Spread Of Lumpy Skin Disease Virus Research Articles

274 Evaluation of recombinant Capripoxvirus antigens in the development of indirect enzyme linked immunosorbent assays

Abstract Capripoxvirus is a genus of DNA viruses that includes sheep pox virus, goat pox virus and lumpy skin disease virus (LSDV). These viruses are considered high consequence viruses due to the severe clinical disease leading to economic losses to production and impact on trade. The recent spread of LSDV in Europe and Asia has demonstrated the transboundary nature of LSDV. The vaccines used to control Capripoxvirus infections currently do not have the ability to differentiate infected from vaccinated animals (DIVA) and the enzyme linked immunosorbent assays (ELISA) available for detection of antibodies to Capripoxvirus infections are not ideal. Previous research has been done to evaluate different Capripoxvirus antigens using E. coli expressed antigens; however, there has been no prior evaluation of baculovirus expressed Capripoxvirus antigens for use in ELISA. The objective of the current research was to produce 6 recombinant Capripoxvirus antigens using a baculovirus expression vector system (BEVS) and to evaluate these antigens in ELISAs to test bovine, sheep, and goat serum. The sequences used to produce the recombinant antigens were based on a consensus obtained using reference genomes consisting of all three viruses within the genus. All six antigens were produced and purified in-house using BEVS followed by benchtop or FPLC purification (Figure 1). To date, the antigens have been fully validated for performance in indirect ELISA using sheep sera (Figure 2) and partially using cattle sera, with goat sera validation to follow. The ELISAs were developed and optimized using known reference sera as controls. The performance of the ELISAs developed was assessed in comparison with the only commercially available Capripoxvirus serological test. The results demonstrate that some of the antigens used for the ELISAs completely outperformed the commercial test. Several antigens were found to be useful for ELISAs to detect responses in sheep and cattle sera. The sensitivities and specificities of the different ELISAs for sheep sera ranged from 99.54% to 53.57% sensitivity and 99.54 to 94.95% specificity with likelihood ratios above 10 using receiver operating characteristic curve analysis, while the commercial kit had a 42.85% sensitivity using the same positive sheep serum panel evaluated. The development of these serological assays allows for the simultaneous evaluation of immunogenicity of Capripoxvirus antigens through the testing of serum from experimentally infected animals. This study demonstrates the proof of principle, that sensitive and specific ELISAs can be developed for Capripoxviruses.

Epidemiological Risk Factors and Modelling Approaches for Risk Assessment of Lumpy Skin Disease Virus Introduction and Spread: Methodological Review and Implications for Risk-Based Surveillance in Australia

Lumpy skin disease (LSD) is a vector-borne infection caused by the poxvirus lumpy skin disease virus (LSDV) and is a serious disease of cattle, water buffalo, and banteng. While the disease has never occurred in Australia, it is regarded as a growing threat to the Australian cattle industry as there is on-going spread of the disease throughout Asia. The development of geospatial decision support tools, such as spatial epidemiological modelling, may assist in assessing areas at greater risk of this threat. To guide the design of disease modelling approaches to support future risk-based surveillance, existing LSDV epidemiological models need to be evaluated. In this study, we performed a literature review to evaluate existing LSDV epidemiological models, identify key risk factors for introduction and spread of LSDV, and consider previously adopted control strategies. The PRISMA guidelines were used to establish the processes for article selection and information extraction, and the PICO process was used to formulate search terms. From studies that met our inclusion criteria, we extracted information on LSDV epidemiological model structure and parameterisation, risk factors for LSDV transmission and spread, and biosecurity control strategies. The literature search retrieved a total of 402 articles from four databases, of which 68 were identified for inclusion in this review following screening. Of the 68 articles reviewed, 47 explored risk factors associated with LSDV transmission and spread, four explored risk factors of LSDV introduction, four explored existing surveillance strategies in LSD-free countries, and 14 presented epidemiological models. Our findings indicate that there are various risk factors for LSDV transmission in LSD endemic countries, including long-distance airborne movement of infected vectors such as stable flies and cattle movement between countries over land borders. Key risk factors for LSDV spread in LSD endemic countries include physical environmental characteristics, weather conditions, and population distributions of livestock and vectors. Our results indicate that while a variety of modelling studies have been conducted, the majority of studies experimentally explored LSD transmission mechanisms in vectors and cattle. Spatial and spatio-temporal models have primarily been developed for LSD endemic countries and focus on the spread of the disease in terms of environmental factors in relation to previous LSD events. There were very few studies on LSD-free countries, and these only focussed on risk of LSD introduction through specific entry pathways. This review did not identify any literature exploring the risk of spread of LSDV following introduction in LSD-free countries or geospatial modelling of the suitability of LSD-free countries for LSDV incursions. In conjunction with the risk parameters and models described in the identified literature, there is need to consider a wide range of risk factors specific to Australia to inform the design of risk-based surveillance for LSD in Australia.

Lumpy Skin Disease: A Review on Etiopathogenesis, Transmission, Diagnosis and Treatment

Lumpy Skin Disease: A Review on Etiopathogenesis, Transmission, Diagnosis and Treatment

An Exemplary Computational Approach to Investigate Lumpy Skin Disease in Indian Cattle

Lumpy Skin Disease (LSD) is a highly consequential infectious ailment that affects cattle caused by the Lumpy Skin Disease Virus (LSDV), which is a DNA virus classified under the Capripoxvirus genus of the Poxviridae family. This affliction presents a significant obstacle in the cattle industries of several Asian and African countries. Although the virus may be found in many physiological fluids and excretions, such as sperm, skin lesions are the primary source of infection. Hematophagous arthropods, such as biting flies, mosquitoes, and ticks, act as mechanical vectors for transmission. The geographical expansion of LSDV is believed to have been assisted by vector-borne transmission. However, a lack of quantitative understanding of the transmission of LSDV hinders the implementation of efficient disease control measures. Obstacles as mentioned earlier, this work focuses on developing a mathematical model to analyze the phenomenon of Lumpy Skin Disease, with a specific emphasis on its implications for the cattle sectors in African and Asian countries. The model encompasses a set of differential equations incorporating the influences of infection forces originating from sick and asymptomatic cattle, along with infected vectors. The research demonstrates a plausible correlation between Lumpy Skin Disease and increased death rates in cattle. Employing rigorous examination and computational modelling, a valuable understanding of the fundamental dynamics of disease outbreaks is obtained. The mathematical model shows potential for predicting the future transmission of Lumpy Skin Disease. This presents a prospective opportunity for understanding and alleviating the disease's effects on bovine populations. Moreover, the analysis reveals that the impact of direct contact transmission on the spread of LSDV during documented outbreaks was negligible, therefore providing valuable insights into the dynamics of disease transmission. As the model is rigorously analyzed to gain insights into its qualitative dynamics of epidemics, which are present in the numerical simulations, this mathematical model can be allowed to estimate the future spread of the disease.

Lumpy skin disease virus: An updated overview

Lumpy skin disease virus (LSDV) is the virus that causes LSD, which belongs to the genus Capripoxvirus, family Poxviridae. It is a transboundary, non-zoonotic, and vector-borne disease. It is transmitted by infected arthropod species such as Aedes aegypti mosquitoes, Ixodid ticks, Stomoxys calcitrans, and Tabanids haematopota spp. For the 1st time in India, LSD has been reported to cause 7.1% morbidity among cattle. Clinical features are high fever, anorexia, reducing milk production, enlarged lymph nodes, nasal discharge, oval and round skin lesions with a diameter of 1 to 5 cm (sometimes big), tears discharge from the eyes, saliva discharge from the mouth, leg swellings, lameness in dairy cattle, and pregnant cows may miscarry, and cattle cannot come into heat for long months. Borders with India, like China and Bangladesh, are currently suffering. We should pay attention to vector control, vaccination with quarantine measures, and vector control to stop the LSDV spread. This review article talks about the introduction and background, etiology, epidemiology, transmission, clinical features, prevention and control measures, vaccination, and the LSD outbreak in India.

Prevalence and Management Practices of Lumpy Skin Disease (LSD) in Cattle at Natore District of Bangladesh

Lumpy skin disease (LSD) is a potentially contagious viral disease in cattle, caused by the Lumpy skin disease virus (LSDV), which belongs to the family Poxviridae. The virus is suspected to spread via biological vectors such as mosquitoes, flies, ticks, and direct contact. It is a significant economic disease caused by a virus that causes significant losses in milk production, fertility, abortions, import restrictions, and, in some cases, death in the livestock animals. This study aimed to assess the current state of LSD and its management on several farms in the north-western region of Bangladesh. Data were obtained from two Upazilas in the Natore district (Natore Sadar and Baraigram) using a structured questionnaire. During the study period of 1 June to 20 December 2020, a total of 34 small farms and 87 animals were monitored. The OIE guidelines directed the diagnosis of LSD based on current clinical indicators. MS Excel and SPSS statistical software were used to evaluate all of the data. Morbidity, mortality, and case-fatality rates were found to be 64.70%, 2.94 %, and 4.53 % in Natore Sadar and 83.02 %, 3.77 %, and 4.55 % in Baraigram Upazilas, respectively. Female animals that were newly matured (2-4 years) were a larger prone to LSD infection (43.1%) than animals of other ages. A total of 34.43% illness was found in young bull cattle aged (2-4). Bull and heifer calves are also vulnerable populations, with reports of LSD infection leading to mortality. Limb swelling is a common clinical symptom, and LSD-positive young mature (2-4 year) cattle had the most significant rate (18.39%) of limb swelling. The farm hygiene practice is a critical determinant in the spread of LSDV, and a large proportion of cattle (48.27 %) infected with LSD were on farms with poor hygienic management, compared to good (01.14 %) and medium (01.14 %) hygienic management practices (26.43 %). Despite the fact that mosquito nets help prevent mosquitoes, most owners (91.17 %) did not use one in their cattle barn at night. More study is needed in Bangladesh to improve the clinical management of LSD, identify risk factors, and understand the molecular characteristics of diseases.

Observations on presumptive lumpy skin disease in native cattle and Asian water buffaloes around the tiger reserves of the central Indian highlands

ABSTRACT Case history Between August and October 2020, following the monsoon, signs of Lumpy skin disease (LSD) were recorded and described in 154 oxen, 34 cows, 13 calves (Bos indicus ) and two Asian water buffalo (Bubalus bubalis) cows belonging to smallholder farmers in 32 villages located around the Kanha and Bandhavgarh tiger reserves in the state of Madhya Pradesh central India. Affected animals were subjected to a full clinical examination and detailed findings were recorded in a clinical register. A semi-structured questionnaire was attached to the existing clinical register format to gather information on the clinical disease history and animal husbandry practices relevant to the spread of LSD virus. Clinical findings The affected animals were between 4 months and 14 years of age (mean 6.4 (SD 2.5) years). Persistent high temperature, depression, anorexia, and characteristic round nodules (lumps) on the skin were reported. The nodules were 2–5 cm in diameter and spread over the face, ears, neck, back, perineum, scrotum, legs, tail, udder, and nasal and oral mucosa. Secondary complications of myiasis (n=39), mastitis (n=16) and ulcerative lesions on legs were noticed. Death was reported for one animal (0.5%). The affected animals' recovery times were variable (mean 18.4 (SD 2.7) days). There was a significant positive correlation between delay in initiating treatment and the duration of sickness. Reduction in milk yield of 30–55% was reported in Bos indicus cows. Diagnosis Clinical findings and treatment responses consistent with lumpy skin disease and its sequelae. Clinical relevance The presumptive LSD outbreak caused serious economic loss to the animal keepers. LSD is a new disease for India and in the absence of active immunisation, efficient vector control, animal movement control and stall-feeding practice, it will inevitably become endemic in the country. The severe impacts resulting from the introduction of a new disease to a previously unaffected country, highlights the need for iterative improvements in global transboundary disease surveillance. The value of clinical examination and recording of findings is demonstrated in the context of smallholder farming systems with limited access to laboratory diagnosis, which are common around the world. The description of an LSD outbreak in naïve populations of cattle and buffalo illustrates the need for increased awareness of the associated clinical signs and maintenance of high levels of biosecurity in hitherto disease-free countries.

Use of an Alignment-Free Method for the Geographical Discrimination of GTPVs Based on the GPCR Sequences.

Goatpox virus (GTPV) belongs to the genus Capripoxvirus, together with sheeppox virus (SPPV) and lumpy skin disease virus (LSDV). GTPV primarily affects sheep, goats and some wild ruminants. Although GTPV is only present in Africa and Asia, the recent spread of LSDV in Europe and Asia shows capripoxviruses could escape their traditional geographical regions to cause severe outbreaks in new areas. Therefore, it is crucial to develop effective source tracing of capripoxvirus infections. Earlier, conventional phylogenetic methods, based on limited samples, identified three different nucleotide sequence profiles in the G-protein-coupled chemokine receptor (GPCR) gene of GTPVs. However, this method did not differentiate GTPV strains by their geographical origins. We have sequenced the GPCR gene of additional GTPVs and analyzed them with publicly available sequences, using conventional alignment-based methods and an alignment-free approach exploiting k-mer frequencies. Using the alignment-free method, we can now classify GTPVs based on their geographical origin: African GTPVs and Asian GTPVs, which further split into Western and Central Asian (WCA) GTPVs and Eastern and Southern Asian (ESA) GTPVs. This approach will help determine the source of introduction in GTPV emergence in disease-free regions and detect the importation of additional strains in disease-endemic areas.

Madin-Darby bovine kidney (MDBK) cells are a suitable cell line for the propagation and study of the bovine poxvirus lumpy skin disease virus

Lumpy skin disease virus (LSDV) is a poxvirus that causes systemic disease in cattle, resulting in substantial economic loss to affected communities. LSDV is a rapidly emerging pathogen of growing global concern that recently spread from Africa and the Middle East into Europe and Asia, impacting the cattle population in these regions. An increase in research efforts into LSDV is required to address key knowledge gaps, however this is hampered by lack of suitable cell lines on which to propagate and study the virus. In this work we describe the replication and spread of LSDV on Madin-Darby bovine kidney (MDBK) cells, and the formation of foci-type poxvirus plaques by LSDV on MDBK cells. Methods utilising MDBK cells to quantify neutralising antibodies to LSDV, and to purify LSDV genomic DNA suitable for short read sequencing are described. These research methods broaden the tools available for LSDV researchers and will facilitate the gathering of evidence to underpin the development of LSD control and prevention programmes.

Mapping changes in the spatiotemporal distribution of lumpy skin disease virus.

Lumpy skin disease virus (LSDV) is an infectious disease of cattle transmitted by arthropod vectors which results in substantial economic losses due to impact on production efficiency and profitability, and represents an emerging threat to international trade of livestock products and live animals. Since 2015, the disease has spread into the Northern Hemisphere including Azerbaijan, Kazakhstan, the Russian Federation and the Balkans. The rapid expansion of LSDV in those regions represented the emergence of the virus in more temperate regions than those in which LSDV traditionally occurred. The goal of this study was to assess the risk for further LSDV spread through the (a) analysis of environmental factors conducive for LSDV, and (b) estimate of the underlying LSDV risk, using a combination of ecological niche modelling and fine spatiotemporally explicit Bayesian hierarchical model on LSDV outbreak occurrence data. We used ecological niche modelling to estimate the potential distribution of LSDV outbreaks for 2014-2016. That analysis resulted in a spatial representation of environmental limits where, if introduced, LSDV is expected to efficiently spread. The Bayesian space-time model incorporated both environmental factors and the changing spatiotemporal distribution of the disease to capture the dynamics of disease spread and predict areas in which there is an increased risk for LSDV occurrence. Variables related to the average temperature, precipitation, wind speed, as well as land cover and host densities were important drivers explaining the observed distribution of LSDV in both modelling approaches. Areas of elevated LSDV risks were identified mainly in Russia, Turkey, Serbia and Bulgaria. The results suggest that, if current ecological and epidemiological conditions persist, further spread of LSDV in Eurasia may be expected. The results presented here advance our understanding of the ecological requirements of LSDV in temperate regions and may help in the design and implementation of prevention and surveillance strategies in the region.

ENTOMOLOGICAL ASPECTS OF LUMPY SKIN DISEASE EPIZOOTOLOGY (REVIEW)

Lumpy skin disease (LSD) is a serious threat to the global cattle farming, including that in the Russian Federation where the frst outbreak was reported in 2015. Since the disease occurred for the frst time, it has continued to spread in this country; however, virus transmission mechanisms have not yet been studied. Transmission through insect bites is considered to be the most likely mechanism of virus shortrange transmission. At present, such arthropod species as stable fly (Stomoxysсalcitrans), Aedes aegyptimosquitoes, as well asAmblyomma hebraeumandRhipicephalus appendiculatusticks are regarded as potential vectors. Viral DNA has also been detected on the exoskeletons of house flies (Musca domestica). The available literature describes the results of many studies on the role of arthropods in LSD virus spread, but the data presented are inconsistent and do not provide an unambiguous answer concerning the level of signifcance of potential LSD virus vectors in the progression of the feld epizootic. These papers investigate the ability of gadflies, flies and ticks to act as mechanical vectors. Currently, there is no unequivocal viewpoint with respect to the proved LSD vector. This paper reviews the entomological papers aimed at studying possible LSD virus transmission by arthropods.

Characterising the cell-mediated immune response to Lumpy skin disease virus

Lumpy skin disease (LSD), a high-impact disease of cattle and water buffalo, is a direct threat to the European cattle industry. The causative agent is the lumpy skin disease virus (LSDV), an enveloped dsDNA virus which belongs to the family Poxviridae. Affected cattle present multiple cutaneous nodules that are characteristic of a LSDV infection. The case fatality rate of LSD is low, however affected animals suffer substantial production losses including weight loss and reduced milk production. On a wider scale, LSD is a high consequence transboundary disease with mandated export restrictions imposed on affected countries leading to substantial economic costs. Currently, there is no cure for LSDV infected cattle. Hence, mass vaccination is an important component in minimizing the spread of LSDV. There are only a handful of commercially available live attenuated vaccines in the current market. These vaccines vary in efficacy, quality, and safety, which leaves some scope for further development. This improvement is hampered by a poor understanding of the immunology of LSDV, particularly the protective immune mechanisms. In this project, we are investigating the immune response to LSDV with a focus on characterising the cell-mediated immune response. Peripheral blood mononuclear cells from LSDV immunised/infected cattle and flow cytometry assays are used to detect the production of IFN-γ by CD4+T-helper cells and CD8+cytotoxic T cells in response to live LSDV stimulation. Our goal is to improve understanding of the immune response to LSDV in order to develop effective vaccines and control programs in the future.

Characterising the insect-borne transmission of the cattle poxvirus lumpy skin disease virus

Lumpy skin disease (LSD) is an emerging poxviral disease of cattle caused by the Capripoxvirus lumpy skin disease virus (LSDV) which generates widespread cutaneous lesions in affected animals. LSD is recognised as a transboundary high consequence disease in Africa where it contributes to rural poverty and food insecurity. In 2015 LSDV spread to southeastern Europe and currently poses a threat to cattle in neighbouring regions. Previous research indicates that LSDV is most likely transmitted by insect vectors however details of transmission pathways are unclear. This study was designed to identify the risk of transmission of LSDV posed by different insect vectors. A bovine experimental model of LSD was established in the high containment facilities at The Pirbright Institute. Potential insect vectors (Aedes aegypti, Culex quinquefasciatus, Stomoxys calcitrans and Culicoides nubeculosus) were fed on LSDV-infected cattle then incubated for up to eight days. Cattle and insects were regularly sampled to quantify LSDV present in different tissues and vector species. This data was then used to model the dynamics of LSDV infection and transmission. All four species of vector successfully acquired LSDV from infected cattle and maintained the virus up to eight days post feeding. The outputs of this research will now be used to design more effective LSD control programmes.

Assessing the probability of introduction and transmission of Lumpy skin disease virus within the United Kingdom

Several emerging exotic diseases are currently oscillating on the eastern borders of the European Union (EU) including the bovine pathogen Lumpy skin disease virus (LSDV). Given the recent transboundary spread of LSDV into the EU, assessing the probability of further expansion is an important part of EU surveillance and can inform policy regarding risk mitigation priorities. This qualitative assessment focuses on the probability of introduction and onward transmission of LSDV into the United Kingdom (UK) for the time period June 2017 to June 2018. Overall the probability of introduction was considered, at most, to be very low. The probability of onward transmission was considered highest for vector mediated routes either via contact of an infected vector with susceptible cattle or contact of a competent native vector with an infected cattle. Factors with high uncertainty were identified to emphasise their impact on the assessment conclusions and for future research requirements. Medium to high uncertainty surrounds the probability of introduction to the UK via several of the routes assessed, in particular, the species of vectors involved and the illegal/legal import of meat and milk products; all estimates made consequential to these probabilities are therefore underpinned by high uncertainty. Whilst the assessment was UK centric the knowledge gaps are relevant to the probability of introduction and spread of LSDV in any geographical region. The value of estimating uncertainty lies in the identification of research required to make conclusions more robust.

Epidemiological characterization of lumpy skin disease outbreaks in Russia in 2016.

In 2015, the lumpy skin disease virus spread throughout the Russian Federation. Following a modified stamping-out campaign, the disease re-emerged with a greater incidence across 16 regions of Southern and Central Russia. A total of 313 outbreaks were reported to OIE. The highest outbreak frequency was observed in the republics of Chechnya (108), Kalmykiya (57), and Ingushetiya (35). The disease cases predominantly occurred in June and July 2016, starting from May to December; however, no association between outbreaks and altitudes was identified (p>.05). Samples taken from infected cattle were subjected to PCR analysis, which identified the genome of the virus most frequently in skin nodules (78%), nasal swabs (23.4%), blood (13%) and sera (14.5%). Interestingly, LSDV genome was occasionally identified in lung and milk samples. Based on the PRO30 sequence analysis, lumpy skin disease virus (LSDV) strains circulating in Russia were all identical and fell within the cluster of field LSDV found worldwide.

Evidence of vertical transmission of lumpy skin disease virus in Rhipicephalus decoloratus ticks

Lumpy skin disease (LSD) is an economically important acute or sub-acute disease of cattle that occurs across Africa and in the Middle East. The aim of this study was to assess whether Rhipicephalus decoloratus ticks were able to transmit lumpy skin disease virus (LSDV) transovarially. Uninfected, laboratory-bred R. decoloratus larvae were placed to feed on experimentally infected “donor” cattle. After completion of the life cycle on donor animals, fully engorged adult female ticks were harvested and allowed to lay eggs. Larvae that hatched from these eggs were then transferred to feed on uninfected “recipient” cattle. The latter became viraemic and showed mild clinical disease with characteristic skin lesions and markedly enlarged precrural and subscapular lymph nodes. This is the first report of transovarial transmission of poxviruses by R. decoloratus ticks, and the importance of this mode of transmission in the spread of LSDV in endemic settings requires further investigation.

Mechanical transmission of lumpy skin disease virus by Rhipicephalus appendiculatus male ticks

Lumpy skin disease (LSD) is an economically important, acute or sub-acute, viral disease of cattle that occurs across Africa and in the Middle East. The aim of this study was to investigate if lumpy skin disease virus (LSDV) can be transmitted mechanically by African brown ear ticks (Rhipicephalus appendiculatus Neum.). Laboratory-bred R. appendiculatus males were fed on experimentally infected viraemic 'donor' cattle. Partially fed male ticks were then transferred to feed on an uninfected 'recipient' cow. The recipient animal became viraemic, showed mild clinical signs of LSD and seroconverted. Additionally, R. appendiculatus males were found to transmit LSDV through feeding on skin lacking visible lesions, demonstrating that viraemic animals without lesions at the feeding site of ticks may be a source of infection. This is the first time that transmission of poxviruses by a tick species has been demonstrated and the importance of this mode of transmission in the spread of LSDV in endemic settings is discussed.

Neutralising antibodies to lumpy skin disease virus in African wildlife

A total of 3445 sera from 44 different wild species collected between 1963 and 1982 in 11 African countries south of the Sahara, were examined for neutralising antibodies to Lumpy Skin Disease (LSD) Virus (prototype Neethling). Antibodies were demonstrated in six species but were of low prevalence. It was concluded from the generally negative results, that wildlife in Africa probably does not play a very important part in the perpetuation and spread of LSD Virus.