High seropositivity against NDO-LID in a group of household contacts of leprosy patients. Are we close to leprosy elimination in Colombia?

INTRODUCTION: Leprosy is a chronic infectious disease caused by two mycobacteria (Mycobacterium leprae and Mycobacterium lepromatosis). The household contacts (HHC) of leprosy index cases are at higher risk of being infected with these mycobacteria. Therefore, serological testing in HHC would be an effective strategy to eliminate leprosy in Colombia. OBJECTIVE: To determine the seroprevalence and factors associated with the infection by M. leprae in HHC. METHODS: An observational study was conducted in 428 HHC located in the Colombian Caribbean, Andean, Pacific, and Amazonian regions. We evaluated the seropositivity and titrations of IgM, IgG, and protein A against NDO-LID. RESULTS: The evaluated HHC showed high seropositivity, precisely 36.9% anti-NDO-LID IgM, 28.3% anti-NDO-LID IgG, and 47.7% protein A. Furthermore, Protein A showed a greater capacity to detect infected individuals than other anti-NDO-LID conjugates (p < 0.0001). This study did not show differences in the seropositivity according to sex or age of the HHC (p > 0.05). Higher seropositivity for IgM was evidenced mainly in HHC located in the Colombian Pacific region (p 0.001). This research did not show differences in the seropositivity for these serological tests between HHC of PB or MB leprosy patients (p > 0.05). CONCLUSION: Leprosy transmission is still active between Colombian HHC. Consequently, controlling leprosy transmission in this population is fundamental to eradicating this disease.

Social and environmental conditions related to Mycobacterium leprae infection in children and adolescents from three leprosy endemic regions of Colombia.

BACKGROUND: Leprosy is is still considered a public health issue and in Colombia 7-10% of new cases are found in children, indicating both active transmission and social inequality. We hypothesized that circulating antibodies against Natural Octyl Disaccharide-Leprosy IDRI Diagnostic (NDO-LID) (a combination of Mycobacterium leprae antigens) could reveal the social and environmental aspects associated with higher frequencies of M. leprae infection among children and adolescents in Colombia. METHODS: An observational cross-sectional study was conducted involving sampling from 82 children and adolescents (younger than 18 years of age) who had household contact with index leprosy patients diagnosed in the last 5 years. Data were analyzed through bivariate analysis made by applying a Pearson x2 test for qualitative variables, while quantitative variables, depending on their distribution, were analyzed using either a Student's t-test or Mann-Whitney U test. Multivariate analysis was performed using a multiple regression and binomial logistic approach. RESULTS: A bivariate analysis demonstrated that antibody titers against NDO-LID were significantly greater in children and adolescents with a low socioeconomic status that had: lived in vulnerable areas of the UAChR shared region; eaten armadillo meat; exposure of over 10 years to an index case and; not received BCG immunization. Moreover, a multivariate analysis showed that residing in the UAChR region has a strong association with a greater possibility of M. leprae infection. CONCLUSIONS: M. leprae transmission persists among young Colombians, and this is associated with social and environmental conditions. An intensification of efforts to identify new leprosy cases in vulnerable and forgotten populations where M. leprae transmission continues therefore appears necessary.

Genetic variants, structural, and functional changes of Myelin Protein Zero and Mannose-Binding Lectin 2 protein involved in immune response and its allelic transmission in families of patients with leprosy in Colombia.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Genetic factors associated with immune response contribute to infection development and disease. M. leprae has the capacity to invade Schwann cells in the peripheral nervous system and cause neuropathy. However, while the responsible molecular mechanisms remain to be fully unveiled, they have begun being elucidated. We studied genetic variants Myelin Protein Zero (MPZ), a major structural component of the myelin sheath, and Mannose Binding Lectin 2 (MBL2), a protein involved in immune response, in 112 family groups of 114 leprosy patients using PCR-RFLP, aiming to calculate the association and allelic transmission of variants associated in first, second and third-degree relatives. Polymorphisms found in MPZ and MBL2 showed association with leprosy. Different probabilities for allelic transmission were found for first and second-degree relatives, a fact that is important to take into account when evaluating risk in contacts of leprosy patients. Structural analysis allows the study of putative amino acids and their possible effect on protein structure and function, as well as on the assembly of a protein homotetramer. Our results suggest that the identified MPZ and MBL2 gene mutations are associated with leprosy in a Colombian population, which correlates with MPZ and MBL2 protein function, and increase the risk of M. leprae infection in leprosy-patients' family members. Additionally, structural analyses were carried out specifically for MPZ protein using information available in databases, and analyzing the substitutions in wildtype and mutant protein. The results show significant structural changes, which may be associated to infection and pathogenicity.