Lumpy Skin Disease: An Economically Significant Emerging Disease

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.

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, 5, 6, 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].

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]).

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 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, 17, 18, 19, 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].

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).

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 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, 25, 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 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). 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].

Figure 3.

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

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 real-time 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, 41, 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, 49, 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.

Acknowledgments

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.