Accuracy of saliva for SARS-CoV-2 detection in outpatients and their household contacts during the circulation of the Omicron variant of concern.

BACKGROUND: While nasopharyngeal (NP) swabs are considered the gold standard for severe acute respiratory coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection, several studies have shown that saliva is an alternative specimen for COVID-19 diagnosis and screening. METHODS: To analyze the utility of saliva for the diagnosis of COVID-19 during the circulation of the Omicron variant, participants were enrolled in an ongoing cohort designed to assess the natural history of SARS-CoV-2 infection in adults and children. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa coefficient were calculated to assess diagnostic performance. RESULTS: Overall, 818 samples were collected from 365 outpatients from January 3 to February 2, 2022. The median age was 32.8 years (range: 3-94 years). RT-PCR for SARS-CoV-2 was confirmed in 97/121 symptomatic patients (80.2%) and 62/244 (25.4%) asymptomatic patients. Substantial agreement between saliva and combined nasopharyngeal/oropharyngeal samples was observed with a Cohen's kappa value of 0.74 [95% confidence interval (CI): 0.67-0.81]. Sensitivity was 77% (95% CI: 70.9-82.2), specificity 95% (95% CI: 91.9-97), PPV 89.8% (95% CI: 83.1-94.4), NPV 87.9% (95% CI: 83.6-91.5), and accuracy 88.5% (95% CI: 85.0-91.4). Sensitivity was higher among samples collected from symptomatic children aged three years and older and adolescents [84% (95% CI: 70.5-92)] with a Cohen's kappa value of 0.63 (95% CI: 0.35-0.91). CONCLUSIONS: Saliva is a reliable fluid for detecting SARS-CoV-2, especially in symptomatic children and adolescents during the circulation of the Omicron variant.

ZIKA Virus Neutralizing Antibody Kinetics in Antenatally Exposed Infants.

BACKGROUND: Zika virus (ZIKV) is associated with severe congenital abnormalities and laboratory diagnosis of antenatal infection is difficult. Here we evaluated ZIKV neutralizing antibody (nAb) kinetics in infants born to mothers with PCR-confirmed ZIKV infection during pregnancy. METHODS: Neonates (n = 98) had serum specimens tested repeatedly for ZIKV nAb over the first 2 years of life using virus neutralization test (VNT). ZIKV neonatal infection was confirmed by RT-PCR in blood or urine and/or presence of ZIKV IgM antibodies, and results were correlated with infant clinical features. RESULTS: Postnatal laboratory evidence of ZIKV vertical transmission was obtained for 60.2% of children, while 32.7% exhibited clinical abnormalities. Congenital abnormalities were found in 37.3% of children with confirmed ZIKV infection and 31.0% of children without confirmed infection (P = .734). All but 1 child displayed a physiologic decline in ZIKV nAb, reflecting maternal antibody decay, despite an early ZIKV-IgM response in one-third of infants. CONCLUSIONS: Infants with antenatal ZIKV exposure do not develop ZIKV nAb despite an early IgM response. Therefore, ZIKV VNT in children is not useful for diagnosis of congenital infection. In light of these findings, it remains to be determined if children infected in utero are potentially susceptible to reinfection.

SARS-CoV-2 variant N.9 identified in Rio de Janeiro, Brazil.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.33-derived lineage named N.9 was described recently in Brazil and it's considered a potential variant of interest (VOI) due to the presence of E484K substitution at the receptor-binding domain (RBD) of the Spike (S) protein. OBJECTIVE: To describe the first detection of variant N.9 in Rio de Janeiro State. METHODS: SARS-CoV-2 N.9 was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), whole-genome sequencing and phylogenetic analysis. FINDINGS: Here, we report two SARS-CoV-2 N.9 lineage strains in Rio de Janeiro. One of them had only the E484K substitution of the six N.9 lineage-defining mutations. Other three strains pre-defined as N.9 have the same genomic profile. These four strains are grouped within the B.1.1.33 lineage and basal to the N.9 lineage in our phylogenetic analysis, and we call them "N.9-like/B.1.1.33 + E484K". MAIN CONCLUSIONS: The phylogenetic analysis shows four independent introductions of N.9 in the state of Rio de Janeiro in October and December 2020, January and March 2021. SARS-CoV-2 N.9 dissemination in the Rio de Janeiro could have been limited by the emergence and dominance of other variants, mainly by the lineage P.2 VOI Zeta that emerged in the same period and co-circulated with N.9, as observed in the neighboring State of São Paulo.

Zika Virus Infection in Pregnant Women in Rio de Janeiro.

BACKGROUND: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. METHODS: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. RESULTS: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester). CONCLUSIONS: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).

The Role of Children in Household Transmission of SARS-CoV-2 Across Four Waves of the Pandemic.

BACKGROUND: It is important to understand the dynamics of SARS-CoV-2 transmission in close-contact settings such as households. We hypothesized that children would most often acquire SARS-CoV-2 from a symptomatic adult caregiver. METHODS: This prospective cohort study was conducted from April 2020 to July 2022 in a low-resource, urban settlement in Brazil. We recruited families who brought their children to a public clinic. We collected nasopharyngeal and oral swabs from household members and tracked symptoms and vaccination. RESULTS: In total, 1256 participants in 298 households were tested for SARS-CoV-2. A total of 4073 RT-PCR tests were run with 893 SARS-CoV-2 positive results (21.9%). SARS-CoV-2 cases were defined as isolated cases (N = 158) or well-defined transmission events (N = 175). The risk of household transmission was lower if the index case was a child (OR: 0.3 [95% CI: 0.16-0.55], P < .001) or was vaccinated (OR: 0.29 [95% CI: 0.1-0.85], P = .024), and higher if the index was symptomatic (OR: 2.53 [95% CI: 1.51-4.26], P < .001). The secondary attack rate for child index cases to child contacts was 0.29, whereas the secondary attack rate for adult index cases to child contacts was 0.47 (P = .08). CONCLUSIONS: In this community, children were significantly less infectious to their household contacts than adolescents or adults. Most children were infected by a symptomatic adult, usually their mother. There was a double benefit of vaccination as it protected the vaccine from severe illness and prevented onward transmission to household contacts. Our findings may also be valid for similar populations throughout Latin America.

Methods to Assess Adult and Adolescent Patients' Adherence to Antimalarial Treatment: A Systematic Review.

Malaria is a curable disease for which early diagnosis and treatment, together with the elimination of vectors, are the principal control tools. Non-adherence to antimalarial treatment may contribute to therapeutic failure, development of antimalarial resistance, introduction or resurgence of malaria in non-endemic areas, and increased healthcare costs. The literature describes several methods to directly or indirectly assess adherence to treatment, but no gold standard exists. The main purpose of this review is to systematize the methods used to assess patient adherence to antimalarial treatment. A systematic review was performed, in accordance with the PRISMA statement, of the following databases: LILACS, EMBASE, PUBMED, COCHRANE, GOOGLE SCHOLAR, WEB OF SCIENCE, SCOPUS, and OPENGREY, through 14 December 2021. A snowball search was also performed by screening the references of the included studies as well as those cited in relevant reviews. Inclusion criteria were reporting assessment of the patient's adherence to antimalarials in individuals with laboratory diagnosis of malaria, the description of antimalarials prescribed, and adherence estimates. Exclusion criteria were studies exclusively about directly observed therapy, studies of populations ≤12 yo and guidelines, commentaries, reviews, letters, or editorials. Study quality was assessed using MINORS and the Cochrane Risk of Bias Tool. Proportions were calculated to measure frequencies considering the number of articles as the denominator. Twenty-one studies were included in this review. Most of them (76.5%) assessed adherence to falciparum malaria treatment. Seventeen studies (80.9%) used a combination of methods. The methods described were pill counts, self-reports, biological assays, use of electronic pillboxes, and clinical cure. It was possible to identify different adherence classifications for all the methods used. Our review found that indirect methods like pill counts and self-reports are the most commonly used. Combining an method that gives solid proof of the ingestion of medication and a method that completes the research with information regarding factors, beliefs or barrier of adherence seems to be the best approach. Future studies of antimalarial treatment should standardize adherence classifications, and collect data on the types and causes of nonadherence, which can contribute to the development of tools to promote medication adherence. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020148054, identifier CRD42020148054.

Incidence of SARS-CoV-2 over four epidemic waves in a low-resource community in Rio de Janeiro, Brazil: A prospective cohort study.

Background: Incidence rates of SARS-CoV-2 infections in low-resource communities can inform vaccination strategies and non-pharmaceutical interventions (NPIs). Our objective was to estimate incidence over four epidemic waves in a slum in Rio de Janeiro, a proxy for economically deprived areas in the Global South. Methods: Prospective cohort of children and household contacts screened for SARS-CoV-2 by PCR and serology (IgG). The incidence density of PCR positive infections estimated for each wave - the first wave, Zeta, Gamma and Delta - was compared to an index combining NPIs and vaccination coverage. Findings: 718 families and 2501 individuals were enrolled, from May 2020 to November 2021. The incidence density of SARS-CoV-2 infection due to the first wave was 2, 3 times that of the other waves. The incidence among children was lower than that of older participants, except in later waves, when vaccination of the elderly reached 90%. Household agglomeration was significantly associated with incidence only during the first wave. Interpretation: The incidence of infection greatly exceeded rates reported in similar cohorts. The observed reduction in incidence in the elderly during the Delta variant wave, in spite of the rollback of NPIs, can be attributed to increased vaccine coverage. The high incidence in young people reinforces the importance of vaccination in this age group, a policy that has yet to receive the full support of some sectors of society. Funding: UK Medical Research Council, Foundation for the Advancement of Science of the State of Rio de Janeiro, National Council for Scientific and Technological Development.

Cohort-profile: Household transmission of SARS-CoV-2 in a low-resource community in Rio de Janeiro, Brazil.

PURPOSE: To better understand the household transmission of SARS-COV-2 in a low-resource community in Rio de Janeiro during the COVID-19 pandemic (2020-2022). PARTICIPANTS: This is an open prospective cohort study of children ≤12 years old and their household contacts. During home visits over 24 months, we collected data on sociodemographic characteristics, behavioural data, clinical manifestations of SARS-CoV-2, vaccination status, SARS-CoV-2 (reverse transcription-polymerase chain reaction) RT-PCR and anti-S antibody tests. Among adults, the majority of participants were women (62%). FINDINGS TO DATE: We enrolled 845 families from May 2020 to May 2022. The median number of residents per household was four. The median household density, defined as the number of persons per room, was 0.95. The risk of SARS-CoV-2 occurrence was higher in households with a high number of persons per room. Children were not the principal source of SARS-CoV-2 infections in their households during the first wave of the pandemic. FUTURE PLANS: Future studies will investigate cellular and humoral immune responses to locally circulating SARS-CoV-2 variants, which is relevant for the design of vaccines, antivirals and monoclonal antibodies. We will also engage in outreach to encourage vaccination as a means of limiting the transmission of novel SARS-CoV-2 variants and other emerging pathogens.

Phenotypic and Genetic Variability of Isolates of ZIKV-2016 in Brazil.

The possibility of a Zika virus epidemic resurgence requires studies to understand its mechanisms of pathogenicity. Here, we describe the isolation of the Zika virus from breast milk (Rio-BM1) and compare its genetic and virological properties with two other isolates (Rio-U1 and Rio-S1) obtained during the same epidemic period. Complete genomic analysis of these three viral isolates showed that they carry characteristics of the American isolates and belong to the Asian genotype. Furthermore, we detected eight non-synonymous single nucleotide variants and multiple nucleotide polymorphisms that reflect phenotypic changes. The new isolate, Rio-BM1, showed the lowest replication rates in mammalian cells, induced lower cell death rates, was more susceptible to treatment with type I IFN, and was less pathogenic than Rio-U1 in a murine model. In conclusion, the present study shows evidence that the isolate Rio-BM1 is more attenuated than Rio-U1, probably due to the impact of genetic alterations in the modulation of virulence. The results obtained in our in vitro model were consistent with the pathogenicity observed in the animal model, indicating that this method can be used to assess the virulence level of other isolates or to predict the pathogenicity of reverse genetic constructs containing other polymorphisms.

Neurodevelopment in the third year of life in children with antenatal ZIKV-exposure.

We report cognitive, language and motor neurodevelopment, assessed by the Bayley-III test, in 31 non-microcephalic children at age 3 with PCR-confirmed maternal Zika virus exposure (Rio de Janeiro, 2015-2016). Most children had average neurodevelopmental scores, however, 8 children (26%) presented delay in some domain. Language was the most affected: 7 children (22.6%) had a delay in this domain (2 presenting severe delay). Moderate delay was detected in the cognitive (3.2%) and motor (10%) domains. Maternal illness in the third trimester of pregnancy and later gestational age at birth were associated with higher Bayley-III scores. Zika-exposed children require long-term follow-up until school age.

Why Did ZIKV Perinatal Outcomes Differ in Distinct Regions of Brazil? An Exploratory Study of Two Cohorts.

The Zika virus (ZIKV) epidemic in Brazil occurred in regions where dengue viruses (DENV) are historically endemic. We investigated the differences in adverse pregnancy/infant outcomes in two cohorts comprising 114 pregnant women with PCR-confirmed ZIKV infection in Rio de Janeiro, Southeastern Brazil (n = 50) and Manaus, in the north region of the country (n = 64). Prior exposure to DENV was evaluated through plaque reduction neutralizing antibody assays (PRNT 80) and DENV IgG serologies. Potential associations between pregnancy outcomes and Zika attack rates in the two cities were explored. Overall, 31 women (27%) had adverse pregnancy/infant outcomes, 27 in Rio (54%) and 4 in Manaus (6%), p < 0.001. This included 4 pregnancy losses (13%) and 27 infants with abnormalities at birth (24%). A total of 93 women (82%) had evidence of prior DENV exposure, 45 in Rio (90%) and 48 in Manaus (75%). Zika attack rates differed; the rate in Rio was 10.28 cases/10,000 and in Manaus, 0.6 cases/10,000, p < 0.001. Only Zika attack rates (Odds Ratio: 17.6, 95% Confidence Interval 5.6-55.9, p < 0.001) and infection in the first trimester of pregnancy (OR: 4.26, 95% CI 1.4-12.9, p = 0.011) were associated with adverse pregnancy and infant outcomes. Pre-existing immunity to DENV was not associated with outcomes (normal or abnormal) in patients with ZIKV infection during pregnancy.

SARS-CoV-2 Infection Dynamics in Children and Household Contacts in a Slum in Rio de Janeiro.

OBJECTIVES: To investigate the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a vulnerable population of children and their household contacts. METHODS: SARS-CoV-2 reverse transcription polymerase chain reaction assays and coronavirus disease 2019 (COVID-19) immunoglobulin G serology tests were performed in children and their household contacts after enrollment during primary health care clinic visits. Participants were followed prospectively with subsequent specimens collected through household visits in Manguinhos, an impoverished urban slum (a favela) in Rio de Janeiro at 1, 2, and 4 weeks and quarterly post study enrollment. RESULTS: Six hundred sixty-seven participants from 259 households were enrolled from May to September 2020. This included 323 children (0-13 years), 54 adolescents (14-19 years), and 290 adults. Forty-five (13.9%) children had positive test results for SARS-CoV-2 polymerase chain reaction. SARS-CoV-2 infection was most frequent in children aged <1 year (25%) and children aged 11 to 13 years (21%). No child had severe COVID-19 symptoms. Asymptomatic infection was more prevalent in children aged <14 years than in those aged ≥14 years (74.3% and 51.1%, respectively). All children (n = 45) diagnosed with SARS-CoV-2 infection had an adult contact with evidence of recent infection. CONCLUSIONS: In our setting, children do not seem to be the source of SARS-CoV-2 infection and most frequently acquire the virus from adults. Our findings suggest that, in settings such as ours, schools and child care potentially may be reopened safely if adequate COVID-19 mitigation measures are in place and staff are appropriately immunized.

Diagnostic performance of anti-Zika virus IgM, IgAM and IgG ELISAs during co-circulation of Zika, dengue, and chikungunya viruses in Brazil and Venezuela.

BACKGROUND: Serological diagnosis of Zika virus (ZIKV) infection is challenging because of the antibody cross-reactivity among flaviviruses. At the same time, the role of Nucleic Acid Testing (NAT) is limited by the low proportion of symptomatic infections and the low average viral load. Here, we compared the diagnostic performance of commercially available IgM, IgAM, and IgG ELISAs in sequential samples during the ZIKV and chikungunya (CHIKV) epidemics and co-circulation of dengue virus (DENV) in Brazil and Venezuela. METHODOLOGY/PRINCIPAL FINDINGS: Acute (day of illness 1-5) and follow-up (day of illness ≥ 6) blood samples were collected from nine hundred and seven symptomatic patients enrolled in a prospective multicenter study between June 2012 and August 2016. Acute samples were tested by RT-PCR for ZIKV, DENV, and CHIKV. Acute and follow-up samples were tested for IgM, IgAM, and IgG antibodies to ZIKV using commercially available ELISAs. Among follow-up samples with a RT-PCR confirmed ZIKV infection, anti-ZIKV IgAM sensitivity was 93.5% (43/46), while IgM and IgG exhibited sensitivities of 30.3% (10/33) and 72% (18/25), respectively. An additional 24% (26/109) of ZIKV infections were detected via IgAM seroconversion in ZIKV/DENV/CHIKV RT-PCR negative patients. The specificity of anti-ZIKV IgM was estimated at 93% and that of IgAM at 85%. CONCLUSIONS/SIGNIFICANCE: Our findings exemplify the challenges of the assessment of test performance for ZIKV serological tests in the real-world setting, during co-circulation of DENV, ZIKV, and CHIKV. However, we can also demonstrate that the IgAM immunoassay exhibits superior sensitivity to detect ZIKV RT-PCR confirmed infections compared to IgG and IgM immunoassays. The IgAM assay also proves to be promising for detection of anti-ZIKV seroconversions in sequential samples, both in ZIKV PCR-positive as well as PCR-negative patients, making this a candidate assay for serological monitoring of pregnant women in future ZIKV outbreaks.

Zika virus vertical transmission in children with confirmed antenatal exposure.

We report Zika virus (ZIKV) vertical transmission in 130 infants born to PCR+ mothers at the time of the Rio de Janeiro epidemic of 2015-2016. Serum and urine collected from birth through the first year of life were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM Zika MAC-ELISA. Four hundred and seven specimens are evaluated; 161 sera tested by PCR and IgM assays, 85 urines by PCR. Sixty-five percent of children (N = 84) are positive in at least one assay. Of 94 children tested within 3 months of age, 70% are positive. Positivity declines to 33% after 3 months. Five children are PCR+ beyond 200 days of life. Concordance between IgM and PCR results is 52%, sensitivity 65%, specificity 40% (positive PCR results as gold standard). IgM and serum PCR are 61% concordant; serum and urine PCR 55%. Most children (65%) are clinically normal. Equal numbers of children with abnormal findings (29 of 45, 64%) and normal findings (55 of 85, 65%) have positive results, p = 0.98. Earlier maternal trimester of infection is associated with positive results (p = 0.04) but not clinical disease (p = 0.98). ZIKV vertical transmission is frequent but laboratory confirmed infection is not necessarily associated with infant abnormalities.

Association of Infants Exposed to Prenatal Zika Virus Infection With Their Clinical, Neurologic, and Developmental Status Evaluated via the General Movement Assessment Tool.

Importance: There is an urgent need to assess neurodevelopment in Zika virus (ZIKV)-exposed infants. Objectives: To perform general movement assessment (GMA) at 9 to 20 weeks' postterm age and to evaluate whether the findings are associated with neurodevelopmental outcomes at age 12 months in infants prenatally exposed to acute maternal illness with rash in Brazil during the ZIKV outbreak and in age-matched controls. Design, Setting, and Participants: In this cohort study, infants prenatally exposed to acute maternal illness with rash were recruited at medical institutions in Rio de Janeiro and Belo Horizonte, Brazil, from February 1, 2016, to April 30, 2017, while infants without any exposure to maternal illness originated from the Graz University Audiovisual Research Database for the Interdisciplinary Analysis of Neurodevelopment. Participants were 444 infants, including 76 infants without congenital microcephaly, 35 infants with microcephaly, and 333 neurotypical children matched for sex, gestational age at birth, and age at GMA. Main Outcomes and Measures: General movement assessment performed at 9 to 20 weeks' postterm age, with negative predictive value, positive predictive value, sensitivity, and specificity generated, as well as clinical, neurologic, and developmental status (Bayley Scales of Infant and Toddler Development, Third Edition [Bayley-III] scores) at age 12 months. Motor Optimality Scores were generated based on the overall quality of the motor repertoire. Adverse outcomes were defined as a Bayley-III score less than 2 SD in at least 1 domain, a score less than 1 SD in at least 2 domains, and/or atypical neurologic findings. Results: A total of 444 infants were enrolled, including 111 children prenatally exposed to a maternal illness with rash and 333 children without any prenatal exposure to maternal illness (57.7% male and mean [SD] age, 14 [2] weeks for both groups); 82.1% (46 of 56) of ZIKV-exposed infants without congenital microcephaly were healthy at age 12 months. Forty-four of 46 infants were correctly identified by GMA at 3 months, with a negative predictive value of 94% (95% CI, 85%-97%). Seven of 10 ZIKV-exposed children without microcephaly with adverse neurodevelopmental outcomes were identified by GMA. The GMA positive predictive value was 78% (95% CI, 46%-94%), sensitivity was 70% (95% CI, 35%-93%), specificity was 96% (95% CI, 85%-99%), and accuracy was 91% (95% CI, 80%-97%). Children with microcephaly had bilateral spastic cerebral palsy; none had normal movements. The Motor Optimality Score differentiated outcomes: the median Motor Optimality Score was 23 (interquartile range [IQR], 21-26) in children with normal development, 12 (IQR, 8-19) in children with adverse outcomes, and 5 (IQR, 5-6) in children with microcephaly, a significant difference (P = .001). Conclusions and Relevance: This study suggests that although a large proportion of ZIKV-exposed infants without microcephaly develop normally, many do not. The GMA should be incorporated into routine infant assessments to enable early entry into targeted treatment programs.

A populational-based birth cohort study in a low-income urban area in Rio de Janeiro, Brazil: implementation and description of the characteristics of the study.

A comprehensive cohort study including an entomological surveillance component can contribute to our knowledge of clinical aspects and transmission patterns of arbovirosis. This article describes the implementation of a populational-based birth cohort study that included an entomological surveillance component, and its associated challenges in a low-income community of Rio de Janeiro, Brazil. The participants were recruited in two periods: from 2012 to 2014, and from 2015 to 2017. The children had scheduled pediatric consultations and in case of fever. Epidemiological, clinical data and biological samples were collected at pediatric visits. Active febrile surveillance was performed by telephone calls, social networking, message apps, and household visits. A total of 387 newborns and 332 new children were included during the first and second recruitment periods, respectively. By July 2017, there were 451 children on follow-up. During the study, 2,759 pediatric visits were performed: 1,783 asymptomatic and 976 febrile/rash consultations. The number of febrile or rash consultations increased 3.5-fold after the use of media tools for surveillance. No temporal pattern, seasonality or peak of febrile cases was observed during the study period. A total of 10,105 adult mosquitoes (including 3,523 Aedes spp. and 6,582 Culex quinquefasciatus) and 46,047 Aedes eggs were collected from households, schools, and key sites. Although challenging, this structured sentinel populational-based birth cohort is relevant to the knowledge of risks and awareness of emerging pathogens.

Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children.

We report neurodevelopmental outcomes in 216 infants followed since the time of PCR-confirmed maternal Zika virus (ZIKV) infection in pregnancy during the Rio de Janeiro epidemic of 2015-2016 (refs. 1,2). Neurodevelopment was assessed by Bayley Scales of Infant and Toddler Development, third edition (Bayley-III; cognitive, language and motor domains) in 146 children and through neurodevelopment questionnaires/neurological examinations in 70 remaining children. Complete eye exams (n = 137) and hearing assessments (n = 114) were also performed. Below-average neurodevelopment and/or abnormal eye or hearing assessments were noted in 31.5% of children between 7 and 32 months of age. Among children assessed by Bayley-III, 12% scored below -2 s.d. (score <70; a score of 100 ± 2 s.d. is the range) in at least one domain; and 28% scored between -1 and -2 s.d. in any domain (scores <85-70). Language function was most affected, with 35% of 146 children below average. Improved neurodevelopmental outcomes were noted in female children, term babies, children with normal eye exams and maternal infection later in pregnancy (P = 0.01). We noted resolution of microcephaly with normal neurodevelopment in two of eight children, development of secondary microcephaly in two other children and autism spectrum disorder in three previously healthy children in the second year of life.

Association of Prenatal Ultrasonographic Findings With Adverse Neonatal Outcomes Among Pregnant Women With Zika Virus Infection in Brazil.

Importance: Congenital Zika virus infection causes a spectrum of adverse birth outcomes, including severe birth defects of the central nervous system. The association of prenatal ultrasonographic findings with adverse neonatal outcomes, beyond structural anomalies such as microcephaly, has not been described to date. Objective: To determine whether prenatal ultrasonographic examination results are associated with abnormal neonatal outcomes in Zika virus-affected pregnancies. Design, Setting, and Participants: A prospective cohort study conducted at a single regional referral center in Rio de Janeiro, Brazil, from September 1, 2015, to May 31, 2016, among 92 pregnant women diagnosed during pregnancy with Zika virus infection by reverse-transcription polymerase chain reaction, who underwent subsequent prenatal ultrasonographic and neonatal evaluation. Exposures: Prenatal ultrasonography. Main Outcomes and Measures: The primary outcome measure was composite adverse neonatal outcome (perinatal death, abnormal finding on neonatal examination, or abnormal finding on postnatal neuroimaging). Secondary outcomes include association of specific findings with neonatal outcomes. Results: Of 92 mother-neonate dyads (mean [SD] maternal age, 29.4 [6.3] years), 55 (60%) had normal results and 37 (40%) had abnormal results on prenatal ultrasonographic examinations. The median gestational age at delivery was 38.6 weeks (interquartile range, 37.9-39.3). Of the 45 neonates with composite adverse outcome, 23 (51%) had normal results on prenatal ultrasonography. Eleven pregnant women (12%) had a Zika virus-associated finding that was associated with an abnormal result on neonatal examination (adjusted odds ratio [aOR], 11.6; 95% CI, 1.8-72.8), abnormal result on postnatal neuroimaging (aOR, 6.7; 95% CI, 1.1-38.9), and composite adverse neonatal outcome (aOR, 27.2; 95% CI, 2.5-296.6). Abnormal results on middle cerebral artery Doppler ultrasonography were associated with neonatal examination abnormalities (aOR, 12.8; 95% CI, 2.6-63.2), postnatal neuroimaging abnormalities (aOR, 8.8; 95% CI, 1.7-45.9), and composite adverse neonatal outcome (aOR, 20.5; 95% CI, 3.2-132.6). There were 2 perinatal deaths. Abnormal findings on prenatal ultrasonography had a sensitivity of 48.9% (95% CI, 33.7%-64.2%) and a specificity of 68.1% (95% CI, 52.9%-80.1%) for association with composite adverse neonatal outcomes. For a Zika virus-associated abnormal result on prenatal ultrasonography, the sensitivity was lower (22.2%; 95% CI, 11.2%-37.1%) but the specificity was higher (97.9%; 95% CI, 88.7%-99.9%). Conclusions and Relevance: Abnormal results on prenatal ultrasonography were associated with adverse outcomes in congenital Zika infection. The absence of abnormal findings on prenatal ultrasonography was not associated with a normal neonatal outcome. Comprehensive evaluation is recommended for all neonates with prenatal Zika virus exposure.

Neurodevelopment in the third year of life in children with antenatal ZIKV-exposure

ABSTRACT We report cognitive, language and motor neurodevelopment, assessed by the Bayley-III test, in 31 non-microcephalic children at age 3 with PCR-confirmed maternal Zika virus exposure (Rio de Janeiro, 2015-2016). Most children had average neurodevelopmental scores, however, 8 children (26%) presented delay in some domain. Language was the most affected: 7 children (22.6%) had a delay in this domain (2 presenting severe delay). Moderate delay was detected in the cognitive (3.2%) and motor (10%) domains. Maternal illness in the third trimester of pregnancy and later gestational age at birth were associated with higher Bayley-III scores. Zika-exposed children require long-term follow-up until school age.