Introduction

Patients with chronic kidney disease (CKD) have a high risk of infections.1 Infections, especially among patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) treatment, are the most common cause of hospital admissions and death after cardiovascular diseases.2 Among deaths due to infections, pneumonia is one of the most frequent causes.3 The risk of death from pneumonia in dialysis patients is 14 to 16 times higher compared to the general population, with streptococcus pneumoniae being the most common pathogen.4,5 To reduce the risk of pneumococcal pneumonia, global and national guidelines recommend dialysis patients receive the pneumococcal vaccine every five years and the influenza vaccine annually.6,7 These vaccines have been shown to reduce hospitalizations and mortality in HD patients, despite having lower antibody titers than in patients without ESRD.8–10 It has also been reported that pneumococcal and influenza vaccines may have beneficial synergistic effects.11

In Turkey, influenza and pneumococcal vaccines (polysaccharide and conjugate) are available. Although not mandatory, they are administered free of charge to risk groups such as HD patients. Influenza vaccine is administered every year in October and November, while pneumococcal vaccine is administered as indicated in Table 1. Patients receive their vaccines at family physicians or HD units. These vaccines are recommended for HD patients by the Ministry of Health of the Republic of Turkey, family physicians, nephrologist, dialysis physicians and nurses.

Table 1 Pneumococcal Vaccination Scheme for Hemodialysis Patients

Studies conducted abroad indicate that awareness of influenza and pneumococcal vaccines among hemodialysis patients is low, and vaccination rates are below the target levels.12 In this study, we aimed to determine the vaccination awareness vaccination rates, factors affecting vaccination and receiving regular hemodialysis treatment in 10 different hemodialysis centers in four provinces.

Materıals and Methods

There are over 1000 private and public HD centers in Turkey. Our study is a cross-sectional and involving patients from 10 hemodialysis centers in Düzce, Sakarya, Istanbul, and Ankara. The study was approved by the Düzce University Non-Interventional Health Research Ethics Committee (Decision no: 2023/120, 02.10.2023). All participants voluntarily gave an informed consent form that contained information about the study; they also gave a written and signed informed consent after being informed about the study’s objective and method.

Study Design

The responsible nephrologists in the centers selected in our study are in contact with each other and can easily reach each other. After excluding patients who had been on hemodialysis for less than a year those with a mental status that prevented them from answering the questions and those under 18, 548 patients remained in the study. A 20-question questionnaire was administered to patients via face-to-face interview and electronic medical records immediately before the hemodialysis session between March 1 and April 30, 2024. The questionnaires were administered by the responsible nephrologists and dialysis physicians. Participants were asked about sociodemographic characteristics such as age, gender, education level, marital status, and residential area, as well as information on pneumococcal and influenza vaccines (type of vaccine and vaccination timing). The vaccine knowledge and the source of information were queried. Information on the cause of CKD, dialysis duration, and comorbid conditions was obtained through the electronic medical record system. Data were collected and analyzed in the second 2-month period. The study was completed in a total of 4 months.

Statistical Analysis

The research data were uploaded and evaluated using IBM SPSS 21 (IBM Statistical Package for Social Sciences). Descriptive statistics for categorical variables were presented as numbers and percentages. Cross-tabulations, the “Pearson Chi-square test”, “Yates Continuity Correction”, and “Fisher’s exact test” were used for comparing categorical variables. In comparisons of more than two categorical groups, Bonferroni correction was applied, and the resulting p-values were considered. Statistical significance levels were accepted as p<0.05, and interpretations were made for p<0.05 and p<0.001.

A score was obtained for the influenza and pneumococcal vaccine questionnaire by scoring each question (0 for negative information and 1 for positive information). Spearman correlation was applied between the influenza and pneumococcal vaccine questionnaire scores. ROC curve analysis was applied to these scoring scores to predict the likelihood of getting the influenza and pneumococcal vaccines. The threshold value found was accepted as representing a higher level of knowledge about the vaccine, and a multivariable logistic regression analysis was performed to identify factors predicting a better level of knowledge about the vaccine.

Results

The demographic characteristics of the patients are shown in Table 2. Of the total 548 patients, 39.6% (n:217) were female and 60.4% (n:331) were male. Among the patients, 46.2% (n:253) were between the ages of 60 and 74, and 72.8% (n:399) were married. A total of 232 patients (42.3%) lived in a district of urban, and 231 patients (42.2%) had an education level of primary school graduate. The majority of patients (35.4%, n:192) had been undergoing hemodialysis for 60 to 119 months. Most patients (67.3%, n:369) used an arteriovenous fistula as their hemodialysis access route. The primary causes of renal failure were hypertensive nephropathy in 37.2% (n:204) and diabetic nephropathy in 36.9% (n:202) of patients. Among comorbidities other than primary renal failure, hypertension was the most common at 27.2%.

Table 2 Demographic Characteristics of the Patients

The survey results according to gender are shown in Table 3. When patients were grouped by gender, 23.5% of women were illiterate, and 22.1% were literate but had no formal education. Among men, 15.4% were middle school graduates, and 18% were high school graduates. There was a statistically significant difference in education levels between men and women, favoring men (p<0.001). There was no difference in influenza vaccination between genders; however, men were less consistent than women in getting the influenza vaccine (45.3% vs 34.6%, p=0.041). The reasons for not getting the influenza vaccine differed between genders (p=0.008), with women being less aware of the vaccine (14.7% vs 8.8%), more fearful of its side effects (15.2% vs 7.3%), while men more often said they did not feel the need because they do not get the flu (16.9% vs 10.6%). The reasons for not getting the pneumococcal vaccine also differed between genders (p=0.046), with more women citing fear of side effects (12.9% vs 6.3%).

Table 3 Statistically Significant Differences in Female and Male Patients

The survey results according to urban/rural residence are shown in Table 4. When grouped by residence, the 18–44 age group was more likely to live in urban areas (9.7% vs 1.7%), while the 60–74 age group was more likely to live in rural areas (54.3% vs 44%) (p=0.012). Patients living in urban areas were more educated than those in rural areas (p<0.001). There was a difference in the reasons for not getting the pneumococcal vaccine between the groups (p=0.002). Patients in urban areas were less aware of the pneumococcal vaccine compared to those in rural areas (42.6% vs 29.2%), while those in rural areas were less aware of its free availability compared to those in urban areas (7.9% vs 1.5%).

Table 4 Statistically Significant Differences in Rural and Urban Patients

Only 19 patients (3.5%) were aware of the pneumococcal vaccine, while 238 patients (43.4%) were aware of the influenza vaccine. The number of patients who were aware of both vaccines was 220 (20.1%). Patients most frequently obtained information about both vaccines from their dialysis doctors and dialysis nurses (36.6% (n:199) and 32.7% (n:179), respectively) (Table 5).

Table 5 The Patients’ Knowledge of the Pneumococcal and Influenza Vaccines and Their Source of Information

Ninety-five patients (17.3%) had received the pneumococcal vaccine, with 41.1% of them having been vaccinated five or more years ago. A significant portion (33.7%) of the patients could not recall the timing of their vaccination. While 183 patients (33.4%) had not received the influenza vaccine, only 140 patients (25.5%) were vaccinated regularly every year (Table 6).

Table 6 Information About Pneumococcal and Influenza Vaccination

The reasons for not getting the influenza and pneumococcal vaccines are shown in Table 7. There was a difference in the reasons for not getting the vaccines between the groups (p<0.001). The most common reason for not getting the influenza vaccine was “I do not feel the need because I do not get the flu“ (25%), while the most common reason for not getting the pneumococcal vaccine was ”I do not know about the vaccine” (36.7%). Among the reasons for not getting the influenza vaccine, missing the vaccination time was more common compared to the reasons for not getting the pneumococcal vaccine (18.3% vs 2.9%). Conversely, the lack of knowledge about the free availability of the vaccine was more common among those who did not get the pneumococcal vaccine compared to those who did not get the influenza vaccine (2.6% vs 0.6%).

Table 7 Reasons for Not Vaccinating for Influenza and Pneumococcal Vaccine

Each question in the influenza and pneumococcal vaccine survey was assigned a score (0 for negative information, 1 for positive information) to obtain a total score. The ROC curve for the influenza questionnaire score showed an AUC of 0.822 (95% CI 0.787–0.856), with a p-value of <0.001. According to the ROC analysis, the statistically significant cutoff value for predicting influenza vaccination was 2.5 (sensitivity 64.1%, specificity 85.2%) (Figure 1).

Figure 1 ROC curve for influenza questionnaire score. AUC 0.822 (CI 95% 0.787–0.856) and p<0.001. Statistically significant cut-off value 2.5 (sensitivity 64.1%, specificity 85.2%).

Univariate and multivariate logistic regression analyses were conducted to identify the factors predicting a higher level of knowledge about the influenza vaccine (with a questionnaire score >2.5) (Table 8). In the univariate analysis, dialysis duration, DM, and vascular access type were found to be statistically significant. In the multivariate logistic regression analysis, dialysis duration and DM were identified as independent factors predicting better knowledge about the influenza vaccine (p=0.009, 0.003, and p=0.041).

Table 8 Univariate and Multivariate Logistic Regression Analysis for Influenza Vaccination

The ROC curve for the pneumococcal questionnaire score showed an AUC of 0.920 (95% CI 0.886–0.955), with a p-value of <0.001. According to the ROC analysis, the statistically significant cutoff value for predicting pneumococcal vaccination was 3.5 (sensitivity 92.6%, specificity 71.5%) (Figure 2).

Figure 2 ROC curve for pneumococcal questionnaire score. AUC 0.920 (CI 95% 0.886–0.955) and p<0.001. Statistically significant cut-off value 3.5 (sensitivity 92.6%, specificity 71.5%).

Univariate and multivariate logistic regression analyses were conducted to identify the factors predicting a higher level of knowledge about the pneumococcal vaccine (with a questionnaire score >3.5) (Table 9). In the univariate analysis, residence, dialysis duration, and education level were found to be statistically significant. In the multivariate logistic regression analysis, dialysis duration and education level were identified as independent factors predicting better knowledge about the pneumococcal vaccine (p=0.038, 0.040, and p=0.010).

Table 9 Univariate and Multivariate Logistic Regression Analysis for Pneumococcal Vaccination

Discussion

This multicenter study on influenza and pneumococcal vaccinations in hemodialysis patients provided insights into vaccination rates and associated factors. Overall, the vaccination rates among patients were below 50%. Patients were unaware of these vaccines, feared side effects, or did not feel the need to get vaccinated as they believed they were not sick. The level of knowledge regarding both influenza and pneumococcal vaccines increased with the duration of HD. It was observed that patients with a diagnosis of DM had lower knowledge about the influenza vaccine, while university-educated patients had higher knowledge about the pneumococcal vaccine.

In addition to protecting against flu infections, several studies worldwide have shown that the influenza vaccine reduces the risk of various diseases. A study in Taiwan demonstrated the beneficial effects of the influenza vaccine in reducing the risk of stroke. This study showed that even a single influenza vaccination significantly reduced the risk of hospitalization due to ischemic stroke, decreasing the risk by up to 24% in one season.13 Similar findings have been confirmed by other studies observing a reduction in the risk of ischemic stroke during the epidemic season.14,15 Another favorable aspect of the influenza vaccine is its impact on cardiovascular events. A significant relationship was found between influenza vaccination and reduced risk of myocardial infarction in patients aged 50 and over. In a study by Siriwardena et al, influenza vaccination was associated with a 19% reduction in the rate of acute myocardial infarction.16

According to our study, 25.5% of patients received the influenza vaccine regularly every year, while 41.1% received it irregularly. In a similar study by Gilbertson et al, influenza vaccination rates were found to be below 50% among hemodialysis and peritoneal dialysis patients when examined separately.17 Another study conducted in 2021, which included 193 hemodialysis patients, found a regular influenza vaccination rate of 45%.18 These rates are well below the World Health Organization’s target of vaccinating 75% of key risk groups for influenza.19

There are two types of pneumococcal vaccines available globally: the 13-valent conjugate pneumococcal vaccine (PCV-13) and the 23-valent polysaccharide pneumococcal vaccine (PPSV23). It has been shown that administering both pneumococcal vaccines provides stronger protection compared to a single vaccine. Therefore, the PCV13 vaccine, in combination with the PPSV23 vaccine, has been included in vaccination schedules designed for immunosuppressive individuals, including patients with chronic kidney disease.20,21 (Table 1) In our study, the pneumococcal vaccination rate was 17.3%, and according to the vaccination schedule, patients were under-vaccinated. Of those who had been vaccinated at least once in their lifetime, 84.2% did not know the type of vaccine they received.

Looking at the literature, Mutlu et al reported a pneumococcal vaccination rate of 14.4% in a study involving 360 hemodialysis patients. Wilmore et al found a rate of 22% in a study conducted in the UK, and Saran et al reported a rate of 23% in a study conducted in the USA, all of which are similar to our findings.12,22,23

In our study, only 20.1% (n=220) of patients had knowledge about both vaccines. The knowledge about both vaccines was low, and those who were informed obtained the information primarily from dialysis physicians and dialysis nurses (36.6% (n=199), 32.7% (n=179), respectively). It is noteworthy that nephrologists were the third source of information at 15%. This may be due to the insufficient number of nephrologists and their heavy workload, preventing them from providing comprehensive care in this issue.24

When examining the reasons for not getting vaccinated against influenza and pneumococcal infections, the most common reasons were the belief that they were not sick and a lack of information about the vaccines. Comparing the responses about influenza and pneumococcal vaccines, patients missed the influenza vaccination timing while their knowledge about the pneumococcal vaccine was lacking, or they were unaware that it was free. Particularly, patients living in urban areas had less knowledge about the pneumococcal vaccine compared to those in rural areas. This might be due to the high workload of doctors and healthcare personnel in urban areas, leaving insufficient time for preventive health services. Similar to our findings, a study by Johnson et al found that the most common reasons for patients not wanting to get vaccinated were the belief that they were healthy and did not see the need for it.25 Patients need to be repeatedly informed that influenza and pneumococcal vaccines are preventive measures, not treatments, even if they feel healthy.

When examining the patients’ knowledge levels regarding influenza and pneumococcal vaccines and the factors influencing this, it was found that the level of knowledge for both vaccines increased with the duration of HD. The increased awareness and interaction with dialysis physicians, nurses, and nephrologists due to the longer HD duration may have played a role in this process. We found that patients with DM had lower knowledge about the influenza vaccine. Additionally, we observed that university-educated patients had higher knowledge about the pneumococcal vaccine. While an increase in education level, as seen in our study, can lead to higher vaccination rates, there are also studies in the literature showing unexpectedly opposite effects.26,27

Unlike the vaccination rates for pneumococcal and influenza vaccines, nearly all Hepatitis B seronegative hemodialysis patients are vaccinated. In many dialysis units worldwide and in our country, hepatitis serologies and vaccination statuses of patients in chronic dialysis programs are meticulously monitored, whereas pneumococcal and influenza vaccinations are overlooked. The widespread acceptance and routine application of the Hepatitis B vaccine might explain this difference. Making the routine administration of not only the Hepatitis B vaccine but also other vaccines in hemodialysis centers and informing patients about them can increase the vaccination rates.

It is important to highlight some limitations of our study. Due to the cross-sectional study design, patients’ views on vaccination were obtained only during the survey, and their opinions may change over time. There may be a subjective element in understanding and responding to the questions in the survey used in the research. Since our data were collected from 10 hemodialysis centers, it may not be representative of the entire hemodialysis population in our country.

Conclusion

Awareness and vaccination rates for the influenza vaccine were low among our patients, while awareness and vaccination rates for the pneumococcal vaccine were very low. Educating doctors and nurses responsible for managing hemodialysis treatment about vaccination programs is a crucial step in ensuring accurate information reaches patients. We believe that a comprehensive program for both the public and professionals will help overcome barriers against vaccination. We think that patient education about vaccines and increased sensitivity of hemodialysis doctors, nurses, and nephrologists in this matter will increase vaccination rates.

Acknowledgments

The authors would like to thank Dr. Abdülkadir Erçalışkan for his support.

Ethics Statement

This study was conducted in line with the principles of the Helsinki declaration. The study protocol was approved by the The study was approved by the Düzce University Non-Interventional Health Research Ethics Committee (Decision no: 2023/120, 02.10.2023). Participants gave informed, written consent.

Funding

There is no funding to report.

Disclosure

The author(s) report no conflicts of interest in this work.

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