1. Leprosy Treatment: BCG and Multidrug therapy Mason Anderson

2. Leprosy Burden Though leprosy is in decline in most countries there are still highly endemic countries around the globe Over two hundred thousand new cases were reported last year [1]. 71% of new cases were reported in South East Asia [1]. 16% of new cases were reported in Brazil [1].

3. Recent Research The World Health Organization’s multidrug therapy has been ineffective at removing dead and persister M. Leprae bacilli. [2-5] BCG injections have shown to reduce treatment time and effectively remove persister antigens[2-4]. However some results on larger populations are inconclusive [5]. If BCG and MDT is more efficient than MDT alone the WHO could stand to save millions on leprosy treatment.

4. Aim The aims of this study examine two separate variables. The first aim is to confirm or reject BCG as an effective immunomodulator for M. Leprae. The second aim of this study is to examine how geographic differences affect the symptoms expressed by M. Leprae.

5. Methods This following methods will take place in Uttar Predesh, India and Mato Grosso, Brazil. Two groups will be formed each with one hundred participants. Each patient will be subject to an initial Slit-skin smear. The experimental group will receive two years of WHO MDT with injections of BCG every three months for two years or until SSS negative.

6. Methods The control group will receive the WHO MDT for two years as well. If a patient is still SSS positive at the end of two years treatment will continue. Bacteriological index tests will be conducted every three months to track treatment development. After all of the individuals in both treatment groups are SSS negative follow up will be conducted annualy for three years.

7. Budget ItemQuantity of ItemCost (U.S. Dollars) Year Long WHO MDT*8000 BCG Injection (105 Bacilli per Dose) 16004800 Slit Skin Smear Package20008000 Computers21400 R-Statistics Package20 Travel Expenses (Uttar Predesh) 1127500 Travel Expenses (Mato Grosso) 1114749 Cost of Researchers11686400 Total Cost729,570

8. Ethics Each patient in this study will be made fully aware of the procedures and possible adverse affects. The patients will be required to sign a written consent form before participating in this study. Multi-Drug Therapy will continue until a patient is SSS negative as it is immoral and dangerous to stop treatment in the midst of a antibiotic regimen.

9. Public Impact This research will clarify if BCG can be used conjunctively with MDT to increase the efficacy of treatment. This research will also clarify how individuals in different regions react to certain treatments. This knowledge could change leprosy treatment.

11. References World Health Organization. 2013. Weekly Epidemiological Record: Global Leprosy and Update. No. 35, 2013. WHO. 365-380. Narang T, Kaur I, Kumar B, Radotra BD, Dogra S. 2005. Comparative evaluation of immunotherapeutic efficacy of BCG and mw vaccines in patients of borderline lepromatous and lepromatous leprosy. Int J Lepr Other Mycobact Dis 73(2):105-14 Katoch K, Katoch VM, Natrajan M, Sreevatsa, Gupta UD, Sharma VD, Shivanavar CT. 2004. 10-12 years follow-up of highly bacillated BL/LL leprosy patients on combined chemotherapy and immunotherapy. Vaccine 22(27-28):3649-57. Gupte MD, Anantharaman DS, De Britto RL, Vallishayee RS, Nagaraju B, Kannan S, Sengupta U. 1992. Sensitization potential and reactogenicity of BCG with and without various doses of killed mycobacterium leprae. Int J Lepr Other Mycobact Dis 60(3):340-52. Shetty VP, Mistry NF, Wakade AV, Ghate SD, Capadia GD, Pai VV. 2013. BCG immunotherapy as an adjunct to chemotherapy in BL-lL patients--its effect on clinical regression, reaction severity, nerve function, lepromin conversion, bacterial/antigen clearance and 'persister' M. leprae. Lepr Rev 84(1):23-40.

12. Budgetary References BCG Injection: http://www.sciencedirect.com/science/article/pii/S01 40673606685073 http://www.sciencedirect.com/science/article/pii/S01 40673606685073 Travel Expenses: http://www.kayak.com/flights/SMF-CGR/2014-06- 28/2014-06-29 http://www.kayak.com/flights/SMF-CGR/2014-06- 28/2014-06-29 SSS package: (http://www.labx.com/ )http://www.labx.com/

13. Questions