Multi-epitope Antigen for Specific Serological Detection of Dengue Viruses.

Dengue is an infectious disease of global health concern that continues to require surveillance. Serological testing has been used to investigate dengue-infected patients, but specificity is affected by the co-circulation of ZIKA virus (ZIKV), which shares extensive antigen similarities. The goal of this study was the development of a specific dengue virus (DENV) IgG ELISA based on a multi-epitope NS1-based antigen for antibody detection. The multi-epitope protein (T-ΔNS1), derived from a fragment of the NS1-protein of the four DENV serotypes, was expressed in Escherichia coli and purified via affinity chromatography. The antigenicity and specificity were evaluated with sera of mice infected with DENV-1-4 or ZIKV or after immunization with the recombinant ΔNS1 proteins. The performance of the T-ΔNS1-based IgG ELISA was also determined with human serum samples. The results demonstrate that the DENV T-ΔNS1 was specifically recognized by the serum IgG of dengue-infected mice or humans but showed no or reduced reactivity with ZIKV-infected subjects. Based on the available set of clinical samples, the ELISA based on the DENV T-ΔNS1 achieved 77.42% sensitivity and 88.57% specificity. The results indicate that the T-ΔNS1 antigen is a promising candidate for the development of specific serological analysis.

Neuroimaging findings using transfontanellar ultrasound in newborns with microcephaly: a possible association with congenital Zika virus infection.

OBJECTIVE: The objective of this study is to determine the main neuroimaging findings of microcephalic newborns with possible Zika virus (ZIKV) intrauterine infection using transfontanellar cranial ultrasound. METHODS: We performed a retrospective study to describe the main neuroimaging findings in newborns with microcephaly and possible association with congenital ZIKV infection. Microcephaly was defined in the postnatal period using transfontanellar cranial examination which was performed using both two- (2D) and three-dimensional (3D) ultrasound. RESULTS: One hundred and fifty newborns with microcephaly were identified during the study period. The mean ± (standard deviation - SD) of cephalic perimeter was 28.5 ± 4.2 cm (range, 25-38 cm). Transfontanellar neuroimaging patterns detected cerebral calcifications, neuronal migrational abnormalities, dysgenesis of the corpus callosum, and cerebellar atrophy in 34.9%, 31.1%, 26%, and 16.2%, respectively. Hydrocephalus was seen in 28% of overall newborns. A history of maculopapular rash was present in almost half of the mothers (46.1%). CONCLUSION: Neuroimaging patterns by means of transfontanellar ultrasound are accurate and diagnostic investigations of brain pathology in newborns affected by microcephaly and possible intrauterine ZIKV infection.

Association of Severe Hydrocephalus With Congenital Zika Syndrome.

Importance: Hydrocephalus is a treatable but potentially fatal complication that has not been previously described in congenital Zika syndrome (CZS). Objective: To describe the clinical features and imaging findings in 24 patients with congenital Zika syndrome (CZS) who developed hydrocephalus. Design, Setting, and Participants: This case series included patients with hydrocephalus who were born in October and November 2015 and followed up until mid-2017 in the 2 largest national referral centers for CZS in Brazil. The participants included consecutively enrolled children with a clinical and laboratorial diagnosis of CZS who developed clinical and/or image findings suggestive of hydrocephalus and who were confirmed to experience increased intracranial hypertension during ventriculoperitoneal shunt procedures. Main Outcomes and Measures: To retrospectively describe clinical and image findings in these 24 patients. Results: This multicenter cohort included 308 patients with CZS; 24 consecutive children were enrolled in this study. These children were aged between 3 to 18 months, and 13 of 24 (54%) were female. All patients presented with at least 1 positive test result for anti-Zika antibodies in cerebrospinal fluid or serum and had classic signs of CZS. At the time of hydrocephalus diagnosis, only 14 of 24 patients (58%) had symptoms and signs suggestive of hydrocephalus (mainly worsening seizures, vomiting, irritability, and/or sudden increase of head circumference percentile). Two of 24 patients (8%) had no symptoms suggestive of hydrocephalus but were found to have reduced brain volume on repeated imaging. Cerebellar or brainstem hypoplasia on baseline imaging were found in 18 of 23 patients (78%). At the second computed tomographic scan, all patients showed a marked increase of ventricular volume, compatible with communicating hydrocephalus, and reduction of brain tissue that was visibly worse than on baseline imaging for the 23 patients with repeated scans. Conclusions and Relevance: We present evidence that hydrocephalus is a complication of CZS in at least a proportion of patients. The clinical spectrum of this condition continues to evolve, but given that presenting signs and symptoms of hydrocephalus can be challenging to recognize in CZS, we provisionally recommend that high suspicion and appropriate monitoring for hydrocephalus should be part of the standard care of patients with CZS.

Neuroimaging findings associated with congenital Zika virus syndrome: case series at the time of first epidemic outbreak in Pernambuco State, Brazil.

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

Follow-up brain imaging of 37 children with congenital Zika syndrome: case series study.

Objective To compare initial brain computed tomography (CT) scans with follow-up CT scans at one year in children with congenital Zika syndrome, focusing on cerebral calcifications.Design Case series study.Setting Barão de Lucena Hospital, Pernambuco state, Brazil.Participants 37 children with probable or confirmed congenital Zika syndrome during the microcephaly outbreak in 2015 who underwent brain CT shortly after birth and at one year follow-up.Main outcome measure Differences in cerebral calcification patterns between initial and follow-up scans.Results 37 children were evaluated. All presented cerebral calcifications on the initial scan, predominantly at cortical-white matter junction. At follow-up the calcifications had diminished in number, size, or density, or a combination in 34 of the children (92%, 95% confidence interval 79% to 97%), were no longer visible in one child, and remained unchanged in two children. No child showed an increase in calcifications. The calcifications at the cortical-white matter junction which were no longer visible at follow-up occurred predominately in the parietal and occipital lobes. These imaging changes were not associated with any clear clinical improvements.Conclusion The detection of cerebral calcifications should not be considered a major criterion for late diagnosis of congenital Zika syndrome, nor should the absence of calcifications be used to exclude the diagnosis.

Early insights into Zika's microcephaly physiopathology from the epicenter of the outbreak: teratogenic apoptosis in the central nervous system.

Fetal infection by the Zika virus has been implicated in the exceptional rise in the number of microcephalic newborns recorded by the end of 2015 in Brazil. The mechanism by which this teratogenic effect is produced in the developing brain has not been fully established. Very early in the outbreak, we addressed this question by evaluating available initial data from a gestational and postnatal clinical investigation in the Brazilian state of Pernambuco. The present study was undertaken to test the hypothesis that the subtractive dysmorphic brain malformations observed in Zika-related microcephaly are primarily due to the massive induction of apoptosis of neuroprogenitor cells. We designed a physiopathological algorithm based on the examination of the following medical findings: epidemiological data, ultrasound images, computed tomography scans, placental tissue, cerebral fluid analysis, eye fundoscopy, neurological examination and necroscopy findings.

Zika infection and the development of neurological defects.

Starting with the outbreak in Brazil, Zika virus (ZIKV) infection has been correlated with severe syndromes such as congenital Zika syndrome and Guillain-Barré syndrome. Here, we review the status of Zika virus pathogenesis in the central nervous system (CNS). One of the main concerns about ZIKV exposure during pregnancy is abnormal brain development, which results in microcephaly in newborns. Recent advances in in vitro research show that ZIKV can infect and obliterate cells from the CNS, such as progenitors, neurons, and glial cells. Neural progenitor cells seem to be the main target of the virus, with infection leading to less cell migration, neurogenesis impairment, cell death and, consequently, microcephaly in newborns. The downsizing of the brain can be directly associated with defective development of the cortical layer. In addition, in vivo investigations in mice reveal that ZIKV can cross the placenta and migrate to fetuses, but with a significant neurotropism, which results in brain damage for the pups. Another finding shows that hydrocephaly is an additional consequence of ZIKV infection, being detected during embryonic and fetal development in mouse, as well as after birth in humans. In spite of the advances in ZIKV research in the last year, the mechanisms underlying ZIKV infection in the CNS require further investigation particularly as there are currently no treatments or vaccines against ZIKV infection.

Tumor maligno primário de intestino delgado: relato de caso / Primary malignant tumor of the small intestine: a case report

Os tumores de intestino delgado são considerados raros, representando apenas 3-6% das neoplasias gastrointestinais. Em geral, possuem sintomatologia inespecífica, diagnóstico difícil e prognóstico ruim. A falta de especificidade dos sintomas e a maior dificuldade de avaliação do intestino delgado têm sido considerados como fatores que contribuem para as apresentações tardias da doença e atraso no diagnóstico. A ressecção cirúrgica é mandatória e as terapias adjuvantes trazem poucos benefícios. Relataremos o caso de uma paciente submetida à enteroscopia de duplo balão por quadro clínico de hemorragia digestiva obscura, sendo diagnosticada uma lesão neoplásica em jejuno proximal.

The small bowel tumors are considered rare, only representing 3-6% of gastrointestinal neoplasms. In general, they exhibit nonspecific symptomatology, difficult diagnosis and a bad prognosis. The lack of symptoms specificity and the small intestine evaluation difficulties are contributing factors to the late appearance of the disease as well as a late diagnosis. The surgical resection is mandatory and the adjuvant therapy offers little benefit. We report a case with clinical presentation of obscure digestive bleeding, submitted to capsule endoscopy followed by double-balloon enteroscopy being diagnosed neoplastic lesion in the proximal jejunum.

Schwannoma em pálpebra superior esquerda em criança de 10 anos / Schwannoma of the left superior eyelid in a 10-year-old child

Schwannoma é um tumor neurogênico benigno raro, originário das células de Schwann da bainha de mielina dos nervos periféricos. Sua localização nos tecidos oculares não é comum, sendo a órbita o local afetado com maior frequência e o acometimento das pálpebras é muito raro. Há poucos relatos descritos na literatura sobre Schwannoma palpebral, apenas dois em crianças. Este é, em nosso conhecimento, o primeiro caso relatado no Brasil.

Schwannoma is a rare benign neurogenic tumor. It arises from Schwann cells located at the myelin sheath of peripheral nerves. Its incidence is frequently associated with the orbit. Ocular tissues in general and eyelids in particular are rarely affected. Very few reports can be found in the literature describing eyelid schwannomas. Amongst these, we have found only two describing it affecting children. To our knowledge, this is the first case report about eyelid schwanomma in Brazil - and it involves a child.

Clinical features, histopathological analysis and surgical treatment of a free floating vitreous cyst: a case report.

The authors present a report of a 44-year-old female patient, with complaints of visual disturbances in the left eye. The symptoms were present for at least 5 years and worsened in the last 2 years, impairing her activities. The patient reported perception of a floating circle, which blurred her vision. There was no previous history of trauma, infectious or inflammatory disease. Clinical evaluation included physical examination, laboratory testing, abdominal ultrasonography, thorax X-ray and head tomography. Ophthalmologic examination consisted of visual acuity, motility tests, biomicroscopy, tonometry and indirect ophthalmoscopy. Complementary investigation was done with a and b scan ocular ultrasonography. The chosen therapeutic approach to excise the cyst was pars plana vitrectomy, successfully performed. Anatomopathologic analysis revealed a pigmented vitreous cyst, of possible congenital origin, described as a cystic choristoma from the primitive hyaloid system. Benign evolution, clinical findings and histopathological analysis corroborated the diagnostic hypothesis of a cystic choristoma of the primitive hyaloid system. Surgery (pars plana vitrectomy) was successful and the patient returned with visual acuity of 20/20 in both eyes, and with no further complaints.

Clinical features, histopathological analysis and surgical treatment of a free floating vitreous cyst: a case report / Achados clínicos, análise histopatológica e tratamento cirúrgico de cisto livre no vítreo posterior: relato de caso

The authors present a report of a 44-year-old female patient, with complaints of visual disturbances in the left eye. The symptoms were present for at least 5 years and worsened in the last 2 years, impairing her activities. The patient reported perception of a floating circle, which blurred her vision. There was no previous history of trauma, infectious or inflammatory disease. Clinical evaluation included physical examination, laboratory testing, abdominal ultrasonography, thorax X-ray and head tomography. Ophthalmologic examination consisted of visual acuity, motility tests, biomicroscopy, tonometry and indirect ophthalmoscopy. Complementary investigation was done with a and b scan ocular ultrasonography. The chosen therapeutic approach to excise the cyst was pars plana vitrectomy, successfully performed. Anatomopathologic analysis revealed a pigmented vitreous cyst, of possible congenital origin, described as a cystic choristoma from the primitive hyaloid system. Benign evolution, clinical findings and histopathological analysis corroborated the diagnostic hypothesis of a cystic choristoma of the primitive hyaloid system. Surgery (pars plana vitrectomy) was successful and the patient returned with visual acuity of 20/20 in both eyes, and with no further complaints.

Os autores apresentam relato de um caso de paciente de 44 anos, com história de dificuldade visual no olho esquerdo há 5 anos. A paciente referia a sensação de um círculo flutuando em sua visão. Os sintomas pioraram nos últimos dois anos, prejudicando suas atividades. Não havia história pessoal prévia de trauma ou de doença ocular inflamatória ou infecciosa. A avaliação clínica incluiu o exame físico, exames de laboratório, ultra-sonografia abdominal, radiografia de tórax e tomografia de crânio e o exame oftalmológico consistiu em medida de acuidade visual, testes de mobilidade, biomicroscopia, tonometria e oftalmoscopia indireta. Investigação complementar foi realizada com ultra-sonografia ocular (modo A e B). A terapêutica escolhida para exérese do cisto foi a vitrectomia via pars plana, que transcorreu sem complicações. A análise anatomopatológica revelou cisto do vítreo, pigmentado, de presumível etiologia congênita, compatível com coristoma cístico do sistema hialóide primitivo. A evolução benigna, os achados clínicos e a análise anatomopatológica reafirmam a hipótese diagnóstica de coristoma cístico do sistema hialóide primitivo. A intervenção cirúrgica (vitrectomia pars plana) obteve sucesso no tratamento da paciente, que retornou apresentando acuidade visual de 20/20 em ambos os olhos, sem outras queixas.

Liver biopsy interpretation for causes of late liver allograft dysfunction.

Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented.

Perfil epidemiológico dos pacientes submetidos a transplante de córnea de emergência em serviço de referência no estado de Pernambuco / Epidemiologic profile from patients submitted of emergency corneal transplantation in reference service of the state of Pernambuco

Objetivo: Avaliar as características epidemiológicas dos pacientes submetidos a transplante de córnea de emergência no período de 1997 a 1999. Local: Fundação Altino Ventura, Recife - Pernambuco, Brasil. Métodos: Selecionou-se os casos de transplantes de córnea de emergência realizados na Fundação Altino Ventura. Analisou-se 49 diagnósticos histopatológicos. Elaborou-se um formulário para apuração de dados clinico-epidemiológicos dos pacientes e analisou-se os resultados através do programa excel e epi-info 6.0. Resultados: Observou-se que estes transplantes foram mais prevalentes em indivíduos do sexo masculino, na faixa etária de 31 a 40 anos, procedentes da zona da mata e com profissão de agricultor e doméstica. Conclusão: As úlceras de córnea representaram uma importante etiologia dos transplantes, com predominância das bacterianas em relação às fúngicas, e que é necessário a elaboração de projetos que visam a esclarecer a população exposta ao risco de trauma de córnea de urgência, para que se possa tomar medidas preventivas eficazes.

Esquistossomose experimental em roedor silvestre (holochilus brasiliensis nanus, Thomas, 1987): estudo histopatológico na fase tardia / Schistosomiasis experimental in wild rodent (holochilus brasiliensis nanus, Thomas,1987): To studyThe histophatology of the late phase

Holochilus brasiliensis nanus, um roedor silvestre da baixada maranhense, tem sido encontrado naturalmente infectado pelo shistosoma mansoni. Para estudar a histopatologia da fase tardia da infecçäo experimental, animais criados em laboratório foram inoculados, por via intraperitoneal, com 100 cercárias de uma limhagem do S. Mansoni obtida de pacientes comprovadamente da mesma regiäo. Granulomas priovulares, sobretudo no fígado, intestino e pâncreas, foram observados em animais cm 90 dias de infecçäo, mas näo naqueles com 120 dias. Apenas um animal apresentou granulomas após 150 dias. Os resultados sugerem que, nas condiçöes experimentais utilizados, o H.brasiliensis manus é capaz de modular eficientemente a reaçäo granulomatosa periovular, näo parecendo representar um modelo adequado para o estudo da fase tardia da esquistossomose