PMID- 34238966 OWN - NLM STAT- MEDLINE DCOM- 20211102 LR - 20240402 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 11 IP - 1 DP - 2021 Jul 8 TI - Retrospective review of 27 European cases of fatal elephant endotheliotropic herpesvirus-haemorrhagic disease reveals evidence of disseminated intravascular coagulation. PG - 14173 LID - 10.1038/s41598-021-93478-0 [doi] LID - 14173 AB - Elephant endotheliotropic herpesvirus haemorrhagic disease (EEHV-HD) is widely acknowledged as the most common cause of mortality in young Asian elephants (Elephas maximus) in captivity. The objective of the current study was to perform a blinded, retrospective pathology review of European EEHV-HD fatalities, constituting the largest systematic assessment of EEHV-HD pathology to date. Findings between viral genotypes were compared with the aim to investigate if disseminated intravascular coagulation (DIC) could be substantiated as a significant complicating factor, thereby increasing the understanding of disease pathophysiology. Immunohistochemical staining confirmed endothelial cell (EC) damage and the presence of EC intranuclear inclusion bodies, demonstrating a direct viral cytopathic effect. Microthrombi were observed in 63% of cases in several organs, including lungs, which, together with widespread haemorrhage and thrombocytopenia reported in EEHV-HD case reports, supports the presence of overt DIC as a serious haemostatic complication of active EEHV infection. Death was attributed to widespread vascular damage with multi-organ dysfunction, including severe acute myocardial haemorrhage and subsequent cardiac failure. Systemic inflammation observed in the absence of bacterial infection may be caused by cytokine release syndrome. Findings reinforce the necessity to investigate cytokine responses and haemostatic status during symptomatic and asymptomatic EEHV viraemia, to potentially support the use of anti-inflammatory treatment in conjunction with anti-viral therapy and cardiovascular support. FAU - Perrin, K L AU - Perrin KL AD - Center for Zoo and Wild Animal Health, Copenhagen Zoo, Roskildevej 38, 2000, Frederiksberg, Denmark. klperrin01@gmail.com. AD - The Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej 16, 1870, Frederiksberg, Denmark. klperrin01@gmail.com. FAU - Kristensen, A T AU - Kristensen AT AD - The Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej 16, 1870, Frederiksberg, Denmark. FAU - Bertelsen, M F AU - Bertelsen MF AD - Center for Zoo and Wild Animal Health, Copenhagen Zoo, Roskildevej 38, 2000, Frederiksberg, Denmark. FAU - Denk, D AU - Denk D AD - International Zoo Veterinary Group, Station House, Parkwood Street, Keighley, BD21 4NQ, UK. AD - Institute for Animal Pathology, Ludwig-Maximilians-University, Veterinarstr. 13, 80539, Munich, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210708 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 SB - IM MH - Animals MH - Disseminated Intravascular Coagulation/pathology/*veterinary/*virology MH - Edema/pathology MH - Elephants/*virology MH - Hemorrhage/pathology/*veterinary/*virology MH - Herpesviridae/*physiology MH - Herpesviridae Infections/pathology/*veterinary/*virology MH - Inclusion Bodies, Viral/metabolism MH - Inflammation/pathology MH - Lymph Nodes/pathology MH - Organ Specificity MH - Retrospective Studies MH - Severity of Illness Index PMC - PMC8266883 COIS- The authors declare no competing interests. EDAT- 2021/07/10 06:00 MHDA- 2021/11/03 06:00 PMCR- 2021/07/08 CRDT- 2021/07/09 06:29 PHST- 2021/01/17 00:00 [received] PHST- 2021/06/25 00:00 [accepted] PHST- 2021/07/09 06:29 [entrez] PHST- 2021/07/10 06:00 [pubmed] PHST- 2021/11/03 06:00 [medline] PHST- 2021/07/08 00:00 [pmc-release] AID - 10.1038/s41598-021-93478-0 [pii] AID - 93478 [pii] AID - 10.1038/s41598-021-93478-0 [doi] PST - epublish SO - Sci Rep. 2021 Jul 8;11(1):14173. doi: 10.1038/s41598-021-93478-0.