Evaluation of herpesvirus members on hospital admission in patients with systemic lupus erythematous shows higher frequency of Epstein-Barr virus and its associated renal dysfunction / Avaliação de membros da família Herpesviridae na admissão hospitalar de pacientes com lúpus eritematoso sistêmico mostra maior frequência do vírus Epstein-Barr e sua disfunção renal associada

Abstract Introduction: Members of the Herpesviridae family have been described in patients with systemic lupus erythematous (SLE), but the clinical impact on renal function is not well known. Methods: HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8 were evaluated by molecular biology on admission in blood samples from 40 consecutive SLE patients hospitalized for lupus activity. Results: Patients were 90.0% female, 77.5% non-white, with average age of 32.7 ± 13.6 years. We found positivity for EBV (65.0%), CMV (30.0%), HSV-1 (30.0%), HHV-6 (12.5%), and HHV-7 (7.5%). For all viruses, age, SLEDAI, hematological tests, ferritin, LDH, C-reactive protein, and erythrocyte sedimentation rate (ESR) were not significant. However, EBV positivity was a significant factor for higher serum creatinine (3.0 ± 2.8 vs. 0.9 ± 0.8; P = 0.001) and urea (86 ± 51 vs. 50 ± 46; P = 0.03). Moreover, positive cases for EBV only or with combined co-infections (66.7%-CMV; 58.3%-HSV-1) or negative for EBV only were evaluated by Kruskal-Wallis test again showed statistical significance for serum creatinine and urea (both P ≤ 0.01), with posttest also showing statistical differences for renal dysfunction and EBV presence (alone or in combined co-infections). The presence of EBV viral load was also significant for nephrotic-range proteinuria, renal flare, and the need for hemodialysis. Conclusion: Members of the Herpeviridae family (mainly EBV, HSV-1 and CMV) are common on hospital admission of SLE patients, reaching 65% for EBV, which seems to be associated with renal dysfunction and could reflect a previous association or overlapping disease, which is not well understood.

Resumo Introdução: Membros da família Herpesviridae tem sido descritos em pacientes com lúpus eritematoso sistêmico (LES), mas o impacto clínico na função renal não é bem conhecido. Métodos: Avaliou-se HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8 por biologia molecular na admissão em amostras sanguíneas de 40 pacientes com LES consecutivos hospitalizados por atividade lúpica. Resultados: Pacientes 90,0% mulheres, 77,5% não brancos, idade média 32,7 ± 13,6 anos. Encontramos positividade para EBV (65,0%), CMV (30,0%), HSV-1 (30,0%), HHV-6 (12,5%), HHV-7 (7,5%). Para todos os vírus, idade, SLEDAI, exames hematológicos, ferritina, LDH, proteína C reativa, velocidade de hemossedimentação não foram significativos. Entretanto, positividade para EBV foi estatisticamente significativo para creatinina (3,0 ± 2,8 vs. 0,9 ± 0,8; P = 0,001) e ureia (86 ± 51 vs. 50 ± 46; P = 0,03) séricas mais elevadas. Ademais, casos positivos para EBV isolado ou com coinfecções combinadas (66,7%-CMV; 58,3%-HSV-1) ou negativos apenas para EBV foram avaliados pelo teste Kruskal-Wallis e novamente mostraram significância estatística para creatinina e ureia séricas (ambas P ≤ 0,01), com pós-teste mostrando também diferenças estatísticas para disfunção renal e presença de EBV (sozinho ou em coinfecções combinadas). A presença de carga viral do EBV também foi significativa para proteinúria de faixa nefrótica, inflamação aguda, necessidade de hemodiálise. Conclusão: Membros da família Herpeviridae (principalmente EBV, HSV-1, CMV) são comuns na admissão de pacientes com LES, chegando a 65% para EBV, que parece associar-se à disfunção renal podendo refletir associação prévia ou doença sobreposta, o que não é bem compreendido.

Atypical pityriasis rosea in a young colombian woman. case report

ABSTRACT Introduction: Pityriasis rosea is an acute and self-limited exanthem first described by Gilbert in 1860. Its treatment is symptomatic, and although there is no conclusive evidence, it has been associated with the reactivation of the human herpesviruses 6 and 7 (HHV-6 and HHV-7). Case presentation: A 28-year-old woman, from Bogotá, Colombia, a health worker, attended the emergency room due to the onset of symptoms that began 20 days earlier with the appearance of punctiform lesions in the left arm that later spread to the thorax, abdomen, opposite arm, and thighs. The patient reported a history of bipolar II disorder and retinal detachment. After ruling out several infectious diseases, and due to the evolution of the symptoms, pityriasis rosea was suspected. Therefore, treatment was started with deflazacort 30mg for 21 days, obtaining a favorable outcome and improvement of symptoms after 2 months. At the time of writing this case report, the patient had not consulted for recurrence. Conclusion: Primary care physicians should have sufficient training in dermatology to recognize and treat dermatological diseases since many of them are diagnosed based on clinical findings. This is an atypical case, in which the patient did not present with some of the pathognomonic signs associated with pityriasis rosea.

RESUMEN Introducción. La pitiriasis rosada es un exantema agudo y autolimitado que fue descrito formalmente por Gilbert en 1860. Su tratamiento es sintomático y, aunque faltan pruebas concluyentes, su aparición se ha asociado a la reactivación de los herpevirus humanos 7 y 6 (HHV6 y HHV7). Presentación del caso. Mujer de 28 años procedente de Bogotá, Colombia, quien se desempeñaba como trabajadora de la salud y consultó al servicio de urgencias por un cuadro clínico de 20 días de evolución que inició con la aparición de lesiones punteadas en el brazo izquierdo que se expandieron posteriormente a tórax, abdomen, brazo contralateral y muslos. La paciente informó antecedente de trastorno bipolar tipo II y desprendimiento de retina. Después de descartar varias enfermedades infecciosas, y debido a la evolución del cuadro clínico, se sospechó pitiriasis rosada, por lo que se instauró tratamiento con 30mg de deflazacort por 21 días, con el cual se logró una evolución favorable y la mejoría total de los síntomas a los 2 meses. Hasta el momento de la elaboración del presente reporte de caso la joven no había consultado por recurrencia. Conclusión. Es indispensable que los médicos de atención primaria tengan una educación adecuada en dermatología para poder reconocer y tratar la pitiriasis rosada, pues su diagnóstico es eminentemente clínico y puede tener múltiples presentaciones atípicas, como en el caso aquí reportado donde la paciente no tuvo algunos de los signos patognomónicos característicos.

Opportunistic infections in pediatrics: when to suspect and how to approach / Infecções oportunistas em pediatria: quando suspeitar e como abordar

Abstract Objectives To describe the characteristics of opportunistic infections in pediatrics regarding their clinical aspects, as well as the diagnostic strategy and treatment. Source of data Non-systematic review of literature studies in the PubMed database. Synthesis of data Opportunistic infections caused by non-tuberculous mycobacteria, fungi, Herpesvirae, and infections affecting individuals using immunobiological agents are analyzed. Because these are severe diseases with a rapid evolution, diagnostic suspicion should be early, associated with the patient's clinical assessment and history pointing to opportunistic infections. Whenever possible, samples of secretions, blood, and other fluids and tissues should be collected, with early therapy implementation. Conclusions Despite the improved diagnosis of opportunistic infections in recent years, they remain a challenge for pediatricians who are not used to these infections. They should raise the suspicion and start treating the case, but should also resort to specialists in the management of these infections to provide a better outcome for these patients, who still have high mortality.

Resumo Objetivos Descrever as características das infecções oportunistas em pediatria em seus aspectos clínicos, bem como a estratégia diagnóstica e o tratamento. Fonte dos dados Revisão de trabalhos de literatura de forma não sistemática na base de dados Pubmed. Síntese dos dados São apresentadas as infecções oportunistas causadas por micobactérias não tuberculosas, fungos, herpervírus e as infecções que acometem indivíduos em uso de imunobiológicos. Por se tratar de doenças graves e de evolução rápida, a suspeita diagnóstica deve ser precoce, associada à clínica do paciente e aos dados de história que apontam para infecções oportunistas. Sempre que possível, amostras de secreções, sangue e outros fluidos e de tecidos devem ser coletadas, com instituição precoce de terapia. Conclusões Apesar da melhoria do diagnóstico de infecções oportunistas nos últimos anos, elas ainda são um desafio para o pediatra pouco habituado a essas infecções. Ele deve fazer a suspeita e iniciar a condução do caso, mas recorrer a especialistas com prática no manejo dessas infecções de modo a propiciar um melhor desfecho para esses pacientes que ainda apresentam alta mortalidade.

Active human herpesvirus infections in adults with systemic lupus erythematosus and correlation with the SLEDAI score

Abstract Background: Human herpesviruses (HHVs) are responsible for a significant number of clinical manifestations in systemic lupus erythematous (SLE) patients. The aim of this study was to determine the frequency of active HHV infections in SLE patients and correlating them with disease activity. Methods: Serum samples were collected from 71 SLE patients and their DNAs were extracted and analyzed to detect HHV-DNA viruses using the nucleic acid amplification technique. Results: Fifteen out of the 71 (21.1%) patients tested positive for the HHV-DNA virus. Of them, 11/15 HHV-DNA-positive patients (73.3%) had SLE activity index (SLEDAI - Systemic Lupus Erythematosus Disease Activity Index) ≥8 (p = 0.0001). Active HCMV infection was the mostly frequently observed infection, occurring in 6/15 patients (40%). The frequencies of other active viral infections were 22% for HSV-1, 16.7% for HHV-7, and 5.5% for HSV-2. Viral coinfection (two or more viruses detected in the same sample) occurred in three patients (16.7%). Active HHV infections in SLE patients are more frequent in those with active SLE (≥8), who is at high risk of HHV reactivation and HCMV disease. Conclusion: Viral surveillance is important to identify active HHV infections that can cause clinical symptoms and other complication in SLE patients.

Herpes virus and Alzheimer's disease: the debate and new evidence / 中华神经科杂志

Alzheimer's disease is a chronic progressive neurodegeneration disease,currently the pathogenesis of which is not fully elucidated and no disease-modifying therapies are available.The amyloid-beta cascade hypothesis is still predominant in the field.Although has been proposed for decades,the herpes virus hypothesis remains controversial due to lack of solid evidence.New evidence supporting the hypothesis is emerging while debates remain,which would be the focus of this paper.

Detection of herpes simplex-1 and -2 and varicella zoster virus by quantitative real-time polymerase chain reaction in corneas from patients with bacterial keratitis / Detecção de vírus herpes simplex tipo 1 e 2 e varicella zoster por reação em cadeia de polimerase em tempo real em córneas de pacientes com ceratites bacterianas

ABSTRACT Objective: Bacterial keratitis occurs worldwide, and despite recent developments, it remains a potentially blinding condition. This study assesses the presence of herpes simplex virus (HSV-1 and -2) and varicella zoster virus (VZV) by quantitative real-time polymerase chain reaction (qPCR) in corneal scrapings from patients with bacterial keratitis. Methods: A total of 65 patients with clinical diagnoses of infectious corneal ulcers prospectively underwent clinical eye examinations. Corneal scrapings were investigated by Gram staining, Giemsa staining, culture, and qPCR (the study group). Risk factors and epidemiological data were recorded. The control group comprising 25 eyes with typical herpes dendritic keratitis was also analyzed by qPCR. Results: From the study group (n=65), nine patients (13.8%) had negative smears, cultures, and qPCR findings. Fifty-six (86.2%) patients had positive cultures: 51 for bacteria, 4 for fungi, and 1 for amoebae. Of the patients who had positive bacterial cultures, qPCR identified 10 patients who were also positive for virus: one for VZV and nine for HSV-1. Of the 25 patients in the control group, 21 tested positive for HSV-1 by qPCR analysis. Conclusions: Herpes may be present in patients with bacterial corneal ulcers, and qPCR may be useful in its detection.

RESUMO Objetivo: Ceratites bacterianas ocorrem mundialmente e apesar dos novos desenvolvimentos permanece como uma condição que pode levar à cegueira. Avaliar a presença de herpes simples (-1 e -2) e vírus varicella zoster (VZV) por reação em cadeia quantitativa de polimerase em tempo real (qPCR) em raspados corneanos de pacientes com ceratite bacteriana. Métodos: Sessenta e cinco pacientes com ceratite infecciosa foram submetidos a raspados corneanos estudados para gram, Giemsa, cultura e qPCR (grupo de estudo). Foram avaliados fatores de risco e epidemiológicos. O grupo controle foi composto por 25 casos de úlcera dendrítica típica por herpes analisados por qPCR. Resultados: Do grupo de estudo (n=65), nove pacientes (13,8%) apresentaram cultura, qPCR e raspado negativos. Cinquenta e seis (86,2%) pacientes apresentaram cultura positiva, 51 para bacteria, 4 para fungo e 1 para ameba. A qPCR identificou 10 pacientes do grupo de cultura positiva para bactéria que também foram positivos para vírus, um VZV e 9 para HSV-1. Dos 25 pacientes que compunham o grupo controle, 21 apresentaram qPCR positivo para HSV-1. Conclusão: Herpes pode estar presente em pacientes com úlceras de córnea bacterianas e a qPCR pode ser útil na sua detecção.

Descarga de HSV-1, HSV-2, CMV y EBV en la saliva de receptores de trasplante de precursores hematopoyéticos de la Fundación HOMI - Hospital de la Misericordia, Bogotá, DC / Shedding of HSV-1, HSV-2, CMV, and EBV in the saliva of hematopoietic stem cell transplant recipients at Fundación HOMI - Hospital de la Misericordia, Bogotá, DC

Introducción. El trasplante de precursores hematopoyéticos es una alternativa en el tratamiento de diversas condiciones en la población pediátrica. La intensidad del acondicionamiento para el trasplante predispone al desarrollo de complicaciones en los receptores. Las infecciones por el virus herpes simple 1 (HSV-1), el virus herpes simple 2 (HSV-2), el citomegalovirus (CMV) humano y el virus de Epstein-Barr (EBV) son una causa importante de morbimortalidad en estos pacientes. La reactivación de infecciones latentes puede producir descargas virales asintomáticas detectables en la saliva, lo cual ayuda a determinar el comportamiento de dichas infecciones en pacientes con trasplante y a establecer el diagnóstico temprano de la reactivación. Objetivo. Evaluar el comportamiento de la descarga viral de HSV-1, HSV-2, CMV y EBV en la saliva de pacientes hospitalizados en la Unidad de Trasplante de la Fundación HOMI - Hospital de la Misericordia, entre enero y noviembre de 2012. Materiales y métodos. Se evaluaron muestras de saliva de 17 receptores de trasplante. La presencia de ADN de HSV-1, HSV-2, CMV y EBV en las muestras de saliva se detectó mediante reacción en cadena de la polimerasa convencional. Resultados. Se detectó el ADN del HSV-2 en la saliva de cuatro pacientes, del CMV en la de cuatro y del EBV en la de nueve, lo cual se asoció con leucopenia. Cuatro de los 17 pacientes presentaron cargas simultáneas de CMV y EBV. No se detectó el ADN del HSV-1. Conclusiones: Se demostró una descarga asintomática de HSV-2, CMV y EBV asociada a leucopenia en la saliva de los pacientes.

Introduction: Hematopoietic stem cell transplantation in pediatric patients is an alternative treatment for different diseases. The conditioning regimen for transplant predisposes recipients to the development of infections. Viral infections by herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), human cytomegalovirus (CMV), and Epstein-Barr virus (EBV), are the most common, and the leading cause of morbidity and mortality among these patients. These viruses lie dormant in various cell types and the reactivation of latent infections may lead to asymptomatic viral shedding in saliva. The detection of these viruses in secretions may contribute to understand the behavioral dynamics of these viral infections in transplanted patients, and to the early diagnosis of reactivation. Objective: To assess HSV-1, HSV-2, CMV and EBV viral shedding in the saliva of patients admitted for hematopoietic stem cell transplantation at Fundación HOMI - Hospital de la Misericordia between January and November of 2012. Materials and methods: We evaluated stimulated saliva samples of 17 hematopoietic stem cell transplantation recipients weekly. We performed DNA extraction from saliva, and we evaluated the presence of DNA for HSV-1, HSV-2, CMV, and EBV by PCR. Results: While we detected HSV-2 and CMV DNA in the saliva of four patients, EBV DNA was detected in nine patients with leukopenia. In contrast, we did not detect HSV-1 DNA in saliva. Additionally, four out of the 17 patients showed a simultaneous shedding of CMV and EBV. Conclusions: By conventional PCR, we demonstrated asymptomatic HSV-2, CMV, and EBV viral shedding in saliva, associated with leukopenia.

Epidemiological surveillance of herpes viral encephalitis in Cordoba, Colombia / Vigilancia epidemiológica de encefalitis por herpes virus en Córdoba, Colombia

Objective To establish an epidemiological surveillance of viral herpes encephalitis in major hospitals of Monteria, Cordoba. Methods From September 2009 to December 2011, a descriptive study of cases of viral encephalitis was made in three hospitals in the city of Monteria. Cerebrospinal fluid (CSF) samples from 118 patients were included in the study. Clinical aspects, as well as cytochemical and microbiological analysis (Gram stain and culture) of CSF, were used for selecting the patients. Virus detection was performed by using multiplex nested PCR for Herpes simplex virus 1 and 2, Epstein Barr virus, Cytomegalovirus and Varicella zoster virus. Results Viral DNA of herpesvirus was detected in the CSFs of 30 (25.4 %) participants, as follows: 22 (18.6 %) Herpes simplex 1 and 2 viruses, 4 (3.3 %) Cytomegalovirus and 1 (0.8 %) Varicella zoster virus. Co-infections were observed in 3 patients (2.5 %), 1 case by HSV-VZV and 2 cases by CMV/HSV. The clinical manifestations of the patients included: headache (18.6 %), fever (14.4 %), asthenia (10.1 %), seizures (9.3 %), vomiting (8.4 %), and stiff neck (5.9 %). Thirty percent of the patients also had HIV-AIDS. A case fatality rate of 20 % was observed for the patients. Conclusions This paper shows that herpesvirus is a cause of infection of the CNS in patients from Cordoba. This study contributes to the epidemiology of encephalitis, as well as to patient management.(AU)

Objetivo Establecer una vigilancia epidemiológica de la encefalitis viral herpética en los principales hospitales de Montería, Córdoba. Materiales y Métodos Se realizó un estudio descriptivo de los casos de encefalitis viral entre septiembre de 2009 diciembre de 2011 en tres hospitales en la ciudad de Montería. Las muestras líquido cefalorraquídeo (LCR) de 118 pacientes fueron incluidos en el estudio. Los aspectos clínicos como el análisis citoquímico y microbiológico (tinción de Gram y cultivo) de LCR fueron utilizados para la selección de los pacientes. La detección de virus se realizó por PCR anidada multiplex para Herpes simplex virus 1 y 2, virus de Epstein Barr, virus zoster de la varicela y el citomegalovirus. Resultados Se detectó ADN viral del virus del herpes en 30 (25,4 %) muestras de LCR en los pacientes de la siguiente manera: 22 (18,6 %) Herpes simplex virus 1 y 2, 4 (3,3 %) Citomegalovirus y 1 (0,8 %) del virus de la varicela zóster. Se observaron Co-infecciones en 3 pacientes (2,5 %), 1 caso por el VHS-VZV y 2 casos por CMV / HSV. Las manifestaciones clínicas de los pacientes fueron: cefalea (18,6 %), fiebre (14,4 %), astenia (10,1 %), convulsiones (9,3 %), vómitos (8,4 %), y rigidez de nuca (5,9 %). El treinta por ciento de los pacientes también tenía VIH-SIDA. Se observó una tasa de letalidad del 20 % de los pacientes. Conclusiones Se demuestra que el herpesvirus es causa de infección del SNC en pacientes en Córdoba. Este estudio contribuye a la caracterización serológica viral epidemiológica de la encefalitis viral, así como en el manejo del paciente ya que se describen hallazgos clínicos importante en la población adulta estudiada.(AU)

Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue / 대한배뇨장애요실금학회지

PURPOSE: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. METHODS: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. RESULTS: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). CONCLUSIONS: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.

Homology Modeling of DNA polymerases of Herpesviridae family and structure-based virtual screening for inhibitor identification.

Human herpes viruses are responsible for the several transmitted infections in human. It is known that the DNA polymerase enzyme is one of the putative targets for herpes. Therefore, it is of interest to model all known DNA polymerases of Herpesviridae family. Here, all the DNA polymerases of Herpesviridae without any crystal structure were modeled using HHV-1 DNA polymerase as a template. Modeled structures were screened by ramachandran plot and Descrete Optimization of Protein Energy (DOPE) score. To find out multi-target inhibitor for Herpesviridae, 21 natural antiviral compounds were selected from literature and screened using Lipinski’s rule of five. Binding pose of acyclovir with HHV-1 DNA polymerase was taken for the comparative docking study. Comparative binding analysis was done after settling of 120 and eight partial mono flexible protein-ligand docking sets for natural compounds and acyclovir, respectively. From the study it is found that alliin and gallic acid exhibit good binding affinity than acyclovir and other natural compounds. So, here we purpose that these two compounds can be potential candidates to inhibit Herpesviridae family.

Herpes viruses and human papilloma virus in nasal polyposis and controls / Herpesvírus e vírus do papiloma humano na polipose nasal e controles

ABSTRACT INTRODUCTION: Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. OBJECTIVE: To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. METHODS: Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. RESULTS: Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p = 0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%,p = 0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). CONCLUSION: Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis.

RESUMO INTRODUÇÃO: A rinossinusite crônica com pólipos é uma doença multifatorial de etiopatogênese ainda não definida. Existem dados contraditórios na literatura sobre a implicação potencial de elementos virais na etiologia de pólipos nasossinusais. OBJETIVO: Comparar a prevalência de herpes vírus humanos (1-6) e papiloma vírus humano em pacientes adultos com rinossinusite crônica com pólipos nasais (CRwNP) e controles saudáveis. MÉTODO: A presença de DNA viral foi avaliada por PCR em tempo real, em amostras de pólipos nasais de 91 pacientes com CRwNP e na mucosa das conchas nasais de 38 controles saudáveis. RESULTADOS: A positividade do EBV foi maior nos pólipos nasais (24/91; 26,4%) do que nos controles (4/38; 10,5%), mas a diferença não foi significante (p = 0,06). O HHV-6 apresentou positividade menor nos pólipos nasais (13/91; 14,29%) do que os controles (10/38; 26,32%), (p = 0,13). No grupo CRwNP, uma amostra foi positiva para o vírus herpes simples (HSV-1) (1/91; 1,1%), e uma para citomegalovírus (CMV) (1/91; 1,1%); e nenhuma amostra foi positiva no grupo controle. Não houve amostra positiva para HSV-2, VZV, HR-HPV (16,18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) e LR-HPV (6,11). CONCLUSÃO: Diferenças de positividade do EBV e HHV-6 entre pacientes com CRwNP e controles saudáveis não são estatisticamente significantes, enfraquecendo a probabilidade de sua implicação na patogênese da CRwNP.

CD4+ and CD8+ T cell levels as well as clinical features in HIV-positive patients with drug eruption / 中华皮肤科杂志

Objective To explore the role of viral infection in the development of drug eruption in patients with HIV infection, and to evaluate the efficacy of antiviral treatment. Methods This study enrolled 87 HIV-positive patients, including 11 with and 76 without drug eruption, all of whom received highly active antiretroviral therapy(HAART). Clinical data on, baseline CD4+ and CD8+ T cell counts and CD4/CD8 ratio in these subjects were retrospectively analyzed. Results The severity of drug eruption was mild in the 11 HIV-positive patients, with a mean latency period of (14.00 ± 8.10)(range, 8 - 34)days. Of the 11 patients with drug eruption, 7 had liver function impairment, which was not in accordance with the severity of skin lesions. Drug eruption was controlled in all the 11 patients after anti-anaphylactic treatment without withdrawal of antiviral drugs. Compared with 75 HIV-positive patients without drug eruption, the 11 HIV-positive patients with drug eruption showed significantly increased baseline CD4 + T cell counts (493.00 ± 245.68 (range, 42 - 810)/μl vs. 347.81 ± 167.00 (range, 11 - 814)/μl, t = 647.50, P 0.05), CD4/CD8 ratio(0.40 ± 0.27 vs. 0.29 ± 0.16, P > 0.05), or percentage of patients with a CD4/CD8 ratio below the lower limit of normal (9/10 vs. 68/69 (98.55%), P >0.05). Conclusions The latency period of drug eruption seems to be long in HIV-positive patients receiving HAART, and mild drug eruption can be complicated by liver function impairment in the patients. Relatively high CD4 + counts may be a risk factor for the development and aggravation of drug eruption in HIV-positive patients.

Formulação vacinal trivalente voltada para o controle profilático/terapêutico de tumores induzidos pelo vírus do papiloma humano tipo 16 (HPV-16) e infecções pelos vírus da imunodeficiência adquirida (HIV) e herpes vírus humano (HSV) / Trivalent vaccine formulation focused on the prophylactic / therapeutic control of tumors induced by human papillomavirus type 16 (HPV-16) and infection by human immunodeficiency virus (HIV) and human herpes virus (HSV)

As proteínas E7 (HPV), p24 (HIV) e gD (HSV) são exclusivamente expressas por células infectadas ou tumorais e, por isso, são utilizadas como alvos para vacinas com características terapêuticas. Foram desenvolvidas duas vacinas de DNA capazes de expressar as três proteínas virais por meio de um vetor de expressão bicistrônico baseado na sequência IRES. As vacinas, denominadas pIRES I e pIRES II, diferem entre si por transportarem os genes que codificam as proteínas E7 do HPV-16 e p24 do HIV fusionadas à proteína gD do HSV-1 em ordem inversa. Células COS-7 transfectadas com os plasmídeos vacinais expressaram as proteínas alvo, como determinado por imunofluorecência com anticorpos específicos para as proteínas gD, p24 e E7. As vacinas foram testadas em modelo murino quanto à capacidade de gerar anticorpos e células T CD8+ específicas. Observamos que animais vacinados desenvolveram baixas taxas de anticorpos contra gD, p24 e E7. Em contrapartida, demonstramos a indução de células T CD8+ específicas para os três antígenos testados. Os plasmídeos vacinais foram capazes de proteger camundongos inoculados com células tumorais TC-1 (que expressam a proteína E7 do HPV-16), embora apresentando diferentes níveis de proteção em ensaios profiláticos e terapêuticos. As formulações foram testadas em relação à capacidade de proteger animais frente a desafio com o HSV-1 sendo que apenas um deles gerou efeito protetor. Em conclusão, os resultados demonstram que vacinas voltadas para o controle terapêutico de infecções ou processos tumorais associados aos vírus HPV, HIV e HSV representam uma meta viável e promissora

The proteins E7 (HPV), p24 (HIV) and gD (HSV) are exclusively expressed by infected cells or tumors and therefore are used as targets for vaccines with therapeutic characteristics. We developed two DNA vaccines capable of expressing these three viral proteins using a bicistronic expression vector based on IRES sequence. The plasmid vaccines, named pIRES I and pIRES II, differ by carrying the genes that encode proteins of HPV-16 E7 and p24 fused to the HIV protein gD of HSV-1 in reverse order. Transfected COS-7 cells expressed the target proteins, as determined by immunofluorescence with specific antibodies for gD, p24 and E7. The vaccines were tested in mice for their ability to generate antibodies and specific CD8+ T cells. We observed that vaccinated animals developed low levels of antibodies against gD, E7 and p24. In contrast, we demonstrate the induction of specific CD8+ T cells for the three antigens. The plasmid vaccines were able to protect mice inoculated with TC-1 tumor cells (which express the E7 protein of HPV-16), although with different levels of protection in prophylactic and therapeutic trials. The formulations were tested for ability to protect animals against challenge with HSV-1 and only one of them generated a protective effect. In conclusion, the results show that vaccines directed to therapeutic control of infections or tumor process associated with HPV, HSV or HIV represents a promising and viable goal

Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment / Linfocitopenia T CD4+ grave, en individuos negativos para virus de immunodeficiencia humana, mejoró con tratamiento antivirus herpes humanos

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings' health.

Múltiples enfermedades bacterianas, micóticas, parasitarias y virales pueden asociarse con linfocitopenia y linfocitopenia CD4+. También enfermedades autoinmunes, neoplásicas, inmunodeficiencia común variable, estrés físico, sicológico o traumático, la malnutrición y el tratamiento con inmunosupresores. Esta condición también se presenta sin causa aparente y es conocida como linfocitopenia T CD4+ idiopática. Entre las infecciones virales, los retrovirus, especialmente el virus de inmunodeficiencia humana, es la más frecuente causa, pero muchas otras infecciones virales agudas, entre ellas, la mononucleosis por citomegalovirus y por Epstein Barr virus, se asocian con linfocitopenia total y linfocitopenia T CD4+, que son transitorias y se recuperan cuando la enfermedad mejora. Una linfocitopenia grave asociada con infección crónica por virus herpes humanos y que mejore con el tratamiento de ellos, no ha sido publicada. Se describen 6 pacientes, negativos para virus de inmunodeficiencia humana, con linfocitopenia total y linfocitopenia T CD4+ graves y con manifestaciones clínicas de inmunodeficiencia celular, quienes respondieron rápidamente al tratamiento con ganciclovir o valganciclovir. Es importante considerar la infección crónica por virus herpes humanos en el diagnóstico diferencial de la etiología de la linfocitopenia T CD4+ en individuos no infectados por el virus de inmunodeficiencia humana, para iniciar un tratamiento efectivo de los pacientes y determinar en futuros estudios el impacto de la infección crónica por herpes virus en la salud humana.

Simultaneous lymph node involvement by Castleman disease and Kaposi sarcoma

Both multicentric Castleman disease and Kaposi sarcoma are more frequently observed in HIV infected patients. The coexistence of these Human herpesvirus 8 related lesions, in the same tissue, has been observed, but literature reports are scant. On the other hand, the expression of HHV-8-LANA-1 is easily demonstrable by immunohistochemistry. This has been shown to be a powerful tool for the diagnosis of these entities. The aim of this report is to communicate our experience with a case of multicentric Castleman disease occurring in the setting of HIV infection, which demonstrated microscopic Kaposi sarcoma in the same lymph node during the pathological work-up.

The clinical pathological analysis of Epstein-Barr virus active infection during the middle-late pregnancy / 中国医师杂志

Objective To explore the relationship of acute infections of Epstein-Barr virus and hydrops fetalis and explore the harm to fetuses and the affection on pregnancy outcomes caused by acute EBV infection during pregnancy. Methods 40 cases hydrops fetalis were diagnosed by ultrasonography. The difference between the EBEA-IgM positive and negative patients blood were studied. 101 cases over the same period of pregnant women with normal fetuses were enrolled as a control group. Results The positive rate of EBEA-IgM in pregnant women (95%) was significantly higher than that of control group(48.5%,P＜0.01). And the differences of the ratio of still birth and live birth and abnormal fetuses induction of labor between the groups were statistically significant（P＜0.01）. Premature birth among the live birth (40%) was obviously higher than that of control group (10.9%,P＜0.05). Conclusions Active infection of EBV in pregnancy was relevant to the hydrops fetalis and there need to pay attention to the detection of EBV during pregnancy.

Hepatitis viruses: Not always what it seems to be / Los virus de las hepatitis no siempre son habituales

The classic hepatotropic viruses, hepatitis A through E, are not the only viral agents able to infect the liver. Other systemic viruses may cause hepatic injury that can range from mild and transient elevation of aminotransferases to acute hepatitis and occasionally acute liver failure and fulminant hepatitis. The clinical presentation may be indistinguishable from that associated with classic hepatotropic viruses. These agents include cytomegalovirus; Epstein-Barr virus; herpes simplex virus; varicella-zoster virus; human herpesvirus 6, 7, and 8; human parvovirus B19; adenoviruses among others. Wide spectrums of clinical syndromes are associated with cytomegalovirus disease. Unique clinical syndromes may present in neonates, young adults and immunocompromised hosts infected with cytomegalovirus. Cases of fulminant hepatitis have been reported in both immunocompromised and immunocompetent hosts infected with Epstein Barr virus. Occasionally, these patients with acute hepatic failure may need liver transplantation. Herpes simplex viruses may involve the liver in neonatal infections, pregnancy, immunocompromised hosts and occasionally, immunocompetent adults. Varicella-Zoster virus has also been associated with severe acute hepatitis and fulminant hepatitis in adults. The drug of choice for these conditions is intravenous acyclovir. These may also need liver transplantation in the more severe forms of clinical presentation. Typical liver biopsy findings can be useful in determining the diagnosis of these viral infections. Human herpesviruses 6, 7, and 8, human parvovirus B19, and adenoviruses can also be present with features of acute liver injury and occasionally as fulminant hepatitis. The clinical syndromes are less well delineated than those associated with herpesviruses. It is important to consider these viruses as possible etiologic agents in patients who have acute liver injury and their serologic markers for the classic hepatotropic viruses are not indicative of an active infection.

Los agentes de la hepatitis viral A, B, C, D y E no son los únicos virus que pueden causar un síndrome de daño hepático agudo. Agentes virales como el citomegalovirus, Epstein-Barr, herpes simplex 1 y 2, Varicella-Zoster, virus herpes humano 6, 7, y 8, parvovirus B19 y adenovirus pueden causar daño hepático agudo e inclusive presentarse como hepatitis fulminante. Los cuadros clínicos de daño hepático agudo por citomegalovirus, Epstein Barr y herpes simplex 1 y 2 han sido caracterizado mejor. Se ha intentado el uso de drogas antivirales específicas como el uso intravenoso de aciclovir. Ocasionalmente, se ha requerido el trasplante hepático para rescatar pacientes con hepatitis fulminantes por estos agentes virales. La biopsia hepática puede ser de utilidad en estos casos puesto que los hallazgos son bastante característicos. La expresión clínica asociada a infecciones por virus herpes humano 6, 7 y 8, parvovirus B19 y adenovirus son menos características. Ha habido varios casos de hepatitis fulminante causada por estos agentes virales. Estos agentes virales deben ser considerados en el diagnóstico de casos de daño hepático agudo e inclusive hepatitis fulminante cuando los marcadores virales para los virus de hepatitis A-E son negativos.

Caso para diagnóstico / Case for diagnosis

Desde as primeiras descrições da aids, no início da década de 1980, a infecção herpética é vista como uma das doenças oportunistas mais prevalentes em pacientes com retrovirose. A infecção pelo herpes-vírus simples tipo 2, agente etiológico de 60 a 90 por cento dos casos de herpes genital, é bastante comum em pacientes com aids. O acometimento mucocutâneo pelo herpes-vírus simples tipo 2 pode ser grave e prolongado (persistente por mais de um mês), sendo caracterizado como doença definidora de aids.

Since the first reports and descriptions of AIDS in the early 1980s, herpetic infection has been considered as one of the most prevalent and opportunistic aids related infections in patients with retroviral diseases Infection by Herpes simplex type 2 (HSV-2), the etiologic agent responsible for 60 percent to 90 percent of the cases of genital herpes, is very common among patients suffering from AIDS. Herpes simplex type 2 infection may cause severe and prolonged (over a period of time of one month) mucocutaneous onset of the disease, being characterized as an aids defining clinical condition.

Soroprevalência de anticorpos contra vírus herpes simples 1-2 no Brasil / Seroprevalencia de anticuerpos contra virus herpes simples 1-2 en Brasil / Seroprevalence of herpes simplex 1-2 antibodies in Brazil

OBJETIVO: Estimar a soroprevalência de anticorpos por vírus herpes simples (HSV-1 e HSV-2) e analisar fatores associados no Brasil. MÉTODOS: Estudo transversal realizado entre 1996 e 1997 em 1.090 indivíduos com idade entre um e 40 anos da população geral, em quatro diferentes regiões geográficas no Brasil. Foram analisadas amostras sangüíneas para detecção de anticorpos para HSV-1 e HSV-2 com teste tipo-específico Elisa. Foram descritas freqüências e proporções, comparadas entre grupos utilizando o teste de Fisher bilateral exato. Foi realizada análise de regressão logística para avaliar influência das variáveis sociodemográficas e histórico de DST, sobre a soroprevalência de HSV-1 e/ou HSV-2. RESULTADOS: As soroprevalências de anticorpos para HSV-1 e HSV-2, ajustadas por idade, foram 67,2 por cento e 11,3 por cento respectivamente, sem diferença quanto ao sexo e maiores na Região Norte...

OBJECTIVE: To estimate the seroprevalence of HSV-1 and HSV-2 antibodies in Brazil and to analyze factors associated. METHODS: Cross-sectional study including subjects aged 1-40 years from the general population in four different geographical areas in Brazil between 1996 and 1997. All subjects were stratified by age and gender and 1,090 of them were included in the final analysis. Blood samples were tested for HSV-1 and HSV-2 antibodies by type-specific (gG1 and gG2) ELISA. Frequencies and proportions were described and compared among groups using two-sided Fisher's exact test. A logistic regression analysis was performed to assess the influence of the variables age, gender, geographical area, socioeconomic condition, past history of STD, seropositivity for anti-HSV-1 or anti-HSV-2 and interactions of any of these factors on the seroprevalence of HSV-1 and/or HSV-2. RESULTS: The age-adjusted seroprevalences of HSV-1 and HSV-2 antibodies were 67.2 percent and 11.3 percent, respectively, without sex differences and being higher in the North region...

OBJETIVO: Estimar la seroprevalencia de anticuerpos por virus herpes simples (HSV-1 y HSV-2) en diferentes áreas geográficas en Brasil y analizar factores asociados. MÉTODOS: Estudio transversal realizado entre 1996 y 1997 con individuos de la población en general en cuatro diferentes áreas geográficas en Brasil y estratificados por edad (de uno a 40 años) y sexo, de los cuales 1.090 fueron incluidos en el análisis final. Fueron analizadas muestras de sangre para detección de anticuerpos para HSV-1 y HSV-2 con prueba tipo-específica ELISA gG1-gG2. Fueron descritas frecuencias y proporciones y comparadas entre grupos utilizando la prueba de Fisher bilateral exacta. Fue realizado análisis de regresión logística para evaluar influencia de las variables edad, sexo, geografía, grupo económico, histórico de DST, seropositividad para anti-HSV-1 o anti-HSV-2 e interacciones de cualquiera de esos factores sobre la seroprevalencia de HSV-1 y/o HSV-2. RESULTADOS: La tasa de seroprevalencia de anticuerpos para HSV-1 ajustada por edad fue de 67,2 por ciento, sin diferencia con relación al sexo, siendo mayor en la Región Norte...

Herpes simplex 2 e citomegalovirus: efeitos citopáticos vs mecanismos de infecção: [revisão] / Herpes simplex 2 virus and cytomegalovirus cytophatic effects vs infection mechanics: [review]

O vírus, contrariamente a outras classes de agentes que afetam o organismo, não são observáveis em microscopia óptica, refletindo-se apenas microscopicamente em efeitos virais (ECPV), que permitem identificá-los por constituírem um conjunto de alterações patognomônicas a nível celular. O aumento nuclear, a variação da morfologia celular, a perda do padrão da cromatina, as inclusões intranucleares ou intracitoplasmáticas ou a multinucleação, são alguns dos ECPV mais comuns. Entre os vírus que afetam a mucosa genital na família Herpesviridae, inserem-se Herpes Simplex 2 e o Citomegalovirus, cujo diagnóstico deverá ter em conta a complexidade dos mecanismos de replicação. Assim, e apesar dos vários métodos para a detecção do vírus, a citologia continua a ser um método viável para o diagnóstico destas infecções virais, sendo que a compreensão do processo de infecção contribui para a correta avaliação microscópica. Este trabalho tem como finalidade efetuar uma revisão bibliográfica sobre o grupo Herpes, focando o Herpes Simplex 2 e o Citomegalovirus, assim como, explicar e relacionar os ECPV, associados ao grupo Herpes , tendo por base os mecanismos de infecção.