The journey of special population to vaccination centers in Brazil: knowledge and perceptions

Background: Vaccination is one of the most effective public health strategies to control and prevent diseases. The Brazilian National Immunization Program is an international reference of public healthcare policy. Since 1993 Reference Centers for Special Immunobiologicals (CRIE) were implemented in order to facilitate the access to immunobiologicals, especially for those with congenital or acquired immunodeficiencies and other special morbidity conditions, or subjects exposed to risk situations. To assess knowledge and perceptions concerning the relevance of special patients’ vaccination and the immunization centers (CRIE) structure from patients, physicians and CRIE professional perspectives. Methods: An opinion survey was carried out in 2018 from June to July, including patients, physicians and CRIE professionals. A structured questionnaire was applied in a single interview to each interest group through phone calls. All instruments contained questions on general information, individuals’ profile, and knowledge and perceptions concerning CRIE. Results were obtained from the compilation of each groups’ answers. Data analysis was carried out in a descriptive approach, through measures of central tendency and dispersion for continuous variables, and measures of frequency for categorical variables. Results: The sample was composed by 280 individuals: 135 physicians; 135 patients; and 10 CRIE professionals. Regarding physician’s perspective, most of them reported to know CRIE (79%) and to refer patients (64%), and agreeing that a good quality service with well-trained professionals is offered (91%). Patients reported to receive the recommendation for vaccination by attending physician (91%), and to have never experienced the unavailability of a vaccine (91%) at CRIE. Analysis from CRIE professional’s perspective showed that patients are most frequently referred to CRIE by infectologists (33%) and that vaccination campaigns have a huge influence on demand. However, they also reported that there is no disclosure about CRIE service for population and physicians. Conclusions: Physicians classify vaccination as extremely important and all patients reported to follow recommendation. About immunization centers, a great perception about the service provided by CRIE

was reported, but there is still place for uptake the patient journey.

Background
The main purpose of vaccination is the control of infections transmission and diseases elimination individually and collectively. Children, adolescents and adults immunization should be a goal for doctors in their practice [1,2]. In this scenario, vaccination programs must be consistent, promoting a broad coverage and prioritizing the high quality of epidemiological surveillance, aiming the maintenance of disease control measures [3].
Brazilian National Immunization Program is an international reference for public healthcare policy. The Brazilian government offers vaccines recommended by the World Health Organization free of charge universally. Since its creation in 1973, the program seeks social inclusion, serving throughout the national territory. Health facilities across the country provide vaccines present on the national vaccination calendar, which covers all age groups and is in constant updating in order to incorporate new immunobiologicals or to adapt administration schemes to improve the program effectiveness [4].
Brazil's national vaccination calendar serves not only children but also adolescents, adults, the elderly, pregnant women and indigenous. In general, 19 vaccines are available in the immunization routine, from the neonatal period to the end of life [5].
The Ministry of Health gradually implemented the Reference Centers for Special Immunobiologicals (CRIE) throughout the Brazilian territory from 1993 to 2016. Each Federated Unit have at least one CRIE unit and there are currently 47 units located throughout the national territory [6]. CRIE's purpose is to facilitate population's access to special immunobiologicals, especially those with congenital or acquired immunodeficiencies and other special morbidity conditions, or subjects exposed to risk situations. Investigation, follow-up and elucidation of serious adverse events temporally associated with immunobiologicals administration is also a CRIE's responsibility [6].
A longer life expectancy and the access to new medicines result in a higher prevalence of chronic diseases with varying levels of immune impairment. This scenario creates a demand for immunization beyond official basic calendars, as recommended by international guidelines, preventing infections and its complications through vaccination [7,8].
This study was conducted aiming to assess knowledge and perceptions concerning the relevance of special patients' vaccination and the immunization centers structure from patients, physicians and CRIE professionals' perspectives.

Study design
Data collection was performed using a quantitative approach, through from an opinion survey, in accordance with recommendations of the Brazilian Association of Research Companies. The study also comprised a qualitative approach, but only data from the quantitative phase are presented in this paper, carried out from June 8 th /2018 to July 20 th /2018. According with Resolution No. 510 from April 7 th /2016 (Available from: http://conselho.saude.gov.br/resolucoes/2016/Reso510.pdf), the registry and evaluation by an ethics committee is not necessary for public opinion surveys with unidentified subjects. Additionally, all participants signed an informed consent, after receiving information and agreeing with study procedures.

Sample selection
Study sample was composed by patients, attending physicians and CRIE' professionals, all included according to specific eligibility criteria, from São Paulo, Rio de Janeiro, Porto Alegre, Salvador and Brasília. Physicians were personally interviewed at the clinic and randomly selected from different sources (internet, database, recruitment companies), based on a filter questionnaire and quotas of specialties, diseases and cities. No filter for CRIE knowledge or referral were applied. Inclusion criteria were composed by: clinical practice in the management of patients with asplenia, nephropathy, solid transplant or bone marrow transplant, also called hematopoietic stem cell transplant, cancer, pneumopathy, diabetes mellitus, rheumatologic conditions, down syndrome or HIV; >3 years and <35 years of specialization in endocrinology, hematology, rheumatology, infectology, nephrology, oncology, pediatrics, or pneumology.
Patients were recruited at CRIE entrance or exit and included if presented asplenia, nephropathy, solid or hematopoietic stem cell transplant, cancer, pneumopathy, diabetes mellitus, rheumatologic conditions, down syndrome or HIV; vaccinated for at least 6 months at a CRIE; and followed by one clinical specialties of interest (endocrinology, hematology, rheumatology, infectology, nephrology, oncology, pediatrics, pneumology). CRIE professionals (physicians, nurses or healthcare professionals) with knowledge on the whole process of vaccines acquisition, stock control, patient records and registration of applied vaccines were included, selected by direct contacts at CRIE or by phone.

Study procedures
A structured questionnaire developed for this study (available as a supplementary file) was applied in a single interview to each interest group through phone calls. All instruments contained questions on general information, individuals' profile, and knowledge and perceptions concerning CRIE. Results were obtained from the compilation of each groups' answers.
Physicians' questionnaire presented additional questions concerning perceptions on vaccination (referred diseases, reasons for patient's non-referral, referring moment, and its importance). CRIE section also asked about referral and recommendation, defined as direct patient referral to healthcare, or just advise them, respectively.
At patients' instrument, questions on diagnosis, comorbidities, visits to healthcare professionals, vaccination history and vaccines perception were also present. CRIE professionals' questionnaire carried specific questions such as patients' flow and profile, amount of vaccines provided, medical specialties referring to CRIE, attendance and decision-making process.

Statistical Analysis
Data analysis was carried out in a descriptive approach, through measures of central tendency and dispersion for continuous variables, and measures of frequency for categorical variables. Microsoft Office 365 and SPSS were used.
The sample size was calculated considering a parameter estimation strategy and a 95% confidence interval. A margin of error of nine percentual points was used to calculate the sample needed for patients and physicians and six, for total sample. For CRIE professionals, margin of error was established through an indicative lecture.

Results
The sample was composed by 280 individuals. Among physicians (N=135), infectologists (N=15), nephrologists/hematologists (N=45), oncologists/rheumatologists (N=15), pneumologists (N=30), endocrinologists (N=15), and geneticists/pediatricians (N=15) were included. A total of 135 patients were included with the following diagnosis: HIV (N=15), anatomical or functional asplenia and related diseases (N=15), chronic nephropathies/hemodialysis/nephrotic syndrome (N=15), transplantation of solid organs or hematopoietic stem cells (N=15), immunodeficiency due to cancer or immunodepression therapy (N=15), chronic pneumopathies/moderate and severe persistent asthma (N=15), diabetes mellitus (N=15), down syndrome (N=15) and cystic fibrosis (N=15). Ten CRIE professionals completed the analysis. Regarding physicians' perceptions on vaccination, most of them classify it as extremely important (85%) and introduces the subject up to the third appointment (48% in the first appointment and 43% on second and third appointments). Considering the referral process, most cases are referred to a public healthcare center (84%) and only 62% to CRIE (Table 2). Physicians' perceptions on CRIE are presented in Table 3. Most reported to know CRIE (79%), frequently from a professor in Medical School (19%). The majority of the physicians reports currently referring patients (64%). Those not referring justify the use of a private service by patients (39%) as an explanation. Referring process is most frequently written (84%) and physicians considers the process as a little bureaucratic (78%).
Most of them agreed that CRIE offers a good quality service, with well-trained professionals (91%), offering other healthcare services beyond vaccines (51%). Furthermore, most of them disagree that: vaccines offered on private services are better (73%); CRIE have problems in installations compromising products conservation (56%); there is no lack of products (51%); and CRIE are public places that serve only the low-income population (93%).   Regarding the satisfaction related to provided service, CRIE professionals most frequently classify as great (60%) the attention of the nurse when checking the vaccine and as good (40%) the politeness and cordiality of employees. Regarding length of service from arrival to departure and time spent between submitting documentation and vaccination assessment, CRIE professionals' opinions are divided between needs to improve a little (30%), good (30%) and great (30%) - (Table 5).

Discussion
Data presented in this survey show the perception about vaccination relevance and immunization centers from three different perspectives: physicians specialized in the treatment of risk patients; patients with risk comorbidities; and immunization center professionals.
A high percentage of physicians (85%) have considered immunization as extremely important and reported to mention this subject with patients in first medical appointments. However, rates of vaccine coverage among special patients are still considered low in Brazil. Only 62% of physicians included in the sample reported to refer patients specifically to a CRIE instead of a basic health unit, which may explain the low vaccination coverage. CRIE is the unique center to offer all the vaccines required in the calendar for risk patients, at a public health level. Thus, by referring to the basic health unit, patients could face limitations in access to all vaccines offered by the National Immunization Program for their clinical condition [4,6].
Previous Brazilian studies have assessed vaccine coverage among people living with HIV/AIDS from cities of different regions. Percentages of patients with a vaccination card classified as complete regarding the proposed calendar at the time of the study were 16.7% and 14% in São Paulo and Fortaleza, respectively [9,10]. In another study assessing the same patient profile followed by a specialized healthcare center from Espírito Santo, 20% have never received a vaccine [11].
The influence of referring patients to a basic health unit could be observed in the analysis of people living with HIV/AIDS cohorts from Ceará and Espírito Santo. Vaccines available at these units, such as influenza, diphtheria and tetanus, have shown a greater uptake when compared to those available only at CRIE, such as pneumococcal [10,11].
On the other hand, some concerns regarding vaccination in risk patients in basic health units must be explored. A study involving patients undergoing hematopoietic stem cell transplant from the interior of São Paulo have shown delay or not performing the vaccination schedule when patients were directly referred to a basic health unit instead of a CRIE. Professionals working in basic health units does not follow the same CRIE guidelines, and usually cannot access special vaccines or even deal with adverse events. The most frequently observed problem (about 40%) was lack of staff training in these units, and poor organization [12]. Lack of professional training from basic health units was also reported as a possible gap by another study assessing vaccination status of more than 700 diabetic patients from Ribeirão Preto treated in a specialized service and followed in a basic health unit, where full-coverage of hepatitis B vaccine was reported as only 13.7% [13].
A study conducted with rheumatological patients from Brasília showed that only 7% the sample received orientation regarding vaccination from the specialist, however, 47% have inadvertently received a live component vaccine while using immunosuppressant therapy [14]. The lack of recommendation by health providers was also indicated as a reason for people living with HIV/AIDS low adherence to vaccination, in another study from Ceará [10].
Data reported on the present study show that the service offered by CRIE, as well as training of its employees, were classified as good in terms of quality by 91% of the interviewed physicians, even though they reported the process as a little bureaucratic. CRIE professionals also classified the performance of their teams as great (60%), despite a need for improvement being reported by 30% of interviewees. Regarding patients' perspective, service was also classified as positive and 91% of respondents have never experienced lack of vaccines during their visit to a CRIE.
Data regarding patients' perspective needs to be highlighted. The involvement of a specialist physician is reported as a decision factor for vaccine recommendation by 91% of the interviewed patients. Although 30% of the patients reported fear of being vaccinated, 100% of adherence was observed in the studied sample. The relevance of a specialized physician in the recommendation and in patients' adherence to vaccination schedule was previously reported by other authors and is indicated on guidelines [15,16].
The frequency of visits to specialists by this patient profile is higher, increasing opportunities for immunization. Thus, specialists have an important influence in recommending and providing specific orientation to each patients' clinical condition [16]. A multidisciplinary team at sites receiving risk patients may help disseminate updated information on vaccination schedule [12].
Specialist physicians and CRIE members also have the responsibility to promote vaccination of risk patients' cohabitants. Recommendation is based on the need for creating a herd immunity around immunocompromised patients mainly to reduce the exposure to vaccine preventable diseases [6,16].
Nevertheless, data reported in the present study showed that 84% of interviewed patients deny receiving that recommendation. Another noteworthy point is that specialists most compromised with the vaccination of patients with comorbidities are those who more often know CRIE and patients' adherence to vaccination is higher when referred by these professionals.

Conclusion
Results reported in the present study corroborates the hypothesis that in order to increase

Ethics approval and consent to participate
According with Resolution No. 510 from April 7 th /2016 (Available from: http://conselho.saude.gov.br/resolucoes/2016/Reso510.pdf), the registry and evaluation by an ethics committee is not necessary for public opinion surveys with unidentified subjects. Additionally, all participants signed an informed consent, after receiving information and agreeing with study procedures.

Consent for publication
Not applicable.

Availability of data and material
Data is available upon reasonable request and with permission of Ipsos Healthcare and Pfizer. The supplementary data available was made original in Portuguese and translated into English to accomplish the periodic publication rules.

Competing interests
TCMBP received a Pfizer grant as a consultant during the development of this manuscript. JRS and RSA are formal employees at Pfizer. The study was commissioned by Pfizer from IPSOS.

Funding
The study was funded by Pfizer. Funding was used to provide data collection and medical writing services. The collection, analysis and interpretation of the data was made by IPSOS with no interference of Pfizer. The writing editorial services were provided by SENSE under the authors supervision. TCMBP received a Pfizer grant as a consultant to develop and review this manuscript.