Lumpy Skin Disease Research Articles

The devastation of Lumpy skin disease in third world countries: a mini – review on the current status of the disease focusing phytochemicals

Lumpy skin disease is a rising bovine viral illness that is widespread in most African and Middle Eastern nations, with a high probability of disease transmission throughout the Asia and Europe. The causative agent is capripoxivirus endangering hundreds of dairy cattle across the country in recent years. The LSD virus infects cattle and buffaloes and results in nodular skin sores all over their bodies. This results in chronic debility, decreased milk supply, poor development, infertility, abortion, and other issues in cattle and buffaloes infrequently leading to death of animals. The only infected animal species are cattle and water buffalo, both of which have high morbidity and low mortality rates. However, mortality rates are greater in calf populations. LSD causes sterility in males and abortions in female cattle. This mini review highlights existing information on epidemiology, pathogenesis, clinical manifestations, and potential role of phytochemicals particularly turmeric and aloe vera in treating lumpy skin disease.

Dynamical study of lumpy skin disease model with optimal control analysis through pharmaceutical and non-pharmaceutical controls

Dynamical study of lumpy skin disease model with optimal control analysis through pharmaceutical and non-pharmaceutical controls

Completely Free from PAM Limitations: Asymmetric RPA with CRISPR/Cas12a for Nucleic Acid Assays.

Experimentally, Cas12a can recognize multiple protospacer adjacent motif (PAM) sequences and is not restricted to the "TTTN". However, the application of the CRISPR/Cas12a system is still limited by the PAM for double-stranded DNA (dsDNA). Here, we developed asymmetric RPA (Asy-RPA) to completely break the limitations of PAM. Asy-RPA not only achieved efficient amplification but also converted dsDNA to single-stranded DNA (ssDNA) without complicated steps. The ssDNA products activated the trans-cleavage activity of Cas12a, outputting signals. The application of Asy-RPA completely freed Cas12a from the PAM, which can be more widely used in nucleic acid detection, such as lumpy skin disease virus, with an actual detection limit as low as 1.21 × 101 copies·μL-1. More importantly, Cas12a was intolerant to mutations on ssDNA. This provided technical support for the detection and identification of wild-type Mycobacterium tuberculosis (WT-TB) and rifampin-resistant mutant-type M. tuberculosis (MT-TB). The detection limit was as low as 1 fM for 1% mixed samples. The detection and availability of different treatment options for treatment-resistant and WT-TB were significant for the elimination of TB. In summary, the platform consisting of Asy-RPA and CRISPR/Cas12a was suitable for the detection of various viruses and bacteria and was a boon for the detection of dsDNA without recognizable PAM.

Harnessing Attenuation-Related Mutations of Viral Genomes: Development of a Serological Assay to Differentiate between Capripoxvirus-Infected and -Vaccinated Animals.

Sheeppox, goatpox, and lumpy skin disease caused by the sheeppox virus (SPPV), goatpox virus (GTPV), and lumpy skin disease virus (LSDV), respectively, are diseases that affect millions of ruminants and many low-income households in endemic countries, leading to great economic losses for the ruminant industry. The three viruses are members of the Capripoxvirus genus of the Poxviridae family. Live attenuated vaccines remain the only efficient means for controlling capripox diseases. However, serological tools have not been available to differentiate infected from vaccinated animals (DIVA), though crucial for proper disease surveillance, control, and eradication efforts. We analysed the sequences of variola virus B22R homologue gene for SPPV, GTPV, and LSDV and observed significant differences between field and vaccine strains in all three capripoxvirus species, resulting in the truncation and absence of the B22R protein in major vaccines within each of the viral species. We selected and expressed a protein fragment present in wildtype viruses but absent in selected vaccine strains of all three species, taking advantage of these alterations in the B22R gene. An indirect ELISA (iELISA) developed using this protein fragment was evaluated on well-characterized sera from vaccinated, naturally and experimentally infected, and negative cattle and sheep. The developed wildtype-specific capripox DIVA iELISA showed >99% sensitivity and specificity for serum collected from animals infected with the wildtype virus. To the best of our knowledge, this is the first wildtype-specific, DIVA-capable iELISA for poxvirus diseases exploiting changes in nucleotide sequence alterations in vaccine strains.

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.

Evaluating machine learning methods voting system for predicting the occurrence of lumpy skin condition

Lumpy skin disease is a viral disease that primarily affects cattle. It is caused by the lumpy skin disease, which belongs to the Capripoxvirus genus. LSD is characterized by the formation of nodules or lumps on the skin of infected cattle. This study aimed to evaluate how well some machine learning algorithms could predict the likelihood of LSDV infection based on geographical and meteorological characteristics. Geospatial and climatic factors are crucial to the disease’s epidemiology because of their close connection to the persistence of arthropod vectors. The results of this study suggest that by combining geographical and meteorological factors, a voting system of different machine learning outputs is utilized to forecast the occurrence of LSDV infection with high precision. In locations where there is a high risk of LSDV infection, applying the predicting capability of these methodologies could be very helpful in implementing screening and awareness programs as well as preventative efforts like vaccination

Lumpy Skin Disease (LSD) in Yak (Bos grunniens): An Evidence of Species Spillover from Cattle in India.

Lumpy skin disease (LSD), caused by the lumpy skin disease virus (LSDV), is a global concern that affects cattle and buffalo. Recently, the disease has been reported in new species such as the Indian Gazelle, Camel, Banteng, Gaur, and Giraffe from various parts of the world. This report provides an insight into the occurrence of LSD in Yak from Sikkim, a North-Eastern state of India. During the investigation, both cattle and yak exhibited typical clinical signs of LSD, including skin nodular lesions. The morbidity, mortality, and case fatality rates for cattle were 9.08%, 1.84%, and 20.24%, respectively. Similarly, the morbidity, mortality, and case fatality rates in yak were 7.57%, 1.24%, and 16.33%, respectively. The virus isolation and amplification of LSDV-specific genes confirmed the presence of LSDV in cattle, yak, and vectors. Further, demonstrated antibodies in randomly collected sera from naïve and unvaccinated cattle and yak using indirect Enzyme Linked Immuno-sorbent Assay (iELISA) and Serum Neutralisation test (SNT) from this region. Sequencing and phylogenetic analysis of P32, GPCR, and RPO30 genes revealed that the virus isolated from both species was 100% identical to each other and also closely related to the field LSDV isolates circulating in the Indian subcontinent. The study highlighted the emergence of LSDV in unconventional hosts and underscored the need to include other bovine species in national disease control programs, encompassing disease surveillance initiatives.

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.

Sign of APOBEC editing, purifying selection, frameshift, and in-frame nonsense mutations in the microevolution of lumpy skin disease virus.

The lumpy skin disease virus (LSDV), which mostly affects ruminants and causes huge-economic loss, was endemic in Africa, caused outbreaks in the Middle East, and was recently detected in Russia, Serbia, Greece, Bulgaria, Kazakhstan, China, Taiwan, Vietnam, Thailand, and India. However, the role of evolutionary drivers such as codon selection, negative/purifying selection, APOBEC editing, and genetic variations such as frameshift and in-frame nonsense mutations in the LSDVs, which cause outbreaks in cattle in various countries, are still largely unknown. In the present study, a frameshift mutation in LSDV035, LSDV019, LSDV134, and LSDV144 genes and in-frame non-sense mutations in LSDV026, LSDV086, LSDV087, LSDV114, LSDV130, LSDV131, LSDV145, LSDV154, LSDV155, LSDV057, and LSDV081 genes were revealed among different clusters. Based on the available complete genome sequences, the prototype wild-type cluster-1.2.1 virus has been found in other than Africa only in India, the wild-type cluster-1.2.2 virus found in Africa were spread outside Africa, and the recombinant viruses spreading only in Asia and Russia. Although LSD viruses circulating in different countries form a specific cluster, the viruses detected in each specific country are distinguished by frameshift and in-frame nonsense mutations. Furthermore, the present study has brought to light that the selection pressure for codons usage bias is mostly exerted by purifying selection, and this process is possibly caused by APOBEC editing. Overall, the present study sheds light on microevolutions in LSDV, expected to help in future studies towards disturbed ORFs, epidemiological diagnostics, attenuation/vaccine reverts, and predicting the evolutionary direction of LSDVs.

MiRNA profiling of primary lamb testicle cells infected with lumpy skin disease virus.

In this study, miRNA profiling of cells infected with lumpy skin disease virus (LSDV) was conducted for the first time. When compared to mock-infected cells, LSDV-infected primary lamb testicle (LT) cells showed dysregulation of 64, 85, and 85 miRNAs at 12 hours postinfection (hpi), 48 hpi, and 72 hpi, respectively. While some of these miRNAs were found to be dysregulated at a particular time point following LSDV infection, others were dysregulated at all three time points. Analysis of the differentially expressed miRNA-mRNA interaction networks, Gene Ontology analysis of the predicted targets, and KEGG analysis of highly enriched pathways revealed several cellular factors/pathways involved in protein/ion/enzyme binding, cell differentiation, movement of subcellular components, calcium reabsorption, aldosterone synthesis and secretion, and melanogenesis. Some selected upregulated (oar-mir-379-5p, oar-let-7d, Chr10-18769, Chr2_5162 and oar-miR-493-5p) and downregulated (ChrX-33741, Chr3_8257 and Chr26_32680) miRNAs were further confirmed by quantitative real-time PCR. These findings contribute to our understanding of virus replication, virus-host interactions, and disease pathogenesis, and the differentially expressed miRNAs and their cellular targets may serve as biomarkers as well as novel targets for therapeutic intervention against LSDV.

Lumpy Skin Disease, an Emerging Transboundary Viral Disease in Animal’s: A Review

Lumpy skin disease (LSD) is an arising viral ailment impacting cows and buffaloes in India. Livestock industry suffers enormous financial damages as a result of lumpy skin disease (LSD). Lumpy skin disease virus (LSDV), a part of the Poxviridae family induces it, along with precursor being Neethling variant. Lumpy skin disease virus belongs to Capripox virus genus, it also contains sheep and goat pox viruses. Lumpy skin ailment is a bovine illness that is enzootic, contagious, eruptive, and infrequently lethal. It is characterised by skin lumps. Cows and buffalo are the sole impacted types of animals, with substantial morbidity yet lower fatality levels; although, calves die at a greater rate. Lumpy skin disease lowers milk and meat output, induces female miscarriages, and promotes male impotency. Skin nodules all over the body, fever, lachraimal discharge, nasal discharge, anorexia, decreased milk yield, emaciation, depression, and reluctance to move are all major clinical signs. LSD's origins can be traced back to 1929 in Zambia. Lumpy skin disease is regarded an indigenous illness in the African continent. However, around 1984, this disease spread beyond Africa. It has been reported in Madagascar as well as some Middle Eastern countries and Arabian Peninsula. This sickness has lately been documented in regions where lumpy skin ailment is not available (Syria, Lebanon, Iran, Turkey, and Iraq, Jordan), posing a financial risk to the livestock industry. After the earliest case of lumpy skin ailment was reported in India, it has spread rapidly throughout the country, posing a risk to the cattle and buffalo populations of productivity and mortality.

Unveiling Oxidative Stress-Induced Genotoxicity and Its Alleviation through Selenium and Vitamin E Therapy in Naturally Infected Cattle with Lumpy Skin Disease.

Lumpy skin disease (LSD) is a contagious infection of cattle caused by a virus of the Poxviridae family, genus Capripoxvirus. In Pakistan, recent outbreaks have resulted in significant nationwide mortality and economic losses. A 20-day prospective cohort study was performed on sixty infected cattle with the aim to evaluate LSD-induced oxidative stress's genotoxic role and to determine the ameliorative effect of antioxidant therapy using principal component analysis (PCA) and a multivariable ordinal logistic regression model. LSDV was identified from scab samples and nodular lesions using RPO30-specific gene primers. The infected cattle were divided into control and treated groups. The animals were observed initially and finally on day 20 to evaluate the homeostatic, oxidative, and genotoxic changes. The animals in the treated group were administered a combination of selenium (Se) and vitamin E at the standard dose rate for five consecutive days. A substantial (p < 0.05) improvement in the hematological indices was observed in the treated group. The treated group also showed a significant (p < 0.05) reduction in levels of serum nitric oxide (NO) and malondialdehyde (MDA) post-therapy. The PCA at the final sampling data of the treated group showed that Principal Component (PC1 eigenvalue 1.429) was influenced by superoxide dismutase (SOD; 0.3632), catalase (CAT; 0.2906), and glutathione (GSH; 0.0816) and PC2 (eigenvalue 1.200) was influenced by CAT (0.4362), MDA (0.2056), and NO (0.0693). A significant correlation between serum NO (76%) and MDA levels (80%) was observed with genetic damage index (GDI) scores. The ordinal logistic regression model regarding the use of antioxidant therapy revealed 73.95-times (95%CI; 17.36-314.96) improvement in the GDI in treated animals. The multivariable ordinal logistic regression showed that each unit increase in NO and MDA resulted in a 13% increase in genotoxicity in infected individuals. In conclusion, our study revealed that LSD-induced oxidative stress and lipid peroxidation product causes genotoxicity in affected animals. Furthermore, the combined Se and vitamin E therapy significantly alleviated oxidative stress and genotoxicity in LSD-affected cattle.

Tetrandrine (TET) inhibits African swine fever virus entry into cells by blocking the PI3K/Akt pathway

African Swine Fever Virus (ASFV) infection causes an acute and highly contagious disease in swine, resulting in significant economic losses and societal harm worldwide. Currently, there are no effective vaccines or antiviral drugs available for ASFV. Tetrandrine (TET) is extracted from the traditional Chinese herb Stephania tetrandrae, possesses diverse biological functions such as anti-inflammatory, anti-tumor, and antiviral activities. The study comprehensively evaluated the anti-ASFV effect of TET and validated it through biological assays. The dose-dependent inhibition of TET against ASFV was confirmed and a novel mechanism of TET's anti-ASFV activity was elucidated. TET effectively inhibits ASFV during internalization by blocking macropinocytosis through the inhibition of the PI3K/Akt pathway. The specific inhibitor LY294002, targeting the PI3K/Akt pathway, exhibits similar antiviral activity against ASFV as TET. Furthermore, the inhibitory effect of TET against other viruses such as Lumpy Skin Disease Virus (LSDV) and Porcine Epidemic Diarrhea Virus (PEDV) was also identified. Our findings suggest that TET effectively inhibits ASFV and reveal the potential for broad-spectrum antiviral drugs targeting the PI3K/Akt pathway.

Lumpy skin disease: history, current understanding and research gaps in the context of recent geographic expansion.

Lumpy skin disease is recognized as a transboundary and emerging disease of cattle, buffaloes and other wild ruminants. Being initially restricted to Africa, and since 1989 the Middle East, the unprecedented recent spread across Eurasia demonstrates how underestimated and neglected this disease is. The initial identification of the causative agent of LSD as a poxvirus called LSD virus, was well as findings on LSDV transmission and epidemiology were pioneered at Onderstepoort, South Africa, from as early as the 1940s by researchers such as Weiss, Haig and Alexander. As more data emerges from an ever-increasing number of epidemiological studies, previously emphasized research gaps are being revisited and discussed. The currently available knowledge is in agreement with the previously described South African research experience that LSDV transmission can occur by multiple routes, including indirect contact, shared water sources and arthropods. The virus population is prone to molecular evolution, generating novel phylogenetically distinct variants resulting from a diverse range of selective pressures, including recombination between field and homologous vaccine strains in cell culture that produce virulent recombinants which pose diagnostic challenges. Host restriction is not limited to livestock, with certain wild ruminants being susceptible, with unknown consequences for the epidemiology of the disease.

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

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.

Estimating the Transmission Kernel for Lumpy Skin Disease Virus from Data on Outbreaks in Thailand in 2021.

Nationwide outbreaks of lumpy skin disease (LSD) were observed in Thailand in 2021. A better understanding of its disease transmission is crucial. This study utilized a kernel-based approach to characterize the transmission of LSD between cattle herds. Outbreak data from the Khon Kaen and Lamphun provinces in Thailand were used to estimate transmission kernels for each province. The results showed that the majority of herd-to-herd transmission occurs over short distances. For Khon Kaen, the median transmission distance from the donor herd was estimated to be between 0.3 and 0.8 km, while for Lamphun, it ranged from 0.2 to 0.6 km. The results imply the critical role that insects may play as vectors in the transmission of LSD within the two study areas. This is the first study to estimate transmission kernels from data on LSD outbreaks in Thailand. The findings from this study offer valuable insights into the spatial transmission of this disease, which will be useful in developing prevention and control strategies.

Complete genome sequence of the lumpy skin disease virus reported from Jammu and Kashmir, India, during 2022 outbreak.

Lumpy skin disease virus (LSDV) is the causative agent of an economically important disease of cattle and water buffaloes. Here, we announce the complete genome sequence of the LSDV from Jammu and Kashmir, India. LSDV/02/KASH/IND/2022 was detected in skin biopsy sample of an LSD-infected dairy cow on 24 October 2022.

Testing and Histipathological Description of the Occurrence of Lumpy Skin Disease in Cattle in Kulon Progo, Special Region of Yogyakarta

Testing and Histipathological Description of the Occurrence of Lumpy Skin Disease in Cattle in Kulon Progo, Special Region of Yogyakarta

Fractional order mathematical modeling of lumpy skin disease

In this article, we study the fractional-order SEIR mathematical model of Lumpy Skin Disease (LSD) in the sense of Caputo. The existence, uniqueness, non-negativity and boundedness of the solutions are established using fixed point theory. Using a next-generation matrix, the reproduction number $R_{0}$ is determined for the disease’s prognosis and durability. Using the fractional Routh-Hurwitz stability criterion, the evolving behaviour of the equilibria is investigated. Generalized Adams–Bashforth–Moulton approach is applied to arrive at the solution of the proposed model. Furthermore, to visualise the efficiency of our theoretical conclusions and to track the impact of arbitrary-order derivative, numerical simulations of the model and their graphical presentations are carried out using MATLAB(R2021a).

Molecular detection and phylogenetic analysis of lumpy skin disease virus from clinically infected cattle of Andhra Pradesh

Molecular detection and phylogenetic analysis of lumpy skin disease virus from clinically infected cattle of Andhra Pradesh