Division of Comparative Pathology, Department of Pathology & Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA
Summary
Encephalitozoon cuniculi—a microsporidian with a fungal heritage—can infect a wide range of mammalian species. The pathophysiology of infection and serodiagnostic testing in rabbits have been difficult to define.
Introduction
Encephalitozoon cuniculi (ECUN) is a microsporidian parasite this is an obligate intracellular parasite with diverse mammalian hots including rabbits, companion animals, and humans.1-4 It is acknowledged to be possible zoonoses.1,2 Infection of rabbits can result in clinical or subclinical disease.3,4 Neurological, ocular, renal manifestations are common and can occur in combination. Diagnosis and treatment in rabbits remain difficult. In addition, recent studies have begun to define how this organism eludes the immune system which makes relapsing infection a distinct issue in these patients.
Antibody Detection
Serological titers are commonly observed in rabbits even in the absence of disease.3,4 Serostatus worldwide is more than 50%.3-5 In the U.S., using ELISA, 79% of ECUN suspect rabbis were seropositive vs. 41% of non-suspect rabbits.5
In a previous study by our laboratory using a quantitative ELISA, we reported 1.7-fold higher IgG titers in ECUN suspect rabbits vs. rabbits which were clinically normal or had non-ECUN disease.5 In a study looking at quantitative IgM and IgG titers, 50% of non-ECUN suspect rabbits were seropositive at a 1:32 screening dilution and 95% of ECUN suspect rabbits were IgG positive; this is consistent with the previous reports.6 Importantly, the positive predictive value ranged from 92–100%. That is, negative serology results have a high probability of reflecting true negative rabbits.
Acute Phase Response
While serum protein electrophoresis of samples from rabbits with suspected infection did how elevated globulins, this method alone could not aid in the diagnosis of ECUN.5 In veterinary medicine, especially with that involving dogs and horses, analysis of acute phase proteins has been a focus as an adjunct test to detect inflammation (and thus infection).7 Applications in exotic pets have also been investigated.8 C-reactive protein (CRP) and serum amyloid A (SAA) have been identified in research models as major acute phase proteins in rabbits; this classification reflects a 10–100 fold increase with inflammation as well as negligible levels in normal animals.6,8-10 Laboratory based and point of care options are available for quantitation of these markers.9,10 Non-ECUN suspect rabbits were found to have a mean CRP value of 6.8 mg/L vs. 63.8 mg/L for suspect rabbits.6,9 It should be noted that while elevated CRP is not specific for the diagnosis of ECUN infection, it can serve as a valuable prognostic indicator especially in rabbits with persistently high IgG titers. The combined use of IgM and IgG titers resulted in a 92% positive predictive value; the observation of elevated CRP levels in combination with quantitative titers resulted in a 100% positive predictive value. Decreasing levels of CRP (or SAA) reflect a positive prognosis and can be used to monitor treatment and relapses.7,8
Alternate Methods
As antibody detection continues to be problematic, alternate approaches have been investigated including PCR testing. PCR has been found to not be a reliable test in urine and CSF.11 Additionally, only 30% of animals with seroconversion and/or confirmed infection demonstrating positive results although the use of PCR with eye tissue has utility in diagnosing ECUN infection resulting in phacoclastic uveitis.11,12
References
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