Leonard Wood Memorial Center for Leprosy Research

Cebu City, Philippines

Leonard Wood Memorial Center for Leprosy Research

Cebu City, Philippines

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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 | Year: 2015

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.


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 | Year: 2010

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.


Balagon M.F.,Leonard Wood Memorial Center for Leprosy Research | Cellona R.V.,Leonard Wood Memorial Center for Leprosy Research | Abalos R.M.,Leonard Wood Memorial Center for Leprosy Research | Gelber R.H.,University of California at San Francisco | Saunderson P.R.,Leonard Wood Memorial Center for Leprosy Research
Leprosy Review | Year: 2010

Objectives: To compare the efficacy of a 4-week ofloxacin-containing regimen and the standard WHO-MDT regimen for PB leprosy, in terms of the rate and timing of relapse after treatment completion. Design: 124 PB patients were enrolled in a randomised, double-blind trial. Of these, 66 received the standard 6-month WHO-MDT regimen, whereas 58 received 28 daily supervised doses of rifampicin 600 mg + ofloxacin 400 mg, plus 5 months of placebo. Patients were regularly monitored for clinical response and for signs of relapse after treatment completion. Results: Patients enrolled in the ofloxacin group had a mean follow-up of 10·8 years (628 patient-years) with 1 early relapse at 3 years after treatment completion. On relapse, this patient remained smear negative but was reclassified by current WHO criteria (≥ 6 skin lesions) as multibacillary (MB). Patients on the WHO-MDT regimen had a mean follow-up of 11·3 years (749 patient-years) with two late relapses at 8 and 12 years, both still classified as PB on relapse. Conclusion: In conclusion, both regimens appeared generally efficacious, and, in particular, resulted in few relapses. © Lepra.


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 | Year: 2011

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.


Duthie M.S.,Infectious Disease Research Institute | Balagon M.F.,Leonard Wood Memorial Center for Leprosy Research | Maghanoy A.,Leonard Wood Memorial Center for Leprosy Research | Orcullo F.M.,Leonard Wood Memorial Center for Leprosy Research | And 4 more authors.
Journal of Clinical Microbiology | Year: 2014

Leprosy remains an important health problem in a number of regions. Early detection of infection, followed by effective treatment, is critical to reduce disease progression. New sensitive and specific tools for early detection of infection will be a critical component of an effective leprosy elimination campaign. Diagnosis is made by recognizing clinical signs and symptoms, but few clinicians are able to confidently identify these. Simple tests to facilitate referral to leprosy experts are not widely available, and the correct diagnosis of leprosy is often delayed. In this report, we evaluate the performance of a new leprosy serological test (NDO-LID). As expected, the test readily detected clinically confirmed samples from patients with multibacillary (MB) leprosy, and the rate of positive results declined with bacterial burden. NDO-LID detected larger proportions of MB and paucibacillary (PB) leprosy than the alternative, the Standard Diagnostics leprosy test (87.0% versus 81.7% and 32.3% versus 6.5%, respectively), while also demonstrating improved specificity (97.4% versus 90.4%). Coupled with a new cell phone-based test reader platform (Smart Reader), the NDO-LID test provided consistent, objective test interpretation that could facilitate wider use in nonspecialized settings. In addition, results obtained from sera at the time of diagnosis, versus at the end of treatment, indicated that the quantifiable nature of this system can also be used to monitor treatment efficacy. Taken together, these data indicate that the NDO-LID/Smart Reader system can assist in the diagnosis and monitoring of MB leprosy and can detect a significant number of earlier-stage infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.


Burgos J.,Leonard Wood Memorial Center for Leprosy Research | de la Cruz E.,Leonard Wood Memorial Center for Leprosy Research | Paredes R.,Leonard Wood Memorial Center for Leprosy Research | Andaya C.R.,Leonard Wood Memorial Center for Leprosy Research | Gelber R.H.,Leonard Wood Memorial Center for Leprosy Research
Leprosy Review | Year: 2011

Introduction: Moxifloxacin, rifampicin, rifapentine, linezolid, and PA 824, alone and in combination, have been previously administered, as single doses and five times daily doses, to M. leprae infected mice during lag phase multiplication and were each found to have some bactericidal activity. Design: The fluroquinolones, ofloxacin, moxifloxacin and gatifloxacin, (50 mg/kg, 150 mg/kg and 300 mg/kg) and the rifamycins (5 mg/kg, 10 mg/kg, and 20 mg/kg), rifampicin and rifapentine, were evaluated alone and in combination for bactericidal activity against M. leprae using the mouse footpad model during logarithmic multiplication. Linezolid and PA 824 were similarly evaluated alone and linezolid in combination with rifampicin, minocycline and ofloxacin. Results: The three fluroquinolones and rifamycins were found alone and in combination to be bactericidal at all dosage schedules. PA 824 had no activity against M. leprae, while linezolid at a dose of 25 mg/kg was bacteriostatic, and progressively more bactericidal at doses of 50 mg/kg and 100 mg/kg. No antagonisms were detected between any of these drugs when used in combinations. Conclusion: Moxifloxacin, gatifloxacin, rifapentine and linezolid were found bactericidal against rapidly multiplying M. leprae. © Lepra.


Balagon M.,Leonard Wood Memorial Center for Leprosy Research | Saunderson P.R.,Leonard Wood Memorial Center for Leprosy Research | Gelber R.H.,Leonard Wood Memorial Center for Leprosy Research
Leprosy Review | Year: 2011

Objective: To compare the occurrence, duration and severity of ENL in leprosy patients treated with either 12 or 24 months of standard multi-drug therapy (MDT). Materials and Methods: Study population: 296 patients treated with MDT for 2 years, between 1985 and 1992 and followed up as part of a relapse study; and 293 patients, treated between 1998 and 2004, with MDT for 1 year and also followed up as part of a relapse study. The Chi squared test and multiple logistic regression analysis were used to test for statistical significance. Results: ENL was not significantly more common, but it was longer-lasting and more severe in patients receiving only 12 months of MDT, as compared with those receiving 24 months treatment. A high BI at the start of treatment significantly increased the risk of severe ENL by a factor of between 6 and 12, while treatment with 12 instead of 24 months of MDT significantly increased the risk by a factor of between 3 and 10. Conclusions: This study provides further evidence that a high initial BI is the key risk factor for ENL. It also suggests that the difference between these two cohorts in their experience of ENL as demonstrated in this study, may be related to the different amounts of clofazimine which the two cohorts were given in the early years of their treatment. Further studies are needed to determine whether clofazimine could be used more specifically to reduce the severity of ENL in the small group of patients at high risk for the condition. © Lepra.


Scheelbeek P.F.D.,Imperial College London | Balagon M.V.F.,Leonard Wood Memorial Center for Leprosy Research | Orcullo F.M.,Leonard Wood Memorial Center for Leprosy Research | Maghanoy A.A.,Leonard Wood Memorial Center for Leprosy Research | And 2 more authors.
PLoS Neglected Tropical Diseases | Year: 2013

Background:Cebu has been one of the most leprosy endemic areas in the Philippines. Despite the high coverage rates of multiple drug therapy (MDT) and high BCG-vaccine coverage in children, leprosy control authorities believe that leprosy transmission and incidence (as evidence by continuing new case detection in both adults and children) have not declined as expected, once leprosy had been eliminated.In response to the concerns communicated by the authorities regarding ongoing leprosy transmission in Cebu, this study aims to examine the evidence for the hypothesized ongoing transmission, both in children and adults. Furthermore, it will be assessed which groups and areas are experiencing a continuing risk of leprosy infection; this can form a starting point for more targeted approaches to leprosy control.Methodology & Principal Findings:Case records from 2000-2010 were retrospectively collected from the Leonard Wood Memorial Clinic archives, and all other clinics on the island where leprosy was treated. Between 2000 and 2010, 3288 leprosy cases were detected. The overall five year case notification rate (CNR) dropped significantly from 47.35 (2001-2005) to 29.21 cases (2006-2010) per 100.000 population. Smaller CNRs were reported for children; however the decline in child-CNR over the same period was minimal. Furthermore, no increase in median age of notification in children or adults was found between 2000 and 2010. Population-adjusted clustering of leprosy cases was mainly detected in urban and peri-urban areas.Conclusions & Significance:Although the overall CNR declined significantly, CNR seems to be rather static in lower risk populations and areas. Cases are mainly found in urban areas, however CNRs in these areas decline at a much faster rate than in the lower endemic rural areas. A similar situation was found when comparing adults and children: CNRs observed in children were lower than in adults, but further decline (and elimination) of these childhood CNRs was found to be difficult. Moreover, the median age of notification in children has remained stable, suggesting transmission is still on-going.It is unclear why many years of good MDT-coverage and a gradual decline in CNR have not been accompanied by evidence of reduced transmission, especially beyond a certain threshold level of case notification. We believe that a new approach to leprosy control is required to tackle transmission more directly. The most promising approach may involve chemoprophylaxis and/or immunoprophylaxis interventions, targeted at high risk (urban) areas and groups such as household contacts, followed by a different approach once decline in CNR starts to level off. Identified clusters and trends can form the starting point for implementing this approach. © 2013 Scheelbeek et al.


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 | Year: 2012

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.


Duthie M.S.,Infectious Disease Research Institute | Balagon M.F.,Leonard Wood Memorial Center for Leprosy Research
Risk Management and Healthcare Policy | Year: 2016

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.

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