Effectiveness of vaccines and vaccination programs for the control of foot-and-mouth disease in Uganda, 2001–2010

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. In Uganda, FMD outbreaks are mainly controlled by ring vaccination and restriction of animal movements. Vaccination stimulates immunity and prevents animals from developing clinical signs which include lameness, inappetence, and decreased production. Ring vaccination and restriction of animal movements have, however, not successfully controlled FMD in Uganda and outbreaks reoccur annually. The objective of this study was to review the use of FMD virus (FMDV) vaccines and assess the effectiveness of vaccination programs for controlling FMD in Uganda (2001–2010), using retrospective data. FMD vaccine distribution patterns in Uganda (2001–2010) matched occurrence of outbreaks with districts reporting the highest number of outbreaks also receiving the largest quantity of vaccines. This was possibly due to “fire brigade” response of vaccinating animals after outbreaks have been reported. On average, only 10.3 % of cattle within districts that reported outbreaks during the study period were vaccinated. The average minimum time between onset of outbreaks and vaccination was 7.5 weeks, while the annual cost of FMDV vaccines used ranged from US $58,000 to 1,088,820. Between 2001 and 2010, serotyping of FMD virus was done in only 9/121 FMD outbreaks, and there is no evidence that vaccine matching or vaccine potency tests have been done in Uganda. The probability of FMDV vaccine and outbreak mismatch, the delayed response to outbreaks through vaccination, and the high costs associated with importation of FMDV vaccines could be reduced if virus serotyping and subtyping as well as vaccine matching were regularly done, and the results were considered for vaccine manufacture.     

Occurrence of foot and mouth disease--a historical survey

FMD--the most economically significant animal disease in the world during the last two centuries--has caused the last great panzootic from 1965 to 1967 in Europe. Since then it has become possible to eradicate centres of the epidemic still being present on the continent, mainly by means of the annual mass vaccination of cattle combined with rigid antiepizootic measures which include culling of infected animals. During the years after however there has been sporadic outbreaks again and again. They were mainly caused by virus that escaped from FMD laboratories and by the application of vaccines with residual infectiousity but also to an increasing extent they resulted from virus brought in from endemic regions of the world. The now as before high incidence of FMD in Asia and in wide parts of Africa and South America--after all 71 countries in these regions have been affected by outbreaks of FMD, the classic carrier disease, from 1998 to 2000--resulted in the spread of virus over far distances due to the globalization of world trade and the increasing traveling favoured by modern traffic facilities. Since 1980 in Europe particularly virus strains from the Middle East but also from other parts of Northern Africa and Asia have dominated the epidemiological situation such as the current epizootic in the United Kingdom and the outbreaks resulting from in three other member states of the European Union. In accordance with the EU guidelines the control of occurring outbreaks is exclusively carried out by stamping out. The limits of this procedure have become clearly obvious during the current epizootic in Britain. The use of emergency vaccination in the Netherlands shows a practicable alternative to the excessive mass culling of both infected animals and those being suspected of. The plurality and variability of the causative agent require a permanent observation of the epidemiological situation and of the virus strains involved in order to prevent the disease and to ensure the diagnosis and the topicality of the vaccines being available in the vaccine banks. Long-term success in the global combat against FMD can only be achieved on the basis of close international co-operation intended to restrain the disease significantly in the still endemically infected regions.     

Serological response to a booster foot-and-mouth disease vaccination with strains different from the primary vaccine

Young calves were vaccinated with Belgian foot-and-mouth disease (FMD) vaccine and revaccinated with either the same vaccine or with a foreign FMD vaccine.There was a significant serological response to the primary vaccine strains after the first vaccination which was greater following revaccination. At one and two months after revaccination there was no significant difference between the responses to revaccination with vaccine identical to the primary vaccine or with the foreign FMD vaccine.It was concluded that revaccination of young calves is effective even with an FMD vaccine different from the primary vaccine.     

Evaluation of different adjuvants for foot-and-mouth disease vaccine containing all the SAT serotypes

Foot-and-mouth disease (FMD) is an economically important disease of cloven-hoofed animals that is primarily controlled by vaccination of susceptible animals and movement restrictions for animals and animal-derived products in South Africa. Vaccination using aluminium hydroxide gel-saponin (AS) adjuvanted vaccines containing the South African Territories (SAT) serotypes has been shown to be effective both in ensuring that disease does not spread from the endemic to the free zone and in controlling outbreaks in the free zone. Various vaccine formulations containing antigens derived from the SAT serotypes were tested in cattle that were challenged 1 year later. Both the AS and ISA 206B vaccines adjuvanted with saponin protected cattle against virulent virus challenge. The oil-based ISA 206B-adjuvanted vaccine with and without stimulators was evaluated in a field trial and both elicited antibody responses that lasted for 1 year. Furthermore, the ISA 206 adjuvanted FMD vaccine protected groups of cattle against homologous virus challenge at very low payloads, while pigs vaccinated with an emergency ISA 206B-based FMD vaccine containing the SAT 1 vaccine strains were protected against the heterologous SAT 1 outbreak strain.     

Evaluation of foot and mouth vaccination for yak (<Emphasis Type="Italic">Bos grunniens</Emphasis>) in Pakistan

In northern Pakistan, many farming communities rely on domestic yak (Bos grunniens) as a principle source of income. A 2006 participatory disease surveillance report from this region indicated that foot-and-mouth disease (FMD) is the most prevalent annual disease of yak. Our objectives of this study were to determine exposure levels of yak to FMD virus; implement a vaccination program based on current, regional FMD virus serotypes and subtypes; and quantify immune responses following vaccination. Blood samples were used to determine pre-vaccination exposure of animals to FMD virus by antibody presence to non-structural proteins of FMD virus using a 3-ABC trapping indirect ELISA. Vaccine used consisted of FMD serotypes ‘O’ (PanAsia-2), ‘A’ (Iran-05), and ‘Asia-1’ (Shamir), but changed later during the study to match newly circulating viruses in the country (‘O’-PanAsia-2; ‘A’-Turk-06 and Asia-1-Sindh-08). Three hundred sixty-three blood samples were tested from selected villages to determine pre-vaccination FMD virus exposure in yak with an average of 37.7%. Immune responses from initial vaccination and booster dose 30 days later showed clear protective levels (as mean percent inhibition) of antibodies against structural proteins of serotypes ‘O,’ ‘A,’ and ‘Asia-1.’ These responses remained above threshold positive level even at day 210 following initial vaccination. Results of sero-surveillance and anecdotal information of repeated FMD outbreaks demonstrate the persistence of FMD virus of yak in northern Pakistan. Laboratory results and field observations clearly indicated that yak can be protected against FMD with a good quality vaccine with FMD serotype(s) matching current, regionally circulating FMD virus.     

Foot-and-mouth disease. Challenge of cattle after multiple vaccinations

Four groups of six cattle were vaccinated from two to five times at 6 month intervals with two different trivalent FMD vaccines licensed in the given year. The FMDV type A strains in the vaccines designated A5F and A5B were closely related. Three months after the last vaccination the cattle were challenged by contact with animals inoculated with the original field strain A5B. The inoculated animals developed typical FMD symptoms with vesicles in the mouth and on the feet. Those cattle which had received vaccines that did not contain strain A5B also became severely sick, even after five vaccinations. Animals vaccinated twice with type B containing vaccine were also not completely protected. A safe protection can obviously only be achieved for fairly short periods of time if vaccine and challenge strain are homologous. It is proposed to change the rules of licensing, to speed up the procedure to vaccinate in cases of outbreaks. The need for further research, especially into improving vaccines, is stressed.     

Treatment and control by vaccination of erysipelas in farmed emus (Dromaius novo-hollandiae)

Objective To study erysipelas in farmed emus and the treatment and control of the disease by vaccination.
Design A retrospective study of field outbreaks in emus and challenge experiments in mice using field and vaccine strains of the organism.
Procedure Outbreaks of the disease were described. Field strains of the organism were identified and tested by challenge experiments in mice against commercial vaccine strains.
Results Erysipelas was characterised by sudden death in yearling emus. Deaths mainly occurred during the cold wet months. Mortalities of 6 to 10% were seen within the first 7 to 10 days of an outbreak. Clinical signs were uncommon but some birds exhibited lethargy and greenish diarrhoea. Necropsy findings included marked petechial haemorrhages on the serosal surface of the large intestine in particular, pericardial effusion and congestion and mottling of the liver. Treatment consisted of individual or mass medication with procaine penicillin, reduction of stress factors such as overcrowding, and spelling and rotation of paddocks. Isolates from two field outbreaks were identified as strain 21. Complete protection was provided by a commercial strain 2b vaccine against challenge by strain 21 field isolates in mice. Annual vaccination of birds at 4 weeks and again at 8 weeks of age appeared to control further outbreaks on farms where the disease had previously occurred and vaccination appeared to protect for at least 12 months.
Conclusion Treatment of birds with antibiotics may be feasible in the face of an outbreak. However, annual vaccination of birds with an appropriate vaccine is recommended.     

Immune Effect of Inactivated Vaccines against Foot-and-Mouth Disease and Their Interference on Differential Diagnosis

Vaccination with inactivated vaccine is an important measure to prevent and control foot-and-mouth disease (FMD), however, the immune effect and antigenic purity of inactivated vaccines are two major concerns for the establishment and evaluation of FMD free zones with vaccination. In this study, four groups of FMD type O and type A bivalent inactivated vaccines from 3 FMD vaccine manufacturers (designated as A, B and C) were selected to inoculate healthy juvenile cattle of FMD free. All cattle were immunized 3 or 4 times at a 1-month interval. Serum samples were collected before and after 1 month of every vaccination to determine the level of antibody to structural protein and non-structural protein. Results：(1) The qualified rates of antibody to structural protein: in group a1 (vaccine from company A, different batches), the antibody qualified rate could reach 100% for type O and type A, respectively after each vaccination. In group a2 (vaccines from company A, same batch), the antibody qualified rates were 36.7%, 98.3% and 100% for type O, and 15%, 86.7% and 100% for type A after the first to the third vaccination, respectively. In group b (vaccine from company B, same batch), the antibody qualified rates were 18.3%, 97% and 100% for type O, and 1.7%, 45% and 53.3% for type A after the first to the third vaccination, respectively. In group c (vaccines from company C, same batch), the antibody qualified rates were 26.7%, 96.7% and 100% for type O, and 21.7%, 71.7% and 100% for type A after the first to the third vaccination, respectively. (2) Antibody positive rate to non-structural protein 3ABC (confirmed with second ELISA test): In group a1, the positive rates were 0.7%, 1.4%, 9.5% and 4.8% after the first to the fourth vaccination, respectively; In group a2 and c, no 3ABC antibody-positive animal was detected after 3 repeated vaccination; In Group b, only one animal with a positive rate of 0.6% was detected after the third vaccination. The antibody qualified rates to the structural protein of FMDV in 3 of the 4 groups were far less than 70% after the primary vaccination, however, those were increased significantly after boost and repeated vaccination. The antigen purity of vaccines in three groups (a2, b and c) can meet the requirement of OIE standard on the FMD vaccine, however, the seroconversion to 3ABC antibody was obvious in animals from group a1 after repeated vaccination, which would cause some extent of interference to differential diagnosis. Also, a combination of a primary screening test and a confirmatory ELISA test can further improve the accuracy of differential diagnosis. This study provides an important scientific basis to make a rational program for establishment and evaluation of FMD free zone with vaccination.     

口蹄疫灭活疫苗的免疫效果及其对鉴别诊断的干扰

灭活疫苗免疫是防控口蹄疫的重要措施,但是灭活疫苗的免疫效果及其对感染与免疫鉴别诊断的干扰一直是口蹄疫免疫无疫区建设评估需要明确的重要问题。本研究中选择了3个企业（代号A、B与C）的4组口蹄疫O型与A型二价灭活疫苗,分别免疫口蹄疫抗体阴性健康未成年牛,免疫3～4次,测定免疫前后结构蛋白和非结构蛋白抗体的应答水平。结果显示：（1）结构蛋白抗体合格率：a1组（A企业多批次疫苗）4次免疫后O型和A型均为100%;a2组（A企业同批次疫苗）一~三免O型为36.7%、98.3%与100%,A型为15%、86.7%与100%;b组（B企业疫苗）一~三免O型为18.3%、97%与100%,A型为1.7%、45%与53.3%;c组（C企业疫苗）一~三免O型为26.7%、96.7%与100%,A型为21.7%、71.7%与100%。（2）非结构蛋白3ABC抗体阳性率（两种方法复核结果）：a1组一~四免分别为0.7%、1.4%、9.5%与4.8%;a2组和c组三次免疫均未检测到阳性;b组仅三免后阳性率为0.6%。3组灭活疫苗首次免疫牛的抗体合格率远不及70%,但加强免疫后抗体合格率均显著提高;非结构蛋白抗体检测结果表明有3组疫苗的抗原纯净度符合OIE的要求,但a1组灭活疫苗免疫后,仍然对感染与免疫鉴别诊断存在干扰;采用两种非结构蛋白抗体检测方法进行复核检验,可以提高感染与免疫鉴别诊断的准确性。本研究为口蹄疫免疫无疫评价方案的制定提供了科学依据。     

The foot-and-mouth disease epidemic in The Netherlands in 2001

An outbreak of foot-and-mouth disease (FMD) in Great Britain was reported on 21 February 2001, followed by an outbreak of FMD in The Netherlands a month later. This Dutch index outbreak occurred on a mixed, veal-calf/dairy-goat farm in Oene, in the central part of The Netherlands. The most-likely route of infection was the import of Irish veal-calves to this Dutch herd via an FMD-contaminated staging point in France. With hindsight, more herds seemed to be infected by the time the index outbreak was confirmed. The regular EU control measures were implemented, in combination with pre-emptive culling of herds within 1km of each outbreak. Nevertheless, more outbreaks of FMD occurred. Most of the virus infections on those farms were "neighborhood infections". Because the situation seemed out of control locally and the destruction capacity became insufficient, it was decided to implement an emergency vaccination strategy for all biungulates in a large area around Oene to stop further spread of the virus. All susceptible animals on approximately 1800 farms in this area were vaccinated. All farms subsequently were depopulated, starting from 2 weeks after vaccination. In total, 26 outbreaks were detected (the last outbreak on 22 April 2001). In total, approximately 260,000 animals were killed.     

Endurance of immunity against foot-and-mouth disease in cattle after three consecutive annual vaccinations

Protection against foot-and-mouth disease (FMD) and ability to transmit FMD virus to susceptible contact animals were studied in cattle vaccinated three times in annual field campaigns with the Dutch trivalent vaccine. Eighty vaccinated cattle and 16 susceptible controls were intranasally exposed to an aerosol containing a homologous FMD challenge virus (O1 BFS, A10 Holland or C1 Detmold) or a heterologous virus (A5 Modena or C1 Modena). The day after exposure, vaccinated cattle were stabled individually with an FMD-susceptible contact. All cattle challenged with an homologous virus strain at one year (20 head), at two years (10 head) and at three years (30 head) after the last vaccination were protected against the development of clinical signs of disease; one, zero and five cattle of these groups, respectively, transmitted virus to their contacts. In each group, approximately two out of three exposed cattle had virus-positive oropharyngeal fluid samples and seroconverted. The amount of virus recovered from probang samples increased with the time since the last vaccination. Mean antibody titres of cattle that had not been vaccinated for three consecutive years did not change significantly over the last two-year period. All 10 cattle challenged with the vaccine strain-related C1 Modena virus were protected against clinical disease, whereas three out of 10 challenged with the heterologous A5 Modena strain virus one year after the last vaccination contracted FMD and transmitted the virus. Five others (four in the C1 group and one in the A5 group) spread the virus to their contacts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of genetic and non-genetic factors on foot and mouth disease (FMD) virus vaccine-elicited immune response in Hardhenu (<Emphasis Type="Italic">Bos taurus</Emphasis> x <Emphasis Type="Italic">Bos indicus</Emphasis>) cattle

Foot and mouth disease (FMD) is the most contagious disease of mammals and a major threat to animal husbandry sector. In India, vaccination with the inactivated trivalent (O, A and Asia1) vaccine is one proven way for protecting the livestock from FMD. However, many outbreaks have been reported in different parts of the country. Therefore, present study was aimed at elucidating the effects of genetic and non-genetic factors on FMD viral vaccine-elicited immune response in Hardhenu cattle. The effect of season of vaccination was not consistent. The effect of status of animal was significant for all the pre and post AB titres except for pre AB titre of serotype O and post AB titre of Asia1.The estimates of heritability for response to vaccination were low to high ranging from 0.11 to 0.45. The highest heritability estimate was obtained for serotype O and the lowest for Asia1. The heritability estimates for pre and post AB titres ranged from 0.15 to 0.33. All the pre and post AB titres and responses to vaccination had genetic correlations ranged from high negative to high positive among them. Results of this study highlight the variation in vaccine response which needs to be further exploited on large-scale animal data for better immunization and protection against highly contagious viral vesicular disease of cloven-hoofed animals.     

Simultaneous vaccination of piglets against foot-and-mouth disease and classical swine fever

Six-week-old piglets, born of unvaccinated sows, were vaccinated against foot-and-mouth disease (FMD) with a trivalent, inactivated vaccine containing an adjuvant or vaccinated against classical swine fever (CSF) with a live attenuated vaccine or against both diseases simultaneously at two different sites. The antibody response to the FMD vaccine was not significantly influenced by the simultaneous vaccination against CSF. FMD vaccine administered simultaneously with the CSF vaccine produced a significantly higher antibody response to CSF than occurred with CSF vaccination only.     

Newcastle disease virus outbreaks: Vaccine mismatch or inadequate application?

Newcastle disease (ND) is one of the most important diseases of poultry, and may cause devastating losses in the poultry industry worldwide. Its causative agent is Newcastle disease virus (NDV), also known as avian paramyxovirus type 1. Many countries maintain a stringent vaccination policy against ND, but there are indications that ND outbreaks can still occur despite intensive vaccination. It has been argued that this may be due to antigenic divergence between the vaccine strains and circulating field strains. Here we present the complete genome sequence of a highly virulent genotype VII virus (NL/93) obtained from vaccinated poultry during an outbreak of ND in the Netherlands in 1992-1993. Using this strain, we investigated whether the identified genetic evolution of NDV is accompanied by antigenic evolution. In this study we show that a live vaccine that is antigenically adapted to match the genotype VII NL/93 outbreak strain does not provide increased protection compared to a classic genotype II live vaccine. When challenged with the NL/93 strain, chickens vaccinated with a classic vaccine were completely protected against clinical disease and mortality and virus shedding was significantly reduced, even with a supposedly suboptimal vaccine dose. These results suggest that it is not antigenic variation but rather poor flock immunity due to inadequate vaccination practices that may be responsible for outbreaks and spreading of virulent NDV field strains.     

Experimental evaluation of foot-and-mouth disease vaccines for emergency use in ruminants and pigs: a review

Changes to foot-and-mouth disease (FMD) control policies since 2001 mean that emergency vaccination must be considered more readily as a control measure in the future. Since field application of vaccine for emergency use has only rarely been applied, the effectiveness of single dose administration, as a control measure in an outbreak situation, is poorly understood. In this review we consider all the available experimental data from studies utilizing either experimental or readily available, commercially produced vaccines, in order to assess their likely effectiveness as an additional means of controlling FMD transmission and spread in an emergency. Overall it is concluded that such vaccines offer an additional and valuable means of FMD control for both ruminants and pigs. They are able to reduce clinical disease, sub-clinical infection and excretion and onward transmission of virus. However, to be most effective, vaccination should be rapidly applied to give maximum opportunity for immunity to develop. We also identify areas for future research and emphasize the importance of vaccine efficacy studies in providing data for models that can help to predict the efficacy of differing FMD control strategies.     

Current status of immunoprophylaxis against foot-and-mouth disease]

An analysis is made of the latest developments and importance of immunoprophylaxis against FMD, with reference to the epizootiological situation of the disease and its bearings, today, on industrialized livestock production. Comprehensive immunoprophylactic action (vaccination of all cattle every year) has been taken first by the GDR and later on by more European countries, as well. As a result of such action the disastrous impact of FMD and its associated high loss rate have been considerably mitigated. A decisive role, in that context, has been played by the development of effective inactivated vaccines for swine. An FMD live vaccine has been devised in GDR for after-care of swine. It is not only harmless to the animal, but, as well known, it provides numerous advantages over adsorbate vaccines. FMD immunoprophylaxis for full success depends primarily on the proper selection of virus strains suitable for vaccine produktion, vaccine quality, avoidance of post-vaccination damage or disease, and the availability of an efficient concept for vaccine application. The above problems are expounded in this paper, and derived from them are substantive conclusions for further studies, with the view to improving FMD immunoprophylaxis.     

The effect of foot-and-mouth disease (FMD) vaccination on virus transmission and the significance for the field

Vaccination against foot-and-mouth disease (FMD) might be one of the control measures used during an FMD epidemic depending on the local epidemiological situation, the status of the country, and the opinion of policy makers. A sound decision on vaccination can be made only if there is sufficient scientific knowledge on the effectiveness of vaccination in eliminating the virus from the population. An important question is whether a single vaccination applied as an emergency vaccine can contribute to the control of an epidemic. This paper presents the results of transmission experiments on vaccine efficacy in groups of cattle, pigs, and sheep and concludes that vaccination seemed to be effective in cattle and sheep, but was less effective in pigs. The possible implications for application to field conditions are discussed.     

Risk increase and economic consequences of the introduction of contagious animal diseases in the Netherlands

The paper describes the development of the Monte Carlo simulation model VIRiS (Virus Introduction Risk Simulation) and the results obtained with this model. VIRiS simulates the introduction of Classical Swine Fever (CSF) and Foot and Mouth Disease (FMD) into the Netherlands. The model is based on objective information (research, databases), complemented by expert knowledge. Various questionnaire techniques (Conjoint Analysis, ELI) were used in order to elicit the experts' estimates in an objective and quantitative way. VIRiS provides information on the number of primary outbreaks in a certain period, their geographic location, causative risk factor, and causative country (or region). The information provided by VIRiS in combination with the outcome of models describing the spread and economic consequences of epidemics provides a tool that can be used to evaluate prevention strategies for their ability to reduce annual losses due to outbreaks.