Encephalitozoon Cuniculi (ECUN) in Rabbits

ECUN Infection
Encephalitozoon cuniculi (ECUN) is an obligate intracellular parasite that infects a wide range of mammals (1-6) but greatly impacts the rabbit community. (1-8) One report indicated 62% of all pet rabbits evaluated were seropositive for IgG against ECUN (2) whilst another found 55%. (9) Due to its zoonotic nature, it has developed as an opportunistic parasite in immunocompromised human beings (5) and commands attention. Rabbits are infected by ingestion or inhalation of spores in contaminated urine, food, or bedding (1-8) and foetuses become infected by in utero transmission (1-5,8). The disease may induce a wide range of clinical symptoms including neurological symptoms (ataxia, head tilt, vestibular disease, seizures) kidney disease and ocular lesions. (1-8) However, sometimes the infection lays dormant and these symptoms do not express. (8) One study showed a seroprevalence of IgG antibodies in asymptomatic rabbits ranged from 35 – 68% (5) and another study found 50% of non-ECUN suspect were also IgG positive. (3,4) Infected rabbits without clinical manifestation may undergo stress or develop a concurrent disease triggering reactivation (5) or even sudden death. (1) High serological prevalence among pet rabbits could be due to high exposure rate and/or subclinical infection (3,4,6).
IgG and IgM Antibodies
Antibodies are usually detectable 4 weeks (1,8) after a natural infection with peak titres observed at approximately 9 weeks (1). Naturally, IgM titres are expected to be higher during early stage infections whereas IgG titres would be higher in a matured immune response as the antibodies switch class. (3,4) Most IgM positive rabbits are also IgG positive (5) and suspected infections are more likely to be seropositive for IgG antibodies and demonstrate higher titres than clinically normal rabbits. (2-4) High titres of antibody (exceeding 1:1,600) can be detected several weeks after initial infection (2) with investigations reporting ECUN infected rabbits had antibody titres 1.7x as high as that of clinically normal rabbits. (2,3) Patients present to the veterinarian at different stages of the disease and consequently IgM antibodies may have already matured. (3,4) Nevertheless, it has been proposed the IgG antibodies remain detectable for 7 years (3,4) thus representing active infection, subclinical infection, or exposure. (2-5) Under experimental conditions, rabbits infected with ECUN demonstrate a dominant IgG response 17 days post infection with IgM decreasing to zero by day 35. (5) ECUN suspect rabbits had a significantly higher antibody titre (mean titre of 1:1324 often going beyond 1:3200 – 1:6400). (2-4) In comparison, clinically normal or bacterial infections had mean IgG titres of 1:700. (3,4) A study conducted over a 9-month period demonstrated rabbits had stable IgG titres and some with initially high titres had a 2-fold decrease in antibody (2).
Cerberus Serology
Although definitive diagnosis is difficult, (2,8) serologic testing is a common and inexpensive method of detecting ECUN IgG antibodies. To date, we have provided qualitative (positive or negative) results and now aim to provide IgG Titre results ranging from 1:100 to 1:7812500. Titre results are reported as the last sample dilution to result in positive ELISA test result based on in house statistical analysis.
Negative qualitative and quantitative results are useful in dismissing ECUN infections (3,4) where as positive results can clarify confusion with toxoplasma gondii (1) and bacterial infections of the inner ear (2-4).
Regular routine health screening is beneficial for asymptomatic rabbits and those presenting with clinical signs not associated with ECUN as an underlying infection may exist. (5,7) Our testing in conjunction with veterinary interpretation can help determine specific therapy, prognosis, and assessment of zoonotic risk (5).
References
  1. Jordan C.N, Zajac A.M, Lindsay D.S: Encephalitozoon cuniculi infection in rabbits. Compendium Vet CE Article 1: 108-115, 2006
  2. Cray C, Arcia G, Schneider R, et al: Evaluation of the usefulness of an ELISA and protein electrophoresis in the diagnosis of Encephalitozoon cuniculi infection in rabbits American Journal of Veterinary Research, Vol 70: 1-5, 2009
  3. Cray C, McKenny S, Perritt E, et al: Utility of IgM titres with IgG and c-reactive protein quantitation in the diagnosis of suspected Encephalitozoon cuniculi infection in rabbits. Journal of Exotic Pet Medicine 24: 356-360, 2015
  4. Cray C, Rodriguez M, Fernandez Y: Acute phase protein levels in rabbits with suspected Encephalitozoon cuniculi infection. Journal of Exotic Pet Medicine 22: 280-286, 2013
  5. Jeklova E, Jekl V, Kovarcik K, et al: Usefulness of detection of specific IgM and IgG antibodies for diagnosis of clinical encephalitozoonosis in pet rabbits. Veterinary Parasitology 170: 143-148, 2010
  6. Pan Y, Wang S, Liu X, et al: Seroprevalence of Encephalitozoon cuniculi in humans and rabbits in china. Iranian J Parasitol, Vol 10: 290-295, 2015 
  7. Carhan A, Ozkan O, Ozkaya E: The first identification of Encephalitozoon cuniculi infection in an animal care worker in Turkey. Iranian J Parasitol, Vol 10: 280-285, 2015
  8. Harcourt-Brown F.M: Encephalitozoon cuniculi infection in rabbits. Seminars in Avian and Exotic Pet Medicine, Vol 13: 86-93, 2004
  9. Internal seroprevalence study conducted at Victoria, NSW. Cerberus Sciences. 
Brittany Whitford
Serology Manager, Cerberus Sciences