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Formation of syncytial knots is increased by hyperoxia, hypoxia and reactive oxygen species.

The syncytiotrophoblast contains aggregates of nuclei termed syncytial knots. Increased numbers of syncytial knots have been reported in placentae of pregnancies complicated by pre-eclampsia and fetal growth restriction (FGR). As oxidative stress has been implicated in the pathophysiology of these disorders, we hypothesised that the formation of syncytial knots may be induced by exposure to hypoxia, hyperoxia or reactive oxygen species (ROS). We assessed both the number and morphology of syncytial knots induced by culture in hypoxia, hyperoxia and with ROS. We also investigated whether the presence of syncytial knots in normal tissue was associated with a down-regulation of anti-apoptotic proteins Bcl-2, Mdm2, XIAP and survivin. Using our measurement system we describe an increased number of syncytial knots when tissue is cultured in hypoxia, hyperoxia or in the presence of ROS. The morphology of these syncytial knots was similar to those seen in vitro, although the nuclei from cultured placental explants were morphologically more homogenous, had fewer nuclear pores, and a higher heterochromatin:euchromatin ratio. Despite the apoptotic appearances of nuclei we did not detect a loss of anti-apoptotic proteins in the region of syncytial knots. We conclude that the increased number of syncytial knots in placentae from pregnancies complicated by pre-eclampsia and FGR can be replicated in vitro by ROS or hypoxia, supporting their involvement in the pathogenesis of these conditions.

Adult↗

Central role of the respiratory syncytial virus matrix protein in infection.

Respiratory syncytial virus is the major respiratory pathogen of infants and children worldwide, with no effective treatment or vaccine available. Steady progress has been made in understanding the respiratory syncytial virus life cycle and the consequences of infection, but many areas of respiratory syncytial virus biology remain poorly understood, including the role of subcellular localisation of respiratory syncytial virus gene products such as the matrix protein in the infected host cell. The matrix protein plays a central role in viral assembly and, intriguingly, has been observed to traffic into and out of the nucleus at specific times during the respiratory syncytial virus infectious cycle. Further, the matrix protein has been shown to be able to inhibit transcription, which may be a key to respiratory syncytial virus pathogenesis. This review will focus on the role of the matrix protein in respiratory syncytial virus infection and what is known of its nucleocytoplasmic trafficking, the understanding of which may lead to new therapeutic approaches to combat respiratory syncytial virus, and/or vaccine development.

Animals↗

Respiratory syncytial virus infection and neurologic abnormalities: retrospective cohort study.

Respiratory syncytial virus is a common cause of acute respiratory infection in children. Previous reports have associated respiratory syncytial virus infection and acute neurologic symptoms, including apnea and seizures. This study examined the prevalence of acute neurologic symptoms associated with respiratory syncytial virus and non-respiratory syncytial virus respiratory infections in children requiring admission to a pediatric intensive care unit. We screened all admissions over a 4-year period at a single center, identifying children between birth and 2 years of age with bronchiolitis or acute upper respiratory infection. Children with a history of prematurity, preexisting medical conditions, or prior neurologic problems were excluded. Retrospective chart review of 236 admissions was conducted, identifying the etiology of respiratory infection and the presence or absence of acute neurologic signs or symptoms. This study demonstrated a prevalence of acute neurologic signs or symptoms in 36.4% of respiratory syncytial virus-negative patients (n = 115) and 39.1% in the respiratory syncytial virus-positive group (n = 121). Apnea, the most common symptom, was observed in 19.8% of respiratory syncytial virus-positive cases and 16.5% of negative patients. Seizures were reported in 6.6% of the positive cases and in 12.2% of the negative cohort. These differences showed no statistical significance. Although neurologic signs and symptoms are common in this population of children with acute respiratory infection, there was no significant difference in the prevalence of neurologic problems between respiratory syncytial virus-positive and -negative patients.

Academic Medical Centers↗

Ultrastructural features of lesions in bronchiolar epithelium in induced respiratory syncytial virus pneumonia of calves.

Ultrastructural changes were observed in bronchioles in acute and repair stages of respiratory syncytial virus pneumonia induced in eight young calves (calf Nos. 1-8) using a bovine strain of respiratory syncytial virus. Five of the calves were Friesians and three were Hereford x Friesians and all were male. Tissues from three mock-infected control calves (two Friesian, one Hereford x Friesian) were also examined. Calves were from 3 to 6 days old at the time of first inoculation, with the exception of calf No. 8, which was 2 weeks old. In the acute stage of the induced pneumonia, evidence of respiratory syncytial virus replication and release was demonstrable in both ciliated and non-ciliated bronchiolar epithelial cells, with the virus-releasing process most obvious at 4 and 5 days after infection. Respiratory syncytial virus infection of bronchiolar epithelium was associated with various changes, including hypertrophy, hyperplasia, and formation of syncytia. Necrosis of epithelial cell structures usually appeared to be preceded by their desquamation from bronchiolar walls. Respiratory syncytial virus infection resulted in considerable damage to the bronchiolar ciliary apparatus. Such damage was seen as early as 1 day post-infection and was still obvious at 10 days post-infection. Neutrophils were closely associated with respiratory syncytial virus infected epithelial cells and evidence of neutrophil fusion with infected epithelial cells was seen. These observations suggest that neutrophils may be involved in killing respiratory syncytial virus infected cells and that neutrophils might play an important role in early antiviral defense against respiratory syncytial virus at a time when antibody levels are low and other cellular defenses are not fully in play. Bronchiolar repair was evident from 6 days after infection and was well advanced at 10 and 13 days after infection.

Aged↗

Safety of palivizumab in preterm infants 29 to 32 weeks' gestational age without chronic lung disease to prevent serious respiratory syncytial virus infection.

Respiratory syncytial virus is an important cause of hospitalization in preterm infants. Palivizumab, a humanized monoclonal antibody against the respiratory syncytial virus fusion protein, is currently the only licensed product in Europe available for prophylaxis of respiratory syncytial virus lower respiratory tract infection. This study was conducted to obtain additional European data on the safety of palivizumab in preterm infants 29-32 weeks' gestational age without chronic lung disease. Subjects less than 6 months old were enrolled between October 2000 and April 2001. Demographic information was obtained and physical examination was performed at enrollment. Subjects received 15 mg/kg palivizumab intramuscularly every 30 days for the duration of the respiratory syncytial virus season. Subjects hospitalized for respiratory illness were tested for respiratory syncytial virus infection with respiratory syncytial virus rapid antigen tests. At monthly visits, interim history for adverse events/respiratory illness and physical exam was performed. A total of 285 subjects were enrolled from 35 centers in 18 countries. The mean (+/-SD) gestational age was 30.8+/-1.1 weeks, the mean birth weight 1.5+/-0.4 kg, and 56% were <12 weeks of age at enrollment. Over 80% of patients received at least four palivizumab doses; all received at least one dose. The most commonly reported adverse events (>5%) were rhinitis, increased cough, fever, pharyngitis, bronchiolitis, and diarrhea. Only six subjects reported adverse events that were considered possibly related to palivizumab. No deaths were reported. Twenty subjects were hospitalized during the study; six of these were respiratory syncytial virus positive. Palivizumab is safe and well tolerated in preterm infants 29-32 weeks' gestation without chronic lung disease.

Antibodies, Monoclonal↗

Activation of complement by cells infected with respiratory syncytial virus.

The ability of respiratory syncytial virus (RSV)-infected HE(p)-2 cells in culture to activate complement was investigated. After incubation of cells with various complement sources and buffer, binding of C3b to surfaces of infected cells was demonstrated by immunofluorescence with a double-staining technique. Nonsyncytial and syncytial (i.e., fused, multinucleated) cells were separately enumerated. Also, lysis of RSV-infected cells was assessed by lactic dehydrogenase release. In this system only RSV-infected cells stained for C3b, and they did so only after incubation with functionally active complement. Blocking of classical pathway activation with ethylenediaminetetraacetic acid diminished the number of infected nonsyncytial cells positively stained for C3b, but had no effect on staining of syncytial cells. Blocking of alternative pathway activation with either zymosan incubation or heat treatment decreased the number of both syncytial and nonsyncytial cells stained for C3b. Decreasing immunoglobulin concentration of the serum used as the complement source also decreased numbers of both cell types stained for C3b. Eliminating specific anti-RSV antibody diminished numbers of both cell types stained for C3b, but staining was not eliminated. Lastly, incubation with functionally active complement markedly increased lactic dehydrogenase release from infected cells. This study demonstrated that RSV-infected nonsyncytial and syncytial cells are able to activate complement by both classical and alternative pathways. Activation of complement by syncytial cells appears to be less dependent on the classical pathway than is activation by nonsyncytial cells, and activation by syncytial cells may require immunoglobulin but not specific antibody. These experiments suggest the possibility of complement activation during respiratory tract infection by RSV. Implications of this are discussed.

Antibodies, Viral↗

Prevention of bovine respiratory syncytial virus infection and clinical disease by vaccination.

A double blind field trial was carried out with a live attenuated bovine respiratory syncytial virus vaccine. The trial involved 530 calves, two to 10 months old, on 27 dairy farms, where respiratory problems due to bovine respiratory syncytial virus infections had been observed during the preceding year. In 17 herds either all calves were vaccinated (nine groups) or all calves received a placebo (eight groups). In 10 herds half the number of calves were vaccinated and the other half kept as non-vaccinated controls. Calves were vaccinated intramuscularly twice with an interval of four to five weeks. These groups were under regular clinical observation and animals were tested periodically for antibodies to bovine respiratory syncytial virus and parainfluenza type 3 virus. Serological examination indicated that no bovine respiratory syncytial virus infection had occurred prior to the first vaccination in August. Vaccination did not cause adverse reactions. Low concentrations of neutralising and complement fixing antibodies were induced by vaccination and a sharp increase of antibody titres was observed after natural infection of vaccinated animals. Infections with bovine respiratory syncytial virus occurred in six out of eight non-vaccinated groups, in nine out of 10 partly vaccinated groups and in only two out of nine completely vaccinated groups. Virus infection in completely vaccinated groups was significantly reduced compared with partly vaccinated and non-vaccinated groups. The incidence of bovine respiratory syncytial virus lower respiratory disease was significantly reduced in completely vaccinated groups compared to non-vaccinated groups. Generally only mild signs of upper respiratory disease were present in completely vaccinated groups after bovine respiratory syncytial virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Atopic disposition, wheezing, and subsequent respiratory syncytial virus hospitalization in Danish children younger than 18 months: a nested case-control study.

OBJECTIVES: This study examined whether atopic disposition, wheezing, and atopic disorders increased the risk of hospitalizations because of respiratory syncytial virus in children between birth and 18 months of age. PATIENTS AND METHODS: Relative risks for respiratory syncytial virus hospitalization were studied in a nested 1:5 case-control design using exposure information obtained from interviews with mothers of 2564 case and 12,816 control children who had been followed prospectively from birth and until 18 months of age as participants in the Danish National Birth Cohort. Information on the children's ages at respiratory syncytial virus hospitalization, presentation of infrequent wheezing, recurrent wheezing, and atopic dermatitis were used to study these associations chronologically. RESULTS: The adjusted relative risk of respiratory syncytial virus hospitalization in the offspring was 1.11 for maternal atopic dermatitis, 1.72 for maternal asthma, and 1.23 for paternal asthma. Atopic dermatitis in the child was associated with an increased risk of subsequent respiratory syncytial virus hospitalization among infants <6 months of age. Infrequent wheezing was associated with a relative risk of subsequent respiratory syncytial virus hospitalization of 2.98 and recurrent wheezing with a relative risk of 5.90. These associations were present also if infants with medical risk factors were excluded from the analysis. CONCLUSIONS: Asthmatic disposition and wheezing were strong determinants of subsequent respiratory syncytial virus hospitalization in Danish children <18 months of age.

Case-Control Studies↗

Concurrent respiratory syncytial virus and influenza A infections in the institutionalized elderly and chronically ill.

During a community outbreak of respiratory syncytial virus and influenza A/Texas/77 infections, we investigated 71 cases of upper respiratory illness at a chronic disease hospital using a surveillance system plus viral and serologic studies. Of the 32 patients with an etiologic diagnosis, seven had respiratory syncytial virus, 24 had influenza, and one had dual infections with respiratory syncytial virus and influenza. No definite etiologic diagnosis was made in the remaining 39 patients. A comparison of the clinical features of patients infected with respiratory syncytial virus and influenza revealed no significant differences in the frequency of respiratory or constitutional signs and symptoms except for rhinorrhea, which was commoner in the respiratory syncytial virus group (P less than 0.05). Pneumonia developed in one patient with respiratory syncytial virus and in five patients with influenza. Our findings suggest that respiratory syncytial virus may be an important respiratory pathogen for the elderly and chronically ill, causing illness similar to influenza.

Aged↗

[Evaluation of 5 methods for the diagnosis of infections by respiratory syncytial virus].

BACKGROUND: To compare and evaluate four different rapid methods of respiratory syncytial virus antigen detection with the isolation of the virus in cell culture. METHOD: Ninety-eight nasopharyngeal swabs were studied, for respiratory syncytial virus isolation in Hep-2 cell line and for RSV antigen detection using direct immunofluorescence and three ELISA methods: Abbot RSV EIA (ELISA-1), RSV Antigen Detection System (ELISA-2) and Directigen RSV (Directigen). RESULTS: Of all 98 samples studied using the five mentioned methods, 42 (43%) were positive for respiratory syncytial virus. The most sensitive methods were ELISA-1 (82%) and immunofluorescence (82%). The most specific ones were direct immunofluorescence (86%) and Directigen (84%). The higher percentage of concordant positive results with respiratory syncytial virus culture were direct immunofluorescence (84%) and Directigen (82%). CONCLUSIONS: Rapid diagnostic methods for respiratory syncytial virus infection can not substitute the isolation method using cell line culture. We believe that respiratory syncytial virus isolation in cell culture combined direct with direct immunofluorescence or Directigen methods are the first choice diagnostic techniques for achieve a higher number of positive results in respiratory syncytial virus infected patients.

Antigens, Viral↗

Respiratory syncytial virus infection in children with bronchopulmonary dysplasia.

Little is known about the risk of severe illness from respiratory syncytial virus infection in children with bronchopulmonary dysplasia. A prospective study was done of the natural history of respiratory syncytial virus infection in 30 children less than 2 years of age with bronchopulmonary dysplasia who were in a home oxygen program. Surveillance to identify children with acute respiratory symptoms was done by weekly telephone interview. Symptomatic children were examined, oxygen saturation was determined by oximetry, and nasopharyngeal lavage fluid was collected for virus cultures and rapid respiratory syncytial virus antigen tests. During the 4-month study period (December to April), 27 children had one or more acute respiratory illnesses, and respiratory syncytial virus developed in 16/27 (59%). Passive smoking and greater than or equal to four members in the home increased the risk of symptomatic respiratory syncytial virus (P less than .01 and P less than .03, respectively). Of 16 children, 11 (69%) required hospitalization. Of the 11 hospitalized children with respiratory syncytial virus, nine were either still receiving oxygen at home or required oxygen therapy within the previous 3 months v none of five nonhospitalized children (P less than .005). Five of the hospitalized children were greater than 12 months of age and five had respiratory syncytial virus infection previously that had been confirmed by culture results. Hospitalizations were prolonged and complicated. Seven of 11 children were hospitalized for greater than 1 week; four were admitted to the intensive care unit; four were treated with ribavirin aerosol, and two needed mechanical ventilation. There were no deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchopulmonary Dysplasia↗

Cytological events involved in protein synthesis in cellular and syncytial trophoblast of human placenta. An electron microscope autoradiographic study of [3H]leucine incorporation.

Electron microscope autoradiography has been used to study protein synthesis in syncytial and cellular trophoblast of term human placental villi incubated in vitro with tritiated leucine ([3H]leu). Autoradiographs were analyzed using the hypothetical grain analysis of Blackett and Parry (1973. J. Cell Biol. 57:9-15). The results of this study demonstrated that both cellular and syncytial trophoblast have marked capacities for protein synthesis. Cellular trophoblast synthesized protein in both its rough endoplasmic reticulum (RER) and its ground plasm which contained abundant free ribosomes. The vast majority of 3H-proteins remained within the cell, with some of the proteins synthesized ultimately appearing in the nucleus. A small percentage of grains was ultimately associated with the trophoblast basement membrane. In syncytial trophoblast, the RER was the dominant site for protein synthesis. The autoradiographic data suggested that, as in the cellular trophoblast, the vast majority of 3H-proteins synthesized by the syncytial trophoblast remained within the syncytial trophoblast throughout the incubation period. The major portion of [3H]leu-labeling present in the syncytial trophoblast of villi incubated the longest times (4 h+) remained in association with the RER. Labeled proteins did not become concentrated in syncytial trophoblast Golgi apparatus, vesicles, or granules. In contrast to cellular trophoblast, the nuclei in the syncytium did not contain 3H-proteins at any time-point studied.

Autoradiography↗

Delays in anaphase initiation occur in individual nuclei of the syncytial Drosophila embryo.

The syncytial divisions of the Drosophila melanogaster embryo lack some of the well established cell-cycle checkpoints. It has been suggested that without these checkpoints the divisions would display a reduced fidelity. To test this idea, we examined division error frequencies in individuals bearing an abnormally long and rearranged second chromosome, designated C(2)EN. Relative to a normal chromosome, this chromosome imposes additional structural demands on the mitotic apparatus in both the early syncytial embryonic divisions and the later somatic divisions. We demonstrate that the C(2)EN chromosome does not increase the error frequency of the late larva neuroblast divisions. However, in the syncytial embryonic nuclear divisions, the C(2)EN chromosome produces a 10-fold increase in division errors relative to embryos with a normal karyotype. During late anaphase of the neuroblast divisions, the sister C(2)EN chromosomes cleanly separate from one another. In contrast, during late anaphase of the syncytial divisions in C(2)EN-bearing nuclei, large amounts of chromatin often lag on the metaphase plate. Live analysis of C(2)EN-bearing embryos demonstrates that individual nuclei in the syncytial population of dividing nuclei often delay in their initiation of anaphase. These delays frequently lead to division errors. Eventually the products of the nuclei delayed in anaphase sink inward and are removed from the dividing population of syncytial nuclei. These results suggest that the Drosophila embryo may be equipped with mechanisms that monitor the fidelity of the syncytial nuclear divisions. Unlike checkpoints that rely on cell cycle delays to identify and correct division errors, these embryonic mechanisms rely on cell cycle delays to identify and discard the products of division errors.

Anaphase↗

Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases.

Evidence from a large number of prospective case-control studies shows that respiratory syncytial virus (RSV) bronchiolitis in infancy is often associated with recurrent wheezing and asthma during subsequent years. However, wheezing tends to diminish and most studies show no significant increase in wheezing compared to controls by school age or adolescence. An unresolved question is whether severe RSV infection during infancy causes the respiratory sequelae or inherent abnormalities predispose an infant to develop severe respiratory infection and sequelae, i.e. RSV is associated with the development of pulmonary sequelae. Studies on long-term outcome of RSV bronchiolitis are reviewed from an evidence-based perspective. The majority of prospective placebo-controlled studies do not show any long-term beneficial effects of corticosteroid treatment, i.e. the risk of subsequent wheezing is not diminished by the treatment. The evidence for an increased risk of allergic sensitization after RSV bronchiolitis is not nearly as strong as the evidence for an increased risk of subsequent wheezing. In fact, most studies do not show any significant increase in atopy after RSV bronchiolitis. This suggests that the increased risk of wheezing after RSV is not linked to an increased risk of atopy. There are some indications that infants who develop severe RSV and subsequent wheezing may have aberrations that predate the RSV infection. To decide whether respiratory syncytial virus bronchiolitis causes, or is associated with the respiratory sequelae (or with subsequent allergy), it will be necessary to conduct prospective, randomized studies, where the cytokine profile prior to bronchiolitis onset is known. Such studies should preferably include some form of intervention against respiratory syncytial virus. A more complete understanding of the risk factors for severe respiratory syncytial virus infection and the role of respiratory syncytial virus infection in the initiation of asthma is needed as a basis for large-scale and cost-effective programmes to prevent respiratory syncytial virus-related morbidity.

Airway Obstruction↗

IL-12p40 and IL-18 modulate inflammatory and immune responses to respiratory syncytial virus infection.

Respiratory syncytial virus-induced bronchiolitis has been linked to the development of allergy and atopic asthma. IL-12 and possibly IL-18 are central mediators orchestrating Th1 and/or Th2 immune responses to infection. To determine a possible role for IL-12 in regulating the immune response to acute respiratory syncytial virus infection, IL-12p40 gene-targeted (IL-12p40-/-) and wild-type mice were intratracheally infected with respiratory syncytial virus, and lung inflammatory and immune responses were assessed. Lung inflammation and mucus production were increased in the airways of IL-12p40-/- mice as compared with those of wild-type mice, concurrent with increased levels of the Th2 effector cytokines IL-5 and IL-13. Respiratory syncytial virus clearance and levels of Th1 effector cytokine IFN-gamma were not altered. Interestingly, IL-18, another mediator of IFN-gamma production, was significantly increased in the lungs of IL-12p40-/- mice early during the course of infection. Abrogation of IL-18-mediated signaling in IL-12p40-/- mice further enhanced Th2 immune response and mucus production in the airways during respiratory syncytial virus infection but failed to modulate IFN-gamma production or viral clearance. These findings implicate a role for IL-12 and IL-18 in modulating respiratory syncytial virus-induced airway inflammation distinct from that of viral clearance.

Adjuvants, Immunologic↗

Neurologic complications associated with respiratory syncytial virus.

Encephalopathy has been demonstrated to be associated with respiratory syncytial virus bronchiolitis. In this study, the data on all patients less than 14 years of age hospitalized with respiratory syncytial virus bronchiolitis over the past 4 years was reviewed. Patients who had concomitant diagnoses consistent with neurologic disease underwent detailed chart review. There were 964 patients (age 0.1 to 13.6 years) with a diagnosis of respiratory syncytial virus bronchiolitis. Thirty-six of these patients had concurrent neurologic diagnoses. Twenty-four patients were excluded because of preexistent neurologic disorders, probable simple febrile seizures, or a history of epilepsy. Twelve respiratory syncytial virus-positive patients had definite neurologic complications without another recognized cause. Seven of these patients had seizures (predominantly generalized tonic-clonic and one with status epilepticus), three had generalized encephalopathy (marked hypotonia and decreased responsiveness) of whom two also developed esotropia. Two patients developed isolated esotropia. There was an incidence of neurologic complications of 1.2% (0.7% seizures) in a total of 964 patients with respiratory syncytial virus bronchiolitis. This percentage does not include presumed simple febrile seizures or exacerbations of preexisting seizure disorder (further 1.3%). Neurologic complications occur with respiratory syncytial virus bronchiolitis, and physicians and other caregivers should be aware of this entity as well as the favorable prognosis.

Acute Disease↗

Respiratory outcomes in high-risk children 7 to 10 years after prophylaxis with respiratory syncytial virus immune globulin.

PURPOSE: Respiratory syncytial virus infections have been implicated in the development of asthma. We evaluated the long-term effects of respiratory syncytial virus immune globulin, an effective prophylactic agent for the prevention of these infections in children, on respiratory and allergic outcomes in children at high risk of chronic airway disease. SUBJECTS AND METHODS: Thirteen children at high risk of respiratory disease (mean [+/-SD] age, 8.6 +/- 1.1 years) were evaluated using pulmonary function and allergy skin testing 7 to 10 years after they had received prophylaxis with respiratory syncytial virus immune globulin. For comparison, 26 high-risk control children (mean age, 8.5 +/- 0.9 years) were also evaluated. Health outcomes data were collected from all subjects. The children were matched for age and gestational age. There were more boys, and a lesser frequency of a lower respiratory tract infection with respiratory syncytial virus (P <0.001) in the group that had been treated prophylactically than in the controls. The ratio of the forced expiratory volume in 1 second to forced vital capacity was significantly better in children who had received immune globulin (median, 0.88; interquartile range, 0.81 to 0.91) than in the controls (median, 0.76; interquartile range, 0.67 to 0.86; P = 0.02). Children were also less atopic (2 of 13) in the respiratory syncytial virus immune globulin group than in the control group (13 of 26, P <0.04) and were less likely to have missed school (P = 0.006) or have had an asthma attack (P = 0.03). CONCLUSION: The results suggest that prophylaxis of respiratory syncytial virus infections in infancy may have long-term effects on respiratory and immunologic parameters relevant to the development of asthma. Larger-scale studies are needed.

Bronchial Provocation Tests↗

Successful treatment of severe dysrhythmias in infants with respiratory syncytial virus infections: two cases and a literature review.

OBJECTIVES: To describe severe myocardial manifestations in two infants with respiratory syncytial virus infection and to review published literature reporting cardiac involvement in patients with respiratory syncytial virus disease. DESIGN: Case report and literature review. SETTING: Tertiary care pediatric intensive care unit (ICU). PATIENTS: Two infants admitted to the pediatric ICU for dysrhythmias and severe myocardial dysfunction and infected with respiratory syncytial virus. INTERVENTIONS: Conventional cardiovascular, antidysrhythmic, and respiratory support, as well as extracorporeal membrane oxygenation and high-frequency oscillatory ventilation. MEASUREMENTS AND MAIN RESULTS: Both patients had respiratory syncytial virus infections and clinical evidence of severe myocarditis, with dysrhythmias, cardiomegaly, and cardiogenic shock. Both infants survived their hospitalizations. To our knowledge, these two patients are the first reported cases of myocarditis in infants with respiratory syncytial virus infection. CONCLUSIONS: Severe myocardial dysfunction and dysrhythmias may accompany respiratory syncytial virus infection in some infants and may be reversible with aggressive supportive therapy.

Anti-Arrhythmia Agents↗