Multiplex PCR technique could be an alternative approach for early detection of leprosy among close contacts - a pilot study from India

<p>Abstract</p> <p>Background</p> <p>Implementation of Multi drug Therapy (MDT) regimen has resulted in the decline of the total number of leprosy cases in the world. Though the prevalence rate has been declining, the incidence rate remains more or less constant and high in South East Asian countries particularly in India, Nepal, Bangladesh, Pakistan and Srilanka. Leprosy, particularly that of multibacillary type spreads silently before it is clinically detected. An early detection and treatment would help to prevent transmission in the community. Multiplex PCR (M-PCR) technique appears to be promising towards early detection among contacts of leprosy cases.</p> <p>Methods</p> <p>A total of 234 paucibacillary (PB) and 205 multibacillary (MB) leprosy cases were studied in a community of an endemic area of Bankura district of West Bengal (Eastern India). They were assessed by smear examination for acid-fast bacilli (AFB) and M-PCR technique. These patients were treated with Multidrug Therapy (MDT) as prescribed by WHO following detection. A total of 110 MB and 72 PB contacts were studied by performing M-PCR in their nasal swab samples.</p> <p>Results</p> <p>83.4% of MB patients were observed to be positive by smear examination for AFB and 89.2% by M-PCR. While 22.2% of PB patients were found to be positive by smear examination for AFB, 80.3% of these patients were positive by M-PCR. Among leprosy contacts (using M-PCR), 10.9% were found to be positive among MB contacts and 1.3% among PB contacts. Interestingly, two contacts of M-PCR positive MB cases developed leprosy during the period of two years follow up.</p> <p>Conclusion</p> <p>The M-PCR technique appears to be an efficient tool for early detection of leprosy cases in community based contact tracing amongst close associates of PB and MB cases. Early contact tracing using a molecular biology tool can be of great help in curbing the incidence of leprosy further.</p

Armadillo meat intake was not associated with leprosy in a case control study, Curitiba (Brazil)

Leprosy's progression and its maintained endemic status, despite the availability of effective treatments, are not fully understood and recent studies have highlighted the possibility of involved Mycobacterium leprae ambient reservoirs. Wild armadillos can carry leprosy and, because their meat is eaten by humans, development of the disease among armadillo meat consumers has been investigated. This study evaluated the frequency of armadillo meat intake among leprosy patients as well as age and gender matched controls with other skin diseases from a dermatological unit. Armadillo meat consumption among both groups was adjusted by demographic and socioeconomic covariates based on a conditional multiple logistic regression model. One hundred twenty-one cases and 242 controls were evaluated; they differed in socioeconomic variables such as family income, hometown population and access to treated water. The multivariate analysis did not show an association between the intake of armadillo meat and leprosy (odds ratio = 1.07; CI 95% 0.56-2.04), even when only cases with no known contacts were analyzed. We conclude that leprosy is not associated with the intake of armadillo meat in these patients

Granulomatous Reactivation during the Course of a Leprosy Infection: Reaction or Relapse

Leprosy is a serious infectious disease whose treatment still poses some challenges. Patients are usually treated with a combination of antimicrobial drugs called multidrug therapy. Although this treatment is effective against Mycobacterium leprae, the bacillus that causes leprosy, patients may develop severe inflammatory reactions during treatment. These reactions may be either attributed to an improvement in the immunological reactivity of the patient along with the treatment, or to relapse of the disease due to the proliferation of remaining bacilli. In certain patients these two conditions may be difficult to differentiate. The present study addresses the histopathology picture of and the M. leprae bacilli in sequential biopsies taken from lesions of patients who presented such reactions aiming to improve the differentiation of the two conditions. This is important because these reactions are one of the major causes of the disabilities of the patients with leprosy, and should be treated early and appropriately. Our results show that the histopathology picture alone is not sufficient, and that bacilli's counting is necessary

Global elimination of leprosy by 2020: are we on track?

BACKGROUND: Every year more than 200,000 new leprosy cases are registered globally. This number has been fairly stable over the past 8 years. WHO has set a target to interrupt the transmission of leprosy globally by 2020. The aim of this study is to investigate whether this target, interpreted as global elimination, is feasible given the current control strategy. We focus on the three most important endemic countries, India, Brazil and Indonesia, which together account for more than 80 % of all newly registered leprosy cases. METHODS: We used the existing individual-based model SIMCOLEP to predict future trends of leprosy incidence given the current control strategy in each country. SIMCOLEP simulates the spread of M. leprae in a population that is structured in households. Current control consists of passive and active case detection, and multidrug therapy (MDT). Predictions of leprosy incidence were made for each country as well as for one high-endemic region within each country: Chhattisgarh (India), Pará State (Brazil) and Madura (Indonesia). Data for model quantification came from: National Leprosy Elimination Program (India), SINAN database (Brazil), and Netherlands Leprosy Relief (Indonesia). RESULTS: Our projections of future leprosy incidence all show a downward trend. In 2020, the country-level leprosy incidence has decreased to 6.2, 6.1 and 3.3 per 100,000 in India, Brazil and Indonesia, respectively, meeting the elimination target of less than 10 per 100,000. However, elimination may not be achieved in time for the high-endemic regions. The leprosy incidence in 2020 is predicted to be 16.2, 21.1 and 19.3 per 100,000 in Chhattisgarh, Pará and Madura, respectively, and the target may only be achieved in another 5 to 10 years. CONCLUSIONS: Our predictions show that although country-level elimination is reached by 2020, leprosy is likely to remain a problem in the high-endemic regions (i.e. states, districts and provinces with multimillion populations), which account for most of the cases in a country. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-1143-4) contains supplementary material, which is available to authorized users

Clofazimine Inhibits Human Kv1.3 Potassium Channel by Perturbing Calcium Oscillation in T Lymphocytes

The Kv1.3 potassium channel plays an essential role in effector memory T cells and has been implicated in several important autoimmune diseases including multiple sclerosis, psoriasis and type 1 diabetes. A number of potent small molecule inhibitors of Kv1.3 channel have been reported, some of which were found to be effective in various animal models of autoimmune diseases. We report herein the identification of clofazimine, a known anti-mycobacterial drug, as a novel inhibitor of human Kv1.3. Clofazimine was initially identified as an inhibitor of intracellular T cell receptor-mediated signaling leading to the transcriptional activation of human interleukin-2 gene in T cells from a screen of the Johns Hopkins Drug Library. A systematic mechanistic deconvolution revealed that clofazimine selectively blocked the Kv1.3 channel activity, perturbing the oscillation frequency of the calcium-release activated calcium channel, which in turn led to the inhibition of the calcineurin-NFAT signaling pathway. These effects of clofazimine provide the first line of experimental evidence in support of a causal relationship between Kv1.3 and calcium oscillation in human T cells. Furthermore, clofazimine was found to be effective in blocking human T cell-mediated skin graft rejection in an animal model in vivo. Together, these results suggest that clofazimine is a promising immunomodulatory drug candidate for treating a variety of autoimmune disorders