Poly(I)-poly(C12U) but not ribavirin prevents death in a hamster model of Nipah virus infection.

Clinical nonrandomized trials demonstrate some efficacy for ribavirin in the treatment of patients with severe Nipah virus-induced encephalitis. We report here that EICAR, the 5-ethynyl analogue of ribavirin, and the OMP-decarboxylase inhibitors 6-aza-uridine and pyrazofurin have strong antiviral activity against Nipah virus replication in vitro. Ribavirin and 6-aza-uridine were tested further in hamsters infected with a lethal dose of Nipah virus. The activity of these small-molecule inhibitors was compared with that of the interferon inducer poly(I)-poly(C(12)U). Both ribavirin and 6-aza-uridine were able to delay but not prevent Nipah virus-induced mortality. Poly(I)-poly(C(12)U), at 3 mg/kg of body weight daily from the day of infection to 10 days postinfection, prevented mortality in 5 of 6 infected animals.

Antibody prophylaxis and therapy against Nipah virus infection in hamsters.

Nipah virus (NiV), a member of the Paramyxoviridae family, causes a zoonotic infection in which the reservoir, the fruit bat, may pass the infection to pigs and eventually to humans. In humans, the infection leads to encephalitis with >40 to 70% mortality. We have previously shown that polyclonal antibody directed to either one of two glycoproteins, G (attachment protein) or F (fusion protein), can protect hamsters from a lethal infection. In the present study, we have developed monoclonal antibodies (MAbs) to both glycoproteins and assessed their ability to protect animals against lethal NiV infection. We show that as little as 1.2 mug of an anti-G MAb protected animals, whereas more than 1.8 mug of anti-F MAb was required to completely protect the hamsters. High levels of either anti-G or anti-F MAbs gave a sterilizing immunity, whereas lower levels could protect against a fatal infection but resulted in an increase in anti-NiV antibodies starting 18 days after the viral challenge. Using reverse transcriptase PCR, the presence of NiV in the different organs could not be observed in MAb-protected animals. When the MAbs were given after infection, partial protection (50%) was observed with the anti-G MAbs when the animals were inoculated up to 24 h after infection, but administration of the anti-F MAbs protected some animals (25 to 50%) inoculated later during the infection. Our studies suggest that immunotherapy could be used for people who are exposed to NiV infections.

Nipah virus: vaccination and passive protection studies in a hamster model.

Nipah virus, a member of the paramyxovirus family, was first isolated and identified in 1999 when the virus crossed the species barrier from fruit bats to pigs and then infected humans, inducing an encephalitis with up to 40% mortality. At present there is no prophylaxis for Nipah virus. We investigated the possibility of vaccination and passive transfer of antibodies as interventions against this disease. We show that both of the Nipah virus glycoproteins (G and F) when expressed as vaccinia virus recombinants induced an immune response in hamsters which protected against a lethal challenge by Nipah virus. Similarly, passive transfer of antibody induced by either of the glycoproteins protected the animals. In both the active and passive immunization studies, however, the challenge virus was capable of hyperimmunizing the vaccinated animals, suggesting that although the virus replicates under these conditions, the immune system can eventually control the infection.

Prolongation of heart xenograft survival in a hamster-to-rat model after therapy with a rationally designed immunosuppressive peptide.

BACKGROUND: Modification of the aminoacid sequence of peptides derived from the HLA class I heavy chain in combination with computer rational design resulted in the development of a peptide, RDP1258, with enhanced immunosuppressive activity. METHODS: We evaluated the activity of this peptide, analyzing infiltrate by immunohistology and cytokine transcripts by reverse transcriptase-polymerase chain reaction method, in a hamster-to-rat xenograft model where recipients were treated with cobra venom factor (CVF) and peptide. RESULTS: Although CVF or peptide alone had no effect, a combination of CVF/peptide RDP1258 resulted in a significant prolongation of graft survival (7.9+/-1 vs. 4.5+/-0 and 3.5+/-0 days, P<0.001). This effect was associated with an increased expression of heme oxygenase 1 (HO-1) in spleen, a significant reduced graft infiltrate, and a decrease of tumor necrosis factor-alpha mRNA transcripts (P<0.05) compared with CVF-treated recipients (1.6+/-0.07 vs. 3.3+/-0.3%, P=0.001) on day 3 after transplantation. CONCLUSION: These observations are consistent with the observation that up-regulation of HO-1 results in inhibition of immune effector functions and suggest that the peptide acts, at least partially, through HO-1 regulation.

[Anti-arrhythmia efficacy of propafenone in children. Apropos of 30 cases]. / Efficacité anti-arythmique de la propafénone chez l'enfant. A propos de 30 cas.

Thirty children aged from 3 months to 20 years were treated with propafenone 250 to 650 mg/m2 divided into 2 to 4 daily doses, for a mean period of 14 months (range: 4 days to 5 years); 8 had chronic atrial tachycardia, 9 had junctional arrhythmia and 13 had ventricular arrhythmia. There were 17 good results (suppression of the arrhythmia), 7 fair results (good clinical effect but partial persistence of the arrhythmia) and 6 failures, either because the drug proved ineffective (3 cases) or on account of side-effects (3 cases). In the treatment of chronic atrial tachycardia propafenone seemed to be more effective than amiodarone in 3 cases and as effective as that drug in 2 cases. In junctional arrhythmia propafenone was certainly effective but unpredictably so (3 good results, 2 fair results, 4 failures). Among ventricular arrhythmias, ventricular tachycardia in bursts was the one which benefited most regularly from treatment with propafenone: the results in 8 patients were better than those obtained with other antiarrhythmic agents (class I drugs, beta-blockers, calcium antagonists); only amiodarone proved superior to propafenone in this type of arrhythmia. Despite a 27% incidence of side-effects, propafenone was generally well tolerated by the children, with no significant gastrointestinal disorders. No depressive effect on the myocardium was noted in 6 children with moderate heart failure well controlled by digitalis and diuretics. However, since overdosage may cause severe disorders of conduction with widened ventriculogram, we recommend regular ECG monitoring during the first 3 days of treatment at least: although there is little slowing down of sinus rate (12%) and little modification of the slow phase under treatment, serious toxicity is possible. Thus, propafenone is a drug that should be handled with caution, but it constitutes a major addition to the range of antiarrhythmic agents which can be used in paediatrics.

[The myocardiopathies of glycogenosis]. / Myocardiopathies des glycogénoses.

Thirty-three patients with glycogen abnormalities and myocardial disease were studied. 27 of them has type II glycogen disorders (Pompe's disease, with an intralysozymal deficit of acid maltase) and 6 with type III glycogen disorders Forbes disease, with a deficit in amylo-1-6-glucosidase). The picture of a type II abnormality in the infant is very standard: early onset, often neonatally; the association with asystole and muscular hypotonia and a characteristics clinical picture; invariable cardiomegaly and typical ECG findings (short PR interval, high voltage complexes). Death occurs before one year of age, treatment has limited effect, and attention is centred on the early discovery of heterozygotes and of diagnosis antenatally. The possibility of an obstructive type (4 out of 24) and a type with endocardial fibroelastosis (3 out of 24) must be emphasised. In the late onset myopathic form of type II disorder (3 cases), involvement of the myocardium is always found, but is of secondary importance in determining the clinical picture and natural history. The same can be said of type III disorders in which, despite the infrequency of asystole or significant cardiomegaly, a hypertrophic cardiomyopathy which may be obstructive can lead to sudden death in infancy (2 cases out of 6).

[Long-term results of surgery in total abnormal pulmonary venous return in the infant. Apropos of 32 cases]. / Résultats éloignés de la chirurgie du retour veineux pulmonaire anormal total chez le nourrisson. A propos de 32 cas

Report of 32 cases of infants with total anomalous pulmonary venous return, operated upon, below the age of 9 months. There were three immediate deaths, and one which occured six months after operation. All surviving children were followed-up regularly, and the post-operative follow-up period exceeded 18 months in all cases. 11 children went through control haemodynamic exploration. These were ten excellent post-operative results, 6 were considered as fairly good and two bad ones. For some of them who were markedly improved by the first operation a second intervention consisting in closing the atrial septal defect left patent, should be foreseen in later childhood.

[Right pulmonary artery originating from the ascending aorta. Reimplantation in an infant of 4 kg]. / Artère pulmonaire droite naissant de l'aorte ascendante. Réimplantation chez un nourrisson de 4 kg

Report of the case of a 1-year infant, weighing 4 kgs, with a right pulmonary artery branching from the aorta combined with a wide patent ductus arteriosus. Reimplantation of this artery in the pulmonary artery trunk under extracorporeal circulation was followed by a spectacular result.