Leprosy remains an important health problem worldwide. The disease is caused by a chronic granulomatous infection of the skin and peripheral nerves with Mycobacterium leprae. The clinical range from tuberculoid to lepromatous leprosy is a result of variation in the cellular immune response to the mycobacterium. The resulting impairment of nerve function causes the disabilities associated with leprosy. This review summarises recent advances in understanding of the biology of leprosy, clinical features of the disease, the current diagnostic criteria, and the new approaches to treatment of the infection and the immune-mediated complications. Supervised multi-drug therapy (MDT) for fixed durations is highly effective for all forms of the disease. The widespread implementation of MDT has been associated with a fall in the prevalence of the leprosy but as yet no reduction in the case-detection rate globally. Thus, leprosy control activities must be maintained for decades to interrupt transmission of infection.

Leprosy is a chronic, dermatological and neurological disease that results from infection with the unculturable pathogen Mycobacterium leprae 1 and causes nerve damage that can lead to severe disabilities. There is no known reservoir for M. leprae other than human beings. New opportunities for understanding the transmission of the leprosy bacillus and its phylogeny have arisen following the determination of the complete 3.3-Mb genome sequence of the TN strain, from Tamil Nadu, India 2 .A notable feature of the M. leprae genome is the exceptionally large number of pseudogenes, which occupy almost half of the TN chromosome 2 . The resulting loss of function most likely accounts for the exceptionally slow growth rate of the bacillus and for researchers' failure to culture it in vitro. Given this extensive genome decay, one might expect to find more genetic variability between different isolates of M. leprae, but initial analysis of SNPs demonstrated that these were very rare, occurring roughly once every 28 kb. RESULTS Complete genome sequence of Br4923The Br4923 strain of M. leprae was chosen for complete genome analysis because it was originally isolated from a patient in Brazil, the country with the second highest leprosy burden, and because Brazil is geographically remote from India Recombination between dispersed repeats?The SNPs associated with dispersed repeats deserve some comment, as they provide evidence for genome plasticity in M. leprae. Variation between different copies of repeat family members had previously been reported 18, 19 , but analysis of two complete genomes provided a richer, more comprehensive dataset. Although all four repeat families (RLEP, REPLEP, LEPRPT and LEPREP) were present in the same copy number and location in both genomes, roughly half of the family members displayed sequence polymorphisms when pair-wise comparisons were performed (Fig. 1). The number of polymorphic sites ranged from one in LEPRPT and REPLEP to six in RLEP. With one exception, these resulted from G-A transitions in the RLEP, LEPRPT and LEPREP elements or single-base indels in LEPREP or REPLEP. The polymorphic sites tend to be occupied by A in the TN strain and by G in Br4923. Variation in REPLEP occurs at position 636, which is occupied either by GGG or GG (Fig. 1). Almost 25% of the total SNPs (38/155) occur in these repeats, which account for a mere 1.16% of the genome. The over-representation of SNPs in these elements may indicate that recombination events between different copies of the repetitive elements result in the dispersal of a particular SNP. This interpretation is supported by the strain-specific bias for A and G in the TN and Br4923 strains, respectively, and the finding that more differences are found toward the center of the element rather than near its ends. In turn, these combined findings render polymorphic sites in repetitive DNA unattractive as potential epidemiological tools. Search for informative SNPsFor phylogenetic and phylogeographic purposes, we determined which SNPs had been inhe...

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Leprosy is a granulomatous disease affecting the skin and nerves caused by Mycobacterium leprae. It continues to be a significant public health problem. Multidrug therapy (MDT) cures the infection, but immunological reactions may occur and neuropathy may lead to disability and deformity. It is important that the manifestations of the condition are recognized as early as possible so that early nerve damage can be identified and treated rapidly.