Zika might not be acting alone: Using an ecological study approach to investigate potential co-acting risk factors for an unusual pattern of microcephaly in Brazil

Abstract

Zika virus infections can cause a range of neurologic disorders including congenital microcephaly. However, while Zika infections have been notified across all regions in Brazil, there has been an unusual number of congenital microcephaly case notifications concentrated in the Northeast of the country. To address this observation, we investigated epidemiological data (2014–2016) on arbovirus co-distribution, environmental and socio-economic factors for each region in Brazil. Data on arbovirus reported cases and microcephaly were collected from several Brazilian Ministry of Health databases for each Federal unit. These were complemented by environmental management, social economic and Aedes aegypti infestation index data, extracted from multiple databases. Spatial time “ecological” analysis on the number of arboviruses transmitted by Aedes mosquitoes in Brazil show that the distribution of dengue and Zika was widespread in the whole country, with higher incidence in the West-Central region. However, reported chikungunya cases were higher in the Northeast, the region also with the highest number of microcephaly cases registered. Social economic factors (human development index and poverty index) and environmental management (water supply/storage and solid waste management) pointed the Northeast as the less wealthy region. The Northeast is also the region with the highest risk of Aedes aegypti house infestation due to the man-made larval habitats. In summary, the results of our ecological analysis support the hypothesis that the unusual distribution of microcephaly might not be due to Zika infection alone and could be accentuated by poverty and previous or co-infection with other pathogens. Our study reinforces the link between poverty and the risk of disease and the need to understand the effect on pathogenesis of sequential exposure to arboviruses and co-viral infections. Comprehensive large-scale cohort studies are required to corroborate our findings. We recommend that the list of infectious diseases screened, particularly during pregnancy, be regularly updated to include and effectively differentiate all viruses from ongoing outbreaks.

Expansão da circulação do vírus Zika da África à América, 1947-2018: revisão da literatura*

“…Some reasons indicated for this were presented in an ecological analysis study: joint circulation of the virus that causes Chikungunya feber, which exists in this region, could increase the risk of other communicable diseases being transmitted. 122 Another study found higher ZIKA prevalence infection in poorer social classes. 123 The fact that the first notifications of infections occurred in Northeast Brazil, along with the massive media alerts that followed, helped measures to be taken that may possibly have contained greater spread of the virus in other regions.…”

The cyanobacterial saxitoxin exacerbates neural cell death and brain malformations induced by Zika virus

“…The synergism between cyanobacteria and ZIKV raises awareness that the exposure to STX should also be considered as a public health concern during arbovirus outbreaks. It is important to clarify that microcephaly and other ZIKV-derived congenital abnormalities are multifactorial, therefore, other risk factors may have contributed to foster the uncommon pattern of CZS in Brazil (27). ZIKV outbreaks occurred elsewhere; however, no epidemiological relationship between STX-producing cyanobacteria and congenital malformations derived from ZIKV infection was showed until now.…”

“…In contrast, the total number of cases of ZIKV infection was lower in NE compared to middle-west or southeast (SE) regions (26). Authors have suggested that a co-factor could be acting with ZIKV, contributing to this divergence among NE and other regions of Brazil; however, none has been confirmed until now (27).…”

Hypothetical Human Immune Genome Complex Gradient May Help to Explain the Congenital Zika Symdrome Catastrophe in Brazil: A New Theory

“…In turn, an ecological study at a municipality level across Brazil was unable to correlate the incidence of microcephaly with the incidence of ZIKV infection, but this showed a correlation with poverty index. These data suggested that ZIKV might not be, alone, be responsible for the unusual pattern of microcephaly in Brazil that clustered in the Northeast region (Campos et al 2018).…”