Indo-US STF Research Internship in Science and Engineering (RISE)

March 20th 2011:

I left for India today. The flight left Roanoke to Washington DC, then to Frankfurt, Germany and then to Chennai, India. I will spending the next 4-months in India conducting research on Johne's Disease in sheep.

My Quick Review of Ovine Johne's Disease:

Ovine Johne's Disease (JD) is an chronic enteric inflammatory disease caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection (paratuberculosis). I personal separate out Paratuberculosis from Johne's disease as not being synonymous, though many scientists use them interchangeably. In its purist definition, paratuberculosis is the condition of being infected with MAP and does not denote disease, whereas JD has progressed visible to disease, at least microscopically if not clinical. I consider it analogous to being infected with the Human Immunodeficiency virus (HIV). HIV infection is the predecessor to the disease: Acquired Immunodeficiency Syndrome (AIDS).  I acknowledge the overlap. You can have a ruminant with paratuberculosis that does not have JD, but you cannot have a ruminant with JD that does not have paratuberculosis. – Make sense? Okay, now off my soap box.

Johne’s Disease Pathology:
Paratuberculosis leads to chronic granulomatous enteritis. Microscopically the lamina propria mucosa of the small intestine (most often the ileum) is infiltrated with numerous epithelioid macrophages, few giant cells and neutrophils and there is subsequent bunting and fusion of villi with edema which all result in decreased surface area as well as a dysfunction absorptive area. As a result, the clinical signs manifest as chronic diarrhea and emaciation. The incubation period from paratuberculosis to JD is long! Typically over a year! Slow growing bacteria are some of the most challenging bacteria to treat and therapy requires a long duration of an antibiotic regimen. Johne’s disease is general a disease of ruminants: Cows, Sheep, Goats, and less often detected wildlife ruminants (Elk, deer, bison, etc.). Regardless of the species, the disease process is similar and invariably fatal. In domestic ruminants, the disease is a production problem and treatment is at the herd level and most often in the form of test and cull management practices.

There has been some suggestion that MAP maybe associated with human disease, most often Crohn's disease (CD). While there are similarities between JD and CD, there is one striking notable difference between CD and JD that challenges that association and that is the microscopic visualization of numerous acid fast bacteria within the lamina propria mucosa (present in JD, but absent in CD). As the saying goes: “seeing is believing”, therefore acceptance of MAP as a potential cause of CD is more challenging and many scientists remain skeptical.

The Research:

First, this research was generously supported by the Indo-US Science and Technology Foundation, Research in Science and Engineering fellowship. This is an exchange research program that permits researchers to visit institutions to foster collaborative research.

My research was conducted at the Tamil Nadu University of Veterinary and Animal Science (TANUVAS) and extension of Madras College of Veterinary Medicine in Chennai, India.

Additionally the research was supported by Redhill Biopharma, who provided free of charge a triple antimycobacterial drug, RHB-104® (previously Myoconda®) for testing.

General Overall Goals of the Research:
1. Identify the herd prevalence of Ovine paratuberculosis in university sheep and goat herds.

2. Test the efficacy of triple-antimycobacterial drug on different Mycobacterial isolates from South India.

3. Test the tolerability and efficacy of triple anti-mycobacterial treatment to decrease the fecal and tissue load of MAP.

4. Test the bio-availability of triple anti-mycobacterial treatment as well as screen for any hematologic changes associated with the treatment regimen.

After completion and publication of the generated manuscripts, I will provide links to the manuscripts and data of the results of this research.