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Abstract

Objective

To determine pharmacokinetics of single and multiple doses of rimantadine hydrochloride in horses and to evaluate prophylactic efficacy of rimantadine in influenza virus-infected horses.

Animals

5 clinically normal horses and 8 horses seronegative to influenza A.

Procedure

Horses were given rimantadine (7 mg/kg of body weight, IV, once; 15 mg/kg, PO, once; 30 mg/kg, PO, once; and 30 mg/kg, PO, q 12 h for 4 days) to determine disposition kinetics. Efficacy in induced infections was determined in horses seronegative to influenza virus A2. Rimantadine was administered (30 mg/kg, PO, q 12 h for 7 days) beginning 12 hours before challenge-exposure to the virus.

Results

Estimated mean peak plasma concentration of rimantadine after IV administration was 2.0 µg/ml, volume of distribution (mean ± SD) at steady-state (VdSS) was 7.1 ± 1.7 L/kg, plasma clearance after IV administration was 51 ± 7 ml/min/kg, and β-phase halflife was 2.0 ± 0.4 hours. Oral administration of 15 mg of rimantadine/kg yielded peak plasma concentrations of < 50 ng/ml after 3 hours; a single oral administration of 30 mg/kg yielded mean peak plasma concentrations of 500 ng/ml with mean bioavailability (F) of 25%, β-phase half-life of 2.2 ± 0.3 hours, and clearance of 340 ± 255 ml/min/kg. Multiple doses of rimantadine provided steady-state concentrations in plasma with peak and trough concentrations (mean ± SEM) of 811 ± 97 and 161 ± 12 ng/ml, respectively. Rimantadine used prophylactically for induced influenza virus A2 infection was associated with significant decreases in rectal temperature and lung sounds.

Conclusions and Clinical Relevance

Oral administration of rimantadine to horses can safely ameliorate clinical signs of influenza virus infection. (Am J Vet Med 1999:60:888–894)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To develop and characterize a cold-adapted live attenuated equine-2 influenza virus effective as an intranasal vaccine.

Animals—8 ponies approximately 18 months of age.

Procedures—A wild-type equine-2 virus, A/Equine/ Kentucky/1/91 (H3N8), was serially passaged in embryonated chicken eggs at temperatures gradually reduced in a stepwise manner from 34 C to 30 C to 28 C to 26 C. At different passages, infected allantoic fluids were tested for the ability of progeny virus to replicate in Madin-Darby canine kidney (MDCK) cells at 34 C and 39.5 C. Virus clones that replicated at 26 C in eggs and at 34 C in MDCK cells, but not at 39.5 C in MDCK cells, were tested for stability of the coldadapted, temperature-sensitive (ts), and protein synthesis phenotypes. A stable clone, P821, was evaluated for safety, ability to replicate, and immunogenicity after intranasal administration in ponies.

Results—Randomly selected clones from the 49th passage were all ts with plaquing efficiencies of < 10-6 (ratio of 39.5 C:34 C) and retained this phenotype after 5 serial passages at 34 C in either embryonated eggs or MDCK cells. The clone selected as the vaccine candidate (P821) had the desired degree of attenuation. Administered intranasally to seronegative ponies, the virus caused no adverse reactions or overt signs of clinical disease, replicated in the upper portion of the respiratory tract, and induced a strong serum antibody response.

Conclusion and Clinical Relevance—A candidate live attenuated influenza vaccine virus was derived by cold-adaptation of a wild-type equine-2 influenza virus, A/Equine/Kentucky/1/91, in embryonated eggs. (Am J Vet Res 2001;62:1290–1294)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether streptococcal pneumonia is caused by strains of Streptococcus zooepidemicus similar to those obtained from the tonsils of healthy horses.

Sample Population—5 tonsils from healthy horses, 8 tracheal washes and 6 lung specimens from foals with pneumonia, and 5 nasopharyngeal swab specimens from donkeys with acute bronchopneumonia.

Procedure—Variable M-like protectively immunogenic SzP proteins of 5 isolates of S zooepidemicus from each tonsil and clinical specimen were compared, using immunoblots. The SzP gene of 13 isolates representative of various SzP immunoblot phenotypes from 1 healthy horse and 9 horses and donkeys with pneumonia were sequenced and compared. Cell-associated hyaluronic acid concentration and resistance to phagocytosis of some isolates were measured.

Results—Tonsils of each healthy horse were colonized by several SzP phenotypes similar to those of foals or donkeys with pneumonia. In contrast, multiple isolates from animals with pneumonia had the same SzP phenotype, indicating infection by a single strain or clone. Analysis of the SzP sequence confirmed that differences in immunoblot phenotype were associated with sequence differences and that several SzP genotypes were in healthy horses and animals with pneumonia. Isolates with high concentrations of cell-associated hyaluronic acid were more resistant to phagocytosis.

Conclusions and Clinical Relevance—An SzP-specific immunoblot is a useful, sensitive measure of diversity among strains of S zooepidemicus. Single strains with SzP phenotypes similar to those found in tonsils of healthy horses cause pneumonia. Because of the diversity of SzP phenotype and genotype among isolates from animals with pneumonia, SzP phenotype is not an important determinant of invasiveness or epizootic capabilities. (Am J Vet Res 2000;61:162–166)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine safety, efficacy, and immunogenicity of an intranasal cold-adapted modified- live equine influenza virus vaccine administered to ponies following induction of exercise-induced immunosuppression.

Design—Prospective study.

Animals—Fifteen 9- to 15-month old ponies that had not had influenza.

Procedure—Five ponies were vaccinated after 5 days of strenuous exercise on a high-speed treadmill, 5 were vaccinated without undergoing exercise, and 5 were not vaccinated or exercised and served as controls. Three months later, all ponies were challenged by nebulization of homologous equine influenza virus. Clinical and hematologic responses and viral shedding were monitored, and serum and nasal secretions were collected for determination of influenza-virus-specific antibody isotype responses.

Results—Exercise caused immunosuppression, as indicated by depression of lymphocyte proliferation in response to pokeweed mitogen. Vaccination did not result in adverse clinical effects, and none of the vaccinated ponies developed clinical signs of infection following challenge exposure. In contrast, challenge exposure caused marked clinical signs of respiratory tract disease in 4 control ponies. Vaccinated and control ponies shed virus after challenge exposure. Antibody responses to vaccination were restricted to serum IgGa and IgGb responses in both vaccination groups. After challenge exposure, ponies in all groups generated serum IgGa and IgGb and nasal IgA responses. Patterns of serum hemagglutination inhibition titers were similar to patterns of IgGa and IgGb responses.

Conclusions and Clinical Relevance—Results suggested that administration of this MLV vaccine to ponies with exercise-induced immunosuppression was safe and that administration of a single dose to ponies provided clinical protection 3 months later. (J Am Vet Med Assoc 2001;218:900–906)

Full access
in Journal of the American Veterinary Medical Association