Oral Administration of Valganciclovir Reduces Clinical Signs, Virus Shedding and Cell-Associated Viremia in Ponies Experimentally Infected with the Equid Herpesvirus-1 C2254 Variant

Abstract

Equid alphaherpesvirus-1 (EHV-1) is one of the main pathogens in horses, responsible for respiratory diseases, ocular diseases, abortions, neonatal foal death and neurological complications such as equine herpesvirus myeloencephalopathy (EHM). Current vaccines reduce the excretion and dissemination of the virus and, therefore, the extent of an epizooty. While their efficacy against EHV-1-induced abortion in pregnant mares and the decreased occurrence of an abortion storm in the field have been reported, their potential efficacy against the neurological form of disease remains undocumented. No antiviral treatment against EHV-1 is marketed and recommended to date. This study aimed to measure the protection induced by valganciclovir (VGCV), the prodrug of ganciclovir, in Welsh mountain ponies experimentally infected with an EHV-1 ORF30-C2254 strain. Four ponies were administered VGCV immediately prior to experimental EHV-1 infection, while another four ponies received a placebo. The treatment consisted in 6.5 mg/kg body weight of valganciclovir administered orally three times the first day and twice daily for 13 days. Clinical signs of disease, virus shedding and viraemia were measured for up to 3 weeks. The severity of the cumulative clinical score was significantly reduced in the treated group when compared with the control group. Shedding of infectious EHV-1 was significantly reduced in the treated group when compared with the control group between Day + 1 (D + 1) and D + 12. Viraemia was significantly reduced in the treated group when compared with the control group. Seroconversion was measured in all the ponies included in the study, irrespective of the treatment received. Oral administration of valganciclovir induced no noticeable side effect but reduced clinical signs of disease, infectious virus shedding and viraemia in ponies experimentally infected with the EHV-1 C2254 variant.

Viremia and nasal shedding for the diagnosis of equine herpesvirus‐1 infection in domesticated horses

“…A total of 60 experimental EHV‐1 infection studies met our inclusion criteria 24‐83 . The key characteristics of these studies are reported in Table 2.…”

“…Experimental studies that evaluated viremia using qPCR are shown in Figure 3B. The majority (19/23) of these studies demonstrated 100% sensitivity using this method 25,29,36,37,45,52,53,57,60,65‐67,72,73,75,77,79,80,82 …”

“…Seven studies directly compared cell culture isolation and qPCR techniques for the detection of EHV‐1 in nasal secretions 29,48,52,57,65,77,78 . The duration of EHV‐1 shedding in nasal secretions ranged from 0 to 9 days as assessed by cell culture isolation and from 0 to 21 days by qPCR.…”

“…The majority (19/23) of these studies demonstrated 100% sensitivity using this method. 25,29,36,37,45,52,53,57,60,[65][66][67]72,73,75,77,79,80,82…”

“…31,[42][43][44]50,52,68,70,71 The remaining studies had 100% sensitivity for the detection of EHV-1 in both nasal swabs and PBMC samples using cell culture-based virus isolation methods. 25,26,29,30,[33][34][35]38,[39][40][41]47,49,55,58,59,[61][62][63][64][65][66][67]69,74,[74][75][76][77][78][79]82 Experimental studies that used qPCR to detect the presence of EHV-1 DNA in both nasal swab and PBMC samples are shown in Figure 5B. Two studies reported 100% sensitivity for PCR-based detection of EHV-1 DNA in nasal swabs, while failing to detect the viral DNA in the blood (PBMC) samples.…”