Differences in Placental Histology Between Zika Virus-infected Teenagers and Older Women.

In pregnant women, Zika virus (ZIKV) is associated with a congenital syndrome, most frequently involving damage to embryo brain formation and the development of microcephaly. The mechanism(s) by which ZIKV enters the maternal-fetal interface and is transmitted to the fetus remains incompletely determined. We sought to evaluate histologic changes in the placenta of ZIKV-infected pregnant women and to determine if this varied by maternal age. Placental samples were obtained from 66 women, 33 of whom were positive for ZIKV. Histologic evaluations were performed on 4 areas of the placenta: fetal surface, maternal surface, umbilical cord, and membranes. Samples were analyzed by the tissue microarray technique and tested for CD4, CD8, CD20, CD68, FOXP3, and cyclooxygenase-2 expression. Data were evaluated using Fisher exact test. ZIKV infection was more frequent in women less than 18 yr of age (9/11, 81.8%) than in women above 18 yr old (24/55, 43.6%) (P=0.0440). ZIKV detection was associated with neutrophilic chorioamnionitis (P=0.0332) and with septal (P=0.0244) and villous (P=0.0534) calcification. Hofbauer cell hyperplasia (P=0.0260) and cyclooxygenase-2 expression (P=0.0346) were more prevalent in ZIKV-positive women aged 18 yr and below than in the older ZIKV-positive women. ZIKV infection during pregnancy occurs more frequently in adolescents and induces higher rates of damage at the maternal-fetal interface than in older women.

Knowledge of Zika Virus Transmission and Its Prevention among High-Risk Pregnant Women in Brazil.

Recent outbreaks of Zika virus (ZIKV) infection highlight the urgent need to evaluate the efficacy of current public health measures to educate susceptible groups about how to prevent infection, modes of viral transmission, and consequences of infection. We performed a cross-sectional study in the city of Jundiaí, São-Paulo, from March 2016 to August 2017. In 315 high-risk pregnant women we evaluated the rate of ZIKV infection, knowledge of pathways of ZIKV transmission, and the use of protective measures. Data were analyzed and correlated with sociodemographic variables. The rate of ZIKV infection was 10.8%. ZIKV transmission by mosquitoes was the best-known means of virus acquisition, while transmission of ZIKV by sexual intercourse as well as mother-fetus transmission was known by less than half of the women. The use of insect repellent, reported by 53% of participants, was correlated with higher education and personal directives from health professionals. Condom use was reported by 19.5% of subjects. Improved strategies to increase awareness of ZIKV infection and its consequences, designed to appeal to specific, targeted populations, are clearly necessary to more accurately prevent the spread of this infection and diminish adverse consequences in the pregnant population.

Zika virus infection in pregnancy and adverse fetal outcomes in São Paulo State, Brazil: a prospective cohort study.

Robust epidemiological and biological evidence supports a causal link between prenatal Zika Virus (ZIKV) infection and congenital brain abnormalities including microcephaly. However, it remains uncertain if ZIKV infection in pregnancy also increases the risk for other adverse fetal and birth outcomes. In a prospective cohort study we investigated the influence of ZIKV on the prevalence of prematurity, low birth weight, small-for-gestational-age, and fetal death as well as microcephaly (i.e., overall and disproportionate) in the offspring of women attending a high-risk pregnancy clinic during the recent ZIKV outbreak in Brazil. During the recruitment period (01 March 2016-23 August 2017), urine samples were tested for ZIKV by RT-PCR from all women attending the high-risk pregnancy clinic at Jundiaí University Hospital and from the neonates after delivery. Of the 574 women evaluated, 44 (7.7%) were ZIKV RT-PCR positive during pregnancy. Of the 409 neonates tested, 19 (4.6%) were ZIKV RT-PCR positive in the first 10 days of life. In this cohort, maternal ZIKV exposure was not associated with increased risks of prematurity, low birth weight, small-for-gestational-age, or fetal death. However, relative to ZIKV-negative neonates, ZIKV-positive infants had a five-fold increased risk of microcephaly overall (RR 5.1, 95% CI 1.2-22.5) and a ten-fold increased risk of disproportionate microcephaly (RR 10.3, 95% CI 2.0-52.6). Our findings provide new evidence that, in a high-risk pregnancy cohort, ZIKV RT-PCR positivity in the neonate at birth is strongly associated with microcephaly. However, ZIKV infection during pregnancy does not appear to influence the risks of prematurity, low birth weight, small-for-gestational-age or fetal death in women who already have gestational comorbidities. The results suggest disproportion between neonatal head circumference and weight may be a useful screening indicator for the detection of congenital microcephaly associated with ZIKV infection.

Histopathologic Changes in Placental Tissue Associated With Vertical Transmission of Zika Virus.

Zika virus (ZIKV) is highly neurotropic after crossing the placenta, inducing teratogenic effects that result in delayed development and microcephaly in infants. The available evidence for vertical transmission of this infection is based on placental studies showing alterations in trophoblastic tissue. However, complete characterization of ZIKV-infected placenta and involved pathways has yet to be fully clarified. This case report of placental ZIKV infection describes morphologic and molecular changes in the placenta. Hyperplasia of placental Hofbauer cells in chorionic villi and numerous histiocyte-like cells in the decidua were observed. The decidua, fibroblasts, and chorion, as well as circulating cells in the intravascular compartment stained positive for ZIKV envelop protein. Deciduitis was present on the maternal surface of the placenta, with a prevalence of lymphocytes associated with vasculitis. A high level of uncommitted CD3 T lymphocytes were present, in addition to CD4 and CD8 cells. Elevated expression of the apoptosis inhibitor, Bcl-2, was observed in syncytiotrophoblasts. These parameters may promote the persistence of ZIKV in placental tissue and transmission to the fetus.

Cohort profile: the Jundiaí Zika cohort (JZC), a pregnancy and birth cohort in São Paulo state, Brazil.

PURPOSE: The Jundiaí Zika Cohort (JZC) is a prospective pregnancy and birth cohort setup in the State of São Paulo, Brazil, to investigate the epidemic of cases of microcephaly and other neurological disorders, presumed to be associated with Zika virus (ZIKV) infection. PARTICIPANTS: A total of 748 women with high-risk pregnancies were recruited in the period of March 2016 to August 2017. FINDINGS TO DATE: Baseline sociodemographic and medical data were collected at recruitment from 737 pregnant women. Biological samples (ie, blood, saliva and urine) were collected from 695 of the pregnant women (94.3%), of whom 53 (7.6%) were ZIKV-positive on subsequent testing by reverse transcription polymerase chain reaction (RT-PCR) in urine. Biological sample (ie, blood, saliva, urine and cerebrospinal fluid) were collected within 10 days of birth from 409 (57.4%) of the liveborn infants, of whom 19 (4.6%) were ZIKV-positive on subsequent testing by RT-PCR in urine. All remaining biological specimens, as well as colostrum, umbilical cord and placental samples, have been stored in a secure biorepository. Antenatal and postnatal imaging studies and neonatal anthropometry were carried out. FUTURE PLANS: The JZC provides a unique data set which will continue to be explored to study the effects of pregnancy comorbidities on Zika virus infection during pregnancy, the long-term outcomes of children with congenital Zika infection and how physiotherapy and group interventions can improve outcomes for congenitally-infected children. All women in the cohort have reached the end of their pregnancy and currently the oldest children are 2 years old. The study will continue until all the children reach their third birthday (April 2021).

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children.

INTRODUCTION: Zika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes. METHODS AND ANALYSIS: We will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty. ETHICS AND DISSEMINATION: The IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: PROSPERO International prospective register of systematic reviews (CRD42017068915).

Development of Secondary Microcephaly After Delivery: Possible Consequence of Mother-Baby Transmission of Zika Virus in Breast Milk.

BACKGROUND The Zika virus is an arbovirus that has as main source of transmission the bite of infected insects of the genus Aedes and has been associated with cases of congenital malformation and microcephaly in neonates. However, other sources of transmission have been identified since the emergence of this virus in the world population, such as vertical transmission by semen and possibly other body fluids such as vaginal secretion and breast milk. CASE REPORT An infant, born to a mother whose previous delivery was a baby with severe microcephaly, was normal and was negative for Zika virus at birth but developed secondary microcephaly 1 month later, that persisted. The baby was exclusively breast-fed and Zika virus was present in the mother's milk. CONCLUSIONS We report the detection of Zika virus exclusively in the breast milk of a woman after her second delivery of an infant, who later developed microcephaly. This case is consistent with possible vertical transmission.

Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy / Infecções respiratórias virais agudas em pacientes pediátricos com câncer em tratamento quimioterápico

OBJECTIVE: to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI) and/or fever. METHODS: cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc) and University Hospital (HU), Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland), and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta) for detection of influenza virus (H1N1, B), rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ2 or Fisher's exact test). RESULTS: 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3%) was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%), respiratory syncytial virus AB (8.7%), and coronavirus (6.8%). Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7) were positive for viruses. There were no deaths. CONCLUSIONS: the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs. .

OBJETIVO: estimar a prevalência da infecção pelos vírus respiratórios em pacientes pediátricos com câncer e infecção respiratória aguda (IRA) e/ou febre. MÉTODOS: estudo transversal, de janeiro de 2011 a dezembro de 2012. Foram analisadas secreções de aspirado da nasofaringe de menores de 21 anos, com quadro respiratório agudo, atendidos nos hospitais Grendacc e HU, Jundiaí, SP. Foi aplicado o teste rápido para detecção dos vírus influenza (Kit Biotrin(r)) e a reação em cadeia da polimerase multiplex em tempo real (Kit multiplex/Fast Trade(r)) para detecção dos vírus: influenza (A, H1N1, B), rinovírus, parainfluenza, adenovírus respiratório, vírus respiratório sincicial, parechovírus, bocavírus, metapneumovírus humano e coronavírus humano. Foi estimada a prevalência de infecção viral e usados testes de associação (χ2 ou teste exato de Fisher). RESULTADOS: foram analisadas 104 amostras de aspirado de nasofaringe e sangue. A mediana para a idade foi 12±5,2 anos; masculino (51%); cor branca (68%); IVAS de repetição (32%); uso prévio de antibiótico (32%); tosse (19,8%); e contato com IVAS (8%). Apresentavam-se em bom estado geral 94,3% dos pacientes. A leucemia linfocítica aguda (42,3%) foi mais prevalente. Foram detectados vírus respiratórios em 50% das amostras: rinovírus (23,1%), vírus sincicial respiratório A/B (8,7%) e coronavírus (6,8%). Ocorreu codetecção em 19% entre dois vírus, e de 3% entre três vírus, sendo a mais frequente entre rinovírus e coronavírus 43. Febre em neutropênicos foi de 13%, sendo quatro (30,7%) com vírus positivo. Não houve óbitos. CONCLUSÕES: a prevalência de vírus respiratórios ...

Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy.

OBJECTIVE: to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI) and/or fever. METHODS: cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc) and University Hospital (HU), Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland), and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta) for detection of influenza virus (H1N1, B), rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ(2) or Fisher's exact test). RESULTS: 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3%) was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%), respiratory syncytial virus AB (8.7%), and coronavirus (6.8%). Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7) were positive for viruses. There were no deaths. CONCLUSIONS: the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs.

Incidence and clinical characteristics of the infection by the Respiratory Syncytial Virus in children admitted in Santa Casa de São Paulo Hospital

The purpose of this study was to identify the rate of infections due to RSV and other viruses in children. In addition we have analyzed demographic data and clinical characteristics of the RSV-positive patients comparing with patients infected by other respiratory viruses. We also described the seasonality of the RSV occurrence in a hospital in São Paulo. Children below 5 years old admitted in Santa Casa de São Paulo Hospital between February 2005 and September 2006 due to acute respiratory infections (ARI) were included. A nasopharyngeal specimens were obtained with sterile No. 5 French feeding catheters as soon as possible (usually within 24 h). Specimens were kept refrigerated at 4ºC and transported to Adolfo Lutz Institute, where the indirect immunofluorescent assay was performed. Virus identified by these assay included RSV, Adenovirus, Influenza A and B virus and Parainfluenza 1, 2, and 3. Clinical data from each group was compared. Four hundred and fifty five cases were included in the study, with 30 percent positive for some type of virus. Viruses that were identified included Respiratory Syncytial Virus (73.03 percent), Influenza (8.42 percent), Parainfluenza (8.42 percent) and Adenovirus (3.37 percent). We divided the subjects in 3 groups: Group 1 RSV-Positive, Group 2 Other Positive Viruses and Group 3 Negative for Respiratory Virus. Mean age (months) was of 7.5 for RSV-positive children, 7.6 for other viruses, and 8 for negative for respiratory virus. The RSV-Positive Group was significantly younger than the Group Negative for Respiratory Virus (p<0.05). Signs of UAI were more present in the Positive RSV Group (p<0.05). General mortality was of 2.41 percent. There was a higher incidence of RSV between the months of March and August in the two years of the study. Our study indicates RSV as the most prevalent viral agent in children admitted due to (ARI), especially in infants below 3 months old. We have also found that infections...

Incidence and clinical characteristics of the infection by the respiratory syncytial virus in children admitted in Santa Casa de São Paulo Hospital.

The purpose of this study was to identify the rate of infections due to RSV and other viruses in children. In addition we have analyzed demographic data and clinical characteristics of the RSV-positive patients comparing with patients infected by other respiratory viruses. We also described the seasonality of the RSV occurrence in a hospital in São Paulo. Children below 5 years old admitted in Santa Casa de São Paulo Hospital between February 2005 and September 2006 due to acute respiratory infections (ARI) were included. A nasopharyngeal specimens were obtained with sterile No. 5 French feeding catheters as soon as possible (usually within 24 h). Specimens were kept refrigerated at 4 degrees C and transported to Adolfo Lutz Institute, where the indirect immunofluorescent assay was performed. Virus identified by these assay included RSV, Adenovirus, Influenza A and B virus and Parainfluenza 1, 2, and 3. Clinical data from each group was compared. Four hundred and fifty five cases were included in the study, with 30% positive for some type of virus. Viruses that were identified included Respiratory Syncytial Virus (73.03%), Influenza (8.42%), Parainfluenza (8.42%) and Adenovirus (3.37%). We divided the subjects in 3 groups: Group 1 RSV-Positive, Group 2 Other Positive Viruses and Group 3 Negative for Respiratory Virus. Mean age (months) was of 7.5 for RSV-positive children, 7.6 for other viruses, and 8 for negative for respiratory virus. The RSV-Positive Group was significantly younger than the Group Negative for Respiratory Virus (p<0.05). Signs of UAI were more present in the Positive RSV Group (p<0.05). General mortality was of 2.41%. There was a higher incidence of RSV between the months of March and August in the two years of the study. Our study indicates RSV as the most prevalent viral agent in children admitted due to (ARI), especially in infants below 3 months old. We have also found that infections due to RSV can occur in months others than the classic seasonal period.

Diagnostico da rubeola em pacientes com exantema / Rubella diagnosis in patients with exanthema

O pediatra frequentemente avalia criancas e adolescentes com exantema, ocasiao em que um dos diagnosticos etiologicos e o de rubeola. Esse diagnostico determina, para o paciente, a prescricao, unicamente, de sintomaticos...