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OBJETIVO: Validar o critério diagnóstico clínico-epidemiológico para confirmação de casos suspeitos da cólera. MÉTODOS: Foram estudados pacientes em um hospital público em Maceió, sendo 2.687 do ano de 1992 e 716 de 1997. Nos pacientes admitidos com diarréia, que realizaram pesquisa do Vibrio cholerae O1 (Koch, 1884) pelo cultivo em TCBS-agar, foi aplicado o critério clínico-epidemiológico comparando-o com o padrão-ouro. A análise foi feita por faixa etária - menor que cinco anos e igual ou maior a cinco anos - em 1992 e 1997. RESULTADOS: Foram estudados 833 pacientes, 517 em 1992 e 316 em 1997; 72 com idade menor que cinco anos e 761 com idade igual ou maior a cinco anos. Nos pacientes menores que cinco anos, em 1992, a sensibilidade foi de 40%, enquanto a especificidade foi de 84,6%. Para a mesma faixa etária, em 1997, a sensibilidade foi de 28,6%. Já a especificidade foi de 62,5%. Nos pacientes com idade igual ou superior a cinco anos, em 1992, a sensibilidade e a especificidade foram de 99% e 1,2%; respectivamente. Para a mesma faixa etária, em 1997, a sensibilidade foi de 86,9%, enquanto a especificidade foi de 8,7%. CONCLUSÃO: A elevada sensibilidade do critério diagnóstico clínico-epidemiológico da cólera nos pacientes com idade igual ou maior que cinco anos, nos dois anos estudados, recomenda sua aplicação nos períodos de epidemia. Quando a incidência baixa, todos os casos devem ter confirmação laboratorial.OBJECTIVE: To validate the clinical and epidemiological diagnosis criterion for confirming cholera suspect cases. METHODS: The study comprised 2,687 and 716 patients admitted with diarrhea to a public hospital in Maceió, Brazil, in 1992 and 1997 respectively. Culture of V. cholerae O1 (Koch, 1884) in TCBS-agar was performed and the clinical and epidemiological criterion was applied and compared to the gold standard. The statistical analysis was carried out in two age-groups: less than five years old and five years old or more. RESULTS: There were studied 833 patients, of which 517 in 1992 and 316 in 1997; 72 aged less than five years and 761 aged five years or more. In those aged less than five years in 1992, sensitivity was 40% and specificity 84.6%. For this same age-group in 1997, sensitivity was 28.6% and specificity 62.5%. In patients aged five years or more in 1992, sensitivity was 99% and specificity 1.2%. For this same age-group in 1997, sensitivity was 86.9% and specificity 8.7%. CONCLUSION: The higher sensitivity of the clinical and epidemiological cholera diagnosis criterion in patients aged five years or more found in the study support its application during epidemics periods. In periods of lower incidence, all cases need to be confirmed using laboratory methods.

Abstract Objective To describe the feeding characteristics and growth of children with prenatal exposure to Zika virus (ZIKV) from birth to 48 months. Design Using data from the prospective Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC), children without microcephaly born to mothers with evidence of ZIKV infection during pregnancy (ZIKV-exposed children without microcephaly) and children with Zika-related microcephaly were compared using repeated cross-sectional analyses within the following age strata: birth; 1 to 12; 13 to 24; 25 to 36; and 37 to 48 months. The groups were compared in relation to prematurity, birth weight, breastfeeding, alternative feeding routes, dysphagia and anthropometric profiles based on the World Health Organization Anthro z-scores (weight-length/height, weight-age, length/height-age and BMI-age). Results The first assessment included 248 children, 77 (31.05%) with microcephaly and 171 (68.95%) without microcephaly. The final assessment was performed on 86 children. Prematurity was 2.35 times higher and low birth weight was 3.49 times higher in children with microcephaly. The frequency of breastfeeding was high (> 80%) in both groups. On discharge from the maternity hospital, the frequency of children requiring alternative feeding route in both groups was less than 5%. After 12 months of age, children with microcephaly required alternative feeding route more often than children without microcephaly. In children with microcephaly, the z-score of all growth indicators was lower than in children without microcephaly. Conclusions Children with Zika-related microcephaly were more frequently premature and low birth weight and remained with nutritional parameters, i.e., weight-for-age, weight-for-length/height and length/height-for-age below those of the children without microcephaly.

ABSTRACT This review aimed to provide an update on the morphological and/or functional abnormalities related to congenital Zika virus (ZIKV) infection, based on primary data from studies conducted in Brazil since 2015. During the epidemic years (2015-2016), case series and pediatric cohort studies described several birth defects, including severe and/or disproportionate microcephaly, cranial bone overlap, skull collapse, congenital contractures (arthrogryposis and/or clubfoot), and visual and hearing abnormalities, as part of the spectrum of Congenital Zika Syndrome (CZS). Brain imaging abnormalities, mainly cortical atrophy, ventriculomegaly, and calcifications, serve as structural markers of CZS severity. Most case series and cohorts of microcephaly have reported the co-occurrence of epilepsy, dysphagia, orthopedic deformities, motor function impairment, cerebral palsy, and urological impairment. A previous large meta-analysis conducted in Brazil revealed that a confirmed ZIKV infection during pregnancy was associated with a 4% risk of microcephaly. Additionally, one-third of children showed at least one abnormality, predominantly identified in isolation. Studies examining antenatally ZIKV-exposed children without detectable abnormalities at birth reported conflicting neurodevelopmental results. Therefore, long-term follow-up studies involving pediatric cohorts with appropriate control groups are needed to address this knowledge gap. We recognize the crucial role of a national network of scientists collaborating with international research institutions in understanding the lifelong consequences of congenital ZIKV infection. Additionally, we highlight the need to provide sustainable resources for research and development to reduce the risk of future Zika outbreaks.

Abstract Background BCG vaccination, originally used to prevent tuberculosis, is known to “train” the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 Methods A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of “severe” above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. Results BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74–93%) in subjects aged 60 or less and 35% (95% CI − 44–71%) in older subjects. Conclusions This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

Abstract The number of studies published on postnatal microcephaly in children with Congenital Zika Syndrome is small, clinical presentations vary and aspects of the evolution of these children remain unclarified. The present case series examined clinical characteristics and assessed the growth velocity of the head circumference, weight and height Z-scores in 23 children who developed postnatal microcephaly during follow-up in the Microcephaly Epidemic Research Group Pediatric Cohort. To estimate the change in the head circumference, weight and height Z-scores over time and compare the mean difference between sexes, we used multilevel mixed-effects linear regressions with child-specific random effects. Among these children, 60.9% (n = 14/23) presented with craniofacial disproportion, 60.9% (n = 14/23) with strabismus, 47.8% (n = 11/23) with early onset seizures, 47.8% (n = 11/23) with dysphagia and 43.5% (n = 10/23) with arthrogryposis. Of the 82.7% (n = 19/23) children who underwent neuroimaging, 78.9% (n = 15/19) presented with alterations in the central nervous system. Monthly growth velocity, expressed in Z-scores, of the head circumference was − 0.098 (95% CI % − 0.117 to − 0.080), of weight was: − 0.010 (95%-CI − 0.033 to 0.014) and of height was: − 0.023 (95%-CI − 0.046 to 0.0001). Postnatal microcephaly occurred mainly in children who had already presented with signs of severe brain damage at birth; there was variability in weight and height development, with no set pattern.

Summary: Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%. Funding: National Council for Scientific and Technological Development - Brazil (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq); Wellcome Trust and the United Kingdom's Department for International Development; European Union's Horizon 2020 research and innovation program; Medical Research Council on behalf of the Newton Fund and Wellcome Trust; National Institutes of Health/National Institute of Allergy and Infectious Diseases; Foundation Christophe et Rodolphe Mérieux; Coordination for the improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Capes); Ministry of Health of Brazil; Brazilian Department of Science and Technology; Foundation of Research Support of the State of São Paulo (Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP); Foundation of Research Support of the State of Rio de Janeiro (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ); Foundation of Support for Research and Scientific and Technological Development of Maranhão; Evandro Chagas Institute/Brazilian Ministry of Health (Instituto Evandro Chagas/Ministério da Saúde); Foundation of Research Support of the State of Goiás (Fundação de Amparo à Pesquisa do Estado de Goiás – FAPEG); Foundation of Research Support of the State of Rio Grande do Sul (Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul – FAPERGS); Foundation to Support Teaching, Research and Assistance at Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto (Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto); São Paulo State Department of Health (Secretaria de Saúde do Estado de São Paulo); Support Foundation of Pernambuco Science and Technology (Fundação de Amparo à Ciência e Tecnologia de Pernambuco – FACEPE).

OBJETIVO: Validar o critério diagnóstico clínico-epidemiológico para confirmação de casos suspeitos da cólera. MÉTODOS: Foram estudados pacientes em um hospital público em Maceió, sendo 2.687 do ano de 1992 e 716 de 1997. Nos pacientes admitidos com diarréia, que realizaram pesquisa do Vibrio cholerae O1 (Koch, 1884) pelo cultivo em TCBS-agar, foi aplicado o critério clínico-epidemiológico comparando-o com o padrão-ouro. A análise foi feita por faixa etária - menor que cinco anos e igual ou maior a cinco anos - em 1992 e 1997. RESULTADOS: Foram estudados 833 pacientes, 517 em 1992 e 316 em 1997; 72 com idade menor que cinco anos e 761 com idade igual ou maior a cinco anos. Nos pacientes menores que cinco anos, em 1992, a sensibilidade foi de 40%, enquanto a especificidade foi de 84,6%. Para a mesma faixa etária, em 1997, a sensibilidade foi de 28,6%. Já a especificidade foi de 62,5%. Nos pacientes com idade igual ou superior a cinco anos, em 1992, a sensibilidade e a especificidade foram de 99% e 1,2%; respectivamente. Para a mesma faixa etária, em 1997, a sensibilidade foi de 86,9%, enquanto a especificidade foi de 8,7%. CONCLUSÃO: A elevada sensibilidade do critério diagnóstico clínico-epidemiológico da cólera nos pacientes com idade igual ou maior que cinco anos, nos dois anos estudados, recomenda sua aplicação nos períodos de epidemia. Quando a incidência baixa, todos os casos devem ter confirmação laboratorial.

Abstract: 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.

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.

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.

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.

ABSTRACT 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.

BackgroundWhile 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.MethodsParticipants 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.Findings376 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.

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.

Introduction Zika 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 analysis We 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 dissemination Ethical 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 There is limited knowledge on the influence of concurrent coinfections on the clinical presentation of Zika virus (ZIKV) disease.Methods To 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.Results The 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.Conclusion Based 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 number CRD42018111023.

Leprosy still constitutes a public health problem due to ocular complications. To expose the ocular complications of leprosy, through integrative review, contributing to practice objectivity to help changing attitudes of health professionals in relation to leprosy patients, according to the World Health Organization Vision 2020 Program. The authors conducted a critical integrative review employing inclusion criteria: the research has been published between 1930 and 2013 and be restricted to ocular complications of leprosy, been provided the inclusion of other aspects relate to the disease. Without limiting the search to English language, one employed the descriptors [leprosy], [eye], [ocular], [Hansen’s disease], [Mycobacterium leprae] associated to [sequela], [complications] e [deformity], linked by Boolean connectors AND/OR, applied to MedLine, SCIELO, Lilacs, Scopus. EBSCO, Cochrane and Google Scholar database, using the program JabRef®, version 2.9.2. We found 387 publications, 33 of which were part of the review. Among the ocular complications, lagophthalmos, cataract, uveitis, blindness and iris changes were most frequent, with variable prevalence according to patient age, disease duration, place of study and level of detail of the eye examination. There was consensus that the prevalence of ocular complications can be reduced with the introduction of ophthalmic examination from diagnosis and after completion of multidrug therapy. Ocular complications are still worrying thus health professionals should refer these patients to ophthalmologic exam.

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

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.

Defining cases of Zika virus (ZIKV) infection is a critical challenge for epidemiological research. Due to ZIKV's overlapping clinical features and potential immunologic cross-reactivity with other flaviviruses and the current lack of an optimal ZIKV-specific diagnostic assay, varying approaches for identifying ZIKV infections have been employed to date. This paper presents the laboratory results and diagnostic criteria developed by the Microcephaly Epidemic Research Group for defining cases of maternal ZIKV infection in a cohort of pregnant women with rash (N = 694) recruited during the declining 2015-2017 epidemic in northeast Brazil. For this investigation, we tested maternal sera for ZIKV by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Immunoglobulin (Ig) M and IgG3 enzyme-linked immunosorbent assays (ELISAs), and Plaque Reduction Neutralization Test (PRNT50). Overall, 23.8% of participants tested positive by qRT-PCR during pregnancy (range of detection: 0-72 days after rash onset). However, the inter-assay concordance was lower than expected. Among women with qRT-PCR-confirmed ZIKV and further testing, only 10.1% had positive IgM tests within 90 days of rash, and only 48.5% had ZIKV-specific PRNT50 titers ≥20 within 1 year of rash. Given the complexity of these data, we convened a panel of experts to propose an algorithm for identifying ZIKV infections in pregnancy based on all available lines of evidence. When the diagnostic algorithm was applied to the cohort, 26.9% of participants were classified as having robust evidence of a ZIKV infection during pregnancy, 4.0% as having moderate evidence, 13.3% as having limited evidence of a ZIKV infection but with uncertain timing, and 19.5% as having evidence of an unspecified flavivirus infection before or during pregnancy. Our findings suggest that integrating longitudinal data from nucleic acid and serologic testing may enhance diagnostic sensitivity and underscore the need for an on-going dialogue regarding the optimization of strategies for defining cases of ZIKV in research.

In Brazil, a scoring system was adopted to diagnose tuberculosis in childhood. This study determined the accuracy in diagnosing tuberculosis in children with either a negative smear or with no smear or culture conducted in a reference center in João Pessoa Paraíba – Brazil. It is a phase III validation study, using a cross-section design. The study population consisted of 167 patients attending the outpatient clinics suspected of having tuberculosis. The reference standard for the diagnosis of tuberculosis was a blind and independent review of the medical records, radiology and tuberculin test by two experts. Of the 167 patients, 60 were considered to have tuberculosis (by the reference standard diagnostics). The results for the scoring system with the cut-off of 30 points were: sensitivity 78.57% (95%-CI: 65.56–88.41%), specificity 69.16% (95%-CI: 59.50–77.73%), positive predictive value (PPV): 57.14% (95%-CI: 45.35–68.37%), negative predictive value (NPV): 86.05% (95%-CI: 76.89–92.58%), likelihood ratio (+): 2,55, pre-test probability: 34.36%, and post-test probability (+): 57.14%. This supports the current recommendation for the use of this scoring system in Brazil and similar sites with the cut-off of 30 points. However, as the discriminatory power of the point scoring system may vary across settings, it would be advisable to replicate this phase III study in different settings.

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika.

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.

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.

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.

Post-transcriptional regulatory elements associated with transcript degradation or transcript instability have been described at the 3' untranslated region (3'UTR) of the HLA-G gene. Considering that HPV infection and aneuploidy, which causes gene instability, are associated with cervical cell malignancy, as well as the fact that HIV infection and HLA-G may modulate the immune response, the present study aimed to compare the frequencies of HLA-G 3'UTR polymorphic sites (14-base pair insertion/deletion, +3142C/G, and +3187A/G) between 226 HIV+ women co-infected (n = 82) or not with HPV (n = 144) and 138 healthy women. We also evaluated the relationship between those HLA-G 3'UTR variants and aneuploidy in cervical cells. HPV types and HLA-G polymorphisms were determined by PCR and sequencing of cervical samples DNA. Aneuploidy in cervical cell was measured by flow cytometry. The HLA-G 3'UTR 14-bp ins/del was not associated with either HIV nor HIV/HPV co-infection. The +3142G allele (p = 0.049) and +3142GG genotype (p = 0.047) were overrepresented in all HIV-infected women. On the other hand, the +3187G allele (p = 0.028) and the +3187GG genotype (p = 0.026) predominated among healthy women. The +3142G (p = 0.023) and +3187A (p = 0.003) alleles were associated with predisposition to HIV infection, irrespective of the presence or not of HIV/HPV co-infection. The diplotype formed by the combination of the +3142CX (CC or CG) and +3187AA genotype conferred the highest risk for aneuploidy in cervical cell induced by HPV. The HLA-G 3'UTR +3142 and +3187 variants conferred distinct susceptibility to HIV infection and aneuploidy.

ABSTRACT 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.

FUNDAMENTOS: A radiação ultravioleta B (RUVB) é o mais importante fator ambiental capaz de modificar a função imunológica da pele humana. OBJETIVO: estudar a associação entre o fenótipo de suscetibilidade ou resistência à radiação RUVB e as formas polares da hanseníase. MATERIAL E MÉTODOS: foram avaliados 38 pacientes com hanseníase virchowiana (MHV) e 87 pacientes com hanseníase tuberculoide (MHT) de acordo com a classificação de Ridley e Jopling (1966). Todos os pacientes foram submetidos ao teste para determinação do fenótipo de suscetibilidade ou resistência à RUVB por meio da aplicação de um disco de dinitroclorobenzeno (DNCB) a 2% em uma área de pele previamente irradiada com duas vezes a dose eritematosa mínima (DEM). Após 21 dias, outra aplicação de um disco similar de DNCB a 0,05% na região escapular (área não exposta à RUVB) foi realizada para avaliar se houve sensibilização, com leitura após 48 horas. Os pacientes que apresentaram reação positiva ao DNCB foram considerados UVB-resistentes e o oposto foi considerado para aqueles que não apresentaram resposta (UVB-suscetíveis). RESULTADOS: A frequência de UVB-suscetíveis foi de 63,2% (24 pacientes) no grupo MHV e 34,4% (30 pacientes) no grupo MHT (OR = 3,26; IC = 1,36-7,87; x² = 7,73; p = 0,005). CONCLUSÃO: Os resultados sugerem que a UVB-suscetibilidade é um fator de risco para o desenvolvimento da MHV.BACKGROUNDS: Ultraviolet radiation B (UVRB) is the most important environmental factor capable of altering the immune function of human skin. OBJECTIVE: To evaluate the association of the phenotypes of susceptibility or resistance to ultraviolet radiation B (UVRB) and the polar forms of leprosy. MATERIAL AND METHODS: We evaluated 38 patients with lepromatous leprosy (LL) and 87 patients with tuberculoid (TT) leprosy, according to the classification by Ridley and Jopling (1966). All the patients were submitted to a test to determine the phenotypes of susceptibility or resistance to UVRB through the application of a 2% dinitrochlorobenzene (DNCB) disc to a previously irradiated area with twice the minimal erythema dose (MED). After 21 days, a similar disc soaked in 0.05% DNCB was applied to the scapular area (unexposed to UVRB) to check for sensitiveness, with reading of the results after 48 hours. The patients that showed a positive reaction to DNCB were considered resistant (UVB-R) and those who did not show any reaction were considered susceptible (UVB-S). RESULTS: The frequency of UVB-S individuals was 63.2% (24 patients) in the LL group and 34.4% (30 patients) in the TT group (OR=3.26; IC=1.36 - 7.87; x²=7.73; p=0.005). CONCLUSION: Our results suggest that UVB-susceptibility is a risk factor to the development of lepromatous leprosy (LL).

Cross-sectional study analyzed as case-control to identify risk factors for non-adherence to antiretroviral therapy. We studied 412 out-clinics HIV infected subjects of three public hospitals of Recife, Pernambuco. The objective was to examine the association between non-adherence to the antiretroviral therapy and biological, social-behavior and demographics and economic factors, factors related to the disease and/or treatment, factors related to life habits and depression symptoms. Variables significantly associated with non-adherence to antiretroviral therapy were: time elapsed since HIV diagnosis (p = 0.002), daily dose (p = 0.046), use of alcohol (p = 0.030) and past drug use (p = 0.048), and borderline p-values were found for educational level (p = 0.093) and family monthly income (p = 0.08). In the multivariable analysis, the factors that remained in the final model were family monthly income, time period with HIV infection and use of alcohol. No association was observed between non-adherence to antiretroviral therapy and gender, age, sexual orientation, marital status, educational level and place of residence. Based on our results and the local situation we suggest: assessment of social needs; training of partners and/or families on supporting adherence, creation of "adherence groups" to motivate and to reassure patients on the benefits of treatment; counseling and/or psychotherapy for alcohol drinkers.Estudo transversal com análise tipo caso-controle, que avaliou 412 pacientes de hospitais públicos do Recife - PE, com o objetivo de identificar fatores preditivos de não adesão à terapia antiretroviral. Verificou-se associação entre não adesão à terapia antiretroviral e aspectos biológicos, sócio-comportamentais e demográficos, econômicos, relacionados à doença e ao tratamento, aos hábitos de vida e aos distúrbios do humor. Variáveis com associação estatisticamente significante com não adesão na análise univariada foram: tempo de diagnóstico (p = 0,002), maior número diário de comprimidos (p = 0,046), uso de álcool (p = 0,030) e uso de drogas no passado (p = 0,048). Observou-se associação limítrofe com grau de instrução (p = 0,093) e renda mensal familiar (p = 0,08). Após análise multivariada, permaneceram no modelo final: renda mensal familiar, tempo de diagnóstico e uso de álcool. Não houve associação entre gênero, idade, comportamento sexual, estado civil, grau de instrução, município de residência e não adesão à terapia antiretroviral. Baseados nos nossos resultados e nas características da população estudada sugerimos: valorização das necessidades sociais, sensibilização de parceiros e/ou familiares para estimular a adesão, criação de grupos de adesão para motivar e persuadir os pacientes sobre os benefícios do tratamento, aconselhamento e/ou psicoterapia para alcoolistas.

Apesar da redução na incidência de tétano acidental no Brasil, não houve queda significativa na letalidade. Nesta série de casos, comparamos a letalidade antes e após o estabelecimento padrão de manejo em unidade de terapia intensiva do paciente com tétano no Hospital Universitário Oswaldo Cruz, no período de 1981 a 2004. Em 24 anos, foram internados 1.971 pacientes e antes do manejo em Unidade de terapia intensiva a letalidade era de 35%. Durante 1997 foi instituída a unidade de terapia intensiva para assistência dos pacientes com tétano, e de 1998 a 2004, a letalidade caiu para 12,6%, OR= 0,27 (IC95%= 0,18- 0,39); pDespite reductions in the incidence of accidental tetanus cases in Brazil, there has not been any significant decrease in its mortality. In this case series, the mortality rates before and after establishing standard management practices for tetanus patients in the intensive care unit at the Oswaldo Cruz University Hospital are compared over the period from 1981 to 2004. Over these 24 years, 1.971 patients were admitted. Before establishing the intensive care unit management, the mortality rate was 35%. The Intensive care unit for attending to tetanus patients was established in 1997. From 1998 to 2004, the mortality rate fell to 12.6%: OR = 0.27 (95% CI = 0.18-0.39); p < 0.001. This trend was seen in all age groups and both sexes. The centralization of attendance for these patients into a single specialized service with early treatment in an intensive care unit has therefore been decisive in reducing the mortality rate. This service can count on the medical team's vast experience of tetanus management, with better treatment of symptoms that forestalls the serious complications from this disease.

The authors compared demographic aspects and profile of mutations in 80 patients with subtypes B and F of human immunodeficiency type 1 (HIV-1). Genotyping of the pol region of the reverse transcriptase was performed using the ViroSeqTM Genotyping System. A total of 61 (76.2%) patients had subtype B and 19 (23.8%) subtype F of the HIV-1. Subtype F tended to be more frequent in heterosexuals and women with a low educational level, but without statistical significance. The frequency of mutations related to nucleoside reverse transcriptase inhibitors and protease inhibitors (PI) was the same in the two subtypes, but mutations related to PI at the codons 63, 77, and 71 were more frequent in subtype B, while mutations at the codons 36 and 20 predominated in subtype F. Sixty-two of the 80 patients infected with subtypes B and F were submitted to antiretroviral therapy for an average of 18-22 months. Undetectable viral loads at the end of follow-up were similar in the two groups, representing 63.8% of subtype B and 73.3% of subtype F (p = 0.715). CD4 lymphocyte counts before and after treatment were similar in the two groups. This study, despite pointing to possible epidemiological and genetic differences among subtypes B and F of HIV-1, suggests that the use of highly active antiretroviral therapy is equally effective against these subtypes.

OBJETIVO: Analisar a ocorrência da tuberculose, identificando variáveis definidoras de situações coletivas de risco que determinam sua distribuição espacial, como subsídio à implantação de um sistema de vigilância de base territorial para controle da tuberculose. MÉTODOS: Estudo ecológico realizado no período 1996-2000, em Olinda, município da região metropolitana do Recife, PE. A mediana do número de casos de tuberculose, notificados por setor censitário, serviu como ponto de corte para caracterização das áreas de alta e baixa transmissão. Um modelo de regressão logística, utilizando essa variável resposta, permitiu estimar as "odds-ratio" de algumas variáveis socioeconômicas do Censo Demográfico de 2000 e de outras co-variáveis relacionadas com a transmissão da doença. RESULTADOS: A tuberculose em Olinda apresentou altas taxas de incidência no período (média de 111 casos por 100.000 habitantes). Verificou-se que são significativamente associadas à ocorrência da tuberculose, as variáveis: média de moradores por domicílio (OR=2,2; IC 95%: 1,3; 3,6); existência de famílias com mais de um caso no período (OR=5,1; IC 95%: 2,3; 11,3); e presença de casos de retratamento (OR=6,8; IC 95%: 2,7; 17,1). Setores censitários com a ocorrência desses dois últimos eventos concentraram 45% do total de casos do período, representando apenas 28% da população do município. CONCLUSÕES: Duas das três variáveis explicativas associadas a maiores taxas de incidência da doença são informações que devem ser monitorizadas, em nível local, pelo sistema de vigilância da tuberculose. O simples mapeamento de casos de retratamento e de domicílios com ocorrência de repetidos casos, permitiria refinar o foco de atenção em micro-áreas prioritárias para intervenções intensivas, como forma de enfrentar o problema da tuberculose.OBJECTIVE: To analyze the occurrence of tuberculosis and to identify variables that define situations of collective risk that determine the spatial distribution of the disease, as backing for implementing a territory-based surveillance system for tuberculosis control. METHODS: This was an ecological study performed in Olinda, a municipality in the metropolitan region of Recife, State of Pernambuco, between 1996 and 2000. The median number of notified tuberculosis cases in each census tract served as the cutoff point for characterizing areas of high and low transmission. A logistic regression model using this response variable allowed odds ratios for some socioeconomic variables from the 2000 demographic census and other covariates related to the transmission of the disease to be estimated. RESULTS: Tuberculosis in Olinda presented high incidence rates during the study period (average of 111 cases per 100,000 inhabitants). Significant associations with the occurrence of tuberculosis were found for the variables of average number of inhabitants per household (OR=2.2; 95% CI: 1.3; 3.6); existence of families with more than one case during the study period (OR=5.1; 95% CI: 2.3; 11.3); and presence of cases of retreatment (OR=6.8; 95% CI: 2.7; 17.1). The census tract where the latter two events occurred accounted for 45% of the total number of cases during the study period, while representing only 28% of the population of Olinda. CONCLUSIONS: The two explanatory covariates that were strongly associated with higher incidence rates of the disease are events that need to be carefully monitored at a local level by the tuberculosis surveillance system. Simply by mapping out retreatment cases and households with more than one case, attention could be focused on small areas with high priority for intensive intervention, thus facing up to the tuberculosis problem.

BACKGROUND: The challenge of diagnosing smear-negative pulmonary TB (tuberculosis) in people living with HIV justifies the use of instruments other than the smear test for diagnosing the disease. Considering the clinical-radiological similarities of TB amongst HIV-infected adults and children, the proposal of this study was to assess the accuracy of a scoring system used to diagnose smear-negative pulmonary TB in children and adolescents, in HIV-infected adults suspected of having smear-negative pulmonary TB. METHODS: A Phase III validation study aiming to assess the diagnostic accuracy of a scoring system for diagnosing smear-negative pulmonary TB in HIV-infected adults. The study assessed sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values of the scoring system. Three versions of the scoring system were tested. RESULTS: From a cohort of 2,382 (HIV-infected adults), 1276 were investigated and 128 were diagnosed with pulmonary TB. Variables associated with the diagnosis of TB were: coughing, weight loss, fever, malnutrition, chest X-ray, and positive tuberculin test. The best diagnostic performance occurred with the scoring system with new scores, with sensitivity = 81.2% (95%-CI 74.5% -88%), specificity = 78% (75.6% -80.4%), PPV = 29.2% (24.5% -33.9%) and NPV = 97.4% (96.4% -98.4%), LR+ = 3.7 (3.4-4.0) and LR- = 0.24 (0.2-0.4). CONCLUSION: The proposed scoring system (with new scores) presented a good capacity for discriminating patients who did not have pulmonary TB, in the studied population. Further studies are necessary in order to validate it, thus permitting the assessment of its use in diagnosing smear-negative pulmonary TB in HIV-infected adults.

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%.

Neste artigo, discute-se o eixo metodológico utilizado na construção de modelo de vigilância de endemias em áreas urbanas, orientado por uma análise de situações de risco e por indicadores epidemiológicos espaciais. São apresentadas as premissas básicas do modelo, os critérios de seleção de variáveis sócio-econômicas e as etapas metodológicas necessárias na construção do indicador sintético de risco. Comenta-se, também, como algumas questões operacionais relativas à construção de mapas digitais de setores censitários e vinculação de bancos de dados foram equacionadas. Essa abordagem, incorporando o componente da organização do espaço na vigilância de doenças endêmicas, tendo como exemplo a hanseníase e a tuberculose, privilegia o uso integrado de sistemas de informação já existentes, na perspectiva de estratificar áreas urbanas diferenciadas que permite discriminar riscos desiguais para ocorrência de endemias. Essa é uma ferramenta para o planejamento e o gerenciamento das ações voltadas para o controle das endemias nas cidades.

Resumo: A pandemia de COVID-19 iniciou sua linha do tempo em 31 de dezembro de 2019 na China e o SARS-CoV-2 identificado como agente etiológico. O objetivo deste manuscrito é descrever a dinâmica espacial e temporal da epidemia de COVID-19 nos primeiros cem dias, no Estado de Pernambuco, Brasil. Apresentamos a evolução de casos e óbitos segundo semana epidemiológica. Realizamos a análise da série do acumulado diário de casos da COVID-19 confirmados, com projeções para os 15 dias subsequentes, utilizando o aplicativo JoinPoint. Esse programa possibilita identificar pontos de inflexão testando sua significância estatística. Analisamos também a tendência de interiorização da COVID-19 no estado, considerando a distribuição percentual de casos ocorridos no Recife, municípios da Região Metropolitana de Recife e do interior, por conjuntos de três semanas, com construção de mapas temáticos. Os 100 dias da epidemia de COVID-19 resultaram em 52.213 casos e 4.235 óbitos entre 12 de março, correspondendo se 11, até 20 de junho de 2020 (semana epidemiológica 25). O pico da curva epidêmica ocorreu na semana epidemiológica 21 (23 de maio), seguido por desaceleração do número de casos. Detectou-se, inicialmente, a periferização dos casos na capital e região metropolitana, seguida por rápida disseminação para o interior do estado. Houve redução das taxas de crescimento médio diário a partir de abril, mas com patamar de mais de 6.000 casos semanais de COVID-19, em média. Ao final do período, a série de casos do estado indica persistência da circulação e transmissão comunitária do SARS-CoV-2. Finalmente, questiona-se parafraseando Garcia Marques em Cem Anos de Solidão, se estaríamos diante de “uma estiagem ou prenúncio de recrudescimento”.

AbstractBackground:The Framingham score is used in most studies on human immunodeficiency virus (HIV)-positive patients to estimate the risk for coronary heart disease; however, it may have some limitations for detecting risk among these individuals.Objective:The aim of this study was to evaluate the agreement between the Framingham and Prospective Cardiovascular of Münster (PROCAM) scores among HIV-positive individuals and to investigate the factors associated with disagreement between the two scores.Method:A cross-sectional study was conducted in a population of HIV/acquired immunodeficiency syndrome (AIDS) patients attending the outpatient''s clinics of two reference centers for HIV/AIDS in Pernambuco, Brazil. Agreement between the Framingham and PROCAM scores was evaluated using the kappa index. From this analysis, a variable called “disagreement between scores” was created, and univariate and multivariate analysis were performed to investigate the factors associated with this variable.Results:The prevalence of low, moderate, and high risk were, respectively, 78.7%, 13.5%, and 7.8% by Framingham score and 88.5%, 4.3%, and 7.2% by PROCAM (kappa = 0.64, P≤ 0.0001). Agreement in the subgroup with metabolic syndrome by the International Diabetes Federation (IDF) (kappa = 0.51, P≤ 0.0001) and the National Cholesterol Education Program (NCEP) (kappa = 0.59, P≤ 0.0001) criteria was moderate. The Framingham score identified greater proportion of women with moderate risk. Factors independently associated with disagreement were: smoking, sex, age, low-density lipoprotein cholesterol, diastolic blood pressure, and metabolic syndrome.Conclusion:There was a good agreement between the Framingham and PROCAM scores in HIV-positive patients, but a higher proportion of moderate-high risk was identified by the Framingham score. This disagreement should be evaluated in cohort studies to observe clinical outcomes over the course of time. [ABSTRACT FROM AUTHOR]

AbstractBackground:Although human immunodeficiency virus (HIV)-associated lipodystrophy has been reported for more than a decade, there is still considerable uncertainty regarding the mechanisms involved in its pathogenesis.Methods:A case–control study was performed that aimed to identify the risk factors for lipodystrophy in HIV/acquired immunodeficiency syndrome (AIDS) patients undergoing antiretroviral therapy in Pernambuco, Brazil.Results:Between July and November, 2007, a total of 332 patients were enrolled in the study: 182 cases and 150 controls. The following factors were independently associated with lipodystrophy: Use of stavudine [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.3–6.9], use of didanosine (OR, 1.8; 95% CI, 1.0–3.4), use of lopinavir/ritonavir for less than 3 years (OR, 0.5; 95% CI, 0.2–1.0) and use of nucleoside/nucleotide analogue reverse transcriptase inhibitors (NTRIs) for more than 3 years (OR, 2.9; 95% CI, 1.6–5.2). Other associated factors were: duration of antiretroviral therapy (OR, 4.3; 95% CI, 2.4–7.9) and duration of HIV infection (OR, 2.9; 95% CI, 1.8–4.7). There was no association with the use of protease inhibitor when it was adjusted for the use of NRTIs.Conclusion:In this study, factors related to antiretroviral therapy were the main risk factors for lipodystrophy, corroborating the literature, but the findings also point to the need for further exploration into some of these associations, especially with the use of didanosine and lopinavir/ritonavir, which are less frequently reported. Future studies with a larger number of patients and a prospective design could provide valuable information for understanding this disorder. [ABSTRACT FROM AUTHOR]

Background The objectives were to estimate the prevalence of hepatitis A among children and adolescents from the Northeast and Midwest regions and the Federal District of Brazil and to identify individual-, household- and area-levels factors associated with hepatitis A infection. Methods This population-based survey was conducted in 2004–2005 and covered individuals aged between 5 and 19 years. A stratified multistage cluster sampling technique with probability proportional to size was used to select 1937 individuals aged between 5 and 19 years living in the Federal capital and in the State capitals of 12 states in the study regions. The sample was stratified according to age (5–9 and 10- to 19-years-old) and capital within each region. Individual- and household-level data were collected by interview at the home of the individual. Variables related to the area were retrieved from census tract data. The outcome was total antibodies to hepatitis A virus detected using commercial EIA. The age distribution of the susceptible population was estimated using a simple catalytic model. The associations between HAV infection and independent variables were assessed using the odds ratio and corrected for the random design effect and sampling weight. Multilevel analysis was performed by GLLAMM using Stata 9.2. Results The prevalence of hepatitis A infection in the 5–9 and 10–19 age-group was 41.5 and 57.4%, respectively for the Northeast, 32.3 and 56.0%, respectively for the Midwest and 33.8 and 65.1% for the Federal District. A trend for the prevalence of HAV infection to increase according to age was detected in all sites. By the age of 5, 31.5% of the children had already been infected with HAV in the Northeast region compared with 20.0% in the other sites. By the age of 19 years, seropositivity was ∼70% in all areas. The curves of susceptible populations differed from one area to another. Multilevel modeling showed that variables relating to different levels of education were associated with HAV infection in all sites. Conclusion The study sites were classified as areas with intermediate endemicity area for hepatitis A infection. Differences in age trends of infection were detected among settings. This multilevel model allowed for quantification of contextual predictors of hepatitis A infection in urban areas. [ABSTRACT FROM AUTHOR]

Background: Recent tobacco smoking has been identified as a risk factor for developing tuberculosis, and two studies which have investigated its association with relapse of tuberculosis after completion of treatment had conflicting results (and did not control for confounding). The objective of this study was to investigate risk factors for tuberculosis relapse, with emphasis on smoking.Methods: A cohort of newly diagnosed TB cases was followed up from their discharge after completion of treatment (in 2001-2003) until October 2006 and relapses of tuberculosis ascertained during that period. A case of relapse was defined as a patient who started a second treatment during the follow up.Results: Smoking (OR 2.53, 95% CI 1.23-5.21) and living in an area where the family health program was not implemented (OR 3.61, 95% CI 1.46-8.93) were found to be independently associated with relapse of tuberculosis.Conclusions: Our results establish that smoking is associated with relapse of tuberculosis even after adjustment for the socioeconomic variables. Smoking cessation support should be incorporated in the strategies to improve effectiveness of Tuberculosis Control Programs. [ABSTRACT FROM AUTHOR]

Abstract 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.

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.

Abstract Background Starting in August 2015, there was an increase in the number of cases of neonatal microcephaly in Northeast Brazil. These findings were identified as being an epidemic of microcephaly related to Zika virus (ZIKV) infection. The present study aims to analyse the spatial distribution of microcephaly cases in Recife (2015–2016), which is in Northeast Brazil, and its association with the living conditions in this city. Methods This was an ecological study that used data from reported cases of microcephaly from the State Health Department of Pernambuco (August 2015 to July 2016). The basic spatial unit of analysis was the 94 districts of Recife. The case definition of microcephaly was: neonates with a head circumference of less than the cut-off point of −2 standard deviations below the mean value from the established Fenton growth curve. As an indicator of the living conditions of the 94 districts, the percentage of heads of households with an income of less than twice the minimum wage was calculated. The districts were classified into four homogeneous strata using the K-means clustering algorithm. We plotted the locations of each microcephaly case over a layer of living conditions. Results During the study period, 347 microcephaly cases were reported, of which 142 (40.9%) fulfilled the definition of a microcephaly case. Stratification of the 94 districts resulted in the identification of four strata. The highest stratum in relation to the living conditions presented the lowest prevalence rate of microcephaly, and the overall difference between this rate and the rates of the other strata was statistically significant. The results of the Kruskal-Wallis test demonstrated that there was a strong association between a higher prevalence of microcephaly and poor living conditions. After the first 6 months of the study period, there were no microcephaly cases recorded within the population living in the richest socio-economic strata. Conclusion This study showed that those residing in areas with precarious living conditions had a higher prevalence of microcephaly compared with populations with better living conditions.

Corresponde a estudo descritivo de corte transversal, buscou-se evidenciar o impacto da TARV sobre o perfil lipídico. Realizada com 37 pacientes atendidos no ambulatório de Doenças Infecciosas e Parasitárias do centro de referência para HIV do Hospital Universitário Oswaldo Cruz em Recife-PE/Brasil. Através da realização de entrevistas, coleta de informações sobre terapia antirretroviral, curva de CD4 e carga viral obtidas nos prontuários. Tendo como aprovação no comitê de ética e pesquisa CAAE de nº 11365112.8.0000.5192. Revela o impacto no perfil lipídico associado ao uso contínuo da TARV, demostrando aumento do TG 54%, CT 49%, VLDL (41%), LDL-c 19% e diminuição do HDL-c 24%. As associações de esquemas de ITRN e IRNN apresentaram o maior número de alterações. As drogas da TARV induzem distúrbios metabólicos graves e associados com outros fatores encontrados como HAS 19%, tabagismo 35% e sedentarismo 81% constituem uma forte predisposição de aterosclerose e consequentemente riscos cardiovasculares.

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.

Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN`s mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network.