Abstract
Host genetic susceptibility to leprosy has been intensively investigated over the last decades; however, there are no studies on the role of genetic variants in disease recurrence. A previous initiative identified three recurrent cases of leprosy for which none of the M. leprae strains, as obtained in the first and the second diagnosis, had any known genomic variants associated to resistance to Multidrug therapy; in addition, whole genome sequencing indicated that the same M. leprae was causing two out of the three recurrences. Thus, these individuals were suspected of being particularly susceptible to M. leprae infection, either as relapse or reinfection. To verify this hypothesis, 19 genetic markers distributed across 11 loci (14 genes) classically associated with leprosy were genotyped in the recurrent and in three matching non-recurrent leprosy cases. An enrichment of risk alleles was observed in the recurrent cases, suggesting the existence of a particularly high susceptibility genetic profile among leprosy patients predisposing to disease recurrence.
Highlights
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an obligatory intracellular, slow growing, alcohol-acid resistant bacillus with tropism for skin macrophages and Schwann cells of the peripheral nervous system[1]
Among the recurrent cases of leprosy identified in the U-multidrug therapy (MDT)/CT-BR trial; for three of them, M. leprae isolates obtained in the first and second diagnosis were submitted to whole genome sequencing (WGS); analyses did not show any mutations associated with drug resistance
Considering that (i) all patients were followed and completed the treatment correctly, (ii) uniform six doses MDT (U-MDT) was efficient in treating the disease, and (iii) no mutation associated with drug resistance was detected in the genomes of any M. leprae strain recovered from the three reinvestigated recurrent cases, it is reasonable to assume that leprosy recurrence was not due to characteristics of the etiologic agent but yet, to a combination of continuous exposure to M. leprae associated with an increased host susceptibility genetic background
Summary
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an obligatory intracellular, slow growing, alcohol-acid resistant bacillus with tropism for skin macrophages and Schwann cells of the peripheral nervous system[1]. Among the recurrent cases of leprosy identified in the U-MDT/CT-BR trial; for three of them, M. leprae isolates obtained in the first and second diagnosis were submitted to whole genome sequencing (WGS); analyses did not show any mutations associated with drug resistance. Considering that (i) all patients were followed and completed the treatment correctly, (ii) U-MDT was efficient in treating the disease, and (iii) no mutation associated with drug resistance was detected in the genomes of any M. leprae strain recovered from the three reinvestigated recurrent cases, it is reasonable to assume that leprosy recurrence was not due to characteristics of the etiologic agent but yet, to a combination of continuous exposure to M. leprae associated with an increased host susceptibility genetic background. Allele frequencies were compared across the two groups and with publicly available databases
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