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Open AccessArticle

Electrocardiography Abnormalities in Macaques after Infection with Encephalitic Alphaviruses

Center for Vaccine Research, University of Pittsburgh, 3501 Fifth Avenue, Ste. 9052, Pittsburgh, PA 15213, USA
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Pathogens 2019, 8(4), 240; https://doi.org/10.3390/pathogens8040240
Received: 9 October 2019 / Revised: 8 November 2019 / Accepted: 14 November 2019 / Published: 16 November 2019
(This article belongs to the Special Issue Vaccines against Alphaviruses and Flaviviruses)
Eastern (EEEV) and Venezuelan (VEEV) equine encephalitis viruses (EEVs) are related, (+) ssRNA arboviruses that can cause severe, sometimes fatal, encephalitis in humans. EEVs are highly infectious when aerosolized, raising concerns for potential use as biological weapons. No licensed medical countermeasures exist; given the severity/rarity of natural EEV infections, efficacy studies require animal models. Cynomolgus macaques exposed to EEV aerosols develop fever, encephalitis, and other clinical signs similar to humans. Fever is nonspecific for encephalitis in macaques. Electrocardiography (ECG) metrics may predict onset, severity, or outcome of EEV-attributable disease. Macaques were implanted with thermometry/ECG radiotransmitters and exposed to aerosolized EEV. Data was collected continuously, and repeated-measures ANOVA and frequency-spectrum analyses identified differences between courses of illness and between pre-exposure and post-exposure states. EEEV-infected macaques manifested widened QRS-intervals in severely ill subjects post-exposure. Moreover, QT-intervals and RR-intervals decreased during the febrile period. VEEV-infected macaques suffered decreased QT-intervals and RR-intervals with fever onset. Frequency-spectrum analyses revealed differences in the fundamental frequencies of multiple metrics in the post-exposure and febrile periods compared to baseline and confirmed circadian dysfunction. Heart rate variability (HRV) analyses revealed diminished variability post-exposure. These analyses support using ECG data alongside fever and clinical laboratory findings for evaluating medical countermeasure efficacy. View Full-Text
Keywords: alphavirus; vaccine; arbovirus; animal models; nonhuman primates; electrocardiography; ECG; aerosol; encephalitis; equine alphavirus; vaccine; arbovirus; animal models; nonhuman primates; electrocardiography; ECG; aerosol; encephalitis; equine
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Ma, H.; Lundy, J.D.; O’Malley, K.J.; Klimstra, W.B.; Hartman, A.L.; Reed, D.S. Electrocardiography Abnormalities in Macaques after Infection with Encephalitic Alphaviruses. Pathogens 2019, 8, 240.

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