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Topic:Equine Herpesvirus

Equine Herpesvirus (EHV) is a contagious virus that affects horses, causing a range of clinical conditions. It primarily impacts the respiratory system but can also lead to neurological disorders, abortion in pregnant mares, and neonatal foal death. The virus is transmitted through direct contact with infected horses or through contaminated surfaces and equipment. There are several strains of EHV, with Equine Herpesvirus-1 (EHV-1) and Equine Herpesvirus-4 (EHV-4) being the most commonly studied due to their prevalence and impact on equine health. EHV-1 is associated with more severe outcomes, including equine herpesvirus myeloencephalopathy (EHM). This page aggregates peer-reviewed research studies and scholarly articles that explore the epidemiology, pathogenesis, clinical manifestations, and management strategies related to Equine Herpesvirus in horses.
First Equine Herpes Myeloencephalopathy (EHM) Outbreak in Chile.
Animals : an open access journal from MDPI    August 11, 2025   Volume 15, Issue 16 2344 doi: 10.3390/ani15162344
Durán MC, Suazo M, Maturana A, Vargas MP, García A, Ahumada C, Pezoa A, Goehring LS, Lara F.Equine herpes myeloencephalopathy (EHM) is a neurological disease in horses caused by Equine herpesvirus type 1 (EHV-1). It is a serious condition, often resulting in severe neurological deficits, and can be fatal. In this report, we discuss the first outbreak of EHM in Chile (clinical signs, epidemiology, diagnosis, and control measures). A total of 567 polo horses were kept at the facility: 58.4% mares, 41.6% geldings, and stallions. Mean age was 9.7 ± 0.132 years. Thirteen horses showed clinical signs of EHV-1, eight had fevers (1.4%), and eleven developed EHM (1.9%). Only six of the eleve...
Horse owners needed for equine herpesvirus survey.
The Veterinary record    August 1, 2025   Volume 197, Issue 3 110 doi: 10.1002/vetr.5849
Talbot W.No abstract available
Characteristics and spatio-temporal distribution of fetal loss in thoroughbred mares in New South Wales, Australia.
Preventive veterinary medicine    July 29, 2025   Volume 244 106635 doi: 10.1016/j.prevetmed.2025.106635
Wilson CS, Carrick J, Begg A, Shearer P, Stewart M, Brookes VJ.Despite emerging disease syndromes in Australian Thoroughbred horses in recent years, there is no formal surveillance for fetal loss in the industry. This study aimed to characterise the distribution of equine pregnancy loss > 45 days of gestation in a major Thoroughbred breeding region to provide insights into causes, prevention, and surveillance feasibility. Methods: Data were collected from 574 fetal loss submissions to veterinary pathology services between February 2015 and November 2021. Variables included date of fetal loss, gestational age, diagnosis, foal weight, and mare age. Dia...
Streptococcus equi subsp. zooepidemicus Supernatant Containing Streptolysin S Alters the Equine Nasal and Vaginal Mucosa, Modulating Equine Herpesvirus 1, 3 and 4 Infections.
Viruses    July 14, 2025   Volume 17, Issue 7 980 doi: 10.3390/v17070980
Mohamed E, Van Cleemput J, Şahin B, Van den Broeck W, Boyen F, Nauwynck H.The equine respiratory and reproductive tract microbiomes are complex and subject to constant fluctuations. Among the microbial inhabitants, subsp. (SEZ) is recognized as the dominant bacterium. It is an opportunistic pathogen that may occasionally lead to various types of infections. A key virulence factor of SEZ is the streptolysin S (SLS) toxin, which is responsible for the characteristic β-hemolysis on blood agar and tissue damage. Viruses and bacteria may interact and aggravate lesions and disease. This study aimed to evaluate the impact of an SLS-containing supernatant from SEZ on the...
Serum and mucosal antibody testing to detect viral exposure in contact horses during an equine herpesvirus myeloencephalopathy outbreak.
American journal of veterinary research    July 2, 2025   1-9 doi: 10.2460/ajvr.25.03.0106
Perkins GA, Wagner B, Rollins A, Sfraga H, Pearson E, Cercone M.To apply equine herpesvirus type 1 (EHV-1) antibody testing in nasal swabs and serum in nonclinical horses during a naturally occurring outbreak of (EHV-1). Previous experimental EHV-1 challenge studies showed stable serum anti-EHV-1 antibody concentrations paired with rapidly increasing nasal mucosal antibodies (mucAbs) prevent EHV-1 infection, viral shedding, and cell-associated viremia. From this, we hypothesized that EHV-1 antibody testing can confirm exposure in non-clinical horses during an outbreak. Unassigned: 2 horses with neurological signs from 1 farm were admitted to an equine hosp...
First Molecular Evidence of Equine Herpesvirus Type 1 (EHV-1) in Ocular Swabs of Clinically Affected Horses.
Viruses    June 18, 2025   Volume 17, Issue 6 862 doi: 10.3390/v17060862
Musoles-Cuenca B, Padilla-Blanco M, Vitale V, Lorenzo-Bermejo T, de la Cuesta-Torrado M, Ballester B, Maiques E, Rubio-Guerri C, Velloso Alvarez A.Equine Herpesvirus Type 1 (EHV-1) is a significant pathogen within the subfamily, causing respiratory disease, abortions, and, in severe cases, equine herpesvirus myeloencephalopathy (EHM). While nasal swabs and blood samples are commonly used for real-time polymerase chain reaction (RT-PCR) diagnosis, variability in viral shedding necessitates exploring additional sample types. This study reports the first molecular detection of EHV-1 in ocular swabs from naturally infected horses during an outbreak in the Valencian Community in 2023. Nasal and ocular swabs were collected from ten symptomati...
Reduction in endemic equine herpesvirus type-1 and type-4 infection among Thoroughbred yearlings through an updated vaccination program.
Journal of equine science    June 12, 2025   Volume 36, Issue 2 67-74 doi: 10.1294/jes.36.67
Bannai H, Kambayashi Y, Kume K, Takebe N, Endo Y, Kawanishi N, Nemoto M, Tsujimura K.The endemic situation of respiratory disease caused by equine herpesvirus type-1 (EHV-1) and type-4 (EHV-4) was investigated in a training facility for Thoroughbred yearlings in Japan. Vaccination typically starts in mid-September or early October-only after all yearlings have arrived-leaving those introduced earlier unprotected. To bridge this immunity gap, a revised vaccination program that started earlier was implemented. In 2021-2022 and 2022-2023, yearlings were allocated to three groups according to their introduction dates. Each group received a live EHV-1 vaccine (Equi N Tect ERP, Niss...
Epidemiology of Infectious Pathogens in Horses with Acute Respiratory Disease, Abortion, and Neurological Signs: Insights Gained from the Veterinary Surveillance System for Horses in The Netherlands (SEIN).
Veterinary sciences    June 10, 2025   Volume 12, Issue 6 567 doi: 10.3390/vetsci12060567
van Maanen K, van den Wollenberg L, de Haan T, Frippiat T.Monitoring infectious diseases is essential for safeguarding equine health and ensuring the sustainability of the horse industry. In 2019, the Royal Veterinary Association of the Netherlands (KNMvD) and Royal GD (GD Animal Health) launched SEIN (Surveillance of Equine Infectious diseases in the Netherlands), a voluntary surveillance system for laboratory-confirmed outbreaks of equid alphaherpesvirus 1 (EHV-1), equid alphaherpesvirus 4 (EHV-4), equine influenza virus (EIV), and subsp. . This retrospective study analyzed 364 confirmed outbreaks reported through SEIN between June 2019 and April ...
Clinical Prevalence of Equine Coital Exanthema in a Thoroughbred Covering Station in Türkiye (2021-2024).
Reproduction in domestic animals = Zuchthygiene    June 9, 2025   Volume 60, Issue 6 e70086 doi: 10.1111/rda.70086
Atay YE, Ekinci G, Öztürk AE, Timur MC, Mete A, Altınbay K, Derelli FM, Akar Y, Keleş İ.Equine Coital Exanthema (ECE) is an endemic herpesvirus disease primarily affecting the external genitalia and impairing mating activities in horses. Its extremely contagious nature, latency and subclinical features can result in outbreaks and significant economic losses. Transmission occurs primarily through mating activities; therefore, robust biosecurity measures are crucial in breeding facilities. This study aims to determine the clinical prevalence of ECE among horses in a covering station in Türkiye from 2021 to 2024. It also aims to assess the efficacy of routine PCR implementation wit...
Development and Preclinical Evaluation of a Lyophilized Vaccine Against Equine Herpesvirus Type 4 (EHV-4).
Vaccines    May 31, 2025   Volume 13, Issue 6 604 doi: 10.3390/vaccines13060604
Kutumbetov L, Myrzakhmetova B, Tussipova A, Zhapparova G, Tlenchiyeva T, Bissenbayeva K, Nurabayev S, Kerimbayev A.Equine rhinopneumonia, caused by equine herpesvirus types 1 and 4 (EHV-1 and EHV-4), continues to be a significant health and economic concern in the global equine industry, particularly in Kazakhstan. While vaccines targeting EHV-1 are available, there is currently no licensed monovalent vaccine for EHV-4, and existing formulations offer limited protection against this serotype. This study aimed to develop and evaluate a freeze-dried, live-attenuated EHV-4 vaccine with improved safety, stability, and immunogenicity. Methods: A field isolate of EHV-4 was attenuated through serial passaging in ...
Diseases of the nervous system of equids in Brazil: a review. Carvalho KS, de Barros CSL, Mendonça FS, Machado M, Riet-Correa F.In Brazil, CNS diseases in equids were little known until the 1980s. Since then, several diagnostic laboratories have been operating in different universities, initially in the South and Southeast regions and, later, in the Central-West, Northeast and North regions. However, the knowledge accumulated from the diagnoses of nervous system diseases of equids made at these institutions over the years has not been reviewed comprehensively, and many papers are published in Portuguese. Here, we review 18 diseases that occur in the nervous system of equids in Brazil, including some critical infectious...
Transcriptomic and Proteomic Profiling of Rabbit Kidney Cells Infected with Equine Herpesvirus 8.
Viruses    April 29, 2025   Volume 17, Issue 5 647 doi: 10.3390/v17050647
Ji Y, Xu D, Si W, Zhang Y, Khan MZ, Zhao X, Liu W.The present study investigated the host cell response to EHV-8 infection in rabbit kidney (RK-13) cells through transcriptomic and proteomic approaches. At 24 h post-infection, a total of 2118 differentially expressed genes (DEGs) were identified, with 1338 upregulated and 780 downregulated. At 48 h, 7388 DEGs were detected, with 4342 upregulated and 3046 downregulated genes. Proteomic analysis revealed 932 differentially expressed proteins (DEPs) at 24 h (364 upregulated and 568 downregulated) and 3866 DEPs at 48 h (2285 upregulated and 1581 downregulated). Of these, 237 upregulated and 336 d...
Investigation of Selected Prevalence Factors Associated with EHV-2 and/or EHV-5 Infection in Horses with Acute Onset of Fever and Respiratory Signs.
Viruses    April 25, 2025   Volume 17, Issue 5 612 doi: 10.3390/v17050612
James K, Chappell DE, Craig B, Pariseau C, Wright C, van Harreveld P, Barnum S, Pusterla N.The purpose of this study was to determine any associations of EHV-2, EHV-5, and dual infection with EHV-2/-5 with demographic parameters, clinical signs, and coinfection with other common respiratory pathogens. Nasal swabs collected from 9737 horses were tested for EHV-2 and EHV-5, as well as EHV-1, EHV-4, EIV, , ERAV, and ERBV, by qPCR. Clinical signs and demographic parameters were recorded, and prevalence factors were evaluated for significance regarding EHV-2 and/or EHV-5 infection. Out of the 9737 horses in this study, 17.8% tested EHV-2-positive ( = 1731), 15.8% tested EHV-5-positive ( ...
Management of an Equine Herpesvirus-1 Outbreak During a Multi-Week Equestrian Event.
Viruses    April 24, 2025   Volume 17, Issue 5 doi: 10.3390/v17050608
Pusterla N, Lawton K, Barnum S, Flynn K, Hankin S, Runk D, Mendonsa E, Doherty T.The present study reports on the management of an EHV-1 outbreak at a large, multi-week equestrian event with ongoing showing. Within a 48 h period, 8 horses out of a cohort of 38 horses from the same trainer displayed elevated rectal temperatures ranging from 38.4 to 39.0 °C. Initial testing using a point-of-care PCR assay detected EHV-1 in 2/8 horses, with the results being confirmed at a later time by qPCR. As a precautionary measure and because of the inability to isolate the entire at-risk population, the 38 horses were relocated to an equine facility outside the equestrian event for dai...
Erratum for “Risk Factors and Long-Term Outcomes in Horses After the 2021 Outbreak of Equine Herpesvirus 1 Myeloencephalopathy, Valencia, Spain”.
Journal of veterinary internal medicine    April 11, 2025   Volume 39, Issue 3 e70084 doi: 10.1111/jvim.70084
No abstract available
The Effect of Vaccination Status on Total Lymphocyte Count in Horses Affected by Equine Herpes Virus-1 Myeloencephalopathy.
Animals : an open access journal from MDPI    April 1, 2025   Volume 15, Issue 7 doi: 10.3390/ani15071019
de la Cuesta-Torrado M, Vitale V, Velloso Alvarez A, Neira-Egea P, Diss C, Cuervo-Arango J.Equine herpesvirus 1-induced myeloencephalopathy has a significant impact on the equine industry. Nevertheless, the clinical variables that may affect the severity of the disease are still under investigation. The objective of this research is studying the relationship between the level of lymphopenia and vaccination status with the severity of the disease in horses at an event, considering whether they had been correctly vaccinated or not prior to exposure to EHV-1. Ten horses were admitted to a veterinary teaching hospital following an equine herpesvirus myeloencephalopathy outbreak during a...
[Correction: Statement on the efficacy and immunological safety of EHV vaccines in horses].
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    March 26, 2025   Volume 53, Issue 1 e1 doi: 10.1055/a-2560-3065
No abstract available
Increase in Virus-Specific Mucosal Antibodies in the Upper Respiratory Tract Following Intramuscular Vaccination of Previously Exposed Horses Against Equine Herpesvirus Type-1/4.
Vaccines    March 10, 2025   Volume 13, Issue 3 290 doi: 10.3390/vaccines13030290
Wagner B, Schnabel CL, Rollins A.Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and incomplete viral replication at the URT. Here, we tested whether intramuscular (i.m.) vaccination with a commercial inactivated EHV-1/4 vaccine can induce mucosal antibodies (mucAbs) at the URT. Methods: Adult horses with complete EHV-1 vaccination and/or exposure histories were vacc...
Risk Factors and Long-Term Outcomes in Horses After the 2021 Outbreak of Equine Herpesvirus 1 Myeloencephalopathy, Valencia, Spain.
Journal of veterinary internal medicine    March 9, 2025   Volume 39, Issue 2 e70040 doi: 10.1111/jvim.70040
de la Cuesta-Torrado M, Velloso Alvarez A, Santiago-Llorente I, Armengou L, Nieto F, Ríos J, Cruz-López F, Jose-Cunilleras E.Equine herpesvirus myeloencephalopathy (EHM) is a persistent threat to horses, with unclear risk factors and disease severity. Objective: To evaluate risk factors, effective reproduction rate (Rt), and long-term athletic outcomes of an EHM outbreak. Methods: Retrospective study of the 2021 EHM outbreak in Valencia, Spain, examining associations between risk factors (sex, age, breed, country of origin, and vaccination status) and case fatality rate, EHM development, and odds of returning to competition using odds ratios [95% CI] and Rt via the Robert Kochs Institute method. Results: Among 191 h...
The Genomic Characterization of Equid Alphaherpesviruses: Structure, Function, and Genetic Similarity.
Veterinary sciences    March 3, 2025   Volume 12, Issue 3 228 doi: 10.3390/vetsci12030228
Liu D, Zhao X, Wang X.Equine herpesvirus 1 (EHV-1), EHV-4, EHV-8, and EHV-9, are classified within the subfamily and are recognized as causative agents of respiratory, urogenital, and neurological disorders in horses. These viruses, collectively referred to as αEHVs, exhibits both unique and shared characteristics in terms of host interaction, pathogenesis, epidemiology, and immune evasion, which arise from both the identities and discrepancies among respective genomic homologs. The genomic architecture of αEHVs is similar to other members of the same subfamily, such as well-known HSV-1, VZV, and PRV. However, r...
Detection of equid alphaherpesvirus 1 in serum samples collected from infected horses. Tsujimura K, Bannai H, Kambayashi Y, Nemoto M, Ohta M.Equid alphaherpesvirus 1 (EqAHV1; Orthoherpesviridae, Varicellovirus equidalpha1) spreads by viremia to susceptible organs. Because EqAHV1 circulates in the bloodstream in a cell-associated manner, serum samples are not considered valuable for detecting EqAHV1 and have therefore not been tested by highly sensitive detection methods such as real-time PCR (rtPCR). We investigated whether EqAHV1 could be detected by this method in equine serum samples. We performed rtPCR on archived sera and peripheral blood mononuclear cells (PBMCs) collected from 3 horses experimentally inoculated with EqAHV1. ...
Evaluation of Celastrol Antiviral Activity Against Equid Alphaherpesvirus Type 8 Infection.
Viruses    February 28, 2025   Volume 17, Issue 3 doi: 10.3390/v17030347
Yu Y, Wang J, Ruan L, Chen L, Khan MZ, You A, Wang C, Li L, Ren H, Wang T, Liu W.Equid alphaherpesvirus type 8 (EHV-8) is a contagious pathogen that causes reproductive disorders, respiratory diseases, and viral encephalitis in equids, resulting in significant economic losses for the global horse and donkey industries. Currently, there are no approved antiviral drugs or vaccines available for EHV-8 control. In this study, we investigated the antiviral efficacy of celastrol against EHV-8 both in vitro and in vivo. Our results demonstrated that celastrol significantly inhibited EHV-8 infection in Rabbit kidney (RK-13) and equine dermal cells (NBL-6) in a dose-dependent manne...
Detection and genetic characterization of equine viruses in Sweden using viral metagenomics.
BMC veterinary research    February 27, 2025   Volume 21, Issue 1 119 doi: 10.1186/s12917-025-04613-2
Blomström AL, Källse A, Riihimäki M.Viral infections pose a significant challenge to the equine population, compromising welfare and causing substantial economic losses for the global equine industry. While numerous equine viral pathogens have been identified, many suspected viral infections remain undiagnosed. This highlights the need for further identification and characterization of viruses circulating within the equine population. In this study, we utilized viral metagenomics to investigate viruses present in serum samples and nasal swabs collected from horses in Sweden. The primary focus was on horses presenting with fever,...
[Statement on the efficacy and immunological safety of EHV vaccines in horses].
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    February 18, 2025   Volume 53, Issue 1 39-48 doi: 10.1055/a-2518-1976
In February 2021, a serious EHV-1 outbreak occurred at an international jumping competition in Valencia, with several subsequent outbreaks in various European countries. As a consequence, several equestrian associations introduced compulsory vaccination against EHV-1, and in the immediate aftermath of the outbreak, demand for EHV vaccinations increased sharply. The initial concern has now dissipated. One equestrian association has abolished the compulsory vaccination that had only been introduced a year before, and a general debate began questioning the efficacy and safety of EHV-vaccines. Thi...
[Guidelines for the vaccination of horses – 5th edition].
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    February 18, 2025   Volume 53, Issue 1 33-38 doi: 10.1055/a-2517-4204
Vaccination is one of the most important measures for preventing infectious diseases. Vaccinations against tetanus and West-Nile-Virus are essential to protect the individual horse. These infections are not contagious and are not transmitted from animal to animal. By contrast, Equine Influenza and Equine-Herpes-Virus infections are highly contagious, transmissible diseases. In addition to protecting the vaccinated individual, vaccinating as many horses as possible aims at inducing a broad herd immunity, which interrupts infection chains and thus additionally protects the individual. Vaccinatio...
Investigation of the role of exercise in the detection of selected respiratory pathogens from nose wipes collected from healthy horses.
Journal of equine veterinary science    February 8, 2025   Volume 146 105377 doi: 10.1016/j.jevs.2025.105377
Wright CA, Lawton K, Barnum S, Craig BW, Farwell BR, Blea J, McCook C, Pusterla N.This study aimed to determine if exercise increases the frequency of selected respiratory viruses/bacteria shedding in non-clinical horses using nose wipes. Nose wipes were taken pre- and post- exercise from 133 healthy horses of various ages and disciplines. Wipes were assayed for the presence of selected common (equine herpesvirus-1 (EHV), EHV-4, S. equi spp equi) and commensal (EHV-2, EHV-5, S. equi spp zooepidemicus) respiratory pathogens. The frequency of detection increased significantly (p < 0.05) in the post-exercise wipes for EHV-1, EHV-2, EHV-5, and S. zooepidemicus. EHV-4 and S. ...
Molecular and Serological Investigation of Equine Herpesvirus Type 1 (EHV-1) and Type 4 (EHV-4) in Horses In Ibagué, Tolima.
Veterinary medicine international    January 29, 2025   Volume 2025 1661949 doi: 10.1155/vmi/1661949
Petano-Duque JM, Urueña-Martinez E, Cabezas-Callejas LL, Perilla-Amaya J, Rueda-García V, Rondón-Barragán IS, Lopera-Vásquez R.EHV-1 is one of the most prevalent viral pathogens in horses; however, its prevalence is not well defined by cross-reactions of serological tests. Thus, this study aims to determine EHV-1/-4 prevalence in Colombian creole horses from Ibagué, Tolima, using molecular techniques, as well as to determine possible risk factors associated with viral infection. A cross-sectional study was carried out in 110 equines blood, serum, and semen samples from Ibagué, Tolima. Antibodies against EHV-1/-4 were determined through indirect ELISA. EHV-1 was detected by amplifying the glycoprotein H gene through ...
Investigation of the frequency and selected prevalence factors of equid alphaherpesvirus 4 viremia in horses with acute onset of fever and respiratory signs. Pusterla N, Barnum S, Lawton K, Craig B, James K.Equid alphaherpesvirus 4 (EqAHV4; Orthoherpesviridae, Varicellovirus equidalpha4; equine rhinopneumonitis virus) has seldom been associated with complications such as abortion and myeloencephalopathy, given the low tendency of this virus to induce viremia. We investigated the frequency of EqAHV4 viremia in horses with fever and respiratory signs. Case selection included all equids with EqAHV4 quantitative real-time PCR (qPCR)-positive nasal secretions (defined as EqAHV4 qPCR-positive cases) submitted to a diagnostic laboratory. Controls consisted of each case submitted before and after each Eq...
Equine Herpesvirus-1 Induced Respiratory Disease in Dezhou Donkey Foals: Case Study from China, 2024.
Veterinary sciences    January 14, 2025   Volume 12, Issue 1 56 doi: 10.3390/vetsci12010056
Ruan L, Li L, Yang R, You A, Khan MZ, Yu Y, Chen L, Li Y, Liu G, Wang C, Wang T.Equine herpesvirus-1 (EHV-1) is a significant pathogen that causes substantial economic losses in the equine industry worldwide, which leads to severe respiratory diseases and abortions in horses. However, reports of EHV-1 infection in donkeys are limited, particularly in China. This case study reported an EHV-1-induced respiratory disease in Dezhou donkey foals in Shandong Province, China, in July 2024. Three one-month-old foals exhibited high fever, nasal discharge, and respiratory distress, with a 100% mortality rate. The causative agent, strain LC126, was isolated from a one-month-old donk...
Genomic analysis and replication kinetics of the closely related EHV-1 neuropathogenic 21P40 and abortigenic 97P70 strains.
Veterinary research    January 13, 2025   Volume 56, Issue 1 12 doi: 10.1186/s13567-024-01434-3
Mohamed E, Zarak I, Vereecke N, Theuns S, Laval K, Nauwynck H.Varicellovirus equidalpha 1, formerly known as Equid alphaherpesvirus 1 (EHV-1), is highly prevalent and can lead to various problems, such as respiratory problems, abortion, neonatal foal death, and neurological disorders. The latter is known as equine herpes myeloencephalopathy (EHM). Cases of EHM have significantly increased since the beginning of the twenty-first century. The genomic sequences of five isolates associated with the fatal neurological outbreak in Valencia, Spain, in 2021 were analyzed and documented. The genome and replication kinetics of the Belgian EHM isolate 21P40, associ...