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Carlos Alexandre Antunes de Brito,1– 4 Lívia Medeiros Soares Celani,2,5 Marcelo Vicente Toledo de Araújo,2,6 Maurilio Toscano de Lucena,7 Graciana Bandeira Salgado Vasconcelos,1,2,8 Gustavo André Silva Lima,1,2,4 Fernando Jorge Firmino Nóbrega,2,6 George Tadeu Nunes Diniz,9 Norma Lucena-Silva,9 Germano Tose Toneto,4 João Victor de Carvalho Falcão,4 Pedro Martinelli Barbosa,4 Priscylla Rayanne Fernandes de Oliveira,7 Luan Samy Xavier Dantas,5 Luanna Karen Chagas Fernandes,6 Samara Amorim de Araújo,6 Valéria Ferreira Martinelli1,2,4 1Department of Gastroenterology, Hospital das Clínicas, Federal University of Pernambuco, Recife, Pernambuco, Brazil; 2Department of Gastroenterology, Member of the Brazilian Organization of Crohn’s Disease and Colitis – GEDIIB, São Paulo, Brazil; 3Department of Internal Medicine, Centre of Medical Sciences of the Federal University of Pernambuco, Recife, Pernambuco, Brazil; 4Department of Immunology, Autoimune Research Institute, Recife, Pernambuco, Brazil; 5Department of Gastroenterology, Onofre Lopes Hospital, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil; 6Department of Gastroenterology, Lauro Wanderley Hospital, Federal University of Paraíba, João Pessoa, Paraíba, Brazil; 7Department of Coloproctology, Barão de Lucena Hospital, Recife, Pernambuco, Brazil; 8Department of Gastroenterology, University of Pernambuco, Recife, Pernambuco, Brazil; 9Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, BrazilCorrespondence: Carlos Alexandre Antunes de Brito, Division of Immunology, Autoimune Research Institute, 715 Rui Barbosa Avenue, Recife, Pernambuco, 52011-040, Brazil, Tel +55 81 31480101, Email cbritoc@gmail.comPurpose: Ulcerative colitis (UC) and Crohn’s disease (CD) are inflammatory bowel diseases (IBDs) with multifactorial causes. They are becoming more prevalent in developing countries such as Brazil; however, relevant studies in poorer regions of the country are limited. Here, we report the clinical–epidemiological profile of patients with IBD treated at reference centers in three states of Northeast Brazil.Patients and Methods: This was a prospective cohort study involving patients at referral outpatient clinics for IBD from January 2020 through December 2021.Results: Of 571 patients with IBD, 355 (62%) had UC, and 216 (38%) had CD. The patients were predominantly women (355, 62%) for both UC and CD. Extensive colitis was the pattern present in 39% of the UC cases. For CD, ileocolonic disease was the predominant manifestation (38%), with 67% of cases showing penetrating and/or stenosing behavior. The majority of patients were diagnosed between the ages of 17 and 40, corresponding to 60.2% in CD and 52.7% in UC. The median time between symptom onset and diagnosis was 12 months for CD and 8 months for UC (p=0.042). Joint involvement was the most frequent extraintestinal manifestation, with arthralgia and arthritis present in 41.9% and 18.6% of the patients, respectively. Biological therapy was prescribed to 73% of CD patients and 26% of UC patients. A progressive increase in new cases was observed in every 5-year interval over the last five decades, with 58.6% being diagnosed in the last 10 years.Conclusion: More extensive disease behavior patterns predominated in UC, while forms associated with complications were prevalent in CD. A prolonged time to diagnosis may have contributed to these findings. A progressive increase in IBD incidence was observed and may be related to greater urbanization and better access to specialized outpatient clinics, resulting in improvements in diagnosis.Keywords: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, epidemiology

Valéria Ferreira Martinelli,1,2 Pedro Martinelli Barbosa,3 Lucila Samara Dantas de Oliveira,1 Luísa de Andrade Lima Vieira de Melo,1 João Manoel Casa Nova,1 Carlos Alexandre Antunes de Brito2,4,5 1Department of Gastroenterology, Hospital das Clínicas, Federal University of Pernambuco, Recife, Pernambuco, Brazil; 2Department of Gastroenterology, Member of Organização Brasileira de Doença de Crohn e Retocolite – GEDIIB, São Paulo, Brazil; 3Department of Internal Medicine, Medical Sciences Center, Pernambucana of Health College, Recife, Pernambuco, Brazil; 4Department of Internal Medicine, Center of Medical Sciences of Federal University of Pernambuco, Pernambuco, Brazil; 5Department of Immunology, Autoimune Research Institute, Recife, Pernambuco, BrazilCorrespondence: Carlos Alexandre Antunes de Brito, Department of Immunology, Autoimune Research Institute, Avenue Rui Barbosa 715, Recife, Pernambuco, 52011-040, Brazil, Tel +55 81 31480101, Email cbritoc@gmail.comBackground: Cutaneous involvement is the second-most frequent extraintestinal manifestation of inflammatory bowel disease, with pyoderma gangrenosum (PG) a particularly relevant form because of its frequency, morbidity, and recurrence. The limited number of clinical trials involving PG increases the challenge to gastroenterologists in the management of this condition.Case Presentation: Four cases of atypical presentations of PG are reported. A 25-year-old patient with ulcerative colitis presented an extensive chronic ulcerative lesion on her left leg that was associated with significant bleeding; the intestinal disease was in remission under the use of azathioprine. The patient was on long-term use of 60 mg corticosteroid with no improvement in the skin disease; however, initiation of cyclosporine induced remission. In the second case, a 52-year-old woman was a carrier of Crohn’s disease, with a history of partial colectomy. The patient’s skin condition had evolved with a cutaneous lesion localized in the perineal region, buttocks, and colostomy pouch, simulating a case of impetigo, and this had been treated with antibiotic cycles without improvement. Lesion biopsy suggested a diagnosis of PG. Consequently, the patient was started on biological therapy with infliximab, and the PG regressed. In the third case, a 38-year-old woman with a history of pancolitis presented a picture of PG with an extensive and deep ulcerative lesion in the right breast. The lesion regressed after treatment with oral corticosteroid. The final case was a 44-year-old woman with Crohn’s disease suffering from Crohn’s disease pancolitis. The patient’s condition evolved with a mixed pattern with pustules, bullae, and ulcerative lesions in the vulva, oral cavity, gluteus, right auricular region, scalp, and left flank, and was resolved by administration of adalimumab.Conclusion: PG is an important and frequent manifestation of inflammatory bowel disease, with a spectrum of clinical variants, significant morbidity, and requiring a variety of therapeutic approaches.Keywords: inflammatory bowel disease, pyoderma gangrenosum, Crohn’s disease, ulcerative colitis, extraintestinal manifestations

Jones Silva Lima,1 Carlos Alexandre Antunes de Brito,1– 4 Lívia Medeiros Soares Celani,2,5 Marcelo Vicente Toledo de Araújo,2,6 Maurilio Toscano de Lucena,7 Graciana Bandeira Salgado Vasconcelos,1,2,8 Gustavo André Silva Lima,1,2,4 Fernando Jorge Firmino Nóbrega,6 George Tadeu Nunes Diniz,9 Norma Lucena-Silva,9 Regiane Maio,10 Valéria Ferreira Martinelli1,2,4 1Department of Gastroenterology, Hospital das Clínicas, Federal University of Pernambuco, Recife, Pernambuco, Brazil; 2Department of Gastroenterology, Member of Organização Brasileira de Doença de Crohn e Retocolite – GEDIIB, São Paulo, Brazil; 3Department of Internal Medicine, Center of Medical Sciences of Federal University of Pernambuco, Pernambuco, Brazil; 4Department of Immunology, Autoimune Research Institute, Recife, Pernambuco, Brazil; 5Department of Gastroenterology, Onofre Lopes Hospital, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil; 6Department of Gastroenterology, Lauro Wanderley Hospital, Federal University of Paraíba, João Pessoa, Paraíba, Brazil; 7Department of Coloproctology, Barão de Lucena Hospital, Recife, Pernambuco, Brazil; 8Department of Gastroenterology, University of Pernambuco, Recife, Pernambuco, Brazil; 9Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil; 10Department of Nutrition, Federal University of Pernambuco, Recife, Pernambuco, BrazilCorrespondence: Carlos Alexandre Antunes de Brito, Division of Immunology, Autoimune Research Institute, 715 Rui Barbosa Avenue, Recife, Pernambuco, 52011-040, Brazil, Tel + 55 81 31480101, Email cbritoc@gmail.comPurpose: Inflammatory bowel disease (IBD) is a disease of increasing prevalence in developing countries. Obesity has emerged as a potential risk for IBD; however, the data in the literature are conflicting, and relevant studies in Brazil are limited. Here, we report body mass index profile (BMI) of patients with IBD treated at reference centers in three states of northeastern Brazil.Patients and Methods: Observational descriptive study conducted from January 2021 through December 2021 in patient with IBD.Results: Of 470 patients with IBD, 194 (41%) were classified as normal weight, 42 (9%) as underweight, 155 (33%) as overweight, and 79 (17%) as obese; CD patients were significantly more likely to be underweight than UC patients (p=0.031)Overweight patients were older (median age: 47 years) than normal-weight and underweight patients at diagnosis (38.5 and 35.5 years, respectively [p< 0.0001]). IBD onset and diagnosis among overweight and obese individuals were associated with older age. More extensive disease behavior patterns predominated in UC, while forms associated with complications were prevalent in CD, irrespective of nutritional status. There was a higher frequency of compatible symptoms with axial joint inflammation among obese patients (p=0.005) and a lower frequency of compatible symptoms with peripheral joint inflammation in underweight patients (p=0.044) than in patients of normal weight. No significant difference in the frequency of different drug or surgical treatments was observed among the groups.Conclusion: Despite the predominance of overweight and obesity in patients with IBD, no differences in the patterns of disease were seen between the overweight and normal-weight groups; however, obesity was associated with IBD onset in older adults and a higher frequency compatible symptom with axial joint inflammation. These data reinforce the importance of monitoring the nutritional status of IBD patients and the need for a multidisciplinary approach, as recommended in the current guidelines.Keywords: Crohn’s disease, ulcerative colitis, obesity, overweight

The need for the identification of risk factors associated to COVID-19 disease severity remains urgent. Patients' care and resource allocation can be potentially different and are defined based on the current classification of disease severity. This classification is based on the analysis of clinical parameters and routine blood tests, which are not standardized across the globe. Some laboratory test alterations have been associated to COVID-19 severity, although these data are conflicting partly due to the different methodologies used across different studies. This study aimed to construct and validate a disease severity prediction model using machine learning (ML). Seventy-two patients admitted to a Brazilian hospital and diagnosed with COVID-19 through RT-PCR and/or ELISA, and with varying degrees of disease severity, were included in the study. Their electronic medical records and the results from daily blood tests were used to develop a ML model to predict disease severity. Using the above data set, a combination of five laboratorial biomarkers was identified as accurate predictors of COVID-19 severe disease with a ROC-AUC of 0.80 ​±​ 0.13. Those biomarkers included prothrombin activity, ferritin, serum iron, ATTP and monocytes. The application of the devised ML model may help rationalize clinical decision and care.

Background: The four Dengue viruses (DENV) serotypes were re-introduced in Brazil's Northeast region in a couple of decades, between 1980's and 2010's, where the DENV1 was the first detected serotype and DENV4 the latest. Zika (ZIKV) and Chikungunya (CHIKV) viruses were introduced in Recife around 2014 and led to large outbreaks in 2015 and 2016, respectively. However, the true extent of the ZIKV and CHIKV outbreaks, as well as the risk factors associated with exposure to these viruses remain vague., Methods: We conducted a stratified multistage household serosurvey among residents aged between 5 and 65 years in the city of Recife, Northeast Brazil, from August 2018 to February 2019. The city neighborhoods were stratified and divided into high, intermediate, and low socioeconomic strata (SES). Previous ZIKV, DENV and CHIKV infections were detected by IgG-based enzyme linked immunosorbent assays (ELISA). Recent ZIKV and CHIKV infections were assessed through IgG3 and IgM ELISA, respectively. Design-adjusted seroprevalence were estimated by age group, sex, and SES. The ZIKV seroprevalence was adjusted to account for the cross-reactivity with dengue. Individual and household-related risk factors were analyzed through regression models to calculate the force of infection. Odds Ratio (OR) were estimated as measure of effect., Principal Findings: A total of 2,070 residents' samples were collected and analyzed. The force of viral infection for high SES were lower as compared to low and intermediate SES. DENV seroprevalence was 88.7% (CI95%:87.0-90.4), and ranged from 81.2% (CI95%:76.9-85.6) in the high SES to 90.7% (CI95%:88.3-93.2) in the low SES. The overall adjusted ZIKV seroprevalence was 34.6% (CI95%:20.0-50.9), and ranged from 47.4% (CI95%:31.8-61.5) in the low SES to 23.4% (CI95%:12.2-33.8) in the high SES. The overall CHIKV seroprevalence was 35.7% (CI95%:32.6-38.9), and ranged from 38.6% (CI95%:33.6-43.6) in the low SES to 22.3% (CI95%:15.8-28.8) in the high SES. Surprisingly, ZIKV seroprevalence rapidly increased with age in the low and intermediate SES, while exhibited only a small increase with age in high SES. CHIKV seroprevalence according to age was stable in all SES. The prevalence of serological markers of ZIKV and CHIKV recent infections were 1.5% (CI95%:0.1-3.7) and 3.5% (CI95%:2.7-4.2), respectively., Conclusions: Our results confirmed continued DENV transmission and intense ZIKV and CHIKV transmission during the 2015/2016 epidemics followed by ongoing low-level transmission. The study also highlights that a significant proportion of the population is still susceptible to be infected by ZIKV and CHIKV. The reasons underlying a ceasing of the ZIKV epidemic in 2017/18 and the impact of antibody decay in susceptibility to future DENV and ZIKV infections may be related to the interplay between disease transmission mechanism and actual exposure in the different SES., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Braga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBDs) with multifactorial causes. They are becoming more prevalent in developing countries such as Brazil; however, relevant studies in poorer regions of the country are limited. Here, we report the clinical-epidemiological profile of patients with IBD treated at reference centers in three states of Northeast Brazil., Patients and Methods: This was a prospective cohort study involving patients at referral outpatient clinics for IBD from January 2020 through December 2021., Results: Of 571 patients with IBD, 355 (62%) had UC, and 216 (38%) had CD. The patients were predominantly women (355, 62%) for both UC and CD. Extensive colitis was the pattern present in 39% of the UC cases. For CD, ileocolonic disease was the predominant manifestation (38%), with 67% of cases showing penetrating and/or stenosing behavior. The majority of patients were diagnosed between the ages of 17 and 40, corresponding to 60.2% in CD and 52.7% in UC. The median time between symptom onset and diagnosis was 12 months for CD and 8 months for UC ( p =0.042). Joint involvement was the most frequent extraintestinal manifestation, with arthralgia and arthritis present in 41.9% and 18.6% of the patients, respectively. Biological therapy was prescribed to 73% of CD patients and 26% of UC patients. A progressive increase in new cases was observed in every 5-year interval over the last five decades, with 58.6% being diagnosed in the last 10 years., Conclusion: More extensive disease behavior patterns predominated in UC, while forms associated with complications were prevalent in CD. A prolonged time to diagnosis may have contributed to these findings. A progressive increase in IBD incidence was observed and may be related to greater urbanization and better access to specialized outpatient clinics, resulting in improvements in diagnosis., Competing Interests: Dr Lívia Medeiros Soares Celani reports grants from Takeda Pharmaceutical Company, during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2023 Brito et al.)

Background: In addition to their direct pathogenic effects, arthropod-borne (arboviruses) have been hypothesized to indirectly contribute to hospitalizations and death through decompensation of pre-existing comorbidities. Using nationwide data routinely collected from 1 January 2014 to 31 December 2019 in Brazil, we investigated whether local increases in arbovirus notifications were associated with excess hospitalization., Methods: We estimated the relative risks for the association between municipality- and state-level increases in arboviral case notifications and age-standardized hospitalization rates (i.e., classified as direct or indirect based on ICD-10 codes) using Bayesian multilevel models with random effects accounting for temporal and geographic correlations. For municipality-level analyses, we excluded municipalities with <200 notifications of a given arbovirus and further adjusted the models for the local Gini Index, Human Development Index, and Family Healthcare Strategy (Estratégia de Saúde da Família) coverage. Models for dengue, Zika, and chikungunya were performed separately., Results: From 2014 to 2019, Brazil registered 7,566,330 confirmed dengue cases, 159,029 confirmed ZIKV cases, and 433,887 confirmed CHIKV cases. Dengue notifications have an endemic and seasonal pattern, with cases present in 5334 of the 5570 (95.8%) Brazilian municipalities and most (69.5%) registered between February and May. Chikungunya notifications followed a similar seasonal pattern to DENV but with a smaller incidence and were restricted to 4390 (78.8%) municipalities. ZIKV was only notified in 2581 (46.3%) municipalities. Increases in dengue and chikungunya notifications were associated with small increases in age-standardized arbovirus-related hospitalizations, but no consistent association was found with all-cause or other specific indirect causes of hospitalization. Zika was associated to increases in hospitalizations by neurological diseases., Conclusions: Although we found no clear association between increased incidence of the three arboviruses and excess risks of all-cause or indirect hospitalizations at the municipality- and state-levels, follow-up investigations at the individual-level are warranted to define any potential role of acute arbovirus infection in exacerbating risks of hospitalization from underlying conditions., Competing Interests: The authors have declared that no competing interests exist.

Background: Zika virus infection is commonly described as a mild and self-limiting illness. However, cardiac complications were associated with acute Zika virus infection., Case Presentation: A 46-year-old woman without previous comorbidities with a 1-day history of symptoms tested positive for ZIKV by real time reverse transcriptase polymerase chain reaction (rRT-PCR). She was admitted two days after with clinical worsening, cardiac enzymes elevated, and cardiac imaging findings, and the diagnosis of myopericarditis was made. The patient was treated and presented significant clinical improvement after one year., Conclusions: Cardiac complication following ZIKV infection appears to be infrequent. Here, we report a rare case of viral myopericarditis caused by ZIKV infection., (© 2022. The Author(s).)

Introduction: Since the first reports of coronavirus disease 2019 (COVID-19) in December 2019, the disease has spread worldwide. Different social isolation strategies have been adopted to reduce community transmission, but few studies have evaluated the pattern of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection in a family cluster during periods of isolation. We report an outbreak in 24 members of a family cluster during a period of social distancing., Methodology: We carried out an observational descriptive study of a family cluster infected with SARS-CoV-2 in Pernambuco, Northeast Brazil. Laboratory confirmation included RT-PCR of nasopharyngeal samples or IgM or IgG serology., Results: The attack rates were 75% (19/24) based on laboratory-confirmed cases and 87.5% (21/24) including probable cases. The time of spread was 17 days from the first case. All patients had mild symptoms, requiring no hospitalization, and none of them died. The frequency of symptomatic, laboratory-confirmed patients was higher among adults (94%) than among children (50%); the paediatric age group also had a higher frequency of exposed individuals who remained negative for infection. Ground-glass opacities on chest computed tomography were present in all patients with reported dyspnoea., Conclusion: This study highlights a high risk of intrahousehold transmission from an index case, suggesting the need for (I) specific guidelines during periods of social distancing, (II) minimization of external exposures and, above all, (III) adoption of strict quarantine measures for suspected cases and family members to prevent outbreaks from spreading., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Carlos Alexandre Antunes de Brito, Marina Coelho Moraes de Brito, Thiago Henrique Fernandes Martins, Cecilia Coelho Moraes de Brito, Maria Fatima Militao Albuquerque , Rita de Cassia Coelho Moraes de Brito.)

Chikungunya fever (CHIK) has caused important epidemic outbreaks in the Americas, with musculoskeletal involvement being the main manifestation, causing chronic symptoms in half of the affected patients. This study was performed to evaluate the clinical course of the infection in 168 patients with autoimmune inflammatory disease using biological disease-modifying antirheumatic drugs (bDMARDs), comparing this group with 56 household controls. Anti-CHIKV IgG serology was positive in 42 (25%) of the patients in the bDMARD group and in 15 (27%) of the controls ( p =0.79). Of those with positive serology, 32 (76%) and 14 (93%) were symptomatic among subjects in the bDMARD and control groups, respectively ( p =0.87). Persistence of musculoskeletal symptoms for more than three months occurred in 64% of the patients in the control group and only in 28% in the bDMARD group ( p =0.021), maintaining a statistically significant difference only for users of anti-TNF. This study found that patients affected by chikungunya fever using bDMARDs did not present severe forms or complications in the acute phase of the disease, and patients using anti-TNF biologicals had a lower frequency of chronic joint symptoms than the household controls. This favorable outcome may be related to the cytokine blockade, with a reduction in the inflammatory response and joint damage., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Carlos A. A. de Brito et al.)

In 2013, cases of chikungunya virus (CHIKV) infection were first detected in the Caribbean. Chikungunya virus rapidly spread through Central and South America, causing explosive outbreaks in naive populations. Since its emergence in 2004, the number of case and series reports describing severe, atypical manifestations seen in chikungunya patients has increased substantially, calling into question whether clinicians and health services are failing to diagnose these atypical cases because of not only insufficient knowledge but also limitations in the case classification. Although this classification based on the duration of the musculoskeletal (acute, subacute, and chronic forms) complaints helped guide therapeutic approaches directed to these manifestations, patients presenting severe or complicated forms, which are less frequent but produce most of the fatal outcomes, were not properly addressed. In Brazil and the Caribbean, a clear temporal and spatial association between excess overall mortality and the occurrence of chikungunya epidemics has been shown, supporting the hypothesis that many of these excess deaths were a consequence of CHIKV infections. Thus, accumulated experience has highlighted that the current chikungunya case classification does not encompass the actual needs presented by certain cases with atypical features nor does it contribute to early detection and management of potentially severe cases. With continued CHIKV circulation in three continents and recent reemergence in Asia and Europe, we need a classification that is prospective and informed both by initial clinical presentation and by progression of signs and symptoms.

Since the emergence of the chikungunya virus in Brazil in 2014, more than 700,000 cases have been reported throughout the country, corresponding to one-third of all cases reported in the Americas. In addition to its high attack rates, resulting in hundreds of thousands of cases, the disease has high chronicity rates with persistent joint manifestations for more than 3 months, which can spread to more than half of the patients affected in the acute phase. Pain associated with musculoskeletal manifestations, often disabling, has an effect on patients' quality of life at different stages of the disease. Currently, the challenge faced by specialists is identifying the best therapy to be instituted for symptom relief despite the limited number of published intervention studies. In 2016, a multidisciplinary group published pharmacological treatment protocols for pain in patients with chikungunya, which was incorporated into the guidelines for clinical management of the Brazilian Ministry of Health in 2017; in that same year, a consensus was published by the Brazilian Society of Rheumatology about diagnosis and treatment. After 5 years of experience with chikungunya epidemics, in 2019, specialists involved in the protocols of the Brazilian Society of Rheumatology and Brazilian Ministry of Health prepared an update with the main objective of developing flowcharts for the therapeutic approach of musculoskeletal manifestations in adult patients to enable specialists at different levels of healthcare to spread and apply this guideline in a systematic and simplified manner.

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.

Background: Zika virus (ZIKV) is a recently emerged arbovirus, which infection during pregnancy is associated with a series of congenital malformations, collectively denominated Congenital Zika Syndrome (CZS). Following infection, ZIKV RNA has a median duration period of 10 days in plasma and up to 6 months in semen in immunocompetent adult individuals. Moreover, ZIKV is able to replicate and persist in fetal brains and placentas, consequently, infection is associated with pregnancy loss, albeit the pathogenic mechanisms are still unknown., Case Presentation: Here we report a CZS case of an infant born during the ZIKV outbreak in northeast Brazil, the child presented recurrent episodes of seizures with prolonged presence of ZIKV RNA on the central nervous system (CNS) and blood. ZIKV RNA was identified and partially sequenced from a sample of cerebrospinal fluid (CSF) obtained from the infant with 6 months of life, and later from another sample after the infant completed 17 months of life. Commonly congenital infections were discarded based on STORCH (syphilis, toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus) negative laboratory results. Presence of specific ZIKV antibodies on both mother and children confirmed the association of severe microcephaly and ZIKV infection, diagnosed after birth., Conclusions: Altogether, our data raise the possibility that CZS cases may result in prolonged viral presence, these findings could be useful for therapy and diagnostic recommendations.

Chikungunya has had a substantial impact on public health because of the magnitude of its epidemics and its highly debilitating symptoms. We estimated the seroprevalence, proportion of symptomatic cases, and proportion of chronic form of disease after introduction of chikungunya virus (CHIKV) in 2 cities in Brazil. We conducted the population-based study through household interviews and serologic surveys during October-December 2015. In Feira de Santana, we conducted a serologic survey of 385 persons; 57.1% were CHIKV-positive. Among them, 32.7% reported symptoms, and 68.1% contracted chronic chikungunya disease. A similar survey in Riachão do Jacuípe included 446 persons; 45.7% were CHIKV-positive, 41.2% reported symptoms, and 75.0% contracted the chronic form. Our data confirm intense CHIKV transmission during the continuing epidemic. Chronic pain developed in a high proportion of patients. We recommend training health professionals in management of chronic pain, which will improve the quality of life of chikungunya-affected persons.

Since the detection of the Chikungunya virus in America in 2013, two million cases of the disease have been notified worldwide. Severe cases and deaths related to Chikungunya have been reported in India and Reunion Island, estimated at 1 death per 1,000 inhabitants. Joint involvement in the acute and chronic phase is the main clinical manifestation associated with Chikungunya. The severity of the infection may be directly attributable to viral action or indirectly, owing to decompensation of preexisting comorbidities. In Brazil, the virus was identified in 2014, and recently, there has been a significant increase in the number of deaths caused by the Chikungunya virus infection, especially in Pernambuco. However, the numbers of fatalities are probably underreported, since for many cases, the diagnosis of Chikungunya infection may not be considered, for deaths by indirect causes. An increase in the mortality rate within months of epidemic occurrence, compared to previous years has also been reported and may be associated with Chikungunya virus infection. An in-depth investigation of reported mortality in Brazil is necessary, to measure the actual impact of the deaths, thereby, allowing the identification of possible causes. This will alert professionals about the risks, and hence, enable creation of protocols that target reducing mortality.

In early 2016, it was suspected that there were more deaths in Pernambuco than in previous years during an epidemic of chikungunya. This study tested whether there was an increased number of deaths and, if so, whether this increase could be related to a chikungunya epidemic. Indeed, there was an increase of 4235 deaths in 2016 compared to the average of the four previous years, and the highest differences were found during the peak period of the epidemic. It was evident that not all of these deaths could be attributed to complications of chikungunya. However, considering the temporal overlap, some of these deaths may have been caused by the aggravation of pre-existing comorbidities or complications caused directly by chikungunya virus infection.