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© 1998 Oxford University Press

research-article

Delayed-type hypersensitivity to Mycobacterium leprae soluble antigens as a test for infection with the leprosy bacillus

Jonathan AC Jonathana, Paul EM Fineb, Jörg M Pönnighausc,e, Richard JW Reesd and Dominic Chavulac

aDepartment of Public Health Medicine, United Medical and Dental Schools of Guy's and St Thomas's Hospitals Capital House, 42 Weston Street, London SE1 3QD. UK
bInfectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine London WC1E 7HT, UK
cLEPRA PO Box 46, Chiumba, Malawi
dNational Institute for Medical Research Mill Hill, London, UK

BACKGROUND: Mycobacterium leprae (M. leprae) soluble antigen (MLSA) reagents have been developed with the aim of finding a reagent, comparable to tuberculin, which could identify individuals infected with the leprosy bacillus. They have yet to be evaluated fully in human populations.

METHODS: More than 15 000 individuals living in a leprosy endemic area of northern Malawi were skin tested with one of five batches of MLSA prepared using two different protocols. The main difference in preparation was the introduction of a high G centrifugation step in the preparation of the last three (‘second-generation’) batches.

RESULTS: The prevalence of skin-test positivity (delayed-type hypersensitivity (DTH)) and association with the presence of a BCG scar were greater for first (batches A6, A22) than second (batches AB53, CD5, CD 19) generation reagents. The association of positivity with M. leprae infection was investigated by comparing results among known (household) contacts of leprosy cases, and among newly diagnosed leprosy patients with those in the general population. While positivity to ‘first-generation’ antigens appeared to be associated with M. leprae infection, positivity to later antigens was unrelated either to exposure to leprosy cases or presence of leprosy disease. There were geographical differences in the prevalence of DTH to the various batches, probably reflecting exposure to various mycobactena in the environment.

CONCLUSIONS: Our results suggest that the ‘second-generation’ batches have lost antigens that can detect M. leprae infections, but that they retain one or more antigens which are shared between M. leprae and environmental mycobacteria. Natural exposure to these both sensitizes individuals and provides natural protection against M. leprae infection or disease. Identification of antigens present in these groups of skin test reagents may assist in production of improved skin test reagents.

Keywords leprosy, delayed-type hypersensitivity, Mycobacterium leprae, skin test

Accepted 11 November 1997


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