A 16‑year‑old male with familial haemophagocytic lymphohistiocytosis (HLH) who had undergone haematopoietic stem cell transplantation in infancy and remained profoundly immunodeficient presented with progressive neurological deterioration, seizures and respiratory muscle failure requiring mechanical ventilation. Repeated cerebrospinal fluid investigations were non‑diagnostic, and clinical and radiological findings were initially interpreted as isolated central nervous system HLH, leading to intensive immunosuppression without clinical improvement.
Because of ongoing deterioration, a brain biopsy was performed about two months after symptom onset. Untargeted clinical metagenomic sequencing of brain tissue identified more than one million reads of avian paramyxovirus type 1 (APMV‑1) with complete genome coverage; the diagnosis was confirmed by targeted PCR and immunohistochemistry. Notably, APMV‑1 was detectable only in brain parenchyma, while PCR testing of CSF, blood, respiratory and stool samples remained negative, and phylogenetic analysis showed a virulent pigeon‑associated genotype XXI.1.2. After diagnosis, immunosuppression was reduced and combination antiviral therapy with ribavirin, favipiravir and nitazoxanide was started, but neurological disease continued to progress and the patient died eight months after symptom onset.
APMV‑1 is a neurotropic avian paramyxovirus that circulates globally in birds, causing a spectrum from mild disease to high‑mortality Newcastle disease in poultry. Human APMV‑1 infections are considered rare and typically present as mild conjunctivitis or influenza‑like illness after occupational exposure, but a literature review identified five previous fatal human cases, mostly in profoundly immunocompromised patients and often diagnosed by metagenomics. This case illustrates the diagnostic value of clinical metagenomics and targeted brain biopsy in immunocompromised patients with unexplained encephalitis, in whom pathogens may be confined to brain tissue and remain undetectable in CSF or blood, and underscores that APMV‑1 should be considered among potential causes of severe CNS disease in such high‑risk hosts.
Original case report:
Julianne R. Brown et al. Identifying virulent avian paramyxovirus type‑1: a paediatric case of progressive encephalitis diagnosed by clinical metagenomics with case series review. IDCases 44 (2026) e02555.