Full project title:
International collaboration for translation of Mycobacterium leprae molecular viability assays (MVA) to the clinical setting and MVA to a chemoprophylaxis-of-contacts-model

Project coordination
National Hansen's Disease Program (USA)

Partners
Anandaban Hospital (Nepal)
Armauer Hansen Research Institute (Ethiopia)
Leonard Wood Memorial Hospital (Philippines) 

Aim: The aims of this project were to
1) refine the NHDP-USA  rapid and sensitive genetic test
and determine if it would be useful for patient samples;
2) train individuals from endemic laboratories to perform the test; and
3) continue to use the test to evaluate new drugs and drug regimens
in experimental models.

Final project summary
Hansen’s Disease, or leprosy, is caused by the bacterium, Mycobacterium leprae. Unlike many other  bacteria, M. leprae will not grow on a petri dish but must be grown in animals (e.g., mouse or armadillo). Furthermore, in these animal models, and also in humans, the bacteria grow extremely slowly. To determine if anti-leprosy treatments given to a patient are actually working or if a patient may have relapsed after completion of treatment, leprosy bacteria isolated from the treated patient must be inoculated into mice. The mice must then be kept for several months to see if the bacteria grow. This is expensive, very time-consuming, and requires animal experimentation. New tests that can easily and quickly determine if M. leprae has been killed by antibiotics or other treatments could help doctors monitor drug therapy and help scientists test new drugs.

The National Hansen’s Disease Programs in the United States of America (NHDP-USA) has developed a rapid and sensitive genetic test that can differentiate live from dead M. leprae in mouse tissue. The aims of this project were to 1) refine this genetic test and determine if it would be useful for patient samples; 2) train individuals from endemic laboratories to perform the test; and 3) continue to use the test to evaluate new drugs and drug regimens in experimental models. These studies will aid leprosy patients by offering improved treatment monitoring and an evidence-based streamlined process for implementation of new drug treatment regimens which should ultimately reduce transmission of disease.

In this study, the research group performed extensive testing to refine and optimise the genetic test for evaluating leprosy patient samples. This was accomplished by forming a collaboration among international leprosy laboratories. The Mycobacterial Research Laboratories, Anandaban Hospital, Kathmandu, Nepal (MRL-Nepal), Armauer Hansen Research Institute, Addis Ababa, Ethiopia (AHRI-Ethiopia), and Leonard Wood Memorial Center for Leprosy Research, Cebu, Philippines (LWM-Philippines) evaluated leprosy patients and collected biopsies. Part of the samples from each laboratory were sent to the NHDP-USA laboratory where they were evaluated with the genetic test. A representative from two of the international laboratories (MRL-Nepal and AHRI-Ethiopia) visited to the NHDP-USA laboratory to receive training in this technique using their own samples. The project also provided equipment, supplies, and other resources necessary to implement the genetic test in these referral laboratories. Thus, the international leprosy laboratories attained the expertise, start-up funds, and capacity to perform the test themselves. In addition, the research group performed seven independent studies testing new drugs and drug regimens that will provide important information for treatment and prevention of leprosy.

Impact 

Utility of a Mycobacterium leprae molecular viability assay for clinical leprosy: An analysis of cases from the Philippines, Ethiopia, and Nepal. Lenz SM, Ray NA, Lema T, et al. Frontiers in Tropical Diseases. Frontiers Media SA. 2022

Post-exposure prophylaxis (PEP) efficacy of rifampin, rifapentine, moxifloxacin, minocycline, and clarithromycin in a susceptible-subclinical model of leprosy. Lenz SM, Collins J, Ray N, et al. PLoS neglected tropical diseases. 2020; 14 (9) : e0008583.

Presentations:
- Adams, LB, DL Williams, and R Lahiri. A molecular viability assay (MVA) for Mycobacterium leprae. Presented at the 50th United States-Japan Cooperative Medical Science Program, Bethesda, MD, January 13-14, 2016.
- Adams, LB, DA Hagge, M Balagon, K Bobosha, DM Scollard, and DL Williams. International collaboration for translation of Mycobacterium leprae molecular viability assays (MVA) to the clinical setting and application of MVA to a chemoprophylaxis-of-contacts model. Presented at the Leprosy Research Initiative Spring Meeting, Ede, Netherlands, April 7-8, 2016.
- Adams, LB, DL Williams, R Lahiri, RW Truman, and DM Scollard. A molecular assay to differentiate live from dead leprosy bacilli in tissues. Presented at the HRSA Research Innovations Symposium, Bethesda, MD, June 1, 2016.
- Adams, L, D Hagge, M Balagon, K Bobosha, D Scollard and D Williams. A molecular assay for determining Mycobacterium leprae viability in tissues and its application to clinical samples. Presented at the International Leprosy Congress, Beijing, China, September 2016.
- Adams, LB, DA Hagge, M Balagon, K Bobosha, DM Scollard, and DL Williams. International collaboration for translation of Mycobacterium leprae molecular viability assays (MVA) to the clinical setting and application of MVA to a chemoprophylaxis-of-contacts model. Presented at the Leprosy Research Initiative Spring Meeting, Veenendaal, Netherlands, April 6-7, 2017.
- Adams, LB. Molecular viability assays for Mycobacterium leprae. In: Panel discussion entitled, “Leprosy: M. leprae and M. lepromatosis in humans, armadillos, and squirrels.” 7th Many Hosts of Mycobacteria meeting, August 9-10, 2017.
- Lenz, S.K. and L.B. Adams. Efficacy of short-term intermittent therapy with new potential single and combinatorial drug treatments for leprosy. Presented at the Leprosy Research Initiative Spring Meeting, Veenendaal, Netherlands, April 5, 2018.
- S.M. Lenz, J.H. Collins, N.A. Ray, A.T. Deming, R. Lahiri, and L.B. Adams. Efficacy of short-term or intermittent treatments with alternate combination therapies for leprosy. Presented at the 20th International Leprosy Congress, Manila, Philippines, September 9-13, 2019.
- Collins, J.H., S.M. Lenz, N.A. Ray, D.A. Hagge, R. Thapa, M.F. Balagon, D.M. Scollard, D.L. Williams, R. Lahiri, and L.B. Adams. Defined parameters for molecular viability of Mycobacterium leprae in tissues. Presented at the 20th International Leprosy Congress, Manila, Philippines, September 9-13, 2019.
- Collins, J.H., S.M. Lenz, N.A. Ray, A.T. Deming, R. Lahiri, and L.B. Adams. Efficacy of uniform multi-drug therapy for treating multibacillary leprosy. Presented at the 20th International Leprosy Congress, Manila, Philippines, September 9-13, 2019.
- Lenz, SM, JH Collins, NA Ray, AT Deming, R Lahiri, and LB Adams. The efficacy of different chemoprophylaxis regimens in a highly susceptible subclinical model of leprosy. Presented at the 20th International Leprosy Congress, Manila, Philippines, September 9-13, 2019.