Molecular Characterization of Foot-and-Mouth Disease Viruses Collected in Tanzania Between 1967 and 2009.

This paper describes the molecular characterization of foot-and-mouth disease viruses (FMDV) recovered from outbreaks in Tanzania that occurred between 1967 and 2009. A total of 44 FMDV isolates, containing representatives of serotypes O, A, SAT 1 and SAT 2 from 13 regions of Tanzania, were selected from the FAO World Reference Laboratory for FMD (WRLFMD) virus collection. VP1 nucleotide sequences were determined for RT-PCR amplicons, and phylogenetic reconstructions were determined by maximum likelihood and neighbour-joining methods. These analyses showed that Tanzanian type O viruses fell into the EAST AFRICA 2 (EA-2) topotype, type A viruses fell into the AFRICA topotype (genotype I), type SAT 1 viruses into topotype I and type SAT 2 viruses into topotype IV. Taken together, these findings reveal that serotypes O, A, SAT 1 and SAT 2 that caused FMD outbreaks in Tanzania were genetically related to lineages and topotypes occurring in the East African region. The close genetic relationship of viruses in Tanzania to those from other countries suggests that animal movements can contribute to virus dispersal in sub-Saharan Africa. This is the first molecular description of viruses circulating in Tanzania and highlights the need for further sampling of representative viruses from the region so as to elucidate the complex epidemiology of FMD in Tanzania and sub-Saharan Africa.

Veterinary vaccines and their use in developing countries.

The burden of infectious diseases in livestock and other animals continues to be a major constraint to sustained agricultural development, food security, and participation of developing and in-transition countries in the economic benefits of international trade in livestock commodities. Targeted measures must be instituted in those countries to reduce the occurrence of infectious diseases. Quality veterinary vaccines used strategically can and should be part of government sanctioned-programmes. Vaccination campaigns must be part of comprehensive disease control programmes, which, in the case of transboundary animal diseases, require a regional approach if they are to be successful. This paper focuses on the salient transboundary animal diseases and examines current vaccine use, promising vaccine research, innovative technologies that can be applied in countries in some important developing regions of the world, and the role of public/private partnerships.

Evaluation of the xerovac process for the preparation of heat tolerant contagious bovine pleuropneumonia (CBPP) vaccine.

The study was conducted with the aim of evaluating the xerovac process as a method for preparing contagious bovine pleuropneumonia (CBPP) vaccine with increased heat resistance. The thermo-protective effects of various concentrations of trehalose in mycoplasma growth medium, various concentrations of trehalose in the dehydration stabilizer and the importance of some divalent cations were assessed. The results obtained indicate that a rapid dehydration of CBPP vaccine following the xerovac method and in an excipient composed of a high concentration of trehalose, renders the product more heat tolerant than a similar vaccine prepared using a regular or an extended freeze drying regime. It was also demonstrated that the addition of chitosan as a mycoplasma precipitating agent conferred additional heat resistance to the vaccine. It is suggested that the application of the xerovac process in the dehydration of CBPP vaccine offers the advantages of a faster, cheaper and easier process over the conventional dehydration methods like freeze drying.

The control of rinderpest in Tanzania between 1997 and 1998.

In January 1997, Tanzania requested international assistance against rinderpest on the grounds that the virus had probably entered the country from southern Kenya. Over the next few months, a variety of attempts were made to determine the extent of the incursion by searching for serological and clinical evidence of the whereabouts of the virus. At the clinical level, these attempts were hampered by the low virulence of the strain, and at the serological level by the lack of a baseline against which contemporary interpretations could be made. Once it became apparent that neither surveillance tool was likely to produce a rapid result, an infected area was declared on common-sense grounds and emergency vaccination was initiated. The vaccination programme had two objectives, firstly to prevent any further entry across the international border, and secondly to contain and if possible eliminate rinderpest from those districts into which it had already entered. On the few occasions that clinical rinderpest was subsequently found, it was always within this provisional infected area. Emergency vaccination campaigns within the infected area ran from January to the end of March 1997 but were halted by the onset of the long rains. At this time, seromonitoring in two districts showed that viral persistence was still theoretically possible and therefore a second round of emergency vaccination was immediately organized. Further seromonitoring then indicated a large number of villages with population antibody prevalences of over 85%. These populations were considered to have been 'immunosterilized'. Although no clinical disease had been observed in them, it was decided to undertake additional vaccination in a group of districts to the south of the infected area. Serosurveillance indicated that rinderpest could have been present in a number of these districts prior to vaccination. Serosurveillance in 1998 suggested that numerous vaccinated animals had probably moved into districts outside the infected and additional vaccination areas, but did not rule out the continued presence of field infection.

Global perspective for foot and mouth disease control.

The world distribution of foot and mouth disease (FMD) is almost a mirror image of the global economic structure. In general, industrialised countries are free while the disease is endemic in developing countries. In recent years, several incursions of FMD have been recorded in countries belonging to the Organization for Economic Co-operation and Development (OECD), all of which have been financially and socially costly to eliminate. At the same time, this single disease bars many developing countries from participation in formal trade, both regionally and internationally. However, recent studies have predicted an unprecedented high demand for animal protein, which can only be met through enhanced participation of developing countries in trade in livestock products. Accordingly, globalisation trends will exacerbate the exclusion of poor communities and countries from markets unless a long-term strategy is implemented to progressively build market opportunities for these countries, without placing the livestock of industrialised countries at undue risk from FMD and other major transboundary animal diseases. The authors submit that there is sufficient knowledge of FMD to make an international initiative for the progressive control of FMD a viable objective. Consequently, a four-stage pathway is proposed for developing a global FMD programme. The proposed strategy involves a build-up of the epidemiology and global status of FMD, including establishing an international early warning system, a risk-reduction phase to lower the incidence of FMD in the primary endemic areas and a control phase leading to the creation of zones of assured FMD-freedom. The authors also propose that an international FMD programme be co-ordinated, based on the experience of the Global Rinderpest Eradication Programme, the Hemispheric Plan for the eradication of FMD for the Americas, the South-East Asia Foot and Mouth Disease control and eradication campaign and the European Commission for the Control of FMD.

Disease prevention and preparedness: the Food and Agriculture Organization Emergency Prevention System.

In 1994, the Food and Agriculture Organization undertook to revitalise its activities in the control of transboundary animal disease by establishing a new special programme known as the Emergency Prevention System (EMPRES) against transboundary animal and plant pests and diseases. The emphasis of the EMPRES livestock component is placed on pre-empting outbreaks and losses experienced by agriculture through the enhancement of local capacity to detect and react rapidly to plague events. EMPRES concentrates on the co-ordination of the Global Rinderpest Eradication Programme--a time-bound eradication programme--whilst addressing the progressive control of the most serious epidemic diseases within a broad framework of emergency preparedness. Programme activities are discussed in relation to early warning, early reaction, facilitating research and co-ordination. In addition to rinderpest, particular attention has been paid to contagious bovine pleuropneumonia, a re-emerging disease in Africa targeted for strategic attention, and foot and mouth disease, for which co-ordinated regional control in Latin America and South-East Asia has been initiated. Tactical responses to other disease emergencies such as African swine fever, classical swine fever (hog cholera), Rift Valley fever, peste des petits ruminants and lumpy skin disease are described.

Regulatory framework and requirements for managing risks associated with veterinary biological products in Africa: present systems and future needs.

Veterinary vaccines are considered to be medicinal products. As such, they are subject to assessment for managing risks associated with their marketing and use. The current risk assessment procedures used in Africa are based on the quality testing methods standardised by the Pan-African Veterinary Vaccine Centre (PANVAC). The authors examine the risk assessment procedures related to the importation of products and to the release of live products into the environment. The lack of infrastructures, specialised personnel and financial resources prevents each individual country from establishing its own system for managing the risks associated with the importation of veterinary vaccines. Regional co-operation between African countries is therefore recommended, and must be based on the existing PANVAC network for the quality testing of priority vaccines. This is justified by the results obtained by PANVAC in the standardisation of production technologies for vaccines against rinderpest and contagious bovine pleuropneumonia, and in other areas. The authors recommend that PANVAC be used to aid regional co-operation in Africa in the management of risks associated with the marketing and use of veterinary vaccines.

[Vaccination strategies for contagious bovine pleuropneumonia in Africa]. / Stratégies de vaccination contre la péripneumonie contagieuse bovine en Afrique.

Contagious bovine pleuropneumonia (CBPP) is regarded as the second most important disease of cattle in Africa. The disease was eradicated from Europe through drastic slaughter campaigns with quarantine and restriction of cattle movements. CBPP was mastered in Australia using these methods combined with vaccination. However, the disease remains endemic in Asia and Africa, where it inhibits livestock farming. In these continents, vaccination is the preferred means of control; the aim is to reduce incidence until complementary disease control measures can be applied. The success of a vaccination campaign depends on four main factors: good planning and good organisation; staff who are well-trained, fully equipped and highly motivated; high quality vaccines; good international co-operation. Vaccine strains recommended for use in Africa are strain T1/44 and its variant T1-SR. To improve the immunogenicity of these strains, the Pan African Rinderpest Campaign (PARC) secured financial support for research into immunostimulating complexes (ISCOM). It is hoped that this technology can improve vaccines, leading to effective eradication of the disease. In the meanwhile, systematic and repeated vaccination is the method of choice against CBPP in Africa.

Contagious bovine pleuropneumonia vaccines: the need for improvements.

Contagious bovine pleuropneumonia (CBPP) vaccines are routinely used only in Africa. The vaccines are usually produced from one of two strains (T1/44 and KH3J), each of which has a streptomycin-resistant variant. The necessity for a 'master seed strain' is evident. At least one manufacturer in Africa produces a broth culture vaccine, while others produce a freeze-dried product. A standardised manufacturing protocol needs to be developed, together with in-process and final product quality control procedures. Some CBPP vaccine manufacturing procedures do not allow sufficient leeway for the execution of typical quality control practices. For example, it is difficult to perform batch testing on broth culture vaccine, as the vaccine is produced in its final container. Quality control test results from the Pan African Veterinary Vaccine Centre (PANVAC) are analysed in terms of causes of batch failure and indicators for process development. Taking potency as an example, most vaccine batches tested by PANVAC pass only at the limit of the OIE minimum requirement of 10(7) colony-forming units per dose. To improve the titre of the vaccine, it will be necessary to modify the manufacturing process, either by increasing mycoplasma yield during the culture phase or by minimising losses during downstream processes, especially freeze-drying. Data on inactivated vaccines are scarce. Duration of the immunity achieved with live CBPP vaccines is relatively short, in comparison with other live vaccines. Data may be required on the molecular basis of virulence and immunogenicity, as well as on the molecular immunology of CBPP, to enable the development of improved vaccines.

Immune response in cattle induced by inactivated rabies vaccine adjuvanted with aluminium hydroxide either alone or in combination with avridine.

In a comparative study of two commercial baby hamster kidney rabies vaccines produced in Brazil, the authors were able to demonstrate the following: a) both vaccines provoked a high level of antibody response and protection against challenge in cattle b) in primary vaccination, at least, the addition of avridine (a synthetic lipoidal amine) enhances the immune response in terms of the level and persistence of antibody c) over 90% of cattle vaccinated with either vaccine were protected against experimental challenge one year after revaccination, and the antibody response profile indicated that these vaccines were capable of maintaining antibody titres above protective levels for more than two years after revaccination. On the basis of these results, the authors recommend optional revaccination of young animals (i.e. "primo-vaccinates") at six months of age. Thereafter, annual revaccination should be sufficient to ensure high levels of antibody between vaccination cycles.

Incidence, epidemiology and control of bovine virus diarrhoea virus in South America.

Outbreaks of diarrhoea associated with mucosal erosions of the mouth, tongue and digestive tract, clinically diagnosed as bovine virus diarrhoea-mucosal disease (BVD-MD), have been reported in Argentina and Brazil since the 1960's. However, primary isolation of the virus of BVD-MD is fairly recent, occurring in 1974 for Brazil, 1984 for Argentina, 1985 for Chile and 1981 for Colombia. In Argentina both cytopathogenic and non-cytopathogenic BVD virus strains have been identified. Elsewhere in South America this differentiation does not seem to have been carried out. Serological surveys have confirmed the existence of BVD virus infection in six countries (Argentina, Brazil, Chile, Colombia, Peru and Uruguay), with an incidence rate ranging between 37 and 77% of cattle in the areas surveyed. Diarrhoea in calves between 3 and 18 months of age, often associated with mucosal erosions, has been the most commonly observed syndrome. In some cases an upper respiratory tract involvement was described. In one epizootic, in the Sabana de Bogota plateau of Colombia, reproductive failure associated with abortions or birth of weak calves was the main clinical syndrome.

Efficacy of avridine as an adjuvant for Newcastle disease virus antigen in chickens.

Avridine, a lipoidal amine with interferon-inducing and adjuvant properties, was an effective adjuvant for Newcastle disease antigen (NDA) in chickens. Eleven vaccine lots were evaluated: 2 commercial water-in-oil vaccines, 4 experimental oil emulsion vaccines, 4 avridine-containing vaccines, and a control lot of nonadjuvanted antigen. Avridine significantly enhanced the immunologic responses of chickens against NDA. Chickens vaccinated with the avridine-containing vaccines had significantly higher antibody titers (hemagglutination inhibition) than did chickens vaccinated with the commercial vaccines. Experimental oil emulsion vaccines prepared from the same antigens as avridine-adjuvanted vaccines induced higher hemagglutination inhibition antibody titers after primary but not after booster vaccination. Use of avridine as an adjuvant for NDA in vaccines for chickens induced immunologic protection rates similar to those induced by oil emulsion vaccines, without causing the reactogenic and tissue residue problems associated with the use of oil vaccines in chickens.

Foot-and-mouth disease vaccination: a multifactorial study of the influence of antigen dose and potentially competitive immunogens on the response of cattle of different ages.

Groups of 68 and 66 cattle aged 12 and 24 months respectively were each subdivided into 16 groups and inoculated with foot-and-mouth disease vaccines containing O1 Campos, A24 Cruzeiro and C3 Pando virus strains. The 140S antigen mass of the O1 and A24 valencies was varied while that of C3 was held constant. Multifactorial comparisons between the 21 day serum neutralising antibody titres showed that over most of the range there was a linear log dose response relationship. Doubling the antigen dose increased the serum antibody titres against both A24 Cruzeiro and O1 Campos by approximately 0.15 log10. The A24 antigen was about 30 times more immunogenic than the O1 with C3 intermediate between the two. At high antigen doses the responses flattened but the level at which this occurred depended on the immunogen administered. No difference could be demonstrated between the responses of 12- and 24-month-old cattle and there was no evidence of competitive inhibition or enhancement between the virus strains included in the vaccines.

An indirect sandwich enzyme labelled immunosorbent assay for the detection of foot and mouth disease virus immunizing antigen in tissue culture harvests.

The optimum conditions for an indirect sandwich enzyme-linked immunosorbent assay for foot and mouth disease virus 140S antigen assay are described. Factors which could contribute to the variation in the test were investigated and a calibration coefficient for the conversion of ELISA values to antigen concentration in micrograms of 140S antigen per millilitre was calculated. Antigen mass in nine tissue culture harvests was estimated and these correlated well with estimates made by sucrose density gradients (r = 0.95).

The differentiation of foot and mouth disease virus strains using an indirect sandwich enzyme-linked immunosorbent assay saturation model.

Sigmoid saturation curves were fitted to the results of titrations of antiserum to foot and mouth disease virus against homologous and heterologous virus strains. Differentiation of strains was readily evident from the different levels of the homologous and heterologous curves. These differences could be quantified by comparison of the saturation curve parameters K and PRmax. Factors which affect variations in K and PRmax and their biological significance were investigated by varying the first phase antibody and the antigen used in the test. PRmax was found to represent an overall combining potential of the antigen with both sera used in the sandwich test. K, which was theoretically a measure of affinity, also reflected antibody titre. Relationships measured using this model were found to correlate with the reference test system--two-dimensional microneutralization.