Myocarditis and inflammatory cardiomyopathy: current evidence and future directions.

Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.

Viral meningitis: which patients can be discharged from the emergency department?

BACKGROUND: Even in an era when cases of viral meningitis outnumber bacterial meningitis by at least 25:1, most patients with clinical meningitis are hospitalized. OBJECTIVE: We describe the clinical characteristics of an unusual outbreak of viral meningitis that featured markedly elevated cerebrospinal fluid white blood cell counts (CSF WBC). A validated prediction model for viral meningitis was applied to determine which hospital admissions could have been avoided. METHODS: Data were collected retrospectively from patients presenting to our tertiary care center. Charts were reviewed in patients with CSF pleocytosis (CSF WBC > 7 cells/mm(3)) and a clinical diagnosis of meningitis between March 1, 2003 and July 1, 2003. Cases were identified through hospital infection control and by surveying all CSF specimens submitted to the microbiology laboratory during the outbreak. RESULTS: There were 78 cases of viral meningitis and 1 case of bacterial meningitis identified. Fifty-eight percent of the viral meningitis cases were confirmed by culture or polymerase chain reaction to be due to Enterovirus. Mean CSF WBC count was 571 cells/mm(3), including 20 patients with a CSF WBC count > 750 cells/mm(3) (25%) and 11 patients with values > 1000 cells/mm(3) (14%). Sixty-four of 78 patients (82%) were hospitalized. Rates of headache, photophobia, nuchal rigidity, vomiting, and administration of intravenous fluids in the Emergency Department were no different between admitted and discharged patients. Only 26/78 (33%) patients with viral meningitis would have been admitted if the prediction model had been used. CONCLUSIONS: Although not all cases of viral meningitis are necessarily suitable for outpatient management, use of a prediction model for viral meningitis may have helped decrease hospitalization by nearly 60%, even though this outbreak was characterized by unusually high levels of CSF pleocytosis.

Rapid construction of adeno-associated virus vectors expressing multiple short hairpin RNAs with high antiviral activity against echovirus 30.

RNA interference has proven to be a powerful tool to inhibit viruses. For the prevention of viral escape, multiple short hairpin RNAs (shRNAs) will have to be employed. This article describes a rapid procedure for the generation of shRNA expression cassettes by parallel cloning as well as a simple strategy for the combination of selected units. After delivery of the shRNA expression cassettes with adeno-associated virus vectors, inhibition of echovirus 30 as well as silencing of an important cellular cofactor of virus replication were achieved. The procedure has the potential to be generally applicable for silencing of multiple endogenous targets or viruses.

Fatal illness associated with pulmonary hypertension in a neonate caused by intrauterine echovirus 11 infection.

Nonpolio enterovirus (NPEV) infections are known to cause a wide range of illnesses in the neonatal period. In most cases, NPEV is presumed to be contracted during birth. Intrauterine NPEV infections occur infrequently. A case of intrauterine echovirus 11 infection with pneumonia, persistent pulmonary hypertension of the newborn, and purpura fulminans is presented.

Echovirus 11 sepsis in a neonate: report of one case.

Neonates infected with nonpolio enteroviruses are at high risk for developing significant illness, including sepsis-like illness, meningoencephalitis, myocarditis and/or hepatitis. Echoviruses and group B coxsackieviruses account for the majority of neonatal enterovirus infections. We reported a case of echovirus 11 infection in newborn associated with maternal infection. To our knowledge, this is the first reported fatal case of neonatal echovirus infection in Taiwan. Eventually, the baby expired because of severe sepsis-like illness, fulminant hepatitis, disseminated intravascular coagulation, and extensive hemorrhagic manifestations in spite of intensive care, intravenous immunoglobulin infusion and exchange transfusion.

An outbreak of echovirus 13 meningitis in central Israel.

Until recently, echovirus 13 has been a very rare cause of aseptic meningitis. We investigated an outbreak of echovirus 13 in central Israel during the summer of 2000 using a prospective case control study and a retrospective study. Echovirus 13 was isolated from 79 cerebrospinal fluid (CSF) specimens from different medical centres in central Israel. Patients' ages ranged from 10 days to 41 years (95% < 15 years, M/F ratio 62/38). A total of 128 patients with clinical aseptic meningitis were admitted to the Department of Pediatrics during the outbreak (aged 10 days to 18 years, mean 5.4 years), and 58 CSF samples were processed for viral cultures. Thirty of them did not grow any virus, 26 samples yielded echovirus 13, and 2 samples echovirus 7. The clinical features of patients with echovirus 13 in the CSF were similar to those in whom no virus was isolated or those infected with other enteroviral strains except for higher rate of fever on admission, and prolonged time with fever following the diagnosis in the echovirus 13 patients. CSF cell count varied from 4 to 2,333 cells/mm3 with polymorphonuclears (PMN) predominant in 90% of our patients. In a case-control study there was no significant difference between patients and matched controls with regard to parameters such as: day care attendance, recreation in summer camp, swimming pools and at the beach, and consumption of tap water. All the patients in our series recovered fully with no neurological abnormalities. The illness caused by echovirus 13 was benign and involved mainly patients younger than 15 year of age. Several features that characterized this outbreak include relatively high WBC in the blood and a minent CSF PMN response.

[Life-threatening echovirus 11 infection during first month of life].

Infection with Echovirus 11 is mostly asymptomatic, but it may cause a wide variety of clinical diseases, from gastroenteritis to serious diseases such as meningitis and myocarditis. In small infants, especially during the first days of life, echovirus infection may appear as a sepsis-like illness, and cause disseminated intravascular coagulopathy and shock. We present 2 infants with severe Echovirus 11 infections. A 3.5-month-old died within 24 hours of shock and probably myocarditis. The other, 6-days old, presented with meningitis, hepatitis and disseminated intravascular coagulopathy. It recovered after treatment with intravenous immunoglobulin. Echovirus 11 may cause life-threatening infections in small infants. Pediatricians should be alert to the special characteristics of this disease.

Echovirus 7 infection and necrotizing enterocolitis-like symptoms in a premature infant.

Echovirus type 7 has been previously recognized as a virulent serotype in the premature neonate. However, reports of fatal disseminated infections have often been perinatally acquired from symptomatic mothers at the time of delivery. Nosocomial outbreaks in full-term and premature infants have been reported from newborn intensive care units; however, deaths attributed to Echovirus 7 in convalescing prematures are rare in the literature. We report the case of a growing premature neonate presenting with an overwhelming sepsis-like syndrome, including symptoms consistent with necrotizing enterocolitis. Despite intensive supportive care including ventilatory support, cardiovascular pharmacotherapy, and blood product administration, the infant succumbed to overwhelming Echovirus 7 infection.

[Intrathecal interferon therapy in chronic echovirus meningoencephalitis in Bruton type agammaglobulinemia]. / Intrathekale Interferontherapie einer chronischen Echovirusmeningoenzephalitis bei Agammaglobulinämie vom Typ Bruton.

A 9-year-old body with X-linked agammaglobulinemia developed chronic enteroviral meningoencephalitis (CEMA) caused by echovirus type 6. Intravenous treatment with selected immunoglobulin charges containing high titers against echovirus type 6 or combination with beta-interferon did not result in improvement. After implantation of a Rickham reservoir and periodical administration of intraventricular and intravenous immunoglobulin the virus recurred rapidly each time treatment was stopped. After 20 months of treatment the patient received a combined therapy with beta-interferon and selected immunoglobulin. Both drugs were given by lumbar puncture, intravenously and via Rickham reservoir. Subsequently echovirus type 6 could not be isolated in culture or PCR. Cerebrospinal fluid pleocytosis disappeared. The remission is lasting for more than three years. Intrathecal and intraventricular beta-interferon therapy for CEMA is being reported for the first time. Facing the unfavourable prognosis of the disease this mode of treatment is a new therapeutic approach following failure of other therapies.

Echoviroses / Echovirus infections

Trata das echoviroses sob aspectos da etiologia, epidemiologia, patogenia e patologia, manifestaçöes clínicas e tratamento. (MC)

Septic shock in an elderly patient: unusual presentation of echovirus infection.

We have described a case of fulminant echovirus infection that progressed rapidly to purpura and septic shock. To our knowledge, this is a previously unreported presentation of acute echovirus infection in an immunocompetent adult.

Disseminated echovirus infection in a patient with multiple myeloma and a functional defect in complement. Treatment with intravenous immunoglobulin.

A man with IgG1 multiple myeloma developed fever, confusion, and progressive muscle weakness resulting in paralysis. Echovirus type 11 was isolated from cerebrospinal fluid, pleura, pleural fluid, and muscle, and muscle biopsy disclosed changes consistent with viral myositis. Immunologic evaluation revealed low serum levels of polyclonal IgG subtypes 1 and 3, reduced blood levels of T-helper/inducer and T-suppressor/cytotoxic cells, and a complement abnormality involving the function of the classical pathway C3 convertase, C4b2a. Therapy with intravenous immunoglobulin was associated with clinical recovery. This is the first reported case of disseminated central nervous system enteroviral infection in an adult with a B-cell malignancy, and in association with a documented complement abnormality. The findings suggest the efficacy of immunotherapy in this disease.

Conservative management of an echovirus 11 outbreak in a neonatal unit.

Two babies in a neonatal unit presented on the same day with meningitis due to echovirus 11, which was thought to have been introduced by staff. At this time echovirus 11 was also isolated from the stools of eight other babies; five of them did not have signs of infection. No intervention was made except to emphasise the importance of handwashing. There was evidence of secondary spread to two babies who were both clinically well. The attack rate was twelve (29%) of forty-one babies exposed. Seven of the twelve infected babies were born before 30 weeks' gestation and would have had little or no maternal antibody, yet only two of the seven babies had signs of infection. Despite lack of special measures, all babies recovered. Most cases of horizontally acquired neonatal echovirus infection are mild: extreme measures in the management of outbreaks are unnecessary.