A Mycobacterial Systems Resource for the Research Community.

Functional characterization of bacterial proteins lags far behind the identification of new protein families. This is especially true for bacterial species that are more difficult to grow and genetically manipulate than model systems such as Escherichia coli and Bacillus subtilis To facilitate functional characterization of mycobacterial proteins, we have established a Mycobacterial Systems Resource (MSR) using the model organism Mycobacterium smegmatis This resource focuses specifically on 1,153 highly conserved core genes that are common to many mycobacterial species, including Mycobacterium tuberculosis, in order to provide the most relevant information and resources for the mycobacterial research community. The MSR includes both biological and bioinformatic resources. The biological resource includes (i) an expression plasmid library of 1,116 genes fused to a fluorescent protein for determining protein localization; (ii) a library of 569 precise deletions of nonessential genes; and (iii) a set of 843 CRISPR-interference (CRISPRi) plasmids specifically targeted to silence expression of essential core genes and genes for which a precise deletion was not obtained. The bioinformatic resource includes information about individual genes and a detailed assessment of protein localization. We anticipate that integration of these initial functional analyses and the availability of the biological resource will facilitate studies of these core proteins in many Mycobacterium species, including the less experimentally tractable pathogens M. abscessus, M. avium, M. kansasii, M. leprae, M. marinum, M. tuberculosis, and M. ulceransIMPORTANCE Diseases caused by mycobacterial species result in millions of deaths per year globally, and present a substantial health and economic burden, especially in immunocompromised patients. Difficulties inherent in working with mycobacterial pathogens have hampered the development and application of high-throughput genetics that can inform genome annotations and subsequent functional assays. To facilitate mycobacterial research, we have created a biological and bioinformatic resource (https://msrdb.org/) using Mycobacterium smegmatis as a model organism. The resource focuses specifically on 1,153 proteins that are highly conserved across the mycobacterial genus and, therefore, likely perform conserved mycobacterial core functions. Thus, functional insights from the MSR will apply to all mycobacterial species. We believe that the availability of this mycobacterial systems resource will accelerate research throughout the mycobacterial research community.

The CILAD, a model of an international dermatologic society, united by geographic, linguistic, and cultural nexus.

The Ibero Latin American College of Dermatology, CILAD, the largest dermatologic organization in the region, was established in 1948 during the course of the V International Congress of Leprosy held in Havana, Cuba. Constituted in its beginning with fewer than 100 dermatologists from nine countries, its growth has been exponential, reaching now around 4000 members spread throughout Latin America, the Iberian Peninsula, and other regions of the world. In recent years, academic activity has been intense, such as the development of several institutional programs, like its community health care program, designed for geographic areas lacking dermatologic care in the Latin American region. This contribution presents a review of its history, noting the dermatologists and personalities who ennoble the institution. The multiple areas of interest of this growing dermatologic organization are described, and the projections toward the future are discussed.

Arresting Leprosy: Therapeutic Outcomes Besides Cure.

This essay focuses on the use of the concept of "arrest" in Hansen's disease (leprosy) in the United States in the early to middle part of the 20th century, as well as the transformations the concept underwent with the arrival of sulfone drugs and the implications of these changes for patients and public health officers. An "arrest" was a therapeutic outcome characterized by a long course of treatment, noncontagiousness, a very small chance of reactivation, and a need for postdischarge maintenance that depended on sociomedical infrastructures beyond the clinic as well as self-imposed lifestyle limitations. The concept of disease arrest shows that experts and laypeople alike have valued therapeutic outcomes other than "cure" that signal certain optimal therapeutic milestones, despite the practical difficulties they imply and despite the fact that they do not promise a return to a pre-illness stage.

Patent landscape of neglected tropical diseases: an analysis of worldwide patent families.

BACKGROUND: "Neglected Tropical Diseases" (NTDs) affect millions of people in Africa, Asia and South America. The two primary ways of strategic interventions are "preventive chemotherapy and transmission control" (PCT), and "innovative and intensified disease management" (IDM). In the last 5 years, phenomenal progress has been achieved. However, it is crucial to intensify research effort into NTDs, because of the emerging drug resistance. According to the World Health Organization (WHO), the term NTDs covers 17 diseases, namely buruli ulcer, Chagas disease, dengue, dracunculiasis, echinococcosis, trematodiasis, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil-transmitted helminthes, taeniasis, trachoma, and yaws. The aim of this study is to map out research and development (R&D) landscape through patent analysis of these identified NTDs. To achieve this, analysis and evaluation have been conducted on patenting trends, current legal status of patent families, priority countries by earliest priority years and their assignee types, technological fields of patent families over time, and original and current patent assignees. MAIN BODY: Patent families were extracted from Patseer, an international database of patents from over 100 patent issuing authorities worldwide. Evaluation of the patents was carried out using the combination of different search terms related to each identified NTD. In this paper, a total number of 12,350 patent families were analyzed. The main countries with sources of inventions were identified to be the United States (US) and China. The main technological fields covered by NTDs patent landscape are pharmaceuticals, biotechnology, organic fine chemistry, analysis of biological materials, basic materials chemistry, and medical technology. Governmental institutions and universities are the primary original assignees. Among the NTDs, leishmaniasis, dengue, and rabies received the highest number of patent families, while human African trypanosomiasis (sleeping sickness), taeniasis, and dracunciliasis received the least. The overall trend of patent families shows an increase between 1985 and 2008, and followed by at least 6 years of stagnation. CONCLUSION: The filing pattern of patent families analyzed undoubtedly reveals slow progress on research and development of NTDs. Involving new players, such as non-governmental organizations may help to mitigate and reduce the burden of NTDs.

The social transformation of Singapore medicine through 55 years of the SMJ.

The Singapore Medical Journal (SMJ) has in the past 55 years reflected the phenomenal socioeconomic progress of Singapore. Publications in the pre-independent years were mainly on diseases like cholera, diphtheria, leprosy, tetanus and worm infestation. In the new millennium, the research papers included molecular genetics, health economics, obesity, Internet medicine, cancer, cosmetic surgery and palliative medicine. The annual SMA Lecture published in the SMJ provides an ethical compass for doctors to remind them of primum non nocere.

Estudios de susceptibilidad de cepas de Leishmania aethiopica frente a alcaloides de Galipea longiflora (Evanta) / Susceptibility studies on Leishmania aethiopica strains against total alkaloids from Galipea longiflora (Evanta)

El Instituto de Investigaciones Fármaco Bioquímicas (IIFB), de la Facultad de Ciencias Farmacéuticas y Bioquímicas, de la UMSA, desarrolla trabajos sobre la actividad leishmanicida, de los alcaloides totales (CAT) obtenidos de la corteza de la especie medicinal amazónica conocida como Evanta (Galipea longiflora) por los Pueblos Tacana, Tsimane y Mosetene. Como parte de las actividades del Proyecto UMSA-ASDI Biomoleculas de interés medicinal e industrial (antiparasitarios) hemos podido contar con la estadía, en el IIFB, de un investigador del Armauer Hansen Research Institute (AHRI) de Etiopia, lo que nos ha permitido desarrollar evaluaciones de CAT, Miltefocine y Amfotericina B, frente a cepas de Leishmania aethiopica, agente causante de las diversa formas de Leishmaniais cutánea en Etiopía. Un total de seis cepas, de L. aethiopica, fueron adaptadas a condiciones in vitro y mostraron un comportamiento homogéneo frente a CAT, cinco de estas cepas mostraron un valor promedio de IC50 = 8,68 ±1,56 mg/mL, valor algo inferior a los calculados para nuestras cepas de referencia, L. amazonensis y L. braziliensis con IC50 = 11,73 ± 4,32 mg/mL y IC50 = 12,28 ±- 2,95 mg/mL, respectivamente. Excepto por una cepa de L. aethiopica que mostro valores consistentemente más elevados que el resto con IC50= 14,37 ± 3,58 mg/mL. Como consecuencia de esta interacción científica, la Universidad Mayor de San Andrés (UMSA) ha firmado un Memorandum de Entendimiento para el desarrollo de investigaciones conjuntas, con el Armauer Hansen Research Institute (AHRI), dependiente del Ministerio de Salud de Etiopia y explorar la posibilidad de que nuestra experiencia de validación clínica con Evanta en el tratamiento de leishmaiasis cutánea, en Bolivia, podría ser replicada en Etiopía, donde se reportan entre 20,000 a 30,000 nuevos casos de Leismaniasis por año.

The Instituto de Investigaciones Fármaco Bioquímicas (IIFB), at the Faculty of Pharmaceutical and Biochemical Sciences, from UMSA, carry out work related to the leishmanicidal activity of the total alkaloids (CAT) obtained from the bark of the Amazonian medicinal species known as Evanta (Galipea longiflora) by the Tacana, Tsimane y Mosetene people. As part of the activities develop by the UMSA-ASDI Project Biomolecules of medicinal and industrial Interest (antiparasitic) we had a visit, in our laboratories at IIFB, of a researcher from The Armauer Hansen Research Institute (AHRI) from Ethiopia, during his stay we were able to carry out evaluations of CAT, Miltefocine and Anphotericin B, against strains of L. aethiopica, causative agent of the different manifestations of cutaneous leishmaniasis in Ethiopia. A total of six strains of L. aethiopica, were adapted to in vitro a conditions, at IIFB; and did show homogenous behavior against CAT. Five of the strains, showed an average calculated value for IC50 = 8.68 ±1.56 mg/mL, a value somewhat lower to the calculated for the reference strains L. amazonensis and L. braziliensis with IC50 = 11.73 ± 4.32 mg/mL and IC50 = 12.28 +/- 2.95 mg/mL, respectively. Except for one strain that showed values somewhat higher, to the other strains, consistently through our studies, with IC50 = 14.37 ± 3.58 mg/mL. As a consequence of our scientific interaction, the Universidad Mayor de San Andrés (UMSA) has signed a Memorandum of Understanding for the development of joint research with the Armauer Hansen Research Institute (AHRI) that belongs to the Ministry of Health in Ethiopia, and explore the possibilities to replicate the Bolivian clinical validation experience of Evanta in the treatment of cutaneous leishmaniasis, in Ethiopia where the annual incidence is estimated to be between 20, 000 to 30, 0000.

[What Hansen's disease research learned from tuberculosis research: from molecular biological aspect].

As for the Mycobacterium leprae which is a causative agent of Hansen's disease, many studies had been done since it was identified in 1873. However, those studies, at the same time, experienced many struggles because of the difficulty of culture of M. leprae on the artificial growth media. Hence, the study of Hansen's disease progressed by taking the knowledge from the study of tuberculosis caused by the bacteria belonging to the same genus, genus Mycobacterium. For instance, the knowledge of mutations in specific genes responsible for rifampicin- and quinolone-resistance in M. tuberculosis led the elucidation of drug-resistant acquisition mechanism of M. leprae. Similarly, it is necessary for the researcher of Hansen's disease to get important information from the latest topic of the tuberculosis study and utilize them to the study of the disease.

Report of the Stigma Research Workshop for the development of scientific consensus papers and field guidelines on health-related stigma, held in Amsterdam, the Netherlands from 11-14 october 2010.

Summary In concurrence with the broad body of literature published on health-related stigma, there is a need for practical field guidance to contribute to the fight against leprosy-related stigma and discrimination. To this end, much can be gained by considering the accumulated knowledge and learned from experience with different stigmatising conditions; primarily HIV/AIDS, disability, tuberculosis, and mental health. Therefore a Stigma Research Workshop was organised from 11-14 October in Amsterdam, The Netherlands. The primary aim of the workshop was to produce scientific papers and field guidelines that could be used to target actions against health-related stigma and discrimination. Keynote presentations were offered by scientists and professionals from different health domains who shared their knowledge, experiences and research findings regarding health-related stigma. Group work was subsequently conducted to work towards agreed outputs on four different themes: i.e. research priorities, measurement, interventions, and counselling. The spectrum of expertise present enabled an interdisciplinary and inter-profession sharing of knowledge and practices. This resulted in the commencement of consensus papers and field guidelines related to the four themes. An evaluation by participants concluded that the workshop had been an informative and worthwhile activity that will strengthen the fight against stigma.

Review of leprosy research evidence (2002-2009) and implications for current policy and practice.

INTRODUCTION: The ILEP Technical Commission (ITC) advises ILEP member associations on technical aspects of leprosy. A major review of research evidence in leprosy was published prior to the International Leprosy Congress in 2002. This current report updates that review based on research published between 2002-2009 and focuses on interventions for prevention, early diagnosis, chemotherapy, reactions, prevention of disability, stigma measurement and reduction and rehabilitation in leprosy. METHODS: A systematic search of electronic databases of published literature for systematic reviews, controlled trials and ongoing trials was conducted in July 2009. The search identified 13 reviews and 21 controlled trials. The data from these studies were extracted and the references cited by these studies reviewed. Each member of the ITC took responsibility to review this evidence for each of the 7 topics and prepared a report summarising the evidence and making recommendations. These findings were presented and discussed at a Forum held in London in March 2010. The report was finalised following this Forum. The evidence was graded using a standard grading system for levels of evidence. However for some topics the evidence used qualitative and other designs which do no conform to this grading but was considered relevant and appropriate.

A review of therapeutic nerve decompression for neuropathy in Hansen's disease with research suggestions.

Nerve decompression surgery for leprosy neuritis has a long history and large literature. New understanding of the high frequency of spontaneous recovery from nerve function impairment requires re-evaluation of the value of decompression in acute nerve dysfunction with strong evidence-based protocols. Several reports and theoretical considerations suggest research avenues that might offer hope for prevention of long-term complications and relief of impairment and disabilities.

[Prevalence of disability among leprosy patients and effectiveness of leprosy reaction services with standard prednisolone treatment at field level in an endemic country--some data from joint leprosy research collaboration in Myanmar].

Prevalence of disability among leprosy patients and effectiveness of standard predonisolone treatment for leprosy reaction at field level in some place of Myanmar are shown in this paper as results of joint leprosy research collaboration. WHO disability grading was measured for all newly registered leprosy patients through 2007 in 5 selected townships of Ayeyarwaddy Division, with the results of G0 = 66.3%, GI = 18.9%, GII = 14.7% (N = 95). The cross-sectional disability survey at selected 9 townships in Mandalay, Sagaing and Magway Division for all registered patients who had completed WHO/MDT done by JICA project in 2003/4 showed G0 = 62.5%, GI = 2.4%, GII = 35.1% (N = 10,528). From these two data, it is supposed that considerable number of patients with G1 at registered time developed worsening of disability from G1 to G2. Proportion of G0 also reduced a little bit in patients who completed WHO/MDT. Early detection and proper treatment of leprosy reaction are one of the main issues of prevention of disability. Effectiveness of leprosy reaction services were evaluated at Mandalay Special Skin Clinic, where WHO fixed regimen of prednisolone were given as routine service. 100 cases were evaluated who developed leprosy reactions from 1st December 2007 to 31st December 2008 and identified severe reaction who needed oral prednisolone treatment. Evaluation criteria of "effective" was defined as "no more signs and symptoms of reactions were present after treatment. And "less effective" was defined as "more than one of signs and symptoms were still remained after treatment". Over all "effective" was 36 (36%) and "less effective" was 64 (64%). It was also found that rates of improvement of nerve functions, either in sensory or in motor, were little after the standard treatment.

[Health research priorities in Colombia from the researchers' point of view]. / Prioridades de investigación en salud en Colombia: Perspectiva de los Investigadores.

Colombia lacks experience in identifying health research priorities. A project for identifying health research priorities was begun in 2004 (meaning those arising from weighting and ordering health and disease problems which could be mainly resolved by research and knowledge). The Global Forum for Health Research combined matrix method, and other methods, was used as reference for developing projects and putting two main methodological paths into practice: designing and applying a method for qualitatively and quantitatively weighting and ordering health research problems and building consensus with researchers and scientific community representatives. Two national meetings, two regional meetings and a virtual forum were held for identifying predominant health problems. Once the predominant health problems had been identified (with the respective estimation of disease load), then they were evaluated by politicians and decision-makers and rated by basic science, clinical science and public health researchers in terms of making a contribution towards knowledge for facing, controlling or resolving such problems. Some health research priorities were obtained (by areas and others being overall priorities): chronic diseases, emergent infectious diseases, tuberculosis/leprosy, nosocomial infection and sexually transmitted diseases/HIV/AIDS.

Prioridades de investigación en salud en Colombia: perspectiva de los investigadores / Health research priorities in Colombia from the researchers' point of view

Colombia tiene una escasa experiencia en identificar prioridades de investigación en salud. En el año 2004 se inició un proyecto para identificar prioridades de investigación en salud, entendiendo por tales las que resultan de un ejercicio ordenado de ponderación basado en una valoración juiciosa de problemáticas sanitarias cuya respuesta y/o solución puede lograrse en gran parte por medio de conocimientos y procesos de investigación. Como referentes del proyecto se tuvieron en cuenta algunos de los métodos de priorización utilizados y recomendados en el ámbito internacional, entre ellos la matriz combinada del Global Forum for Health Resarch. Se pusieron en práctica dos trayectos metodológicos principales: por una parte, diseño y aplicación de un método para ponderar u ordenar, de manera cualitativa y cuantitativa, las problemáticas de investigación en salud; por otra parte, construcción de consensos con investigadores y representantes de comunidades científicas. Para identificar las problemáticas de salud predominantes se realizaron dos reuniones nacionales, dos reuniones regionales y un foro virtual. Una vez identificadas las problemáticas de salud predominantes, con su respectiva estimación de carga de enfermedad, estas se valoraron por políticos y decisores y se calificaron por investigadores de ciencias básicas, ciencias clínicas y salud pública, en términos del aporte del conocimiento requerido para afrontar, controlar o resolver tales problemáticas. Se obtuvieron unas prioridades de investigación en salud por áreas globales: enfermedades crónicas, enfermedades infecciosas emergentes, Tuberculosis/Lepra, infección nosocomial e infecciones de transmisión sexual/VIH/SIDA.

Colombia lacks experience in identifying health research priorities. A project for idenifying health research priorities was begun in 2004 (meaning those arising from weighting and ordering health and disease problems which could be mainly resolved by research and knowledge). The Global Forum for Health Research combined matrix method, and other methods, was used as reference for developing projects and putting two main methodological paths into practice: designing and applying a method for qualitatively and quantitatively weighting and ordering health research problems and building consensus with researchers and scientific community representatives. Two national meetings, two regional meetings and a virtual forum were held for identifying predo­minant health problems. Once the predominant health problems had been identified (with the respective estimation of disease load), then they were evaluated by politi­cians and decision-makers and rated by basic science, clinical science and public health researchers in terms of making a contribution towards knowledge for facing, controlling or resolving such problems. Some health research priorities were obtained (by areas and others being overall priorities): chronic diseases, emergent infectious diseases, tuberculosis/leprosy, nosocomial infection and sexually transmitted diseases/HIV/AIDS.

Quality of reporting and of methodology of studies on interventions for trophic ulcers in leprosy: a systematic review.

BACKGROUND: In the process of conducting a systematic review on interventions for skin lesions due to neuritis in leprosy, we assessed several primary papers with respect to the quality of reporting and methods used in the studies. Awareness of what constitutes weak points in previously conducted studies may be used to improve the planning, conducting and reporting of future clinical trials. AIMS: To assess the quality of reporting and of methodology in studies of interventions for skin lesions due to neuritis in leprosy. METHODS: Items of importance for preventing selection bias, detection bias, attrition bias and performance bias were among items assessed. The items for assessing methodological quality were used as a basis for making the checklist to assess the quality of reporting. RESULTS: Out of the 854 references that we inspected eight studies were included on the basis of the inclusion criteria. The interventions tested were dressings, topical agents and footwear and in all studies healing of ulcers was the main outcome measure. Reporting of both, methods and results suffered from underreporting and disorganization. The most under-reported items were concealment of allocation, blinding of patients and outcome assessors, intention to treat and validation of outcomes. CONCLUSION: There is an apparent need to improve the methodological quality as well as the quality of reporting of trials in leprosy ulcer treatment. The most important threat in existing studies is the threat of selection bias. For the reporting of future studies, journals could promote and encourage the use of the CONSORT statement checklist by expecting and requiring that authors adhere to it in their reporting.