CASE NOTES

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Observations on Lumpy Skin Disease in Indonesia

There's a Pox on our Doorstep

Peter Windsor, Production Animal Welfare & Health Services

Posted Flock and Herd July 2023

Introduction

Lumpy skin disease (LSD) is a poxviral disease that has recently emerged as a serious Transboundary Animal Disease (TAD) in the Asia-Pacific region, causing significant morbidity and occasional mortality in cattle. LSD affecting cattle, along with sheeppox and goatpox in small ruminants, have highly characteristic clinical signs affecting multiple body systems. All three diseases reduce meat, milk, wool, and cashmere production, although few studies have formally evaluated their economic impact on affected farms (Limon et al., 2020). The occurrence and severity of the clinical signs and lesions of LSD is often observed to be highly variable within a cohort of affected animals, depending on several factors, including the strain of capripoxvirus and the age, immunological status, and breed of the host. Bos taurus breeds are generally considered more susceptible to clinical disease than Bos indicus, with Asian water buffalo (Bubalus spp.) also reported to be susceptible. Lactating cows appear to be most at risk, although in herds of cattle of the same breed managed under the same conditions, a large variation in the severity of clinical signs, ranging from subclinical infection to death, with failure of the virus to infect every individual in the whole group is frequently observed. These observations suggests that clinical expression of LSD infection probably depends on the virulence of the virus isolate, immunological status of the host, host genotype, and vector prevalence (OIE 2021). The incubation period under field conditions has not been reported, but following experimental inoculation it is 6-9 days until the onset of fever.

Clinical signs

In the acutely infected animal, there is an initial pyrexia, which may exceed 41°C and persist for one week, with some to all superficial lymph nodes becoming enlarged. In lactating cattle there is a marked reduction in milk yield. Lesions develop over the body, particularly on the head, neck, udder, scrotum, vulva and perineum, usually between 7-19 days after virus inoculation. On appearance of nodules, discharges from the eyes and nose may become mucopurulent, with keratitis sometimes developing. Nodules may also develop in the mucous membranes of the mouth and alimentary tract including the abomasum, with lesions in the trachea and lungs occasionally resulting in pneumonia.

The nodules on the mucous membranes of the eyes, nose, mouth, rectum, udder and genitalia quickly ulcerate, with all secretions, including ocular and nasal discharge and saliva, containing LSD virus (LSDv). The limbs may be oedematous and the animal is reluctant to move. Pregnant cattle may abort, with intrauterine transmission reported, and bulls may become temporarily or permanently infertile, with LSDv sometimes excreted in the semen for prolonged periods. Recovery from severe infection is slow, with some animals becoming emaciated, usually attributed to pneumonia and mastitis. The necrotic plugs of skin lesions often develop into deep holes, severely damaging hides.

Lesions

The characteristic integumentary lesions are generally multifocal to locally extensive, well circumscribed to coalescing, measuring 0.5-8 cm in diameter, resembling firm, flat-topped papules, and nodules. They involve the epidermis and dermis, often extending to the subcutis and occasionally to adjacent muscle. The nodules have a creamy grey to white colour on cut section and may initially exude serum. However, over the ensuing two weeks, a cone-shaped central core or sequestrum of necrotising debris forming a necrotic plug ('sit-fast') may appear within the nodule.

The acute histological lesions consist of epidermal vacuolar changes with dermal vasculitis and intracytoplasmic inclusion bodies that are numerous, eosinophilic, and homogenous to occasionally granular, found in endothelial cells, fibroblasts, macrophages, pericytes, and keratinocytes. The dermal lesions include vasculitis with fibrinoid necrosis, oedema, thrombosis, lymphangitis, dermal-epidermal separation, and mixed inflammatory infiltrates. The chronic lesions are characterised by an infarcted tissue with a sequestered necrotic core, often rimmed by granulation tissue gradually replaced by mature fibrosis.

Diagnosis

Laboratory confirmation of LSD is most rapid using a real-time or conventional polymerase chain reaction (PCR) method specific for capripoxviruses in combination with a clinical history of a generalised nodular skin disease and enlarged superficial lymph nodes in cattle. Ultrastructurally, capripoxvirus virions are distinct from the parapoxvirus virions causing bovine papular stomatitis and pseudocowpox, although cannot be readily distinguished morphologically from orthopoxvirus virions, including cowpox and vaccinia viruses, both of which are capable of causing disease in cattle (although neither causes generalised infection and bovine infection is uncommon).

LSDv will grow in tissue culture of bovine, ovine or caprine origin. In cell culture, LSDv causes a characteristic cytopathic effect with intracytoplasmic inclusion bodies. Capripoxvirus antigens can be demonstrated in tissue culture using immunoperoxidase or immunofluorescent staining and the virus can be neutralised using specific antisera. The cell culture lesions are distinct from infection with bovine herpesvirus-2, a cause of pseudo-lumpy skin disease and characterised by production of syncytia and intranuclear inclusion bodies in cell culture. In Africa, infection with the protozoal pathogen Besnoitia sp. causing besnoitiosis and characterised grossly with readily visible epidermal macroschizonts, has also been referred to as pseudo-lumpy skin disease.

Serological tests include validated virus neutralisation test (VNT) and enzyme-linked immunosorbent assays (ELISAs), with agar gel immunodiffusion (AGID) and indirect immunofluorescent antibody (IFT) tests considered less specific than the VNT due to cross-reactions with antibodies to other poxviruses (OIE 2021).

LSD in South-East Asia

LSD was first reported in Asia and the Pacific region in 2019 in north-west China, Bangladesh, India, China, Chinese Taipei, Vietnam, Bhutan, Hong Kong (SAR-RPC), Nepal, and Sri Lanka. It then spread to Myanmar, Thailand, Laos, Cambodia, Indonesia, and Singapore in 2021-22. Even though the mortality rate was reportedly low, economic losses resulting from loss of condition, decreased milk production, abortions, infertility, and damaged hides appeared significant. As LSDv is persistent in the environment in organic matter and spread by both animal and manure movement and locally by blood-feeding insects, including species of flies and mosquitoes or ticks, outbreaks can be widespread and difficult to control.

Case reports & Impacts

In 2021, I was contacted by colleagues in veterinary services positions in Cambodia and Laos seeking access to Lumpyvax® (MSD Animal Health South Africa); I was able to facilitate access through a colleague working for MSD that was a regular attendee at SEACFMD (Southeast Asia China Foot and Mouth Disease Campaign) meetings (Figure 1).

Figure 1. Lumpyvax LSD vaccine

Figure 2. Riau, Samatra & Semarang, Central Java

As capripoxviruses are cross-reactive within the genus, live attenuated strains of capripoxvirus derived from sheep or goats have been used in vaccines to control LSD in cattle (OIE 2021). The outbreaks in South-East Asia (SEA) spread to Riau in northern Sumatra in February 2022, where it appeared contained for much of that year (Figure 2).

Figure 3. Severe LSD lesions on a cow in Farm 1

Then in the week of 12-17 December 2022, I visited Java to gain an understanding of the recent spread of LSD of cattle from Riau to Central Java in Indonesia, a distance of over 1000km (Figure 1). Local advice was that LSD had then also recently spread from the province of Central Java where it had infected eight of 35 districts (Tegal, Kendal, Semarang, Semarang City, Boyolali, Demak, Pekalongan & Rembant), to three districts in the province of East Java (Blitar, Makang and Sidoarjo). I was able to visit several infected farms with the Provincial Veterinarian of Central Java and staff from the Gunupati District Office, examining animals and interviewing owners of affected livestock.

On one farm of several related families, there were seven cattle, including five cows, a bull, and a weaner calf. All animals displayed some lesions consistent with LSD and several were very severely affected. One cow with a body condition score of <1 and displaying a depressed mental state, was extremely affected with multiple raised circular haired lesions of subacute-to-chronic-active dermatitis. These lesions were up to 8cm in diameter, with some having shed the superficial epidermis, leaving dried dark-red scabs, particularly ventrally (Figure 3). Biting insects (mostly flies) appeared implicated in the development and spread of lesions on and between animals, with the cattle pen adjacent to a large overflowing manure pit approximately 10x5x3m (Figure 4a). The biting flies attacked the legs of both cattle and humans (Figure 4b). On discussion with the farmer, the value of the affected animals was R15M (AUD1,5018) when healthy, declining to <R3M (AUD304). The farmer paid R300.000 (AUD30.37) per animal for a single veterinary treatment of antibiotics, a non-steroidal anti-inflammatory drug (NSAID; Flunixin) and multi-vitamins.

We then visited a smallholder feedlot in Gunupati where approximately 30 households co-operatively held and fed their cattle with locally grown forages. The LSD lesions here were less dramatic and appeared more resolved, with a majority of the ~40 animals displaying lesions of mild-to-moderate chronic multifocal dermatitis. These were dark grey to black with measured lesion up to 2cm in diameter (Figure 5).

Evidence to support the implementation of many farm-level biosecurity practices was not readily available despite the Foot-and-Mouth Disease (FMD) outbreak that had occurred earlier in the year (May-July). I was in a team that wore personal protective equipment (PPE) including disposable coveralls, gloves and work boots. At the end of each farm visit we cleaned our boots with soap and water and sprayed disinfectant on the cleaned boots, much to the amusement of the locals.

Figure 4a. Manure pit adjacent to cattle on Farm 1

Figure 4b. Biting flies on cattle on Farm 1

Treatment and Control activities

In Central and East Java ring vaccinating with Lumpyvax® within 3km of severely affected farms was reported, with >900 doses now administered. Treatment for clinically affected animals included extensive use of parenteral (amoxicillin, oxytetracycline) and topical (oxytetracycline; Limoxin) antibiotics, NSAIDs (Flunixin) and injectable multi-vitamins; these appeared to have little impact on clinical expression of disease. Treatment costs were incurred by affected farmers. I was able to trial use of a topical anaesthetic (Tri-Solfen®) sprayed on lesions and observed that treated animals appeared to display signs of relief from the irritation and presumably pain and stress caused by the lesions. The provincial vet and farmers were enthused by use of a product that appeared to diminish the suffering of their animals (Figure 6).

Possibilities of Transmission

A high level of uncertainty around compliance with regional biosecurity measures, including animal movement controls, was reported. It seems most likely that the spread from northern Sumatra to Central and East Java was due to the animal or fomite movements. Despite the uncertainty, local advice was that the cattle demand/supply chain means that most cattle move into and not from Java (apart from some movements to Kalimantan). Although the recent spread of LSD to three districts in East Java is of concern with the transmission route obscure, local authorities were confident that failures in compliance with movement barriers was the most likely explanation. Our impression was that for local spread, manure is a breeding ground for biting flies and other insects, with more severe clinical cases on farms with poor manure management. These insects would be less likely to be the source of long-distance movement of LSDv than failures to control animal movement, although uncertainties remain.

Figure 5. Resolving LSD lesions on Farm 2

Figure 6. A happy Dr Yoyo, Provincial Veterinarian, Central Java

Preliminary Conclusions

Whilst it is disturbing that LSD spread over 1000km last December, with a consequential apparent increase in the threat of LSDv transmission to Australia, experience on infected farms and local knowledge provides some confidence that known transmission routes were responsible for spread. It is probable that long-distance spread involves movement of animals or fomites (LSDv survives in scabs in manure for three months), with biting insects more likely involved in local neighbourhood and intra-district spread, with inter-district spread possible; this is consistent with information in the OIE LSD manual.The initial financial losses described by the farmer suggest socioeconomic impacts of LSD are very significant. Structured research is urgently required to address the issues of LSD transmission risk, control and therapy, with biosecurity, manure management, antimicrobial resistance (AMR) concerns requiring consideration.

Discussion

Uncertainties persist in our knowledge and awareness of the epidemiology, routes of introduction and spread of LSD, with confusion on the most effective prevention and control strategies for the disease in SEA. Further, the impact of LSD on cattle and buffalo value chains needs to be better understood, enabling evidence-based informed decisions, policies, and resourcing priorities to be developed by the various national Veterinary Services in Asia and the Pacific. A review on the economic impact of LSD in Ethiopia found that various agro-climatic conditions, introduction of new animals to herds, and the presence of communal watering bodies were major risk factors for transmission between farms that would facilitate the spread of outbreaks in diverse localities (Gumbe, 2018). Similar studies are required in SEA. The reported total average estimated financial losses due to LSD per head (based on milk, meat, draught power, mortality, treatment, and vaccination costs) of Zebu cattle at USD6.43 per head and Holstein-Friesian cattle at USD58 per head (Limon et al., 2020) indicate that studies in both beef and dairy production systems in SEA are required. High rates of antibiotic use by subsistence farmers in Northeast Nigeria may increase the risk of AMR and anecdotal information and personal observations indicating that antibiotics are frequently administered to cattle with clinical LSD and FMD in SEA.

In response to the escalating threat of LSD, Australian governments in partnership with industry and stakeholder groups, commissioned a literature review (Zalcman & Cowled, 2022) and then developed a National Lumpy Skin Disease Action Plan outlining priorities to strengthen Australia's preparedness and including the development of epidemiological modelling systems for LSD incursion (FAO, 2023). The Australian Animal Disease Spread model (AADIS), originally developed to support FMD preparedness and response, is being adapted to provide national-scale modelling capability to simulate spread and control of LSD within Australia, simulating within- and between-herd transmission of infection and incorporating several control options including: movement restrictions; surveillance and tracing; stamping out; and vaccination. Control measures and resources are guided by AUSVETPLAN with inputs from state and territory animal health authorities, although modelling the spread and control of insect vector-borne livestock diseases such as LSD is challenging, particularly for remote, extensive cattle production systems. Defining the populations at risk, addressing vector distributions and ecology, identifying disease transmission within and between herds, and designing and implementing control measures, is required. Collaboration between governments (federal, state and territory) and universities is enabling model development (Sanderson, 2023) and supporting LSD preparedness action planning in Australia, enabling veterinary authorities to test a range of outbreak scenarios and mitigation strategies.

The recent outbreak of sheeppox in Spain that commenced in mid-2022 and involved ~40 farms is considered most likely to have resulted from fomite transmission by north African shepherds working on Spanish sheep farms. This transmission event suggests the Capripoxviruses are a group of viruses capable of causing TAD threats that are of increasing global importance to international food security and capable of causing severe welfare impacts on farmed livestock (Figures 7, 8 & 9).

 

 

Figures 7,8 & 9. Sheepox lesions in small ruminants can be a very debilitating disorder (images courtesy of Professor M. Houssein, University of Tehran, Iran)

References

1. FAO (2023) Lumpy skin disease symposium: How science can support evidence-based disease management and control www.fao.org
2. Gumbe AAF (2018) Review on lumpy skin disease and its economic impacts in Ethiopia Journal of Dairy, Veterinary & Animal Research 7(2):39-46 doi.org
3. Limon G, Gamawa AA, Ahmed AI, Lyons NA & Beard PM (2022) Epidemiological Characteristics and Economic Impact of Lumpy Skin Disease, Sheeppox and Goatpox Among Subsistence Farmers in Northeast Nigeria Frontiers of Veterinary Science 7:8 doi.org
4. OIE Terrestrial Manual (2021) Lumpy Skin Disease; Chapter 3.4.12 www.woah.org
5. Sanderson J (2023) National Lumpy Skin Disease Action Plan: Progress Report. Biosecurity Animal Division, Department of Agricture, Forestry and Fisheries, Canberra, Australia. February 2023. www.agriculture.gov.au
6. Zalcman E & Cowled B (2022) Lumpy Skin Disease: a literature review. Department of Agriculture, Water and the Environment, Australia. March, 2022. www.agriculture.gov.au