Status of Vaccine Coverage In Venezuelan Children, A Country With A Complex Humanitarian Crisis


 In Venezuela, PAHO has reported an increase in vaccine-preventable diseases since 2016. The goal of this work was to assess vaccination coverage in children hospitalized in the Department of Pediatrics at the Hospital Universitario de Caracas (HUC). Methods: A descriptive cross-sectional study included 0 to 12 years old children hospitalized in HUC admitted between January 2015 and December 2019, and verified immunization scheme. The patient data were compared with the schedule of the Ministry of Health of Venezuela and analyzed by comparing immunization coverage by year of patient hospitalization and patient age. Results: A total of 2903 patients were surveyed, corresponding to 53.2% male, 37.4% infants. A coverage level above 95% was found only for BCG. Comparing vaccination coverage with the vaccination schedule vs year of patient hospitalization, it was observed a mean decrease in vaccine coverage of 21.5% in 2019 relative to 2015 (p = 0.0000). Vaccination rates in children under one year old were lower than in children older than 6 years for all vaccines (p = 0.0000) Conclusions: There is a decline in vaccination coverage in 2019 in relation to previous years, being the most affected children less than one year old


Background
Vaccination has been one of the measures with the greatest impact on public health in the last half century, not only for its effectiveness but also for its pro tability, greatly contributing to two-thirds reduction in child mortality between 1990 and 2015 (1,2). However, there is a gap between the potential use of this practice and its actual contribution to child survival (2). According to the World Health Organization (WHO), by 2017 the global rate of vaccination coverage was 86% They calculated that global vaccination coverage could be improved to prevent 1.5 million deaths, and estimated that there are still 19.5 million infants worldwide who do not receive basic vaccinations, with children in developing countries being the most affected (3).
In developing countries, low vaccination rates are multifactorial (1). Factors that interfere with vaccination coverage can be grouped in four areas: i) immunization system, i.e. structure for vaccine distribution (e.g. limited funding for routine immunization services, barriers to access to primary care); ii) parental knowledge and attitudes about vaccination programs; iii) communication and information (2,(4)(5)(6)(7)(8); and iv) family characteristics, including poverty, rurality, extremes of maternal age, multiple childbirths, low maternal education, family size and lack of knowledge about vaccine-preventable diseases (2,4,5,8).
The Expanded Program on Immunization (EPI) was established in 1974 as an initiative of the WHO / Pan American Health Organization (PAHO) to improve the availability of vaccines worldwide, with the aim of ensuring that all children have access to and receive basic immunizations (1,7). Systematic vaccination programs have allowed the eradication of smallpox, the interruption of transmission of polio and control of tetanus, diphtheria, rubella and invasive bacterial infection by Haemophilus in uenzae type B and Streptococcus pneumoniae (7).
In the EPI, monitoring and evaluation are key tools that contribute to the effective and e cient implementation of actions, since they serve to periodically verify that the work is being developed according to the plan, to identify causes of failure to meet targets and to take timely and appropriate steps to correct the deviations. (9) Vaccination coverage measures the proportion of children who have received the vaccines according to the scheme for their age and are therefore protected (9). The minimum percentage needed to achieve herd immunity varies by disease from 75-95% (2, 7).
According to the report of PAHO's Executive Committee (included on the agenda of the Session 162), "PAHO's Response to Maintaining an Effective Technical Cooperation Agenda in Venezuela and Neighboring Member States", the burden of disease in Venezuela has become more complex and extended and diverse, affecting in particular fragile and vulnerable population. Emerging diseases have not been properly addressed, allowing the re-emergence of infectious diseases in epidemics spread of infectious diseases preventable by vaccination which had been controlled, revealing the ine ciency of epidemiological surveillance and the weakness of the national immunization program (11). The case of the measles epidemic, reemerging disease with indigenous cases since the rst week of July 2017 is highlighted in the document, signaling the failure of mass vaccination campaigns. This results in an important setback which impacts Venezuela and the entire American Continent, which loses the recognition of being free of endemic transmission of the disease, reached since 2016 (11).
The purpose of this study is to evaluate vaccination coverage and its evolution from 2015 until 2018 in pediatric patients attending the University Hospital of Caracas.

Methods
A descriptive cross-sectional study of vaccination coverage in pediatric patients, which were included all children hospitalized in Pediatric and Medical Pediatric Infectious Hospital Universitario de Caracas (HUC) aged between 1 day and 11 years, 11 months and 29 days, in the period January 2015-December 2019, whose immunization scheme could be assessed by their immunization card. For each patient, demographic data, immunization schedule and year of hospitalization in the HUC were recorded.
Immunization coverage was supposed when a child was correctly and fully vaccinated, following the Venezuelan national immunization schedule established by the Ministry of Popular Power for Health (MPPS) (12), which includes: Newborn: a single dose of BCG (Bacillus Calmette-Guérin) Under 1 year old: 3 doses of pentavalent vaccine (tetanus toxoid, diphtheria toxoid, Bordetella pertussis, Haemophilus in uenzae typeB, hepatitis B), 2 doses of rotavirus vaccine, two doses of pneumococcal vaccine, 3 doses of polio vaccine and two doses of seasonal in uenza vaccine. Since July 2017 a dose of viral bivalent vaccine (measles and rubella MR) was included, as ordered by the MPPS in order to control the epidemic of measles in Venezuela for that year 1 to 5 years: two doses of viral trivalent vaccine (MMR: measles, rubella and mumps), reinforcing Pneumococcal a yellow fever vaccine, pentavalent vaccine booster, polio vaccine booster, annual in uenza vaccine.
Older than 6 years: DT vaccine booster (tetanus and diphtheria toxoid), annual in uenza vaccine All patients whose immunization schedule could not be veri ed were excluded from the study.
For evaluation of vaccine coverage 3 groups were considered in response to vaccination cycles. First, patients under 12 months old (basic immunization); a second group involves patients between 12 months and 6 years old, when the reinforcement of different vaccines must be The third included patients older than 6 years, which should already have the basic immunization scheme and reinforcements for the different vaccines considered in the study.
Data were collected through the database of the Pediatric Department of HUC created for collection of egress data of pediatric patients, approved by the ethics committee HUC of 2015, and which was developed using the application Google Drive Forms. The data was analyzed descriptively by frequency and percentages for the qualitative data, and mean and standard deviation for quantitative data; Chi-square was evaluated for comparison the vaccine coverage according to age groups, year of patient egress and the combination of patient age groups vs year of hospitalization; a cutoff value for signi cance of p < 0.05 was established. For statistical data processing the software Epiinfo 7.2 was used.

Results
From January 2015 to December 2019 a total of 3235 patients were registered, meeting the criteria for entry and egress a total of 2903 patients; 332 patients were excluded because they did not have complete data of the immunizations. 1545 (53.2%) were male. Group under 12 months old corresponded to 37.4% (n = 1085 patients); the group between 12 months and 6 years old included 38.2% (n = 1109). The social class Graffar V (extreme poverty) was the most frequent 75.6% (n = 2195). (Table 1). The vaccine with largest general coverage level was BCG (Bacille Calmette-Guérin) with 94.9% (n = 2745) followed by polio 81.8% (n = 2028). The vaccines with lowest coverage were in uenza 17.7% (n = 332) and pneumococcal conjugate with 14.6% coverage (n = 332) ( Table 2).  (Table 3).   Immunization decline above 30% was observed for other vaccines. The only exception was for the MR vaccine, which wasn't administrated the years 2015 and 2016 for children under 12 months old because there was no measles epidemic in those years. Importantly, in 2019 no children less than 1 year was vaccinated against in uenza, and only 3.5% received the pneumococcal vaccine (Table 5).
For the group older than 6 years, signi cant drop in vaccination coverage was only observed for the case of rotavirus 23.8% and in uenza 16.8% (p = 0.0000). (Table 5)

Discussion
Immunization is an essential component of the human right to health, and is the responsibility of individuals, communities and governments. It is estimated that vaccination prevents 2.5 million deaths each year. Children immunized and protected from the threat of diseases preventable by vaccination have the opportunity to develop and more likely to reach their full potential. These advantages are further reinforced by vaccination of adolescents and adults. As part of an intervention plan to prevent and control diseases, vaccines and immunization are an essential investment in the future of a country and even of the world (13).
Vaccination is one of the most bene cial strategies in public health. Scienti c, technological and social advances offer great opportunities to expand basic vaccination schedules. (3).
Maximizing the impact of vaccination on public health requires a number of conditions. Among these factors are the need to generate more preventive awareness among the population, the imperative to ensure political support for the healthcare sector in terms of allocation of nancial resources for the introduction of new vaccines, and the need to counteract the effect of the anti-vaccine groups ( In May 2017, Health Ministers of 194 countries adopted a new resolution to strengthen vaccination in order to achieve the objectives of the Global Vaccine Action Plan. In this resolution, countries are encouraged to show leadership and more robust governance over national immunization programs, to strengthen monitoring and surveillance in order to ensure the use of updated data to guide strategic decisions, to optimize program's performance and impact of immunization. In addition, it is recommended to expand immunization services beyond infancy, to mobilize internal funds and to strengthen international cooperation to achieve the objectives of the Global Vaccine Action Plan (3).
It is estimated that in 2016, 19.5 million infants worldwide were outside the scope of routine immunization services, like the third dose of the triple bacterian (DTP3). About 60% of them live in 10 countries: Angola, Brazil, Ethiopia, India, Indonesia, Iraq, Nigeria, Pakistan, Democratic Republic of Congo and South Africa (3).
Monitoring data at the national level is critical to assist countries prioritizing and tailoring vaccination strategies and operational plans to ll immunization gaps, and to get people all the shots which can save their lives (3).
In the present study it was observed a low coverage for all vaccines in 2019 -a situation already evidenced by WHO in 2017-. An average decrease in vaccine coverage of 21.5% from 2015 to 2019 was veri ed. The smallest decline in coverage was for the BCG vaccine which only decreased by 6.3%. On the contrary, a signi cant decline in coverage in the years evaluated was found for the other vaccines, being the more important coverage decline for the rotavirus vaccine (52.2%) followed by in uenza, where the drop was 21.1%. These de cits are exacerbated when they are analyzed by age group. The worst case is for children under one year old: coverage for rotavirus dropped 69.2%, and in uenza vaccine reaches 0% coverage in the studied population. The coverage drop was less marked for children aged 1 to 6 years, although there was also a signi cant drop in rotavirus and in uenza vaccination rate. In children older than 6 years, signi cant differences were found in terms of vaccination coverage, except for the case of BCG and Pentavalent vaccine. Decline in vaccination coverage is in uenced by several factors, one of the most important being vaccine availability. According to Venezuela's 2017 EPI report, produced and published by PAHO / WHO, vaccine shortages in Venezuela have increased from 2012 to 2017, with shortages reported in 2012 for hepatitis B and polio vaccines, while in 2017 shortages of pneumococcal conjugate, DTP, yellow fever, hepatitis B, Hib, In uenza, IPV, oral polio and rotavirus vaccines are reported (15). This would explain the decrease in compliance with the recommended immunization schemes observed in the present work, when comparing data of 2015 and 2019.
Low vaccination coverage have caused the rise in previously eradicated diseases as measles and diphtheria. In Venezuela, between epidemiological week 26th of 2017 and the 52th of 2018, 9,116 suspected cases of measles were reported (1,307 in 2017 and 7809 in 2018) of which 6,202 were con rmed (727 in 2017 and 5,475 in 2018). The cumulative incidence rate in the country from 2017 to 2019 is 19.6 cases per 100,000 inhabitants (17); despite this epidemic, it was observed a decline in coverage against measles in the years studied, dropping to 61% coverage for 2019.
There is also an epidemic of diphtheria in Venezuela that started in July 2016 and which is still active in March 2019. 2,512 suspected cases of diphtheria have been registered up to the 2nd epidemiological week of the year 2019, of which 1,559 were con rmed, with 270 deaths (18). However, a decrease in diphtheria's vaccine coverage was evidenced in the present study. We found a decrease in pentavalent coverage of 80.2% for 2015 and 59.9% for 2019, this decrease being more pronounced in children under 1 year old, for whom coverage for 2019 was 30.6%.
Immunizations represent, after clean, safe water, the most effective way of preventing infectious diseases, one of the most outstanding public health achievements in child health. Hence, the importance of knowing their application cannot be overestimated; systematic vaccinations, particularly at ages in greater risk, will dramatically decrease the incidence of infectious diseases.
The main limitation of the study was to obtain from parents the information on the immunization schedule that many of them did not know the information and lost the vaccination record of their children.

Conclusions
Even though vaccination has been one of the most important measures of intervention in reducing child mortality over the past 40 years, our ndings determine the absence of optimum vaccination coverage in patients enrolled in the present study.
It is necessary to strengthen preventive medicine; the EPI has to be well implemented to be able to prevent outbreaks of vaccine-preventable diseases, which contrasts with Venezuela's current situation.
Low vaccination rates suggest that the goal of eliminating measles and diphtheria is likely to remain elusive, unless greater efforts to improve vaccination coverage are made As vaccination is less expensive than the burden of diseases, it is essential (and cost-bene cial) to strengthen the national immunization program.