Typical hemophagocytic syndrome associated with cytomegalovirus infection in an immunocompetent patient: a case report and literature review / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cytomegalovirus (CMV) infection is currently prevalent in populations throughout the world, and 56%‍-94% of the global population is seropositive for CMV. CMV infection mainly affects immunocompromised hosts. In these cases, it can cause significant symptoms, tissue-invasive disease, and many sequelae including death (Dioverti and Razonable, 2016). The vast majority of healthy adults with CMV infection experience an asymptomatic course; when symptomatic, it manifests as a mononucleosis-like syndrome in approximately 10% of patients (Sridhar et al., 2018). The gastrointestinal tract and central nervous system appear to be the most frequent sites of severe CMV infection in immunocompetent individuals (Rafailidis et al., 2008). However, CMV infection is relatively rarely recorded in immunocompetent hosts.

Recomendaciones para el diagnóstico y manejo de la infección por citomegalovirus en la mujer embarazada y el recién nacido / Recommendations for the diagnosis and management of cytomegalovirus infection in pregnant woman and newborn infant

Resumen La Sociedad Chilena de Infectología, a través de su Comité de Infecciones Neonatales, en conjunto con la Sociedad Chilena de Obstetricia y Ginecología, proponen un documento de diagnóstico y manejo de la Infección por Citomegalovirus en la Mujer Embarazada y el Recién Nacido. Esta guía aborda el manejo de la infección en el binomio, su enfrentamiento diagnóstico y terapéutico, orientado al equipo de salud que atiende a mujeres embarazadas y recién nacidos con infección por citomegalovirus (CMV) en Chile. Considera la situación epidemiológica global y latinoamericana, con recomendaciones para la evaluación clínica y de laboratorio; establece criterios de diagnóstico, propone enfoques terapéuticos de acuerdo a la situación clínica, analiza las medidas de prevención y establece una propuesta nacional para el seguimiento de esta enfermedad. Se ha puesto especial énfasis en entregar, de forma práctica, y con la mayor evidencia posible, las recomendaciones para el manejo del binomio con infección por CMV.

Abstract The Chilean Society of Infectology, through its Neonatal Infections Committee in conjunction with the Chilean Society of Obstetrics and Gynecology, propose a document for the Diagnosis and Management of Cytomegalovirus Infection in Pregnant Woman and Newborn Infant. This guideline suggests the management of mother and child infection, its diagnostic and therapeutic options. Considers the global and Latin American epidemiology, with recommendations for clinical and laboratory evaluation; diagnostic criteria, therapeutic approaches according to the clinical situation, analyzes prevention measures and establishes a national proposal for monitoring this disease.

Recomendaciones para el diagnóstico y el manejo de la infección por citomegalovirus en la mujer embarazada y el recién nacido / Recommendations for the diagnosis and management of cytomegalovirus infection in pregnant women and newborns

Resumen La Sociedad Chilena de Infectología, a través de su Comité de Infecciones Neonatales, en conjunto con la Sociedad Chilena de Obstetricia y Ginecología, proponen un documento de diagnóstico y manejo de la infección por citomegalovirus (CMV) en la mujer embarazada y el recién nacido. Esta guía aborda el manejo de la infección en el binomio, su enfrentamiento diagnóstico y terapéutico, orientado al equipo de salud que atiende a mujeres embarazadas y recién nacidos con infección por CMV en Chile. Considera la situación epidemiológica global y latinoamericana, con recomendaciones para la evaluación clínica y de laboratorio; establece criterios de diagnóstico, propone enfoques terapéuticos de acuerdo a la situación clínica, analiza las medidas de prevención y establece una propuesta nacional para el seguimiento de esta enfermedad. Se ha puesto especial énfasis en entregar, de forma práctica, y con la mayor evidencia posible, las recomendaciones para el manejo del binomio con infección por CMV.

Abstract The Chilean Society of Infectology, through its Neonatal Infections Committee in conjunction with the Chilean Society of Obstetrics and Gynecology, propose a document for the Diagnosis and Management of Cytomegalovirus Infection in Pregnancy and Newborn. This guideline suggests the management of mother and child infection, its diagnostic and therapeutic options. Considers the global and Latin American epidemiology, with recommendations for clinical and laboratory evaluation, diagnostic criteria, therapeutic approaches according to the clinical situation, analyzes prevention measures and establishes a national proposal for monitoring this disease.

Clinical validation of an in-house quantitative real time PCR assay for cytomegalovirus infection using the 1st WHO International Standard in kidney transplant patients / Validação clínica de um ensaio de PCR in house quantitativo em tempo real para infecção por citomegalovírus usando o 1º Padrão Internacional da OMS em pacientes com transplantados renais

Abstract Introduction: Cytomegalovirus (CMV) is one of the most common agents of infection in solid organ transplant patients, with significant morbidity and mortality. Objective: This study aimed to establish a threshold for initiation of preemptive treatment. In addition, the study compared the performance of antigenemia with qPCR results. Study design: This was a prospective cohort study conducted in 2017 in a single kidney transplant center in Brazil. Clinical validation was performed by comparing in-house qPCR results, against standard of care at that time (Pp65 CMV Antigenemia). ROC curve analysis was performed to determine the ideal threshold for initiation of preemptive therapy based on the qPCR test results. Results: Two hundred and thirty two samples from 30 patients were tested with both antigenemia and qPCR, from which 163 (70.26%) were concordant (Kappa coefficient: 0.435, p<0.001; Spearman correlation: 0.663). PCR allowed for early diagnoses. The median number of days for the first positive result was 50 (range, 24-105) for antigenemia and 42 (range, 24-74) for qPCR (p<0.001). ROC curve analysis revealed that at a threshold of 3,430 IU/mL (Log 3.54), qPCR had a sensitivity of 97.06% and a specificity of 74.24% (AUC 0.92617 ± 0.0185, p<0.001), in the prediction of 10 cells/105 leukocytes by antigenemia and physician's decision to treat. Conclusions: CMV Pp65 antigenemia and CMV qPCR showed fair agreement and a moderate correlation in this study. The in-house qPCR was revealed to be an accurate method to determine CMV DNAemia in kidney transplant patients, resulting in positive results weeks before antigenemia.

Resumo Introdução: Citomegalovírus (CMV) é um dos agentes infecciosos mais comuns em pacientes com transplante de órgãos sólidos, com morbidade e mortalidade significativas. Objetivo: Este estudo visou estabelecer um limite para o início do tratamento preemptivo. Além disso, comparou o desempenho da antigenemia com os resultados da qPCR in house. Desenho do estudo: Este foi um estudo de coorte prospectivo realizado em 2017 em um centro único de transplante renal no Brasil. A validação clínica foi realizada comparando resultados de qPCR in house, com o padrão de atendimento na época (Antigenemia para CMV Pp65). A análise da curva ROC foi realizada para determinar o limite ideal para o início da terapia preemptiva baseado nos resultados do teste qPCR in house. Resultados: 232 amostras de 30 pacientes foram testadas com antigenemia e qPCR, das quais 163 (70,26%) foram concordantes (Coeficiente Kappa: 0,435, p<0,001; Correlação Spearman: 0,663). PCR permitiu diagnósticos precoces. O número médio de dias para o primeiro resultado positivo foi 50 (intervalo, 24-105) para antigenemia e 42 (intervalo, 24-74) para qPCR (p<0,001). A análise da curva ROC revelou que em um limite de 3.430 UI/mL (Log 3,54), qPCR teve sensibilidade de 97,06% e especificidade de 74,24% (AUC 0,92617 ± 0,0185, p<0,001), na previsão de 10 células/10(5) leucócitos por antigenemia e na decisão do médico de tratar. Conclusões: Antigenemia para CMV Pp65 e qPCR para CMV mostraram uma concordância aceitável e uma correlação moderada neste estudo. qPCR in house revelou-se um método preciso para determinar DNAemia do CMV em pacientes transplantados renais, obtendo resultados positivos semanas antes da antigenemia.

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)

Cribado de infección por citomegalovirus congénito en recién nacidos de alto riesgo / Congenital cytomegalovirus infection screening in high risk newborn

INTRODUCCIÓN: La infección congénita por citomegalovirus (CMVc) es la causa más frecuente de infección intrauterina, 90% de los recién nacidos (RN) son asintomáticos al nacer y 6 a 15% desarrollarán secuelas a largo plazo, siendo la principal etiología de hipoacusia sensorio-neural no-genética. OBJETIVO: Determinar la prevalencia de CMVc en RN de alto riesgo. PACIENTES Y MÉTODO: Estudio de cohorte prospectivo, incluyó RN hospitalizados, con uno o más de los siguientes criterios: peso de nacimiento < 1.500 g, < 32 semanas edad gestacional (EG), pequeños para edad gestacional (PEG) severos, sospecha de infección congénita o que "no pasan" en estudio auditivo al nacer, además de hijos de madre con infección por VIH. Se realizó reacción de polimerasa en cadena para CMV en orina antes de 21 días de vida. RESULTADOS: Se enrolaron 193 RN. Prevalencia global CMVc 2,6% (n: 5) y por grupo de riesgo: 1/3 (n: 1) en RN con sospecha activa de infección congénita, 8,3% en RN con resultado "no pasa" en estudio auditivo, 4,9% en hijos de madre con infección por VIH, 3,3% en PEG severo y 1,7% < 1500 g, ninguno con asociación significativa. Sólo un paciente con CMVc fue sintomático, quien falleció en el período neonatal y los restantes RN con CMVc (asintomáticos) tienen seguimiento auditivo normal. DISCUSIÓN: La prevalencia reportada es comparable a las internacionales. Recomendamos cribado de CMVc, al menos en grupos de riesgo, siendo lo ideal el cribado universal. Esto permitiría su tratamiento oportuno y un seguimiento activo.

BACKGROUND: Congenital cytomegalovirus infection (cCMV) is the most frequent cause of congenital infection, 90% of affected newborn (NB) are asymptomatic at birth and 6-15% will develop long term sequalae. It is the main etiology of non-genetic sensorineural hearing loss. AIM: To determine prevalence of CMV in high risk NB. Methods: Cohort prospective study, including inpatient NB with one or more of following criteria: birth weight < 1,500 g, < 32 weeks gestational age (GA), severe small for gestational age (SGA), suspected congenital infection or "refer" in newborn hearing test, also NB to HIV-infected mothers. Urine CMV polymerase chain reaction was performed within 21 day of life. RESULTS: 193 NB were enrolled. Global cCMV prevalence 2.6% (n: 5) and by risk group: one third (n: 1) in NB with suspected congenital infection, 8.3% in NB with "refer" result in hearing test, 4.9% in NB to HIV-infected mothers, 3.3% in severe SGA and 1.7% in < 1,500 g, none with significant association. Only one symptomatic cCMV was detected who died in neonatal period and the remaining (asymptomatic) cCMV patients have normal hearing follow-up. DISCUSSION: Reported prevalence was comparable to international reports. We recommend cCMV screening, at least in risk groups, being ideal the universal screening. This would allow timely treatment and active follow-up.

Optimización del diagnóstico de hepatitis por citomegalovirus en receptores de trasplante hepático: diez años de experiencia / Cytomegalovirus hepatitis diagnosis optimization in liver transplant recipients: 10 years of experience

Resumen Introducción: Para los pacientes receptores de trasplante hepático (TH) la hepatitis por citomegalovirus (CMV) constituye una entidad de difícil diagnóstico. Nuestro objetivo fue determinar la real incidencia de hepatitis por CMV aplicando técnicas diagnósticas más específicas. Material y Métodos: Estudio retrospectivo/ prospectivo, en un centro de trasplante hepático. Período de estudio: años 2009 al 2019. Se incluyeron los TH que presentaron elementos sugestivos y/o específicos de CMV en la histopatología de la punción biopsia hepática (PBH), a los que se les realizó inmunohistoquimica (IHQ) en la PBH. Población control n = 17. Resultados: 41 casos cumplieron los criterios de inclusión. La IHQ fue positiva en n = 6 (14,6%). En la población control, la IHQ fue negativa en el 100% de los casos. Esto traduce un valor predictor negativo de 100% para la histopatología en el diagnóstico de hepatitis por CMV, con un valor predictor positivo de 14,6%. En 85% de los pacientes con IHQ negativa, hubo diagnósticos alternativos. La terapia antiviral en la fase retrospectiva se indicó en 48% y en la prospectiva en 21%. Conclusiones: Combinar la histopatología con la IHQ optimiza el diagnóstico de hepatitis por CMV; lo que permite la racionalización del uso de antivirales de alto costo y la búsqueda de etiologías diferenciales.

Abstract Background: Cytomegalovirus (CMV) hepatitis constitutes a challenging diagnostic entity in liver transplant (LT) recipients. Aim: To determine the real incidence of CMV hepatitis using more specific diagnostic tools as those currently used before. Methods: Retrospective/prospective study conducted in a hepatic transplant unit from 2009 to 2019. LT recipients with CMV specific or suggestive elements in histopathology of hepatic biopsies were included. Immunohistochemistry (IHQ) was performed in tissue samples of the studied cohort as well as in a control one. Results: 41 patients met the inclusion criteria. IHQ was diagnostic in 6 (14.6%), and was negative in 100% of the control population. The negative predictive value of the histopathology for CMV hepatitis diagnosis was 100% and the positive predictive value was 14.6%. 85% of patients in whom the IHQ was negative had alternative diagnosis Antiviral therapy in the retrospective analysis was indicated in 48% of patients and in 21% of the prospectively analyzed cohort. Conclusions: Histopathology and IHQ combination improves the diagnostic accuracy of CMV hepatitis which translates into a rational us of expensive antiviral therapy and to search for differential diagnosis

Cost minimization analysis of an in-house molecular test for cytomegalovirus in relation to a commercial molecular system

ABSTRACT Introduction: Cytomegalovirus may cause severe disease in immunocompromised patients. Nowadays, quantitative polymerase chain reaction is the gold-standard for both diagnosis and monitoring of cytomegalovirus infection. Most of these assays use cytomegalovirus automated molecular kits which are expensive and therefore not an option for small laboratories, particularly in the developing world. Objective: This study aimed to optimize and validate an in-house cytomegalovirus quantitative polymerase chain reaction test calibrated using the World Health Organization Standards, and to perform a cost-minimization analysis, in comparison to a commercial cytomegalovirus quantitative polymerase chain reaction test. Study design: The methodology consisted of determining: optimization, analytical sensitivity, analytical specificity, precision, curve variability analysis, and inter-laboratorial reproducibility. Patients (n = 30) with known results for cytomegalovirus tested with m2000 RealTime System (Abbott Laboratories, BR) were tested with the in-house assay, as well as patients infected with other human herpes virus, in addition to BK virus. A cost-minimization analysis was performed, from a perspective of the laboratory, assuming diagnostic equivalence of the methodologies applied in the study. Results: The in-house assay had a limit of detection and quantification of 60.3 IU/mL, with no cross-reactivity with the other viral agents tested. Moreover, the test was precise and had a R 2 of 0.954 when compared with the m2000 equipment. The cost analysis showed that the assay was economically advantageous costing a median value of 37.8% and 82.2% in comparison to the molecular test in use at the hospital and the m2000 equipment, respectively. Conclusions: These results demonstrated that in-house quantitative polymerase chain reaction testing is an attractive alternative in comparison to automated molecular platforms, being considerably less expensive and as efficacious as the commercial methods.

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.

Pneumonia por toxoplasmose em paciente imunocompetente / Toxoplasma pneumonia in an immunocompetent patient: case repor

Com grande distribuição mundial e incidência significativa, a toxoplamose é uma doença comum em mamíferos e pássaros, causada pelo protozoário Toxoplasma gondii. No homem, o parasitismo na fase proliferativa intracelular pode se apresentar sem sintomas, ou causar clínica transitória caracterizada por febre, fadiga e linfadenopatia. Por se tratar de patologia com sintomas inespecíficos e comuns a muitas outras, é fundamental a correta pesquisa de diagnósticos diferenciais, como citomegalovírus e Epstein-Barr. Relatamos o caso de um jovem e hígido, que desenvolveu pneumonia e, após confirmação sorológica para toxoplasmose e o tratamento adequado, apresentou melhora clínica.

With great worldwide distribution and significant incidence, toxoplamosis is a common disease in mammals and birds, caused by the protozoan Toxoplasma gondii. In humans, the parasitism in its intracellular proliferative phase may present no symptoms, or cause a transient condition characterized by fever, fatigue, and lymphadenopathy. Because it is a pathology with nonspecific symptoms that are common to many other conditions, it is fundamental to find the correct research of differential diagnoses, such as for Cytomegalovirus and Epstein Barr. We report a case of a young and healthy man who developed pneumonia and, after serological confirmation for toxoplasmosis and the appropriate treatment, presented clinical improvement

Seroprevalence of cytomegalovirus and its coinfection with Epstein-Barr virus in adult residents from Manaus: a population-based study

Abstract INTRODUCTION: This study assessed the seroprevalence of cytomegalovirus, associated factors, and Epstein-Barr virus coinfection among adult residents of Manaus. METHODS: Using a cross-sectional study design, we collected blood samples from 136 individuals in a household survey in 2016. Prevalence ratios were calculated using Poisson regression. RESULTS: Cytomegalovirus and Epstein-Barr virus seroprevalences were 67.6% (95% CI: 9.7-75.6%) and 97.8% (95% CI: 95.3-100.0%), respectively. Coinfection was observed in 66.2% (95% CI: 58.1-74.2%) of participants. Bivariate analysis showed no statistical association. CONCLUSIONS: Seroprevalences were high among participants and approximately 7 out of 10 individuals had cytomegalovirus and Epstein-Barr virus coinfection.

Síntesis intratecal de IgG anti-herpes virus como evidencia neuroinmunológica en pacientes pediátricos / Intrathecal synthesis of IgG against herpes virus as neuroimmunological evidence in pediatric patients

En los procesos neuroinflamatorios se produce a nivel de líquido cefalorraquídeo una activación policlonal y poliespecífica. Esta activación se produce desde los primeros días y puede permanecer por períodos prolongados. Luego por mecanismos de apoptosis los clones que no responden directamente contra los agentes biológicos involucrados no proliferan. El Reibergrama permite saber si las inmunoglobulinas presentes en el líquido cefalorraquídeo se sintetizaron o no en el sistema nervioso central (SNC) y el Índice de Anticuerpo (IA) determina la especificidad de las mismas en caso de que exista síntesis intratecal. Con estas herramientas nos propusimos identificar la respuesta neuroinmunológica frente a agentes de la familia herpesvirus en pacientes pediátricos con proceso inflamatorio del SNC a partir de sus respectivos IA. Para lograr esto se cuantificaron los niveles de IgG y albúmina en suero y líquido cefalorraquídeo (LCR) mediante inmunodifusión radial simple y por ensayo inmunoenzimático, con lo cual se construyó el Reibergrama que permitió la selección de 85 pacientes pediátricos con síntesis intratecal de inmunoglobulinas, que se diferenciaron en cuatro grupos según sus edades. Mediante ensayo inmunoenzimático se cuantificaron los niveles de IgG específica contra citomegalovirus, virus varicela zoster y virus herpes simple, tanto en suero como en LCR y se determinó el IA específico. La respuesta contra los virus estudiados fue similar para los distintos grupos de edades, lo cual nos permite afirmar la exposición temprana a los mismos(AU)

In a neuroinflammatory process a polyclonal and poly-specific activation is produced in cerebrospinal fluid. This activation starts from the first days and may persist for a long time. The clones not related directly against the biological agent do not proliferate by apoptosis. Reibergram determine if part of the immunoglobulins content in cerebrospinal fluid belongs from the blood or it is synthesized in the central nervous system. Antibody index determines if the specific antibodies was synthesized intrathecally. By these tools it can be possible to identify the humoral immune response against some herpes virus in pediatric patients suffering from a central nervous system inflammatory process. Quantification of specific IgG against citomegalovirus, varicella zoster and herpes simplex virus in serum and cerebrospinal fluid was done by ELISA. Specific Antibody index against these viruses were similar for the different age groups, which confirm the early exposure of the population(AU)

Infección por citomegalovirus humano en neonatos de un hospital público de Mérida, Yucatán / Human cytomegalovirus infection in neonates from a public hospital in Mérida, Yucatán

Resumen Introducción: El citomegalovirus humano es reconocido como la causa más común de infección viral congénita, la cual puede darse como resultado de infección primaria, reinfección o reactivación en la mujer embarazada; además, puede ocasionar retraso en el desarrollo neuronal y pérdida auditiva sensoneural en el neonato. Objetivo: Identificar la infección por citomegalovirus humano en neonatos por PCR en tiempo real (PCR-TR) y cultivo celular. Método: Estudio observacional, longitudinal y retrospectivo con muestras de hisopado oral provenientes de 362 neonatos nacidos en un periodo de 10 meses en un hospital público de Mérida, Yucatán. Se realizó PCR-TR para la detección de citomegalovirus humano. Se obtuvo cultivo celular primario de fibroblastos a partir de tejido de prepucio humano para recuperar el virus. Se siguieron solo los casos positivos. Resultados: Se encontró 0.86 % de infección por citomegalovirus humano por PCR-TR. No se recuperó el virus en cultivo. En las visitas de seguimiento, la salud sensorial y el neurodesarrollo fueron adecuados. Conclusión: La prevalencia de infección por citomegalovirus humano en neonatos fue similar a la de reportes mundiales y solo pudo evidenciarse por PCR. La infección asintomática detectada entre las 12 a 24 horas del nacimiento no tuvo consecuencias a largo plazo.

Abstract Introduction: Human cytomegalovirus (HCMV) is recognized as the most common cause of congenital viral infection, which can occur as a result of primary infection, reinfection or infection reactivation in the pregnant woman and be the cause of delay in neuronal development and sensorineural hearing loss in the neonate. Objective: To identify CMVH infection in newborns by real-time polymerase chain reaction (RT-PCR) and cell culture. Method: Observational, cross-sectional, retrospective study with oral swab samples from 362 neonates born within a 10-month period in a public hospital of Mérida, Yucatán. RT-PCR was carried out for the detection of HCMV. Fibroblast primary cell culture was obtained from human foreskin tissue to isolate the virus. Only positive cases were followed. Results: A prevalence of HCMV infection of 0.86 % was found by RT-PCR. No virus was isolated with cell culture. In the follow-up visits, sensory health and neurodevelopment were adequate. Conclusion: The prevalence of HCMV infection is similar to that of worldwide reports, and only was detected by RT-PCR. Asymptomatic infection detected 12-14 h after birth had no long-term health consequences.

Serological status of childbearing-aged women for Toxoplasma gondii and cytomegalovirus in northern Kosovo and Metohija

Abstract INTRODUCTION: Toxoplasma gondii and cytomegalovirus (CMV) are pathogens associated with congenital anomalies. METHODS: Serum was collected from 79 reproductive-age women and tested for IgM and IgG antibodies to T. gondii and CMV. RESULTS: Seropositivity for T. gondii was detected in 24.1% of women and CMV in 96.2%. High seropositivity for CMV was found for all ages. The highest seropositivity for T. gondii was observed among older participants. CONCLUSIONS: T. gondii remains an important pathogen owing to low seropositivity.

Standardization of antigenemia and qpcr cut-off values in whole blood for the detection of cytomegalovirus disease in hiv patients

Abstract INTRODUCTION: We defined the cut-off values of the antigenemia and cytomegalovirus (CMV) DNA tests in HIV/AIDS patients to identify CMV disease. METHODS: A total of 97 samples from 68 patients with and without CMV disease were analyzed by viral DNA detection and antigenemia assay. RESULTS: Qualitative and quantitative results significantly differed between assays. The cut-off values for the antigenemia and qPCR assays were 1.5 positive cells/200,000 leukocytes and 3.715 log/mL, respectively. CONCLUSIONS: Antigenemia and qPCR are suitable for monitoring CMV disease in HIV patients, however, the threshold values should be determined within the centers where the patients are monitored.

Risk factors for cytomegalovirus disease in systemic lupus erythematosus (SLE): a systematic review

Abstract Background: Cytomegalovirus (CMV) is an opportunistic pathogen causing reactivation and disease in Systemic Lupus Erythematosus (SLE) patients. This study aims to systematically review the literature for risk factors associated with CMV disease in SLE patients, in order to identify those more susceptible to CMV infection during their treatment. Methods: A systematic review was conducted on 4 different search engines and via hand search until May 2017. Studies were included after quality assessment via the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields (HTA KMET). Results: Two studies on CMV disease were included. Elevated CMV viral load, higher steroid doses, use of immunosuppressants and disease duration were the most commonly associated risk factors for CMV disease. Conclusion: High CMV viral loads, longer SLE disease duration and higher steroid doses were associated with CMV disease. Further studies studying the risk of treatment drugs and role of interventions in the development of CMV infection are needed.

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)