Canine Meningoencephalitis of Unknown Origin-The Search for Infectious Agents in the Cerebrospinal Fluid via Deep
Jasmin Nicole Nessler1, Wendy Karen Jo2, Albert D M E Osterhaus2
1Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Foundation, Hannover, Germany.
Abstract:
Meningoencephalitis of unknown origin (MUO) describes a group of meningoencephalitides in dogs with a hitherto unknown trigger. An infectious agent has been suggested as one possible trigger of MUO but has not been proven so far. A relatively new method to screen for viral RNA or DNA is next-generation sequencing (NGS) or deep sequencing. In this study, a metagenomics analysis of the virome in a sample is analyzed and scanned for known or unknown viruses. We examined fresh-frozen CSF of 6 dogs with MUO via NGS using a modified sequence-independent, single-primer amplification protocol to detect a possible infectious trigger. Analysis of sequencing reads obtained from the six CSF samples showed no evidence of a virus infection. The inability to detect a viral trigger which could be implicated in the development of MUO in the examined population of European dogs, suggests that the current techniques are not sufficiently sensitive to identify a possible virus infection, that the virus is already eliminated at the time-point of disease outbreak, the trigger might be non-infectious or that there is no external trigger responsible for initiating MUO in dogs.
Insights
Next-generation sequencing (NGS) did not detect viral infections in dogs with meningoencephalitis of unknown origin (MUO). This suggests current methods may lack sensitivity or the cause is non-infectious.
Area of Science:
- Veterinary Neurology
- Infectious Diseases
- Molecular Diagnostics
Background:
- Meningoencephalitis of unknown origin (MUO) is a serious neurological condition in dogs with an unidentified cause.
- Infectious agents are suspected but have not been definitively proven as triggers for MUO.
- Next-generation sequencing (NGS) offers advanced capabilities for detecting viral RNA or DNA.
Purpose of the Study:
- To investigate the potential role of viral infections in canine MUO using metagenomics analysis.
- To screen cerebrospinal fluid (CSF) samples from dogs with MUO for known and unknown viruses.
- To evaluate the efficacy of NGS in identifying infectious triggers for MUO.
Main Methods:
- Metagenomic analysis of cerebrospinal fluid (CSF) from six dogs diagnosed with MUO.
- Utilized next-generation sequencing (NGS) with a modified sequence-independent, single-primer amplification protocol.
- Analyzed sequencing reads to detect viral RNA or DNA, searching for potential infectious agents.
Main Results:
- No evidence of viral infection was detected in the CSF samples from the six dogs with MUO.
- The metagenomic analysis did not identify any known or novel viruses associated with the canine MUO cases.
- The study failed to confirm a viral etiology for MUO in the examined population of European dogs.
Conclusions:
- Current NGS techniques may not be sensitive enough to detect a potential viral trigger for MUO.
- The causative agent of MUO might be non-infectious, or a virus may be cleared before sample collection.
- Further research is needed to explore non-infectious causes or refine diagnostic methods for canine MUO.


