Clinical, pathological and microbiological profiles of spontaneous enteropathies in growing rabbits

[EN] In a rabbit production facility, health monitoring for enteropathies was performed in 15 production cycles for 20 mo. For each cycle, up to a hundred 35 d old rabbits weaned the same day were randomly selected, reared in the same fattening unit, but separately from the source batch and fed with the same feed except for antimicrobial supplementation. Clinical symptoms and enteric lesions of the selected group were recorded, using two checklists with binomial response (yes/no answer to a list of 54 clinical and enteric variables). The day after weaning, one week later, at the beginning of the enteric symptoms and 4-5 d after the start of the symptoms, inocula from the small intestine and caecum of selected animals were subjected to microbiological, C. spiroforme, Eimeria oocyst and rotavirus antigen detection tests. Representative samples of E. coli and C. perfringens isolates were tested, respectively, for serotype, biotype, eae, afr/2 genes and for a, b1, b2, e, i and enterotoxin toxin genes. The answers to the clinical-pathological variables were subjected to statistical analysis with a cluster analysis programme in order to obtain homogeneous, statistically significant groups of diseased animals (clusters). Then, the clusters were statistically associated with the laboratory outcomes. The cluster to which the enterotyphlitis lesions significantly contributed was associated with E. coli detection, E. coli O103 serotype detection and C. spiroforme ("several elements" variable). C. spiroforme ("rare elements" variable) was significantly associated with a cluster, characterised by a pathological profile consisting of bloating/rumbling noise and liquid content in stomach and caecum, without enteric inflammation. C. perfringens was significantly associated with a cluster, characterised by a pathological profile consisting of dilation/liquid content of small intestine, caecal impaction and mucoid content in the colon. Eighteen out of twenty-fi ve C. perfringens strains, examined for their toxin genotypes, proved to be toxin type A, while 7 out of 25 strains showed the a and b2 toxin genes in combination. The rotavirus antigen and Eimeria oocysts were detected from healthy rabbits (specimens of the day after weaning and one week later) in about 15% of specimens examined, but their presence in the sick animals was not significantly associated with any cluster.This study was supported by a financial contribution from Avitalia, Unione Nazionale Associazioni di Produttori Avicunicoli, Forlì, Italy, as part of the programme entitled “Miglioramento della qualità, della gestione dell’offerta delle produzioni cunicole e di rafforzamento dei rapporti di filiera. Azione 4.3”. Our thanks go to breeder Leta Covelli and Dasco srl for supplying the rabbits, to our colleague Romolo Salini and to Fabrizio Agnoletti of the Istituto Zooprofilattico Sperimentale del Veneto, Trevise, ItalyBadagliacca, P.; Letizia, A.; Candeloro, L.; Di Provvido, A.; Di Gennaro, A.; Scattolini, S.; Pompei, G.... (2010). Clinical, pathological and microbiological profiles of spontaneous enteropathies in growing rabbits. World Rabbit Science. 18(4):187-198. doi:10.4995/wrs.2010.77518719818

Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial

Peginterferon plus ribavirin achieves sustained virological response (SVR) in fewer than half of patients with genotype 1 chronic hepatitis C virus infection treated for 48 weeks. We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin. In part 1 of this trial, undertaken in 67 sites in the USA, Canada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C virus infection were randomly assigned to receive peginterferon alfa-2b 1·5 μg/kg plus ribavirin 800–1400 mg daily for 48 weeks (PR48; n=104); peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PRB24; n=103) or 44 weeks (PR4/PRB44; n=103); or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107) or 48 weeks (PRB48; n=103). In part 2, 75 patients were randomly assigned to receive either PRB48 (n=16) or low-dose ribavirin (400–1000 mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB48; n=59). Randomisation was by computer-generated code, and study personnel and patients were not masked to group assignment. The primary endpoint was SVR 24 weeks after treatment. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00423670. Patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 [54%, 95% CI 44–64], p=0·013 for PRB28; 58/103 [56%, 44–66], p=0·005 for PR4/PRB24; 69/103 [67%, 57–76], p<0·0001 for PRB48; and 77/103 [75%, 65–83], p<0·0001 for PR4/PRB44; vs 39/104 [38%, 28–48] for PR48 control). Low-dose ribavirin was associated with a high rate of viral breakthrough (16/59 [27%]), and a rate of relapse (six of 27 [22%]) similar to control (12/51 [24%]). Boceprevir-based groups had higher rates of anaemia (227/416 [55%] vs 35/104 [34%]) and dysgeusia (111/416 [27%] vs nine of 104 [9%]) than did the control group. In patients with untreated genotype 1 chronic hepatitis C infection, the addition of the direct-acting antiviral agent boceprevir to standard treatment with peginterferon and ribavirin after a 4-week lead-in seems to have the potential to double the sustained response rate compared with that recorded with standard treatment alone. Merck

Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Treatment of Hepatitis C Infection

Background Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. Methods At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 μg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa- 2b regimen and the peginterferon alfa-2a regimen. Results Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose peginterferon alfa-2b, 38.0% with low-dose peginterferon alfa-2b, and 40.9% with peginterferon alfa-2a (P=0.20 for standarddose vs. low-dose peginterferon alfa-2b; P=0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], −2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and −1.1% (95% CI, −5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for lowdose peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for peginterferon alfa- 2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively. Conclusions In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon– ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials. gov number, NCT00081770.

Peginterferon alfa-2b plus weight-based ribavirin for 24 weeks in patients with chronic hepatitis C virus genotype 1 with low viral load who achieve rapid viral response

In chronic hepatitis C (CHC), treatment duration may be individualized according to time to first undetectable hepatitis C virus (HCV) RNA, with patients who attain undetectable HCV RNA early in treatment being candidates for shorter regimens. The aim of this study was to determine the relapse rate in patients with CHC genotype (G) 1 infection and low baseline viral load who achieved undetectable HCV RNA by week 4 [rapid virologic response (RVR)] when treated for 24 weeks. This was an open-label, multicentre, noninterventional study. Adult patients with G1 CHC infection and baseline viral load <600,000 IU/mL who attained RVR were treated with peginterferon alfa-2b (1.5 μg/kg/week) plus ribavirin (800-1200 mg/day) for 24 weeks, then followed for a further 24 weeks. The primary endpoint was relapse rate, defined as the proportion of patients with undetectable HCV RNA at treatment week 24 and detectable HCV RNA at week 24 follow-up. The secondary efficacy endpoint was sustained virologic response (SVR). Overall, 170 patients were included in the efficacy-evaluable population. The relapse rate was 9.7% (16/165, 95% confidence interval: 0.06-0.15), and SVR was attained by 149 of 170 patients (87.6%). Virologic outcomes were consistent regardless of age, gender, body weight and genotype. Seven patients reported treatment-emergent serious adverse events (AEs), and four patients discontinued treatment because of an AE. This study further demonstrates that peginterferon alfa-2b plus weight-based ribavirin for 24 weeks is an effective treatment strategy for treatment-naive patients with G1 CHC and low viral load who attain RVR. © 2011 Blackwell Publishing Ltd