Prävention der equinen Herpesvirus-Myeloenzephalopathie – Ist Heparin eine vielversprechende Option?

Walter, Jasmin; Seeh, Christoph; Fey, Kerstin; Bleul, Ulrich; Osterrieder, Nikolaus

doi:10.15653/tpg-150451

Cited by 12 publications

(4 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, the neurologic disease in the UFH-treated horses may be due to neural injury that is unrelated to thrombosis, such as edema or the incited inflammatory response to virus replication ( 12 ). The results of the previously reported heparin treatment trial in a natural outbreak ( 32 ) and the study herein do support the use of heparin-based anticoagulants to help reduce the incidence or severity of neurologic disease in EHV-1-infected horses, however it is unlikely that this and other clinical syndromes related to EHV-1, including abortion, will be completely prevented by such treatments.…”

Section: Discussionsupporting

confidence: 70%

“…It is conceivable that high virus concentrations can be locally produced after efficient viral replication in endothelial cells and could result in localized thrombosis despite heparin therapy. In support of this possibility, neurologic disease was still observed in 1/31 horses treated with 25000 units of UFH twice daily for 3 days versus 7/30 untreated horses after an EHV-1 outbreak in a single facility in Germany ( 32 ). Alternatively, the neurologic disease in the UFH-treated horses may be due to neural injury that is unrelated to thrombosis, such as edema or the incited inflammatory response to virus replication ( 12 ).…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation

et al. 2018

View full text Add to dashboard Cite

Equine herpesvirus type 1 (EHV-1) is a major cause of infectious respiratory disease, abortion and neurologic disease. Thrombosis in placental and spinal vessels and subsequent ischemic injury in EHV-1-infected horses manifests clinically as abortion and myeloencephalopathy. We have previously shown that addition of heparin anticoagulants to equine platelet-rich plasma (PRP) can abolish ex vivo EHV-1-induced platelet activation. The goal of this study was to test whether platelets isolated from horses treated with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) were resistant to ex vivo EHV-1-induced activation. In a masked, block-randomized placebo-controlled cross-over trial, 9 healthy adult horses received 4 subcutaneous injections at q. 12 h intervals of one of the following treatments: UFH (100 U/kg loading dose, 3 maintenance doses of 80 U/kg), 2 doses of LMWH (enoxaparin) 80 U/kg 24 h apart with saline at the intervening 12 h intervals, or 4 doses of saline. Blood samples were collected before treatment and after 36 h, 40 h (4 h after the last injection) and 60 h (24 h after the last injection). Two strains of EHV-1, Ab4 and RacL11, were added to PRP ex vivo and platelet membrane expression of P selectin was measured as a marker of platelet activation. Drug concentrations were monitored in a Factor Xa inhibition (anti-Xa) bioassay. We found that LMWH, but not UFH, inhibited platelet activation induced by low concentrations (1 × 106 plaque forming units/mL) of both EHV-1 strains at 40 h. At this time point, all horses had anti-Xa activities above 0.1 U/ml (range 0.15–0.48 U/ml) with LMWH, but not UFH. By 60 h, a platelet inhibitory effect was no longer detected and anti-Xa activity had decreased (range 0.03 to 0.07 U/ml) in LMWH-treated horses. Neither heparin inhibited platelet activation induced by high concentrations (5 × 106 plaque forming units/mL) of the RacL11 strain. We found substantial between horse variability in EHV-1-induced platelet activation at baseline and after treatment. Minor injection site reactions developed in horses given either heparin. These results suggest that LMWH therapy may prevent thrombotic sequelae of EHV-1, however further evaluation of dosage regimens is required.

show abstract

Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 96%

Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation

et al. 2018

View full text Add to dashboard Cite

show abstract

“…However, the susceptibility to EHV-1 infection was retained following discontinuation of valacyclovir, as exemplified by five horses that developed abnormal clinical signs during the second or third week of the outbreak. The medical management of EHV-1 outbreaks with anti-herpetic, antiinflammatory and anti-thrombotic drugs is generally aimed at reducing the risk of EHM by either reducing or preventing viremia and by mitigating the interactions of EHV-1 with endothelial cells [18,19]. Unfortunately, there are too few placebo-controlled studies to evaluate the efficacy of such medical protocols in the prevention of EHM.…”

Section: Discussionmentioning

confidence: 99%

Investigation of an EHV-1 Outbreak in the United States Caused by a New H752 Genotype

Pusterla

Barnum

Miller³

et al. 2021

Pathogens

View full text Add to dashboard Cite

Here we report on an EHV-1 outbreak investigation caused by a novel genotype H752 (histidine in amino acid position 752 of the ORF 30 gene). The outbreak involved 31 performance horses. Horses were monitored over a period of 35 days for clinical signs, therapeutic outcome and qPCR results of EHV-1 in blood and nasal secretions. The morbidity of the EHV-1 outbreak was 84% with 26 clinically infected horses displaying fever and less frequently anorexia and distal limb edema. Four horses showed mild transient neurological deficits. Clinically diseased horses experienced high viral load of EHV-1 in blood and/or nasal secretions via qPCR, while subclinically infected horses had detectable EHV-1 mainly in nasal secretions. The majority of infected horses showed a rise in antibody titers to EHV-1 during the outbreak. All 31 horses were treated with valacyclovir, while clinically infected horses further received flunixin meglumine and sodium heparin. This investigation highlights various relevant aspects of an EHV-1 outbreak caused by a new H752 genotype: (i) importance of early detection of EHV-1 infection; (ii) diagnostic challenge to assess H752 genotype; (iii) apparent benefit of valacyclovir use in the early stage of the outbreak; and (iv) weekly testing of blood and nasal secretions by qPCR in order to monitor individual infection status and lift quarantine.

show abstract

“…Accordingly, using of anticoagulants that suppress thrombin generation or platelet inhibitors that impede post-receptor thrombin signaling (phosphodiesterase antagonists) would inhibit EHV-1-induced platelet activation (Stokol et al, 2016). Interestingly, subcutaneous injection of 25000 IU heparin to horses during EHV-1 outbreak resulted in lower EHM incidence (3.2%) than untreated horses (23.3%) (Walter et al, 2016). So, it could be used as adjunctive therapy to reduce the EHV-1serious complications.…”

Section: Treatmentmentioning

confidence: 99%

Equine Herpesvirus-1 Infection, Clinical Features, Treatment and Control

Ata¹,

Ghazy²,

Shaapan³

2020

Adv. Anim. Vet. Sci.

View full text Add to dashboard Cite

E quine herpesvirus type-1 (EHV-1) is Equine herpesvirus type-1 (EHV-1) is belong to the family Herpesviridae, subfamily alphaherpesvirinae, genus Varicellovirus, and species Equid alphaherpesvirus 1. It is a ubiquitous and highly contagious pathogen that causes a range of disease severities with outbreaks of notable economic impact (Ata et al.,2 018a, b; Tallmadge et al., 2018). It is a serious worldwide threaten to the horse industry (Lunn et al., 2009). The output of this disease includes one or more of the following clinical signs; severe respiratory manifestations, abortion storm in mares, neurological signs or even death (Walter et al., 2013; Damiani et al., 2014; Ata et al., 2018b). Inhalation of the virus infectious particle to the respiratory tract is the main route of infection, the initial replication of the virus occurs at the upper respiratory tract results in virus shedding in the nasal discharge (Kydd et al., 1994). Fever and respiratory clinical signs may appear, although some horses express subclinical shedding (Burgess et al., 2012). Within the first two weeks of infection, the clinical respiratory signs usually cease but returning of the lymph review Article Abstract | Equine herpesvirus type 1 (EHV-1) is a worldwide threaten affects the equine industry. The clinical features of EHV-1 infection included the respiratory, abortion, neonatal disease, and neurological forms with a frequently fatal outcome especially in the old age cases. The respiratory form characterized by fever, anorexia and nasal discharges. The abortion could occur in the last third of pregnancy either sporadically or progress into a storm. While in the case of myelencephalopathy, the signs ranged from mild ataxia to severe neurological deficits. Treatment of such cases depends on decreasing the inflammatory signs through using symptomatic and supportive treatment. So, a combination of free-radical scavengers, anticoagulants, and anti-inflammatory drugs, specific anti-herpesvirus drugs (e.g. acyclovir and valacyclovir) especially with the injection route rather the oral one are recommended. Because of the ubiquitous nature of the EHV-1 and the establishment of lifelong latency, elimination of the pathogen from the equine population is difficult. EHV-1 infection results in short-lived immunity which does not prevent re-infection. Although the modified live virus (MLV) and inactivated vaccines are available, it was shown to suppress EHV-1 disease not to limit the viral load. The MLV vaccines have an excellent safety record and can protect horses against clinical disease; however, their efficacy in preventing viremia, abortion, and neurological disease is unclear. Early diagnosis, prevention of further spread and management of clinical cases are the major priorities to control an outbreak. Prevention of virus spreading can be relatively achieved through sound biosecurity measures. This entails quarantine and isolation of new additions for at least a month, cleaning and disinfection of transportation equipment, fomites, and the ar...

show abstract

Prävention der equinen Herpesvirus-Myeloenzephalopathie – Ist Heparin eine vielversprechende Option?

Cited by 12 publications

References 22 publications

Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation

Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation

Investigation of an EHV-1 Outbreak in the United States Caused by a New H752 Genotype

Equine Herpesvirus-1 Infection, Clinical Features, Treatment and Control

Contact Info

Product

Resources

About