Equine Coital Exanthema: New Insights on the Knowledge and Leading Perspectives for Treatment and Prevention.

Equine coital exanthema (ECE) is a highly contagious, venereally-transmitted mucocutaneous disease, characterized by the formation of papules, vesicles, pustules and ulcers on the external genital organs of mares and stallions, and caused by equid alphaherpesvirus 3 (EHV-3). The infection is endemic worldwide and the virus is transmitted mainly through direct contact during sexual intercourse and by contaminated instruments during reproductive maneuvers in breeding facilities. The disease does not result in systemic illness, infertility or abortion, yet it does have a negative impact on the equine industry as it forces the temporary withdrawal of affected animals with the consequent disruption of mating activities in breeding facilities. The purpose of this review is to provide up-to-date relevant information on the knowledge of EHV-3 infection and to analyze new approaches on diagnostics, treatment and prevention in the interest of minimizing the negative consequences of ECE in light of the current situation of the equine industry.

Equine coital exanthema caused by equid alphaherpesvirus 3: a report of an outbreak in northeastern Brazil / Exantema coital equino causado pelo alphaherpesvirus equídeo tipo 3: relato de um surto no nordeste do Brasil

Equine coital exanthema is a venereal infectious disease poorly reported in horses in Brazil and was never described in the northeastern region of the country. This work aims to describe the clinical and pathological aspects of an outbreak of equine coital exanthema caused by equid alphaherpesvirus 3, occurred in a herd of horses at the semiarid region of the State of Rio Grande do Norte. Main clinical signs consisted of anorexia, hiporexia, fibrinous or purulent secretion in the penis mucosa and vagina. Two mares presented mild to minimal lesions that consisted of scars in the mucosa of the vagina and in the perivulvar region. In a stallion the disease consisted of severe, multifocal, umbilicated-exanthematous ulcers of approximately 1cm in diameter on the penis mucosa. Other areas where ulcers and crusts were focally observed included the skin of the scrotum and on the lips and mucocutaneous junctions of the oral cavity. Histologically, the main lesion consisted of multifocal severe ulcerative and fibrinous necrotizing balanoposthitis and mild multifocal necrotizing, lymphocytic dermatitis in the lips and scrotum. The equide alphaherpesvirus 3 DNA was amplified in blood samples and penis mucosa using the PCR technique. This is the first report of molecular diagnosis of equine coital exanthema affecting horses in northeastern Brazil. Further studies should be carried out in order to investigate the epidemiology and the importance of this herpetic disease in the country.(AU)

O exantema coital equino é uma doença infecciosa venérea pouco relatada em equinos no Brasil e nunca descrita na região Nordeste do país. Este trabalho tem como objetivo descrever os aspectos clínicos e patológicos de um surto de exantema coital equino causado pelo alphaherpesvirus equídeo 3, que ocorreu em um haras na região semiárida do Estado do Rio Grande do Norte. Os principais sinais clínicos consistiram em anorexia, hiporexia, secreção fibrinosa ou purulenta na mucosa do pênis e vagina. Duas éguas apresentavam lesões discretas que consistiam em cicatrizes na mucosa da vagina e na região perivulvar. Em um garanhão, a doença consistia em úlceras umbilicadas-exantematosas severas, multifocais, de aproximadamente 1 cm de diâmetro na mucosa do pênis. Outras áreas onde úlceras e crostas foram observadas focalmente incluíram a pele do escroto, lábios e junções mucocutâneas da cavidade oral. Histologicamente, as principais lesões consistiam em balanopostite multifocal ulcerativa e necrosante fibrinosa grave e dermatite linfocítica necrosante multifocal leve nos lábios e escroto. O DNA do alphaherpesvirus equídeo tipo 3 foi amplificado em amostras de sangue e mucosa do pênis pela técnica de PCR. Este é o primeiro relato de diagnóstico molecular de exantema coital equino afetando cavalos no nordeste do Brasil. Novos estudos devem ser realizados a fim de investigar a epidemiologia e a importância dessa doença herpética no país.(AU)

Equine coital exanthema caused by equid alphaherpesvirus 3: a report of an outbreak in northeastern Brazil

ABSTRACT: Equine coital exanthema is a venereal infectious disease poorly reported in horses in Brazil and was never described in the northeastern region of the country. This work aims to describe the clinical and pathological aspects of an outbreak of equine coital exanthema caused by equid alphaherpesvirus 3, occurred in a herd of horses at the semiarid region of the State of Rio Grande do Norte. Main clinical signs consisted of anorexia, hiporexia, fibrinous or purulent secretion in the penis mucosa and vagina. Two mares presented mild to minimal lesions that consisted of scars in the mucosa of the vagina and in the perivulvar region. In a stallion the disease consisted of severe, multifocal, umbilicated-exanthematous ulcers of approximately 1cm in diameter on the penis mucosa. Other areas where ulcers and crusts were focally observed included the skin of the scrotum and on the lips and mucocutaneous junctions of the oral cavity. Histologically, the main lesion consisted of multifocal severe ulcerative and fibrinous necrotizing balanoposthitis and mild multifocal necrotizing, lymphocytic dermatitis in the lips and scrotum. The equide alphaherpesvirus 3 DNA was amplified in blood samples and penis mucosa using the PCR technique. This is the first report of molecular diagnosis of equine coital exanthema affecting horses in northeastern Brazil. Further studies should be carried out in order to investigate the epidemiology and the importance of this herpetic disease in the country.

RESUMO: O exantema coital equino é uma doença infecciosa venérea pouco relatada em equinos no Brasil e nunca descrita na região Nordeste do país. Este trabalho tem como objetivo descrever os aspectos clínicos e patológicos de um surto de exantema coital equino causado pelo alphaherpesvirus equídeo 3, que ocorreu em um haras na região semiárida do Estado do Rio Grande do Norte. Os principais sinais clínicos consistiram em anorexia, hiporexia, secreção fibrinosa ou purulenta na mucosa do pênis e vagina. Duas éguas apresentavam lesões discretas que consistiam em cicatrizes na mucosa da vagina e na região perivulvar. Em um garanhão, a doença consistia em úlceras umbilicadas-exantematosas severas, multifocais, de aproximadamente 1 cm de diâmetro na mucosa do pênis. Outras áreas onde úlceras e crostas foram observadas focalmente incluíram a pele do escroto, lábios e junções mucocutâneas da cavidade oral. Histologicamente, as principais lesões consistiam em balanopostite multifocal ulcerativa e necrosante fibrinosa grave e dermatite linfocítica necrosante multifocal leve nos lábios e escroto. O DNA do alphaherpesvirus equídeo tipo 3 foi amplificado em amostras de sangue e mucosa do pênis pela técnica de PCR. Este é o primeiro relato de diagnóstico molecular de exantema coital equino afetando cavalos no nordeste do Brasil. Novos estudos devem ser realizados a fim de investigar a epidemiologia e a importância dessa doença herpética no país.

Period of excretion of equine herpesvirus 3 (EHV-3) from a stallion before showing clinical signs of equine coital exanthema and the effect of acyclovir treatment on the duration of EHV-3 excretion.

In 2017, two Thoroughbred stallions, A and B in Farms A and B, respectively, in Hokkaido in Japan showed clinical signs of equine coital exanthema (ECE). In 2020, stallion C in Farm B showed clinical signs of ECE. Eighteen mares were mated within five days before stallion A developed ECE. Ten mares that mated within 3 days before onset showed clinical signs of ECE on the external genitalia. Equine herpesvirus 3 (EHV-3) was isolated from vaginal swabs from three mares that mated within 2 days before onset. Swabs from 12 mares that mated within 4 days before onset were real-time PCR (rPCR)-positive and nine of those mares had an increased EHV-3 antibody titer. The three stallions were administered valaciclovir orally and topical acyclovir ointment was applied. Treatment started on the next day after onset in stallion A and on the day of onset in stallions B and C. EHV-3 was firstly isolated from penis swabs of stallions A and B before treatment and from penis swabs of stallion C 2 days after treatment. EHV-3 was not isolated after 8, 5 and 8 days from onset in stallions A, B and C, respectively. However, swabs were rPCR-positive for at least 12, 9 and 15 days after onset of stallions A, B and C, respectively. EHV-3 was excreted from the stallions at least within 4 days before the onset of ECE, and acyclovir treatment resulted in the termination of excretion within 8 days after onset.

In vitro comparison of acyclovir, ganciclovir and cidofovir against equid alphaherpesvirus 3 and evaluation of their efficacy against six field isolates / Comparación in vitro de aciclovir, ganciclovir y cidofovir contra alfa-herpesvirus equino 3 y evaluación de la eficacia de los mismos frente a 6 aislamientos de campo del virus

Equid alphaherpesvirus 3 (EHV3) is the etiological agent of equine coital exanthema (ECE), which is a venereal, highly contagious disease, characterized by the formation of papules, vesicles, pustules and ulcers on the external genitalia of mares and stallions. EHV3 remains in a latent state after a successful infection and there are latently infected animals in which the virus is reactivated and generally re-excreted subclinically. There are no available vaccines for this condition and prevention is based on the clinical examination of mares prior to mating, which allows to segregate those showing clinical signs. As this approach does not eliminate the risk of contagion in stallions from subclinically infected mares, there is a need for a specific EHV3 treatment. Nowadays, there exist various antiviral compounds of proven effectiveness for other alphaherpesviruses affecting humans and animals. The aim of the present study was to compare the efficacy of three antiviral compounds, acyclovir, ganciclovir and cidofovir against EHV3 in vitro, and to assess their efficacy against six EHV3 Argentinian field isolates. To determine the efficacy of these compounds in vitro, three parameters were analyzed: reduction of plaque number, reduction of plaque size and reduction of viral production. Additionally, the effectiveness of the three compounds at an optimum concentration previously determined in this study was investigated for the EHV3 field isolates. Based on our results, ganciclovir was the most potent antiviral compound to reduce EHV3 replication in vitro and may thus be a valuable candidate for treatment and prevention of ECE in mares and stallions.

El alfa-herpesvirus equino 3 (EHV3) es el agente etiológico del exantema coital equino (ECE), enfermedad venérea, altamente contagiosa y caracterizada por la aparición de pápulas, vesículas, pústulas y úlceras en los genitales externos de yeguas y padrillos. Luego de la primo-infección, el EHV3 se mantiene en el animal en un estado de latencia a partir del cual puede reactivar y excretarse, generalmente de manera subclínica. No existen vacunas, por lo que la prevención se basa en la detección de las lesiones clínicas previo al servicio, y la segregación de estos animales. Sin embargo, este abordaje no previene la infección del padrillo por parte de yeguas que excretan el virus de manera subclínica, y por lo tanto existe la necesidad de un tratamiento específico contra el EHV3. En la actualidad, existen varios compuestos antivirales de probada eficacia contra herpesvirus humanos y veterinarios. El objetivo de este trabajo es comparar la eficacia de 3 compuestos antivirales, aciclovir, ganciclovir y cidofovir, contra EHV3 in vitro, y evaluar la eficacia de los mismos contra 6 cepas de campo argentinas de EHV3. Para determinar la eficacia de los compuestos in vitro se evaluaron 3 parámetros: reducción del número de placas de lisis, reducción del tamaño de placas de lisis y reducción de la producción de virus. Adicionalmente, la efectividad de los compuestos en una concentración óptima, previamente determinada en este estudio, fue determinada para 6 cepas de campo argentinas de EHV3. De acuerdo con los resultados obtenidos, ganciclovir fue el compuesto más potente en reducir la replicación del EHV3 in vitro, y por lo tanto podría considerarse un potencial candidato para el tratamiento y la prevención del ECE en yeguas y padrillos.

In vitro comparison of acyclovir, ganciclovir and cidofovir against equid alphaherpesvirus 3 and evaluation of their efficacy against six field isolates.

Equid alphaherpesvirus 3 (EHV3) is the etiological agent of equine coital exanthema (ECE), which is a venereal, highly contagious disease, characterized by the formation of papules, vesicles, pustules and ulcers on the external genitalia of mares and stallions. EHV3 remains in a latent state after a successful infection and there are latently infected animals in which the virus is reactivated and generally re-excreted subclinically. There are no available vaccines for this condition and prevention is based on the clinical examination of mares prior to mating, which allows to segregate those showing clinical signs. As this approach does not eliminate the risk of contagion in stallions from subclinically infected mares, there is a need for a specific EHV3 treatment. Nowadays, there exist various antiviral compounds of proven effectiveness for other alphaherpesviruses affecting humans and animals. The aim of the present study was to compare the efficacy of three antiviral compounds, acyclovir, ganciclovir and cidofovir against EHV3 in vitro, and to assess their efficacy against six EHV3 Argentinian field isolates. To determine the efficacy of these compounds in vitro, three parameters were analyzed: reduction of plaque number, reduction of plaque size and reduction of viral production. Additionally, the effectiveness of the three compounds at an optimum concentration previously determined in this study was investigated for the EHV3 field isolates. Based on our results, ganciclovir was the most potent antiviral compound to reduce EHV3 replication in vitro and may thus be a valuable candidate for treatment and prevention of ECE in mares and stallions.