Recombinant Bactericidal/Permeability-Increasing Protein (rBPI21) for Treatment of Parvovirus Enteritis: A Randomized, Double-Blinded, Placebo-Controlled Trial

Abstract

We evaluated the ability of an antimicrobial and endotoxin-neutralizing agent, the recombinant amino terminal fragment of bactericidal permeability-increasing protein (rBPI21), to decrease plasma endotoxin concentration and severity of clinical signs of canine parvovirus and to improve survival. This randomized, double-blinded, placebo-controlled clinical trial included 40 client-owned dogs and 9 normal puppies from a closed research colony. Dogs weighing >5 kg (11 lb) with fecal antigen-confirmed parvovirus and clinical signs of vomiting and diarrhea were randomly assigned to receive placebo or rBPI21 infusion over 6 hours. Plasma endotoxin concentration was measured at 0, 3, and 6 hours of infusion. Owners chose continued medical care with either the Veterinary Hospital of the University of Pennsylvania Internal Medicine Service or a local veterinarian. Telephone follow-up was conducted at 14 days. Surviving dogs were reevaluated at >30 days (recovered group), at which time plasma samples for measurement of endotoxin concentration were obtained. Plasma endotoxin concentrations were significantly higher in dogs with parvovirus than in normal or recovered dogs. Despite 90% survival, the rBPI21 treatment did not have a significant effect on outcome, duration of hospitalization, or plasma endotoxin concentrations. Treatment in a tertiary care hospital, however, significantly improved survival but resulted in a significantly increased duration of hospitalization. Endotoxemia occurs in dogs with parvovirus enteritis, but rBPI21 is not associated with improved survival.

Effect of Early Enteral Nutrition on Intestinal Permeability, Intestinal Protein Loss, and Outcome in Dogs with Severe Parvoviral Enteritis

“…D isease caused by canine parvovirus (CPV) affects more than a million dogs per year in the United States. 1 Parvoviral infection is characterized by severe enteritis, anorexia, vomiting, hemorrhagic diarrhea, and shock. 2 The published fatality rate is 16-35%, 3 although intensive therapy has achieved survival rates of up to 85-96%.…”

“…2 The published fatality rate is 16-35%, 3 although intensive therapy has achieved survival rates of up to 85-96%. 1,2 Treatment is primarily supportive and symptomatic. Novel adjunctive drugs have been investigated, but results have been disappointing or variable.…”

“…Novel adjunctive drugs have been investigated, but results have been disappointing or variable. 1,[4][5][6] There is a distinct need for therapies that decrease disease severity and hospitalization time, improve survival, and reduce treatment cost. 1,7 Despite the lack of controlled clinical studies, conventional wisdom has dictated that ''gut rest,'' achieved by allowing no ingestion of food, remains the nutritional therapy of choice for CPV enteritis.…”

Canine parvovirus: where are we in the 21st Century?

“…Release of free lipopolysaccharide is a potent stimulator of sepsis, so rBPI21 binding prevents lipopolysaccharides from interacting with host cells, reducing the septic response. Although shown to be beneficial when used in humans with meningococcal sepsis (Levin et al, 2000), the only veterinary study on rBPI21 use on dogs with CPV enteritis reported no benefit (Otto et al, 2001).…”

“…Since the virus was first discovered in 1978 it has evolved and there are now three known strains that can cause enteritis; CPV-2a, b and c. In experimentally infected dogs, mortality without treatment is as high as 91% (Prittie, 2004). Although no definitive treatment has been reported, survival rates with intensive therapy can be up to 90%; however, survival rates in tertiary, referral hospitals have been shown to be higher than those in first opinion practice (Otto et al, 2001). This article will cover the pathophysiology of CPV infection and discuss the current and experimental treatments available.…”