Prevalence of urologic sequelae and bladder and bowel dysfunctions in patients with congenital Zika syndrome: A multicenter evaluation of the Zika virus bladder and bowel sequelae assistance network.

INTRODUCTION: Neurogenic bladder was first confirmed as a urological sequela of Congenital Zika Syndrome (CZS) in 2018. Further clinical-epidemiological evidence also confirmed neurogenic bowel dysfunction and cryptorchidism. To strengthen the care for these children, the Congenital Zika Virus Bladder and Bowel Sequelae Network (RASZ in Brazilian) was created, including six integrated centers in Brazil. This article represents the initial outcome of the efforts by RASZ. OBJECTIVE: To evaluate the prevalence of bladder and bowel dysfunction, cryptorchidism and other urological sequelae related to CZS in cohorts attended in six Brazilian states. STUDY DESIGN: Observational, prospective, multicenter study including children with CZS assisted in one of six RASZ collaborative centers between June 2016 and February 2023. Data were collected from patient's first assessment using the same protocols for urological and bowel evaluation. Categorical variables were analyzed by frequency of occurrence and numerical variables by mean, median, and standard deviation. The study was approved by the Research Ethics Committees of each center, all parents/caregivers provided written informed consent. RESULTS: The study included 414 children aged 2 months to 7 years (mean 2.77 years, SD 1.73), 227 (54.8 %) were male and 140 (33,8 %) referred urological and bowel symptoms on arrival. Prevalence of both urological and bowel sequelae was 66.7 %, 51 % of children aged 4 years and older had urinary incontinence (UI). UTI was confirmed in 23.4 % (two presented toxemia) and among males, 18.1 % had cryptorchidism. Renal ultrasonography, performed in 186 children, was abnormal in 25 (13.4 %), 7 had hydronephrosis. Among the 287 children who performed urodynamics, 283 (98.6 %) were altered: 232 had a lower bladder capacity, 144 a maximum bladder pressure of ≥40 cm H2O, and 127 did not satisfactorily empty their bladder. DISCUSSION: A higher prevalence of NLUTD, neurogenic bowel and cryptorchidism was confirmed in children with CZS. Early diagnosis and appropriate treatment, including a multidisciplinary approach, may reduce the risk of UTIs, UI and kidney damage. A limitation of the study was the inability of children to complete the protocol, specifically urodynamic evaluation, and ultrasonography. In both exams, the percentage of abnormal cases was higher than that expected in the normal population. CONCLUSION: A 66,7 % prevalence of combined urological sequelae and bladder-bowel dysfunction related to CZS was confirmed in patients evaluated in six Brazilian cohorts. The most frequent changes were related to NLUTD, neurogenic bowel, and cryptorchidism. Prevalence may be underestimated due to access restrictions to diagnostic tests.

Evaluation of renal markers and liver enzymes in patients infected with the Chikungunya virus.

Chikungunya virus (CHIKV) is an arbovirus (Togaviridae family, Alphavirus genus) that was first identified in 1953 in Tanzania. In 2014, the Asian and East/Central/South/African (ECSA) genotypes were identified in Brazil, although the genotype that spread the most in the following years across the Brazilian territory was the ECSA. The clinical symptoms associated with the infection caused by CHIKV include mainly fever, myalgia, headache, and arthralgia. In infections caused by other arboviruses (such as the ones caused by Dengue and West Nile viruses), changes in biochemical markers are often observed. This study aims to evaluate the biochemical markers profile of kidney and liver injury in acute patients infected with CHIKV. Two groups of correlations were found between the variables analyzed, namely, one between liver enzymes (r = 0.91), and another for kidney markers (r = 0.54-0.66). A significant elevation in the percentage of altered creatinine in CHIKV-infected patients was observed, followed by uric acid and AST. Altogether, in 8 different comparisons, it was possible to observe statistically significant differences between the levels of the markers when compared to the manifestation of symptoms (presence and absence). These noticeable changes in marker measurements could potentially be connected to the range of clinical symptoms seen in the disease.

Assessing the hearing of children exposed to zika virus with an initially normal newborn hearing screen: a longitudinal cohort study.

BACKGROUND: Zika virus (ZIKV) infection can result in hearing loss in babies, consequently, audiological monitoring is necessary. AIMS: This study aimed to evaluate the frequency of hearing impairment in neonates and children exposed to ZIKV during the intrauterine period. MATERIALS AND METHODS: A cohort of 30 children born to mothers infected with ZIKV during pregnancy (March 2016-January 2017) underwent repeated hearing assessments performed 48 h after birth. Universal Newborn Hearing Screening revealed normal results in all children at 6, 13, 24, and 36 months. Children were divided into two subgroups based on real-time polymerase chain reaction: RT-PCR(+) and RT-PCR(-). RESULTS: At 24 months, the cumulative incidence of hearing alteration was 57.1%. There was no significant difference in the detection of hearing alteration between RT-PCR(+) and (-) groups. None of the children had sensorineural hearing loss. CONCLUSIONS AND SIGNIFICANCE: None of the children had sensorineural hearing loss. Total incidence conductive type (per 1000 live births), RT-PCR ZIKV (-) 2.2, prevalence 20% and RT-PCR ZIKV 3.1, prevalence 35.7%.The incidence of hearing alteration was highest at 24 months of age (57.1%, n = 8; only conductive type).

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

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%.

HLA-G, LILRB1 and LILRB2 Variants in Zika Virus Transmission from Mother to Child in a Population from South and Southeast of Brazil.

During the 2015-2016 epidemic, Brazil was the country with the highest rate of Zika virus (ZIKV) infection in the Americas. Twenty-nine percent of pregnant women positive for ZIKV exhibited ultrasound scans with fetus anomalies. Human leukocyte antigen-G (HLA-G) exerts immunoregulatory effects by binding to inhibitory receptors, namely LILRB1 and LILRB2, thus preventing mother-fetus rejection and vertical pathogen transmission. The binding of HLA-G to one of its receptors modulates both innate and adaptive immunity. However, in a viral infection, these molecules may behave as pathogenic mediators shifting the pregnancy environment from an anti-inflammatory profile to a pro-inflammatory phenotype. Genetic mutations might be associated with the change in phenotype. This study aimed to explore the possible role of polymorphic sites in HLA-G, LILRB1 and LILRB2 in mother-fetus ZIKV transmission. Polymorphisms were detected by direct sequencing. Differences in allele and/or genotype frequencies for each SNP analyzed among ZIKV non-transmitting and transmitting mother-child pairs, among ZIKV-transmitting and non-transmitting mothers and between ZIKV-infected and non-infected children were compared by Mid-P exact test or Yates' correction. Significant susceptibility of ZIKV vertical transmission is suggested in ZIKV-transmitting and non-transmitting mothers and ZIKV-infected and non-infected children for LILRB1_rs1061684 T/T (p = 0.03, Pc = 0.06, OR = 12.4; p = 0.008, Pc = 0.016, OR = 16.4) and LILRB1_rs16985478 A/A (p = 0.01, Pc = 0.02, OR = 19.2; p = 0.008, Pc = 0.016, OR = 16.4). HLA-G_rs1710 (p = 0.04, Pc = 0.52, OR = 4.30) was also a susceptibility factor. LILRB2_rs386056 G/A (p = 0.02, Pc = 0.08, OR = 0.07), LILRB2_rs7247451 G/G (p = 0.01, Pc = 0.04, OR = 0.04) and HLAG_rs9380142 T/T (p = 0.04, Pc = 0.52, OR = 0.14) were suggested as protective factors against vertical transmission. The current study suggests that polymorphic sites in the LILRB1 and HLA-G genes might be associated with mother-to-child ZIKV transmission while LILRB2 might be associated with protection against ZIKV transmission in the womb in a population from the south and southeast of Brazil.

Mild and Asymptomatic Coronavirus Disease in Children, Adolescents, and Household Contacts and Prolonged Viral Excretion.

Method: This was a prospective, observational, and descriptive cohort study. Nasopharyngeal swabs and blood were collected six times at weekly intervals. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) tests and immunoglobulin (Ig) G and IgA assays were used to test for COVID-19. Results: Overall, 419 children and 253 adults were enrolled. There was a significant correlation between qRT-PCR confirmation and the 1 to <5 years age group (p=0.038). Serology changes or recent infections were detected significantly in children <6 months (IgG, p=0.006; IgA, p=0.001) and >5 years of age (IgA, p=0.040; IgG, p=0.031). The mean and median time-to-positivity (using qRT-PCR) was 17 days, with a minimum of 6 and a maximum of 34. Among adults, the mean and median time-to-positivity was 12.6 and 9 days, respectively, with a minimum of 6 and a maximum of 45. Conclusion: Oligosymptomatic conditions may delay diagnosis and facilitate viral transmission. Pediatric-focused research is required, and specific protective measures for children <6 months of age should be considered.

Accuracy of the Hammersmith infant neurological examination for the early detection of neurological changes in infants exposed to Zika virus: A case-cohort study.

ABSTRACT: The Hammersmith infant neurological examination (HINE) is a highly predictive tool for the easy and low-cost detection of cerebral palsy. Between 2015 and 2016, the rapid spread of the Zika virus (ZIKV) in Brazil was responsible for an increase in microcephaly cases. This study aimed to verify the accuracy of the HINE for the early detection of neurological problems in Brazilian babies exposed to ZIKV.This was a cross sectional case-control study of children exposed to ZIKV. This study was part of the Jundiaí ZIKV Cohort. Of a total sample of 782 children, 98 were evaluated (26 in the exposed group and 63 in the control group). We included late preterm infants and term infants who were exposed to the ZIKV and were participants in the ZIKV Cohort study. Student's t-test and stepwise multivariate logistic regression were used to compare groups.Of the 26 items evaluated in the five scored categories of the HINE (cranial nerve function, posture, movements, tone, reflexes, and reactions), only the difference in ankle dorsiflexion between the exposed and the control groups was statistically significant. However, some items showed a significant trend in relation to the control group.Our results demonstrated the importance of early neurological assessment of infants exposed to ZIKV, even in those without a microcephaly diagnosis.

Epidemiological Study of Violence against Children and Its Increase during the COVID-19 Pandemic.

The aim of this study was to identify the epidemiological profiles of violence against children, victims, and their aggressors, and their correlations between socioeconomic and demographic factors analyzed before and during the COVID-19 pandemic. This was a cross-sectional, retrospective observational study based on a review of Individual Notification Forms from the Information System for Notifiable Diseases, including child victims of violence, under 18 years, assisted by a pediatric emergency service in Brazil, from 2016-2020. Data were stratified, then statistical analysis was performed using the two-proportion equality test and the Chi-square test, with p < 0.05 and a 95% confidence interval. A total of 609 notifications were analyzed and a prevalence of sexual violence (63.2%) was reported. The prevalent profile of victim was female (76.7%), aged between 2-9 years (38.1%) and 14-18 years (35.6%). The violence occurs in the victim's home (58.9%). The prevalent profile of perpetrator was male (82.4%), young adolescent (59.2%), living as family (64%), mainly the parents (18.4%). No correlation was found between the classified socioeconomic and demographic variables and violence. There was an increase in notifications during the COVID-19 pandemic, compared to the same period in the previous year; self-harm was reported in 59.7% of physical violence in 2020. Prevalence of sexual violence was higher for females, aged between 2-9 and 14-18 years, victimized in their homes, by male offenders, living as family, mainly by their parents. No association was found between child violence and the socioeconomic and demographic.

Prevalence and diagnostic accuracy of microcephaly in a pediatric cohort in Brazil: a retrospective cross-sectional study

Abstract Objective We sought to describe the prevalence of microcephaly and to compare the different cutoff points established by the Brazilian Ministry of Health at various times during a Zika virus epidemic. As a secondary aim, we investigated the possible etiology of the microcephaly. Method This retrospective study utilized newborn participants in the Zika Cohort Study Jundiaí. Newborns from the Zika Cohort Study Jundiaí with an accurate gestational age determination and complete anthropometric data were analyzed, and microcephaly was diagnosed according to the INTERGROWTH-21st curve. At delivery, fluids were tested for specific antibodies and for viruses. Brain images were evaluated for microcephaly. Receiver Operating Characteristic curves were plotted to define the accuracy of different cutoff points for microcephaly diagnosis. Results Of 462 eligible newborns, 19 (4.1%) were positive for microcephaly. Cutoff points corresponding to the curves of the World Health Organization yielded the best sensitivity and specificity. Three of the microcephaly cases (15.8%) were positive for Zika virus infections; nine (47.4%) had intrauterine growth restriction; one had intrauterine growth restriction and was exposed to Zika virus; three had a genetic syndrome (15.8%); and three had causes that had not been determined (15.8%). Conclusions Microcephaly prevalence was 4.1% in this study. Cutoff values determined by the World Health Organization had the highest sensitivity and specificity in relation to the standard IG curve. The main reason for microcephaly was intrauterine growth restriction. All possible causes of microcephaly must be investigated to allow the best development of an affected baby.

Zika Brazilian Cohorts (ZBC) Consortium: Protocol for an Individual Participant Data Meta-Analysis of Congenital Zika Syndrome after Maternal Exposure during Pregnancy.

Despite great advances in our knowledge of the consequences of Zika virus to human health, many questions remain unanswered, and results are often inconsistent. The small sample size of individual studies has limited inference about the spectrum of congenital Zika manifestations and the prognosis of affected children. The Brazilian Zika Cohorts Consortium addresses these limitations by bringing together and harmonizing epidemiological data from a series of prospective cohort studies of pregnant women with rash and of children with microcephaly and/or other manifestations of congenital Zika. The objective is to estimate the absolute risk of congenital Zika manifestations and to characterize the full spectrum and natural history of the manifestations of congenital Zika in children with and without microcephaly. This protocol describes the assembly of the Consortium and protocol for the Individual Participant Data Meta-analyses (IPD Meta-analyses). The findings will address knowledge gaps and inform public policies related to Zika virus. The large harmonized dataset and joint analyses will facilitate more precise estimates of the absolute risk of congenital Zika manifestations among Zika virus-infected pregnancies and more complete descriptions of its full spectrum, including rare manifestations. It will enable sensitivity analyses using different definitions of exposure and outcomes, and the investigation of the sources of heterogeneity between studies and regions.

Neonatal consequences of maternal exposure to the chikungunya virus: Case reports.

RATIONALE: The chikungunya virus (CHIKV) was first isolated in a Tanzanian epidemic area between 1952 and 1953. The best description of the CHIKV transmission during pregnancy can be found in a well-documented epidemic in 2005, in the "La Reunion" island, a French territory located in the Indian Ocean, in which about one-third of the population was infected. Reports of arbovirus infections in pregnancy are increasing over time, but the spectrum of clinical findings remains an incognita among researchers, including CHIKV. PATIENT CONCERNS: In this report, it was possible to verify 2 cases exposed to CHIKV during foetal period and the possible implications of the infection on gestational structures and exposed children after the birth. DIAGNOSIS: In both cases, the mothers were positive by laboratory tests in serologic analysis for CHIKV, as ezyme-linked immunossorbent assay (ELISA), plaque reduction neutralisation testing (PRNT) and immunofluorescence (IF); but there were no positive tests in quantitative polymerase chain reaction (qPCR) for mothers or children. INTERVENTIONS: The exposed children were followed up in a paediatrics clinic in order not only to provide the medical assistance, but also to verify child development and the possible implications and neurocognitive changes caused by gestational infection. OUTCOMES: There were neurological and developmental changes in one of the children followed up on an outpatient basis. There was an improvement in the neurological situation and symptoms only 3 years and 1 month after birth. LESSONS: Based on the cases presented, we can conclude that clinical symptoms of CHIKV maternal infection may occur late in new-borns and can affect their development.

Three-Year Clinical Follow-Up of Children Intrauterine Exposed to Zika Virus.

Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women and/or newborns were considered ZIKV exposed and/or infected. Laboratory diagnosis was made by polymerase chain reaction in the pregnant mothers and their respective newborns, as well as Dengue virus, Chikungunya virus, and ZIKV serology. Serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis infections were also performed in microcephalic newborns. The newborns included in the study were followed up until their third birthday. Developmental delay was observed in nine patients (13.2%): mild cognitive delay in three patients, speech delay in three patients, autism spectrum disorder in two patients, and severe neurological abnormalities in one microcephalic patient; sensorineural hearing loss, three patients and dysphagia, six patients. Microcephaly due to ZIKV occurred in three patients (3.6%). Clinical manifestations can appear after the first year of life in children infected/exposed to ZIKV, emphasizing the need for long-term follow-up.

Prevalence and diagnostic accuracy of microcephaly in a pediatric cohort in Brazil: a retrospective cross-sectional study.

OBJECTIVE: We sought to describe the prevalence of microcephaly and to compare the different cutoff points established by the Brazilian Ministry of Health at various times during a Zika virus epidemic. As a secondary aim, we investigated the possible etiology of the microcephaly. METHOD: This retrospective study utilized newborn participants in the Zika Cohort Study Jundiaí. Newborns from the Zika Cohort Study Jundiaí with an accurate gestational age determination and complete anthropometric data were analyzed, and microcephaly was diagnosed according to the INTERGROWTH-21st curve. At delivery, fluids were tested for specific antibodies and for viruses. Brain images were evaluated for microcephaly. Receiver Operating Characteristic curves were plotted to define the accuracy of different cutoff points for microcephaly diagnosis. RESULTS: Of 462 eligible newborns, 19 (4.1%) were positive for microcephaly. Cutoff points corresponding to the curves of the World Health Organization yielded the best sensitivity and specificity. Three of the microcephaly cases (15.8%) were positive for Zika virus infections; nine (47.4%) had intrauterine growth restriction; one had intrauterine growth restriction and was exposed to Zika virus; three had a genetic syndrome (15.8%); and three had causes that had not been determined (15.8%). CONCLUSIONS: Microcephaly prevalence was 4.1% in this study. Cutoff values determined by the World Health Organization had the highest sensitivity and specificity in relation to the standard IG curve. The main reason for microcephaly was intrauterine growth restriction. All possible causes of microcephaly must be investigated to allow the best development of an affected baby.

Longitudinal visual acuity development in ZIKV-exposed children.

PURPOSE: To follow the visual acuity development of children exposed to or infected with the Zika virus (ZIKV) during gestation and to relate potential visual acuity deficits to their clinical condition. METHODS: In this prospective study, visual acuity was measured via Teller Acuity Cards in three groups of children: (1) those with confirmed ZIKV exposure (ZE) through the mother only, (2) those with confirmed infection (ZI), and (3) unaffected controls. Visual acuity was measured 2-4 times in each child during the first 30 months of age. RESULTS: The study included 22 children in the ZE group, 11 in the ZI group, and 27 controls. Visual acuity developed normally in both patient groups, including infected patients (ZI) that did not manifest clinical symptoms. In a small subgroup of patients with characteristics consistent with congenital Zika syndrome (CZS), visual acuity was within normative values, with the exception of single child with chorioretinal atrophy. CONCLUSIONS: In this southeastern Brazil study cohort, visual acuity development seemed to progress normally in infected children without CZS symptoms.

Detection of Zika virus in paired urine and amniotic fluid samples from symptomatic and asymptomatic women and their babies during a disease outbreak: association with neurological symptoms in newborns.

Paired maternal and newborn urine and amniotic fluid from 138 subjects collected during a Zika virus (ZIKV) outbreak was analyzed for ZIKV by gene amplification (RT-qPCR), and the findings were correlated with clinical symptoms and neurological anomalies in the babies. ZIKV was detected in 1 of 9 symptomatic women (11.1%) and in 19 of 129 asymptomatic women (14.7%). Neurological manifestations were present in 19 babies (13.7%), 10 of 20 (50%) positive and 9 of 119 (7.6%) negative (p < 0.001) for ZIKV. Twelve (8.6%) urines collected during gestation were ZIKV-positive; only 2 remained positive for ZIKV postpartum. Six (4.1%) newborn urines collected within 1 day of delivery were ZIKV-positive cases. In 3 of these cases, ZIKV was detected in mother's urine pre- and postpartum and in both mother's urine and babies' urine. Four of the amniotic fluid samples (2.9%) were ZIKV-positive. Among ZIKV-negative babies with neurological sequel, 87.5% were female; in contrast, 72.7% ZIKV-positive babies with neurological abnormalities were male (p = 0.019). We conclude that during a ZIKV outbreak, clinical symptoms and ZIKV detection in biological fluids are poor predictors of infection and adverse neurologic sequel in newborns.

Severe pertussis in childhood: update and controversy - systematic review / Coqueluche grave na infância: atualização e controvérsias - revisão sistemática

ABSTRACT Objective: Through a systematic review, this essay aimed at revising the concepts of severe pertussis, updating the epidemiology, pathophysiology, clinical presentation, antibiotic therapy and auxiliary therapeutic options for symptomatology and complications. Data sources: This review considered publications from the last 30years in the databases US National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO), Literatura Latino-americana e do Caribe em Ciências da Saúde (LILACS), Cochrane, Google Scholar, as well as protocols of the Ministry of Health and recommendations of the Centers for Disease Control and Prevention, related to childhood pertussis (whooping cough), with emphasis on its severe form. This research was based on keywords derived from the terms "pertussis", "azithromycin", "antitussives", "leukocyte reduction" in Portuguese and English. Duplicate studies and those with unavailable full-text were excluded. Data synthesis: Among 556 records found, 54 were selected for analysis. Pertussis, as a reemerging disease, has affected all age groups, evidencing the transient immunity conferred by infection and vaccination. Severe cases occur in neonates and infants, with secondary viral and bacterial complications and malignant pertussis, a longside hyperleukocytosis, respiratory failure and shock. Macrolides continue to be the chosen antibiotics, while antitussives for coughing remain without efficacy. The prompt treatment in Intensive Care Units improved the prognostic in severe cases, and transfusion was promising among procedures for leukoreduction. Conclusions: Approaching severe pertussis in childhood remains a challenge for diagnostic and therapy, as the available therapeutic options are still unsatisfactory. Strategies of prevention are expected to reduce the occurrence of severe cases, while new studies should confirm the role of auxiliary therapies.

RESUMO Objetivo: Rever os conceitos de coqueluche grave, atualizar epidemiologia, fisiopatologia e apresentação clínica, verificar as recomendações de antibioticoterapia e conhecer opções terapêuticas auxiliares na sintomatologia e complicações, por meio de revisão sistemática. Fontes de dados: Foram pesquisados trabalhos publicados nos últimos 30 anos nas bases US National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO), Literatura Latino-americana e do Caribe em Ciências da Saúde (LILACS), Cochrane e Google Scholar, bem como protocolos do Ministério da Saúde e recomendações do Centers for Disease Control and Prevention, relacionados à coqueluche na infância, com ênfase na forma grave. Apesquisa baseou-se em palavras-chave derivadas dos termos "coqueluche", "azitromicina", "antitussígenos" e "redução de leucócitos", nos idiomas português e inglês. Foramexcluídos estudos em duplicata ou texto integral indisponíveis. Síntese dos dados: Dos 556 registros encontrados, foram selecionados 54 para análise. A coqueluche, como doença reemergente, tem acometido todas as faixas etárias, evidenciando a imunidade transitória conferida pela infecção e pela vacinação. Quadros graves ocorrem em neonatos e lactentes, com complicações virais e bacterianas secundárias e pertussis maligna, com hiperleucocitose, insuficiência respiratória e choque refratário. Os macrolídeos continuam como antibióticos de escolha. Os sintomáticos da tosse não demonstraram eficácia. O suporte precoce em Unidade de Terapia Intensiva melhorou o prognóstico dos casos graves e a exsanguineotransfusão se mostrou a mais promissora entre os procedimentos para leucorredução. Conclusões: A abordagem da coqueluche grave na infância segue como desafio diagnóstico e terapêutico. As opções terapêuticas disponíveis ainda são insatisfatórias. Espera-se que as estratégias de prevenção reduzam a ocorrência de casos graves e que novos estudos confirmem o papel das terapias adjuvantes.

SEVERE PERTUSSIS IN CHILDHOOD: UPDATE AND CONTROVERSY - SYSTEMATIC REVIEW.

OBJECTIVE: Through a systematic review, this essay aimed at revising the concepts of severe pertussis, updating the epidemiology, pathophysiology, clinical presentation, antibiotic therapy and auxiliary therapeutic options for symptomatology and complications. DATA SOURCES: This review considered publications from the last 30years in the databases US National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO), Literatura Latino-americana e do Caribe em Ciências da Saúde (LILACS), Cochrane, Google Scholar, as well as protocols of the Ministry of Health and recommendations of the Centers for Disease Control and Prevention, related to childhood pertussis (whooping cough), with emphasis on its severe form. This research was based on keywords derived from the terms "pertussis", "azithromycin", "antitussives", "leukocyte reduction" in Portuguese and English. Duplicate studies and those with unavailable full-text were excluded. DATA SYNTHESIS: Among 556 records found, 54 were selected for analysis. Pertussis, as a reemerging disease, has affected all age groups, evidencing the transient immunity conferred by infection and vaccination. Severe cases occur in neonates and infants, with secondary viral and bacterial complications and malignant pertussis, a longside hyperleukocytosis, respiratory failure and shock. Macrolides continue to be the chosen antibiotics, while antitussives for coughing remain without efficacy. The prompt treatment in Intensive Care Units improved the prognostic in severe cases, and transfusion was promising among procedures for leukoreduction. CONCLUSIONS: Approaching severe pertussis in childhood remains a challenge for diagnostic and therapy, as the available therapeutic options are still unsatisfactory. Strategies of prevention are expected to reduce the occurrence of severe cases, while new studies should confirm the role of auxiliary therapies.

Publisher Correction: Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.

The original PDF version of this Article contained errors in the spelling of Luiz Carlos Caires-Júnior, Uirá Souto Melo, Bruno Henrique Silva Araujo, Alessandra Soares-Schanoski, Murilo Sena Amaral, Kayque Alves Telles-Silva, Vanessa van der Linden, Helio van der Linden, João Ricardo Mendes de Oliveira, Nivia Maria Rodrigues Arrais, Joanna Goes Castro Meira, Ana Jovina Barreto Bispo, Esper Abrão Cavalheiro, and Robert Andreata-Santos, which were incorrectly given as Luiz Carlos de Caires Jr., UiráSouto Melo, Bruno Silva Henrique Araujo, Alessandra Soares Schanoski, MuriloSena Amaral, Kayque Telles Alves Silva, Vanessa Van der Linden, Helio Van der Linden, João Mendes Ricardo de Oliveira, Nivia Rodrigues Maria Arrais, Joanna Castro Goes Meira, Ana JovinaBarreto Bispo, EsperAbrão Cavalheiro, and Robert Andreata Santos. Furthermore, in both the PDF and HTML versions of the Article, the top panel of Fig. 3e was incorrectly labeled '10608-1' and should have been '10608-4', and financial support from CAPES and DECIT-MS was inadvertently omitted from the Acknowledgements section. These errors have now been corrected in both the PDF and HTML versions of the Article.

Doenças respiratórias agudas em crianças brasileiras: os cuidadores são capazes de detectar os primeiros sinais de alerta? / Acute respiratory diseases in brazilian children: are caregivers able to detect early warning signs?

RESUMO Objetivo: Avaliar o nível de conhecimento do cuidador em relação aos sinais e sintomas respiratórios de Infecções Respiratórias Agudas (IRA) e a percepção dos mesmos em relação às crianças que necessitam de assistência médica. Métodos: Estudo prospectivo e transversal, no qual um questionário padronizado com itens relacionados à percepção da gravidade dos sinais e sintomas de IRA foi administrado a cuidadores de pacientes pediátricos admitidos no serviço de emergência de um hospital universitário no período de agosto de 2011 a maio de 2012. A análise estatística foi realizada com os testes do qui-quadrado e t-Student para determinar quais variáveis contribuíram para o reconhecimento pelos cuidadores da gravidade das doenças respiratórias agudas. Resultados: Foram entrevistados 499 cuidadores. As causas de IRA mais citadas foram Síndrome gripal (78,6%), Resfriado comum (73,9%), Faringites (64,1%) e Pneumonia (54,5%). Febre (34,1%) e Tosse (15,8%) foram as principais razões para a procura de atendimento. Os sinais de gravidade mais citados pelos cuidadores foram: febre (99,6%), dispneia (91,4%), sibilância (86,4%), adinamia (80,2%), tosse (79,8%) e taquipneia (78,6%). O histórico de doença respiratória anterior do paciente (p=0,002), a idade (p=0,010) e o estado civil do cuidador (p=0,014) foram as variáveis significativamente associadas com taquipneia, o sintoma mais grave de IRA. Conclusões: Embora cuidadores pediátricos possam perceber os principais sinais de IRA, eles não são capazes de reconhecer a gravidade destes, o que pode atrasar os cuidados médicos e impedir o tratamento precoce.

ABSTRACT Objective: To assess the level of caregiver knowledge about respiratory signs and symptoms of acute respiratory infection (ARI) as well as their ability to detect the early warning signs and need for medical assistance in children referred to an emergency service. Methods: This is a prospective, cross-sectional study. A standardized questionnaire with questions on the perception of the severity of ARI signs and symptoms was applied to caregivers of pediatric patients assisted in the emergency room of a university hospital from August 2011 to May 2012. Chi-square and Student's t-tests were used to determine which variables contributed with caregivers' recognition of severity of acute respiratory diseases. Results: 499 caregivers were interviewed. The most cited causes of ARI were flu syndrome (78.6%), common cold (73.9%), pharyngitis (64.1%), and pneumonia (54.5%). Fever (34.1%) and cough (15.8%) were major reasons for referral to hospital. The most cited signs of severity recognized by caregivers were fever (99.6%), dyspnea (91.4%), wheezing (86.4%), adynamia (80.2%), coughing (79.8%), and tachypnea (78.6%). Children's history of respiratory diseases (p=0.002), caregiver's age (p=0.010) and marital status (p=0.014) were significantly associated with tachypnea, the most severe ARI symptom. Conclusions: Although caregivers of children can recognize ARI most important signs and symptoms, they are unable to judge severity, which may delay medical care and early treatment.

ACUTE RESPIRATORY DISEASES IN BRAZILIAN CHILDREN: ARE CAREGIVERS ABLE TO DETECT EARLY WARNING SIGNS? / DOENÇAS RESPIRATÓRIAS AGUDAS EM CRIANÇAS BRASILEIRAS: OS CUIDADORES SÃO CAPAZES DE DETECTAR OS PRIMEIROS SINAIS DE ALERTA?

OBJECTIVE: To assess the level of caregiver knowledge about respiratory signs and symptoms of acute respiratory infection (ARI) as well as their ability to detect the early warning signs and need for medical assistance in children referred to an emergency service. METHODS: This is a prospective, cross-sectional study. A standardized questionnaire with questions on the perception of the severity of ARI signs and symptoms was applied to caregivers of pediatric patients assisted in the emergency room of a university hospital from August 2011 to May 2012. Chi-square and Student's t-tests were used to determine which variables contributed with caregivers' recognition of severity of acute respiratory diseases. RESULTS: 499 caregivers were interviewed. The most cited causes of ARI were flu syndrome (78.6%), common cold (73.9%), pharyngitis (64.1%), and pneumonia (54.5%). Fever (34.1%) and cough (15.8%) were major reasons for referral to hospital. The most cited signs of severity recognized by caregivers were fever (99.6%), dyspnea (91.4%), wheezing (86.4%), adynamia (80.2%), coughing (79.8%), and tachypnea (78.6%). Children's history of respiratory diseases (p=0.002), caregiver's age (p=0.010) and marital status (p=0.014) were significantly associated with tachypnea, the most severe ARI symptom. CONCLUSIONS: Although caregivers of children can recognize ARI most important signs and symptoms, they are unable to judge severity, which may delay medical care and early treatment.

OBJETIVO: Avaliar o nível de conhecimento do cuidador em relação aos sinais e sintomas respiratórios de Infecções Respiratórias Agudas (IRA) e a percepção dos mesmos em relação às crianças que necessitam de assistência médica. MÉTODOS: Estudo prospectivo e transversal, no qual um questionário padronizado com itens relacionados à percepção da gravidade dos sinais e sintomas de IRA foi administrado a cuidadores de pacientes pediátricos admitidos no serviço de emergência de um hospital universitário no período de agosto de 2011 a maio de 2012. A análise estatística foi realizada com os testes do qui-quadrado e t-Student para determinar quais variáveis contribuíram para o reconhecimento pelos cuidadores da gravidade das doenças respiratórias agudas. RESULTADOS: Foram entrevistados 499 cuidadores. As causas de IRA mais citadas foram Síndrome gripal (78,6%), Resfriado comum (73,9%), Faringites (64,1%) e Pneumonia (54,5%). Febre (34,1%) e Tosse (15,8%) foram as principais razões para a procura de atendimento. Os sinais de gravidade mais citados pelos cuidadores foram: febre (99,6%), dispneia (91,4%), sibilância (86,4%), adinamia (80,2%), tosse (79,8%) e taquipneia (78,6%). O histórico de doença respiratória anterior do paciente (p=0,002), a idade (p=0,010) e o estado civil do cuidador (p=0,014) foram as variáveis significativamente associadas com taquipneia, o sintoma mais grave de IRA. CONCLUSÕES: Embora cuidadores pediátricos possam perceber os principais sinais de IRA, eles não são capazes de reconhecer a gravidade destes, o que pode atrasar os cuidados médicos e impedir o tratamento precoce.