Saeed et al. Journal of Animal Science and Technology (2015) 57:10 DOI 10.1186/s40781-015-0042-8 REVIEW Open Access Foot-and-mouth disease: overview of motives of disease spread and efficacy of available vaccines Ali Saeed1†, Sehrish Kanwal1, Memoona Arshad2, Muhammad Ali1, Rehan Sadiq Shaikh1 and Muhammad Abubakar3*† Abstract Control and prevention of foot and mouth disease (FMD) by vaccination remains unsatisfactory in endemic countries. Indeed, consistent and new FMD epidemics in previously disease-free countries have precipitated the need for a worldwide control strategy. Outbreaks in vaccinated animals require that a new and safe vaccine be developed against foot and mouth virus (FMDV). FMDV can be eradicated worldwide based on previous scientific information about its spread using existing and modern control strategies. Keywords: Attenuated virus, Foot-and-mouth disease, In-activated virus, Recombinant virus, Transgenic vaccines Introduction serotypes are additional challenges associated with con- Foot-and-mouth disease (FMD) is one of the most eco- ventional inactivated vaccines [8]. nomically and socially devastating diseases affecting Recently, transgenic vaccines were demonstrated as a cloven-hoofed livestock worldwide. It is caused by a novel and safe strategy for the control and prevention of highly variable RNA virus with seven serotypes (A, O, C, FMD. Specifically, animal fodder-based edible transgenic Asia 1, SAT 1, SAT 2, and SAT 3) and a large number of vaccines containing protein-expressing viral genomes are topotypes [1]. Millions of animals are sacrificed every year feasible to immunize animals. Many studies have sug- worldwide under FMDV eradication programmes [2]. gested that FMD plant-derived edible vaccines will be- FMDV has continuously circulated ever since after the come common within the next few years [9]. first outbreak in America in 1870 [3,4]. Further, new sub- types of FMDV are continuously evolving due to an infin- Review ite mutation rate in the RNA genome of the virus [5]. Continent disease spread Over the last few decades, disease-free countries have pri- Control of FMD is difficult due to variations in viral marily adopted the strategy of slaughtering carrier animals serotype and consistency, effectiveness of control mea- combined with transport restrictions and other sanitary sures, and emergence of new subtypes. FMD outbreaks measures. Additionally, rapid vaccination is applied to limit also originate from transportation of carrier animals to thespreadofinfectioninoutbreakregions[6,7]. susceptible populations or disease-free regions. More- Currently, inactivated vaccines are used as a major tool over, prevalence of FMD increases due to seasonal or in FMD eradication programmes in Europe as well as periodic cycling, host susceptibility, and predisposal to other parts of the world. However, these vaccines have a epizootic risk [10]. There are still many gaps in our un- number of limitations such as propagation of virulent derstanding of FMD, especially in Asian countries. Rapid virus, threat of virus escape from manufacturing sites, investigation of outbreaks samples and interpretation of limited shelf-life, and booster injection requirement after data are made possible due to recent development of 4–12 months [8]. Sterility, safety, cost-effectiveness, easy tools and techniques. Independent and collaborative delivery, and long-lasting immunity against multiple works by various national animal health services, key control initiatives, laboratory networks, and many other * Correspondence: [email protected] groups have improved our knowledge of FMD [10]. †Equal contributors 3National Veterinary Laboratory, Park Road, Islamabad, Pakistan Many countries have obtained FMD-free status from Full list of author information is available at the end of the article the International Organization of Animal Health (OIE) © 2015 Saeed et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Saeed et al. Journal of Animal Science and Technology (2015) 57:10 Page 2 of 7 with or without vaccination. However, FMD has ree- Major causes of FMD spread in Asian/developing countries merged in previously disease-free countries due to in- Asian countries suffering from FMD outbreaks often lack creased viral escape from vaccinated animals and import coordinated or serious mandatory measures for control of of animal products from FMDV-circulating countries. this disease. Further, movement and exchange of animals Many countries have maintained their disease-free status and animal products across neighboring countries are very by strict monitoring and culling of infected animals common. The amount of FMD vaccines produced locally [11,12]. The southern part of South America achieved is insufficient to fulfill the demands of large populations of FMD-free status from the OIE in the late 1990s with the animals in developing countries [5,15,16]. Moreover, FMD help of a strict eradication program, and other countries outbreaks among vaccinated animals in this region may be such as Uruguay, Argentina, Paraguay, and Brazil due to poor vaccine quality, lack of knowledge of circulat- achieved FMD-free status via vaccination in 1994, 1997, ing subtypes, and suboptimal vaccination strategies such 1997, and 1998, respectively [13]. as single vaccine injection without any booster [15]. Recently, FMD has reemerged in Japan and South Korea. Japan first achieved FMD-free status without vac- Virus distribution cination in 2000, and FMD O serotype has not been re- Serotypes O, A, and Asia 1 are continuously circulating ported in Mongolia and Russia since 2003 and 2004, in many FMD endemic countries in Asia, Europe, and as respectively. In 2010, FMD serotype A and O outbreaks well as Africa. Moreover, serotype C was reported in the were reported in South Korea and Japan, respectively. Philippines in 1995, whereas SAT 1, 2, and 3 are com- However, FMD A outbreak in South Korea was con- mon in African countries. Recently, disease-reporting trolled by March 2010 while the FMD O outbreak in transparency has improved due to increased field sur- Japan was controlled by June 2010 [12]. FMD outbreaks veillance, outbreak investigation, and submission of virus of serotype O continue to pose a threat to livestock in- samples for analysis by central reference laboratories dustries in this region (Table 1) [14]. such as the World Reference Laboratory (WRL) and FAO/OIE Reference Laboratory. However, efforts are still insufficient for comprehensive control and complete Table 1 Countries with FMD free status in 2011 according disease eradication [10,17]. to OIE [12] Albania Germany New Caledonia Serotype O Australia Greece New Zealand FMDV serotype O is the predominant serotype of FMD Austria Guatemala Nicaragua worldwide. It is the most prevalent serotype in many Belarus Guyana Norway parts of Africa, the Middle East such as Pakistan, and Belgium Haiti Panama some parts of Europe. However, an accurate genetic ex- planation for the higher prevalence of O serotype is not Belize Honduras Poland yet available [18,19]. Serotype O has been responsible Bosnia and Herzegovina Hungary Portugal for severe disease outbreaks in Taiwan, Korea, Pakistan, Brunei Iceland Romania Iran, Afghanistan, Israel, China, North Korea, and Bulgaria Canada Indonesia San Marino [17,20,21]. O1Manisa vaccine has been proven to be a ro- Chile Ireland Serbia bust immune dominant strain in many FMD O outbreaks, Costa Rica Italy Singapore but it still does not protect against all epidemics. More- over, several other O serotype vaccines have been used to Croatia Japan Slovakia improve vaccine efficacy for circulating outbreaks [10]. Cuba Latvia Slovenia Cyprus Lesotho Spain Serotype A Czech Rep. Lithuania Swaziland Members of this serotype show high antigenic diversity Denmark Luxembourg Sweden and no cross-protection between strains [16,22-24]. Dominican Republic Madagascar Switzerland Genetic recombination is more common in serotype A than in other serotypes of FMD [25,26]. Serotype A is El Salvador Malta Ukraine prevalent in ruminant populations of Thailand and Estonia Mauritius United Kingdom Malaysia. The most recent outbreaks of serotype A were Finland Mexico United States reported in Pakistan, Turkey, Egypt, India, China, and of America South Korea. Serotype A has been successfully con- Former Yug. Rep. Montenegro Vanuatu trolled and eradicated in South Korea [17]. Different of Macedonia vaccines for serotypes A confer variable levels of protec- France Netherlands tion. A Iran-05, A22 Iraq, and A24Cruzeiro serotypes Saeed et al. Journal of Animal Science and Technology (2015) 57:10 Page 3 of 7 were found to be very useful as vaccines against serotype Virus immune response and vaccines A [10,17]. Insufficient FMDV immunity can be attributed to the epitope between amino acids 140 to 160 having affinity Serotype Asia 1 for only B lymphocytes and not T lymphocytes. Identifi- Serotype Asia 1 is the most antigenically stable serotype cation of T lymphocyte-stimulating epitopes is thus a re- and shows relatively low levels of antigenic variation, al- quirement