Spatiotemporal analysis of foot‐and‐mouth disease outbreaks in the Republic of Kazakhstan, 1955 – 2013

Foot‐and‐mouth disease (FMD ) poses a significant obstacle to international trade and economic development, and for that reason, FMD prevention, control and eradication are major goals guiding animal health policy in most countries. The purpose of this study was to conduct a retrospective spatiotemporal analysis of FMD outbreaks among livestock in the Republic of Kazakhstan (RK ) from 1955 to 2013. During that time, several FMD control strategies were implemented in RK , which culminated with the World Organization for Animal Health (OIE ) recognition of RK as a country that is FMD ‐free with partial vaccination (2015). Here, we describe and analyse the changes in spatial and temporal dynamics of FMD under different control strategies that were utilized as the country progressively moved towards eradication of the disease. A total number of 5,260 FMD outbreaks of serotype O and A (including the A₂₂ lineage) were recorded in the cattle, pig and small ruminant populations of RK during that period. We found that outbreaks occurred in spatiotemporal clusters only prior to 1970, which is before ring vaccination around outbreaks was first employed. This finding suggests that ring vaccination substantially reduced local spread and prevented large FMD epidemics in the country. Disease incidence steadily decreased after the implementation of ring vaccination and culling of infected animals, with spatiotemporal clusters only occurring as a result of an introduction of an antigenically distinct variant of serotype A. From 1955 to 1984, FMD outbreaks demonstrated two seasonal peaks of incidence in the spring and fall. In contrast, only the peak in spring was observed between 1984 and 2013. Quantitative knowledge on how different policy and alternative control strategies contributed to RK achieving FMD ‐free status could improve prospects for continued control in RK and inform control strategies in other FMD ‐endemic regions.     

Risk Factors for Foot‐and‐Mouth Disease in Tanzania, 2001–2006

We developed a model to quantify the effect of factors influencing the spatio‐temporal distribution of foot‐and‐mouth disease (FMD) in Tanzania. The land area of Tanzania was divided into a regular grid of 20 km × 20 km cells and separate grids constructed for each of the 12‐month periods between 2001 and 2006. For each year, a cell was classified as either FMD positive or negative dependent on an outbreak being recorded in any settlement within the cell boundaries. A Bayesian mixed‐effects spatial model was developed to assess the association between the risk of FMD occurrence and distance to main roads, railway lines, wildlife parks, international borders and cattle density. Increases in the distance to main roads decreased the risk of FMD every year from 2001 to 2006 (ORs ranged from 0.43 to 0.97). Increases in the distance to railway lines and international borders were, in general, associated with a decreased risk of FMD (ORs ranged from 0.85 to 0.99). Increases in the distance from a national park decreased the risk of FMD in 2001 (OR 0.80; 95% CI 0.68–0.93) but had the opposite effect in 2004 (OR 1.06; 95% CI 1.01–1.12). Cattle population density was, in general, positively associated with the risk of FMD (ORs ranged from 1.01 to 1.30). The spatial distribution of high‐risk areas was variable and corresponded to endemic (2001, 2002 and 2005) and epidemic (2003, 2004 and 2006) phases. Roads played a dominant role in both epidemiological situations; we hypothesize that roads are the main driver of FMD expansion in Tanzania. Our results suggest that FMD occurrence in Tanzania is more related to animal movement and human activity via communication networks than transboundary movements or contact with wildlife.     

Temporospatial Clustering of Foot‐and‐Mouth Disease Outbreaks in Israel and Palestine, 2006–2007

Foot‐and‐mouth disease (FMD) is endemic to the Middle East and there is a perception that political instability and limited resources have led to the uncontrolled circulation of FMD virus throughout the region. Certain aspects of FMD epidemiology in the Middle East remain unknown. The goal of this study was to identify the geographical location, temporal extent and direction of spread of clusters of 70 FMD outbreaks reported in Israel and Palestine from February 4, 2006, through July 15, 2007. The space–time permutation model of the scan statistic test detected nine significant (P < 0.1) clusters. Significant (P < 0.05) direction of spread was identified in four of the nine clusters. The Gaza Strip, where no outbreaks were reported, or a nearby location, seemed to be the origin of a cluster of outbreaks located in Hadarom (April 2007); a cluster of outbreaks centered in West Bank (February 2006) may be linked with spread from Northern Israel; a cluster in Hazafon (January 2007) seemed to have originated from nearby the Jordan borders; and a cluster located in Northern Hazafon was likely related to areas next to the Lebanon and Syrian borders. The association between the clusters in West Bank and earlier Israeli samples and between the cluster in Hazafon and Jordan was also supported (P < 0.05) by phylogenetic analysis of samples collected from the outbreaks. These results suggest that the FMD outbreaks reported in Israel and Palestine in 2006 and 2007 were likely a consequence of different epidemics associated with the circulation and spread of FMD virus strains from different regions of the Middle East.     

Financial Impacts of Foot‐and‐Mouth Disease at Village and National Levels in Lao PDR

To assist policies on Foot‐and‐Mouth Disease (FMD) control in Laos and the Mekong region, the financial impact of recent outbreaks at village and national levels was examined. Village‐level impacts were derived from recent research on financial losses due to FMD per smallholder household and number of households with FMD‐affected livestock in the village. National‐level impacts of FMD were determined from examination of 2011–2013 FMD reported to the Lao Department of Livestock and Fisheries (DLF), with the 2011 epidemic reported separately due to the large number and size of outbreaks of FMD in that year. Estimates of the national financial impact of FMD were based on (i) total FMD financial losses at the village level and (ii) the costs of FMD responses and other related costs at the DLF, provincial and district levels where FMD was reported, but excluding the costs of revenue forgone. A Monte Carlo simulation was utilized to account for likelihood of FMD over‐ and under‐reporting. Foot‐and‐mouth disease was recorded in four provinces of Phonsaly, Bokeo, Xayyabouli and Champasak in three consecutive years from 2011 to 2013. However, the FMD epidemic in 2011 was more widely distributed and involved 414 villages in 14 provinces, with thousands of cases of morbidity in cattle and buffalo and some mortalities. The estimated financial losses due to FMD in 2011 were USD 30 881(±23 176) at the village level and USD 13 512 291 at the national level based on the number of villages with FMD outbreaks reported. However, when the likelihood of FMD under‐reporting was accounted for, the estimated financial losses at the national level could potentially increase to USD 102 094 464 (±52 147 261), being almost 12% of the estimated farm gate value of the national large ruminant herd. These findings confirm that FMD causes substantial financial impacts in villages and to the national economy of Laos, providing justification for sustained investments in FMD control programmes.     

Spatio‐temporal patterns of foot‐and‐mouth disease transmission in cattle between 2007 and 2015 and quantitative assessment of the economic impact of the disease in Niger

Foot‐and‐mouth disease (FMD ) is endemic in Niger, with outbreaks occurring every year. Recently, there was an increasing interest from veterinary authorities to implement preventive and control measures against FMD . However, for an efficient control, improving the current knowledge on the disease dynamics and factors related to FMD occurrence is a prerequisite. The objective of this study was therefore to obtain insights into the incidence and the spatio‐temporal patterns of transmission of FMD outbreaks in Niger based on the retrospective analysis of 9‐year outbreak data. A regression tree analysis model was used to identify statistically significant predictors associated with FMD incidence, including the period (year and month), the location (region), the animal‐contact density and the animal‐contact frequency. This study provided also a first report on economic losses associated with FMD . From 2007 to 2015, 791 clinical FMD outbreaks were reported from the eight regions of Niger, with the number of outbreaks per region ranging from 5 to 309. The statistical analysis revealed that three regions (Dosso, Tillabery and Zinder), the months (September, corresponding to the end of rainy season, to December and January, i.e., during the dry and cold season), the years (2007 and 2015) and the density of contact were the main predictors of FMD occurrence. The quantitative assessment of the economic impacts showed that the average total cost of FMD at outbreak level was 499 euros, while the average price for FMD vaccination of one outbreak was estimated to be more than 314 euros. Despite some limitations of the clinical data used, this study will guide further research into the epidemiology of FMD in Niger and will promote a better understanding of the disease as well as an efficient control and prevention of FMD .     

Foot‐and‐Mouth Disease Virus Serotype O Phylodynamics: Genetic Variability Associated with Epidemiological Factors in Pakistan

One of the most challenging aspects of foot‐and‐mouth disease (FMD) control is the high genetic variability of the FMD virus (FMDV). In endemic settings such as the Indian subcontinent, this variability has resulted in the emergence of pandemic strains that have spread widely and caused devastating outbreaks in disease‐free areas. In countries trying to control and eradicate FMD using vaccination strategies, the constantly evolving and wide diversity of field FMDV strains is an obstacle for identifying vaccine strains that are successful in conferring protection against infection with field viruses. Consequently, quantitative knowledge on the factors that are associated with variability of the FMDV is prerequisite for preventing and controlling FMD in the Indian subcontinent. A hierarchical linear model was used to assess the association between time, space, host species and the genetic variability of serotype O FMDV using viruses collected in Pakistan from 2005 to 2011. Significant (P < 0.05) amino acid and nucleotide variations were associated with spatial distance, but not with differences in host species, which is consistent with the frequent multi‐species infection of this serotype O FMDV. Results from this study will contribute to the understanding of FMDV variability and to the design of FMD control strategies in Pakistan. Viruses sequenced here also provide the earliest reported isolate from the Pan Asia II^ANT‐10 sublineage, which has caused several outbreaks in the Middle East and spread into Europe (Bulgaria) and Africa (Libya).     

Incursions of Foot‐and‐Mouth Disease Virus into Europe between 1985 and 2006

Foot‐and‐mouth disease (FMD) is one of the biggest threats to animal health in European countries. In the last 22 years (1985–2006), FMD has occurred 37 times in 14 European countries. Serotype O was most frequently involved in these outbreaks followed by A, C and Asia 1. Sometimes, epidemics were very limited and at other times, they were the cause of devastating economic losses. In most cases (22/37), the origin of the outbreaks could not be determined. For some of these outbreaks, however, routes of introduction and spread were identified through epidemiological inquiries. Moreover, in some cases, the origin of the virus was also traced by phylogenetic analysis of the partial or complete sequences of VP1 genes. Lessons learned from the outbreaks are still useful as most of the same risk factors persist. However, efforts made by FMD‐free countries to help those where the disease is endemic are a valuable strategy for the reduction of the global risk. The present and the future potential sources of FMD infection need to be identified to best focus European efforts.     

Foot‐and‐Mouth Disease Seroprevalence in Cattle in Eritrea

Information about seroprevalence of foot‐and‐mouth disease (FMD) and virus serotypes in Eritrea is unavailable, but is very important as it may guide the choice of intervention measures including vaccination to be implemented. We carried out a cross‐sectional study from February to June 2011 in Eritrea with a two‐stage cluster design, sampling cattle in 155 villages with the objective of determining the seroprevalence of FMD in four administrative regions of the country. We analysed cattle sera (n = 2429) for FMD virus antibodies using the non‐structural ELISA (NS ELISA) and virus neutralization test (VNT). The overall seroprevalence was 26% and 30% for the NS ELISA and VNT, respectively. FMD virus serotypes O (14%) and A (11%) were the most prevalent. Gash Barka showed the highest (39%) seroprevalence both in NS ELISA and VNT compared to the other three administrative regions. Strategic FMD virus vaccination with type O and A (matching circulating strains) in combination of zoo‐sanitary measures would be the best control option for Eritrea which could be started in areas where the disease is less endemic.     

Direct detection and characterization of foot‐and‐mouth disease virus in East Africa using a field‐ready real‐time PCR platform

Effective control and monitoring of foot‐and‐mouth disease (FMD ) relies upon rapid and accurate disease confirmation. Currently, clinical samples are usually tested in reference laboratories using standardized assays recommended by The World Organisation for Animal Health (OIE ). However, the requirements for prompt and serotype‐specific diagnosis during FMD outbreaks, and the need to establish robust laboratory testing capacity in FMD ‐endemic countries have motivated the development of simple diagnostic platforms to support local decision‐making. Using a portable thermocycler, the T‐COR ™ 8, this study describes the laboratory and field evaluation of a commercially available, lyophilized pan‐serotype‐specific real‐time RT ‐PCR (rRT ‐PCR ) assay and a newly available FMD virus (FMDV) typing assay (East Africa‐specific for serotypes: O, A, Southern African Territories [SAT ] 1 and 2). Analytical sensitivity, diagnostic sensitivity and specificity of the pan‐serotype‐specific lyophilized assay were comparable to that of an OIE ‐recommended laboratory‐based rRT ‐PCR (determined using a panel of 57 FMDV ‐positive samples and six non‐FMDV vesicular disease samples for differential diagnosis). The FMDV ‐typing assay was able to correctly identify the serotype of 33/36 FMDV ‐positive samples (no cross‐reactivity between serotypes was evident). Furthermore, the assays were able to accurately detect and type FMDV RNA in multiple sample types, including epithelial tissue suspensions, serum, oesophageal–pharyngeal (OP ) fluid and oral swabs, both with and without the use of nucleic acid extraction. When deployed in laboratory and field settings in Tanzania, Kenya and Ethiopia, both assays reliably detected and serotyped FMDV RNA in samples (n  = 144) collected from pre‐clinical, clinical and clinically recovered cattle. These data support the use of field‐ready rRT ‐PCR platforms in endemic settings for simple, highly sensitive and rapid detection and/or characterization of FMDV.     

Characteristics of Foot‐and‐Mouth Disease Viral Strains Circulating at the Wildlife/livestock Interface of the Great Limpopo Transfrontier Conservation Area

Foot‐and‐mouth disease (FMD) inflicts severe economic losses within infected countries and is arguably the most important trade‐restricting livestock disease in the world. In southern Africa, infected African buffaloes (Syncerus caffer) are the major reservoir of the South African Territories (SAT) types of the virus. With the progressive expansion of transfrontier conservation areas (TFCAs), the risk of FMD outbreaks is expected to increase due to a higher probability of buffalo/livestock contacts. To investigate the dynamics of FMD within and around the Great Limpopo TFCA (GLTFCA), 5 herds of buffaloes were sampled in June 2010 to characterize circulating viruses in South Africa and Zimbabwe. Three SAT‐2 and three SAT‐3 viral strains were isolated in both countries, including one that was genetically linked with a recent SAT‐2 outbreak in Mozambique in 2011. In addition, two groups of unvaccinated cattle (n = 192) were serologically monitored for 1 year at the wildlife/livestock interface of Gonarezhou National Park (GNP) in Zimbabwe between April 2009 and January 2010, using the liquid‐phase blocking ELISA (LPBE) and a test for antibodies directed against non‐structural proteins (NSP). Neither clinical signs nor vaccination of cattle were reported during the study, yet a high proportion of the monitored cattle showed antibody responses against SAT‐3 and SAT‐1. Antibodies against NSP were also detected in 10% of the monitored cattle. The results of this study suggest that cattle grazing in areas adjacent to the GLTFCA can be infected by buffalo or other infected livestock and that cattle trade movements can act as efficient disseminators of FMD viruses to areas several hundred kilometres from the virus source. Current methods of surveillance of FMD at the GLTFCA interface seem insufficient to control for FMD emergence and dissemination and require urgent reassessment and regional coordination.     

Serotype Specificity of Antibodies against Foot‐and‐Mouth Disease Virus in Cattle in Selected Districts in Uganda

Uganda had an unusually large number of foot‐and‐mouth disease (FMD) outbreaks in 2006, and all clinical reports were in cattle. A serological investigation was carried out to confirm circulating antibodies against foot‐and‐mouth disease virus (FMDV) by ELISA for antibodies against non‐structural proteins and structural proteins. Three hundred and forty‐nine cattle sera were collected from seven districts in Uganda, and 65% of these were found positive for antibodies against the non‐structural proteins of FMDV. A subset of these samples were analysed for serotype specificity of the identified antibodies. High prevalences of antibodies against non‐structural proteins and structural proteins of FMDV serotype O were demonstrated in herds with typical visible clinical signs of FMD, while prevalences were low in herds without clinical signs of FMD. Antibody titres were higher against serotype O than against serotypes SAT 1, SAT 2 and SAT 3 in the sera investigated for serotype‐specific antibodies. Only FMDV serotype O virus was isolated from one probang sample. This study shows that the majority of the FMD outbreaks in 2006 in the region studied were caused by FMDV serotype O; however, there was also evidence of antibodies to both SAT 1 and SAT 3 in one outbreak in a herd inside Queen Elizabeth national park area.     

Foot‐and‐mouth disease outbreaks in captive scimitar‐horned oryx (Oryx dammah)

This paper describes three episodes of foot‐and‐mouth disease (FMD) that were detected during 2013–2015 in scimitar‐horned oryx (Oryx dammah) (SHO), a large Sahelo‐Saharan antelope extinct in the wild housed in a wild ungulate breeding facility located 50 km east of Abu Dhabi, United Arab Emirates. While no mortality attributable to FMD was noted in the population of nearly 4,000 SHO during two of the three outbreaks, the morbidity varied according to the circulating strains and seroconversion reached a plateau of 78.0% within two weeks and remained at this level for at least nine months. Partial or complete sequencing of the VP1 encoding region demonstrated that the three outbreaks were caused by three different FMDV lineages (O/ME‐SA/PanAsia‐2, A/ASIA/Iran‐05 and O/ME‐SA/Ind‐2001), consistent with FMD viruses that are circulating elsewhere in the region. These findings demonstrate that SHO are susceptible to FMD and highlight the risks of virus incursion into zoos and captive facilities in the Arabian Peninsula.     

Outbreak investigations and molecular characterization of foot‐and‐mouth disease viruses circulating in south‐west Niger

In Niger, the epidemiological situation regarding foot‐and‐mouth disease is unclear as many outbreaks are unreported. This study aimed (i) to identify Foot‐and‐mouth disease virus (FMDV ) strains currently circulating in cattle herds, and (ii) to identify risk factors associated with Foot‐and‐mouth disease (FMD )‐seropositive animals in clinical outbreaks. Epithelial tissues (n  = 25) and sera (n  = 227) were collected from cattle in eight districts of the south‐western part of Niger. Testing of clinical material revealed the presence of FMDV serotype O that was characterized within the O/WEST AFRICA topotype. The antigenic relationship between one of the FMDV isolates from Niger (O/NGR /4/2015) and three reference vaccine strains was determined by the two‐dimensional virus neutralization test (2dmVNT ), revealing a close antigenic match between the field isolate from Niger and three FMDV serotype O vaccine strains. Serological analyses using a non‐structural protein (NSP ) test provided evidence for previous FMDV infection in 70% (158/227) of the sera tested. Multivariate logistic regression analysis revealed that only the herd composition (presence of both cattle and small ruminants) was significantly associated with FMDV seropositivity as defined by NSP ‐positive results (p ‐value = .006). Of these positive sera, subsequent testing by liquid‐phase blocking ELISA (LPBE ) showed that 86% (136/158) were positive for one (or more) of four FMDV serotypes (A, O, Southern African Territories (SAT ) 1 and SAT 2). This study provides epidemiological information about FMD in the south‐western part of Niger and highlights the complex transboundary nature of FMD in Africa. These findings may help to develop effective control and preventive strategies for FMD in Niger as well, as other countries in West Africa.     

Herd Immunity Against Foot‐and‐Mouth Disease Under Different Vaccination Practices in India

A systematic vaccination programme is ongoing in India to control the three prevailing serotypes (A, O, Asia1) of foot‐and‐mouth disease (FMD) virus. Under the programme, more than 120 million bovine (term bovine applicable to both cattle and buffalo in this study) population of 221 of the 666 districts in the country are being bi‐annually vaccinated with trivalent vaccine since 2010. Although clinical disease has reduced in these districts because of the systematic vaccinations, an abrupt increase in the number of FMD cases was recorded in 2013. Hence, a longitudinal field study was conducted in the year 2014 to estimate the serological herd immunity level in bovines, the impact of systematic vaccinations and field efficacy of the vaccines used. Serum samples (n = 115 963) collected from 295 districts of the 18 states of the country were analysed to estimate antibody titres against structural proteins of the three serotypes. The efficacy of the vaccine was demonstrated in the control group (group‐D) where animals of the group were identified by ear tags for the purpose of repeated sampling after vaccination. Progressive building of the herd immunity in the field after systematic vaccination was demonstrated. The mean antibody titre against the serotypes O, A and Asia1 was estimated as log₁₀ 1.93 (95% CI 1.92–1.93), 2.02 (2.02–2.02) and 2.02 (2.02–2.02), respectively, in the states covered under the control programme. However, in other states herd immunity was significantly low [mean titre log₁₀ 1.68 (95% CI 1.67–1.69), 1.77 (1.76–1.78) and 1.85 (1.84–1.86) against the three serotypes]. Inverse relationship between the herd immunity and FMD incidences was observed the states following different vaccination practices. The study helped in demarcation of FMD risk zones in the country with low herd immunity. Estimation of herd immunity kinetics in the field helped in refining the vaccination schedule under the control programme.     

Analysis of Recent Serotype O Foot‐and‐Mouth Disease Viruses from Livestock in Kenya: Evidence of Four Independently Evolving Lineages

Foot‐and‐mouth disease (FMD) is endemic in Kenya where four serotypes (O, A, SAT 1 and SAT 2) of the virus are currently in circulation. Within 2010 and 2011, the National Laboratory recorded an increase in the number of FMD outbreaks caused by serotype O virus. The characteristics of these viruses were determined to ascertain whether these were independent outbreaks or one single strain spreading throughout the country. The sequences of the complete VP1‐coding region were analysed from viruses sampled within different areas of Kenya during 2010 and 2011. The results indicated that the 2010 to 2011 outbreaks in Kenya were caused by four independent strains. By comparison with earlier type O isolates from Eastern Africa, it was apparent that the outbreaks were caused by viruses from three different lineages of topotype EA‐2 and a fourth virus strain belonging to topotype EA‐4. The topotypes EA‐1 and EA‐3 were not detected from these outbreaks. Implications of these results for FMD control in Eastern Africa are discussed.     

Isolation,identification and retrospective study of foot‐and‐mouth disease virus from affected Mithun (Bos frontalis) in north‐eastern India

Foot‐and‐mouth disease (FMD ) is a contagious disease of cloven‐hoofed animals that causes substantial and perpetual economic loss. Apart from the contagious nature of the disease, the FMD virus can establish in a “carrier state” among all cloven‐hoofed animals. The Mithun (Bos frontalis ), popularly called the “Cattle of Mountain,” is found in the geographically isolated, hilly region of north‐east India: Arunachal Pradesh, Nagaland, Manipur and Mizoram. Despite the geographical inaccessibility, infection by FMD virus has emerged as the single most devastating disease among Mithun after the eradication of rinderpest from this region. Samples from outbreaks of FMD in Mithun were analysed by sandwich ELISA , multiplex RT ‐PCR (MRT ‐PCR ) and liquid‐phase blocking enzyme‐linked immunosorbent assay and isolated in the BHK ‐21 cell line. The results indicate the presence of FMDV serotype “O.” The sequencing and molecular phylogenies have revealed close relationships in the lineage of type “O” isolates from Bangladesh. The findings will provide useful information for further research and development of a sustainable programme for the progressive control of FMD in the Mithun population.