Vaccine hesitancy and refusal among parents: An international ID-IRI survey

Introduction: Although vaccines are the safest and most effective means to prevent and control infectious diseases, the increasing rate of vaccine hesitancy and refusal (VHR) has become a worldwide concern. We aimed to find opinions of parents on vaccinating their children and contribute to available literature in order to support the fight against vaccine refusal by investigating the reasons for VHR on a global scale. Methodology: In this international cross-sectional multicenter study conducted by the Infectious Diseases International Research Initiative (ID-IRI), a questionnaire consisting of 20 questions was used to determine parents’ attitudes towards vaccination of their children. Results: Four thousand and twenty-nine (4,029) parents were included in the study and 2,863 (78.1%) were females. The overall VHR rate of the parents was found to be 13.7%. Nineteen-point three percent (19.3%) of the parents did not fully comply with the vaccination programs. The VHR rate was higher in high-income (HI) countries. Our study has shown that parents with disabled children and immunocompromised children, with low education levels, and those who use social media networks as sources of information for childhood immunizations had higher VHR rates ( p < 0.05 for all). Conclusions: Seemingly all factors leading to VHR are related to training of the community and the sources of training. Thus, it is necessary to develop strategies at a global level and provide reliable knowledge to combat VHR.


Introduction
Vaccines contribute greatly to the prevention and control of infectious diseases [1].Once vaccinated, an individual helps in protecting society from communicable diseases by preventing transmission in addition to the individual's protection [2].It is estimated that vaccines prevent 2-3 million deaths each year [3].Globally, vaccination programs have helped completely eradicate smallpox and successfully control infectious diseases, polio and measles in particular [4].
Although vaccines are the safest and most effective means available to prevent and control infectious diseases, the increasing rate of vaccine refusal has become a threat to public health worldwide [5].The inadequate vaccination rates in the community could be attributed to the fact that parents refuse or delay the vaccination doses of their children [6].Seemingly, increasing numbers of parents have doubts about the safety and necessity of vaccines and distrust in pharmaceutical industries [7].
In this study, we aimed to find the opinions of parents on vaccinating their children and contribute to the available literature to support the fight against vaccine hesitancy and refusal (VHR) by investigating the reasons on a global scale.

Methodology
Ethics committee approval dated 01.27.2021 and numbered 514/194/3 was obtained from the ethics committee of University of Health Sciences, Kartal Dr. Lütfi Kırdar City Hospital in Istanbul, Turkey for this international and cross-sectional multicenter survey.The study was conducted in accordance with the ethical principles of the Declaration of Helsinki.

Participating researchers/centers
Physicians from 16 countries (Bangladesh, Egypt, India, Nigeria, Pakistan, Turkey, Jordan, Bulgaria, Iran, Bosnia and Herzegovina, Italy, Croatia, Puerto Rico, Romania, Saudi Arabia, and Poland) participated in our study.They were contacted through the Infectious Diseases International Research Initiative (ID-IRI), which is an international clinical research platform.In minimizing the selection bias for the participating countries, we used cluster sampling method for the selection of the hospitals our researchers are working in.Each hospital itself is a mini representation of the other hospitals in their country.In addition, we did not provide comparisons based on the countries of the researchers in our study.Rather, we stratified the countries according to their economical statuses.

Data Collection
A questionnaire consisting of 20 questions was prepared to investigate the parents' demographic data such as country of residence, age, gender, education level (None, Primary school, High school, University, Master/Doctorate), occupation, whether they have a child with a chronic disease, whether they have a disabled child, as well as their views on childhood vaccines, their reasons for vaccine refusal or hesitation if they had any, and whether they comply with the vaccination programs in their own countries (see Supplementary-1).The questionnaire was pretested to minimize the chance of misinterpreting questions.The questionnaire was sent to the participants online via Google Drive between 1st March and 1st April 2021 and was administered face-to-face to a total of 4,029 parents (aged 18-63 years) with children aged < 13 years after obtaining their verbal consent.The participants have performed the survey through face-toface interviews and submitted them via Google Drive.

Classifying parents/respondents
The parents were asked to choose one of the following responses to the statement "We should make childhood vaccinations to protect our children from infectious diseases": "1.Strongly disagree, 2. Disagree, 3. Undecided, 4. Agree, or 5. Strongly agree".Among these options, "Agree" or "Strongly agree" were considered vaccine approval, "Strongly disagree" or "Disagree" were considered vaccine refusal, and "Undecided" was considered vaccine hesitancy.

Economic concerns
The countries where the study was conducted were examined under 3 groups according to their economic development levels as follows: lower-middle-income (LMI) countries (Bangladesh, Egypt, India, Nigeria, and Pakistan), upper-middle-income countries (Turkey, Jordan, Bulgaria, Iran, and Bosnia, and Herzegovina), and high-income (HI) countries (Italy, Croatia, Puerto Rico, Romania, Saudi Arabia, and Poland) [8].

Statistical analysis
Descriptive statistics of the answers given to the questions in the survey were calculated as Mean, Standard Deviation (SD), count, and percentage frequencies.The relations between the answers given to the first 14 questions and the answers to the questions 15-21 were evaluated with Pearson chi-square analysis or Fisher-Freeman-Halton exact test.The statistical significance level was accepted as p < 0.05.The relationship between VHR and parameters like age, gender, education level, occupation, whether their child has a chronic disease and/or disability, economic development levels of countries, and sources of information on vaccines was statistically investigated.

Results
Four thousand and twenty-nine parents were included in the study, and 2,863 (78.1%) among them were females.Their mean age was 37.1 ± 7.0 years (range, 18-63 years), and the mean age of the youngest children of the parents included was 5.2 ± 3.7 years (range, 0.10-13 years).In addition, the mean number of children of parents was 2.1 ± 1.1 children (range, 0-10 children).

Parental characteristics
The parent's education level, occupation, country, income level of their country, and status of having a disabled child, a child with a chronic disease, or an immunocompromised child of the parents included were given in Table 1.

Sources of information on childhood immunizations
Responses given to the multiple-choice question in the survey regarding the sources of information on childhood immunizations for the parents were as follows: from healthcare institutions, physicians, and other healthcare professionals (90.2%); from print, visual, and audio media (newspaper, magazine, TV, radio, etc.) (20.2%); from the internet and social media networks (20.2%); from their relatives and friends (18.2%); and other sources (0.6%) (Table 2).

Vaccine hesitancy and refusal rates
The number of parents in the vaccine approval group was 3,477 (86.3%), "undecided" (vaccine hesitancy) group was 314 (7.8%), and vaccine refusal group was 238 (5.9%) (Table 2).The overall vaccine hesitancy and refusal rate of the parents were found to be 13.7%.Reasons for vaccine refusal and vaccine hesitancy are presented in Figure 1, Figure 2, and Table 2.

Compliance with vaccination programs
We found that 3,283 (80.7%) parents had their children vaccinated completely and routinely, 495 (12.3%) had their children vaccinated completely but with some delays, 234 (5.8%) had their children vaccinated incompletely, and 47 (1.2) did not have their children vaccinated at all (Table 2).In total, 19.3% of the parents did not fully comply with the vaccination programs.

Parental VHR and its' relations
The highest VHR rate was detected in HI countries (p < 0.005).The lowest VHR rate was among healthcare workers and the highest VHR rate was among self-employed individuals (p < 0.001).The lowest VHR rate was found to be among university graduates and the highest VHR rate was among individuals with no education (p < 0.001).The VHR rate was found to be higher in parents with disabled children (p < 0.001), among parents with children having hearing loss and visual disturbances and blindness (p < 0.05), and in parents with immunocompromised children (p < 0.05).VHR rate was found to be lowest for parents who made a joint decision whether to vaccinate their children and at the highest rate in cases where the father made the decision alone (p < 0.001).No statistically significant difference was found between VHR and gender and having a child with a chronic disease (p > 0.05) (Table 3).

VHR and sources of information for vaccination
VHR rate was lower in parents receiving information on childhood immunizations from healthcare institutions, physicians, and other healthcare professionals, whereas it was higher among those who responded to this question as "from print, visual, and audio media (newspaper, magazine, TV, or radio)," "from the internet and social media networks," and "from my relatives and friends" (p < 0.001) (Table 3).The letters next to the frequencies show the differences between the rows.A significantly different option of the question carries a different letter.

Discussion
Although vaccination is currently one of the most effective tools in protecting public health, parental doubts about the safety and necessity of vaccines are on the rise [7].These concerns subsequently prevent or delay vaccination in children, thereby paving a path for preventable infectious diseases and epidemics [9].Measles increased by 30% globally in 2018, with the highest rates having been found in Italy and Romania between 2017 and 2018 [10].In our survey, we analyzed the reasons for VHR at the international level by the opinions of parents for vaccinating their children, and we found that VHR rate was 13.7%.It was observed that the likelihood of preservatives in the vaccine may cause adverse effects in their children, and this was the most common cause of VHR.We found that 19.3% of the parents did not fully comply with the vaccination programs.The highest VHR rate was found in HI countries in parents with low education levels, with disabled and immunocompromised children, and in parents deciding on vaccination of their children individually.In addition, we have observed that the VHR rate was higher among parents who used social media networks as sources of information for childhood immunizations.
Parental VHR rates may vary across societies, regions, and countries [11][12][13][14][15].In our study, which included respondents from 16 countries, the VHR rates of countries were different from each other; the overall vaccine hesitancy rate was 7.8% and the overall vaccine refusal rate was 5.9%.Alternatively, as in this study, various studies have reported that individuals against vaccination were more common in HI countries [9,16,17].In addition, the low education level of parents was reportedly associated with VHR confirming our results [11,15].Unsurprisingly, VHR increased as the education level of parents with VHR decreased.
In addition to individual factors such as parents' knowledge, attitudes, and beliefs, other complex and multidimensional factors were already known to affect the decisions made by parents to have their children vaccinated [18].Thus, precise communication is essential for vaccination programs to achieve success.Providing effective and transparent information to the public about vaccines and considering people's concerns about vaccines are essential elements for decision-makers related to vaccination [19].Misinformation about the efficacy and safety of vaccines affects vaccination programs undesirably and leads to VHR.Thus, preventable diseases may reemerge and turn into epidemics owing to the reduced vaccination rates.One of the relatively new examples is the vaccine-preventable outbreak in the former Soviet Union countries due to the break in the chain of vaccination between 1990 to 1995 [20,21].Currently, it appears that the internet and social media are the most important communication tools for influencing the parents' attitudes of distrust and refusal of vaccines [10,22].The anti-vaccination movement has been prevalent since the first vaccine was invented and is now stronger than ever because of the internet, which has the potential to reach and influence every single parent.We are reporting in this study, as in the previous studies, that parents with VHR used the internet and social media tools more commonly as a source of information about immunization [13,23,24].
The main factor influencing parental decisions on whether or not to vaccinate their children was reported to be the safety of vaccines [25].Concerns about serious side effects of vaccines and their ingredients were reported to be among the most important reasons that led to parental VHR for childhood vaccines [2,12,15,26,27] and our data supported this inference.Although there is no direct relationship between vaccination and disability, VHR rates were found to be high in parents with disabled children in this study.The probable reason seems that parents with disabled children are already stunned by the misinformation against vaccination.
The World Health Organization (WHO) stated that the vaccination rates should be above 95% for particular vaccines such as measles, to provide herd immunity for protection against vaccine-preventable diseases [28].Although in this international multicenter study, we found that the rate of full compliance with the vaccination programs recommended by the decisionmakers was 80.7%, 1.2% chose not to have any vaccinations at all, and 5.8% had their children vaccinated incompletely.This result is below the WHO recommended threshold.This inadequate compliance may cause the re-emergence of epidemics and can put the whole world in danger as well.
The main limitation of this study was that the number of questionnaires was not homogeneously distributed in the participating countries.Nevertheless, the strengths of the study were that either there was participation from 16 different countries or the centers that can represent country averages were included in the survey.In addition, the fact that the number of men participating in this study was less than women may have partially affected the results.
In conclusion, the factors leading to VHR are seemingly related to training of the community and the sources of training.Unfortunately, the current level of full compliance for vaccination is below the WHO target.It is crucial to develop strategies at the global level to combat VHR.

Figure 1 .
Figure 1.The reasons for vaccine refusal.Figure 2. The reasons for vaccine hesitancy.

Figure 2 .
Figure 1.The reasons for vaccine refusal.Figure 2. The reasons for vaccine hesitancy.

Table 1 .
Sociodemographic characteristics of parents.
* One who delivers care and services to the sick and ailing either directly as doctors and nurses or indirectly as aides, helpers, laboratory technicians, or even medical waste handlers.

Table 2 .
Parents' responses to survey questions.

Table 3 .
Relationship between parents' characteristics with VHR.