Date Presented 03/26/20
Transmission of Zika virus from a mother to an infant results in a spectrum of mild to severe deficits. Using a rhesus macaque model, the impact of Zika on gait development was examined using the Noldus Catwalk XT. Infants exposed to the Zika virus in utero, compared to control animals, used a less mature gait over the first month of life, specifically related to their use of diagonal walking patterns.
Primary Author and Speaker: Sabrina Kabakov
Additional Authors and Speakers: Sarah Navin, Natalie Dulaney, Kathryn Bach, Karla Ausderau
BACKGROUND: Transmission of Zika Virus (ZIKV) from a mother to a fetus during pregnancy can lead to congenital Zika syndrome (CZS) in about 1 in 10 infants, including birth defects such as microcephaly, hearing loss, vision problems, and motor deficits. An additional, 40% of infants have been found to have late-onset developmental delays with 17% related to motor deficits. With the new data showing that there are late-onset developmental delays, we believe there is a full spectrum of deficits currently unknown and affecting infants exposed in utero to ZIKV. To understand the range of deficits associated with in utero exposure to ZIKV requires a controlled longitudinal study in rhesus macaques where a full range of comprehensive assessments will be conducted on the infants. To determine if infants are experiencing delays in their motor development, we used the Noldus CatWalkTM XT to assess gross and subtle aspects of gate development over the first month of life.
OBJECTIVES: Determine differences in motor development of infant rhesus macaques exposed in utero to ZIKV compared to the mock injection control group. We hypothesized that prenatal exposure to ZIKV in rhesus macaques will cause a developmental delay in motor skills resulting in less developed gait patterns shown through a decrease in balance and coordination compared to the mock injection control group.
METHODS: Pregnant rhesus macaques were injected with Puerto Rican ZIKV PRVABC59 (n=4) or a mock injection control group (n=4) at day 35-45 of gestation. Infants were then placed into the Noldus CatWalkTM XT at three different time points of 14, 21, and 28 +/- 1 day. We collected 3 useable runs classified by the infant having at least two consecutive footfalls per limb. The data was analyzed for duty cycle, max contact, the base of support and walking pattern. A two-way ANOVA was used to test for significance with a p-value less than .05.
RESULTS: ZIKV group (n=4) at day 21 used a diagonal gait pattern 30.9%+/-22.2 of the time with the control group (n=2) using a diagonal gait pattern 45.3%+/-0.7 (p=.0095). In the ZIKV group, we found that one of the infants was consistently an outlier in the data, dragging one limb while ambulating. At day 21 the mean for right front duty cycle for the ZIKV group was 68.8%+/-3.603 with the infant duty cycle being 73.7. In addition, the max contact for the right hind was 41.08%+/- 14.3 with the infant having a max contact of 61.4%.
CONCLUSION: A mature gait pattern for a rhesus macaque consists of a diagonal gait pattern. At day 21 the infant rhesus macaques exposed to ZIKV used a diagonal gait pattern less frequently shows a deficit in motor development. Finding that one infant was an outlier represents the range in deficits experienced by infants exposed in utero to ZIKV. The results of this study will help to determine early indicators to identify children at risk of developing developmental deficits, related to the subtle early gate challenges. Identifying children early will lead to early intervention to help decrease the risk of developing longterm motor delays.
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