Retrospective study of immunization errors reported in an online Information System*

Objective: to analyze the immunization errors reported in an online Information System. Method: retrospective study conducted with data from the Adverse Event Following Immunization Surveillance Information System. Immunization errors were analyzed with respect to demographic characteristics and the vaccination process. Frequencies and error incidence rates have been calculated. Binomial and chi-square tests were used to verify differences in the proportions of the variables. Results: 501 errors were analyzed, the majority involving routine doses (92.6%), without Adverse Event Following Immunization (90.6%) and in children under five years old (55.7%). The most frequent types of errors were inadequacy in the indication of the immunobiological (26.9%), inadequate interval between doses (18.2%) and error in the administration technique (14.2%). The overall error incidence rate was 4.05/100,000 doses applied; the highest incidences of routine vaccines were for human rabies vaccine, human papillomavirus and triple viral; the incidence rate of errors with Adverse Events Following Immunization was 0.45/100,000 doses applied. Conclusion: it was found that immunization errors are a reality to be faced by the health systems, but they are amenable to prevention through interventions such as the adoption of protocols, checklists and permanent education in health.


Introduction
Immunization is a key component of the efforts made by the World Health Organization (WHO) to achieve the United Nations' third Sustainable Development objective by 2030, which is to ensure a healthy life, promote wellbeing to be for all, at all ages, by reducing the infant and maternal mortality rate, from communicable and non-communicable diseases, including ensuring access to safe and quality vaccines (1) .
In the last few decades, the number of vaccinepreventable diseases has almost doubled and, to that end, the number of vaccine doses has increased for children and adults (2) . With the increase in the number of doses applied, the potential for immunization errors (IE) has also increased globally (2) . Furthermore, despite advances in immunization surveillance systems worldwide, IE are often underreported (2) . The IE can be conceptualized as any preventable events arising from the inappropriate use of vaccines, which may be related to professional practice and the imprudent use of immunobiologicals, which, outside the norms and appropriate techniques, can lead to negative impacts, such as inadequate immune protection, increased costs for health services, reduction confidence and potential injuries of health system users (3) . The IE may cause adverse events following immunization (AEFI) and result in severe harms to the users (4)(5)(6) .
The IE occur at an alarming frequency (7) . Studies conducted in developed countries have found a high rate of IE involved in vaccine administration (3,(8)(9) .
Approximately one third of users experience at least one IE (7) . In a systematic review carried out in five Englishspeaking countries, a prevalence of vaccination error of 1.15 per 10,000 doses of vaccines was identified (10) .
In Europe, a study that analyzed data from the AEFI surveillance system showed that of 233,285 vaccination records, in 3.0%, reports of at least one IE were identified, and of these, more than half (59.9% ) resulted in severe outcomes (8) . In Canada, a retrospective study of 3,504 reports of AEFI, estimated an IE rate of 0.39 per 100,000 applied doses (a.d.) (11) . In the United States of America (USA), analysis of the AEFI surveillance system showed that out of 21,843 IE in the country, among which, in 25% of the cases, there was some harm to the user (3) .
International literature shows that the most common IE are related to the inappropriate scheme (for example: incomplete vaccination), storage and distribution errors, incorrect vaccine, incorrect doses, incorrect interval/time and administration errors (3,(8)(9) .
Many IE occur at the expense of the complexity of vaccination programs. Brazil offers immunobiologicals to its population, through the National Immunization Program (PNI), one of the most expressive Brazilian public policies, considered one of the most complete and complex vaccination programs in the world, internationally recognized for its excellence (12)(13) .
The PNI has considerably expanded the supply of immunobiologicals in recent years, thus facing new challenges (12)(13) . Currently, makes available 300 million annual doses of 44 different types of immunobiologicals, including routine vaccines, serums and immunoglobulins in around 34,000 existing vaccination rooms (14) .
Since 2009, the PNI has adopted the PNI Information System (IS-PNI) as the AEFI Information System module (IS-AEFI), which, since 2014, has existed in online format, with the objective of favoring better obtaining, description, surveillance and analysis of AEFI and IE data (12,(15)(16) .
In Brazil, studies on the epidemiology of IE are scarce, among them, few have analyzed the types of errors involved in immunization (6,15,(17)(18) . For example, a national study that analyzed 1,622 notifications with closure of IS-AEFI, showed that 9.3% represented IE without AEFI and 0.8% IE with AEFI (15) . Another study in Paraná (South Region) showed the occurrence of 604 records of types of AEFI resulting from IE, with frequent hot subcutaneous abscess, cold subcutaneous abscess and suppurated regional lymphadenopathy (6) . In Goiânia (State of Goiás, Central-West Region), a study showed that among the 373 AEFI analyzed in children, in 16.1% IE occurred, with the most frequent vaccine administered outside the recommended age, vaccine administered with expiration date, inadequate interval between doses and vaccine applied in the wrong place (18) .
There is a gap in the literature on IE, as there are few studies conducted in developing countries, such as Brazil, that show IE magnitude. Most existing studies do not report IE incidence rate stratified by type of immunobiological element. Although the risk to vaccinerelated AEFI has received considerable attention in the recent years (4)(5)(6) , studies on AEFI related to IE have also been underdeveloped. In addition, the IE incidence rate without AEFI and with AEFI separately was estimated. All measures of descriptive analysis and incidence rate were followed by the respective 95% confidence intervals (95% CI).
In the following, the differences between the

Results
In this study, all 404 notification forms were analyzed and, among them, 72 (17.8%) had a record of two or more IE, totaling 501 IE analyzed in Goiás.   and other errors (6.8%; 95% CI: 4.9-9.3%) (data not shown in tables).

Discussion
In the public health, vaccination is a safe strategy capable for significantly impacting the control or elimination of preventable diseases (21)(22) . In this sense, safe vaccination is a worldwide concern and a determining factor in the immunization programs success or failure (23)(24) . In this study, 501 IE were analyzed, the majority involving routine doses (92.6%), without AEFI  institutions, since those with a well-established safety culture are likely to contribute to more complete notifications and information than those whose punitive culture still prevails (9,25) . Thus, the results of this study may not represent IE real magnitude for the analyzed location.
The quality of immunization programs depends on how vaccines are produced, transported, packaged, prepared and administered (26) , as well as the quality of the notifications and the analysis of the occurred IE, one of the great challenges for the immunization services is to certify safe vaccination practices. The analysis of events reported to the USA National Vaccine Adverse Event Reporting System shows that IE remain present in the clinical practice (3,25) . This study confirms this reality and points out that the IE are found in the Brazilian reality, being more frequent in children under five years old, especially in children under one year old.
The children under one year old have been hardest hit by AEFI (15,18) and by IE with AEFI (6) . This fact may be due to the greater vaccine exposure to which this age group is exposed, considering that the majority of vaccines that make up the calendar are indicated for children under one year old (14) .
In this study, proportionally, the majority of IE occurred with immunobiologicals administered intramuscularly, followed by those administered subcutaneously. In Brazil, most routine vaccines are composed of those administered intramuscularly, in addition to special immunobiologicals and serums (14) , a fact that may explain the result of this study.
In this investigation, it was found that the IE majority occurred during routine vaccination. Also, a higher proportion of IE was observed related to triple viral vaccines, yellow fever, HPV, pentavalent and OVHR.
These findings corroborate a study carried out in the Southeast Region of Brazil, in which there was also a higher proportion of IE related to routine vaccines (79.0%) and human rotavirus vaccines (22.0%), fever yellow (15.6%) and tetravalent (12.9%) (17) . In another study carried out in the Midwest Region of Brazil, AEFI notification forms for children under five years of age were analyzed, among them, the majority of IE involved the administration of yellow fever and OPV vaccines (18) .
When comparing with international literature, an investigation conducted in the USA showed that HPV(26.0%) and rotavirus (15.0%) vaccines were the most involved in the IE in the clinical practice (3) .
In this study, it was found that the most prevalent incorrect vaccine (15.0%) (3) . Other studies have pointed out that errors that occur in the administration stage are the most common (3,9,(25)(26) and included wrong number of doses, inadequate dose interval and wrong vaccine (9) .
Of the total analyzed IE, 9.4% were IE with AEFI.
The IE IT with AEFI was 0.45 IE/100,000 a.d. Similar results have been identified in other studies conducted in Brazil (6,15,18) . The results reported in the international literature reveal divergent data regarding the magnitude of the AEFI followed by IE. A report drawn up from an Australian database revealed 2,924 AEFI related to IE cases in 2015, which represented 12.3 events for every 100,000 vaccinated people (27) . In Canada, a study on 3,504 AEFI reports estimated an IE rate of 0.39 per 100,000 a.d. (11) . In the USA, an analysis of the AEFI surveillance system showed that in the period from 2000 to 2013, 21,843 IE cases were reported in the country and that, in 25% of the cases, there was some harm to the user (3) .
In addition, the analysis of IE with AEFI showed the occurrence, mainly, of local manifestations, such as pain, edema or flushing, erythema, heat and nodules. Other studies conducted in Brazil identified that more than half of the manifestations related to the AEFI reported were local and self-limited, spontaneously resolved and without the need for medical intervention (15,18) . On the www.eerp.usp.br/rlae 9 Barboza TC, Guimarães RA, Gimenes FRE, Silva AEBC other hand, a study conducted in a state in the Southern Region showed that AEFI followed by more frequent IE showed hot subcutaneous abscess, cold subcutaneous abscess and suppurated regional lymphadenopathy (6) .
A Canadian study found that the majority of IE with AEFI were mild or of moderate severity, indicating that the commonly reported reactions included extensive, prolonged or painful local reactions in a member of the injection site (28) .
It is worth considering that severe IE-related AEFI are rare, so the benefits of immunization are significantly greater than the problems that may eventually occur (29) .
However, many of these events can be prevented if health services establish effective infrastructure to monitor and promote safe practices, including the release of annual reports (30) .

Regarding the vaccines most involved in IE
with AEFI, Bacillus Calmette-Guérin (BCG) and the pentavalent were the most common. BCG intradermal vaccination is associated with specific errors (31) which can cause adverse events ranging from local manifestations to more severe manifestations (32) .

Although most IE do no harm to users, efforts
should be directed towards planning actions aimed at improving the quality of care provided to the population (2)(3) . Monitoring the AEFI, particularly those caused by IE, is important for the success of immunization programs, as such events can influence the acceptance of immunization by the population, as well as negatively impact costs for the health system (3) .
Therefore, IE epidemiological assessment may come to contribute to the changes in practice, directing efforts to reduce errors and harm caused to users, as well as reducing costs incurred in the AEFI treatment.
It is highlighted that, with the inclusion of new immunobiologicals (12) , the profile of the vaccination calendar in Brazil has changed considerably in recent years. Complexity of immunization makes the work of health managers and professionals challenging to guarantee safety in the vaccination process. Managers and professionals must continually pay attention to the fact that the production of safe and effective vaccines is not enough, but also to ensure adequate structures and processes that favor the safe development of all stages that make up the immunization system (33) .
Vaccination is an action that has been carried out by nursing and, in Brazil, more frequently by nursing technicians, considering that nurses accumulate other activities, both managerial and assistance related (34) .
Ensuring the skills and updates for this practice, adopting systemic measures that help them not to make mistakes, is essential to increase safety in this process. in order to prevent future occurrences (3,33) .
Other strategies for preventing IE concern using checklists (31) ; investments in information technology infrastructure to support clinical decision-making; aid in identifying IE risk factors (9) and permanent education in health for all professionals involved with immunization in the country's health services. Such strategies can be considered as transforming practices aimed at the safety of the users (36)(37) .
However, it is worth mentioning that the educational activities carried out in the permanent education in health actions must be planned based on the problematization of daily life and the analysis of care failures so that they generate reflections, improvement actions and serve as learning for all (36) . Teaching strategies with active methodologies, realistic simulation and discussion of errors that occurred are also important to bring students and professionals closer to the reality to be faced (34) .
In addition to permanent education in health, it is essential to develop skills for immunization safety in undergraduate courses for health professionals, with an emphasis on nurses, responsible for vaccination rooms (34) . www.eerp.usp.br/rlae Rev. Latino-Am. Enfermagem 2020;28:e3303.
The users of the system also need to be involved in the immunization process, so that they are able to not only serve as a barrier to a possible error, but also to detect and report signs of adverse events (27) , having as one of the possible strategies the verification by the user of their own data, the child under his responsibility and the immunological one before its preparation and administration.
Careful surveillance and IE investigation are necessary to identify the causes of these events that require correction (38) . Effective spontaneous reporting of the IE is the first step in ensuring that vaccines are safe and that they are being administered correctly (39) .

Conclusion
Vaccination has brought immeasurable benefits to collective health, significantly reducing, controlling and eradicating preventable diseases. Thus, in order to ensure your success it is important that failures do not occur during the process. However, the evidences from that study indicate that the immunization errors are a reality to be faced by health systems and nursing, impacting the quality of care and the safety of users who seek to prevent the illness in the population.
Most IE occurred in children under the age of five, it did not cause harm and the incidence rate found was low and close to the few studies carried out, nationally and internationally. However, when it comes to lives, actions to prevent and minimize these occurrences must be adopted, focused on analyzing the structure and processes of immunization.
This study carried out an analysis of immunization errors, which can subsidize management in decisionmaking towards strengthening the quality of vaccination procedures. Thus, it fulfills the role of disseminating information on issues related to the safety of users of the health system in the context of immunization and amplifying the access of management, professionals and the population on this theme.
The study also has implications on the care practice and for the teaching in the health and nursing field, as it displays situations that alert for a closer approach to nurses in the vaccination room, aiming to improve supervision, permanent education in health, risk management and the direct assistance to the system users. Using protocols, tools and dynamics with a systemic and non-individual view is also fundamental, not only to mitigate errors, but also to maintain the confidence, quality and positive impact of the PNI, at all instances.