Immunopreventable Diseases: Differences Between Genders in Brazil

Immunopreventable diseases are a public health reality in Brazil and worldwide. The international literature dened that there is difference between sexes at the answer to the infectious diseases. Objective: to discriminate the hospitalizations associated with immunopreventable diseases in Brazil and their care costs, within the scope of the SUS, between 2008 and 2018, differentiating the data by gender. Methods: A population, observational, descriptive, retrospective study was conducted with secondary information from DATASUS. Results: A total of 457,479 hospitalizations were evaluated, totaling a direct cost of R$389,243,264.85, 53.17% in males and 46.83% in the female group (p-value 0.036). The trend analysis showed 6 diseases in decreasing situation (with statistical signicance) and 4 in stationary tendency in the number of hospitalizations in the analyzed period. The direct costs of these hospitalizations were predominantly stationary for both sexes. Conclusions: the number of hospitalizations varied during the period analyzed, however the care costs of Immunopreventable diseases hospitalizations remained high, regardless of gender. hospitalizations were associated with inuenza disease, with the main hospitalization in direct costs observed, with R$108,903,219.58 in costs associated with males and R$107,882,552.40 to females. The lower direct cost problem associated with hospitalizations observed in this analysis was rubella, with a value of R$144,992.82 (R$35,156.59 associated with males and R$109,836.23 for females).


Introduction
The World Health Organization (WHO) estimated that a quarter of deaths in children under 5 years are caused by immunopreventable diseases [1][2][3][4][5][6][7] . According to international literature 8-10, a considerable proportion of health care is attributed to communicable diseases: one in six cases attended by primary care and about 128,000 hospitalizations (84% in public hospitals) were related to these conditions, data from 2010. Vaccination is important in the care of these diseases, since it makes possible both avoiding their incidence, their complications and their sequels 8 . Only basic sanitation and drinking water have greater public health bene ts than vaccination 5,6 . Vaccines prevent between 2 and 3 million deaths per year worldwide 10 .
The international literature has already evidenced the existence of a difference not only genetic between the sexes, but hormonal and immune in the response to infectious pathogens, vaccines and autoimmune diseases [11][12][13] . Both sexes have the same cells, however, the innate humonal immunological response and mediated cell is different between the sexes, with different responses to the same stimuli (both pathogenic and vaccine), caused mainly by the interactions of sex hormones to the immune system, and by the speci c genetic determinants for each sex [14][15][16][17][18] (besides the socio-cultural-economic determinants that also interfere in the individual response to infections).
In this context, the main objective of this manuscript will be to discriminate the direct costs of hospitalizations under the Uni ed Health System, immunopreventable diseases (diphtheria, tetanus, pertussis, mumps, rubella, measles, hepatitis B, yellow fever, in uenza virus respiratory syndrome, meningococcal disease, chickenpox), through DATASUS data, from 2008 to 2018, understanding the impact of gender difference by preventable diseases in Brazil. This analysis is important in the sense that it can guide speci c public health policies for each gender or population group.

AREA OF STUDY
In this manuscript, data referring to Brazil were chosen for analysis. According to data from the Brazilian Institute of Geography and Statistics (IBGE, 2019/2020 -https://cidades.ibge.gov.br/brasil/panorama and https://cidades.ibge.gov.br/brasil/pesquisa/53/0?ano=2020 ), Brazil has an estimated population in 2020 of 211,755,692 people, with a population density of 22.43 inhabitants/km2, with a predominance of the population in the age groups of 10 to 29 years, a predominance of the female population, with a life expectancy at birth of 7 years more for females. It has a predominantly urban population, with GDP per capita of R$31,833.50 (year 2017) and Human Development Index (HDI) of 0.761 (79th position in the world in 2019http://hdr.undp.org/en/content/2019-human-development-index-ranking ).

STUDY DESIGN
A population, observational, descriptive, retrospective study was conducted with multiple groups and time series, with aggregated secondary data, through information provided by The variables analyzed were the immunopreventable diseases mentioned above, year, age group, gender and economic variables. The socio-demographic data were tabulated and evaluated by descriptive statistics (mean, standard deviation, median and percentages) and probability associated with the student t test, by the Excel® (Microsoft Corp., United States version 2007) and Stata® (StataCorpLP, College Station, United States version 14.0), by the research team itself. For the continuous (numerical) variables, linear regression analysis was used in the cases of veri cation of the correlations of the economic variables of each immunopreventable disease. The time trends (Yt) of the economic variables in relation to hospitalizations, age groups and genders were also analyzed, de ned by the equation of linear regression given by Y t = b 0 + b 1t + and t . In this expression, parameter b 0 corresponds to a constant, b 1 corresponds to the slope of the line, by the Prais-Winsten method, speci c for time series analysis. When the Beta parameter was positive, the time series was considered rate of variation of the line that adjusts the points of the time series, the basic logarithmic transformation 10 of the coe cients (Y) was performed, as it contributes to the reduction of the heterogeneity of the variance of the residuals of the linear regression analysis 19  Regarding the distribution of hospitalizations related to immunopreventable diseases studied in Brazil, the time series analyses were presented in Table 3, demonstrating, mostly, a stationary or decreasing trend in relation to the total number of hospitalizations, for both sexes, without differences in trends between the male and female groups. Some particularities were observed, as in the case of mumps disease that presented an increasing trend in the country, with statistical signi cance (p-value 0.005 in the male group and 0.000 in the female group). Regarding the distribution of total direct costs related to hospitalizations related to immunopreventable diseases researched in Brazil, the time series analyses were presented in Table 4, demonstrating, for the most part, a stationary or decreasing trend for both sexes, without differences in trends between the groups.
Some particularities were observed, as in the case of mumps disease that presented an increasing trend in the country, with statistical signi cance (p-value of 0.000 for both sexes). And the case of rubella disease, which showed a decreasing trend in the male group (p-value of 0.008) and stationary in the female group (p-value of 0.480).

Discussion
The international literature [11][12][13] has already shown greater intensity and e cacy in the immune response in females, against pathogens, in developing autoimmune diseases and at responding to different vaccine agents (immune response and post-vaccine adverse events) [14][15][16][17][18] . As IBGE data, based on the population estimate for 2020, the population projected for females (108,228,003) is higher than for males (103,527,689). However, what was presented in 10 years of records was a discrete predominance of hospitalizations for immunopreventable diseases in the male group. This situation was also observed in the analysis of the total direct values related to these hospitalizations, also with statistical signi cance of 0.036. There is a need for public health policies aimed at the male population, regarding the importance of immunopreventable diseases and awareness of the importance of vaccination coverage to remain high in

Limitations Of The Study
All studies based on public secondary databases have the limitation, already known, of underreporting and underreporting of the analyzed system itself, because these are dependent on the databases being fed by the employees responsible for the system. In the case of the SUS, these data are feeders in a decentralized manner and regionalized by States and Municipalities, that could update the data in any time even after the data had been publicized at the DATASUS site. However, despite the notorious underutilization of the system, these are the o cial data that are used for the development of public health policies in Brazil.