Because of the changes to be expected in the methods for testing disinfectants deemed to be used in the veterinary field, candidate viral species were evaluated for their suitability as test virus. Considered viral species included different non-enveloped viruses [bovine enterovirus type 1 (ECBO (Enteric Cytopathogenic Bovine Orphan) virus), mammalian reovirus type 1, feline calici virus (FCV), and bovine parvovirus (BPV)], as well as enveloped viruses, as equine arteritisvirus (EAV), bovine herpesvirus type 1 (BHV1), Newcastle disease virus (NDV) and vaccinia virus. Viruses were tested for their tenacity against different biocidal agents (formaldehyde, formic acid, peracetic acid, and sodium hypochlorite) in the suspension test at a temperature of 20 degrees C which is given as an optional test temperature according to prEN 14675 "Quantitative suspension test for the evaluation of virucidal activity of chemical disinfectants and antiseptics used in veterinary field--Test method and requirements"elaborated by the "Comite Européen de Normalisation"(CEN)(Anonym, 2004). Of the animal viruses tested for their tenacity highest tenacity against the disinfectants. FCV and the enveloped viruses were of lower resistance. In addition to the tenacity of viruses, other parameters, such as the ability of the virus to replicate in permanent cells, the magnitude of the virus titre that can be obtained from such cultures, as well as the threat a virus poses to humans and animals are to be considered when selecting a suitable test virus. Based on these criteria and despite its tenacity being inferior to that of BPV, the ECBO virus was chosen as the most suitable test virus. The result of the efficacy of disinfectants is not based on the most resistant virus in this case. This circumstance is to be considered when giving recommendations for the practical use of disinfectants.

Enteroviruses usually cause self-limited disease that, although associated with high morbidity, is rarely fatal. In certain patient populations, however, the enteroviruses may cause potentially life-threatening infections. Pleconaril is a novel compound that integrates into the capsid of picornaviruses, including enteroviruses and rhinoviruses, preventing the virus from attaching to cellular receptors and uncoating to release RNA into the cell. Pleconaril was used on a compassionate-release basis to treat patients with potentially life-threatening enterovirus infections, and for 38 of these patients sufficient follow-up data were available for determining responses to therapy. Response was evaluated in 4 categories: clinical, virological, laboratory, and radiological. Most patients (28 [78%] of 36), including 12 of 16 with chronic enterovirus meningoencephalitis, were judged to have a clinical response temporally associated with pleconaril therapy. Similarly, nearly all patients whose virological responses (12 [92%] of 13), laboratory responses (14 [88%] of 16), and radiological responses (3 [60%] of 5) could be evaluated were judged to have responded favorably to a course of pleconaril treatment. Adverse effects were minimal and the drug was generally well-tolerated.

Enterovirus infections are common in both children and adults and range from benign short-lived febrile illnesses to life-threatening infections. Recent developments in nucleic acid amplification techniques now allow the rapid and sensitive diagnosis of enterovirus infections, which in turn can lead to improvements in patient management that shorten hospitalizations and reduce costs. New antiviral drugs have been developed that inhibit enterovirus replication, and early clinical trials of these compounds suggest that effective therapy for enterovirus infections is now possible.

A statewide outbreak of enterovirus meningitis occurred in Rhode Island in the summer of 1991. A comprehensive chart review was conducted for determining the demographic and clinical characteristics of the epidemic and for assessing the interinstitutional variation in treatment strategies. Four hundred eight cases were reported, and enteroviruses were recovered in 61 (68%) of 90 cases in which viral isolation was attempted. Of six isolates that were serotyped, all were echovirus 30. Analysis of cerebrospinal fluid revealed that an increased total white blood cell count and an increased protein concentration were associated with increasing patient age; however, the percentage of polymorphonuclear leukocytes in the cerebrospinal fluid decreased with increasing patient age and longer durations of illness. Marked variations in treatment strategies between institutions were noted in the use of computed tomography of the head, the administration of empirical antimicrobial agents, and the duration of hospitalization. Considerable health resources could have been saved by rapid detection of the virus, dissemination of information about the outbreak, and a conservative approach to clinical management.

Pleconaril (VP-63843) 3-[3,5-dimethyl-4[[3-(3-methyl-5-isoxazolyl)propyl] oly]phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole is a novel, broad spectrum antipicornaviral agent. Pleconaril binds to a hydrophobic pocket in the viral capsid inducing conformational changes, which lead to altered receptor binding and viral uncoating. Pleconaril is orally bioavailable and achieves serum concentrations in excess of those required to inhibit 90% of clinical rhino- and enteroviral isolates in vitro. It possesses the additional advantage of achieving several fold higher concentrations within the central nervous system and nasal secretions than in serum, a characteristic that is highly desirable for an antiviral targeted towards viruses known to cause central nervous system and upper respiratory tract infections. Approximately 80% of an orally administered dose is excreted in the faeces within 48 h. Urine excretion accounts for the remainder of the drug. Pleconaril has demonstrated an excellent safety profile in dose escalation and clinical studies. Clinical studies have reported a reduction in the duration and intensity of symptoms in children and adults with enteroviral meningitis and in adults with rhinoviral respiratory tract infections treated with pleconaril. Lastly, pleconaril has demonstrated efficacy in the treatment of severe life-threatening enteroviral infections of the newborn and in immunosuppressed individuals. Pleconaril appears to be a promising drug for the treatment of enteroviral and rhinoviral infections.

Foscarnet (trisodium phosphonoformate) is a new antiviral compound with in vitro inhibitory effects against the DNA polymerases of hepadna viruses. To study the effects of the drug in chronic hepadna virus infection, we treated ducks chronically infected with duck hepatitis B virus for 10 days with either low-dose foscarnet (50 mg/kg i.p. b.i.d.), high-dose foscarnet (250 mg/kg i.p. b.i.d.), or sterile water injections. Serum duck hepatitis B virus DNA and intrahepatic replicative forms of the virus were measured using molecular biological techniques with both a double-stranded radiolabeled DNA probe and a plus-strand (noncoding) specific RNA probe. We found a dose-related decrease in serum and intrahepatic duck hepatitis B virus DNA during treatment, with a rapid return toward baseline values after the cessation of treatment. There was a disproportionate decrease in the plus strand of viral DNA with treatment. We conclude that foscarnet exerts its effect in hepadna virus infection through inhibition of viral DNA polymerase. Further study is necessary to determine whether foscarnet, by itself or in combination with other treatment modalities, has a role to play in the treatment of chronic hepatitis B infections in humans.

To explain the progression from infectious viral myocarditis to congestive cardiomyopathy an infection/immune hypothesis has been proposed stating that the primary viral process incites an excessive or disordered immunologic response against the myocardium. To test whether one form of immunosuppressive therapy might ameliorate this process, we used cyclosporine in a murine preparation of infectious myocarditis (encephalomyocarditis [EMC] virus), which has been shown to result in a congestive cardiomyopathy pathologically similar to that seen in man. Eight-week-old male DBA-2 mice were infected with EMC virus and randomized to a treatment or control group. Cyclosporine (25 mg/kg/day) was administered subcutaneously for 3 weeks, starting (1) at 1 week after infection during viral replication, and (2) at 3 weeks after infection, after the period of active viral replication. In mice treated during viral replication there was a significantly higher mortality rate compared with that of control mice (15/21 vs 9/29, p =.01). There was no evident reduction in myocardial pathology (inflammation, necrosis, or calcification) in the treated compared with the control groups. In mice treated after the period of viral replication, there was no improvement in mortality (8/22 vs 2/19, NS) compared with control. Treated mice showed no reduction in myocardial histopathologic lesions. Furthermore, treated mice had significantly greater heart weight/body weight ratios (1.3 +/- 0.4% vs 1.0 +/- 0.3%, p less than .005), lung weight/body weight ratios (1.1 +/- 0.5% vs 0.8 +/- 0.3%, p less than .05), and liver weight/body weight ratios (6.0 +/- 0.8% vs 5.4 +/- 0.6%, p less than .005) than control mice, suggesting more severe myocardial failure.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND: A distinctive pattern of enterovirus 71 (EV71) infection, characterized by fever, exanthem, acute pulmonary edema (PE), brainstem encephalitis, and flaccid paresis, affects infants and young children. Most die rapidly owing to respiratory failure and fulminant PE. METHOD: The authors report short- and long-term outcome of six survivors of the acute illness. RESULTS: In the context of acute PE and widespread weakness, recognition of the underlying neurologic disorder was facilitated by the distinctive pattern of MRI signal abnormalities in posterior pons and medulla. EV71-specific PCR of clinical samples helped confirm the diagnosis. Acute PE was managed with mechanical ventilation, afterload reduction, and inotrope support, and resolved completely over days. One patient with minimal neurologic recovery died 9 weeks after disease onset. The other patients have residual neurologic dysfunction, varying from subtle monoparesis to severe bulbar dysfunction, central and peripheral respiratory failure, and flaccid quadriparesis. Faster neurologic recovery was associated with less long-term deficit. Long-term outcome was similar in patients treated with and without pleconaril or IV immunoglobulin. Three long-term survivors treated with IV corticosteroids had less severe long-term neurologic disability than two not treated with steroids. CONCLUSION: Acute pulmonary edema and encephalomyelitis occurs with EV71 infection in infants. Long-term neurologic outcome varied from minor, focal weakness to profound, global motor dysfunction with respiratory failure.

The aim of this study was to assess the tolerability and efficacy of N-chlorotaurine (NCT), an endogenous antimicrobial agent, in epidemic keratoconjunctivitis. In a prospective double-blind, randomized phase 2b study, the infected eyes were treated for 7 days with eye drops containing 1% aqueous solution of N-chlorotaurine (33 subjects) or gentamicin (27 subjects, control group). Adenovirus types 3, 4, 8, 19, and 37 were detected in 39 subjects (65%), enteroviruses in 8 (13.3%), and staphylococci in 5 (8.3%). Subjective and objective symptoms were scaled and added to a subjective and objective score, respectively, on day 1 (baseline), day 4, and day 8. Analyzing the whole study population, the subjective score on day 8 was lower in the NCT group (P = 0.016), whereas there were no differences in the objective score. However, in severe infections caused by adenovirus type 8 (n = 20) both the subjective and objective score were lower in the NCT group on day 4 (P = 0.003 and 0.015, respectively), which was also true for the subjective score on day 8 (P = 0.004) in this subgroup. The frequency of subepithelial infiltrates was similar in both groups. N-chlorotaurine was well-tolerated, shortened the duration of illness, and seems to be a useful causative therapeutic approach in severe epidemic keratoconjunctivitis.

Enteroviruses can cause persistent central nervous system (CNS) infections in agammaglobulinemic individuals. Because these infections are rarely cured by passive administration of antibody, a chemotherapeutic approach would be advantageous. In this study, the efficacy of the antienterovirus (and antipicornavirus) drug disoxaril was demonstrated in a murine model of persistent enterovirus infection. Disoxaril is a hydrophobic antiviral compound that blocks picornavirus uncoating. The W-2 strain of human poliovirus type 2 (PV2) persists in the CNS of immunosuppressed mice and causes late paralysis. Mice were inoculated intracerebrally with PV2, immunosuppressed with cyclophosphamide, and treated intragastrically with disoxaril at 50, 100, or 200 mg/kg per day in two divided doses beginning on postinfection day 20. At 200 mg/kg per day, disoxaril significantly decreased the incidence of clinical disease, i.e., paralysis and death. Assays for virus revealed more rapid clearance of virus from the CNS in the drug-treated group. No drug-associated toxicity was observed. Residual isolates of virus were not drug-resistant, suggesting that the appearance of drug resistance during prolonged treatment may not be a clinical problem.