The new age of paratuberculosis research was ushered in with the discovery of a genetic element unique to M. paratuberculosis. This nucleotide sequence in the chromosomal DNA of the organism was simultaneously and independently discovered by Des Collins in New Zealand and the research team led by J.J. McFadden in England in 1989. The sequence was found to be an insertion element and was designated IS900. It was the first insertion element ever reported in mycobacteria. The importance of this discovery was its enabling the development of genetic tools for the detection of M. paratuberculosis without having to cultivate the bacterium on laboratory media, a process typically requiring 12 to 16 weeks.
Today, IS900-based
"gene probes" are providing new and intriguing information on the ecology and
host range of this intestinal pathogen. Most provocative are reports that M.
paratuberculosis is found in the tissues of over half of humans with Crohn's
disease. This chronic, untreatable intestinal disease bears marked clinical and
pathological similarity to Johne's disease. To date, the cause of Crohn's disease
is unknown.
Researchers around the globe developed several other diagnostic tests
many of which became both validated and commercialized in the 1990s. Among
the most widely used is the absorbed ELISA, a test for serum antibodies.
Multiple companies around the world currently market diagnostic kits based
on the absorbed ELISA technique (IDEXX Laboratories, Inc, USA; ImmuCell,
USA; Synbiotics, USA; CSL Limited, Australia; SVANOVA, Sweden; and Institut
Porquier, France). Agar-gel immunodiffusion (AGID) technology also was
adopted and commercialized for serologic diagnosis of paratuberculosis
in cattle, sheep and goats (ImmuCell, USA).Automated culture methods were
adapted from products designed to detect M.tuberculosis in humans
and the BACTEC system (Becton-Dickinson, USA) became a mainstay of for
routine culture of M.paratuberculosis in some countries. The Australian
immunologist, Paul Wood, developed a method for detecting cellular immune
responses to infectious agents based on the principle of measuring gamma-interferon
released from peripheral blood leukocytes (Bovigam, CSL Limited).
These paratuberculosis assays gave veterinarians the tools needed to operate effective prevention and control programs. Australia was the first to establish comprehensive programs to identify herds that were paratuberculosis-free, or of low risk of being infected, to facilitate safe trade of animals. The cattle Market Assurance Program (MAP is being expanded to include sheep, goats, llamas and alpacas. The Animal Health Service of The Netherlands was next to design and promote national programs for control of bovine paratuberculosis. The USA, with leadership provided by a special committee of the U.S. Animal Health Association called the National Johne's Working Group, created a Voluntary Johne's Disease Herd Status Program modeled after the Dutch and Australian programs. Virtually all states in the U.S. adopted this program.
The zoonotic potential of MAP (meaning the ability of the organism to cause disease, primarily Crohn’s disease, in humans) continued to be discussed and studied. A number of studies were completed ranging from assessments of the ability of MAP to withstand milk pasteurization methods to the effectiveness of antibiotic therapy in Crohn’s disease patients targeted against mycobacteria. (See "Zoonotic Potential".)
The International Association for Paratuberculosis became even more vital as an organization to facilitate the exchange of scientific information among researchers and regulatory veterinarians operating paratuberculosis control programs in different countries.
2000-2010
Another busy decade
Significant progress was made in the last ten years across many MAP realms: development of control programs, new diagnostics focused on different target samples, plus effective collaborations across institutions and countries. Capitalizing on global communication systems, both scientific and education advances were made by the JDIP (Johne's Disease Integrated Program) collaboration in the United States (http://www.jdip.org/) and the European ParaTB Tools (http://www.ucm.es/info/paratbtools/) endeavors. With the complete description of the MAP genome in 2005 (based on strain K-10), both functional and comparative genomic analyses became feasible. This new field of research is expected to expand opportunities for diagnostic, vaccine and perhaps even therapeutic methods.
This decade saw an expansion of national and regional control programs, based on new approaches for determining the infection status of herds, flocks or mobs. Culture of pooled fecal samples was found to be accurate (much reducing costs for producers) and environmental sampling (soil, water) also expanded the ability to describe the distribution of the organism in the environment. Vaccination for small ruminants was more widely adopted as a control tool in small ruminant herds, particularly in Spain and Australia. Antibody testing using milk samples instead of blood samples became possible. National programs such as the ones in the Netherlands, Denmark, and Ontario, Canada’s provincial program swung their attention to herd classification and risk-based control programs based on assays for antibodies in serum or milk, with costs covered by dairy producer organizations or milk processors provided herd owners comply with paratuberculosis control recommendations. Not all news was good however: in the USA after a greater than $100 million dollar national investment in Johne’s disease control infrastructure (veterinarian certification, risk assessment and herd certification programs, demonstration herds, educational tools, program managers in every state, etc.), the prevalence in dairy cattle has increased from 22% in 1996 to 68% in 2007.
Additional ruminant species were added to the array known to be infected by MAP and resulting in disease (e.g. guanaco in Chile) but accumulating data on MAP infection of non-ruminants (birds, rodents, fox, weasel, etc.) seem to indicate that while infection (the presence of MAP in tissues) may occur, it is rare for it to cause disease in these omnivores/carnivores. Research continues to determine if these “dead-end” hosts are also reservoirs of the infection for domestic agriculture ruminant species.
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