Characterization of Equine Rhinitis B Virus Infection in Clinically Ill Horses in the United States during the Period 2012-2023.

Equine rhinitis B virus is a lesser-known equine respiratory pathogen that is being detected with increasing frequency via a voluntary upper respiratory biosurveillance program in the United States. This program received 8684 nasal swab submissions during the years 2012-2023. The nasal swabs were submitted for qPCR testing for six common upper respiratory pathogens: Streptococcus equi subspecies equi (S. equi), equine influenza virus (EIV), equine herpesvirus type 1 (EHV-1), equine herpesvirus type 4 (EHV-4), equine rhinitis A virus (ERAV), and equine rhinitis B virus (ERBV). The overall ERBV qPCR-positivity rate was 5.08% (441/8684). ERBV was detected as a single pathogen in 291 cases (65.99% of positives, 291/441) and was detected as a coinfection with at least one other respiratory pathogen in 150 cases (34.01%, 150/441). Young horses, less than a year of age, with acute onset of fever and respiratory signs and horses used for competition are more likely to test qPCR-positive for ERBV. Horses with ERBV may present with fever, nasal discharge, ocular discharge, and/or cough. Coinfection is a common feature of ERBV infection and S. equi, EHV-4 and EIV were the most common pathogens coinfected with ERBV. This report provides important information regarding the clinical relevance of ERBV in the horse and begins investigating the impact of coinfection on clinical disease.

Voluntary Surveillance Program for Equine Influenza Virus in the United States during 2008-2021.

A voluntary upper respiratory biosurveillance program in the USA received 9740 nasal swab submissions during the years 2008-2021 from 333 veterinarians and veterinary clinics. The nasal swabs were submitted for qPCR testing for six common upper respiratory pathogens:equine influenza virus (EIV), equine herpesvirus-1 (EHV-1), equine herpesvirus-4 (EHV-4), Streptococcus equi subspecies equi (S. equi), equine rhinitis A virus (ERAV), and equine rhinitis B virus (ERBV). Additional testing was performed for equine gamma herpesvirus-2 (EHV-2) and equine gamma herpesvirus-5 (EHV-5) and the results are reported. Basic frequency statistics and multivariate logistic regression models were utilized to determine the associations between risk factors and EIV positivity. The EIV qPCR-positivity rate was 9.9%. Equids less than 9 years of age with a recent history of travel and seasonal occurrence in winter and spring were the most common population that were qPCR positive for EIV. This ongoing biosurveillance program emphasizes the need for molecular testing for pathogen identification, which is critical for decisions associated with therapeutics and biosecurity intervention for health management and vaccine evaluations and development.

Voluntary Biosurveillance of Streptococcus equi Subsp. equi in Nasal Secretions of 9409 Equids with Upper Airway Infection in the USA.

This study aimed to describe selected epidemiological aspects of horses with acute onset of fever and respiratory signs testing qPCR-positive for S. equi and to determine the effect of vaccination against S. equi on qPCR status. Horses with acute onset of fever and respiratory signs from all regions of the United States were included in a voluntary biosurveillance program from 2008 to 2020 and nasal secretions were tested via qPCR for S. equi and common respiratory viruses. A total of 715/9409 equids (7.6%) tested qPCR-positive for S. equi, with 226 horses showing coinfections with EIV, EHV-1, EHV-4, and ERBV. The median age for the S. equi qPCR-positive horses was 8 ± 4 years and there was significant difference when compared to the median age of the S. equi qPCR-negative horses (6 ± 2 years; p = 0.004). Quarter Horse, Warmblood, and Thoroughbred were the more frequent breed in this horse population, and these breeds were more likely to test qPCR-positive for S. equi compared to other breeds. There was not statistical difference for sex between S. equi qPCR-positive and qPCR-negative horses. Horses used for competition and ranch/farm use were more likely to test qPCR-positive for S. equi (p = 0.006). Horses that tested S. equi qPCR-positive were more likely to display nasal discharge, fever, lethargy, anorexia, and ocular discharge compared to horses that tested S. equi qPCR-negative (p = 0.001). Vaccination against S. equi was associated with a lower frequency of S. equi qPCR-positive status.

Pharmacokinetics of a FDA-labeled dose of diclazuril administered orally once weekly to adult horses.

Equine protozoal myeloencephalitis (EPM) has remained a devastating neurological disease of the Americas, especially in young performance horses. Prophylactic treatment strategies with diclazuril have shown to reduce seroprevalence and titer levels to Sarcocystis neurona in healthy horses continuously exposed to the apicomplexan parasite. The goal of this study was to determine if the FDA-labeled dose of 1 mg/kg of 1.56% diclazuril (ProtazilTM) given once weekly to healthy adult horses would achieve steady-state concentrations in plasma known to be inhibitory to S. neurona in cell culture. Five individual diclazuril doses were administered at weekly intervals to 8 adult horses. Blood was collected via venipuncture immediately before (trough concentration) and 10 hours after (peak concentration) each diclazuril administration. Following the fifth dose, additional blood samples were collected every 24 hours after the peak blood collection for 7 days. All plasma samples were analyzed by high-pressure liquid chromatography. The pharmacokinetic analysis was performed using a nonlinear mixed effects model. The mean population-derived peak concentration was 264 ng/mL and the mean terminal half-life was 3.6 days. Thus, the oral administration of an FDA-labeled dose of diclazuril to healthy horses once a week was able to produce steady-state plasma drug concentrations known to inhibit S. neurona in vitro.

Frequency of Detection and Prevalence Factors Associated with Common Respiratory Pathogens in Equids with Acute Onset of Fever and/or Respiratory Signs (2008-2021).

A voluntary biosurveillance program was established in 2008 in order to determine the shedding frequency and prevalence factors for common respiratory pathogens associated with acute onset of fever and/or respiratory signs in equids from the USA. Over a period of 13 years, a total of 10,296 equids were enrolled in the program and nasal secretions were analyzed for the qPCR detection of equine influenza virus (EIV), equine herpesvirus-1 (EHV-1), EHV-4, equine rhinitis A and B virus (ERVs), and Streptococcus equi subspecies equi (S. equi). Single infections with respiratory pathogens were detected in 21.1% of the submissions with EIV (6.8%) and EHV-4 (6.6%) as the two most prevalent viruses, followed by S. equi (4.7%), ERVs (2.3%), and EHV-1 (0.7%). Multiple pathogens were detected in 274 horses (2.7%) and no respiratory pathogens in 7836 horses (76.2%). Specific prevalence factors were determined for each of the six respiratory pathogen groups; most differences were associated with age, breed, and use of the horses, while the clinical signs were fairly consistent between viral and bacterial respiratory infections. Monitoring the frequency of detection of common respiratory pathogens is important in order to gain a better understanding of their epidemiology and to implement management practices aimed at controlling disease spread.

Investigation of the Bi-Weekly Administration of Diclazuril on the Antibody Kinetics to Sarcocystis Neurona in Healthy Horses.

The aim of this study was to determine if bi-weekly administration of diclazuril at half the label dose would reduce seroprevalence and magnitude of titers to S. neurona in healthy horses naturally exposed to the apicomplexan protozoal parasite. 12 healthy adult horses were moved from a low-risk exposure to a farm with high exposure rate to S. neurona in their horse population. The horses were randomly assigned to either a treatment or a control group. Treatment consisted in the administration of half the label dose (0.5 mg/kg) of diclazuril (Protazil) pelleted top dress twice weekly (every 3-4 days) for 12 months. Prior to initiation of treatment and monthly thereafter, blood was collected for the detection of antibodies to S. neurona using a quantitative immunoassay. Further, trough plasma diclazuril levels were determined every 60 days. All 20 horses remained healthy during the entire study period. Seroprevalence to S. neurona decreased initially in the treatment group to 50% at 30 days post-treatment commencement. This was followed by a slow increase in seroprevalence in the treatment group before reaching 100% in both groups by 90 days post-treatment commencement. The seroprevalence remained 100% in both groups from 90 to 360 study days. While titer distribution between the two groups was similar at study commencement, treated horses had significantly lower titers throughout the treatment period (P < 0.05). All treated study horses had detectable plasma trough diclazuril levels at the 6 time points and the levels were above the concentration known to inhibit S. neurona in vitro (1.0 ng/mL). The administration of diclazuril pelleted top dress at half the label dose twice weekly was able to maintain low titers to S. neurona in healthy adult horses naturally exposed to the protozoal parasite. Further, trough diclazuril levels were in excess of the minimal concentration known to inhibit S. neurona.

The binding of learning to action in motor adaptation.

In motor tasks, errors between planned and actual movements generally result in adaptive changes which reduce the occurrence of similar errors in the future. It has commonly been assumed that the motor adaptation arising from an error occurring on a particular movement is specifically associated with the motion that was planned. Here we show that this is not the case. Instead, we demonstrate the binding of the adaptation arising from an error on a particular trial to the motion experienced on that same trial. The formation of this association means that future movements planned to resemble the motion experienced on a given trial benefit maximally from the adaptation arising from it. This reflects the idea that actual rather than planned motions are assigned 'credit' for motor errors because, in a computational sense, the maximal adaptive response would be associated with the condition credited with the error. We studied this process by examining the patterns of generalization associated with motor adaptation to novel dynamic environments during reaching arm movements in humans. We found that these patterns consistently matched those predicted by adaptation associated with the actual rather than the planned motion, with maximal generalization observed where actual motions were clustered. We followed up these findings by showing that a novel training procedure designed to leverage this newfound understanding of the binding of learning to action, can improve adaptation rates by greater than 50%. Our results provide a mechanistic framework for understanding the effects of partial assistance and error augmentation during neurologic rehabilitation, and they suggest ways to optimize their use.