RP210 - Effects of Congenital Zika Virus on Hearing Determined by ABR in Macaques (0-3 Years Old)

Abstract:
Research has shown that the transmission of the Zika virus in-utero causes congenital fetal abnormalities. Currently, there is little data available on the association between hearing loss and the Zika virus. Researching animal models may provide insight into the effect of Zika Virus on hearing loss. Using auditory brainstem response testing, fifteen rhesus macaques were evaluated over three years. Monitoring these responses, as a correlation to hearing sensitivity over a period of time, can help determine the audiological effect of Zika virus and lead to improved future protocols.

Summary:
As of 2020, there have been over 22,000 reported cases of Zika Virus (ZIKV) throughout the Americas. ZIKV is known to cause multiple congenital abnormalities such as microcephaly and central nervous system deficits which are now categorized as Congenital Zika Syndrome. There are still questions about the association of other pathologies and ZIKV, including the link with childhood hearing loss. The data available to date does not confirm an association between hearing loss and ZIKV, nor does it rule out progressive hearing impairment. Research from animal models may provide insight into understanding the severity and progression of hearing loss associated with ZIKV.

In this study, 15 rhesus macaques exposed to ZIKV in-utero underwent auditory brainstem response (ABR) testing at 3 months, 6 months, 12 months, and 36 months. Previous research shows ABR testing is a reliable and valid measurement to test hearing sensitivity in macaques and is translatable to a human population. This study aims to measure ABR responses of macaques to help establish a ZIKV transmission model that can be applied to human auditory function. Specifically, the research question is: In rhesus macaques, does the presence of ZIKV acquired through in-utero transmission cause abnormal hearing thresholds measured using ABR at ages 3, 6, 12, and 36 months?

ABR testing was completed with subdermal electrodes placed behind the left mastoid, right mastoid, low forehead (ground), and high forehead (vertex). Clicks were recorded at 70, 50, and 30 dB nHL. Tone bursts at 500 and 1000 Hz were recorded at 80, 60, and 40dB nHL. Each threshold was recorded twice for reliability, with the noise floor being < 10% of the number of sweeps (1000 sweep minimum).

Previous research has shown that due to the smaller head size and auditory nerve in rhesus macaques, only four waveforms are generated. Due to this, wave IV should be examined for threshold estimations in rhesus macaques. Threshold is defined as the lowest level (30 dB nHL for clicks and 40 dB nHL for 500 and 1000 Hz tone burst) at which a response at wave IV could be identified. For click stimulus, all subjects had present responses at the lowest level tested (30 dB nHL) at 36 months of age. For 1000 Hz tone-burst stimulus, all subjects had present responses at the lowest level tested (40 dB nHL) at 36 months of age. For 500 Hz tone-burst stimulus, 13 out of 15 subjects had present responses at the lowest level tested (40 dB nHL) and two subjects had absent responses (one unilateral and one bilateral) at the lowest level tested.

At this time, the causality between increased thresholds for click stimulus and 500 and 1000 Hz stimuli, and ZIKV could not be determined. However, results show a possible effect at 500 Hz, but due to the limited sample size, this cannot be determined. Further research looking at results of tone burst ABR testing needs to be completed to determine if there is a link between hearing loss and ZIKV.