Identifying virulent avian paramyxovirus type-1: A paediatric case of progressive encephalitis diagnosed by clinical metagenomics with case series review.

Background: Immunocompromised patients presenting with encephalitis can present a diagnostic conundrum as infection can be caused by a broad range of pathogens, many of which are not detected by standard of care testing pathways. Untargeted metagenomics has proven utility in the diagnosis of such infections, particularly for immunocompromised patients. Methods: An immunosuppressed adolescent presented with idiopathic progressive muscle weakness resulting in respiratory failure, 16 years after haematopoeitic stem cell transplant for familial haemophagocytic lymphohistiocytosis type 5. Clinical and radiological findings suggested a diagnosis of isolated central nervous system haemophagocytic lymphohistiocytosis, however the patient demonstrated no improvement on immunosuppressive therapy. Untargeted metagenomics was performed on brain biopsy tissue. Results: Clinical metagenomics detected avian paramyxovirus 1 (APMV-1) in the brain tissue 12 days after biopsy, confirmed by targeted PCR and immunohistochemistry. The metagenomics results guided treatment; immunosuppression was stopped and medication with potential activity against RNA viruses started. The patient died 8 months after symptom onset. Conclusions: We describe the third published case of fatal encephalitis caused by APMV-1, detectable only in brain parenchyma and only by clinical metagenomics, demonstrating the utility of brain biopsy and metagenomics when investigating encephalitis in immunocompromised patients. Case series review suggests profoundly immunocompromised patients are at risk of severe infection caused by AMPV-1.