Informe diário de evidências COVID-19: busca realizada em 6 de agosto de 2020 / Daily evidence report COVID-19: Search conducted on August 6, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 11 artigos e 10 protocolos.

Informe diário de evidências COVID-19: busca realizada em 17 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 17, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 13 protocolos.

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.

Ganciclovir attenuates the respiratory disease induced by Equid alphaherpesvirus 1 in rabbits / O ganciclovir atenua a doença respiratória produzida pelo alfaherpesvírus equino 1 em coelhos

Equid alphaherpesvirus 1 (EHV-1) is an important pathogen of horses, associated with respiratory, neurological disease and abortions. As vaccination is not always effective, anti-herpetic therapy may represent an alternative to prevent the losses caused by the infection. We herein investigated the activity of ganciclovir (GCV), an anti-herpetic human drug, in rabbits experimentally infected with EHV-1. Thirty-days-old New Zealand rabbits were allocated in three groups (6 animals each) and submitted to different treatments: G1 (non-infected controls), G2 (inoculated with EHV-1) - 107 TCID50 intranasally - IN) and G3 (inoculated IN with EHV-1 and treated with GCV - 5mg/kg/day for 7 days) and monitored thereafter. All animals of G2 developed systemic signs (moderate to severe apathy, anorexia), ocular discharge and respiratory signs (serous to mucopurulent nasal discharge), including mild to severe respiratory distress. Viremia was detected in all rabbits of G2 for up to 11 days (mean duration = 6.5 days). One animal died after severe respiratory distress and neurological signs (bruxism, opistotonus). In addition, these animals gained less weight than the control (G1) and GCV-treated rabbits (G3) from days 4 to 14pi (p<0.05). The clinical score of rabbits of G2 was statistically higher than the other groups from days 3 to 6pi (p<0.05), demonstrating a more severe disease. In contrast, G3 rabbits did not present systemic signs, presented only a mild and transient nasal secretion and gained more weight than G2 animals (p<0.05). In addition, viremia was detected in only 3 rabbits and was transient (average of 2.3 days). Thus, administration of GCV to rabbits inoculated IN with EHV-1 resulted in an important attenuation of the clinical disease as demonstrated by full prevention of systemic signs, maintenance of weight gain and by drastic reduction in viremia and in the magnitude of respiratory signs. These results are promising towards further testing of GCV as a potential drug for anti-herpetic therapy in horses.(AU)

O alfaherpesvírus equino 1 (EHV-1) é um importante patógeno de equinos, associado com doença respiratória, neurológica e abortos. Como a vacinação nem sempre é eficaz, a terapia anti-herpética pode representar uma alternativa para prevenir as perdas causadas pela infecção. Para tal, investigou-se a atividade do ganciclovir (GCV), uma droga anti-herpética de uso humano, em coelhos infectados experimentalmente com o EHV-1. Coelhos da raça Nova Zelândia com 30 dias de idade foram alocados em três grupos (6 animais cada) e submetidos a diferentes tratamentos: G1 (controles não infectados), G2 (inoculados com o EHV-1) - 107 TCID50 intranasal - IN) e G3 (inoculados IN com o EHV-1 e tratados com GCV - 5mg/kg/dia por 7 dias), e monitorados posteriormente. Todos os animais do G2 desenvolveram sinais sistêmicos (apatia moderada a grave, anorexia), secreção ocular e sinais respiratórios (secreção nasal serosa a mucopurulenta), incluindo dificuldade respiratória leve a grave. Viremia foi detectada em todos os coelhos do G2 por até 11 dias (duração média = 6,5 dias). Um animal morreu após dificuldade respiratória grave e sinais neurológicos (bruxismo, opistótono). Além disso, esses animais ganharam menos peso que os coelhos controle (G1) e tratados com GCV (G3) entre os dias 4 e 14pi (p<0,05). O escore clínico de coelhos do G2 foi estatisticamente maior que os demais grupos dos dias 3 a 6pi (p<0,05), demonstrando uma doença mais grave. Em contraste, os coelhos do G3 não apresentaram sinais sistêmicos, apresentaram apenas secreção nasal leve e transiente e ganharam mais peso que os animais do G2 (p<0,05). Além disso, a viremia foi detectada em apenas 3 coelhos e foi transitória (média de 2,3 dias). Assim, a administração de GCV a coelhos inoculados com EHV-1 resultou em uma importante atenuação da doença clínica, como demonstrado pela prevenção completa de sinais sistêmicos, manutenção do ganho de peso e pela redução drástica da viremia e da magnitude dos sinais respiratórios. Estes resultados são promissores para testes adicionais com o GCV para potencial terapêutico anti-herpética em equinos.(AU)

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)

Perfil clínico de la infección congénita por citomegalovirus / Clinical profile of congenital infection by cytomegalovirus

La infección por Citomegalovirus (CMV) se considera la infección viral más frecuente en la gestante, el feto y el recién nacido. Con el objetivo de describir el perfil clínico de la infección congénita por Citomegalovirus en pacientes que ingresaron al Servicio Desconcentrado Hospital Pediátrico Dr. Agustín Zubillaga durante el lapso 2012-2016, se realizó un estudio retrospectivo seleccionando un total de 33 historias clínicas para su evaluación; 60,6% de pacientes presentaron infección congénita por CMV mientras que 39,3% fueron diagnosticados con síndrome de TORCH. El mayor porcentaje de pacientes tenían una edad menor a 7 días (63,6%), con predominio del sexo masculino (63,6%), edad gestacional menor de 36 semanas (69,7%) y un peso al nacer entre 2501-3000 grs (51,5%). La edad promedio del diagnóstico fue de 17,9 ± 10,4 días. El 96,9% de los pacientes presentaron ictericia, petequias (42,4%), enteritis y hepatoesplenomegalia (27,2%, respectivamente). Entre los resultados paraclínicos, 96,9% de los pacientes presentó hiperbilirrubinemia, leucocitosis (72,7%), trombocitopenia (81,8%), aumento de las transaminasas glutámico oxalacética y pirúvica (78,7% y 42,4%, respectivamente). El 96,9% de los pacientes reportaron PCR positivo en sangre, mientras que en 18,1% de los casos el PCR fue positivo en orina y 3% presentaron IgM positiva. Sólo 12,1% de los pacientes recibieron inmunoglobulina humana y 6% recibieron ganciclovir. El tiempo de evolución promedio fue de 25,2 ± 12,5 días y 90,9% de los pacientes evolucionaron satisfactoriamente. En conclusión, este estudio aporta información relevante sobre el perfil clínico de la infección congénita por CMV con el fin de contribuir a mejorar la atención de este tipo de casos en nuestro centro de salud(AU)

Cytomegalovirus (CMV) infection is considered the most common cause of viral infection in pregnant women, the fetus and newborn. With the aim of describing the clinical profile of congenital cytomegalovirus infection in patients admitted in the Servicio Desconcentrado Hospital Pediátrico Dr. Agustín Zubillaga during the 2012-2016 period, we conducted a retrospective study selecting 33 clinical histories to review; 60.6% of patients had congenital CMV infection while 39.3% had TORCH syndrome. 63.6% of patients were < 7 days at the moment of diagnosis, predominantly male (63.6%), with a gestational age < 36 weeks (69.7%) and a birth weight between 2501-3000 grs (51.5%). The average age of diagnosis was 17.9 ± 10.4 days; 96.9% of patients had jaundice, petechial rash (42.4%), enteritis and hepatosplenomegaly (27.2%, respectively). Hyperbilirubinemia was found in 96,9% of patients, leukocytosis in 72,7%, thrombocytopenia in 81.8% and high glutamic oxalacetic and pyruvic transaminase levels in 78.7% and 42.4% of cases. 96.9% of cases reported positive blood PCR, 18.1% positive PCR in urine and 3% positive IgM. Only 12.1% of patients received human immunoglobulin and 6% received ganciclovir. The average hospital stay was 25.2 ± 12.5 days and 90.9% of patients responded satisfactorily. This study provides relevant information on the clinical profile of congenital CMV infection in order to help improve the management of this type of cases in our hospital(AU)

Retinite por citomegalovírus em paciente com Síndrome de Good / Cytomegalovirus retinitis in Good Syndrome

Resumo A Síndrome de Good é uma síndrome paraneoplásica caracterizada pela associação de timoma e hipogamaglobulinemia, cursando com imunossupressão. Relatamos um caso raro de retinite por citomegalovírus em paciente com esta síndrome.

Abstract Good syndrome is a paraneoplastic syndrome characterized by the association of thymoma and hypogammaglobulinemia, with immunosuppression. We report a rare case of cytomegalovirus retinitis in a patient with this syndrome.

Reporte de caso de resistencia al ganciclovir en enfermedad por citomegalovirus postrasplante cardiaco: case report / Resistance to ganciclovir in cytomegalovirus infection after heart transplant

La infección por citomegalovirus postrasplante cardiaco es una condición médica recurrente. Su frecuencia se incrementa cuando los donantes poseen serología positiva y los receptores presentan serología negativa para el virus. En la población pediátrica, la enfermedad solo se desarrolla en un porcentaje pequeño y raramente presentan resistencia al tratamiento convencional con ganciclovir y valganciclovir. Presentamos el primer reporte de caso pediátrico de enfermedad por citomegalovirus resistente a ganciclovir y valganciclovir postrasplante cardiaco en un hospital público peruano, con una presentación inusual. La resistencia a estos fármacos fue evidente luego de 277 días de evolución de la enfermedad, ante la no remisión de la sintomatología y la persistencia de una carga viral elevada. La posterior administración de foscarnet condujo a una mejora clínica y de laboratorio, hasta la remisión de la enfermedad.

Cytomegalovirus infection after a heart transplant is a recurrent medical condition. Its frequency increases when the donors are serum-positive, and the recipients are serum-negative to this virus. In the pediatric population, the infection only develops in a small percentage and the patients rarely present resistance to conventional treatment with ganciclovir and valganciclovir. We presented the first report of a pediatric case of the cytomegalovirus infection resistant to ganciclovir and valganciclovir after a heart transplant in a Peruvian public hospital with an unusual presentation. The resistance to these drugs was evident after 277 days of evolution of the disease considering the non-remission of the symptomatology and the persistence of an elevated viral load. The administration of foscarnet led to a clinical and laboratory improvement until remission of the disease.

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.

Clinical correlates of pp65 antigenemia monitoring in the first months of post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy

Abstract Introduction: Human cytomegalovirus is a major cause of morbidity in kidney transplant patients. Objectives: We aimed to study viral replication and serological response in the first months post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy and correlate the findings with the clinical course of Human cytomegalovirus infection. Patients and methods: Independent from the clinical strategy adopted for managing Human cytomegalovirus infection, prophylaxis versus preemptive therapy, the pp65 antigenemia assay and serological response were assessed on the day of transplantation, and then weekly during the first three months of post-transplant. Results: From the 32 transplant recipients, 16 were positive for pp65 antigenemia, with a similar incidence rate in each group. There were no positive results in the first three weeks of monitoring; the positivity rate peaked at week eight. There was a trend for a higher and earlier frequency of positivity in the universal prophylaxis group in which the course of the Human cytomegalovirus infection was also more severe. Despite the differences in clinical picture and in the initial immunosuppressant schedule, the serological response was similar in both groups. Conclusion: Routine monitoring during the first three post-transplant months has a positive impact on the early detection of Human cytomegalovirus viral replication allowing for timely treatment in order to reduce morbidity of the disease. The strategy of universal therapy employing intravenous ganciclovir was associated to a worse clinical course of the Human cytomegalovirus infection suggesting that the use of >10 cells/2 × 105 leukocytes as a cut-off in this setting may be inappropriate.

Enfermedad por citomegalovirus en pacientes receptores de trasplante de corazón en un centro de referencia nacional / Cytomegalovirus disease in post-heart-transplant patients at a national reference center

Introduction: Heart transplantation remains as the treatment of choice when the heart failure is refractory to the medical or surgical therapy. Therefore, cytomegalovirus disease is an important post-heart-transplant infectious complication. Aims: To describe the prevalence and clinical characteristics of the cytomegalovirus disease after heart transplant surgery. Materials and Methods: A retrospective, descriptive study was conducted. It enrolled 35 heart-transplant patients attended in the Cardiovascular National Institute (INCOR), between 2010 and 2015. The information was obtained through the review of medical records. The demographic and relevant clinical variables were analyzed for the cytomegalovirus disease cases. Results: The population mean age was 39.49 ± 15.07 years and most of them were male patients (63%). The prevalence of the cytomegalovirus disease was 5.7% (two patients), both were seronegative for cytomegalovirus before transplantation. One of the patients had the disease before finishing the valganciclovir prophylaxis and the other after the end of it. Conclusion: The prevalence of the cytomegalovirus disease is slightly lower than in other studies. Moreover, the cytomegalovirus disease can remit with a prompt diagnosis and the proper medical treatment.

Introducción: El trasplante cardiaco es el tratamiento de elección ante la falla cardiaca refractaria a la terapia médica o quirúrgica. En base a ello, la enfermedad por citomegalovirus (CMV) es una importante complicación infecciosa post-trasplante de corazón. Objetivos: Describir la prevalencia y las características clínicas de los pacientes que desarrollaron enfermedad por CMV posttrasplante de corazón. Materiales y Métodos: Se realizó un estudio retrospectivo y descriptivo, donde se incluyó a los 35 pacientes que recibieron trasplante de corazón en el Instituto Nacional Cardiovascular entre el período 2010-2015. La información se obtuvo mediante la revisión de historias clínicas. Se analizaron las variables demográficas y clínicas relevantes de los casos con enfermedad por CMV. Resultados: La edad media de la población fue de 39,49 ± 15,07 años, siendo la mayoría de sexo masculino (63%). La prevalencia de la enfermedad por CMV fue de 5,7%, -dos pacientes-, ambos con serología negativa para CMV previa al trasplante. Uno de ellos presentó la enfermedad antes de terminar la profilaxis con valganciclovir y el otro luego del cese de la misma. Conclusión: La prevalencia de la enfermedad por CMV es ligeramente menor que en otros estudios. Asimismo, ésta puede remitir con un pronto diagnóstico y el adecuado tratamiento médico.

Late emergence of A594V and L595W mutations related to ganciclovir resistance in a patient with HCMV retinitis and long-term HIV progression

The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient.

The Cumulative Colectomy Rate in Patients with Cytomegalovirus-Positive Ulcerative Colitis

No abstract available.

Reply: Careful Assessment Is Needed in Patients with Ulcerative Colitis with Evidence of Cytomegalovirus Reactivation

No abstract available.

Comparison of Quantitation of Cytomegalovirus DNA by Real-Time PCR in Whole Blood with the Cytomegalovirus Antigenemia Assay

BACKGROUND: Quantitation of cytomegalovirus (CMV) DNA using real-time PCR has been utilized for monitoring CMV infection. However, the CMV antigenemia assay is still the 'gold standard' assay. There are only a few studies in Korea that compared the efficacy of use of real-time PCR for quantitation of CMV DNA in whole blood with the antigenemia assay, and most of these studies have been limited to transplant recipients. METHOD: 479 whole blood samples from 79 patients, falling under different disease groups, were tested by real-time CMV DNA PCR using the Q-CMV real-time complete kit (Nanogen Advanced Diagnostic S.r.L., Italy) and CMV antigenemia assay (CINA Kit, ArgeneBiosoft, France), and the results were compared. Repeatedly tested patients were selected and their charts were reviewed for ganciclovir therapy. RESULTS: The concordance rate of the two assays was 86.4% (Cohen's kappa coefficient value=0.659). Quantitative correlation between the two assays was a moderate (r=0.5504, P<0.0001). Among 20 patients tested repeatedly with the two assays, 13 patients were transplant recipients and treated with ganciclovir. Before treatment, CMV was detected earlier by real-time CMV DNA PCR than the antigenemia assay, with a median difference of 8 days. After treatment, the antigenemia assay achieved negative results earlier than real-time CMV DNA PCR with a median difference of 10.5 days. CONCLUSIONS: Q-CMV real-time complete kit is a useful tool for early detection of CMV infection in whole blood samples in transplant recipients.

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.

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.

Infección congénita por citomegalovirus. Primer reporte nacional de tratamiento con valganciclovir vía oral en recién nacidos / Congenital cytomegalovirus infection. First national report treatment with oral valganciclovir in neonates

La infección congénita por citomegalovirus (CMV) es la principal etiología de hipoacusia neurosensorial de causa no genética. El uso de valganciclovir, un profármaco del ganciclovir con buena biodisponibilidad oral, es utilizado a nivel internacional como parte del tratamiento farmacológico. La indicación de tratamiento incluye a los recién nacidos sintomáticos con compromiso neurológico o con enfermedad órgano focal severa, dentro de los primeros 30 días de vida. El mayor beneficio del tratamiento en neonatos es la reducción del deterioro de la audición evitando la peoría de los umbrales auditivos, así como la mejoría en el neurodesarrollo. Un tratamiento inicial con ganciclovir, seguido de valganciclovir vía oral, ha demostrado mejor desempeño del desarrollo auditivo que el uso de terapia a corto plazo. Se reportan dos casos de citomegalovirus congénito, de diferente presentación clínica, en el período setiembre-octubre 2013. Se reporta mejoría sintomática tras el tratamiento con ganciclovir-valganciclovir en ambos casos. En el seguimiento con carga viral en orina, se observó una disminución mantenida de la misma durante el tratamiento. El principal efecto adverso fue la apariciónde anemia...