Open Veterinary Journal, (2024), Vol. 14(10): 2525–2538

Review Article

10.5455/OVJ.2024.v14.i10.3

Infectious bovine rhinotracheitis: Unveiling the hidden threat to livestock productivity and global trade

Rimayanti Rimayanti^1*, Aswin Rafif Khairullah², Tita Damayanti Lestari¹, Ikechukwu Benjamin Moses³, Suzanita Utama¹, Ratna Damayanti⁴, Sri Mulyati¹, Hartanto Mulyo Raharjo⁵, Muhammad Khaliim Jati Kusala², Ricadonna Raissa⁶, Syahputra Wibowo⁷, Syafiadi Rizki Abdila⁸, Kartika Afrida Fauzia^9,10, Sheila Marty Yanestria¹¹, Ima Fauziah² and Josephine Elizabeth Siregar⁷

¹Division of Veterinary Reproduction, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

²Research Center for Veterinary Science, National Research and Innovation Agency (BRIN), Bogor, Indonesia

³Department of Applied Microbiology, Faculty of Science, Ebonyi State University, Abakaliki, Nigeria

⁴Division of Basic Veterinary Medicine, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

⁵Division of Veterinary Microbiology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

⁶Department of Pharmacology, Faculty of Veterinary Medicine, Universitas Brawijaya, Malang, Indonesia

⁷Eijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Bogor, Indonesia

⁸Research Center for Structural Strength Technology, National Research and Innovation Agency (BRIN), Tangerang, Indonesia

⁹Research Center for Preclinical and Clinical Medicine, National Research and Innovation Agency (BRIN), Bogor, Indonesia

¹⁰Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan

¹¹Faculty of Veterinary Medicine, Universitas Wijaya Kusuma Surabaya, Surabaya, Indonesia

*Corresponding Author: Rimayanti Rimayanti. Division of Veterinary Reproduction, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia. Email: rimayanti [at] fkh.unair.ac.id

Submitted: 07/07/2024 Accepted: 18/09/2024 Published: 31/10/2024

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Abstract

An infectious disease called infectious bovine rhinotracheitis (IBR) can lead to a number of disorders affecting cattle’s respiratory system. The disease is caused by bovine alphaherpesvirus type 1 (BoAHV-1). Based on antigenic and genetic characteristics, BoAHV-1 strains are divided into subtypes 1.1, 1.2a, 1.2b, and 1.3. IBR is currently widespread throughout the world, with the exception of a few nations that have achieved eradication. The most significant characteristic of this illness is that, after a clinical or subclinical infection, the virus typically establishes a latent condition that can later be reactivated in the presence of stress, immunosuppressive conditions/substances, or other diseases. Primarily, the virus spreads by direct or indirect contact between animals. It may also be transmitted via the reproductive system, causing infectious balanoposthitis or vulvovaginitis. Most virus subtypes are associated with reproductive failure, such as fetal or embryonic resorption and abortions. The virus may also be transmitted through semen, which could lead to genital transfer. Bovine herpesvirus type 1 (BoHV-1) infection produces a variety of lesions. Lesion in the mucosal surface usually consists of white necrotic material. Regular methods for diagnosing BoHV-1 infections include isolation in cell culture, enzyme linked immunosorbent assay, virus neutralisation test, and methods based on identification of nucleic acids, like PCR. The interplay of several host, pathogen, environmental, and management factors affects the spread of IBR. Through its impacts on health and fitness, IBR can lead to production losses. In order to minimize the severity of clinical signs and stop the infection from spreading, the veterinarian may advise that sick or at-risk animals be placed under immediate isolation and vaccinated (such as intranasal vaccination, including the use of both killed and live attenuated virus vaccines) as soon as an IBR diagnosis is obtained.

Keywords: BoHV-1, Cattle, IBR, Infectious disease, Virus.

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Introduction

Infectious bovine rhinotracheitis (IBR) is a condition that can lead to a number of disorders affecting cattle’s respiratory systems (Wang et al., 2023). The disease is caused by bovine alphaherpesvirus type 1 (BoAHV-1) which belongs to the Herpesviridae family, subfamily Alphaherpesvirinae, and genus Varicellovirus (Kaddour et al., 2019). The illness was initially identified as a respiratory condition affecting feedlot cattle in the United States in 1955 (Graham, 2013). IBR is a significant illness that affects cattle with typical signs such as runny nose and eyes, pyrexia (high temperature), decreased appetite, ulceration of mouth and nose, reduced milk yield, abortion, and death in severe cases (Hostnik et al., 2021). The term “infectious pustular balanoposthitis (IPB)” refers to Bovine herpesvirus type 1 (BoHV-1)-mediated clinical syndromes/disease in bulls, whereas and “infectious pustular vulvovaginitis (IPV)” is the name of the clinical syndromes/disease in females (Pandey et al., 2014). BoHV-1 primarily infects cattle; however, it is increasingly being detected in other ruminant animals such as buffalo and domesticated bison. The disease seriously impairs animal products exchange and costs the global livestock industry more than $3 billion annually in losses (Ortiz-González et al., 2022).

BoHV-1 infection primarily affects animals older than 6 months in most cases (Brock et al., 2020). There are now two identified subtypes of BoHV-1, which are further subdivided into subtypes. Subtype 1 comprises strains responsible for respiratory complications, such as IBR, typified mainly by exudative rhinotracheitis affecting the cattle’s nose, trachea, and bronchi (Ostler and Jones, 2023). Subtype 2 is made up of strains that can lead to reproductive issues such IPV and IPB (Righi et al., 2023). The virus can be transmitted directly through the air or through contact with excrement from the eyes, respiratory system, or reproductive system of infected animals (Pastenkos et al., 2018). The virus can spread indirectly through contaminated objects, people, semen, and embryo transfer (Benavides et al., 2021).

The most significant characteristic of BoAHV1, like other alphaherpesviruses, is that the infection typically establishes a latent condition that may eventually be reactivated in the presence of immunosuppressive conditions or substances (Bettini et al., 2023). In the latent condition, the animal gets infected and harbours the virus for the rest of its life without showing any visible and strong signs; as such, the removal of the infected animal is challenging (Canova et al., 2024). Reactivation of the latent virus occurs when animals with a latent infection with BoHV-1 are exposed to various stressors, such as harsh weather and immunosuppressive therapy (Toomer et al., 2022). This allows the virus to spread to other animals.

IBR can cause discomfort, fever, respiratory issues, as well as a decrease in appetite, milk output, and body weight (Nettleton and Russell, 2017). There are biotic, environmental, and climatic factors that affect the incidence of IBR transmission and dispersion (Uwishema et al., 2023). In crowded settings, the disease’s transmission is more likely to occur (Engdawork and Aklilu, 2024), and the survival of viruses increases in lower temperatures (Ostler and Jones, 2023). The virus can be identified from swabs of nasal and vaginal secretions as well as from other tissues during necropsy (Yatsentyuk et al., 2022). Furthermore, a range of molecular and serological methods are available for the diagnosis of IBR. Disease control is challenging due to the latent nature of IBR infection and the lack of a specific treatment (Bettini et al., 2023). However, biosecurity protocols including movement restrictions, testing and quarantine, and immunization are crucial for managing and preventing IBR (Ackermann and Engels, 2006; Engdawork and Aklilu, 2024).

The global expansion of IBR illness has resulted in significant economic losses due to decreased livestock productivity, increased rates of morbidity and mortality, and limitations on international trade (Iscaro et al., 2021). The aim of this review is to explain the etiology, history, epidemiology, pathogenesis, immune response, pathology, clinical signs, diagnosis, differential diagnosis, transmission, risk factors, economic impact, treatment, and control of IBR.

Etiology

There are currently eight herpes viruses that can naturally infect cattle, the most significant of which is BoAHV-1 (Barrett et al., 2024). This virus belongs to the family Herpesviridae, subfamily Alphaherpesvirus, genus Varicellovirus (Ostler and Jones, 2023). It shares close kinship with the human herpesvirus type 3 varicella-zoster virus (chickenpox) and the pseudorabies virus (Suid herpesvirus type 1) (Davison, 2010). This virus is about 150 nm in diameter with an enclosed icosahedral capsid that contains double-stranded DNA and codes for about 73 different proteins (Barber et al., 2017). A thorough sequencing of the BoHV-1 genome has revealed that it encodes about 35 virion proteins that are identical to those of human herpesviruses from a previous report (Tan et al., 2023).

The herpesvirus proteins labeled g (for glycoprotein) and a letter identifying their identification are among the minimum 10 envelope glycoproteins found in the BoHV-1 virion proteins (Barber et al., 2017). gB is the primary envelope glycoprotein (Marawan et al., 2021). Each gene from BoHV-1 has been shown to be either necessary or non-essential for the virus to grow in culture by means of deletion or mutation. Viruses with the non-essential gene for glycoprotein E (gE) removal proliferate well in cell culture and can be employed as vaccine markers because, unlike cattle infected with the BoAHV-1 field strain, vaccinated animals do not develop an antibody response to gE (Petrini et al., 2019).

There is little chance that new antigenic variants will emerge because BoAHV-1 isolates share antigenic and genetic characteristics and are stable (Tan et al., 2023). Restrictions endonuclease analysis and viral peptide patterns allow isolates to be classified into two primary subtypes: BoHV-1.1 and BoHV-1.2 (Zhou et al., 2020). Subtype 1.1 included isolates from severe respiratory diseases that were initially observed in North American feedlots, while subtype 1.2 included early European virus isolates that were mostly linked to minor respiratory diseases and genital infections (d’Offay et al., 2016). A further division of subtype 1.2 is made into 1.2a and 1.2b. Subtype 1.1 is now thought to be the most common, with subtypes 1.2b and 1.1 only thought to occur in North America (Petrini et al., 2019). Compared to calves infected with the BoHV-1.2b strain, cows infected with the BoHV-1.1 strain shed 10–100 times as much virus and had a higher propensity to transmit the infection (Graham, 2013). Isolates of BoHV-1.1 and BoHV-1.2b have been found in respiratory disease cases in North America (Steukers et al., 2011). Intravenous administration of specific BoAHV-1 strains to pregnant heifers demonstrated the ability of strains 1.1 and 1.2a to induce abortion, while strain 1.2b infected the fetus but did not result in fetal mortality (Ostler and Jones, 2023).

BoHV-1, which causes neurological pathology, was previously categorized as BoHV-1.3; however, alterations in its antigenic and genomic characteristics caused it to be reclassified as a different species of bovine herpesvirus type 5 (BoHV-5) (Dagalp et al., 2020). A previous study reported some cross-protection between BoHV-1 and BoHV-5, suggesting some antigenic similarity (Kumar et al., 2020). The BoHV-1 genome was recently sequenced, and the results indicated that the previously identified viral subtypes represent genome sequence similarity. BoHV-1.1 and 1.2b strains share at least 99% nucleotide sequence identity within each subtype, but only 2.5% identifies them as being different from one another (Chen et al., 2018). Conversely, the sequence identities shared by BoHV-1 and BoHV-5 are less than 85% (Kumar et al., 2020).

The vaginal or respiratory tracts have also been reported not to exhibit any specific tropism to BoAHV-1 isolates (Steukers et al., 2011). The IBR strain replicated effectively in the vaginal epithelium and the IPV strain replicated well in the nasal epithelium in experiments, suggesting that the route of infection influences clinical presentation more than the strain of the virus (Biswas et al., 2013). Viruses genetically and antigenically related to BoAHV-1 are carried by several ungulate species.

BoAHV-1 and BoAHV-5 are among a group of related alphaherpesviruses that have been isolated from buffaloes, raindeer, goats, elk, and red deer (Yatsentyuk et al., 2022).

History

In 1841, Trommsdrof and Buchner in Germany reported the first cases of BoHV-1 infection in animals, characterized by reproductive abnormalities like IPV (Graham, 2013). In 1928, Reimann and Reisinger made the initial suggestion that viruses were linked to this sickness (Osman et al., 2017). In the 1950s, the emergence of new forms of respiratory infections such as IBR became known in America (Nettleton and Russell, 2017). The term “IBR” was coined during a 1955 US Livestock Sanitary Association meeting in response to the 1950–1954 outbreak of “red nose,” “dust pneumonia,” “necrotizing rhinotracheitis,” and “necrotic rhinitis” in cattle feedlots and dairy farms in the western United States (Graham, 2013).

The first time the virus was recognized was in 1958, when its antigenic identity was found. The herpes virus, also known as the IBR virus (IBRV), was thereafter identified as the cause in the mid 1950s (Çeribasi et al., 2016). IBRV was formally designated as (BHV-1 or, more recently, BoHV-1) when more livestock herpesviruses were found in the 20th Century (Bahari et al., 2013). Currently, BoHV-1 is widely distributed worldwide, as evidenced by samples found in the US, Canada, Zaire, Italy, Belgium, India, and Turkey (Dagalp et al., 2020; Ince and Sevik 2022). Cattle is the natural host of IBRV, which is extremely contagious and frequently manifests as inflammation of the trachea and nose (Fulton, 2009).

Though sexually transmitted infections in cows and bulls were known in Europe prior to their introduction into the US, IBR is presently the most prevalent disease in cattle arising from BoHV-1 infection (Hostnik et al., 2021). The sexually transmitted BoHV-1 diseases became known as IPV in female cattle and IPB in male cattle. In 1963, it was discovered that early herpesvirus isolates from IPV and IPB cases in the US and Europe were comparable to IBRV (Majumder et al., 2015).

Epidemiology

A viral disease called IBR significantly affects cattle productivity all around the world (Ortiz-González et al., 2022). This disease results in large financial losses for the dairy and beef industries. IBR typically occurs when an infected animal is introduced into a herd or when a number of cattle are kept in close quarters in a feedlot (Waldeck et al., 2021). Cattle can contract this disease from both domestic (goats) and wild (deer) ruminants, which can also spread the virus (Thiry et al., 2006). The most significant epidemiological feature of BoHV-1 is that infection typically results in latency (Ostler and Jones, 2023). IBR frequently causes case mortality because of its synergism with bacterial illnesses, particularly pasteurellosis, and other viral infections including bovine viral diarrhea (Gomez-Romero et al., 2021).

IBR is currently widespread throughout the world, with the exception of a few nations that have achieved eradication (Ackermann and Engels, 2006; Engdawork and Aklilu, 2024). The illness has been completely eradicated in Austria, Denmark, Finland, Sweden, Switzerland, and Norway; in contrast, IBR control operations are being carried out in Australia, Belgium, Canada, India, Poland, Turkey, and the United States (Boelaert et al., 2005; Ackermann and Engels, 2006; Engdawork and Aklilu, 2024). Numerous investigations have been carried out worldwide to ascertain the seroprevalence of IBR in cattle (Ortiz-González et al., 2022).

Despite the disease’s global distribution, there are notable regional variations in its incidence and prevalence. At the moment, IBR is spreading rapidly throughout Asia, Latin America, and Africa (Engdawork and Aklilu, 2024). The primary elements influencing transmission of the disease include breeding systems, geographic location, and disease control techniques. It is challenging to control and eradicate the disease in nations (especially Asia, Africa, and Latin America) with the disease prevalence due to the latent nature of the virus (Petrini et al., 2022).

Pathogenesis

Primary infection

Newborn calves are usually immune to illness if they consume colostrum containing high levels of lipid peroxidation malondialdehyde (MDA) against BoHV-1 (Petrini et al., 2020a). MDA against BoHV-1 is typically not found until 4–6 months of age, and in exceptional cases, not till 9 months. Calves with MDA are immune to the disease, but they can still get infected and have late onset without showing any humoral immune response (Righi et al., 2023). Calves with MDA are the rarest of animals known as seronegative latent carriers.

When older calves are infected by BoHV-1 in the nasal region, the virus multiplies quickly in the upper respiratory tract. The maximal viral titers, which are typically 10⁷ to 10⁸ infectious particles/ml of nasal secretions, appear 3–6 days later (Jones, 2019). Nasal swabs can reliably yield infectious virus recovery for 10 days. Eye swabs can be used to detect the virus for up to 8 days after it spreads to the eyes (Marawan et al., 2021). Clinical signs start to show 2–3 days following infection and include fever (40°C to 42°C), dullness, and discharge from the eyes and nose (Ostler and Jones, 2023). The discharge is initially serous, but as a nasal ulcer develops on day 5, it becomes mucoid and eventually mucopurulent (Biswas et al., 2013). There is frequently halitosis and coughing. Clinical signs might last up to 10 days, after which the animal often makes a remarkable recovery given the mucosal injury (Muylkens et al., 2007). Purulent rhinotracheitis and pneumonia can result in death, and additional bacterial infections impact the disease’s severity (Nettleton and Russell, 2017). Although viral replication is restricted to the respiratory tract, animals can also experience brain invasion and low, hard-to-detect levels of viremia (Stults et al., 2022).

The generation of interferon and humoral and cellular immunity, in the immunological response to an initial BoHV-1 infection, all aid in the recovery process (Dummer et al., 2014). Serum levels of specific antibodies peak 2–3 weeks after infection, with detection beginning 10 days after infection. The type of virus causing the infection and the sensitivity of the laboratory test being utilized can affect the duration of the detection period (Barrett et al., 2024). Any cow with antibodies to BoHV-1 usually harbours a latent infection for the rest of their lives and pose a threat to other animals (Benavides et al., 2020).

Latency

Through terminal sensory neurons innervating the diseased mucosa, neuroinvasion during primary respiratory infections happens quickly (Stults et al., 2022). Via the trigeminal nerve, the virus ascends to the central nervous system, where latent infection predominantly manifests as an initial, transient lytic infection in the trigeminal ganglion (Muylkens et al., 2007). Viral gene expression stops during latency, and there is no discernible viral DNA replication. Virus-encoded genes, particularly those that express BoHV-1 latency-associated transcripts, which stop the virus from replicating, are responsible for maintaining the latent state of the virus (Farooq et al., 2019). The immune system’s development in tandem with the virus’s establishment of latency undoubtedly contributes to the virus’s confinement in the ganglia while it is in its latent form (Chowdhury et al., 2021). There is data that suggests the tonsils and possibly peripheral blood leukocytes are potential minor latency sites (Favier et al., 2014). A significant contributing aspect to the virus’s effectiveness is its capacity to endure in all infected animals in the face of a strong immune response.

Reactivation

Reactivation from latency happens when an animal undergoes stress for any of the following reasons: transport, herd structure changes, introduction to new animals, calving and the start of lactation, poor nutrition, concurrent diseases, debilitating weather and high doses of corticosteroids (e.g., 0.1 mg/kg daily for 5 days) (Toomer et al., 2022).

Viral amplification happens at the site of viral entrance, where the reactivated infectious virus passes via the nerves and may or may not cause clinical signs and viral re-excretion (Khaneabad et al., 2023). Reactivation might happen often or not at all over extended periods of time. Although it is impossible to forecast when the virus may reactivate and propagate, animals with high antibody titers are less likely to re-shed the virus (Ruiz-Sáenz et al., 2013). Antibody levels in animals with low antibody titers will rise with reactivation and re-excretion (Furtado et al., 2014).

Herpes virus reactivation brought on by stress is still being thoroughly investigated, particularly in connection to human illness. The intricate interplay among the immunological, endocrine, and neurological systems must underlie the molecular processes that connect viral reactivation, cell cycle regulation, and cellular stress. These processes are gradually coming to light (Khaneabad et al., 2023).

Immune response

A live IBR vaccine or an IBR viral infection causes the immune system’s humoral and cell-mediated components to become active. Serum neutralization tests are typically used to measure the humoral reaction, which has historically been used as a proxy for resistance and a prior infection signal (Petrini et al., 2019). A growing body of research indicates that the establishment of resistance after recovering from the original BoHV-1 infection entails the immune response being mediated by local tissue cells (Dwiyatmo et al., 2021). Consequently, serum neutralizing antibody levels may not always be a reliable measure of immunity. Still, neutralizing antibodies will continue to be the foundation of IBR immunologic considerations until better serologic alternatives are acknowledged (Chase et al., 2008). Hence, it is possible to classify cattle as partially immune if they have actively produced serum antibodies. Both a good vaccine and a natural infection can promote this partial immunity (Righi et al., 2023). Long-term persistence of immunity/antibodies is possible, but in order to keep it at detectable levels, it may occasionally need to be re-stimulated by endogenous virus release or exogenous exposure (Raaperi et al., 2014).

Cattle that are partially immune may get superficial infections on their mucosal surfaces, but they are less likely than susceptible cattle that have a primary infection to develop a serious systemic illness (Fulton, 2009). If vaccinations are administered before pregnancy, cows will not be susceptible to abortion due to IBR. Since some inactivated vaccinations may not help cattle to survive a deadly challenge even if they have detectable antibodies, cellular immunity may be the primary means of protection (Petrini et al., 2020a).

Colostrally obtained antibodies appear in the serum of weaning calves (Lemaire et al., 2000). Depending on the amount of colostrum consumed and the effectiveness of intestinal absorption, the duration of this passive immunity varies from calf to calf and is quickly reduced through metabolic breakdown (Hajihashemi et al., 2024). Some calves may have detectable antibodies at 6 months of age, whereas some shed their mother’s antibodies as early as 1 month (Chase et al., 2008).

There is ongoing debate on the protective properties of BoHV-1 antibodies. Their protective benefit has been demonstrated in controlled laboratory research (Nettleton and Russell, 2017). Certain vaccinations, particularly those given intranasally, have been proposed to be enough for actively immunizing calves that have passively acquired immunity (Windeyer and Gamsjäger, 2019). Nevertheless, success with vaccination against BoHV antibodies is not assured. Therefore, in order to ensure long-term protection, calves that received their vaccinations prior to the age of 4 months should receive another dose (Petrini et al., 2022).

Pathology

BoHV-1 infection produces a variety of lesions. A lesion that occurs at the mucosal surface usually consists of white necrotic material (Martínez-Burnes et al., 2024). These lesions are frequently called plaques. These lesions which are made up of necrotic epithelial cells, fibrin, and leukocytes, are the consequence of many merging pustules (Fathima et al., 2023). Histological characteristics of the lesions are intranuclear inclusion bodies. Lesions frequently develop at the infection site or in other target organs once macrophages have spread the virus throughout the body (Petrini et al., 2022). It frequently develops in the trachea and nasal passageways of the respiratory system, leading to upper respiratory tract illness (Callan and Garry, 2002). The tracheal mucosa may be blocked and present petechial hemorrhages, ecchymoses, and mucopurulent material, in addition to pustular lesions (López and Martinson, 2017). The identical lesion on the mucosal surface of the reproductive system is known as infectious balanoposthitis in bulls and IPV in cows (Righi et al., 2023). The typical lesion in organ parenchyma is localized necrosis (Crook et al., 2012). Compared to adult animals, aborted fetuses and newborn calves are more likely to experience severe systemic consequences (Jawor et al., 2021).

Clinical signs

The clinical signs due to BoHV-1 include the following contagious and acute illnesses which affects the respiratory and reproductive systems:

Respiratory infection

Respiratory infection is most frequently identified in animals kept in intensive systems, and it is occasionally absent from animals kept in grazing environments (Fernández et al., 2020). Animals infected with BoHV-1 are usually affected by anomalies common to multiple infections that need to be confirmed through laboratory testing (Graham, 2013). The period of incubation is 4–7 days. A simple infection may just cause a slight increase in body temperature and modest serous nasal discharge for 1–2 days during the course of the disease (Jones, 2019). Many cases are overlooked. Fever between 40°C and 42°C may appear in more severe cases, and may also temporarily stop for a few days (Martínez-Burnes et al., 2024).

Affected animals experience depression, exhibiting elevated heart rates and reduced milk yield (Nettleton and Russell, 2017). Sometimes, within a few days, nasal discharge turns mucopurulent. The nasal mucous membrane turns red, and superficial erosion are visible (Caswell et al., 2012). Certain animals drool excessively. Surface erosions of the oral mucosa are among the frequently occurring oral lesions (Damena, 2024). Certain animals get clear discharge from their conjunctiva in one or both eyes, which later turns mucopurulent (Biswas et al., 2013). Pneumonia and severe necrotizing laryngotracheitis in feedlots and other intensively managed farms can be made worse by secondary bacterial contamination (Risalde et al., 2013). Usually, the illness manifests itself in the first 3–4 weeks following the animal’s feedlot entry. From time to time, after entering the feedlot, a serious pneumonia outbreak may occur as a result of exposure to BoHV-1 (Hay et al., 2016). It has been common to observe abortions when a BoHV-1 infection causes respiratory difficulties (Khaneabad et al., 2023).

Reproductive infection

BoHV-1 reproductive infection is a disease that affects both sexes and is typically a sign of herpes virus infection in pastured dairy cattle (Elhassan et al., 2015). This infection can cause erosions, ulcers, pustules, and vesicles on the vaginal mucosa, as well as on the prepuce and penis (Chatterjee et al., 2016).

Balanoposthitis: Pustules on the mucosal surface of the prepuce and penis are indicative of the condition known as IPB in bulls, which takes 2–3 days to incubate (Saha et al., 2010). The male cannot mate because these pustules can cause pain with mucopurulent discharge (Muylkens et al., 2007). Bulls with the virus can also shed it through their semen. Contaminated semen can then spread to vulnerable females through artificial insemination or natural mating (El-Mohamady et al., 2020).

Vulvovaginitis: It is a painful condition that can be identified after mating and is also known as IPV (Nuotio et al., 2007). The primary signs are recurrent urination and possible edema or hyperemia in the vulva and posterior portion of the vagina (Fischer and Bradford, 2021). Tiny white to pink boils develop into pustules. A thick mucopurulent discharge that is yellow or white may be seen, particularly in cases when a subsequent bacterial infection is a consequence (Chatterjee et al., 2016).

Conjunctivitis: This uncommon form of BoHV-1 infection is similar to “pink eye” (Kneipp, 2021). Typically, corneal involvement and panophthalmitis are possible. In certain situations, conjunctival irritation is the most observable sign of an infection (O’Toole and Li, 2014).

Diagnosis

At the moment, diagnostic techniques are exclusive to lab settings and necessitate the employment of specialized technicians and adapted equipment. Several techniques, including antigen-specific monoclonal antibodies and DNA fingerprinting via boundary section detection are employed to identify the subtypes of BoHV-1. Regular methods for identifying BoHV-1 include cell culture, enzyme linked immunosorbent assay (ELISA), virus neutralisation test (VNT), and molecular methods like PCR (Dagalp et al., 2020). The most reliable method for detecting BoHV-1 is PCR, yet it has drawbacks in terms of cost, time, and sensitivity (Dima and Abdisa, 2022). Numerous PCR methods for identifying BoHV-1 have shown to be successful. For natural infections, Large Multidomain Protein Annotator has been suggested as a practical, quick, and optional molecular pathogen assay (Gulyaeva et al., 2020). Recently, full gene sequencing has become necessary to separate BoHV-1 field strains from strains in vaccines that depend on single nucleotide polymorphism (Fulton et al., 2016).

Serology

The serological VNT, competitive ELISA, and indirect ELISA are frequently used to help analyze serum for BoHV-1 antibodies (Righi et al., 2022). Indirect ELISA is most commonly employed since it takes less time to deliver findings and also convenient for testing more serum samples for BoHV-1 detection. Furthermore, finding serologically positive and healthy animals may be a useful indicator of BoHV-1 infection at the herd level (Nettleton and Russell, 2017). Therefore, when an animal is infected with BoHV-1, it is best to consider animals with antibody-positive samples (with two exceptions: serological response owing to inactivated vaccine vaccination or colostral antibodies) (Petrini et al., 2019). Consequently, IBR gE blocking ELISA distinguishes antibodies against non-existent antigens, making infected and immunized animals identifiable (Bertolotti et al., 2015). Blood samples should be taken for antibody testing during the intensive period and a follow-up testing additional 2–4 weeks because the virus can reactivate during stress or illness (Petrini et al., 2020b).

Polymerase chain reaction

In recent years, conventional PCRs targeting BoHV-1 genes have been successfully used to detect these pathogens (Diallo et al., 2011). The Uniq-10 viral DNA extraction kit can be used to extract DNA from 200 µl of infected cell cultures, including BoHV-1 and several herpes viruses (Maidana et al., 2020). Using the Revert AidTM first-strand cDNA synthesis kit, the recovered DNA can be used as a template for DNA replicon synthesis. The recovered DNA is eluted in 50 µl of nuclease-free water, and the complete template can be kept at −70°C for subsequent use (Coradini et al., 2023). RT-PCR has been shown to be the most effective technique for identifying BoHV-1 and for analyzing BoHV-1 abortions, including those from infected fetuses (Wernike et al., 2011).

Differential diagnosis

IBR differential diagnosis is related to a number of illnesses, particularly to: virus-induced diarrhea - a mucosal illness in which diarrhea typically starts and gets worse enough that a lab test is needed (Assunção et al., 2022); malignant catarrhal fever—has a high fatality rate, more variable symptoms, and sporadic occurrence (Ricer, 2015); rinderpest—an enzootic-epizootic disease that has a high death rate and a harsh course of development (Roeder et al., 2013); during grazing—an animal suffering from allergic rhinitis may sneeze, exhibit dyspnea, and produce greenish-orange nasal discharge without experiencing a rise in body temperature (Mauldin and Peters-Kennedy, 2016). Additionally, consideration will be given to viral pneumonia, calf diphtheria, and pasteurellosis in the differential diagnosis (Caswell et al., 2012).

Transmission

During the initial infection, infected animals release a lot of viruses (Jones, 2019). Additionally, latently infected animals are capable of re-excreting large amounts of virus (Graham, 2013). Primarily, this virus spreads by direct contact between animals (Khaneabad et al., 2023). It may also emerge from the reproductive system, including semen, which could lead to genital transfer (Bielanski et al., 2014). Although it normally only happens over short distances, aerosol transmission can happen up to 5 m away (Mars et al., 2000). The virus can also spread indirectly inside or between herds/farms through sharing or moving contaminated persons, equipment, or facilities since it is robust enough to environmental variables (Waldeck et al., 2021). During their first few months of life, calves in infected herds are protected against clinical illness by antibodies inherited from their mothers (Meyer et al., 2023). Typically, dairy cows do not get sick until they get into a herd with older cows with possible weakend immune system. BoHV-1 antibodies were detected in 80% of bulk milk from 305 dairy farms in Ireland, according to a study by Barrett et al. (2024). When replacement heifers from the herd were examined separately at the animal level, only 5.4% of them tested positive for BoHV-1.

Risk factors

The interplay of several hosts, pathogens, environmental, and management factors affects the spread of IBR (Muylkens et al., 2007). Changes in microclimatic conditions, livestock density, and management techniques, among other things, cause the influence of risk factors to differ between areas, farms, or herds (Licitra et al., 2021). Numerous environmental and climatic conditions affect the survival and spread of BoHV-1 (Benavides et al., 2021). Conditions in the microclimate are crucial in the spread of IBR in animals.

Animal risk factors

Associated animal risk factors, including species, age, status of vaccinations, and physiological state, affect the incidence and severity of IBR in different ways (Brock et al., 2020). Domestic and wild cattle (such as Asian water buffalo, African or Cape buffalo, bison, gaur, bantengs, and yaks) are among the naturally vulnerable animal species. BoHV-1 can also infect pigs, goats, and sheep (Waldeck et al., 2021). Ruminants, both domestic and wild, have the ability to spread viruses and serve as disease reservoirs for cattle (Hostnik et al., 2021). Latently infected cattle from IBR endemic areas are known to be virus carriers and are a common source of infection (Engdawork and Aklilu, 2024). This sickness is more common in animals that are overly stressed and in animals that also have bacterial or viral diseases (Ostler and Jones, 2023). Infections that have already reached the latent stage can resurface in animals with weakened immune systems (Meurens et al., 2004).

Livestock management factors

The management of cattle has a major impact on the epidemiology of the disease. BoHV-1 can spread to all of the livestock on a farm when latently infected animals are brought in Hostnik et al. (2021). In confined pens and feedlots, high stock densities promote virus transmission through the respiratory pathway (Pastenkos et al., 2018). The impact of herd size and housing plan on the spread of disease is higher. The occurrence and spread of IBR are increased by stressful livestock management techniques and immune-suppressive environments, such as inadequate or low-quality feed and water, overcrowding, careless disease control, and the lack of necessary vaccinations (Mahmoud et al., 2009).

Environmental and climatic factors

Numerous climatic and environmental conditions affect the survival and transmission of pathogenic organisms. In seasons with low ambient temperatures, there is a comparatively high rate of virus transmission and survival (van Reenen et al., 2000). BoHV-1 is quite resistant to environmental influences. Viral survival in the environment is influenced by factors such as temperature, pH, light, humidity, and the media the virus lives in Bøtner and Belsham (2012). Virus infectivity is stable for up to 1 month at 4°C, but higher temperatures will inactivate the virus more quickly (Liu et al., 2022). In cold weather with relative humidity exceeding 90%, BoHV-1 can live for 30 days (Petrini et al., 2022). It has been observed that viruses can survive for 5–13 days in warmer settings (Torma et al., 2023). In feedstuffs, the virus can live for over 30 days in favorable environmental circumstances (Brock et al., 2021). The virus is susceptible to a wide range of disinfectants, including formalin, quaternary ammonium compounds, and phenol derivatives (Biswas et al., 2013).

Economic impact

Through its impacts on health, BoHV-1 could also lead to production losses. These effects can take the shape of respiratory issues, venereal diseases, decreased fertility, decreased milk production, and abortion (Tadeg et al., 2021). An estimated €3.1 million is lost annually in the UK as a result of this disease and its treatment (Bennett and Ijpelaar, 2005). A large-scale observation conducted in Ireland calculated that cows with multiple calf herds that tested positive for BoHV-1 in milk samples would yield an annual productivity drop of 250 l (Sayers, 2017; Barrett et al., 2024).

During a 14-day incubation period, losses resulting from decreased milk production linked to subclinical BoHV-1 infection in dairy cattle were calculated to be 9.5 l (Hage et al., 1998). A semen collection facility epidemic might be so costly that it would be necessary to remove every bull there (Oliveira et al., 2011). Nine weeks following infection, an average of 0.95 l of milk per cow was lost each day, according to modeling information from 133 farms in the Netherlands (van Schaik et al., 1999). A 2-year period of fact modeling for animals with subclinical cases in the UK indicates an estimated 2.6 l/day less of milk produced by seropositive cows than by seronegative cows (Statham et al., 2015).

Treatment

The way sick animals are treated varies depending on the circumstances. In order to minimize clinical signs and stop the infection from spreading, the veterinarian may advise that sick and at-risk animals be placed under immediate isolation and given an intranasal vaccination as soon as an IBR diagnosis is obtained (Mahan et al., 2016). Latent infections in animals are incurable with any form of treatment (Ostler and Jones, 2023). To prevent reactivation and the transmission of the BoHV-1 to other animals, latently infected animals should receive routine vaccinations (Petrini et al., 2024). Nonsteroidal anti-inflammatory medications reduce damage to the upper respiratory tract and improve the condition of the afflicted animal, making them the most crucial component of IBR treatment (Orr et al., 2014).

Vaccination

An important part of controlling and preventing IBR in animals is the vaccination of those that are susceptible. There are a number of vaccines available, including both killed and live attenuated vaccines; the selection of one relies on the vaccine’s effectiveness and the state of the disease in the nation (Righi et al., 2023). Vaccinating animals that are latently infected also lessens the quantity of infectious virus released during reactivation (Krishnagopal and van Drunen Littel-van den Hurk, 2024). To control IBR, both marker and conventional vaccinations are sold commercially. Conventional vaccinations reduce the quantity of virus shedding following infection and avoid serious clinical illness (Petrini et al., 2019). The development of next-generation vaccines involved the removal of non-essential viral glycoproteins, particularly gE from BoHV-1 (Weiss et al., 2015). This vaccine makes it possible to distinguish between animals immunized with the gE marker deleted vaccine and animals with field infection using serological antibody differentiation.

Control

Inactivated and live vaccines are available on the market, consisting of products with Differentiating Infected from Vaccinated Animals properties (Lee et al., 2012). It plays a crucial role in carrying out programs for prevention and control. The timing of vaccination depends on the age of the calf, the antibodies in the colostrum of the vaccinated animal, and the type of product used (Meyer et al., 2023). Primary/original and booster shots typically last six months, although in the case of calves, this no longer holds true for other vaccination programs that last 12 months (Chase et al., 2008). This vaccination can be given intramuscularly, intranasally, or subcutaneously, depending on the product.

There are known significant hazard factors associated with BoHV-1 infection. These generally involve the exchange (incoming or outgoing) of humans, livestock, semen, egg cells, and embryos, as well as infection through air contamination by BoHV-1 (Bielanski et al., 2014). It is necessary to take action in order to block the transmission route. In addition to providing information on the condition of the imported livestock and its group of origin, quarantine combined with serological testing might lessen the risks related to animal exchange (Benavides et al., 2021). These actions are pertinent to nations who wish to increase trade assurances, and add value with official control and eradication programs on a regional and national level. Limiting interaction between animals and animals in other groups can also be achieved by implementing measures like sufficient border fences (Waldeck et al., 2021). Short-distance aerosol transfer is another possibility (Mars et al., 2000).

Risk factors related to objects from other farms and personnel can be addressed by using appropriate disinfection measures, traffic issues, and the frequency of contact with livestock in addition to implementing appropriate disinfection systems or making provisions for the use of special livestock boots and clothing (Benavides et al., 2021). Semen and embryos imported from third nations must likewise meet similar restrictions, and bulls entering semen collection sites approved for intercommunity trade must comply with subsequent quarantine and monitoring regulations (Givens, 2018). These actions are typically seen as successful. The slaughter of animals must be carried out in a slaughterhouse. When prevalence has dropped to low levels, culling is the most effective strategy to eradicate seropositive animals at the herd level, albeit it is not always carried out in the event of a disease epidemic (Ferreira et al., 2018; Valas et al., 2019).

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Conclusion

IBR is an infectious disease that attacks livestock, especially cattle. This disease has spread throughout the world and has an important economic impact. Biosecurity protocols need to be implemented to prevent the spread of this disease.

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Acknowledgments

The authors thank Universitas Airlangga and Badan Riset dan Inovasi Nasional (BRIN).

Conflict of interest

The authors declare that there is no conflict of interest.

Funding

The authors thank Universitas Airlangga for managerial support.

Author’s contributions

RR, ARK, IBM, and TDL drafted the manuscript. SM, SMY, HMR, and MKJK revised and edited the manuscripts. RR, JES, SW, and KAF took part in preparation and critical checking of the manuscript. RD, IF, SU, and SRA edited the references. All authors read and approved the final version of the manuscript.

Data availability

All references are open access, so data can be obtained from the online web.

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