Myopericarditis associated with acute Zika virus infection: a case report.

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.

The neurological complications of chikungunya virus: A systematic review.

We performed a systematic review on the neurological complications of chikungunya virus. Such complications are being reported increasingly, owing primarily to the scale of recent epidemics but also to a growing understanding of the virus' neurovirulence. We performed a thorough literature search using PubMed and Scopus databases, summating the data on all published reports of neurological disease associated with chikungunya virus. We appraised the data for each major condition in adults, children, and neonates, as well as evaluating the latest evidence on disease pathogenesis and management strategies. The review provides a comprehensive summary for clinicians, public health officials, and researchers tackling the challenges associated with this important emerging pathogen.

Lessons Learned at the Epicenter of Brazil's Congenital Zika Epidemic: Evidence From 87 Confirmed Cases.

Congenital Zika virus infection has stimulated great international concern. A prospective case series of 87 infants with laboratory-confirmed congenital Zika syndrome (CZS) at the epicenter of the Brazilian Zika epidemic in Pernambuco state is presented. Mothers were interviewed for symptoms of possible Zika virus (ZIKV) infection during pregnancy, and fetal ultrasounds were obtained. Infant cerebrospinal fluid (CSF) samples were tested for ZIKV-specific antibodies, and sera were screened for other congenital infections. Neuroimaging and ophthalmologic evaluations were also performed. Sixty-six mothers (76%) reported symptoms of ZIKV infection during gestation. Fetal ultrasounds were available from 90% of the mothers, and all demonstrated brain structural abnormalities. All of the CSF samples tested positive for ZIKV immunoglobulin M. The majority of infants (89%) were term; the mean birth weight was 2577 ± 260 g, and the mean head circumference was 28.1 ± 1.8 cm. Severe microcephaly, defined as head circumference 3 SD below the mean for sex and gestational age, was found in 72 (82%) infants. All infants had an abnormal neurological exam, and 18 (20.7%) had arthrogryposis. The main abnormalities detected in computed tomography scans were calcifications (99%), followed by ventricular enlargement (94%), cortical hypogyration (81%), and less commonly, cerebellar hypoplasia (52%). Unilateral diaphragm paralysis was identified in 3 infants. Maternal young age, term infant, small for gestational age, and the presence of ophthalmologic abnormalities were significantly associated with a smaller head circumference Z score. Our findings, based on laboratory-confirmed ZIKV infection, add valuable evidence for the understanding of CZS.

Increased number of deaths during a chikungunya epidemic in Pernambuco, Brazil.

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.

Prevalence of cagA, cagM, vacA and oipA genes in isolates of Helicobacter pylori obtained from hospital patients in Northeast Brazil.

Helicobacter pylori is a major cause of gastrointestinal disorders such as chronic gastritis, peptic ulcers, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. It is estimated that around half of the world's population is infected with this pathogen, with underdeveloped countries reporting the highest frequencies. The genes cagA, cagM, vacA, and oipA are some of the most important virulence factors of H. pylori; however, there are no recent studies from Recife-PE demonstrating their frequency, and their relationship with severe gastric modifications. This work aims to use qualitative PCR to detect the virulence genes cagA, cagM, vacA, and oipA in H. pylori isolates obtained from patients in a public hospital in Recife (PE). We collected samples from the stomach's body and antrum of 147 patients, from which 71 (48%) tested positive for H. pylori. Among positive samples, the most frequently infected gender was female (44/71, 62%), and the most frequently infected age group was those above the age of 46 (31/71, 44%). Histological examination of H. pylori-positive samples revealed alterations other than chronic gastritis, including metaplasia and atrophy. The frequency of cagA, cagM, and oipA genes were identified in 84%, 56%, and 69% of the samples tested, respectively, as well as the vacA-s1m1 allelic combination (77%). However, there was no statistically significant variation in the occurrence of these genes, therefore they cannot be considered unique markers of severity in our setting. New research with larger samples and investigations of other genetic markers can aid uncover local risk factors and lead to a better understanding of H. pylori's pathogenesis.

Safety and immunogenicity of a live-attenuated chikungunya virus vaccine in endemic areas of Brazil: interim results of a double-blind, randomised, placebo-controlled phase 3 trial in adolescents.

BACKGROUND: Chikungunya outbreaks have been reported in Brazil since 2014. Adolescents are a sensitive population who would benefit from a prophylactic vaccine. This study assessed the immunogenicity and safety of the vaccine VLA1553 in adolescents in Brazil. With an overall trial duration of 12 months, we now report data on safety and immunogenicity over a period of 28 days after vaccination. METHODS: In this double-blind, randomised, placebo-controlled phase 3 trial, adolescents aged 12 to <18 years were recruited. The trial was performed at ten trial sites across Brazil. Eligible participants were generally healthy. The main exclusion criteria comprised immune-mediated or chronic arthritis or arthralgia, a known or suspected defect of the immune system, or any live vaccine received within the 4 weeks before trial vaccination. Randomisation was stratified by baseline serostatus in a 2:1 ratio to receive VLA1553 (at a dose of 1 × 104 TCID50 per 0·5 mL [ie, 50% tissue culture infectious dose]) or placebo. VLA1553 or placebo was administered intramuscularly as a single-dose immunisation on day 1. The primary endpoint was the proportion of baseline seronegative participants with chikungunya virus neutralising antibody levels of 150 or more in µPRNT50 (a micro plaque reduction neutralisation test), which was considered a surrogate of protection. The safety analysis included all participants receiving a trial vaccination. Immunogenicity analyses were performed in a subset. The trial is registered with ClinicalTrials.gov, NCT04650399. FINDINGS: Between Feb 14, 2022, and March 14, 2023, 754 participants received a trial vaccination (502 received VLA1553 and 252 received placebo) with a per-protocol population of 351 participants for immunogenicity analyses (303 in the VLA1553 group and 48 in the placebo group). In participants who were seronegative at baseline, VLA1553 induced seroprotective chikungunya virus neutralising antibody levels in 247 of 250 (98·8%, 95% CI 96·5-99·8) participants 28 days after vaccination. In seropositive participants, the baseline seroprotection rate of 96·2% increased to 100% after vaccination with VLA1553. Most (365 [93%] of 393) adverse events were of mild or moderate intensity, VLA1553 was generally well tolerated. When compared with placebo, participants exposed to VLA1553 had a significantly higher frequency of related adverse events (351 [69·9%] of 502 vs 121 [48·0%] of 252; p<0·0001), mostly headache, myalgia, fatigue, and fever. Among four reported serious adverse events (three in the VLA1553 group and one in the placebo group), one was classified as possibly related to VLA1553: a high-grade fever. Among 20 adverse events of special interest (ie, symptoms suggesting chikungunya-like disease), 16 were classified as related to trial vaccination (15 in the VLA1553 group and one in the placebo group), with severe symptoms reported in four participants (fever, headache, or arthralgia). 17 adverse events of special interest resolved within 1 week. Among 85 participants with arthralgia (68 in the VLA1553 group and 17 in the placebo group), eight adolescents had short-lived (range 1-5 days), mostly mild recurring episodes (seven in the VLA1553 group and one in the placebo group). The median duration of arthralgia was 1 day (range 1-5 days). The frequency of injection site adverse events for VLA1553 was higher than in the placebo group (161 [32%] vs 62 [25%]), but rarely severe (two [<1%] in the VLA1553 group and one [<1%] in the placebo group). After administration of VLA1553, there was a significantly lower frequency of solicited adverse events in participants who were seropositive at baseline compared with those who were seronegative (53% vs 74%; p<0·0001) including headache, fatigue, fever, and arthralgia. INTERPRETATION: VLA1553 was generally safe and induced seroprotective titres in almost all vaccinated adolescents with favourable safety data in adolescents who were seropositive at baseline. The data support the use of VLA1553 for the prevention of disease caused by the chikungunya virus among adolescents and in endemic areas. FUNDING: Coalition for Epidemic Preparedness Innovation and EU Horizon 2020. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Body Mass Index Profile of Adult Patients with Inflammatory Bowel Disease in a Multicenter Study in Northeastern Brazil.

Purpose: 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.

A Multicentre Study of the Clinical and Epidemiological Profile of Inflammatory Bowel Disease in Northeast Brazil.

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.

Atypical Forms of Pyoderma Gangrenosum in Inflammatory Bowel Disease: Report of Four Cases and Literature Review.

Background: 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.

Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study.

OBJECTIVE: To determine the clinical phenotype of Guillain-Barré syndrome (GBS) after Zika virus (ZIKV) infection, the anti-glycolipid antibody signature, and the role of other circulating arthropod-borne viruses, we describe a cohort of GBS patients identified during ZIKV and chikungunya virus (CHIKV) outbreaks in Northeast Brazil. METHODS: We prospectively recruited GBS patients from a regional neurology center in Northeast Brazil between December 2014 and February 2017. Serum and CSF were tested for ZIKV, CHIKV, and dengue virus (DENV), by RT-PCR and antibodies, and serum was tested for GBS-associated antibodies to glycolipids. RESULTS: Seventy-one patients were identified. Forty-eight (68%) had laboratory evidence of a recent arbovirus infection; 25 (52%) ZIKV, 8 (17%) CHIKV, 1 (2%) DENV, and 14 (29%) ZIKV and CHIKV. Most patients with a recent arbovirus infection had motor and sensory symptoms (72%), a demyelinating electrophysiological subtype (67%) and a facial palsy (58%). Patients with a recent infection with ZIKV and CHIKV had a longer hospital admission and more frequent mechanical ventilation compared to the other patients. No specific anti-glycolipid antibody signature was identified in association with arbovirus infection, although significant antibody titres to GM1, GalC, LM1, and GalNAc-GD1a were found infrequently. CONCLUSION: A large proportion of cases had laboratory evidence of a recent infection with ZIKV or CHIKV, and recent infection with both viruses was found in almost one third of patients. Most patients with a recent arbovirus infection had a sensorimotor, demyelinating GBS. We did not find a specific anti-glycolipid antibody signature in association with arbovirus-related GBS.

Second Episode of COVID-19 in Health Professionals: Report of Two Cases.

Although primary infection has been shown to prevent reinfection of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in animal models, gaps in the understanding of the immune response to the virus have not been adequately addressed, and some cases of possible reinfection have been reported; however, the frequency, relevance and proof of these events have yet to be determined. We report cases of two doctors who had two episodes of COVID-19 with positive RT-PCR (reverse transcriptase polymerase chain reaction) test results, raising the probability of reinfection. Case 1 was a 40-year-old male physician who presented fever and respiratory symptoms on April 10, with a positive RT-PCR test for SARS-CoV-2, with complete improvement of symptoms in five days. After 44 days, the patient presented the same symptoms of the previous episode, associated with anosmia and dysgeusia. The results of a new RT-PCR test performed two days later were positive for SARS-CoV-2. Case 2 was a 44-year-old female physician who worked in a reference clinic for COVID-19 (coronavirus disease 2019) and had onset of symptoms indicative of the disease on April 30. The RT-PCR test was positive for SARS-CoV-2, with improvement of symptoms in six days. On May 24, the patient presented fever, cough, and sore throat accompanied by headache, asthenia, myalgia, and diarrhea, and in this new episode, anosmia and dysgeusia were also present. A new RT-PCR test from nasopharyngeal swabs was performed with a positive result. Our two patients described here and other patients with possible reinfection who are now being observed in clinical practice reinforce the need to expand the investigation. Then, if the risk of reinfection is confirmed, these findings will be relevant from a clinical-epidemiological perspective to define isolation strategies and develop vaccines.

Clinical laboratory and dispersion pattern of COVID-19 in a family cluster in the social-distancing period.

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.

Chikungunya Case Classification after the Experience with Dengue Classification: How Much Time Will We Lose?

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.

Update on the treatment of musculoskeletal manifestations in chikungunya fever: a guideline.

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.

Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: a prospective observational study.

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

Updated Imaging Findings in Congenital Zika Syndrome: A Disease Story That is Still Being Written.

In congenital Zika virus syndrome (CZS), the most frequent radiological findings are calcifications in the cortical-white matter junction and malformations of cortical development (pachygyria or polymicrogyria, which occur predominantly in the frontal lobes, or a simplified gyral pattern), ventriculomegaly, enlargement of the cisterna magna and the extra-axial subarachnoid space, corpus callosum abnormalities, and reduced brain volume. This syndrome can also result in a decrease in the brainstem and cerebellum volumes and delayed myelination. Infants with CZS may show venous thrombosis and lenticulostriate vasculopathies. Over a 3-year follow-up period, many infants with CZS showed hydrocephalus, reduction in brain calcifications, and greater reduction in brain thickness.

HLA-G is expressed in intestinal samples of ulcerative colitis and Crohn's disease patients and HLA-G5 expression is differentially correlated with TNF and IL-10 cytokine expression.

HLA-G is an immunomodulatory molecule that can be produced by epithelial cells. Considering that TNF and IL-10 participate in bowel inflammatory disorders and that both cytokines modulate HLA-G, we evaluated HLA-G, TNF and IL-10 mRNA expression by qPCR and HLA-G protein levels by immunohistochemistry in two intestinal samples exhibiting different degree of inflammation within a patient suffering from Crohn's disease (CD) or ulcerative colitis (UC). Tissue HLA-G5 (P < 0.0001), TNF (P = 0.0004) and IL-10 (P = 0.0169) mRNA expression levels were higher in intestinal areas exhibiting intense inflammation compared to areas of low inflammation, and HLA-G protein levels were not associated with degree of mucosal inflammation. In CD, the expression of TNF was correlated with IL-10 in low inflamed areas, exhibiting a TNF:IL-10 ratio = 3, but in inflamed areas the ratio increased to 9-folds. In UC, the expression of TNF was correlated to IL-10, irrespective of the inflammation grade, with little variation of the TNF:IL-10 ratio in the various inflamed areas. TNF and IL-10 expression was correlated with HLA-G5 expression in mild inflamed areas. Both CD and UC samples exhibited gene and protein expression of HLA-G; and the HLA-G5 expression is differentially correlated with TNF and IL-10 levels depending on the type of the underlying inflammatory bowel disorder.

The microcephaly epidemic and Zika virus: building knowledge in epidemiology. / Epidemia de microcefalia e vírus Zika: a construção do conhecimento em epidemiologia.

In August 2015, pediatric neurologists at public hospitals in Recife, Pernambuco State, Brazil, observed an increase in the number of disproportional microcephaly cases associated with other congenital anomalies. The fact caused social commotion and mobilization of the academic community and led the Brazilian Ministry of Health to declare a national public health emergency, followed by the declaration of a Public Health Emergency of International Concern by the World Health Organization. The hypothesis for the phenomenon was congenital Zika virus (ZIKV) infection, based on spatial-temporal correlation and the clinical-epidemiological characteristics of the two epidemics. Further evidence accumulated, and within the scope of epidemiologial reasoning fulfilled criteria that gave support to the hypothesis. The plausibility of the hypothesis is based on the neurotropism of ZIKV, demonstrated in animals, affecting neural progenitors in the developing brain, and in humans, due to neurological complications in adults following infection. Isolation of viral RNA and antigens in the amniotic fluid of infected mothers and in brains of newborns and fetuses with microcephaly further demonstrated the consistency of the hypothesis. The criterion of temporality was met by identifying adverse pregnancy outcomes in a cohort of mothers with a history of rash and positive ZIKV serology. Finally, the first case-control study demonstrated a strong association between microcephaly and congenital ZIKV infection. The knowledge built with the epidemiological paradigm was supported by the scientific community, thereby establishing the consensus for a causal relationship between ZIKV and the microcephaly epidemic.

Em agosto de 2015, neuropediatras de hospitais públicos do Recife, Pernambuco, Brasil, observaram um aumento do número de casos de microcefalia desproporcional associado a anomalias cerebrais. Esse fato gerou comoção social, mobilização da comunidade acadêmica e levou o Ministério da Saúde a decretar emergência de saúde pública nacional, seguida pela declaração de emergência de saúde pública de interesse internacional da Organização Mundial da Saúde. A hipótese formulada para o fenômeno foi a infecção congênita pelo vírus Zika (ZIKV), com base na correlação espaço-temporal e nas características clínico-epidemiológicas das duas epidemias. Evidências se acumularam e no âmbito do raciocínio epidemiológico preencheram critérios que deram sustentação à hipótese. Sua plausibilidade está ancorada no neurotropismo do ZIKV demonstrado em animais, atingindo neurônios progenitores do cérebro em desenvolvimento, e em seres humanos devido às complicações neurológicas observadas em adultos após a infecção. O isolamento do RNA e antígenos virais no líquido amniótico de mães infectadas e em cérebros de neonatos e fetos com microcefalia contribuíram para demonstrar a consistência da hipótese. O critério de temporalidade foi contemplado ao se identificar desfechos desfavoráveis em uma coorte de gestantes com exantema e positivas para o ZIKV. Finalmente, o primeiro estudo caso-controle conduzido demonstrou existir uma forte associação entre microcefalia e infecção congênita pelo ZIKV. O conhecimento construído no âmbito do paradigma epidemiológico recebeu a chancela da comunidade científica, construindo o consenso de uma relação causal entre o ZIKV e a epidemia de microcefalia.

En agosto de 2015, neuropediatras de hospitales públicos de Recife, Pernambuco, Brasil, observaron un aumento desproporcional del número de casos de microcefalia, asociado a anomalías cerebrales. Este hecho generó conmoción social, movilización de la comunidad académica y obligó al Ministerio de Salud a decretar la emergencia de salud pública nacional, seguida de la declaración de interés internacional de la Organización Mundial de la Salud. La hipótesis formulada para este fenómeno fue la infección congénita por el virus Zika (ZIKV), en base a la correlación espacio-temporal y a las características clínico-epidemiológicas de las dos epidemias. Se acumularon evidencias, y en el ámbito del raciocinio epidemiológico se cumplieron los criterios que dieron apoyo a la hipótesis. Su plausibilidad está anclada en el neurotropismo del ZIKV, demostrado en animales, alcanzando progenitores neuronales del cerebro en desarrollo, y en seres humanos, debido a las complicaciones neurológicas observadas en adultos tras la infección. El aislamiento del ARN y antígenos virales en el líquido amniótico de madres infectadas, en cerebros de neonatos y fetos con microcefalia, contribuyeron a demostrar la consistencia de la hipótesis. El criterio de temporalidad se contempló al identificarse desenlaces desfavorables en una cohorte de gestantes con exantema y positivas en ZIKV. Finalmente, el primer estudio caso-control realizado demostró que existía una fuerte asociación entre microcefalia e infección congénita por el ZIKV. El conocimiento construido en el ámbito del paradigma epidemiológico recibió la aprobación de la comunidad científica, existiendo consenso en cuanto a la relación causal entre el ZIKV y la epidemia de microcefalia.

Alert: Severe cases and deaths associated with Chikungunya in Brazil.

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.