Autoimmune-associated systemic vasculitis as the cause of sudden-onset bilateral sensorineural hearing loss following Lassa virus exposure in a cynomolgus macaque deafness model
Abstract
Lassa virus (LASV) causes a severe, often fatal hemorrhagic disease in endemic regions of Africa and sudden-onset sensorineural hearing loss is a consequence of infection in approximately 30% of recovering patients. The causal mechanism of hearing loss in LASV-infected patients has not been identified. To develop a model for LASV deafness, we experimentally infected four cynomolgus macaque nonhuman primates (NHPs) with LASV. All four NHPs developed typical signs and symptoms of Lassa fever and two succumbed during the acute phase of disease. Two NHPs survived to the study endpoint, 45 days post-exposure. Both of these survivors remained chronically ill and apparent hearing loss was observed using daily subjective measurements, including response to auditory stimulation and tuning fork tests. Bilateral sensorineural hearing loss at 75 dB was confirmed for one of the survivors by brainstem auditory evoked response (BAER) analysis. Histologic examination of inner ear structures and other tissues revealed the presence of severe vascular lesions consistent with autoimmune-associated systemic vasculitides. These autoimmune disorders have been associated with sudden hearing loss. Other vascular-specific damage was also observed to be present in many of the sampled tissues. Serological analyses revealed the presence of autoimmune disease markers supporting this diagnosis. Our findings point toward an autoimmune etiology for Lassa fever-associated sudden-onset hearing loss.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 10, 2017
- Accession Number
- AD1024094
Entities
People
- Carl I. Shaia
- Connie S Schmaljohn
- Eric R. Wilkinson
- Kathleen A. Cashman
- Paul R. Facemire
- Todd M. Bell
Organizations
- United States Army Medical Research Institute of Infectious Diseases