Managing viral challenges in dairy calves: strategies for controlling viral infections

Abstract

Bovine coronavirus (BCoV), bovine respiratory syncytial virus (BRSV), bovine viral diarrhea virus (BVDV), and bovine rotavirus (BRV) are common viral infections in dairy calves, resulting in significant economic losses in the dairy industry. BCoV causes severe diarrhea and respiratory disease, with transmission primarily occurring through the fecal-oral and respiratory routes, respectively. BRSV causes acute respiratory tract infections and is primarily transmitted via direct contact with aerosol droplets. BVDV induces diarrhea, respiratory infections, and decreases weight gain. BRV poses a global threat to the dairy sector, causing acute diarrhea and high mortality in neonatal calves. This highly contagious virus results in economic losses for farmers owing to reduced weight gain, treatment costs, and calf fatalities. BRV, primarily affecting 1–3-week-old calves, is caused by serogroup A rotaviruses, constituting 95% of cases. Its resistance to disinfectants, high infectivity, and persistence make it a formidable infectious agent. The diagnosis of these infections involves a combination of clinical signs, laboratory testing, and epidemiological investigations. Diagnostic methods, including immunological tests, culture, PCR, and serology, assist in the diagnosis of these pathogens. The treatment includes supportive care and antibiotics for secondary bacterial infections. Prevention and control strategies encompass early colostrum feeding, vaccination, proper housing, feeding, and management practices, along with biosecurity measures and rigorous hygiene practices to minimize their impact on calf health and industry. The dairy industry can prevent and control these infections by implementing appropriate measures and using effective vaccines to minimize the impact on animal health, welfare, and productivity. Further research is needed to better understand the epidemiology and characterization of viral infections in dairy calves.

Keywords:

• Virus
• diarrhea
• pneumonia
• septicemia
• vaccination
• dairy calves

REVIEWING EDITOR:

• Pedro Gonzalez-Redondo, Universidad de Sevilla, Spain

SUBJECTS:

• Plant & Animal Ecology
• Agriculture & Environmental Sciences
• Natural History - Evolution and General Biology

1. Introduction

Dairy farming is an essential component of the agricultural industry, and the health and well-being of dairy calves are crucial for the success of the farm (Henchion et al., 2022). Productivity loss in the dairy industry is multifactorial. Infectious diseases are a major threat to dairy calves worldwide. Among the infectious diseases affecting dairy calves, viral diseases are the most frequent, accounting for the largest economic losses in the dairy industry in many countries around the world (Doss et al., 2012; Cho & Yoon, 2014; Rathor et al., 2021). The most common viral infections affecting dairy calves include bovine viral diarrhea virus (BVDV), bovine coronavirus (BCoV), bovine rotavirus (BRV), and bovine respiratory syncytial virus (BRSV) (Liu et al., 2021). These viruses can cause respiratory and gastrointestinal issues in dairy calves, which can result in increased mortality and decreased growth rates. The economic losses from viral diseases in the dairy industry are associated with reduced productivity, calf death, growth retardation, culling of affected animals, and treatment costs (Gaudino et al., 2022). Moreover, these infections can predispose calves to secondary bacterial infections, further exacerbating the severity of the disease (Dhama et al., 2009).

Managing viral infections in dairy calves is challenging and depends on the specific virus and the age of the animal. The primary strategies to reduce the burden of viral infections in dairy calves include good management practices coupled with the vaccination of dams to protect young calves (Dhama et al., 2009; Geletu et al., 2021; Vlasova & Saif, 2021). Management strategies for viral infections in dairy calves include understanding disease complexities, implementing biosecurity measures, vaccinating pregnant cows, good colostrum management, which includes feeding of good quality colostrum in sufficient quantity and at the right time, and providing supportive care (fluid therapy and nutritional support) for infected animals (McGuirk, 2008; Izzo et al., 2011). New generation prophylactic strategies, including DNA vaccines, subunit vaccines, virus-like particles, and edible vaccines, have been found to induce sufficient levels of passive immunity (Dhama et al., 2009; Dotiwala & Upadhyay, 2023). Vaccination against common viral infections can reduce the incidence and severity of clinical signs and improve the overall health and productivity of herds (Bullen et al., 2023). Biosecurity measures (quarantine and disinfection protocols) limit the introduction and spread of infectious agents on farms (Ndungu et al., 2023). Supportive care alleviates the clinical signs of viral infections, reduces the risk of secondary bacterial infections, and improves the recovery rate of calves (Gaudino et al., 2022).

Several studies have focused on the effects of viral infections on dairy calf health and the effectiveness of various management strategies (Wathes et al., 2020; Geletu et al., 2021; Otten et al., 2023). Through a comprehensive review of relevant literature, we explored the key factors that contribute to the transmission and spread of viral infections in dairy calves. Furthermore, we discuss the latest research findings and best practices for the prevention and control of common viral infections. By understanding the impact of viral infections and implementing appropriate management protocols, farmers can ensure the health and productivity of their herds. Therefore, this review aims to provide an overview of common viral infections associated with diarrheal and respiratory diseases in dairy calves, their effects on calf health and productivity, application of appropriate diagnostic methods, and current intervention strategies for managing viral infections in dairy calves.

2. Methodology

The search process began with the identification of primary keywords, followed by refining search strings to optimize relevance and specificity. Articles were screened based on titles, abstracts, and full texts to determine their suitability for inclusion in the review. Relevant studies were then extracted and synthesized to provide a comprehensive overview of strategies for controlling specified viral infections in dairy calves. The keywords included terms such as ‘dairy calves,’ ‘viral infections,’ ‘management strategies,’ and ‘control measures.’ Boolean operators (AND, OR) were strategically used to refine the search and capture the most relevant literature. The literature search was conducted between October 2022 and October 2023. Several reputable databases were utilized to gather a diverse range of sources. PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar were primary databases, providing access to a wealth of peer-reviewed articles. Moreover, books from renowned publishers and conference proceedings were consulted to ensure a holistic overview of the subject.

Studies were included if they focused on strategies for managing viral infections in dairy calves, particularly targeting BVDV, BCoV, BRV, and BRSV. Both experimental and observational studies, as well as reviews, were considered for inclusion. Studies were excluded if they did not pertain specifically to the targeted viruses or if they were not relevant to management strategies in dairy calves. The literature search was conducted with a focus on recent developments while also considering historical perspectives. It encompassed publications from January 2000 to January 2023, ensuring the inclusion of recent research and advancements in the field of dairy calf management and virology. This time frame allowed for the incorporation of up-to-date information relevant to the topic of managing viral challenges in dairy calves.

3. Common causes of viral infections in dairy calves

3.1. Bovine coronavirus

BCoV is a highly infectious viral pathogen that causes enteritis in dairy calves (Gomez & Weese, 2017; Soules et al., 2022). The virus is strongly associated with neonatal calf diarrhea, upper and lower respiratory tract infections, and bovine respiratory disease complex (BRD) in young cattle. The virus causes morbidity in young cattle worldwide (Salem et al., 2020). This poses a significant threat to the dairy sector and leads to economic loss owing to the high mortality of calves, and treatment costs in dairy cattle (Zhu et al., 2022). Studies have shown that age is significantly associated with the risk of BCoV infection (Lee et al., 2019; Izzo et al., 2011). Calves from one day to three months old are considered to be the most susceptible age group to BCoV infections (Ammar et al., 2014; Cho & Yoon, 2014). Clinical signs of diarrhea occur between one and two weeks of age. Winter dysentery is a contagious diarrhea in young cattle that has significant impact on growth rate, and animal welfare (Sunniva, 2018). BCoV poses a significant threat to the health of calves, being a virulent pathogen that can lead to various complications. However, its impact on adult cattle, particularly causing dysentery, is less common unless specific conditions are met (Hodnik et al., 2020; Vlasova & Saif, 2021). Poor air ventilation, often exacerbated in winter months in tie-stall barns, create an environment conducive to the spread of the BCoV and subsequent development of dysentery in cattle (Sarentonglaga et al., 2019).

BCoV is an enveloped RNA virus with a positive-sense, non-segmented, pleomorphic, and single-stranded RNA genome. BCoV is a member of Beta coronavirus genus, Beta coronavirus 1 species in the family Coronaviridae (Compton, 2021; Vlasova & Saif, 2021). The virus contains five major structural proteins. These include nucleocapsid protein (N), integral membrane protein (M), spike glycoprotein (S), small membrane protein (E), and haemagglutinin-esterase (HE) (Cologna & Hogue, 2000). Spike and HE proteins play a significant role in viral entry into host cells and induce an immune response (Ellis, 2019). The spike protein contains S1 and S2 subunits. The S1 subunits contain neutralizing epitopes, while the S2 subunits mediate viral membrane fusion (Vlasova & Saif, 2021). HE acts as a receptor-destroying enzyme that reverses hemagglutination. The virus also contains 16 non-structural proteins and is highly conserved. The N protein is the most homologous between different BCoV and is used for molecular diagnosis (Hodnik et al., 2020).

The severity of BCoV enteritis depends on age, immunological status of the host, infective dose, stress, co-infections, environmental conditions, and the strain of the virus (Boileau & Kapil, 2010). Virus infection can present three distinct clinical signs in cattle: calf diarrhea in calves at one-two weeks of age, winter dysentery with hemorrhagic diarrhea and bovine respiratory disease complex in young cattle (Salem et al., 2020). The major clinical signs of BCoV are yellowish diarrhea, dullness, anorexia, pyrexia, and dehydration in calves. The BCoV infection is severe in calves deprived of colostrum. The virus is shed in the feces and nasal secretions of infected animals (Cho & Yoon, 2014). Pneumoenteric BCoVs replicate in the upper respiratory and intestinal tracts and can be detected in nasal secretions and feces (Vlasova & Saif, 2021).

Several diagnostic methods are available, including molecular detection, immunological testing, fecal examination using electron microscope and viral isolation from fecal and nasal swab samples. These include fecal examination using electron microscopy, virus isolation, molecular detection, and immunological testing (Fulton, 2009; Rahe et al., 2022). The virus can be detected based on its biological and antigenic characteristics using viral neutralization, hemagglutination inhibition (HI), and Enzyme-linked immunosorbent assay (ELISA) tests (Fulton et al., 2013). Hemagglutination (HA) and hemagglutination inhibition (HAl) tests used to assess the BCoV specificity. The ELISA tests are the most widely used diagnostic tests for BCoV using monoclonal antibodies (mAbs). The monoclonal antibodies improved the specificity of the assay. Immunoglobulin G (IgG) persists for an extended period, while Immunoglobulin M (IgM) remains detectable approximately one-month post-infection; both antibodies serve in the diagnosis of recent and acute infections (Boileau & Kapil, 2010). Dot-blot hybridization assays with cDNA probes have also been used to detect BCV (Geletu et al., 2021). Reverse transcriptase (RT-PCR) and reverse transcriptase quantitative real time PCR (RT-qPCR) are sensitive and specific diagnostic methods for detecting viral nucleic acids in nasal and fecal samples. RT-qPCR is less laborious than the traditional gel-based RT-PCR (Decaro et al., 2008).

The virus is highly contagious and rapidly spreads in herds. The transmission of BCoV occurs mainly through the fecal-oral and respiratory routes. Both direct and indirect transmission is possible between or within different herds. The indirect transmission of the virus is influenced by its ability to remain infective outside the host or environment (Parkhe & Verma, 2021; Colina et al., 2021). Therefore, the virus, is likely stable enough for indirect transmission (Otter et al., 2016). Calves become infected by the ingestion of contaminated milk, water, or feed. The virus initially replicates in the respiratory and gastrointestinal tract, causing respiratory and digestive clinical signs. Clinical signs of BCoV infection in dairy calves include fever, cough, nasal discharge, dehydration, and diarrhea. In severe cases, pneumonia, septicemia, and death can occur (Robi et al., 2024).

Treatment of BCoV infection in dairy calves is mainly supportive of preventing dehydration (Bok et al., 2023). Antibiotic therapy has been used to treat secondary bacterial infections. Vaccination is one of the prevention and control methods for BCoV infection in dairy calves (Stokstad et al., 2020). Modified live or inactivated vaccinations of pregnant cows can also provide passive immunity to calves (Fulton, 2009; Ammar et al., 2014). A few vaccines are available for BCoV, and their effectiveness varies depending on the specific strain of the circulating virus (Saif, 2010).

Effective disinfectants for BCoV are crucial for maintaining biosecurity and preventing the spread of the virus. Cleaning before disinfecting is crucial to ensure that organic matter is removed, preventing it from inactivating the disinfectants during the disinfection process. Chlorine-based disinfectants, such as sodium hypochlorite (bleach), are highly effective against BCoV and are widely used in agricultural settings. Chlorine-based disinfectants work by oxidizing viral proteins and disrupting their structure, rendering them inactive. They are particularly advantageous as they are relatively easy to obtain, cost-effective, and have a rapid onset of action (Totaro et al., 2021). Hydrogen peroxide works by producing reactive oxygen species that damage the viral envelope and nucleic acids, thereby inhibiting viral replication. It is also environmentally friendly as it decomposes into water and oxygen, leaving behind no harmful residues (Caruso et al., 2020; Elveborg et al., 2022). Both chlorine-based disinfectants and hydrogen peroxide offer effective means of decontaminating surfaces and environments contaminated with BCoV. Regular use of these disinfectants in conjunction with other biosecurity measures is essential for mitigating the spread of BCoV and protecting animal health (Boyce, 2016; Lineback et al., 2018).

3.2. Bovine respiratory syncytial virus

BRSV is a major cause of respiratory diseases in dairy calves worldwide. It is also associated with the bovine respiratory disease complex. BRSV has a high morbidity rate and results in the death of young and immunocompromised animals (Kamdi et al., 2020; Makoschey & Berge, 2021). The virus is the most common and important cause of lower respiratory disease of young calves (Larsen, 2000). The host species infected by the virus are cattle, sheep, and goats (Murcia et al., 2009). More than 70% of calves are serologically positive to BRSV by the age of 12 months (Valarcher et al., 2000). Currently, BRSV belongs to the genus Orthopneumovirus and the Pneumoviridae family, and is a major etiological agent of respiratory tract disease in calves, resulting in substantial economic loss. Thus, BRSV is known as Bovine Orthopneumovirus (Valarcher & Taylor, 2007; Rima et al., 2017).

The virus is an enveloped, single-stranded, negative-sense, non-segmented RNA virus that causes respiratory infection in dairy calves. BRSV contains both structural and non-structural proteins. The structural proteins include surface glycoprotein (G), fusion protein (F), nucleoprotein (N), phosphoprotein (P), viral RNA-dependent polymerase protein (L), matrix protein (M), and small hydrophobic protein (SH). The two major membrane proteins, fusion (F) and attachment glycoprotein (G), small hydrophobic protein (SH), and matrix protein, are associated to the viral envelope (Larsen, 2000; Schlender et al., 2002; Livares & Ood, 2004). The glycoprotein and fusion protein play a significant role in mediating the attachment and fusion of the virus to cells and delivery of the nucleocapsid into the cytoplasm of host cells. The F and G proteins also stimulate cellular and humoral immune responses and confer resistance to BRSV infection. Fusion glycoproteins are responsible for the penetration of the virus into the host cell, the spread of the virus in the organism, and the formation of characteristic syncytia (Valentova, 2003). Glycoprotein interacts with the immune system (Makoschey & Berge, 2021). Fusion proteins are highly conserved among BRSV isolates (97–99% homology). The antigenic groups of the BRSV isolates are based on distinct antigenic reactivity patterns determined using a set of G-protein-specific mAbs. Genetic diversity of the G protein is employed in epidemiological investigations of BRSV. There is continual genetic drift within G protein sequences. The F and G proteins stimulate the production of neutralizing antibodies. G, the most variable viral protein associated with immunopathologic impact, is an important consideration in vaccine development (Valentova, 2003).

BRSV viruses are classified into antigenic groups based on the variability of glycoprotein G. BRSV is thus divided into groups A, B, and AB, using monoclonal antibodies produced against glycoprotein G. The virus also contains two non-structural proteins (NS1 and NS2). Non-structural proteins inhibit viral RNA transcription and replication. It also mediates resistance to the alpha/beta interferon (IFN)-mediated antiviral response in the host cell. NS proteins also play a significant role in the pathogenesis and host-range restriction of BRSV (Bossert et al., 2003; Sedeyn et al., 2019).

Cattle are the natural hosts of BRSV, but other species, such as ovine and caprine, play an epidemiological role in certain circumstances. The virus is distributed worldwide and causes regular winter outbreaks of respiratory disease in cattle. The incidence of viral infection is notably high, with cases accounting for as much as 60% and 70% of dairy and beef herds, respectively, in certain instances (Sarmiento-Silva et al., 2012; Zewde et al., 2022). The viral infection rate is correlated with the density of the cattle population in an area and the age of the animal. The infection occurs at any age, but calves less than six months old are more susceptible (Klem et al., 2013). Severe clinical signs are more frequently observed in young calves than adult cattle. This is because of the level of specific immunity following frequent exposure to the virus. The virus is associated with high morbidity rates, which range from 20% to 80% (Fulton, 2013; Topalidou et al., 2023). The virus may persist in infected animals and be shed in nasal secretions and lung tissues. The clinical signs observed in infected calves include fever, coughing, nasal discharge, and difficulty breathing. The incubation period of the virus is estimated to be 2–5 days (Makoschey & Berge, 2021).

The main route of virus transmission is direct contact between infected and susceptible animals. The virus also spreads via contaminated fomites or aerosol droplets expelled by infected animals during coughing or sneezing (Ince et al., 2021). Diagnostic approaches to the virus are based on a combination of molecular detection, immunological tests and virus isolation from nasal swabs and lung tissue samples. Immunofluorescent antibody (IFA) staining is a quick, accurate, and sensitive method for determining the presence of the BRSV antigen in clinical samples (Larsen, 2000; Kamdi et al., 2020). The virus neutralization (VN) test, complement fixation test, immune precipitation, and ELISA are used for antibody detection in paired acute and convalescent specimens. Molecular diagnostic assays, such as RT-qPCR and RT-PCR are used to detect and quantify BRSV in cell cultures and clinical samples of dairy calves (Focosi et al., 2021).

There are no treatment options for BRSV infection. However, antibiotics and nonsteroidal anti-inflammatory drugs are used to treat secondary bacterial infections and inflammation, respectively . Several measures can be implemented to prevent and control BRSV infection in dairy calves. Vaccination is the most effective method for preventing viral infections. Several injectable BRSV vaccines are available and can be administered to calves between two and six months of age. Vaccination helps reduce the severity and duration of clinical signs and lowers the risk of secondary bacterial infections. Vaccination at an early age is not recommended because of the neutralization by maternally derived antibodies. To circumvent maternal antibodies, intranasal vaccines are also available. Intranasal BRSV vaccination boosts mucosal immunity, crucial for fighting the virus. Unlike injectable vaccines, it triggers local defenses, such as secretory IgA antibodies and memory T cells, in the respiratory tract, reducing viral replication and symptoms (Boley et al., 2023). Follow-up doses maintain and enhance immunity, countering BRSV’s evolving nature. Regular vaccinations sustain antibody levels and memory cells, ensuring long-term protection (Meyer et al., 2023). However, it is possible to vaccinate young animals using non-essential gene-deleted vaccines (Chamorro & Palomares, 2020; Masset et al., 2020; Kolb et al., 2020).

3.3. Bovine viral diarrhea virus

BVDV is a highly contagious infectious agent that is endemic to most cattle populations worldwide (Booth et al., 2013). The virus causes diarrhea, respiratory infection, reproductive problems, immunosuppression, and weight loss in dairy calves. BVDV virus is also associated with the bovine respiratory disease complex (Gomez-Romero et al., 2021). The reproductive disturbances associated with BVDV include fetal infections, decreased fertility, abortions, teratogenesis, embryonic resorption, fetal mummification, still birth and congenital defects (Khodakaram-Tafti & Farjanikish, 2017; Oguejiofor et al., 2019). The economic losses resulting from BVDV disease are associated with decreased performance, reproductive disturbances, and an increased risk of morbidity and mortality (Wernicki et al., 2015).

BVDV is a small, spherical, enveloped, single-stranded, positive-sense RNA virus that belongs to the genus Pestivirus in the family Flaviviridae. The virus is classified into two biotypes based on the presence or absence of visible cytopathology in infected cell cultures: cytophatic and non-cytopathic (Chi et al., 2022). The predominant biotypes found in isolates from clinically sick cattle are noncytopathic strains (Booth et al., 2013; Sevik, 2021). Cytopathic biotypes of the virus cause severe clinical signs such as high fever, hemorrhagic syndrome, and death, whereas non-cytopathic biotypes cause persistent infection in the fetus approximately between days 60 and 120 of gestation, which can lead to chronic disease and shedding of the virus (Fulton, 2009). Cross-protection among some strains of BVDV have been recognized (Kelling et al., 2007). Three main species of the genus Pestivirus have been identified in cattle: Pestivirus A (BVDV-1), Pestivirus B (BVDV-2), and Pestivirus H (BVDV-3), with Pestivirus A (BVDV-1) being the most prevalent. Pestivirus D or Border Disease Virus (BDV), is a fourth species that affect cattle less frequently (Rivas et al., 2022). There are also different subtypes: 1a, 1b, 2a, and 2b. Each subtype may exhibit variations in virulence, transmission dynamics, and response to vaccination. This knowledge aids in devising targeted control strategies and developing effective vaccines tailored to specific subtypes. Furthermore, identifying the predominant subtype in a given area can enhance surveillance efforts, allowing for better management and prevention of BVDV outbreaks (Pogranichniy et al., 2011; Fulton et al., 2020; Grange et al., 2023).

The viral genome encodes four structural proteins (capsid protein (C), ribonuclease (Erns), E1, and E2) and eight non-structural (NSP) proteins. Three glycoproteins, Erns, E1, and E2, are associated with the outer envelope of the virion and play a significant role in the induction of neutralizing antibodies (Kalaycioglu, 2007; Al-Kubati et al., 2021; Yi et al., 2022). The E2 protein is an immunodominant structural protein and a principal epitope for viral neutralizing antibodies. Protective antibodies induced by killed vaccines are predominantly against E2. Monoclonal antibodies (Mab) produced against the E2 have been used to differentiate between BVDV1 and BVDV2 strains (Ridpath, 2006). Non-structural proteins are used to understand the viral replication process and molecular mechanism of persistent viral infection (Chi et al., 2022).

Cattle are natural hosts of pestiviruses. However, the virus also infects other species, such as sheep, mouse, deer, and goats (Gao et al., 2011). BVDV is transmitted through both horizontal and vertical routes. Horizontal transmission occurs when infected animals come into direct contact with susceptible animals or share equipment, feed, or water sources. Vertical transmission occurs when a pregnant cow is infected with BVDV and the virus crosses the placenta to infect the developing fetus (Nelson et al., 2015). This can result in a range of outcomes, from transient infections to persistent infections (PI) in the calves. Transient BVDV infection typically occurs when a susceptible animal is exposed to the virus. The BVDV infection is characterized by a short duration, and the animal may experience mild symptoms such as fever, diarrhea, and respiratory issues. In most cases, the immune system of an animal effectively clears the virus, and the infection does not persist (Goto et al., 2021). Persistent BVDV infection occurs when a fetus is exposed to the virus during a critical period of gestation. The virus can integrate into the developing cells of the fetus, leading to a lifelong infection. This is a result of the immunotolerance induced during fetal development (Smirnova et al., 2009; Knapek et al., 2020). PI calves are a significant source of viral transmission in dairy herds. These calves are born infected with BVDV and continue to shed the virus throughout their lives (Yitagesu et al., 2021). They may appear healthy; however, their immune systems do not recognize the virus as foreign, and they are unable to mount an effective immune response. As a result, PI calves are a reservoir for BVDV and can infect other calves and cows in the herd (Khodakaram-Tafti & Farjanikish, 2017). Animals that are PI release viruses through secretions and excretions such as feces, urine, milk, colostrum, saliva, and secretions from the nose, eyes, and reproductive tract. The determinants that affect the transmission of the virus are the rate of animal-to-animal contact, virulence of the virus strains, and susceptibility of the host (Chamorro et al., 2011; Tulu et al., 2018).

Different diagnostic approaches are used to detect active or past infections. PI animals should be screened early by immunohistochemistry, antigen capture ELISA, or nucleic acid detection by RT-PCR (Lanyon et al., 2014). RT-PCR is the most sensitive and specific diagnostic tool for the early identification of calves with PI. Both acute and persistent infections can be detected using RT-PCR. The antigen capture ELISA test was also used for the detection of PI in animals. This is a robust, simple, and cost–efficient diagnostic method. Detection of BVDV in newborn calves using antibody-based assays is difficult because of the presence of maternally derived antibodies in newborn calves. Maternal antibodies bind to the virus and prevent its recognition in antibody-based assays (Al-Kubati et al., 2021; Schweizer et al., 2021).

There is no treatment to fully cure an animal with a viral infection, rather than providing supportive treatment. The most effective way to control and prevent BVDV infection is through the detection of PI animals at an early stage (Khodakaram-Tafti & Farjanikish, 2017). Persistently BVDV-infected animals should be culled from herds following the early detection of the virus using different diagnostic methods. Immunohistochemistry (IHC), ELISA, and RT-PCR were used to detect PI in representative samples based on animal age (Werid et al., 2023). Therefore, the culling of PI is the most effective way to stop the spread of the disease. BVDV-1 has also been detected in semen and causes vertical transmission. Thus, the detection of bulls is important for effective control of transmission (Chi et al., 2022).

Killed and modified live vaccines are used to prevent BVDV infections in dairy calves (Antos et al., 2021). However, BVDV infection cannot be eradicated by vaccination alone because of the presence of heterogeneity among the viruses and lack of complete fetal protection afforded by vaccination. Therefore, effective early detection methods and compulsory culling policies should be applied worldwide to prevent and control this disease (Moennig and Bencher, 2018). Promising approaches to eradicate BVD worldwide have emerged from advancing research on the relationship between BVDV and the host, as well as from investigating the interplay between structural and non-structural proteins of the virus (Chi et al., 2022). Knowledge of environmental factors and herd management is important for controlling and impeding transmission and minimizing the unfavorable effects of BVD infection on herd health and productivity (Tulu et al., 2018).

It is imperative to acknowledge that BVDV prevalence in herds is often underestimated, as testing and measurement are typically only initiated once the virus manifests as a problem. Consequently, it is highly probable that some herds may have high prevalence depending on these factors. This highlights a critical need for enhanced research efforts and proactive strategies to address BVDV in dairy farming operations (Hou et al., 2019).

3.4. Bovine rotavirus

BRV is a highly contagious virus that affects young animals. It is a leading cause of acute diarrhea and mortality in neonatal calves worldwide (Geletu et al., 2021). The virus can cause significant economic losses for dairy farmers owing to reduced weight gain, increased treatment costs, and even death of affected calves. Diarrhea occurs due to virus mediated-destruction of enterocytes, activation of the enteric nervous system, and enterotoxin production by the virus (Dhama et al., 2009; Jiang et al., 2023). The BRV is most commonly affected in calves between 1–3 weeks of age but can also affect older animals (Geletu et al., 2021). BRV is transmitted through fecal-oral contact, and infection can occur through the ingestion of contaminated food, water, or bedding (Larson et al., 2004).

This virus belongs to the genus BRV in the family Sedoreoviridae. The virus genome is a non-enveloped, double-stranded RNA virus with 11 segments (Uprety et al., 2021). The seven serogroups (A-G) of BRV depend on the antigenic and genetic similarity of the intermediate capsid protein six (VP6) . Serogroup A BRVs are the major cause of BRV infections in domestic animals (Geletu et al., 2021). A total of 95% of BRV belongs to group A. BRV belonging to groups A, B, C, and H have been associated with acute gastroenteritis in humans and animals (Ghosh et al., 2007; Luchs & Timenetsky, 2016).

BRV has six structural proteins (VP1-VP4, VP6, and VP7) and six non-structural proteins (NPS1-NPS6) based on the analysis of the gene encoding segment. The structural proteins build up the viral particle, and NSP facilitates the viral replication cycle of interaction with host proteins to influence the pathogenesis of the immune response (Table 1). The outer capsid proteins VP7 and VP4 are the targets of neutralizing antibodies. VP7, VP4, and VP6 structural proteins play major roles in maintaining the viral structure, virus attachment and antigenicity. VP4 also determines the host specificity and virulence. It binds to receptors and enables the entry of the virus into the cell (Maunula & Von Bonsdorff, 2002; Kumar et al., 2022).

Table 1. Localization of BRV proteins, genome segments, and their respective functions within cellular structures.

Protein	dsRNA segment no	Location in virus capsid	Function
VP1	1	Core	dsRNA synthesis (RNA-dependent RNA polymerase)
VP2	2	Core	Replication intermediate
VP3	3	Core	Capping enzyme
VP4	4	Outer capsid	Viral attachment, P-type neutralization antigen
VP6	6	Inner capsid	Middle shell protein
VP7	9	Outer capsid	G type neutralization antigen
NSP1	5	Outer capsid	INF antagonist
NSP2	8	Outer capsid	INF antagonist Viroplasm formation
NSP3	7	Outer capsid	Enhance viral mRNA synthesis, associated with systemic spread
NSP4	10	Outer capsid	Outer capsid assembly, regulate calcium homeostasis, enterotoxin
NSP5	11	Outer capsid	Viroplasm formation
NSP6	11	Outer capsid	Viroplasm formation

The virus causes economic losses due to mortality, treatment costs, and impaired growth. The presence of very large numbers of particles per milliliter in infected feces and the resistance of the virus to commonly used disinfectants make BRV a highly infectious agent. The virus remains infectious for nine months at room temperature (Uddin Ahmed et al., 2022; Alotaibi et al., 2022). BRV survives for more than one year in a contaminated environment and serves as a source of infection during an outbreak. However, adults are a major source of infection for calves. Calves are frequently infected with BRV in the first week of life (Crawford et al., 2017; Geletu et al., 2021). Infected calves shed a large amount of the virus via feces for five-seven days and can survive in the environment for several weeks, making it easy to spread from infected calves to others (Cho & Yoon, 2014). BRV infection causes severe diarrhea, depression, dehydration, and electrolyte imbalance, leading to poor growth and death in calves (Liu et al., 2021). The virus is highly prevalent in cattle worldwide. The infection rate of BRV in newborn calves is estimated to be 27–36%. The mortality rate of calves infected with BRV due to diarrhea is 80% (Chen et al., 2022).

The diagnosis of BRV infection is based on isolation of the virus in cell lines, electron microscopy examination, electron serotyping, and different serological assays (Dhama et al., 2009). Serological tests such as immunofluorescence test (IFT), immunoperoxidase test (IPT), latex agglutination test (LAT), and ELISA were used to detect the infectious agent of the virus. ELISA is a highly sensitive and specific test used to the identify BRV (Dhama et al., 2009; Geletu et al., 2021). Antigen capture ELISA is used to detect pathogens based on the antibody recognition of the target antigen (Gichile, 2022). Molecular diagnosis is performed using serotype-specific RT-PCR, semi-nested/multiplex RT-PCR, restriction fragment length polymorphism (RFLP), sequencing, or genomic hybridization techniques. RT-PCR using VP4 or VP7 gene primers is widely used for the detection of bovine rotavirus infections (Dhama et al., 2009; Fujii et al., 2019).

The primary strategy to reduce the burden of BRV infections is good management practices coupled with vaccination of dams to protect young calves (Dhama et al., 2009; Geletu et al., 2021). New generation prophylactic strategies, including DNA vaccines, subunit vaccines, virus-like particles, and edible vaccines have been found to induce sufficient levels of passive immunity (Chen et al., 2022).

BRV thrives in warmer temperatures, making it particularly prevalent in environments with elevated heat levels. However, its susceptibility to higher temperatures also renders it vulnerable to control measures (Dhama et al., 2009). In contrast to its resilience in warmer climates, BRV struggles to maintain viability in cold temperatures. This characteristic serves as a notable deviation from other viral pathogens like Coronaviruses, which exhibit greater stability in colder environments (Boileau & Kapil, 2010). Understanding this sensitivity to cold is pivotal in implementing measures to limit the transmission and persistence of BRV, particularly in regions prone to lower temperatures (Dhama et al., 2009).

4. Management and prevention of viral infections in dairy calves

There are no precise therapeutic agents for viral infections (Tompa et al., 2021). Vaccines alone do not fix the problem unless they are used in combination with other prevention techniques (Dawson, 2004). Therefore, an effective immunization program, hygiene procedures, reliable animal sourcing, and quarantine and/or effective biosecurity practices are all essential components of a successful prevention and control program for viral and other dairy calves’ diseases (Renault et al., 2021).

Biosecurity is an essential component of fighting antibiotic resistance. Biosecurity measures serve a dual purpose: mitigating the introduction of new diseases from external sources and controlling the spread of infectious diseases within the farm environment (Baraitareanu & Vidu, 2020). Bio-containment and control programs are critical backup systems for biosecurity plans because they prevent new or endemic infectious diseases from spreading among farm animals. The four major components of biosecurity measures are the selection of purchased animals, isolation of purchased or sick animals, movement control, and sanitation. Animals should be purchased from known sources with a health status equal to or higher than that of the owner to minimize the risk of infection. Strict isolation of sick and newly purchased animals reduces the risk of the spread of infectious diseases (Maunsell & Donovan, 2008). Movement control includes all vehicle, animal, and human traffic that could introduce infection to the farm. Employees and visitors contribute to the spread of infectious agents on the dairy farm. Therefore, sanitation of employees, visitors, and equipment should be under consideration on dairy farms (Moje et al., 2023; Otieno et al., 2023). Employees should be trained in good practices such as principles of hygiene and disease security, working with younger animals before working on older animals to prevent the spread of disease. Sanitation addresses the disinfection of materials/equipment entering the farm, using clean overalls during farm visits, and washing hands before and after working with sick or young animals (Baraitareanu & Vidu, 2020). The access of visitors should be limited, and tours must start from younger animals to older groups. Proper ventilation and sanitation practices play a pivotal role in mitigating the risk of viral outbreaks, emphasizing the importance of maintaining optimal husbandry conditions to safeguard cattle health and welfare (Wallace et al., 2003).

Prevention of viral infection in dairy calves involves good colostrum management, which includes feeding of good quality colostrum in sufficient quantity and at the right time, vaccination of pregnant cows 60 and 30 days before calving, and improving management practices (Izzo et al., 2011). Vaccination of pregnant cows increases the number of viral-specific antibodies in the colostrum, which can protect calves against viral infection (Civra et al., 2019). Colostrum, the first milk produced by the dam, is rich in antibodies such as immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM), which provide immediate protection against a wide range of pathogens (Lora et al., 2019; Fischer-Tlustos et al., 2021). Colostrum also contains various immune cells, such as lymphocytes, macrophages, and neutrophils. These cells play a role in the cell-mediated immune response, which involves the direct action of immune cells to recognize and destroy infected or abnormal cells (Ghosh et al., 2007). The process of colostrum absorption is time-sensitive, with optimal absorption occurring within the first 24 hours of life. This is because calves lose their ability to absorb colostrum antibodies as they grow older (Larson et al., 2004; Godden et al., 2019; Lorenz, 2021). Inadequate colostrum intake renders the calf susceptible to infections (Hammon et al., 2020; Osorio, 2020). However, there is minimal transfer of immunoglobulins from the dam to the calf during gestation. While this provides some degree of protection, its significance is often overshadowed by the superior quality and quantity of antibodies obtained through colostrum consumption (Palmeira et al., 2012; Pongsatha et al., 2023).

Colostrum plays a vital role in bolstering the immune system of newborn calves, providing passive immunity against a wide range of pathogens. The antibodies present in colostrum, particularly immunoglobulin A (IgA), neutralize and prevent the attachment of viruses to the intestinal lining, thus reducing the risk and severity of infections (Hurley & Theil, 2011; DuBourdieu, 2019). Colostrum provides crucial protection against various infectious agents, offering newborn calves a vital defense mechanism during the vulnerable early stages of life (Civra et al., 2019). Therefore, promoting and supporting colostrum feeding of newborn calves, especially during the initial days postpartum when colostrum production is at its peak, is imperative for ensuring optimal health and immunity against various diseases in newborn calves (Godden, 2019).

Measurement of serum total protein (STP) using a refractometer is used to evaluate the amount of immunoglobulin in calf serum and indicates adequate passive transfer of immunoglobulins in calves. This is because the correlation between STP and IgG in blood is very strong in the first days of life. IgG is the most abundant protein ingested through colostrum. Serum total protein values above 5.2 g/dL are associated with appropriate passive immunity transfer (Windeyer et al., 2014). Therefore, appropriate colostrum feeding should be given to calves within 4 to 6 hours after birth and ensure at least 4 to 5 liters of colostrum intake during the first 8 hours of life. This allows high blood levels of circulating maternal immunoglobulins in 48-hour-old calves until their immune system becomes fully functional (Heinrichs & Elizondo Salazar, 2009). Milk pasteurization also improves health status and decreases mortality during the first 21 days of life in neonatal calves receiving appropriate colostrum ingestion (Armengol & Fraile, 2016). Different studies showed that animals fed colostrum treated at 60 °C for 30 to 60 minutes had significantly greater STP when compared with calves fed with raw colostrum. Therefore, feeding pasteurized colostrum and milk improves calf health status and reduces fecal-oral transmission of pathogens, morbidity, and mortality during the first three weeks of life (Gelsinger et al., 2014; Armengol & Fraile, 2016).

Calves are born with functioning thermoregulatory systems. Consequently, housing for dairy calves should provide dry, well-bedded, ventilated, and draft-free environments for healthy calves to thrive in Bonizzi et al. (2022). The temperature important for healthy calves in the first two weeks of life ranges between 10 °C and 15 °C, and then decreases to 6–10 °C in older calves depending on air speed (Lorenz et al., 2011). Both individual and group housing of dairy calves is associated with improved calf health (Sinnott et al., 2022). Several studies have discussed the advantages and disadvantages of outdoor versus indoor housing for calves. Outdoor housing in hutches helps prevent diarrhea and respiratory infectious diseases, thereby benefiting dairy calf health (Lorenz et al., 2011; Sinnott et al., 2022; Breen et al., 2023). However, caring for calves in outdoor hutches is inconvenient in inclement weather, whereas indoor calves are more comfortable (Sinnott et al., 2022). Therefore, the use of heat abatement strategies in summer and windbreaks in winter is necessary. Housing calves individually in naturally ventilated calf barns, with solid dividers on the side of pens with high nesting scores, lowers the risk of respiratory infectious diseases. Rearing calves inside sheds at higher stocking densities can provide an ideal environment for calf disease to proliferate (Moran, 2002; Robi et al., 2023), and studies have reported higher mortality and morbidity among group-housed pre-weaned dairy calves compared to individually housed ones. In general, outdoor individual hutches are superior to indoor housing, and individual or small group housing appears superior to large group housing with regards to calf health. All the prevention and control methods discussed above have critical advantages in reducing the occurrence of outbreaks and the development of antibiotic resistance (Lorenz et al., 2011; Robi et al., 2024).

5. Passive and acquired immunity in calves

Passive immunity in calves refers to the transfer of pre-formed antibodies from the dam to the calf, either via colostrum or placental transfer. Passive immunity offers immediate protection and broad-spectrum immunity. These, in turn, reduce the risk of morbidity and mortality during the vulnerable neonatal period and safeguard against a wide range of pathogens (Chase et al., 2008; DuBourdieu, 2019). However, passive immunity also comes with its limitations. Over time, the duration of protection diminishes as maternally derived antibodies gradually decrease, leaving the calf susceptible to infections once antibody levels fall below protective thresholds (Marcotte & Hammarström, 2015; Tizard, 2021). Moreover, maternal antibodies can interfere with the ability of a calf to respond effectively to vaccinations, particularly if administered shortly after birth (Cinicola et al., 2021). Maternal antibodies are specific to the pathogens encountered by the dam, limiting their effectiveness against novel or endemic pathogens present in the environment of calf. Thus, while passive immunity provides immediate protection, it also poses challenges that must be carefully managed to optimize the calf health and immunity (Niewiesk, 2014).

Acquired immunity, also known as active immunity, in calves develops over time through exposure to antigens, either naturally or through vaccination. Unlike passive immunity, acquired immunity involves the immune system of a calf producing its antibodies upon encountering specific pathogens. This process entails the activation of B and T lymphocytes, leading to the formation of memory cells that confer long-term protection against subsequent infections (Chase et al., 2008; DuBourdieu, 2019). Vaccination plays a pivotal role in stimulating acquired immunity in calves by exposing them to attenuated or inactivated pathogens or their antigens. Through vaccination, calves develop immunity without experiencing the clinical signs of disease, thereby boosting their defenses against potential threats (Dudek et al., 2014; Gonzalez et al., 2021).

Acquired immunity presents several advantages for calves in their defense against pathogens. Firstly, it offers long-lasting protection, surpassing the temporary shield provided by passive immunity. This enduring defense stems from the activation of the immune system of a calf and the establishment of immunological memory, ensuring heightened resilience over time (Vlasova & Saif, 2021). Moreover, acquired immunity boasts specificity, tailoring its response to the particular pathogens encountered by the calf. This targeted defense mechanism ensures effective protection against specific diseases, bolstered further by the vaccine response of calf (Marshall et al., 2018). Vaccination acts as a catalyst, prompting the immune system to generate protective antibodies and memory cells, thereby fortifying the defenses of the calf against anticipated threats. However, despite its strengths, acquired immunity also exhibits limitations. One such drawback is the time required for its development post-exposure or vaccination, rendering the calf vulnerable to infections during this latency period (Clem, 2011). The efficacy of acquired immunity can fluctuate, influenced by factors like the age of a calf, health condition, and the antigenic diversity of encountered pathogens (Young et al., 2023). Maintenance of protective immunity may require booster doses of certain vaccines, underscoring the importance of adhering to vaccination schedules for sustained defense (Lord, 2013; Gustafson et al., 2020).

6. Conclusion

Viral infections in dairy calves can significantly impact animal welfare and the dairy industry. Bovine coronavirus, bovine respiratory syncytial virus, bovine viral diarrhea virus, and bovine rotavirus are four common viruses that cause respiratory, digestive, reproductive, and weight loss issues in dairy calves. The transmission of these viruses can occur through various means, including direct contact with infected animals, ingestion of contaminated milk or feed, and contact with contaminated fomites. Early diagnosis and prompt management of infected animals are crucial to limit the spread of these viruses. Preventive measures such as vaccination, proper management practices, biosecurity, and hygiene can help minimize the impact of these viral infections in dairy calves. Implementing thorough management practices is crucial to mitigate calf diarrhea’s impact on dairy industry productivity. This involves optimizing colostrum protocols for immunity transfer, enhancing biosecurity to prevent disease transmission, and improving housing and nutrition for calf health. Sustainable antimicrobial stewardship combats bacterial infections. Integrating these strategies maintains calf health, welfare, and productivity while minimizing economic losses. There is a need for further study and development to improve vaccine efficacy, broaden vaccine coverage, and optimize vaccination protocols to ensure maximum protection against these pathogens. Moreover, identifying novel vaccine targets and developing innovative vaccine delivery systems could offer promising avenues for enhancing calf immunity and reducing the disease burden. Furthermore, strengthening surveillance systems and conducting epidemiological studies to monitor the prevalence, distribution, and transmission dynamics of these viruses can provide valuable insights for targeted control strategies and outbreak prevention.

Author contributions

Dereje Tulu Robi contributed to the conception and design, analysis and interpretation of the data, and the drafting of the paper. Tesfa Mossie and Shiferaw Temteme were involved in revising it critically for intellectual content. All authors have given final approval for the version to be published and agree to be accountable for all aspects of the work.

Acknowledgements

We express our sincere gratitude to the Ethiopian Institute of Agricultural Research (EIAR), Ethiopia for their invaluable assistance in this review. Their expertise and support have been essential for maintaining the accuracy and quality of my work. Furthermore, I extend heartfelt thanks to all the individuals and organizations who have contributed to this review. Whether by providing data, perspectives, or comments, their assistance is crucial in helping me achieve the objectives of this review.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The corresponding author will provide the data used in the current study upon reasonable request.

Additional information

Notes on contributors

Dereje Tulu Robi

Dereje Tulu Robi is a senior researcher at the Ethiopian Institute of Agricultural Research (EIAR), Tepi Agricultural Research Center. His research work focuses on veterinary epidemiology. He has published several papers in various scientific journals.

Tesfa Mossie

Tesfa Mossie is a researcher at EIAR, Jimma Agriculture Research Center. His research work focuses on veterinary microbiology. He has published several papers in various scientific journals.

Shiferaw Temteme

Shiferaw Temteme is a researcher at EIAR, Tepi Agricultural Research Center. He has conducted various research projects on animal production and forage agronomics. He has published several papers in various scientific journals.