**5. Conclusions**

The possible origins and interrelationships of all agents causing leprosy-like disease are summarised in **Figure 9**. The phylogeny of *M. haemophilum* with *M. leprae* and '*M. lepromatosis*' indicates a deep common ancestor for all three taxa [16]; this ancestor is provisionally labelled

24 Hansen's Disease - The Forgotten and Neglected Disease

**Figure 9.** Origins and interrelationships of agents causing leprosy-like disease. Proposed relationships requiring further study are indicated (?). 'PROTOLEP' represents a prototype taxon with the specific type of outer membrane lipids expressed in *M. haemophilum, M. leprae* and possibly '*M. lepromatosis*'. *M. simiae* complex (**1**) represents species (*M. florentinum*, *M. interjectum*, *M. sherrissii*, *M. triplex*) apparently expressing genes for PDIM synthesis; *M. simiae*

complex (**2**) includes the remaining species [128].

An understanding of the origins and spread of leprosy depends on establishing detailed knowledge of the ancient genotypes and their correlation with modern disease. The overall scenario has been expanded by the recent characterisation of the distinct modern clade, currently labelled '*M. lepromatosis*'. The availability of a full genome for '*M. lepromatosis*' is allowing specific probes to be developed to search for ancient expression of this biotype. Ongoing research is demonstrating that subtle lipid biomarker differences may be of value in distinguishing '*M. lepromatosis*' from *M. leprae*. The overall picture for the global development of leprosy suggests that the ancient disease evolved into a number of recognisable clades in Africa/Eurasia. It is clear that leprosy was introduced into the Americas by human migration, and the disease was passed on to indigenous armadillos. The deeper origins of leprosy appear to be inextricably linked to relatives of the environmental taxon *M. haemophilum*. Diseases in cats, cattle and goats, with affiliations and resemblances to leprosy, require detailed investigation.

## **Acknowledgements**

For basic studies on leprosy and related mycobacteria, DEM and GSB are grateful for support from LEPRA (www.lepra.org.uk), in the form of Studentships: Gary Dobson 1980–1983, Gurdyal S. Besra 1987–1990, Susanne Hartmann 1991–1994. The Leverhulme Trust Project Grant F/00 094/BL supported the development of lipid biomarker detection of ancient leprosy (OY-CL, DEM, GSB). GSB acknowledges support in the form of a Personal Research Chair from Mr. James Bardrick and the UK Medical Research Council (grant MR/K012118/1) and Wellcome Trust (grant 081569/Z/06/Z).
