This study showed a continuous increase in the temporal RR of SPW from 2007 to 2018, and CS, from 2007 to 2017. Over these years, the incidence of SPW and CS increased 8.7 and 6.6 times, respectively. Moreover, this increase occurred in en bloc in approximately all the municipalities of SP. This occurred in the richest and most populated state of Brazil. SP represents more than 31% of the Brazilian gross domestic product, with approximately 46 million inhabitants, and is ranked the third most populous and cosmopolitan political unit in South America13.
In the analyses of the socioeconomic and demographic conditions, link to health services, and presence of a transmissible comorbidities such as aids, which also indirectly involved aspects related to programmatic vulnerability, we observed that the increase in SPW was influenced by teenage pregnancy, municipalities with a large number of inhabitants, and aids incidence. The conditions that influenced the increase of CS were municipalities with a large number of inhabitants, incomplete antenatal care, inadequate technology to perform deliveries in the municipality, and aids incidence.
Ecological studies set the stage for examining causal mechanisms and provide a better approach for exploring exposures that are easier to measure in groups of individuals than at the individual level14. An important aspect of ecological modeling is the consideration of whether the response variables are independent. This study, which uses space-time architecture, had both the possibility of spatial and temporal dependence. Here, this aspect can be considered through the use of Bayesian latent Gaussian models, so that the results obtained are adjusted for the spatial and temporal autocorrelations and the interactions between them7,8. Moreover, the malleability of these models for the use of negative binomial probability distribution inflated to zero proved to be the appropriate for analyzing the occurrence of SPW15.
Since space and time were part of the modeling, the Bayesian inference allowed us to obtain the RR describing the behavior of the diseases studied according to time (years), space (municipalities), and space-time (municipalities according to years). These last two results, related to the mapping of diseases and their risk, are invaluable tools, in view of the possibility of knowledge of areas with higher risks, in assisting in health decision-making, interpreting the implementation of existing actions, and intervening to reduce injuries through prevention programs6.
Our results showed a continuous increase in the incidence of SPW and CS. Since these two diseases display synergistic behavior, an increase in the second4 can lead to management difficulties in the first16. This demonstrated the importance of studies on this dynamic. An analysis of the global load of SPW and CS showed that Europe was the only region that presented a level close to elimination, despite estimates of declines in Southeast Asia. The Eastern Mediterranean and American regions showed the largest estimated increases in the prevalence of SPW4. A study in Mexico showed that only 53% of pregnant women underwent diagnostic tests17 and recently, a study conducted between 2012 and 2016 in the United States, demonstrated a significant increase in CS, from 8.4% to 15.7 cases/100,000-LB18.
This incidence can be explained by the expansion of the coverage of tests to detect diseases and by the improvement in surveillance19. In Brazil, the availability of a rapid test for syphilis increased from 31,500 in 2011 to 3,156,410 in 201420. In SP, this increase was greater: from 1,000 tests being available in 2011 to 1,314,700 in 201721. Such progress was also probably due to funds from the Unified Health System (Sistema Único de Saúde - SUS) in the “Rede Cegonha” program, whose aims are the improvement of care for women during pregnancy, childbirth and postpartum, for newborns and children up to 2 years old22, and investing in the mother and child binomial23. A study conducted in Brazil confirmed this tendency, showing that the increase in the capacity to identify asymptomatic cases of syphilis resulted in an increase in the notifications of acquired, gestational, and congenital syphilis20.
This increase was also influenced by the decreased use of condoms and loss of opportunity for treatment when penicillin was not administered in primary health care (PHC), as well as the global crisis supply shortages between 2014 and 20169. This evidence was consistent with the results of this research, which showed a positive association between SPW and the proportion of live births to adolescent mothers, municipalities with a large number of inhabitants, and the incidence rate of aids. The evidence was also consistent with the results obtained for CS, which showed a positive association with the proportion of pregnant women with inadequate antenatal care, proportion of mothers with fewer than four antenatal care consultations, municipalities with a large number of inhabitants, municipalities that do not have support for delivery, and aids incidence rate. Some of the variables associated with CS were also associated with SPW, highlighting the finding of a previous study that the control of CS is directly linked to the management of syphilis in pregnant women during antenatal care24.
A recent study4 pointed out that the increase in SPW and CS is closely related to the expressive increase in AS rates in the general population and people socially vulnerable to HIV and sexually transmitted infections (STI), such as men who have unprotected sex with men and those not covered by the search actions, such as those in the antenatal care protocol. Furthermore, authors12, 24, 25 demonstrated the importance of adequate antenatal care, syphilis screening, and the correct and timely treatment for the prevention of syphilis. For Kimball et al. (2020)25, late seroconversion and the lack of early identification of cases were reflections of the increase in groups at risk and issues of social vulnerabilities such as the lack of adequate housing, low education, and lower access to information.
Other factors that influenced the spread of syphilis were related to the accelerated urbanization process seen in recent decades in Brazil. Consequently, there is increased social exclusion, generating segregated populations, difficulties in accessing urban services and infrastructure, greater exposure to violence, racial discrimination, and discrimination against women and children26. These situations, among others, affect the way a person falls ill and health needs of a population27. Nevertheless, in terms of health, larger populations can provide the impetus for a municipality to present a more comprehensive care network with greater investments due to greater demand28. However, municipalities with larger population sizes present greater disparities in their social determinants of health, including access to health services27.
SP, with more than 20% of the Brazilian population, is a good example of this dichotomy. On the one hand, 32.5% of municipalities in SP have been classified as dynamic with high wealth and good levels of social indicators (longevity and education) while in contrast, 43.9% of its municipalities demonstrate inequalities, with high levels of wealth, but with unsatisfactory social indicators29. People are diverse in terms of culture and education, and they move indistinctly from capital to the interior or vice versa30.
This dichotomous context may also be indirectly linked to one of our research findings, due to the possible relationship of the increase in cases of CS in municipalities without adequate health technology to perform deliveries. Usually, larger municipalities also have more health technology available, and if PHC fails at some point, a population still has, indirectly, the hospital scope for acute cases. However, this factor denotes the great difficulties experienced in coordinating health care networks using PHCs, since strategic syphilis should not require hospital care being a condition that is treated nationally as a condition that is responsive to PHC31.
Neves et al. (2018)28 reported that in Brazil, for every ten basic health units, not even one is adequate for the care of chronic conditions. Nonetheless, in spite of the many obstacles, Brazilian PHCs contributed to the control of syphilis. In 2019, of the 12,650 cases of SPW registered in SP, 4,013 evolved to CS, approximately 72% of CS cases were avoided. Of those who progressed to CS, 28% had maternal reinfections close to delivery, even after adequate treatment, including a change of partner or untreated partner, and 14% of cases were diagnosed with syphilis only in the third trimester of pregnancy32.
Major challenges that needs to be overcome on a worldwide scale is the issues related to the incorrect treatment of syphilis during pregnancy and the lack of audits to identify flaws in the care process and the adequacy of the qualifications of health professionals. A study conducted in Brazil demonstrated these difficulties33 and another one conducted in Argentina pointed out that of the children identified with CS and born in hospitals (corresponding to 96% of the total CS cases), only 47% of their mothers completed the antenatal care serological screening, and only four were adequately treated34.
The lack of knowledge and the importance of health monitoring during pregnancy have been associated with populations of greater social vulnerability, with low schooling and non-white color/race. Women with low education have less access to information, which limits their knowledge of health care and, mainly, measures to prevent sexually transmitted diseases such as syphilis infection35,36. Equally, it is worth mentioning the existence of more vulnerable population groups in each municipality, especially with regard to adolescents, as evidenced by the results. A national study showed the association of so-called young people “nemnem” (NEET - Not in Education, Employment or Training) to the low parental education, lower income and rural areas37. A study in the United Kingdom indicated that young people were more likely to become unemployed, use drugs and alcohol, be involved in crimes, have poor health, and become pregnant in adolescence38.
Regarding the association of both situations of the disease (SPW and CS) with the aids incidence rate, HIV and syphilis affect populations with similar profiles in which co-infection is common. According to the literature, people infected with other STI, including syphilis, are three to five times more likely to acquire HIV39. Moreover, the prevalence of syphilis also occurs more frequently among HIV-positive pregnant women than among HIV-negative women, because pregnant women living with HIV may have a weaker immune systems than other pregnant women40.
Considering this study followed all the precepts of ecological design, it is necessary to indicate the need for research that can analyze, as robustly as this study, issues directly related to individual characteristics and that can contribute to the evaluation of the persistence of SPW and CS, as well as the facilitation of qualified audits to assess programmatic vulnerabilities involving their management, care and prevention. Although Brazil has an extensive range of technical materials and well-established clinical protocols that regulate the management of SPW and CS, it is still necessary to standardize the therapeutic conduct of health professionals and identifying treatments with alternative drugs that can be used in periods of worldwide shortages of penicillin, among other factors.
This study had some limitations. Since these were secondary data, underreported cases may have coexisted. Another limitation was we were not able to consider variables indicative of programmatic vulnerability, such as the availability of penicillin in primary care and testing coverage for syphilis, due to the lack of free access to this type of data. This information have assisted in our discussion on aspects that may be related to the persistence of congenital syphilis. Furthermore, to avoid any misunderstanding regarding the interpretation of the research findings, due to ecological fallacy, inferences were always made for aggregates and not for individuals. We interpreted our results based on the characteristics of the regions and not individually in relation to pregnant women and LB.
The results obtained in this study may also be useful in the design of new studies for the evaluation of SPW and CS surveillance and control in SP, both from a spatial and temporal point of view. The en bloc increase in the occurrence of both injuries indicates that actions are required in almost all the municipalities of SP. However, the identification of municipalities and RDS at the greatest risk for these diseases also points to priority areas for the development and implementation of these actions. If, on the one hand, the growing tendency of SPW points to difficulties in its control, the reversal of the temporal tendency of CS, even if not statistically significant, can be an indication of the resoluteness of the actions that have been developed.