Peste des Petits Ruminants Virus

Taxonomy and Genomic Diversity of Peste des Petits Ruminants Virus

Taxonomic Classification and Nomenclature

Peste des petits ruminants virus (PPRV) is the etiological agent of a highly contagious and often fatal disease of small ruminants, designated peste des petits ruminants (PPR). Taxonomically, PPRV is classified within the family Paramyxoviridae, subfamily Orthoparamyxovirinae, genus Morbillivirus [1, 4, 8]. The genus Morbillivirus comprises a group of closely related, antigenically conserved viruses that cause significant diseases in their respective hosts, including measles virus (MeV) in humans, canine distemper virus (CDV) in dogs and other carnivores, and the now-eradicated rinderpest virus (RPV) in cattle and buffalo. The International Committee on Taxonomy of Viruses (ICTV) formally designates the species as Morbillivirus caprinae, reflecting its primary host family, Caprinae [8]. This taxonomic placement is underpinned by shared structural and biological properties, including a non-segmented, negative-sense single-stranded RNA genome, an enveloped virion, and a characteristic propensity for inducing profound immunosuppression in the host [10, 13, 20]. PPRV is distinguished from other morbilliviruses by its host range, antigenic profile, and specific genetic markers, particularly as the global eradication of RPV was achieved in 2011, leaving PPRV as the most prominent extant member of the genus threatening agricultural biosecurity and wildlife conservation.

Virion Structure and Genome Organization

The PPRV virion, like all morbilliviruses, is pleomorphic and enveloped, encasing a helical ribonucleoprotein (RNP) complex. The genome is a single molecule of negative-sense, single-stranded RNA, approximately 15,948 nucleotides in length for most wild-type strains, as exemplified by isolates from China (e.g., ChinaSX2020) and Europe [10, 25]. The genome conforms to the canonical morbillivirus “rule of six,” wherein the total nucleotide count is a multiple of six, a requirement for efficient replication. The virion structure is composed of six structural proteins and at least two non-structural proteins. The RNA-dependent RNA polymerase (RdRp, L gene product), phosphoprotein (P), and the large nucleocapsid protein (N) encapsidate the genome to form the RNP, which is the template for transcription and replication. The matrix protein (M) lines the inner surface of the viral envelope and is critical for virion assembly and budding. Embedded in the lipid envelope are two surface glycoproteins: the fusion protein (F) and the hemagglutinin protein (H). The H protein mediates attachment to host cellular receptors, primarily signaling lymphocyte activation molecule (SLAM, CD150) on immune cells and nectin-4 (PVRL4) on epithelial cells, while the F protein drives pH-independent membrane fusion, facilitating viral entry [7, 37].

The genomic organization is highly conserved, with genes arranged in the order 3′-N-P-M-F-H-L-5′. The P gene is transcriptionally complex and, through a process of RNA editing (co-transcriptional insertion of non-templated G residues), gives rise to multiple protein products. These include the P protein itself, as well as the V and C non-structural proteins [20, 30]. The V protein is produced from edited P mRNAs and is a key virulence factor, playing a central role in antagonizing the host innate immune response by targeting STAT proteins and inhibiting interferon (IFN) signaling [26, 31]. The C protein, produced from an alternative translational start site in the P mRNA, is also implicated in immune evasion, notably by suppressing IFN-β induction through interactions with MAVS and RIG-I signaling molecules [20, 29]. The N protein, the most abundant viral protein, is a multifunctional scaffold that not only protects the genome but also interacts with a wide array of host proteins to subvert cellular defenses and promote viral replication. These interactions include binding to protein kinase R-activating protein (PACT) to induce stress granule formation [11], interacting with MyD88 and NLRP3 to potentiate inflammatory responses [13], and suppressing type I IFN production by interacting with IRF3 and blocking its activation [28, 31].

The Four Genetic Lineages of PPRV: Distribution and Dynamics

Phylogenetic analyses of partial nucleoprotein (N) and fusion (F) gene sequences, and increasingly whole-genome data, have consistently classified PPRV into four distinct genetic lineages (I, II, III, and IV) [5, 6, 14, 21]. These lineages are defined by robust nucleotide sequence divergence, generally exceeding 5-10% across the N gene, and they display strong, though not absolute, geographic associations that reflect historical virus spread and contemporary epidemiological dynamics.

Lineage I is considered the historically predominant lineage in West Africa. However, contemporary surveillance has shown that it is no longer the dominant circulating strain. A study in Mali and Senegal identified the persistence of Lineage I in Mali as late as 2014, suggesting that while it may have been largely supplanted, it has not been completely extinguished [22]. This remnant presence highlights the potential for residual endemic foci of older lineages even in the face of incursion by newer ones. Lineage II is also predominantly found in West Africa, particularly across a belt spanning from Senegal to Nigeria. For decades, Lineages I and II defined the PPRV landscape of West Africa [5, 21]. However, the epidemiological situation has been dramatically altered by the incursion of Lineage IV. Lineage III has a distinct geographic distribution, being primarily associated with East Africa. It has been identified as the principal lineage circulating in countries such as Tanzania, Kenya, Uganda, and the Democratic Republic of Congo, as well as historically in parts of the Arabian Peninsula [24, 33, 36]. For example, isolates from Tanzania and Burundi have consistently been characterized as Lineage III, with genomes showing close relationships with viruses from Kenya and Uganda [24, 36].

Lineage IV is the most geographically widespread and genetically diverse of the four lineages. Originally identified in Asia, it has demonstrated a remarkable capacity for transboundary spread, emerging as the dominant lineage across Asia, the Middle East, and, crucially, most of Africa [3, 12, 21]. The global spread of Lineage IV has been one of the most significant events in PPRV epidemiology in the 21st century. Molecular epidemiological data suggests that Lineage IV spread from Asia into Africa, with incursions documented across the continent. For instance, in West Africa, studies have demonstrated that Lineage IV is actively replacing the historically endemic Lineage II in countries like Burkina Faso, Côte d’Ivoire, Ghana, Guinea, and Nigeria [6, 9, 19]. A longitudinal study in Burkina Faso clearly indicated a dynamic shift, with Lineage IV viruses now detected in regions where they were previously absent, suggesting a competitive advantage or introduction through livestock movement [6]. In East and Northeast Africa, Lineage IV has also become highly prevalent, with recent isolates from Ethiopia, Sudan, and Egypt all belonging to this lineage, co-circulating with or displacing Lineage III in some regions [3, 27, 39, 42]. Even in Europe, a dramatic illustration of the lineage’s reach occurred in 2024, when outbreaks in Greece, Romania, and Bulgaria were all traced to a common origin within Lineage IV, with genomic analyses pointing towards an introduction from Northern Africa [2]. This event underscores that PPRV is not a static threat but a dynamic pathogen capable of jumping continents and causing severe outbreaks in previously free regions.

Genomic Diversity and Evolutionary Dynamics

The genomic diversity of PPRV is not uniformly distributed across the genome or across lineages. Whole-genome sequencing has provided critical insights into the evolutionary forces shaping this diversity. The PPRV genome evolves at a rate typical of RNA viruses, with the time to the most recent common ancestor (TMRCA) for modern Lineage II and IV strains estimated to be in the 1960s–1980s [5]. This period appears to have been a crucial phase for global diversification, possibly linked to changes in livestock trade, agricultural practices, or the cessation of rinderpest vaccination campaigns, which may have allowed PPRV to fill a vacated ecological niche [5, 21].

Selection pressures vary markedly between lineages. Comparative evolutionary analyses of Lineage II and IV genomes reveal that they operate under different selective constraints [5]. Codon usage patterns also differ, reflecting different evolutionary pathways and host adaptation pressures [16]. For instance, Lineage IV viruses have been found to have higher rates of non-synonymous substitutions in certain genes, such as the H protein, which is under strong positive selection for immune escape and host receptor adaptation [40]. This adaptability is likely a key factor in its global dominance. Detailed sequence analysis within Lineage IV has further revealed distinct sub-clusters. Viruses circulating in West and Central Africa form a sister clade to other Lineage IV sequences, suggesting an early introduction and subsequent independent evolution in West Africa [5]. In contrast, isolates from Asia and the Middle East form a monophyletic group that has spread widely.

Specific mutations with potential functional significance have been identified. For example, in a study of an Indian outbreak, four unique mutations were found in the N protein, including one located in the RNA-binding region, which could influence genome encapsidation and transcription [41]. In Bangladesh, comparative analysis of F and N gene sequences revealed new amino acid substitutions, including a mutation in the F protein that could potentially impact fusion activity [23]. The analysis of the Turkey/Central_Anatolia/2018 Lineage IV isolate showed its close relationship, but not identical identity, to a strain from 2000, indicating continuous drift within the endemic population [38]. The recent European Lineage IV isolates showed multiple nucleotide and amino acid differences from other global Lineage IV sequences, raising questions about potential functional changes in viral proteins following introduction into a new environment [2]. Furthermore, analysis of wild ungulate isolates from Mongolia demonstrated that the virus circulating in wildlife was closely related to livestock strains, but carried specific positively selected sites that may have facilitated its emergence in novel host species like the critically endangered saiga antelope [18].

Implications for Eradication and Surveillance

The genetic diversity and lineage dynamics of PPRV present a major challenge for the global PPR eradication program set forth by the Food and Agriculture Organization (FAO) and the World Organisation for Animal Health (WOAH). The extensive genetic and antigenic variation does not, however, preclude the use of the current live-attenuated vaccines (e.g., PPRV/Nigeria/75/1 and PPRV/Sungri/96), which have been shown to provide complete heterologous protection against challenge with virulent viruses from all four lineages [35]. This is a critical finding, as it means a single vaccine can be used globally. However, the replacement of endemic lineages by Lineage IV has significant implications for molecular diagnostics and surveillance. Diagnostic assays, such as RAA-CRISPR Cas12a [8] and RT-LAMP [32], must be validated against all circulating lineages to ensure they can detect the full spectrum of field viruses. The high genetic heterogeneity within Lineage IV, as seen in Nigeria [19] and Burkina Faso [6], underscores the need for robust and broadly reactive detection methods.

The role of wildlife as reservoirs and potential incubators of novel genetic diversity is a growing concern. PPRV has been documented in a wide range of wild artiodactyls, including African buffalo, impala, and Mongolian saiga [15, 17, 18]. The ability of PPRV to cross species barriers and circulate in wildlife-livestock interfaces creates a complex epidemiological landscape where allopatric evolution can occur. The detection of positively selected sites unique to wildlife-origin genomes from Mongolia suggests that adaptation to non-captive wild hosts may facilitate emergence of new viral strains with altered host tropism or pathogenicity [18]. This highlights the critical need for integrated genomic surveillance that spans both domestic and wild ungulate populations. The use of portable sequencing technologies, such as the Oxford Nanopore MinION, which has been successfully deployed to generate full-length genomes from field samples in Tanzania and Mongolia, is essential to overcome logistical barriers and provide the real-time, high-resolution data required to track PPRV evolution and inform the logistics of the 2030 eradication target [18, 24, 34].

Molecular Pathogenesis and Viral Protein Function

Peste des petits ruminants virus (PPRV), a member of the genus Morbillivirus within the family Paramyxoviridae, is the etiological agent of one of the most devastating viral diseases affecting small ruminants globally. The virus, classified under the species Small ruminant morbillivirus, encodes a single-stranded, negative-sense RNA genome of approximately 15,954 nucleotides that comprises six structural proteins, nucleocapsid (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin (H), and large polymerase (L), and two non-structural proteins, C and V, generated from the P gene via an alternative open reading frame and RNA editing, respectively [1, 25, 52]. The molecular pathogenesis of PPRV is a highly orchestrated process that involves the coordinated function of these viral proteins to subvert host innate immunity, manipulate cellular stress responses, hijack autophagic machinery, and promote inflammatory signaling cascades. A comprehensive understanding of these molecular mechanisms is critical for the ongoing Global Strategy for the Control and Eradication of PPR, a joint initiative of the Food and Agriculture Organization (FAO) and the World Organisation for Animal Health (WOAH), which aims to eradicate this pathogen by 2030 [15, 45, 59].

Viral Entry and Receptor Engagement

The initial steps of PPRV infection are governed by the H glycoprotein, which mediates attachment to host cellular receptors. PPRV H utilizes signaling lymphocyte activation molecule (SLAM, also known as CD150) expressed on cells of the immune system as its primary receptor, facilitating early infection of lymphoid tissues and the subsequent profound immunosuppression characteristic of morbillivirus infections [37]. A critical advance in understanding PPRV pathogenesis was the identification of nectin-4 (also known as poliovirus receptor-like 4, PVRL4) as the epithelial receptor responsible for viral entry and dissemination at the later stages of infection [56]. This dual-receptor usage is a hallmark of morbillivirus pathogenesis: initial infection via SLAM on alveolar macrophages, dendritic cells, and lymphocytes allows viral amplification and systemic spread, while subsequent engagement of nectin-4 on basolateral surfaces of epithelial cells permits viral shedding from the respiratory and gastrointestinal tracts [53, 56]. The interaction of H with nectin-4 is a critical checkpoint for epithelial invasion, and experimental studies using recombinant H protein have confirmed that receptor engagement alone can activate downstream signaling cascades, including the induction of autophagy via the AKT-MTOR pathway [29]. The H protein also serves as a potent immunogen, and monoclonal antibodies directed against its ectodomain form the basis of competitive ELISA assays for detecting neutralizing antibodies, which correlate with protective immunity [43]. Furthermore, the H protein activates Toll-like receptor 2 (TLR2) signaling, leading to the production of pro-inflammatory cytokines such as IL-8 and IL-12, thereby bridging innate and adaptive immune responses [51].

Fusion and Membrane Penetration

Following receptor binding, the F protein mediates the fusion of the viral envelope with the host cell plasma membrane at neutral pH, a process that requires prior proteolytic cleavage of the precursor F0 into disulfide-linked F1 and F2 subunits by host furin-like proteases [23, 52]. The F protein is a class I viral fusion protein that undergoes dramatic conformational rearrangements to drive membrane coalescence. The interaction between H and F is essential for fusion competence, and the F protein itself has emerged as a critical determinant of virulence. Comparative pathogenesis studies have demonstrated that PPRV strains of differing virulence, such as the highly virulent Morocco 2008 (MA08) strain versus the mild Côte d’Ivoire 1989 (IC89) strain, exhibit distinct fusion activities that correlate with disease severity in goats [47]. Importantly, the F protein is a target of host antiviral defenses. The host serine protease plasminogen activator urokinase (PLAU) has been identified as an F-interacting partner that inhibits PPRV replication. Mechanistically, PLAU binds to the F protein and prevents F-mediated degradation of virus-induced signaling adapter (VISA, also known as MAVS), thereby preserving the integrity of the RIG-I-like receptor (RLR) signaling axis and promoting type I interferon (IFN) production [7]. This discovery highlights a novel host defense strategy that directly antagonizes the fusogenic and immunosuppressive activities of the F protein.

The Nucleocapsid Protein: A Multifunctional Hub of Pathogenesis

The N protein is the most abundant viral protein and serves as the structural scaffold for encapsidation of the viral genomic RNA, protecting it from cellular nucleases and providing the template for transcription and replication by the viral RNA-dependent RNA polymerase (RdRp) complex [11, 55]. However, beyond its structural role, the N protein has emerged as a central orchestrator of PPRV pathogenesis, engaging in a remarkable array of host protein interactions that modulate innate immunity, stress responses, autophagy, and inflammation.

Immune Evasion and Interferon Antagonism. The N protein is a potent suppressor of the host type I IFN response. It inhibits IFN-β production by targeting interferon regulatory factor 3 (IRF3). Specifically, N interacts directly with IRF3, blocking the interaction between TBK1 and IRF3, which prevents IRF3 phosphorylation, dimerization, and nuclear translocation [28]. This mechanism is shared with the P protein, which also targets IRF3 via its N-terminal 1-102 region, further underscoring the redundancy in viral antagonism of the RLR pathway [30]. Additionally, both the N and P proteins inhibit JAK-STAT signaling downstream of the IFN receptor, N blocks STAT1 nuclear translocation without preventing its phosphorylation, while P interacts directly with STAT1 to inhibit its activation [31, 57]. This multi-layered suppression of IFN signaling is a key virulence strategy that facilitates unchecked viral replication and explains the profound immunosuppression observed in PPRV-infected animals.

Subversion of Cellular Stress and Autophagy Pathways. The N protein is a master regulator of cellular stress responses. A landmark proteomic study of the N interactome revealed that N binds protein kinase R (PKR)-activating protein (PACT), thereby disrupting the inhibitory interaction between PACT and TAR RNA-binding protein (TRBP). This liberates PACT to activate PKR, leading to phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) and the assembly of stress granules (SGs) [11]. While SG formation is generally considered an antiviral response, PPRV N hijacks this process to sequester cellular mRNAs away from the translation machinery, thereby favoring viral mRNA translation and promoting viral replication [11]. The N protein also potently induces autophagy through multiple mechanisms. It interacts with the core components of the class III phosphatidylinositol-3-kinase (PI3K) complex-I, specifically VPS34, VPS15, BECN1, and ATG14L, leading to the formation of double-membrane autophagosomes [49]. Furthermore, N induces endoplasmic reticulum (ER) stress and activates the PERK/eIF2α branch of the unfolded protein response (UPR), which in turn triggers autophagy that supports viral replication [46]. The virus also exploits the STING-dependent autophagy pathway: PPRV infection upregulates STING expression via the innate sensor MDA5, which subsequently activates the ATF6 branch of the UPR to induce protective autophagy that enhances viral replication [48]. This interconnection between innate sensing and autophagy is a unique feature of PPRV pathogenesis.

Inflammatory Signaling and Inflammasome Activation. The N protein functions as a critical pro-inflammatory factor. It directly binds to the adaptor protein MyD88, potentiating the assembly of the MyD88 signaling complex and activating the NF-κB pathway. Simultaneously, N interacts with NLRP3, facilitating the formation of an N-NLRP3-ASC ring-like structure that promotes NLRP3 inflammasome assembly, caspase-1 cleavage, and maturation of interleukin-1β (IL-1β) [13]. This N-mediated inflammasome activation is responsible for the robust inflammatory response and fever observed during acute PPRV infection. The interplay between N-induced autophagy and inflammasome activation represents a delicate balance: autophagy typically limits inflammasome activation, but PPRV appears to have evolved mechanisms to synchronize both processes to maximize viral fitness.

Phosphoprotein and the Polymerase Complex

The P protein is an essential cofactor for the viral RdRp, functioning as a tether to recruit the L protein to the N-encapsidated RNA template. Beyond its role in transcription and replication, P is a multifaceted antagonist of host immunity. As noted, it independently suppresses IFN-β production by interacting with IRF3 and blocking TBK1 recruitment, a function mapped to its N-terminal domain [30]. The P protein also interacts with IRF5 and IRF8, though the functional consequences of these interactions remain to be fully elucidated [30]. The P, V, and C proteins are all expressed from the bicistronic P gene, with V and C generated through RNA editing and alternative translation initiation, respectively. The V protein is a well-characterized IFN antagonist that targets STAT1 and STAT2, preventing their nuclear translocation and thereby blocking IFN-stimulated gene (ISG) expression [26, 31]. The C protein, a small non-structural protein, inhibits IFN-β induction by potentially interacting with MAVS and RIG-I, and additionally suppresses JAK-STAT signaling by interfering with STAT1 phosphorylation [20]. The C protein also contributes to autophagy induction through the IRGM-HSPA1A-dependent pathway, working in concert with the N protein to sustain the autophagic flux required for efficient viral replication [29].

Matrix Protein and Viral Assembly

The M protein is a peripheral membrane protein that orchestrates viral assembly and budding by bridging the ribonucleocapsid complex with the cytoplasmic tails of the H and F glycoproteins at the plasma membrane. Although less studied in terms of direct immune modulation, the M protein is immunogenic and contains predicted B-cell and T-cell epitopes that contribute to the host adaptive immune response [23, 57]. Comparative analyses of codon usage and selection pressures across PPRV lineages have revealed that the M gene, like other structural genes, is subject to lineage-specific evolutionary constraints that may influence viral fitness and transmissibility [5, 16].

Epigenetic Regulation and Non-Coding RNAs

Recent discoveries have unveiled that PPRV pathogenesis extends to the epigenetic landscape of the host cell. The viral genome and transcripts are subject to N6-methyladenosine (m6A) modification, and the modulation of host m6A machinery profoundly affects viral replication. Knockdown of the m6A writer METTL3 or the eraser FTO demonstrated that either increasing or decreasing m6A levels negatively impacts PPRV replication, indicating that an optimal m6A microenvironment is required for viral fitness. Mechanistically, m6A-modified viral transcripts exhibit enhanced stability and translation efficiency compared to unmodified mRNAs [44]. Furthermore, PPRV infection induces the expression of host microRNAs, such as novel miR-3, which is upregulated by the V protein through NF-κB and p38 pathways. miR-3 targets interleukin-1 receptor-associated kinase 1 (IRAK1), a crucial signaling intermediate for type I IFN production, thereby establishing a negative feedback loop that suppresses IFN-α expression and facilitates viral escape from innate immunity [26]. The virus also dysregulates long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in infected B lymphocyte cells, creating a complex competing endogenous RNA (ceRNA) network that may modulate host gene expression to favor viral replication [50].

Viral Protein Degradation and Host Restriction Factors

The host cell deploys intrinsic antiviral mechanisms to limit PPRV replication, including the ubiquitin-proteasome system. The intermediate filament protein vimentin interacts with the N protein and, in a striking example of host restriction, recruits the E3 ubiquitin ligase NEDD4L to catalyze K48-linked polyubiquitination of N, targeting it for proteasomal degradation. Overexpression of vimentin suppresses PPRV replication, while its knockdown enhances viral growth [4]. Similarly, the autophagy-related protein ATG13 exerts antiviral activity against PPRV by stimulating interferon expression and activating the JAK-STAT cascade, leading to ISG induction [58]. These findings highlight the dynamic tug-of-war between viral persistence strategies and host restriction factors.

Tissue Tropism and Comparative Pathogenesis

The interplay of these viral proteins dictates the tissue tropism and clinical outcome of PPRV infection. In susceptible goats, the virus initially infects lymphoid tissues of the respiratory tract, causing massive lymphocytolysis and immunosuppression, followed by viremia and spread to epithelial surfaces [53, 54]. In contrast, cattle and camelids are considered dead-end hosts; they seroconvert but do not develop clinical signs or shed infectious virus, and transmission to contact animals does not occur [56, 60]. However, subclinical infection in atypical hosts, including wild ungulates such as the critically endangered Mongolian saiga antelope, poses significant challenges for eradication efforts, as these animals may serve as sentinels or spillover hosts that maintain viral circulation [15, 18]. The comparative pathogenesis of lineage IV versus lineage II strains reveals differences in selection pressures acting on viral genes, which may influence cross-species transmission potential and virulence [5, 6]. The ongoing replacement of lineage II by lineage IV in West Africa underscores the dynamic evolutionary landscape of PPRV and the need for continued genomic surveillance [6, 9].

Global and European Epidemiology of PPRV Outbreaks

Global Burden and Historical Emergence

Peste des petits ruminants virus (PPRV) represents one of the most economically devastating pathogens affecting small ruminant production systems across Africa, Asia, and the Middle East. The virus, a member of the genus Morbillivirus within the family Paramyxoviridae, causes an acute, highly contagious disease characterized by fever, oculonasal discharges, necrotic stomatitis, gastroenteritis, and pneumonia, with mortality rates approaching 100% in naive populations [1, 10, 54]. The global significance of PPR is underscored by the joint Food and Agriculture Organization of the United Nations (FAO) and World Organisation for Animal Health (WOAH) Global Strategy for the Control and Eradication of PPR (PPR GCES), which set an ambitious target of global eradication by 2030 [45, 59]. Achieving this goal requires a granular understanding of the virus's epidemiological dynamics across diverse ecological and production landscapes.

Phylogenetically, PPRV is classified into four distinct lineages (I, II, III, and IV), each with a unique geographic footprint and evolutionary history. Lineage IV, historically considered the "Asian" lineage, has demonstrated a remarkable capacity for transboundary spread and is now the predominant lineage globally, having supplanted endemic lineages in many regions [5, 21]. The time to the most recent common ancestor (TMRCA) for modern lineages suggests that the divergence of lineage II and lineage IV strains occurred between the 1960s and 1980s, a period marked by significant diversification and global dissemination of PPRV [5]. Importantly, genomic analyses have challenged the traditional view of an Asian origin for lineage IV, with evidence indicating that this lineage also has African roots, with West and Central African strains forming a sister clade to all other lineage IV sequences [5, 21]. This finding implies that the current global dominance of lineage IV may represent a re-emergence or expansion of an African-origin strain rather than a purely Asian incursion.

African Epidemiology: Lineage Dynamics and Endemicity

Africa remains the continent with the highest PPRV genetic diversity, where all four lineages have historically circulated [5, 19]. However, the epidemiological landscape is undergoing a profound transformation driven by the progressive westward expansion of lineage IV. In West Africa, lineage II has been the dominant endemic lineage for decades, but mounting evidence indicates that lineage IV is now actively replacing it [6, 9]. Surveillance in Burkina Faso between 2021 and 2022 identified only lineage IV in three studied regions, with genetic heterogeneity among the sequences, suggesting multiple introductions or sustained circulation [6]. Similarly, studies in Côte d’Ivoire, Ghana, Guinea, and Burkina Faso have demonstrated the co-circulation of lineages II and IV, with this being the first report of lineage IV in Ghana [9]. In Mali, lineage IV was detected in the southeastern region in 2017, representing the furthest westward penetration of this lineage recorded at that time [22]. The persistence of lineage I, once thought to be extinct, was also documented in Mali as recently as 2014, indicating that relic lineages may still circulate at low levels in refugia [22].

The situation in Nigeria, the most populous country in West Africa, is particularly instructive. Analysis of PPRV strains collected between 2017 and 2020 revealed that 90 out of 91 sequenced samples belonged to lineage IV, with only a single lineage II isolate remaining [19]. Phylogenetic analysis identified at least four distinct lineage IV sub-clusters circulating across multiple regions, highlighting extensive endemic transmission and cross-border movement with neighboring countries. This lineage replacement is not merely a genetic curiosity; it has practical implications for vaccine efficacy and diagnostic surveillance, as different lineages may exhibit subtle differences in antigenicity and pathogenesis.

In East Africa, the epidemiological picture is more complex, with both lineage III and lineage IV circulating. Tanzania, where PPR was first confirmed in 2008, harbors lineage III viruses that are closely related to isolates from Kenya and Uganda [24, 33]. Complete genome sequencing of Tanzanian field isolates from 2016 and 2018 using Oxford Nanopore technology confirmed a high nucleotide identity (96.19–99.24%) with other East African lineage III strains, indicating a common regional origin [24]. However, in Ethiopia, a country with a long history of PPR dating back to 1977, lineage IV has become dominant. Analysis of samples collected between 2010 and 2017 showed that all 14 positive samples belonged to sub-clade II of clade I of lineage IV, with no lineage III viruses detected [42]. This suggests that lineage IV is progressively displacing lineage III in the Horn of Africa, mirroring the trend observed in West Africa.

Seroprevalence studies provide a sobering measure of the disease's endemicity. In Sudan, a c-ELISA survey of 368 sera from unvaccinated sheep and goats in Central and Western Sudan revealed an overall seroprevalence of 88.9%, with 100% seropositivity in South Kordofan [61]. In the Ngorongoro District of northern Tanzania, household-level seroprevalence in pastoralist flocks is high, and the force of infection (FOI) shows significant spatial variation, with seasonal grazing camps and animal introductions identified as major risk factors [66]. In the Greater Serengeti ecosystem, serological evidence of PPRV infection has been documented in multiple wild artiodactyl species, including African buffalo, wildebeest, topi, Grant’s gazelle, and impala, with weighted seroprevalence estimates of 12.0% in buffalo and 1.1% in Grant’s gazelle [17]. These findings underscore the role of the wildlife-livestock interface in PPRV maintenance and the potential for spillover events, a critical knowledge gap for eradication efforts [15].

Asian and Middle Eastern Epidemiology: A Continuum of Lineage IV Transmission

Across Asia and the Middle East, lineage IV is the exclusive lineage circulating in domestic and wild small ruminants. The virus is endemic across a vast belt stretching from Turkey and the Arabian Peninsula through Iran, Pakistan, India, Bangladesh, China, and into Central Asia. In Turkey, genomic surveillance has revealed that strains circulating as recently as 2018 share 97.63% nucleotide identity with a Turkish isolate from 2000, indicating long-term endemic circulation of a relatively stable viral population [38]. In Bangladesh, analysis of complete genomes from isolates spanning 2008 to 2020 confirmed that all belong to lineage IV and are closely related to Chinese and Indian strains from 2007-2014 [23]. The mean TMRCA for Bangladeshi isolates was estimated at the year 2000, suggesting that the virus has been circulating in the country for at least two decades before the study period.

The situation in China is particularly dynamic, with lineage IV viruses continuously causing sporadic outbreaks despite vaccination efforts. The strain ChinaSX2020, isolated from an outbreak in 2020, showed 99.55% nucleotide identity with Chinese isolates from 2013-2014, indicating that similar viral variants are persistently circulating rather than being replaced by novel introductions [25]. Ecological niche modeling has identified the Pan-Pamir Plateau region, encompassing parts of China, Kazakhstan, Tajikistan, Pakistan, and India, as a high-risk corridor for transboundary transmission [62]. The model predicted five least-cost paths for PPRV spread, confirming that wild and domestic animal movements across these borders pose a genuine risk for disease introduction.

The expanding host range of PPRV in Asia is a major epidemiological concern. In Mongolia, a devastating outbreak in 2016-2017 caused mass mortality among critically endangered Mongolian saiga antelope, as well as infections in Siberian ibex and goitered gazelle [18]. Phylogenomic analysis demonstrated that PPRV genomes from Mongolian wildlife and livestock formed a monophyletic cluster within lineage IV, with the most likely origin being Xinjiang Province, China. Crucially, molecular clock estimates indicated that the virus was circulating undetected in Mongolia for at least six months before the first reported outbreak in August 2016, and wildlife were likely infected before livestock vaccination began in October 2016 [18]. In China, PPRV has been documented infecting Procapra przewalskii (Przewalski's gazelle), a wild ruminant species, with the ChinaGS2018 strain showing high identity to livestock isolates from Xinjiang [40]. These findings highlight the potential for wildlife to serve as sentinels or reservoirs, complicating eradication efforts.

In the Middle East, lineage IV viruses are also dominant. In the United Arab Emirates (UAE), four outbreaks in goats and Dama gazelle in 2021 were confirmed as lineage IV, clustering closely with strains from Pakistan, Tajikistan, and Iran [12]. This represents the first description of PPRV in domestic small ruminants in the UAE, previously limited to wildlife reports. In Saudi Arabia, a nationwide prevalence study between 2014 and 2016 found that 24.1% of tested specimens were PPRV-positive, and sequence analysis of multiple genes confirmed lineage IV circulation [67]. The epidemiological significance of atypical hosts in this region is notable: dromedary camels infected with PPRV can transmit the virus to sheep and goats even when they themselves develop only mild clinical signs [63], and serological surveys in Nigeria have now provided field evidence of frequent PPRV exposure in pigs, with an apparent seroprevalence of 4.24% [64].

European Epidemiology: The 2024 Emergence and Its Implications

The most significant event in the recent global epidemiology of PPRV is its unprecedented emergence in Europe in 2024. Outbreaks were reported in Greece and Romania in July 2024, followed by central Bulgaria in November 2024 [2]. Prior to these events, Europe had remained free of PPR, with only sporadic, rapidly contained incursions. The 2024 outbreaks represent the largest European epizootic to date and have profound implications for the global eradication timeline.

Genomic analysis of PPRV isolates from the first affected farms in each of the three European countries has provided critical insights into the origins of this incursion [2]. Whole-genome sequencing and phylogenetic analyses confirmed that the viruses responsible for the outbreaks in Greece, Romania, and Bulgaria share a common origin, strongly suggesting a single introduction event rather than multiple independent spillovers. The data point towards an introduction from Northern Africa, although the authors caution that additional sequencing from globally circulating strains is needed to definitively confirm this hypothesis [2]. Importantly, the European genomes exhibit multiple nucleotide and amino acid differences compared to other available sequences, with potential functional implications for viral protein activity that warrant further investigation.

The pathway of PPRV transmission between and within the three European countries remains unresolved. The temporal sequence, Greece and Romania in July, Bulgaria in November, raises several possibilities. Direct animal movements between these nations may have facilitated spread, although regulatory restrictions were implemented rapidly. Wild ungulate populations, such as wild boar and deer, could theoretically act as mechanical vectors or transient hosts, though their role in morbillivirus transmission is poorly understood. Alternatively, the virus may have been introduced via contaminated fomites, feed, or personnel, with subsequent cryptic circulation before detection. The fact that the initial outbreaks in Greece and Romania were reported nearly simultaneously suggests a common source, perhaps at a livestock market, assembly point, or through shared trade networks.

The European incursion underscores the fragility of the continent's PPRV-free status and highlights several critical vulnerabilities. First, the proximity of Europe to enzootic regions in North Africa and the Middle East creates a constant risk of reintroduction, particularly through illegal animal movements or contaminated animal products. Ecological niche modeling published in 2020 had already identified southern Spain, France, Albania, Montenegro, Macedonia, Italy, Armenia, and Azerbaijan as highly suitable territories for PPRV [65], a prediction that has now been partially realized. Second, the large, naive small ruminant populations in Europe, combined with high-density livestock production systems, create conditions for rapid and explosive spread if containment measures are inadequate. Third, the limited experience of European veterinary services with PPRV diagnosis and control, given that the disease has been historically absent, may lead to delays in detection and response.

The European outbreaks also have significant implications for the global eradication program. The emergence of PPRV on a new continent demonstrates that the virus has not yet been adequately contained in its endemic strongholds, and that international coordination for surveillance, movement control, and vaccination must be strengthened. The genomic data from Europe will be invaluable for tracing future incursions and for understanding the evolutionary dynamics of lineage IV as it expands its geographic range. As of early 2025, the situation remains fluid, with ongoing epidemiological investigations to determine whether the virus has established local transmission cycles in European wildlife or livestock reservoirs. The potential for PPRV to become endemic in Europe, as it has in Africa and Asia, represents a worst-case scenario for the eradication campaign.

Host Range and Atypical Infections in Cattle and Wildlife

The canonical host range of Peste des Petits Ruminants Virus (PPRV) is defined by its devastation of domestic small ruminants, primarily goats and sheep, where mortality rates can approach 100% in naïve populations [1, 3, 10]. However, the ecological and epidemiological reality of PPRV is far more complex. Over the past two decades, a growing body of evidence has fundamentally challenged the notion that PPRV is solely a pathogen of caprines and ovines. The virus has demonstrated a remarkable and concerning capacity for cross-species transmission, spilling over into a diverse array of atypical hosts, including domestic cattle, water buffalo, camels, pigs, and a wide range of wild artiodactyls [72]. Understanding the dynamics of infection in these species, whether they act as true reservoirs, dead-end hosts, or “spillover” victims, is not merely an academic exercise; it is a critical prerequisite for the success of the Global PPR Eradication Programme (PPR GEP) spearheaded by the Food and Agriculture Organization (FAO) and the World Organisation for Animal Health (WOAH) [15, 45]. The implications for biodiversity conservation are equally profound, as outbreaks in endangered species, such as the Mongolian saiga antelope, highlight the acute threat PPRV poses to wildlife populations [18].

Domestic Atypical Hosts: Potential Reservoirs or Dead-Ends?

The role of large domestic ruminants in the epidemiology of PPRV has been a source of considerable scientific contention. Early reports were conflicting, with some studies suggesting cattle could act as silent carriers capable of transmitting the virus, while others concluded they were dead-end hosts [3, 60]. Recent, highly controlled experimental infections have substantially clarified this issue, although important nuances remain.

Cattle and Water Buffalo. Experimental inoculation of cattle with wild-type PPRV strains from all four genetic lineages (I-IV) consistently demonstrates that infection is subclinical. In a landmark study using the Ethiopia/Habru/2014 lineage IV strain, Aklilu et al. (2024) showed that while goats developed severe clinical signs and high viral loads, cattle exhibited only minimal signs, with seroconversion delayed until day 8 post-inoculation and viral RNA detection restricted to tissues, with only a single nasal swab testing positive at day 8 [3]. This pattern of infection, seroconversion without significant clinical disease, viremia, or robust shedding, has been replicated by multiple independent research groups. Schulz et al. (2019) demonstrated that cattle infected intranasally with the virulent Kurdistan/2011 strain developed no clinical signs, no viremia, and shed negligible PPRV RNA, failing entirely to transmit the virus to in-contact sentinel animals [56]. Similarly, Couacy-Hymann et al. (2019) infected cattle with wild-type isolates from lineages I, II, III, and IV, and although the animals seroconverted, with some showing high percentage inhibition in c-ELISA, they remained clinically healthy, and all nasal and oral swabs were negative for viral presence. Crucially, naïve goats co-housed with these infected cattle for 30 days did not seroconvert or show any signs of disease, providing strong evidence that horizontal transmission from cattle to small ruminants does not occur under these experimental conditions [60].

These convergent findings strongly support the classification of cattle as “dead-end” hosts. The pathogenesis appears to be fundamentally different from that in goats. While PPRV replicates in lymphoid organs of cattle, the virus distribution is generally lower and more restricted compared to small ruminants or suids [56]. This likely limits the seeding of epithelial tissues required for efficient shedding. The mechanism for this restriction may involve differences in the expression or accessibility of the primary PPRV receptors, signaling lymphocyte activation molecule (SLAM) on immune cells and nectin-4 on epithelial cells, or downstream blocks in the viral replication cycle [37, 72]. This is not to say cattle are epidemiologically irrelevant. They can serve as sentinel animals; their seroconversion acts as a reliable indicator of PPRV circulation in a given area, a principle that could be strategically integrated into surveillance programs [60].

However, a note of caution arises from serosurveillance data in Bangladesh, where Chowdhury et al. (2022) reported a seroprevalence of 42.36% in buffalo, compared to only 3.68% in cattle [69]. This remarkably high prevalence in buffalo raises the possibility of a differential host susceptibility. It is plausible that buffalo, which share a closer phylogenetic relationship with traditional small ruminant hosts than do cattle, might sustain a more permissive infection. Further experimental studies comparing the pathogenesis of PPRV in buffalo versus cattle are urgently needed to determine if the buffalo’s role is truly that of a dead-end host or if it could represent a more significant epidemiological risk.

Pigs and Suidae. The role of pigs in PPRV epidemiology is a more recent and concerning discovery. Early thinking suggested suids were refractory to infection. This paradigm was shattered by transmission trials using the virulent Kurdistan/2011 lineage IV strain, which confirmed that pigs and wild boar are susceptible. Infected pigs can shed the virus and transmit it to in-contact pigs, fulfilling the necessary criteria to act as a disease reservoir [56]. The first large-scale field evidence supporting this came from a study by Adedeji et al. (2025) in Nigeria, where serological surveillance of 495 pigs in an endemic area revealed an apparent seroprevalence of 4.24% [64]. While this prevalence is lower than in co-grazing small ruminants (25.68%), it provides definitive proof that PPRV infections in pigs are not rare events and occur under natural field conditions. The authors argue that in countries with large pig populations under extensive husbandry systems, where pigs are in frequent contact with infected small ruminants, pigs could theoretically act as a maintenance host, complicating eradication efforts. The precise role of pigs as a true reservoir that can perpetuate the virus independently of small ruminant populations remains to be definitively proven, but the evidence is mounting that they cannot be ignored in eradication strategies [64, 72].

Camelids. Similar to cattle, dromedary camels appear to be dead-end hosts. Experimental infection with PPRV results in mild to subclinical disease. In a transmission study by Saeed et al. (2022), infected camels developed only mild clinical signs, but importantly, they were capable of transmitting the infection to in-contact sheep and goats. The source of infection was likely the camels themselves, as naive sheep and goats housed with previously infected camels developed severe clinical PPR [63]. This demonstrates that even without showing overt disease, camels can excrete sufficient virus to cause infection in highly susceptible small ruminants, posing a risk at the livestock interface. However, a critical counterpoint comes from Schulz et al. (2019), who found that intranasally infected camels and alpacas did not transmit to in-contact animals [56]. This discrepancy highlights the importance of strain virulence, route of exposure, and shedding dynamics. Notably, a serosurvey at a slaughterhouse in Sudan found that 98% of pneumonic lung samples from apparently healthy camels contained PPRV antigen, confirming frequent subclinical exposure and viral persistence in pulmonary tissues [71]. The consensus is that camelids can be infected and shed virus, but their ability to act as long-term maintenance hosts remains unconfirmed, and they likely serve as spillover rather than maintenance populations [56].

Wildlife: A Threat to Biodiversity and a Challenge to Eradication

The expansion of PPRV into wildlife represents one of the most alarming developments in the disease’s recent history. The primary hosts are wild goats and sheep, but the virus has been documented in an astonishingly broad range of wild artiodactyls, including African buffalo, wildebeest, topi, impala, gazelles, kudu, warthog, and the critically endangered Mongolian saiga antelope [12, 17, 18, 40]. The implications are twofold: first, PPRV poses a direct threat to the conservation of vulnerable species; second, wildlife populations could potentially act as sustainable reservoirs, seeding new outbreaks into domestic livestock even after the virus is controlled in domestic animals.

The Wildlife-Livestock Interface. The classical model for PPRV in wildlife is “spillover” from infected domestic small ruminants. Evidence from the Greater Serengeti Ecosystem supports this. Jones et al. (2021) detected seroprevalence (19.7%) in multiple wild ungulates, but the spatial pattern and the absence of clinical disease in wildlife strongly suggested infection was driven by contact with infected livestock, not sustained wildlife-to-wildlife transmission [17]. A similar pattern was observed in the UAE, where lineage IV was identified in both domestic goats and Dama gazelles ( Nanger dama ) during the same outbreak period [12].

Evidence for Sustained Transmission and Adaptation. The incident that most dramatically underscored the threat to wildlife was the 2016-2017 outbreak in Mongolia that killed a significant proportion of the critically endangered Mongolian saiga antelope ( Saiga tatarica mongolica ). This event moved the discussion from spillover to potential maintenance. Sequencing of multiple full genomes from saiga, as well as from infected Siberian ibex and goitered gazelle, revealed a monophyletic group of viruses. Crucially, phylogeographic analysis indicated that the virus had been circulating undetected in Mongolia for at least six months before the first reported outbreak, and that wildlife were likely infected before livestock vaccination began [18]. This suggests that PPRV can establish itself in naive wildlife populations and be maintained by wildlife-to-wildlife transmission for a significant period, independent of a continuous livestock source. Similarly, the first report of PPRV infection in Przewalski’s gazelle ( Procapra przewalskii ) in western China, a species already under severe ecological pressure, raises the specter of PPRV becoming established in migratory wild populations and threatening other sympatric ungulates [40]. The presence of positively selected sites in the viral genomes from Mongolian wildlife raises the disturbing yet scientifically critical question of whether the virus is undergoing adaptive evolution to better replicate in these new hosts [18, 72].

Pathogenesis and Risk Factors in Wildlife. Susceptibility varies dramatically by species. In an outbreak investigation in the Abu Dhabi Emirate, Dama gazelle showed clinical and pathological signs indistinguishable from those seen in domestic goats, including severe respiratory distress and enteritis [12]. In contrast, species like waterbuck, lesser kudu, and impala appear to be seropositive but less clinically affected [17]. This differential susceptibility is hypothesized to be related to the conservation and structure of the viral receptors, particularly SLAM and nectin-4, across different artiodactyl clades [72].

Implications for the Global Eradication Programme. The FAO and WOAH-led PPR GEP aims for global eradication by 2030 [15, 45, 65]. The presence of a susceptible wildlife reservoir is a massive, perhaps existential, threat to this goal. A meeting convened in Rome in 2019 explicitly addressed this, concluding that “knowledge gaps limit the inclusion of wildlife in the FAO/OIE Global Strategy for the Control and Eradication of PPR” [15]. The fear is that if PPRV establishes an independent transmission cycle in a wildlife population, as it may have done in the Mongolian saiga, it creates an ineradicable source of the virus that can reinfect livestock at any time, analogous to the role of wildlife in the persistence of rabies or Ebola virus. The current strategy does not adequately address how to conduct surveillance, manage, or vaccinate wildlife populations at a scale necessary for eradication. The need for validated serological tools for use in these atypical species is critical, as a recent large-scale study showed that the performance of standard c-ELISA and VNT tests drops significantly when applied to sera from wild species, potentially leading to a gross underestimation of the true extent of wildlife infection [68]. The development of robust, cross-species diagnostics, such as nanobody-based assays or CRISPR-based methods, is a key research priority for ensuring that wildlife is not a hidden pathway to failure for the global PPR eradication campaign [8, 70].

Advanced Diagnostics: Competitive ELISA and Neutralizing Antibody Detection

The global initiative to eradicate peste des petits ruminants (PPR) by 2030, orchestrated by the Food and Agriculture Organization (FAO) and the World Organisation for Animal Health (WOAH), mandates a robust arsenal of diagnostic tools capable of detecting both viral antigen and host immune responses [1, 45]. Among these, serological assays are indispensable for post-vaccination monitoring, surveillance of disease circulation in both typical and atypical hosts, and for the eventual declaration of freedom from infection. Within this serological framework, the detection of neutralizing antibodies, which are the primary correlate of protective immunity against morbilliviruses, represents the gold standard for evaluating vaccine efficacy and population-level immunity [43, 74]. The competitive enzyme-linked immunosorbent assay (c-ELISA), particularly those designed to measure neutralizing antibody titers, has emerged as a critical technology, bridging the gap between the operational simplicity of classical ELISA and the functional relevance of the time-consuming and biohazard-dependent virus neutralization test (VNT). This section provides a deep, mechanistic analysis of these advanced diagnostic methodologies, their validation, and their pivotal role in the epidemiology and control of PPRV.

The central rationale for developing a c-ELISA targeting neutralizing antibodies lies in its ability to overcome the fundamental limitations of both the VNT and conventional indirect ELISAs. The VNT, while functionally measuring the capacity of sera to block viral entry, a direct correlate of protection, is labor-intensive, requires live virus (posing biocontainment challenges), takes several days to yield results, and depends on cell culture systems, which are often impractical for large-scale field surveillance in resource-limited settings [35, 43, 68]. Indirect ELISAs, while faster, can detect non-neutralizing antibodies that bind to irrelevant epitopes, leading to potential overestimation of protective immunity and cross-reactivity with other morbilliviruses. The c-ELISA elegantly addresses these issues by using a format where a labeled monoclonal antibody (mAb), directed against a specific functional epitope on a viral protein, competes with antibodies in the test serum for binding to the plate-coated antigen. The degree of competition is inversely proportional to the titer of antibodies in the serum that recognize the same or a spatially overlapping epitope. Crucially, when the mAb is selected to recognize a site critical for virus neutralization, the c-ELISA becomes a surrogate for the VNT, directly quantitating functionally relevant antibodies without the need for live virus.

A landmark advance in this domain is the work by Hu et al. (2025), who developed a c-ELISA utilizing the extracellular domain of the PPRV hemagglutinin (tH) protein as the coating antigen and a specific mAb against this tH protein [43]. The H protein is the primary attachment protein of PPRV, mediating viral entry by binding to the SLAM (signaling lymphocyte activation molecule) receptor on immune cells and, subsequently, nectin-4 on epithelial cells [29, 37]. Antibodies that block this interaction are potent neutralizers. In their study, the mAb used was selected for its ability to neutralize PPRV in vitro, ensuring that the c-ELISA measured only those antibodies that could compete for this neutralizing epitope. The assay demonstrated exceptional performance: a diagnostic specificity of 99.38% and a sensitivity of 100% when compared against a panel of known positive and negative sera. The most critical validation was the agreement rate of 96.65% between the c-ELISA and the standard VNT, confirming its function as a robust surrogate for the gold-standard neutralization assay [43]. This level of concordance is remarkable and suggests that the tH protein, refolded and presented in its native conformation, displays the key neutralizing epitopes effectively. This approach not only obviates the need for live PPRV in serological testing but also allows for rapid, high-throughput screening of large animal populations, which is essential for the PPR Global Eradication Programme.

Despite the power of this c-ELISA, the interpretation of serological data becomes profoundly more complex when moving from typical hosts (goats and sheep) to the expanding range of atypical hosts, including cattle, camels, pigs, and various wildlife species. The escalating recognition of PPRV infection in these hosts is a major epidemiological concern, as they may act as silent reservoirs or dead-end hosts with implications for viral maintenance and spillback [15, 63, 64, 69, 72]. A seminal comparative study by Tully et al. (2023) systematically evaluated the performance of five serological assays, including the VNT, two commercial ELISAs (the ID VET N-ELISA targeting the nucleocapsid protein and the AU-PANVAC H-ELISA), the luciferase immunoprecipitation system (LIPS), and a pseudotyped virus neutralization assay (PVNA), across a large panel of sera from both typical and atypical species [68]. The findings were starkly illuminating. While the agreement between VNT and the commercial ELISAs for detecting PPRV antibodies in goats and sheep was acceptable (75.0–88.0%), this concordance dropped precipitously to only 44.4–62.3% for sera from atypical species like cattle and camels, exhibiting significant inter-species variation [68]. This discrepancy arises from several biological and technical factors. Atypical hosts may produce a different repertoire of antibodies upon PPRV infection, potentially with lower affinity or against different epitopes, compared to the classic caprine/ovine response. Furthermore, the structure of immunoglobulins from diverse species can differ, affecting their binding to the anti-species conjugates used in indirect ELISAs. The c-ELISA, which uses a universal, labeled mAb rather than a species-specific conjugate, theoretically circumvents this problem. However, the Tully study revealed that even the c-ELISA format (the H-ELISA) showed reduced agreement with VNT in atypical hosts, likely because the antibody response in these species still competes less effectively for the specific mAb-binding site [68]. This highlights a critical diagnostic gap: current ELISAs, validated for typical hosts, may significantly underestimate or misclassify seropositivity in cattle, camels, and wildlife, leading to flawed epidemiological models. For instance, experimental infections in cattle have shown seroconversion with minimal clinical signs [3, 56, 60], and serological surveys have detected antibodies in buffalo (42.36% in Bangladesh) and pigs (4.24% in Nigeria) [64, 69], yet the true infection prevalence, especially exposure to neutralizing epitopes, remains uncertain due to these assay limitations.

To address the challenges in atypical species, innovative alternatives to the VNT have been developed that do not rely on live virus and can be adapted for high-throughput use. The pseudotyped virus neutralization assay (PVNA) represents a powerful tool. By constructing lentiviral or retroviral particles pseudotyped with the PPRV H and F proteins, these assays measure neutralizing antibodies against the viral entry machinery in a single round of infection, quantifiable by a reporter gene (e.g., luciferase) [68]. This PVNA negates the need for high-containment facilities and provides a standardized, highly sensitive readout. Similarly, the luciferase immunoprecipitation system (LIPS) offers a completely cell-free format. It uses recombinantly expressed, luciferase-tagged PPRV antigens (e.g., the N protein or H protein) which, when bound by antibodies in the test serum, are immunoprecipitated, and the luminescence signal directly correlates with antibody titer [68]. Tully et al. found that LIPS and PVNA showed strong correlation with VNT for typical species, but still varied for atypical species, suggesting that the fundamental differences in the host's humoral immune response to PPRV remain a hurdle regardless of the assay technology [68]. The LIPS assay, in particular, offers the ability to multiplex antigens (e.g., N and H) to simultaneously measure antibodies against non-structural and structural proteins, which is invaluable for DIVA (Differentiating Infected from Vaccinated Animals) strategies [45, 75].

The integration of these advanced serological tools with DIVA-capable vaccines is the cornerstone of the PPR eradication strategy. The current live-attenuated vaccines (e.g., PPRV/Nigeria/75/1 and PPRV/Sungri/96) induce antibodies against all viral proteins, making it impossible to distinguish a vaccinated animal from one that has been infected with wild-type virus using standard assays [35, 45, 59]. The development of marker vaccines, such as those based on poxvirus or Newcastle disease virus vectors expressing only the PPRV H protein (e.g., rNDV_HKur), allows for a serological DIVA approach [75]. In this paradigm, vaccinated animals will only seroconvert to the H protein, whereas naturally infected animals will have antibodies against multiple viral proteins, such as the N protein. This necessitates companion diagnostic tests that can differentially detect antibodies to N versus H [45, 75]. The c-ELISA for neutralizing antibodies, therefore, plays a dual and critical role: it confirms the induction of protective (neutralizing) H-specific immunity post-vaccination, while a separate N-protein-based ELISA identifies field exposure (since vaccinated animals lack anti-N antibodies). The high specificity and sensitivity of the mAb-based c-ELISA described by Hu et al. [43] makes it an ideal candidate for measuring the H-specific immune response in vaccinated populations, providing a direct readout of the functional quality of the vaccine response. This is far more informative than a simple total antibody ELISA.

Furthermore, the geographic expansion of PPRV, including the recent emergence of lineage IV in Europe (Greece, Romania, Bulgaria) and the ongoing replacement of lineage II by lineage IV in West Africa, underscores the need for serological assays that are robust against genetic drift [2, 6, 9]. The H protein, while subject to immune pressure, contains conserved neutralizing epitopes that are critical for receptor binding. The mAb used in the c-ELISA by Hu et al. [43] must target such a conserved region to be effective across all four lineages. The genomic diversity observed, with multiple amino acid substitutions in the H protein across different lineages (e.g., between lineage II and IV), could potentially impact the binding of a specific mAb [5, 16]. While the 96.65% agreement with the VNT suggests broad reactivity, continuous surveillance of the antigenic profile of field isolates is imperative. Should a novel lineage emerge that is not recognized by the mAb, the c-ELISA's sensitivity would plummet, leading to false-negative results and a dangerous underestimation of population immunity.

Finally, the development of novel reagents, such as nanobodies (single-domain antibodies from camelids), opens new avenues for c-ELISA design [70, 73]. Nanobodies are small, stable, and easily produced, and can be selected to target highly specific, cryptic epitopes on the H or F proteins. They offer the potential for creating ultra-sensitive, thermostable diagnostic tests suitable for field deployment in the remote environments where PPR is most prevalent [70]. The combination of these advanced reagents with portable readers could revolutionize point-of-care serological testing, allowing for real-time assessment of herd immunity during vaccination campaigns. In essence, the evolution of PPRV diagnostics from the classical VNT to sophisticated, high-throughput c-ELISAs and surrogate neutralization assays represents a critical enabling factor for the 2030 eradication goal. However, the biological complexity of the host-virus interface, particularly the species-specific antibody responses, demands that these tools be rigorously cross-validated in every target species to ensure that the serological picture they paint is accurate and actionable, rather than an artifact of species-specific immune biology.

Vaccination Strategies and Protective Immunity Evaluation

The global initiative to eradicate Peste des Petits Ruminants (PPR) by 2030, spearheaded by the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (WOAH), rests fundamentally on the deployment of effective vaccination strategies and a robust understanding of the protective immunity they engender [15, 45]. The cornerstone of current control efforts is the use of live-attenuated vaccines, which have demonstrated remarkable efficacy in reducing disease burden across endemic regions. However, the path to eradication necessitates a critical evaluation of these existing tools and the development of next-generation vaccines that address inherent limitations, particularly thermostability and the inability to differentiate infected from vaccinated animals (DIVA). This section provides an exhaustive analysis of the vaccination landscape for PPRV, dissecting the immunological mechanisms of protection, the comparative efficacy of existing vaccines, and the innovative strategies being pursued to achieve global eradication.

The Immunological Basis of Vaccine-Induced Protection

Understanding the correlates of protection against PPRV is paramount for the rational design and evaluation of vaccination strategies. The immune response to PPRV infection, whether natural or vaccine-induced, is multifaceted, involving both humoral and cellular arms. The hemagglutinin (H) and fusion (F) envelope glycoproteins are the primary targets of neutralizing antibodies, which are considered a critical component of protective immunity [43, 51]. The H protein mediates viral attachment to host cellular receptors, such as signaling lymphocyte activation molecule (SLAM) and nectin-4, while the F protein facilitates membrane fusion and viral entry [7, 37]. Consequently, antibodies directed against these proteins can effectively block viral entry and cell-to-cell spread. A competitive ELISA (c-ELISA) targeting the H protein has been developed, demonstrating a 96.65% agreement rate with the gold-standard virus neutralization test (VNT), validating its utility for serological monitoring of neutralizing antibody levels post-vaccination [43].

While the humoral response is crucial, the role of cell-mediated immunity (CMI) is equally significant, particularly for long-term protection and viral clearance. Live-attenuated PPRV vaccines are known to elicit robust T-cell responses. A seminal study comparing the two major vaccine strains, PPRV/Nigeria/75/1 (N75) and PPRV/Sungri/96 (S96), revealed distinct immunological profiles [35]. Although N75 induced a stronger antibody response, S96 elicited a more pronounced cellular immune response, characterized by higher levels of virus-specific CD4+ T-cell proliferation and interferon-gamma (IFN-γ) production [35]. This dichotomy suggests that the qualitative nature of the immune response can vary between vaccine strains, yet both conferred complete clinical protection against challenge with virulent viruses from all four genetic lineages [35]. This cross-lineage efficacy is a testament to the conserved nature of protective epitopes within the virus.

A critical question in vaccinology is which component of the adaptive immune response is indispensable for protection. Elegant depletion studies have provided compelling answers. The selective depletion of CD8+ T cells from vaccinated goats did not abrogate protection against wild-type PPRV challenge; vaccinated animals remained afebrile, aviremic, and exhibited minimal clinical signs [74]. This finding strongly suggests that virus-specific CD8+ cytotoxic T lymphocytes are not the primary mediators of vaccine-induced protection. Instead, the data implicate virus-specific antibodies and/or CD4+ T-helper cells as the main drivers of immunity [74]. This has profound implications for the development of new vaccines, as it suggests that a vaccine capable of eliciting a strong, sustained antibody response and functional CD4+ T-cell help may be sufficient for protection, even in the absence of a robust CD8+ T-cell response.

Comparative Efficacy of Live-Attenuated Vaccines

The live-attenuated PPRV vaccines, primarily derived from the N75 (lineage II) and S96 (lineage IV) strains, have been the workhorses of PPR control for decades [35, 45]. Their safety and efficacy are well-documented, providing lifelong immunity after a single dose. The study by Hodgson et al. (2018) provided the first systematic, head-to-head comparison of these two vaccines in a controlled experimental setting [35]. The results were unequivocal: both N75 and S96 provided sterile immunity against a heterologous challenge with virulent PPRV strains from lineages I, II, III, and IV [35]. This complete cross-protection is a critical attribute, given the co-circulation of multiple lineages in Africa and Asia [5, 6, 9, 19]. The study confirmed that despite differences in the magnitude and composition of the immune response, both vaccines are equally effective in preventing clinical disease and virus transmission.

However, the practical application of these vaccines is not without challenges. The most significant limitation is their thermolability. These vaccines are based on attenuated morbilliviruses, which are inherently sensitive to heat, requiring an uninterrupted cold chain from manufacture to administration [45]. In many PPR-endemic regions, particularly in tropical and sub-tropical areas with limited infrastructure, maintaining this cold chain is a formidable logistical and financial burden, leading to vaccine failure and reduced program effectiveness. This has spurred the development of thermostabilized formulations and novel vaccine platforms that can withstand higher ambient temperatures.

Next-Generation Vaccine Strategies and the DIVA Principle

The global eradication campaign has catalyzed the development of novel vaccine technologies designed to overcome the limitations of traditional live-attenuated vaccines. A primary objective is the creation of a vaccine that enables DIVA, a capability absent in current vaccines. DIVA is essential for serological surveillance, as it allows authorities to distinguish between naturally infected animals and those that have been vaccinated, a prerequisite for declaring freedom from infection in the final stages of eradication [45, 75].

Several innovative platforms are being explored. One promising approach involves the use of recombinant viral vectors. A proof-of-concept study demonstrated that a recombinant Newcastle disease virus (rNDV) expressing the PPRV H protein (rNDV_HKur) could protect goats against a virulent PPRV challenge [75]. This vectored vaccine offers several advantages: it is inherently more thermostable than conventional PPRV vaccines, and it is a DIVA vaccine, as vaccinated animals will only develop antibodies against the PPRV H protein and not against other viral proteins like the N protein [75]. This allows for the use of companion diagnostic tests, such as an N-protein-specific ELISA, to differentiate vaccinated from infected animals.

Other recombinant platforms include poxvirus-vectored vaccines (e.g., capripoxvirus, adenovirus) and reverse genetics-derived marker vaccines [45]. These approaches allow for the precise deletion of specific viral genes or epitopes, creating a negative marker. For instance, a vaccine lacking a specific non-structural protein would not induce antibodies to that protein, enabling serological differentiation. Subunit vaccines, virus-like particles (VLPs), and even edible plant-based vaccines are also under investigation, though many remain at the preclinical stage [45, 57]. Immunoinformatics approaches have identified multiple B-cell and T-cell epitopes from the H, M, F, and N proteins, providing a rational basis for the design of multiepitope peptide vaccines [57].

Evaluating Protective Immunity in Atypical Hosts

The success of the PPR eradication program hinges on understanding the role of atypical hosts in virus transmission and maintenance. PPRV has been shown to infect a wide range of wild and domestic artiodactyls, including cattle, camels, pigs, and various wildlife species [3, 15, 17, 56, 63, 64, 68, 69, 72]. The evaluation of protective immunity in these species is therefore critical, but presents unique challenges.

In cattle and camelids, experimental infections have consistently shown that these species act as dead-end hosts. They develop subclinical infections, with seroconversion occurring later and at lower titers compared to goats, and they do not transmit the virus to in-contact small ruminants [3, 56, 60]. A comparative pathogenesis study using the Ethiopia/Habru/2014 strain showed that while goats developed severe clinical signs and high viral loads, cattle exhibited only minimal signs and seroconverted by day 8 post-infection [3]. This suggests that while cattle can be infected, they are unlikely to play a significant role in PPRV epidemiology. However, serological surveys in cattle and buffalo in Bangladesh and Sudan have revealed substantial seroprevalence (3.68% to 42.36%), indicating frequent exposure [61, 69]. This highlights the importance of including these species in surveillance programs as sentinels for virus circulation.

The role of pigs is more controversial. While some studies suggest they are dead-end hosts, recent evidence from Nigeria has shown a 4.24% seroprevalence in free-roaming pigs, indicating that PPRV infections in swine are not rare events [64]. This raises the possibility that pigs, under certain husbandry conditions, could contribute to virus maintenance. Similarly, dromedary camels have been shown to transmit PPRV to in-contact sheep and goats, despite showing only mild clinical signs themselves [63]. These findings underscore the need for a nuanced approach to vaccination strategies, particularly in mixed-species production systems. The evaluation of vaccine efficacy in these atypical hosts is largely unexplored, but is a critical knowledge gap. The serological tools used to assess immunity in typical hosts (sheep and goats) may not perform as well in atypical species, as demonstrated by a study showing that the agreement between VNT and commercial ELISAs dropped from 75-88% in typical hosts to 44-62% in atypical hosts [68]. This necessitates the validation and development of species-specific serological assays to accurately evaluate vaccine-induced immunity across the diverse host range of PPRV.

Strategic Deployment and Monitoring for Global Eradication

The success of the PPR Global Eradication Programme (PPR GEP) is not solely dependent on vaccine efficacy but also on strategic deployment. Ecological niche modeling has identified high-risk areas for PPRV transmission, including regions in India, Mongolia, the Middle East, and large swathes of Africa [65]. Vaccination campaigns must be targeted to these high-risk areas, taking into account animal movement patterns, transboundary trade routes, and the livestock-wildlife interface [17, 18, 62]. The emergence of PPRV in Europe in 2024, with genomic evidence pointing to a common origin in Northern Africa, underscores the virus's potential for long-distance transboundary spread and the need for coordinated, regional vaccination strategies [2].

Monitoring the effectiveness of vaccination campaigns requires robust diagnostic tools. The development of rapid, field-deployable tests, such as the recombinase-aided amplification (RAA)-CRISPR Cas12a assay and RT-LAMP, allows for the quick identification of outbreaks and assessment of vaccine coverage [8, 32]. Furthermore, the use of environmental sampling at livestock markets has proven to be a non-invasive and effective method for detecting PPRV circulation, providing valuable data for surveillance in areas where active sampling is difficult [76]. The integration of these advanced diagnostic tools with DIVA-compatible vaccines will create a powerful framework for monitoring progress towards eradication, enabling the rapid identification of residual pockets of infection and the verification of freedom from disease. The ultimate goal is to transition from widespread vaccination to targeted, strategic vaccination, and finally to surveillance-only phases, mirroring the successful eradication of rinderpest. The path forward requires a sustained commitment to vaccine research, strategic deployment, and rigorous immunological evaluation across all susceptible host species.

Emerging Threats and Control Implications from Recent European Emergence

The incursion of Peste des Petits Ruminants Virus (PPRV) into the European continent represents a seminal event in the epizootiology of this pathogen and a profound challenge to the Global Strategy for the Control and Eradication of PPR (PPR GCES), championed jointly by the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (WOAH). For decades, Europe was considered free of PPR, with the disease confined to Africa, the Middle East, and Asia. The confirmation of outbreaks in Greece and Romania in July 2024, followed by central Bulgaria in November 2024, shattered this epidemiological complacency and signaled a dangerous paradigm shift [2]. This emergence is not an isolated, stochastic event but a manifestation of deep-seated vulnerabilities in global biosecurity, viral evolutionary dynamics, and the complexities of multi-host pathogen ecology. The threat is multi-faceted, encompassing the immediate epizootic risk to naïve European small ruminant populations, the potential for the virus to establish endemicity within a new geographic and ecological context, and the profound implications this carries for the feasibility of global eradication by the ambitious WOAH and FAO target of 2030.

The most critical insight from the European outbreak sequence comes from high-resolution genomic epidemiology. Source [2] provides definitive evidence that the PPRV strains responsible for the outbreaks in all three countries share a common origin, with genomic analyses strongly pointing towards an introduction from Northern Africa. This finding is of paramount importance. It demonstrates that despite decades of international effort and surveillance, the trans-Mediterranean barrier remains permeable to PPRV. The incursion pathway, likely involving the movement of infected animals or contaminated animal products across the Mediterranean, mirrors historical patterns of pathogen spread (e.g., bluetongue virus serotype 8) but introduces a novel and highly virulent morbillivirus into a completely immunologically naïve landscape. The fact that a single introduction event could lead to geographically disparate outbreaks across Greece, Romania, and Bulgaria within months highlights the efficiency of interconnected livestock trade networks and the movement of animals, even under official restrictions, in facilitating rapid transboundary spread [2]. This challenges the assumption that Europe is insulated by its geographical position and advanced veterinary infrastructure, revealing critical gaps in border surveillance and pre-import risk assessment. The threat is not merely the virus itself, but the network of legal and illegal animal movements that can propagate it across vast distances before clinical signs are even apparent.

Furthermore, the genomic analyses from [2] revealed multiple nucleotide and amino acid differences separating the European PPRV sequences from other known lineages and strains. While the functional impact of these changes on viral proteins remains to be fully characterized through reverse genetics and in vitro studies, the existence of such genetic divergence is deeply concerning. It raises the possibility that this particular PPRV variant possesses unique adaptive traits, perhaps enhancing its transmissibility, virulence, or ability to evade pre-existing immunity from different lineages. The virus is not static; it is evolving under selection pressure from its hosts and environment. The incursion of a genetically distinct lineage IV variant into an immunologically naïve host population in Europe could be a catalyst for rapid viral evolution, potentially leading to the emergence of strains with novel phenotypes. This underscores the urgent need for sustained genomic surveillance not just in the affected European countries, but across the entire putative source region in Northern Africa, to track the movement of this lineage and anticipate future incursions.

Beyond the immediate epizootic, the European emergence underscores a profound threat relating to host range expansion and the role of atypical hosts. The traditional view of PPRV as a disease primarily of sheep and goats is no longer tenable. The virus has demonstrated a remarkable capacity to infect a widening array of domestic and wild artiodactyls, a point exhaustively documented in sources [72] and [15]. Critically, the presence of these atypical hosts in Europe, including wildlife like the various deer species, European bison, and chamois, as well as domestic livestock like cattle, creates a complex ecological and epidemiological web. Source [3] demonstrated that while cattle exhibit minimal clinical signs after PPRV infection, they seroconvert and can shed viral RNA, raising the contentious question of their role as potential reservoirs or transmission bridges. Conversely, [56] and [60] argue that cattle and camelids are dead-end hosts, unable to transmit to in-contact animals. This dichotomy in the literature is a critical knowledge gap with direct implications for Europe. If cattle, which are ubiquitous across the European landscape, can act as sub-clinical shedders, they could serve as an undetected maintenance host, frustrating eradication efforts by allowing the virus to persist even after small ruminant flocks are cleansed. The experimental evidence from [63] demonstrating that dromedary camels can transmit PPRV to sheep and goats adds another layer of complexity, particularly given the presence of camelid populations in some European zoos and private holdings.

However, the most alarming atypical host threat for Europe is perhaps the pig. The recent serological evidence from Nigeria presented in source [64] provides the first compelling field evidence of frequent PPRV exposure in pigs, with an apparent seroprevalence of 4.24% across the country. While the study stops short of proving autonomous transmission within swine populations, the detection of antibodies in pigs raised under extensive husbandry systems with contact to small ruminants indicates that spillover from small ruminants is not a rare event. For Europe, where domestic pig populations are immense and wild boar are abundant and highly mobile, this is a catastrophic potential threat. Wild boar, in particular, could act as a bridge host, carrying the virus from infected small ruminant flocks into the wider environment and into contact with other susceptible wildlife. The combination of high population densities, synanthropic behavior, and lack of any pre-existing immunity makes the European wild boar population a perfect tinderbox for a PPRV outbreak. The control implications are staggering: current vaccination strategies are focused on sheep and goats; a wildlife reservoir in pigs or wild boar would be virtually impossible to eliminate with existing vaccines, requiring novel oral bait vaccines for suids and fundamentally changing the nature of the eradication campaign from a livestock-focused to a wildlife-livestock interface problem of immense complexity.

The threat to European wildlife extends beyond suids. Source [18] detailed a mass mortality event in critically endangered Mongolian saiga antelope due to PPRV lineage IV, demonstrating the catastrophic potential of this virus for naïve ungulate populations. Europe is home to numerous wild artiodactyl species, including the Alpine ibex, chamois, various deer species, and the European bison, that have never been exposed to PPRV. An incursion of this virus into a national park or mountainous region could trigger an epizootic of unprecedented conservation impact. The 2019 international meeting on PPR at the livestock-wildlife interface [15] identified this as a top priority knowledge gap, emphasizing that wildlife conservation and PPR eradication are not competing priorities but are intrinsically linked. The European emergence makes these recommendations urgent. Surveillance of wildlife for PPRV antibodies and viral RNA must be immediately integrated into national monitoring programs across the continent. The absence of disease in wildlife cannot be assumed; it must be confirmed through active, systematic sampling.

The control implications for Europe are, therefore, profound and must be re-conceptualized as a multi-pronged, intelligence-led strategy, not a simple stamping-out campaign. First, the genomic analysis from [2] must underpin a regional and intercontinental epidemiological investigation. Tracing the exact origin and pathway of introduction requires far more sequencing from North Africa, the Middle East, and the Balkans. This is not merely an academic exercise; it is essential for identifying the specific trade routes, animal gatherings, or vectors that allowed this incursion. This information must be fed back into risk-based surveillance and biosecurity protocols at points of entry (e.g., ports, airports, and land borders).

Second, diagnostic capacity must be ramped up and made field-deployable for all potential host species. The development of rapid, cost-effective molecular diagnostics such as the RAA-CRISPR Cas12a method [8], which can provide visual results in under an hour without complex equipment, is a game-changer. These must be validated for use in pigs, cattle, and wildlife species, not just sheep and goats. Similarly, serological tools like the c-ELISA developed in [43] and the luciferase immunoprecipitation system (LIPS) evaluated in [68] must be validated across the wider host range to ensure they are detecting true infection and not cross-reacting with other morbilliviruses. The use of nanobodies, as explored in [70] and [73], offers a novel platform for developing ultrarapid, point-of-care antigen tests that are highly specific and thermostable, ideal for field use in a European eradication context.

Third, the vaccine landscape must adapt. While the existing live-attenuated PPRV vaccines (e.g., Nigeria/75/1 and Sungri/96) are highly effective and cross-protective against all lineages [35], they are thermolabile and, critically, do not allow for DIVA (Differentiating Infected from Vaccinated Animals). The global PPR eradication programme requires a DIVA-capable vaccination strategy to serologically monitor field virus circulation in vaccinated populations [45]. The development of recombinant vectored DIVA vaccines, such as the Newcastle disease virus-vectored vaccine expressing the PPRV H protein (rNDV_HKur) which provided complete clinical protection in goats and DIVA capability [75], is a critical step. For the European context, a DIVA vaccine is not just desirable; it is mandatory. The European Union's veterinary authorities need a tool that allows them to vaccinate in a ring or barrier strategy without losing the ability to detect a re-introduction or a missed infection through serological surveillance. Furthermore, the thermostability advantages of vectored vaccines (e.g., the rNDV vectored vaccine is significantly more heat-stable than the conventional live-attenuated PPRV) are crucial for deployment in field conditions, especially during summer months or in regions with limited cold chain infrastructure.

Fourth, the control strategy must explicitly address the livestock-wildlife interface. This means establishing sentinel surveillance in wild ungulate populations, particularly in areas adjacent to the outbreak zones in Bulgaria, Romania, and Greece. Any vaccination campaign in domestic livestock must be coordinated with wildlife authorities to minimize the risk of spillover. Modeling efforts, such as those using MaxEnt to predict transboundary risk [62], must be updated with European landscape data to identify high-risk corridors for PPRV spread from the current foci, considering the movements of both domestic animals and wildlife (e.g., wild boar migration corridors).

Finally, the European emergence serves as a stark warning to the global community. The goal of eradicating PPRV by 2030 under the PPR GCES [45] appears increasingly ambitious, if not unrealistic, in the face of such a major transcontinental incursion. The virus has demonstrated a capacity for long-distance, intercontinental spread that surpasses previous assumptions. The failure to control the disease in its endemic heartlands of Africa and Asia directly resulted in this European exposure. This event should galvanize a renewed, fully-funded, and resourced global eradication effort. It is no longer a problem for developing nations alone; it is now a direct threat to a highly susceptible, economically valuable livestock sector in Europe, with potential consequences for wildlife conservation and continental food security. The control implications are clear: investment in global surveillance, rapid diagnostic deployment, DIVA vaccine stockpiles, and coordinated cross-border eradication campaigns in affected regions is not charity; it is enlightened self-interest for the entire international community.

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