Dapsone is an anticatalysis for Alzheimer’s disease exacerbation

This study investigated leprosy patients with Alzheimer's disease (AD) treated with dapsone (4,4’-diaminodiphenyl sulfone, DDS) as a cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway and neuroinflammasome competitor. We searched the Sorokdo National Hospital medical records and the National Health Insurance Service in South Korea with the International Classification of Diseases (ICD)-10 code and Electronic Data Interchange (EDI) from January 2005 to June 2020. Four groups were defined: Treatment (T) 1: DDS prescription (+) AD prevalence (+), T 2: DDS (+) AD nondiagnosed (-), T 3: DDS nonprescription (-) AD (+), T 4: DDS (-) AD (-). The T1:T3 tests demonstrate that the incidence of AD is significantly reduced in the presence of dapsone among AD patients. The T1:T3 tests demonstrate that the incidence of AD is significantly reduced in the presence of dapsone among AD patients. T1 (M = 0.18, SD = 0.074):T2 (M = 0.55, SD = 0.14) and T3 (M = 0.18, SD = 0.074):T4 (M = 0.55, SD = 0.14) explain that dapsone effects on AD can be clearly distinguished according to its presence or absence.The T1:T4 and the T2:T3 test demonstrate a causal relationship in which the presence or absence of dapsone determines the onset of AD. The T1:T3 test proved that the incidence of AD was significantly reduced by dapsone. (The t-value is -23.1, p-value is < .00001, significant at p < .05) The T2:T3 test proved that the prevalence of AD was significantly high without dapsone, and without AD was increased with dapsone. (The t-value is -6.38, p-value is < .00001, significant at p < .05) AD is increased in the absence of dapsone. Our study has demonstrated that dapsone has the potential for the prevention of AD. This study indicates that dapsone is a valid preventive therapeutic for AD. KEYWORD: Neuroinflmmasome, Alzheimer's disease, Dapsone

Prediction of the Occurrence of Leprosy Reactions Based on Bayesian Networks

Background: Leprosy reactions (LR) are severe episodes of intense activation of the host inflammatory response, of uncertain etiology, today the leading cause of permanent nerve damage in leprosy patients. Several genetic and non-genetic risk factors for LR have been described; however, there are limited attempts to combine this information in order to estimate the risk of a leprosy patient to develop LR. Here we present an artificial intelligence (AI)-based system able to estimate risk of LR using clinical, demographic and genetic data.Methods: The study includes four datasets from different regions of Brazil, totalizing 1,450 leprosy patients followed prospectively for at least two years to assess the occurrence of LR. Data mining using WEKA software was performed following a two-step protocol to select the variables included in the AI system, based on Bayesian Networks and developed using the NETICA software.Results: Analysis of the complete database resulted in a system able to estimate LR-risk with 82.7% accuracy, 79.3% sensitivity, and 86.2% specificity. When using only databases for which host genetic information associated with LR was included, the performance increased to up to 87.7% accuracy, 85.7% sensitivity, and 89.4% specificity.Conclusion: We produced an easy-to-use, online, free-access system that allows the identification of leprosy patients at high risk of developing LR. Risk assessment of LR for individual patients may detect candidates close monitoring, with potential positive impact upon the prevention of permanent disabilities, the quality of life of the patients, as well as upon leprosy control programs.

Effect of mental imagery on depression, anxiety and stress in instituitionalised leprosy patients – An experimental study

Leprosy, also known as Hansen’s disease is caused by Mycobacterium Leprae. Despite being curable, it continues to be a significant health problem in many parts of the world. The prevalence of psychiatric disorders is higher in the leprosy affected population than in the general population. Physical activity has been associated with reduced symptoms of depression and anxiety. It is also associated with improved life satisfaction and psychological well-being. Mental Imagery holds belief as an intervention in the treatment of psychological disorders. This is attributable to its harmless, time and cost effective nature. The study aimed to assess the effect of mental imagery on Depression, Anxiety and Stress in institutionalised Leprosy patients using the DASS-21 (Depression, Anxiety and Stress Scale -21). It was carried out in 34 subjects divided equally in the control and experimental groups. The control group received an aerobic exercise program whereas the experimental group received an aerobic exercise program with mental imagery. It was thus concluded that a statistically significant difference was obtained in the scores of Depression in the experimental group. However, only clinically significant differences could be obtained in the scores of Anxiety and Stress. Thus, mental imagery can be used as an effective adjunct with conventional aerobic exercises for reducing Depression, Anxiety and Stress in institutionalised Leprosy patients.

Pengaruh Penggunaan Sandal Drop Foot Terhadap Perbaikan Pola Jalan Penderita Drop Foot Akibat Kusta Di Rumah Sakit Kusta Sumberglagah Mojokerto

In handling Drop Foot due to leprosy, Prosthetic Orthotics can provide services in the form of ortosis, namely Sandal Drop Foot, which aims to reduce the drop foot in the ankle joint caused by a decrease in flexor dorsal muscle tone. Sampling is done by purposive sampling. The sample count consisted of 10 drop foot sufferers due to leprosy at Sumberglagah Mojokerto Leprosy Hospital. The instrument used is Rivermead Visual Gait Assessment form, video gait analysis equipment (handycam, goniometre, stationery). Drop Foot sandals have a big effect on leprosy patients who experience drop foot in improving road patterns compared to without when using Drop foot sandals. Drop foot sandals are sutu aids or correction tools to prevent prolonged drop foot or prevent further disability, but can not cure and restore normal in people with drop foot due to leprosy. The purpose of this study is to find out the Effect of Using Drop Foot Sandals On Improving Road Patterns of People With Drop Foot Due to Leprosy. This study uses the research design" Quasi experiment pre post test with out control design" one groups pre and post design, where in this study there is only one group of conscientious subjects who will be measured the pattern of the path before and after being given treatment. From the alternative test Wilcoxon obtained a value of significance with a value of p = 0.004, because p < 0.05, it can be said that there is an effect on the use of Drop Foot Sandals on improving the road pattern of drop foot sufferers due to leprosy

Transcriptomic Analysis of Mycobacterium leprae-Stimulated Response in Peripheral Blood Mononuclear Cells Reveal Potential Biomarkers for Early Diagnosis of Leprosy

We aimed to identify an unique host transcriptional signature in peripheral blood mononuclear cells (PBMCs) in response to Mycobacterium leprae antigens to distinguish between patients with leprosy and non-leprosy controls for early diagnosis of the disease. Sixteen individuals were enrolled in the discovery cohort [eight patients with leprosy, comprising four multibacillary (MB) and four paucibacillary (PB); and eight non-leprosy controls, comprising four healthy house contacts (HHCs) and four endemic controls (ECs)]. The differences in the transcriptome response of PBMCs to M. leprae sonicate antigen were evaluated between leprosy patients and non-leprosy controls, and 12 differentially expressed genes (CCL2/MCP-1, IL-8, JAKM, ATP, ND1, SERP, FLJ10489, LINC00659, LOC34487, LOC101928143, MIR22, and NCF1C) were identified. The accuracy of the 12 differentially expressed genes was further validated for the diagnosis of leprosy using real-time quantitative PCR in 82 individuals (13 MB, 10 PB, 37 HHCs, and 22 ECs) in the validation cohort. We found that a 5 gene signature set IL-8, CCL2/MCP-1, SERP, LINC00659 and FLJ10489 had a suitable performance in discriminating leprosy from ECs. In addition, elevated expression of IL-8, CCL2/MCP-1, SERP and LINC00659 was associated with MB diagnosis compared with ECs, whereas increased expression of IL-8, CCL2/MCP-1, SERP and FLJ10489 was found to be useful biomarkers for PB diagnosis from ECs. Moreover, we found decreased expression of NCF1C among leprosy patients could distinguish leprosy from HHCs, whereas higher expression of CCL2 among MB than PB could distinguish different leprosy patients. In conclusion, among the 12 candidate host genes identified, a three gene signature IL-8, CCL2/MCP-1, and SERP showed the best performance in distinguishing leprosy patients from healthy controls. These findings may have implications for developing a rapid blood-based test for early diagnosis of leprosy.

A simple assay to quantify mycobacterial lipid antigen-specific T cell receptors in human tissues and blood

T cell receptors (TCRs) encode the history of antigenic challenge within an individual and have the potential to serve as molecular markers of infection. In addition to peptide antigens bound to highly polymorphic MHC molecules, T cells have also evolved to recognize bacterial lipids when bound to non-polymorphic CD1 molecules. One such subset, germline-encoded, mycolyl lipid-reactive (GEM) T cells, recognizes mycobacterial cell wall lipids and expresses a conserved TCR-ɑ chain that is shared among genetically unrelated individuals. We developed a quantitative PCR assay to determine expression of the GEM TCR-ɑ nucleotide sequence in human tissues and blood. This assay was validated on plasmids and T cell lines. We tested blood samples from South African subjects with or without tuberculin reactivity or with active tuberculosis disease. We were able to detect GEM TCR-ɑ above the limit of detection in 92% of donors but found no difference in GEM TCR-ɑ expression among the three groups after normalizing for total TCR-ɑ expression. In a cohort of leprosy patients from Nepal, we successfully detected GEM TCR-ɑ in 100% of skin biopsies with histologically confirmed tuberculoid and lepromatous leprosy. However, GEM TCR-ɑ expression was not different between leprosy patients and control subjects after normalization. Thus, GEM T cells constitute part of the T cell repertoire in the skin. Further, these results reveal the feasibility of developing a simple, field deployable molecular diagnostic based on mycobacterial lipid antigen-specific TCR sequences that are readily detectable in human tissues and blood independent of genetic background.

A comparison of three types of targeted, community-based methods aimed at promoting early detection of new leprosy cases in rural parts of three endemic states in India

Background India achieved elimination of leprosy nationally in 2005, but since then the number of patients with grade 2 disability at diagnosis increased steadily indicating delay in diagnosis. Therefore, there was a need for public health interventions which can increase case finding in their earlier stage. The objective of this study is to compare the effectiveness of three such community-based interventions; 1) Enhancement of community awareness on leprosy; 2) Education and motivation of “Index” leprosy cases; and 3) Involvement of Non-Formal Health Practitioners (NFHPs) to promote early detection of new cases of leprosy. Methodology/principal findings Three community-based interventions were implemented between April 2016 and March 2018, embedded within the National Leprosy Eradication Program (NLEP) of India. Interventions were 1) increasing awareness through involvement of Gram Panchayat (local government) in the community regarding early signs of leprosy (Awareness), 2) providing health education and motivating newly diagnosed leprosy patients to bring suspects from their contacts (Index) and 3) training local non-formal health practitioners (NFHP). Each intervention was implemented in a group of ten blocks (sub-division of district) with an additional ten blocks as control (with no intervention). The main outcomes were number of new cases detected and number of grade 2 disability among them. They were obtained from the routine NLEP information system and compared between these interventions. On an average, there was an addition of 1.98 new cases in Awareness blocks, 1.13 in NFHP blocks and 1.16 cases in Index intervention blocks per month per block after adjusting for changes in control blocks during the same period. In terms of ratio, there was a 61%, 40% and 41% increase in case notification in awareness, Index and NFHP intervention, respectively. Overall, the percentage of grade 2 disability across intervention blocks declined. Conclusion The Awareness intervention appears to be more effective in detection of new cases, compared to Index case motivation and sensitization of NFHPs. However, it is important to stress that while selecting strategies to increase early diagnosis it is important to determine, which is the most appropriate for each context or area and must be decided depending on the local context.

Standardization of SYBR Green-Based Real-Time PCR Through the Evaluation of Different Thresholds for Different Skin Layers: An Accuracy Study and Track of the Transmission Potential of Multibacillary and Paucibacillary Leprosy Patients

The development of new molecular techniques is essential for the early diagnosis of leprosy. Studies in the field have failed to elucidate the performance of these tests in clinical practice. We aimed to design a new primer pair for the repetitive element (RLEP) target of Mycobacterium leprae and to test the accuracy of SYBR green-based real-time PCR through the evaluation of different thresholds for different skin layers. We also aimed to track the transmission potential of multibacillary and paucibacillary leprosy patients. The in vitro validation of our reaction resulted in a quantification limit of 0.03 bacilli. We then conducted a cross-sectional/cohort-based study of diagnostic accuracy. Patients were included, and skin samples were divided into four layers: epidermis, superior dermis, inferior dermis, and hypodermis. We also quantified M. leprae in nasal swabs of the included patients and compared the results to the number of household contacts also diagnosed with leprosy. One hundred patients with a clinical presentation compatible with leprosy were allocated to the leprosy or control group. Although the parasite load was greater in the superior and inferior dermis, M. leprae DNA was found in all skin layers. The best sensitivity was observed for the superior dermis using the presence of any quantifiable bacillus DNA as the threshold [sensitivity=59.26% (95% CI=45.97–71.32)]. In the epidermis, setting 1 quantifiable bacillus as the threshold resulted in 100% specificity (95% CI=92.29–100). The number of bacilli found in nasal swabs was not significantly related to the number of household contacts also diagnosed with leprosy. Paucibacillary patients tested positive only for bacillus fragments in nasal swabs but not for the entire bacilli. We can conclude that superficial biopsies might result in sensitivity loss, although different skin sample types will have little influence on the final accuracy. In contrast, threshold changes greatly influence these properties. Paucibacillary patients may not be a relevant source of disease transmission.