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.

Awareness and knowledge of congenital cytomegalovirus infection among pregnant women and the general public: a web-based survey in Japan

BACKGROUND@#The best approach to reduce congenital cytomegalovirus infection (cCMVi) is to practice behaviors that reduce cytomegalovirus (CMV) transmission during pregnancy. Expanding awareness and knowledge of CMV is expected to result in increased practice of preventative behaviors. To this end, it is necessary to understand current awareness and knowledge of CMV.@*METHODS@#This web-based cross-sectional survey assessed the awareness and knowledge of cCMVi among pregnant women and the general public in Japan. Participants aged 20-45 years (pregnant and non-pregnant women, and men) were identified from a consumer panel. Study outcomes (all participants) included awareness of cCMVi and other congenital conditions. Among those aware of cCMVi, outcomes included knowledge of CMV transmission routes, long-term outcomes of cCMVi, and behaviors to prevent CMV transmission during pregnancy. Outcomes limited to pregnant women included the practice of preventative behaviors and opinion on how easy it is to implement these behaviors. The data of the pregnant group (pregnant at the time of the survey) were compared with those of the general group (non-pregnant women and men).@*RESULTS@#There were 535 participants in the pregnant group and 571 in the general group. Awareness of cCMVi was generally low (pregnant, 16.1%; general, 10.2%). Pregnant participants were significantly more aware of most congenital conditions than those in the general group, including cCMVi (P = 0.004). Knowledge about CMV/cCMVi was limited; there were no significant differences between the two groups for 24 of the 26 knowledge questions. A small proportion (one third or less) of pregnant women practiced behaviors to prevent the transmission of CMV, though most (73.3-95.3%) pregnant women who were aware of cCMVi considered such behaviors easy to implement.@*CONCLUSIONS@#Awareness and knowledge of CMV/cCMVi is low among pregnant women in Japan; the level of knowledge is similar to that among the general public. This needs to be improved. Most pregnant women considered behaviors to prevent CMV transmission easy to perform, which indicates that effectively educating pregnant women regarding the long-term outcomes of cCMVi, CMV transmission routes, and preventative behaviors will contribute to a reduced incidence of cCMVi.@*TRIAL REGISTRATION@#UMIN Clinical Trials Registry, UMIN000041260 .

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

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

Alemtuzumab as graft-versus-host disease (GVHD) prophylaxis strategy in a developing country: lower rate of acute GVHD, increased risk of cytomegalovirus reactivation

Acute graft-versus-host disease (aGVHD) and cytomegalovirus reactivation are important complications after allogeneic stem cell transplantation (alloHSCT). Here, we evaluated the impact of treatment with alemtuzumab on the occurrence of aGVHD, cytomegalovirus reactivation and survival after alloHSCT. This was a prospective cohort study conducted at the allo-HSCT unit of Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, from January 2009 to December 2011. Fifty-seven patients who underwent alloHSCT were included. Forty-five (79%) patients had a malignant disease. Alemtuzumab was administered before the conditioning regimen at a dose of 1 mg/kg in children and 30 mg/day for 2 days in adults or children weighing more than 40 kg (a total dose of 60 mg) with a non-malignant disease or patients with a malignant disease and high-risk for GVHD mortality. Alemtuzumab was used in 23 (40%) patients, of whom 17 received a reduced-intensity conditioning. Eleven patients presented aGVHD (grade 2–4) and only 1 of them received alemtuzumab. Cumulative incidence of aGVHD (grade 2–4) at day 100 after transplantation (D+100) was 4 for patients receiving alemtuzumab and 29% for patients not receiving alemtuzumab. Cumulative incidence of cytomegalovirus reactivation for patients receiving or not alemtuzumab was 62 and 38%, respectively. Sixteen patients died in the first 100 days after alloHSCT, most of them due to bacterial sepsis. Only 2 patients died of aGVHD until D+100. Overall survival was 50% without any impact of alemtuzumab. Alemtuzumab effectively controlled aGVHD but increased the risk of cytomegalovirus reactivation without improving survival.

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

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

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

Targeted preemptive therapy according to perceived risk of CMV infection after kidney transplantation

ABSTRACT Background: The identification of the best strategy to manage cytomegalovirus infection is hampered by uncertainties regarding the risk/benefit ratios of universal prophylaxis versus preemptive therapy, the impact of indirect cytomegalovirus effects and the associated costs. This study investigated the efficacy and safety of targeted preemptive therapy according to perceived risk of cytomegalovirus infection after kidney transplantation. Methods: 144 adult kidney transplant recipients were enrolled in this 12-month study. None received cytomegalovirus pharmacological prophylaxis. Only high risk patients (positive donor/negative recipient (D+/R−), use of induction therapy with antithymocyte globulin, treatment of rejection) received preemptive therapy based on the result of pp65 antigenemia test. Low-risk patients with symptoms related to cytomegalovirus were screened for pp65 antigenemia and treatment initiated if confirmed cytomegalovirus disease. Blinded cytomegalovirus DNAemia was collected weekly during the first three months. Results: The incidence of cytomegalovirus infection was 34% and cytomegalovirus disease was 17%. The incidence was 25% in D+/R−, 69% in those receiving induction with rabbit antithymocite globulin (r-ATG), 46% in those treated for acute rejection, and 28% in low risk patients. By week 3 DNAemia was observed in 30% of patients who were not treated for cytomegalovirus infection/disease, and values ≥2.169 UI/mL showed 61% sensitivity and 85% specificity to detect cytomegalovirus disease (AUC = 0.849 ± 0.042, p < 0.001). Using multivariate analysis, only anti-thymocyte globulin induction was associated with cytomegalovirus infection/disease whereas only expanded donor criteria and renal function at 30 days were associated with renal function 12 months after transplantation. Conclusion: Targeted preemptive therapy in patients with perceived higher risk for cytomegalovirus infection/disease was effective in preventing severe clinical presentation, including tissue invasive and late cytomegalovirus infection. This strategy is associated with direct and indirect cost-savings.

Manejo de las infecciones por citomegalovirus y virus herpes simple en gestantes y recién nacidos / Management of Cytomegalovirus Infections and Herpes Simplex Virus in Pregnant Women and Newborns

Existe un grupo de infecciones que pueden producir defectos congénitos graves cuando se adquieren durante la gestación. Estas inciden en la morbilidad y mortalidad infantil, especialmente si la infección ocurre antes de las 20 semanas de embarazo. Entre ellas se encuentran las producidas por el citomegalovirus y el virus del herpes simple que con frecuencia se asocian con infección congénita y daño al recién nacido. El citomegalovirus humano está mundialmente distribuido entre las poblaciones humanas, desde los países desarrollados hasta las comunidades aborígenes. En países en vías de desarrollo y en los estratos socioeconómicos bajos de los países desarrollados, la prevalencia es mayor (más de 90 por ciento) y el virus se adquiere en edades más tempranas de la vida. Es la infección viral congénita más frecuente, ocurre de 0,3 a 2 por ciento de los nacimientos y en el 40 por ciento la transmisión es vertical. La distribución del virus del herpes simple es amplia y la seroprevalencia en el adulto es entre 60 y 75 por ciento para virus del herpes simple -1 y de 11-30 por ciento para virus del herpes simple -2. El objetivo de la presente revisión es describir estas dos entidades al abordar las características más comunes de estas afecciones, la epidemiología, el diagnóstico, la clínica y la terapéutica. Es necesario que el médico de asistencia las conozca a profundidad para realizar un correcto manejo de estas(AU)

There is a group of infections, which can cause serious birth defects when acquired during pregnancy. They affect infant morbidity and mortality, especially if the infection occurs before 20 weekspregnant. These include those caused by cytomegalovirus and herpes simplex virus that are often associated with congenital infection and damage to the newborn.Human cytomegalovirus (HCMV)is globally distributed among human populations from developed countries to Aboriginal communities. In developing and low socioeconomic strata of the developed countries, the prevalence is higher (over 90 percent) and the virus is acquired in earlier stages of life. It is the most common congenital viral infection. It occurs 0.3 to 2 percent of births and 40 percent transmission is vertical. The distribution of herpes simplex virus is broad and seroprevalence in adults is between 60 and 75 percent for herpes simplex 1 virus and 11-30 percent for herpes simplex virus -2. The aim of this review is to describe these two entities in addressing the most common features of these conditions as epidemiology, diagnosis, clinical and therapeutic. A profound knowledge is necessary for the attending physician to the proper handling of them(AU)

Infección por citomegalovirus en pacientes VIH/sida / Cytomegalovirus infection in HIV/ aids patients

El citomegalovirus (CMV) se considera un microorganismo oportunista común entre individuos con infección por el virus de inmunodeficiencia humana (VIH), agente causal del síndrome de inmunodeficiencia adquirida (Sida). La principal consecuencia de la replicación persistente del VIH es la reducción gradual del número de linfocitos T CD4+, lo que eventualmente conduce a la pérdida de la competencia inmunológica. El CMV humano pertenece a la familia de los herpes virus y con frecuencia produce enfermedades en diferentes órganos, principalmente cuando el conteo de linfocitos T CD4+ es muy bajo(AU)

The cytomegalovirus (CMV) is considered a common opportunist microorganism among individuals with human immunodeficiency virus (HIV), the causal agent of the acquired immunodeficiency syndrome (Aids). The main consequence of the persistent transduction of HIV is the gradual reduction of the number of T cells CD4+, which eventually causes loss of immunologic competition. This human virus belongs to the family of herpes virus and frequently produces diseases mainly in different organs when the T CD4+ count is very low(AU)

Cytomegalovirus infection in renal transplantation: clinical aspects, management and the perspectives / Infecção pelo citomegalovírus no transplante de rim: aspectos clínicos, manejo e perspectivas

Cytomegalovirus infection is one of most frequent infectious complications after renal transplantation, and can be classified as primo-infection, when the transmission occurs through the graft, or reactivation, when the recipient is cytomegalovirus seropositive. After transplantation, cytomegalovirus can appear as an infection, when the patient presents with evidence of viral replication without symptoms or disease, which has two clinical spectra: typical viral syndrome or invasive disease, which is a less common form. Their effects can be classified as direct, while the disease is developed, or indirect, with an increase of acute rejection and chronic allograft dysfunction risks. Diagnosis must be made based on viremia by one of the standardized methods: antigenemia or PCR, which is more sensitive. The risk factors related to infection after transplantation are the serologic matching (positive donor and negative recipient) and anti-lymphocyte antibody drugs. One of the strategies to reduce risk of disease should be chosen for patients at high risk: preemptive treatment or universal prophylaxis. Recent clinical research has described ganciclovir resistance as an emergent problem in management of cytomegalovirus infection. Two types of mutation that cause resistance were described: UL97 (most frequent) and UL54. Today, sophisticated methods of immunologic monitoring to detect specific T-cell clones against cytomegalovirus are used in clinical practice to improve the management of high-risk patients after renal transplantation.

A infecção pelo citomegalovírus é uma das principais complicações após o transplante de rim, podendo ser classificada em primoinfecção, quando a transmissão ocorre por meio do enxerto, ou em reativação, quando o receptor é soropositivo. Do ponto de vista clínico, pode se apresentar como infecção, na ausência de sintomas, ou como doença, com dois diferentes espectros: a síndrome viral típica ou, menos comumente, a doença invasiva. Os efeitos podem ser diretos, que é o desenvolvimento da doença, ou indiretos, como aumento no risco de rejeição aguda e de disfunção crônica do enxerto. O diagnóstico deve ser feito por pesquisa de viremia por meio de um dos dois métodos padronizados: antigenemia ou PCR − sendo essa última a mais sensível. Os fatores de risco relacionados com a infecção após o transplante são o match sorológico (doador positivo e receptor negativo) e o uso de anticorpos antilinfócitos. Uma das estratégias de redução de risco de doença deve ser escolhida após o transplante nos pacientes de alto risco: tratamento preemptivo ou profilaxia. Recentemente, linhas de pesquisa clínica têm apontado a resistência ao ganciclovir como um problema emergente no manejo da infecção pelo citomegalovírus. Duas formas de mutação que causam resistência são descritas: UL97, que é a mais frequente, e a UL54. Atualmente, sofisticados métodos de monitorização imunológica, como a detecção de clones específicos de células T contra o citomegalovírus podem ser utilizados na prática clínica para o melhor manejo após o transplante renal dos pacientes de alto risco.

Infección por citomegalovirus en receptores de trasplante alogénico de células progenitoras hematopoyéticas: terapia temprana basada en el estudio de la antigenemia y la carga viral en sangre / Cytomegalovirus infection in allogeneic hemapotopoietic stem-cell transplantation: early treatment based on the study of antigenemia assay and viral load determination in blood

La prevención de la enfermedad por CMV en los receptores de trasplante de células progenitoras hematopoyéticas se basa en la terapia temprana de la reactivación viral. La Antigenemia y el estudio de la carga viral por PCR son las dos técnicas diagnósticas actualmente vigentes. Se siguió una cohorte de 35 pacientes con estudios semanales con ambos métodos desde la recuperación de la neutropenia hasta el día 100 días postrasplante. Se inició tratamiento empírico con antivirales (Ganciclovir o Foscarnet) con un resultado positivo (antigenemia > 1 cel/200.000 o carga viral > 500 copias / ml) y se mantuvo 3-6 semanas. La serología previa fue positiva en R y D en 66% de los casos, en R o D en 20%, negativa en 3% y no evaluable en 11%. Se detectó infección por CMV en el 50% de los pacientes. En 15 ptes el diagnóstico fue por PCR, en 2 ambas pruebas fueron positivas y en uno solo la antigenemia. Un paciente presentó neumonía por CMV y falleció dentro de los 100 días de seguimiento. En 11,4% de los casos se detectó reactivación viral luego de los 100 días y dos ptes presentaron neumonía por CMV tardía que fue causa de muerte. Conclusión: Con los umbrales utilizados la carga viral precedió a la antigenemia en el diagnóstico de reactivación de CMV. La terapia temprana previene la enfermedad temprana por CMV en la mayoría de los casos pero la enfermedad tardía es un problema pendiente de resolución (AU)

Prevention of CMV disease in hematopoietic stem-cell transplantation recipients is based on the early management of viral reactivation. Antigenemia assay and PCR viral load detection are the current diagnostic techniques of choice. We followed a cohort of 35 patients with weekly studies using both methods from recovery from neutropenia to day 100 post-transplant. Empirical viral treatment (Ganciclovir or Foscarnet) was started after a positive result (antigenemia > 1 cell/200,000 or viral load > 500 copies / ml) and maintained for 3-6 weeks. Previous serology was positive in R and D in 66% of the cases, in R or D in 20%, negative in 3%, and not evaluable in 11%. CMV infection was detected in 50% of the patients. In 15 patients the diagnosis was made using PCR, in 2 both tests were positive, and in one only the antigenemia assay was positive. One patient presented with pneumonia due to CMV and died within the 100 days of follow-up. In 11.4% of the cases viral activation was detected after 100 days and two patients developed late pneumonia due to CMV and consequently died. Conclusion: Using these thresholds viral load detection preceded antigenemia assay in the diagnosis of CMV reactivation. Early treatment prevents early disease due to CMV in the majority of cases, but late disease remains a problem to be solved (AU)

Profilaxis de citomegalovirus en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against cytomegalovirus infection in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation

CMV is one of the main infectious problems for SOT and HSCT. The severity of the complications are mainly associated with the type of transplant and immune status against the virus of the transplant donor and the transplant recipient. It is important to prevent exposure, using safe blood transfusion CMV seronegative donors (B1) and/or use of blood leucocytes-depleted by filtration (Al). In addition to preventing exposure, there are two widely used prevention strategies: universal prophylaxis with antiviral therapy or "pre-emptive" strategy based on the use of antivirals only to the early detection of CMV replication in blood. The first option is most used in the SOT management, especially for those identified as the high risk group of CMV disease: R (+), with D (+) or D (-) (Al), where the recommended drug is ganciclovir or valganciclovir . The second approach is preferable for HSCT, which recommends weekly monitoring for CMV viral load from day 10 to 100 post transplant (A3). This strategy requires having a viral laboratory support (A2). The selected antiviral in the case of pre emptive therapy is intravenous ganciclovir (A1).

La infección y enfermedad por CMV son problemas comunes en pacientes con TOS y TPH. La gravedad de las complicaciones asociadas a este virus dependen fundamentalmente del tipo de trasplante y de la experiencia inmunológica previa contra el virus del donante y el receptor. Es importante prevenir la exposición, utilizando transfusiones de sangre segura para CMV con donantes seronegativos (B1) y/o uso de sangre leuco-depletada por iltración (A1). Además de prevenir la exposición, existen dos estrategias de prevención ampliamente utilizadas: La proilaxis universal con antivirales y la terapia adelantada o estrategia "pre-emptive" basada en el uso de antivirales sólo ante la detección precoz de replicación del CMV en sangre. La primera opción es de mayor uso en TOS, especialmente para aquellos binomios identficados como de mayor riesgo de enfermedad por CMV: R (+), con D (+) o D (-) (A1), siendo el medicamento recomendado ganciclovir o valganciclovir. La segunda opción es de elección en TPH, en cuyo caso se recomienda monitoreo semanal con carga viral para CMV desde el día 10 al 100 post trasplante (A3), lo que implica contar con un laboratorio de apoyo en diagnóstico virológico (A2). El antiviral de elección en este caso es ganciclovir iv (A1).

Infecção pelo citomegalovírus na gestação:uma visão atual / Cytomegalovirus infection in pregnancy: a current view

A infecção pelo citomegalovírus representa a mais prevalente infecção correlacionada com deficiência neurológica congênita. Apesar da ocorrência da transmissão vertical em taxas consideravelmente elevadas, nem sempre o feto é atingido. O risco de danos ao concepto é maior quando a infecção materna se desenvolve no primeiro trimestre ou no início do segundo trimestre. O recente desenvolvimento de testes sorológicos que visam a detecção de IgM e IgG específico, além do teste de avidez pelo IgG, representam os métodos mais confiáveis de diagnóstico da infecção materna, enquanto a amniocentese (PCR no líquido amniótico), em conjunto com exames de imagem possuem um papel significativo na detecção da infecção fetal. Apesar dos promissores estudos envolvendo novas técnicas de tratamento, a prevenção da doença continua sendo fundamental, por meio dos bons hábitos de higiene pessoal. O presente artigo busca revisar os aspectos mais atuais da infecção congênita pelo citomegalovírus, assim como técnicas de diagnóstico, tratamento e prevenção.

Cytomegalovirus infection represents the most prevalent infection correlated with congenital neurological deficit. Despite the high occurrence of vertical transmission rates, the fetus is not always committed. The risk of fetal damage is higher when maternal infection develops in the first trimester or early second trimester. The recent development of serological tests to detect specific IgM and IgG, as well as by IgG avidity testing, represents the most reliable methods for diagnosis of maternal infection, whereas amniocentesis (amniotic fluid PCR) associated with imaging methods have significant role in the detection of fetal infection. Despite the promising new techniques for studies involving treatment, prevention remains crucial through the good personal hygiene habits. The aim of this article is to review the most current aspects about the cytomegalovirus congenital infection, as well as techniques for diagnosis, treatment and prevention.

Infecciones tras el trasplante hepático: infecciones por citomegalovirus / Infections after liver transplantation: cytomegalovirus infection

La infección por Citomegalovirus representa un desafío considerable tras el trasplante hepático, limitando la supervivencia del injerto a través de efectos directos, pero también a través de una modulación del sistema inmune, favoreciendo otras infecciones y el rechazo al injerto. La identificación de la condición serológica del donante y el receptor permite establecer el riesgo posterior de contraer la infección, además de la administración juiciosa de la profilaxis antiviral, lo cual limita ostensiblemente el riesgo de desarrollar una infección por Citomegalovirus tras el trasplante hepático. Hoy en día se cuenta con terapias antivirales efectivas pero que, lamentablemente también tienen efectos adversos importantes, lo cual hace aún más relevante la administración de profilaxis en los casos que lo ameritan y estar alerta al desarrollo de la infección en el post trasplante.

Cytomegalovirus infection is an important challenge to liver transplant clinicians, because it can be life threatening and because of its indirect effects on the immune system and the graft. Identification of the serologic condition of the donor and the receptor and risk factors to develop this condition allow us to establish a rational prophylaxis and to rapidly detect the infection. Currently there are effective antiviral treatments; which unfortunately also have important adverse effects. This emphasizes the importance of antiviral prophylaxis after liver transplantation.

Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant

OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05). A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94 percent, p<0.01) and an increase in CD57+ lymphocytes (5.60 percent, p<0.01). This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant), also had an impact on the CD57+ subset, triggering an increase of 4.9 percent in CD57+ lymphocytes (p<0.05). CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

combined pretransplantation seropositivity of kidney transplant recipients for cytomegalovirus antigens [pp150 and pp28] a predictor for protection against infection?

This study was aimed at detecting antibodies to the antigens which may contribute to protection against cytomegalovirus [CMV] infection after organ transplantation. A total of 203 kidney transplant patients were enrolled in the study. Based on CMV antigenemia assay, 23 patients were antigen-positive and of the remaining 180 antigen-negative patients, 46 were selected as controls matched for age, gender and source of kidney. The 69 kidney recipients [KR] had CMV antibody due to previous infection and were followed up for a period of 6 months after transplantation for the development of active CMV infections by the antigenemia assay. Antibody responses to five CMV-related peptide antigens [pp65, gB, pp150, pp28 and pp38] were investigated by enzyme immunoassay and their presence was correlated with the results of the CMV antigenemia assay. Of the five CMV-related peptide antigens, only gB antigen showed response to the antibody in 10/23 [43.5%] antigen-positive patients and 9/46 antigen-negative patients and the difference was statistically significant [p = 0.048]. On the other hand, there was no significant difference in antibody responses between the antigen-positive and antigen-negative KR to the other four CMV peptide antigens [p > 0.05]. However, among the antigen-positive KR there was only 1 patient who had antibodies to both pp150 and pp28 antigen, while among the antigen-negative KR, 22 of 46 [47.8%] had the antibodies [p < 0.001]. The findings suggest that the combined presence of antibodies against the pp150 and pp28 antigens may indicate a lower risk of CMV reactivation after kidney transplantation