• Safety: evaluate safety of skin test antigens in healthy non-contacts, assessing whether, and to what degree, individuals are sensitized to the antigens; evaluate safety of skin test antigens in leprosy patients and contacts of leprosy patients. [ Time Frame: Stage A-day 0, 45-51h and 69-75h; Stage B-69-75h and day 6-8; Stage C-days 2-4 and 6-8; subjects with induration greater than 10 mm at day 25-31; subjects with any persistent reaction/AE followed until resolution or stabilization of symptoms. ] [ Designated as safety issue: Yes ]
  

This double-blind Phase II clinical trial will be conducted in 3 stages to evaluate 2 new leprosy skin test antigens, MLSA-LAM and MLCwA, as diagnostic-epidemiological tools designed to measure incidence of leprosy infection in Kathmandu, Nepal, a leprosy endemic area. Stage A will provide an initial indication of safety of the 2 new test antigens in 10 healthy members of the leprosy endemic population (5 subjects per antigen at 2 dosages each). Stage B will expand this analysis by an additional 90 healthy subjects (45 subjects per antigen). If any subjects in Stage A or B show ulcerations at the 1.0mcg dose of MLSA-LAM or MLCwA test sites, then only the 0.1mcg dose will be used for Stage C. The final stage, Stage C, is divided into 2 parts. The first part, Stage C-1, will assess safety of both antigens at the high dose (1.0mcg) in populations at a higher risk of developing ulcerations at skin test sites. Eighty subjects will be recruited: 20 household contacts of BL/LL (borderline lepromatous/lepromatous) leprosy patients, 20 BL/LL leprosy patients, 20 BT/TT (borderline tuberculoid/tuberculoid) leprosy patients and 20 tuberculosis (TB) patients. If any of these first 80 subjects show ulcerations at the 1.0 mcg dose of MLCwA or MLSA-LAM test sites, then only the 0.1 mcg dose will be used for Stage C-2. After safety data is found acceptable by the Safety Monitoring Committee following each stage, the study will further enroll 345 BT/TT and BL/LL leprosy patients, contacts of BL/LL or BT/TT leprosy patients, TB patients, and non-contacts into Stage C-2. This study will define a positive skin test reaction for MLSA-LAM and MLCwA, and this definition will be used in estimating sensitivity and specificity for each skin test antigen and dosage. It is expected that the BT/TT leprosy patients and healthy contacts of leprosy patients will have larger indurations at both M. leprae-derived antigen sites, and a variable reaction at the tuberculin/PPD site. The non-contacts, BL/LL leprosy patients, and TB patients will have smaller indurations at all leprosy skin test sites and a variable reaction at the tuberculin/PPD site. Finally, the TB patients will react with a large induration at the tuberculin/PPD site. Primary study objectives are to evaluate safety of these 2 new leprosy skin test antigens and to estimate specificity and sensitivity of these skin test antigens in detecting M. leprae infection by: selecting a dosage of the MLSA-LAM and MLCwA antigens that causes minimal induration in healthy non-exposed subjects; selecting a size of induration that will serve as a definition of a positive skin test reaction for MLSA-LAM and MLCwA in leprosy patients; and comparing proportion of positive skin test reactors in healthy subjects to proportion in BT/TT and BL/LL leprosy patients, contacts of leprosy patients, and TB patients. Secondary study objectives are to compare mean size of induration in response to each test antigen in healthy subjects versus BT/TT and BL/LL leprosy patients, contacts of leprosy patients, and TB patients as a measure of specificity and sensitivity; to compare the specificity and sensitivity of the 2 new antigens with tuberculin/PPD in patients with clinical leprosy, contacts of leprosy patients, and healthy unexposed subjects (non-patient contacts); to quantify release of IFN-gamma from lymphocytes in whole blood from leprosy patients, leprosy patient contacts, TB patients, and healthy nonexposed subjects, following in vitro stimulation with leprosy skin test antigens and PPD, using the QuantiFERON-CMI kit (with results being compared to the magnitude of the skin test response); and to determine if antibodies against a M. leprae specific antigen, Phenolic Glycolipid - I (PGL-I) are present in serum from leprosy patients, leprosy patient contacts, TB patients, and healthy non-exposed subjects, using a lateral flow immunodiffusion rapid test kit. Results will be compared to the magnitude of skin test response.