Evidência molecular para a via aérea de infecção do Mycobacterium leprae e o papel dos portadores assintomáticos na persistência da hanseníase

Abstract

Leprosy persists as public health problem, particularly in Brazil, the second most endemic country in the world. The chain of transmission and mechanisms of infection are not completely understood. Here we investigated the route of infection and disease onset, from airways exposure, colonization, and bloodstream dissemination. This is the first study to evaluate in the same individual the detection of M. leprae DNA through real-time quantitative polymerase chain reaction (qPCR) in nasal vestibule, nasal turbinate mucosa, and peripheral blood samples; in addition to anti- PGL-I serology by enzyme-linked immunosorbent assay (ELISA), and the delayed hypersensitive response through the Mitsuda test (intradermal reaction), of 113 leprosy patients and 104 household contacts of leprosy patients (HHCs). Data exploratory bivariate statistics and multiple correspondence analysis were employed. The DNA positivity among patients: 66.4% (75/113) in nasal swabs, 71.7% (81/113) in nasal turbinate biopsies, 19.5% (22/113) in blood samples, and seropositivity of 62.8% (71/113); with increasing incidences towards the multibacillary (MB) pole of the clinical spectrum. The mean quantities of M. leprae detected in the different patient samples were: 1.8E+07 bacilli/reaction in nasal swabs, 4.1E+07 bacilli/reaction in nasal turbinate biopsies, and 9.3E+03 bacilli/reaction in peripheral blood samples. Statistically significant relationships between every pairwise comparison of data and an intricate multivariate congruence were observed for patients’ data (P<0.05). The positivity among HHCs: 18.3% (19/104) for anti-PGL-I, 49% (51/104) for nasal swabs, 53.8% (56/104) for nasal biopsies, and 6.7% (7/104) for blood samples. The mean quantities of M. leprae among the different samples were: 1.8E+04 bacilli/reaction for nasal swabs, 1.3E+05 bacilli/reaction for nasal turbinate biopsies, and 1.4E+04 bacilli/reaction for peripheral blood samples. The comparison between the mean ELISA indexes obtained for the HHCs of PB patients versus the results from contacts of MB patients were significantly different (P=0.00γ7). The multiple correspondence analysis of HHCs’ data revealed associations between: positive results to both qPCR in blood and anti-PGL-I, and positive results to both qPCR in nasal swab and nasal turbinate biopsies. The comparison between the mean values obtained for patients vs. HHCs, shown that for the both sites in the nose (surface and mucosa), and for the anti-PGL-I, the means differed significantly (P<0.0001). During a minimum follow-up period from 5 to 7 years, out of 104 HHCs, 7 developed leprosy (6.7%). Risk for the disease outcome was estimated comparing results of HHCs WHO develop leprosy with those not affected. Neither nasal passage nor mucosa positivity was determinant of later disease onset; howsoever, blood presence increased the risk for disease development [RR/LR+ 5.54 (IC 95% 1.30 - 23.62)], as well did the seropositivity [LR+ 3.69 (95%CI 1.67 - 8.16); RR 5.97 (95%CI 1.45 - 24.5)]. Our findings strongly suggest that the aerial route of infection and transmission is predominant. The overall frequency of positivity among HHCs revealed that: M. leprae is widespread among them; HHCs experience high bacillary burden regardless of their index case disease manifestation; and that, HHCs comprise a recognizable group of individuals that contribute to the infection risk to themselves and most probably to others.