Here, we have documented CDV infection in six captive endangered giant pandas during an outbreak in the Shanxi Rare Wild Animal Rescue and Research Center in China. Five of six CDV-infected giant pandas died as a result of the infection. Affected giant pandas presented with clinical illness beginning the first week of December, 2014 through March, 2015. All affected giant pandas were housed in the same room or adjacent rooms, suggesting that CDV may have been transmitted between pandas via direct contact and/or respiratory droplets. The surviving panda tested positive for CDV by RT-PCR, but did not develop overt clinical signs of CDV infection and was previously vaccinated against CDV, strongly supporting the utility of CDV vaccination in giant pandas.

CDV transmission to captive animals may potentially occur via direct or indirect contact with infected domestic dogs or wild carnivores. Domestic dogs were considered the likely source of infection for canine distemper in Serengeti lions in 199421. In North America, wild raccoons (Procyon lotor) were thought to be the source of CDV infection in large captive cats in 1991 and 19929. In Japan, raccoon dogs were considered to be the source of outbreak for canine distemper in tigers in 2009 and 201022. In Denmark, it was speculated that wildlife species, such as foxes, raccoon dogs, and ferrets were the sources of CDV infection of farmed mink (Neovison vison)23. In China, CDV infection has been observed in domestic dogs, wild canids (fox, raccoon dogs), and non-canids (mink, monkey) demonstrating the remarkable ability of this pathogen to cross species barriers15,24. The reservoir source of CDV leading to the outbreak among giant pandas remains unclear. While there were no carnivores in the Shanxi Rare Wild Animal Rescue and Research Center, it is possible that domestic dogs or other susceptible wild animals carrying CDV in the area were responsible.

The highly variable nature of H gene sequences among viruses belonging to the Morbillivirus genus has been exploited to characterize CDV field strains and investigate relationships among various strains. Sequencing of CDV from giant pandas revealed five unique amino acid changes (V26M, T213A, K281R, S300N, P340Q) encoded by the H gene that have not been observed previously in Asia-1 strains. Amino acid residues at positions 549 in the CDV H protein are implicated in CDV host range restriction and pathogenesis25,26. Notably, the H gene of CDV from giant pandas possessed a Y549H substitution which has been associated with the emergence of highly pathogenic CDV and host range expansion. Before this outbreak, the Y549H substitution had only observed in twelve CDV strains isolated from mink, fox and raccoon dogs in Shandong province and an isolate from a mink in Liaoning province in China24. While the Shanxi Rare Wild Animal Rescue and Research Center is located a significant distance away from these provinces (>900 kilometers), these species may represent potential sources of CDV leading to this outbreak among giant pandas. Previous work has shown that serial passage of dog-derived CDV strain 5804 in ferrets led to acquisition of the Y549H substitution27. CDV isolates with a histidine residue at position 549 also showed enhanced virulence in raccoons relative to strains lacking histidine at this position28. We therefore speculate that the high-level of virulence associated with giant panda/SX/2014 infection of giant pandas may be related to the presence of a histidine residue at position 549 of the H protein. The additional unique H protein amino acid substitutions identified may reflect adaptive changes facilitating CDV infection of giant pandas. As an RNA virus, CDV is capable of rapid mutation leading to viral variants that are potentially better equipped for replication in giant pandas, as has been documented for the emergence of the Y549H substitution during serial passage in ferrets27.

Vaccination represents an effective approach to prevent CDV infection of domestic dogs and may have utility in captive giant panda populations. Currently, there are no standard vaccination strategies in place for the prevention of infectious diseases in captive giant pandas in China. The effectiveness of CDV vaccination in giant pandas is supported by the observation that the single panda to survive CDV infection during this outbreak (Zhuzhu) was previously vaccinated against CDV and had high-titer SN antibodies. This animal did not display clinical signs despite recovery of CDV genomic material from blood and nasal swab samples, suggesting that the protective immune responses elicited by CDV vaccination were not sufficient to prevent naturally-acquired CDV infection but may have attenuated disease. Ultimately, universal CDV vaccination of captive giant pandas may be warranted but must be also weighed against potential vaccination risks. Additional studies to better understand the safety and efficacy of CDV vaccines in giant pandas are needed as CDV vaccines are more widely implemented. In a study involving two giant pandas, a commercially available canarypox-vectored CDV vaccine safely elicited SN antibody titers above a level considered to be protective against CDV disease29. Due to the limited supply of the canarypox-vectored CDV vaccine and the potential risks associated with live-attenuated CDV vaccines, most giant pandas in the Shanxi Rare Wild Animal Rescue and Research Center and other organizations involved in giant panda breeding programs are not routinely vaccinated. The documentation of a CDV outbreak among captive giant pandas in China suggests that heightened surveillance and CDV vaccination should be considered in all facilities housing captive giant pandas for successful conservation of this endangered species.