Recomendaciones para el diagnóstico y manejo de la infección por citomegalovirus en la mujer embarazada y el recién nacido / Recommendations for the diagnosis and management of cytomegalovirus infection in pregnant woman and newborn infant

Resumen La Sociedad Chilena de Infectología, a través de su Comité de Infecciones Neonatales, en conjunto con la Sociedad Chilena de Obstetricia y Ginecología, proponen un documento de diagnóstico y manejo de la Infección por Citomegalovirus en la Mujer Embarazada y el Recién Nacido. Esta guía aborda el manejo de la infección en el binomio, su enfrentamiento diagnóstico y terapéutico, orientado al equipo de salud que atiende a mujeres embarazadas y recién nacidos con infección por citomegalovirus (CMV) en Chile. Considera la situación epidemiológica global y latinoamericana, con recomendaciones para la evaluación clínica y de laboratorio; establece criterios de diagnóstico, propone enfoques terapéuticos de acuerdo a la situación clínica, analiza las medidas de prevención y establece una propuesta nacional para el seguimiento de esta enfermedad. Se ha puesto especial énfasis en entregar, de forma práctica, y con la mayor evidencia posible, las recomendaciones para el manejo del binomio con infección por CMV.

Abstract The Chilean Society of Infectology, through its Neonatal Infections Committee in conjunction with the Chilean Society of Obstetrics and Gynecology, propose a document for the Diagnosis and Management of Cytomegalovirus Infection in Pregnant Woman and Newborn Infant. This guideline suggests the management of mother and child infection, its diagnostic and therapeutic options. Considers the global and Latin American epidemiology, with recommendations for clinical and laboratory evaluation; diagnostic criteria, therapeutic approaches according to the clinical situation, analyzes prevention measures and establishes a national proposal for monitoring this disease.

Toxoplasmosis diseminada en un paciente con trasplante de corazón a pesar de la profilaxis con trimetoprim-sulfametoxazol / Disseminated toxoplasmosis in a heart transplant patient despite cotrimoxazole prophylaxis: A case report

Resumen Se reporta el caso de un paciente de sexo masculino, de 61 años de edad, quien ocho meses después de someterse a un trasplante de corazón presentó una enfermedad sistémica con compromiso del sistema nervioso central y del sistema inmunológico, así como de pulmón, riñón, colon y piel, y a quien finalmente se le diagnosticó toxoplasmosis diseminada, a pesar de haber recibido profilaxis con trimetoprim-sulfametoxazol, debido a que el órgano provenía de un donante positivo para toxoplasmosis siendo él un receptor negativo. Se discuten las opciones de profilaxis en nuestro medio.

Abstract We report the case of a 61 year-old male who underwent heart transplantation eight months before developing a systemic condition with central nervous system, lung, kidney, colonic, cutaneous, and hematologic involvement, found to be secondary to a systemic toxoplasmosis despite co-trimoxazole prophylaxis in a previous-to-transplant seronegative patient receiving a heart from a seropositive donor. A review of prophylactic options in our environment is discussed.

Nonprimary Cytomegalovirus Fetal Infection / Infeção fetal não primária por citomegalovírus

Abstract Cytomegalovirus (CMV) is the most common congenital viral infection, causing hearing, visual and psychomotor impairment. Preexisting maternal CMV immunity substantially reduces, but not eliminates, the risk of fetal infection and affectation. This article is about a case of nonprimary maternal CMV infection during pregnancy, with vertical transmission, resulting in severe fetal affectation. Preconceptional analysis indicated maternal CMV past infection. Pregnancy progressed uneventfully until the 20th week ultrasound (US), which revealed cerebral abnormalities: thin and hyperechogenic cerebral cortex with prominent lateral ventricles, bilateral periventricular hyperechogenicities, cerebellar vermis hypoplasia and absent corpus callosum. The MRI suggested these findings were compatible with congenital infection rather than primary brain malformation. The fetal karyotype was normal. The title of CMV's IgG antibodies almost tripled. Since the first semester,analysisof the polymerasechainreaction(PCR)forCMVDNAintheamniotic fluid was negative. The pregnancy was terminatedat 23weeks. Neuropathologicalfindings at autopsy showed severe brain lesions associated with CMV infection.

Resumo O citomegalovírus (CMV) é a infeção viral congénita que mais comumente causa deficiência auditiva, visual e psicomotora. A preexistência de imunidade materna reduz substancialmente, mas não elimina, o risco de infeção e afetação fetal. Trata-se de um caso de infeção materna não primária por CMV durante a gravidez, com transmissão vertical, resultando em afetação fetal severa. As análises preconcepção indicavam infecção passada por CMV. A gravidez decorreu sem intercorrências até a ecografia efetuada na 20ª semana, que revelou alterações cerebrais: córtex cerebral fino e hiperecogénico com ventrículos laterais proeminentes, hiperecogenecidades periventriculares bilaterais, hipoplasia do vérmis cerebeloso e ausência de corpo caloso. A ressonância magnética sugeriu que estes achados eram mais favoráveis a uma infeção congénita do que com uma malformação cerebral primária. O cariótipo fetal era normal. O título de anticorpos IgG para CMV havia triplicado desde a dosagem do primeiro trimestre. O PCR para o DNA do CMV no líquido amniótico foi negativo. A gravidez foi interrompida na 23ª semana. Os achados neuropatológicos na autópsia mostraram lesões cerebrais severas associadas a infeção por CMV.

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.

Infección congénita por citomegalovirus: nuevos aspectos terapéuticos / Congenital cytomegalovirus infection: new therapeutic aspects

La infección por citomegalovirus es la infección congénita más frecuente, presentando morbimortalidad perinatal y secuela neurológica tanto en primoinfección como en reactivación durante el embarazo. Se presenta el caso de una embarazada con lupus eritematoso sistémico, en tratamiento inmunosupresor, que presentó reactivación de infección por citomegalovirus. Se discuten los mecanismos de transmisión y de diagnóstico prenatal, así como nuevas alternativas terapéuticas in útero.

Cytomegalovirus infection is the most common congenital infection, causing perinatal morbidity and neurological sequel in both primary infection and reactivation during pregnancy. A case of a pregnant woman with lupus, in immunosuppressive therapy that suffered reactivation of the cytomegalovirus infection is presented. We discuss the mechanisms of transmission and prenatal diagnosis, as well as new therapeutic alternatives wail in uterus.

[Diagnostic and virological follow up of human cytomegalovirus infection]

The Human cytomegalovirus [HCMV] is a ubiquitous herpes virus and is a common virus worldwide. It is important in human pathology and causes serious diseases. Our study is to specify the biological, anatomical and epidemiological aspects, as well as the circumstance of the diagnostics and the principal treatments of infections with HCMV. The descriptive study covered all articles published in with the key words Cytomegalovirus, Immunocompromised patients, bone-marrow transplants, renal transplants, AIDS patients, PCR, pp65 antigenemia We found 200 articles published in international reviews. That has been eligible to the study. Most of these articles were concerned about experimental and clinical work [67%and 21%respectively]. The majority [80%] of the articles is written in English. The human cytomegalovirus is the origin of serious infections in patients having an immunity deficit. The study of the place of the HCMV in immunocompromised, is thus of an indisputable interest to understand the factors associated with this infection

Infections transmitted from donors to recipients following organ transplantation.

There is an ever-increasing gap between the number of donors and those waiting for organ grafts, resulting in increased waiting times and mortality on transplant waiting lists. Consequently, every potential donor must be considered for possible transplantation even if they are outside the conventional donor criteria. To address this imbalance, organs are currently transplanted from living donors, older donors, haemodynamically unstable and non-heart-beating donors, and donors with prior infections. There is a potential to transmit infections and, to a lesser extent, malignancy from the donor organ to the immunosuppressed recipient, and this may also have an effect on subsequent organ function in the recipient. Thus, transmission of infections from organ donors to recipients represents low but serious potential risks that must be weighed against a candidate's risk of dying before a transplant becomes available.

evaluation of cytomegalovirus in infants following exchange transfusion in Children Medical Hospital

During the infancy period, exchange transfusion is the main and effective method of cure for hyperbilirubineamia in hemolytic neonates. One of the risks involved in these patients is CMV infection. Since CMV can inflict and kill children with immunodeficiency, we decided to evaluate blood transmitted CMV infection in infants for the first time in Iran. In this prospective study, the levels of IgG and IgM antibody against CMV in infants blood sera before and after exchange transfusion, sera of their mothers, and the plasma of donors were evaluated by ELISA method and conventional kits. The data were then analyzed by nonparameteric and mac nemar test. The level of specific IgM antibody of CMV was 14% in the serum of infants before exchange transfusion and 48% two months after exchange which came out to be significant [p<0.0001]. This indicates transmittability of CMV infection through blood transfusion since the amount of primary infection of CMV in mothers [IgM] was only 1%. According to the high level of CMV infection in infants [14%] compared to mothers [1%], it can be concluded that some mothers have latent CMV infection. On the other hand, the high level of CMV infection in infants [48%] 2 months after transfusion is caused by post-transfusion CMV infection. Analysis of the data obtained from dependent varibles such as volume of transfused blood, number of exchange transfusion attempts, weight, age, sex and blood group analyzed by the nonpara-meteric method indicated that the volume of transfused blood to infants has a direct correlation with the rate of transmission of infection to them but other variables do not have any correlation

Transfusion transmitted diseases.

Transfusion transmitted disease (TTD) is a major challenge to the transfusion services all over the world. The problem of TTD is directly proportionate to the prevalence of the infection in the blood donor community. In India, hepatitis B/C, HIV, malaria, syphilis, cytomegalo virus, parvo-virus B-19 and bacterial infections are important causes of concern. Hepatitis B and C infections are prevalent in India and carrier rate is about 1-5% and 1%, respectively. Post transfusion hepatitis B/C is a major problem in India (about 10%) because of low viraemia and mutant strain undetectable by routine ELISA. HIV prevalence among blood donors is different in various parts of the country. It may not be so alarming as projected by some agencies. In one study from north India, confirmed HIV positivity was found in 0.2/1000 blood donor. Post transfusion CMV is difficult to prevent but use of leukocyte filters may help to reduce it significantly. Parvo virus B-19 infection in blood donors is 39.9% which may increase morbidity in multitransfused or immunocompromised patients. Current symphilis tests may not be sensitive but it should be continued to exclude high-risk donors. Malaria is a real problem for India due to the lack of a simple and sensitive screening test. Incidence of bacterial contamination is greatly reduced due to improved collection/preservation techniques and use of antibiotics in patients. However, proper vigilance and quality control is needed to prevent this problem. Total dependence of altruistic repeat voluntary donors and use of sensitive laboratory tests may help Indian blood transfusion services to reduce incidences of TTDs.

Cytomegalovirus seroepidemiology in an urban community of Säo Paulo, Brazil

Introdução: Após a era da vacinação contra a rubéola, a citomegalovirose tornou-se uma das causas mais freqüentes de surdez congênita e retardamento mental. Estudos soroepidemiológicos são necessários para entender a dinâmica de transmissão da doença. O objetivo do estudo foi quantificar a transmissão dessa doença em comunidade do Estado de São Paulo, Brasil. Métodos: Foi realizado estudo sorológico retrospectivo utilizando anticorpos contra o citomegalovírus (CMV) de classe IgG, pelo método ELISA, em soros congelados de 443 indivíduos, randomizados e selecionados pela técnica de Cluster, provenientes da comunidade de Caieiras, uma pequena cidade localizada nos arredores de São Paulo. As amostras foram colhidas entre novembro de 1990 e janeiro de 1991. No estudo da soroprevalência estratificada por idade (0 a 40 anos), foram aplicadas técnicas matématicas para a determinação da função de decaimento de anticorpos maternos durante o primeiro ano de vida, da função de soroprevalência por idade e da força de infecção para o CMV na comunidade. Resultados: Foi observada uma fase descendente da soropositividade durante os primeiros nove meses, porém ocorreram mudanças nos títulos de anticorpos entre oito meses e um ano de vida. A idade média de aquisição da primeira infecção foi de 5,02 meses e 18,84 anos, quando se analisaram a soroprevalência e a força de infecção, idade dependentes, respectivamente entre 10 meses e 10 anos e 10 e 40 anos. Conclusões: A citomegalovirose é altamente prevalente na população estudada e ocorre precocemente já no primeiro ano de vida. O estudo demonstrou que mulheres em idade reprodutiva se encontravam vulneráveis à primeira infecção, aumentando a chance de doença congênita

Cytomegalovirus infection in children with Down syndrome in a day-care center in Brazil

This study evaluates the transmission of CMV infection in 120 children aged 1 to 15 years with Down syndrome who attended a day-care center for handicapped children in São Paulo, Brazil. A blood sample was obtained from each children at the beginning of the study for detection of IgG and IgM cytomegalovirus (CMV) antibodies by an immunofluorescence assay. Samples of saliva and urine were obtained every 3 months from the children with CMV antibodies to detect shedding of the virus by culture in human foreskin fibroblasts, by detection of pp65 CMV-antigen and by a nested PCR assay. The prevalence of anti CMV-IgG antibodies was 76.6 per cent (92/120), and IgM anti-CMV antibodies were detected in 13 per cent (12/92) of the seropositive children. During the first viral evaluation, CMV was detected in the urine and/or saliva in 39/90 (43.3 per cent) of the seropositive children. In the second and third evaluations, CMV was detected in 41/89 (46 per cent) and in 35/89 (39.3 per cent) children, respectively. Detection of CMV was shown both in urine and saliva in 28/39 (71.8 per cnet), 19/41(46.3 per cent) and 20/35 (57.1 per cent) of the children excreting the virus, respectively...

Viral infections in newborns through exchange transfusion.

Preprocedure sera of thirty one neonates requiring exchange transfusion were tested for serological markers of HBV, HCV, CMV, HIV and LFT. All the babies were investigated for these parameters one week and two months after transfusion to evaluate the risk of transmission of viral infection. Serological markers for these viral infections were also studied in the mothers and donors' blood to establish the route of infection. Donors' blood used for transfusion was pretested for HBsAg, VDRL and anti-HIV. HBsAg was detected one week post exchange in one baby and two months post exchange in two babies. Exchange transfusion was implicated in two of them, where one donor had HBsAg and the other anti-HBc. Vertical transmission accounted for the remaining one. Out of these HbsAg positive cases, one showed evidence of recently acquired CMV infection. Vertical transmission of anti-HCV was observed in one case. None of the neonates, mothers and donors were positive for anti-HIV. In view of probable serious consequences of HBV and HCV infections, blood used for exchange transfusion ought to be screened for anti-HBc and anti-HCV, besides routine HBsAg, VDRL and anti-HIV screening.

SIDA y saliva. Aspectos actuales / AIDS and saliva. Current aspects

El sindrome de inmunodeficiencia adquirida (SIDA) se caracteriza por una marcada disminución inmunológica, teniendo como consecuencia una mayor susceptibilidad a enfermedades oportunistas, pasando por varios estadios hasta llegar invariablemente a la muerte. Dentro de las enfermedades oportunistas características del sindrome, existen varias trasmitidas por saliva: hepatitis B, tuberculosis, herpes zoster, herpes simple, citomegalovirus y mononucleosis. Por otra parte, aunque la evidencia ocupacional, familiar y prácticas sexuales establecen que el SIDA no se trasmite por vía oral (saliva), muchos individuos continúan expresando miedo acerca del contagio de VIH por esta vía. Para tratar de esclarecer y conocer los aspectos actuales acerca de este rubro, el principal objetivo de este trabajo es conocer y discutir la relación que guarda la saliva con el virus de inmunodeficiencia humana (VIH)

La importancia clínica del citomegalovirus humano / The clinical importance of human citomegalovirus

La frecuencia del citomegalovirus humano (CMVH) es aún más elevada que la de muchos otros destacados agentes patógenos e incluye infecciones sintomáticas y asintomáticas que se transmiten por las vías aérea, oral, genital, transplacentaria, transfusional y/o a través de transplantes de órganos. En diversos casos, los daños implicados pueden conducir a serios trastornos neurológicos o hacia la muerte, sobre todo cuando las personas afectadas padecen de inmadurez o depresión inmunitarias, tal como ocurre durante la etapa de gestación, en los recién nacidos, en los receptores de órganos provenientes de donadores seropositivos para CMVH y en quienes padecen patologías altamente debilitantes, tales como el síndrome de inmunodeficiencia adquirida (SIDA). El material nucleico del CMVH contiene abundante información genética que le permite a este agente infeccioso evadir y/o reducir eficazmente el sistema inmunitario de su hospedero, a fin de garantizar su propia sobrevivencia