Date Published: April 9, 2008
Publisher: Public Library of Science
Author(s): Saroj K. Young, Jorg M. Ponnighaus, Suman Jain, Sebastian Lucas, Sujai Suneetha, Diana N. J. Lockwood, Douglas B. Young, Paul E. M. Fine, Mathieu Picardeau
Abstract: BackgroundInadequate understanding of the transmission of Mycobacterium leprae makes it difficult to predict the impact of leprosy control interventions. Genotypic tests that allow tracking of individual bacterial strains would strengthen epidemiological studies and contribute to our understanding of the disease.Methodology/Principal FindingsGenotyping assays based on variation in the copy number of short tandem repeat sequences were applied to biopsies collected in population-based epidemiological studies of leprosy in northern Malawi, and from members of multi-case households in Hyderabad, India. In the Malawi series, considerable genotypic variability was observed between patients, and also within patients, when isolates were collected at different times or from different tissues. Less within-patient variability was observed when isolates were collected from similar tissues at the same time. Less genotypic variability was noted amongst the closely related Indian patients than in the Malawi series.Conclusions/SignificanceLineages of M. leprae undergo changes in their pattern of short tandem repeat sequences over time. Genetic divergence is particularly likely between bacilli inhabiting different (e.g., skin and nerve) tissues. Such variability makes short tandem repeat sequences unsuitable as a general tool for population-based strain typing of M. leprae, or for distinguishing relapse from reinfection. Careful use of these markers may provide insights into the development of disease within individuals and for tracking of short transmission chains.
Partial Text: Implementation of standardised multidrug regimens in the 1980s and 1990s has had a major impact on global leprosy prevalence, through shortening the duration of treatment. While it was reasoned that effective treatment of individual patients would reduce the spread of Mycobacterium leprae within communities, there is little evidence that the elimination programme has had a significant impact on disease incidence . Continued controversies over global trends in the epidemiology of leprosy highlight gaps in our knowledge of the basic mechanisms of infection transmission and pathogenesis of this poorly understood disease . While direct spread by aerosol or contact with infected individuals is thought to be the major route for dissemination of M. leprae, a role for zoonotic or environmental reservoirs cannot be excluded.
Our findings in the Malawi patients are consistent with previous publications demonstrating extensive polymorphism in the copy number of short tandem repeat sequences of M. leprae–. Comparison with the relative paucity of SNP polymorphisms suggests that M. leprae may have acquired a specific lesion in the mechanisms required for maintenance of fidelity during replication of repeat sequences, possibly as one of the consequences of the overall pattern of gene decay in this organism . Comparison of different repeat loci indicates that changes are most extensive in the case of very short repeat motifs comprising only 2 or 3 base pairs. This is consistent with the reported absence of polymorphism in longer repeat sequences resembling the mycobacterial interspersed repeat units (MIRU) that have proved useful in typing of M. tuberculosis.