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Increased rates of Zika virus have been identified in economically deprived areas in Brazil at the population level; yet, the implications of the interaction between socioeconomic position and prenatal Zika virus exposure on adverse neurodevelopmental outcomes remains insufficiently evaluated at the individual level. Using data collected between September 2015 and September 2019 from 163 children with qRT-PCR and/or IgM-confirmed prenatal exposure to Zika virus participating in a prospective cohort study in Rio de Janeiro, Brazil (NCT03255369), this study evaluated the relationships of socioeconomic indicators with microcephaly at birth and Bayley-III neurodevelopmental scores during the early life course. Adjusted logistic regression models indicated increased odds of microcephaly in children born to families with lower household income (OR, 95% CI: 3.85, 1.43 to 10.37) and higher household crowding (OR, 95% CI: 1.83, 1.16 to 2.91), while maternal secondary and higher education appeared to have a protective effect for microcephaly compared to primary education (OR, 95% CI: 0.33, 0.11 to 0.98 and 0.10, 0.03 to 0.36, respectively). Consistent with these findings, adjusted linear regression models indicated lower composite language (-10.78, 95% CI: -19.87 to -1.69), motor (-10.45, 95% CI: -19.22 to -1.69), and cognitive (-17.20, 95% CI: -26.13 to -8.28) scores in children whose families participated in the Bolsa Família social protection programme. As such, the results from this investigation further emphasise the detrimental effects of childhood disadvantage on human health and development by providing novel evidence on the link between individual level socioeconomic indicators and microcephaly and delayed early life neurodevelopment following prenatal Zika virus exposure.

Objective: Estimate inpatient hospitalization costs for patients with microcephaly, and predict cost increases due to a potential Zika virus outbreak., Methods: We identified Texas-wide inpatient hospitalization discharge records (2008-2015), for newborns and non-newborns with microcephaly. We estimated the cost of each hospitalization by applying cost-to-charge ratios on the actual hospitalization charge. For comparison, newborn visits for patients without microcephaly were also identified, and hospital costs were compared between patients with and without microcephaly. We estimated costs for microcephaly during the first year of life following a Zika outbreak (possible 1-50% increase in birth prevalence) in Texas., Results: There were 8005 microcephaly hospitalizations ($203,899,042; total cost). The median admission cost for newborns with microcephaly (N = 1393) was higher compared to those without microcephaly ($6751 vs $725, p < 0.001). Microcephaly hospitalizations of newborns had a lower median cost compared to non-newborns ($6751 vs $9754, p < 0.001). Based on these observed hospitalization costs, we estimated that a potential Zika virus outbreak in Texas could result in an additional $1-6 million per year for hospitalizations., Conclusion: Hospitalizations of patients with microcephaly are associated with high costs. An increase in microcephaly prevalence due to a Zika outbreak in Texas could have a considerable impact on health care costs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Evidence suggests that caring for a child with special health care needs can affect many domains of family life, including caregiver mental health. However, few studies have examined these outcomes among families impacted by the Zika virus (ZIKV). This study examines depressive symptom severity and care demands among primary caregivers of children, aged 15 to 26 months, with evidence of congenital Zika virus infection (ZVI)., Methods: A sample of primary caregivers of children with evidence of congenital ZVI in northeastern Brazil (n = 150) reported on depressive symptoms, care demands, and their children's development. Children were categorized into groups according to their developmental delay status. Bivariate analyses were run to test for differences between groups. A path analysis model was used to examine the indirect effects of developmental delay on depressive symptoms through economic challenges and time spent providing health care at home and whether these associations varied by child care support., Results: Compared to primary caregivers of children without developmental delay, primary caregivers of children with developmental delay had higher depression scores (p = 0.002), reported more economic (p < 0.001) and child care (p < 0.001) challenges, and spent more time providing health care at home (p < 0.001). Among primary caregivers who did not have child care support, developmental delay had a significant indirect effect on depressive symptoms through economic challenges but not through time spent providing health care at home., Conclusion: For families impacted by the ZIKV outbreak in Brazil, economic and child care challenges may be associated with primary caregiver mental health.

The Brazilian Federal Constitution of 1988 introduced the Continuous Cash Benefits (BCP), allowing the inclusion of people with disabilities. This is a descriptive study with aggregate municipal data about the time and geographic distribution of the incidence of microcephaly related to the Zika virus in Brazil and data of the BCP grants to children diagnosed with microcephaly. Data on the demand and BCP grants to children with microcephaly since 2009 are shown. Cases of microcephaly and/or central nervous system disorders were obtained from the Ministry of Health and totaled 2,366 confirmed cases from January 1, 2015 to December 31, 2016. The historical series of BCP granted from 2009 to 2016 was based on data from the National Institute of Social Security and showed, until 2014, a baseline with an average of 200 annual benefits for children younger than 48 months with microcephaly. In 2016, grants increased eight times, reaching 1,603 benefits granted to children of 731 municipalities spread in the 27 States. The Northeast accounted for 73% of the BCPs granted, however, this was less than 65% of the demand for incident cases. The implementation of the integrated referral system, including active search, should be strengthened to ensure access to all children entitled to BCP.

We modeled the potential cost-effectiveness of increasing access to contraception in Puerto Rico during a Zika virus outbreak. The intervention is projected to cost an additional $33.5 million in family planning services and is likely to be cost-saving for the healthcare system overall. It could reduce Zika virus-related costs by $65.2 million ($2.8 million from less Zika virus testing and monitoring and $62.3 million from avoided costs of Zika virus-associated microcephaly [ZAM]). The estimates are influenced by the contraception methods used, the frequency of ZAM, and the lifetime incremental cost of ZAM. Accounting for unwanted pregnancies that are prevented, irrespective of Zika virus infection, an additional $40.4 million in medical costs would be avoided through the intervention. Increasing contraceptive access for women who want to delay or avoid pregnancy in Puerto Rico during a Zika virus outbreak can substantially reduce the number of cases of ZAM and healthcare costs.

The ongoing Zika virus epidemic in the Americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (Guillain-Barré syndrome) has brought attention to this neglected pathogen. While initial case studies generated significant interest in the Zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of Zika viral infection and associated pathophysiology are only now starting to be published. In this review, we analyze Zika fetal neuropathogenesis from a comparative pathology perspective, using the historic metaphor of "TORCH" viral pathogenesis to provide context. By drawing parallels to other viral infections of the fetus, we identify common themes and mechanisms that may illuminate the observed pathology. The existing data on the susceptibility of various cells to both Zika and other flavivirus infections are summarized. Finally, we highlight relevant aspects of the known molecular mechanisms of flavivirus replication., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Drs. Robert Malone and Jill Glasspool-Malone are principal stockholders of Atheric Pharmaceutical, LLC. Robert Malone is the managing partner of Atheric Pharmaceutical. Dr. Michael Callahan is the Chief Medical Officer of the Zika Foundation.