1409. Next-Generation Sequencing-based Detection of Angiostrongylus cantonensis (AC) Using Microbial Cell-free DNA Sequencing of Plasma in Atypical Cases of Rat Lungworm Meningitis Presenting with Ascending Paralysis

Abstract

BackgroundAC or Rat Lungworm meningitis usually presents as a self-limited illness with headache and sensory changes, rarely progressing to coma, death, or permanent brain damage. It is usually diagnosed by eosinophils in the CSF. Once limited to Asia and the tropical Pacific AC transmission via slugs and snails documented on US mainland in 2018. We describe 2 unusual, severe examples of AC infection in infants presenting with ascending paralysis and initial CSF without eosinophilia suggesting Guillain–Barre syndrome (GBS).MethodsConventional lab testing of serum and CSF, brain and spine MRI, AC PCR by Hawaii Department of Health, and mcfDNA next-generation sequencing (NGS) of plasma (Karius).ResultsTwo infants, aged 8 and 11 months, presented with fever, lower extremity weakness, and ascending paralysis. An initial evaluation in both included normal brain/spine imaging and CSF with modest lymphocytic pleocytosis without eosinophils. Paralysis progressed despite IVIG. Case 1: 11-month male: Admitted on fever day 5. Paralysis progressed to respiratory failure requiring ventilation for 20 days. Illness day 16: MRI showed spinal cord swelling C3-C7, Brain normal. CSF#3: WBC 269 28% eos, ↑ protein. Visible 8 mm long young adult worms, PCR positive for AC. Rx high-dose corticosteroids, albendazole for >4 weeks. Day 29 illness MRI: Cerebral infarct L frontal lobe, worm tracks medulla, inflammation cauda equina. Slow improvement over 5 months. Case 2: 8-month-old female: Admitted fever day 8. Weakness progressed to arms and trunk. Day 10 illness: CSF #2: Visible worms present, WBC 84, 26% eos. PCR positive for AC. Rx: High-dose steroids and albendazole x4 weeks. MRI spine illness day 30: inflammation cauda equina. Weakness improved by illness day 37. McfDNA sequencing of plasma detected AC in acute stage peaks of 123 and 12 molecules/microliter in cases 1 and 2. Serial mcfDNA testing showed a decline in the AC DNA level in plasma which correlated with treatment and clinical response.ConclusionAC infection may mimic GBS or transverse myelitis. AC diagnosis may require repeat CSF testing. NGS detection of AC in plasma holds promise as rapid, noninvasive diagnosis and assessment of response to therapy. High-dose steroids with albendazole may be effective even in severe AC.Disclosures All authors: No reported disclosures.