Clinical Study of Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To explore the risk factors of cytomegalovirus (CMV) and refractory CMV infection (RCI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influences on survival.@*METHODS@#A total of 246 patients who received allo-HSCT from 2015 to 2020 were divided into CMV group (n=67) and non-CMV group (n=179) according to whether they had CMV infection. Patients with CMV infection were further divided into RCI group (n=18) and non-RCI group (n=49) according to whether they had RCI. The risk factors of CMV infection and RCI were analyzed, and the diagnostic significance of Logistics regression model was verified by ROC curve. The differences of overall survival (OS) and progression-free survival (PFS) between groups and the risk factors affecting OS were analyzed.@*RESULTS@#For patients with CMV infection, the median time of the first CMV infection was 48(7-183) days after allo-HSCT, and the median duration was 21 (7-158) days. Older age, EB viremia and gradeⅡ-Ⅳacute graft-versus-host disease (aGVHD) significantly increased the risk of CMV infection (P=0.032, <0.001 and 0.037, respectively). Risk factors for RCI were EB viremia and the peak value of CMV-DNA at diagnosis≥1×104 copies/ml (P=0.039 and 0.006, respectively). White blood cell (WBC)≥4×109/L at 14 days after transplantation was a protective factor for CMV infection and RCI (P=0.013 and 0.014, respectively). The OS rate in CMV group was significantly lower than that in non-CMV group (P=0.033), and also significantly lower in RCI group than that in non-RCI group (P=0.043). Hematopoietic reconstruction was a favorable factor for OS (P<0.001), whereas CMV-DNA≥1.0×104 copies/ml within 60 days after transplantation was a risk factor for OS (P=0.005).@*CONCLUSION@#The late recovery of WBC and the combination of EB viremia after transplantation are common risk factors for CMV infection and RCI. CMV-DNA load of 1×104 copies/ml is an important threshold, higher than which is associated with higher RCI and lower OS risk.

El citomegalovirus en los receptores de trasplante hematopoyético / Cytomegalovirus in hematopoietic stem cell transplant recipients

Introducción: La infección por citomegalovirus es muy frecuente en pacientes sometidos a trasplante de progenitores hematopoyéticos, debido a tratamientos mieloablativos de acondicionamiento, disparidad genética y al tratamiento inmunosupresor, y ocurre fundamentalmente después de la toma del implante. Objetivos: Actualizar el diagnóstico, manejo y seguimiento de la infección por citomegalovirus en pacientes trasplantados. Métodos: Se realizó revisión bibliográfica en los idiomas español e inglés, utilizando los motores de búsqueda de Pubmed, Google Académico y Scielo sobre el diagnóstico y manejo del citomegalovirus en pacientes receptores de trasplante hematopoyético. Análisis y síntesis de la información: Se recolectó y organizó la información obtenida siguiendo cronológicamente el surgimiento de técnicas para diagnóstico y la aparición de nuevos medicamentos en los últimos años. Se seleccionaron artículos recientes de expertos en el tema en revistas prestigiosas, donde se evidencia la importancia del diagnóstico adelantado y el inicio del tratamiento. Conclusiones: En la actualidad se cuenta con nuevas formas de diagnóstico y medicamentos novedosos para el citomegalovirus, pero la mortalidad puede llegar a ser alta, si el paciente no es tratado antes de que aparezcan los síntomas de la enfermedad e incluso a pesar del tratamiento. En ocasiones, no es posible erradicar el virus, lo que lleva a complicaciones importantes y a la muerte. La enfermedad citomegálica continúa siendo una complicación frecuente en estos pacientes a pesar de las medidas para evitar su reactivación(AU)

Introduction: Cytomegalovirus infection is very common in patients undergoing hematopoietic progenitor transplantation, due to myeloablative conditioning treatments, genetic disparity, and immunosuppressive treatment, and occurs mainly after the engrafment. Objective: A review and update of the diagnosis and management of cytomegalovirus is made in hematopoietic transplant recipients. Method: A bibliographic review was carried out in Spanish and English, using the search engines of Pubmed, Scholar Google and Scielo about the diagnosis and management of cytomegalovirus in hematopoietic transplant recipients. Development: The information obtained was collected and organized chronologically about the emergence of techniques for diagnosis and the appearance of new drugs in recent years. Recent articles by experts in prestigious journals were reviewed and the importance of early diagnosis and initiation of treatment is evidenced. Conclusions: There are currently new forms of diagnosis and novel medications, but mortality can be high, if the patient is not treated before the symptoms of the disease appear and even despite treatment, sometimes it is not possible to eradicate the virus, leading to major complications and death. Cytomegalic disease continues to be a frequent complication in these patients despite measures to prevent virus reactivation(AU)

Cytomegalovirus infection in AIDS patients. An illustrative case series / Infección por citomegalovirus en pacientes con SIDA. Una serie ilustrativa

ABSTRACT Background: Cytomegalovirus (CMV) is an opportunistic infection (OI) in immunosuppressed patients. However, there are no clear cut-off values available for quantitative plasmatic CMV measures (viral load [VL]) to discriminate those with CMV illness from those infected suffering a transient viral reactivation. Aim: To estimate a CMV VL cut-off point that discriminates infected patients and those with CMV related diseases, and to clinically characterize AIDS patients with this OI. Patients and Methods: Retrospective analysis of AIDS patients admitted by any reason between years 2017 and 2019 and who had a positive plasma CMV VL at any titer. Cases were categorized with illness or infected using accepted criteria and the cut-off value was obtained by receiver operating characteristic curve (ROC) analysis. Results: Twelve patients were identified as having a CMV-associated illness and seven with CMV infection. A CMV VL of 3,800 copies/mL had a sensitivity of 91.6% and 100% specificity to discriminate both states. Of the 12 patients with CMV illness, all were in AIDS stage and only five were receiving HIV therapy. Predominant clinical presentations were gastrointestinal (50%), followed by liver involvement (25%) and CMV disease (25%). All patients were treated with ganciclovir or valganciclovir. Ten patients had a favorable response (83.3%), one patient only had a laboratory improvement (8.3%) and one died during treatment (8.3%). Drug toxicity was recorded in nine patients but in only three cases, a dose adjustment was necessary. Conclusions: The predominant clinical manifestation in our series was gastrointestinal. A CMV VL cutoff level of CMV VL of 3,800 copies / mL is useful to discriminate infected patients from those with CMV related disease.

Antecedentes: Citomegalovirus (CMV) es una infección oportunista (IO) en pacientes inmunosuprimidos. Sin embargo, se requieren puntos de corte de carga viral (CV) para discriminar a aquellos con enfermedad por CMV de aquellos infectados que sufren una reactivación viral transitoria. Objetivos: Estimar un punto de corte de la CV de CMV que discrimine a los enfermos de los infectados y, además, caracterizar clínicamente a los pacientes con sida que presentan esta IO. Pacientes y Métodos: Análisis retrospectivo de pacientes con sida hospitalizados por cualquier motivo entre los años 2017 y 2019, y que presentaron un CV de CMV plasmática positiva a cualquier título. Los casos se clasificaron como enfermos utilizando criterios aceptados y el valor de corte se obtuvo mediante análisis de una curva ROC. Resultados: Durante el período de estudio, 12 pacientes fueron identificados con enfermedad asociada al CMV y siete con infección. Una CV de 3.800 copias/ml logró una sensibilidad de 91,6% y una especificidad de 100% para discriminar ambos estados. De los 12 pacientes enfermos, todos estaban en etapa de sida y solo 5 recibían terapia contra el VIH. La presentación clínica predominante fue gastrointestinal (50%) seguida del compromiso hepático (25%) y de la enfermedad por CMV (25%). Todos los pacientes fueron tratados con ganciclovir o valganciclovir. Diez pacientes tuvieron una respuesta favorable (83,3%), uno solo tuvo mejoría de laboratorio (8,3%) y otro paciente falleció durante el tratamiento (8,3%). Nueve pacientes evolucionaron con toxicidad farmacológica, pero en solo 3 casos fue necesario ajustar las dosis. Conclusiones: La forma predominante de presentación de la enfermedad fue gastrointestinal. Un punto de corte de 3.800 copias/ml discrimina pacientes infectados de aquellos con la enfermedad.

Cistitis hemorrágica por infección viral en receptores de trasplante hematopoyético haploidéntico: reporte de dos casos / Hemorrhagic cystitis due to viral infection in patients who received hematopoietic haploidentical transplantation: two case reports

Introducción: Las infecciones por virus o la reactivación de virus en estado latente son frecuentes durante el estado de inmunosupresión que sigue al trasplante de progenitores hematopoyéticos, y constituyen una causa importante de complicaciones, como la cistitis hemorrágica, que se caracteriza por disuria, polaquiuria, dolor abdominal y hematuria. La aparición precoz se asocia a la administración de citostáticos como la ciclofosfamida, y el comienzo tardío a la primoinfección o reactivación de virus como citomegalovirus, los adenovirus o los poliomavirus como el BK y el JC. Objetivo: Describir las características clínicas, la evolución y el manejo de la cistitis hemorrágica postrasplante. Casos clínicos: Se presentan dos pacientes con leucemia mieloide aguda que desarrollaron cistitis hemorrágica asociada a infección viral por virus BK y citomegalovirus después del trasplante haploidéntico con ciclofosfamida postrasplante. La cistitis hemorrágica de causa viral después del trasplante hematopoyético en estos pacientes estuvo asociada a una severa inmunosupresión, por lo que constituyó una complicación potencialmente letal. Los dos pacientes presentaron cistitis hemorrágica grado IV y fallecieron a pesar del tratamiento. Conclusiones: El trasplante haploidéntico con la administración de ciclofosfamida postrasplante incrementa la posibilidad de donantes de progenitores hematopoyéticos para los pacientes sin un hermano HLA idéntico pero el mayor nivel de inmunosupresión podría aumentar la incidencia de cistitis hemorrágica de causa viral(AU)

Introduction: Viral infections or latent-virus reactivation are frequent during the immunosuppressed cincition that follows hematopoietic stem-cell transplantation, and an important cause of complications, such as hemorrhagic cystitis, characterized by dysuria, urinary frequency, abdominal pain, and hematuria. The early appearance is associated with the administration of cytostatic drugs such as cyclophosphamide, and the late onset is associated with primary infection or reactivation of viruses such as cytomegalovirus, adenoviruses, or polyomaviruses such as BK and JC. Objective: To describe the clinical characteristics, evolution and management of post-transplant hemorrhagic cystitis. Clinical cases: The cases are presented of two patients with acute myeloid leukemia who developed hemorrhagic cystitis associated with viral infection by BK virus and cytomegalovirus after haploidentical transplantation with post-transplant cyclophosphamide. Viral hemorrhagic cystitis after hematopoietic transplantation in these patients was associated with severe immunosuppression, making it a potentially lethal complication. Both patients presented grade IV hemorrhagic cystitis and died despite treatment. Conclusions: Haploidentical transplantation with the of post-transplant cyclophosphamide administration increases the possibility for donors of hematopoietic progenitor cells to patients without an identical HLA match, but the higher level of immunosuppression could increase the incidence of viral hemorrhagic cystitis(AU)

Fatal disseminated cytomegalovirus infection with necrotizing oophoritis in a patient with acquired immunodeficiency syndrome

Disseminated human cytomegalovirus (CMV) disease occurs mainly as a congenital infection and among immunocompromised hosts. Patients with acquired immunodeficiency syndrome (AIDS) are at increased risk for CMV infection, and the most prevalent clinical manifestation is retinitis, followed by colitis, esophagitis, pneumonitis, and encephalitis. CMV oophoritis is poorly described in the literature with some cases reported in patients with hematological or solid malignancies, bone marrow or solid organ transplantation, immunosuppressive therapy, and advanced AIDS cases. We report the case of a 61-year-old woman with a recent diagnosis of AIDS, which was associated with a wasting syndrome. The patient presented with abdominal pain, headache, cutaneous vesicular lesions on the abdomen, anemia, lymphopenia, and hyponatremia; she died suddenly on the fourth day of hospitalization. The autopsy was performed and demonstrated disseminated CMV infection with hemorrhagic encephalitis as the immediate cause of death. Additionally, pneumonitis, extensive adrenalitis, ulcerated enteritis, focal hepatitis, and necrotizing oophoritis were found.

Citomegalovirus congénito: ¿El diagnóstico y el tratamiento precoz pueden revertir una discapacidad permanente? / Congenital cytomegalovirus: Can early diagnosis and treatment revert permanent disability?

Introducción: La infección congénita por citomegalovirus (CMV) es la causa más frecuente de hipoacusia neurosensorial (HNS) no genética en países desarrollados. La incidencia de HNS en los lactantes sintomáticos oscila entre el 30 y el 65%. Objetivos: Describir las formas de presentación clínica de la infección por CMV congénita en pacientes sintomáticos y la evolución auditiva en los pacientes tratados con antivirales y aquellos sin tratamiento. Diseño: Estudio retrospectivo, descriptivo, observacional y longitudinal. Población: Se incluyeron niños, menores de 2 meses, con CMV congénito (confirmado por viruria positiva con método de PCR), sintomáticos, internados en la Unidad de Neonatología, desde el año 2005 al 2013. Método: Diagnóstico y seguimiento auditivo utilizando otoemisiones acústicas (OEA), potenciales evocados auditivos de tronco cerebral (PEAT) y audiometría (AT) según edad e indicación en cada caso en particular. El tratamiento antiviral se realizó con ganciclovir (GCV) y/o valganciclovir (VGCV). Resultados: Clínicamente se estudiaron 16 pacientes con diagnóstico de CMV congénito sintomáticos. Se excluyeron tres. Se describen los motivos de internación más frecuentes. Para el estudio y seguimiento audiológico los pacientes se dividieron en dos grupos de acuerdo a que recibieran o no tratamiento: A: no recibieron tratamiento antiviral (n: 5) y B: recibieron tratamiento antiviral (n: 8). En los pacientes que recibieron tratamiento, las secuelas auditivas fueron menores y en dos de los casos se produjo una mejoría importante en la audición. Conclusiones: El tratamiento de neonatos con infección congénita por CMV con GCV y/o VGCV ofrece resultados alentadores en la prevención de la hipoacusia (AU)

Introduction: Congenital cytomegalovirus (CMV) infection is the most common cause of non-genetic sensorineural hearing loss (SNH) in developed countries. The incidence of SNH in symptomatic infants ranges between 30% and 65%. Objectives: To describe different forms of clinical presentation of congenital CMV infection in symptomatic patients as well as outcome in patients treated with antiviral drugs and those in whom treatment was withheld. Study design: A retrospective, longitudinal, observational, descriptive study. Population: Symptomatic infants younger than 2 months of life with congenital CMV infection (confirmed by positive viruria using PCR), admitted to the Neonatology Unit between 2005 and 2013. Method: Diagnosis and audiological follow-up with otoacoustic emissions (OAE), brainstem auditory evoked potentials (BAEP) and audiometry (AT) according to age and indication for the individual patient. Antiviral treatment consisted of ganciclovir (GCV) and/or valganciclovir (VGCV). Results: Sixteen patients with symptomatic congenital CMV infection were clinically studied. Three were excluded. Main reasons for admission are described. For evaluation and audiological follow-up the patients were divided into two groups according to whether or not they received treatment. Group A: did not receive antiviral treatment (n: 5) and B: received antiviral treatment (n: 8). In patients that received treatment hearing sequelae were less severe and in two patients significant hearing improvement was observed. Conclusions: Treatment with GCV and/or VGCV of neonates with congenital CMV was found to have promising results for the prevention of hearing loss (AU)

The diagnosis of multiple opportunistic infections in advanced stage AIDS: when Ockham's Razor doesn't cut it

In the advanced stage of AIDS, the diagnosis of the opportunistic infections may be challenging due to the high risk of performing invasive diagnostic methods in a patient with a critical clinical condition, as well as the correct interpretation of the results of microbiological exams. One of the challenges for the diagnosis and treatment of the opportunistic infections is that they may occur concomitantly in the same patient and they may mimic each other, leading to a high discrepancy between clinical and autopsy diagnoses. We describe the case of a 52-year-old man who was hospitalized because of weight loss, anemia, cough, and hepatosplenomegaly. During the investigation, the diagnosis of AIDS was made, and the patient developed respiratory failure and died on the fourth day of hospitalization. At autopsy, disseminated non-tuberculosis mycobacteriosis was found, affecting mainly the organs of the reticuloendothelial system. Also, severe and diffuse pneumonia caused by multiple agents (Pneumocystis jirovecii, Histoplasma capsulatum, suppurative bacterial infection, non-tuberculosis mycobacteria, and cytomegalovirus) was seen in a morphological pattern that could be called "collision pneumonia." The lesson from this case, revealed by the autopsy, is that in advanced AIDS, patients often have multiple opportunistic infections, so the principle of Ockham's razor­that a single diagnosis is most likely the best diagnosis­fails in this clinical context.

Costo-efectividad de dos esquemas de prevención de la infección por citomegalovirus en pacientes con trasplante renal y riesgo intermedio en Colombia / Cost-effectiveness of two prevention cytomegalovirus infection schemes in renal transplant patients at intermediate risk in Colombia

Resumen Introducción. El citomegalovirus es la causa más frecuente de infección en pacientes con trasplante renal. Existen dos estrategias de similar efectividad para prevenirlo: la profilaxis universal con valganciclovir durante 90 días o el tratamiento anticipado verificando la carga viral semanal y aplicándolo solo si esta es positiva. Objetivo. Determinar cuál de estas dos estrategias sería más costo-efectiva en pacientes de riesgo intermedio en Colombia. Materiales y métodos. Se diseñó un árbol de decisiones bajo la perspectiva del tercer pagador considerando únicamente los costos médicos directos en pesos colombianos (COP) del 2014 durante un periodo de un año en una población de pacientes con riesgo intermedio para citomegalovirus (donante positivo y receptor positivo, o donante negativo y receptor positivo). Las probabilidades de transición se extrajeron de los estudios clínicos y se validaron con expertos mediante el método Delphi. Los costos de los procedimientos se basaron en el manual tarifario ISS 2001, con un incremento del 33 % a partir del índice de precios al consumidor (IPC) en salud de 2014, en tanto que los de los medicamentos se extrajeron de las circulares del Ministerio de Salud y del Sistema de Información de Medicamentos (Sismed). Resultados. La profilaxis universal con valganciclovir resultó ser menos costosa y se asoció con una menor probabilidad de infección. El costo promedio del primer año de tratamiento anticipado sería de COP$ 30'961.290, mientras que el universal sería de COP$ 29'967.834, es decir, un costo 'incremental' de COP$ 993.456. Conclusiones. Para los pacientes de riesgo intermedio con trasplante renal en Colombia, la profilaxis universal es la mejor estrategia por ser menos costosa y reducir el riesgo de infección.

Abstract Introduction: Cytomegalovirus (CMV) is the most frequent opportunistic infection after renal transplantation. There are two strategies for its prevention: Universal prophylaxis, with valganciclovir for 90 days, and anticipated therapy, using weekly viral load surveillance, and therapy only if positive. Meta-analysis directly comparing both strategies have shown them to have similar effectiveness. Objective: To determine which strategy is more cost-effective in intermediate risk patients in Colombia. Materials and methods: We designed a third-party payer perspective decision tree, considering only direct medical costs in 2014 Colombian pesos (COP) (USD$ 1=COP$ 2,000) and a time horizon of one year. The target population was intermediate CMV risk patients (positive receptor). Transition probabilities were extracted from clinical studies, validated with a Delphi expert panel method; procedural costs were obtained from the ISS 2001 manual with a 33% increment based on the Consumer Price Index for 2014, while medication costs were obtained from the official Ministry of Health information system. Results: Universal prophylaxis with valganciclovir was dominant, with lower costs and less probability of infection. The average cost of the first year in anticipated therapy would be COP$ 30,961,290, whereas in the case of universal therapy the cost would be COP$ 29,967,834 (incremental cost of COP$ 993,456). Conclusions: For Colombian renal transplant patients at intermediate risk for CMV infection, universal prophylaxis strategy is the best option.

Presentación del síndrome de Wernicke-Korsakoff secundario a encefalitis por citomegalovirus, a propósito de un caso / Wernicke-Korsakoff syndrome secondary to cytomegalovirus encephalitis: A case report

Resumen El citomegalovirus (CMV) es uno de los microorganismos oportunistas con mayor prevalencia en pacientes inmunocomprometidos, aunque su reactivación ha descendido después de la introducción de la terapia antirretroviral altamente activa (Highly Active Antiretroviral Therapy, HAART). En las coinfecciones, la encefalitis se ha reportado como una de las condiciones más frecuentes. Se presenta el caso de un paciente adulto joven con infección por virus de la inmunodeficiencia humana (HIV) que tuvo un rápido deterioro neurológico evidenciado en síntomas y signos clínicos clásicos del síndrome de Wernicke-Korsakoff y que no presentaba factores de riesgo para deficiencia de tiamina. En las imágenes de la resonancia magnética cerebral, se detectaron hallazgos típicos del síndrome, y se identificó citomegalovirus (CMV) en el líquido cefalorraquídeo. Con el tratamiento específico para el CMV, se logró el control de los síntomas, aunque hubo secuelas neurológicas que mejoraron. Este es uno de los pocos casos reportados a nivel mundial de síndrome de Wernicke secundario a encefalitis por citomegalovirus.

Abstract Cytomegalovirus (CMV) is one of the opportunistic microorganisms with the highest prevalence in immunocompromised patients. Reactivation has decreased after the introduction of highly active antiretroviral therapy (HAART). Encephalitis has been reported in the coinfection as one of the most frequent presentations. We present the case of a young adult patient with HIV infection and rapid neurological deterioration due to classic clinical symptoms and signs of the Wernicke-Korsakoff syndrome, with no risk factors for thiamine deficiency, with images by nuclear magnetic resonance typical of the syndrome, and identification of cytomegalovirus in cerebrospinal fluid. The specific treatment for CMV managed to control the symptoms with neurological sequelae in progression towards improvement. This is one of the few cases reported in the literature of Wernicke syndrome secondary to cytomegalovirus encephalitis.

Hipoacusia neurosensorial secundaria a infecciones perinatales / Sensorioneural hearing loss secondary to perinatal infections / A perda auditiva neurossensoral secundária a infecções perinatais

Introducción: 1 a 2 de cada 1.000 recién nacidos tienen una pérdida auditiva neurosensorial significativa. De las deficiencias auditivas congénitas, el 50% resultan de infecciones en el embarazo y/o parto; como las provocadas por: Toxoplasmosis, rubéola, citomegalovirus, herpes y sífilis. Métodos: Se realizó una búsqueda bibliográfica sistemática de artículos utilizando bibliotecas virtuales y libros de texto de relevancia dentro de la especialidad. Resultados: La rubéola en mujeres susceptibles puede producir el síndrome de rubéola congénita. La sordera es la manifestación más frecuente de la enfermedad y es la secuela más importante. El 15% de los niños infectados por Citomegalovirus padecen una pérdida auditiva por daño coclear y alteraciones en el sistema nervioso central al nacer. Otro 15% pueden desarrollar luego del nacimiento hipoacusia, retardo mental o dificultades en el desarrollo del lenguaje y del aprendizaje. Aproximadamente el 80% de los recién nacidos infectados por toxoplasmosis son asintomáticos; el resto presentará manifestaciones clínicas de afectación sistémica incluyendo compromiso auditivo como parte del cuadro. La infección por Herpes simple suele ser devastadora en el recién nacido. Se ha descrito hipoacusia en más del 50% de los casos. La sordera se asocia frecuentemente con la sífilis congénita. Junto con la queratitis intersticial y las malformaciones dentarias, forma parte de la tríada de Hutchinson. Conclusiones: La hipoacusia es un problema de gran importancia en la infancia. Las infecciones agrupadas en el término TORCHS causan hipoacusia neurosensorial adquirida en forma prenatal, dando lugar a sorderas presentes al nacer o de desarrollo diferido o progresivo.

Introduction: 1 to 2 of every 1,000 newborns have significant sensorineural hearing loss. From all the congenital hearing empairments, 50% take place during pregnancy and/or childbirth; such as those caused by: toxoplasmosis, rubella, cytomegalovirus, herpes and syphilis. Methods: A systematic literature research was performed using virtual libraries and relevant specialty textbooks. Results: Rubella in susceptible women may cause congenital rubella syndrome. Deafness is the most common manifestation of the disease and is the most important sequel. 15% of those children infected with Cytomegalovirus children suffer hearing loss from cochlear damage and alterations in the central nervous system at birth. Another 15% can then develop birth hearing loss, mental retardation or difficulties in language development and learning. Approximately 80% of newborns infected with toxoplasmosis are asymptomatic; the rest will present clinical manifestations of systemic disease including hearing impairment as part of the picture. Herpes simplex infection is devastating in the new born. Hearing loss has been described in over 50% of cases. Deafness is often associated with congenital syphilis. Along with interstitial keratitis and dental malformations, it is part of the Hutchinson triad. Conclusions: Hearing loss is a major problem in childhood. Gathered as TORCHS acquired infections cause sensorineural hearing loss prenatally, resulting in hearing loss present at birth or deferred or progressive development.

Introdução: 1 a 2 em cada 1.000 recém-nascidos têm perda auditiva neurossensorial significativo. Das deficiências auditivas congênitas, 50% das infecções resultar em gravidez e / ou parto; tais como aquelas causadas por: toxoplasmose, rubéola, citomegalovírus, herpes e sífilis. Métodos: Uma busca sistemática da literatura foi realizada utilizando bibliotecas virtuais e livros relevantes no art. Resultados: A rubéola em mulheres suscetíveis pode causar a síndrome da rubéola congênita. A surdez é a manifestação mais comum da doença e é a sequela mais importante. 15% das crianças infectadas com Citomegalovírus sofrer perda de audição de danos e alterações coclear no sistema nervoso central no nascimento. Outros 15% podem desenvolver perda auditiva nascimento, retardo mental ou dificuldades no desenvolvimento da linguagem e aprendizagem. Cerca de 80% dos recém-nascidos infectados com toxoplasmose é assintomática; o resto vai apresentar manifestações clínicas da doença sistêmica, incluindo a deficiência auditiva como parte da imagem. Infecção Herpes simplex geralmente devastadores no recém-nascido. A perda de audição tem sido descrita em mais de 50% dos casos. A surdez é frequentemente associada a sífilis congênita. Junto com ceratite intersticial e malformações dentárias, faz parte da tríade Hutchinson. Conclusões: A perda auditiva é um problema grave na infância. Agrupados nas infecções TORCHS causam perda auditiva neurossensorial pré-natal, resultando em perda auditiva presente no nascimento ou em diferido ou desenvolvimento progressivo.

Human Cytomegalovirus DNA Quantification and Gene Expression in Gliomas of Different Grades

Gliomas are the most common type of primary brain tumors. The most aggressive type, Glioblastoma multiforme (GBM), is one of the deadliest human diseases, with an average survival at diagnosis of about 1 year. Previous evidence suggests a link between human cytomegalovirus (HCMV) and gliomas. HCMV has been shown to be present in these tumors and several viral proteins can have oncogenic properties in glioma cells. Here we have investigated the presence of HCMV DNA, RNA and proteins in fifty-two gliomas of different grades of malignancy. The UL83 viral region, the early beta 2.7 RNA and viral protein were detected in 73%, 36% and 57% by qPCR, ISH and IHC, respectively. Positivity of the viral targets and viral load was independent of tumor type or grade suggesting no correlation between viral presence and tumor progression. Our results demonstrate high prevalence of the virus in gliomas from Brazilian patients, contributing to a better understanding of the association between HCMV infection and gliomas worldwide and supporting further investigations of the virus oncomodulatory properties.

Diarrea aguda en trasplantes renales y reno-pancreáticos

La diarrea es una complicación frecuente y potencialmente grave del trasplante renal. Se describen aquí, en un estudio de corte transversal, las características epidemiológicas y microbiológicas de la diarrea aguda y persistente en pacientes internados con trasplante renal o reno-páncreas. Se incluyeron 52 pacientes internados en un hospital de la Ciudad de Buenos Aires, 42 (80.8%) habían recibido un trasplante renal y 10 (19.2%) reno-páncreas. La diarrea fue el motivo de ingreso en 34 casos (65.4%). La etiología de la diarrea pudo estudiarse en 50 pacientes: en 25 (50%) no se arribó a un diagnóstico etiológico y en 18 (36%) se constató diarrea con causa microbiológica específica: 3 (6%) enfermedad por citomegalovirus, 6 (12%) diarrea atribuida a citomegalovirus, 5 (10%) a rotavirus y 4 (8%) a Clostridium difficile. En 7 (14%) la diarrea fue atribuida a fármacos (mofetil micofenolato y sirolimus). Aquellos con diarrea con causa microbiológica habían recibido recientemente inmunosupresores a altas dosis con mayor frecuencia que el resto (p = 0.048). Los pacientes con diarrea atribuida a fármacos recibían más frecuentemente mofetil micofenolato (p = 0.039). En 16 (30.8%) se realizaron modificaciones de los inmunosupresores como medida terapéutica, y a 47 (90.4%) se les indicó antibioticoterapia empírica. La mediana de duración de internación fue de 6 días y 7 pacientes (14.6%) persistieron con diarrea al quinto día. Todos tuvieron resolución de la diarrea al alta y un tercio persistió con insuficiencia renal. La información de este estudio puede servir para mejorar las medidas preventivas, diagnósticas y terapéuticas en estos pacientes.

Diarrhea is a frequent and potentially severe complication of kidney transplantation. We describe here, in a cross-sectional study, the epidemiological and microbiological characteristics of acute and persistent diarrhea in 52 inpatients with kidney and kidney-pancreas transplant in a hospital in Buenos Aires, 42 (80.8%) of whom had received a kidney and 10 (19.2%) a kidney-pancreas transplant. Diarrhea was the reason of admission of 34 cases (65.4%). The etiology could be studied in 50 patients: 25 (50%) had no etiological diagnosis of diarrhea and 18 (36%) had a specific infectious etiology: 3 (6%) cytomegalovirus disease, 6 (12%) diarrhea attributed to cytomegalovirus, 5 (10%) to rotavirus and 4 (8%) to Clostridium difficile. In 7 (14%) diarrhea was attributed to drugs (mycophenolate mofetil and sirolimus). Patients with infectious diarrhea had recently received high doses of immunosuppressive therapy more frequently than the rest (p = 0.048). Those with diarrhea attributed to drugs were more frequently on mycophenolate mofetil than the rest (p = 0.039). Empirical modification of the immunosuppressive treatment was done in 16 (30.8%) and empirical antibiotic therapy was given to 47 patients (90.4%). Median length of hospital stay was 6 days. Seven patients (14.6%) persisted with diarrhea at the fifth day of admission. At hospital discharge all cases had complete resolution of symptoms and one third persisted with kidney failure. Information provided in this study can be useful as a starting point for improving preventive, diagnostic and therapeutic measures in these patients.

Serological mareers of viral, syphilitic and tooplasmic infection in children and teenagers with nephrotic syndrome: case series from mato grosso state, Brazil / Marcadores sorológicos de infecções virais, sífilis e toxoplasmose em crianças e adolescentes com síndrome nefrótica: série de casos de Mato Grosso, Brasil

Some infections can be the cause of secondary nephrotic syndrome. The aim of this study was to describe the experience of a Renal Disease Reference Clinic from Central Brazil, in which serological markers of some infectious agents are systematically screened in children with nephrotic syndrome. Data were obtained from the assessment of medical files of all children under fifteen years of age, who matched nephrotic syndrome criteria. Subjects were tested for IgG and IgM antibodies against T. gondii and cytomegalovirus; antibodies against Herpes simplex, hepatitis C virus and HIV; and surface antigen (HBsAg) of hepatitis B virus. The VDRL test was also performed. 169 cases were studied. The median age on the first visit was 44 months and 103 (60.9%) patients were male. Anti-CMV IgG and IgM were found in 70.4% and 4.1%, respectively. IgG and IgM against Toxoplasma gondii were present in 32.5% and 5.3%, respectively. Two patients were positive for HBsAg, but none showed markers for HIV, hepatitis C, or Treponema pallidum. IgG and IgM against herpes simplex virus were performed on 54 patients, of which 48.1% and 22.2% were positive. IgM antibodies in some children with clinical signs of recent infection suggest that these diseases may play a role in the genesis of nephrotic syndrome.

Algumas infecções podem ser causa de síndrome nefrótica. O objetivo desse estudo foi descrever a experiência de clínica pediátrica de doenças renais do Brasil Central, onde marcadores sorológicos de algumas doenças infecciosas são sistematicamente avaliados em crianças com síndrome nefrótica. Dados foram obtidos de registros médicos de todas as crianças com menos de 15 anos que preenchiam critérios de síndrome nefrótica. Os participantes foram testados para presença de IgG e IgM contra Toxoplasma gondii e citomegalovirus; anticorpos contra herpes simples, vírus da hepatite C e HIV, além do antígeno de superfície da hepatite B (HBsAg). VDRL também foi testado. 169 casos foram estudados. A idade média na primeira visita foi 44 meses e 103 eram do sexo masculino (60.9%). Anti-CMV IgG e IgM foram identificados em 70,4% e 4,1%, respectivamente. IgG e IgM contra T. gondii eram positivos em 32,5% e 5,3%. Dois pacientes eram HBsAg positivos, mas nenhum mostrou positividade para HIV, hepatite C ou sífilis. IgG e IgM contra herpes simples foram realizados em 54 pacientes, dos quais 48,1% e 22,2% eram positivos. Anticorpos IgM positivos em algumas crianças com sinais clínicos de infecção recente sugerem que essas doenças podem exercer um papel na gênese da síndrome nefrótica.

Hemorragia cerebrovascular asociada con infección por citomegalovirus en un lactante menor / Cerebrovascular hemorrhage associated with acquired cytomegalovirus infection in an infant

El citomegalovirus es el agente de infección perinatal más frecuente y una de las principales causas de infecciones virales adquiridas. En la presentación del siguiente caso se describe el amplio espectro clínico de la infección por citomegalovirus. La clasificación correcta de la infección como congénita o adquirida y el tratamiento oportuno pueden evitar complicaciones y secuelas en los casos graves. Se describe el caso de un lactante menor que presentaba una infección por citomegalovirus con la manifestación poco frecuente de hemorragia cerebral. Después del tratamiento con ganciclovir, los síntomas clínicos evolucionaron favorablemente. La infección por citomegalovirus es muy frecuente en la edad pediátrica, tanto en la forma congénita como en la adquirida. La forma adquirida, como la de este caso, se caracteriza principalmente por el compromiso hematológico, al producirse una importante trombocitopenia, lo que puede originar, aunque infrecuentemente, sangrado del sistema nervioso central; la mayoría de las infecciones adquiridas, sin embargo, son de resolución espontánea y no requieren tratamiento. En este paciente no se presentaron repercusiones clínicas de importancia.

Cytomegalovirus is the most frequent causative agent of perinatal infection and a major cause of acquired viral infections. This case report aims to show the broad clinical spectrum of the presentation of cytomegalovirus infection. The correct classification of congenital or acquired infection and its prompt treatment can prevent complications and sequelae in severe cases. We report the case of an infant with acquired cytomegalovirus infection, which presented an unusual feature of cerebral hemorrhage. The patient was treated with ganciclovir, with a favorable evolution of the clinical symptoms. Cytomegalovirus infection is common in children, both in its congenital and acquired forms. Acquired infection, as portrayed in this case, is mainly characterized by hematological compromise given by the marked thrombocytopenia, which may rarely result in cases of bleeding in the central nervous system. In this patient, no important clinical implications occurred. In addition, most of the acquired infections are self-limited and require no treatment.

Neumonitis por citomegalovirus en pacientes con sida fallecidos / Pneumonitis caused by cytomegalovirus in dead aids patients

Introducción: El citomegalovirus (CMV) es considerado un germen oportunista común entre individuos con infección por el virus de inmunodeficiencia humana (VIH) y con frecuencia produce enfermedades en diferentes órganos. Objetivo: Conocer la incidencia de esta entidad en nuestro medio. Material y método: Se realizó un estudio descriptivo ambispectivo que incluyó 105 de las 674 autopsias realizadas en pacientes con sida fallecidos en el Instituto de Medicina Tropical Pedro Kourí, con el diagnóstico postmorten de enfermedad por CMV en el período comprendido entre 1986 y 2008. Se describe el comportamiento de variables sociodemográficas, principales órganos afectados, correlación clínico-patológica, hallazgos clínicos y de laboratorio, relación entre el conteo de linfocitos T CD4+ y las formas clínicas de la enfermedad. Resultados: Predominó el sexo masculino en una proporción 4:1 y el color de piel blanco (80,2 por ciento). El 66,6 por ciento de los casos tenía enfermedad diseminada. Las glándulas suprarrenales (41,9 por ciento), el tubo digestivo (30,5 por ciento) y el encéfalo (17,1por ciento) fueron los órganos más afectados. La fiebre (51,4 por ciento), la diarrea (42,9 por ciento), las convulsiones (31,4 por ciento) y el desgaste físico (17,1 por ciento) fueron los síntomas más frecuentes. Los niveles de lactato deshidrogenasa (LDH) mayores de 600 mmol/L se asociaron fuertemente a CMV como causa de muerte (p= 0,005). Aproximadamente el 70 por ciento de los pacientes tenía menos de 100 células/µL y el 37,5 por ciento menos de 50 células/µL, aunque esto no influyó de manera significativa en las formas clínicas de presentación (p0,641). Conclusiones: La enfermedad por CMV se diagnosticó mayormente postmorten, diseminada y asociada con niveles elevados de LDH y conteo de linfocitos T CD4 menor de 100 células/µL...

Introduction : Cytomegalovirus (CMV) is considered a common opportunistic germ in individuals infected with human immunodeficiency virus (HIV) often causing disease in different organs. Objective: To determine the incidence of this condition in our environment. Material and Methods: A descriptive, ambispective study that included 105 of the 674 autopsies of AIDS patients died at the Institute of Tropical Medicine Pedro Kouri, with postmortem diagnosis of CMV disease, between 1986 and 2008. Sociodemographic variables, main organs affected, clinical and pathological correlation, clinical and laboratory findings, relation between CD4 + T cells count and clinical forms of the disease are described. Results: Males predominated in a ratio 4:1 as well as white skin color (80.2 percent). 66.6 percent of patients had disseminated disease. Adrenal glands (41.9 percent), gastrointestinal tract (30.5 percent) and brain (17.1percent) were the most affected organs. Fever (51.4 percent), diarrhea (42.9 percent), seizures (31.4 percent) and physical consumption (17.1 percent) were the most frequent symptoms. LDH levels >600 mmol/L were strongly associated to CMV as cause of death (p = 0.005). Nearly 70 percent of patients had less than 100 cells/µL and 37.5 percent less than 50 cells/µL, although this had no significant influence in the clinical forms of presentation (p = 0.641). Conclusions: CMV disease was mainly diagnosed postmortem, usually spread and in association with high levels of LDH and CD4 count lesser than 100 cells/µL...

Long-Term Outcomes of Cytomegalovirus Reactivation in Patients with Moderate to Severe Ulcerative Colitis: A Multicenter Study

BACKGROUND/AIMS: Cytomegalovirus (CMV) reactivations are frequently observed in patients with active ulcerative colitis (UC), and ganciclovir therapy is effective in patients with steroid-refractory UC. This study aimed to determine the long-term outcomes of CMV reactivation and the long-term therapeutic efficacy of ganciclovir treatment. METHODS: This retrospective multicenter study included a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV reactivation at the time of their initial UC flare. Colectomy, disease relapse, and the recurrence rate of CMV reactivation were investigated. RESULTS: The mean duration of follow-up for the 72 patients was 43.16+/-19.78 months (range, 1 to 67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of the 11 patients who were successfully treated with ganciclovir in the initial treatment, three patients (27.3%) experienced CMV reactivation, and six patients (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid-dependent state. CONCLUSIONS: The patients who had CMV-reactivated UC showed poor outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir therapy was marginal. Careful assessment is necessary for patients who exhibit evidence of CMV reactivation.

Auditory steady state response in hearing assessment in infants with cytomegalovirus / Importancia de lainclusion de larespuesta auditiva de estado estable en la evaluacion auditiva en lactantes concitomegalovirus / Resposta auditiva de estado estavel na avaliacao auditiva em lactentes com citomegalovirus

OBJECTIVE: To report an infant with congenital cytomegalovirus and progressive sensorineural hearing loss, who was assessed by three methods of hearing evaluation. CASE DESCRIPTION: In the first audiometry, at four months of age, the infant showed abnormal response in Otoacoustic Emissions and normal Auditory Brainstem Response (ABR), with electrophysiological threshold in 30dBnHL, in both ears. With six months of age, he showed bilateral absence of the ABR at 100dBnHL. The behavioral observational audiometry was impaired due to the delay in neuropsychomotor development. At eight months of age, he was submitted to Auditory Steady State Response (ASSR) and the thresholds were 50, 70, absent in 110 and in 100dB, respectively for 500, 1,000, 2,000 and 4,000Hz in the right ear, and 70, 90, 90 and absent in 100dB, respectively for 500, 1,000, 2,000 and 4,000Hz in the left ear. COMMENTS: In the first evaluation, the infant had abnormal Otoacoustic Emission and normal ABR, which became altered at six months of age. The hearing loss severity could be identified only by the ASSR, which allowed the best procedure for hearing aids adaptation. The case description highlights the importance of the hearing status follow-up for children with congenital cytomegalovirus. .

OBJETIVO: Relatar el caso de un lactante con citomegalovirus congénito y disacusianeurosensorial progresiva, analizado por tres métodos de evaluación auditiva. DESCRIPCIÓN DEL CASO: En la primera evaluación auditiva, a los cuatro meses de edad, el lactante presentó ausencia de Emisiones Otoacústicas (EOA) y Potencial Evocado Auditivo de Tronco Encefálico (PEATE) dentro de los estándares de normalidad para la franja de edad, con umbral electrofisiológico en 30dBnHL, bilateralmente. Con seis meses, presentó ausencia de PEATE bilateral en 100dBnHL. La evaluación comportamental de la audición se mostró perjudicada debido al retardo en el desarrollo neuropsicomotor. A los ocho meses, fue sometido al examen de Respuesta Auditiva de Estado Estable (RAEE) y los umbrales encontrados fueron 50, 70, ausente en 110 y en 100dB, respectivamente para 500, 1.000, 2.000 y 4.000Hz, a la derecha, y 70, 90, 90 y ausente en 100dB, respectivamente para 500, 1.000, 2.000 y 4.000, a la izquierda. COMENTARIOS: En la primera evaluación, el lactante presentó alteración auditiva en el examen de EOA y PEATE normal, que pasó a ser alterado a los seis meses de edad. La intensidad de la pérdida auditiva solo puede identificarse por el examen de RAEE, permitiendo establecer la mejor conducta en la adaptación de aparato de amplificación sonora individual. Se subraya la importancia del seguimiento audiológico para niños con CMV congénito. .

OBJETIVO: Relatar o caso de um lactente com citomegalovírus congênito e disacusia neurossensorial progressiva, analisado por três métodos de avaliação auditiva. DESCRIÇÃO DO CASO: Na primeira avaliação auditiva, aos quatro meses de idade, o lactente apresentou ausência de Emissões Otoacústicas (EOA) e Potencial Evocado Auditivo de Tronco Encefálico (PEATE) dentro dos padrões de normalidade para a faixa etária, com limiar eletrofisiológico em 30dBnHL, bilateralmente. Com seis meses, apresentou ausência de PEATE bilateral em 100dBnHL. A avaliação comportamental da audição mostrou-se prejudicada devido ao atraso no desenvolvimento neuropsicomotor. Aos oito meses, foi submetido ao exame de Resposta Auditiva de Estado Estável (RAEE) e os limiares encontrados foram 50, 70, ausente em 110 e em 100dB, respectivamente para 500, 1.000, 2.000 e 4.000Hz, à direita, e 70, 90, 90 e ausente em 100dB, respectivamente para 500, 1.000, 2.000 e 4.000Hz, à esquerda. COMENTÁRIOS: Na primeira avaliação, o lactente apresentou alteração auditiva no exame de EOA e PEATE normal, que passou a ser alterado aos seis meses de idade. A intensidade da perda auditiva só pôde ser identificada pelo exame de RAEE, permitindo estabelecer a melhor conduta na adaptação de aparelho de amplificação sonora individual. Ressalta-se a importância do acompanhamento audiológico para crianças com CMV congênito. .

Neumonía por citomegalovirus en el adulto inmunocompetente / Cytomegalovirus pneumonia in immunocompetent adult patient

Introducción: la Neumonía por Citomegalovirus (CMV) es una entidad rara en los pacientes inmunocompetentes, pero cuando se asocia con otras enfermedades como la neumonía, puede ser altamente letal. Objetivo: presentar un caso infrecuente de infección primaria por Citomegalovirus complicado con neumonía. Presentación del caso: se presenta el caso de una paciente de 36 años de edad, que trabajaba directamente con pacientes trasplantados renales, y que acudió a consulta por presentar fiebre de 38 oC en un período de más de 10 días, precedida de escalofríos, dolor de garganta, tos seca al inicio y luego expectoración de color verde claro; examen físico negativo; todo lo anterior acompañado de astenia marcada durante todo el día y anorexia. La falta de respuesta adecuada al tratamiento con Levofloxacino y Azitromicina nos hizo sospechar la presencia de una Neumonía viral por un germen de etiología no habitual, por lo que se le indicaron exámenes de anticuerpos anti-virales, resultando positivo para Citomegalovirus. Conclusiones: existen procesos inflamatorios pulmonares agudos reversibles de causa infecciosa sin manifestaciones auscultatorias, es decir con disociación clínico-radiológica, que en su mayoría corresponden a procesos de índole viral, y que además no son exclusivos de pacientes inmunodeprimidos...

Introduction: Cytomegalovirus pneumonia is a rare disease in immunocompetent patients, but when associated to other diseases such as pneumonia, it becomes deadly. Objective: to present an uncommon case of primary Cytomegalovirus infection complicated with pneumonia. Case presentation: this is the case of a 36years-old patient who directly worked with renal transplanted patients and went to the doctor´s because of 38o fever for more than 10 days, thrills, throat ache, dry cough at the beginning and clear green colored sputum, negative physical examination results, and marked asthenia during the day and anorexia. The inadequate response to Levofloxacine and Azitromycin treatment made us suspect of viral pneumonia caused by an infrequent germ. Anti-viral antibodies tests were indicated to reveal positive results for Cytomegalovirus. Conclusions: there are reversible acute pulmonary inflammatory processes of infective origin without any manifestation on physical exam, that is, a clinical-radiological dissociation; the majority of these processes are of viral origin but they do not occur only in immunodepressed patients...

Síndrome hemofagocítico secundario: reporte de 5 casos / Secondary hemophagocytic syndrome: report of 5 cases

Secondary hemophagocytic syndrome (HFS) is an uncommon entity with a high mortality rate in adults, if no therapy is given. It is characterized by a severehipercytokinemia due to a highly stimulated but ineffective immune system. Theprincipal causes are infections, malignancy or autoimmune diseases. It appears asa serious illness, similar to a multiorgan failure. Treatment is not well defined. Wereport five patients with HFS, aged 17 to 51 years (three females). The etiology wasonco-hematological in three patients. In two patients, the diagnosis was performedduring necropsy. One case was due to cytomegalovirus (CMV) infection in a hepatictransplant patient and the other, due to parenteral lipid administration. All presentedfever, cytopenia, hepatosplenomegaly and hemophagocytosis. Four of them requiredadmission in an Intensive Care Unit. All received different treatment modalities. Onlyone survived. Median survival time was 75 days. In conclusion, HFS has differentetiologies and a high mortality in adults.