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Hand, foot, and mouth disease: a case report.

Hand, foot, and mouth disease is a viral infection related to coxsackieviruses A5, A6, A9, and A10, coxsackieviruses B2 and B5, and echovirus 11. It generally affects children, but this article presents a clinical case of a young woman with hand, foot, and mouth disease. Patients with this disease have oral and skin lesions that may be confused with other diseases. The differential diagnosis is very important because both dental and medical professionals may misdiagnose the disease and sometimes prescribe an inappropriate medication.

Adult↗

Models of foot-and-mouth disease.

During the 2001 foot-and-mouth disease outbreak in the UK, three very different models were used in an attempt to predict the disease dynamics and inform control measures. This was one of the first times that models had been used during an epidemic to support the decision-making process. It is probable that models will play a pivotal role in any future livestock epidemics, and it is therefore important that decision makers, veterinarians and farmers understand the uses and limitations of models. This review describes the utility of models in general before focusing on the three foot-and-mouth disease models used in 2001. Finally, the future of modelling is discussed, analysing the advances needed if models are to be successfully applied during any subsequent epidemics.

Animals↗

Development and performance of inactivated vaccines against foot and mouth disease.

The historical background of foot and mouth disease (FMD) vaccine production is briefly described. Improvements achieved through the use of monolayer and suspension cultures are outlined. Elements that are crucial in the production of modern vaccines are discussed, such as inactivation of viral antigen, successive concentration and purification of the antigen and the final formulation of the vaccine. Storage of concentrated antigen at ultra-low temperatures creates greater flexibility for the producer and has also enabled national and international organisations to establish vaccine banks. The purification of FMD viral antigens, including the removal of non-structural proteins (NSPs), enables the immune responses of vaccinated animals to be distinguished from the responses of animals infected with live FMD virus. Consequently, the combined use of purified vaccine and tests for the detection of antibodies against NSPs essentially provides a marker system to distinguish between vaccinated animals that subsequently become infected and those that have not. Bearing in mind the good record of modern vaccines in the control of outbreaks and the possibility of screening vaccinated herds for carriers, the author proposes that the OIE reconsider the differences between the requirements for regaining export status following the use of stamping-out as opposed to vaccination in outbreak situations.

Animals↗

International approach to eradication and surveillance for foot-and-mouth disease in the Americas.

Foot-and-mouth disease (FMD) was introduced into the Americas in 1870. At that time the disease was described simultaneously in the North coast of the United States of North America, the Province of Buenos Aires in Argentina, the central region of Chile, Uruguay, and South Brazil. At the beginning of the twentieth century the disease spread to the rest of Brazil, Bolivia, Paraguay, and Perú. In 1950 the disease was introduced into Venezuela, and in the same year to Colombia, and from there to Ecuador. The United States of America eradicated an outbreak of FMD in 1929. Outbreaks of FMD were also eradicated from Mexico in 1947 and from Canada in 1952. The last outbreak that occurred in Mexico in 1954 was also eradicated. In 1951 the Americas Animal Health Authorities decided to establish a Pan-American Foot-and-Mouth Disease Center (PANAFTOSA), initially as a special program within the American States Organization (OAS). The center was later transferred to the Pan-American Health Organization (PAHO). In the early 1970s PANAFTOSA developed a proposal for a continental surveillance system for vesicular diseases, which was approved by Agriculture Ministers at an International Meeting for FMD and Zoonoses (RICAZ). Since then, PANAFTOSA dedicated all efforts to collaborate with each country in the implementation of the system and to receive, analyze, and distribute a weekly report of vesicular diseases. The model was elaborated using coordinate grid maps, one for the South American Continent, others for each country in the region. The reports from each country consist of the grid location for any suspicious outbreak of vesicular disease. Using the information gathered during visits to the countries, as well as weekly reports, and by studying the most frequent animal movements within the region, PANAFTOSA developed a proposal for FMD eradication. This plan was approved by the Government of South America and implemented in cooperation with PANAFTOSA. The hemispheric plan for FMD eradication (PHEFA), has been implemented and today Chile and Uruguay are FMD free without vaccination; Argentina, Paraguay, and the states of Rio Grande do Sul and Santa Catarina in Brazil are also recognized by the OIE to be FMD Free, with vaccination. The use of the continental surveillance system is the main strategy for achieving the eradication of FMD in South America. At this time PANAFTOSA is working to improve the system, and to add other diseases indicated by the governments of the Americas.

Animals↗

Development of novel strategies to control foot-and-mouth disease: marker vaccines and antivirals.

Foot-and-mouth disease (FMD) is economically the most important viral-induced livestock disease worldwide. The disease is highly contagious and FMD virus (FMDV) replicates and spreads extremely rapidly. Outbreaks in previously FMD-free countries, including Taiwan, the United Kingdom, and Uruguay, and the potential use of FMDV by terrorist groups have demonstrated the vulnerability of countries and the need to develop control strategies that can rapidly inhibit or limit disease spread. The current vaccine, an inactivated whole virus preparation, has a number of limitations for use in outbreaks in disease-free countries. We have developed an alternative approach using a genetically engineered FMD subunit vaccine that only contains the portions of the viral genome required for virus capsid assembly and lacks the coding region for most of the viral nonstructural (NS) proteins including the highly immunogenic 3D protein. Thus, animals inoculated with this marker vaccine can readily be differentiated from infected animals using diagnostic assays employing the NS proteins not present in the vaccine and production of this vaccine, which does not contain infectious FMDV, does not require expensive high-containment manufacturing facilities. One inoculation of this subunit vaccine delivered in a replication-defective human adenovirus vector can induce rapid, within 7 days, and relatively long-lasting protection in swine. Similarly cattle inoculated with one dose of this recombinant vector are rapidly protected from direct and contact exposure to virulent virus. Furthermore, cattle given two doses of this vaccine developed high levels of FMDV-specific neutralizing antibodies, but did not develop antibodies against viral NS proteins demonstrating the ability of FMD subunit vaccinated animals to be differentiated from infected animals. To stimulate early protection prior to the vaccine-induced adaptive immune response we inoculated swine with the antiviral agent, type I interferon, and induced complete protection within 1 day. Protection can last for 3-5 days. The combination of the FMD marker vaccine and type I interferon can induce immediate, within 1 day, and long-lasting protection against FMD. Thus, this combination approach successfully addresses a number of concerns of FMD-free countries with the current disease control plan. By rapidly limiting virus replication and spread this strategy may reduce the number of animals that need to be slaughtered during an outbreak.

Adenoviruses, Human↗

Vaccines and foot-and-mouth disease eradication in South America.

Foot-and-mouth disease (FMD) vaccines have been a component of disease control and eradication strategies in South America ever since the first national programmes were created in the 1960s. By the mid 1970s, with the aid of international loans, FMD control programmes were implemented in almost every country and control measures strengthened. Livestock production forms are still a determining factor in the spread and prevalence of FMD and regional control/eradication strategies based on these forms were developed during the 1980s, as part of the Hemispheric Plan for FMD Eradication, developed by Panaftosa-PAHO/WHO and the South American countries. The widespread use of oil-adjuvant vaccines and the development of strategic schemes of coverage were instrumental in decreasing clinical disease and in controlling FMD to a point that eradication could be sought. This resulted in the recognition of countries and regions as free with and without vaccination Reappearance of FMD in Argentina, Southern Brazil and Uruguay were controlled with the aid of mass vaccination of bovines and other susceptible species, under special circumstances. Clinical FMD has been absent from Uruguay since August 2001; from Argentina since January 2002 and from Rio Grande do Sul, Brazil since July 2001. To prevent reintroduction of FMDV into free areas, national programmes must stress primary prevention activities with regional approaches and vaccination campaigns based on homogeneous coverage and timing, especially along international borders.

Animals↗

Foot and mouth disease: the experience of South Africa.

Foot and mouth disease (FMD) is endemic in African buffalo (Syncerus caffer) in the Kruger National Park (KNP) and surrounding game parks in South Africa. The last outbreak of the disease in domestic stock outside the FMD control zone occurred in 1957. Due to the success in containing the disease, the country was accorded zone freedom from FMD without vaccination by the Office International des Epizooties (OIE: World organisation for animal health) in 1995. This status was lost in September 2000 when the first-ever recorded case of serotype O in South Africa was diagnosed in a piggery in KwaZulu-Natal after the illegal feeding of untreated swill. In November 2000, an outbreak of FMD caused by serotype South African Territories (SAT) 1 was diagnosed in a feedlot within the free zone of Mpumalanga Province. The SAT 1 outbreak was traced to cattle in the FMD control zone south of the KNP after the game-proof fence surrounding the KNP was severely damaged by floods. This enabled buffalo to come into direct contact with cattle outside the KNP. A further outbreak caused by SAT 2 was diagnosed within the FMD control zone in February 2001, also as a result of buffalo having escaped from the KNP. All these outbreaks were successfully contained, with the re-instatement of zone freedom from FMD without vaccination by the OIE in May 2002. These outbreaks made it necessary to re-examine the methods of control and containment of FMD that have been practised for many years and which are in line with accepted international practices. The authors describe the rationale for the different control strategies that were followed, the need for a multidisciplinary approach to disease control, the interface between control and technological and diagnostic support and the lessons learned. Some suggestions for future control strategies are also offered.

Animals↗

The epidemiology of foot-and-mouth disease: implications for New Zealand.

Foot-and-mouth disease is an acute, highly communicable disease affecting cloven-hoofed animals, both domesticated and wild. It may well be the most contagious disease known in the animal kingdom. The key features that contribute to this include its ability to gain entry and initiate infection through a variety of sites, the small infective dose, the short incubation period, the release of virus before the onset of clinical signs, the massive quantities of virus excreted from infected animals, its ability to spread large distances due to airborne dispersal, and the persistence of the virus in the environment. These features, plus the ability of the virus to be disseminated through the movements of animals, animal products, people, and plant and equipment makes the disease very difficult to control. New Zealand has never experienced a foot-and-mouth disease epidemic, and the economic consequences of an outbreak would be disastrous, due to the eradication costs, the loss of productivity and the impact on the export of animals and animal products. The smuggling of meat products, embryos or semen into the country are perceived as the most likely ways in which the disease could be introduced. The New Zealand Ministry of Agriculture and Fisheries therefore operates a two-tier system of defense against foot-and-mouth disease. The first tier involves border protection through stringent import controls to prevent the entry of infectious material. If this barrier is breached, an emergency response programme is activated, involving a stamping-out eradication strategy. This paper attempts to draw on overseas historical outbreak experiences and research findings to gain insights into the epidemiology of foot-and-mouth disease as it would relate to New Zealand.

Journal Article↗

Observations on the carrier state and related antibody titres during an outbreak of foot-and-mouth disease.

An outbreak of foot-and-mouth disease in a partially immune population of cattle in Botswana is described. The results show that when cattle immunized by vaccination were presented with natural field challenge of FMD, many animals with immunity sufficient to protect them against clinical disease were, however, susceptible to pharyngeal infection and subsequently became virus carriers. The proportion of animals becoming carriers appeared to vary with the degree of severity of the challenge.Vaccination before exposure to virus appeared to have little effect on the duration of the carrier state. No evidence was obtained of the spread of carrier virus to immune herds following the outbreak.Antibody titres during the outbreak were higher in the clinically infected animals than in the carrier animals and the uninfected animals. Evidence suggested that natural challenge boosted the titres of immune animals. After the outbreak, however, it was not possible to distinguish by their antibody titres between the carrier animal and the virus-negative animal.Antigenic studies on the strains of virus isolated are described.

Animals↗

Future research on foot and mouth disease.

The recent outbreaks of foot and mouth disease (FMD) in Argentina, Europe, Japan, the Republic of Korea, South Africa and Uruguay have brought to world attention the devastating effects of the disease in a naïve population and the social and economic costs of control and eradication. The fact that much still remains unknown about the natural history of FMD virus came as a surprise to some. This paper attempts to identify where research should be directed in order to be better prepared in the future.

Animals↗

Foot-and-mouth disease: current world situation.

Foot-and-mouth disease (FMD) has increased in significance as a major constraint to international trade in live animals and animal products as the World Trade Organization agreements remove other obstructions. A consequence will be reluctance to immediately declare the presence of FMD if it is thought possible to quickly eliminate its presence and so avoid trade embargoes. This will predispose to spread of disease between trading partners. In addition, as countries tend to increase the requirements for testing and certification of imported animals with the objective of reducing the risk of importing disease, the increased costs and delays that this involves will encourage the illegal trade and therefore have the converse result.

Africa↗

Utility of automated real-time RT-PCR for the detection of foot-and-mouth disease virus excreted in milk.

Foot-and-mouth disease virus (FMDV) can be excreted in milk and thereby spread infection to susceptible animals in other holdings. The feasibility of using real-time reverse transcription polymerase chain reaction (rRT-PCR) as a diagnostic tool for detection of FMDV in milk was assessed by studying the excretion of virus from experimentally-infected cattle. Fore- and machine milk samples were collected over a 4-week period from two dairy cows infected with FMDV and from two in-contact cows held in the same pen. The whole, skim, cream and cellular debris components of the milks were tested by automated rRT-PCR and results compared to virus isolation (VI) in cell culture. The onset of clinical signs of FMD in all four cows correlated with viraemia, and the presence of FMDV in other clinical samples. rRT-PCR results matched closely with VI in detecting FMDV in all milk components and generally coincided with, but did not consistently precede, the onset of clinical signs. rRT-PCR detected FMDV in milk up to 23 days post inoculation which was longer than VI. Furthermore, the detection limit of FMDV in milk was greater by rRT-PCR than VI and, in contrast to VI, rRT-PCR detected virus genome following heat treatment that simulated pasteurisation. rRT-PCR was also able to detect FMDV in preservative-treated milk. In conclusion, this study showed that automated rRT-PCR is quicker and more sensitive than VI and can be used to detect FMDV in whole milk as well as milk fractions from infected animals.

Animals↗

Avridine and LPS from Brucella ovis: effect on the memory induced by foot-and-mouth disease virus vaccination in mice.

Foot-and-mouth disease is one of the more economically important diseases among meat-producing biungulate species. In contrast to natural infection, current foot-and-mouth disease virus (FMDV) vaccines, prepared with inactivated virus and adjuvants, elicit short-lived protection. The immunomodulating effect on FMDV vaccines of avridine and lipopolysaccharide of Brucella ovis (LPS) was tested in a murine model. The duration of immunity, protection, stimulation of immunocompetent cells producing a long-lasting secondary response and immunoglobulin (Ig) isotypes were examined. The incorporation of either immunomodulator into aqueous and oil vaccines induced a long-lasting specific antibody response. The neutralizing titres and protection were significantly higher than those observed in animals immunized with control vaccines. Data collected from repopulation assays indicated that the immunomodulators used participate in the activation of immune cell populations involved in long-lasting memory. This resulted in an efficient B-cell secondary response even in the absence of T cells, which were necessary for the stimulatory effect of the immunomodulators in donor mice. Avridine and LPS stimulated IgG1, IgG2a and IgG2b production, which was correlated with the improvement of the protection induced by these vaccines.

Adjuvants, Immunologic↗

Decision-support tools for foot and mouth disease control.

Recent experience with foot and mouth disease (FMD) has shown that large and very costly epidemics can occur in countries considered extremely unlikely to experience the disease. The consequences of an introduction are much more severe than in the past and effective control is more difficult to achieve. Few countries have developed effective risk management strategies and information-based response systems to respond to these developments. The authors describe the tools which can be employed to minimise the impact of a disease incursion, using the example of FMD. To make such systems effective, the development of a national farms database in advance, including geo-referencing, is highly desirable. This greatly enhances the power of the decision-support tools, which can then be applied as soon as a serious disease incursion has been detected. These tools include procedures to detect infected farms promptly, to protect as yet uninfected farms against exposure to virus and to manage control policies. Epidemiological evaluation and prediction tools have advanced particularly rapidly and can guide the choice of control policies during an outbreak. Integrated decision-support systems offer the best method of managing FMD outbreaks to minimise the cost and size of the epidemics.

Animal Husbandry↗

Immune enhancing effects of recombinant bovine IL-18 on foot-and-mouth disease vaccination in mice model.

Foot-and-mouth disease (FMD) is a highly contagious disease in cloven-hoofed animals and can cause a considerable socio-economic loss for affected countries. Interleukin-18 (IL-18) is a pleiotropic cytokine and plays important role in both the development of a functional immune system as well as the response of the organism to infection. In the present study, bovine IL-18 (BoIL-18), Foot-and-mouth disease virus VP1 and VP1/BoIL-18 fusion genes were cloned and expressed in pichia pastoris (P. pastoris) and subsequently immune effects were evaluated to study the immune enhancing effects of recombinant BoIL-18 (rBoIL-18) on FMD vaccination. The results showed that the genes encoding for BoIL-18, VP1 and VP1/BoIL-18 are successfully expressed in P. pastoris and the expressed recombinant VP1 (rVP1) proteins could induce both humoral and marginal cell-mediated immune responses in mice, while the co-inoculation with rBoIL-18 could markedly enhance both of immune responses, and the inoculation of the fusion product rVP1/BoIL-18 showed even more dramatic immune responses, suggesting rBoIL-18 has a potential to enhance the efficacy of vaccination against FMDV infection.

Adjuvants, Immunologic↗