Are all nonsolid Mycobacterium leprae dead? Does a negative finding in the mouse foot pad indicate that there is actually no growth of M. leprae in the animals?

Ever since the discovery of the foot pad technic for growth of M. leprae in mice, investigators have overemphasized the laboratory results in clinical applications. Overenthusiasm has led to some dire results in the leprosy field. Two well-known examples can be cited, which are based on the presumption that: a) all the nonsolidly stained M. leprae are dead, and b) that a negative finding in the mouse foot pad indicates no growth of M. leprae in the animals. The former led clinical investigators to claim a false emergence of drug resistance after one year's treatment with a potent antileprosy drug, B663, which was almost abandoned for later clinical use. The latter led investigators to introduce a low-dose drug treatment, which resulted in a worldwide appearance of DDS resistance in leprosy. This paper outlines the reasoning that not all nonsolid M. leprae are dead, and that not all the organisms in the foot pads are detectable by the present standard foot pad/ M. leprae technic.