The Significance of the Lepromin Reaction in Man (Part 1 of 2)

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Abstract
Because the human bacillus has not been cultured in vitro and there is still no definite evidence that the infection can be transmitted to experimental animals, many of the investigations on leprosy have had to be carried out in man rather than in animals. In particular, the lepromin reaction cannot be investigated satisfactorily in animals because they cannot be infected with leprosy and, because the only source of leprosy bacilli is from infected human tissue, any attempts to sensitize animals with human leprosy bacilli will result in sensitization to both bacilli and human tissue antigen. Lepromin as a skin-test antigen in leprosy has been compared with the use of tuberculin in tuberculosis; on the other hand, the nature of the antigen is entirely different, for whereas tuberculin is prepared from a culture filtrate of tubercle bacilli, lepromin is prepared from the only available source of leprosy bacilli, namely infected human tissue. Two types of positive skin reactions are described in the lepromin test, (1) a reaction seen after one or two days, essentially similar to the tuberculin reaction, and referred to as the early reaction; (2) a late reaction, presenting as a distinct nodule, beginning about the seventh day and reaching its maximum in the third or fourth week. Both reactions are elicited with the cruder type of lepromin whereas the early reaction predominates when the more purified bacillary type of lepromins are used. Although the bacillary moiety, particularly protein fractions, is an important constituent, the tissue moiety also plays a part in the skin reaction. More recent studies have shown that "lepromins" prepared from normal skin can elicit late reactions, albeit weaker reactions, in patients and normal persons who are lepromin positive. The lepromin reaction is positive in patients with the tuberculoid type of leprosy and negative in those with the more severe, lepromatous type of disease. Thus a positive lepromin reaction is not specific for leprosy since patients with the lepromatous type of disease are lepromin negative and positive lepromin reactions can be obtained in many non-contacts, even in countries where there is no leprosy. There is good evidence to show that there is a strong association between the lepromin and tuberculin reactions in healthy persons, indicating cross-sensitization between the tubercle bacillus and the leprosy bacillus. Furthermore, BCG vaccination results in a positive conversion to both tuberculin and lepromin. Although patients with lepromatous type leprosy always fail to react to lepromin, many (more than 50%) react to tuberculin and "tuberculins" or bacillary antigens prepared from many other species of mycobacteria. The patients with lepromatous type leprosy appear to have, therefore, a specific anergy to lepromin or a skin-test antigen prepared from normal human skin. There is evidence to suggest that this lepromin-negative or anergic state predetermines the chances of a healthy person developing the lepromatous type of disease when infected with the leprosy bacillus, rather than the established infection determining the anergic state.