An insight into emergence of lumpy skin disease virus: a threat to Indian cattle.

Lumpy skin disease (LSD) is a highly infectious and economically devastating viral disease of cattle. It is caused by Lumpy Skin Disease Virus (LSDV) belonging to the genus Capripoxvirus and family Poxviridae. The origin of lumpy skin disease has been traced to Zambia, (an African nation) in Southern part during the year 1929. The first reported case of LSD besides Africa was from Israel, a Middle Eastern nation, thus proving inter-continental spread. Subsequently, the disease entered Middle East, Eastern Europe and Asia with numerous outbreaks in the recent years. LSD has emerged as a significant concern in the Indian sub-continent, due to outbreaks reported in countries such as Bangladesh, India, China in 2019. In the following years, other South and East Asian countries like Taipei, Nepal, Sri Lanka, Myanmar, Bhutan, Vietnam, Hong Kong, Thailand, Malaysia, Laos, Cambodia, Pakistan, Indonesia and Singapore also faced severe outbreaks. At present, LSD is considered to be an emerging disease in the Indian sub-continent due to the recent status of disease. Considering the global scenario, LSDV is changing its transmission dynamics as evidenced by a shift in its epidemiology. As a result of high morbidity and mortality rate among cattle, the current outbreaks have been a major cause of socio-economic catastrophe. This contagious viral disease has eminent repercussions as the estimated monetary damage incurred is quite high. Despite having networked surveillance and comprehensive databases, the recurring outbreaks have raised major concern among researchers. Therefore, this review offers brief insights into the emergence of LSDV by amalgamating the newest literature related to its biology, transmission, clinico-pathology, epidemiology, prevention strategies, and economic consequences. Additionally, we have also provided the epidemiological insights of the recent outbreaks with detailed state wise studies.

First evidence of lumpy skin disease in mithun (Bos frontalis) in India.

Lumpy skin disease (LSD) is a disease of cattle that is also known to cause mild infection in buffaloes. To date, there have been no reports of LSD in mithun (Bos frontalis), a bovine species distributed in Northeast India, Bangladesh, Myanmar, and parts of China. In the present study, the presence of typical clinical signs, virus isolation, PCR amplification, sequence analysis, and the demonstration of antibodies in serum by indirect enzyme-linked immunosorbent assay and serum neutralization test, confirmed the occurrence of LSD in mithun for the first time in India. Phylogenetic analysis based on the full-length RPO30 and P32 genes of LSD virus from mithun and cattle revealed 100% sequence identity, indicating circulation of the same strain in both species in India and the possibility of spillover between species.

Detection and Genome Sequencing of Lumpy Skin Disease Viruses in Wildlife Game Species in South Africa.

Lumpy skin disease virus (LSDV) has recently undergone rapid spread, now being reported from more than 80 countries, affecting predominantly cattle and to a lesser extent, water buffalo. This poxvirus was previously considered to be highly host-range restricted. However, there is an increasing number of published reports on the detection of the virus from different game animal species. The virus has not only been shown to infect a wide range of game species under experimental conditions, but has also been naturally detected in oryx, giraffe, camels and gazelle. In addition, clinical lumpy skin disease has previously been described in springbok (Antidorcas marsupialis), an African antelope species, in South Africa. This report describes the characterization of lumpy skin disease virus belonging to cluster 1.2, from field samples from springbok, impala (Aepyceros melampus) and a giraffe (Giraffa camelopardalis) in South Africa using PCR, Sanger and whole genome sequencing. Most of these samples were submitted from wild animals in nature reserves or game parks, indicating that the disease is not restricted to captive-bred animals on game farms or zoological gardens. The potential role of wildlife species in the transmission and maintenance of LSDV is further discussed and requires continuing investigation, as the virus and disease may pose a serious threat to endangered species.

Unravelling the genomic origins of lumpy skin disease virus in recent outbreaks.

Lumpy skin disease virus (LSDV) belongs to the genus Capripoxvirus and family Poxviridae. LSDV was endemic in most of Africa, the Middle East and Turkey, but since 2015, several outbreaks have been reported in other countries. In this study, we used whole genome sequencing approach to investigate the origin of the outbreak and understand the genomic landscape of the virus. Our study showed that the LSDV strain of 2022 outbreak exhibited many genetic variations compared to the Reference Neethling strain sequence and the previous field strains. A total of 1819 variations were found in 22 genome sequences, which includes 399 extragenic mutations, 153 insertion frameshift mutations, 234 deletion frameshift mutations, 271 Single nucleotide polymorphisms (SNPs) and 762 silent SNPs. Thirty-eight genes have more than 2 variations per gene, and these genes belong to viral-core proteins, viral binding proteins, replication, and RNA polymerase proteins. We highlight the importance of several SNPs in various genes, which may play an essential role in the pathogenesis of LSDV. Phylogenetic analysis performed on all whole genome sequences of LSDV showed two types of variants in India. One group of the variant with fewer mutations was found to lie closer to the LSDV 2019 strain from Ranchi while the other group clustered with previous Russian outbreaks from 2015. Our study highlights the importance of genomic characterization of viral outbreaks to not only monitor the frequency of mutations but also address its role in pathogenesis of LSDV as the outbreak continues.

Surveillance for lumpy skin disease and foot and mouth disease in the Kimberley, Western Australia.

We quantified the sensitivity of surveillance for lumpy skin disease (LSD) and foot and mouth disease (FMD) in cattle in the Kimberley region of Western Australia. We monitored producer and veterinary activity with cattle for 3 years commencing January 2020. Each year, ~274,000 cattle of 685,540 present on 92 pastoral leases (stations) were consigned to other stations, live export or slaughter. Veterinarians examined 103,000 cattle on the stations, 177,000 prior to live export, and 10,000 prior to slaughter. Detection probabilities for the disease prior to transport or during veterinary procedures and inspections were elicited by survey of 17 veterinarians working in Northern Australia. The veterinarians estimated the probabilities that they would notice, recognise, and submit samples from clinical cases of LSD and FMD, given a 5% prevalence of clinical signs in the herd. We used scenario tree methodology to estimate monthly surveillance sensitivity of observations made by producers and by veterinarians during herd management visits, pre-export inspections, and ante-mortem inspections. Average monthly combined sensitivities were 0.49 for FMD and 0.37 for LSD. Sensitivity was high for both diseases during the dry season and low in the wet season. We estimated the confidence in freedom from the estimated surveillance sensitivity given one hypothetically infected herd, estimated probability of introduction, and prior confidence in freedom. This study provided assurance that the Kimberley is free of these diseases and that routine producer and veterinary interactions with cattle are adequate for the timely detection of the disease should they be introduced.

Genome sequence characterization of the unique recombinant vaccine-like lumpy skin disease virus strain Kurgan/2018.

In 2018, the molecular epidemiology of lumpy skin disease in Russia was characterized by a surge in novel recombinant vaccine-like strains causing outbreaks along the southern border, spreading in an easterly direction. Currently, five distinct novel recombinant vaccine-like lineages have been described, designated as clusters 2.1 to 2.5. Based on the complete genome sequence analysis of the causative lumpy skin disease virus (Kurgan/Russia/2018), obtained from an eponymous outbreak, the genome was shown to be composed of a Neethling vaccine strain virus as the dominant parental strain and KSGPO vaccine virus as its minor parental strain. These features are similar to those of Saratov/Russia/2017 and Tyumen/Russia/2018, representing clusters 2.1 and 2.4, respectively. However, Kurgan/Russia/2018 has 16 statistically significant recombination events unique to this sequence, contributing to the phylogenetic clustering of Kurgan/Russia/2018 in yet another cluster designed cluster 2.6, based on analysis involving the complete genome sequences.

Lumpy skin disease: Insights into current status and geographical expansion of a transboundary viral disease.

Lumpy skin disease (LSD) is an emerging transboundary viral disease of livestock animals which was first reported in 1929 in Zambia. Although LSD is a neglected disease of economic importance, it extends a direct impact on the international trade and economy in livestock-dependent countries. Lumpy skin disease virus (LSDV) has been endemic in African countries, where several outbreaks have been reported previously. However, the virus has spread rapidly across the Middle East in the past two decades, reaching Russia and, recently, the Asian subcontinent. With unprecedented cluster outbreaks being reported across Asian countries like India, China, Nepal, Bangladesh, and Pakistan, LSDV is certainly undergoing an epidemiological shift and expanding its geographical footprint worldwide. Due to high mortality among livestock animals, the recent LSD outbreaks have gained attention from global regulatory authorities and raised serious concerns among epidemiologists and veterinary researchers. Despite networked global surveillance of the disease, recurrent LSD cases pose a threat to the livestock industry. Hence, this review provides recent insights into the LSDV biology by augmenting the latest literature associated with its pathogenesis, transmission, current intervention strategies, and economic implications. The review critically examines the changing epidemiological footprint of LSDV globally, especially in relation to developing countries of the Asian subcontinent. We also speculate the possible reasons contributing to the ongoing LSD outbreaks, including illegal animal trade, climate change, genetic recombination events between wild-type and vaccine strains, reversion of vaccine strains to virulent phenotype, and deficiencies in active monitoring during the COVID-19 pandemic.

Identifying the patterns and sizes of the first lumpy skin disease outbreak clusters in Northern Thailand with a high degree of dairy farm aggregation using spatio-temporal models.

Lumpy skin disease (LSD) is one of the most important notifiable transboundary diseases affecting cattle in many parts of the world. In Thailand, LSD outbreaks in cattle farming areas have been reported in 69 out of 77 provinces, indicating a serious nationwide situation. Understanding the dynamics of spatial and temporal LSD epidemic patterns can provide important information on disease transmission and control. This study aims to identify spatial and temporal clusters in the first LSD outbreaks in dairy farming areas with a high degree of aggregation in Northern Thailand using spatio-temporal models. The data were obtained from an official LSD outbreak investigation conducted between June and August 2021 on dairy farms (n = 202). The outbreak of LSD was confirmed by employing clinical observations and laboratory analysis. The spatio-temporal models including space-time permutation (STP), Poisson, and Bernoulli were applied to the outbreak data with the settings of 10%, 25%, and 50%, respectively, for the maximum reported cluster size (MRCS). Overall, the number of most likely and secondary clusters varied depending on the model and MRCS settings. All MRCS settings in the STP model detected the most likely clusters in the same area and the Poisson models in different areas, with the largest being defined by a 50% MRCS. Although the sizes of the most likely clusters identified by the Bernoulli models were different, they all had the same cluster period. Based on the sizes of the detected clusters, strict LSD insect-vector control should be undertaken within one kilometer of the outbreak farm in areas where no LSD vaccination has been administered. This study determines the sizes and patterns of LSD outbreak clusters in the dairy farming area with a high degree of farm aggregation. The spatio-temporal study models used in this study, along with multiple adjusted MRCS, provide critical epidemiological information. These models also expand the options for assisting livestock authorities in facilitating effective LSD prevention and control programs. By prioritizing areas for resource allocation, these models can help improve the efficiency of such programs.

Molecular characterization of lumpy skin disease virus from recent outbreaks in Pakistan.

Lumpy skin disease (LSD) is a contagious viral transboundary disease listed as a notifiable disease by the World Organization of Animal Health (WOAH). The first case of this disease was reported in Pakistan in late 2021. Since then, numerous outbreaks have been documented in various regions and provinces across the country. The current study primarily aimed to analyze samples collected during LSD outbreaks in cattle populations in the Sindh and Punjab provinces of Pakistan. Phylogenetic analysis was conducted using partial sequences of the GPCR, p32, and RP030 genes. Collectively, the LSDV strains originating from outbreaks in Pakistan exhibited a noticeable clustering pattern with LSDV strains reported in African, Middle Eastern, and Asian countries, including Egypt, the Kingdom of Saudi Arabia, India, China, and Thailand. The precise reasons behind the origin of the virus strain and its subsequent spread to Pakistan remain unknown. This underscores the need for further investigations into outbreaks across the country. The findings of the current study can contribute to the establishment of effective disease control strategies, including the implementation of a mass vaccination campaign in disease-endemic countries such as Pakistan.

Complete genome reconstruction of the global and European regional dispersal history of the lumpy skin disease virus.

IMPORTANCE: Lumpy skin disease virus (LSDV) has a complex epidemiology involving multiple strains, recombination, and vaccination. Its DNA genome provides limited genetic variation to trace outbreaks in space and time. Sequencing of LSDV whole genomes has also been patchy at global and regional scales. Here, we provide the first fine-grained whole genome sequence sampling of a constrained LSDV outbreak (southeastern Europe, 2015-2017), which we analyze along with global publicly available genomes. We formally evaluate the past occurrence of recombination events as well as the temporal signal that is required for calibrating molecular clock models and subsequently conduct a time-calibrated spatially explicit phylogeographic reconstruction. Our study further illustrates the importance of accounting for recombination events before reconstructing global and regional dynamics of DNA viruses. More LSDV whole genomes from endemic areas are needed to obtain a comprehensive understanding of global LSDV dispersal dynamics.

Global Burden of Lumpy Skin Disease, Outbreaks, and Future Challenges.

Lumpy skin disease (LSD), a current global concern, causes economic devastation in livestock industries, with cattle and water buffalo reported to have higher morbidity and lower mortality rates. LSD is caused by lumpy skin disease virus (LSDV), a member of the Poxviridae family. It is an enzootic, rapidly explorative and sometimes fatal infection, characterized by multiple raised nodules on the skin of infected animals. It was first reported in Zambia in 1929 and is considered endemic in Africa south of the Sahara desert. It has gradually spread beyond Africa into the Middle East, with periodic occurrences in Asian and East European countries. Recently, it has been spreading in most Asian countries including far East Asia and threatens incursion to LSD-free countries. Rapid and accurate diagnostic capabilities, virus identification, vaccine development, vector control, regional and international collaborations and effective biosecurity policies are important for the control, prevention, and eradication of LSD infections. This review critically evaluates the global burden of LSD, the chronological historical outbreaks of LSD, and future directions for collaborative global actions.

Lumpy Skin Disease: A Systematic Review of Mode of Transmission, Risk of Emergence and Risk Entry Pathway.

The spread of lumpy skin disease (LSD) to free countries over the last 10 years, particularly countries in Europe, Central and South East Asia, has highlighted the threat of emergence in new areas or re-emergence in countries that achieved eradication. This review aimed to identify studies on LSD epidemiology. A focus was made on hosts, modes of transmission and spread, risks of outbreaks and emergence in new areas. In order to summarize the research progress regarding the epidemiological characteristics of LSD virus over the last 40 years, the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement guidelines were followed, via two databases, i.e., PubMed (biomedical literature) and Scopus (peer-reviewed literature including scientific journals, books, and conference proceedings). A total of 86 scientific articles were considered and classified according to the type of epidemiological study, i.e., experimental versus observational. The main findings and limitations of the retrieved articles were summarized: buffaloes are the main non-cattle hosts, the main transmission mode is mechanical, i.e., via blood-sucking vectors, and stable flies are the most competent vectors. Vectors are mainly responsible for a short-distance spread, while cattle trade spread the virus over long distances. Furthermore, vaccine-recombinant strains have emerged. In conclusion, controlling animal trade and insects in animal transport trucks are the most appropriate measures to limit or prevent LSD (re)emergence.

First Molecular Investigation of lumpy Skin Disease in Buffaloes Using the Qualitative and Quantitative Polymerase Chain Reaction Assays, Iraq.

Lumpy skin disease (LSD) is one of the most important infectious bovine diseases in Iraq in the last 10 years; however, the current study represents the first investigation to confirm the disease in buffaloes as well as ticks with estimation the association of positivity to clinical vital signs and risk factors. A total of 150 buffaloes were subjected for blood sampling, skin lesions and ticks. All the collected samples; 150 blood, 13 skin lesions, and 29 tick samples, were examined molecularly using the conventional and real-time PCR assays. The total positive results of blood, skin and ticks by conventional PCR were 5.33, 7.69 and 0%, respectively; while for real-time PCR, it was 15.33, 7.69 and, 0%, respectively. Insignificant differences were showed between values of temperature, pulse and respiratory rates of LSD positive and negative buffaloes by the conventional and real-time PCR assays. The association of positive conventional PCR results to risk factors (age, sex and region) was revealed a significant increase in prevalence and risk of LSD in buffaloes aged < 1 year; but for gender, insignificant variation in prevalence but not risk was seen between females and males. In case of different geographical region, significant higher prevalence was reported in Wasit; while, buffaloes of Maysan and Wasit were appeared at higher risk than those of Dhi-Qar. Regarding real-time PCR, insignificant differences were found between values of < 1, 1-4 and > 4-8 years age old, but not in group of >8 that showed a significant decline in positivity (0%). For sex, insignificant variation in prevalence, but not risk, was seen between females and males. Concerning region, buffaloes of Wasit province were recorded a significant higher values of prevalence and risk than other regions. LSD in buffaloes is mainly sub-acute, and PCR appeared to be a suitable diagnostic method in detection of infection; however, furthermore studies are necessary.

Forecasting of daily new lumpy skin disease cases in Thailand at different stages of the epidemic using fuzzy logic time series, NNAR, and ARIMA methods.

Lumpy skin disease (LSD) is an important transboundary disease affecting cattle in numerous countries in various continents. In Thailand, LSD is regarded as a serious threat to the cattle industry. Disease forecasting can assist authorities in formulating prevention and control policies. Therefore, the objective of this study was to compare the performance of time series models in forecasting a potential LSD epidemic in Thailand using nationwide data. For the forecasting of daily new cases, fuzzy time series (FTS), neural network auto-regressive (NNAR), and auto-regressive integrated moving average (ARIMA) models were applied to various datasets representing the different stages of the epidemic. Non-overlapping sliding and expanding window approaches were also employed to train the forecasting models. The results showed that the FTS outperformed other models in five of the seven validation datasets based on various error metrics. The predictive performance of the NNAR and ARIMA models was comparable, with NNAR outperforming ARIMA in some datasets and vice versa. Furthermore, the performance of models built from sliding and expanding window techniques was different. This is the first study to compare the forecasting abilities of the FTS, NNAR, and ARIMA models across multiple phases of the LSD epidemic. Livestock authorities and decision-makers may incorporate the forecasting techniques demonstrated herein into the LSD surveillance system to enhance its functionality and utility.

Lumpy Skin Disease Virus Genome Sequence Analysis: Putative Spatio-Temporal Epidemiology, Single Gene versus Whole Genome Phylogeny and Genomic Evolution.

Lumpy Skin Disease virus is a poxvirus from the genus Capripox that mainly affects bovines and it causes severe economic losses to livestock holders. The Lumpy Skin Disease virus is currently dispersing in Asia, but little is known about detailed phylogenetic relations between the strains and genome evolution. We reconstructed a whole-genome-sequence (WGS)-based phylogeny and compared it with single-gene-based phylogenies. To study population and spatiotemporal patterns in greater detail, we reconstructed networks. We determined that there are strains from multiple clades within the previously defined cluster 1.2 that correspond with recorded outbreaks across Eurasia and South Asia (Indian subcontinent), while strains from cluster 2.5 spread in Southeast Asia. We concluded that using only a single gene (cheap, fast and easy to routinely use) for sequencing lacks phylogenetic and spatiotemporal resolution and we recommend to create at least one WGS whenever possible. We also found that there are three gene regions, highly variable, across the genome of LSDV. These gene regions are located in the 5' and 3' flanking regions of the LSDV genome and they encode genes that are involved in immune evasion strategies of the virus. These may provide a starting point to further investigate the evolution of the virus.

Long-term monitoring of immune response to recombinant lumpy skin disease virus in dairy cattle from small-household farms in western Thailand.

Lumpy skin disease (LSD) was firstly reported in Thailand in 2021 which affected the cattle industry. However, there is limited information on the immune response of LSDV infection in Thailand where recombinant vaccine strain circulated. The aim of this research was to study the duration of LSD immune response of subclinical and clinical animals after natural infection in dairy cattle. Sixty-six dairy cattle from ten farms in central and western regions of Thailand were investigated. Antibody was detected by virus neutralization test and ELISA. Cell mediated immunity (CMI)-related cytokine gene expressions were evaluated. Antibody was detected until at least 15 months after the noticeable symptom. Cattle with subclinical disease had lower antibody levels compared to animals which had clinical disease. IFN-γ and TNF-α levels were increased, while IL-10 level was decreased in the infected animals compared to the controls. This study elucidated immune responses in dairy cattle herd affected by recombinant LSDV.

Biological properties and diverse cytokine profiles followed by in vitro and in vivo infections with LSDV strain isolated in first outbreaks in Vietnam.

Preliminary information about LSD virus isolated from the first outbreaks in Vietnam has been reported by our laboratory. In the current study, LSDV strain, LSDV/Vietnam/Langson/HL01(HL01) was further analyzed to provide a better understanding of this viral pathogen. HL01 LSDV strain was propagated at MOI 0.01 in MDBK cells and then given to cattle at dose of 106.5 TCID50/ml (2ml/animal). The production of proinflammatory (IFN-γ, IL-1α, and TNF-α) and anti-inflammatory (IL-6, IL-10, and TGF-ß1) cytokines were measured by real-time PCR, both In vitro and In vivo. The results demonstrated that HL01 strain caused the typical signs of LSD and LSDV In vitro and In vivo, respectively suggesting a virulent field LSDV strain. Additionally, different cytokine profiles were observed in these In vitro and In vivo studies. In MDBK cells, different cytokines profiles were observed in two phases: in the early phase, the expression levels of all examined cytokines were significantly increased at 6 h (p < 0.05). In the later phase, the peak levels of the cytokine secretion were recognized from 72 to 96 h, with the exception of IL-1α when compared to controls. In cattle, the expression levels of all six cytokines were significantly higher at day 7 following LSDV challenge (p < 0.05) when compared to controls, especially expression levels of TGF-ß1 and IL-10. These findings suggest the important roles of these cytokines in protection against LSDV infections. Additionally, the data from diverse cytokine profiles followed by this LSDV strain challenge provides key understanding of the underlying cellular immune mechanisms in the host against LSDV infection In vitro and In vivo.

Phylogenetic and pathogenic characterization of lumpy skin disease virus circulating in China.

The genomic characterization of emerging pathogens is critical for unraveling their origin and tracking their dissemination. Lumpy skin disease virus (LSDV) is a rapidly emerging pathogen in Asia including China. Although the first Lumpy skin disease (LSD) outbreak was reported in 2019, the origin, transmission, and evolutionary trajectory of LSDV in China have remained obscure. The viral genome of a circulating LSDV strain in China, abbreviated LSDV/FJ/CHA/2021, was sequenced using the next-generation sequencing technique. The morphology and cytoplasmic viral factory of these LSDV isolates were observed using transmission electron microscopy. Subsequently, the genomic characterization of this LSDV isolate was systematically analyzed for the first time using the bioinformatics software. The current study revealed that several mutations in the genome of LSDV isolates circulating in China were identified using single nucleotide polymorphisms (SNPs) analysis, an instrument to evaluate for continuous adaptive evaluation of a virus. Furthermore, phylogenomic analysis was used to identify the lineage using the whole genome sequences of 44 LSDV isolates. The result revealed that the isolates from China were closely similar to that of the LSDV isolates from Vietnam, which are divided into a monophyletic lineage sub-group I. The SNPs and Simplot analysis indicate no significant occurrence of the recombinant event on the genome of LSDV isolates in China. Notably, the live virus challenge experiment demonstrated that the pathogenic characterization of this LSDV isolate belongs to a virulent strain. Collectively, we gain the first insight into the evolutionary trajectory, spatiotemporal transmission, and pathogenic characterization of circulating LSDV in China. This study provides a unique reference for risk assessment, guiding diagnostics, and prevention in epizootic and non-epizootic areas.

Lumpy skin disease as an emerging infectious disease.

Lumpy skin disease (LSD) is one of the most important emerging transboundary diseases. Recently, LSD has emerged in many countries in the northern hemisphere. The LSD virus has a huge genome and is highly resistant to environmental conditions. The virus is also host-specific and large ruminants, such as cattle and domestic water buffalo, are particularly susceptible. In addition, wild ruminants can serve as potential reservoirs for spreading the LSD virus. The emergence might be related to climate change in various regions because LSD is an arthropod-borne infectious disease. This disease causes enormous economic losses, such as leather damage, decreased milk production, abortion, and death in infected ruminants. The economic importance of LSD in the bovine industry has forced countries to develop and implement control strategies against the disease. With the recent global spread and the economic impact, LSD will be discussed intensively. In addition, effective preventive measures are suggested based on the presence or absence of LSD outbreaks.