Background: The implications of congenital Zika Virus (ZIKV) infections for pediatric neurodevelopment and behavior remain inadequately studied. The aim of this study is to investigate patterns of neurodevelopment and behavior in groups of children with differening severities of ZIKV-related microcephaly and children with prenatal ZIKV exposure in the absence of microcephaly.Methods: We conducted a cross-sectional study, nested in a cohort, of 274 children (aged 10-45 months) who were born during the peak and decline of the microcephaly epidemic in Northeast Brazil. Participants were evaluated between February 2017 and August 2019 at two tertiary care hospitals in Recife, Pernambuco, Brazil. We analyzed the children in four groups assigned based on clinical and laboratory criteria: Group 1 had severe microcephaly; Group 2 had moderate microcephaly; Group 3 had prenatal ZIKVexposure confirmed by maternal RT-PCR testing but no microcephaly; and Group 4 was a neurotypical control group. Groups were evaluated clinically for neurological abnormalities and compared using the Survey of Wellbeing of Young Children (SWYC), a neurodevelopment and behavior screening instrument validated for use in Brazil. Children with severe delays underwent further evaluation with an adapted version of the SWYC.Results: Based on the SWYC screening, we observed differences between the groups for developmental milestones but not behavior. Among the 114 children with severe microcephaly of whom 98.2% presented with neurological abnormalities, 99.1% were ‘at risk of development delay’ according to the SWYC instrument. Among the 20 children with moderate microcephaly of whom 60% presented with neurological abnormalities, 65% were ‘at risk of development delay’. For children without microcephaly, the percentages found to be ‘at risk of developmental delay’ were markedly lower and did not differ by prenatal ZIKV exposure status: Group 3 (N=94), 13.8%; Group 4 (N=46), 21.7%.Conclusions: Among children with prenatal ZIKV exposure, we found a gradient of risk of development delay according to head circumference. Children with severe microcephaly were at highest risk for delays, while normocephalic ZIKV-exposed children had similar risks to unexposed control children. We propose that ZIKV-exposed children should undergo first-line screening for neurodevelopment and behavior using the SWYC instrument. Early assessment and follow-up will enable at-risk children to be referred to a more comprehensive developmental evaluation and to multidisciplinary care management.

Background: Leprosy continues to be an important cause of physical disability in endemic countries such as Brazil. Knowledge of determinants of these events may lead to better control measures and targeted interventions to mitigate its impact on affected individuals. This study investigated such factors among the most vulnerable portion of the Brazilian population.Methods: A large cohort was built from secondary data originated from a national registry of applicants to social benefit programs, covering the period 2001- 2015, including over 114 million individuals. Data were linked to the leprosy notification system utilizing data from 2007 until 2014. Descriptive and bivariate analyses lead to a multivariate analysis using a multinomial logistic regression model with cluster-robust standard errors. Associations were reported as Odds Ratios with their respective 95% confidence intervalsResults: Among the original cohort members 21,565 new leprosy cases were identified between 2007-2014. Most of the cases (63.1%) had grade zero disability. Grades 1 and 2 represented 21% and 6%, respectively. Factors associated with increasing odds of grades 1 and 2 disability were age over 15 years old (ORs 2,39 and 1,95, respectively), less schooling (with a clear dose response effect) and being a multibacillary patient (ORs 3,5 and 8,22). Protective factors for both grades were being female (ORs 0,81 and 0,61) and living in a high incidence municipality (ORs 0,85 and 0,65).Conclusions: The findings suggest that the developing of physical disabilities remains a public health problem which increases the burden of leprosy, mainly for those with severe clinical features and worse socioeconomic conditions. Early diagnosis is paramount to decrease the incidence of leprosy-related disability and our study points to the need for strengthening control actions in non-endemic areas in Brazil, where cases may be missed when presented at early stages in disease. Both actions are needed, to benefit patients and to achieve the WHO goal in reducing physical disabilities among new cases of leprosy.

Leprosy remains an important health problem in Brazil - the country register the second largest number of new leprosy cases each year, accounting for 14% of the world's new cases in 2019. Although there was increasing advances in leprosy surveillance worldwide, the true number of leprosy cases is expected to be much larger than the reported. Leprosy underreporting impair planning effective interventions and thoughful decisions about the distribution of financial and health resources. In this study, we estimated leprosy underreporting for each Brazilian microregion in order to guide effective interventions and resouce allocation to improve leprosy detection in the country. We extracted the number of new cases of leprosy from 2007 to 2015 and population and socioeconomic information from the 2010 Census for each Brazilian municipality and grouped data in microregions. We applied a Bayesian hierarchical model to obtain the best explicative model for leprosy underreporing using Grade 2 of leprosy-related disabilities as a proxy to explain the incidence rates. Then, we estimated the number of missing leprosy cases (underreported cases) and the corrected leprosy incidence rates for each Brazilian microrregion.

The number of studies published on postnatal microcephaly in children with Congenital Zika Syndrome is small, clinical presentations vary and aspects of the evolution of these children remain unclarified. The present case series examined clinical characteristics and assessed the growth velocity of the head circumference, weight and height Z-scores in 23 children who developed postnatal microcephaly during follow-up in the Microcephaly Epidemic Research Group Pediatric Cohort. To estimate the change in the head circumference, weight and height Z-scores over time and compare the mean difference between sexes, we used multilevel mixed-effects linear regressions with child-specific random effects. Among these children, 60.9% (n = 14/23) presented with craniofacial disproportion, 60.9% (n = 14/23) with strabismus, 47.8% (n = 11/23) with early onset seizures, 47.8% (n = 11/23) with dysphagia and 43.5% (n = 10/23) with arthrogryposis. Of the 82.7% (n = 19/23) children who underwent neuroimaging, 78.9% (n = 15/19) presented with alterations in the central nervous system. Monthly growth velocity, expressed in Z-scores, of the head circumference was − 0.098 (95% CI % − 0.117 to − 0.080), of weight was: − 0.010 (95%-CI − 0.033 to 0.014) and of height was: − 0.023 (95%-CI − 0.046 to 0.0001). Postnatal microcephaly occurred mainly in children who had already presented with signs of severe brain damage at birth; there was variability in weight and height development, with no set pattern.

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Background: In utero transmission of Zika virus (ZIKV) can lead to adverse infant outcomes, but vertical transmission rates are unknown.Methods: Antenatally ZIKV-exposed children were followed prospectively since the time of the Rio de Janeiro epidemic in 2015-16. Serum and urine specimens were collected from infants from birth throughout the first year of life. Specimens were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM antibody capture Zika MAC-ELISA.Infants had neurodevelopmental evaluations, brain imaging, eye examinations, and hearing assessments.Results: Over time 130 in utero ZIKV-exposed (mothers PCR+) children were tested with 407 specimens evaluated: 161 sera were tested by PCR and IgM assays, 85 urines by PCR; 84 children (65%) were positive in at least one assay. Among 94 children tested within 3 months of age, 70% were positive (39% serum PCR, 48% urine PCR, 39% IgM). After 3 months, 33%were positive by any laboratory method. Five children were intermittently PCR+ beyond 200 days of life. Concordance between IgM and PCR results was 52%, sensitivity 65%, specificity 40% (with any positive PCR result as the gold standard); IgM and serum PCR were 61% concordant; serum and urine PCR 55%. Most children (65%) were clinically normal. Positive results were seen in 29 of 45 children (64%) with abnormal findings and 55 of 85 normal children (65%), p=0٠98. Earlier maternal trimester of infection was associated with positive infant laboratory results but not infant clinical disease (p=0٠04).Conclusions: ZIKV has a high in utero transmission rate. Laboratory confirmed infection is not necessarily associated with abnormal infant findings.

This study aimed to estimate the risks of adverse infant outcomes in the first year of life related to prenatal Zika virus (ZIKV) exposure. A prospective cohort of pregnant women with rash was recruited in Central-West Brazil in a post-epidemic period (January 2017 to April 2019). We evaluated participants’ medical histories and performed ZIKV diagnostic testing using molecular (reverse transcription polymerase chain reaction [RT-PCR]) and serologic (immunoglobulin [Ig]M and plaque reduction neutralization tests [PRNT90]) assays. The ZIKV-positive group included both RT-PCR-confirmed cases as well as IgM and/or PRNT90-positive probable cases. Children were evaluated at birth and in the first 12 months of life. Transfontanellar ultrasound, central nervous system computed tomography, eye fundoscopy and retinography were performed. We estimated the absolute risk and 95% confidence interval (95% CI) of adverse infant outcomes among confirmed prenatally ZIKV-exposed children. Among 81 pregnant women with rash, 43 (53.1%) were ZIKV infected. The absolute risk of microcephaly among offspring of ZIKV-infected pregnant women was 7.0% (95% CI: 1.5–19.1), including the two cases of microcephaly detected prenatally and one detected postnatally. In total, 54.5% (95% CI: 39.8–68.7) of children in the ZIKV-exposed group had at least one ophthalmic abnormality, with the most frequent abnormalities being focal pigmentary mottling and chorioretinal atrophy or scarring. Our findings reinforce the importance of long-term monitoring of prenatally ZIKV-exposed children born apparently asymptomatic for Congenital Zika Syndrome.