Section 1 Health and Diseases

#### **Chapter 1**

## Lumpy Skin Disease: An Economically Significant Emerging Disease

*Abdelmalik Khalafalla*

#### **Abstract**

Lumpy skin disease (LSD) is a severe viral disease of cattle caused by the lumpy skin disease virus (LSDV), a member of the *Capripoxvirus* genus of the poxviridae family. Fever and flat disk-like skin nodules on the skin characterize the disease. It can also lead to death and significant economic losses, especially in herds, that have never been exposed to the virus. Blood-feeding insects, such as specific types of flies, mosquitoes, and ticks, are thought to be the primary vectors of LSDV transmission. Most African and middle eastern countries have a high prevalence of lumpy skin disease. The disease extended to southeast Europe, the Balkans, and the Caucasus in 2015 and 2016 and is still spreading throughout Asia. The World Organization for Animal Health [WOAH] has designated LSD as a notifiable illness due to the likelihood of fast transmission. The rapid spread of disease in formerly disease-free areas emphasizes the need to know the disease epidemiology and the virus's interaction with its host. This chapter aims to provide the latest developments in the etiology, epidemiology, diagnosis, and control of LSD.

**Keywords:** lumpy skin disease, etiology, epidemiology, diagnosis, control

#### **1. Introduction**

LSD is the best example of an emerging infectious disease owing to its recent rapid spread and geographic expansion in disease-free Asian countries. Initially limited to Africa, since 2019, the disease has spread through China and Southeast Asia. In 2021, the disease was confirmed in Pakistan, Mongolia, Vietnam, Thailand, Laos, Cambodia, and Malaysia. Starting from March 2022, it was officially reported by Indonesia, Afghanistan, and Singapore [1]. Many variables could be at play, including the effects of climate change, increased animal and animal product trafficking patterns, and increased illegal animal trade, which could contribute to the spread of the disease [2, 3]. Capripox viruses are considered the most economically significant members of the Poxviridae family of viruses that attack domestic ruminants. LSDV is a host-specific virus genetically related and shares genetic ancestry with the sheep pox (SPPV) and goat pox (GTPV) viruses.

Though the disease has a mortality rate of less than 10%, it leads to animal welfare issues, significant production losses, and substantial trade impacts, indicating the

importance of understanding the epidemiology of the disease. Damaged skins, a decrease in the growth rate of beef cattle, temporary or permanent sterility, miscarriage, treatment and immunization expenditures, and the death of afflicted animals are some additional effects of the disease [4–7].

The present chapter is designed to provide up-to-date information on the various aspects of the disease, such as its etiology, epidemiology, diagnosis, and control.

#### **2. The etiology**

Lumpy skin disease virus (LSDV) belongs to the family poxviridae, subfamily Chordopoxviridae, and genus *Capripoxvirus*. This genus is made up of the goat pox virus (GTPV), sheep pox virus (SPPV), and lumpy skin disease virus (LSDV). GTPV infects goats, sheep are infected by SPPV, and LSDV infects cattle and buffalo. There is only one serotype of LSDV, which is phylogenetically distinct but serologically related to SPPV and GTPV. In common with other poxviruses, LSDV replicates in the cytoplasm of an infected cell, forming distinct perinuclear viral factories and the presence of immature spherical virus particles and ovoid or cylindrical mature particles (**Figure 1**) [8].

The LSD virion is large and brick-shaped, measuring 293–299 nm (length) and 262–273 nm (width). The LSDV genome structure is also similar to other poxviruses, consisting of double-stranded linear DNA 25% GC-rich, approximately 150,000 bp in length, and encodes around 156 open reading frames (ORFs). The central region of the LSDV genome contains ORFs predicted to encode proteins required for virus

#### **Figure 1.**

*Electron micrograph of mature lumpy skin disease virus in skin biopsy collected from a sick cow (x 14,400). Arrows point to mature virus particles (Khalafalla et al., [8]).*

#### *Lumpy Skin Disease: An Economically Significant Emerging Disease DOI: http://dx.doi.org/10.5772/intechopen.108845*

replication and morphogenesis and exhibit a high degree of similarity with genomes of other mammalian poxviruses. The ORFs in the outer regions of the LSDV genome have lower similarity and likely encode proteins involved in viral virulence and host range determinants [9].

According to recent studies, using homologous live attenuated vaccines cause LSDVs to undergo faster evolutionary changes due to recombination. In Kazakhstan and surrounding countries of Russia and China, multiple vaccine-like recombinant strains of the lumpy skin disease virus (LSDV) were found between 2017 and 2019. Recombinant LSDV strains isolated prior to 2020 were composed of unique combinations of open reading frames. From 2020 onwards, all circulating strains in Russia and South-Eastern Asia belonged to a single lineage radiating out in the region [10]. According to Vandenbussche et al. [11], the vaccine-like recombinant strains can be divided into four groups, and each group has a distinct breakpoint pattern resulting from multiple recombination events. The author claimed that the recent emergence of vaccine-like LSDV strains in large parts of Asia is likely the result of a spillover from animals vaccinated with the Lumpivax vaccine. Furthermore, Suwankitwa et al. [12], in Thailand, by genetic analysis, detected a recombinant LSDV derived from a vaccine strain previously appearing in China and Vietnam. Investigation revealed that the Thailand LSDV possesses a mosaic hybrid genome containing the vaccine virus DNA as the backbone and a field strain DNA as the minor donor.

LSDV can remain viable for long periods in the environment at ambient temperatures, especially in dried scabs. Capripox viruses are highly resistant and can remain viable in infected tissues for more than 120 days. The virus can also be found in blood, nasal discharge, lacrimal secretion, semen, and saliva, which are considered the main sources of direct LSDV transmission [13, 14]. The virus can be inactivated at a temperature of 55°C for 2 hours and 65°C for 30 minutes [15].

#### **3. The epidemiology of LSD**

Lumpy skin disease is endemic in Africa, with the first outbreak reported in Zambia in 1929. The disease spread into Botswana by 1943 and then into South Africa in the same year and affected over 8 million cattle, causing significant economic loss. In 1957, LSD reached Kenya, and by 1974 it had spread into Sudan and moved west as far as Nigeria, and in 1977 the disease was reported from Mauritania, Mali, Ghana, and Liberia. The disease reemerged between 1981 and 1986 and affected Tanzania, Kenya, Zimbabwe, Somalia, and Cameroon, with reported mortality rates of 20%. Later, LSD was confirmed for the first time in Egypt in 1988, followed, later, by spread within the middle east identified in Saudi Arabia, Lebanon, Jordan, Iraq, Israel, Turkey, and Iran [16–20]. Between 2012 and 2022, LSD spread into southeast Europe, the Balkans, the Caucasus, and further throughout most of Asia (**Figure 2**). LSD is an economically significant disease. For instance, the economic impact of LSD on south, east, and southeast Asia countries was estimated to be up to US 1.45 billion in direct losses of livestock and production [21].

#### **3.1 Transmission**

The transboundary spread of LSD is supported by the traditional system of production and seasonal nomadism, where cattle herds in arid and semi-arid conditions move long distances in search of food and water. The disease can appear several hundred

#### **Figure 2.**

*Lumpy skin disease prevalence worldwide and over time from 1929 to 2022. The impacted nations are shown in yellow between 1929 and 1970, orange between 1971 and 1988, pink between 1989 and 2011, and red between 2012 and 2022. This map was prepared using the MapChart platform (World Map - Simple | MapChart).*

kilometers away from initial outbreak sites within a short period, probably via the movement of infected animals. In the past, LSD was known to be mainly transmitted by biting arthropods via a mechanical form of vector-borne transmission without any multiplication of the virus in the vector. However, some researchers suggest that direct contact without vector involvement is a common mechanism of LSDV transmission [22]. Recently, non-vector-borne transmission has been studied in Russia. According to Aleksandr et al. [23], contact transmission mitigates the factor of seasonality, which is linked to insect activity and widens the possibilities for spread regardless of the presence of biting insects. Transmission through contaminated feed and water and direct transmission in the later stages of the disease via saliva, nasal secretions, and semen was also reported [13, 14, 24–26]. The primary infection source is skin lesions, as the virus persists in the lesions or scabs for long periods. The virus is also excreted via the blood, nasal and lachrymal secretions, saliva, semen, and milk [14].

The most likely vectors for LSDV transmission are blood-sucking arthropods, such as stable flies *(Stomoxys calcitrans*), mosquitoes (*Aedes aegypti*), and hard ticks (*Rhipicephalus* and *Amblyomma* species) [14]. Experimentally *Haematopota* spp., horse flies, the biting flies *S. calcitrans*, *Stomoxys sitiens*, and *Stomoxys indica can also transmit the disease to cattle* [27]. Additionally, according to Sprygin et al. [28], a house fly (*Musca domestica*) may also play a role in LSDV transmission.

#### **3.2 Host range, morbidity, and mortality rates**

The severity of the clinical signs of LSD is highly variable. It depends on several factors, including the virus's strain, the host's age, immunological status, and breed. Bos taurus is generally more susceptible to clinical disease than Bos indicus; the Asian buffalo (*Bubalus spp*.) has also been reported to be susceptible [9]. Besides, wildlife can also be susceptible, and a recent report described clinical diseases and deaths of giraffes in a Vietnamese zoo [29]. Previously, the susceptibility of springbok, impala, and giraffe to the virus has been experimentally documented [14, 30]. Generally, high

#### *Lumpy Skin Disease: An Economically Significant Emerging Disease DOI: http://dx.doi.org/10.5772/intechopen.108845*

milk-producing European cattle breeds are more susceptible than indigenous African and Asian animals [13, 31]. Morbidity can range from 1% to almost 100%, with mortality most often between 1 and 3%. In European cattle breeds, LSD mortality remains typically below 10%, while morbidity can vary from 5–45% but, in some cases, may be higher (up to 100%) [13, 32]. All animal age groups are susceptible to this viral infection, although calves and animals with impaired immune systems are much more susceptible. The case fatality rate of LSD in adult animals is, in many cases, lower than 10%, although exceptions may occur, and mortality in young animals may be higher.

### **4. Clinical signs**

The disease is characterized by fever, nodules on the skin, mucous membranes, and internal organs, emaciation, enlarged lymph nodes, edema of the skin, and sometimes death [9]. The characteristic skin lesions are multiple, well-circumscribed to coalescing, 0.5–5 cm in diameter, firm, flat-topped papules, and nodules (**Figure 3**).

**Figure 3.** *A cow showing typical lumpy skin disease skin lesions (arrow).*

The nodules involve the dermis and epidermis and may extend to the underlying subcutis and occasionally to the adjacent striated muscle. The skin on the head, neck, perineum, genitalia, udder, and limbs are the predilection sites. These nodules have a creamy gray-to-white color on the cut section, which may initially exude serum. However, over the ensuing 2 weeks, a cone-shaped central core or sequestrum of necrotic material/necrotic plug ("sit-fast") may appear within the nodule [9]. As soon as the nodules on the mucous membranes of the eyes, nose, mouth, rectum, udder, and genitalia begin to ulcerate, the virus is present in all secretions, including saliva, ocular and nasal discharge, and the nodules on the genitalia. Many cattle suffer severe emaciation and loss of production for several months. The skin lesions cause permanent damage to the hides. The disease is of economic importance as it can cause a temporary reduction in milk production, temporary or permanent sterility in bulls, damage to hides, and, occasionally, death. LSD can lead to mastitis, orchitis, and abortion. However, nodules were not observed in aborted fetuses [14]. Intrauterine transmission of LSD is possible; pregnant cattle may abort, bulls may become permanently or temporarily infertile, and the virus can be excreted in the semen for prolonged periods [9].

#### **5. Risk factors**

In general, conditions favoring large vector populations, such as the heavy rainy season, warm, humid weather, and the purchase and introduction of new animals to a herd, are risk factors associated with the spread of LSD. In Bangladesh, LSD attack risk was significantly higher in small herds than in large herds, and the disease was observed in semi-intensive management systems than intensive management systems [33]. Communal grazing, communal water points, the introduction of a new animal, and contact with other animals were identified as significant risk factors for LSDV infection in cattle in Egypt [34]. Kiplagat et al. [35] pointed to raising exotic breeds, outside sources of stock replacement, and large herd size as the main factors associated with LSD outbreaks in Kenya. Calves and young animals (1–2.5-years-old) were at higher risk for LSD cases in Mongolia. At the same time, locations near the tube well and pond water are major risk areas for viral transmission due to the high density of insects [36]. In a study by Sethi et al. [37], grazing of animals and the age of cows (> 3 years old) were potential risk factors for the presence of LSD in India.

#### **6. Diagnosis**

Based on the clinical manifestation of the distinctive skin lesions, a provisional diagnosis of LSD can be made in an endemic setting. However, LSD diagnosis is usually tricky in previously unaffected regions because of logistical issues and a lack of familiarity with uncommon diseases.

Although distinctive clinical LSD symptoms allow for a preliminary diagnosis, test confirmation is required. Test methods recommended for diagnosing LSD are available in chapter 3.4.12 (lumpy skin disease) of the WOAH terrestrial manual [9]. The most accurate ways to detect LSDV are molecular techniques, such as conventional or realtime polymerase chain reaction (PCR) and loop-mediated isothermal amplification. The PCR is a sensitive test used to confirm clinical cases, individual animal freedom from infection before movement, and population freedom from disease. The second

diagnostic option is virus isolation, which is recommended for confirmation of clinical cases, followed by transmission electron microscopy to prove a clinical case.

#### **6.1 Pathology and histopathology**

LSD nodules are firm and may extend to the underlying subcutis and muscle. Histopathological analysis of infected tissue samples shows pathognomonic eosinophilic intracytoplasmic inclusion bodies in the keratinocytes, macrophages, endothelial cells, and pericytes associated with the ballooning degeneration of spinosum cells. Infiltration of the superficial dermal tissue of affected areas by inflammatory cells, such as macrophages, lymphocytes, and eosinophils, is also seen. In addition, widespread vasculitis and severe coagulative necrosis in subcutaneous muscles may be observed in some cases [14, 38, 39].

#### **6.2 Molecular diagnosis**

LSD diagnosis is confirmed by using conventional gel-based PCR [40–42] or real-time PCR techniques that are reported to be faster and have higher sensitivity than conventional PCRs [9, 43, 44]. Besides, a real-time PCR technique has also been established, differentiating between LSDV, SPPV, and GTPV [30].

A new rapid on-site LSDV detection method using an *orf068* gene-based recombinase polymerase amplification assay (RPA) coupled with a CRISPR-Cas12a-based fluorescence assay (RPA-Cas12a-fluorescence assay) has been described to be a specific and highly sensitive detected five copies/μL plasmid DNA [45]. Additionally, a CRISPR-powered platform providing a novel diagnostic tool for portable, ultra-sensitive, rapid, and highly adaptable disease screening of LSD that could identify lumpy skin disease virus from vaccine strains of GTPV and SPPV was recently developed [46]. For genotyping and phylogenetic study of LSDV and other *capripox* viruses, P32, RPO30, and GPCRs, as well as ORF103 genes, were targeted for partial genome sequencing.

#### **6.3 Virus isolation**

Virus isolation in cell culture or embryonated fowl eggs is the gold standard for LSDV diagnosis, but it may require several weeks to isolate the virus. LSDV can be isolated in the tissue culture of bovine, ovine, or caprine origin. In contrast to infection with bovine herpesvirus-2, which results in pseudo-lumpy skin condition and induces syncytia and intranuclear inclusion bodies in cell culture, LSDV causes a distinctive cytopathic effect and intracytoplasmic inclusion bodies [9]. According to Wang et al. [47], the most sensitive cell line for the isolation of LSDV, is primary cattle testicular (PCT) cells, while vero cells cannot be used for the isolation of this virus.

#### **6.4 Differential diagnosis**

Differential diagnosis is required to distinguish LSD from pseudo-LSD caused by bovine herpesvirus-2 (BoHV-2), dermatophilosis, dermatophytosis, bovine farcy, photosensitization, actinomycosis, actinobacillosis, urticaria, insect bites, besnoitiosis, nocardiosis, demodicosis, onchocerciasis, pseudo-cowpox, bovine papular stomatitis, cowpox, foot and mouth disease, bluetongue, mucosal disease, malignant catarrhal fever, and infectious bovine rhinotracheitis.

#### **7. Treatment, prevention, and control**

There is no specific treatment for lumpy skin disease. Nonspecific therapy using antibiotics, anti-inflammatory drugs, and vitamin injections is typically used to treat secondary bacterial complications, inflammation, and fever, as well as to increase the animal's appetite.

Mass vaccination of cattle is the most efficient method of disease management once it has spread throughout a country. To provide immunization against LSDV in susceptible cattle, several live attenuated homologous (based on the LSDV Neethling strain) and heterologous vaccines (based on strains of SPPV or GTPV have been produced. Attenuated vaccines are widely used and readily available on the market. However, the level of protection they give is still debatable because they may be ineffective or result in moderate side effects. Inactivated vaccines, on the other hand, are safe and stable and allow combinations with different antigens to make polyvalent vaccines, and they can be applied in disease-free countries. Adult cattle must receive a vaccination every year. In addition to other control strategies (such as vector control, quarantine, and biosecurity), mass immunization utilizing live homologous vaccines is presently the most efficient way to control LSD [48–50]. According to the recommendations of the EU's (EFSA) expert panel (20160812.4410864) [51], it is necessary to implement vaccination of the entire susceptible cattle population in regions facing LSDV introduction or already affected. This is in order to minimize the number of outbreaks. High vaccination coverage at animal and farm levels should be achieved. Diseased animals should not be vaccinated. However, it is necessary that the use of live homologous vaccines to protect against LSDV infection requires the use of molecular tools to differentiate between infected and vaccinated animals (DIVA). There are many commercial PCR kits that correctly identify classical field isolates (European lineage) and vaccines (Neethling vaccine) [52].

Additional control measures at the event level involve control of vectors; disinfection; movement control; official destruction of animal products; official disposal of carcasses, by-products, and waste; quarantine; vaccination in response to the outbreak.

#### **8. Conclusions**

Due to its recent rapid geographic expansion and widespread distribution, LSD is the best illustration of an emerging infectious disease. The disease is caused by the lumpy skin disease virus (LSDV), a member of the *Capripoxvirus* genus of the poxviridae family. Clinical signs of the illness include fever and flat, disk-shaped skin lesions. Blood-feeding insects are the primary vectors of LSDV transmission, and the disease spread to large distances via movement of cattle and their products. From Africa, where the disease remained endemic until 1989 lumpy skin disease extended to middle east, southeast Europe, the Balkans, and the Caucasus and is still spreading throughout Asia. Understanding the disease's epidemiology is crucial since it affects animal welfare, causes considerable production losses, and has a significant influence on trade.

#### **Acknowledgements**

I thank Dr. Hassan Z Ishag for reading and organizing the references.

### **Conflict of interest**

The authors declare no conflict of interest or delete this entire section.

### **Author details**

Abdelmalik Khalafalla Veterinary Laboratory Division, Agriculture and Food Safety Authority, Abu Dhabi, United Arab Emirates

\*Address all correspondence to: abdokhlf@yahooco.uk

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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#### **Chapter 2**

## Diagnosis and Identification of Zoonotic Diseases Associated with Cattle at Abattoirs: Current Trends and Future Prospectus

*Maryam Abdul Sattar, Muawuz Ijaz, Mubarik Mahmood, Muhammad Kashif Yar, Jawad Ashraf, Moiz Ali Younas, Sadia Ilyas and Sana Ullah*

#### **Abstract**

Zoonoses are illnesses and infections that spread spontaneously from animals to people. They account for over 70% of recently developing infectious illnesses. Meat from cattle is one of the main sources of red meat and essential element of human diet. Meat inspection (MI) is an important aspect to ensure the safety during handling and consuming of meat and meat by-products. Abattoir or modern slaughterhouse is the place where infections are acquired by the workers or veterinary professional as zoonoses. Bacterial zoonotic diseases such as erysipelothricosis, brucella, listeria, and anthrax and viral zoonotic diseases like cow pox, foot and mouth disease, and rift valley fever are causing great economic losses and are important in terms of zoonoses. These zoonotic diseases are mostly diagnosed at abattoir levels using conventional approaches; however, diagnosis and identification of these diseases using latest methods is an important aspect for ensuring meat safety and hygiene. This chapter will discuss the current trends and future prospects about diagnosis and identification of these zoonotic diseases.

**Keywords:** zoonotic diseases, cattle diseases, meat inspection, human health, abattoirs

#### **1. Introduction**

Zoonoses are illnesses that spread spontaneously from vertebrate animals to humans and vice versa [1–3]. Many farm animal species can transmit various zoonotic diseases in the livestock industry. Zoonotic diseases are typically present in killed animals, raw hides/skin, blood, meat, and farm surroundings in the beef industry, but they can be challenging to identify. Additionally, livestock transported for slaughter into metropolitan areas originates from rural communities with ineffective, disorganized, and frequently nonexistent disease control programs. Remoteness, limited infrastructure, a shortage of experienced veterinary staff, poor transportation, and a lack of funding to support surveillance activities or buy reagents and drugs all

contribute to the low quality of animal healthcare services in rural areas. Due to the scarcity of veterinary services, there is a significant risk of widespread sickness in the livestock population and concurrent human exposure to zoonotic disease agents in these areas. Additionally, many of the butchered animals brought to the abattoir run the danger of harboring chronic or subclinical illnesses that are infrequently found during a standard antemortem inspection (AMI).

A lack of knowledge about meat-borne zoonoses can endanger the lives of livestock owners, butchers, and public. There is an even greater risk of meat-borne zoonoses in this facility, given that most home slaughter slabs and abattoirs are not fully controlled and that there is a higher level of interaction with raw meat. The dangers posed by meat-borne zoonoses that are common in certain regions must be clear to cattle owners, dealers, butchers, and policymakers. The information presented should describe how zoonoses are spread to empower persons at risk to decide how to protect themselves best [4, 5]. Many bacterial and viral diseases are frequently seen and described in abattoirs [6, 7].

One of the biggest threats to the security of the world's health is the introduction of novel zoonotic viruses. Our ability to identify and respond to these health concerns more quickly than ever before has been revolutionized by the introduction of increasingly powerful diagnostic techniques. Even yet, the initial detection of new infectious illnesses starts at the local community level, regardless of how advanced these tools have become. Here is where the original human or animal case is located, and early pathogen detection would be most helpful. Unfortunately, many regions with the highest risk of zoonotic disease introduction need to be equipped with a strong enough infrastructure to support laboratory diagnostic systems. Understanding the complex sociological and ecological factors influencing the risk of disease transmission, community involvement, surveillance along high-risk human-animal interfaces, and a skilled laboratory workforce are just a few of the factors crucial for pathogen detection networks. The growing disease paradigm, current technical developments in diagnostic techniques, and plans for comprehensive and long-term methods of quick zoonotic disease detection are all covered in this chapter.

#### **2. Methodology**

In many developing countries, disease identification and diagnosis at abattoirs is compromised and a major concern of the meat industry. Bacterial zoonotic diseases such as erysipelothricosis, brucella, listeria, and anthrax and viral zoonotic diseases like cow pox, foot and mouth disease, and rift valley fever are causing great economic losses and are important in terms of zoonoses. These zoonotic diseases are mostly diagnosed at abattoir levels using conventional approaches; however, diagnosis and identification of these diseases using latest methods is an important aspect for ensuring meat safety and hygiene. Consequently, keeping in view this scenario, the current chapter has been developed to highlight the issue and spread the awareness about latest approaches by explaining its zoonotic aspects. Therefore, it is expected that such countries also take interest in proper cattle disease identification and diagnosis by adopting modern techniques in order to avoid zoonoses at abattoirs and to ensure the meat safety and hygiene.

#### **3. Zoonoses occupationally acquired by abattoir workers**

Zoonoses are illnesses and infections that spread spontaneously from animals to people. They account for over 70% of recently developing infectious illnesses [8].

#### *Diagnosis and Identification of Zoonotic Diseases Associated with Cattle at Abattoirs… DOI: http://dx.doi.org/10.5772/intechopen.109984*

More than 300 zoonotic diseases with various etiologies are known to have considerable morbidity and mortality [9]. Zoonotic infections can affect people of either sex, of any age, in any season, in any climatic zone, and both urban and rural settings [9, 10]. Together with the migration of animals across international borders to increase the local supply and the rising demand for meat and meat products, human interaction with animals has reached record levels, raising the danger of zoonotic diseases, particularly in endemic zones [11]. Numerous methods exist for zoonotic infection transmission [12, 13]. But among those who work in slaughterhouses, direct contact appears to be the


#### **Table 1.**

*Diseases, causative agents (microorganism), reservoirsm and hosts of cattle-related abattoir zoonoses.*

most typical way for pathogenic agents to enter [14]. Due to their intimate contact with animals and animal tissue during slaughter or processing, workers in the meat industry are particularly at risk of contracting several zoonotic illnesses [9, 10, 15]. The current study focuses on the zoonoses that abattoir employees who kill food animals mainly cattle. The diseases, causative agents (microorganism), reservoirs, and hosts of cattlerelated abattoir zoonoses are summarized in **Table 1**.

#### **3.1 Bacterial zoonoses**

#### *3.1.1 Erysipelothricosis*

*Erysipelothrix rhusiopathiae* is the causative agent of this contagious bacterial illness. The condition is also known as Whale finger, Pork finger, and Fish finger [9]. Infections in humans are typically acquired from occupational exposure at slaughterhouses for meat, poultry, or fish. *E. rhusiopathiae* is widely distributed, with domestic pigs serving as its primary reservoir. Pigs, sheep, cattle, horses, fish, birds, and reindeer have all been shown to be infected [9]. The most susceptible occupations to disease are those handling and inspecting meat [14].

#### *3.1.2 Brucellosis*

This is one of the most significant anthropozoonoses in terms of public health, and it is brought on by *Brucella abortus, Brucella suis, and Brucella melitensis* [16]. Buffalo, cattle, camels, horses, pigs, sheep, goats, deer, and birds have all been recorded to have it [9]. Known as "undulant fever" or "Malta fever," human brucellosis is a severe zoonose that frequently affects livestock. All slaughterhouse employees who handle livestock directly, dress carcasses, or dispose of condemned organs run a higher risk of contracting brucellosis.

#### *3.1.3 Listeriosis*

*Listeria monocytogenes*, a rod-shaped bacterium that is the etiologic agent, was discovered by Murray in 1926 in rabbits and guinea pigs [9]. Buffalo, cattle, goats, sheep, houses, birds, rabbits, and fish are all susceptible to infection [9]. Direct contact with sick animals or contaminated discharges or tissues can cause veterinarians and butchers to develop primary cutaneous listeriosis [14]. The first sign of cutaneous listeriosis is a reddish rash, which progresses to vesicular or pustular lesions that are about 1–2 mm in diameter and have either a dark or light center [14]. It can occasionally result in a more widespread illness.

#### *3.1.4 Anthrax*

*Bacillus anthracics*, a Gram-positive, aerobic, sporulated bacterium, is the source of this occupational disease [17]. All food animals have been shown to have the illness. When conditions are right, the spores can survive in contaminated soil for 40–50 years and in dead host bones for 150–250 years. Between 20,000 and 100,000 cases of anthrax in humans are thought to occur annually on a global scale. 95–99% of all human cases worldwide are of the cutaneous type, also called malignant pustule [13]. It is widespread throughout the world, including Asia and Africa. Most often, an illness spreads to abattoir employees through a skin wound. The hands and arms of

#### *Diagnosis and Identification of Zoonotic Diseases Associated with Cattle at Abattoirs… DOI: http://dx.doi.org/10.5772/intechopen.109984*

meat handlers appear to be more frequently affected by cutaneous anthrax [14]. The so-called "Malignant Pustule," a tiny pimple that quickly grows into a large blister with a dark necrotic centre, distinguishes it.

#### *3.1.5 Leptospirosis*

Weil's illness, mud fever, canicola fever, and rice-field worker's disease are just a few of the many names for this widespread bacterial zoonosis by pathogenic *Leptospira spirochetes* [18]. The illness, widespread in underdeveloped nations and reemerging in the United States [19], affects humans and animals. Numerous food animals, including cattle, buffalo, camels, horses, goats, sheep, deer, and pigs, are susceptible to leptospirosis [9]. Leptospira infection is thought to be resistant in poultry. Direct interaction with infected animals and their tissues can cause transmission, as indirect contact with a contaminated environment, particularly water tainted with the urine of infected food animals [20]. Brown and colleagues [21] investigated the environmental risk factors for leptospirosis in butchers in Jamaica.

#### *3.1.6 Tularemia*

*Francisella tularensis*, a Gram-negative, aerobic, non-sporulated bacterium, is the disease's cause and is often referred to as Deerfly fever or Rabbit fever [9]. Rabbit, deer, horse, pig, and calf cases of the disease have been documented [9]. It affects butchers of rabbits as a profession. The most prevalent way humans become infected is through skinning infected rabbits and hares. The USA annually reports roughly 2000 cases of human tularemia [14]. The first indication in men is typically a papule at the primary infection location, frequently an ulcerated finger.

#### *3.1.7 Tetanus*

It is a bacterial illness brought on by the spore-forming, Gram-positive, anaerobic bacterium *Clostridium tetani*. Horses, sheep, cattle, and pigs are all known to get natural infections [9]. The pathogen entered the body when contaminated soil or dust contaminated with *C. tetani* spores infected the incision, injury, or laceration. Incubation lasts 4–10 days. The first sign of tetanus is a tightening of the jaw muscles. The condition known as "Lock Jaw" affects men [9].

#### *3.1.8 Melioidosis*

*Burkholderia pseudomallei*, a Gram-negative, mobile aerobe, is the culprit [9]. Man contracts the virus through direct skin-to-contaminated-soil or water contact. The disease can also be transmitted by inhaling infected dust through the respiratory system. Cattles, camels, goats, horses, pigs, sheep, and kangaroos all contract diseases [9]. In dirt and water, organisms can endure for several months. Vesicles and pustules appear on the patient's hands and feet. There are septicemic, extrapulmonary, and pulmonary types. Australia has a high endemicity of disease in humans and animals [14].

#### *3.1.9 Tuberculosis*

Bovine tuberculosis, a severe zoonotic disease, is caused by *Mycobacterium bovis*. The occurrence of *M. Bovis* infection in animals and humans varies

significantly globally. *M. Bovis* causes 5–10% of all cases of human tuberculosis in several underdeveloped nations [22]. Cattle, buffalo, sheep, goats, horses, pigs, and deer have all been recorded to have the disease [9]. Direct contact with an infected animal or carcass in an abattoir results in the spread of bacteria from an animal to a human (occupational exposure). The epidermis, tendons, and regional lymph nodes of people who touch infected carcasses in the slaughterhouse develop tuberculosis sores.

#### *3.1.10 Necrobacillosis*

A bacterial infection caused in humans, cattle, and goats. By touching infected animal tissues through a wound or damaged area of skin, a disease can be transmitted from an animal to a human. *Fusobacterium necrophorum*, an anaerobic, Gramnegative, non-sporulated bacteria, is the source of disease. At the location of the organism's injection, necrotic pustules form [9].

#### *3.1.11 Dermatophilosis*

*Dermatophilus congolensis*, a facultative anaerobic actinomycete, is the diseasecausing agent. Due to how frequently it appears raindrops have just landed on the skin, the disease is occasionally called "rain scald." Initial symptoms of the illness include pustules, which are frequently disregarded. However, once the longer hairs become entangled in the scab, the pustules quickly clump together to create enormous oval crusts [11]. It affects cattle, goats, sheep, horses, camels, deer, and rabbits [23]. It has a widespread distribution.

#### *3.1.12 Chlamydiosis*

*Chlamydophila psittaci*, an intracellular organism, is the cause of this highly contagious disease that affects people all over the world. Animals, including cattle, sheep, horses, goats, pigs, buffalo, and birds, have been known to be infected [11]. Infection may develop from human exposure to infectious aerosols, dust, bird droppings, nasal discharge, and sheep fetuses and membranes [14, 24]. With good care, the illness seldom results in death. Early diagnosis and awareness are crucial as a result. A bird handler in India was found to have chlamydial infection.

#### *3.1.13 Q fever*

It is a severe rickettsial illness brought on by *Coxiella burnetii*. The organism has been contagious in farm dust and wool for a long time. Sheep, goats, and cattle are most frequently affected by the disease. Man can become inflected from inhalation, direct contact, or tick bites [9]. Fever, anorexia, chills, frontal headache, myalgia, weakness, cough, chest pain, pneumonia, and excessive sweating are the typical symptoms [9]. Pericarditis, endocarditis, and hepatitis are seen in more severe cases. In a study of employees at an Edinburgh slaughterhouse, 21.1% displayed antibodies to the phase 2 antigen of *C. burnetii* [14]. Infection among abattoir employees has been documented in Australian investigations during the past 20 years [25–27].

*Diagnosis and Identification of Zoonotic Diseases Associated with Cattle at Abattoirs… DOI: http://dx.doi.org/10.5772/intechopen.109984*

#### **3.2 Viral zoonoses**

#### *3.2.1 Cowpox*

Man can contract this viral zoonosis from infected cattle through close contact, which is how the cowpox virus (DNA virus) that causes it spreads. Acute viral illnesses like cowpox are distinguished by typical vesicular skin and mucous membrane outbreaks. Erythema, vesicles, pustules, and scab development are observed in men [9]. Some lesions on the hands, arms, and face are frequently accompanied by lymphadenitis and fever. The illness is self-contained. The hand of a butcher showed the characteristic cowpox lesions.

#### *3.2.2 Contagious ecthyma*

It is an occupational disease caused by Orfvirus (DNA) of family Poxviridae. There are cases of disease in cattle, sheep, goats, and camels. Abrasions or injuries to the skin can allow the virus to enter [3]. Man contracts the disease through direct contact with infected animals. The majority of instances are found in adults, particularly men. Butchers, meat handlers, and employees at abattoirs frequently contract diseases. Papule, vesicle, and pustule occur mainly on the finger, hand, wrist, fore arm, and sometimes on the face [14]. The lesions heal in 15–30 days, and occasionally, ocular lesions may occur [9].

#### *3.2.3 Foot and mouth disease*

It is an economically important infectious disease caused by FMD virus (RNA) of the family Picornaviridae and is reported in cattle, buffalo, camel, goat, sheep, pig, and deer [9]. Abraded skin that has been exposed to diseased animals or their excretions comes into close contact and spreads the infection. Viruses can persist for a very long time in animal hides. It is a mild disease in man and vesicles occur on the finger, palm of hand, sole of feet, or oral cavity [9].

#### *3.2.4 Rift valley fever*

Rift valley fever is caused by the rift valley fever virus (RNA), which belongs to the Bunyaviridae family and was first identified in Kenya in 1931. Man gets infection by direct contact with diseased animals or infected tissues [28]. A mosquito bite can infect both humans and animals with sickness. There are cases of disease in sheep, goats, camels, and cattle. A mosquito bite can infect both humans and animals with sickness. There are cases of disease in sheep, goats, camels, and cattle.

#### **4. Diagnosis and identification of zoonotic diseases**

Different goals are achieved by meat inspection (MI) operations carried out in slaughterhouses. MI activities were initially created with the primary goals of safeguarding consumers from foodborne dangers and assuring food safety and quality [29]. More recently, MI activities have expanded their scope to include, in particular, the supervision of animal health and welfare status [30]. Regulation (EU) 2017/625 of the European Parliament and the Council [31] and Commission Implementing Regulation (EU) 2019/627 [32] both contain regulations governing MI in Europe. The Competent Authority (CA) of each Member State conducts a series of actions at the slaughterhouse under the auspices of MI that are designed using a risk-based methodology. These actions take place before and after the animals are stunned or killed, and some of them include antemortem inspections (AMI) and postmortem inspections (PMI) [33]. At the European [34–37] and Italian levels, there are a number of recently published studies that mostly focused on lesions produced from PMI rather than AMI [38–40]. The information gathered at the abattoir during PMI is unquestionably crucial because it may be a sign of specific diseases or of subpar welfare [41]. However, the outcomes of AMI can help with a number of pig health and welfare issues as well as recommend what should be done when specific criteria are met at the abattoir.

In reality, although PMI in animals in European slaughterhouses is only visual [38], official veterinarians (OVs) can decide regarding additional procedures like physical examination and incision of organs in cases of a suspected risk for public health, animal health, or animal welfare during the AMI [42]. This is unless otherwise specified by procedures required for exporting meat and meat products in non-EU countries. Therefore, AMI operations may aid OVs in recognizing the batches of pigs that are unsuitable for visual inspection alone and that need more involved inspection techniques [43]. In reality, although PMI in animals in European slaughterhouses is only visual [38], official veterinarians (OVs) can decide regarding additional procedures like physical examination and incision of organs in cases of a suspected risk for public health, animal health, or animal welfare during the AMI [42]. This is unless otherwise specified by procedures required for exporting meat and meat products in non-EU countries. Therefore, AMI operations may aid OVs in recognizing the batches of pigs that are unsuitable for visual inspection alone and that need more involved inspection techniques [43].

In order to apply such measures, both OVs and food business operators (FBOs) need specific and reliable indicators that can facilitate the decision-making process. Little is known concerning the relationship between findings reported during AMI and those found during PMI in abattoirs [44]. To the best of our knowledge, a determination of the predictive value of certain conditions presents during AMI with respect to lesions assessable during PMI in slaughtered animals should be focused.

#### **5. Emerging pathogen detection pathway**

As people, animals, and viruses interact more intensely and intricately across local and global environments, there is a greater chance that a zoonotic pathogen with actual pandemic potential could emerge, endangering the life of millions of animals and humans. By necessity, the first signs of this threat must be observed locally, with sick people (or animals) being observed by someone acquainted with the local diseases. This initial discovery is typically never reported outside the surrounding area because the disease is not rare and spreads slowly. However, in some cases, the identification of initial cases or the subsequent chain of multiple events may result in the eventual involvement of the local or national state authorities as well as the potential intervention of international health responders. In many nations, centralized systems have been established, where epidemiologic and laboratory diagnostic capabilities are housed in national-level centers that serve as referrals and are located far from the

#### *Diagnosis and Identification of Zoonotic Diseases Associated with Cattle at Abattoirs… DOI: http://dx.doi.org/10.5772/intechopen.109984*

majority of the high-risk human-animal interfaces that are the forerunners of disease emergence [45]. In these situations, clinical data on patients or animals, news of mass deaths or other uncommon illnesses, and finally diagnostic samples for examination are pulled up to these referral centers from the local level.

Despite its benefits, this centralized pull method has a number of failure points, since it might be challenging to get information and diagnostic samples from the home to the national level. Delays in the identification, diagnosis, and ultimately control of emerging health threats are caused by a variety of factors, including inadequate transportation or information systems, a lack of trained health workers, inadequate laboratory frameworks, poor multidisciplinary or ministerial communication channels between the animal and public healthcare organizations, mistrust of government officials, and occasionally less-than-ideal national reporting systems.

How to best build robust and durable surveillance networks that can identify the rare and isolated health event at the regional level and correlate those evaluations with highly qualified public health laboratory workers is the main challenge in the early screening of growing zoonoses at a systems level [46]. Is it more likely for a distributed network of local partner-driven surveillance teams with basic laboratory capacity for point-of-care rule-in/out diagnosis to be successful than a highly centralized and concentrated network in national- or regional-level reference institutions or government ministries, or even a combination of both? The sustainability of money, the requirement for training, and the sophistication of laboratory procedures required for pathogen detection are important factors that determine which of these approaches is most suited for a given nation. In various nations, examples of accomplishments from a combined effects of national and local monitoring networks with assistance from international organizations have been produced [47, 48].

The best-positioned disease surveillance systems to quickly identify emerging zoonotic hazards are probably those that strive to connect the animal and human health sectors as closely as is practical. The objective of these combined surveillance operations is to identify novel emerging diseases from susceptible animals and the human population as promptly as feasible. Field ecology teams and human and animal health professionals will collaborate on these activities. It may be best to combine this integrated strategy with initiatives to bring the technical expertise and laboratory facilities required for zoonotic disease detection as near to the local levels as possible. Systems that use a locally driven and distributed component may be more expensive and challenging to manage than exclusively centralized systems, but because they are closer to and more integrated into the local community, they are more likely to be able to quickly identify rare health events for follow-up.

#### **6. Building an effective approach**

The development of local or regional surveillance centers is necessary for integrated approaches to be viable. This requires long-term, sustainable financing and investments in human capital, infrastructure, laboratory equipment, and these areas. In response to the SARS outbreak in 2001, 196 World Health Organization (WHO) member countries adopted International Health Regulations (IHR) in 2005, which has accelerated the establishment of integrated animal and human health surveillance systems for zoonoses [49]. The opportunity to more closely link the human and animal disease surveillance sectors has been made possible by these restrictions, together with the growing understanding that the appearance of a disease in one nation might

quickly spread to another through the movement of animals or humans. IHR requires the timely notification (<24 h) of outbreaks "of disease with the ability to cause serious public health impact and to spread internationally" and may constitute a "Public Health Emergency of International Concern" [50]. The regulations do not stipulate the source of the infection (human or animal) and are meant to be applied as broadly as possible by all member nations.

Finding local, national, and regional partners to work with these multinational organizations, create structures with them, and find bright and motivated people is a crucial initial step in this process. To create a knowledgeable and well-coordinated network of people and institutions for zoonotic disease detection, these individuals should ideally come from a variety of scientific backgrounds and work in all fields, including human, animal, and wildlife health specialists, epidemiologists, laboratory and behavioral scientists, and other junior and senior staff.

#### **7. Conclusion**

A lack of latest approaches in diagnosis and identification of zoonotic diseases at abattoirs can endanger the lives of livestock owners, butchers, and public. There is an even greater risk of meat-borne zoonoses in this facility, given that most home slaughter slabs and abattoirs are not fully controlled and that there is a higher level of interaction with raw meat. In most of the countries, diagnosis and identification of these zoonotic diseases at abattoirs is performed by conventional ways such as by antemortem and postmortem examinations. However, latest approaches should be adopted to avoid such bacterial and viral zoonoses.

#### **Conflict of interest**

The authors declare no conflict of interest.

*Diagnosis and Identification of Zoonotic Diseases Associated with Cattle at Abattoirs… DOI: http://dx.doi.org/10.5772/intechopen.109984*

### **Author details**

Maryam Abdul Sattar1 , Muawuz Ijaz2 \*, Mubarik Mahmood2 , Muhammad Kashif Yar2 , Jawad Ashraf<sup>3</sup> , Moiz Ali Younas2 , Sadia Ilyas2 and Sana Ullah4

1 Department of Biological Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan

2 Department of Animal Sciences, University of Veterinary and Animal Sciences, Jhang, Pakistan

3 College of Agriculture, University of Layyah, Layyah, Pakistan

4 Quality Operational Laboratory, International Development and Research Centre, University of Veterinary and Animal Sciences, Lahore, Pakistan

\*Address all correspondence to: muawuz.ijaz@uvas.edu.pk

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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[34] Sánchez P, Pallarés FJ, Gómez MA, Bernabé A, Gómez S, Seva J. Importance of the knowledge of pathological processes for risk-based inspection in pig slaughterhouses (Study of 2002 to 2016). Asian-Australasian Journal of Animal Sciences. 2018;**31**:1818-1827

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[37] Kongsted H, Sørensen JT. Lesions found at routine meat inspection on finishing pigs are associated with production system. The Veterinary Journal London England. 2017;**223**:21-26

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#### **Chapter 3**

## Effect of Cattle-Specific Diseases on Carcass Inspection and Meat Quality

*Muhammad Kashif Yar, Mubarik Mahmood, Muawuz Ijaz, Muhammad Hayat Jaspal, Zayrah Rafique, Iftikhar Hussain Badar and Kanwal Rafique*

#### **Abstract**

There are severe cattle-specific viral (foot and mouth, vesicular stomatitis, rinderpest, rift valley fever, malignant catarrhal fever, lumpy skin, rabies, bovine leukosis, bovine viral diarrhea, and bovine spongiform encephalopathy), bacterial (tuberculosis, black quarter, botulism, malignant oedema, leptospirosis, brucellosis, anthrax, hemogenic septicemia, actinomycosis, actinobacillosis, mastitis, and metritis), parasitic (lungworm, fasciolosis, cysticercosis, hydatid disease, and onchocercosis), and protozoal (trypanosomiasis, theileriosis, anaplasmosis, babesiosis, and sarcosporidiosis) diseases that affect the carcass judgment and meat quality. These diseases adversely affect cattle health, welfare, and red meat production. This chapter aims to describe the etiology, mode of transmission, ante-mortem and post-mortem findings, carcass and meat quality judgment, and differential diagnosis of these diseases.

**Keywords:** cattle-specific diseases, carcass judgment, meat production, meat quality, carcass inspection

#### **1. Introduction**

Beef carcasses are commonly inspected to deliver safe and healthy meat for human consumption all over the world. An abattoir is an approved and registered place by the authorities for hygiene slaughtering, inspecting, processing, and storage of meat for human consumption [1]. It also helps to detect economic and public health important diseases [2]. The veterinarians and the meat inspectors are mainly responsible for inspecting the carcasses and the meat at the abattoir phase. The data collected from ante-mortem and post-mortem inspections at the abattoirs are useful to evaluate the disease condition and decide the fate of the carcass either approved for human consumption or should be condemned [3].

Cattle are one of the major sources of red meat all over the world including Pakistan, where the demand for animal protein is increasing with time due to the increase in population [4, 5]. There are severe cattle-specific viral, bacterial, parasitic, and protozoal diseases that are of economic and public importance [6]. Beef production is one of the most important livelihoods of rural families, especially in developing nations and the condemnation of the carcasses or specific organs causes severe economic losses to the farmers and the livestock sector [7, 8]. Besides carcass and meat inspection, the abattoirs in the most developed nations have helped to detect and eradicate several diseases in cattle [9]. However, in developing nations like Pakistan, the abattoirs are not fully utilized, and carcasses are not properly inspected before defining their fates.

In developing nations, veterinarian and meat checkers often lack the basic guidelines to determine the fate of the carcasses whether it should be approved, conditionally approved or condemned. Therefore, this chapter aims to describe the etiology, mode of transmission, ante-mortem and post-mortem findings, carcass and meat quality judgment, and differential diagnosis of cattle-specific diseases. These guidelines will help the meat inspector to determine carcass fate and prevent the spread of public health important diseases through meat consumption.

#### **2. Carcass and meat inspection procedures**

There are two main objectives of meat inspection. Firstly, physically normal, healthy animals should be slaughtered and processed for human consumption. Secondly, the slaughtered animal should be disease free, and there should be no risk to human health. These aims could be attained by performing ante-mortem and postmortem inspections at the abattoirs.

#### **2.1 Ante-mortem examination**

The word ante-mortem examination indicates the examination of cattle "before death". Thus, the examination of cattle before slaughtering is termed as "anti-mortem examination". All the animals presented for slaughtering should receive ante-mortem examination. The purposes of ante-mortem examinations are to screen cattle before slaughter, to ensure the proper rest [10, 11], to get clinical information for disease diagnosis and identifying the reportable diseases, and lastly, to identify the animals treated with antibiotics and other chemotherapeutic agents [12]. Animal should be examined from both sides in both standing and moving conditions. Ante-mortem examination should be carried out within 24 h of slaughtering and perform again if the slaughtering has been delayed over a day. Cattle showing the clinical signs should be separated from the healthy animals and treated as "suspects" and must be held for veterinary inspection and judgment. Ante-mortem examination should be performed in adequate lightening at rest and motion [13]. The general behavior along with the nutritional status, signs of disease, and abnormalities should be observed. The abnormality in behavior, posture, gait, structure, and conformation should be monitored.

#### **2.2 Post-mortem examination**

The term post-mortem means "after death". Thus, the inspection of the animals after slaughtering is termed as "post-mortem inspection" [14]. The post-mortem examination majorly comprises head, viscera, and carcass inspection. The postmortem inspection of the carcass should be carried out just after the dressing of the carcass to notice any abnormality or diseased condition to pass or reject the carcass

#### *Effect of Cattle-Specific Diseases on Carcass Inspection and Meat Quality DOI: http://dx.doi.org/10.5772/intechopen.110384*

for human consumption. The carcass and organs inspections should be corelated before making the final diagnosis. The post-mortem examination is done by viewing, incising, palpating, and using olfaction techniques [15]. The lesions are classified into acute or chronic, localized or generalized and relevancy of lesions to major organs or systems. The ante-mortem and post-mortem findings should be corelated before making the final judgment.

#### **3. Cattle-specific viral diseases**

#### **3.1 Foot and mouth disease (FMD)**

Foot and mouth disease (FMD) is a highly contagious viral disease of clovenhooved animals such as cattle [16]. FMD is caused by Aphthovirus, belonging to Picornaviridae family. There are seven serotypes of the virus, termed: A, O, C, Asia 1, and SAT (Southern African Territories) 1, 2, and 3. FMD is spread through direct or indirect contact with infected cattle, their secretions, animal products, and byproducts. Ante-mortem examination shows vesicles and erotic lesions on the muzzle, mouth, feet, teats, and udder region. The cattle show high fever, dullness, reduced appetite, dropping milk production drastically, and muscle termers. Post-mortem examination shows a necrotic heart, usually in young cattle and the ulcerative lesion on the tongue, gums, palate, pillars of the rumen, and feet [15]. In the FMD-free countries and zones, the cattle are prohibited to enter the abattoir. If the FMD is diagnosed on post-mortem inspection, then carcass and visceral organs are condemned, and proper measures should be taken as suggested by the regulatory authorities of the country. If the FMD is present in the country, then the judgment should be done by considering the animal health status and public health concerns.

#### **3.2 Vesicular stomatitis (VS)**

Vesicular stomatitis (VS) is a viral disease that majorly affects cattle and horses. VS is a viral disease caused by New Jersey and Indiana serotypes of vesicular stomatitis virus [17]. VS is transmitted through aerosol, direct contact, fomites, and also through insects vectors [18]. Ante-mortem examination shows vesicular lesions in the mouth, teats, and around feet. The animal shows a decrease in weight, ending of lactation in lactating cattle, profuse salivation, and lips ribbing on mangers edges in horses. Post-mortem examination shows lesions resembling the lesions of other mucosal diseases; however, like FMD, heart and rumen lesions do not appear in VS. The carcass displaying acute changes and the systematic lesions is condemned. If the animal is not affected by the acute stage and showing no secondary bacterial infection, the carcass is approved; however, the visceral organs are condemned.

#### **3.3 Rinderpest (RP)**

Rinderpest (RP) is an acute, viral, highly contagious disease of cattle, buffalo, and some wildlife species [19]. RP is caused by RNA virus of Paramyxoviridae family. RP is spread through air, direct contact, and fomites. Ante-mortem examination shows high fever, nasal discharge, extreme salivation, mouth erosion, decrease in appetite, depression, and bloody diarrhea. Post-mortem examination shows erotic or necrotic lesions throughout GIT and upper respiratory tract leading to the classical

"zebra-striping" in the rectum. Enlarged edematous lymph nodes and necrotic foci are also observed in the Peyer's patches. In the RP-free countries and zones, the cattle are prohibited to enter the abattoir. If the RP is diagnosed on post-mortem inspection, then carcass and visceral organs are condemned, and suitable measures should be taken as recommended by the regulatory authorities of the country. In RP, prevalent countries, if symptoms are mild, then the carcass can be conditionally approved.

#### **3.4 Rift Valley fever (RVF)**

Rift Valley fever (RVF) is a viral disease of cattle mostly seen in domesticated animals in sub-Saharan Africa. The disease is caused by the rift valley fever virus (RVFV), a member of the genus Phlebovirus. RVFV is majorly spread through biting insects and mosquitoes [20]. Humans are mostly infected through direct or indirect contact with infected organs. Ante-mortem examination in cattle shows edematous skin, discharge from the nose, weakness, diarrhea, decreased milk production, and abortion [21]. Post-mortem findings show cyanotic visible mucosa, edematous and hemorrhagic gall bladder, and spleen and peripheral lymph nodes are enlarged and edematous and may show petechiae and purple udder with invisible inflammation. The carcass of cattle affected with RVFV is condemned. The carcass of recovered animals can be conditionally approved; however, the affected visceral organs must be condemned.

#### **3.5 Malignant catarrhal fever (MCF)**

Malignant catarrhal fever (MCF) is an acute viral disease of cattle. The disease is caused by bovine herpesvirus 6 in cattle [22]. It is transmitted by close contact between cattle and wildebeest, through common water troughs. Ante-mortem examination in cattle shows high fever, lachrymation, erotic lips, tongue, gums, inappetence, and decreased milk yields. Furthermore, the cattle show photophobia linked with corneal opacity and blindness. Superficial lymph nodes might be enlarged and swollen limb joints. On post-mortem, the cattle show erosions and hemorrhages in GIT: contents may be hemorrhagic, white areas in the kidneys and enlarged lymph nodes with varying degrees in different regions of the animal [23]. Typically, "Tiger stripings" in colon region are observed. In mild disease cases, the carcasses can be conditionally approved; however, if systemic signs appear, then carcasses are condemned.

#### **3.6 Lumpy skin disease**

Lumpy skin disease is an acute viral disease of cattle. It is caused by the poxvirus. It is transmitted through blood-feeding insects, such as specific species of flies, mosquitoes, and ticks [24]. The diseased cattle show fever, nasal discharge, and hypersalivation skin eruption of different body parts. The nodular lesions are round, firm, and painful. The secondary infection can cause joint and tendon inflammation [25]. The post-mortem inspection shows ulcerative lesions of respiratory and digestive tract mucosa, edema, and nodules in the lungs. In mild disease cases, the carcasses can be conditionally approved; however, if generalized acute infection appears, then carcasses are condemned.

#### **3.7 Rabies**

Rabies is an acute lyssaviruses disease, causes encephalomyelitis. It is transmitted through infected saliva or the bite of a rabid animal [26]. It has different forms.

*Effect of Cattle-Specific Diseases on Carcass Inspection and Meat Quality DOI: http://dx.doi.org/10.5772/intechopen.110384*

On ante-mortem examination, the furious form shows restlessness, aggression, paralysis, and death. Whereas, the paralytic form shows ataxia leading to paralysis of the throat and masseter muscles, hypersalivation, the inability of swallowing, and death after 48 h of laying down. On post-mortem, the cattle show inflammation of gastrointestinal mucosa. If rabies is present in the country and the animal was bitten eight days before slaughter and within 48 hours of slaughter,then the carcass can be approved after removing bitten tissues.

#### **3.8 Bovine leukosis**

Bovine leukosis in cattle is caused by the bovine leukosis virus (BLV) [27]. It is found in sporadic or enzootic forms. Between these two forms, the sporadic is observed in young, whereas the enzootic is reported in adult cattle. The infection is spread through the blood and from the dam to the calf through vertical transmission. Ante-mortem findings show weight loss, bloat, fever, tachycardia, and posterior paresis. Moreover, edema in the brisket and intermandibular region is also reported. Cutaneal nodules have also been seen in some cases. The post-mortem findings show lymph node enlargement, splenomegaly, and necrotic lesions in the heart and intestine. Furthermore, ventral edema is also reported. Carcasses are condemned for human consumption in this disease [28].

#### **3.9 Bovine viral diarrhea (BVD)**

Bovine viral diarrhea (BVD) is a cattle disease caused by the bovine viral diarrhea virus (BVDV). It is transmitted through congenital infection of the fetus [29]. This disease can lead to abortion or stillbirth. The ante-mortem findings show lethargy, fever, decreased appetite, ocular and nasal discharge, and diarrhea. On post-mortem, BVD shows erotic lesions on the nostrils, mouth, larynx, esophagus, rumen, omasum, abomasum, and caecum [30]. Cecum and colon show stripping similar to the RP. If generalized acute infection appears along with fever and emaciation, then carcasses are condemned.

#### **3.10 Bovine spongiform encephalopathy (BSE)**

Bovine spongiform encephalopathy (BSE), commonly known as "mad cow disease", is a fatal neurologic disease of cattle [31]. BSE is caused by prions, an abnormal virus-like protein. Contaminated feed is the major reason for disease spread.

Ante-mortem examination shows behavioral changes, tremors, and abnormal ear position. Hyperesthesia, nervousness, reluctance for milking, and aggression toward other animals are also reported [32]. Post-mortem findings show microscopic lesions including degenerative lesions in the cerebral cortex, medullary region, and central gray matter of the midbrain. The carcass of cattle affected with BSE is condemned.

#### **4. Cattle-specific bacterial diseases**

#### **4.1 Tuberculosis**

Bovine tuberculosis (TB), caused by the bacterium *Mycobacterium bovis*, is an infectious disease of cattle. It can also cause disease in other mammals including

humans, goats, pigs, deer, and dogs [33]. This infection is mainly spread through inhalation or ingestion of the bacteria. Contaminated water and food are also sources of infection. The ante-mortem examination shows fluctuating fever, chronic intermittent hacking cough associated with pneumonia, weakness, difficulty in breathing, loss of appetite, and emaciation. Post-mortem findings show tuberculous granuloma in the lymph nodes of the head, lungs, intestine, and carcass. Lesions also appear in the lungs, liver, spleen, and kidney. In the country where TB has been eradicated or the eradication program is ongoing, the carcasses will be condemned. In mild cases, carcasses could be conditionally approved.

#### **4.2 Black quarter (black leg)**

The black quarter also recognized as black leg is an acute infectious disease of cattle caused by *Clostridium chauvoei* [34]. It causes inflammation of the muscles, toxemia, and high mortality. It is soil-borne infection transmitted through a wound, injection needle, or ingestion (especially when there are oral abrasions). Ante-mortem findings initially show high fever, lameness, with severe depression are classical signs of black quarter disease. Animal stops eating and ruminating. Crepitating and gaseous swelling of the affected muscles of hind quarters and shoulders leading to hot and painful swelling is very characteristic. If not treated immediately, death may occur within 12**–**36 h due to severe toxemia. On post-mortem, skin over the swelling appears dark with oozing dark-colored offensive-smelling fluid. Crepitating swelling when cut open shows oozing of a dark red fluid with bubbles with a rancid odor. The affected muscles on palpation appear sponge-like with the presence of gas bubbles indicating necrotizing hemorrhagic myositis (due to toxin). Usually, the spleen is enlarged and hemorrhagic. The slaughtering of affected cattle is prohibited, and if the cattle have been slaughtered, then carcass and visceral organs are condemned [15].

#### **4.3 Botulism**

Botulism is caused by the toxins produced by *Clostridium botulinum*. It causes paralysis of different muscles. Decomposed flesh and bones are the sources of infection for cattle [35]. Ante-mortem examination shows flaccid muscular paralysis, disturbed vision, difficulty in chewing and swallowing, and generalized progressive paresis. On post-mortem, foreign material in the rumen or reticulum may be found. The carcasses are condemned due to human hazards.

#### **4.4 Malignant edema**

Malignant edema is caused by *Clostridium septicum* in cattle. Infection ordinarily occurs through contamination of wounds containing devitalized tissue or soil [36]. On ante-mortem examination, the cattle show anorexia, high fever, depression, weakness, muscle tremors, and lameness. Post-mortem findings show gangrenous skin in the affected area, foul putrid odor, accumulation of sero-sanguineous fluid in body cavities, and darkening of muscles. The carcasses are condemned due to human hazards.

#### **4.5 Leptospirosis**

Leptospirosis is a bacterial disease caused by Leptospira genus in cattle. Leptospirosis can be transmitted directly or indirectly between animals and through the environment, respectively [37]. The ante-mortem examination shows fever, loss of appetite, and mastitis in mild cases; however, severely affected cattle show anemia, jaundice, pneumonia, and abortion with retained placenta. Post-mortem findings show anemia, jaundice, submucosal hemorrhage, interstitial nephritis, and septicemia. In the case of acute leptospirosis, carcasses are condemned, whereas, in the case of chronic and localized conditions, carcasses can be conditionally approved [15].

#### **4.6 Brucellosis**

Brucellosis is an infectious and contagious disease of cattle that is caused by *Brucella abortus*. It is transmitted by contaminated feed, pasture, water, milk, an aborted fetus, uterine fluid, and discharges [38]. Ante-mortem examination shows stillborn or weak calves, retained placentas, and reduced milk yield. Post-mortem examination shows an edematous fetus and placenta. Carcasses of affected cattle are approved as *Brucella abortus* remains viable only for a shorter period after slaughter. However, in acute aortic form, carcasses are condemned.

#### **4.7 Anthrax**

Anthrax is a noncontagious zoonotic disease. It is caused by *Bacillus anthracis*. Anthrax is transmitted through inhalation, ingestion, and a wound in the skin [39]. Biting flies are also a source of transmission. In per acute and acute cases, no clinical signs are reported as it causes sudden death. On post-mortem examination, the cattle show dark-colored blood discharge from natural orifices, no rigor mortis development, splenomegaly, and rapid decomposition of the carcasses. Carcasses are commended and buried almost six feet below ground with a surrounding layer of lime [15].

#### **4.8 Hemorrhagic septicemia (HS)**

Hemorrhagic septicemia (HS) is a systemic disease of cattle. It is caused by specific serotypes of *Pasteurella multocida*. It is spread by the ingestion of contaminated feedstuff. The ante-mortem examination of cattle shows high fever, salivation, difficulties in swallowing, cough, difficult breathing, and pneumonia [40]. The cattle also show edematous swelling of the throat, dewlap, and brisket region. In per acute cases, HS causes death within 8–24 h. The post-mortem findings show subcutaneous swelling and yellowish gelatinous fluid around the throat and brisket areas. Lymph nodes are enlarged hemorrhages in the organs and pneumonia [41]. If the HS is diagnosed on ante-mortem examination, then cattle are not allowed to enter or be slaughter in the abattoirs. The carcasses of HS-affected cattle are condemned.

#### **4.9 Actinomycosis**

Actinomycosis is caused by *Actinomyces bovis*. It is a chronic granulomatous disease of cattle. The causative agent is a normal inhabitant of the bovine mouth. The bacteria enter through cuts or abrasions and migrate to the bone, leading to osteomyelitis [42]. The mandible is affected more commonly than the maxilla. Ante-mortem findings show a hard, immobile, bony mass on the mandible, ulceration of cheeks and gums, and wart-like granulations outward on the head. Fever, excessive salivation, and dropping of feed from the mouth are also observed. On post-mortem examination, the cattle show mandibular lesions (lumpy jaw). Lower part of the esophagus and anterior reticulum also show granulomatous lesions [43]. In severe cases of actinomycosis, the carcasses are condemned; however, in mild cases, carcasses are conditionally approved.

#### **4.10 Actinobacillosis**

Actinobacillosis is caused *Actinobacillus lignieresi*, a chronic disease of cattle. The causative agent is a normal inhabitant of the bovine mouth. The bacteria enter through cuts or abrasions. The ante-mortem examination shows salivation, loss of appetite, erosions in the mouth, swallowed tongue, and enlarged parotid and retropharyngeal lymph nodes. Post-mortem findings show an enlarged fibrous tongue (wooden tongue), granular lesion in the lymph nodes, and the thickening of the lower part of the esophagus and stomach wall [44]. The erosions in the mucosa of the rumen and reticulum are also reported. In severe cases of actinobacillosis, the carcasses are condemned; however, in mild cases, carcasses are conditionally approved.

#### **4.11 Mastitis**

Mastitis in cattle is caused by bacteria, fungi, and yeasts. It is spread through milk, especially through milker hands. Ante-mortem examination show variable temperature, swallowed painful udder, depression, loss of appetite, and exudate from teats [45]. Post-mortem findings show pale yellow edematous udder parenchyma and enlarged supramammary, iliac, and lumbar lymph nodes. In severe cases, if mastitis is associated with systemic changes, then carcasses are condemned. In case of localized conditions, carcasses are approved for human consumption.

#### **4.12 Metritis**

Inflammation of the uterus is termed as metritis mostly originated from bacteria. It occurs majorly due to calving problems such as retention of placenta, abortion, twin births, abnormal labor, traumatic lesions of the uterus cervix, and vagina [46]. Ante-mortem examination of cattle shows high fever, retained placenta, and reddish discharge from the vulva. The post-mortem findings show an enlarged flaccid uterus, an inflamed uterus with foul-smelling exudate, and congestion in muscles. In acute disease conditions, the carcasses are condemned, whereas in case of mild infection and carcasses lacking systemic signs may be approved.

#### **5. Cattle-specific parasitic diseases**

#### **5.1 Lungworms**

Lungworms (*Dictyocaulus viviparus*) cause verminous pneumonia in cattle. The eggs are engulfed by the host while coughing [47]. On ante-mortem examination, the cattle show high temperature, nasal discharge, labored breathing, and recumbency. Post-mortem findings show hemorrhagic inflammation of the bronchi along with froth, edema in the lungs, enlarged lymph nodes, and lungworms are also present in lungs. In mild cases, carcasses are approved, while the affected lungs are condemned. In severe cases, if lungworm infestation led to pneumonia along with emaciation and anemia, the caresses are condemned.

#### **5.2 Fascioliasis**

Fascioliasis is majorly caused by liver fluke (*Fasciola hepatica*). It is a zoonotic and public health important disease. It is spread by the ingestion of cysts by the host cattle [48]. Ante-mortem findings show emaciation, weight loss, anemia, chronic diarrhea, and swallowing in the mandibular region. Post-mortem examination shows anemic, emaciated carcasses, the presence of flukes in enlarged and thickened bike ducts, calcification of bile ducts, and blackish lymph nodes of the liver due to fluke excrement [15]. Carcasses are condemned if heavily infested along with the emaciation. If the condition is mild, then carcasses are conditionally approved.

#### **5.3 Cysticercosis**

Cysticercosis in cattle is caused by *Cysticercus bovis*. It is the cystic form of the human tapeworm *Taenia saginata*. Cattle become infested by the ingestion of ova. In human, infection occurs by eating raw or undercooked beef containing viable cisticerci [49]. Cattle may show muscle stiffness on ante-mortem examination only in heavily infested cases. Post-mortem examination shows small white lesions in the muscles and later on calcification also occurs. Carcasses and visceral organs are condemned.

#### **5.4 Hydatid disease**

Hydatid disease in cattle is caused by *Echinococcus granulosus*. This disease is also known as hydatidosis or echinococcosis. Eggs are dispersed in the environment via the feces of infected dogs [50]. Cattle become infested by the ingestion of ova. No significant ante-mortem findings are reported. On post-mortem examination, carcasses show hydatid cysts in the heart, liver, kidney, and muscle tissues including the bones. In case of edema, emaciation, and muscular involvement, carcasses are condemned. In mild cases, carcasses may be conditionally approved, however, visceral organs are condemned.

#### **5.5 Onchocercosis**

Onchocercosis in cattle is majorly caused by nematode *Onchocerca gibsoni* [51]. The midguts of the Cullicoides are the common vectors. However, the other biting flies may act as the intermediate host. The larvae are developed to the infective stage in the midguts of the Cullicoides. Cattle are infected through the biting flies. Ante-mortem examination show sub-cutaneous nodules in the brisket and buttock areas. On postmortem examination, cattle show single or clusters of fibrous nodules in the brisket, buttock, and thigh region. The worms may be live, dead, or in the calcified form in nodules. The carcasses are approved by removing the affected parts.

#### **6. Cattle-specific protozoal diseases**

#### **6.1 Trypanosomiasis**

Trypanosomiasis in cattle is caused by Trypanosoma genus. It is transmitted mechanically by biting flies. Ante-mortem examination of cattle shows intermittent fever, anemia, weakness, weight loss, enlarged lymph nodes, edema, and opacity of the cornea. Post-mortem examination shows edematous and emaciated carcasses, enlargement of the liver and spleen, and enlarged lymph nodes. The carcasses are condemned in acute cases, showing systemic enrollment. In mild cases, carcasses are conditionally approved; however, affected parts and visceral organs are condemned.

#### **6.2 Theileriosis**

Theileriosis in cattle is caused by a blood-borne parasite Theileria parva. It is spread through ixodid ticks of the species Rhipicephalus [52]. Ante-mortem examination of cattle shows high temperature, difficulty in breathing, nasal discharge, and swallowed lymph nodes. One-sided circling and convulsions leading to death are also reported. Post-mortem examination shows pulmonary edema, emphysema, enlarged hemorrhagic lymph nodes, enlarged liver, white spots of lymphoid aggregates in kidneys, and brownish coloration of fat. In mild cases with no systemic involvement, the carcasses and visceral organs are approved. However, in acute cases of theileriosis, showing fever and generalized lesions, the carcasses and affected organs are condemned.

#### **6.3 Anaplasmosis**

Anaplasmosis in cattle is majorly caused by a blood cell parasite *Anaplasma marginale*. It is transmitted through Boophilus tick. Whereas, the horsefly and mosquitoes are the mechanical transmitters. Ante-mortem examination of cattle show high fever, jaundice, anemia, and emaciation [53]. Post-mortem examination shows congested splenomegaly, watery blood with poor clotting ability, enlarged, icteric liver, deep orange in color, distended bile ducts, and yellow-colored carcasses. Confirmation can be done by detecting the parasite Giemsa stain. In case of acute infection, carcasses are condemned. In recovered and suspect cases, showing mild or inconclusive signs is conditionally approved.

#### **6.4 Babesiosis**

Babesiosis is a tick-born disease, and in cattle, it is caused by different protozoan of genus Babesia [54]. Ixodidae family of ticks serve as vectors in different locations. Ante-mortem examination of cattle shows high fever and dark reddish-brown urine. Post-mortem findings show enlarged liver and spleen, edematous congested lungs, anemia, jaundice, edematous and hemorrhagic lymph nodes, and pink-colored hemorrhages in cattle brain. In case of acute infection, carcasses are condemned. In mind cases, carcasses are conditionally approved.

#### **6.5 Sarcosporidiosis**

Sarcosporidiosis also termed as sarcocystosis is caused by different species of Sarcocystis genus. Cattle become infested by ingesting contaminating feed, pasture, or water that contains Sarcocystis spp. cysts. Ante-mortem examination of cattle shows fever, loss of appetite, excessive salivation, anemia, and loss of hair from tip of the tail [15]. On post-mortem examinations, cysts are invisible due to their smaller size, and cysts become associated with eosinophilic myositis. Heavily infested carcasses showing macroscopic cysts are condemned. In mild infestation, unaffected parts of the carcass are approved for human consumption.

*Effect of Cattle-Specific Diseases on Carcass Inspection and Meat Quality DOI: http://dx.doi.org/10.5772/intechopen.110384*

#### **7. Conclusion**

The purpose of carcass inspection is to ensure meat quality and its suitability for human consumption. Ante-mortem and post-mortem findings are helpful to diagnose any diseased condition and to give final judgment regarding meat consumption. This chapter covered cattle-specific disease and their effect on carcass judgment and meat quality. The recommendation given in this chapter regarding carcass judgment related to cattle-specific diseases will be helpful to find out the suitability of the carcass for human consumption.

### **Conflict of interest**

The authors declare no conflict of interest.

### **Author details**

Muhammad Kashif Yar1 \*, Mubarik Mahmood1 , Muawuz Ijaz1 , Muhammad Hayat Jaspal<sup>2</sup> , Zayrah Rafique3 , Iftikhar Hussain Badar2 and Kanwal Rafique1

1 Department of Animal Sciences, University of Veterinary and Animal Sciences, Jhang, Pakistan

2 Department of Meat Science and Technology/Faculty of Animal Production and Technology, University of Veterinary and Animal Sciences, Lahore, Pakistan

3 Department of Basic Sciences, University of Veterinary and Animal Sciences, Jhang, Pakistan

\*Address all correspondence to: kashif.yar@uvas.edu.pk

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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#### **Chapter 4**

### Paraoxonase 1 in Cattle Health and Disease

### *Abdulsamed Kükürt and Volkan Gelen*

#### **Abstract**

Paraoxonase is a family of enzymes with diverse biological functions. This study investigates the role and effects of the paraoxonase enzyme, particularly in relation to cattle health and disease. The findings reveal that the paraoxonase enzyme mitigates oxidative stress, regulates the immune system, preserves liver function, and exerts other biological effects in cattle. Moreover, certain genetic variations associated with the paraoxonase enzyme may be linked to health issues, such as cattle diseases. Therefore, further research aimed at comprehending the relationship between the paraoxonase enzyme and cattle health may assist in the development of novel treatment and prevention strategies in future cattle breeding and veterinary applications.

**Keywords:** Paraoxonase 1, cattle, oxidative stress, acute phase response, antioxidant

#### **1. Introduction**

The Paraoxonase (PON) molecule comprises three distinct subtypes of enzymes: PON1, PON2, and PON3. PON1 is the most extensively studied subtype in humans and is typically the focus of research [1, 2]. The enzyme Paraoxonase 1 (PON1) was first discovered as an organophosphate pesticide-hydrolyzing enzyme in mammalian tissues by Mazur in the 1940s [3]. In 1953, Aldridge identified it as an α-esterase enzyme due to its ability to hydrolyze diethyl p-nitrophenyl phosphate [4]. Subsequently, PON1 was classified as an "aryl dialkyl phosphatase" by the International Union of Biochemistry and Molecular Biology Enzyme Commission owing to its ability to hydrolyze an aryl-dialkyl phosphate into a dialkyl phosphate and an aryl alcohol [5]. Further investigations have revealed that PON1 also functions as a lactonase and an arylesterase [6]. Moreover, PON1 has been shown to exhibit peroxidase-like activity by reducing H2O2 produced under oxidative stress conditions and converting lipid hydroperoxides in oxidized high-density lipoprotein (HDL) to hydroxides [7, 8].

PON1 is considered an antioxidant enzyme and is secreted by the liver. It is responsible for hydrolyzing organophosphate pesticides and neurotoxic compounds in the body [9, 10]. Additionally, PON1 has been reported to increase macrophages associated with cholesterol (CHOL) efflux, prevent protein modification by breaking down homocysteine thiolactone, and stabilize free radicals, thereby preserving membrane integrity [11].

PON1 exhibits genetic polymorphisms, with multiple alleles present in humans. As a result, individuals with different genetic variations may exhibit varying levels of activity. These variations play a significant role in many conditions believed to be associated with PON1 and disease risk [12].

Paraoxonase is also considered a negative acute phase reactant protein, which means its levels decrease during inflammation and may be a risk factor for inflammatory and infectious diseases [13–16].

In cattle, we believe that research on paraoxonase enzyme activity is still insufficient. Therefore, the objective of this chapter is to provide an overview of the current research on paraoxonase enzyme in cattle health and disease.

#### **2. General characteristics and structure of Paraoxonase 1**

The PON1 protein consists of approximately 355 amino acids and is composed of two distinct regions: the N-terminal and the C-terminal. The N-terminal region of the protein binds a cofactor copper ion, which is essential for PON1's catalytic activity. The C-terminal region, on the other hand, aids in substrate binding [17]. The N-terminal region also contains a hydrophobic signal sequence necessary for binding the enzyme with HDL [5]. The protein contains a central tunnel that houses two Ca+2 ions, with one ion necessary for catalytic activity and the other for protein stability. This central tunnel forms the active site of the enzyme. The hydrophobic nature of PON1's substrate is attributed to the hydrophobicity of the enzyme's active site. Among the critical structural features of PON1 are active site amino acids, such as cysteine and histidine, that confer PON1 with the ability to hydrolyze toxic compounds, including organophosphates, which are responsible for PON1's cellular anti-oxidative damage-reducing properties [8, 18].

#### **3. Association of Paraoxonase 1 with oxidative stress**

Oxidative stress arises from an imbalance between the generation of reactive oxygen species (ROS), including free radicals, and the body's capacity to detoxify and neutralize them. ROS are highly reactive molecules that can harm cells, proteins, and DNA. Accumulation of ROS due to inefficient neutralization can lead to oxidative stress, resulting in cellular damage and contributing to the development of various diseases, such as cancer, cardiovascular disease, and neurodegenerative disorders. Factors contributing to oxidative stress include environmental pollutants, smoking, alcohol consumption, poor diet, and specific medications [19–23].

Antioxidants are molecules that can prevent or slow down oxidative damage to cells caused by free radicals. Free radicals are unstable molecules that can damage cells and contribute to the development of various diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. Antioxidants neutralize free radicals by donating an electron, thereby reducing their potential to cause harm. The consumption of antioxidant-rich foods and supplements has been associated with numerous health benefits. Antioxidants can help mitigate ROS and protect against oxidative stress [24–28].

The PON1 enzyme provides protective effects against cellular oxidative stress by reducing the damage induced by free radicals and other oxidant molecules. Specifically, PON1 hydrolyzes toxic compounds, such as organophosphates, thereby reducing oxidative stress and safeguarding cells [9, 29]. Moreover, PON1 is known to

#### *Paraoxonase 1 in Cattle Health and Disease DOI: http://dx.doi.org/10.5772/intechopen.110844*

bind to high-density lipoprotein (HDL) in the bloodstream. This binding decreases the risk of atherosclerosis by preventing oxidation of low-density lipoprotein (LDL) or "bad" cholesterol. Decreased PON1 activity can lead to an increase in oxidative stress and an increased risk of atherosclerosis. The antioxidant activity of PON1 is derived from the free sulfhydryl group located on cysteine-284 [30]. It has been noted that the hydrolytic function of PON1 undergoes some degree of inactivation during the prevention of LDL oxidation [7].

PON1 also reduces cholesterol ester hydroperoxides associated with HDL more efficiently than those associated with LDL, likely due to the predominance of PON1 associated with HDL in the body. Thus, PON1 protects HDL against oxidative stress, rather than LDL [31]. The serum PON1 enzyme is found in association with HDL in plasma, and it prevents plasma lipoprotein oxidation [32]. PON1 enzyme is associated with apolipoprotein A1 and apolipoprotein J (clusterin) proteins of HDL [33]. PON1 binds to phospholipids and lipoproteins through the C-terminal hydrophobic termination region [34]. There is a close relationship between circulating PON1 and HDL, and PON1 can only interact with its endogenous substrate and exhibit its biological properties after being released by HDL. In return, PON1 protects HDL from oxidation [35].

PON1 is believed to play a significant role in protecting against oxidative stress by hydrolyzing both H2O2 and lipid peroxides, such as cholesteryl linoleate hydroperoxides [36]. As the O-P type ester bond found in paraoxon could also be present in lipoproteins associated with phospholipid peroxides and cholesteryl ester peroxides, the phosphotriesterase property of PON1 may contribute to the protection against oxidative stress [37]. In addition to its protective role against H2O2-induced lipid peroxidation, it has been found that PON1 also prevents the accumulation of peroxynitrite (ONOO- ) and oxidized phospholipids [38].

#### **4. Paraoxonase-1 enzyme activity in some cattle diseases and metabolic conditions**

Paraoxonase, an endogenous antioxidant produced by liver cells [39], plays a crucial role in protecting lipids, particularly HDL and LDL, from oxidative stress [37]. Paraoxonase is also considered a negative acute phase reactant protein [16]. In cattle with paratuberculosis, knowing the changes in acute-phase proteins will be beneficial for diagnosing and controlling the disease [40]. In a study by Akyüz et al. [41], a study was conducted on cows with paratuberculosis and found that PON1 activity was lower in the diseased animals compared to the control group, likely due to liver dysfunction and hepatocyte destruction. The authors suggested that PON1 activity could be used as a new biomarker for this infection. Similarly, in cows with clinical mastitis, Deveci et al. [42] observed a decrease in PON1 activity and HDL levels, and suggested that PON1 activity could be an antioxidant mediator in mastitis-induced inflammation. In addition, PON1 has been proposed as a potential marker for the detection of subclinical mastitis in dairy cows [43].

In lactating cows, PON1 activity has been found to be significantly higher in heifers during lactation compared to lactating cows [44]. However, the PON1 activity was found to be lower in postpartum and dry periods compared to lactating cows [45, 46], which was suggested to be related to changes in the lipid profile. Moreover, the observed low-serum PON1 activity at the end of pregnancy and early postpartum period in dairy cows was suggested to indicate an oxidative stress/antioxidant imbalance affected by reproductive stress and metabolic adaptation during the transition

period [47]. PON1 activity was also found to increase toward the end of the colostrum period in transition period cattle [48].

PON1 activity has also been investigated in relation to fertility in dairy cows. In a study investigating the relationship between pregnancy rates and PON1 activity in dairy cows following synchronization using an intravaginal device protocol for progesterone secretion, the application of an intravaginal progesterone-releasing device was found to affect serum PON1 activity. The study showed a significant difference in PON activity at day 5 of progesterone releasing intravaginal device (PRID) application, which was suggested to be an indicator of fertility [49].

Researchers have also evaluated PON1 activity as a biomarker for fatty liver in dairy cows. They found that serum PON1 activity was lower in cows suffering from hepatic lipidosis and suggested that the addition of serum PON1 activity measurement to the biochemical profile could improve the diagnosis of fatty liver in dairy cows [50]. Future studies should focus on the diagnostic validation of serum PON1 testing for early prediction of fatty liver development and its correlation with hepatic triglyceride content in both healthy and diseased dairy cows. Additionally, the focus on the diagnostic validation of serum PON1 testing for early prediction of fatty liver development in dairy farms could lead to significant clinical impact and greater profitability in the dairy industry.

#### **5. Conclusion**

In conclusion, PON1 is an enzyme that plays a crucial role in reducing oxidative stress and safeguarding cells by hydrolyzing toxic compounds, such as organophosphates, in the body. PON1 is also known to bind with HDL, which reduces the risk of atherosclerosis by preventing the oxidation of LDL. Genetic variations in PON1 activity can affect an individual's risk for various diseases, and decreased PON1 activity may increase oxidative stress and the risk of atherosclerosis. PON1 activity has been investigated in various contexts in cattle, including as a biomarker for infectious diseases and inflammation, fertility, and fatty liver. The findings suggest that PON1 activity could serve as a useful diagnostic tool for detecting and monitoring health issues in cattle. In cattle, the research on PON1 enzyme activity is limited, and further investigation is necessary to understand its role in cattle health and disease.

*Paraoxonase 1 in Cattle Health and Disease DOI: http://dx.doi.org/10.5772/intechopen.110844*

### **Author details**

Abdulsamed Kükürt1 \* and Volkan Gelen<sup>2</sup>

1 Faculty of Veterinary Medicine, Department of Biochemistry, Kafkas University, Kars, Türkiye

2 Faculty of Veterinary Medicine, Department of Physiology, Kafkas University, Kars, Türkiye

\*Address all correspondence to: samedkukurt@gmail.com

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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#### **Chapter 5**

## Clinical Significance of Some Acute Phase Proteins in Cattle

*Kadir Bozukluhan and Oguz Merhan*

#### **Abstract**

Acute phase proteins are proteins synthesized by the liver in response to the acute phase response. While these proteins are insignificant in healthy animals, their concentrations increase rapidly during infection, inflammation, or tissue damage and are used as an indicator of inflammation. Since the blood concentrations and importance levels of these clinically important proteins differ according to the animal species, they are evaluated separately for each animal species. Most of the acute phase proteins have been studied in detail in the field of human medicine and are routinely used in the diagnosis and prognosis of diseases. In the field of veterinary medicine, it has not been used sufficiently. In this book chapter, we will provide up-to-date information about acute phase proteins that are important for cattle, as well as explain that acute phase proteins can be used in the early diagnosis of diseases, in the differentiation of viral and bacterial infections, in guiding the treatment of sick animals and in determining their prognosis.

**Keywords:** cattle, ceruloplasmin, clinical significance, haptoglobin, serum amyloid A

#### **1. Introduction**

Acute phase response (APR) is a response following inflammation, tissue injury, infection, neoplastic growth, or immunological disorders, and this response is characterized by metabolic and systemic changes [1]. APR can be briefly expressed as changes in the concentrations of many plasma proteins that occur in relation to the response of the organism [2]. The function of APR is to protect organs from further injury, to eliminate infectious agents, to clear harmful molecules and residues for the organism, and to restore homeostasis by activating the repair process necessary for the organism to return to its normal function [3]. APR emerges as a complex reaction initiated by inflammatory mediators in the area where tissue destruction occurs and is characterized by local and systemic changes [2, 4]. Increase in capillary permeability, leukocyte migration to the inflammation site, and release of various chemical mediators take place among the local reactions occurring during APR [2]. Among the systemic reactions created by APR, there are changes in the level of acute phase proteins (APP) formed by mediators. Systemic reactions are initiated by mediators such as cytokines, glucocorticoids, and growth factors. Cytokines, which act as intracellular and intercellular signaling molecules and are soluble biological mediators, are in peptide or glycoprotein structure [5–8]. Macrophages and neutrophils arriving

at the inflammation site together with endothelial cells secrete pro-inflammatory cytokines (Interleukin "IL"-6, IL-1β, tumor necrosis factor "TNF"-α, interferon γ, IL-8, and macrophage inhibitor protein-1) [9]. While the production of APPs is accelerated by many cytokines (especially IL-6), it is inhibited by insulin and okadaic acid [10]. Cytokines, which have many different effects such as gene expression, metabolic process, and regulation of oxidation-reduction potential in the cell and ion flow in the cell membrane [9], generally stimulate APP synthesis and corticosteroids regulate cytokine activity. Pro-inflammatory cytokines such as IL-6 and IL-1 activate fibroblast and endothelial cells in the local inflammation area and allow cytokines to be secreted again. Thus, APP is synthesized from the liver as a result of the systemic inflammatory response initiated by the cytokines that enter the circulation [3, 7]. In addition to giving information about the formation of the inflammatory process and being a good marker in the diagnosis of the disease, the use of fast and sensitive measurement methods has made the measurement of APP popular [3, 11].

#### **2. Acute phase proteins**

Acute phase proteins are known as proteins whose concentrations change in the blood in cases of inflammation, infection, tissue damage, neoplastic developments, etc. [2, 12]. APPs are species specific and their diagnostic importance varies according to animal species [13, 14]. APPs whose levels change in the case of infection and inflammation are accepted as a nonspecific indicator of the tissue damage [3, 15]. In general, APPs, which can directly destroy inflammatory agents, also contribute to the tissue healing and regeneration. In addition, they have functions such as restoring useful molecules, cleaning residues, transporting cholesterol, preventing oxidation, and activating complement [12, 16].

#### **3. Some acute phase proteins important for cattle**

Haptoglobin with positive APP, serum amyloid A (SAA), ceruloplasmin, α1-acid glycoprotein, and albumin with negative APP take place among APPs that are important for cattle [2, 12, 17].

*Haptoglobin*: Haptoglobin, with a molecular weight of about 125 kDa, got its name from its ability to form a stable complex (haptein = binding) with hemoglobin [18]. In cattle, haptoglobin is found together with albumin as a polymer with a molecular weight of 1000–2000 kDa. It is captured by the reticuloendothelial system when bound with hemoglobin [2, 3, 19]. Haptoglobin is absent or very low (<0.1 mg/mL) in the serum of healthy cattle [20]. As soon as the immune system is stimulated for various reasons, its level in the serum increases up to 100 times [13, 21]. Haptoglobin concentration, which starts to increase within 24 hours after the onset of the inflammation, peaks on the 3–5th day and then decreases and reduces to its normal limits on the 8–21st day [20]. It has been reported that the prognosis is good when the level of haptoglobin used to determine the prognosis in cattle is between 0.1 and 1 g/L, and if this level is >1 g/L, the prognosis is poor and it is necessary to start treatment. In addition, the haptoglobin level can be used to determine the severity of the disease, and a level of 0.2–0.4 g/L is defined as mild infection, while a level of 1–2 g/L is defined as severe infection [20, 22].

Although haptoglobin has many functions, its main function is to prevent iron loss by forming stable complexes with free hemoglobin in the blood [23]. Haptoglobin

#### *Clinical Significance of Some Acute Phase Proteins in Cattle DOI: http://dx.doi.org/10.5772/intechopen.108152*

binds hemoglobin and the formed haptoglobin hemoglobin complex is transported to the liver and metabolized. The binding of haptoglobin to hemoglobin is very important in terms of the anti-inflammatory property of haptoglobin [24]. However, haptoglobin hydrolyzes the peroxides released from neutrophils in the inflamed region and renders them harmless. It has been reported that haptoglobin, which acts as an immunomodulator in the regulation of lipid metabolism and lymphocyte functions, will be able to be used to monitor the immune functions of cattle [14]. Although haptoglobin is an important APP studied in many species, its serum concentration can be also affected by factors other than APR. For example, in cases where the level of free hemoglobin in the circulation increases, even if haptoglobin synthesis is stimulated by inflammation, its circulating level will be seen as low because hemoglobin binds the existing haptoglobin. Therefore, in cases where the concentration of free hemoglobin in the serum increases, the amount of haptoglobin decreases. The best example of this is the absence of haptoglobin from circulation in acute hemolysis in cattle babesiosis [2].

Measurement of APP levels gives accurate and clear results in the diagnosis of inflammatory diseases in ruminants compared with hematological findings. It has been reported that it can be a helpful parameter in the diagnosis in the diseases such as neonatal diarrhea [25–27], omphalitis [28, 29], pneumonia [30], ascaridiosis [31], besnoitiosis [32], *Trypanosoma evansi* [33], anaplasmosis [34–36], hypodermosis [37], in the bacterial and viral diseases such as brucellosis [38], tuberculosis [39], reticuloperitonitis traumatica [40, 41], foot-and-mouth disease [42], as well as in fatty liver [43] including dystocia [44] and subclinical ketosis (**Table 1**) [45, 46]. In addition, in another study conducted in cattle with endometritis, it has been reported that haptoglobin and TNF-α levels decreased significantly after the treatment compared to the pre-treatment values [47] and that progesterone-releasing intravaginal device (PRID) administration increases haptoglobin and ceruloplasmin levels, but decreases albumin levels in another study conducted by Kuru et al. [48] in cattle.

*Serum amyloid A*: SAA has a molecular weight of approximately 180 kDa and exists in a complex with lipoprotein. Although SAA is synthesized by the liver with the effect of SAA-stimulating factor during inflammation, it is also synthesized locally in the udder ("milk SAA," MAA) outside the liver [2, 49]. The serum concentration of SAA, which is α globulin, is reported as <24 μg/mL [14] in healthy cattle. SAA, which rises within 2–5 hours after inflammatory stimulation and reaches a peak level within 24 hours, can be used for earlier diagnosis of acute cases [12]. SAA is used to determine the prevalence as well as the activity of inflammatory events, to monitor the course of the diseases and to evaluate the success of the treatment applied [50]. The functions of SAA include transport of cholesterol to hepatocytes, inhibition of oxidative degradation of neutrophil granulocytes, stimulation of calcium mobilization by monocytes, endotoxin detoxification, inhibition of lymphocyte and endothelial cell proliferation, prevention of platelet aggregation, and adhesion of T lymphocytes to extracellular matrix proteins [2, 13]. It has been reported that determining the haptoglobin/SAA ratio will be able to be also used in the differential diagnosis of acute and chronic cases [12]. SAA, one of the important APPs in cattle, has been reported to increase in nonfed for more than 3 days [51] in the infections such as foot-and-mouth disease [42], coryza gangrenosa bovum [52], hypomagnesemic tetany [53], enzootic bovine leukosis [54], subclinical ketosis [46], postpartum [55], mastitis [56–58], subclinical endometritis [59], and pneumonia (**Table 1**) [60, 61]. In addition, it has been reported that it increases in relation to the severity of clinical symptoms in viral respiratory system diseases [2]. It has been reported that there was no significant difference in the levels of APPs between double-infected animals and single-infected


#### **Table 1.**

*A brief summary of APPs-related studies on cattle.*

animals in a study conducted in dual- and single-infected cattle [62]. In another study conducted in cattle with bovine respiratory disease complex, it has been reported that haptoglobin and SAA levels increased compared to healthy animals, and the level of APPs decreased with the treatment [63].

*Ceruloplasmin*: Ceruloplasmin, which consists of a single polypeptide chain, is a copper-binding α-2 globulin. The functions of ceruloplasmin is (i) lipid peroxidation, (ii) oxidation of toxic ferrous iron to nontoxic ferric form, (iii) obtainment of increasing immune function by acting on various enzyme levels, (iv) mediation of copper transporting to enzymes such as lysyl oxidase and copper-zinc superoxide dismutase involved in tissue repair, (v) role in the antioxidant system, and (vi) regulation of phagocytosis and antimicrobial activity [13, 64, 65].

It has been reported that ceruloplasmin is very useful in monitoring the inflammatory process in cattle [66]. The studies conducted have reported that APP levels increase in cattle with reticuloperitonitis traumatica [41], endometritis [67], and subclinical mastitis (**Table 1**) [68]. In addition, it has been reported that the level of APPs increases in cattle infected with foot-and-mouth disease and can be used in the diagnosis of the disease [42].

*α1-Acid glycoprotein*: α1-Acid glycoprotein is a sialoprotein synthesized from hepatocytes, containing 180 amino acids and released at a molecular weight of

*Clinical Significance of Some Acute Phase Proteins in Cattle DOI: http://dx.doi.org/10.5772/intechopen.108152*

41 kDa [69]. This protein has two important functions: drug binding and immunomodulation. α1-Acid glycoprotein, a natural anti-inflammatory agent, increases IL-1 receptor antagonist release by macrophages by inhibiting neutrophil activation. It also inhibits lymphocyte proliferation and natural killer cell activity [2, 13]. When the albumin concentration formed during APR decreases, α1-acid glycoprotein, which has good drug binding properties, helps to maintain the total drug-binding level [13]. α1-Acid glycoprotein, whose concentration in the blood increases moderately and slowly [2], increases in chronic cases rather than acute inflammation [18]. It has been reported that α1-acid glycoprotein, which is of moderate importance for cattle, will be able to be used especially in monitoring the inflammatory process [12]. The studies conducted have reported that its concentration increased in cattle with hepatic abscess and leukosis [12, 20] in traumatic pericarditis [40], *Pasteurella haemolytica* [12], and digestive system disease (**Table 1**) [70].

*Albumin*: Cattle albumin, a negative APP, is synthesized by the liver and its molecular weight is 67 kDa and consists of 583 amino acids [71, 72]. Albumin is a very important protein that maintains and stabilizes the plasma oncotic pressure. Because it is a small molecule, its extravascular concentration changes are an important indicator of membrane integrity [73, 74]. In addition, the decrease in blood concentration due to the fact that it is produced only by the liver is accepted as an important finding indicating liver failure [75]. Binding and transport, acting as a source for endogenous amino acids, and maintaining plasma pressure take place among its main biological functions. It is reported that its concentration decreases in liver diseases, anorexia during APR, kidney and intestinal diseases, and malabsorption syndrome [8, 76]. It has been reported in the studies conducted that albumin levels decrease in neonatal diarrhea [26], pneumonia [30], hypodermosis [37], tuberculosis [39], and foot-andmouth disease (**Table 1**) [42].

#### **4. Conclusion**

Acute phase proteins, which are nonspecific markers synthesized by the liver as a result of APR in cattle, are very useful in terms of diagnosis and monitoring of diseases, as well as determining the prognosis of patients. In particular, the measurement of APPs is important in terms of distinguishing bacterial or viral infection and guiding the treatment to be applied. When used for this purpose, it strengthens the diagnosis and provides more accurate information in determining the prognosis of sick animals.

#### **Author details**

Kadir Bozukluhan1 \* and Oguz Merhan2

1 Kars School of Higher Vocational Education, Kafkas University, Kars, Turkey

2 Faculty of Veterinary, Department of Biochemistry, Kafkas University, Kars, Turkey

\*Address all correspondence to: kbozukluhan@hotmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Section 2
