title: Surviving and fatal Elephant Endotheliotropic Herpesvirus-1A infections in juvenile Asian elephants - lessons learned and recommendations on anti-herpesviral therapy.
abstract: BACKGROUND
  Elephant Endotheliotropic Herpesviruses (EEHVs) can cause acute haemorrhagic disease in young Asian elephants (Elephas maximus) and clinical EEHV infections account for the majority of their fatalities. The anti-herpesviral drug famciclovir (FCV) has been used routinely to treat viraemic at-risk elephants, but thus far without proven efficacy. This paper presents clinical and virological investigations of two EEHV-1A infected elephants treated with FCV, and discusses anti-herpesvirus therapies of viraemic elephants.
  
  
  METHODS
  Two 1.5 year old male Asian elephants at a zoological collection in the UK developed clinical EEHV-1A infections. Case 1 showed signs of myalgia for the duration of 24 hours before returning back to normal. EEHV-1A DNAemia was confirmed on the day of clinical signs and continued to be present for 18 days in total. Trunk shedding of the virus commenced 10 days after detection of initial DNAemia. Case 2 tested positive for EEHV-1A DNAemia in a routine blood screening sample in the absence of clinical signs. The blood viral load increased exponentially leading up to fatal clinical disease seven days after initial detection of DNAemia. Both calves were treated with 15 mg/kg FCV per rectum on detection of DNAemia and penciclovir, the FCV metabolite, could be detected in the blood at assumed therapeutic levels. The early indicators for clinical disease were a marked absolute and relative drop in white blood cells, particularly monocytes prior to the detection of viraemia. The most prognostic haematological parameter at later stages of the disease was the platelet count showing a continuous sharp decline throughout, followed by a dramatic drop at the time of death.
  
  
  CONCLUSIONS
  The EEHV-1A viraemic animals investigated here further highlight the ongoing threat posed by these viruses to juvenile Asian elephants. The findings call into question the efficacy of rectal FCV in clinical cases and direct towards the use of alternative anti-herpesvirus drugs and complementary treatments such as plasma infusions if no improvement in either viral load or the above-mentioned blood parameters are observed in the initial days of viraemia despite anti-herpesvirus therapy.
authors: Animal and Plant Health Agency-Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK. akbar.dastjerdi@apha.gsi.gov.uk.
authors: Akbar
authors: A
authors: Dastjerdi
authors: Animal and Plant Health Agency-Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK.|School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK.
authors: Katharina
authors: K
authors: Seilern-Moy
authors: School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK.
authors: Karin
authors: K
authors: Darpel
authors: Animal and Plant Health Agency-Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK.|School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK.
authors: Falko
authors: F
authors: Steinbach
authors: ZSL Whipsnade Zoo, Dunstable, Bedfordshire, LU6 2LF, UK.
authors: Fieke
authors: F
authors: Molenaar
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000836:Animals, Zoo; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004606:Elephants; D000077595:Famciclovir; D017809:Fatal Outcome; D006564:Herpesviridae / Q000502:physiology; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000662:veterinary*; D008297:Male; D016896:Treatment Outcome; D006113:United Kingdom; D014766:Viremia / Q000188:drug therapy / Q000662:veterinary* / Q000821:virology
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D015075:2-Aminopurine; D000077595:Famciclovir
keywords: EEHV-1; EEHV-HD; EEHV-haemorrhagic disease; elephantid herpesvirus; famciclovir; ganciclovir