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Al-Mubarak R.,Colorado State University | Vander Heiden J.,Colorado State University | Broeckling C.D.,Colorado State University | Balagon M.,Leonard Wood Memorial Center for Leprosy Research | And 2 more authors.
PLoS Neglected Tropical Diseases

Background: Leprosy is a disease of the skin and peripheral nervous system caused by the obligate intracellular bacterium Mycobacterium leprae. The clinical presentations of leprosy are spectral, with the severity of disease determined by the balance between the cellular and humoral immune response of the host. The exact mechanisms that facilitate disease susceptibility, onset and progression to certain clinical phenotypes are presently unclear. Various studies have examined lipid metabolism in leprosy, but there has been limited work using whole metabolite profiles to distinguish the clinical forms of leprosy. Methodology and Principal Findings: In this study we adopted a metabolomics approach using high mass accuracy ultrahigh pressure liquid chromatography mass spectrometry (UPLC-MS) to investigate the circulatory biomarkers in newly diagnosed untreated leprosy patients. Sera from patients having bacterial indices (BI) below 1 or above 4 were selected, subjected to UPLC-MS, and then analyzed for biomarkers which distinguish the polar presentations of leprosy. We found significant increases in the abundance of certain polyunsaturated fatty acids (PUFAs) and phospholipids in the high-BI patients, when contrasted with the levels in the low-BI patients. In particular, the median values of arachidonic acid (2-fold increase), eicosapentaenoic acid (2.6-fold increase) and docosahexaenoic acid (1.6-fold increase) were found to be greater in the high-BI patients. Significance: Eicosapentaenoic acid and docosahexaenoic acid are known to exert anti-inflammatory properties, while arachidonic acid has been reported to have both pro- and anti-inflammatory activities. The observed increase in the levels of several lipids in high-BI patients may provide novel clues regarding the biological pathways involved in the immunomodulation of leprosy. Furthermore, these results may lead to the discovery of biomarkers that can be used to investigate susceptibility to infection, facilitate early diagnosis and monitor the progression of disease. © 2011 Al-Mubarak et al. Source

Duthie M.S.,Infectious Disease Research Institute | Saunderson P.,American Leprosy Missions | Saunderson P.,Leonard Wood Memorial Center for Leprosy Research | Reed S.G.,Infectious Disease Research Institute
Memorias do Instituto Oswaldo Cruz

Despite the huge effort and massive advances toward the elimination of leprosy over the last two decades, the disease has proven stubborn; new case detection rates have stabilised over the last few years and leprosy remains endemic in a number of localised regions. The American Leprosy Missions and Infectious Disease Research Institute have undertaken a large research effort aimed at developing new tools and a vaccine to continue the push for leprosy elimination. In this paper, we outline our strategy for the integration of rapid diagnostic tests and lab-based assays to facilitate the detection of early or asymptomatic leprosy cases, as well as the efficient and focused implementation of chemoprophylaxis and immunisation to intervene in leprosy development and transmission. Source

Duthie M.S.,Infectious Disease Research Institute | Balagon M.F.,Leonard Wood Memorial Center for Leprosy Research
Risk Management and Healthcare Policy

Leprosy is a complex infectious disease caused by Mycobacterium leprae that is a leading cause of nontraumatic peripheral neuropathy. Current control strategies, with a goal of early diagnosis and treatment in the form of multidrug therapy, have maintained new case reports at ~225,000 per year. Diagnostic capabilities are limited and even with revisions to multidrug therapy regimen, treatment can still require up to a year of daily drug intake. Although alternate chemotherapies or adjunct immune therapies that could provide shorter or simpler treatment regimen appear possible, only a limited number of trials have been conducted. More proactive strategies appear necessary in the drive to elimination. As a prevention strategy, most chemoprophylaxis campaigns to date have provided about a 2-year protective window. Vaccination, in the form of a single bacillus Calmette-Guérin (BCG) immunization, generally provides ~50% reduction in leprosy cases. Adapting control strategies to provide both chemoprophylaxis and immunoprophylaxis has distinct appeal, with chemoprophylaxis theoretically buttressed by vaccination to generate immediate protection that can be sustained in the long term. We also discuss simple assays measuring biomarkers as surrogates for disease development or replacements for invasive, but not particularly sensitive, direct measures of M. leprae infection. Such assays could facilitate the clinical trials required to develop these new chemoprophylaxis, immunoprophylaxis strategies, and transition into wider use. © 2016 Duthie and Balagon. Source

Scollard D.M.,National Hansens Disease Programs | Martelli C.M.T.,Federal University of Goais | Stefani M.M.A.,Federal University of Goais | De Fatima Maroja M.,Fundacao de Dermatologia Tropical Alfredo da Matta | And 3 more authors.
American Journal of Tropical Medicine and Hygiene

The objective of this study was to ascertain risk factors for complications (reactions or neuritis) in leprosy patients at the time of diagnosis in three leprosy-endemic countries. Newly diagnosed patients were enrolled in Brazil, the Philippines, and Nepal, and risk factors for reactions and neuritis were assessed using a case-control approach: "cases" were patients with these complications, and controls were patients without complications. Of 1,972 patients enrolled in this study, 22% had complications before treatment. Type 1 reaction was diagnosed in 13.7% of patients, neuritis alone in 6.9.%, and type 2 reaction in 1.4%. The frequency of these complications was higher in Nepal, in lepromatous patients, in males, and in adults versus children. Reactions and neuritis were seen in patients at diagnosis, before treatment was started. Reactions were seen in adults and children, even in patients with only a single lesion. Neuritis was often present without other signs of reaction. Reactions and neuritis were more likely to occur in lepromatous patients, and were more likely to be seen in adults than in children. Copyright © 2015 by The American Society of Tropical Medicine and Hygiene. Source

Balagon Ma.V.F.,Leonard Wood Memorial Center for Leprosy Research | Gelber R.H.,University of California at San Francisco | Abalos R.M.,Leonard Wood Memorial Center for Leprosy Research | Cellona R.V.,Leonard Wood Memorial Center for Leprosy Research
American Journal of Tropical Medicine and Hygiene

We evaluated the incidence, severity, and duration of reactional states in 139 multibacillary (MB) leprosy patients in the first 2 years after the completion of the 1 year regimen of multidrug therapy (MDT) currently recommended by the World Health Organization (WHO) and compared those findings with 295 MB leprosy patients treated with the same regimen previously recommended for 2 years. During the first year after the completion of 1 year MDT, patients experienced 1 or more reactional states 27% of the time, the vast majority being lepra type 1 reactions (reversal reactions, RR), whereas patients who received 2 year MDT experienced a reactional state during that time period only 8% of the time ( P < 0.001). Furthermore, during the first year after the completion of therapy, and during the first 2 years, both the number of reactional states and reversal reactions were significantly ( P ≤ 0.004) more frequent, severe, of longer duration, and more commonly associated with neuritis. Copyright © 2010 by The American Society of Tropical Medicine and Hygiene. Source

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