Foot-and-mouth disease virus (FMDV), a member of the Aphthovirus genus in the Picornaviridae family, poses a threat to livestock worldwide. This is because of its highly contagious nature, rapid transmission, leading to severe economic consequences. FMDV is a genetically diverse virus with an 8.5 Kb single-stranded RNA genome, structurally basic and lacks an envelope, and its icosahedral capsid is made up of the VP1, VP2, VP3, and VP4 proteins. Of these, VP1 is the most variable, containing critical immunogenic epitopes that are essential for eliciting protective immunity against the virus [1]. FMDV is classified into seven distinct serotypes (A, C, O, Asia1, and South African Territories [SAT] 1, SAT2, and SAT3), each of which is further subdivided into topotypes based on the VP1 sequence analysis, reflecting distinct geographical distributions and evolutionary trajectories [2]. These topotypes are based on the inherent genetic variability of the FMDV [2]. The most common serotypes are A and O, which have been reported in South America, Africa, and Asia. Currently, Africa is home to SAT1 and SAT3, while Asia 1 is found exclusively on the Asian continent. Additionally, serotype C has not caused any outbreaks since it was initially identified in Kenya and Brazil in 2004 [2]. Serotype SAT2 is particularly significant due to its ongoing presence and epidemiological impact in various regions, primarily within Africa and parts of the Middle East. SAT2 is one of the three South African Territories (SAT) serotypes, along with SAT1 and SAT3, and has been responsible for numerous outbreaks across sub-Saharan Africa [3, 4]. Unlike SAT1 and SAT3, SAT2 has exhibited a broader geographical spread and has been detected outside of Africa. Notably, SAT2 has caused outbreaks in countries like Egypt, Libya, and the wider Middle East, illustrating its ability to transcend the traditional geographic boundaries of the SAT serotypes [3, 4]. The persistence of SAT2 in endemic regions, particularly within the African wildlife-livestock interface, makes control challenging, as the virus can circulate within wildlife populations, notably African buffalo, and spill over into domestic livestock [3]. The genetic diversity within the SAT2 serotype, reflected in its multiple topotypes, complicates vaccine development and the establishment of herd immunity in affected areas. Therefore, while SAT1 and SAT3 remain largely confined to southern Africa, SAT2’s epidemiological impact extends to both Africa and neighboring regions, underscoring the importance of vigilance and control efforts to mitigate its spread.

Foot-and-mouth disease (FMD) is one of the most serious diseases impacting animals worldwide affecting around 70 species with cloven hooves, such as pigs, cattle, sheep, goats, and African buffaloes [5]. Typical FMD symptoms include fever, decreased appetite, and the formation of distinctive blisters on the feet, udders, and oral cavity [6]. Even with low mortality rates, high morbidity has a significant economic impact due to reduced production and the enforcement of trade restrictions and regional quarantine measures [7]. FMD spreads via inhaling viral particles or direct contact with infected animals’ breath. Furthermore, transmission can occur through contaminated environments, where FMDV can survive for extended periods under favorable conditions [8].

Egypt has a high prevalence of FMD; cases involving serotypes O, A, and SAT2 have been reported across the country [1, 8, 9]. Egypt first reported FMD in 1950 when serotype SAT2 first emerged. After going missing for 62 years, SAT2 emerged in 2012 causing significant losses [10]. Egypt’s SAT2 strains have been linked to the 2012 Libyan strain based on the phylogenomics and were responsible for the catastrophic outbreaks in 2018. In Egypt, serotype SAT2 is classified as topotype VII, clustering within the Alx-12 and Ghb-12 lineages [11]. Moreover, serotype O has predominant since its first report in 1951, exhibiting multiple topotypes such as the Middle East-South Asian (ME-SA) and East Africa-3 (EA-3). EA-3 first reported in 2012 and become endemic [12]. Serotype A outbreaks began in 1953, escalating in 2006 resulting in high economic losses. In Egypt, serotype A topotypes from both Asia and Africa have been reported [13, 14].

The Asian topotype of serotype A, referred to as Iran-05, was prevalent until 2010 and continued its circulation until 2015 [12, 15]. Subsequently, the African topotype emerged in early 2012, leading to the introduction of the A-Africa topotype G-IV, and continued to cause outbreaks in 2016, 2018, and 2020 [14, 16]. In 2022, routine surveillance in a single Egyptian farm identified a novel strain of FMDV serotype A, belonging to the EURO-SA lineage with genetic relationship to reported sequences identified in Venezuela and Colombia [17]. In addition, a mutant strain of FMDV/A classified as African type G-IV was reported in 2022 exhibiting a 9.3% difference in the nucleotide sequences compared to previously reported strains in 2020 [18]. These sequences were linked to the African topotype of FMD serotype A, which originated from the prototype Sudan/77 with 98.48% ± 1.2% similarity [18].

Foot-and-mouth disease (FMD) is categorized as an enzootic disease in Egypt, signifying its consistent presence within the population and its recurring nature at frequent intervals. The country is still grappled with FMD outbreaks even after deployment of various commercial vaccines. An important note is that FMD strains that are currently circulating in Egypt have been introduced by the annual importation of cattle from neighboring countries (Ethiopia, Sudan, and Somalia) [19]. There is a significant risk of introducing new variants when importing animals from areas where FMD is endemic or where various FMD lineages are prevalent, spreads to Egyptian livestock, leading to epidemics [19].

Effective management and control of foot-and-mouth disease (FMD) in Egypt requires not only the implementation of vaccination strategies but also the control of animal movements and strict biosecurity measures, monitoring the imported animals, surveillance, and collaboration with neighboring countries [20]. Through comprehensive FMD monitoring systems, widespread vaccination campaigns, and strict enforcement of biosecurity regulations, Egypt has been actively working to manage and eventually eradicate the FMD. Even in areas where vaccination campaigns are regularly conducted, occasional outbreaks still occur, despite the fact that the implementation of these control measures has resulted in a significant reduction in FMD cases. Therefore, a comprehensive strategy for FMD control and eradication must include efforts to improve the vaccination efficacy, detect and manage carriers, and strict the biosecurity measures. Egypt has implemented a comprehensive program to control the FMD, which includes vaccination using locally manufactured inactivated vaccines targeting multiple FMDV serotypes. These vaccines are tailored especially to match the virus strains that are common in particular regions [21]. However, because of RNA replication errors and inter-serotype recombination, the genetic diversity of FMDV among its seven serotypes poses a challenge [13]. Therefore, the purpose of this study is to isolate, identify, and characterize new FMDV strains by molecular means in Egyptian cattle between 2022 and 2023. This study aims to isolate, identify, and molecularly characterize the latest FMDV strains circulating in the Egyptian cattle between 2022 and 2023. This will help to improve disease surveillance, inform more targeted vaccination strategies, and promote regional cooperation for efficient FMD control and prevention.