Association between congenital Zika virus syndrome disease burden and socioeconomic data in Brazil

In March 2015, Brazilian surveillance systems detected the first case of ZIKV fever in Brazil.^{twenty four}Meanwhile, the first possible case of ZIKV-associated microcephaly was recorded in Brazil in October of the same year.^{twenty five,26}since then, several studies have been conducted to improve our understanding of events associated with ZIKV infection.^27,28. However, few studies have yet investigated the magnitude and burden of microcephaly associated with CZS or ZIKV.²⁹, and potential socioeconomic factors associated with this disease. In addition to demonstrating a correlation between this disease and socioeconomic indicators, particularly schooling, our study demonstrated that there was a substantial loss of 30,027.44 DALY over the cumulative 6-year period assessed in the study.

ZIKV epidemics remain a serious public health problem for children with CZS. Despite a sharp decline in the number of cases since 2018, Brazil is a continental country with a predominantly tropical climate, with favorable environmental conditions for the emergence of new epidemics caused by arboviruses such as ZIKV.³⁰.

The number of births with microcephaly in Brazil increased significantly in 2015, nine times the number of births recorded between 2000 and 2014.³¹. This peak was also observed during the epidemic in several other countries, such as Colombia.³²,usa³³French Polynesia³⁴ and Costa Rica³⁵a four-fold increase in the prevalence of microcephaly.

Previous reports documenting regional patterns in the spatial distribution of microcephaly risk associated with ZIKV in Brazil highlighted the northeastern region as the most disproportionately affected region, with high spatial heterogeneity between regions.²⁹, which is consistent with our results. These findings corroborate the data reported by Marinho et al.³⁶, in that the northeastern region has the highest burden of several diseases, including infectious diseases. In contrast, the state of Rio Grande do Sul, located in southern Brazil, was minimally affected by the epidemic. In contrast, the state of Rio Grande do Sul, located in southern Brazil, was minimally affected by the epidemic. This disparity may be attributed to the region’s climate, which is characterized by the coldest temperatures in Brazil, and may create an unfavorable environment for the growth and persistence of the mosquito vectors responsible for the transmission of certain arboviruses.^31,37.

As already demonstrated in previous studies, the peak of CZS cases occurred in 2016 and the incidence declined rapidly in the years that followed.^Five,38. This decrease in the number of cases can be associated with control and preventive measures against ZIKV applied primarily to control ZIKV. ah.egyptianthe main vector of the virus^Five,17,30As a result, not only Zika cases but also CZS cases have decreased year by year. The cyclical behavior of the incidence of some arboviruses should also be considered.^39,40,41, which may also explain the decline in ZIKV virus circulation in Brazil. Brazil reported 5,699 probable ZIKV cases from January to June 2022, despite a decline in reporting of new cases of ZIKV infection and CZS cases.¹⁶.

CZS-specific mortality was high in all regions in 2016, with particularly high incidence in the northeastern region, where DALYs also decreased. It was noted that mortality decreased significantly from 2018 over the 6 years observed in this study. Mortality rates were high in 2017, but still low compared to 2016.

No specific studies on the disease burden of CZS were found in the literature, but there were two studies of ZIKV-associated microcephaly.^12,19. Details – Salamanca et al.¹⁹, the estimated 9.48 Dalys lost in each case of microcephaly associated with the Colombian Zika virus from 2015 to 2016 is higher than the 8.36 Dalys lost in each case from 2015 to 2020. This difference may be attributed to the fact that the study by More-Salamanca et al. focused only on confirmed cases of CZS, whereas our study focused only on confirmed cases of CZS.¹⁹ This included both probable and confirmed cases of ZIKV-associated microcephaly. The inclusion of probable cases in their analysis may have contributed to the overall increased disease burden in Colombia compared to the analysis of confirmed CZS cases in Brazil. It is important to consider these differences when interpreting and comparing results between the two studies. Alfaro-Murillo et al.¹² We also conducted a study on the disease burden associated with microcephaly, as previously discussed by More-Salamanca et al.¹⁹the value estimated by these authors was very high, with 29.95 DALY lost in each case of microcephaly. This difference may be due to the different parameters used for DALY estimation, only the same disability weights were used in both studies.

The number of CZS diseases estimated in our study in 2015 (7506.82 DALYs) was high compared to other congenital anomalies (same year) according to the WHO global estimate (649.2 DALYs), with 59.7 DALYs attributed to breast and neural tube defects and 300 DALYs to other unspecified congenital anomalies.⁴². For comparison, the CZS estimate for 2019 was 1072.4 DALYs, which was lower than the WHO estimate for birth defects for the same year (1158.8 DALYs).⁴². Finally, based on the results obtained in this study, it can be suggested that if CZS were considered in the burden of disease analysis conducted by WHO, most of the value obtained would be for his CZS.

It should be noted that ZIKV fever, and therefore CZS, is a relatively new disease and our data refer only to the 6 years since the disease first appeared in Brazil. In this sense, the maximum age of a child was her 6 years, highlighting the need for future studies validating survival and disease burden (in terms of DALYs) of individuals with CZS.

ZIKV, like other arboviruses, ah.egyptianThe risk of infection is higher in tropical areas where basic hygiene is poor and household incomes are low.⁴³. Given that Brazil is a country of high social inequalities, studies have shown that lack of access to schooling, employment opportunities, and poverty are determinants for the prevalence of ZIKV in the country and for children born with CZS.⁴⁴. The fact that our results show that CZS is directly related to illiteracy, low income, and poor basic hygiene conditions confirms that the more vulnerable the family, the more likely the mother is to become infected with ZIKV and, consequently, the higher the risk of vertical transmission of ZIKV and the development of CZS. A descriptive study reported that during the 2015-2016 epidemic, mothers of children with CZS were out of school and unemployed, especially after the birth of their children.^45,46.

Considering that the CZS epidemic in Brazil started in 2015, only children up to 6 years old were included in our analysis. Therefore, it is important to conduct comprehensive and longitudinal studies that examine the developmental progression of children affected by CZS. Through such research efforts, it is possible to gain valuable insight into the developmental trajectories of these children and the specific challenges facing their families.

As one of the pioneering studies conducted in Brazil to assess the overall burden of CZS, our study provides valuable insight into the potential impact of this disease within Brazil. Moreover, our results strongly indicate a consistent decline in new cases of CZS since 2017 as a result of collective efforts to combat the CZS epidemic in Brazil. Access to the results of all reported and confirmed cases and deaths by CZS provided a broad picture of the disease situation in Brazil. Our results may also be useful in understanding future research. Previous reports have mapped the risk of ZIKV-associated microcephaly in Brazil,^29,44, our study advanced the analysis of associations between socioeconomic factors and CZS, reinforcing the hypothesis that inequalities in health act as determinants of health disease processes and the development of CZS. An important limitation of our study is the use of sociodemographic data from the 2010 census, as the 2020 Brazilian census was not conducted due to COVID-19. It is worth noting, however, that our study analyzed his CZS data from 2015 onwards, so the 2010 Census data may not have undergone abrupt and significant changes in that period. Although this limitation affects the completeness of our analysis, we believe it has no material impact on the overall results and conclusions of the study. Another limitation is that since CZS is a new disease, specific values ​​for disability weights for CZS do not yet exist.

To date, this is the first study conducted to estimate the disease burden from CZS conducted in Brazil, and one of the few in South America. Our results show that the Northeast region caused the largest DALY loss from 2015 to 2020, with 2016 having the largest loss of all years. Based on the weaknesses of our study, we found that there are still questions that could be addressed in future research, such as assessing the quality and life expectancy of people born with CZS and studies conducted to assess the weight of disability due to CZS and ZIKV. Our results and methodology may aid new research processes and future comparisons.