Relação entre marcadores moleculares do Mycobacterium leprae com a resposta imune, características individuais, de convívio e o adoecimento em uma coorte de contatos de casos de hanseníase

Abstract

The development of leprosy is related not only to biological determinants but also to living conditions. In recent decades, progress has been made in identifying Mycobacterium leprae (M. leprae) in clinical samples. Given the complexity of leprosy, analyzing the relationship between its many determinants is necessary for a better understanding of the illness process related to it. This study aimed to investigate the relationship between the molecular viability of M. leprae and individual characteristics, living conditions, the immune response, and the illness of contacts of leprosy cases. A systematic review and an epidemiological study were carried out. The review aimed to identify the relationship between the presence and/or molecular viability of M. leprae and the process of infection and/or illness of contacts of leprosy cases. The epidemiological study was observational carried out with a cohort of contacts with four follow-ups between 2014 and 2024, in six municipalities in Minas Gerais state. Clinical, epidemiological, social and sorological data obtained through access to a previous research database of the Núcleo de Estudos e Pesquisas em Hanseníase (NEPHANS) were evaluated. In this study, molecular analyses were carried out to identify the RLEP, 16S, and hsp18 targets of M. leprae in nasal swabs. The study population was characterized using descriptive data analysis. The Kolmogorov-Smirnov, McNemar, Kappa, Chi-Square (X²) or Fisher's exact, Mann-Whithney, and Phi coefficient (ϕ) tests were used for statistical analysis. A significance level of 5% was used in all the analyses. The results obtained from the systematic review showed a great diversity of molecular markers already tested for identifying M. leprae DNA in contacts; however, none of the studies retrieved evaluated the molecular viability of the bacillus among contacts regarding infection and illness. It was concluded that detecting M. leprae DNA per se does not provide sufficient evidence to link molecular positivity to infection development and illness among contacts. The molecular analyses conducted in this study identified a positivity for RLEP in over 90% of contacts. The 16S and hsp18 targets were 79.4%, and 39.2% positive, respectively, in the first year. Considering the transience of exposure, 92.2% had a viable bacillus in the nasal mucosa at some point during follow-up, identified by 16S, and 64.7% by hsp18. Despite this, the permanence of viability was observed in 51% by 16S and 11.8% by hsp18. In the bivariate analysis, only the household density variable showed a significant association with the hsp18 target, with higher positivity observed among contacts living in households with a higher density of people. Illness was identified in only one contact. The results demonstrate a high prevalence of viable M. leprae among the evaluated contacts. It was not possible to define a model linking the characteristics of the contacts to the identification of viable bacilli in their bodies. However, household and dormitory density, variables related to the index case, and serology results exhibited similar behavior in relation to 16S and hsp18. It is suggested that, in the evaluated region, exposure to viable bacilli is favored by higher household and dormitory densities and the clinical characteristics of the index case. Furthermore, in the presence of viable bacilli, the absence of antibodies highlights the important role of innate immunity in this population. The results provide insights for future investigations to develop a model that could guide contact surveillance, identifying those to be assessed for M. leprae viability before the onset of clinical signs. In this way, they contribute to the development of measures to achieve early infection identification and consequently interrupt leprosy transmission.