Congenital Cytomegalovirus Pneumonitis and Treatment Response Evaluation Using Viral Load during Ganciclovir Therapy: a Case Report.

Cytomegalovirus (CMV) is the most common cause of congenital infection. Pneumonitis is considered to be a rare manifestation although congenital CMV infection presents with various non-specific findings. Ganciclovir and valganciclovir are beneficial for improving neurodevelopmental sequelae and hearing outcomes of congenital CMV infection; however, treatment response evaluation is not well reported. We report a female case of congenital CMV infection presenting with pneumonitis, meningoencephalitis, and chorioretinitis. She was treated with intravenous ganciclovir for 6 weeks, and clinical features improved. Measurement of the CMV genome load by real-time polymerase chain reaction assay was performed during treatment. After the administration of ganciclovir, the CMV genome was not detected in the blood and levels decreased gradually in the urine. Physicians should consider the possibility of congenital CMV infection in neonates who present with respiratory distress. Furthermore, measurement of the CMV genome load in blood and urine may be useful for evaluating treatment response.

Cytokine Signatures Associated With Early Onset, Active Lesions and Late Cicatricial Events of Retinochoroidal Commitment in Infants With Congenital Toxoplasmosis.

BACKGROUND: Ocular toxoplasmosis is a prominent and severe condition of high incidence in Brazil. The current study provides new insights into the immunological events that can be associated with retinochoroiditis in the setting of congenital toxoplasmosis in human infants. METHODS: Flow cytometry of intracytoplasmic cytokines in leukocyte subsets following in vitro short-term antigenic recall in infants with congenital T. gondii infection. RESULTS: Our data demonstrates that whereas neutrophils and monocytes from T. gondii-infected infants display a combination of proinflammatory and regulatory cytokine profiles, natural killer cells showed a predominantly proinflammatory profile upon in vitro T. gondii stimulation. The proinflammatory response of CD4(+) and CD8(+) T cells, characterized by the production of interferon γ (IFN-γ) and interleukin 17 in patients with an active retinochoroidal lesion, revealed the presence of IFN-γ and tumor necrosis factor α during early and late immunological events. This specific proinflammatory pattern is associated with early events and active retinochoroidal lesion, whereas a robust monocyte-derived interleukin 10-mediated profile is observed in children with cicatricial ocular lesions. CONCLUSIONS: These findings support the existence of a progressive immunological environment concomitant with the initial, apical, and cicatricial phases in the process of retinochoroidal lesion formation in infants with congenital toxoplasmosis that may be relevant in the establishment of stage-specific clinical management.

A perinatal cytomegalovirus infection in an immunocompetent patient with chorioretinitis.

Cytomegalovirus (CMV) infection is the most common viral infection of newborns in all periods worldwide. Perinatal form of infection is usually less severe than the congenital form because of having a lower rate for serious organ involvement like central nervous system. In this article, we report a 3-month-old immunocompetent patient who was diagnosed as having perinatal CMV infection with a scar of chorioretinitis after presenting with gastroenteritis and hepatitis.

[Congenital CMV infections]. / Congenitale CMV-infecties.

Only 10-15% of neonates with congenital cytomegalovirus infection have symptoms at birth. The most common symptoms are intrauterine growth retardation, microcephaly, petechiae, jaundice, hepatosplenomegaly, intracranial abnormalities, ophthalmological abnormalities and hearing loss. Symptomatic and asymptomatic CMV infections can both have long-term effects. CMV infection during pregnancy is diagnosed using a blood test and possible testing of the amniotic fluid for viral DNA. Infection of the fetus may be prevented by treating the mother with CMV hyperimmune globulin. In the neonate a diagnosis can be made by viral culture or PCR in urine. PCR in saliva could be an alternative. Blood testing is of limited value. If symptoms of CMV infection occur in the neonate, such as petechiae, microcephaly, central nervous system abnormalities, sensorineural hearing loss or chorioretinitis, antiviral treatment should be considered. Long-term follow-up is advisable because of the possibility of delayed-onset hearing loss and chorioretinitis.

Review for disease of the year: differential diagnosis of ocular toxoplasmosis.

The diagnosis of ocular toxoplasmosis is mainly clinical, based in the presence of focal necrotizing retinochoroiditis often associated with a preexistent chorioretinal scar, and variable involvement of the vitreous, retinal blood vessels, optic nerve, and anterior segment of the eye. Recognition of this clinical spectrum of toxoplasmic retinochoroiditis is crucial, but other infectious, noninfectious, and neoplastic entities should also be considered in the differential diagnosis. Investigations such as serological tests, polymerase chain reaction of ocular fluids, and assessment of intraocular antibody synthesis are helpful in uncertain cases. This article provides an overview of the differential diagnosis of ocular toxoplasmosis, focusing on the most important entities to be considered and emphasizing distinctive features of each one of them in the clinical setting. Ocular toxoplasmosis has multiple clinical manifestations, which partially overlap with those of other entities and these should be carefully considered when making the differential diagnosis, particularly in less typical cases.

[Congenital toxoplasmosis: severe ocular and neurological complications]. / Congenitale toxoplasmose: ernstige oculaire en neurologische complicaties.

Two infants with congenital toxoplasmosis are presented. A girl born prematurely was treated postnatally after the mother had received antimicrobial treatment during pregnancy for acute toxoplasmosis. Apart from being small for gestational age, she remained without symptoms and treatment was ceased after 13 months. A 2-month-old boy presented with hydrocephalus and chorioretinitis, consistent with congenital toxoplasmosis. Despite antimicrobial treatment, at 12 months of age he suffered from epilepsy, cerebral palsy and vision impairment. Most infants with congenital toxoplasmosis (2 per 1000 live births in the Netherlands) are asymptomatic at birth. The education of pregnant women is crucial for the prevention of congenital toxoplasmosis. Awareness of antenatal and postnatal presenting signs and symptoms is important for clinicians, because early diagnosis and treatment may minimize sequelae. Untreated, the majority of affected infants will develop chorioretinitis, deafness and/or neurological symptoms.

Is a 6-week course of ganciclovir therapy effective for chorioretinitis in infants with congenital cytomegalovirus infection?

Effective treatment for chorioretinitis caused by congenital cytomegalovirus (CMV) infection remains unknown. We report an infant with congenital CMV infection, who required a 6-month course of antiviral therapy to control his chorioretinitis. Long-term treatment may be necessary for managing congenital CMV-associated chorioretinitis.

Toxoplasmose congênita em filho de mãe cronicamente infectada com reativação de retinocoroidite na gestação / Congenital toxoplasmosis from a chronically infected woman with reactivation of retinochoroiditis during pregnancy an underestimated event?

Objetivo: Apresentar um caso raro de toxoplasmose congênita de uma mãe imunocompetente com infecção crônica que teve reativação da doença ocular durante a gestação. Descrição: O recém-nascido estava assintomático no nascimento e foi identificado através de triagem neonatal (IgM anti-Toxoplasma gondii em sangue seco) entre outros 190 bebês com toxoplasmose congênita durante um período de 7 meses. Sua mãe tinha tido um episódio não tratado de reativação de retinocoroidite toxoplásmica durante a gestação, com títulos de IgG estáveis e resultados negativos para IgM. Os resultados de IgM e IgG no soro do recém-nascido e o teste de immunoblotting para IgG foram positivos, e detectou-se lesões retinocoroideanas ativas na periferia da retina. O recém-nascido foi tratado com sulfadiazina, pirimetamina e ácido folínico. Aos 14 meses de vida, a criança permanecia assintomática, com regressão das lesões retinocoroideanas e persistência de IgG. Comentários: É possível que a triagem neonatal sistemática em áreas com alta prevalência de infecção possa identificar esses casos.

Objectives: To report a rare case of congenital toxoplasmosis from an immunocompetent mother with chronic infection who had reactivation of ocular disease during pregnancy. Descriptions:The newborn was asymptomatic at birth and identified by neonatal screening (IgM anti-Toxoplasma gondii in dried blood) among other 190 infants with congenital toxoplasmosis during a 7-month period. His mother had had a non-treated episode of reactivation of toxoplasmic retinochoroiditis during pregnancy, with stable IgG titers and negative IgM results. Results of IgM and IgG in the newborn’s serum, as well as IgG immunoblotting were positive and active retinochoroidal lesions were detected in his peripheral retina. The neonate was treated with sulfadiazine, pyrimethamine and folinic acid. At 14 months of life, the child remained asymptomatic, with regression of retinochoroidal lesions and persistence of IgG. Comments: It is possible that systematic neonatal screening in areas with high prevalence of infection may identify these cases.

Congenital toxoplasmosis from a chronically infected woman with reactivation of retinochoroiditis during pregnancy.

OBJECTIVE: To report a rare case of congenital toxoplasmosis from an immunocompetent mother with chronic infection who had reactivation of ocular disease during pregnancy. DESCRIPTION: The newborn was asymptomatic at birth and identified by neonatal screening (IgM anti-Toxoplasma gondii in dried blood) among other 190 infants with congenital toxoplasmosis during a 7-month period. His mother had had a non-treated episode of reactivation of toxoplasmic retinochoroiditis during pregnancy, with stable IgG titers and negative IgM results. Results of IgM and IgG in the newborn's serum, as well as IgG immunoblotting were positive and active retinochoroidal lesions were detected in his peripheral retina. The neonate was treated with sulfadiazine, pyrimethamine and folinic acid. At 14 months of life, the child remained asymptomatic, with regression of retinochoroidal lesions and persistence of IgG. COMMENTS: It is possible that systematic neonatal screening in areas with high prevalence of infection may identify these cases.

Microcephaly, lymphedema, chorioretinopathy and atrial septal defect: a case report and review of the literature.

BACKGROUND: The rare congenital combination of microcephaly, lymphedema and chorioretinopathy (MLCD) has been described. Recently, three cases with these clinical characteristics have been diagnosed as having, in addition, various congenital cardiac anomalies, which may be part of this genetic entity that presents with variable expression. CLINICAL OBSERVATION: Here we present a new case of a one-year-old infant who was born with microcephaly and lymphedema and atrial septal defect (ASD) and developed chorioretinopathy at the age of 6 months. This infant had normal neurodevelopment at one year of age. CONCLUSION: We recommend that cardiac evaluation and long-term ophthalmologic follow-up should be part of the evaluation in each child born with microcephaly and lymphedema. Family counseling should include the fact that normal to near-normal development may be possible, despite the presence of microcephaly.

Terapia con valganciclovir en coriorretinitis congénita por citomegalovirus: reporte de un caso / Valganciclovir therapy Chorioretinitis in congenital cytomegalovirus: a purpose of a case

La infección por citomegalovirus solamente es sintomática en un 2 por ciento de los recién nacidos vivos. Sin embargo, la expresión clínica es generalmente desbastante en el neonato, ocasionando procesos de Síndrome de Respuesta Inflamatoria Sistémica hasta generar daños irreversibles como ceguera por coriorretinitis y retardo psicomotor. El tratamiento de los casos sintomáticos se realiza a través de un inhibidor de la replicación viral como lo es el ganciclovir; cuya vía de administración es exclusivamente endovenosa, teniendo que hospitalizar al paciente por espacio de un intervalo mínimo de 21 días; ocasionando costos de hospitalización, riesgos de sobreinfección por agentes nosocomiales y separación temporal de la madre. Se presenta el siguiente caso de una lactante con coriorretinitis congénita, ocasionado por citomegalovirus, por comprobación de Reacción de Cadena de Polimerasa. Se inicia tratamiento ambulatorio con valganciclovir a una dosis de 30mg/kg/día. A los 03 meses del tratamiento, se realiza control de la actividad del citomegalovirus por Reacción de la Cadena de Polimerasa, la cual reporta negativa. Entre los efectos adversos se apreció un incremento leve de las transaminasas, las cuales se mantuvieron en dichos niveles a lo largo del tratamiento. No se observaron citopenias con el tratamiento ni otros efectos de importancia. El valganciclovir, una prodroga del ganciclovir, puede ofrecer una alternativa viable para el manejo de este tipo de pacientes, restando gastos de hospitalización y otras complicaciones derivadas a la vía endovenosa, pero con igual efecto terapéutico.

Cytomegalovirus antibodies in tear fluid of patients with retinitis.

The diagnosis of cytomegalovirus retinitis (CMV-R) is difficult and usually based on clinical criteria or invasive diagnostic procedures. The purpose of this study was to investigate a possible association between CMV-R and specific anti-CMV antibodies in tears. Paired tear and serum samples were obtained from 96 individuals, which included 20 children with congenital CMV infection and chorioretinitis, 56 adults with retinitis with clinical signs suggestive of viral infection, and 20 healthy control subjects, and were tested for CMV antibodies using ELISA. The prevalence of anti-CMV antibodies in tears was found to be 80% (16/20) in children, 35% (20/56) in adults, and 5% (1/20) in control subjects. Furthermore, high antibody levels were detected in 35% (7/20) of children and 10.7% (6/56) of adults with retinitis, and were not found in control subjects. There was a strong association between high tear levels of anti-CMV antibodies and active ocular infection. No correlations were found between tear and serum antibodies. ELISA sensitivity was 80% and specificity 95%. Further studies are needed to compare the tear and intraocular levels of CMV-specific antibodies in patients with retinitis to find out if CMV antibody testing in tear fluid could substitute for more invasive diagnostic procedures.

Severe sulfadiazine hypersensitivity in a child with reactivated congenital toxoplasmic chorioretinitis.

A 7-year-old with congenital toxoplasmosis who took pyrimethamine and sulfadiazine for reactivated chorioretinitis developed fever, severe cutaneous involvement, swelling, abdominal pain and transaminitis, persisting weeks after withholding medicines. Symptoms resolved when systemic corticosteroids were administered. This case underscores problems in clinical management with sulfadiazine hypersensitivity, potential immunosuppression from corticosteroids and selection of medications for recurrences of toxoplasmic chorioretinitis.

[Postnatal follow-up of infants born to mothers with certain Toxoplasma gondii infection: evaluation of prenatal management]. / Follow-up post-natale in nati da madre con infezione certa da Toxoplasma gondii: considerazioni sul management prenatale.

UNLABELLED: The clinical management of perinatal toxoplasmosis involves a gynaecologist during pregnancy and a neonatologist after delivery. Then, in the absence of a uniform approach, early evaluation of infected infants requires a thorough long-term follow-up also in asymptomatic children, who have to be observed for at least one year due to unpredictable sequelae in later life. We retrospectively analyzed pregnancy management of 54 women with certain infection from Toxoplasma gondii (TG) and prospectively enrolled their infants to compare prenatal management with postnatal clinical outcome. All mothers with seroconversion for TG infection were from the Palermo area and were retrospectively analyzed, whereas their newborns referred to G. Di Cristina Children Clinical Hospital between 1999-2004 were prospectively enrolled in a 48-month follow-up. Timing of infection was dated for 24 women (45%) to the first trimester, 18 (33%) to the second and 12 (22%) the third. The maternal-fetal transmission rate was 17.2%. Prenatal diagnosis from amniotic fluid was performed in 25/54 pregnant subjects and showed positive results in 6. Despite diagnosis of TG infection, 9 women were untreated and only 2 with positive amniocentesis received combined therapy. 10/55 enrolled infants were infected and half of them were preterm and/or SGA at birth. None showed peculiar signs of TG at birth but 4 had abnormalities during the follow-up. 9/10 infected children were born to mothers who had undergone neither amniocentesis nor combined therapy. CONCLUSIONS: Our work confirms the difficulty of applying standardized therapeutic protocol for TG infection during pregnancy. The asymptomatic course of TG infection at birth confirms the importance of an instrumental long-term follow-up to identify typical TG lesion to prevent sequelae.

[Congenital varicella: limits of prenatal diagnosis]. / La varicelle congénitale: les limites du diagnostic prénatal.

INTRODUCTION: Primary varicella infection during pregnancy is uncommon. Fetal varicella syndrome is unusual when varicella occurs after 20 weeks of gestation. CASE REPORT: A mother contracted chicken pox at 21 weeks and 3 days of gestation. Monthly monitoring was assured by the center for prenatal diagnosis, starting from 23 weeks. At 36 weeks, foetal echography detected liver calcifications, without other lesions. At 38 weeks, the patient went into spontaneous labour and delivered a male baby. The baby presented cicatricial skin lesions all over the body and scalp. The cerebral scan detected calcifications and a bilateral chorioretinitis was noticed. At 12 months, the infant had delayed psychomotor acquisitions, a cerebral cortical atrophy and blindness. CONCLUSION: The presence of fetal liver calcifications after chicken pox in the mother is a seldom reported sign. In our observation, liver calcifications were the single sign of a severe fetal damage.

Lymphocytic choriomeningitis virus: an underdiagnosed cause of congenital chorioretinitis.

PURPOSE: To elucidate the role and clinical spectrum of congenital lymphocytic choriomeningitis virus infection as a cause of chorioretinopathy, congenital hydrocephalus, and macrocephaly or microcephaly in the United States. METHODS: We performed complete ophthalmologic surveys of all residents at Misericordia, a home for the severely mentally retarded in Chicago, and prospectively evaluated all patients with chorioretinitis or chorioretinal scars during a 36-month period at Children's Memorial Hospital, also located in Chicago. Sera for patients demonstrating chorioretinal scars (a sign of intrauterine infection) were tested for Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes simplex virus and lymphocytic choriomeningitis virus antibodies. RESULTS: Four of 95 patients examined at the home had chorioretinal scars, and two of these patients had normal T. gondii, rubella virus, cytomegalovirus, and herpes simplex virus titers and dramatically elevated titers for lymphocytic choriomeningitis virus. Three of 14 cases of chorioretinitis at the hospital had normal T. gondii, rubella virus, cytomegalovirus, and herpes sim-plex virus titers and elevated lymphocytic choriomeningitis virus antibody titers. (A fourth case, diagnosed in 1996, was reported 2 years ago.) CONCLUSIONS: Lymphocytic choriomeningitis virus was responsible for visual loss in two of four children secondary to chorioretinitis in a population of severely retarded children. The six new cases of lymphocytic choriomeningitis virus chorioretinitis identified in these two populations over the last 3 years, compared with the total number ever reported in the United States (10 cases), suggests that lymphocytic choriomeningitis virus may be a more common cause of congenital chorioretinitis than previously believed. Because its consequences for visual and psychomotor development are devastating, we conclude that the workup for congenital chorioretinitis should include lymphocytic choriomeningitis virus serology, especially if T. gondii, rubella virus, cytomegalovirus, and herpes simplex virus titers are negative.

Coriorretinitis por toxoplasma en niños / Coriorretinitis for toxoplasma in children

En un período de 5 años fueron atendidos en el Instituto de Medicina Tropical Pedro Kourí, 21 niños con lesiones oculares, debidas al toxoplasma (coriorretinitis por toxoplasma). De los 21 niños, 5 presentaron lesiones en ambos ojos (23,8 por ciento), y 16 (76,1 por ciento) en un solo ojo (9 en el ojo izquierdo y 7 en el ojo derecho). El 42,8 por ciento (9) llegó con lesiones activas con resultados satisfactorios al tratamiento médico, y el 57,1 por ciento (12) con lesiones cicatrizadas, que en este estadio no necesitan tratamiento. Todos los niños fueron seguidos por consulta externa con una evolución favorable(AU)