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BACKGROUND: The public order and safety (POS) sector remains susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks, as workplace attendance is typically compulsory and close physical contact is often needed. Here, we report on a SARS-CoV-2 outbreak with an attack rate of 39% (9/23), which occurred between 19 and 29 June 2021 among a cohort of new POS recruits participating in a mandatory 18-week training programme in England. METHODS: The COVID-OUT (COVID-19 Outbreak investigation to Understand Transmission) study team undertook a multidisciplinary outbreak investigation, including viral surface sampling, workplace environmental assessment, participant viral and antibody testing, and questionnaires, at the two associated training facilities between 5 July and 24 August 2021. RESULTS: Environmental factors, such as ventilation, were deemed inadequate in some areas of the workplace, with carbon dioxide (CO2) levels exceeding 1,500 ppm on multiple occasions within naturally ventilated classrooms. Activities during safety training required close contact, with some necessitating physical contact, physical exertion, and shouting. Furthermore, most participants reported having physical contact with colleagues (67%) and more than one close work contact daily (97%). CONCLUSIONS: Our investigation suggests that site- and activity-specific factors likely contributed to the transmission risks within the POS trainee cohort. Potential interventions for mitigating SARS-CoV-2 transmission in this POS training context could include implementing regular rapid lateral flow testing, optimizing natural ventilation, using portable air cleaning devices in classrooms, and expanding use of well-fitted FFP2/FFP3 respirators during activities where prolonged close physical contact is required.
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COVID-19 , Brotes de Enfermedades , SARS-CoV-2 , Lugar de Trabajo , Humanos , COVID-19/transmisión , COVID-19/epidemiología , Inglaterra/epidemiología , Brotes de Enfermedades/prevención & control , Masculino , Adulto , Femenino , Exposición Profesional/prevención & control , Ventilación/métodosRESUMEN
BACKGROUND: Although polioviruses (PVs) replicate in lymphoid tissue of both the pharynx and ileum, research on polio vaccine-induced mucosal immunity has predominantly focused on intestinal neutralizing and binding antibody levels measured in stool. METHODS: To investigate the extent to which routine immunization with intramuscularly injected inactivated polio vaccine (IPV) may induce nasal and pharyngeal mucosal immunity, we measured PV type-specific neutralization and immunoglobulin (Ig) G, IgA, and IgM levels in nasal secretions, adenoid cell supernatants, and sera collected from 12 children, aged 2 to 5 years, undergoing planned adenoidectomies. All participants were routinely immunized with IPV and had no known contact with live PVs. RESULTS: PV-specific mucosal neutralization was detected in nasal and adenoid samples, mostly from children who had previously received four IPV doses. Across the three PV serotypes, both nasal (Spearman's rho ≥ 0.87, p≤0.0003 for all) and adenoid (Spearman's rho ≥0.57, p≤0.05 for all) neutralization titers correlated with serum neutralization titers. In this small study sample, there was insufficient evidence to determine which Ig isotype(s) was correlated with neutralization. CONCLUSIONS: Our findings provide policy-relevant evidence that routine immunization with IPV may induce nasal and pharyngeal mucosal immunity. The observed correlations of nasal and pharyngeal mucosal neutralization with serum neutralization contrast with previous observations of distinct intestinal and serum responses to PV vaccines. Further research is warranted to determine which antibody isotype(s) correlate with polio vaccine-induced nasal and pharyngeal mucosal neutralizing activity and to understand the differences from intestinal mucosal immunity.
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An outbreak of SARS-CoV-2 (1 March to 10 May 2021) with an attack rate of 26.5% among approximately 1150 workers at a storage and distribution centre in England prompted a multidisciplinary outbreak investigation (5 May to 6 August 2021), with the aim of better understanding worker- and workplace-related risk factors for viral transmission in the warehousing sector. Overall, environmental factors (e.g., ventilation, humidity and temperature) were assessed to be appropriate at the facility. Nevertheless, 39 (51.3%) surface samples from across the site tested positive for low/ very low levels of SARS-CoV-2 RNA (Ct value ≥ 32.0 for all). Among the study participants, of whom 35.6% were confirmed or suspected cases, 95.5% reported having received COVID-19 prevention training, 100.0% reported handwashing, and 80.0% reported use of face coverings at work. Notably, 43.9% and 19.0% reported working with a symptomatic and a positive contact respectively. Furthermore, 80.5% and 46.3% had concerns regarding reduction in their income and future unemployment, respectively, due to self-isolation. The findings of this study suggest that, in addition to targeted workplace infection control measures and tailored work area specific risk assessments, an enhanced and equitable sick leave policy may help limit presenteeism and viral transmission in large workplaces.
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COVID-19 , Brotes de Enfermedades , SARS-CoV-2 , Lugar de Trabajo , Humanos , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/prevención & control , COVID-19/virología , Inglaterra/epidemiología , Factores de Riesgo , Adulto , SARS-CoV-2/aislamiento & purificación , Masculino , Femenino , Persona de Mediana Edad , Adulto Joven , AncianoRESUMEN
OBJECTIVE: To describe the feeding characteristics and growth of children with prenatal exposure to Zika virus (ZIKV) from birth to 48 months. DESIGN: Using data from the prospective Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC), children without microcephaly born to mothers with evidence of ZIKV infection during pregnancy (ZIKV-exposed children without microcephaly) and children with Zika-related microcephaly were compared using repeated cross-sectional analyses within the following age strata: birth; 1 to 12; 13 to 24; 25 to 36; and 37 to 48 months. The groups were compared in relation to prematurity, birth weight, breastfeeding, alternative feeding routes, dysphagia and anthropometric profiles based on the World Health Organization Anthro z-scores (weight-length/height, weight-age, length/height-age and BMI-age). RESULTS: The first assessment included 248 children, 77 (31.05%) with microcephaly and 171 (68.95%) without microcephaly. The final assessment was performed on 86 children. Prematurity was 2.35 times higher and low birth weight was 3.49 times higher in children with microcephaly. The frequency of breastfeeding was high (> 80%) in both groups. On discharge from the maternity hospital, the frequency of children requiring alternative feeding route in both groups was less than 5%. After 12 months of age, children with microcephaly required alternative feeding route more often than children without microcephaly. In children with microcephaly, the z-score of all growth indicators was lower than in children without microcephaly. CONCLUSIONS: Children with Zika-related microcephaly were more frequently premature and low birth weight and remained with nutritional parameters, i.e., weight-for-age, weight-for-length/height and length/height-for-age below those of the children without microcephaly.
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Lactancia Materna , Microcefalia , Complicaciones Infecciosas del Embarazo , Efectos Tardíos de la Exposición Prenatal , Infección por el Virus Zika , Humanos , Microcefalia/epidemiología , Microcefalia/etiología , Microcefalia/virología , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/epidemiología , Femenino , Embarazo , Recién Nacido , Lactante , Masculino , Complicaciones Infecciosas del Embarazo/epidemiología , Preescolar , Estudios Transversales , Estudios Prospectivos , Desarrollo Infantil , Brasil/epidemiologíaRESUMEN
BACKGROUND: Although mpox has been detected in paediatric populations in central and west Africa for decades, evidence synthesis on paediatric, maternal, and congenital mpox, and the use of vaccines and therapeutics in these groups, is lacking. A systematic review is therefore indicated to set the research agenda. METHODS: We conducted a systematic review and meta-analysis, searching articles in Embase, Global Health, MEDLINE, CINAHL, Web of Science, Scopus, SciELO, and WHO databases from inception to April 17, 2023. We included studies reporting primary data on at least one case of confirmed, suspected, or probable paediatric, maternal, or congenital mpox in humans or the use of third-generation smallpox or mpox vaccines, targeted antivirals, or immune therapies in at least one case in our population of interest. We included clinical trials and observational studies in humans and excluded reviews, commentaries, and grey literature. A pooled estimate of the paediatric case fatality ratio was obtained using random-effects meta-analysis. This study is registered with PROSPERO (CRD420223336648). FINDINGS: Of the 61 studies, 53 reported paediatric outcomes (n=2123 cases), seven reported maternal or congenital outcomes (n=32 cases), two reported vaccine safety (n=28 recipients), and three reported transmission during breastfeeding (n=4 cases). While a subset of seven observational studies (21 children and 12 pregnant individuals) reported uneventful treatment with tecovirimat, there were no randomised trials reporting safety or efficacy for any therapeutic agent. Among children, the commonest clinical features included rash (86 [100%] of 86), fever (63 [73%] of 86), and lymphadenopathy (40 [47%] of 86). Among pregnant individuals, rash was reported in 23 (100%) of 23; fever and lymphadenopathy were less common (six [26%] and three [13%] of 23, respectively). Most paediatric complications (12 [60%] of 20) arose from secondary bacterial infections. The pooled paediatric case fatality ratio was 11% (95% CI 4-20), I2=75%. Data from 12 pregnancies showed half resulted in fetal death. Research on vaccine and immune globulin safety remains scarce for children and absent for pregnant individuals. INTERPRETATION: Our review highlights critical knowledge gaps in the epidemiology, prevention, and treatment of mpox in children and pregnant individuals, especially those residing in endemic countries. Increased funding, international collaboration, and equitable research is needed to inform mpox control strategies tailored for at-risk communities in endemic countries. FUNDING: None. TRANSLATIONS: For the French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.
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Humanos , Femenino , Embarazo , Niño , Preescolar , Lactante , Recién NacidoRESUMEN
BACKGROUND: Chikungunya virus outbreaks have been associated with excess deaths at the ecological level. Previous studies have assessed the risk factors for severe versus mild chikungunya virus disease. However, the risk of death following chikungunya virus disease compared with the risk of death in individuals without the disease remains unexplored. We aimed to investigate the risk of death in the 2 years following chikungunya virus disease. METHODS: We used a population-based cohort study and a self-controlled case series to estimate mortality risks associated with chikungunya virus disease between Jan 1, 2015, and Dec 31, 2018, in Brazil. The dataset was created by linking national databases for social programmes, notifiable diseases, and mortality. For the matched cohort design, individuals with chikungunya virus disease recorded between Jan 1, 2015, and Dec 31, 2018, were considered as exposed and those who were arbovirus disease-free and alive during the study period were considered as unexposed. For the self-controlled case series, we included all deaths from individuals with a chikungunya virus disease record, and each individual acted as their own control according to different study periods relative to the date of disease. The primary outcome was all-cause natural mortality up to 728 days after onset of chikungunya virus disease symptoms, and secondary outcomes were cause-specific deaths, including ischaemic heart diseases, diabetes, and cerebrovascular diseases. FINDINGS: In the matched cohort study, we included 143â787 individuals with chikungunya virus disease who were matched, at the day of symptom onset, to unexposed individuals using sociodemographic factors. The incidence rate ratio (IRR) of death within 7 days of chikungunya symptom onset was 8·40 (95% CI 4·83-20·09) as compared with the unexposed group and decreased to 2·26 (1·50-3·77) at 57-84 days and 1·05 (0·82-1·35) at 85-168 days, with IRR close to 1 and wide CI in the subsequent periods. For the secondary outcomes, the IRR of deaths within 28 days after disease onset were: 1·80 (0·58-7·00) for cerebrovascular diseases, 3·75 (1·33-17·00) for diabetes, and 3·67 (1·25-14·00) for ischaemic heart disease, and there was no evidence of increased risk in the subsequent periods. For the self-controlled case series study, 1933 individuals died after having had chikungunya virus disease and were included in the analysis. The IRR of all-cause natural death within 7 days of symptom onset of chikungunya virus disease was 8·75 (7·18-10·66) and decreased to 1·59 (1·26-2·00) at 57-84 days and 1·09 (0·92-1·29) at 85-168 days. For the secondary outcomes, the IRRs of deaths within 28 days after disease onset were: 2·73 (1·50-4·96) for cerebrovascular diseases, 8·43 (5·00-14·21) for diabetes, and 2·38 (1·33-4·26) for ischaemic heart disease, and there was no evidence of increased risk at 85-168 days. INTERPRETATION: Chikungunya virus disease is associated with an increased risk of death for up to 84 days after symptom onset, including deaths from cerebrovascular diseases, ischaemic heart diseases, and diabetes. This study highlights the need for equitable access to approved vaccines and effective anti-chikungunya virus therapeutics and reinforces the importance of robust vector-control efforts to reduce viral transmission. FUNDING: Brazilian National Research Council (CNPq), Fundação de Amparo à Pesquisa do Estado da Bahia, Wellcome Trust, and UK Medical Research Council. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.
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Fiebre Chikungunya , Humanos , Fiebre Chikungunya/mortalidad , Fiebre Chikungunya/epidemiología , Brasil/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios de Cohortes , Factores de Riesgo , Anciano , Adulto Joven , Adolescente , Niño , Preescolar , Virus Chikungunya , Brotes de EnfermedadesRESUMEN
BACKGROUND: Although household contacts of patients with tuberculosis are known to be particularly vulnerable to tuberculosis, the published evidence focused on this group at high risk within the low-income and middle-income country context remains sparse. Using nationwide data from Brazil, we aimed to estimate the incidence and investigate the socioeconomic and clinical determinants of tuberculosis in a cohort of contacts of tuberculosis patients. METHODS: In this cohort study, we linked individual socioeconomic and demographic data from the 100 Million Brazilian Cohort to mortality data and tuberculosis registries, identified contacts of tuberculosis index patients diagnosed from Jan 1, 2004 to Dec 31, 2018, and followed up the contacts until the contact's subsequent tuberculosis diagnosis, the contact's death, or Dec 31, 2018. We investigated factors associated with active tuberculosis using multilevel Poisson regressions, allowing for municipality-level and household-level random effects. FINDINGS: We studied 420 854 household contacts of 137 131 tuberculosis index patients. During the 15 years of follow-up (median 4·4 years [IQR 1·9-7·6]), we detected 8953 contacts with tuberculosis. The tuberculosis incidence among contacts was 427·8 per 100 000 person-years at risk (95% CI 419·1-436·8), 16-times higher than the incidence in the general population (26·2 [26·1-26·3]) and the risk was prolonged. Tuberculosis incidence was associated with the index patient being preschool aged (<5 years; adjusted risk ratio 4·15 [95% CI 3·26-5·28]) or having pulmonary tuberculosis (2·84 [2·55-3·17]). INTERPRETATION: The high and sustained risk of tuberculosis among contacts reinforces the need to systematically expand and strengthen contact tracing and preventive treatment policies in Brazil in order to achieve national and international targets for tuberculosis elimination. FUNDING: Wellcome Trust and Brazilian Ministry of Health.
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Tuberculosis , Preescolar , Humanos , Estudios de Cohortes , Brasil/epidemiología , Incidencia , Tuberculosis/epidemiología , Factores de Riesgo , Trazado de ContactoRESUMEN
BACKGROUND: We investigated perinatal outcomes among live births from international migrant and local-born mothers in a cohort of low-income individuals in Brazil. METHODS: We linked nationwide birth registries to mortality records and socioeconomic data from the CIDACS Birth Cohort and studied singleton live births of women aged 10-49 years from 1st January 2011 to 31st December 2018. We used logistic regressions to investigate differences in antenatal care, adverse pregnancy outcomes, and neonatal (i.e., ≤28 days) mortality among international migrants compared to non-migrants in Brazil; and explored the interaction between migration, race/ethnicity and living in international border municipalities. RESULTS: We studied 10,279,011 live births, of which 9469 (0.1 %) were born to international migrants. Migrant women were more likely than their Brazilian-born counterparts to have a previous foetal loss (ORadj: 1.16, 1.11-1.22), a delayed start of antenatal care (i.e., beyond 1st trimester) (1.22, 95%CI:1.16-1.28), a newborn who is large for gestational age (1.29, 1.22-1.36), or a newborn with congenital anomalies (1.37, 1.14-1.65). Conversely, migrant women were less likely to deliver prematurely (0.89, 0.82-0.95) or have a low birth weight infant (0.74, 0.68-0.81). There were no differences in neonatal mortality rates between migrants and non-migrants. Our analyses also showed that, when disparities in perinatal outcomes were present, disparities were mostly concentrated among indigenous mothers in international borders and among live births of Black mothers in non-borders. CONCLUSION: Although live births of international migrants generally have lower rates of adverse birth outcomes, our results suggest that indigenous and Black migrant mothers may face disproportionate barriers to accessing antenatal care.
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Migrantes , Recién Nacido , Lactante , Femenino , Embarazo , Humanos , Brasil/epidemiología , Cohorte de Nacimiento , Almacenamiento y Recuperación de la Información , Evaluación de Resultado en la Atención de SaludRESUMEN
To better understand the declining rates of routine childhood vaccination in Brazil, we investigated the association between measles, mumps, and rubella (MMR) first dose vaccine coverage and deprivation at the municipality level. Using routinely collected data from 5565 Brazilian municipalities from 2006 to 2020, we investigated the association between municipality-level MMR vaccine first dose coverage (i.e., as a continuous variable and as a percentage of municipalities attaining the 95% target coverage) in relation to quintiles of municipality-level deprivation, measured by the Brazilian Deprivation Index (Índice Brasileiro de Privação, IBP), and geographic regions. From 2006 to 2020, the mean municipality-level MMR vaccine coverage declined across all deprivation quintiles and regions of Brazil, by an average of 1.2% per year. The most deprived quintile of municipalities had higher coverage on average, but also the steepest declines in coverage (i.e., an annual decline of 1.64% versus 0.61% in the least deprived quintile) in the period of 2006-2020, and the largest drop in coverage at the beginning of the COVID-19 pandemic (2019-2020). Across all deprivation quintiles and regions (except for the Southeast region), less than 50% of municipalities in Brazil met the 95% MMR coverage target in 2020.The decrease in MMR first dose vaccine coverage in Brazil is widespread, but steeper declines have been observed in the most deprived municipalities. To promote vaccine equity and prevent future outbreaks, further research is urgently needed to understand the causal mechanisms underlying the observed associations between municipality-level MMR vaccine coverage and deprivation.
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OBJECTIVE: To assess the longitudinal evolution of EEG findings in children with Zika related-microcephaly (ZRM) and to evaluate the associations of these patterns with the children's clinical and neuroimaging characteristics. METHODS: As part of the follow-up of the Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC) in Recife, Brazil, we performed serial EEG recordings in a subgroup of children with ZRM to evaluate changes in background rhythms and epileptiform activity (EA). Latent class analysis was used to identify patterns in the evolution of EA over time; clinical and neuroimaging findings were compared across the identified groups. RESULTS: Out of the 72 children with ZRM who were evaluated during 190 EEGs/videoEEGs, all participants presented with abnormal background activity, 37.5% presented with an alpha-theta rhythmic activity, and 25% presented with sleep spindles, which were less commonly observed in children with epilepsy. EA changed over time in 79.2% of children, and three distinct trajectories were identified: (i) multifocal EA over time, (ii) no discharges/focal EA evolving to focal/multifocal EA, and (iii) focal/multifocal EA evolving to epileptic encephalopathy patterns (e.g., hypsarrhythmia or continuous EA in sleep). The multifocal EA over time trajectory was associated with periventricular and thalamus/basal ganglia calcifications, brainstem and corpus callosum atrophy and had less focal epilepsy, whereas the children in the trajectory which evolved to epileptic encephalopathy patterns had more frequently focal epilepsy. SIGNIFICANCE: These findings suggest that, in most children with ZRM, trajectories of changes in EA can be identified and associated with neuroimaging and clinical features.
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Electroencefalografía , Epilepsia , Microcefalia , Infección por el Virus Zika , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Edad de Inicio , Ritmo alfa , Investigación Biomédica , Corteza Cerebral/anomalías , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Epilepsias Parciales/diagnóstico por imagen , Epilepsias Parciales/etiología , Epilepsias Parciales/patología , Epilepsias Parciales/fisiopatología , Epilepsia/diagnóstico por imagen , Epilepsia/etiología , Epilepsia/patología , Epilepsia/fisiopatología , Movimientos Oculares , Estudios de Seguimiento , Análisis de Clases Latentes , Estudios Longitudinales , Microcefalia/diagnóstico por imagen , Microcefalia/etiología , Microcefalia/patología , Microcefalia/fisiopatología , Neuroimagen , Fases del Sueño , Ritmo Teta , Vigilia , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/diagnóstico por imagen , Infección por el Virus Zika/patología , Infección por el Virus Zika/fisiopatologíaRESUMEN
BACKGROUND: A SARS-CoV-2 outbreak with an attack rate of 14.3% was reported at a plastics manufacturing plant in England. METHODS: Between 23rd March and 13th May 2021, the COVID-OUT team undertook a comprehensive outbreak investigation, including environmental assessment, surface sampling, molecular and serological testing, and detailed questionnaires, to identify potential SARS-CoV-2 transmission routes, and workplace- and worker-related risk factors. RESULTS: While ventilation, indicated using real-time CO2 proxy measures, was generally adequate on-site, the technical office with the highest localized attack rate (21.4%) frequently reached peaks in CO2 of 2100ppm. SARS-CoV-2 RNA was found in low levels (Ct ≥35) in surface samples collected across the site. High noise levels (79dB) were recorded in the main production area, and study participants reported having close work contacts (73.1%) and sharing tools (75.5%). Only 20.0% of participants reported using a surgical mask and/or FFP2/FFP3 respirator at least half the time and 71.0% expressed concerns regarding potential pay decreases and/or unemployment due to self-isolation or workplace closure. CONCLUSIONS: The findings reinforce the importance of enhanced infection control measures in manufacturing sectors, including improved ventilation with possible consideration of CO2 monitoring, utilising air cleaning interventions in enclosed environments, and provision of good-quality face masks (i.e., surgical masks or FFP2/FFP3 respirators) especially when social distancing cannot be maintained. Further research on the impacts of job security-related concerns is warranted.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevención & control , Plásticos , ARN Viral , Dióxido de Carbono , Brotes de Enfermedades , Instalaciones Industriales y de FabricaciónRESUMEN
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.
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Exantema , Microcefalia , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Virus Zika , Recién Nacido , Niño , Humanos , Embarazo , Lactante , Femenino , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiología , Microcefalia/epidemiología , Microcefalia/etiología , Complicaciones Infecciosas del Embarazo/epidemiología , Estudios Prospectivos , Brasil/epidemiología , Parto , Exantema/epidemiología , Exantema/etiologíaRESUMEN
Background: To understand if migrants living in poverty in low and middle-income countries (LMICs) have mortality advantages over the non-migrant population, we investigated mortality risk patterns among internal and international migrants in Brazil over their life course. Methods: We linked socio-economic and mortality data from 1st January 2011 to 31st December 2018 in the 100 Million Brazilian Cohort and calculated all-cause and cause-specific age-standardised mortality rates according to individuals' migration status for men and women. Using Cox regression models, we estimated the age- and sex-adjusted mortality hazard ratios (HR) for internal migrants (i.e., Brazilian-born individuals living in a different Brazilian state than their birth) compared to Brazilian-born non-migrants; and for international migrants (i.e., people born in another country) compared to Brazilian-born individuals. Findings: The study followed up 45,051,476 individuals, of whom 6,057,814 were internal migrants, and 277,230 were international migrants. Internal migrants had similar all-cause mortality compared to Brazilian non-migrants (aHR = 0.99, 95% CI = 0.98-0.99), marginally higher mortality for ischaemic heart diseases (aHR = 1.04, 95% CI = 1.03-1.05) and higher for stroke (aHR = 1.11, 95% CI = 1.09-1.13). Compared to Brazilian-born individuals, international migrants had 18% lower all-cause mortality (aHR = 0.82, 95% CI = 0.80-0.84), with up to 50% lower mortality from interpersonal violence among men (aHR = 0.50, 95% CI = 0.40-0.64), but higher mortality from avoidable causes related to maternal health (aHR = 2.17, 95% CI = 1.17-4.05). Interpretation: Although internal migrants had similar all-cause mortality, international migrants had lower all-cause mortality compared to non-migrants. Further investigations using intersectional approaches are warranted to understand the marked variations by migration status, age, and sex for specific causes of death, such as elevated maternal mortality and male lower interpersonal violence-related mortality among international migrants. Funding: The Wellcome Trust.
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BACKGROUND: Children with congenital Zika syndrome (CZS) have severe damage to the peripheral and central nervous system (CNS), greatly increasing the risk of death. However, there is no information on the sequence of the underlying, intermediate, immediate, and contributing causes of deaths among these children. The aims of this study are describe the sequence of events leading to death of children with CZS up to 36 months of age and their probability of dying from a given cause, 2015 to 2018. METHODS AND FINDINGS: In a population-based study, we linked administrative data on live births, deaths, and cases of children with CZS from the SINASC (Live Birth Information System), the SIM (Mortality Information System), and the RESP (Public Health Event Records), respectively. Confirmed and probable cases of CZS were those that met the criteria established by the Brazilian Ministry of Health. The information on causes of death was collected from death certificates (DCs) using the World Health Organization (WHO) DC template. We estimated proportional mortality (PM%) among children with CZS and among children with non-Zika CNS congenital anomalies (CA) by 36 months of age and proportional mortality ratio by cause (PMRc). A total of 403 children with confirmed and probable CZS who died up to 36 months of age were included in the study; 81.9% were younger than 12 months of age. Multiple congenital malformations not classified elsewhere, and septicemia unspecified, with 18 (PM = 4.5%) and 17 (PM = 4.2%) deaths, respectively, were the most attested underlying causes of death. Unspecified septicemia (29 deaths and PM = 11.2%) and newborn respiratory failure (40 deaths and PM = 12.1%) were, respectively, the predominant intermediate and immediate causes of death. Fetuses and newborns affected by the mother's infectious and parasitic diseases, unspecified cerebral palsy, and unspecified severe protein-caloric malnutrition were the underlying causes with the greatest probability of death in children with CZS (PMRc from 10.0 to 17.0) when compared to the group born with non-Zika CNS anomalies. Among the intermediate and immediate causes of death, pneumonitis due to food or vomiting and unspecified seizures (PMRc = 9.5, each) and unspecified bronchopneumonia (PMRc = 5.0) were notable. As contributing causes, fetus and newborn affected by the mother's infectious and parasitic diseases (PMRc = 7.3), unspecified cerebral palsy, and newborn seizures (PMRc = 4.5, each) were more likely to lead to death in children with CZS than in the comparison group. The main limitations of this study were the use of a secondary database without additional clinical information and potential misclassification of cases and controls. CONCLUSION: The sequence of causes and circumstances involved in the deaths of the children with CZS highlights the greater vulnerability of these children to infectious and respiratory conditions compared to children with abnormalities of the CNS not related to Zika.
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Parálisis Cerebral , Malformaciones del Sistema Nervioso , Complicaciones Infecciosas del Embarazo , Sepsis , Infección por el Virus Zika , Virus Zika , Embarazo , Femenino , Recién Nacido , Niño , Humanos , Brasil , Causas de Muerte , ConvulsionesRESUMEN
Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.
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Understanding functioning and disabilities in children with Congenital Zika Syndrome (CZS) is essential for health planning. We describe disabilities present in children with CZS followed in a reference hospital in Rio de Janeiro, Brazil, based on the biopsychosocial model of the International Classification of Functioning, Disability and Health (ICF). This was a cohort study of children >3 years of age with CZS. Disability was characterized through outcomes related to ICF components assessed via clinical and motor development evaluations. Among 50 children, with a median age of 40 months, 47 (94%) presented with severe impairment and 46 (92%) had microcephaly. Damage to the head and neck was found in most children, with abnormal central nervous system imaging universally present. Most children had cognitive impairment (92%), muscle tone problems (90%), and speech deficits (94%). We found movement limitations in all categories but more pervasively (80−94%), in postural transfers and displacements. The main environmental factors identified in the ICF model were the use of products or substances for personal consumption and access to health services. Children with CZS have extremely high rates of disability beyond aged 3 years, particularly regarding motor activity. ICF-based models can contribute to the assessment of health domains.
Asunto(s)
Microcefalia , Infección por el Virus Zika , Virus Zika , Niño , Preescolar , Humanos , Lactante , Infección por el Virus Zika/congénito , Estudios de Cohortes , Brasil/epidemiologíaRESUMEN
Prenatal exposure to ZIKV can cause neurologic and auditory damage. The electrophysiological responses obtained by Cortical Auditory Evoked Potentials (CAEP) may provide an objective method to investigate the function of cortical auditory pathways in children exposed to ZIKV. This case series analyzed the findings of CAEP in prenatal-period ZIKV-exposed children with and without microcephaly. The CAEP was performed in a total of 24 children. Five magnetic resonance imaging (MRI) images of the inner ear and brain of microcephalic children were analyzed and compared with CAEP measurements. Ventriculomegaly (80%), cortical/subcortical calcification (80%), and brain reduction (60%) were the most common alterations in the MRI. The P1-N1-P2 complex of the CAEP was observed in all children evaluated. The peak N2 was absent in two children. In the comparison of the CAEP measurements between the groups, children with microcephaly presented a higher amplitude of P2 (p = 0.017), which may reflect immaturity of the auditory pathways. Microcephalic and normocephalic children with prenatal exposure to ZIKV presented with the mandatory components of the CAEPs, regardless of changes in the CNS, suggesting that this population has, to some extent, the cortical ability to process sound stimuli preserved.
Asunto(s)
Microcefalia , Efectos Tardíos de la Exposición Prenatal , Infección por el Virus Zika , Virus Zika , Niño , Potenciales Evocados Auditivos/fisiología , Femenino , Humanos , Embarazo , Infección por el Virus Zika/complicacionesRESUMEN
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.
Asunto(s)
Microcefalia , Malformaciones del Sistema Nervioso , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Virus Zika , Brasil/epidemiología , Niño , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Microcefalia/diagnóstico , Microcefalia/epidemiología , Neuroimagen , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/congénito , Infección por el Virus Zika/epidemiologíaRESUMEN
While it is well known that socioeconomic markers are associated with a higher risk of arbovirus infections, research on the relationship between socioeconomic factors and congenital Zika syndrome (CZS) remains limited. This study investigates the relationship between socioeconomic risk markers and live births with CZS in Brazil. We conducted a population-based study using data from all registered live births in Brazil (Live Births Information System) linked with the Public Health Event Record from 1 January 2015 to 31 December 2018. We used logistic regression models to estimate the OR and 95% CIs of CZS based on a three-level framework. In an analysis of 11 366 686 live births, of which 3353 had CZS, we observed that live births of self-identified black or mixed race/brown mothers (1.72 (95% CI 1.47 to 2.01) and 1.37 (95% CI 1.24 to 1.51)) were associated with a higher odds of CZS. Live births from single women compared with married women and those from women with less than 12 years of education compared with those with more than 12 years of education also had higher odds of CZS. In addition, live births following fewer prenatal care appointments had increased odds of CZS in the nationwide data. However, in the analyses conducted in the Northeast region (where the microcephaly epidemic started before the link with Zika virus was established and before preventive measures were known or disseminated), no statistical association was found between the number of prenatal care appointments and the odds of CZS. This study shows that live births of the most socially vulnerable women in Brazil had the greatest odds of CZS. This disproportionate distribution of risk places an even greater burden on already socioeconomically disadvantaged groups, and the lifelong disabilities caused by this syndrome may reinforce existing social and health inequalities.
Asunto(s)
Infección por el Virus Zika , Virus Zika , Brasil/epidemiología , Femenino , Humanos , Embarazo , Sistema de Registros , Factores Socioeconómicos , Infección por el Virus Zika/epidemiologíaRESUMEN
BACKGROUND: In addition to their direct pathogenic effects, arthropod-borne (arboviruses) have been hypothesized to indirectly contribute to hospitalizations and death through decompensation of pre-existing comorbidities. Using nationwide data routinely collected from 1 January 2014 to 31 December 2019 in Brazil, we investigated whether local increases in arbovirus notifications were associated with excess hospitalization. METHODS: We estimated the relative risks for the association between municipality- and state-level increases in arboviral case notifications and age-standardized hospitalization rates (i.e., classified as direct or indirect based on ICD-10 codes) using Bayesian multilevel models with random effects accounting for temporal and geographic correlations. For municipality-level analyses, we excluded municipalities with <200 notifications of a given arbovirus and further adjusted the models for the local Gini Index, Human Development Index, and Family Healthcare Strategy (Estratégia de Saúde da Família) coverage. Models for dengue, Zika, and chikungunya were performed separately. RESULTS: From 2014 to 2019, Brazil registered 7,566,330 confirmed dengue cases, 159,029 confirmed ZIKV cases, and 433,887 confirmed CHIKV cases. Dengue notifications have an endemic and seasonal pattern, with cases present in 5334 of the 5570 (95.8%) Brazilian municipalities and most (69.5%) registered between February and May. Chikungunya notifications followed a similar seasonal pattern to DENV but with a smaller incidence and were restricted to 4390 (78.8%) municipalities. ZIKV was only notified in 2581 (46.3%) municipalities. Increases in dengue and chikungunya notifications were associated with small increases in age-standardized arbovirus-related hospitalizations, but no consistent association was found with all-cause or other specific indirect causes of hospitalization. Zika was associated to increases in hospitalizations by neurological diseases. CONCLUSIONS: Although we found no clear association between increased incidence of the three arboviruses and excess risks of all-cause or indirect hospitalizations at the municipality- and state-levels, follow-up investigations at the individual-level are warranted to define any potential role of acute arbovirus infection in exacerbating risks of hospitalization from underlying conditions.