Tuberculosis and leprosy: Evidence for interaction of disease • 25 



factors as pregnancy, intercurrent infection, and malnutri- 

 tion, for an infected individual of relatively high resistance 

 type of leprosy to downgrade toward the lepromatous pole. 

 This concept of immune spectrum is of epidemiological im- 

 portance and is of significance in the history and develop- 

 ment of leprosy. 



However, the immunity in the cell mediated response is 

 not absolutely specific. Mackaness (1967:337) has demon- 

 strated that the simultaneous exposure of /W. titherculosis and 

 another bacillus, Listeria monocytogenes, to a host sen- 

 sitized by previous exposure to M. tuberculosis induces im- 

 munity to both pathogens. The lone exposure of L. mono- 

 cytogenes to the M. tuberculosis-sensiiiicd host does not, 

 however, induce immunity. It is the dual and coincident ex- 

 posure which is significant in immunity induction. To what 

 extent this duality of exposure and immunity applies in M. 

 leprae and M. tuberculosis in clinical context is not, at pres- 

 ent, known. If the same conditions apply as in M. tuber- 

 culosis and Listeria invasion, then there may be relevance to 

 human exposure and immunity in the medieval period in 

 Britain when both infections were present and when tuber- 

 culosis was of increasing incidence. 



A further response of CMI, of diagnostic significance in 

 tuberculosis and of pathological tissue significance in both 

 leprosy and tuberculosis, is delayed hypersensitivity reac- 

 tion. This reaction in which granulomata, lesions typical of 

 leprosy and tuberculosis, are induced, is not considered sig- 

 nificant in the present discussion of bacterial interrelation- 

 ship. 



Within the context of immunity, prophylactic immuniza- 

 tion by Bacille Calmette Guerin (BCG) is relevant to tuber- 

 culosis and to leprosy. BCG, produced from M. hovis. is used 

 in clinical circumstances to induce immunity to tuberculosis 

 in persons demonstrated by Mantoux hypersensitivity testing 

 to be nonimmune to the infection. The phenomenon of BCG 

 immunization does, itself, demonstrate the phenomenon of 

 mycobacterial cross specificity, since the vaccine is not pro- 

 duced from M. tuberculosis but is produced from M. bovis. a 

 subspecies or variant. In clinical trials in areas of the world in 

 which leprosy is endemic, BCG immunization has a proven, 

 but variable, efficacy in the prevention of leprosy. The range 

 of variability is from 20% efficacy in a Burmese trial to 80% 

 efficacy in Uganda. Fine ( 1984: 147) suggested a number of 

 reasons for this variability. Differences between these popu- 

 lations exhibiting such diverse BCG efficacy may, in part, be 

 attributable to a degree of immunity to leprosy acquired by 

 contact with environmental mycobacteria. Administration of 

 BCG vaccine to a people already in possession of such partial 

 immunity may merely augment the overall population immu- 

 nity to leprosy, and indeed to tuberculosis also, thereby 

 falsely overestimating the value of BCG vaccination. 



In summary, the acquired defensive mechanism in tuber- 

 culosis and leprosy is CMI. The immune reaction is not 

 absolutely pathogen specific, but a degree of cross immunity 

 between the pathogens is noted. Delayed hypersensitivity 



Zagreb Paleopathology Symp. 1988 



reaction is of significance in the development of post primary 

 tuberculosis and probably in the granulomatous development 

 in leprosy. Genetic immunity is of unknown, but probably 

 little, significance in leprosy and tuberculosis. Innate immu- 

 nity is a nonspecific entity and is dependent upon biological 

 adaptive mechanisms in the host to environmental and meta- 

 bolic change and to intercurrent infection. 



There is no evidence to suggest that the bacteria responsi- 

 ble for the clinical diseases of leprosy and tuberculosis were 

 in any way different in antiquity from those of today. Neither 

 is there evidence to indicate that the immunological mecha- 

 nism of the host to bacterial invasion has changed through 

 time. 



It is temporal change in the immunological status of popu- 

 lations, modified by previous bacterial exposure, which is, in 

 part, the basis of the present hypothesis. 



Epidemiology 



Because, in the main, tuberculosis and leprosy are diseases 

 of the undeveloped and developing nations, in which statis- 

 tics are either absent or unreliable, the prevalence of these 

 diseases in the world at the present time is not known. It is 

 estimated, however, that there are 1 1 .5 million cases of lep- 

 rosy (World Health Organization 1985:10), although it is 

 suggested (Andersen 1987) that the figure may be nearer to 

 20 million. The total number of persons with tuberculosis is 

 not known, but it is estimated that 10 million persons develop 

 tuberculosis each year and at least 3 million die of the disease 

 (World Health Organization 1982:10). 



Against this stark statistic it is necessary to consider as- 

 pects of the epidemiology of these two diseases. Much of the 

 data are determined from current practice with only minimal 

 input from paleopathological studies. Because, as osteoar- 

 cheological evidence indicates, there has been no change in 

 host tissue response to infection by M. tuberculosis or M. 

 leprae, and there has, thereby, been no change in clinical 

 presentation through time, it is considered justifiable to ex- 

 trapolate current epidemiological data to archaic popula- 

 tions. The inherent risks in moving from the known to the 

 unknown are accepted. 



TRANSMISSION AND DEVELOPMENT 



There are, essentially, two portals of entry of the organisms 

 causing tuberculosis in man: ingestion of bacilli or inhalation 

 of bacilli. Reference to the taxonomic debate on A/, bovis and 

 M. tuberculosis has already been made, and the irrelevance 

 of this in immunology is noted. However, in terms of trans- 

 mission, and in the context of a hypothesis of historic devel- 

 opment of disease, the two bacilli, be they strains or species, 

 are of significance. Transmission of M. bovis is via the gas- 

 trointestinal tract from the ingestion of cattle meat or milk 

 infected with M. bovis. The primary tuberculous lesion is 

 therefore in the gut. Transmission of M. tuberculosis is via 



