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Human Genetic Susceptibility of Leprosy Recurrence.

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.

SUBMITTER: Uaska Sartori PV

PROVIDER: S-EPMC6987179 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Human Genetic Susceptibility of Leprosy Recurrence.

Uaska Sartori Priscila Verchai PV Penna Gerson O GO Bührer-Sékula Samira S Pontes Maria A A MAA Gonçalves Heitor S HS Cruz Rossilene R Virmond Marcos C L MCL Dias-Baptista Ida M F IMF Rosa Patricia S PS Penna Maria L F MLF Medeiros Fava Vinicius V Stefani Mariane M A MMA Távora Mira Marcelo M

Scientific reports 20200128 1

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 ...[more]

PMID: 31992776

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Project description:BACKGROUND:The multidrug therapy (MDT) for leprosy treatment adopted by Brazil in the 1990s was important for reducing leprosy in the country; however, recurrent cases remained problematic. Mechanisms involved in leprosy recurrence are heterogeneous and can be sorted into three groups: insufficient therapy, bacillary persistence and new infections. This study aimed to analyse the time interval of leprosy recurrence in relation to the therapeutic scheme in the state of Acre. The hypotheses were as follows: 1) treatments (a) rifampicin, ofloxacin and minocycline (ROM) and (b) dapsone (DDS) have a short leprosy recurrence time, 2) treatments based on MDT have a long leprosy recurrence time, 3) there is a dose-response relationship between MDT and the time interval between leprosy episodes. METHODS:This retrospective cohort study included 201 patients with a second episode of clinical leprosy at the reference centers for leprosy control in the state of Acre. Exposure was the type of therapeutic scheme as follows: 1) ROM, 2) DDS, 3) MDT0-9 doses, 4) MDT10-19 doses, 5) MDT20-29 doses, and 6) MDT30+ doses. Outcome was the time interval between release from treatment and a diagnosis of a recurrent leprosy case. Incidence rate ratios and relative risk Poisson regressions adjusted by age and sex were calculated with 95% confidence intervals. RESULTS:The 201 patients studied during this retrospective follow-up resulted in a total of 224 cases of recurrent leprosy. Incidence rate ratios within this therapeutic scheme were as follows: 3.3 (2.39, 4.2; ROM/MDT30+), 1.12 (0.33, 1.92; DDS/MDT30+), 2.17 (1.39, 2.94; MDT0-9/MDT30+), 1.94 (1.13, 2.75; MDT10-19/MDT30+) and 1.26 (0.47, 2.05; MDT20-29/MDT30+). Relative risk Poisson regressions showed a protective effect of MDT30+ in comparison with ROM (0.22; 0.07, 0.72), MDT0-9 (0.42; 0.21, 0.85), and MDT10-19 (0.44; 0.21, 0.92). No differences among MDT30+ and DDS (0.71; 0.36, 1.41) and MDT20-29 (0.76; 0.38, 1.49) were observed. CONCLUSIONS:New infection is an important-yet neglected-mechanism in leprosy recurrence in the state of Acre and can challenge the leprosy elimination plan in Brazil. MDT with few doses might be associated with leprosy recurrence due to insufficient therapy or bacillary persistence.

Dataset Information

Human Genetic Susceptibility of Leprosy Recurrence.

Publications

Human Genetic Susceptibility of Leprosy Recurrence.

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