Historically endemic to parts of South America, Oropouche virus (OROV) has caused an estimated 500,000 infections since its discovery, with a marked geographic expansion beyond the Amazon basin into other regions of South America and the Caribbean since late 2023. This Review synthesises current evidence on OROV epidemiology, transmission dynamics, clinical manifestations, diagnostics, viral diversity, and public health impact, with the primary objective of identifying critical knowledge gaps and outlining priorities for surveillance, research, and control. Human transmission occurs primarily via Culicoides paraensis midges, while the competence of other vectors, the role of animal reservoirs in sustaining sylvatic transmission, and the contribution of vertical and sexual transmission remain incompletely understood. Although most infections are self-limiting, reports of neurological disease, Guillain-Barré syndrome, adverse pregnancy outcomes, and rare fatalities highlight uncertainties regarding pathogenicity, risk factors for severe disease, and long-term sequelae. The known teratogenicity of related Simbu serogroup orthobunyaviruses in animals further raises concerns about foetal risk in humans. Environmental change, expanding vector ranges, and viral evolution are likely contributing to outbreak emergence and geographic spread. Based on the available evidence, this review highlights priority gaps in epidemiological surveillance, diagnostics and genomic monitoring, vector competence and ecology, transmission pathways, and countermeasure development. Addressing these gaps through coordinated surveillance, improved laboratory capacity, targeted vector control, and focused research will be essential to mitigate the public health impact of OROV and reduce the risk of further spread.
ABSTRACT Foot-and-mouth disease (FMD) virus is one of the most feared and most consequential pathogens of livestock worldwide. It can be spread rapidly by the transboundary movement of animals, animal products and byproducts. In January 2025, Germany detected its first FMD outbreak since 1988 in extensively reared water buffalo on a small farm in the state of Brandenburg, directly outside Berlin, the federal capital. Immediate control measures including a standstill for movements of susceptible animals and pre-emptive culling were implemented by the veterinary authorities. Whole-genome sequencing identified the virus as serotype O, topotype ME-SA, lineage SA-2018 and revealed extensive recombination, but cross-neutralization assays suggested good heterologous protection by an O/PanAsia-2 vaccine strain. Epidemiological back-calculation placed the time of virus introduction in late December 2024. Although the entry route remains unresolved, human-associated introduction is most likely. Network analysis revealed minimal farm connectivity, and simulations predicted low potential for onward transmission, which is consistent with the outbreak being ultimately restricted to a single herd. This event underscores the constant and unpredictable risk of introduction of the virus. Early detection through increased awareness and comprehensive differential diagnostics as well as the international collaboration of veterinary services, laboratories and experts are essential in the face of the global presence of FMD.
African swine fever (ASF) remains a global threat to pig production and wild pig conservation. While some Asian countries have approved vaccines, like the live attenuated vaccine ASFV-G-ΔI177L , a licensed vaccine for the European market is still pending and requires extensive animal testing, including assessment of safety in breeding animals. In the present study, we evaluated the safety of vaccination with ASFV-G-ΔI177L in reproductively competent sows, focusing on vaccination during gestation. Sows were either pre-immunized before pregnancy and boosted in early (40th day) or late (80th day) gestation, vaccinated for the first time in early or late gestation, or unvaccinated controls. This study evaluated maternal health implications, vaccine virus dissemination, vertical transmission potential, and antibody responses in sows and piglets. Pre-immunized sows tolerated booster vaccination in early or late gestation without adverse effects, showed declining viraemia, and maintained normal reproductive performance and piglet survival. In contrast, naïve sows vaccinated during pregnancy developed severe clinical signs associated with high viral loads, and widespread tissue dissemination, which led to euthanasia, abortions, and stillbirths, particularly after vaccination in late gestation. Examination of fetuses and piglets indicated that vertical transmission was confined to one naïve sow vaccinated during early pregnancy, whose litter had the highest rate of stillbirths and high viral loads in multiple organs. All remaining piglets sampled on the 7th day of life remained ASFV-negative in blood. Serological analyses showed robust ASFV-specific antibody responses in all live piglets on the 7th and 28th day of life. These data demonstrate that ASFV-G-ΔI177L can potentially be used safely in reproductively competent sows when administered before pregnancy, providing passive immunity transfer to offspring. However, first time vaccination of naïve sows during gestation holds substantial risks for the health of the female animal, as well as for reproduction.
The emergence of SARS-CoV-2 variants, like XBB.1.5, causing immune evasion and frequent breakthrough infections, emphasizes the need for vaccines that limit transmission and target newly emerging variants. Mucosal vaccines, particularly live attenuated vaccines (LAV), are promising candidates for inducing strong mucosal immune responses to prevent viral replication and transmission. Vaccination with the previously described "one-to-stop" codon-modified LAV OTS-228, carrying the ancestral spike protein, induced sterilizing immunity against ancestral SARS-CoV-2 but also broad protection against Omicron variants, including XBB.1.5, but transmission of XBB.1.5 to contacts could not be prevented completely. As a proof-of-concept, we updated OTS-228 by replacing the sequence coding for the ancestral SARS-CoV-2 spike protein with that of the XBB.1.5 variant. We applied flow cytometry to detect SARS-CoV-2-specific T cell responses, as well as ELISA and qPCR, to characterize systemic and mucosal immune responses in Syrian hamsters in detail. The new OTS construct designated as "OTS-300" exhibited an optimal safety profile in Syrian hamsters comparable to the original candidate vaccine. A single-dose intranasal (i.n.) vaccination with OTS-300 protects against disease, substantially limits XBB.1.5 replication, and reduces transmission in Syrian hamsters, showcasing the adaptability of the OTS platform for other emerging variants. OTS-300 induced accelerated mucosal and systemic antibody responses and reduced virus-mediated inflammation as compared with an intramuscularly delivered mRNA vaccine encoding the XBB.1.5 Spike.
An increasing number of mpox cases caused by the monkeypox virus (MPXV; Orthopoxvirus monkeypox ), are reported in West and Central Africa, driven by frequent zoonotic spillovers into human populations that sometimes give rise to epidemic lineages. Designing mitigation strategies to reduce spillover requires a better understanding of the ecology underlying the zoonotic emergence of MPXV. Here, we show that orthopoxviruses, including MPXV, infect duikers, which are popular bushmeat in many mpox endemic regions. In bushmeat markets from the Democratic Republic of the Congo (DRC), we detected orthopoxvirus DNA in a Weyns's duiker ( Cephalophus weynsi ) and a common duiker ( Sylvicapra grimmia ) using PCR. High throughput sequencing (HTS) detected a small number of reads assigned to MPXV, and 25% of the genome of a close relative to the taterapox virus (TATV; Orthopoxvirus taterapox ), respectively. In the Taï National Park (TNP), Côte d’Ivoire, tissue samples from a Maxwell’s duiker ( Philantomba maxwellii ) carcass were also MPXV PCR positive, and 50% of the viral genome could be recovered. Suspecting scavenging as a route of exposure, we ran metabarcoding analyses on duiker faeces from TNP, which revealed that more than 21% contained non-duiker mammal DNA, including species linked to previous MPXV infections in this ecosystem. Revisiting western chimpanzee ( Pan troglodytes verus ) diet data from an mpox outbreak in TNP in 2017, supported an epidemiological link to duiker consumption.
Abstract Since mid-June 2026, an acute, non-fatal syndrome with high herd morbidity, reduced milk yield, diarrhea, fever and lethargy affected dairy cattle in southern Germany and Switzerland. Major viral pathogens were excluded. Pan-Simbuvirus PCR first detected an orthobunyavirus, subsequently confirmed by metagenomic sequencing, which enabled recovery of a complete “Shamonda-like” genome. One sentence summary line More than a decade after the emergence of Schmallenberg virus in 2011, a novel “Shamonda-like” orthobunyavirus of the Simbu serogroup has now emerged in Central Europe.
We tested wild ruminants, boar, and carnivores in northeast Germany for highly pathogenic avian influenza subtype H5 antibodies. Wild ruminants were seronegative, but 3.5% of boar and 12.5%-21.9% of carnivores were seropositive, indicating frequent spillover. Because such events might accelerate mammalian (and ultimately human) adaptation, sustained monitoring remains essential.
In autumn 2025, highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus, genotype EA-2024-DI.2.1, caused systemic infections leading to a mass mortality event among the western migrating subpopulation of Eurasian cranes (Grus grus) in Germany. Gregarious behavior at feeding and resting sites likely promoted rapid viral spread within the population.
Zoos with avian populations are vulnerable to incursions of the high pathogenicity avian influenza virus (HPAIV) H5Nx due to the free-range husbandry, bird population density and shared open water areas between zoo birds and wild waterfowl. An outbreak of HPAIV H5N1, clade 2.3.4.4b, genotype EA AB, at the Zoological Garden Karlsruhe, Germany, in 2022, was managed applying legal restriction measures but exceptionally exempting culling orders for RT-qPCR-positive but clinically healthy birds. A critical factor in the zoo’s response was the implementation of a segregation concept approved in advance. The entire bird population could be rapidly separated into epidemiological housing units (epUs) cared for by separate staff. A total of 79 birds initially tested RT-qPCR-positive, but only 21 (26.6%) clinically diseased birds had to be euthanized or succumbed. Seroconversion amounted to 94.8% of the remaining 58 birds. Extensive RT-qPCR investigations of 3,634 samples confirmed infections remained confined to three initially infected epUs out of a total of 25. Spread of virus in the infected epUs was limited to 3 weeks after segregation. In the cohort of infected pelicans, surviving individuals remained seropositive with elevated levels of H5-specific antibody titers for the following 2 years suggesting ongoing protection. The described science-based control measures rested on a legally binding yet interpretive statement regarding the pertinent animal health legislation are exemplary for managing an outbreak of high pathogenicity avian influenza (HPAI) in zoos.
Abstract Vaccination against high pathogenicity avian influenza virus (HPAIV) is increasingly used to protect poultry, but vaccine performance is commonly inferred from clinical protection and virus shedding rather than measured transmission. We asked whether reproduction numbers from controlled transmission experiments can quantify how vaccination changes infection dynamics in virus-exposed geese, i.e. susceptibility and infectiousness. Domestic geese were prime-boost vaccinated with an H5 clade 2.3.4.4b RNA-amplicon vaccine and challenged with homologous HPAIV H5N1. Replicats of seeder-sentinel groups represented transmission among unvaccinated animals, to vaccinated contacts, and from vaccinated breakthrough-infected animals. Vaccinated directly challenged geese remained clinically protected although all became productively infected. Estimated reproduction numbers were R 0 =4.7 (95% CI, 2.8-8.0) among unvaccinated geese, R s =2.6 (1.6-4.5) for transmission to vaccinated contacts, R i =3.7 (2.0-6.8) for transmission from vaccinated infected geese, and R vacc =2.0 (0.8-4.9) for a fully vaccinated population. Vaccination reduced transmission but, under these experimental exposure conditions, did not reduce the point estimate for R vacc below one. Even though vaccinated infected geese shed substantially less viral RNA, infectiousness was sufficient to sustain transmission in vaccinated geese, indicating that RNA shedding alone may not reliably predict efficacy of transmission reduction. Experimental reproduction numbers therefore provide a direct population-level complement to conventional vaccine testing protocols and can separate effects on susceptibility from effects on onward transmission. Author Summary Vaccines against high pathogenicity avian influenza are usually evaluated by asking whether they prevent disease and reduce the amount of virus shed by infected birds. For disease control, however, it is equally important to know whether vaccination prevents onward transmission. We used domestic geese infected with H5N1 avian influenza virus to test whether this effect can be measured directly in small transmission experiments. By co-housing vaccinated and unvaccinated infected birds with vaccinated or unvaccinated contact birds, we estimated reproduction numbers for different transmission circumstances. Vaccination fully protected geese from clinical disease and reduced viral RNA shedding, but it did not prevent infection or transmission. The estimated reproduction number fell from 4.7 among unvaccinated geese to 2.0 for transmission to a fully vaccinated population, although the confidence interval was wide. Notably, the reduction in viral RNA shedding overestimated the effect on infectiousness. Thus, shedding alone may overstate how strongly a vaccine limits transmission. Directly estimating transmission can therefore add important information to conventional vaccine- efficacy studies and may improve comparisons between vaccines.
Rustrela virus (RusV) is a newly discovered member of the genus Rubivirus . RusV causes a fatal, non-suppurative meningoencephalomyelitis in a variety of mammals. Various aspects of RusV biology remain poorly understood, e.g. the excretion of infectious virus and its transmission. To address these questions, we performed in vivo experiments including putative reservoir (wood mice) as well as potential dead-end hosts (Lewis rats). To investigate the natural route of RusV infection and transmission, subgroups of wood mice and Lewis rats were either inoculated intranasally or orally. Successful infection was only observed in animals inoculated via the intranasal route, leading to the assumption that the virus could enter via olfactory neurons and subsequently spread throughout the central nervous system. To gain an initial understanding of the mechanisms of viral transmission, we co-housed RusV-inoculated wood mice with non-infected sentinels. In addition, wood mice or Lewis rats were placed in cages previously occupied by infected wood mice as donor animals for indirect transmission via the environment. Successful RusV transmission was observed solely in co-housed sentinels. These findings suggest that RusV transmission requires direct contact with bodily fluids, such as saliva or nasal secretions or at least a higher infective dose. In contrast, indirect exposure to a presumably contaminated cage does not seem to be sufficient for transmission between reservoir animals or reservoir and dead-end hosts.
Global SARS-CoV-2 surveillance based on consensus genome sequences has enabled unprecedented tracking of viral spread and evolution but provides limited resolution of intra-sample diversity and limited sensitivity for the reliable detection of recombinant genomes. Here, we analyzed 3,360 SARS-CoV-2 genomes generated through regional surveillance in northeastern Germany (Mecklenburg–Western Pomerania) between 2022 and 2025. Reconstruction of local spatio-temporal variant dynamics revealed substantial lineage diversity, regional deviations from global circulation patterns, and periods of intense co-circulation favoring co-infection and recombination. To systematically identify recombinant genomes, we implemented a two-stage framework combining high-sensitivity consensus-based screening (REcombination BARcode detector REBAR) with targeted raw-read validation. Among 61 candidate recombinants, 21 were supported by read-level evidence, including 17 previously unrecognized genomes. Recombinant breakpoints clustered in functionally relevant genomic regions, particularly around ORF1b and the spike gene, indicating non-random patterns of genome exchange. Despite frequent co-infections, only a small subset of recombinants showed evidence of onward transmission, suggesting that successful establishment represents a major constraint on recombinant SARS-CoV-2 evolution. Our findings demonstrate that recombination-aware genomic surveillance complements routine consensus genome surveillance by resolving intra-sample diversity and recombinant diversity while remaining scalable for population-level implementation.
Arboviruses evolve under unique ecological constraints imposed by their dual replication cycles in vertebrate and arthropod hosts. This dual-host requirement results in markedly low substitution rates, which complicate molecular clock calibration, particularly when temporal sampling spans only narrow time windows. For RNA arboviruses, wide sampling windows are especially rare due to the intrinsic instability of RNA. Here, we demonstrate that ethanol-preserved museum specimens can help overcome these temporal limitations. We successfully recovered the coding-complete genome of a bandavirus, a negative-sense segmented RNA virus that clusters with the highly pathogenic human severe fever with thrombocytopenia syndrome virus. The virus was detected in a Common pipistrelle (Pipistrellus pipistrellus) bat collected in northern Germany in 1919, making it one of the oldest sequenced mammalian RNA viruses, only comparable to historic measles and influenza A viruses from 1912 and 1918. Screening 1086 contemporary bat samples revealed strains of the same virus species in nine Common pipistrelle bats (2010-2018) and one Serotine bat (Eptesicus serotinus, 1999) from Germany and the Netherlands. Coding-complete genomes indicate frequent genome segment reassortment and widespread circulation of reassortants of this understudied virus species (Bandavirus zwieselense). We detected an exceptionally low substitution rate (< 6.88 × 10-5 substitutions/site/year) between the RdRp coding sequence of the ancient genome and its nearest modern counterpart. Additionally, functional assays demonstrated that the virus's non-structural (NSs) protein effectively inhibits interferon induction in human HEK-293T cells. Our findings highlight the feasibility and scientific value of extracting and analysing ancient viral RNA from ethanol-preserved museum specimens to substantially enhance our understanding of RNA arbovirus evolution.
The highly pathogenic avian influenza viruses of subtype H5N1 represent a major threat to animal and public health. The current panzootic with H5 clade 2.3.4.4b has caused numerous, widespread outbreaks in various domestic and wild avian species with high mortalities, massive losses, and a high frequency of spillover events to unexpected novel mammalian hosts, such as dairy cows. The global H5N1 situation raises serious concerns about zoonotic risks due to effective mammal-to-mammal transmission. Therefore, it is critical to increase surveillance intensity of a broadened species range, particularly at the human-animal interface. For this purpose, reliable and cost-effective serological tools that are easy to perform and suitable for high-throughput screening are critically needed. The newly developed double-antigen enzyme-linked immunosorbent assay format employing a luminescence-based detection technology has demonstrated compliance with such prerequisites. The assay allowed sensitive and specific detection of antibodies directed against H5 hemagglutinin of clade 2.3.4.4b in a wide range of birds and mammals, including humans. Furthermore, it allowed differentiating H5 anti-head-specific from cross-reacting anti-stalk antibodies, which represents a valuable feature with regard to the monitoring of future vaccination programs with H5-specific vaccines. Thus, the assay is a significant contribution to existing serological diagnostic tests for a clade-optimized and species-independent detection of influenza A virus antibodies. IMPORTANCE:The ongoing highly pathogenic avian influenza virus H5N1 panzootic has caused numerous outbreaks in domestic and wild animals, with frequent spillover events to unexpected host species, which underscores the importance of intensified surveillance. However, sensitive and specific multi-species serological assays represent a major gap. For this purpose, we developed a novel double-antigen enzyme-linked immunosorbent assay that employs an innovative luminescence-based readout strategy. The test allowed a highly sensitive and specific detection of H5-specific antibodies in a wide range of avian and mammalian species, including humans. It therefore represents a valuable contribution to improving species-independent serological diagnostic tools for the detection of influenza A virus antibodies.
African swine fever virus (ASFV) poses a significant threat to pork production and wild pig populations worldwide. The study assessed the long-term fate and immunity of animals recovering from a moderately virulent ASFV infection, following the principles of a duration of immunity study for live vaccines. Pigs inoculated with the moderately virulent ASFV strain Estonia14 largely developed mild clinical signs and only transient viremia. Six months after the initial inoculation and once fully recovered, all the animals were challenged with highly virulent ASFV Armenia08. Only one of the previously exposed pigs exhibited mild clinical signs, while all control animals showed typical signs of acute, lethal ASF. Moreover, only a subset of pigs inoculated with the ASF strain Estonia14 displayed temporary detectability of ASFV genomes following challenge infection. Virus isolation corroborated these findings, with low levels of infectious virus in organs of previously inoculated pigs (28 days post challenge). Furthermore, monitoring of ASFV-specific IgM and IgG kinetics enabled the analysis of humoral responses. IgG levels were sustained over the study period and increased slightly upon challenge infection. Lastly, plasma analysis revealed elevated complement factor C3a levels post inoculation and challenge in the recovered pigs, directly correlating with challenge virus presence. In contrast, both C3a and C5a levels were increased in the control group. It could be shown that complement system activation was mediated by the lectin pathway, possibly by interaction of mannose-binding lectins and ASFV particles. This study suggests that protective immunity following recovery can last at least six months. No cases of persistent or chronic disease were observed in convalescent pigs. These findings have implications for both vaccine development and assessment, as well as for disease control strategies including surveillance actions.
African swine fever poses an ongoing threat to Eurasian wild pigs and the associated global swine production, with no internationally licensed vaccine available. Live attenuated vaccines like ASFV-G-ΔI177L demonstrated promising safety and protection in young domestic pigs, but comprehensive safety evaluations in breeding animals are necessary for regulatory licensing in the EU. This study investigated the safety of intramuscular immunization with ASFV-G-ΔI177L in adult breeding boars (Sus scrofa domesticus). Eight healthy boars were intramuscularly vaccinated and monitored for clinical manifestation, viral genome and infectious virus in blood, oral fluid, semen, and tissues. Furthermore, ASFV-specific antibodies and effects on semen quality were assessed over an observation period of 28 days. Clinical signs appeared in all boars at 6 days post vaccination (dpv), including high fever, lethargy, and anorexia in most animals by 8 dpv. Four animals developed severe disease and were euthanized at humane endpoints or succumbed between 11 and 15 dpv, while four animals recovered. Viral genome was detected in blood, oral fluid, and semen of all animals, with higher loads in succumbed individuals. Infectious ASFV-G-ΔI177L was found in reproductive tissues, spleens, salivary glands, and semen samples from acutely affected boars and one recovered boar. All boars developed ASFV-targeting antibodies, but titers remained low. Semen quality was significantly reduced after vaccination and failed to recover in surviving boars by 28 dpv. These findings raise concerns regarding vaccine safety in reproductively active boars and highlight the risk of virus transmission through semen.
Mpox, caused by the monkeypox virus (MPXV; Orthopoxvirus monkeypox ), is on the rise in West and Central Africa 1–3 . African rodents, especially squirrels, are suspected to be involved in MPXV emergence, but no evidence of a direct transmission to humans or non-human primates has been established 4–9 . Here we describe an outbreak of MPXV in a group of wild sooty mangabeys ( Cercocebus atys ) in Taï National Park (Côte d’Ivoire). The outbreak affected one-third of the group, killing four infants. To track its origin, we analysed rodents and wildlife carcasses from the region. We identified a MPXV-infected fire-footed rope squirrel ( Funisciurus pyrropus ), found dead 3 km from the mangabey territory 12 weeks before the outbreak. MPXV genomes from the squirrel and the mangabey were nearly identical. A video record from 2014 showed a mangabey from this group eating the same squirrel species and diet metabarcoding of faecal samples collected from mangabeys before the outbreak identified two samples containing fire-footed rope squirrel DNA. One of these samples was also the first positive for MPXV. This represents a rare case of direct detection of interspecies transmission. Our findings indicate that rope squirrels were the source of the MPXV outbreak in mangabeys. Because squirrels and non-human primates are hunted, traded and consumed by humans in West and Central Africa 10,11 , exposure to these animals probably represents risk for zoonotic transmission of MPXV.
Borna disease virus 1 (BoDV-1) causes encephalitis with a fatality rate of >= 90% in domestic mammals and humans. Currently, the bicolored white-toothed shrew is the only known reservoir host. We report BoDV-1 infections in 15 wild European hedgehogs from an endemic area in Germany. Because hedgehogs are distant relatives of shrews and often cared for by humans, the cases raise concern regarding a potential zoonotic risk. All the hedgehogs that tested positive for BoDV-1 died of neurological disease and exhibited severe polio-predominant lymphoplasmohistiocytic meningoencephalitis. However, because of the detection of viral antigens in nonneural cells in 1 animal, we cannot completely exclude that some infected hedgehogs shed the virus. Although direct BoDV-1 transmission is known to be inefficient, our results emphasize the necessity of hygiene measures when handling hedgehogs, especially those with neurological signs who are from BoDV-1-endemic regions.
Despite its importance for Culicoides-borne disease risk assessment, the winter activity of species of this biting midge genus remains poorly characterized. Moreover, information on virus circulation in winter-active Culicoides vectors, both under endemic conditions and during outbreaks, is almost non-existent. UV-light traps to collect Culicoides biting midges were operated once a week for 24 h in cattle, sheep, goat and horse stables at 12 to 55 locations during four consecutive winter periods (November 1 to March 31, 2021 to 2025) throughout Germany. Collected females of the genus Culicoides were morphologically assigned to Obsoletus Group or Pulicaris Complex. Temperature data were recorded to relate biting midge activity to temperatures. Screening for bluetongue virus (BTV), Schmallenberg virus and epizootic hemorrhagic disease virus was done by real-time RT-PCR on 1,581 pools (46,358 females) of both groups collected before (winter 2022/2023) and during the BTV serotype 3 (BTV-3) outbreak (winters 2023/2024 and 2024/2025). Culicoides collections displayed notable variation between sites and months. November and March accounted for 95
Following the emergence of Shamonda virus (SHAV) in Europe in 2026, we identified a second, genetically distinct SHAV clade in cattle in Germany. Consistent differences across all three genome segments together with divergent regional distribution patterns indicate independent introductions. We have designated the two clades as SHAV Europe 1 (SHAV-EU1) and SHAV Europe 2 (SHAV-EU2). The unexpected co-circulation of these two clades has important implications for diagnostics, surveillance, host range assessment, risk evaluation, and control measures.