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Objective To assess the protective effect of exclusive breastfeeding and the effectiveness of maternal vaccination in reducing pertussis-like illness. Method This was a case-control study conducted in sentinel hospitals for pertussis in Recife between July 2016 and July 2018. Cases included children aged under six months with symptoms compatible with pertussis (pertussis-like illness). Controls included children aged under six months, living in the metropolitan region of Recife with no diagnosis of pertussis-like illness and matched by the same hospital and birth date. Results Seventy-three cases and 194 controls were included. The diagnosis of pertussis-like illness was predominantly clinical (97,2%). Amongst the main symptoms, paroxysmal cough was observed in 95.89% of cases and vomiting in 53.4%. There were 29 hospitalized cases and no deaths. Out of the 73 cases, 47 were born to mothers vaccinated against pertussis during pregnancy, and the mothers of 144 of the 194 controls had been vaccinated. The protective effect of breastfeeding was of 74% (95% CI;38%, 89%). Children younger than six months, who were exclusively breastfed and with mothers vaccinated against pertussis during pregnancy were 5 times less likely to develop pertussis-like illness, corresponding to a protection of 79% (95% CI;31%, 94%). The effectiveness of maternal vaccination against pertussis-like illness in children under six months was low (27%) and not statistically significant (CI 95%; −34% a 60%). Conclusions Exclusive breastfeeding protects children under six months from pertussis-like illness and may be enhanced when associated with maternal vaccination. These strategies should be encouraged because they also protect against pertussis-like illnesses.

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.

Introduction In 2014, there was an epidemic of pertussis in Brazil that caused the death of 129 infants. To control the disease amongst infants under 6 months of age, and especially those under 2 months, the Brazilian Ministry of Health introduced Tdap immunization for all pregnant women. Methods This study aimed to describe the morbidity and mortality variables of pertussis cases in 969 infants aged under 6 months, comparing the periods before and after the introduction of Tdap vaccine in pregnant women. Data was extracted from the Information System on Notifiable Diseases (SINAN) including every case of pertussis that occurred in the metropolitan region of Recife-Brazil in infants under 6 months from January 2009 to October 2018. In order to analyze the variables, patients were divided into two groups Pre-Tdap(2009–2014), and Post-Tdap (2016–2018). Results There were no significant differences between the age groups and gender distribution in the period compared. In the Post- Tdap group compared with the Pre-Tdap group, the clinical presentation of pertussis in infants differed with more paroxysmal cough, and more vomiting, less apnea, and cyanosis. During this period, there were fewer complications and no deaths occurred. Conclusions Maternal immunization with Tdap decreased disease severity, complication rates, and no deaths occurred in infants under 6 months of age diagnosed with pertussis.

Introduction and objective: Hepatotoxicity during tuberculosis (TB) treatment is frequent and may be related to the Arylamine N-Acetyltransferase (NAT2) acetylator profile, in which allele frequencies differ according to the population. The aim of this study was to investigate functional polymorphisms in NAT2 associated with the development of hepatotoxicity after initiating treatment for TB in people living with HIV/AIDS (PLWHA) in Pernambuco, Northeast Brazil. Material and methods: This was a prospective cohort study that investigated seven single nucleotide polymorphisms located in the NAT2 coding region in 173 PLWHA undergoing TB treatment. Hepatotoxicity was defined as elevated aminotransferase levels and identified as being three times higher than it was before initiating TB treatment, with associated symptoms of hepatitis. A further 80 healthy subjects, without HIV infection or TB were used as a control group. All individuals were genotyped by direct sequencing. Results: The NAT2*13A and NAT2*6B variant alleles were significantly associated with the development of hepatotoxicity during TB treatment in PLWHA (p < 0.05). Individual comparisons between the wild type and each variant genotype revealed that PLWHA with signatures NAT2*13A/NAT2*13A (OR 4.4; CI95% 1.1–18.8; p 0.037) and NAT2*13A/NAT2*6B (OR 4.4; CI95% 1.5–12.7; p 0.005) significantly increased the risk of hepatotoxicity. Conclusion: This study suggests that NAT2*13A and NAT2*6B variant alleles are risk factors for developing hepatotoxicity, and PLWHA with genotypes NAT2*13A/NAT2*13A and NAT2*13A/NAT2*6B should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis.

Objective To estimate the incidence of epilepsy in children with Zika‐related microcephaly in the first 24 months of life; to characterize the associated clinical and electrographic findings; and to summarize the treatment responses. Methods We followed a cohort of children, born during the 2015‐2016 Zika virus (ZIKV) epidemic in Brazil, with congenital microcephaly and evidence of congenital ZIKV infection on neuroimaging and/or laboratory testing. Neurological assessments were performed at ≤3, 6, 12, 15, 18, 21, and 24 months of life. Serial electroencephalograms were performed over the first 24 months. Results We evaluated 91 children, of whom 48 were female. In this study sample, the cumulative incidence of epilepsy was 71.4% in the first 24 months, and the main type of seizure was infantile spasms (83.1%). The highest incidence of seizures occurred between 3 and 9 months of age, and the risk remained high until 15 months of age. The incidence of infantile spasms peaked between 4 and 7 months and was followed by an increased incidence of focal epilepsy cases after 12 months of age. Neuroimaging results were available for all children, and 100% were abnormal. Cortical abnormalities were identified in 78.4% of the 74 children evaluated by computed tomography and 100% of the 53 children evaluated by magnetic resonance imaging. Overall, only 46.1% of the 65 children with epilepsy responded to treatment. The most commonly used medication was sodium valproate with or without benzodiazepines, levetiracetam, phenobarbital, and vigabatrin. Significance Zika‐related microcephaly was associated with high risk of early epilepsy. Seizures typically began after the third month of life, usually as infantile spasms, with atypical electroencephalographic abnormalities. The seizure control rate was low. The onset of seizures in the second year was less frequent and, when it occurred, presented as focal epilepsy.

Aims: Describing the urodynamic parameters of children aged 3 to 5 years with microcephaly related to congenital Zika syndrome and verifying the association with clinical, imaging and neurological characteristics. Methods: From October 2018 to March 2020, children with Zika-related microcephaly underwent urological, ultrasonographic and urodynamic evaluation. In selected cases, complementary exams such as urethrocystography and scintigraphy were performed. The children also underwent a complete neurological evaluation. To compare frequency between groups, we used Pearson’s chi-squared test or Fisher’s exact test. Results: This study evaluated 40 children, of whom 85% were 4 years old, and all had abnormalities on the urodynamic study, with low bladder capacity (92.5%) and detrusor overactivity (77.5%) as the most frequent findings. Only three children had ultrasound abnormalities, but no child had cystographic or scintigraphic abnormalities, and the postvoid residual volume was normal in 80% of cases. In spite of a frequency of 67.5% of intestinal constipation, there was no record of febrile urinary tract infection after the first year of life. All children presented severe microcephaly and at least one neurological abnormality in addition to microcephaly. The homogeneity of the children in relation to microcephaly severity and neurological abnormalities limited the study of the association with the urodynamic parameters. Conclusions: Urodynamic abnormalities in children aged 3 to 5 years with Zika-related microcephaly do not seem to characterize a neurogenic bladder with immediate risks for the upper urinary tract. The satisfactory bladder emptying suggests that the voiding pattern is reflex.

Global health research partnerships with institutions from high-income countries and low- and middle-income countries are one of the European Commission's flagship programmes. Here, we report on the ZikaPLAN research consortium funded by the European Commission with the primary goal of addressing the urgent knowledge gaps related to the Zika epidemic and the secondary goal of building up research capacity and establishing a Latin American-European research network for emerging vector-borne diseases. Five years of collaborative research effort have led to a better understanding of the full clinical spectrum of congenital Zika syndrome in children and the neurological complications of Zika virus infections in adults and helped explore the origins and trajectory of Zika virus transmission. Individual-level data from ZikaPLAN`s cohort studies were shared for joint analyses as part of the Zika Brazilian Cohorts Consortium, the European Commission-funded Zika Cohorts Vertical Transmission Study Group, and the World Health Organization-led Zika Virus Individual Participant Data Consortium. Furthermore, the legacy of ZikaPLAN includes new tools for birth defect surveillance and a Latin American birth defect surveillance network, an enhanced Guillain-Barre Syndrome research collaboration, a de-centralized evaluation platform for diagnostic assays, a global vector control hub, and the REDe network with freely available training resources to enhance global research capacity in vector-borne diseases. ispartof: GLOBAL HEALTH ACTION vol:14 issue:sup1 ispartof: location:United States status: published

Zika virus (ZIKV) infections during pregnancy can lead to adverse neurodevelopmental and clinical outcomes in congenitally infected offspring. As the city of Recife in Pernambuco State, Brazil—the epicentre of the Brazilian microcephaly epidemic—has considerable disparities in living conditions, this study used an ecological approach to investigate the association between income at the neighbourhood level and the risk of ZIKV infections in pregnant individuals between December 2015 and April 2017. The spatial distribution of pregnant individuals with ZIKV infection was plotted on a map of Recife stratified into four categories based on mean monthly income of household heads. Additionally, a Poisson regression model with robust variance was fitted to compare proportions of ZIKV infections among pregnant individuals in relation to the mean monthly income of household heads, based on the 2010 census data, across 94 neighbourhoods in Recife. The results provide evidence that the risk of ZIKV infection to pregnant individuals was higher among those residing in lower-income neighbourhoods: relative to neighbourhoods that had a mean monthly income of ≥5 times minimum wage, neighbourhoods with

This study aimed to compare the anthropometric measurements and body proportionalities of neonates born before the Zika virus epidemic with those born during this period. We compared 958 neonates born during the pre-Zika epidemic with 264 neonates born during the epidemic period. The newborns had their head circumference, weight, and length classified according to the Fenton & Kim growth chart. We considered disproportionate those individuals that presented microcephaly and adequate weight or length for sex and gestational age, and those whose head circumferences were lower than the ratio ((length / 2) + 9.5) - 2.5cm. We estimated the frequencies of Zika positivity and brain imaging findings among neonates with microcephaly born during the epidemic period, concerning the anthropometric and body proportionality parameters. Low weight and proportionate microcephaly were similar among newborns from both periods. However, the frequencies of newborns with microcephaly with a very low length and disproportionate microcephaly were higher among the neonates of the epidemic period with brain abnormalities and positive for Zika virus. We conclude that, at birth, the disproportion between head circumference and length can be an indicator of the severity of microcephaly caused by congenital Zika. Resumo: O estudo buscou comparar as medidas antropométricas e proporções corporais de recém-nascidos do período pré-Zika com os nascidos durante a epidemia de microcefalia congênita pelo vírus Zika. Comparamos 958 recém-nascidos do período pré-Zika com 264 nascidos durante o período epidêmico. Foram classificados o perímetro cefálico, peso e comprimento dos neonatos de acordo com a escala de crescimento de Fenton & Kim. Consideramos desproporcionais aqueles neonatos que apresentaram microcefalia e peso ou comprimento adequado para sexo e idade gestacional, além daqueles cujo perímetros cefálicos eram menores que a razão ((comprimento / 2) + 9,5) -2,5cm. Estimamos as frequências de positividade para Zika e resultados de imagens de cerebrais entre bebês com microcefalia nascidos no período epidêmico, em relação aos parâmetros antropométricos e de proporcionalidade corporal. Baixo peso e microcefalia proporcional foram semelhantes entre recém-nascidos de ambos os períodos. Entretanto, as frequências de neonatos com microcefalia e com comprimento muito curto e microcefalia desproporcional foram muito maiores entre os nascidos no período epidêmico com anomalias cerebrais e positivos para Zika. Concluímos que a desproporção entre perímetro cefálico e comprimento ao nascer pode ser um indicador da gravidade da microcefalia causada pela síndrome congênita do Zika vírus. Resumen: El objetivo del estudio fue comparar las medidas antropométricas y de proporcionalidad corporal en neonatos nacidos durante un período pre-Zika, con quienes nacieron durante la epidemia de microcefalia por el síndrome congénito Zika. Comparamos a 958 neonatos nacidos durante la epidemia pre-Zika, con 264 neonatos nacidos durante el período epidémico. A los recién nacidos se les clasificó su circunferencia de la cabeza, peso y longitud según la tabla de crecimiento Fenton & Kim. Consideramos desproporcionados a quienes presentaron microcefalia y peso o longitud adecuada para sexo y edad gestacional, y quienes tenían unas circunferencias de cabeza cuyo ratio era menor que ((longitud / 2) + 9.5) - 2.5cm. Estimamos las frecuencias de positividad para Zika, así como los resultados de imágenes cerebrales entre neonatos nacidos con microcefalia durante el período epidémico, en relación con parámetros antropométricos y de proporcionalidad corporal. Bajo peso y microcefalia proporcional fueron similares entre los recién nacidos de ambos períodos. No obstante, las frecuencias de recién nacidos con microcefalia con una longitud muy baja y microcefalia desproporcionada fueron mayores entre los neonatos del período epidémico, con anormalidades cerebrales y positivos para Zika. Concluimos que la desproporción entre la circunferencia de cabeza y longitud al nacer puede ser un indicador de la gravedad de la microcefalia, causada por el Zika congénito.

OBJECTIVE To analyze the epidemic of COVID-19 in northeastern Brazil, one of the regions most affected by the virus. METHODS The official data for COVID-19, from March 2020 to March 2021 in the states of the Northeast Region (NE), were used. The analysis of capital cities and states for accumulated weekly cases and confirmed deaths was made using the JoinPoint Trend Analysis application. RESULTS In one year, the Northeast region reported 22.9% of the cases and 21.5% of the deaths in the country due to COVID-19. At the beginning of the pandemic, all states showed a growing number of cases, first in the capitals and then in the interior. Following this wave, decreases are observed in all states and their capitals, but with many still reporting a large number of cases. In the middle of the 2nd semester of 2020 the number of cases begins to increase again simultaneously in states and their capitals—some at explosive speed—especially in late 2020 and early 2021. A similar pattern is observed in deaths, which exceed or approach the peak seen in the first wave. In the first wave, all capitals and northeastern states adopted intense isolation measures. Fortaleza, Recife and Teresina reached the highest isolation index of all capitals, close to 0.60. This index decreases, with a slight growth trend until the end of December. With the exception of Fortaleza and Salvador, the other capitals fell to less than 0.40. CONCLUSION The Brazilian NE and the country are in increasingly complicated health, social and economic situations. It is necessary to speed up vaccinations and maintain non-pharmacological measures: face masks, social distancing measures and hygiene care, in addition to policies to protect workers who have lost their incomes and to subsidize small business owners.

Resumo Mesmo no período em que a pandemia de Covid-19 encontrava-se em crescimento no Nordeste do Brasil, iniciou-se a adoção de medidas de flexibilização do distanciamento social. O objetivo do estudo é o de avaliar a pertinência das propostas de flexibilização, tomando-se em conta a situação da pandemia em cada local e o momento em que foram adotadas. Tendo como referência as diretrizes da OMS, foram construídos e analisados indicadores operacionais para cada diretriz, no contexto da região Nordeste. Para análise do comportamento da epidemia, conforme indicadores selecionados, foram usadas técnicas de Joinpoint Trend Analysis, mapas de calor, razão de taxas e comparação da tendência temporal entre capitais e interior dos estados. O pico do crescimento semanal ocorreu em maio-julho/2020 (semanas epidemiológicas 19 a 31). Na maioria das capitais não se observou tendência decrescente simultânea do número de casos e óbitos nos 14 dias prévios à flexibilização. Em todos os estados o quantitativo de testes realizados foi insuficiente. Na semana epidemiológica 24 os percentuais estaduais de ocupação de leitos de UTI/Covid-19 foram próximos ou superiores 70%. A situação epidemiológica das nove capitais dos estados do Nordeste, no momento em que a decisão de flexibilização foi tomada, mostra que nenhuma delas atendia aos critérios e parâmetros recomendados pela OMS. Abstract Even in the period when the Covid-19 pandemic was on the rise in the Northeast of Brazil, the relaxation of social distancing measures was introduced. The scope of the study is to assess, in the light of the epidemiological-sanitary situation in the region, the suitability of relaxation of social distancing measures. Based on the WHO guidelines for relaxation of social distancing, operational indicators were created and analyzed for each guideline in the context of the Northeast. To analyze the behavior of the epidemic, according to selected indicators, Joinpoint trend analysis techniques, heat maps, rate ratios and time trends between capitals and the state interior were compared. The weekly growth peak of the epidemic occurred in May-July 2020 (epidemiological weeks 19 to 31). In most capitals, there was no simultaneous downward trend in the number of cases and deaths in the 14 days prior to flexibilization. In all states the number of tests performed was insufficient. In epidemiological week 24, the state percentages of ICU/Covid-19 bed occupancy were close to or above 70%. The epidemiological situation of the nine Northeastern state capitals analyzed here did not meet criteria and parameters recommended by the World Health Organization for the relaxation of social distancing measures.

This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG–PC). The profile details the context and aims of the study, study population, methodology including assessments, and key results and publications to date. The children that make up MERG–PC were born in Recife or within 120 km of the city, in Pernambuco/Brazil, the epicentre of the microcephaly epidemic. MERG–PC includes children from four groups recruited at different stages of the ZIKV microcephaly epidemic in Pernambuco, i.e., the Outpatient Group (OG/n = 195), the Microcephaly Case–Control Study (MCCS/n = 80), the MERG Pregnant Women Cohort (MERG-PWC/n = 336), and the Control Group (CG/n = 100). We developed a comprehensive array of clinical, laboratory, and imaging assessments that were undertaken by a ‘task force’ of clinical specialists in a single day at 3, 6, 12, 18 months of age, and annually from 24 months. Children from MCCS and CG had their baseline assessment at birth and children from the other groups, at the first evaluation by the task force. The baseline cohort includes 711 children born between February 2015 and February 2019. Children’s characteristics at baseline, excluding CG, were as follows: 32.6% (184/565) had microcephaly, 47% (263/559) had at least one physical abnormality, 29.5% (160/543) had at least one neurological abnormality, and 46.2% (257/556) had at least one ophthalmological abnormality. This ongoing cohort has contributed to the understanding of the congenital Zika syndrome (CZS) spectrum. The cohort has provided descriptions of paediatric neurodevelopment and early epilepsy, including EEG patterns and treatment response, and information on the frequency and characteristics of oropharyngeal dysphagia, cryptorchidism and its surgical findings, endocrine dysfunction, and adenoid hypertrophy in children with Zika-related microcephaly. The study protocols and questionnaires were shared across Brazilian states to enable harmonization across the different studies investigating microcephaly and CZS, providing the opportunity for the Zika Brazilian Cohorts Consortium to be formed, uniting all the ZIKV clinical cohorts in Brazil.

In HIV-infected patients, antiretroviral therapy (ART) is associated to adipose tissue redistribution known as lipodystrophy (LD). This study aimed at verifying the association between the polymorphism of the

ObjectivesWe assessed the prevalence of SARS-CoV-2 infection, personal protective equipment (PPE) shortages and occurrence of biological accidents among front-line healthcare workers (HCW).Design, setting and participantsUsing respondent-driven sampling, the study recruited distinct categories of HCW attending suspected or confirmed patients with COVID-19 from May 2020 to February 2021, in the Recife metropolitan area, Northeast Brazil.Outcome measuresThe criterion to assess SARS-CoV-2 infection among HCW was a positive self-reported PCR test.ResultsWe analysed 1525 HCW: 527 physicians, 471 registered nurses, 263 nursing assistants and 264 physical therapists. Women predominated in all categories (81.1%; 95% CI: 77.8% to 84.1%). Nurses were older with more comorbidities (hypertension and overweight/obesity) than the other staff. The overall prevalence of SARS-CoV-2 infection was 61.8% (95% CI: 55.7% to 67.5%) after adjustment for the cluster random effect, weighted by network, and the reference population size. Risk factors for a positive RT-PCR test were being a nursing assistant (OR adjusted: 2.56; 95% CI: 1.42 to 4.61), not always using all recommended PPE while assisting patients with COVID-19 (OR adj: 2.15; 95% CI: 1.02 to 4.53) and reporting a splash of biological fluid/respiratory secretion in the eyes (OR adj: 3.37; 95% CI: 1.10 to 10.34).ConclusionsThis study shows the high frequency of SARS-CoV2 infection among HCW presumably due to workplace exposures. In our setting, nursing assistant comprised the most vulnerable category. Our findings highlight the need for improving healthcare facility environments, specific training and supervision to cope with public health emergencies.

Upper respiratory obstruction is a common sequela in children with Zika-related microcephaly (ZRM). As a cross-sectional analysis nested in a cohort study, this study aims to investigate the prevalence of adenoid hypertrophy (AH) in children with ZRM and symptoms of respiratory obstruction. The data were collected in the first three years of life from children with ZRM who were followed in two reference centers for otorhinolaryngological care of patients with congenital Zika syndrome. Out of 92 children with confirmed ZRM, 57 were evaluated by nasopharyngoscopy after presenting with upper respiratory obstruction symptoms. In this study, 31 of the 57 (54%) children with ZRM who were evaluated had obstructive AH. Thirteen children with obstructive AH were submitted to surgery, which resulted in the complete resolution of symptoms for 11, partial resolution in 1, and no improvement in 1. No evidence of direct involvement by Zika virus (ZIKV) infection in the adenoid tissues was demonstrated by histology or immunohistochemistry. Our results suggest that there is a high prevalence and early presentation of AH in children with ZRM, with consequent upper airway obstruction causing upper airway obstructive disorder, secretory otitis media, and dysphagia.

IntroductionZika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean.Methods and analysisWe will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach.Ethics and disseminationEthical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities.

Background Complications in the urinary tract related to congenital Zika syndrome have recently been reported. One complication, cryptorchidism, has been reported by the Microcephaly Epidemic Research Group/MERG, in Pernambuco/Brazil. The present article describes for the first time the surgical findings in a case series of boys with Zika-related microcephaly and cryptorchidism, who underwent surgical testicular exploration as a contribution to better understand the possible mechanisms involved in gonads formation and descent. Methods A total of 7 children (11 testicular units), aged 3 to 4 years, were submitted to inguinal or scrotal orchidopexy for the treatment of palpable cryptorchidism between August 2019 and January 2020. Characteristics of the gonads and its annexes related to appendixes, testis-epididymis dissociation, gubernacular insertion, and associated hydroceles and/or hernias were described. Measures in centimetres were taken for volume calculate. Results We found a low prevalence of testicular and epididymal appendix (66.7%), a high prevalence of testis-epididymis dissociation (55.6%), low mean testicular volume for their ages (lower for older boys) and ectopic gubernacular insertion in all cases. There was no evidence of associated hydroceles and/or hernias in any case. No surgical complication was registered or reported, and all explored gonads were properly placed in the scrotal sac. Conclusions We herein describe the surgical findings of these children's orchidopexies and discuss the possible mechanisms of viral action in embryogenesis and postnatal growth and development of the testes and annexes. These children need to be followed over time due to the higher risk of testicular atrophy and malignancy. Surgical timing seems to be relevant to avoid loss of testicular volume.

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

Resumo No Brasil, a pandemia da COVID-19 tem sido severa nos estados das regiões mais pobres, como o Nordeste. A falta de políticas nacionais para controle da pandemia levou as autoridades estaduais e municipais a implementarem medidas de saúde pública. O objetivo deste estudo é mostrar o efeito dessas medidas na epidemia. A maior incidência da COVID-19 entre os nove estados do Nordeste foi registrada em Sergipe, Paraíba e Ceará. O Piauí, a Paraíba e Ceará foram os que mais testaram. Muitos estados apresentavam alta proporção de pessoas em trabalho informal. Estados com aeroportos internacionais tiveram importante papel na entrada e disseminação inicial do vírus, em especial o Ceará. Todos os estados aplicaram medidas de distanciamento social, proibição de eventos públicos e fechamento de unidades de ensino. As respostas foram o aumento significativo de distanciamento social, em especial Ceará e Pernambuco, a queda do número de reprodução (Rt) e a separação da curva dos casos observados da curva dos casos esperados sem as intervenções não medicamentosas em todos os estados. A pobreza, a desigualdade e as altas taxas de trabalho informal fornecem pistas do porquê da intensidade da COVID-19 na região. Por outro lado, as medidas de mitigação tomadas precocemente pelos governantes amenizaram os efeitos da pandemia. Abstract The COVID-19 pandemic has been most severe in the poorest regions of Brazil, such as the states of the Northeast Region. The lack of national policies for pandemic control forced state and municipal authorities to implement public health measures. The aim of this study is to show the effect of these measures on the epidemic. The highest incidence of COVID-19 among the nine states in the Northeast was recorded in Sergipe, Paraíba and Ceará. Piauí, Paraíba and Ceará were the states that most tested. Factors associated with transmission included the high proportion of people in informal work. States with international airports played an important role in the entry of the virus and the initial spread, especially Ceará. All states applied social distancing measures, banned public events and closed schools. The response was a significant increase in social distancing, especially in Ceará and Pernambuco, a decline in the reproduction rate (Rt), and a separation of the curve of observed cases versus expected cases if the non-pharmacological interventions had not been implemented in all states. Poverty, inequality, and the high rates of informal work provide clues to the intensity of COVID-19 in the region. On the other hand, the measures taken early by the governments mitigated the effects of the pandemic.

Severe brain damage associated with Zika-related microcephaly (ZRM) have been reported to result in oropharyngeal dysphagia (OPD); however, it is unknown if OPD presents in children with prenatal Zika virus (ZIKV) exposure but only mild or undetectable abnormalities. The aims of this study were: to compare the frequency and characteristics of OPD in children with ZRM and in children without microcephaly born to mothers who tested polymerase chain reaction positive (PCR+) for ZIKV during pregnancy; and to investigate the concordance of caregiver reports of OPD with the diagnosis from the clinical swallowing assessment (CSA). Between Mar/2017 and May/2018, we evaluated 116 children (n = 58 with microcephaly, n = 58 children without microcephaly born to ZIKV PCR + mothers) participating in the Microcephaly Epidemic Research Group (MERG) cohort of children born during the 2015–2016 ZIKV epidemic in Pernambuco, Brazil. To assess OPD we used: a CSA; a clinical assessment of the stomatognathic system; and a questionnaire administered to caregivers. The frequency of OPD was markedly higher in children with ZRM (79.3%) than in the exposed but normocephalic group (8.6%). The children with microcephaly also presented more frequently with anatomic and functional abnormalities in the stomatognathic system. There was a high degree of agreement between the caregiver reports of OPD and the CSA (κ = 0.92). In conclusion, our findings confirm that OPD is a feature of Congenital Zika Syndrome that primarily occurs in children with microcephaly and provide support for policies in which children are referred for rehabilitation with an OPD diagnosis based on caregiver report.

BackgroundThere is limited knowledge on the influence of concurrent coinfections on the clinical presentation of Zika virus (ZIKV) disease.MethodsTo better understand the types, frequencies and clinical manifestations of ZIKV coinfections, we did a systematic review of four databases (PubMed, Embase, Web of Science, LILACS) without restrictions for studies on ZIKV coinfections confirmed by nucleic acid (quantitative real-time-PCR) testing of ZIKV and coinfecting pathogens. The review aimed to identify cohort, cross-sectional, case series and case report studies that described frequencies and/or clinical signs and symptoms of ZIKV coinfections. Conference abstracts, reviews, commentaries and studies with imprecise pathogen diagnoses and/or no clinical evaluations were excluded.ResultsThe search identified 34 articles from 10 countries, comprising 2 cohort, 10 cross-sectional, 8 case series and 14 case report studies. Coinfections were most frequently reported to have occurred with other arthropod-borne viruses (arboviruses); out of the 213 coinfections described, ZIKV infections co-occurred with chikungunya in 115 cases, with dengue in 68 cases and with both viruses in 19 cases. Other coinfecting agents included human immunodeficiency, Epstein-Barr, human herpes and Mayaro viruses, Leptospira spp, Toxoplasma gondii and Schistosoma mansoni. ZIKV-coinfected cases primarily presented with mild clinical features, typical of ZIKV monoinfection; however, 9% of cases in cohort and cross-sectional studies were reported to experience complications.ConclusionBased on the evidence collated in this review, coinfections do not appear to strongly influence the clinical manifestations of uncomplicated ZIKV infections. Further research is needed to confirm whether risk of severe complications is altered when ZIKV infection co-occurs with other infections.PROSPERO registration numberCRD42018111023.

The genitourinary tract was recently identified as a potential site of complications related to the congenital Zika syndrome (CZS). We provide the first report of a series of cryptorchidism cases in 3-year-old children with Zika-related microcephaly who underwent consultations between October 2018 and April 2019 as part of the follow-up of the children cohort of the Microcephaly Epidemic Research Group, Pernambuco, Brazil. Of the 22 males examined, eight (36.4%) presented with cryptorchidism. Among 14 undescended testis cases, 11 (78.6%) could be palpated in the inguinal region. Seven of the eight children had severe microcephaly. Conventional risk factors for cryptorchidism were relatively infrequent in these children. We hypothesize that cryptorchidism is an additional manifestation of CZS present in children with severe microcephaly. As in our cases, for most of the children, the testes were located in the inguinal region, and the possible mechanisms for cryptorchidism were gubernaculum disturbance or cremasteric abnormality.

Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.

The aim of the study was to evaluate the temporal patterns of dengue incidence from 2001 to 2014 and forecast for 2015 in two Brazilian cities. We analysed dengue surveillance data (SINAN) from Recife, 1.6 million population, and Goiania, 1.4 million population. We used Auto-Regressive Integrated Moving Average (ARIMA) modelling of monthly notified dengue incidence (2001-2014). Forecasting models (95% prediction interval) were developed to predict numbers of dengue cases for 2015. During the study period, 73,479 dengue cases were reported in Recife varying from 11 cases/100,000 inhab (2004) to 2418 cases/100,000 inhab (2002). In Goiania, 253,008 dengue cases were reported and the yearly incidence varied from 293 cases/100,000 inhab (2004) to 3927 cases/100,000 inhab (2013). Trend was the most important component for Recife, while seasonality was the most important one in Goiania. For Recife, the best fitted model was ARIMA (1,1,3)12 and for Goiania Seasonal ARIMA (1,0,2) (1,1,2)12. The model predicted 4254 dengue cases for Recife in 2015; SINAN registered 35,724 cases. For Goiania the model predicted 33,757 cases for 2015; the reported number of cases by SINAN was 74,095, within the 95% prediction interval. The difference between notified and forecasted dengue cases in Recife can be explained by the co-circulation of dengue and Zika virus in 2015. In this year, all cases with rash were notified as "dengue-like" illness. The ARIMA models may be considered a baseline for the time series analysis of dengue incidence before the Zika epidemic.

Background Measures of health-related quality of life (HRQoL) have been used to express the impact of neglected diseases and to generate indicators for health economic assessments. Schistosomiasis mansoni is a neglected disease with various clinical manifestations, including severe repercussions, caused by parasitic worms. Here we describe the quality of life of chronic schistosomiasis mansoni patients and estimate the quality-adjusted life years (QALYs) associated with chronic schistosomiasis mansoni in Brazil in 2015. Methods A HRQoL study was carried out using the three-level European Quality of Life 5-Dimensions (EQ-5D-3L) questionnaire in 147 chronic schistosomiasis mansoni patients at an outpatient monitoring facility of an endemic state for schistosomiasis. Results Losses in HRQoL were observed in all five dimensions of the EQ-5D-3L. Patients >60 y and 40-49 y of age reported the highest frequencies of problems. The average utility index was 0.71, and the median index was significantly lower among female patients and patients with comorbidities (0.68; p

This study aimed to describe the prenatal and postnatal neuroimaging and clinical findings in a clinical series following congenital Zika virus syndrome during the first epidemic Zika virus (ZIKV) outbreak in the State of Pernambuco, Brazil. We (the authors) conducted a retrospective study of a prospectively collected case series of fetuses and neonates with microcephaly born to mothers with presumed/confirmed congenital ZIKV syndrome. Prenatal ultrasound findings were reviewed to identify potential central nervous system (CNS) abnormalities. Neonates underwent postnatal neuroimaging follow up by computed tomography (CT)-scan or magnetic resonance (MR) imaging. The prenatal and postnatal outcomes of eight fetuses/neonates born to mothers with presumed/confirmed congenital ZIKV syndrome were examined. The mean gestational age at ultrasound was 31.3 weeks. Severe microcephaly was identified in seven fetuses (87.5%), while ventriculomegaly and brain calcifications were detected in all fetuses. The mean gestational age at delivery and head circumference were 38 weeks and 30.2 cm, respectively. All cases of microcephaly but one was confirmed postnatally. Brain CT scans or MRIs were performed in seven newborns, and all had periventricular and/or parenchymal calcifications, symmetrical or asymmetrical ventriculomegaly, pachygyria, and reduced sulcation and gyration. MR imaging aided the detection of one undetected case of corpus callosum dysgenesis and was essential in documenting reduced mantel of the cerebral cortex and reduced gyration and sulcation, especially involving the parietal lobe. In addition, MR imaging was also able to display irregular interfaces with the subcortical white matter, a finding consistent with polymicrogyria, more frequently seen at the level of the frontal lobe and atrophic and thinned pons. Severe microcephaly and CNS abnormalities may be associated with congenital ZIKV syndrome.

The implementation of rapid HIV testing in Brazil began in 2006 for specific groups, and from 2009 was extended to the Counseling and Testing Centers (CTC) in certain Brazilian capitals. The aim of this study was to compare two groups of individuals: those diagnosed with HIV infection by conventional testing and those diagnosed with rapid testing, with respect to: the waiting time before receiving medical care, the time of the first laboratory tests and the virological, immune and clinical status. This is a cross-sectional study to compare a group with individuals diagnosed by conventional testing (2006-2008) and another with those diagnosed by rapid testing (2010-2011).The median time between blood collection and diagnosis of HIV in the conventional test group was 76 days, while in the rapid test group 94.2% of the subjects received their results on the same day of blood collection (p 0.001). In the conventional test group, the median period of time before the first consultation with an infectious disease specialist was 99 days, and for the rapid test group the time was 14 days (p 0.001). The median time between the first blood sample and the first results of the CD4 count and viral load was approximately 2.5 times lower in the rapid test group (p 0.001 for both). The median CD4 count in the rapid test group (472) was higher than in the conventional test group (397) (p = 0.01). The introduction of rapid HIV testing as a diagnostic strategy has reduced the waiting times for medical care and laboratory tests and also allowed earlier diagnosis of HIV infection than with the conventional test.

Summary Background Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity. Methods We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauracao, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. We grouped patients according to their arbovirus laboratory diagnosis and then compared demographic and clinical characteristics. Findings Between Dec 4, 2014, and Dec 4, 2016, 1410 patients were admitted to the hospital neurology service; 201 (14%) had symptoms consistent with arbovirus infection and sufficient samples for diagnostic testing and were included in the study. The median age was 48 years (IQR 34–60), and 106 (53%) were women. 148 (74%) of 201 patients had laboratory evidence of arboviral infection. 98 (49%) of them had a single viral infection (41 [20%] had Zika, 55 [27%] had chikungunya, and two [1%] had dengue infection), whereas 50 (25%) had evidence of dual infection, mostly with Zika and chikungunya viruses (46 [23%] patients). Patients positive for arbovirus infection presented with a broad range of CNS and peripheral nervous system (PNS) disease. Chikungunya infection was more often associated with CNS disease (26 [47%] of 55 patients with chikungunya infection vs six [15%] of 41 with Zika infection; p=0·0008), especially myelitis (12 [22%] patients). Zika infection was more often associated with PNS disease (26 [63%] of 41 patients with Zika infection vs nine [16%] of 55 with chikungunya infection; p≤0·0001), particularly Guillain-Barre syndrome (25 [61%] patients). Patients with Guillain-Barre syndrome who had Zika and chikungunya dual infection had more aggressive disease, requiring intensive care support and longer hospital stays, than those with mono-infection (median 24 days [IQR 20–30] vs 17 days [10–20]; p=0·0028). Eight (17%) of 46 patients with Zika and chikungunya dual infection had a stroke or transient ischaemic attack, compared with five (6%) of 96 patients with Zika or chikungunya mono-infection (p=0·047). Interpretation There is a wide and overlapping spectrum of neurological manifestations caused by Zika or chikungunya mono-infection and by dual infections. The possible increased risk of acute cerebrovascular disease in patients with dual infection merits further investigation. Funding Fundacao do Amparo a Ciencia e Tecnologia de Pernambuco (FACEPE), EU's Horizon 2020 research and innovation programme, National Institute for Health Research. Translations For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

The integrase inhibitor dolutegravir was included in initial antiretroviral therapy in Brazil in January 2017. Studies have demonstrated that the efficacy and safety of antiretrovirals have improved with the introduction of new classes of antiretrovirals, such as integrase inhibitors. This study aimed to estimate the frequency of individuals with a virologic response by week 24 of antiretroviral treatment and to describe the adverse events of the regimen containing dolutegravir. This was a cohort of people living with HIV followed up at a referral hospital. Patients were included who had initiated their first treatment between January and August 2017. Data were obtained from medical records, the Drug Logistics Management System and from the Laboratory Tests Control System. Two hundred and twenty-two patients were included for the tolerability analysis and one hundred and thirty-seven for the virologic response analysis. The mean age was 34 years, the median time between diagnosis and initiating treatment was 1.9 months and the median time on antiretroviral therapy was 13.2 months. The frequency of adverse events was 10% (95% CI: 7% to 15.2%), of these, amongst the most frequent events, 91% presented gastrointestinal effects, and 47.8% neuropsychiatric. By week 24 the estimated incidence of virologic response was 89.1% (95% CI: 83% to 93.5%), with an increase during the first 6 months in the number of T-CD4 lymphocytes of 50.7 cells/mm 3 (95% CI: 42 to 59.3). Initial antiretroviral regimens containing dolutegravir were well tolerated and effective in viral suppression during the first 24 weeks after initiating treatment. The occurrence of adverse events was low, either mild or moderate.

Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal transfer of antibodies among mothers and neonates after the ZIKV microcephaly outbreak in Northeast Brazil (2016). We included 89 microcephaly cases and 173 neonate controls at time of birth and their mothers. Microcephaly cases were defined as newborns with a particular head circumference (2 SD below the mean). Two controls without microcephaly were matched by the expected date of delivery and area of residence. We tested maternal serum for recent (ZIKV genome, IgM and IgG3 anti-NS1) and previous (ZIKV and DENV neutralizing antibodies [NAbs]) markers of infection. Multiple markers of recent or previous ZIKV and DENV infection in mothers were analyzed using principal component analysis (PCA). At delivery, 5.6% of microcephaly case mothers and 1.7% of control mothers were positive for ZIKV IgM. Positivity for ZIKV IgG3 anti-NS1 was 8.0% for case mothers and 3.5% for control mothers. ZIKV NAbs was slightly higher among mothers of cases (69.6%) than that of mothers of controls (57.2%; p = 0.054). DENV exposure was detected in 85.8% of all mothers. PCA discriminated two distinct components related to recent or previous ZIKV infection and DENV exposure. ZIKV NAbs were higher in newborns than in their corresponding mothers (p, Author summary The epicenter of the ZIKV epidemic was located in Northeast Brazil (2015/16) and was followed by a space and time cluster of congenital microcephaly cases. This region is also a dengue hyperendemic setting. Laboratory confirmation of ZIKV infection during pregnancy is challenging due to cross-reactivity with other flaviviruses, especially dengue. The neutralization test, which is the gold standard to discriminate between these viruses, is time-consuming, performed in few laboratories and does not define the time when the infection occurred. This study described the serological markers of ZIKV and DENV among participants (mothers and neonates) of a microcephaly case-control study conducted in Northeast Brazil (2016). Our results showed a strikingly high frequency of ZIKV exposure among mothers after the first wave of the ZIKV outbreak in this setting. Additionally, ZIKV and DENV immune status, as detected by the neutralization test, showed distinct patterns among pregnant women in this endemic area. We detected a low frequency of serological markers of recent ZIKV infection in samples collected just after delivery, highlighting the need for screening for ZIKV immune status in the early stage and throughout pregnancy to monitor congenital ZIKV syndrome.

Zika virus (ZIKV) is a vectorborne infectious agent of global public health significance due to its potential to cause severe teratogenic outcomes. The question of whether health systems should consider adopting screening programmes for ZIKV infections during pregnancy warrants consideration. In this analysis, we apply the Wilson-Jungner framework to appraise the potential utility of a prenatal ZIKV screening programme, outline potential screening strategies within the case-finding pathway, and consider other epidemiological factors that may influence the planning of such a screening programme. Our evaluation of a potential prenatal ZIKV screening programme highlights factors affirming its usefulness, including the importance of Congenital Zika Syndrome as a public health problem and the existence of analogous congenital prenatal screening programmes for STORCH agents (syphilis, toxoplasmosis, others (eg, human immunodeficiency virus, varicella-zoster virus, parvovirus B19), rubella, cytomegalovirus, and herpes simplex virus). However, our assessment also reveals key barriers to implementation, such as the need for more accurate diagnostic tests, effective antiviral treatments, increased social service capacity, and surveillance. Given that the reemergence of ZIKV is likely, we provide a guiding framework for policymakers and public health leaders that can be further elaborated and adapted to different contexts in order to reduce the burden of adverse ZIKV-related birth outcomes during future outbreaks.

National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico? CNPq) (grant number 404861/2018-0); Wellcome Trust and the United Kingdom?s Department for International Development (grant numbers: 205377/Z/16/Z; 201870/Z/16/Z). European Union?s Horizon 2020 research and innovation programme under ZikaPLAN (grant number 734584). Wellcome Trust - Research Enrichment in Epidemic Situation (grant number 107779/Z/15/Z; with ER1505 & ER1601). Medical Research Council on behalf of the Newton Fund and Wellcome Trust (grant number MC_PC_15088). National Institutes of Health/National Institute of Allergy and Infectious Diseases (grant number RO1/AI140718). Fondation Christophe et Rodolphe M?rieux. National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico?CNPq) (grant numbers 443875/2018-9; 440573/2016-5; 441098/2016-9; 305090/2016-0; 307282/2017-1; 304476/2018- 8; 465549/2014-4; 440763/2016-9; 309722/2017-9; 306708/2014-0; 440577/2016-0). Coordination for the improvement of Higher Education Personnel (Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior-Capes) (grant numbers 88881.130813/2016-01; 88887.116627/2016-01; 88887.136366/2017-00). Ministry of Health of Brazil-Emergency Response in Public Health-Zika virus and Microcephaly (Minist?rio da Sa?de de Brasil-Resposta ? Emerg?ncia em Sa?de P?blica?Zika v?rus e Microcefalia) (grant number 837058/2016). Department of Science and Technology (Departamento de Ci?ncia e TecnologiaDECIT) (grant numbers 25000.072811/2016-19; 440839/2016-5). Foundation of Research Support of the State of S?o Paulo (Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo?FAPESP) (grant numbers 2016/08578-0; 2017/21688-1; 2013/21719-3; 2016/15021-1; 2015/12295-0; 2016/05115-9). Foundation of Research Support of the State of Rio de Janeiro (Funda??o de Amparo ? Pesquisa do Estado do Rio de Janeiro ?FAPERJ) (grant numbers E-26/201.351/2016; E-18/2015TXB; E-26/202.862/2018; E-26/010.002477/2016). Foundation of Support for Research and Scientific and Technological Development of Maranh?o (Funda??o de Amparo ? Pesquisa e ao Desenvolvimento Cient?fico e Tecnol?gico do Maranh?o?FAPEMA) (grant number 008/2016). Brazilian Ministry of Health (Minist?rio da Sa?de?MS) (grant number 929698560001160-02). Evandro Chagas Institute/Brazilian Ministry of Health (Instituto Evandro Chagas/Minist?rio da Sa?de). Foundation of Research Support of the State of Goi?s (Funda??o de Amparo ? Pesquisa do Estado de Goi?s?FAPEG) (number grant 2017/10267000531). Foundation of Research Support of the State of Rio Grande do Sul (Funda??o de Amparo ? Pesquisa do Estado do Rio Grande do Sul?FAPERGS) (grant number 17/2551-0000521-0). Foundation to Support Teaching, Research and Assistance at Hospital das Cl?nicas, Faculty of Medicine of Ribeir?o Preto (Funda??o de Apoio ao Ensino, Pesquisa e Assist?ncia do Hospital das Cl?nicas da Faculdade de Medicina de Ribeir?o Preto) and S?o Paulo State Department of Health (Secretaria de Sa?de do Estado de S?o Paulo). Support Foundation of Pernambuco Science and Technology (Funda??o de Amparo ? Ci?ncia e Tecnologia de Pernambuco?FACEPE) (grant numbers APQ-0172-4.01/16; APQ-0192-4.01/17; APQ-0793-4.01/17). Funda??o de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil. Universidade Federal de Campina Grande. Campina Grande, PB, Brasil / Instituto de Medicina Integral Professor Fernando Figueira. Recife, PE, Brazil. Universidade Federal de Pernambuco. Departamento de Medicina Social. Recife, PE, Brazil. Funda??o Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brazil. London School of Hygiene & Tropical Medicine. London, UK. Funda??o de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil. Universidade Federal de Pernambuco. Centro de Ci?ncias da Sa?de. Recife, PE, Brazil. Universidade Federal do Rio de Janeiro. Departamento de Pediatria. Rio de Janeiro, RJ, Brazil. Universidade de S?o Paulo, Ribeir?o Preto. Faculdade de Medicina de Ribeir?o Preto. Ribeir?o Preto, SP, Brasil. Universidade Federal de Sergipe. Aracaju, SE, Brazil. Secretaria Municipal de Tangar? da Serra. Tangar? da Serra, MT, Brazil. Universidade Federal do Rio de Janeiro. Departamento de Pediatria. Rio de Janeiro, RJ, Brazil. Universidade Federal de Sergipe. Aracaju, SE, Brazil. Funda??o Oswaldo Cruz. Instituto Aggeu Magalh?es. Recife, PE, Brazil. Universidade Federal de Campina Grande. Campina Grande, PB, Brasil / Instituto Paraibano de Diagn?stico. Campina Grande, PB, Brazil. Universidade de Pernambuco. Faculdade de Ci?ncias M?dicas. Recife, PE, Brazil. Universidade de Pernambuco. Instituto de Ci?ncias Biol?gicas. Recife, PE, Brazil. Funda??o Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil. Universidade de S?o Paulo. Faculdade de Medicina de Ribeir?o Preto. Ribeir?o Preto, SP, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil Faculdade de Medicina de Jundia?. Jundia?, SP, Brasil. Instituto D?Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brazil. Universidade Federal da Bahia. Instituto Sa?de Coletiva. Salvador, BA, Brazil. Universidade Federal do Rio Grande do Sul. Porto Alegre, RS, Brazil. Universidade Federal do Maranh?o. Departamento de Sa?de P?blica. S?o Lu?s, MA, Brazil. Centro de Pesquisas Gon?alo Moniz. Salvador, BA, Brazil. Secretaria de Sa?de do Estado do Maranh?o. Assist?ncia e Reabilita??o de Crian?as. Centro de Refer?ncia em Neurodesenvolvimento. S?o Lu?s, MA, Brazil. Universidade Federal de Goi?s. Departamento de Saude Coletiva. Goi?nia, GO, Brazil. Faculdade de Medicina de S?o Jos? do Rio Preto. S?o Jos? do Rio Preto, SP, Brasil. 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.

Background While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood. Methods Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy. Findings 376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages., Author summary The ability to meaningfully quantify the absolute and relative risks of Congenital Zika Syndrome is contingent on the accurate identification of ZIKV infections in pregnant women and the long-term follow-up of children at risk. This study builds on the evidence base on ZIKV in pregnancy by not only examining pregnancy and birth outcomes, but also considering later onset manifestations of Congenital Zika Syndrome, conducting a deep and standardized investigation of infant outcomes. In addition, it used unprecedented repeated testing and the use of multiple diagnostic platforms, including qRT-PCR, IgM and IgG3 ELISAs, and PRNTs to identify ZIKV cases. The absolute risk of microcephaly was 2.9%, of calcifications and/or ventriculomegaly was 7.2%, of additional neurologic alterations was 5.3%, of ophthalmologic abnormalities was 7% and of dysphagia was 1.8%. The manifestations presented more frequently in isolation than in combination (i.e., less than 1% of the children experienced abnormalities across all of the domains simultaneously). Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination

Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common&mdash, and clinically important&mdash, endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary.

The aim of this study was to compare 4 different ARV regimens in a clinical cohort in Brazil, with regard to the virologic and immunologic responses, clinical failure and reasons for changing. To compare the virologic response and clinical failure between groups we used the Cox and Kaplan Meier proportional hazard models. To analyze the immunologic outcome, we used multilevel GLLAMM and mixed effect linear regression models. To compare regimen change outcomes we used the Pearson's chi-square test. We included 840 participants distributed across the groups according to the initial ART regimen. The mean follow-up period was 27.8 months. Almost half the sample initiated ART with AIDS-related signs/symptoms. Virologic response was effective in 79.6% of participants within 12 months. The tenofovir/lamivudine/efavirenz group presented a higher proportion of virologic response (VL

BACKGROUND Schistosomiasis mansoni is a poverty-related parasitic infection that has a variety of clinical manifestations. We consider the disability and deaths caused by schistosomiasis unacceptable for a tool-ready disease. Its condition in Brazil warrants an analysis that will enable better understanding of the local health losses and contribute to the complex decision-making process. OBJECTIVE This study estimates the cost of schistosomiasis in Brazil in 2015. METHODS We conducted a cost of illness study of schistosomiasis mansoni in Brazil in 2015 based on a prevalence approach and from a societal perspective. The study included 26,499 schistosomiasis carriers, 397 hepatosplenic cases, 48 cases with the neurological form, 284 hospitalisations, and 11,368.26 years of life lost (YLL) of which 5,187 years are attributable to economically active age groups. RESULTS The total cost of schistosomiasis mansoni in Brazil was estimated to be US$ 41,7million in 2015 with 94.61% of this being indirect costs. CONCLUSIONS The economic burden of schistosomiasis mansoni in Brazil is high and results in the loss of productivity. Its persistence in Brazil is a challenge to public health and requires inter-sectorial interventions in areas such as indoor water supply, basic sanitation, and education.

In August 2015, pediatric neurologists at public hospitals in Recife, Pernambuco State, Brazil, observed an increase in the number of disproportional microcephaly cases associated with other congenital anomalies. The fact caused social commotion and mobilization of the academic community and led the Brazilian Ministry of Health to declare a national public health emergency, followed by the declaration of a Public Health Emergency of International Concern by the World Health Organization. The hypothesis for the phenomenon was congenital Zika virus (ZIKV) infection, based on spatial-temporal correlation and the clinical-epidemiological characteristics of the two epidemics. Further evidence accumulated, and within the scope of epidemiologial reasoning fulfilled criteria that gave support to the hypothesis. The plausibility of the hypothesis is based on the neurotropism of ZIKV, demonstrated in animals, affecting neural progenitors in the developing brain, and in humans, due to neurological complications in adults following infection. Isolation of viral RNA and antigens in the amniotic fluid of infected mothers and in brains of newborns and fetuses with microcephaly further demonstrated the consistency of the hypothesis. The criterion of temporality was met by identifying adverse pregnancy outcomes in a cohort of mothers with a history of rash and positive ZIKV serology. Finally, the first case-control study demonstrated a strong association between microcephaly and congenital ZIKV infection. The knowledge built with the epidemiological paradigm was supported by the scientific community, thereby establishing the consensus for a causal relationship between ZIKV and the microcephaly epidemic.Em agosto de 2015, neuropediatras de hospitais públicos do Recife, Pernambuco, Brasil, observaram um aumento do número de casos de microcefalia desproporcional associado a anomalias cerebrais. Esse fato gerou comoção social, mobilização da comunidade acadêmica e levou o Ministério da Saúde a decretar emergência de saúde pública nacional, seguida pela declaração de emergência de saúde pública de interesse internacional da Organização Mundial da Saúde. A hipótese formulada para o fenômeno foi a infecção congênita pelo vírus Zika (ZIKV), com base na correlação espaço-temporal e nas características clínico-epidemiológicas das duas epidemias. Evidências se acumularam e no âmbito do raciocínio epidemiológico preencheram critérios que deram sustentação à hipótese. Sua plausibilidade está ancorada no neurotropismo do ZIKV demonstrado em animais, atingindo neurônios progenitores do cérebro em desenvolvimento, e em seres humanos devido às complicações neurológicas observadas em adultos após a infecção. O isolamento do RNA e antígenos virais no líquido amniótico de mães infectadas e em cérebros de neonatos e fetos com microcefalia contribuíram para demonstrar a consistência da hipótese. O critério de temporalidade foi contemplado ao se identificar desfechos desfavoráveis em uma coorte de gestantes com exantema e positivas para o ZIKV. Finalmente, o primeiro estudo caso-controle conduzido demonstrou existir uma forte associação entre microcefalia e infecção congênita pelo ZIKV. O conhecimento construído no âmbito do paradigma epidemiológico recebeu a chancela da comunidade científica, construindo o consenso de uma relação causal entre o ZIKV e a epidemia de microcefalia.En agosto de 2015, neuropediatras de hospitales públicos de Recife, Pernambuco, Brasil, observaron un aumento desproporcional del número de casos de microcefalia, asociado a anomalías cerebrales. Este hecho generó conmoción social, movilización de la comunidad académica y obligó al Ministerio de Salud a decretar la emergencia de salud pública nacional, seguida de la declaración de interés internacional de la Organización Mundial de la Salud. La hipótesis formulada para este fenómeno fue la infección congénita por el virus Zika (ZIKV), en base a la correlación espacio-temporal y a las características clínico-epidemiológicas de las dos epidemias. Se acumularon evidencias, y en el ámbito del raciocinio epidemiológico se cumplieron los criterios que dieron apoyo a la hipótesis. Su plausibilidad está anclada en el neurotropismo del ZIKV, demostrado en animales, alcanzando progenitores neuronales del cerebro en desarrollo, y en seres humanos, debido a las complicaciones neurológicas observadas en adultos tras la infección. El aislamiento del ARN y antígenos virales en el líquido amniótico de madres infectadas, en cerebros de neonatos y fetos con microcefalia, contribuyeron a demostrar la consistencia de la hipótesis. El criterio de temporalidad se contempló al identificarse desenlaces desfavorables en una cohorte de gestantes con exantema y positivas en ZIKV. Finalmente, el primer estudio caso-control realizado demostró que existía una fuerte asociación entre microcefalia e infección congénita por el ZIKV. El conocimiento construido en el ámbito del paradigma epidemiológico recibió la aprobación de la comunidad científica, existiendo consenso en cuanto a la relación causal entre el ZIKV y la epidemia de microcefalia.

The objective of this study was to estimate the protective effect of Bacille Calmette-Guérin (BCG) vaccine against tuberculosis among (predominantly immunodeficient) HIV-infected children in Angola. A hospital-based case-control study was conducted with 230 cases, children coinfected with tuberculosis, and 672 controls, HIV-infected children from the same hospital, aged 18 months to 13 years. The presence of a vaccination scar was taken as a proxy marker for BCG vaccination. The crude effectiveness was 8% (95% CI: −26 to 32) and the adjusted effectiveness was 30% (95% CI: −75 to 72). The present study suggests that BCG does not have a protective effect against tuberculosis among immunodeficient HIV-infected children. Since BCG is no longer given to HIV-infected children, the study may not be replicated. Accepting that these findings should be considered with caution, they are nonetheless likely to be the last estimate of BCG efficacy in a sufficiently powered study.

A population-based hepatitis survey was carried out to estimate the prevalence of hepatitis B virus (HBV) infection and its predictive factors for the state capitals from the north, south, and southeast regions of Brazil. A multistage cluster sampling was used to select, successively, census tracts, blocks, households, and residents in the age group 10-69 years in each state capital. The prevalence of hepatitis B surface antigen (HBsAg) was lower than 1% in the north, southeast, and south regions. Socioeconomic condition was associated with HBV infection in north and south regions. Variables related to the blood route transmission were associated with HBV infection only in the south whereas those related to sexual behavior were associated with HBV infection in the north and south regions. Drug use was associated in all regions, but the type of drug differed. The findings presented herein highlight the diversity of the potential transmission routes for hepatitis B transmission in Brazil. In one hand, it reinforces the importance of national control strategies of large impact already in course (immunization of infants, adolescents, and adults up to 49 years of age and blood supply screening). On the other hand, it shows that there is still room for further control measures targeted to different groups within each region.

OBJECTIVE Describe the coding process of death causes for people living with HIV/AIDS, and classify deaths as related or unrelated to immunodeficiency by applying the Coding Causes of Death in HIV (CoDe) system. METHODS A cross-sectional study that codifies and classifies the causes of deaths occurring in a cohort of 2,372 people living with HIV/AIDS, monitored between 2007 and 2012, in two specialized HIV care services in Pernambuco. The causes of death already codified according to the International Classification of Diseases were recoded and classified as deaths related and unrelated to immunodeficiency by the CoDe system. We calculated the frequencies of the CoDe codes for the causes of death in each classification category. RESULTS There were 315 (13%) deaths during the study period; 93 (30%) were caused by an AIDS-defining illness on the Centers for Disease Control and Prevention list. A total of 232 deaths (74%) were related to immunodeficiency after application of the CoDe. Infections were the most common cause, both related (76%) and unrelated (47%) to immunodeficiency, followed by malignancies (5%) in the first group and external causes (16%), malignancies (12 %) and cardiovascular diseases (11%) in the second group. Tuberculosis comprised 70% of the immunodeficiency-defining infections. CONCLUSIONS Opportunistic infections and aging diseases were the most frequent causes of death, adding multiple disease burdens on health services. The CoDe system increases the probability of classifying deaths more accurately in people living with HIV/AIDS. RESUMO OBJETIVO Descrever o processo de codificação das causas de morte em pessoas vivendo com HIV/Aids, e classificar os óbitos como relacionados ou não relacionados à imunodeficiência aplicando o sistema Coding Causes of Death in HIV (CoDe). MÉTODOS Estudo transversal, que codifica e classifica as causas dos óbitos ocorridos em uma coorte de 2.372 pessoas vivendo com HIV/Aids acompanhadas entre 2007 e 2012 em dois serviços de atendimento especializado em HIV em Pernambuco. As causas de óbito já codificadas a partir da Classificação Internacional de Doenças foram recodificadas e classificadas como óbitos relacionados e não relacionados à imunodeficiência pelo sistema CoDe. Foram calculadas as frequências dos códigos CoDe das causas do óbito em cada categoria de classificação. RESULTADOS Ocorreram 315 (13%) óbitos no período do estudo; 93 (30%) tinham como causa uma doença definidora de Aids da lista do Centers for Disease Control and Prevention. No total 232 óbitos (74%) foram relacionados à imunodeficiência após aplicar o CoDe. As infecções foram as causas mais comuns, tanto nos óbitos relacionados (76%) como não relacionados (47%) à imunodeficiência, seguindo-se de malignidades (5%) no primeiro grupo e de causas externas (16%), malignidades (12%) e doenças cardiovasculares (11%) no segundo. A tuberculose compreendeu 70% das infecções definidoras de imunodeficiência. CONCLUSÕES Infecções oportunistas e doenças do envelhecimento foram as causas mais frequentes de óbito, imprimindo carga múltipla de doenças aos serviços de saúde. O sistema CoDe aumenta a probabilidade de classificar os óbitos com maior precisão em pessoas vivendo com HIV/Aids.

OBJECTIVE To determine the sociodemographic, behavioral, and health care factors related to the occurrence of syphilis in women treated at public maternity hospitals. METHODS This is a case-control study (239 cases and 322 controls) with women admitted to seven maternity hospitals in the municipality of Recife, Brazil, from July 2013 to July 2014. Eligible women were recruited after the result of the VDRL (Venereal Disease Research Laboratory) under any titration. The selection of cases and controls was based on the result of the serology for syphilis using ELISA (enzyme-linked immunosorbent assay). The independent variables were grouped into: sociodemographic, behavioral, clinical and obstetric history, and health care in prenatal care and maternity hospital. Information was obtained by interview, during hospitalization, with the application of a questionnaire. Odds ratios and 95% confidence intervals were estimated using logistic regression to identify the predicting factors of the variable to be explained. RESULTS The logistic regression analysis identified as determinant factors for gestational syphilis: education level of incomplete basic education or illiterate (OR = 2.02), lack of access to telephone (OR = 2.4), catholic religion (OR = 1.70 ), four or more pregnancies (OR = 2.2), three or more sexual partners in the last year (OR = 3.1), use of illicit drugs before the age of 18 (OR = 3.0), and use of illicit drugs by the current partner (OR = 1.7). Only one to three prenatal appointments (OR = 3.5) and a previous history of sexually transmitted infection (OR = 9.7) were also identified as determinant factors. CONCLUSIONS Sociodemographic, behavioral, and health care factors are associated with the occurrence of syphilis in women and should be taken into account in the elaboration of universal strategies aimed at the prevention and control of syphilis, but with a focus on situations of greater vulnerability. RESUMO OBJETIVO Determinar os fatores sociodemográficos, comportamentais e de assistência à saúde relacionados à ocorrência de sífilis em mulheres atendidas em maternidades públicas. MÉTODOS Trata-se de um estudo caso-controle (239 casos e 322 controles) com mulheres admitidas em sete maternidades do município do Recife, no período de julho de 2013 a julho de 2014. As mulheres elegíveis foram recrutadas após o resultado do VDRL (Venereal Disease Research Laboratory) sob qualquer titulação. A seleção dos casos e controles considerou o resultado da sorologia por ELISA (enzyme-linked immunosorbent assay), variável dependente utilizada como diagnóstico para sífilis neste estudo. As variáveis independentes foram agrupadas em: sociodemográficas; comportamentais; e antecedentes clínicos e obstétricos; e assistência à saúde no pré-natal e na maternidade. As informações foram obtidas por meio de entrevista, durante o internamento, por aplicação de um questionário. Foi calculado odds ratio (OR), intervalo de confiança de 95% e realizada análise de regressão logística para identificar os fatores preditores da variável a ser explicada. RESULTADOS A análise de regressão logística identificou como fatores determinantes para a sífilis gestacional: nível de escolaridade fundamental incompleto ou analfabeta (OR = 2,02), ausência de acesso a telefone (OR = 2,4), religião católica (OR = 1,70), quatro ou mais gestações (OR = 2,2), três ou mais parceiros sexuais no último ano (OR = 3,1), uso de drogas ilícitas antes dos 18 anos (OR = 3,0) e uso de drogas ilícitas por parte do atual companheiro (OR = 1,7). Além desses, foram observadas a ocorrência de apenas uma a três consultas ao pré-natal (OR = 3,5) e história anterior de infecção sexualmente transmissível (OR = 9,7). CONCLUSÕES Fatores sociodemográficos, comportamentais e de assistência à saúde estão associados à ocorrência de sífilis em mulheres e devem ser levados em consideração na elaboração de estratégias universais direcionadas à prevenção e controle da sífilis, porém com foco em situações de maior vulnerabilidade.

Summary Background A Zika virus epidemic emerged in northeast Brazil in 2015 and was followed by a striking increase in congenital microcephaly cases, triggering a declaration of an international public health emergency. This is the final report of the first case-control study evaluating the potential causes of microcephaly: congenital Zika virus infection, vaccines, and larvicides. The published preliminary report suggested a strong association between microcephaly and congenital Zika virus infection. Methods We did a case-control study in eight public maternity hospitals in Recife, Brazil. Cases were neonates born with microcephaly, defined as a head circumference of 2 SD below the mean. Two controls without microcephaly were matched to each case by expected date of delivery and area of residence. We tested the serum of cases and controls and the CSF of cases for detection of Zika virus genomes with quantitative RT-PCR and for detection of IgM antibodies with capture-IgM ELISA. We also tested maternal serum with plaque reduction neutralisation assays for Zika and dengue viruses. We estimated matched crude and adjusted odds ratios with exact conditional logistic regression to determine the association between microcephaly and Zika virus infection. Findings We screened neonates born between Jan 15 and Nov 30, 2016, and prospectively recruited 91 cases and 173 controls. In 32 (35%) cases, congenital Zika virus infection was confirmed by laboratory tests and no controls had confirmed Zika virus infections. 69 (83%) of 83 cases with known birthweight were small for gestational age, compared with eight (5%) of 173 controls. The overall matched odds ratio was 73·1 (95% CI 13·0–∞) for microcephaly and Zika virus infection after adjustments. Neither vaccination during pregnancy or use of the larvicide pyriproxyfen was associated with microcephaly. Results of laboratory tests for Zika virus and brain imaging results were available for 79 (87%) cases; within these cases, ten were positive for Zika virus and had cerebral abnormalities, 13 were positive for Zika infection but had no cerebral abnormalities, and 11 were negative for Zika virus but had cerebral abnormalities. Interpretation The association between microcephaly and congenital Zika virus infection was confirmed. We provide evidence of the absence of an effect of other potential factors, such as exposure to pyriproxyfen or vaccines (tetanus, diphtheria, and acellular pertussis, measles and rubella, or measles, mumps, and rubella) during pregnancy, confirming the findings of an ecological study of pyriproxyfen in Pernambuco and previous studies on the safety of Tdap vaccine administration during pregnancy. Funding Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations.

The present study analysed the concordance among four different molecular diagnostic methods for tuberculosis (TB) in pulmonary and blood samples from immunocompromised patients. A total of 165 blood and 194 sputum samples were collected from 181 human immunodeficiency virus (HIV)-infected patients with upper respiratory complaints, regardless of suspicious for TB. The samples were submitted for smear microscopy, culture and molecular tests: a laboratory-developed conventional polymerase chain reaction (PCR) and real-time quantitative PCR (qPCR) and the Gen-Probe and Detect-TB Ampligenix kits. The samples were handled blindly by all the technicians involved, from sample processing to results analysis. For sputum, the sensitivity and specificity were 100% and 96.7% for qPCR, 81.8% and 94.5% for Gen-Probe and 100% and 66.3% for Detect-TB, respectively. qPCR presented the best concordance with sputum culture [kappa (k) = 0.864)], followed by Gen-Probe (k = 0.682). For blood samples, qPCR showed 100% sensitivity and 92.3% specificity, with a substantial correlation with sputum culture (k = 0.754) and with the qPCR results obtained from sputum of the corresponding patient (k = 0.630). Conventional PCR demonstrated the worst results for sputa and blood, with a sensitivity of 100% vs. 88.9% and a specificity of 46.3% vs. 32%, respectively. Commercial or laboratory-developed molecular assays can overcome the difficulties in the diagnosis of TB in paucibacillary patients using conventional methods available in most laboratories.

Apesar da eficácia da terapêutica antirretroviral combinada para o tratamento de pessoas vivendo com HIV/Aids, a não adesão aos medicamentos tem se tornado uma das maiores ameaças à efetividade dessa terapêutica. O objetivo desse estudo foi estimar a prevalência de uso irregular autorreferido da terapia antirretroviral e os fatores associados com essa irregularidade em pessoas vivendo com HIV. Foi realizado um estudo seccional de pessoas vivendo com HIV/Aids atendidas em dois centros de referência no Recife, Nordeste do Brasil, entre junho 2007 e outubro de 2009. Foram analisados os fatores socioeconômicos, de apoio social e de hábitos do indivíduo, ajustados através de análise de regressão logística multivariada. A prevalência de pessoas vivendo com HIV/Aids que relataram o uso irregular da terapia antirretroviral combinada (TARC) foi de 25,7%. No modelo multivariado final, o uso irregular da TARC esteve associado às seguintes variáveis: ter menos de 40 anos (OR = 1,66, IC95%: 1,29-2,13), fumantes (OR = 1,76, IC95%: 1,31-2,37) ou ex-fumantes (OR = 1,43, IC95%: 1,05-1,95) e ser usuário de crack (OR = 2,79, IC95%: 1,24-6,32). Medidas especiais devem ser direcionadas para cada um dos seguintes grupos: adultos com menos de 40 anos, fumantes, ex-fumantes e usuários de crack. Ações voltadas para a cessação do tabagismo e do crack devem ser incorporadas ao programa de controle dos infectados pelo HIV, visando promover a maior adesão aos antirretrovirais e, consequentemente, aumentar a expectativa e a qualidade de vida. Despite the effectiveness of combination antiretroviral therapy in the treatment of people living with HIV/AIDS (PLWHA), nonadherence to medication has become a major threat to its effectiveness. This study aimed to estimate the prevalence of self-reported irregular use of antiretroviral therapy and the factors associated with such an irregularity in PLWHA. A cross-sectional study of PLWHA who attended two referral centers in the city of Recife, in Northeastern Brazil, between June 2007 and October 2009 was carried out. The study analyzed socioeconomic factors, social service support and personal habits associated with nonadherence to antiretroviral therapy, adjusted by multivariable logistic regression analysis. The prevalence of PLWHA who reported irregular use of combination antiretroviral therapy (cART) was 25.7%. In the final multivariate model, the irregular use of cART was associated with the following variables: being aged less than 40 years (OR = 1.66, 95%-CI: 1.29-2.13), current smokers (OR = 1.76, 95%-CI: 1.31-2.37) or former smokers (OR = 1.43, 95%-CI: 1.05-1.95), and crack cocaine users (OR = 2.79, 95%-CI: 1.24-6.32). Special measures should be directed towards each of the following groups: individuals aged less than 40 years, smokers, former smokers and crack cocaine users. Measures for giving up smoking and crack cocaine should be incorporated into HIV-control programs in order to promote greater adherence to antiretroviral drugs and thus improve the quality of life and prolong life expectancy.

BACKGROUND The lipodystrophy syndrome is characterized by selective loss of subcutaneous fat on the face and extremities (lipoatrophy) and/or accumulation of fat around the neck, abdomen, and thorax (lipohypertrophy). The aim of this study has been to assess the impact of polymethylmethacrylate facial treatment on quality of life, self-perceived facial image, and the severity of depressive symptoms in patients living with HIV/AIDS. METHODS A non-randomized before and after interventional study was developed. Fifty-one patients underwent facial filling. The self-perceived quality of life, facial image, and degree of depressive symptoms were measured by the Short-Form 36 and HIV/AIDS--Targeted quality of life questionnaires, by a visual analogue scale and by the Beck depression inventory, respectively, before and three months after treatment. RESULTS Six of the eight domains of Short-Form 36 and eight of the nine dimensions of the HIV/AIDS--Targeted quality of life questionnaires, together with the visual analogue scale and by the Beck depression inventory scores, revealed a statistically significant improvement. The only adverse effects registered were edema and ecchymosis. CONCLUSION The treatment of facial lipoatrophy improved the self-perceived quality of life and facial image as well as any depressive symptoms among patients with HIV/AIDS.

Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes.At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained.With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure.NCT02856984 . Registered August 5, 2016. Retrospectively registered.

To test the validity of the polymerase chain reaction for diagnosing American visceral leishmaniasis, 88 suspected cases were studied. Diagnosis was confirmed in 47 (53.5%) and ruled out in 41 (46.5%) patients. Samples of bone marrow and peripheral blood were processed by polymerase chain reaction to evaluate the sensitivity and specificity of the test and its agreement beyond chance with microscopy examination. The polymerase chain reaction was positive in bone marrow of 100% of the patients with amastigotes seen with microscopy examination, and in 59.5% in those where no parasite were seen. Agreement beyond chance between visualization of the parasite in bone marrow aspirates and polymerase chain reaction was considered weak (Kappa = 0.41). Concordance between polymerase chain reaction of bone marrow aspirates and of peripheral blood was considered excellent (Kappa = 0.88). The test turned out positive in all bone marrow aspirates of those with the disease and whereas the positivity rate was 58.5% among those without the disease, with specificity rate of 41.5%. Keywords: American visceral leishmaniasis, Diagnosis, Polymerase chain reaction, Peripheral blood, Bone marrow blood

Objectives. To provide an initial description of the congenital syndrome presumably associated with infection by Zika virus compared with other syndromes including congenital infections of established etiologies. Methods. We provide an overview of a published case series of 35 cases, a clinical series of 104 cases, and published and unpublished reports of clinical and laboratory findings describing cases diagnosed since the beginning of the epidemic of microcephaly in Brazil. Results. About 60% to 70% of mothers report rash during pregnancy; mainly in the first trimester. Principal features are microcephaly, facial disproportionality, cutis girata, hypertonia/spasticity, hyperreflexia, and irritability; abnormal neuroimages include calcifications, ventriculomegaly, and lissencephaly. Hearing and visual abnormalities may be present. Conclusions. Preliminary data suggest that severe congenital abnormalities are linked to Zika virus infection. Cases have severe abnormalities, and although sharing many characteristics with congenital abnormalities associated with other viral infections, abnormalities presumably linked to the Zika virus may have distinguishing characteristics. These severe neurologic abnormalities may result in marked mental retardation and motor disabilities for many surviving offspring. Policy Implications. Affected nations need to prepare to provide complex and costly multidisciplinary care that children diagnosed with this new congenital syndrome will require.

Purpose To correlate the expression of high-risk HPV E6 mRNA with pap smear, colposcopy, and biopsy results in women with high grade squamous intraepithelial lesion (HSIL). Methods A cross-sectional study was performed on women referred for primary care services after cytological diagnosis of HSIL. We evaluated the expression of E6/E7 mRNA of HPV types 16,18,31,33, and 45 and correlated the results with those of Pap smear, colposcopy, and biopsy. For amplification/detection of mRNA E6 / E7 we used NucliSENSEasyQ kit to detect HPV mRNA by polymerase chain reaction with primers/ probes for HPV types 16, 18, 31, 33, and 45. Results Out of 128 valid tests, the results of 30 (23.4%) tests were negative and 98 (70%) tests were positive. Only one type of HPV was detected in 87.7% of the E6/E7 mRNA positive cases. HPV16 was detected in 61.2% of the cases, followed by HPV33 (26.5%), HPV31 (17.3%), HPV18 (10%), and HPV45 (4.08%). Pap smear tests revealed that the E6/E7 test was positive in 107 (83.8%) women with atypical squamous cells - high grade (ASC-H), HSIL, or higher. The E6/E7 test was positive in 69 (57.5%) specimens presenting negative cytology results. When analyzing the association with colposcopy results, the frequency of positive E6/E7 results increased with the severity of the injury, ranging from 57.1% in women without colposcopy-detected injury to 86.5% in those with higher levels of colposcopy findings. Of the 111 women who underwent biopsy and E6/E7 testing, the E6/E7 test was positive in 84.7% of the women who presented with lesions of cervical intraepithelial neoplasia (CIN) grade 2 or higher. Finally, 41.2% of women with a negative biopsy presented a positive E6/E7 test. Conclusions E6/E7mRNA expression was higher in women with HSIL and CIN grade 2 or higher. Objetivo Correlacionar a expressão mRNAE6/E7 do HPV de alto risco com os exames de Papanicolau, colposcopia e biópsia em mulheres com lesão intraepitelial escamosa de alto grau (HSIL). Métodos Estudo transversal com mulheres encaminhadas aos serviços de atenção primária com diagnóstico citológico de HSIL. Foi avaliada a expressão do mRNAE6/E7 dos tipos de HPV 16,18,31,33 e 45, correlacionando-se a expressão com os exames de Papanicolau, colposcopia e biópsia. Para a amplificação/detecção demRNA de E6/E7 foi usado o kit NucliSENS EasyQ(r) HPV que detecta mRNA do HPV por meio da reação em cadeia da polimerase com primers/probes HPV dos tipos 16, 18, 31, 33 e 45. Resultados Foram obtidos 128 testes válidos. Destes: 30 (23,4%) foram negativos e 98 (70%) dos testes foram positivos. Foi encontrado apenas um tipo de HPV em 87,7% dos positivos. O HPV16 foi omais encontrado em61,2%, seguido pelos HPV33 (26,5%); HPV31 (17,34%); HPV 18 (10,0%) e HPV (45 4,0%). Quanto ao exame de Papanicolau, o teste E6/E7 foi positivo em 107 (83,8%) das mulheres com ASC-H, HSIL ou superior, enquanto em citologia negativa foi encontrado um resultado positivo em 69 (57,5%) colposcopia. A frequência de teste E6/E7 positivo aumentou com a gravidade da lesão, detectada na colposcopia variando de 57,1% em mulheres sem lesão identificada em colposcopia até 86,5% naqueles com achado de colposcopia de grau maior. Das 111 mulheres que se submeteram a biópsia e o teste E6/E7, o teste foi positivo em 84,7% das que apresentaramlesão igual ou superior a NIC 2 (neoplasia intraepitelial cervical) e 41,2% daqueles com biópsia negativa. Conclusões A expressão de E6, E7 RNAm ocorreu commaior frequência emlesões de alto grau citológica e em casos com biópsias de NIC2 ou maior.

The increase in the number of reported cases of microcephaly in Pernambuco State, and Northeast Brazil, characterized an epidemic that led the Brazilian Ministry of Health to declare a national public health emergency. The Brazilian Ministry of Health initially defined suspected cases as newborns with gestational age (GA) ≥ 37 weeks and head circumference (HC) ≤ 33cm, but in December 2015 this cutoff was lowered to 32cm. The current study aimed to estimate the accuracy, sensitivity, and specificity of different cutoff points for HC, using ROC curves, with the Fenton and Intergrowth (2014) curves as the gold standard. The study described cases reported in Pernambuco from August 8 to November 28, 2015, according to sex and GA categories. The Fenton and Intergrowth methods provide HC growth curves according to GA and sex, and microcephaly is defined as a newborn with HC below the 3rd percentile in these distributions. Of the 684 reported cases, 599 were term or post-term neonates. For these, the analyses with ROC curves show that according to the Fenton criterion the cutoff point with the largest area under the ROC curve, with sensitivity greater than specificity, is 32cm for both sexes. Using the Intergrowth method and following the same criteria, the cutoff points are 32cm and 31.5cm for males and females, respectively. The cutoff point identified by the Fenton method (32cm) coincided with the Brazilian Ministry of Health recommendation. Adopting Intergrowth as the standard, the choice would be 32cm for males and 31.5cm for females. The study identified the need to conduct critical and on-going analyses to evaluate cutoff points, including other characteristics for microcephaly case definition.