Seroprevalence of Elephant Endotheliotropic Herpesvirus in Elephants
This study investigates the seroprevalence of Elephant Endotheliotropic Herpesvirus (EEHV) in Asian and African elephants in human care. It covers the background, epidemiology, types, and hemorrhagic disease associated with EEHV. The research sheds light on the impact of EEHV on elephants in captivity.
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SEROPREVALENCE OF ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS (EEHV) IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS) AND AFRICAN ELEPHANTS (LOXODONTA AFRICANA) IN HUMAN CARE Abigail Hsu, Jie Tan, Rongsheng Peng, Jennifer Yu, Lauren Howard, Christine Molter, Paul Ling, Tierra Smiley Evans
EEHV: BACKGROUND Index case: 1995 at the National Zoo Taxonomy Family: Herpesviridae Subfamily: Betaherpesvirinae (proposed Deltaherpesvirinae) Genus: Proboscivirus Herpesviruses are very host-specific (EEHV in elephants only) EEHV co-evolved with elephants over millions of years Prevalent in human care AND in range countries
EEHV: EPIDEMIOLOGY Most herpesviruses do NOT kill their host Host becomes latently infected Recrudescent infection -> shedding Stimulus for shedding not well understood Shed by asymptomatic elephants Primary infection can cause clinical disease in serona ve elephants
EEHV TYPES Table 1. EEHV types in Asian (Elephas maximus) and African (Loxodonta Africana) elephants. Asian Elephants (Elephas maximus) African Elephants (Loxodonta africana) EEHV2* EEHV3* EEHV6* EEHV7 EEHV1A* and 1B EEHV4 EEHV5 *responsible for majority of clinical disease
EEHV-HD (HEMORRHAGIC DISEASE) Table 2. EEHV versus EEHV-HD. EEHV Ubiquitous, co-evolved with elephants of both species Virus found incidentally (shed in trunk secretions, saliva, feces, etc.) Associated with recrudescent infection Can manifest with low-level viremia Non-clinical/asymptomatic EEHV-HD Fulminant, rapidly progressive Abnormal CBC Primary infection HIGH viremia Clinical signs: cyanosis of tongue, petechiae of mucous membranes, edema, lameness, anorexia, colic, lethargy, GI upset Treat aggressively No treatment necessary
EEHV-HD (HEMORRHAGIC DISEASE) Asian calves: 1-8 years of age African calves: <15 years of age Viremia detected by qPCR of whole blood >5,000 vge/mL indicates treatment CBC changes: leukopenia, monocytopenia, thrombocytopenia Clot destruction and internal hemorrhage EEHV viremia Systemic disease Endothelial damage Clot Death formation Dec Inc D- dimers fibrinogen and plts
CURRENT EEHV-HD MANAGEMENT Standing sedation Rectal fluids Famciclovir Plasma transfusion Fortified plasma Whole blood transfusion IV fluids Mesenchymal stem cells Gastroprotectants Antibiotics NSAIDs Aminocaproic acid
EEHV IS A NATURAL INFECTION OF ELEPHANTS BUT CAN CAUSE SEVERE CLINICAL DISEASE AND DEATH IN ELEPHANTS LACKING SUFFICIENT IMMUNE PROTECTION
EEHV SEROLOGY Valuable monitoring tool: fatal EEHV-HD cases are associated with seronegativity for the EEHV type responsible for disease Luciferase Immunoprecipitation System (LIPS) assay Asian elephant panel: EEHV1A (ORF-Q), EEHV1B (ORF-Q), EEHV4 (E34), Pan (EEHV1A gB) African elephant panel: EEHV3 (E34), EEHV2 (E34), EEHV6 (E34), Pan (EEHV3 gB) Role in informing future practices for herds under human management Utility in selection of vaccine candidates and evaluation of post-vaccine immune response
PROJECT OBJECTIVES Aim 1: Quantify EEHV seropositivity in North American elephants to compare prevalence between Association of Zoo and Aquarium (AZA) institutions. Aim 2: Stratify serology based on demographic factors relating to seroexposure to examine the effects of herd/institution, herd size, age group, sex, and exposure to social structural changes on seropositivity and EEHV antibody levels.
HYPOTHESES Circulating EEHV antibody profiles will differ between AZA institutions due to variation in management strategies, as well as between age groups; however, sex will have no impact on EEHV seropositivity or antibody levels. Because larger herds facilitate the critical primary infection to EEHV when calves are sufficiently protected by maternal antibodies, smaller herds are more at risk for EEHV-related mortalities. Larger herds will have a higher prevalence of EEHV seropositivity than small herds. Herds with frequent herd structure changes will have a higher frequency of EEHV antibodies because of increased opportunities to transmit primary infections.
METHODS Compiled existing serology data for each elephant species Completed available LIPS serology panel for banked samples to fill in any unknowns or confirm marginal results Collected demographic data Studbook ZIMS The Elephant Database Nationwide survey pending Stratified serostatus based on the demographic parameter of interest Case-control design, modeling species and EEHVs separately
STUDY POPULATION Table 3. Demographics of Elephas maximus study population. Table 4. Demographics of Loxodonta africana study population.
1. WHAT IS THE SEROPREVALENCE OF PARTICIPATING AZA INSTITUTIONS?
ASIAN ELEPHANTS (ELEPHAS MAXIMUS) Table 5. Prevalence of EEHV types within Elephas maximus study population. EEHV Type EEHV1A EEHV1B EEHV4 Seroprevalence 85/87 = 0.977 58/87 = 0.667 59/87 = 0.678
AFRICAN ELEPHANTS (LOXODONTA AFRICANA) Table 6. Prevalence of EEHV types within Loxodonta africana study population. EEHV Type EEHV2 EEHV3 EEHV6 Seroprevalence 69/69 = 1.000 104/106 = 0.981 68/69 = 0.986
2. WHAT RISK FACTORS INFLUENCE EEHV SEROPREVALENCE AMONG ASIAN AND AFRICAN ELEPHANTS?
PRELIMINARY RESULTS Table 7. Fisher's exact test for binary risk factors associated with EEHV types from both species. *OR = odds ratio **NC = not calculated (data with perfect prediction or no data available)
PRELIMINARY RESULTS CONTINUED Table 8. Prevalence (P) of categorical risk factors associated with Elephas maximus EEHV types.
PRELIMINARY RESULTS CONTINUED Table 9. Prevalence (P) of categorical risk factors associated with Loxodonta africana EEHV types. *NC = not calculated (seronegative elephants not captured in this study population).
CONCLUSIONS Origin was a statistically significant risk factor for EEHV4 serostatus, with wild-born elephants and elephants born under human care exhibiting a seroprevalence of 23/23 and 34/62, respectively. Age was a statistically significant risk factor for EEHV4 serostatus of Asian elephants and EEHV3 serostatus of African elephants. No test statistic was calculated for age as a risk factor for EEHV2 seroprevalence, as EEHV2 seronegative African elephants were not captured in the sampled population.
FUTURE DIRECTIONS Incorporate demographic, management, and herd history data from nationwide serosurvey responses. Provide insight into the selection of EEHV mRNA vaccine candidates. Tool for evaluating vaccine-induced immune response. Inform future management practices to minimize the population of EEHV-HD vulnerable elephants in human care.
ACKNOWLEDGEMENTS Houston Zoo Lauren Howard, DVM, Dipl. ACZM Christine Molter, DVM, Dipl. ACZM UC Davis Elephant Team Tierra Smiley Evans, DVM Clinic Staff Jennifer Yu, DVM, Graduate Group in Epidemiology Baylor College of Medicine Donors and Houston Zoo community Paul Ling, PhD Jie Tan Rongsheng Peng Jessica Watts
