RESUMEN
BACKGROUND: Congenital cytomegalovirus (cCMV) infection can lead to a range of adverse outcomes. The majority of cCMV neonates with clinical symptoms are infected postnatally; however, established cases of intrauterine infection are uncommon, resulting in a paucity of reports on clinical findings and lymphocytes expression in CMV-infected neonates. CASE PRESENTATION: We followed a neonate with cCMV infection from the onset of hospitalization to several months of follow-up. This infant was intrauterine CMV-positive in the amniotic fluid of the mother at 21 weeks' gestation and received intravenous ganciclovir infusion and sequential oral valganciclovir after birth. The typical clinical signs manifested in the nervous system, liver, and peripheral blood and were documented during the hospitalizaion period and up to the follow-up visit. Flow cytometry was employed to examine the expression of T cells, their subsets, and the associated cytokines in peripheral blood samples at various time points. The flow data for the cCMV neonate were compared with those of the controls at each time point. Following treatment, clinical symptoms improved and the infant became CMV negative. However, developmental delays occurred later in life. The proportion of CD8+CD28- Tregs in the peripheral blood of the neonate with congenital CMV infection was higher than that in the controls at the three time points. The expression levels of perforin and granzyme B secreted by γδ T cells (Vδ1 and Vδ2 T cells), increased during the course of hospitalization until follow-up and were higher than those in the controls at the three time points. CONCLUSIONS: Despite the alleviation of clinical symptoms, developmental delay in later life remains inevitable in this intrauterine cCMV neonate. CD8+CD28- Tregs and Vδ1 and Vδ2 T cells secreting perforin and granzyme B may be involved in congenital CMV infection, although this hypothesis requires validation in a larger study. This report may contribute to our understanding of the effect of current treatment and the immune status of intrauterine cCMV-infected neonates.
Asunto(s)
Infecciones por Citomegalovirus , Linfocitos T Reguladores , Humanos , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Recién Nacido , Femenino , Linfocitos T Reguladores/inmunología , Embarazo , Linfocitos T CD8-positivos/inmunología , Antígenos CD28 , Complicaciones Infecciosas del Embarazo , Perforina/metabolismo , Antivirales/uso terapéutico , Masculino , Ganciclovir/uso terapéutico , Granzimas/metabolismoRESUMEN
PURPOSE: Evaluate cytomegalovirus (CMV) post-prophylaxis surveillance in high-risk (D+/R-) kidney and liver transplant recipients. METHODS: Adult D+/R- patients were included if transplanted between 6/1/15 and 11/30/22 and divided into a pre-CMV-stewardship-era (6/1/15-5/31/18), CMV-stewardship-era (6/1/18-6/30/20), and a surveillance-era (7/1/2020-11/30/2022) then followed through 12 months. The primary objective was to evaluate CMV-related outcomes. The secondary objective was to assess graft and patient survival by era. RESULTS: There were 328 patients in the study period; 133 in the pre-stewardship-era, 103 in the stewardship-era, and 92 in the surveillance-era. Replication rates in the surveillance-era were significantly higher, as anticipated due to increased sampling (pre 38.4%, stewardship 33.0%, surveillance 52.2%, p = 0.02). Time from transplant to first replication was similar (pre 214.0 ± 79.0 days, stewardship 231.1 ± 65.5, surveillance 234.9 ± 61.4, p = 0.29). CMV viral load (VL) at first detection, maximum-VL, and incidence of VL > 100 000 IU/mL were numerically lower in the surveillance era, although not statistically significant. CMV end-organ disease (p < 0.0001) and ganciclovir-resistance (p = 0.002) were significantly lower in the surveillance era than in both previous eras. Rejection was not different between eras (p = 0.4). Graft (p = 0.0007) and patient survival (p = 0.008) were significantly improved in the surveillance era. CONCLUSIONS: Post-prophylaxis surveillance significantly reduced CMV end-organ disease and resistance. Despite observing increased replication rates in the surveillance era, rejection was not significantly different and there was no graft loss or patient mortality at 12 months.
Asunto(s)
Antivirales , Infecciones por Citomegalovirus , Citomegalovirus , Farmacorresistencia Viral , Ganciclovir , Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Riñón , Trasplante de Hígado , Humanos , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Citomegalovirus/aislamiento & purificación , Citomegalovirus/efectos de los fármacos , Antivirales/uso terapéutico , Ganciclovir/uso terapéutico , Estudios de Seguimiento , Trasplante de Hígado/efectos adversos , Factores de Riesgo , Trasplante de Riñón/efectos adversos , Pronóstico , Rechazo de Injerto/prevención & control , Rechazo de Injerto/etiología , Rechazo de Injerto/virología , Complicaciones Posoperatorias/prevención & control , Adulto , Tasa de Supervivencia , Estudios Retrospectivos , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
Ganciclovir (GCV) and its prodrug valganciclovir (VGCV) are antiviral medications primarily used to treat infections caused by cytomegalovirus (CMV), particularly in immunocompromised individuals such as solid organ transplant (SOT) recipients. Therapy with GCV is associated with significant side effects, including bone marrow suppression. Therefore, therapeutic drug monitoring (TDM) is mandatory for an appropriate balance between subtherapeutic and toxic drug levels. This study aimed to develop and validate three novel methods based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for GCV determination in serum (reference methodology), dried serum spots (DSS), and VAMS-Mitra™ devices. The methods were optimized and validated in the 0.1-25 mg/L calibration range. The obtained results fulfilled the EMA acceptance criteria for bioanalytical method validation. Assessment of DSS and VAMS techniques extended GCV stability to serum for up to a minimum of 49 days (at room temperature, with desiccant). Developed methods were effectively evaluated using 80 clinical serum samples from pediatric renal transplant recipients. Obtained samples were used for DSS, and dried serum VAMS samples were manually generated in the laboratory. The results of GCV determination using serum-, DSS- and VAMS-LC-MS/MS methods were compared using regression analysis and bias evaluation. The conducted statistical analysis confirmed the interchangeability between developed assays. The DSS and VAMS samples are more accessible and stable during storage, transport and shipment than classic serum samples.
Asunto(s)
Antivirales , Pruebas con Sangre Seca , Monitoreo de Drogas , Ganciclovir , Espectrometría de Masas en Tándem , Humanos , Monitoreo de Drogas/métodos , Pruebas con Sangre Seca/métodos , Espectrometría de Masas en Tándem/métodos , Ganciclovir/análogos & derivados , Ganciclovir/sangre , Ganciclovir/uso terapéutico , Antivirales/sangre , Antivirales/uso terapéutico , Cromatografía Liquida/métodos , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/tratamiento farmacológico , Valganciclovir/uso terapéutico , Valganciclovir/sangre , NiñoRESUMEN
Cytomegalovirus (CMV) infection is the main opportunistic infection observed after kidney transplantation. Despite the use of prevention strategies, CMV disease still occurs, especially in high-risk patients (donor seropositive/recipient seronegative). Patients may develop complicated CMV, i.e. recurrent, refractory or resistant CMV infection. CMV prevention relies on either universal prophylaxis or preemptive therapy. In high-risk patients, universal prophylaxis is usually preferred. Currently, valganciclovir is used in this setting. However, valganciclovir can be responsible for severe leucopenia and neutropenia. A novel anti-viral drug, letermovir, has been recently compared to valganciclovir. It was as efficient as valganciclovir to prevent CMV disease and induced less hematological side-effects. It is still not available in France in this indication. Recent studies suggest that immune monitoring by ELISPOT or Quantiferon can be useful to determine the duration of prophylaxis. Other studies suggest that prophylaxis may be skipped in CMV-seropositive kidney-transplant patients given mTOR inhibitors. Refractory CMV is defined by the lack of decrease of CMV DNAemia of at least 1 log10 at 2 weeks after effective treatment. In case of refractory CMV infection, drug resistant mutations should be looked for. Currently, maribavir is the gold standard therapy for refractory/resistant CMV. At 8 weeks therapy and 8 weeks later, it has been shown to be significantly more effective than other anti-viral drugs, i.e. high dose of ganciclovir, foscarnet or cidofovir. However, a high rate of relapse was observed after ceasing therapy. Hence, other therapeutic strategies should be evaluated in order to improve the sustained virological rate.
L'infection à cytomégalovirus (CMV) est la principale infection opportuniste après transplantation rénale. Malgré les stratégies préventives, il persiste des maladies à CMV, notamment chez les patients à haut risque (donneur séropositif/receveur séronégatif). Certains patients présentent des formes complexes avec des récurrences et des infections réfractaires et/ou résistantes aux antiviraux. La prévention de l'infection à CMV repose soit sur une prophylaxie universelle, soit sur une stratégie préemptive. Chez les patients à haut risque, la stratégie prophylactique est le plus souvent utilisée. Elle repose sur l'utilisation du valganciclovir, qui peut être responsable de leucopénies et de neutropénies sévères. Un nouvel antiviral, le létermovir, qui n'est pas encore disponible sur le marché en France dans cette indication, a montré une efficacité similaire au valganciclovir avec peu d'effets secondaires hématologiques. Des études récentes suggèrent l'intérêt de l'immuno-surveillance par ELISPOT ou Quantiféron pour guider la durée de la prophylaxie. D'autres études suggèrent également la possibilité de se passer d'un traitement prophylactique anti-CMV chez des transplantés rénaux CMV-séropositifs recevant des inhibiteurs de la mTOR. Le CMV réfractaire est défini par une absence de baisse de la charge virale d'au moins 1 log10 après deux semaines de traitement efficace. En cas d'absence de baisse de la charge virale, une recherche de mutations de résistance aux antiviraux doit être effectuée. Actuellement, le maribavir constitue le traitement de référence pour les formes réfractaires et résistantes. La clairance virale à la fin du traitement, ou huit semaines plus tard, est significativement supérieure à celle observée avec les autres antiviraux tels que le ganciclovir donné à forte dose, le foscarnet, ou le cidofovir. Cependant, le taux de rechute à l'arrêt du traitement par maribavir reste important. D'autres stratégies thérapeutiques doivent être évaluées pour améliorer ce taux de réponse virologique soutenue.
Asunto(s)
Antivirales , Infecciones por Citomegalovirus , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/prevención & control , Antivirales/uso terapéutico , Valganciclovir/uso terapéutico , Quinazolinas/uso terapéutico , Ganciclovir/uso terapéutico , Ribonucleósidos/uso terapéutico , Acetatos , Diclororribofuranosil Benzoimidazol/análogos & derivadosRESUMEN
BACKGROUND/AIM: The mortality rate for alimentary tract hemorrhage remains high due to a variety of contributing factors. In this report, we present a case of post-severe trauma patient with life-threatening gastrointestinal bleeding caused by cytomegalovirus (CMV)-induced damage to the terminal ileum. CASE REPORT: A 76-year-old female with a history of hypertension and gastrointestinal bleeding developed CMV ileitis post-severe trauma. Despite negative CMV IgM antibodies, PCR testing confirmed CMV infection in the biopsy tissue. Histopathological examination revealed viral inclusion bodies, with immunohistochemistry confirming CMV presence. RESULTS: Intravenous ganciclovir effectively managed symptoms and halted bleeding. CMV ileitis, typically seen in immunocompromised states, may occur sporadically in immunocompetent individuals, including post-orthopedic surgery patients. The exact mechanism remains unclear, possibly related to surgical stress. Diagnosis relies on histopathology and immunohistochemistry. CONCLUSION: Early recognition and treatment are vital for optimal outcomes, emphasizing the need for awareness among orthopedic surgeons regarding CMV as a potential cause of postoperative complications.
Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Ileítis , Humanos , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/diagnóstico , Femenino , Anciano , Citomegalovirus/genética , Ileítis/diagnóstico , Ileítis/etiología , Ileítis/virología , Ileítis/complicaciones , Ileítis/patología , Antivirales/uso terapéutico , Ganciclovir/uso terapéutico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/virología , Heridas y Lesiones/complicacionesAsunto(s)
Antivirales , Infecciones por Citomegalovirus , Citomegalovirus , Quimioterapia Combinada , Trasplante de Riñón , Recurrencia , Humanos , Trasplante de Riñón/efectos adversos , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/virología , Antivirales/uso terapéutico , Citomegalovirus/efectos de los fármacos , Citomegalovirus/aislamiento & purificación , Masculino , Persona de Mediana Edad , Ganciclovir/uso terapéutico , Receptores de Trasplantes , Resultado del Tratamiento , Inmunosupresores/uso terapéutico , Femenino , Farmacorresistencia ViralRESUMEN
Human herpesviruses (HHVs) cause a wide variety of central nervous system (CNS) infections including meningitis and encephalitis. While HHV-8 is not typically associated with neurological diseases, several studies have indicated a relationship, such as secondary central nervous system (CNS) metastases and a few isolated cases of HHV-8 encephalitis in acquired immunodeficiency syndrome (HIV). However, it has not been previously linked to encephalitis in solid organ transplantation (SOT). This case presents the first-ever instance of HHV-8 encephalitis in a SOT recipient. Our case highlights the association of HHV-8-related diseases, such as post-transplant Kaposi's Sarcoma (KS), with encephalitis. The patient was diagnosed with KS before developing neurological symptoms and received a prompt clinical response through intravenous foscarnet and ganciclovir treatment for 14 days. It is important to note that HHV-8 is a rare cause of encephalitis, and diagnosis requires a high index of suspicion in the appropriate clinical context, allowing for the use of antiviral therapy. This case also underscores the importance of considering the possibility of HHV-8-related diseases in SOT recipients, as they are at risk of developing such infections.
Asunto(s)
Antivirales , Encefalitis Viral , Ganciclovir , Infecciones por Herpesviridae , Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Herpesvirus Humano 8/aislamiento & purificación , Sarcoma de Kaposi/virología , Antivirales/uso terapéutico , Masculino , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/diagnóstico , Encefalitis Viral/virología , Encefalitis Viral/diagnóstico , Encefalitis Viral/tratamiento farmacológico , Ganciclovir/uso terapéutico , Foscarnet/uso terapéutico , Persona de Mediana Edad , Receptores de Trasplantes , Trasplante de Órganos/efectos adversosRESUMEN
This retrospective cohort study investigated patients with cytomegalovirus anterior uveitis (CMV AU) and compared treatment outcomes between regional and systemic antiviral therapies. Treatment modalities included topical (2% ganciclovir [GCV] eye drops or 0.2% GCV eye gel) and systemic (intravenous GCV or oral valganciclovir) groups. The comparison parameters included response rates, time to response, recurrence rates, time to recurrence, and complications. Forty-four patients (54.5% male) with a mean age of 56 ± 9.87 years were enrolled, with 31 eyes in the topical group and 13 eyes in the systemic group. The median response time was significantly slower in the topical group (63 days [IQR 28-112]) compared to the systemic group (28 days [IQR 24-59]) (p = 0.04). Treatment response rates were 87.1% (27/31) in the topical group and 100% (13/13) in the systemic group (p = 0.30), while recurrence rates were 37% (10/27) and 69.2% (9/13) (p = 0.056), with a median time to recurrence of 483 days [IQR 145-1388] and 392 days [IQR 203.5-1907.5] (p = 0.20), respectively. In conclusion, both topical and systemic GCV treatments demonstrated favorable outcomes for CMV AU. Systemic GCV showed rapid control of intraocular inflammation.
Asunto(s)
Antivirales , Infecciones por Citomegalovirus , Ganciclovir , Uveítis Anterior , Humanos , Masculino , Femenino , Persona de Mediana Edad , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/virología , Uveítis Anterior/tratamiento farmacológico , Uveítis Anterior/virología , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Estudios Retrospectivos , Resultado del Tratamiento , Ganciclovir/uso terapéutico , Ganciclovir/administración & dosificación , Anciano , Citomegalovirus , Adulto , Valganciclovir/uso terapéutico , Recurrencia , Soluciones OftálmicasRESUMEN
BACKGROUND: Acquired human cytomegalovirus (CMV) is a noteworthy disease in infants. This case study will highlight the influence of early diagnosis of CMV retinitis (CMVR) on avoid visual impairment. CLINICAL FINDINGS: We describe a preterm female infant with a birth weight of 2060 gr that was admitted for tracheostomy placement due to hypoxic-ischemic encephalopathy. There were no signs of CMV infection or sepsis in laboratory results upon admission such as serology (IgG, IgM antibodies), Toxoplasma gondii , Rubella virus, Herpes simplex virus, CMVR and urine polymerase chain reaction (PCR). PRIMARY DIAGNOSIS: Incidentally, upon screening for retinopathy of prematurity, diffuse occlusive vasculitis was detected in the retinal image on the 112th day of life. INTERVENTION: Intravenous and intraocular ganciclovir were administered for 4 weeks. OUTCOMES: In the follow-up visit 6 weeks after discharge from the hospital, visual impairment was detected on both sides. PRACTICE RECOMMENDATIONS: This is a report of a case of acquired CMVR, a silent finding, as an uncommon complication in preterm neonates during the hospital stay. This diagnosis should be taken into consideration in preterm infants, since early diagnosis and treatment are crucial to avoid visual impairment.
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Antivirales , Retinitis por Citomegalovirus , Ganciclovir , Recien Nacido Prematuro , Humanos , Recién Nacido , Femenino , Retinitis por Citomegalovirus/diagnóstico , Retinitis por Citomegalovirus/tratamiento farmacológico , Ganciclovir/uso terapéutico , Antivirales/uso terapéutico , Unidades de Cuidado Intensivo NeonatalAsunto(s)
Antivirales , Implantes de Medicamentos , Endoftalmitis , Ganciclovir , Vitrectomía , Humanos , Vitrectomía/métodos , Endoftalmitis/diagnóstico , Endoftalmitis/microbiología , Endoftalmitis/cirugía , Antivirales/uso terapéutico , Ganciclovir/uso terapéutico , Ganciclovir/administración & dosificación , Remoción de Dispositivos/métodos , Enfermedades de la Retina/cirugía , Enfermedades de la Retina/diagnóstico , Migración de Cuerpo Extraño/diagnóstico , Migración de Cuerpo Extraño/cirugía , Infecciones Virales del Ojo/diagnóstico , Infecciones Virales del Ojo/virología , Infecciones Virales del Ojo/cirugíaRESUMEN
OBJECTIVES: Prophylaxis (P) or pre-emptive strategy (PS) in high-risk liver transplant recipients (LTRs) are either recommended. We compared the results of each strategy. METHODS: Two groups of LTR transplanted during two consecutive periods were compared. Only cytomegalovirus (CMV)-mismatched LTR (Donor +/ Recipient -) were included. The primary endpoints were: the onset of polymerase chain reaction-based DNAemia and the proportion of patients with CMV disease. A number of episodes of CMV infection, antiviral therapy, ganciclovir resistance, infectious or immunological complications, cost of both strategies, and survival (1, 5, and 10 years) were also compared. RESULTS: Forty-eight and 60 patients were respectively included in the P and PS groups. Eighteen (38%) in the P group and 56 (93%) in the PS group had CMV DNAemia (p <.0001) with a similar CMV disease rate (16.7% and 15%). Duration of curative therapy was longer in the PS group: 91 days versus 16 (p <.0001). Acute rejection was less frequent (p = .04) and more patients experienced a ganciclovir-resistant CMV infection in the PS group (10% vs. 0, p = .03). The drug-associated cost of PS was higher (10 004 vs. 4804) and the median number of rehospitalization days tended to be higher (6 vs. 4, p = .06). Survival at any time was similar. CONCLUSION: We reported more CMV DNAemias and ganciclovir-resistant CMV events with PS. The cost of the PS strategy was higher.
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Antivirales , Infecciones por Citomegalovirus , Citomegalovirus , Ganciclovir , Trasplante de Hígado , Humanos , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/virología , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Femenino , Citomegalovirus/efectos de los fármacos , Ganciclovir/uso terapéutico , Ganciclovir/administración & dosificación , Adulto , Anciano , Receptores de Trasplantes/estadística & datos numéricos , ADN Viral/sangre , Rechazo de Injerto/prevención & control , Estudios Retrospectivos , Farmacorresistencia ViralRESUMEN
Cytomegalovirus (CMV) infection and disease is a condition usually described in immunocompromised patients, but among them, those with connective tissue diseases are poorly represented. Here we present the clinical, laboratory characteristics, management and outcomes of systemic lupus erythematosus (SLE) patients who presented with a CMV infection/disease to a high complexity hospital in southwestern Colombia between 2011 and 2020. 16 SLE patients were found to have a CMV infection. SLE was predominantly characterized by renal involvement (10 patients; 62.50%), and 14 patients (87.5%) were receiving steroids previous to the CMV infection. The entire sample required hospital admission, mainly related to acute kidney injury, and nine patients were admitted to the intensive care unit (ICU). Gastrointestinal organ damage was the most common CMV disease manifestation. All patients received ganciclovir, five of them (31.25%) suffered from septic shock, and seven (43.75%) died. Age ≥38 years and the presence of septic shock at admission were correlated to the mortality outcome. To our knowledge, this is the first publication evaluating SLE patients with CMV infection/disease in a Colombian population.
Asunto(s)
Infecciones por Citomegalovirus , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/epidemiología , Colombia/epidemiología , Femenino , Adulto , Masculino , Persona de Mediana Edad , Antivirales/uso terapéutico , Adulto Joven , Ganciclovir/uso terapéutico , Huésped Inmunocomprometido , Choque Séptico/etiología , Estudios Retrospectivos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Hospitalización/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricosRESUMEN
PURPOSE OF REVIEW: Universal and targeted screening of newborns for congenital cytomegalovirus (CMV) infection is increasing globally. Questions remain concerning the management of infants who have been identified with congenital CMV infection, especially those with "minimally symptomatic" or clinically inapparent infection. Our objective is to discuss current management of CMV-infected neonates with a focus on less affected infants with or without sensorineural hearing loss (SNHL). RECENT FINDINGS: Valganciclovir is being prescribed increasingly in neonates with congenital CMV infection for improvement in hearing outcomes through 2 years of age. Treatment initiated in the first month of age is recommended for clinically apparent disease. A recent study showed hearing improvement at 18-22âmonths of age when therapy was initiated at age 1-3 months in infants with clinically inapparent CMV infection and isolated SNHL. SUMMARY: Antiviral therapy with either ganciclovir or valganciclovir has shown moderate benefit in prevention of hearing deterioration among infants with clinically apparent CMV infection or isolated SNHL. Sustainability of benefit beyond 2 years of age remains unknown. At present, infants with clinically inapparent CMV infection (normal complete evaluation including hearing) should not receive antiviral therapy. All CMV-infected infants require close audiological and neurodevelopmental follow-up.
Asunto(s)
Antivirales , Infecciones por Citomegalovirus , Ganciclovir , Pérdida Auditiva Sensorineural , Valganciclovir , Humanos , Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/complicaciones , Antivirales/uso terapéutico , Pérdida Auditiva Sensorineural/virología , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Recién Nacido , Valganciclovir/uso terapéutico , Ganciclovir/uso terapéutico , Ganciclovir/análogos & derivados , Lactante , Tamizaje Neonatal/métodosAsunto(s)
Caspasa 3 , Ganciclovir , Neoplasias Ováricas , Simplexvirus , Timidina Quinasa , Humanos , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Timidina Quinasa/genética , Timidina Quinasa/metabolismo , Simplexvirus/genética , Ganciclovir/farmacología , Ganciclovir/uso terapéutico , Caspasa 3/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular TumoralRESUMEN
BACKGROUND: The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis to prevent the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008 and 2013. OBJECTIVES: To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause death in solid organ transplant recipients. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 5 February 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications or different regimens of the same antiviral medications for CMV prophylaxis in recipients of any solid organ transplant. Studies examining pre-emptive therapy for CMV infection are studied in a separate review and were excluded from this review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility, risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This 2024 update found four new studies, bringing the total number of included studies to 41 (5054 participants). The risk of bias was high or unclear across most studies, with a low risk of bias for sequence generation (12), allocation concealment (12), blinding (11) and selective outcome reporting (9) in fewer studies. There is high-certainty evidence that prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment is more effective in preventing CMV disease (19 studies: RR 0.42, 95% CI 0.34 to 0.52), all-cause death (17 studies: RR 0.63, 95% CI 0.43 to 0.92), and CMV infection (17 studies: RR 0.61, 95% CI 0.48 to 0.77). There is moderate-certainty evidence that prophylaxis probably reduces death from CMV disease (7 studies: RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduces the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but probably makes little to no difference to fungal infection, acute rejection or graft loss. No apparent differences in adverse events with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment were found. There is high certainty evidence that ganciclovir, when compared with aciclovir, is more effective in preventing CMV disease (7 studies: RR 0.37, 95% CI 0.23 to 0.60). There may be little to no difference in any outcome between valganciclovir and IV ganciclovir compared with oral ganciclovir (low certainty evidence). The efficacy and adverse effects of valganciclovir or ganciclovir were probably no different to valaciclovir in three studies (moderate certainty evidence). There is moderate certainty evidence that extended duration prophylaxis probably reduces the risk of CMV disease compared with three months of therapy (2 studies: RR 0.20, 95% CI 0.12 to 0.35), with probably little to no difference in rates of adverse events. Low certainty evidence suggests that 450 mg/day valganciclovir compared with 900 mg/day valganciclovir results in little to no difference in all-cause death, CMV infection, acute rejection, and graft loss (no information on adverse events). Maribavir may increase CMV infection compared with ganciclovir (1 study: RR 1.34, 95% CI: 1.10 to 1.65; moderate certainty evidence); however, little to no difference between the two treatments were found for CMV disease, all-cause death, acute rejection, and adverse events at six months (low certainty evidence). AUTHORS' CONCLUSIONS: Prophylaxis with antiviral medications reduces CMV disease and CMV-associated death, compared with placebo or no treatment, in solid organ transplant recipients. These data support the continued routine use of antiviral prophylaxis in CMV-positive recipients and CMV-negative recipients of CMV-positive organ transplants.
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Antivirales , Infecciones por Citomegalovirus , Ganciclovir , Trasplante de Órganos , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Aciclovir/uso terapéutico , Aciclovir/efectos adversos , Antivirales/uso terapéutico , Antivirales/efectos adversos , Sesgo , Causas de Muerte , Infecciones por Citomegalovirus/prevención & control , Ganciclovir/uso terapéutico , Ganciclovir/efectos adversos , Ganciclovir/análogos & derivados , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias/prevención & control , Receptores de Trasplantes , Valaciclovir/efectos adversos , Valaciclovir/uso terapéutico , Valganciclovir/efectos adversos , Valganciclovir/uso terapéuticoRESUMEN
Kaposi sarcoma (KS) is the most common cancer in persons living with HIV. It is caused by KS-associated herpesvirus (KSHV). There exists no animal model for KS. Pronuclear injection of the 170,000-bp viral genome induces early-onset, aggressive angiosarcoma in transgenic mice. The tumors are histopathologically indistinguishable from human KS. As in human KS, all tumor cells express the viral latency-associated nuclear antigen (LANA). The tumors transcribe most viral genes, whereas endothelial cells in other organs only transcribe the viral latent genes. The tumor cells are of endothelial lineage and exhibit the same molecular pattern of pathway activation as KS, namely phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR, interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF). The KSHV-induced tumors are more aggressive than Ha-ras-induced angiosarcomas. Overall survival is increased by prophylactic ganciclovir. Thus, whole-virus KSHV-transgenic mice represent an accurate model for KS and open the door for the genetic dissection of KS pathogenesis and evaluation of therapies, including vaccines.
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Modelos Animales de Enfermedad , Hemangiosarcoma , Herpesvirus Humano 8 , Ratones Transgénicos , Sarcoma de Kaposi , Animales , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/patogenicidad , Ratones , Hemangiosarcoma/virología , Hemangiosarcoma/genética , Hemangiosarcoma/patología , Sarcoma de Kaposi/virología , Sarcoma de Kaposi/patología , Genoma Viral , Humanos , Antígenos Virales/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Ganciclovir/uso terapéutico , Ganciclovir/farmacología , Interleucina-10/genéticaRESUMEN
Cytomegalovirus (CMV), a beta-herpes virus, is the most common viral infection in infants. Transmission may occur congenitally (cCMV) or postnatally (pCMV). Early detection and intervention are crucial in reducing morbidities, notable developmental delays, and sensorineural hearing loss. However, more than 90% of infants are asymptomatic at birth. Treatment involves intravenous ganciclovir or the oral prodrug, valganciclovir, drugs usually reserved for use with symptomatic infants because of the toxicity profile. Research currently supports standardized antenatal CMV screening and treatment of affected pregnant patients with hyperimmune globulin as well as vaccination against CMV in unaffected pregnant patients, although widespread adoption is lacking. Standardized postnatal CMV screening is a proven, cost-effective way to detect and diagnose CMV and optimize outcomes across the lifespan. This article presents a case series of cCMV and pCMV and a review of the state of science of CMV as well as promising scientific advances that are on the horizon.
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Infecciones por Citomegalovirus , Citomegalovirus , Femenino , Humanos , Recién Nacido , Embarazo , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Ganciclovir/farmacología , Ganciclovir/uso terapéutico , Tamizaje Neonatal , Valganciclovir/farmacología , Valganciclovir/uso terapéuticoRESUMEN
BACKGROUND: Valganciclovir (valG), a cytomegalovirus (CMV) prophylactic agent, has dose-limiting side effects. The tolerability and effectiveness of valacyclovir (valA) as CMV prophylaxis is unknown. METHODS: We conducted a randomized, open-label, single-center trial of valA versus valG for all posttransplant CMV prophylaxis in adult and pediatric kidney recipients. Participants were randomly assigned to receive valA or valG. Primary endpoints were the incidence of CMV viremia and side-effect related drug reduction with secondary assessment of incidence of EBV viremia. RESULTS: Of the 137 sequential kidney transplant recipients enrolled, 26 % were positive and negative for CMV antibody in donor and recipient respectively. The incidence of CMV viremia (4 of 71 [6 %]; 8 of 67 [12 %] P = 0.23), time to viremia (P = 0.16) and area under CMV viral load time curve (P = 0.19) were not significantly different. ValG participants were significantly more likely to require side-effect related dose reduction (15/71 [21 %] versus 1/66 [2 %] P = 0.0003). Leukopenia was the most common reason for valG dose reduction and granulocyte-colony stimulating factor was utilized for leukopenia recovery more frequently (25 % in valG vs 5 % in valA: P = 0.0007). Incidence of EBV viremia was not significantly different. CONCLUSIONS: ValA has significantly less dose-limiting side effects than valG. In our study population, a significant increase in CMV viremia was not observed, in adults and children after kidney transplant, compared to valG. TRIAL REGISTRATION NUMBER: NCT01329185.
Asunto(s)
Antivirales , Infecciones por Citomegalovirus , Ganciclovir , Trasplante de Riñón , Receptores de Trasplantes , Valaciclovir , Valganciclovir , Humanos , Valaciclovir/uso terapéutico , Infecciones por Citomegalovirus/prevención & control , Valganciclovir/uso terapéutico , Valganciclovir/administración & dosificación , Trasplante de Riñón/efectos adversos , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Antivirales/efectos adversos , Masculino , Femenino , Adulto , Niño , Persona de Mediana Edad , Adolescente , Ganciclovir/análogos & derivados , Ganciclovir/uso terapéutico , Ganciclovir/administración & dosificación , Ganciclovir/efectos adversos , Viremia/prevención & control , Carga Viral , Adulto Joven , Valina/análogos & derivados , Valina/uso terapéutico , Valina/administración & dosificación , Citomegalovirus/inmunología , Citomegalovirus/efectos de los fármacos , Preescolar , Aciclovir/uso terapéutico , Aciclovir/análogos & derivados , Aciclovir/administración & dosificación , Aciclovir/efectos adversos , Anciano , Resultado del Tratamiento , IncidenciaRESUMEN
We present the first published case of simultaneous pneumonitis and immune thrombocytopenic purpura secondary to primary cytomegalovirus (CMV) infection in an immunocompetent patient. Treatment with oral valganciclovir for 2 weeks successfully led to complete clinical recovery. CMV is traditionally associated with infection in immunocompromised patients and neonates; however, evidence of severe CMV infections in immunocompetent hosts is emerging. It is important to highlight the broad range of clinical presentations of CMV infections to prevent diagnostic delay and associated morbidity and expense.