The proposed multi-state initiative will focus on two of the most important mycobacterial diseases of animals; paratuberculosis (Johne’s disease; JD) and the bovine tuberculosis complex (TB). These two mycobacterial diseases represent some of the most prevalent and economically significant infections of livestock, and each has a long and rich history. A brief background, including significance and need for work, on each of these diseases, is provided below. Johne’s Disease (JD) is a chronic granulomatous inflammatory intestinal disease that results from infection with Mycobacterium avium subspecies paratuberculosis. JD is recognized as a serious economic and animal health problem in domesticated ruminants including dairy and beef cattle, sheep, and goats throughout the world. It results in more than $200 million in annual losses to the United States (US) dairy industry each year with additional losses incurred by the other species. The growing recognition of M. paratuberculosis infection in wildlife species is also of considerable concern. Similarly, recent evidence of the presence of M. paratuberculosis in retail milk sources is of concern from a milk quality and potential food safety standpoint. The growing recognition of MAP infection in wildlife species is also of considerable concern, as well as contaminations in environments such as grassland, soil, and even water-supply systems. Despite considerable efforts, JD remains a major concern for producers with very high prevalence rates (68% of all US dairy herds and 95% of those with over 500 cows have at least one JD positive animal) based on culturing of fecal samples. MAP and JD are now considered endemic in the US and in most dairy producing nations, and without major breakthroughs, efforts at controlling pathogen are likely to remain salutary and the disease will continue to spread unabated.

There have been considerable ongoing efforts made to identify knowledge gaps, define research priorities, and develop recommendations for implementing JD control measures in the field. For instance, a 2003 report from the National Research Council of the US National Academies of Sciences on JD comprehensively reviewed the literature, identified major gaps in knowledge, and provided clear recommendations for future research priorities and strategies for the prevention and control of JD. In brief, the report concluded that JD is a significant animal health problem whose study and control deserves high priority from the USDA. It was recognized that the problems associated with JD stem from: (i) difficulties in diagnosis because of an unusually long incubation period and a lack of specific and sensitive diagnostic tests for detecting early infections; (ii) a lack of vaccines or other effective measures for infection control; and, (iii) general lack of awareness of the disease and its true economic and animal health consequences by producers and veterinarians. The report made 25 specific recommendations regarding implementation of strategies for the control of JD, educating and training of producers and veterinarians, and filling of key gaps in knowledge relating to JD. In 2005 and 2006, specialty working groups were formulated by the USDA-APHIS-VS and the Johne’s Disease Integrated Program (JDIP; http://mycobacterialdiseases.org/) to review knowledge gaps and opportunities for research, extension, and training in JD.

Some of the community needs that were identified as gaps included: (i) the development of new and improved diagnostics and candidate vaccines; (ii) improving research efficiencies by developing shared resources and guidelines for basic and translational research in JD; and, (iii) developing strong education and extension programs. While considerable progress has been made in all areas, the proposed multi-state initiative will facilitate meeting remaining major unmet needs.

The TB complex of diseases of livestock results from infection of animals with mycobacterial pathogens, primarily M. bovis and Mycobacterium avium subspecies avium (MAA). These organisms can cause disease in multiple livestock and wild animal species and can be readily transmitted to humans. M. bovis, whose disease and infections will be the primary focus of the activities proposed in this multi-state initiative, is closely related to the organism that causes human tuberculosis, Mycobacterium tuberculosis (MTB).

TB is a disease of antiquity that has resulted in a considerable economic loss to animal agriculture and, as a zoonotic disease, contributed greatly to human suffering prior to the widespread requirement for milk pasteurization. In fact, at the turn of the 20th century, M. bovis was considered to be the cause of greater economic losses to livestock production than all other infectious diseases combined. The implementation of rigorous control and disease eradication programs, including test and slaughter or test and segregate programs, have reduced or eliminated tuberculosis in cattle in the US and most developed countries. However, reservoirs in wildlife have precluded complete eradication. TB continues to be a significant recurring concern in many countries, including Ireland, the United Kingdom (UK) and New Zealand. In addition, both bovine tuberculosis and M. bovis infections in humans remain common in less developed countries, resulting in considerable economic losses due to disease and trade restrictions.

While TB incidence in the US remains low, there is considerable concern that we may be experiencing a resurgence of this disease in livestock species, primarily cattle. In 1994, a white-tailed deer (WT deer) from northeastern Michigan was found to be infected with M. bovis. This led to the wide-scale testing of cattle and deer with subsequent identification of M. bovis in both populations within this area. The spread of M. bovis in Michigan was slowed by a strict policy of total herd depopulation upon identification of positive cattle, as well as large-scale hunter education programs and a massive testing initiative in WT deer. Still, in Michigan, over 650 cases of M. bovis infection in WT deer and 49 positive cattle herds have been identified to date. Alarmingly, M. bovis has now spread to other states. M. bovis was recently detected in 27 WT deer and 12 cattle herds in Minnesota and has been confirmed in cattle from Colorado, Nebraska, Indiana, Kentucky, North Dakota, South Dakota, New Mexico, and California. Detection of M. bovis infection has lead to quarantine and depopulation of nearly all affected herds. Clearly, this disease is continuing its resurgence throughout the US, particularly where cattle and WT deer commingle.

A second major source of M. bovis infected cattle in the US is imported animals from other countries where the disease is endemic, particularly Mexico. Indeed, molecular epidemiology studies have demonstrated that M. bovis cases in all states other than Michigan are likely of Mexican origin. Although USDA regulations stipulate that imported cattle must be tested within 60 days of import, the low sensitivity of most approved M. bovis diagnostic tests suggests that some infected animals will be missed.   Because cattle are only held at the border for 48 to 72 hours, there is little time to conduct additional testing at the point of entry. In addition, the lack of mandatory animal identification in the US limits the ability to track cattle after introduction into the country. Clearly, it is crucial to have rapid diagnostics with improved sensitivity that could be deployed at points of entry. It is equally important to improve information on cattle movements to control importation of M. bovis infected cattle.

1. bovis is of significant concern to government agencies and cattle industries due to associated economic, social and potential public health problems. The inclusion of M. bovis research, teaching and extension in this multi-state project will address serious concerns from cattle industry representatives, government agencies, and public health officials that the US is experiencing a resurgence of M. bovis that will have devastating economic effects, cause a disruption or severe restrictions in movements of cattle including exports, and have profound effects on producers, who own positive herds and must suffer depopulation or quarantine.

Finally, the generation of new knowledge relative to the diagnosis, management, and control of mycobacterial diseases of animals is critical if we are to prevent the spread, lower the prevalence and minimize the impact of the diseases in our livestock populations. USDA NAHMS studies and other work, including the National Dairy Producer Johne’s survey, have shown that while producers are increasingly aware of the diseases, they often lack knowledge relative to their management and control. Therefore, there is a critical need for developing coordinated approaches for education and outreach programs related to mycobacterial diseases of animals.

Taken together, the proposed multi-state initiative described below will facilitate the development of shared research as well as the leveraging of intellectual and physical resources to address some of the most important mycobacterial diseases of animals.