Isolation and Potential for Transmission of Mycobacterium bovis at Human-livestock-wildlife Interface of the Serengeti Ecosystem, Northern Tanzania.

Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), is a multihost pathogen of public health and veterinary importance. We characterized the M. bovis isolated at the human-livestock-wildlife interface of the Serengeti ecosystem to determine the epidemiology and risk of cross-species transmission between interacting hosts species. DNA was extracted from mycobacterial cultures obtained from sputum samples of 472 tuberculosis (TB) suspected patients and tissue samples from 606 livestock and wild animal species. M. bovis isolates were characterized using spoligotyping and Mycobacterial Interspersed Repetitive Units-Variable Tandem Repeats (MIRU-VNTR) on 24 loci. Only 5 M. bovis were isolated from the cultured samples. Spoligotyping results revealed that three M. bovis isolates from two buffaloes (Syncerus caffer) and 1 African civet (Civettictis civetta) belonged to SB0133 spoligotype. The two novel strains (AR1 and AR2) assigned as spoligotype SB2290 and SB2289, respectively, were identified from indigenous cattle (Bos indicus). No M. bovis was detected from patients with clinical signs consistent with TB. Of the 606 animal tissue specimens and sputa of 472 TB-suspected patients 43 (7.09%) and 12 (2.9%), respectively, yielded non-tuberculous mycobacteria (NTM), of which 20 isolates were M. intracellulare. No M. avium was identified. M. bovis isolates from wildlife had 45.2% and 96.8% spoligotype pattern agreement with AR1 and AR2 strains, respectively. This finding indicates that bTB infections in wild animals and cattle were epidemiologically related. Of the 24 MIRU-VNTR loci, QUB 11b showed the highest discrimination among the M. bovis strains. The novel strains obtained in this study have not been previously reported in the area, but no clear evidence for recent cross-species transmission of M. bovis was found between human, livestock and wild animals.

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.

Incidence and distribution of foot-and-mouth disease in Asia, Africa and South America; combining expert opinion, official disease information and livestock populations to assist risk assessment.

Risk assessment procedures frequently require quantitative data on the prevalence of the disease in question. Although most countries are members of the World Organization for Animal Health (OIE), the importance attached to foot-and-mouth disease (FMD) reporting or surveillance for infection varies enormously between infected countries. There is a general consensus that FMD outbreaks in endemic countries are greatly under-reported, to a degree related either to the economic or the political development level of the country. This exploratory study was first undertaken by FAO, but thereafter extended and reviewed by the working group on FMD risk co-ordinated by the European Food Safety Authority (EFSA). The paper attempts to overcome the lack of reporting through using expert opinion to extrapolate incidence indices from countries considered to have 'representative' levels of FMD. These were combined with livestock density distributions to provide maps of prevalence indices, which were found to be highest in China (pigs), India (cattle), the Near East (small ruminants) and the Sahel (small ruminants and cattle). Similar patterns were found when weighted expert rankings of a range of additional ranked disease parameters were also produced, and then combined with susceptible animal densities to produce a weighted multi-species density. Results suggest that the methods can provide useful information at both national and sub-national resolution, even for countries for which quantitative FMD data is currently unavailable: two of the regions identified provide little or no data on a regular basis to the OIE and therefore may be overlooked if the level of officially reported FMD is only used. As the estimated prevalences are based on recent disease history and expert opinion, they are most likely to be inaccurate where FMD incursions are infrequent as a result of the preventive measures and geographical and trade isolation. This study, therefore, highlights the need for specific detailed country risk assessments where livestock trade is under consideration. Validating the approach including ground truthing, will require collaboration between a number of agencies and institutions, in critical countries, particularly those with high disease burdens that share borders or trade livestock with currently FMD-free nations.

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.

Epidemiological patterns of foot-and-mouth disease worldwide.

Foot-and-Mouth Disease (FMD) is a clinical syndrome in animals due to FMD virus that exists in seven serotypes, whereby recovery from one sero-type does not confer immunity against the other six. So when considering intervention strategies in endemic settings, it is important to take account of the characteristics of the different serotypes in different ecological systems. FMD serotypes are not uniformly distributed in the regions of the world where the disease still occurs. For example, the cumulative incidence of FMD serotypes show that six of the seven serotypes of FMD (O, A, C, SAT-1, SAT-2, SAT-3) have occurred in Africa, while Asia contends with four sero-types (O, A, C, Asia-1), and South America with only three (O, A, C). Periodically there have been incursions of Types SAT-1 and SAT-2 from Africa into the Middle East. This paper describes the global dynamics for the seven sero-types and attempts to define FMD epidemiological clusters in the different regions of the world. These have been described on a continent by continent basis. The review has reaffirmed that the movement of infected animals is the most important factor in the spread of FMD within the endemically infected regions. It also shows that the eco-system based approach for defining the epidemiological patterns of FMD in endemic, which was originally described in South America, can apply readily to other parts of the world. It is proposed that any coordinated regional or global strategy for FMD control should be based on a sound epidemiological assessment of the incidence and distribution of FMD, identifying risk sources as either primary or secondary endemic eco-systems.

Planning for the progressive control of foot-and-mouth disease worldwide.

In the wake of on-going successful programmes for global eradication of rinderpest and the current effort to contain the spread of avian influenza, the progressive world-wide control of FMD must be regarded as a major contribution to the international public good. FMD is the single most animal disease constraint to international trade in animal products. Its control is relevant, on the one hand, to protecting the livestock industries of industrialised countries and, on the other, to the livelihoods and income generation of developing countries, where, as a general rule, FMD continues to be endemic. The strategy that is advocated in this paper is one that is based on progressive risk reduction of FMD in the context of progressive market access of livestock commodities from developing countries. It is suggested that FMD control should be linked to improvement in livelihoods of livestock dependent communities in the FMD endemic settings. It is expected that this in turn will lead to increasing demand for effective national veterinary services and disease surveillance. This strategy has also taken lessons from the global rinderpest eradication programme and regional FMD control programmes in Europe and South America. The strategy that is advocated for the progressive control of FMD in the endemic settings is based on a seven stage process within a horizon of about 30 years, namely: (1) Assessing and defining national FMD status; (2) instituting vaccination and movement control; (3) suppressing virus transmission to achieve absence of clinical disease; (4) achieving freedom from FMD with vaccination in accordance with the OIE standards; (5) achieving freedom from FMD without vaccination in accordance with the OIE standards; (6) extending FMD free zones; and (7) maintaining FMD Freedom. Concomitant with progressive FMD control, there needs be the encouragement of such risk reduction measures as in-country commodity processing in order to encourage regulated trade in livestock commodities without unduly increasing the risk of disease spread. Finally, the progressive control of FMD should also be seen as part of reducing the overall, world-wide threat of infectious diseases to human health and economic development.

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.

Emerging diseases of Africa and the Middle East.

The term "emerging diseases" has been used recently to refer to different scenarios, all of which indicate changes in the dynamics of disease in the population. Of the OIE List A diseases, major changes have been experienced with rinderpest, peste des petit ruminants (PPR), contagious bovine pleuropneumonia (CBPP), foot-and-mouth disease, African swine fever, lumpy skin disease, and Rift Valley fever. Rinderpest represents a success story of the 1990s, thanks to the programs of the Pan African Rinderpest Campaign (PARC). The situation has changed from that of the 1980s when rinderpest was widespread throughout most of Tropical Africa and the Middle East. PPR is a disease that has become of increasing importance throughout Tropical Africa and the Middle East. CBPP, which had previously been reduced to sporadic incidence within endemic areas, invaded new areas, causing heavy mortality. African swine fever has extended to West Africa and to Madagascar, in both regions resulting in heavy losses. Climatic changes in both East and West Africa were associated with an upsurge of Rift Valley fever. Deficiencies in national veterinary services have contributed to failures in early detection and response; in many regions investigation and diagnosis services have deteriorated. The continuing structural adjustment program for national veterinary services will need to take into account their transformation from providers of services (e.g., vaccinations, medicines) to inspection and quality assurance services. Surveillance, early warning, and disease emergency preparedness will need to be pursued more vigorously in Africa and the Middle East as vital components of national veterinary services.

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.