Casualty or carrier? Understanding the pathogenesis of elephant endotheliotropic herpesvirus haemorrhagic-disease in Asian elephants (Elephas maximus)

PhD Student: Kathryn Louise Perrin, BVetMed, PhD, Dipl ACZM, Dipl ECZM (ZHM), Zoo Veterinarian
Thesis defended: 4th June 2021


Elephant endotheliotropic herpesvirus (EEHV) infection is endemic within the worldwide Asian elephant (Elephas maximus) population. An acute and often fatal haemorrhagic syndrome, EEHV-haemorrhagic disease (EEHV-HD), is associated with EEHV infection and is reported to be the most common cause of death of young Asian elephants. This disease was first reported in 1990, since which there has been development of diagnostic tests and increased understanding of EEHV infection and disease. However, there is a paucity of objective data regarding epidemiology, risk factors and pathogenesis of EEHV-HD. Overall there is a lack of understanding as to why a virus that has co-evolved alongside Asian elephants, and is ubiquitous in the adult population, causes so many fatalities in young individuals.

Purpose of the Project

The aim of this thesis was to provide insights into the pathogenesis of EEHV-HD in Asian elephants by:

  1. Quantifying and reviewing EEHV-HD fatalities in Europe and investigating potential risk factors.
  2. Describing end-stage EEHV-HD lesions in a large cohort of Asian elephants.
  3. Providing tools for monitoring disease progression during EEHV viraemia.

Results so far

A comprehensive retrospective review of all Asian elephant calves born in Europe and surviving more than 24 hours identified EEHV-HD as the most common cause of death between 1985 and 2017, with no difference in the age of EEHV death between males and females. Cox proportional hazards regression analysis did not find evidence that moving elephants between herds was associated with an increased risk of death, however once an EEHV fatality had occurred in a herd, future juveniles in that herd had a 3.8-fold higher risk of dying from EEHV. Systematic, blinded, histological examination was performed on 27 cases and indicated that death is caused by multiorgan dysfunction, particularly acute cardiac failure. The combination of severe acquired thrombocytopenia, a bleeding diathesis characterised by widespread petechiae and ecchymoses and the documentation of microthrombi in approximately two thirds of the investigated cases, supports that disseminated intravascular coagulation is a severe haemostatic complication of EEHV-HD.

As there was no information in the peer-reviewed literature regarding coagulation testing in EEHV-HD cases, kaolin-activated thromboelastography (TEG) was investigated in healthy Asian elephants, and population-derived reference intervals were calculated. The study showed that whole blood TEG, performed 60 minutes after sample collection is the method of choice in healthy elephants. 

A biological variation study was performed to investigate anecdotal reports of large between-elephant individuality for elephant haematology and biochemistry parameters. The index of individuality was high for most parameters, confirming that these parameters are highly individual in Asian elephants, and strongly supporting the need to establish normal values for each individual.


Future research should focus on characterising the pathophysiological responses to active EEHV infection. This PhD project has provided tools for monitoring cellular and haemostatic responses. Further, and of particular interest, would be investigating whether a dysregulated cytokine response is responsible for the development of clinical signs associated with EEHV-HD.