Efficacy of the paramunity inducer PIND-ORF in the treatment of canine parvovirus infection A.L. Proksch a, *, S. Unterer a , U. Truyen b , K. Hartmann a a Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universitaet, Germany Veterinärstrasse 13, 80539 Munich, Germany b Institute for Animal Hygiene and Veterinary Public Health, University of Leipzig, Germany An den Tierkliniken 1, 04103 Leipzig, Germany ARTICLE INFO Article history: Accepted 13 August 2014 Keywords: Canine parvovirosis Dog Parapoxvirus ovis Clinical trial Innate immunity A B ST R AC T Canine parvovirus (CPV) infection is a common and severe disease particularly affecting young dogs. The paramunity inducer PIND-ORF is reported to stimulate the innate immune system and, if used as a sup- plementary medication, might lead to a more rapid improvement in clinical signs in dogs with CPV infection. The aim of this study was to evaluate the efficacy of PIND-ORF in dogs with CPV infection in a prospec- tive, placebo-controlled, double-blinded trial using 38 dogs randomly assigned to two groups. Inclusion criteria were clinical signs consistent with CPV infection and a positive faecal CPV PCR. Dogs received either PIND-ORF (n = 20) or placebo (n = 18) and additional symptomatic treatment. Time to recovery and mortality rate were compared between the two groups. Clinical signs, complete blood counts (CBC), and serum protein and albumin concentrations were evaluated daily during hospitalisation and on day 14. Viral shedding and antibody titres were measured by faecal CPV PCR and serum neutralisation assay. There was no significant difference in time to recovery, clinical signs, blood parameters, duration of virus shedding, and antibody titres between the two groups. The only significant difference was an in- crease in lymphocyte counts and antibody titres observed in the PIND-ORF group only. Three dogs receiving placebo did not survive, but the mortality rate was not significantly different between groups (P = 0.097). No significant effect of PIND-ORF on recovery and outcome could be demonstrated. © 2014 Elsevier Ltd. All rights reserved. Introduction Canine parvovirosis is caused by canine parvovirus (CPV) strains 2a, 2b, and 2c. CPV can lead to asymptomatic infection, mild clin- ical signs, or severe and fatal disease (Meunier et al., 1985; Otto et al., 1997; Decaro et al., 2005a). At present, canine parvovirosis still has a high mortality rate (Goddard and Leisewitz, 2010), especially in young puppies, and treatment is intensive and costly. Disease outcome depends predominantly on the dogs’ immune system, and disease is most severe in dogs that have no specific immunity. Puppies are especially at high risk of developing the disease during the time when maternal antibodies wane and the development of specifically acquired immunity post-vaccination has not been com- pleted (Pollock and Carmichael, 1982; Goddard and Leisewitz, 2010). Innate immunity is the first line of defence against virus infec- tions and is initiated by recognition of specific viral elements by pattern recognition receptors (PRR) initiating the innate immune response (Janeway and Medzhitov, 2002). The interaction between PRR and the virus activates signalling pathways that lead to the tran- scription of genes encoding for antiviral cytokines contributing to the establishment of an antiviral state of both the infected and non- infected cells (Janeway and Medzhitov, 2002; Yokota et al., 2010; Raykov et al., 2013). There are several studies evaluating the influence of CPV on the adaptive immune system (Chappuis, 1998; Toman et al., 2002; Schultz et al., 2010) but the innate immune response to parvovirus infec- tions has received little attention (Paglino et al., 2014). In human peripheral blood mononuclear cells, activation of an antiviral re- sponse by production and release of interferon (IFN)-α and IFN-β in rodent parvovirus infection was demonstrated (Raykov et al., 2013), whereas porcine parvovirus did not induce type 1 interferons. Little is known about the mechanisms by which parvoviruses can evade the innate immune system (Lin et al., 2013), but the initial antiviral immune response of the mammalian host plays an essen- tial role in determining the outcome of viral infections (Robert-Tissot et al., 2011) and a functional innate immune system is critical to host defence (Alper et al., 2008). Therefore, stimulation of the innate immunity by paramunity inducers could be advantageous in dogs infected by CPV that lack specific immunity so reducing the risk of severe illness and accelerating recovery. Paramunity can be defined as acquired non-pathogen-specific and non-antigen-specific protection of limited duration against a * Corresponding author. Tel.: +49 89 2180 2650. E-mail address: L.Proksch@medizinische-kleintierklinik.de (A.L. Proksch). http://dx.doi.org/10.1016/j.tvjl.2014.08.012 1090-0233/© 2014 Elsevier Ltd. All rights reserved. The Veterinary Journal ■■ (2014) ■■–■■ ARTICLE IN PRESS Please cite this article in press as: A.L. Proksch, S. Unterer, U. Truyen, K. Hartmann, Efficacy of the paramunity inducer PIND-ORF in the treatment of canine parvovirus infection, The Veterinary Journal (2014), doi: 10.1016/j.tvjl.2014.08.012 Contents lists available at ScienceDirect The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl