First outbreak of lumpy skin disease in Japan, 2024

Abstract

In November 2024, the animal health authority of Japan reported the nation’s first case of lumpy skin disease (LSD) at a dairy farm in Fukuoka, Kyushu. Although a total of 22 farms were affected—17 dairy, 3 beef, and 2 mixed—the epidemic was effectively contained within two months through strict control measures. PCR testing confirmed the presence of LSD virus in skin nodules from suspected cattle at the index farms, and infectious virus was isolated. Phylogenetic analysis based on the complete genome sequence indicated that the virus detected in Japan was closely related to strains that have recently circulated in East and Southeast Asia.

Lumpy skin disease (LSD) is a viral disease of cattle and buffaloes caused by the LSD virus (LSDV) belonging to the family Poxviridae, subfamily Chordopoxviridae, genus Capripoxvirus [2]. This disease is a World Organisation for Animal Health (WOAH)−listed disease [28]. Infected animals develop clinical signs, including fever and nodular lesions (5–50 mm in diameter) on the body, particularly on the head, neck, udder, scrotum, and vulva [28]. Morbidity ranges from 3% to 85%, while mortality is generally low [25]. Transmission occurs primarily through blood-feeding vectors, such as mosquitoes, stable flies, and ticks [2].

The control and eradication of the disease requires vaccination, movement restrictions, and culling of infected animals [26]. In Eastern and Southern Europe, well-organized vaccination campaigns with sufficient coverage have successfully controlled LSD outbreaks [24]. Live-attenuated LSDV vaccines based on the Neethling and KSGP strains are widely used and confer effective protection against virulent field strains [2]. However, recent virulent field strains have been identified as vaccine strain-derived recombinants, exhibiting genetic characteristics of both Neethling and KSGP LSDVs, as well as goatpox virus [27]. These recombinant strains are genetically distinct from previously known LSDV strains and were therefore classified into Cluster 2 [20]. They have spread across almost all East and Southeast Asian countries, including China (2019) [13], Vietnam, Taiwan (2020) [22, 23], Thailand (2021) [4], and South Korea (2023) [7].

On November 5, 2024, two dairy farms in Fukuoka, Kyushu, Japan, reported cattle exhibiting skin nodules. At the index farm, several cattle were identified with papular skin lesions in varying sizes (up to 50 mm in diameter) that were distributed over the trunk, limbs, nasal cavity, and head (Fig. 1). Skin nodule, whole blood, and nasal swab samples were collected from six cattle with clinical signs at two farms. Conventional PCR was performed on tissue homogenates of nodule samples with p32 gene-specific primers (forward: 5ʹ-TCCGAGCTCTTTCCTGATTTTTCTTACTAT-3ʹ, reverse: 5ʹ-TATGGTACCTAAATTATATACGTAAATAAC-3ʹ) following the WOAH Terrestrial Manual [28]. All tested samples were confirmed positive for Capripoxvirus. In addition, the same assay applied to whole blood and nasal swab samples was positive in two and three samples, respectively. Furthermore, targeted sequencing of the G-protein-coupled chemokine receptor (GPCR) and 30 kDa RNA polymerase subunit (RPO30) genes [15] confirmed that the detected virus was LSDV. To isolate the causative agent, a homogenate of skin nodules from a suspected animal on the first farm was inoculated onto LSDV-permissive embryonic sheep skin cells (ESH-L [17]), resulting in marked cytopathic effects within a few days (Fig. 2A). The first isolate was designated LSDV/JPN/FKO/A/1-D/2024. Furthermore, transmission electron microscopic examination for the nodules from which the virus had been isolated revealed Poxvirus virions (Fig. 2B). Poxvirus virions were identified by their characteristic hourglass-shaped core surrounded by lateral bodies and enclosed in viral membranes.

Fig. 1.

Clinical appearance of lumpy skin disease in a cow. (A) Papular skin lesions distributed over the trunk, limbs and head. (B) Lesions on the head. (C) Lesions in the nasal cavity. (D) Close-up view of representative lesions.

Fig. 2.

The first lumpy skin disease virus detected in Japan. (A) Cytopathic effects observed in ESH-L cells with LSDV/JPN/FKO/A/1-D/2024. The area enclosed by dashed lines indicates CPE. (B) Transmission electron microscopy of a skin nodule. Many brick-shaped viral particles characteristic of poxviruses are observed within the lesion. Immature virions are also visible (white arrowhead). Scale bar, 500 nm.

Whole-genome sequencing of LSDV/JPN/FKO/A/1-D/2024 was performed using a previously described protocol with slight modification [14]. Briefly, infected cells were harvested and treated with 250 U benzonase nuclease (Merck, Darmstadt, Germany) at 37°C for 1 hr. Viral DNA was extracted with the High Pure Viral Nucleic Acid Kit (Roche, Basel, Switzerland) and subjected to next-generation sequencing on an iSeq platform (Illumina, San Diego, CA, USA) according to the manufacturer’s instructions. Adapter-trimmed reads were mapped to the reference genome LSDV/China/2022 (accession number OQ555660) with the Galaxy web platform [1]. The resulting consensus sequence was deposited in DDBJ under accession number LC865643 and subsequently used for phylogenetic reconstruction with the maximum-likelihood method implemented in MEGA 11 [21]. Accession numbers of the reference sequences used in this analysis are described in Fig. 3. The results indicated that LSDV/JPN/FKO/A/1-D/2024 is almost identical to LSDV/China/2022, which was isolated in China in 2022, except for two nucleotide mutations across the 151,189 bp genome. This result suggested that the isolate belongs to Cluster 2.5, which comprises “vaccine-like” recombinant LSDVs currently circulating in neighboring countries (Fig. 3).

Fig. 3.

Phylogenetic tree of lumpy skin disease virus. The LSDV strain that emerged in Japan in 2024 is highlighted in red. The Maximum Likelihood method based on Tamura-Nei model was used to construct the phylogenetic tree and implemented in MEGA 11 software. Numbers at each node indicate the confidence level in bootstrap analysis with 1,000 replications. Only confidence levels ≥50 are indicated. For each isolate, the GenBank accession number is provided in LSDV/Isolation Country/Year format.

Thus, LSDV isolated in Japan is genetically close to strains circulating in neighboring countries, suggesting that the virus was introduced from an outbreak region. The introduction of LSDV into non-endemic areas is often associated with the movement of infected livestock [5]. However, given Japan’s geographical isolation and strict animal quarantine measures, the direct importation of infected live animals seems unlikely. An alternative route of virus entry could be through haematophagous arthropods [5]. Biting midges (Ceratopogonidae) and mosquitoes (Culicidae) are well-known vectors of arboviruses and capable of long-distance movement across regions via wind currents for example, along north-to-south trajectories in East Asia [10]. Although the distance from the southern coast of Korea to the northern tip of Kyushu is approximately 200 km and that from mainland China to Kyushu is roughly 1,000 km, indeed, Culex tritaeniorhynchus mosquitoes have been shown to carry Japanese encephalitis virus across the East China Sea to Kyushu [3]. Although LSDV is not an arbovirus [19], vectors such as stable flies, biting midges, Aedes aegypti, and Culex quinquefasciatus have been reported to retain infectious virus for 2.4 to 5.9 days [18]. Other vector species, such as horse botflies, also travel over 200 km within 24 hr via wind [9]. In addition, inadvertent human-mediated transport, such as international flights or domestic freight, could introduce virus-carrying vectors or virus-contaminated fomites into Japan. Taken together, these findings suggest that blood-feeding arthropod vectors may constitute one potential pathway for the introduction of LSDV into Kyushu; however, further investigation is necessary to elucidate the route of incursion.

Outbreak reports from Fukuoka Prefecture showed expansion following the initial outbreak at a single farm, indicating that the infection spread locally over time rather than through multiple, simultaneous introductions of the virus. This pattern suggests that the disease was also transmitted locally by arthropod vectors or by the movement of people and vehicles. Further outbreaks were confirmed in other locations in the same prefecture, however, no significant connections among the affected farms with respect to veterinary personnel, artificial insemination technicians, feed suppliers, or livestock traders (Fig. 4). Although no clear epidemiological links were identified, the potential involvement of vectors suggests that strengthening biosecurity measures may be necessary even at farms located far from the initial outbreak site. In Kumamoto Prefecture, the first reported case of LSD was linked to cattle transported from the initial outbreak farm in Fukuoka Prefecture. Subsequent cases in Kumamoto were confined to neighboring farms within roughly 1 km, supporting the notion of localized transmission described above (Fig. 4).

Fig. 4.

Geographical distributions of lumpy skin disease outbreak farms in Japan from November 2024 to January 2025. An enlarged map of Fukuoka and Kumamoto Prefectures, which became the lumpy skin disease (LSD) outbreak areas in Japan. Cities, towns, and districts in which outbreaks occurred are marked in red. Pref., Prefecture.

LSDV can infect cattle irrespective of age or breed, but clinical cases are observed most frequently in young animals and those at peak lactation [25]. In Kyushu, the principal breeds raised are Holstein (dairy) and Japanese Black (beef). The combined population of Japanese Black cattle and Japanese Black ×Holstein F1 crosses reared for beef production is approximately twice that of Holsteins in both prefectures [8, 12]. Nevertheless, during the recent LSD outbreak in Kyushu, the numbers of affected animals by breed were three Japanese Black cattle, two F1 crosses, and 225 Holsteins (Table 1). Although few comparative data are available on breed-related susceptibility to viral infections in these populations, a Japanese sero-epidemiological study reported bovine leukemia virus seroprevalence rates of 40.9 % in dairy cattle and 28.7 % in beef cattle, with corresponding differences in disease occurrence, indicating marked disparities in infection rates between these categories [16]. Reports from Korea have documented breed-dependent differences in responsiveness to LSD vaccination among Holstein, Hanwoo, and Jersey cattle [6]. Therefore, whether Japanese Black cattle—phylogenetically close to Hanwoo [11]—are indeed more resistant to LSDV than dairy breeds remains to be determined, and the factors underlying any such difference require elucidation.

Table 1. The cumulative number of lumpy skin disease (LSD) cases in cattle in Japan as of May 30, 2025.

	Cumulative number of cattle with LSD
	Japanese Black cattle (Beef cattle)	Crossbreeds (F1) (Beef cattle)	Holstein (Dairy cattle)	Total
Fukuoka Pref.	3	0	192	195
Kumamoto Pref.	0	2	33	35
Total	3	2	225	230

The recent outbreaks were successfully controlled in less than two months through comprehensive countermeasures, combined restriction of animal movement, premises disinfection using cationic detergent, and a seasonal decline in vector activity, and at several farms, emergency vaccination with the internationally validated Neethling LSDV-based live attenuated vaccine (cluster 1.1; Lumpyvax, MSD, Rahway, NJ, USA) [24] together with voluntary culling of affected animals. Farms that did not adopt vaccination or culling experienced ongoing cases for almost one month, whereas those that employed both interventions recorded virtually no new cases and achieved rapid cessation of transmission. These observations indicate that emergency vaccination together with culling of affected animals is highly effective for the prompt containment of this disease. To prevent the recurrence of the disease, the animal health authority of Japan has focused on disseminating information to stakeholders and implementing proactive measures. These include early detection and notification, movement restrictions for animals with clinical signs, and the establishment of an effective vaccination program [24].

CONFLICTS OF INTEREST

The authors have nothing to disclose.