Nirsevimab for the prevention of respiratory syncytial virus disease in children. Statement of the Spanish Society of Paediatric Infectious Disease (SEIP).

INTRODUCTION: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain. OBJECTIVES: To provide recommendations for the administration of nirsevimab for prevention of RSV disease. METHODS: The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. The group engaged in three rounds to define the questions, express support or opposition, grade recommendations and establish the agreement or disagreement with the conclusions. RESULTS: In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirsevimab is recommended for all infants born in high-incidence RSV season and infants aged less than 6 months at the season onset. In infants born preterm between 29 and 35 weeks of gestation, with haemodynamically significant heart disease or with chronic lung disease, routine administration of nirsevimab is recommended to reduce the incidence of disease and hospitalisation due to bronchiolitis and RSV lower respiratory tract infection. In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis. CONCLUSIONS: Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis.

Interleukin-21 overexpression dominates T cell response to Epstein-Barr virus in a fatal case of X-linked lymphoproliferative syndrome type 1.

Interleukin-21 (IL-21) is a cytokine whose actions are closely related to B cell differentiation into plasma cells as well as to CD8(+) cytolytic T cell effector and memory generation, influencing the T lymphocyte response to different viruses. X-linked lymphoproliferative syndrome type 1 (XLP-1) is a primary immunodeficiency syndrome that is characterized by a high susceptibility to Epstein-Barr virus. We observed in a pediatric patient with XLP-1 that IL-21 was expressed in nearly all peripheral blood CD4(+) and CD8(+) T cells. However, IL-21 could not be found in the lymph nodes, suggesting massive mobilization of activated cells toward the infection's target organs, where IL-21-producing cells were detected, resulting in large areas of tissue damage.

Peculiaridades del manejo de la infección por citomegalovirus en el trasplante de órgano sólido en pacientes pediátricos / Special considerations in the management of cytomegalovirus infection in pediatric solid organ transplant recipients

Durante años, ganciclovir intravenoso ha sido el tratamiento recomendado para la enfermedad por citomegalovirus (CMV) en pacientes trasplantados. En los últimos años, valganciclovir oral ha mostrado una similar respuesta frente a CMV que ganciclovir intravenoso, por lo que puede ser utilizado alternativamente a ganciclovir en pacientes con enfermedad no grave. La terapia secuencial con ganciclovir seguido de valganciclovir, tras iniciarse la mejoría clínica, reduce costes y evita hospitalizaciones prolongadas, lo que supone un beneficio para los pacientes. La duración óptima del tratamiento irá guiada por la respuesta clínica y los controles virológicos (PCR o antigenemia), manteniéndose hasta que éstos sean negativos. Algunos grupos utilizan profilaxis secundaria ante la presencia de factores de riesgo de recidiva de la enfermedad por CMV. Reducir la intensidad de la inmunosupresión o complementar la terapia antiviral con inmunoglobulinas son medidas a considerar en casos graves o en grandes inmunodeprimidos. No hay datos firmes acerca del mejor tratamiento alternativo ante la evidencia de CMV resistente a ganciclovir. Las decisiones terapéuticas deberán sustentarse en el estudio genotípico de resistencias, el estado inmune del paciente y en la gravedad de la enfermedad. El tratamiento consiste en foscarnet solo o con ganciclovir en las formas más graves y en mutaciones de alta resistencia, o en el incremento de las dosis de ganciclovir en las formas clínicas o de resistencia más benignas. No hay datos concluyentes acerca de antivirales alternativos o de terapia complementaria con inhibidores de mTOR. Se ensayan diversas vacunas frente a CMV con resultados preclínicos esperanzadores (AU)

In pediatric patients, the main risk factor for the development of post-transplantation cytomegalovirus (CMV) is the absence of specific immunity to the virus in the pretransplantation period. CMV infection has become less of a problem in pediatric solid organ transplant (SOT) recipients mainly due to the availability of sensitive diagnostic techniques, the development of prevention strategies, and the possibility of starting effective antiviral treatments. Both polymerase chain reaction (PCR) techniques and pp65 antigenemia have proved to be effective in the diagnosis and monitoring of children with CMV infection. However, in some types of transplantation, such as lung transplantation, CMV infection continues to be an important risk factor for mortality or retransplantation in D+/R-1 patients. Prophylaxis with ganciclovir followed by valganciclovir for between 3 and 6 months is recommended over preemptive therapy. In the treatment of CMV disease, the use of ganciclovir is recommended until a negative weekly result of PCR or pp65 antigenemia is obtained. The total duration of treatment, both in viral syndrome and organ disease, is the same as in adults. Treatment can be completed by substituting intravenous ganciclovir for oral treatment in older children and adolescents (AU)

Recomendaciones GESITRA-SEIMC/REIPI para el manejo de la infección por citomegalovirus en pacientes trasplantados de órgano sólido / GESITRA-SEIMC/REIPI recommendations for the management of cytomegalovirus infection in solid-organ transplant patients

La infección por citomegalovirus (CMV) constituye una complicación importante en los pacientes sometidos a trasplante de órgano sólido (TOS). En el año 2005 el Grupo de Estudio de Infección en el Trasplante (GESITRA) de la Sociedad Española de Microbiología Clínica y Enfermedades Infecciosas (SEIMC) elaboró un documento de consenso para la profilaxis y el tratamiento de la infección por CMV en pacientes sometidos a TOS. Desde entonces han sido numerosas las publicaciones que o bien han aclarado, o bien han planteado nuevas dudas respecto a los aspectos tratados en el anterior documento. Entre estos aspectos se encuentran las situaciones y poblaciones que deben recibir profilaxis y su duración, la elección de la mejor técnica para el diagnóstico y monitorización y la elección de la mejor estrategia terapéutica. Todo ello justifica la necesidad de elaborar un nuevo documento de consenso que incluya las últimas recomendaciones en el manejo de la infección por CMV post-trasplante en base a las nuevas evidencias disponibles (AU)

Abstract Cytomegalovirus infection remains a major complication of solid organ transplantation. In 2005 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, numerous publications have clarified or questioned the aspects covered in the previous document. These aspects include the situations and populations who must receive prophylaxis and its duration, the selection of the best diagnosis and monitoring technique and the best therapeutic strategy. For these reasons, we have developed new consensus guidelines to include the latest recommendations on post-transplant CMV management based on new evidence available (AU)

GESITRA-SEIMC/REIPI recommendations for the management of cytomegalovirus infection in solid-organ transplant patients.

Cytomegalovirus infection remains a major complication of solid organ transplantation. In 2005 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, numerous publications have clarified or questioned the aspects covered in the previous document. These aspects include the situations and populations who must receive prophylaxis and its duration, the selection of the best diagnosis and monitoring technique and the best therapeutic strategy. For these reasons, we have developed new consensus guidelines to include the latest recommendations on post-transplant CMV management based on new evidence available.

[Special considerations in the management of cytomegalovirus infection in pediatric solid organ transplant recipients]. / Peculiaridades del manejo de la infección por citomegalovirus en el trasplante de órgano sólido de pacientes pediátricos.

In pediatric patients, the main risk factor for the development of post-transplantation cytomegalovirus (CMV) is the absence of specific immunity to the virus in the pretransplantation period. CMV infection has become less of a problem in pediatric solid organ transplant (SOT) recipients mainly due to the availability of sensitive diagnostic techniques, the development of prevention strategies, and the possibility of starting effective antiviral treatments. Both polymerase chain reaction (PCR) techniques and pp65 antigenemia have proved to be effective in the diagnosis and monitoring of children with CMV infection. However, in some types of transplantation, such as lung transplantation, CMV infection continues to be an important risk factor for mortality or retransplantation in D+/R(-1) patients. Prophylaxis with ganciclovir followed by valganciclovir for between 3 and 6 months is recommended over preemptive therapy. In the treatment of CMV disease, the use of ganciclovir is recommended until a negative weekly result of PCR or pp65 antigenemia is obtained. The total duration of treatment, both in viral syndrome and organ disease, is the same as in adults. Treatment can be completed by substituting intravenous ganciclovir for oral treatment in older children and adolescents.

Assessment of the efficacy of joint lavage versus joint lavage plus corticoids in patients with osteoarthritis of the knee.

PURPOSE: Joint lavage (JL), involves the passage of cold sterile 0.9% saline through the knee joint in order to have the fluid reach the inside of the joint capsule. This technique was evaluated as a local treatment for osteoarthritis (OA) of the knee alone (JL) and in combination with intra-articular infiltration with glucocorticoids (JLC). PATIENTS AND METHODS: An overall 299 knees belonging to 205 patients (22% males, 78% females) with a mean age of 67 +/- 8 years and osteoarthritis of the knee of radiological grade II or III on the Kellgren scale were randomised in the ratio of 1:4 into two therapeutic groups, namely: JL (n = 62) and JLC (n = 237). All patients received joint lavage on day 0; in those of the JLC group, joint lavage was followed by infiltration of 40 mg of triamcinolone acetonide. The efficacy of both treatments was assessed by recording the corresponding values for the following variables: pain strength as measured by a visual analogy scale (VAS), effusion, crepitation, restricted motion, of osteoarthritis of the knee. spontaneous pain, pain on pressure, pain on passive motion and pain on active motion; all of these were recorded at the onset of the study, and after 1 and 3 months. RESULTS: There were no significant differences in the values of the variables at the different followup times. Also, pain severity was similar in both treatment groups. Thus, VAS for pain was 7.3 +/- 0.3 for the JL group and 7.1 +/- 0.2 for the JLC group at the onset, and decreased to 3.0 +/- 0.3 in the former and 2.8 +/- 0.2 in the latter after 1 month; the decrease was statistically significant in both cases. After 3 months, the JL and JLC groups had a VAS of 3.5 +/- 0.3 and 3.8 +/- 0.2, respectively. CONCLUSIONS: The results of this work suggest the absence of significant differences between the two treatments, such that both joint lavage alone and with infiltration with corticoids can be concluded as similarly effective for the symptomatic management