

Vilchez

McCurry

Dauber

, et al. Influenza virus infection in adult solid organ transplant recipients. Am J Transplant 2002; 2: 287–291.

Danzinger-Isakov

Kumar

and AST Infectious Diseases Community of Practice. Guidelines for vaccination of solid organ transplant candidates and recipients. Am J Transplant 2009; 9 (Suppl. 4): S258–S262.

Harris

Baggs

Davis

, et al. Influenza vaccination coverage among adult solid organ transplant recipients at three health maintenance organizations, 1995–2005. Vaccine 2009; 27: 2335–2341.

Health Promotion Board, Singapore. Influenza. https://www.healthhub.sg/a-z/diseases-and-conditions/103/topics_influenza (2019, accessed 12 September 2020).

Kumar

Ferreira

Blumberg

, et al. A 5-year prospective multicenter evaluation of influenza infection in transplant recipients. Clin Infect Dis 2018; 67: 1322–1329.

Tan

Lim

Teoh

, et al. Influenza and seasonal influenza vaccination among diabetics in Singapore: knowledge, attitudes and practices. Singapore Med J 2010; 51: 623–630.

10.

Macroepidemiology of Influenza Vaccination (MIV) Study Group. The macro-epidemiology of influenza vaccination in 56 countries, 1997–2003. Vaccine 2005; 23: 5133–5143.

11.

Ministry of Health, Singapore. MediSave. https://www.moh.gov.sg/cost-financing/healthcare-schemes-subsidies/medisave (2018, accessed 1 November 2018).

12.

Hanslik

Boelle

Flahault

Preliminary estimation of risk factors for admission to intensive care units and for death in patients infected with A(H1N1)2009 influenza virus, France, 2009–2010. PLoS Curr 2010; 9; 2: RRN115.

13.

Koegelenberg

Irusen

Cooper

, et al. High mortality from respiratory failure secondary to swine-origin influenza A (H1N1) in South Africa. QJM 2010; 103: 319–325.

14.

Grohskopf

Sokolow

Broder

, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices – United States, 2018–19 influenza season. MMWR Recomm Rep 2018; 67: 1–20.

15.

Cecka

JM.

The UNOS Scientific Renal Transplant Registry – ten years of kidney transplants. Clin Transpl 1997; 1–14.

16.

Kasiske

Vazquez

Harmon

, et al. Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation. J Am Soc Nephrol 2000; 11 (Suppl. 15): S1–86.

17.

Lynfield

Davey

Dwyer

, et al. Outcomes of influenza A(H1N1)pdm09 virus infection: results from two international cohort studies. PLoS One 2014; 9: e101785.