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Epidemiological profile of pertussis in Brazil from 2010 to 2019: a systematic review

Pertussis is a respiratory infection that severely affects humans, caused by bacteria of the genus Bordetella, especially the species B. pertussis and B. parapertussis, presenting an important cause of infant morbidity and mortality. This disease has received little attention from government authorities over the years, which can cause the disease to reemerge in the future. This study aimed to carry out a systematic literature review on the epidemiology of pertussis in Brazil between the years 2010 to 2019. The study was carried out based on information collected in national (BVS, ANVISA, DATASUS) and international databases (PubMed, SciELO, CDC). When performing the statistical analysis of confirmed cases by region, there was a significant change in 2014 compared to other years in the Northeast region. While in the Southeast region, in 2013 there was a significant increase compared to 2012 and only reduced in 2015. In the South region, the increase in the number of cases occured sharply in 2012 and only decreased in 2017. In the CenterWest region, 2014 was the only year that showes considerable statistical variety. Regarding the age group, children under 1 year old and between 10 and 14 years old are the ones with the highest number of pertussis cases. Regarding gender, no significant changes were detected. Health surveillance, compulsory notification of cases added to social participation are essential, so this disease can be eradicated from Brazil and the world.


Introduction
Pertussis is an acute respiratory infection of worldwide distribution, characterized by whooping cough that compromises the human upper respiratory tract, such as the trachea and bronchi. It is considered a public health problem because of its high mortality in children, which over time has affected adolescents and adults, due to changes in the behavioral pattern of individuals through immunization Polakok, 2017).
It is caused by bacteria of the genus Bordetella, especially the species Bordetella pertussis and Bordetella parapertussis, the main cause of diseases in humans (Koneman, 2018). Transmission occurs through direct contact with infected individuals who eliminate via aerosols (sneezing, coughing and speaking), respiratory droplets containing the microorganism, which has a high virulence power (Castro et al., 2017;Araújo, 2019;Tortora, 2012).
Diagnosis can be performed through microbiological culture of samples collected from the nasopharyngeal region for species isolation. Currently, other tests are also carried out, such as molecular assays, direct immunofluorescence and serology, which aim to detect the bacterial genotype and thus confirm the analysis (Brasil, 2014;Castro & Milagres, 2017;Torres et al, 2015).
Later, with the introduction of the triple and tetravalent vaccines in Brazil in the 1990s, the country started to identify significant changes in the course of the disease, causing a reduction in the incidence of pertussis cases of 10.6 per 100,000 inhabitants in 2010 (vaccine coverage above 95%) .
However, in 2011, the Disease Notification System (SINAN) reported a sporadic and inexplicable increase in the number of pertussis cases. This situation lasted until 2014, in some Brazilian regions, such as the Southeast, Northeast and South. These regions were the most affected, raising questions about whether it is eradicated or re-emerging in the country (Medeiros et al, 2017; Since pertussis can cause severe signs and symptoms in children, which can lead to death and even cause significant cases in adults, this study aims to systematically gather epidemiological data in order to assess the current panorama of the infection in Brazil.

Methodology type
This work is a systematic, quantitative and descriptive review, which aims to investigate the incidence of pertussis in Brazil, during the years 2010-2019.

Database
The keywords "Pertussis in Brazil" and "Coqueluche no Brasil" were used to search for relevant articles, manuals and epidemiological bulletins on the subject, with an emphasis on the 5 regions (north, northeast, south, southeast and midwest) of the country. The main databases used were: SUS Portal (DATASUS), Virtual Health Library (BVS), US National Library Of Medicine (Pubmed), Scientific Electronic Library Online (ScieLO), Google Scholar, Ministry of Health (MS), National Health Surveillance Agency (ANVISA) and Centers for Disease Control and Prevention (CDC).

Inclusion criteria
As inclusion criteria, existing and published literature about pertussis in the period from 2010 to 2019 were used. 29 studies written in Spanish, English and Portuguese were included. Publications with epidemiological data from the 5 Brazilian regions, containing a diversity of information, such as: age, gender, diagnostic confirmation and case evolution were used as relevant methods.

Exclusion criteria
Any material with publication date prior to the year of 2010 were excluded, as well as articles that do not meet nor provide information relevant to the purpose of the research.
Initially, 100 articles were selected, and among these, 56 met the inclusion criteria, and the remaining 44 entered the exclusion criteria. The analysis was redone, so the most relevant works could be filtered, with analytical objectivity, and finally, 11 articles were selected.

Statistical analysis
The obtained data were registered in Microsoft Excel 365 software, and for analysis of the results, T-student and ANOVA tests were performed, that later were analyzed by Prism Graph 7.0 software (Prism, INC), considering the value of p<0.05.

Results and Discussion
It was observed that during the years 2010 to 2019 shown in Figure 1  Pertussis is a respiratory and infectious disease that affects mostly infants and children, as shown in Figure 2.
Therefore, through Portal do SUS notifications (DATASUS), the age group affected by the disease, during the study period When relating the number of cases with age groups, the ones with a considerable difference are the age groups under 1 year old (p=0.0245) and from 10 to 14 years old (p=0.0276). Therefore, only these two groups have a number of relevant pertussis cases.
Pertussis has a worldwide distribution and can affect male and female persons, as shown in Figures 3 and 4  In addition, according to notifications from the Brazilian Ministry of Health, a total of 32,882 cases of pertussis were reported in male and female populations. In the statistical analyses, we were able to assess that regarding gender, there was no significant change.
Pertussis, in the past, had already affected many infants and was an important cause of childhood morbidity and mortality.
However, through the advent of vaccination, as well as antibiotic therapy, which is an excellent therapeutic method with new changes in its pathway, it is visible that the number of cured patients is significant when compared to deaths, as demonstrated in  The number of cured patients was 29,922, representing 90.95% of the total amount. There were 467 deaths. The criteria for confirming the disease helps in its early detection, so that therapeutic prophylaxis reduces the pathology's incidence, leading the cases to significantly progress to cure, as shown in Figure 5. Therefore, there was an exponential growth from 2011 to 2014, since, theoretically, all regions were affected. The Southeast was one of the most affected regions in this regard, due to the fact that this place is home to a large portion of the population, being the most populous region in the country, with more than 70 million inhabitants, as well as its seasonality characteristics.
In Southeastern Brazil, there is great social agglomeration, in addition to the predominance of a tropical weather, with well-defined seasons, where there is an increase in the circulation of Bordetella pertussis strains, especially between spring and summer, where temperatures vary around 30ºC, thus facilitating bacterial metabolism and the consequent transmission of the disease. In the South, this reality is very similar, with changes in the region's climate, facilitating disease transmission in a period similar to the previous region. In the Northeast region, the onset of the disease remained fluctuating and also on the rise from 2012, being similarly associated with the Southeast, due to a large population influx in the states that comprise it, due to the predominant tourism in beaches, restaurants and other facilities. Furthermore, the equatorial-tropical weather in the Northeast facilitates the spread of the disease, with its coastal and semi-arid incidence and high temperatures that can vary from 28 ºC to 32 ºC. In the North, the number of cases is less incident, being correlated with a wider territory and a good population distribution, in addition to temperature variations around 24 ºC to 32 ºC, which reduces the occurrence of cases of the disease, since the pathogen needs a stable temperature to propagate. Finally, the Midwest region, similarly to the North region, has the social distribution expanded in its vast territory, also causing a reduction in the number of cases of Bordetella pertussis (Castro & Milagres, 2017;Dias, 2017;Nogueira, 2015;Oliveira et al, 2018;Silva, 2017). Therefore, the age group most affected by pertussis are still infants under 1 years old, corroborating the findings that explain that this is attributed to the lack of vaccination of infants, and/or inadequate vaccination, where they did not receive the three doses of the vaccine Aguiar et al, 2015;Gryninger, 2016).
Pertussis can reach different groups in society, however, the number of cases were more extensive in females, and studies suggest that the detection of cases incidentally happens due to more intense surveillance of pertussis in women, especially during the gestational period, through prenatal examinations. Furthermore, with the replacement of erythromycin by azithromycin, there was an improvement in the treatment of pertussis, which became a disease that in most cases evolves towards a cure, due to the existing vaccination and effective therapeutic protocols (Castro & Milagres, 2017;Medeiros et al, 2017). Therefore, the clinical diagnosis is essential, considering that the laboratory method for bacterial isolation may be more difficult, as even if the microbiological detection of B. pertussis and B. parapertussis is considered the gold standard, it may have a low sensitivity, with variance in the positivity if the collection of biological sample from nasopharyngeal aspirate is not performed in the first weeks of symptoms and prior to antibiotic therapy (Brasil, 2017;Machado, 2019).
The incidence of cases is still apparent in Brazil and signs of reemergence of pertussis can be observed through the increase in the number of sporadic cases that happen annually due to several reasons: problems in the epidemiological surveillance system facing the disease, loss of immunity of vaccinated persons over the years, lack of vaccine boosters, in addition to the lack of diagnostic methods, such as qPCR, which are more sensitive and guarantee reliability in the results (Telles, 2012;Torres, 2015).
Pertussis is still an assiduous disease in the Brazilian territory, constituting a considerable portion of cases during a sporadic period of 3 to 5 years. Therefore, social participation is highly important, so the disease can be prevented, in addition to greater attention from government authorities regarding vaccine distribution in places of difficult access and the intensification of vaccine campaigns that help the population in decision-making to protect from the disease (Korppi, 2013;Berezin, 2014)

Conclusion
Thus, it could be observed that the possible significant changes in pertussis prevalence occurred in some parameters analyzed statistically, such as region of residence and age group affected by the disease. Therefore, it is notorious that pertussis is still impactful in Brazil. For this reason, it is of great importance to continue health surveillance, compulsory notification of cases, added to the knowledge of health professionals in the execution and provision of reliable laboratory and clinical results, in addition to social participation in immunization campaigns, so that pertussis can be eradicated in the future.
As previously reported, whooping cough, despite being a notifiable disease, is still included in the group of neglected diseases in Brazil and worldwide. In this way, it is suggested that new epidemiological studies be carried out constantly, covering not only the child population, which in fact is the most affected, but also the adult age group, so that it is possible to verify if the disease is presenting a new pattern of involvement and to assist health professionals and government authorities, as well as the population, in raising awareness of the importance of vaccination and for early combating the disease, as well as subsequent health surveillance.