Leprosy is a chronic infectious disease caused by Mycobacterium leprae. This disease is characterized by skin and peripheral nerve trunk damage. The mechanisms responsible for the observed nerve damage in leprosy could be directly related to the ability of M. leprae to infect Schwann cells, leading to triggering of signaling events. Therefore, we hypothesize that in response to M. leprae infection, activation of the Notch signaling pathway in Schwann cells could play a crucial role in glial cell dedifferentiation. On the other hand, nerve damage evidenced in this disease may be additionally explained by indirect mechanisms such as the immune response and genetic susceptibility of the host. The understanding of the mechanisms leading to nerve damage induced by M. leprae infection will allow us to generate valuable tools for the early detection of leprosy as well as for the mitigation of the effects of this disabling disease.
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 x 2 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. Electronic supplementary material The online version of this article (10.1186/s12879-019-4120-2) contains supplementary material, which is available to authorized users.
Introduction: Leprosy is an infectious disease caused by Mycobacterium leprae, a debilitating disease that affects the skin and peripheral nerves. It is possible that tissue changes during infection with leprosy are related to alterations in the activity of the Notch signaling pathway, an innate signaling pathway in the physiology of the skin and peripheral nerves. Methods: This is a descriptive observational study. Thirty skin biopsies from leprosy patients and 15 from individuals with no history of this disease were evaluated. In these samples, gene expressions of cellular components associated with the Notch signaling pathway, Hes-1, Hey-1, Runx-1 Jagged-1, Notch-1, and Numb, were evaluated using q-PCR, and protein expression was evaluated using immunohistochemistry of Runx-1 and Hes-1. Results: Changes were observed in the transcription of Notch signaling pathway components; Hes-1 was downregulated and Runx-1 upregulated in the skin of infected patients. These results were confirmed by immunohistochemistry, where reduction of Hes-1 expression was found in the epidermis, eccrine glands, and hair follicles. Increased expression of Runx-1 was found in inflammatory cells in the dermis of infected patients; however, it is not related to tissue changes. With these results, a multivariate analysis was performed to determine the causes of transcription factor Hes-1 reduction. It was concluded that tissue inflammation was the main cause. Conclusions: The tissue changes found in the skin of infected patients could be associated with a reduction in the expression of Hes-1, a situation that would promote the survival and proliferation of M. leprae in this tissue.
Our data indicate that testing for serum anti-NDO-LID antibodies can be a useful screen to identify patients at risk of developing LRs and neuritis.
Leprosy is a chronic infectious disease with a broad spectrum of manifestations. Delays in attaining correct diagnosis permit progressive peripheral nerve damage that can produce irreversible disabilities. Tests detecting antigen-specific antibodies can aid the diagnostic process and potentially detect patients earlier. Reported tests have lacked optimal sensitivity and specificity; however, the need to develop new tests to aid early diagnosis still remains. In this study, we determined the sensitivity, specificity, positive predictive value, and negative predictive value of enzyme-linked immunosorbent assay (ELISA) using natural octyl disaccharide-leprosy IDRI diagnostic (NDO-LID). Serum samples from confirmed multibacillary patients ( = 338) and paucibacillary patients ( = 58) were evaluated and contrasted against samples from individuals without leprosy (100 healthy persons, 36 leishmaniasis or tuberculosis patients). ELISA detecting either antigen-specific IgM, IgG, or the combination of IgG and IgM (with protein A) were conducted. At a sensitivity of 78% among all patients, serum IgM antibodies against the NDO-LID conjugate were detected at a greater level than those recognizing phenolic glycolipid-I antigen (64% overall sensitivity), while providing similar specificity (97% versus 100%, respectively). Given the inclusion of the LID-1 protein within NDO-LID, we also detected conjugate-specific IgG within patient sera at a sensitivity of 81.6%. The use of protein A to simultaneously detect both antigen-specific IgG and IgM isotypes yielded the highest overall sensitivity of 86.3%. Taken together, our data indicate that the detection of both IgG and IgM antibodies against NDO-LID with protein A provided the best overall ability to detect Colombian leprosy patients.
Pure neural leprosy, defined as a peripheral neuropathy in which the patient has no skin lesions, is difficult to diagnose. Its verification by bacteriological index and histopathology is not possible in the majority of the patients.We describe four cases of pure neural leprosy diagnosed by clinical criteria. The clinical outcome of three of the patients after specific treatment was satisfactory, while the other one developed progressive neural damage despite the therapy. All patients were treated in a specialized center for the management and control of Hansen's disease in the municipality of Contratación, Santander, Colombia.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, has evolved to have a wide range of hosts, including non-human primates, wild and domestic animals. The ACE2 protein has a high level of conservation and is the common receptor invertebrate species for a viral infection to occur; this receptor could give rise to anthroponotic events. This article describes the first event of symptomatic transmission in Latin America from a human to a dog by the B.1.625 lineage of SARS-CoV-2. We found 21 shared mutations in the complete genomes of viral sequences from owners and dogs. Further phylogenetic and molecular analysis showed that 100% co-localization of the clade helps to understand human-animal transmission. Prediction of the Spike protein structure of the sequenced virus and docking analyzes showed that the E484K mutation in the receptor-binding domain (RBD) could contribute to the viral affinity of dACE2. Therefore, close contact between SARS-CoV-2-infected humans and pets should be avoided to prevent the emergence of novel mutations of public health importance from anthroponotic events.
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