Infección congénita por citomegalovirus, hipoacusia y tamizaje neonatal. Una actualización / Congenital cytomegalovirus infection, hearing loss and newborn screening. An update

El citomegalovirus congénito (CMVc) es la infección congénita más común y la principal causa no genética de hipoacusia congénita. Gran parte de los recién nacidos (RN) con CMVc sintomático desarrolla secuelas graves permanentes, donde la hipoacusia es la más frecuente. Sin embargo, el 90% de los casos se presenta en forma asintomática, pudiendo desarrollar secuelas auditivas tardías. El diagnóstico precoz de CMVc requiere un alto índice de sospecha. Actualmente, técnicas eficientes para su detección están disponibles, lo que facilita el diagnóstico en las primeras 3 semanas de vida. La terapia antiviral es la primera línea de tratamiento para el CMVc sintomático, logrando buenos resultados auditivos. A pesar de los avances en los métodos de detección y beneficios del tratamiento, los RN no son tamizados para CMVc. El tamizaje selectivo de CMVc en pacientes que no pasan el screening auditivo facilita la intervención precoz en los casos identificados, pero no permite detectar el número significativo de niños que presenta hipoacusia de aparición tardía. El tamizaje universal permite hacer seguimiento auditivo a los pacientes en riesgo de desarrollar hipoacusia sensorioneural (HSN) por CMVc, identificando así los casos de hipoacusia de aparición tardía, pero la costo-efectividad es aún controversial. Es necesario avanzar en una estrategia local para el tamizaje de CMVc, buscando reducir su impacto a nivel nacional.

Congenital cytomegalovirus (cCMV) is the most common congenital infection and the main non-genetic cause of congenital hearing loss. A significant number of newborns (NB) with symptomatic cCMV will develop permanent serious sequelae, being hearing loss the most frequent. However, 90% of the cases are asymptomatic and may develop late auditory sequelae. Early diagnosis of cCMV requires a high index of suspicion. Currently, efficient detection techniques for its detection are available, which facilitates diagnosis within the first 3 weeks of life. Antiviral therapy is the first line of treatment for symptomatic cCMV, achieving good hearing results. Despite advances in detection methods and the benefits of antiviral therapy, NB are not routinely screened for cCMV. Selective screening for cCMV in patients who fail newborn hearing screening facilitates early intervention in identified cases but fails to detect a significant number of children with late onset hearing loss. Universal screening allows hearing follow up in patients at risk of developing sensorineural hearing loss (SNHL) due to cCMV, thus identifying late-onset hearing loss cases, but cost-effectiveness is still controversial. It is necessary to advance in a local strategy for cCMV screening, aiming to reduce its national impact.

Guías Latinoamericanas de Infecciones Congénitas y Perinatales de la Sociedad Latinoamericana de Infectología Pediátrica (SLIPE). Parte II / Latin American Guidelines on Congenital and Perinatal Infections from the Latin-American Society of Pediatric Infectious Diseases (SLIPE). Part II

Las infecciones perinatales son una causa de morbilidad, tanto fetal como neonatal, y que compromete la salud de la mujer embarazada, por lo que su diagnóstico, tratamiento, e intento de eliminación son una prioridad en América Latina y el Caribe. Este documento representa la segunda entrega realizada por expertos en la región dentro de la Sociedad Latinoamericana de Infectología Pediátrica (SLIPE), brindando una mirada actualizada en el manejo de las infecciones congénitas y entrega herramientas para detectar posibles momentos estratégicos de intervención y cambio en el manejo de las infecciones congénitas.

Perinatal infections are a major cause of morbidity and mortality in the fetus, neonate, and the health of the pregnant woman. Diagnosis, treatment, and the search for elimination of these diseases are a priority in Latin America and the Caribbean. This document represents the second delivery by a group of experts in the region inside the Latin-American Society of Pediatric Infectious Diseases (SLIPE), presenting a up-to-date look into the management of congenital infectious diseases and give a tool to detect possible strategic sceneries and a change in the management of congenital infections in our region.

Infección congénita por citomegalovirus en neonatos muy bajo peso / Congenital cytomegalovirus infection in very low birth weight neonates

Introducción: La infección congénita por el citomegalovirus en neonatos menores de 1500 gramos puede ser causa de morbilidad, mortalidad y discapacidad. Objetivo: Describir el comportamiento de la infección congénita por citomegalovirus en un servicio de neonatología. Métodos: Se realizó un estudio descriptivo y transversal con 61 neonatos. Se les realizó detección de citomegalovirus en la primera semana de vida en suero y orina, mediante reacción en cadena de la polimerasa, para determinar infección congénita. Se evaluaron variables perinatales en todos los neonatos, así como elementos clínicos y resultados de exámenes complementarios en los infectados. Resultados: La incidencia de infección congénita fue de un 10 por ciento (6/61). El 5 por ciento de los estudios fueron positivos (6/122). Ninguna muestra de orina resultó positiva (0/61) y en el 10 por ciento de las muestras de suero (6/61) se detectó el genoma del virus. Se encontró asociación entre valoración nutricional al nacer e infección por citomegalovirus (p< 0,05). El 83 por ciento de los neonatos infectados presentaron algún signo clínico y el síndrome de dificultad respiratoria fue el más frecuente (67 por ciento). En todos los neonatos con infección congénita el ultrasonido cerebral fue normal y en el 33 por ciento se detectó retinopatía de la prematuridad en el fondo de ojo. Conclusiones: La incidencia de infección congénita por citomegalovirus es alta en este grupo de riesgo. Los signos clínicos encontrados y los resultados del fondo de ojo en neonatos con infección congénita se relacionaron con la prematuridad y la valoración nutricional de hipotrófico se asoció con esta infección(AU)

Introduction: Congenital cytomegalovirus infection in neonates weighing less than 1500 grams can be a cause of morbidity, mortality, and disability. Objective: To describe the behavior of congenital cytomegalovirus infection in a neonatal service. Methods: A descriptive and cross-sectional study was conducted with 61 neonates. Cytomegalovirus was detected in the first week of life in serum and urine, by polymerase chain reaction, to determine congenital infection. Perinatal variables were evaluated in all neonates, as well as clinical elements and results of complementary examinations in infected infants. Results: The incidence of congenital infection was 10 percent (6/61). 5 percent of the studies were positive (6/122). No urine samples were positive (0/61) and the virus genome was detected in 10 percent of serum samples (6/61). An association was found between nutritional assessment at birth and cytomegalovirus infection (p < 0.05). A total of 83 percent of infected neonates had some clinical sign, with respiratory distress syndrome being the most common (67 percent). In all neonates with congenital infection, brain ultrasound was normal, and retinopathy of prematurity was detected in 33 percent of patients with fundus retinopathy. Conclusions: The incidence of congenital cytomegalovirus infection is high in this risk group. The clinical signs found and the results of the fundus in neonates with congenital infection were related to prematurity and the nutritional assessment of hypotrophic was associated with this infection(AU)

Letermovir para prevención de la infección por citomegalovirus en receptores de trasplante alogénico de progenitores hematopoyéticos / Letermovir for prevention of cytomegalovirus infection in allogeneic stem cell transplant receivers

INTRODUCCIÓN: La infección por citomegalovirus (CMV) sigue siendo la infección con relevancia clínica más frecuente luego del trasplante alogénico de progenitores hematopoyéticos (TPHa), presentando alta morbilidad y mortalidad. Por este motivo, es importante implementar estrategias de prevención para reducir la frecuencia de la infección por CMV. OBJETIVO: Describir la frecuencia de infección, infección clínicamente significativa (ICS) y enfermedad por CMV en pacientes seropositivos que recibieron un TPHa y profilaxis primaria con letermovir. PACIENTES Y MÉTODOS: Estudio descriptivo de cohorte longitudinal, en pacientes con TPHa seropositivos para CMV que recibieron profilaxis primaria con letermovir hasta el día 100 posTPH. RESULTADOS: Se incluyeron 25 pacientes adultos con una mediana de edad de 41 años, el 44% fue de donante no relacionado y 36% de donante haploidéntico. Ochenta por ciento tenía tres o más factores de riesgo para infección por CMV y a 52% se le estratificó como de alto riesgo para enfermedad por CMV. La profilaxis con letermovir tuvo una mediana de duración de 97 días. Durante los 100 días pos-TPH, 20% de los pacientes presentaron infección por CMV, con carga viral plasmática detectable no cuantificable, que se negativizó en el siguiente control semanal sin discontinuación del letermovir. Ningún paciente presentó ICS ni enfermedad por CMV durante este período. CONCLUSIÓN: La profilaxis con letermovir fue efectiva para prevenir la ICS y la enfermedad por CMV.

BACKGROUND: Cytomegalovirus (CMV) infection remains the most common clinically significant infection after allogeneic stem cell transplantation (aSCT), with a high morbidity and mortality rate. In order to reduce its frequency, prevention strategies should be implemented. AIM: To describe the frequency of infection, clinically significant infection (CSI) and CMV disease in seropositive patients who received aSCT and primary prophylaxis with letermovir. METHODS: Longitudinal descriptive cohort study in seropositive patients who received aSCT and primary prophylaxis with letermovir until day 100 post-SCT. RESULTS: Twenty-five adult patients with a median age of 41 years were included; 44% were unrelated donors, and 36% were haploidentical donors. Eighty percent had three or more risk factors for CMV infection, and 52% were stratified as high risk for CMV disease. Letermovir prophylaxis had a median duration of 97 days. Twenty percent of the patients developed CMV infection through day 100 post-SCT, with detectable non-quantifiable CMV viral load in plasma. This became negative in the following weekly control without discontinuation of letermovir. No patient developed CSI or CMV organ disease during this period. CONCLUSION: Letermovir prophylaxis proved to be effective in preventing CSI and CMV disease.

Botulismo del lactante: estudio descriptivo en una unidad de cuidados intensivos pediátricos / Infant botulism: a descriptive study in a pediatric intensive care unit

Introducción. El botulismo del lactante (BL) es la forma más frecuente de botulismo humano en Argentina. El objetivo es describir aspectos esenciales del diagnóstico y tratamiento de pacientes con BL internados en el servicio de terapia intensiva pediátrica (STIP). Métodos. Estudio observacional, descriptivo y retrospectivo. Se utilizó la base de datos del STIP con diagnóstico de BL en el período 2005-2020. Se registraron variables demográficas, métodos de diagnóstico, días de asistencia respiratoria mecánica convencional (ARMC), de ventilación no invasiva (VNI), estadía en STIP, mortalidad al alta hospitalaria. Resultados. Se registraron 21 pacientes con BL; 14 pacientes fueron varones, con una mediana de edad de 5 meses (RIC 2-6 m). El diagnóstico se realizó mediante técnica de bioensayo y se detectó la toxina en suero en 12 pacientes. Uno solo no requirió ARMC; 1 paciente fue traqueostomizado; 18 pacientes recibieron antibióticos; 5 recibieron VNI. Ningún paciente recibió antitoxina y no hubo fallecidos. La mediana de estadía hospitalaria fue 66 días (RI: 42-76); de internación en STIP, 48 días (RI: 29-78); y de ARMC, 37 días (RI: 26-64). La demora en la confirmación diagnóstica fue 15,8 ± 4,8 días. Conclusiones. La totalidad de los pacientes fueron diagnosticados con la técnica de bioensayo, que generó un tiempo de demora diagnóstica que excede los lapsos recomendados para la administración del tratamiento específico. Ningún paciente recibió tratamiento específico. El BL presentó baja mortalidad, pero tiempos de ARM e internación prolongados, que se asocian a infecciones sobreagregadas y uso frecuente de antibióticos.

Introduction. Infant botulism (IB) is the most common form of human botulism in Argentina. Our objective was to describe the main aspects of diagnosis and management of patients with IB admitted to the pediatric intensive care unit (PICU). Methods. Observational, descriptive, and retrospective study. The PICU database with IB diagnosis in 2005­2020 period was used. Demographic variables, diagnostic methods, days of conventional mechanical ventilation (CMV), non-invasive ventilation (NIV), length of stay in the PICU and mortality upon hospital discharge were recorded. Results. In total, 21 patients with IB were recorded; 14 were male, their median age was 5 months (IQR: 2­6 m). Diagnosis was made by bioassay, and the toxin was identified in the serum of 12 patients. Only 1 patient did not require CMV; 1 patient had a tracheostomy; 18 patients received antibiotics; 5 received NIV. No patient was administered antitoxin and no patient died. The median length of stay in the hospital was 66 days (IQR: 42­76); in the PICU, 48 days (IQR: 29­78); and the median use of CMV, 37 days (IQR: 26­64). The delay until diagnostic confirmation was 15.8 ± 4.8 days. Conclusions. All patients were diagnosed using the bioassay technique, which resulted in a diagnostic delay that exceeds the recommended period for the administration of a specific treatment. No patient received a specific treatment. IB was related to a low mortality, but also to prolonged use of MV and length of hospital stay, which were associated with cross infections and frequent antibiotic use.

Hemophagocytic syndrome in a patient with Fanconi anemia and VACTERL association / Síndrome hemofagocítica em paciente com anemia de Fanconi e associação VACTERL

INTRODUCTION: Hemophagocytic syndrome results from hyperactivity of histiocytes and lymphocytes, triggered by infections, mainly viral by cytomegalovirus, Epstein-Barr and herpes. Fanconi anemia (FA) is a rare genetic disease with heterogeneous symptoms common to other diseases such as VACTERL, a disease of unknown etiology in which there are several congenital malformations. The concomitance of Fanconi and VACTERL anemia occurs in 5 to 30% of FA patients. REPORT: A 14-month-old male infant was admitted to investigate fever, hepatosplenomegaly, and granulopenia. The patient was diagnosed with hemophagocytic syndrome due to hyperferritinemia, bone marrow hemophagocytosis, transaminase elevation, decreased fibrinogen, and cytomegalovirus (CMV) infection confirmed by serology and PCR. The test with mitomycin C (MMC) showed chromosomal fragility. The patient was diagnosed with a VACTERL/FA association for having a clinic and a test compatible with both FA and VACTERL. CONCLUSION: The VACTERL/FA association is seldom described, but is present in pediatric medical practice. This study presented the main clinical-laboratory aspects and reviewed the main aspects of the concurrence of this pathology.

INTRODUÇÃO: A síndrome hemofagocítica decorre da hiperatividade de histiócitos e linfócitos e é desencadeada por infeções, principalmente virais por citomegalovírus, Epstein-barr e herpes. A anemia de Fanconi (AF) é uma doença genética rara com sintomas heterogêneos em comum a outras doenças como a associação VACTERL, uma doença de etiologia desconhecida na qual existe diversas mal formações congênitas. A concomitância da anemia de Fanconi e VACTERL é descrita em 5 a 30% dos pacientes AF. RELATO: Lactente de 14 meses, sexo masculino, admitido para investigar um quadro de febre, hepatoesplenomegalia e granulopenia. Os exames laboratoriais mostraram a hiperferritemia, elevação da transaminases, medula óssea com hemofagocitose e, sorologia e PCR positivos para citomegalovírus (CMV). O paciente foi diagnosticado com síndrome hemofagocítica por citomegalovírus. Como havia também hipoplasia do polegar esquerdo, presença de hemivértebra, agenesia renal e teste positivo de fragilidades cromossômicas com mitomicina C (MMC), o paciente foi diagnosticado com associação VACTERL/AF. CONCLUSÃO: O citomegalovírus quando infecta pacientes com problemas de imunidade como AF, apresenta risco de desencadear a síndrome hemofagocítica. A associação VACTERL/AF é pouco descrita, mas presente na prática médica da pediatria. Esse estudo descreveu os principais aspectos clínicos-laboratoriais e revisou os aspectos fundamenais descritos sobre a concomitância dessas patologias.

"Blueberry muffin": Manifestación atípica de una infección congénita frecuente / Blueberry muffin baby: an atypical manifestation of a common congenital infection

El síndrome "blueberry muffin" es una dermatosis maculopapular eritematoviolácea como resultado de una hematopoyesis extramedular. Se ha asociado con infecciones del espectro TORCH y causas no infecciosas. Presentamos el caso de un recién nacido pretérmino, quien desde el control prenatal presentó una ecografía con signos sugerentes de infección congénita por citomegalovirus (microcefalia, ventriculomegalia y calcificaciones intracerebrales). Al examen físico presentaba una dermatosis macular violácea compatible con síndrome "blueberry muffin". Se detectó carga viral de citomegalovirus en orina (81,200 copias/ml) e inició tratamiento con ganciclovir, con desenlace fatal. La infección congénita por CMV debe considerarse ante el síndrome "blueberry muffin"; el adecuado abordaje diagnóstico debe ser oportuno y debe incluir antecedentes maternos y perinatales, así como estudios serológicos para infecciones por TORCH con el fin del inicio precoz de tratamiento para evitar complicaciones y secuelas.

Blueberry muffin syndrome is characterized by an erythematousviolaceous maculopapular dermatosis due to extramedullary hematopoiesis. This entity has been associated with TORCH spectrum infections and noninfectious causes. We present the case of a preterm newborn, who since the prenatal control gave an ultrasound with data suggestive of congenital infection by cytomegalovirus (microcephaly, ventriculomegaly, intracerebral calcifications). On physical examination, he presented a violaceous macular dermatosis compatible with blueberry muffin syndrome. Cytomegalovirus viral load was detected in urine (81,200 copies/ml), with fatal outcome. Congenital cytomegalovirus infection should be considered in the presence of a blueberry muffin syndrome; an adequate diagnostic approach that includes maternal and perinatal history is essential, as well as serology studies for diseases of the TORCH spectrum in order to start early with treatment and avoid major comorbidities.

Effect of breastfeeding on immune function in infants with human cytomegalovirus infection / 中国当代儿科杂志

OBJECTIVES@#To study the effect of breastfeeding on immune function in infants with human cytomegalovirus (HCMV) infection.@*METHODS@#A retrospective analysis was performed on the medical data of 135 infants with HCMV infection who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2021 to May 2022, and all these infants received breastfeeding. According to the results of breast milk HCMV-DNA testing, the infants were divided into two groups: breast milk HCMV positive (n=78) and breast milk HCMV negative (n=57). According to the median breast milk HCMV-DNA load, the infants in the breast milk HCMV positive group were further divided into two subgroups: high viral load and low viral load (n=39 each). Related indicators were compared between the breast milk positive and negative HCMV groups and between the breast milk high viral load and low viral load subgroups, including the percentages of peripheral blood lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells), CD4+/CD8+ ratio, IgG, IgM, IgA, and urine HCMV-DNA load.@*RESULTS@#There were no significant differences in the percentages of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells, CD4+/CD8+ ratio, IgG, IgM, IgA, and urine HCMV-DNA load between the breast milk HCMV positive and HCMV negative groups, as well as between the breast milk high viral load and low viral load subgroups (P>0.05).@*CONCLUSIONS@#Breastfeeding with HCMV does not affect the immune function of infants with HCMV infection.

Infections sévères vue au service des urgences du Centre Hospitalier Universitaire Mahavoky Atsimo: Facteurs pronostics et Issue / Severe infections at the emergency department of the Mahavoky Atsimo teaching hospital: prognosis factors and outcome

: Une infection sévère constitue une situation préoccupante, car elle s'accompagne d'un taux élevé mortalité dans le monde. L'objectif de cette étude était de déterminer les facteurs pronostiques des infections sévères vues dans le service Accueil­triage­Urgence (ATU) du Centre Hospitalier Universitaire (CHU) Mahavoky Atsimo. Méthodes : Il s'agit d'une étude rétrospective et analytique réalisée dans le service ATU du CHU Mahavoky Atsimo durant 24 mois (Janvier 2020-Décembre 2021). Nous avons inclus tous les patients avec une infection sévère, âgés de 15 et plus ayant un score qSOFA≥2. Résultats : la prévalence d'infection sévère était de 9,8% dont 68,3% de sepsis et 31,7% de choc septique. Les principales étiologies étaient la pneumopathie (26,8%), le paludisme (22%), les méningites (14,6%). Le taux de létalité était de 43,9%. L'âge moyen des patients était de 48,34ans ±2,46 avec une majorité masculine (61%). Les facteurs prédictifs d'un mauvais pronostic étaient : l'HTA (p=0,009), la présence de cardiopathie (p=0,001), l'antécédent d'infection urinaire (p=0,000), le score de Glasgow (p=0,006), le score qSOFA (p=0,010), l'extrémité froide (p=0,000), la présence des signes de lutte (p = 0,005), les râle s crépitants (p = 0,005), la VS élevée (p=0,002), l'élévation de la procalcitonine (p<0,0005), le traitement par quinolone (p=0,048), l'utilisation d'amine Vasopressive (p=0,040), la durée longue de perfusion de catécholamines (p=0,039), l'oxygénothérapie (p= 0,014) et l'utilisation de canule oropharyngée (p=0,003). Conclusions: L'infection sévère est une situation difficile à maîtriser. Le pronostic reste dépendant à la fois de la rapidité du diagnostic et de l'instauration rapide d'un traitement adapté au germe en cause

Sepsis por citomegalovirus en el paciente pediátrico / Cytomegalovirus Sepsis in the Pediatric Patient

Introducción: La infección severa por citomegalovirus resulta inusual en pacientes inmunocompetentes, sin embargo, cuando se presenta tiene una alta carga de morbilidad. Objetivo: Examinar el caso de un paciente nacido a término, con desnutrición aguda severa que presentó sepsis secundaria a una infección por citomegalovirus. Presentación del caso: Paciente de 2 meses y 7 días de edad que se llevó al servicio de urgencias por cuadro de un día de evolución de inapetencia, y fiebre. Sin antecedentes de prematurez o de infecciones oportunistas, y adecuado desarrollo para su edad. Se trasladó a un centro de mayor complejidad por deshidratación. En dicho centro el paciente presentó deterioro pulmonar con hallazgo de bronconeumonía, deterioro gastrointestinal por distensión severa de asas, deposiciones sanguinolentas, y deterioro hematológico por anemia hemolítica. Se descartó infección de origen bacteriano y fúngico, y se estableció que la etiología presentada se debía a citomegalovirus. Se trató con valganciclovir con una buena evolución clínica. Se discutió la fisiopatología, el diagnóstico, y tratamiento en relación con el caso presentado. Conclusiones: La infección grave por citomegalovirus en el periodo posnatal resultó muy rara, sin embargo, de presentar síntomas, son principalmente gastrointestinales o pulmonares; y ante la no respuesta al tratamiento convencional de enfermedades más comunes, se debe sospechar de manera oportuna una infección por este agente, dada la alta carga de morbilidad que produce(AU)

Introduction: Severe cytomegalovirus infection is unusual in immunocompetent patients; however, when it occurs it has a high burden of morbidity. Objective: To examine the case of a patient born at term who presented sepsis secondary to cytomegalovirus infection. Presentation of the case: A 2 months and 7 days old patient was taken to the emergency department for one day of evolution of inappetence and fever, with no history of prematurity or opportunistic infections and adequate development for his age. The patient was transferred to a more complex center due to dehydration, and in that center the patient presented pulmonary deterioration with bronchopneumonia, gastrointestinal deterioration due to severe distension of the loops, bloody stools, and hematologic deterioration due to hemolytic anemia. Bacterial and fungal infection was ruled out and the etiology was established as cytomegalovirus. She was treated with valganciclovir with a good clinical evolution. The pathophysiology, diagnosis and treatment are discussed in relation to the presented case. Conclusions: Severe cytomegalovirus infection in the postnatal period was very rare, however, if symptoms are present, they are mainly gastrointestinal or pulmonary; and in the absence of response to conventional treatment of more common diseases, an infection by this agent should be suspected in a timely manner, given the high burden of morbidity it produces(AU)

Síndrome de Evans asociada a infección por citomegalovirus en una niña de 13 meses / Evans Syndrome Associated With Cytomegalovirus Infection In A 13-Month-Old Girl

Introducción: El síndrome de Evans es un desorden autoinmune poco frecuente, caracterizado por el descenso de al menos dos líneas celulares hemáticas. Las publicaciones del síndrome de Evans e infección por citomegalovirus resultan escasas. Objetivo: Examinar el caso de una niña con síndrome de Evans e infección activa por citomegalovirus que respondió favorablemente a la terapia antiviral. Presentación del caso: Niña de 13 meses con antecedentes de prematuridad y bajo peso al nacer, que acudió a consulta por presentar palidez y equimosis en tórax, abdomen y extremidades. En los exámenes de laboratorio se encontró trombocitopenia y anemia severa con prueba de Coombs directo positiva. Recibió pulsos de metilprednisolona con respuesta desfavorable. La carga viral resultó positiva para citomegalovirus (4019 copias de ADN) y recibió valganciclovir con evolución favorable en el seguimiento. Conclusiones: El síndrome de Evans asociado a infección por CMV es infrecuente. El tratamiento con valganciclovir podría ser beneficioso para cierto grupo de pacientes; sin embargo, hacen falta más estudios que demuestren la eficacia y seguridad de este tratamiento en este síndrome; más aún si está asociado a una elevada carga viral(AU)

Introduction: Evans syndrome is a rare autoimmune disorder, characterized by the descent of at least two blood cell lines. Publications of Evans syndrome and cytomegalovirus infection are scarce. Objective: To examine the case of a girl with Evans syndrome and active cytomegalovirus infection who responded favorably to antiviral therapy. Case presentation: A 13-month-old girl with a history of prematurity and low birth weight, who attended the consultation for presenting pallor and ecchymosis in the thorax, abdomen and extremities. Laboratory tests found thrombocytopenia and severe anemia after a positive direct Coombs test. She received pulses of methylprednisolone with unfavorable response. The viral load was positive for cytomegalovirus (4019 copies of DNA) and received valganciclovir with favorable evolution at follow-up. Conclusions: Evans syndrome associated with CMV infection is uncommon. Treatment with valganciclovir may be beneficial for a certain group of patients. However, more studies are needed to demonstrate the efficacy and safety of this treatment in this syndrome; even more so if it is associated with a high viral load(AU)

Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation / 中华预防医学杂志

Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.

Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation / 中华预防医学杂志

Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.

Therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation on respiratory failure in preterm infants with a gestational age of 28-34 weeks: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To investigate the therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation (HFOV-VG) versus conventional mechanical ventilation (CMV) in the treatment of preterm infants with respiratory failure.@*METHODS@#A prospective study was conducted on 112 preterm infants with respiratory failure (a gestational age of 28-34 weeks) who were admitted to the Department of Neonatology, Jiangyin Hospital Affiliated to Medical School of Southeast University, from October 2018 to December 2022. The infants were randomly divided into an HFOV-VG group (44 infants) and a CMV group (68 infants) using the coin tossing method based on the mode of mechanical ventilation. The therapeutic efficacy was compared between the two groups.@*RESULTS@#After 24 hours of treatment, both the HFOV-VG and CMV groups showed significant improvements in arterial blood pH, partial pressure of oxygen, partial pressure of carbon dioxide, and partial pressure of oxygen/fractional concentration of inspired oxygen ratio (P<0.05), and the HFOV-VG group had better improvements than the CMV group (P<0.05). There were no significant differences between the two groups in the incidence rate of complications, 28-day mortality rate, and length of hospital stay (P>0.05), but the HFOV-VG group had a significantly shorter duration of invasive mechanical ventilation than the CMV group (P<0.05). The follow-up at the corrected age of 6 months showed that there were no significant differences between the two groups in the scores of developmental quotient, gross motor function, fine motor function, adaptive ability, language, and social behavior in the Pediatric Neuropsychological Development Scale (P>0.05).@*CONCLUSIONS@#Compared with CMV mode, HFOV-VG mode improves partial pressure of oxygen and promotes carbon dioxide elimination, thereby enhancing oxygenation and shortening the duration of mechanical ventilation in preterm infants with respiratory failure, while it has no significant impact on short-term neurobehavioral development in these infants.

Effect of Plasmacytoid Dendritic Cell Dose in Grafts on CMV Infection after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation between plasmacytoid dendritic cell (pDC) dose in grafts and the occurrence of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 80 children who received allo-HSCT in Children's Hospital of Soochow University from August 20, 2020 to June 11, 2021 were retrospectively analyzed. Proportions of DC subsets and T-cell subsets in grafts were detected by flow cytometry in order to calculate infused cell dose of each cell. Weekly monitoring of CMV-DNA copies in peripheral blood for each child were performed after transplantation. The last follow-up date was December 31, 2021.@*RESULTS@#All the children gained hematopoietic reconstitution. CMV infection was observed in 51 children (63.8%±5.4%) within the first 100 days after transplantation, including 2 cases developing CMV disease. Univariate analysis indicated that infused doses of DC and pDC were significantly associated with CMV infection within 100 days after allo-HSCT (P <0.05). Multivariate analysis indicated that a high dose infusion of pDC was an independent protective factor for CMV infection within 100 days after allo-HSCT (P <0.05). By the end of follow-up, 7 children died of transplantation-related complications, including 2 deaths from CMV disease, 2 deaths from extensive chronic graft-versus-host disease, and 3 deaths from capillary leak syndrome. The overall survival rate was 91.2%.@*CONCLUSION@#The pDC in grafts may be associated with early infection of CMV after allo-HSCT, while a high infused pDC dose may serve as a protective factor for CMV infection after transplantation.

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.

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

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

Evaluación neurológica durante el primer año en niños muy bajo peso al nacer con infección por citomegalovirus / Neurological evaluation during the first year in very low birth weight children with cytomegalovirus infection

Introducción: La infección congénita por citomegalovirus es causa de pérdida auditiva y alteraciones cognitivas. La infección perinatal por este virus es más frecuente en neonatos< 1500 g y produce menos secuelas neurológicas. Objetivo: Describir la evaluación neurológica en el primer año de vida en niños muy bajo peso al nacer con infección por citomegalovirus. Métodos: Estudio descriptivo y longitudinal en el que se incuyeron 14 neonatos< 1500 g, con diagnóstico de infección congénita o perinatal por citomegalovirus; a los cuales se les realizó evaluación del neurodesarrollo, ultrasonido craneal, potenciales evocados auditivos de tallo cerebral y potenciales visuales a las 40 semanas, a los seis meses y al año de edad gestacional corregida. En la primera evaluación se realizó además, electroencefalograma. Resultados: El 43 por ciento tuvo infección congénita y 57 por ciento infección perinatal. A las 40 semanas se evaluaron completamente 79 % de los casos, a los seis meses 64 por ciento y al año 36 por ciento. No se observaron anormalidades en el ultrasonido craneal, ni en el electroencefalograma. Al año de edad corregida, se detectaron alteraciones ligeras del neurodesarrolo en 33,3 por ciento del total de casos (2/6) y con igual porcentaje en los niños con infección congénita (1/3) y perinatal (1/3). En ningún paciente evaluado se detectó sordera neurosensorial, ni daño del nervio visual. Conclusiones: Las alteraciones del neurodesarrollo encontradas al año de edad corregida pueden estar relacionadas con la prematuridad o la infección por citomegalovirus. El seguimiento a mediano y largo plazo es necesario para detectar otras secuelas neurológicas de debut tardío(AU)

Introduction: Congenital cytomegalovirus infection is a cause of hearing loss and cognitive impairments. Perinatal infection by this virus is more frequent in neonates< 1500 g and produces fewer neurological sequelae. Objective: To describe neurological evaluation in the first year of life in very low birth weight children with cytomegalovirus infection. Methods: A descriptive and longitudinal study involving 14 neonates< 1500 g, with a diagnosis of congenital or perinatal cytomegalovirus infection; to which neurodevelopmental evaluation, cranial ultrasound, auditory brain stem evoked potentials and visual potentials were performed at 40 weeks, six months and one year of corrected gestational age. In the first evaluation, electroencephalogram was also performed. Results: 43 percent had congenital infection and 57 percent perinatal infection. At 40 weeks, 79 percent of cases were fully evaluated, at six months 64 percent and at one year 36 percent. No abnormalities were observed on the cranial ultrasound or electroencephalogram. At one year of corrected age, slight alterations in neurodevelopment were detected in 33.3 percent of all cases (2/6) and with the same percentage in children with congenital (1/3) and perinatal (1/3) infection. In no patient evaluated, sensorineural deafness or visual nerve damage was detected. Conclusions: The neurodevelopmental alterations found at one year of corrected age may be related to prematurity or cytomegalovirus infection. Medium- and long-term follow-up is necessary to detect other late-onset neurological sequelae(AU)