Comparing Phylogeographies to Reveal Incompatible Geographical Histories within Genomes.

Modern phylogeography aims at reconstructing the geographic movement of organisms based on their genomic sequences and spatial information. Phylogeographic approaches are often applied to pathogen sequences and therefore tend to neglect the possibility of recombination, which decouples the evolutionary and geographic histories of different parts of the genome. Genomic regions of recombining or reassorting pathogens often originate and evolve at different times and locations, which characterise their unique spatial histories. Measuring the extent of these differences requires new methods to compare geographic information on phylogenetic trees reconstructed from different parts of the genome. Here we develop for the first time a set of measures of phylogeographic incompatibility, aimed at detecting differences between geographical histories in terms of distances between phylogeographies. We study the effect of varying demography and recombination on phylogeographic incompatibilities using coalescent simulations. We further apply these measures to the evolutionary history of human and livestock pathogens, either reassorting or recombining, such as the Victoria and Yamagata lineages of influenza B and the O/Ind-2001 foot-and-mouth disease virus strain. Our results reveal diverse geographical paths of migration that characterise the origins and evolutionary histories of different viral genes and genomic segments. These incompatibility measures can be applied to any phylogeography, and more generally to any phylogeny where each tip has been assigned either a continuous or discrete "trait" independent of the sequence. We illustrate this flexibility with an analysis of the interplay between the phylogeography and phylolinguistics of Uralic-speaking human populations, hinting at patrilinear language transmission.

In vitro phenotypic characterisation of two genotype I African swine fever viruses with genomic deletion isolated from Sardinian wild boars.

African swine fever virus (ASFV) causes a devastating disease affecting domestic and wild pigs. ASF was first introduced in Sardinia in 1978 and until 2019 only genotype I isolates were identified. A remarkable genetic stability of Sardinian ASFV isolates was described, nevertheless in 2019 two wild boar isolates with a sustained genomic deletion (4342 base pairs) were identified (7303WB/19, 7212WB/19). In this study, we therefore performed in vitro experiments with monocyte-derived macrophages (moMФ) to unravel the phenotypic characteristics of these deleted viruses. Both 7303WB/19 and 7212WB/19 presented a lower growth kinetic in moMФ compared to virulent Sardinian 26544/OG10, using either a high (1) or a low (0.01) multiplicity of infection (MOI). In addition, flow cytometric analysis showed that both 7303WB/19 and 7212WB/19 presented lower intracellular levels of both early and late ASFV proteins. We subsequently investigated whether deleted virus variants were previously circulating in wild boars in Sardinia. In the four years preceding the last genotype I isolation (February 2015-January 2019), other eight wild boar isolates were collected, all belonging to p72 genotype I, B602L subgroup X, but none of them presented a sustained genomic deletion. Overall, we observed the deleted virus isolates in Sardinia only in 2019, at the end of a strong eradication campaign, and our data suggest that it might possess an attenuated phenotype in vivo. A better understanding of ASFV evolution in endemic territories might contribute to development of effective control measures against ASF.

Re-emergence of foot-and-mouth disease in the Republic of Korea caused by the O/ME-SA/Ind-2001e lineage.

The O/ME-SA/Ind-2001e foot-and-mouth disease virus (FMDV) lineage is a pandemic strain that has recently become dominant within East and Southeast Asia. During May 2023, this viral lineage spread to the Republic of Korea, where 11 outbreaks were detected on cattle and goat farms located in Cheongju and Jeungpyeong. Infected animals displayed typical FMD signs including vesicular lesions with drooling and anorexia. Molecular diagnostic testing and genetic analysis (VP1 sequencing) showed that the causative FMDVs belonged to the O/ME-SA/Ind-2001e lineage and shared the closest nucleotide identity (97.95-99.21%) to viruses that have been collected from Mongolia and South-East Asian countries. Phylogenetic analyses showed that these sequences were distinct to those collected from the previous Korean O/ME-SA/Ind-2001e lineage outbreaks in 2019, demonstrating that these cases are due to a new incursion of the virus into the country. Prompt implementation of emergency vaccination using antigenically matched serotype O vaccines (r1 value: 0.74-0.93), together with intensive active surveillance on farms surrounding the infected premises has successfully prevented further spread of FMD. These recent FMD outbreaks reinforce the importance of research to understand the risks associated with transboundary pathways in the region, in order to reduce the possibility of a further reintroduction of FMD into the Republic of Korea.

Detection of foot-and-mouth disease viruses from the A/AFRICA/G-I genotype in the Sultanate of Oman.

Rapid identification and characterization of circulating foot-and-mouth disease virus (FMDV) strains is crucial for effective disease control. In Oman, a few serological and molecular studies have been conducted to identify the strains of FMDV responsible for the outbreaks that have been occurring within the country. In this study, 13 oral epithelial tissue samples from cattle were collected from suspected cases of FMD in Ash Sharqiyah North, Al Batinah North, Dhofar and Ad Dhakhyilia governorates of Oman between 2018 and 2021. FMDV RNA was detected in all samples by real-time RT-PCR and viruses were isolated after one- or two-blind passages in the porcine Instituto Biologico-Rim Suino-2 cell line. Antigen capture ELISA characterized all isolates as serotype A and VP1 phylogenetic analysis placed all sequences within a single clade of the G-I genotype within the A/AFRICA topotype. These sequences shared the closest nucleotide identities to viruses circulating in Bahrain in 2021 (93.5% to 99.5%) and Kenya in 2017 (93.4% to 99.1%). To the best of our knowledge, this is the first time that A/AFRICA/G-I viruses have been detected in Oman. Together with the closely related viruses detected recently in Bahrain, these findings reinforce the importance of deploying effective quarantine control measures to minimize the risks of transboundary transmission of FMD associated with the importation of cattle from East Africa.

Establishing a molecular toolbox of lineage-specific real-time RT-PCR assays for the characterization of foot-and-mouth disease viruses circulating in Asia.

Foot-and-mouth disease (FMD) is endemic in many Asian countries, with outbreaks occurring regularly due to viruses from serotypes O, A, and Asia1 that co-circulate in the region. The ability to rapidly characterize new virus occurrences provides critical information to understand the epidemiology and risks associated with field outbreaks, and helps in the selection of appropriate vaccines to control the disease. FMD lineage-specific characterization is usually determined through sequencing; however, this capacity is not always readily available. In this study, we provide a panel of real-time RT-PCR (rRT-PCR) assays to allow differentiation of the FMD virus (FMDV) lineages known to have been co-circulating in Asia during 2020. This panel included five new rRT-PCR assays designed to detect lineages O/ME-SA/PanAsia-PanAsia-2, O/ME-SA/Ind-2001, O/SEA/Mya-98, O/CATHAY, and A/ASIA/Sea-97, along with three published rRT-PCR assays for A/ASIA/Iran-05, A/ASIA/G-VII, and Asia1 serotypes. Samples of known FMD lineage (n = 85) were tested in parallel with all eight lineage-specific assays and an established 3D pan-FMD rRT-PCR assay, and comparative limit of detection (LOD) experiments were conducted for the five newly developed assays. All samples (85/85) were assigned to the correct serotype, and the correct lineage was assigned for 70 out of 85 samples where amplification only occurred with the homologous assay. For 13 out of 85 of the samples, there was amplification in two assays; however, the correct lineage could be designated based on the strongest Ct values for 12 out of 13 samples. An incorrect lineage was assigned for 3 out of 85 samples. The amplification efficiencies for the five new rRT-PCR assays ranged between 79.7 and 100.5%, with nucleic acid dilution experiments demonstrating broadly equivalent limits of detection when compared to the 3D pan-FMD rRT-PCR assay. These new tests, together with other published lineage-specific rRT-PCR assays, constitute a panel of assays (or molecular toolbox) that can be selected for use in FMD endemic countries (individually or a subset of the assays depending on region/lineages known to be circulating) for rapid characterization of the FMDV lineages circulating in Asia at a relatively low cost. This molecular toolbox will enhance the ability of national laboratories in endemic settings to accurately characterize circulating FMDV strains and facilitate prompt implementation of control strategies, and may be particularly useful in settings where it is difficult to access sequencing capability.

Enhancing global preparedness during an ongoing pandemic from partial and noisy data.

As the coronavirus disease 2019 spread globally, emerging variants such as B.1.1.529 quickly became dominant worldwide. Sustained community transmission favors the proliferation of mutated sub-lineages with pandemic potential, due to cross-national mobility flows, which are responsible for consecutive cases surge worldwide. We show that, in the early stages of an emerging variant, integrating data from national genomic surveillance and global human mobility with large-scale epidemic modeling allows to quantify its pandemic potential, providing quantifiable indicators for pro-active policy interventions. We validate our framework on worldwide spreading variants and gain insights about the pandemic potential of BA.5, BA.2.75, and other sub- and lineages. We combine the different sources of information in a simple estimate of the pandemic delay and show that only in combination, the pandemic potentials of the lineages are correctly assessed relative to each other. Compared to a country-level epidemic intelligence, our scalable integrated approach, that is pandemic intelligence, permits to enhance global preparedness to contrast the pandemic of respiratory pathogens such as SARS-CoV-2.

Origin, Genetic Variation and Molecular Epidemiology of SARS-CoV-2 Strains Circulating in Sardinia (Italy) during the First and Second COVID-19 Epidemic Waves.

Understanding how geography and human mobility shape the patterns and spread of infectious diseases such as COVID-19 is key to control future epidemics. An interesting example is provided by the second wave of the COVID-19 epidemic in Europe, which was facilitated by the intense movement of tourists around the Mediterranean coast in summer 2020. The Italian island of Sardinia is a major tourist destination and is widely believed to be the origin of the second Italian wave. In this study, we characterize the genetic variation among SARS-CoV-2 strains circulating in northern Sardinia during the first and second Italian waves using both Illumina and Oxford Nanopore Technologies Next Generation Sequencing methods. Most viruses were placed into a single clade, implying that despite substantial virus inflow, most outbreaks did not spread widely. The second epidemic wave on the island was actually driven by local transmission of a single B.1.177 subclade. Phylogeographic analyses further suggest that those viral strains circulating on the island were not a relevant source for the second epidemic wave in Italy. This result, however, does not rule out the possibility of intense mixing and transmission of the virus among tourists as a major contributor to the second Italian wave.

A Naturally Occurring Microhomology-Mediated Deletion of Three Genes in African Swine Fever Virus Isolated from Two Sardinian Wild Boars.

African swine fever virus (ASFV) is the etiological agent of a lethal disease of domestic pigs and wild boars. ASF threatens the pig industry worldwide due to the lack of a licensed vaccine or treatment. The disease has been endemic for more than 40 years in Sardinia (Italy), but an intense campaign pushed it close to eradication; virus circulation was last detected in wild boars in 2019. In this study, we present a genomic analysis of two ASFV strains isolated in Sardinia from two wild boars during the 2019 hunting season. Both isolates presented a deletion of 4342 base pairs near the 5' end of the genome, encompassing the genes MGF 360-6L, X69R, and MGF 300-1L. The phylogenetic evidence suggests that the deletion recently originated within the Sardinia ecosystem and that it is most likely the result of a non-allelic homologous recombination driven by a microhomology present in most Sardinian ASFV genomes. These results represent a striking example of a genomic feature promoting the rapid evolution of structural variations and plasticity in the ASFV genome. They also raise interesting questions about the functions of the deleted genes and the potential link between the evolutionary timing of the deletion appearance and the eradication campaign.

PRAGMATIST: A tool to prioritize foot-and-mouth disease virus antigens held in vaccine banks.

Antigen banks have been established to supply foot-and-mouth disease virus (FMDV) vaccines at short notice to respond to incursions or upsurges in cases of FMDV infection. Multiple vaccine strains are needed to protect against specific FMDV lineages that circulate within six viral serotypes that are unevenly distributed across the world. The optimal selection of distinct antigens held in a bank must carefully balance the desire to cover these risks with the costs of purchasing and maintaining vaccine antigens. PRAGMATIST is a semi-quantitative FMD vaccine strain selection tool combining three strands of evidence: (1) estimates of the risk of incursion from specific areas (source area score); (2) estimates of the relative prevalence of FMD viral lineages in each specific area (lineage distribution score); and (3) effectiveness of each vaccine against specific FMDV lineages based on laboratory vaccine matching tests (vaccine coverage score). The output is a vaccine score, which identifies vaccine strains that best address the threats, and consequently which are the highest priority for inclusion in vaccine antigen banks. In this paper, data used to populate PRAGMATIST are described, including the results from expert elicitations regarding FMD risk and viral lineage circulation, while vaccine coverage data is provided from vaccine matching tests performed at the WRLFMD between 2011 and 2021 (n = 2,150). These data were tailored to working examples for three hypothetical vaccine antigen bank perspectives (Europe, North America, and Australia). The results highlight the variation in the vaccine antigens required for storage in these different regions, dependent on risk. While the tool outputs are largely robust to uncertainty in the input parameters, variation in vaccine coverage score had the most noticeable impact on the estimated risk covered by each vaccine, particularly for vaccines that provide substantial risk coverage across several lineages.

A Deeper Insight into Evolutionary Patterns and Phylogenetic History of ASFV Epidemics in Sardinia (Italy) through Extensive Genomic Sequencing.

African swine fever virus (ASFV) is the etiological agent of the devastating disease African swine fever (ASF), for which there is currently no licensed vaccine or treatment available. ASF is defined as one of the most serious animal diseases identified to date, due to its global spread in regions of Africa, Europe and Asia, causing massive economic losses. On the Italian island of Sardinia, the disease has been endemic since 1978, although the last control measures put in place achieved a significant reduction in ASF, and the virus has been absent from circulation since April 2019. Like many large DNA viruses, ASFV mutates at a relatively slow rate. However, the limited availability of whole-genome sequences from spatial-localized outbreaks makes it difficult to explore the small-scale genetic structure of these ASFV outbreaks. It is also unclear if the genetic variability within outbreaks can be captured in a handful of sequences, or if larger sequencing efforts can improve phylogenetic reconstruction and evolutionary or epidemiological inference. The aim of this study was to investigate the phylogenetic patterns of ASFV outbreaks between 1978 and 2018 in Sardinia, in order to characterize the epidemiological dynamics of the viral strains circulating in this Mediterranean island. To reach this goal, 58 new whole genomes of ASFV isolates were obtained, which represents the largest ASFV whole-genome sequencing effort to date. We provided a complete description of the genomic diversity of ASFV in terms of nucleotide mutations and small and large indels among the isolates collected during the outbreaks. The new sequences capture more than twice the genomic and phylogenetic diversity of all the previously published Sardinian sequences. The extra genomic diversity increases the resolution of the phylogenetic reconstruction, enabling us to dissect, for the first time, the genetic substructure of the outbreak. We found multiple ASFV subclusters within the phylogeny of the Sardinian epidemic, some of which coexisted in space and time.

Retrospective Characterization of the 2006-2007 Swine Vesicular Disease Epidemic in Northern Italy by Whole Genome Sequence Analysis.

Advances in the epidemiological tracing of pathogen transmission have been largely driven by the increasing characterisation of whole-genome sequence data obtained at a finer resolution from infectious disease outbreaks. Dynamic models that integrate genomic and epidemiological data further enhance inference on the evolutionary history and transmission dynamics of epidemic outbreaks by reconstructing the network of 'who-infected-whom'. Swine Vesicular Disease (SVD) was present in Italy from 1966 until 2015, and since the mid-1990s, it has mainly been circulating within Italy's central-southern regions with sporadic incursions to the north of the country. However, a recrudescence of SVD in northern Italy was recorded between November 2006 and October 2007, leading to a large-scale epidemic that significantly affected the intensive pig industry of the Lombardy region. In this study, by using whole-genome sequence data in combination with epidemiological information on disease occurrences, we report a retrospective epidemiological investigation of the 2006-2007 SVD epidemic, providing new insights into the transmission dynamics and evolutionary mode of the two phases that characterised the epidemic event. Our analyses support evidence of undetected premises likely missed in the chain of observed infections, of which the role as the link between the two phases is reinforced by the tempo of SVD virus evolution. These silent transmissions, likely resulting from the gradual loss of a clear SVD clinical manifestation linked to sub-clinical infections, may pose a risk of failure in the early detection of new cases. This study emphasises the power of joint inference schemes based on genomic and epidemiological data integration to inform the transmission dynamics of disease epidemics, ultimately aimed at better disease control.

Evolutionary and Ecological Drivers Shape the Emergence and Extinction of Foot-and-Mouth Disease Virus Lineages.

Livestock farming across the world is constantly threatened by the evolutionary turnover of foot-and-mouth disease virus (FMDV) strains in endemic systems, the underlying dynamics of which remain to be elucidated. Here, we map the eco-evolutionary landscape of cocirculating FMDV lineages within an important endemic virus pool encompassing Western, Central, and parts of Southern Asia, reconstructing the evolutionary history and spatial dynamics over the last 20 years that shape the current epidemiological situation. We demonstrate that new FMDV variants periodically emerge from Southern Asia, precipitating waves of virus incursions that systematically travel in a westerly direction. We evidence how metapopulation dynamics drive the emergence and extinction of spatially structured virus populations, and how transmission in different host species regulates the evolutionary space of virus serotypes. Our work provides the first integrative framework that defines coevolutionary signatures of FMDV in regional contexts to help understand the complex interplay between virus phenotypes, host characteristics, and key epidemiological determinants of transmission that drive FMDV evolution in endemic settings.

The history of foot-and-mouth disease virus serotype C: the first known extinct serotype?

Foot-and-mouth disease (FMD) is a highly contagious animal disease caused by an RNA virus subdivided into seven serotypes that are unevenly distributed in Asia, Africa, and South America. Despite the challenges of controlling FMD, since 1996 there have been only two outbreaks attributed to serotype C, in Brazil and in Kenya, in 2004. This article describes the historical distribution and origins of serotype C and its disappearance. The serotype was first described in Europe in the 1920s, where it mainly affected pigs and cattle but as a less common cause of outbreaks than serotypes O and A. No serotype C outbreaks have been reported in Europe since vaccination stopped in 1990. FMD virus is presumed to have been introduced into South America from Europe in the nineteenth century, although whether serotype C evolved there or in Europe is not known. As in Europe, this serotype was less widely distributed and caused fewer outbreaks than serotypes O and A. Since 1994, serotype C had not been reported from South America until four small outbreaks were detected in the Amazon region in 2004. Elsewhere, serotype C was introduced to Asia, in the 1950s to the 1970s, persisting and evolving for several decades in the Indian subcontinent and for eighteen years in the Philippines. Serotype C virus also circulated in East Africa between 1957 and 2004. Many serotype C viruses from European and Kenyan outbreaks were closely related to vaccine strains, including the most recently recovered Kenyan isolate from 2004. International surveillance has not confirmed any serotype C cases, worldwide, for over 15 years, despite more than 2,000 clinical submissions per year to reference laboratories. Serology provides limited evidence for absence of this serotype, as unequivocal interpretation is hampered by incomplete intra-serotype specificity of immunoassays and the continued use of this serotype in vaccines. It is recommended to continue strengthening surveillance in regions of FMD endemicity, to stop vaccination against serotype C and to reduce working with the virus in laboratories, since inadvertent escape of virus during such activities is now the biggest risk for its reappearance in the field.

Inter-laboratory comparison of 2 ELISA kits used for foot-and-mouth disease virus nonstructural protein serology.

Serologic assays used to detect antibodies to nonstructural proteins (NSPs) of foot-and-mouth disease virus (FMDV) are used for disease surveillance in endemic countries, and are essential to providing evidence for freedom of the disease with or without vaccination and to recover the free status of a country after an outbreak. In a 5-site inter-laboratory study, we compared the performance of 2 commercial NSP ELISA kits (ID Screen FMD NSP ELISA single day [short] and overnight protocols, ID.Vet; PrioCHECK FMDV NS antibody ELISA, Thermo Fisher Scientific). The overall concordance between the PrioCHECK and ID Screen test was 93.8% (95% CI: 92.0-95.2%) and 94.8% (95% CI: 93.1-96.1%) for the overnight and short ID Screen incubation protocols, respectively. Our results indicate that the assays (including the 2 different formats of the ID Screen test) can be used interchangeably in post-outbreak serosurveillance.

Molecular characterization of foot-and-mouth disease viruses circulating in Ethiopia between 2008 and 2019.

One of the constraints to controlling foot-and-mouth disease (FMD) in East Africa is the incomplete knowledge of the specific FMD virus (FMDV) strains circulating and the way in which these viruses move across countries in the region. This retrospective study focuses on Ethiopia, which has one of the largest FMD-susceptible livestock populations in Africa. Analyses of FMDV positive samples collected between 2008 and 2019 demonstrate that serotypes O (n = 175), A (n = 51) and SAT 2 (n = 33) were present in the country. Phylogenetic analysis of the VP1 sequences for these viruses showed that there were at least seven different FMD viral clades circulating during this period: O/EA-3, O/EA-4, A/AFRICA/G-I, A/AFRICA/G-IV, A/AFRICA/G-VII, SAT2/VII and SAT2/XIII. Although these results only represent a snapshot and might not reflect all FMDV lineages that were present, they highlight the importance of serotype O, as well as the complexity and co-existence of FMDV serotypes in Ethiopia and surrounding countries. These sequence data also support the idea that there are two FMDV ecosystems existing in East Africa. Data from retrospective studies, such as these presented here, will be beneficial for vaccine selection and vaccination campaigns to control FMDV within Ethiopia.

Utilizing milk from pooling facilities as a novel approach for foot-and-mouth disease surveillance.

This study investigated the potential of pooled milk as an alternative sample type for foot-and-mouth disease (FMD) surveillance. Real-time RT-PCR (rRT-PCR) results of pooled milk samples collected weekly from five pooling facilities in Nakuru County, Kenya, were compared with half-month reports of household-level incidence of FMD. These periodic cross-sectional surveys of smallholder farmers were powered to detect a threshold household-level FMD incidence of 2.5% and collected information on trends in milk production and sales. FMD virus (FMDV) RNA was detected in 9/219 milk samples, and using a type-specific rRT-PCR, serotype SAT 1 was identified in 3/9 of these positive samples, concurrent with confirmed outbreaks in the study area. Four milk samples were FMDV RNA-positive during the half-months when at least one farmer reported FMD; that is, the household-level clinical incidence was above a threshold of 2.5%. Additionally, some milk samples were FMDV RNA-positive when there were no reports of FMD by farmers. These results indicate that the pooled milk surveillance system can detect FMD household-level incidence at a 2.5% threshold when up to 26% of farmers contributed milk to pooling facilities, but perhaps even at lower levels of infection (i.e., below 2.5%), or when conventional disease reporting systems fail. Further studies are required to establish a more precise correlation with estimates of household-level clinical incidence, to fully evaluate the reliability of this approach. However, this pilot study highlights the potential use of this non-invasive, routinely collected, cost-effective surveillance tool, to address some of the existing limitations of traditional surveillance methods.

Knowledge and risk factors for foot-and-mouth disease among small-scale dairy farmers in an endemic setting.

Foot-and-mouth disease (FMD) is a highly contagious viral infection of cloven-hoofed animals. In Kenya, the disease is endemic with outbreaks typically occurring throughout the year. A cross-sectional study was undertaken in Nakuru County to investigate farmer knowledge and risk factors for clinical disease. Semi-structured interviews were conducted on 220 smallholder farmers, selected using random spatial sampling. The majority of respondents (207/220 [94.1%]) knew of FMD and 166/207 (80.2%) of them could correctly identify the disease based on their knowledge of the clinical signs. Forty-five out of 220 farmers (20.4%) vaccinated their livestock against FMD in the previous 6 months, although of those who knew of FMD only 96/207 (46.4%) perceived it as a preventive measure undertaken to reduce the risk of disease in their farm. FMD had occurred in 5.9% of the surveyed farms within the previous 6 months (from May to November 2016). Using multivariate analysis, the use of a shared bull (OR = 9.7; p = 0.014) and the number of sheep owned (for each additional sheep owned OR = 1.1; p = 0.066) were associated with an increased likelihood of a farm experiencing a case of FMD in the previous 6 months, although the evidence for the latter was weak. This study reports risk factors associated with clinical FMD at the farm level in a densely populated smallholder farming area of Kenya. These results can be used to inform the development of risk-based strategic plans for FMD control and as a baseline for evaluating interventions and control strategies.

Reconstructing the evolutionary history of pandemic foot-and-mouth disease viruses: the impact of recombination within the emerging O/ME-SA/Ind-2001 lineage.

Foot-and-mouth disease (FMD) is a highly contagious disease of livestock affecting animal production and trade throughout Asia and Africa. Understanding FMD virus (FMDV) global movements and evolution can help to reconstruct the disease spread between endemic regions and predict the risks of incursion into FMD-free countries. Global expansion of a single FMDV lineage is rare but can result in severe economic consequences. Using extensive sequence data we have reconstructed the global space-time transmission history of the O/ME-SA/Ind-2001 lineage (which normally circulates in the Indian sub-continent) providing evidence of at least 15 independent escapes during 2013-2017 that have led to outbreaks in North Africa, the Middle East, Southeast Asia, the Far East and the FMD-free islands of Mauritius. We demonstrated that sequence heterogeneity of this emerging FMDV lineage is accommodated within two co-evolving divergent sublineages and that recombination by exchange of capsid-coding sequences can impact upon the reconstructed evolutionary histories. Thus, we recommend that only sequences encoding the outer capsid proteins should be used for broad-scale phylogeographical reconstruction. These data emphasise the importance of the Indian subcontinent as a source of FMDV that can spread across large distances and illustrates the impact of FMDV genome recombination on FMDV molecular epidemiology.

Systematic literature review of Rift Valley fever virus seroprevalence in livestock, wildlife and humans in Africa from 1968 to 2016.

BACKGROUND: Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes severe disease in livestock and humans. The virus has caused recurrent outbreaks in Africa and the Arabian Peninsula since its discovery in 1931. This review sought to evaluate RVFV seroprevalence across the African continent in livestock, wildlife and humans in order to understand the spatio-temporal distribution of RVFV seroprevalence and to identify knowledge gaps and areas requiring further research. Risk factors associated with seropositivity were identified and study designs evaluated to understand the validity of their results. METHODOLOGY: The Preferred Reporting of Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to produce a protocol to systematically search for RVFV seroprevalence studies in PubMed and Web of Science databases. The Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement guided the evaluation of study design and analyses. PRINCIPAL FINDINGS: A total of 174 RVFV seroprevalence studies in 126 articles fulfilled the inclusion criteria. RVFV seroprevalence was recorded in 31 African countries from 1968 to 2016 and varied by time, species and country. RVFV seroprevalence articles including either livestock and humans or livestock and wildlife seroprevalence records were limited in number (8/126). No articles considered wildlife, livestock and human seroprevalence concurrently, nor wildlife and humans alone. Many studies did not account for study design bias or the sensitivity and specificity of diagnostic tests. CONCLUSIONS: Future research should focus on conducting seroprevalence studies at the wildlife, livestock and human interface to better understand the nature of cross-species transmission of RVFV. Reporting should be more transparent and biases accounted for in future seroprevalence research to understand the true burden of disease on the African continent.

Foot-and-Mouth Disease in the Middle East Caused by an A/ASIA/G-VII Virus Lineage, 2015-2016.

Phylogenetic analyses of foot-and-mouth disease type A viruses in the Middle East during 2015-2016 identified viruses belonging to the A/ASIA/G-VII lineage, which originated in the Indian subcontinent. Changes in a critical antigenic site within capsid viral protein 1 suggest possible evolutionary pressure caused by an intensive vaccination program.