WorldWideScience

Sample records for neglected disease drug

  1. EDITORIAL Drugs for Neglected Diseases Initiative

    African Journals Online (AJOL)

    Dr.Kofi-Tsekpo

    disease, and malaria have a devastating impact on humanity, yet R&D for new drugs for these diseases has been progressively marginalised because they are not considered a lucrative investment. DNDi, a needs-driven initiative, keeps the needs of patients suffering from neglected diseases paramount in its search for.

  2. Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

    Science.gov (United States)

    Ioset, Jean-Robert; Chang, Shing

    2011-09-01

    The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

  3. In Silico Chemogenomics Drug Repositioning Strategies for Neglected Tropical Diseases.

    Science.gov (United States)

    Andrade, Carolina Horta; Neves, Bruno Junior; Melo-Filho, Cleber Camilo; Rodrigues, Juliana; Silva, Diego Cabral; Braga, Rodolpho Campos; Cravo, Pedro Vitor Lemos

    2018-03-08

    Only ~1% of all drug candidates against Neglected Tropical Diseases (NTDs) have reached clinical trials in the last decades, underscoring the need for new, safe and effective treatments. In such context, drug repositioning, which allows finding novel indications for approved drugs whose pharmacokinetic and safety profiles are already known, is emerging as a promising strategy for tackling NTDs. Chemogenomics is a direct descendent of the typical drug discovery process that involves the systematic screening of chemical compounds against drug targets in high-throughput screening (HTS) efforts, for the identification of lead compounds. However, different to the one-drug-one-target paradigm, chemogenomics attempts to identify all potential ligands for all possible targets and diseases. In this review, we summarize current methodological development efforts in drug repositioning that use state-of-the-art computational ligand- and structure-based chemogenomics approaches. Furthermore, we highlighted the recent progress in computational drug repositioning for some NTDs, based on curation and modeling of genomic, biological, and chemical data. Additionally, we also present in-house and other successful examples and suggest possible solutions to existing pitfalls. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Fragment-based drug discovery as alternative strategy to the drug development for neglected diseases.

    Science.gov (United States)

    Mello, Juliana da Fonseca Rezende E; Gomes, Renan Augusto; Vital-Fujii, Drielli Gomes; Ferreira, Glaucio Monteiro; Trossini, Gustavo Henrique Goulart

    2017-12-01

    Neglected diseases (NDs) affect large populations and almost whole continents, representing 12% of the global health burden. In contrast, the treatment available today is limited and sometimes ineffective. Under this scenery, the Fragment-Based Drug Discovery emerged as one of the most promising alternatives to the traditional methods of drug development. This method allows achieving new lead compounds with smaller size of fragment libraries. Even with the wide Fragment-Based Drug Discovery success resulting in new effective therapeutic agents against different diseases, until this moment few studies have been applied this approach for NDs area. In this article, we discuss the basic Fragment-Based Drug Discovery process, brief successful ideas of general applications and show a landscape of its use in NDs, encouraging the implementation of this strategy as an interesting way to optimize the development of new drugs to NDs. © 2017 John Wiley & Sons A/S.

  5. Prospects for the control of neglected tropical diseases by mass drug administration

    NARCIS (Netherlands)

    Smits, Henk L.

    2009-01-01

    The prospects for the control of neglected tropical diseases, including soil-transmitted helminthiasis, shistosomiasis, lymphatic filariasis, onchocerciasis and trachoma, through mass drug administration, are exemplified by the elimination of the trachoma as a public-health problem in Morocco. In

  6. Monitoring the efficacy of drugs for neglected tropical diseases controlled by preventive chemotherapy.

    Science.gov (United States)

    Albonico, M; Levecke, B; LoVerde, P T; Montresor, A; Prichard, R; Vercruysse, J; Webster, J P

    2015-12-01

    In the last decade, pharmaceutical companies, governments and global health organisations under the leadership of the World Health Organization (WHO) have pledged large-scale donations of anthelmintic drugs, including ivermectin (IVM), praziquantel (PZQ), albendazole (ALB) and mebendazole (MEB). This worldwide scale-up in drug donations calls for strong monitoring systems to detect any changes in anthelmintic drug efficacy. This review reports on the outcome of the WHO Global Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, which consists of three subgroups: (i) soil-transmitted helminthiases (ALB and MEB); (ii) onchocerciasis and lymphatic filariasis (IVM); and (iii) schistosomiasis (PZQ). Progress of ongoing work, challenges and research needs for each of the four main drugs used in helminthic preventive chemotherapy (PC) are reported, laying the ground for appropriate implementation of drug efficacy monitoring programmes under the co-ordination and guidelines of the WHO. Best practices for monitoring drug efficacy should be made available and capacity built as an integral part of neglected tropical disease (NTD) programme monitoring. Development of a disease-specific model to predict the impact of PC programmes, to detect outliers and to solicit responses is essential. Research studies on genetic polymorphisms in relation to low-efficacy phenotypes should be carried out to identify markers of putative resistance against all NTD drugs and ultimately to develop diagnostic assays. Development of combination and co-administration of NTD drugs as well as of new drug entities to boost the armamentarium of the few drugs available for NTD control and elimination should be pursued in parallel. Copyright © 2015 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  7. Overcoming the challenges of drug discovery for neglected tropical diseases: the A·WOL experience.

    Science.gov (United States)

    Johnston, Kelly L; Ford, Louise; Taylor, Mark J

    2014-03-01

    Neglected tropical diseases (NTDs) are a group of 17 diseases that typically affect poor people in tropical countries. Each has been neglected for decades in terms of funding, research, and policy, but the recent grouping of them into one unit, which can be targeted using integrated control measures, together with increased advocacy has helped to place them on the global health agenda. The World Health Organization has set ambitious goals to control or eliminate 10 NTDs by 2020 and launched a roadmap in January 2012 to guide this global plan. The result of the launch meeting, which brought together representatives from the pharmaceutical industry, donors, and politicians, was the London Declaration: a series of commitments to provide more drugs, research, and funds to achieve the 2020 goals. Drug discovery and development for these diseases are extremely challenging, and this article highlights these challenges in the context of the London Declaration, before focusing on an example of a drug discovery and development program for the NTDs onchocerciasis and lymphatic filariasis (the anti-Wolbachia consortium, A·WOL).

  8. A Multilayer Network Approach for Guiding Drug Repositioning in Neglected Diseases.

    Directory of Open Access Journals (Sweden)

    Ariel José Berenstein

    2016-01-01

    Full Text Available Drug development for neglected diseases has been historically hampered due to lack of market incentives. The advent of public domain resources containing chemical information from high throughput screenings is changing the landscape of drug discovery for these diseases. In this work we took advantage of data from extensively studied organisms like human, mouse, E. coli and yeast, among others, to develop a novel integrative network model to prioritize and identify candidate drug targets in neglected pathogen proteomes, and bioactive drug-like molecules. We modeled genomic (proteins and chemical (bioactive compounds data as a multilayer weighted network graph that takes advantage of bioactivity data across 221 species, chemical similarities between 1.7 105 compounds and several functional relations among 1.67 105 proteins. These relations comprised orthology, sharing of protein domains, and shared participation in defined biochemical pathways. We showcase the application of this network graph to the problem of prioritization of new candidate targets, based on the information available in the graph for known compound-target associations. We validated this strategy by performing a cross validation procedure for known mouse and Trypanosoma cruzi targets and showed that our approach outperforms classic alignment-based approaches. Moreover, our model provides additional flexibility as two different network definitions could be considered, finding in both cases qualitatively different but sensible candidate targets. We also showcase the application of the network to suggest targets for orphan compounds that are active against Plasmodium falciparum in high-throughput screens. In this case our approach provided a reduced prioritization list of target proteins for the query molecules and showed the ability to propose new testable hypotheses for each compound. Moreover, we found that some predictions highlighted by our network model were supported by

  9. A Multilayer Network Approach for Guiding Drug Repositioning in Neglected Diseases.

    Science.gov (United States)

    Berenstein, Ariel José; Magariños, María Paula; Chernomoretz, Ariel; Agüero, Fernán

    2016-01-01

    Drug development for neglected diseases has been historically hampered due to lack of market incentives. The advent of public domain resources containing chemical information from high throughput screenings is changing the landscape of drug discovery for these diseases. In this work we took advantage of data from extensively studied organisms like human, mouse, E. coli and yeast, among others, to develop a novel integrative network model to prioritize and identify candidate drug targets in neglected pathogen proteomes, and bioactive drug-like molecules. We modeled genomic (proteins) and chemical (bioactive compounds) data as a multilayer weighted network graph that takes advantage of bioactivity data across 221 species, chemical similarities between 1.7 105 compounds and several functional relations among 1.67 105 proteins. These relations comprised orthology, sharing of protein domains, and shared participation in defined biochemical pathways. We showcase the application of this network graph to the problem of prioritization of new candidate targets, based on the information available in the graph for known compound-target associations. We validated this strategy by performing a cross validation procedure for known mouse and Trypanosoma cruzi targets and showed that our approach outperforms classic alignment-based approaches. Moreover, our model provides additional flexibility as two different network definitions could be considered, finding in both cases qualitatively different but sensible candidate targets. We also showcase the application of the network to suggest targets for orphan compounds that are active against Plasmodium falciparum in high-throughput screens. In this case our approach provided a reduced prioritization list of target proteins for the query molecules and showed the ability to propose new testable hypotheses for each compound. Moreover, we found that some predictions highlighted by our network model were supported by independent

  10. The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases

    Directory of Open Access Journals (Sweden)

    Peter Mubanga Cheuka

    2016-12-01

    Full Text Available Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Natural products have been a valuable source of drug regimens that form the cornerstone of modern pharmaceutical care. In this review, we highlight the potential that remains untapped in natural products as drug leads for NTDs. We cover natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of NTDs. Our coverage is limited to four major NTDs which include human African trypanosomiasis (sleeping sickness, leishmaniasis, schistosomiasis and lymphatic filariasis.

  11. Adverse event management in mass drug administration for neglected tropical diseases.

    Science.gov (United States)

    Caplan, Arthur; Zink, Amanda

    2014-03-01

    The ethical challenges of reporting and managing adverse events (AEs) and serious AEs (SAEs) in the context of mass drug administration (MDA) for the treatment of neglected tropical diseases (NTDs) require reassessment of domestic and international policies on a global scale. Although the World Health Organization has set forth AE/SAE guidelines specifically for NTD MDA that incorporate suspected causality, and recommends that only SAEs get reported in this setting, most regulatory agencies continue to require the reporting of all SAEs exhibiting even a merely temporal relationship to activities associated with an MDA program. This greatly increases the potential for excess "noise" and undue risk aversion and is not only impractical but arguably unethical where huge proportions of populations are being treated for devastating diseases, and no good baseline exists against which to compare possible AE/SAE reports. Other population-specific variables that might change the way drug safety ought to be assessed include differing efficacy rates of a drug, background morbidity/mortality rates of the target disease in question, the growth rate of the incidence of disease, the availability of rescue or salvage therapies, and the willingness of local populations to take risks that other populations might not. The fact that NTDs are controllable and potentially eradicable with well-tolerated, effective, existing drugs might further alter our assessment of MDA safety and AE/SAE tolerability. At the same time, diffuseness of population, communication barriers, lack of resources, and other difficult surveillance challenges may present in NTD-affected settings. These limitations could impair the ability to monitor an MDA program's success, as well as hinder efforts to obtain informed consent or provide rescue therapy. Denying beneficial research interventions and MDA programs intended to benefit millions requires sound ethical justification based on more than the identification of

  12. Ethical issues in funding research and development of drugs for neglected tropical diseases.

    Science.gov (United States)

    Oprea, L; Braunack-Mayer, A; Gericke, C A

    2009-05-01

    Neglected and tropical diseases, pervasive in developing countries, are important contributors to global health inequalities. They remain largely untreated due to lack of effective and affordable treatments. Resource-poor countries cannot afford to develop the public health interventions needed to control neglected diseases. In addition, neglected diseases do not represent an attractive market for pharmaceutical industry. Although a number of international commitments, stated in the Millennium Development Goals, have been made to avert the risk of communicable diseases, tropical diseases still remain neglected due to delays in international assistance. This delay can be explained by the form international cooperation has generally taken, which is limited to promoting countries' national interests, rather than social justice at a global level. This restricts the international responsibility for global inequalities in health to a humanitarian assistance. We propose an alternative view, arguing that expanding the scope of international cooperation by promoting shared health and economic value at a global level will create new opportunities for innovative, effective and affordable interventions worldwide. It will also promote neglected diseases as a global research priority. We build our argument on a proposal to replace the patenting system that currently regulates pharmaceutical research with a global fund to reward this research based on actual decreases in morbidity and mortality at a global level. We argue that this approach is beneficent because it will decrease global health inequalities and promote social justice worldwide.

  13. Informatics for neglected diseases collaborations.

    Science.gov (United States)

    Bost, Frederic; Jacobs, Robert T; Kowalczyk, Paul

    2010-05-01

    Many different public and private organizations from across the globe are collaborating on neglected diseases drug-discovery and development projects with the aim of identifying a cure for tropical infectious diseases. These neglected diseases collaborations require a global, secure, multi-organization data-management solution, combined with a platform that facilitates communication and supports collaborative work. This review discusses the solutions offered by 'Software as a Service' (SaaS) web-based platforms, despite notable challenges, and the evolution of these platforms required to foster efficient virtual research efforts by geographically dispersed scientists.

  14. Neglected tropical diseases

    Directory of Open Access Journals (Sweden)

    David Molyneux

    2013-08-01

    Full Text Available Seventeen neglected tropical diseases (NTDs have been identified by the World Health Organization (WHO. It is estimated that over 1 billion people are infected with NTDs, with a further 1 billion at risk. The majority of NTDs occur in the tropics and sub-tropics and have particular characteristics in common.

  15. Prodrugs for the Treatment of Neglected Diseases

    Directory of Open Access Journals (Sweden)

    Lorena Blau

    2007-03-01

    Full Text Available Recently, World Health Organization (WHO and Medicins San Frontieres (MSF proposed a classification of diseases as global, neglected and extremely neglected. Global diseases, such as cancer, cardiovascular and mental (CNS diseases represent the targets of the majority of the R&D efforts of pharmaceutical companies. Neglected diseases affect millions of people in the world yet existing drug therapy is limited and often inappropriate. Furthermore, extremely neglected diseases affect people living under miserable conditions who barely have access to the bare necessities for survival. Most of these diseases are excluded from the goals of the R&D programs in the pharmaceutical industry and therefore fall outside the pharmaceutical market. About 14 million people, mainly in developing countries, die each year from infectious diseases. From 1975 to 1999, 1393 new drugs were approved yet only 1% were for the treatment of neglected diseases [3]. These numbers have not changed until now, so in those countries there is an urgent need for the design and synthesis of new drugs and in this area the prodrug approach is a very interesting field. It provides, among other effects, activity improvements and toxicity decreases for current and new drugs, improving market availability. It is worth noting that it is essential in drug design to save time and money, and prodrug approaches can be considered of high interest in this respect. The present review covers 20 years of research on the design of prodrugs for the treatment of neglected and extremely neglected diseases such as Chagas’ disease (American trypanosomiasis, sleeping sickness (African trypanosomiasis, malaria, sickle cell disease, tuberculosis, leishmaniasis and schistosomiasis.

  16. Identification of attractive drug targets in neglected-disease pathogens using an in silico approach.

    Directory of Open Access Journals (Sweden)

    Gregory J Crowther

    Full Text Available BACKGROUND: The increased sequencing of pathogen genomes and the subsequent availability of genome-scale functional datasets are expected to guide the experimental work necessary for target-based drug discovery. However, a major bottleneck in this has been the difficulty of capturing and integrating relevant information in an easily accessible format for identifying and prioritizing potential targets. The open-access resource TDRtargets.org facilitates drug target prioritization for major tropical disease pathogens such as the mycobacteria Mycobacterium leprae and Mycobacterium tuberculosis; the kinetoplastid protozoans Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi; the apicomplexan protozoans Plasmodium falciparum, Plasmodium vivax, and Toxoplasma gondii; and the helminths Brugia malayi and Schistosoma mansoni. METHODOLOGY/PRINCIPAL FINDINGS: Here we present strategies to prioritize pathogen proteins based on whether their properties meet criteria considered desirable in a drug target. These criteria are based upon both sequence-derived information (e.g., molecular mass and functional data on expression, essentiality, phenotypes, metabolic pathways, assayability, and druggability. This approach also highlights the fact that data for many relevant criteria are lacking in less-studied pathogens (e.g., helminths, and we demonstrate how this can be partially overcome by mapping data from homologous genes in well-studied organisms. We also show how individual users can easily upload external datasets and integrate them with existing data in TDRtargets.org to generate highly customized ranked lists of potential targets. CONCLUSIONS/SIGNIFICANCE: Using the datasets and the tools available in TDRtargets.org, we have generated illustrative lists of potential drug targets in seven tropical disease pathogens. While these lists are broadly consistent with the research community's current interest in certain specific proteins, and suggest

  17. Neglected tropical diseases in Brazil.

    Science.gov (United States)

    Lindoso, José Angelo L; Lindoso, Ana Angélica B P

    2009-01-01

    Poverty is intrinsically related to the incidence of Neglected Tropical Diseases (NTDs). The main countries that have the lowest human development indices (HDI) and the highest burdens of NTDs are located in tropical and subtropical regions of the world. Among these countries is Brazil, which is ranked 70th in HDI. Nine out of the ten NTDs established by the World Health Organization (WHO) are present in Brazil. Leishmaniasis, tuberculosis, dengue fever and leprosy are present over almost the entire Brazilian territory. More than 90% of malaria cases occur in the Northern region of the country, and lymphatic filariasis and onchocerciasis occur in outbreaks in a particular region. The North and Northeast regions of Brazil have the lowest HDIs and the highest rates of NTDs. These diseases are considered neglected because there is not important investment in projects for the development of new drugs and vaccines and existing programs to control these diseases are not sufficient. Another problem related to NTDs is co-infection with HIV, which favors the occurrence of severe clinical manifestations and therapeutic failure. In this article, we describe the status of the main NTDs currently occurring in Brazil and relate them to the HDI and poverty.

  18. Neglected tropical diseases, neglected data sources, and neglected issues.

    Directory of Open Access Journals (Sweden)

    Burton H Singer

    Full Text Available BACKGROUND: Lymphatic filariasis (LF is a so-called neglected tropical disease, currently overshadowed by higher-profile efforts to address malaria, tuberculosis, and HIV/AIDS. Despite recent successes in arresting transmission, some 40 million people who already have the disease have been largely neglected. This study aims to increase understanding of how this vulnerable, neglected group can be helped. METHODS: We used purposive sampling to select 60 men and women with filarial lymphoedema (45 with filarial elephantiasis and 15 men with filarial hydrocoele from the south of Sri Lanka in 2004-2005. Participants were selected to give a balance of men and women and poor and nonpoor, and a range of stages of the disease. Participants' experiences and the consequences of their disease for the household were explored with in-depth qualitative, semistructured interviews. FINDINGS: LF was extremely debilitating to participants over long periods of time. The stigma attached to the condition caused social isolation and emotional distress, and delayed diagnosis and treatment, resulting in undue advancement of the disease. Free treatment services at government clinics were avoided because the participants' condition would be identifiable in public. Loss of income due to the condition was reported by all households in the sample, not just the poorest. Households that were already on low incomes were pushed into near destitution, from which it was almost impossible to escape. Affected members of low-income households also had less opportunity to obtain appropriate treatment from distant clinics, and had living and working conditions that made hygiene and compliance difficult. SIGNIFICANCE: This highly vulnerable category of patients has low visibility, thus becoming marginalized and forgotten. With an estimated 300,000 total cases of elephantiasis and/or oedema in Sri Lanka, and around 300,000 men with filarial hydrocoele, the affected households will need

  19. From Medicinal Chemistry to Human Health: Current Approaches to Drug Discovery for Cancer and Neglected Tropical Diseases

    Directory of Open Access Journals (Sweden)

    LEONARDO G. FERREIRA

    2018-02-01

    Full Text Available ABSTRACT Scientific and technological breakthroughs have compelled the current players in drug discovery to increasingly incorporate knowledge-based approaches. This evolving paradigm, which has its roots attached to the recent advances in medicinal chemistry, molecular and structural biology, has unprecedentedly demanded the development of up-to-date computational approaches, such as bio- and chemo-informatics. These tools have been pivotal to catalyzing the ever-increasing amount of data generated by the molecular sciences, and to converting the data into insightful guidelines for use in the research pipeline. As a result, ligand- and structure-based drug design have emerged as key pathways to address the pharmaceutical industry’s striking demands for innovation. These approaches depend on a keen integration of experimental and molecular modeling methods to surmount the main challenges faced by drug candidates - in vivo efficacy, pharmacodynamics, metabolism, pharmacokinetics and safety. To that end, the Laboratório de Química Medicinal e Computacional (LQMC of the Universidade de São Paulo has developed forefront research on highly prevalent and life-threatening neglected tropical diseases and cancer. By taking part in global initiatives for pharmaceutical innovation, the laboratory has contributed to the advance of these critical therapeutic areas through the use of cutting-edge strategies in medicinal chemistry.

  20. Mass Drug Administration and beyond: how can we strengthen health systems to deliver complex interventions to eliminate neglected tropical diseases?

    Science.gov (United States)

    Macpherson, Eleanor E; Adams, Emily R; Bockarie, Moses J; Hollingsworth, T Deirdre; Kelly-Hope, Louise A; Lehane, Mike; Kovacic, Vanja; Harrison, Robert A; Paine, Mark Ji; Reimer, Lisa J; Torr, Stephen J

    2015-01-01

    Achieving the 2020 goals for Neglected Tropical Diseases (NTDs) requires scale-up of Mass Drug Administration (MDA) which will require long-term commitment of national and global financing partners, strengthening national capacity and, at the community level, systems to monitor and evaluate activities and impact. For some settings and diseases, MDA is not appropriate and alternative interventions are required. Operational research is necessary to identify how existing MDA networks can deliver this more complex range of interventions equitably. The final stages of the different global programmes to eliminate NTDs require eliminating foci of transmission which are likely to persist in complex and remote rural settings. Operational research is required to identify how current tools and practices might be adapted to locate and eliminate these hard-to-reach foci. Chronic disabilities caused by NTDs will persist after transmission of pathogens ceases. Development and delivery of sustainable services to reduce the NTD-related disability is an urgent public health priority. LSTM and its partners are world leaders in developing and delivering interventions to control vector-borne NTDs and malaria, particularly in hard-to-reach settings in Africa. Our experience, partnerships and research capacity allows us to serve as a hub for developing, supporting, monitoring and evaluating global programmes to eliminate NTDs.

  1. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond

    Science.gov (United States)

    Van Voorhis, Wesley C.; Adams, John H.; Adelfio, Roberto; Ahyong, Vida; Akabas, Myles H.; Alano, Pietro; Alday, Aintzane; Alemán Resto, Yesmalie; Alsibaee, Aishah; Alzualde, Ainhoa; Andrews, Katherine T.; Avery, Simon V.; Avery, Vicky M.; Ayong, Lawrence; Baker, Mark; Baker, Stephen; Ben Mamoun, Choukri; Bhatia, Sangeeta; Bickle, Quentin; Bounaadja, Lotfi; Bowling, Tana; Bosch, Jürgen; Boucher, Lauren E.; Boyom, Fabrice F.; Brea, Jose; Brennan, Marian; Burton, Audrey; Caffrey, Conor R.; Camarda, Grazia; Carrasquilla, Manuela; Carter, Dee; Belen Cassera, Maria; Chih-Chien Cheng, Ken; Chindaudomsate, Worathad; Chubb, Anthony; Colon, Beatrice L.; Colón-López, Daisy D.; Corbett, Yolanda; Crowther, Gregory J.; Cowan, Noemi; D’Alessandro, Sarah; Le Dang, Na; Delves, Michael; Du, Alan Y.; Duffy, Sandra; Abd El-Salam El-Sayed, Shimaa; Ferdig, Michael T.; Fernández Robledo, José A.; Fidock, David A.; Florent, Isabelle; Fokou, Patrick V. T.; Galstian, Ani; Gamo, Francisco Javier; Gold, Ben; Golub, Todd; Goldgof, Gregory M.; Guha, Rajarshi; Guiguemde, W. Armand; Gural, Nil; Guy, R. Kiplin; Hansen, Michael A. E.; Hanson, Kirsten K.; Hemphill, Andrew; Hooft van Huijsduijnen, Rob; Horii, Takaaki; Horrocks, Paul; Hughes, Tyler B.; Huston, Christopher; Igarashi, Ikuo; Ingram-Sieber, Katrin; Itoe, Maurice A.; Jadhav, Ajit; Naranuntarat Jensen, Amornrat; Jensen, Laran T.; Jiang, Rays H. Y.; Kaiser, Annette; Keiser, Jennifer; Ketas, Thomas; Kicka, Sebastien; Kim, Sunyoung; Kirk, Kiaran; Kumar, Vidya P.; Kyle, Dennis E.; Lafuente, Maria Jose; Landfear, Scott; Lee, Nathan; Lee, Sukjun; Lehane, Adele M.; Li, Fengwu; Little, David; Liu, Liqiong; Llinás, Manuel; Loza, Maria I.; Lubar, Aristea; Lucantoni, Leonardo; Lucet, Isabelle; Maes, Louis; Mancama, Dalu; Mansour, Nuha R.; March, Sandra; McGowan, Sheena; Medina Vera, Iset; Meister, Stephan; Mercer, Luke; Mestres, Jordi; Mfopa, Alvine N.; Misra, Raj N.; Moon, Seunghyun; Moore, John P.; Morais Rodrigues da Costa, Francielly; Müller, Joachim; Muriana, Arantza; Nakazawa Hewitt, Stephen; Nare, Bakela; Nathan, Carl; Narraidoo, Nathalie; Nawaratna, Sujeevi; Ojo, Kayode K.; Ortiz, Diana; Panic, Gordana; Papadatos, George; Parapini, Silvia; Patra, Kailash; Pham, Ngoc; Prats, Sarah; Plouffe, David M.; Poulsen, Sally-Ann; Pradhan, Anupam; Quevedo, Celia; Quinn, Ronald J.; Rice, Christopher A.; Abdo Rizk, Mohamed; Ruecker, Andrea; St. Onge, Robert; Salgado Ferreira, Rafaela; Samra, Jasmeet; Robinett, Natalie G.; Schlecht, Ulrich; Schmitt, Marjorie; Silva Villela, Filipe; Silvestrini, Francesco; Sinden, Robert; Smith, Dennis A.; Soldati, Thierry; Spitzmüller, Andreas; Stamm, Serge Maximilian; Sullivan, David J.; Sullivan, William; Suresh, Sundari; Suzuki, Brian M.; Suzuki, Yo; Swamidass, S. Joshua; Taramelli, Donatella; Tchokouaha, Lauve R. Y.; Theron, Anjo; Thomas, David; Tonissen, Kathryn F.; Townson, Simon; Tripathi, Abhai K.; Trofimov, Valentin; Udenze, Kenneth O.; Ullah, Imran; Vallieres, Cindy; Vigil, Edgar; Vinetz, Joseph M.; Voong Vinh, Phat; Vu, Hoan; Watanabe, Nao-aki; Weatherby, Kate; White, Pamela M.; Wilks, Andrew F.; Winzeler, Elizabeth A.; Wojcik, Edward; Wree, Melanie; Wu, Wesley; Yokoyama, Naoaki; Zollo, Paul H. A.; Abla, Nada; Blasco, Benjamin; Burrows, Jeremy; Laleu, Benoît; Leroy, Didier; Spangenberg, Thomas; Wells, Timothy; Willis, Paul A.

    2016-01-01

    A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal

  2. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond.

    Directory of Open Access Journals (Sweden)

    Wesley C Van Voorhis

    2016-07-01

    Full Text Available A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34% of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments

  3. High-throughput screening platform for natural product-based drug discovery against 3 neglected tropical diseases: human African trypanosomiasis, leishmaniasis, and Chagas disease.

    Science.gov (United States)

    Annang, F; Pérez-Moreno, G; García-Hernández, R; Cordon-Obras, C; Martín, J; Tormo, J R; Rodríguez, L; de Pedro, N; Gómez-Pérez, V; Valente, M; Reyes, F; Genilloud, O; Vicente, F; Castanys, S; Ruiz-Pérez, L M; Navarro, M; Gamarro, F; González-Pacanowska, D

    2015-01-01

    African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography-mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites. © 2014 Society for Laboratory Automation and Screening.

  4. The use of the United States FDA programs as a strategy to advance the development of drug products for neglected tropical diseases.

    Science.gov (United States)

    Sachs-Barrable, Kristina; Conway, Jocelyn; Gershkovich, Pavel; Ibrahim, Fady; Wasan, Kishor M

    2014-11-01

    Neglected tropical diseases (NTDs) are infections which are endemic in poor populations in lower- and middle-income countries (LMIC). Approximately one billion people have now or are at risk of getting an NTD and yet less than 5% of research dollars are focused on providing treatments and prevention of these highly debilitating and deadly conditions. The United States Food and Drug Administration (FDA) Orphan Drug Designation program (ODDP) provides orphan status to drugs and biologics, defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and/or disorders that affect fewer than 200 000 people in the United States, or that affect more than 200 000 persons but are not expected to recover the costs of developing and marketing a treatment drug. These regulations have led to the translation of rare disease knowledge into innovative rare disease therapies. The FDA Guidance for Industry on developing drugs for the treatment and prevention of NTDs describes the following regulatory strategies: Orphan Product Designation, Fast Track Designation, Priority Review Designation, Accelerated Approval and Tropical Disease Priority Review Voucher. This paper will discuss how these regulations and especially the ODDP can improve the clinical development and accessibility of drug products for NTDs.

  5. Current pipelines for neglected diseases.

    Science.gov (United States)

    di Procolo, Paolo; Jommi, Claudio

    2014-09-01

    This paper scrutinises pipelines for Neglected Diseases (NDs), through freely accessible and at-least-weekly updated trials databases. It updates to 2012 data provided by recent publications, and integrates these analyses with information on location of trials coordinators and patients recruitment status. Additionally, it provides (i) disease-specific information to better understand the rational of investments in NDs, (ii) yearly data, to understand the investment trends. The search identified 650 clinical studies. Leishmaniasis, Arbovirus infection, and Dengue are the top three diseases by number of clinical studies. Disease diffusion risk seems to be the most important driver of the clinical trials target choice, whereas the role played by disease prevalence and unmet need is controversial. Number of trials is stable between 2005 and 2010, with an increase in the last two years. Patient recruitment was completed for most studies (57.6%), and Phases II and III account for 35% and 28% of trials, respectively. The primary purpose of clinical investigations is prevention (49.3%), especially for infectious diseases with mosquitoes and sand flies as the vector, and treatment (43.2%), which is the primary target for parasitic diseases Research centres and public organisations are the most important clinical studies sponsors (58.9%), followed by the pharmaceutical industry (24.1%), foundations and non-governmental organisations (9.3%). Many coordinator centres are located in less affluent countries (43.7%), whereas OECD countries and BRICS account for 34.7% and 17.5% of trials, respectively. Information was partially missing for some parameters. Notwithstanding, and despite its descriptive nature, this research has enhanced the evidence of the literature on pipelines for NDs. Future contributions may further investigate whether trials metrics are consistent with the characteristics of the interested countries and the explicative variables of trials location, target

  6. Community Attitudes Toward Mass Drug Administration for Control and Elimination of Neglected Tropical Diseases After the 2014 Outbreak of Ebola Virus Disease in Lofa County, Liberia.

    Science.gov (United States)

    Bogus, Joshua; Gankpala, Lincoln; Fischer, Kerstin; Krentel, Alison; Weil, Gary J; Fischer, Peter U; Kollie, Karsor; Bolay, Fatorma K

    2016-03-01

    The recent outbreak of Ebola virus disease (EVD) interrupted mass drug administration (MDA) programs to control and eliminate neglected tropical diseases in Liberia. MDA programs treat entire communities with medication regardless of infection status to interrupt transmission and eliminate lymphatic filariasis and onchocerciasis. Following reports of hostilities toward health workers and fear that they might be spreading EVD, it was important to determine whether attitudes toward MDA might have changed after the outbreak. We surveyed 140 community leaders from 32 villages in Lofa County, Liberia, that had previously participated in MDA and are located in an area that was an early epicenter of the EVD outbreak. Survey respondents reported a high degree of community trust in the MDA program, and 97% thought their communities were ready to resume MDA. However, respondents predicted that fewer people would comply with MDA after the EVD epidemic than before. The survey also uncovered fears in the community that EVD and MDA might be linked. Respondents suggested that MDA programs emphasize to people that the medications are identical to those previously distributed and that MDA programs have nothing to do with EVD. © The American Society of Tropical Medicine and Hygiene.

  7. R&D Incentives for Neglected Diseases

    Science.gov (United States)

    Dimitri, Nicola

    2012-01-01

    Neglected diseases are typically characterized as those for which adequate drug treatment is lacking, and the potential return on effort in research and development (R&D), to produce new therapies, is too small for companies to invest significant resources in the field. In recent years various incentives schemes to stimulate R&D by pharmaceutical firms have been considered. Broadly speaking, these can be classified either as ‘push’ or ‘pull’ programs. Hybrid options, that include push and pull incentives, have also become increasingly popular. Supporters and critics of these various incentive schemes have argued in favor of their relative merits and limitations, although the view that no mechanism is a perfect fit for all situations appears to be widely held. For this reason, the debate on the advantages and disadvantages of different approaches has been important for policy decisions, but is dispersed in a variety of sources. With this in mind, the aim of this paper is to contribute to the understanding of the economic determinants behind R&D investments for neglected diseases by comparing the relative strength of different incentive schemes within a simple economic model, based on the assumption of profit maximizing firms. The analysis suggests that co-funded push programs are generally more efficient than pure pull programs. However, by setting appropriate intermediate goals hybrid incentive schemes could further improve efficiency. PMID:23284648

  8. R&D incentives for neglected diseases.

    Directory of Open Access Journals (Sweden)

    Nicola Dimitri

    Full Text Available Neglected diseases are typically characterized as those for which adequate drug treatment is lacking, and the potential return on effort in research and development (R&D, to produce new therapies, is too small for companies to invest significant resources in the field. In recent years various incentives schemes to stimulate R&D by pharmaceutical firms have been considered. Broadly speaking, these can be classified either as 'push' or 'pull' programs. Hybrid options, that include push and pull incentives, have also become increasingly popular. Supporters and critics of these various incentive schemes have argued in favor of their relative merits and limitations, although the view that no mechanism is a perfect fit for all situations appears to be widely held. For this reason, the debate on the advantages and disadvantages of different approaches has been important for policy decisions, but is dispersed in a variety of sources. With this in mind, the aim of this paper is to contribute to the understanding of the economic determinants behind R&D investments for neglected diseases by comparing the relative strength of different incentive schemes within a simple economic model, based on the assumption of profit maximizing firms. The analysis suggests that co-funded push programs are generally more efficient than pure pull programs. However, by setting appropriate intermediate goals hybrid incentive schemes could further improve efficiency.

  9. R&D incentives for neglected diseases.

    Science.gov (United States)

    Dimitri, Nicola

    2012-01-01

    Neglected diseases are typically characterized as those for which adequate drug treatment is lacking, and the potential return on effort in research and development (R&D), to produce new therapies, is too small for companies to invest significant resources in the field. In recent years various incentives schemes to stimulate R&D by pharmaceutical firms have been considered. Broadly speaking, these can be classified either as 'push' or 'pull' programs. Hybrid options, that include push and pull incentives, have also become increasingly popular. Supporters and critics of these various incentive schemes have argued in favor of their relative merits and limitations, although the view that no mechanism is a perfect fit for all situations appears to be widely held. For this reason, the debate on the advantages and disadvantages of different approaches has been important for policy decisions, but is dispersed in a variety of sources. With this in mind, the aim of this paper is to contribute to the understanding of the economic determinants behind R&D investments for neglected diseases by comparing the relative strength of different incentive schemes within a simple economic model, based on the assumption of profit maximizing firms. The analysis suggests that co-funded push programs are generally more efficient than pure pull programs. However, by setting appropriate intermediate goals hybrid incentive schemes could further improve efficiency.

  10. Therapeutics for Rare and Neglected Diseases

    Data.gov (United States)

    Federal Laboratory Consortium — There are more than 6,500 identified rare and neglected diseases, yet only about 250 treatments are available for these conditions. The limited numbers of patients...

  11. EDITORIAL Neglected Diseases: Burden and attention

    African Journals Online (AJOL)

    Preferred Customer

    Neglected diseases are largely infectious diseases that have burdened humanity for centuries, but currently receiving little attention. Infectious diseases in their long histories have resulted in considerable morbidities, disabilities and deformities, often subjecting to stigma. The magnitude of their impact on health and labor.

  12. Types of Neglected Tropical Diseases

    Science.gov (United States)

    ... Trichuriasis (whipworm disease) Contracted by ingesting soil or vegetables contaminated with feces containing whipworm eggs, trichuriasis can cause dehydration and anemia and impair growth and cognition. Content ...

  13. Podoconiosis, a neglected tropical disease

    NARCIS (Netherlands)

    Korevaar, D. A.; Visser, B. J.

    2012-01-01

    Podoconiosis or 'endemic non-filarial elephantiasis' is a tropical disease caused by exposure of bare feet to irritant alkaline clay soils. This causes an asymmetrical swelling of the feet and lower limbs due to lymphoedema. Podoconiosis has a curable pre-elephantiasic phase. However, once

  14. Vaccines to combat the neglected tropical diseases

    Science.gov (United States)

    Bethony, Jeffrey M.; Cole, Rhea N.; Guo, Xiaoti; Kamhawi, Shaden; Lightowlers, Marshall W.; Loukas, Alex; Petri, William; Reed, Steven; Valenzuela, Jesus G.; Hotez, Peter J.

    2012-01-01

    Summary The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low- and middle-income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. Despite their global public health importance, progress on developing vaccines for NTD pathogens has lagged because of some key technical hurdles and the fact that these infections occur almost exclusively in the world’s poorest people living below the World Bank poverty line. In the absence of financial incentives for new products, the multinational pharmaceutical companies have not embarked on substantive research and development programs for the neglected tropical disease vaccines. Here, we review the current status of scientific and technical progress in the development of new neglected tropical disease vaccines, highlighting the successes that have been achieved (cysticercosis and echinococcosis) and identifying the challenges and opportunities for development of new vaccines for NTDs. Also highlighted are the contributions being made by non-profit product development partnerships that are working to overcome some of the economic challenges in vaccine manufacture, clinical testing, and global access. PMID:21198676

  15. Review of the factors influencing the motivation of community drug distributors towards the control and elimination of neglected tropical diseases (NTDs.

    Directory of Open Access Journals (Sweden)

    Alison Krentel

    2017-12-01

    Full Text Available Community drug distributors or neglected tropical disease (NTD volunteers have played a crucial role in ensuring the success of mass drug administration (MDA programs using preventive chemotherapy (PC for lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminths. In recent years however, a noticeable decline in motivation of some of these volunteers has been perceived, potentially negatively impacting the success of these programs. Potential hypotheses for this change in motivation include the long duration of many MDA programs, the change in sociocultural environments as well as the changes to the programs over time. This literature review identifies factors that affect NTD volunteer performance and motivation, which may be used to influence and improve future programming.A systematic search was conducted to identify studies published between January 1995 and September 2016 that investigate factors pertaining to volunteer motivation and performance in NTD drug distribution programs. Searches from several databases and grey literature yielded 400 records, of which 28 articles from 10 countries met the inclusion criteria. Quality assessment of studies was performed using the Critical Appraisal Skills Programme(CASP checklist. Data pertaining to motivation, performance, retention and satisfaction was extracted and examined for themes. Recurring themes in the literature included monetary and material incentives, intrinsic motivation, gender, cost to participate, and health systems and community support. Of these, community support and the health system were found to be particularly impactful. Very few studies were found to explicitly look at novel incentives for volunteers and very few studies have considered the out of pocket and opportunity costs that NTD volunteers bear carrying out their tasks.There is currently great interest in incorporating more attractive incentive schemes for NTD volunteers. However

  16. Review of the factors influencing the motivation of community drug distributors towards the control and elimination of neglected tropical diseases (NTDs).

    Science.gov (United States)

    Krentel, Alison; Gyapong, Margaret; Mallya, Shruti; Boadu, Nana Yaa; Amuyunzu-Nyamongo, Mary; Stephens, Mariana; McFarland, Deborah A

    2017-12-01

    Community drug distributors or neglected tropical disease (NTD) volunteers have played a crucial role in ensuring the success of mass drug administration (MDA) programs using preventive chemotherapy (PC) for lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminths. In recent years however, a noticeable decline in motivation of some of these volunteers has been perceived, potentially negatively impacting the success of these programs. Potential hypotheses for this change in motivation include the long duration of many MDA programs, the change in sociocultural environments as well as the changes to the programs over time. This literature review identifies factors that affect NTD volunteer performance and motivation, which may be used to influence and improve future programming. A systematic search was conducted to identify studies published between January 1995 and September 2016 that investigate factors pertaining to volunteer motivation and performance in NTD drug distribution programs. Searches from several databases and grey literature yielded 400 records, of which 28 articles from 10 countries met the inclusion criteria. Quality assessment of studies was performed using the Critical Appraisal Skills Programme(CASP) checklist. Data pertaining to motivation, performance, retention and satisfaction was extracted and examined for themes. Recurring themes in the literature included monetary and material incentives, intrinsic motivation, gender, cost to participate, and health systems and community support. Of these, community support and the health system were found to be particularly impactful. Very few studies were found to explicitly look at novel incentives for volunteers and very few studies have considered the out of pocket and opportunity costs that NTD volunteers bear carrying out their tasks. There is currently great interest in incorporating more attractive incentive schemes for NTD volunteers. However, our results show

  17. Neglected Tropical Diseases: Epidemiology and Global Burden

    Directory of Open Access Journals (Sweden)

    Amal K. Mitra

    2017-08-01

    Full Text Available More than a billion people—one-sixth of the world’s population, mostly in developing countries—are infected with one or more of the neglected tropical diseases (NTDs. Several national and international programs (e.g., the World Health Organization’s Global NTD Programs, the Centers for Disease Control and Prevention’s Global NTD Program, the United States Global Health Initiative, the United States Agency for International Development’s NTD Program, and others are focusing on NTDs, and fighting to control or eliminate them. This review identifies the risk factors of major NTDs, and describes the global burden of the diseases in terms of disability-adjusted life years (DALYs.

  18. Staphylococcal disease in Africa: another neglected 'tropical' disease

    NARCIS (Netherlands)

    Herrmann, Mathias; Abdullah, Salim; Alabi, Abraham; Alonso, Pedro; Friedrich, Alexander W.; Fuhr, Günther; Germann, Anja; Kern, Winfried V.; Kremsner, Peter G.; Mandomando, Inacio; Mellmann, Alexander C.; Pluschke, Gerd; Rieg, Siegbert; Ruffing, Ulla; Schaumburg, Frieder; Tanner, Marcel; Peters, Georg; von Briesen, Hagen; von Eiff, Christof; von Müller, Lutz; Grobusch, Martin P.

    2013-01-01

    The term 'neglected tropical diseases' predominantly refers to single-entity, mostly parasitic diseases. However, a considerable morbidity and mortality burden is carried by patients infected with Gram-positive cocci and Gram-negative bacilli that are prevalent all over the world, yet have impact in

  19. Staphylococcal disease in Africa : another neglected 'tropical' disease

    NARCIS (Netherlands)

    Herrmann, Mathias; Abdullah, Salim; Alabi, Abraham; Alonso, Pedro; Friedrich, Alexander W.; Fuhr, Guenther; Germann, Anja; Kern, Winfried V.; Kremsner, Peter G.; Mandomando, Inacio; Mellmann, Alexander C.; Pluschke, Gerd; Rieg, Siegbert; Ruffing, Ulla; Schaumburg, Frieder; Tanner, Marcel; von Briesen, Hagen; von Eiff, Christof; von Mueller, Lutz; Grobusch, Martin P.; Peters, Georg

    The term 'neglected tropical diseases' predominantly refers to single-entity, mostly parasitic diseases. However, a considerable morbidity and mortality burden is carried by patients infected with Gram-positive cocci and Gram-negative bacilli that are prevalent all over the world, yet have impact in

  20. Ebola and Marburg Hemorrhagic Fevers: Neglected Tropical Diseases?

    Science.gov (United States)

    MacNeil, Adam; Rollin, Pierre E.

    2012-01-01

    Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are rare viral diseases, endemic to central Africa. The overall burden of EHF and MHF is small in comparison to the more common protozoan, helminth, and bacterial diseases typically referred to as neglected tropical diseases (NTDs). However, EHF and MHF outbreaks typically occur in resource-limited settings, and many aspects of these outbreaks are a direct consequence of impoverished conditions. We will discuss aspects of EHF and MHF disease, in comparison to the “classic” NTDs, and examine potential ways forward in the prevention and control of EHF and MHF in sub-Saharan Africa, as well as examine the potential for application of novel vaccines or antiviral drugs for prevention or control of EHF and MHF among populations at highest risk for disease. PMID:22761967

  1. Reviewing dengue: still a neglected tropical disease?

    Science.gov (United States)

    Horstick, Olaf; Tozan, Yesim; Wilder-Smith, Annelies

    2015-04-01

    Dengue is currently listed as a "neglected tropical disease" (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003-2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.

  2. Reviewing dengue: still a neglected tropical disease?

    Directory of Open Access Journals (Sweden)

    Olaf Horstick

    2015-04-01

    Full Text Available Dengue is currently listed as a "neglected tropical disease" (NTD. But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D (2003-2013. NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a poverty related, b endemic to the tropics and subtropics, c lacking public health attention, d having poor research funding and shortcomings in R&D, e usually associated with high morbidity but low mortality, and f often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.

  3. Neglected tropical diseases outside the tropics.

    Directory of Open Access Journals (Sweden)

    Francesca F Norman

    Full Text Available BACKGROUND: The neglected tropical diseases (NTDs cause significant morbidity and mortality worldwide. Due to the growth in international travel and immigration, NTDs may be diagnosed in countries of the western world, but there has been no specific focus in the literature on imported NTDs. METHODS: Retrospective study of a cohort of immigrants and travelers diagnosed with one of the 13 core NTDs at a Tropical Medicine Referral Unit in Spain during the period April 1989-December 2007. Area of origin or travel was recorded and analyzed. RESULTS: There were 6168 patients (2634 immigrants, 3277 travelers and 257 VFR travelers in the cohort. NTDs occurred more frequently in immigrants, followed by VFR travelers and then by other travelers (p<0.001 for trend. The main NTDs diagnosed in immigrants were onchocerciasis (n = 240, 9.1% acquired mainly in sub-Saharan Africa, Chagas disease (n = 95, 3.6% in immigrants from South America, and ascariasis (n = 86, 3.3% found mainly in immigrants from sub-Saharan Africa. Most frequent NTDs in travelers were: schistosomiasis (n = 43, 1.3%, onchocerciasis (n = 17, 0.5% and ascariasis (n = 16, 0.5%, and all were mainly acquired in sub-Saharan Africa. The main NTDs diagnosed in VFR travelers were onchocerciasis (n = 14, 5.4%, and schistosomiasis (n = 2, 0.8%. CONCLUSIONS: The concept of imported NTDs is emerging as these infections acquire a more public profile. Specific issues such as the possibility of non-vectorial transmission outside endemic areas and how some eradication programmes in endemic countries may have an impact even in non-tropical western countries are addressed. Recognising NTDs even outside tropical settings would allow specific prevention and control measures to be implemented and may create unique opportunities for research in future.

  4. Neglected diseases amid wealth in the United States and Europe.

    Science.gov (United States)

    Hotez, Peter

    2009-01-01

    Neglected tropical diseases are not exclusive to low-income countries. In the United States, such infections account for a sizable but largely hidden disease burden among minority populations living in poverty and among people of African descent in particular. Similar infections also occur in Europe. As efforts to control neglected tropical diseases expand throughout Africa, parallel efforts should also target poor and forgotten people in wealthy nations.

  5. First Universities Allied for Essential Medicines (UAEM) Neglected Diseases and Innovation Symposium.

    Science.gov (United States)

    Musselwhite, Laura W; Maciag, Karolina; Lankowski, Alex; Gretes, Michael C; Wellems, Thomas E; Tavera, Gloria; Goulding, Rebecca E; Guillen, Ethan

    2012-01-01

    Universities Allied for Essential Medicines organized its first Neglected Diseases and Innovation Symposium to address expanding roles of public sector research institutions in innovation in research and development of biomedical technologies for treatment of diseases, particularly neglected tropical diseases. Universities and other public research institutions are increasingly integrated into the pharmaceutical innovation system. Academic entities now routinely undertake robust high-throughput screening and medicinal chemistry research programs to identify lead compounds for small molecule drugs and novel drug targets. Furthermore, product development partnerships are emerging between academic institutions, non-profit entities, and biotechnology and pharmaceutical companies to create diagnostics, therapies, and vaccines for diseases of the poor. With not for profit mission statements, open access publishing standards, open source platforms for data sharing and collaboration, and a shift in focus to more translational research, universities and other public research institutions are well-placed to accelerate development of medical technologies, particularly for neglected tropical diseases.

  6. Eliminating the Neglected Tropical Diseases: Translational Science and New Technologies.

    Directory of Open Access Journals (Sweden)

    Peter J Hotez

    2016-03-01

    Full Text Available Today, the World Health Organization recognizes 17 major parasitic and related infections as the neglected tropical diseases (NTDs. Despite recent gains in the understanding of the nature and prevalence of NTDs, as well as successes in recent scaled-up preventive chemotherapy strategies and other health interventions, the NTDs continue to rank among the world's greatest global health problems. For virtually all of the NTDs (including those slated for elimination under the auspices of a 2012 London Declaration for NTDs and a 2013 World Health Assembly resolution [WHA 66.12], additional control mechanisms and tools are needed, including new NTD drugs, vaccines, diagnostics, and vector control agents and strategies. Elimination will not be possible without these new tools. Here we summarize some of the key challenges in translational science to develop and introduce these new technologies in order to ensure success in global NTD elimination efforts.

  7. Drug Use, the Drug Environment, and Child Physical Abuse and Neglect.

    Science.gov (United States)

    Freisthler, Bridget; Wolf, Jennifer Price; Wiegmann, Wendy; Kepple, Nancy J

    2017-08-01

    Although drug use is considered a risk factor for child maltreatment, very little work has examined how the drug environment may affect physical abuse and neglect by parents. Utilizing information from a telephone survey with 2,597 respondents from 43 cities with valid police data on narcotics incidents, we analyzed the relationship between drug use, drug availability, and child maltreatment using multilevel models. City-level rates of drug abuse and dependence were related to more frequent physical abuse. Parents who use drugs in areas with greater availability of drugs reported more physical abuse and physical neglect. Emotional support was protective of all types of maltreatment. While most child welfare interventions focus on reducing parental drug use in order to reduce child abuse, these findings suggest environmental prevention or neighborhood strengthening approaches designed to reduce the supply of illicit drugs may also reduce child abuse through multiple mechanisms.

  8. New vaccines for neglected parasitic diseases and dengue.

    Science.gov (United States)

    Beaumier, Coreen M; Gillespie, Portia M; Hotez, Peter J; Bottazzi, Maria Elena

    2013-09-01

    Neglected tropical diseases (NTDs) are a significant source of morbidity and socioeconomic burden among the world's poor. Virtually all of the 2.4 billion people who live on less than $2 per d, more than a third of the world's population, are at risk for these debilitating NTDs. Although chemotherapeutic measures exist for many of these pathogens, they are not sustainable countermeasures on their own because of rates of reinfection, risk of drug resistance, and inconsistent maintenance of drug treatment programs. Preventative and therapeutic NTD vaccines are needed as long-term solutions. Because there is no market in the for-profit sector of vaccine development for these pathogens, much of the effort to develop vaccines is driven by nonprofit entities, mostly through product development partnerships. This review describes the progress of vaccines under development for many of the NTDs, with a specific focus on those about to enter or that are currently in human clinical trials. Specifically, we report on the progress on dengue, hookworm, leishmaniasis, schistosomiasis, Chagas disease, and onchocerciasis vaccines. These products will be some of the first with specific objectives to aid the world's poorest populations. Copyright © 2013 Mosby, Inc. All rights reserved.

  9. Brazil's neglected tropical diseases: an overview and a report card.

    Science.gov (United States)

    Hotez, Peter J; Fujiwara, Ricardo T

    2014-08-01

    Today, the nation of Brazil leads the Western Hemisphere in terms of the number of its citizens living with neglected tropical diseases (NTDs). These diseases continue to trap Brazil's "bottom 20 million" in extreme poverty. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  10. Novelties on amoebiasis: A neglected tropical disease

    Directory of Open Access Journals (Sweden)

    Cecilia Ximénez

    2011-01-01

    Full Text Available In accordance with the 1997 documents of the World Health Organization (WHO, amoebiasis is defined as the infection by the protozoan parasite Entamoeba histolytica with or without clinical manifestations. The only known natural host of E. histolytica is the human with the large intestine as major target organ. This parasite has a very simple life cycle in which the infective form is the cyst, considered a resistant form of parasite: The asymptomatic cyst passers and the intestinal amoebiasis patients are the transmitters; they excrete cysts in their feces, which can contaminate food and water sources. E. histolytica sensu stricto is the potentially pathogenic species and E. dispar is a commensal non-pathogenic Entamoeba. Both species are biochemical, immunological and genetically distinct. The knowledge of both species with different pathogenic phenotypes comes from a large scientific debate during the second half of the 20 th century, which gave place to the rapid development of diagnostics technology based on molecular and immunological strategies. During the last ten years, knowledge of the new epidemiology of amoebiasis in different geographic endemic and non-endemic areas has been obtained by applying mostly molecular techniques. In the present work we highlight novelties on human infection and the disease that can help the general physician from both endemic and non-endemic countries in their medical practice, particularly, now that emigration is undoubtedly a global phenomenon that is modifying the previous geography of infectious diseases worldwide.

  11. Addressing the social determinants of neglected tropical diseases to ...

    African Journals Online (AJOL)

    ... work brings to focus the determinants, which have been found to be particularly important for the perpetuation of Neglected Tropical Diseases (NTDs) in endemic communities: water and sanitation, housing and clustering, environment, migration, disasters and conflicts, socio-cultural factors and gender, and finally poverty.

  12. Short Communication: Be careful for neglected diseases | He ...

    African Journals Online (AJOL)

    Neglected diseases boost (Nature, 457: 772, 2009), which will become greater threat to human health especially in tropical regions. In my opinion, it is the inherent result of climate warming. An allometrical scaling is suggested to support my opinion, this can also explain why swine flu does not affect pigs very much, but ...

  13. Socioeconomic Inequalities in Neglected Tropical Diseases: a Systematic Review

    NARCIS (Netherlands)

    A.J. Houweling (Tanja); H.E. Karim-Kos (Henrike); M.C. Kulik (Margarete); W.A. Stolk (Wilma); J.A. Haagsma (Juanita); E.J. Lenk (Edeltraud J.); J.H. Richardus (Jan Hendrik); S.J. de Vlas (Sake)

    2016-01-01

    markdownabstract__Background:__ Neglected tropical diseases (NTDs) are generally assumed to be concentrated in poor populations, but evidence on this remains scattered. We describe within-country socioeconomic inequalities in nine NTDs listed in the London Declaration for intensified control and/or

  14. The rise of neglected tropical diseases in the "new Texas"

    Science.gov (United States)

    2018-01-01

    Within the last five years, the State of Texas has experienced either transmission or outbreaks of Ebola, chikungunya, West Nile, and Zika virus infections. Autochthonous transmission of neglected parasitic and bacterial diseases has also become increasingly reported. The rise of such emerging and neglected tropical diseases (NTDs) has not occurred by accident but instead reflects rapidly evolving changes and shifts in a “new” Texas beset by modern and globalizing forces that include rapid expansions in population together with urbanization and human migrations, altered transportation patterns, climate change, steeply declining vaccination rates, and a new paradigm of poverty known as “blue marble health.” Summarized here are the major NTDs now affecting Texas. In addition to the vector-borne viral diseases highlighted above, there also is a high level of parasitic infections, including Chagas disease, trichomoniasis, and possibly leishmaniasis and toxocariasis, as well as typhus-group rickettsiosis, a vector-borne bacterial infection. I also highlight some of the key shifts in emerging and neglected disease patterns, partly due to an altered and evolving economic and ecological landscape in the new Texas, and provide some preliminary disease burden estimates for the major prevalent and incident NTDs. PMID:29346369

  15. The rise of neglected tropical diseases in the "new Texas".

    Directory of Open Access Journals (Sweden)

    Peter J Hotez

    2018-01-01

    Full Text Available Within the last five years, the State of Texas has experienced either transmission or outbreaks of Ebola, chikungunya, West Nile, and Zika virus infections. Autochthonous transmission of neglected parasitic and bacterial diseases has also become increasingly reported. The rise of such emerging and neglected tropical diseases (NTDs has not occurred by accident but instead reflects rapidly evolving changes and shifts in a "new" Texas beset by modern and globalizing forces that include rapid expansions in population together with urbanization and human migrations, altered transportation patterns, climate change, steeply declining vaccination rates, and a new paradigm of poverty known as "blue marble health." Summarized here are the major NTDs now affecting Texas. In addition to the vector-borne viral diseases highlighted above, there also is a high level of parasitic infections, including Chagas disease, trichomoniasis, and possibly leishmaniasis and toxocariasis, as well as typhus-group rickettsiosis, a vector-borne bacterial infection. I also highlight some of the key shifts in emerging and neglected disease patterns, partly due to an altered and evolving economic and ecological landscape in the new Texas, and provide some preliminary disease burden estimates for the major prevalent and incident NTDs.

  16. Increasing European Support for Neglected Infectious Disease Research

    Directory of Open Access Journals (Sweden)

    Ole F. Olesen

    Full Text Available Neglected infectious diseases (NIDs are a persistent cause of death and disability in low-income countries. Currently available drugs and vaccines are often ineffective, costly or associated with severe side-effects. Although the scale of research on NIDs does not reflect their disease burden, there are encouraging signs that NIDs have begun to attract more political and public attention, which have translated into greater awareness and increased investments in NID research by both public and private donors. Using publicly available data, we analysed funding for NID research in the European Union's (EU's 7th Framework Programme for Research and Technological Development (FP7, which ran from 2007 to 2013. During FP7, the EU provided €169 million for 65 NID research projects, and thereby placed itself among the top global funders of NID research. Average annual FP7 investment in NID research exceeded €24 million, triple that committed by the EU before the launch of FP7. FP7 NID projects involved research teams from 331 different institutions in 72 countries on six continents, underlining the increasingly global nature of European research activities. NID research has remained a priority in the current EU Framework Programme for research and innovation, Horizon 2020, launched in 2014. This has most notably been reflected in the second programme of the European & Developing Countries Clinical Trials Partnership (EDCTP, which provides unprecedented opportunities to advance the clinical development of new medical interventions against NIDs. Europe is thus better positioned than ever before to play a major role in the global fight against NIDs.

  17. Emerging and Neglected Infectious Diseases: Insights, Advances, and Challenges.

    Science.gov (United States)

    Nii-Trebi, Nicholas Israel

    2017-01-01

    Infectious diseases are a significant burden on public health and economic stability of societies all over the world. They have for centuries been among the leading causes of death and disability and presented growing challenges to health security and human progress. The threat posed by infectious diseases is further deepened by the continued emergence of new, unrecognized, and old infectious disease epidemics of global impact. Over the past three and half decades at least 30 new infectious agents affecting humans have emerged, most of which are zoonotic and their origins have been shown to correlate significantly with socioeconomic, environmental, and ecological factors. As these factors continue to increase, putting people in increased contact with the disease causing pathogens, there is concern that infectious diseases may continue to present a formidable challenge. Constant awareness and pursuance of effective strategies for controlling infectious diseases and disease emergence thus remain crucial. This review presents current updates on emerging and neglected infectious diseases and highlights the scope, dynamics, and advances in infectious disease management with particular focus on WHO top priority emerging infectious diseases (EIDs) and neglected tropical infectious diseases.

  18. Control of neglected tropical diseases needs a long-term commitment

    Directory of Open Access Journals (Sweden)

    Mubila Likezo

    2010-10-01

    Full Text Available Abstract Background Neglected tropical diseases are widespread, particularly in sub-Saharan Africa, affecting over 2 billion individuals. Control of these diseases has gathered pace in recent years, with increased levels of funding from a number of governmental or non-governmental donors. Focus has currently been on five major 'tool-ready' neglected tropical diseases (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis and trachoma, using a package of integrated drug delivery according to the World Health Organization guidelines for preventive chemotherapy. Discussion Success in controlling these neglected tropical diseases has been achieved in a number of countries in recent history. Experience from these successes suggests that long-term sustainable control of these diseases requires: (1 a long-term commitment from a wider range of donors and from governments of endemic countries; (2 close partnerships of donors, World Health Organization, pharmaceutical industries, governments of endemic countries, communities, and non-governmental developmental organisations; (3 concerted action from more donor countries to provide the necessary funds, and from the endemic countries to work together to prevent cross-border disease transmission; (4 comprehensive control measures for certain diseases; and (5 strengthened primary healthcare systems as platforms for the national control programmes and capacity building through implementation of the programmes. Conclusions The current level of funding for the control of neglected tropical diseases has never been seen before, but it is still not enough to scale up to the 2 billion people in all endemic countries. While more donors are sought, the stakeholders must work in a coordinated and harmonised way to identify the priority areas and the best delivery approaches to use the current funds to the maximum effect. Case management and other necessary control measures should be

  19. Update on Neglected Tropical Diseases of the Western Hemisphere

    Directory of Open Access Journals (Sweden)

    Esther Fischer

    2011-01-01

    Full Text Available Neglected Tropical Diseases (NTDs are responsible for millions of deaths and disabilities yearly, around the globe. The largest burden of these diseases falls on communities with poor access to basic sanitation, healthcare facilities, and educational programs. This review focuses on advances in vaccination, treatment and control programs over the past decade for the major NTDs of the Western Hemisphere: malaria, schistosomiasis, leishmaniasis, ankylostomiasis, lymphatic filiariasis, Chagas disease (American trypanosomiasis, and onchocerciasis. The discussion centers on challenges for NTD eradication and prospects for the future.

  20. Venezuela and its rising vector-borne neglected diseases

    OpenAIRE

    Hotez, Peter J.; Bas??ez, Mar?a-Gloria; Acosta-Serrano, Alvaro; Grillet, Maria Eugenia

    2017-01-01

    Poverty remains the overriding social determinant for the neglected tropical diseases (NTDs), but over the last several decades, we have also seen how political destabilization or even outright conflict can hasten economic declines and promote a substantial uptick in NTD incidence and prevalence [1]. Recent examples include the emergence of Ebola virus infection in West Africa [2], visceral leishmaniasis and other NTDs in East Africa [3, 4], and cutaneous leishmaniasis in the Middle East and ...

  1. Poverty-related and neglected diseases - an economic and epidemiological analysis of poverty relatedness and neglect in research and development.

    Science.gov (United States)

    von Philipsborn, Peter; Steinbeis, Fridolin; Bender, Max E; Regmi, Sadie; Tinnemann, Peter

    2015-01-01

    Economic growth in low- and middle-income countries (LMIC) has raised interest in how disease burden patterns are related to economic development. Meanwhile, poverty-related diseases are considered to be neglected in terms of research and development (R&D). Developing intuitive and meaningful metrics to measure how different diseases are related to poverty and neglected in the current R&D system. We measured how diseases are related to economic development with the income relation factor (IRF), defined by the ratio of disability-adjusted life-years (DALYs) per 100,000 inhabitants in LMIC versus that in high-income countries. We calculated the IRF for 291 diseases and injuries and 67 risk factors included in the Global Burden of Disease Study 2010. We measured neglect in R&D with the neglect factor (NF), defined by the ratio of disease burden in DALYs (as percentage of the total global disease burden) and R&D expenditure (as percentage of total global health-related R&D expenditure) for 26 diseases. The disease burden varies considerably with the level of economic development, shown by the IRF (median: 1.38; interquartile range (IQR): 0.79-6.3). Comparison of IRFs from 1990 to 2010 highlights general patterns of the global epidemiological transition. The 26 poverty-related diseases included in our analysis of neglect in R&D are responsible for 13.8% of the global disease burden, but receive only 1.34% of global health-related R&D expenditure. Within this group, the NF varies considerably (median: 19; IQR: 6-52). The IRF is an intuitive and meaningful metric to highlight shifts in global disease burden patterns. A large shortfall exists in global R&D spending for poverty-related and neglected diseases, with strong variations between diseases.

  2. Introduction of European priority review vouchers to encourage development of new medicines for neglected diseases.

    Science.gov (United States)

    Ridley, David B; Sánchez, Alfonso Calles

    2010-09-11

    Every year 1 billion people worldwide are affected by traditionally neglected diseases, such as malaria, tuberculosis, leishmaniasis, and lymphatic filariasis, which impose tremendous public health burdens. Governments, foundations, and drug manufacturers have, however, started to support development of new treatments. European Union Member States have been leaders in implementing so-called push mechanisms (payment for drug development) and pull funding (reward for output), such as the advance market commitment, which creates a market for vaccines by guaranteeing prices. We propose an additional step that could be taken to encourage development of medicines for neglected diseases. A priority review voucher scheme, as is already in place in the USA, would reward a manufacturer that developed a new medicine for neglected diseases with a voucher that could be redeemed for priority review of a future medicine, probably a potential blockbuster drug. Unlike the US system a European voucher would also accelerate pricing and reimbursement decisions. This scheme would be likely to provide substantial benefits to voucher holders, society, and public health organisations. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. PLOS Neglected Tropical Diseases: Ten years of progress in neglected tropical disease control and elimination … More or less.

    Directory of Open Access Journals (Sweden)

    Peter Hotez

    2017-04-01

    Full Text Available This year PLOS Neglected Tropical Diseases (PLOS NTDs celebrates its tenth anniversary following the publication of the first issue in 2007 [1]. When PLOS NTDs was founded, the framework of the neglected tropical diseases (NTDs as an alternative to "other diseases" (as they were then referred to in the Millennium Development Goals was just getting started-especially for Africa [2, 3]. In the decade since, PLOS NTDs has overseen enormous successes in NTD control and elimination. Here, we want to briefly review the ten year progress made towards the control or elimination of the diseases now identified by the WHO as NTDs. Many of the details are highlighted in PLOS NTDs papers cited here, but the summary information is based on the recently released Global Burden of Disease (GBD Study 2015 (also launched with Gates Foundation support that summarized past-decade changes in disease prevalence, mortality, or disability rates (from the years 2005 to 2015 [4-6], as well as the GBD Study 2013 that summarizes disease prevalence changes over a longer time horizon from 1990 to 2013 [7].

  4. Leprosy-related mortality in Brazil: a neglected condition of a neglected disease.

    Science.gov (United States)

    Martins-Melo, Francisco Rogerlândio; Assunção-Ramos, Adriana Valéria; Ramos, Alberto Novaes; Alencar, Carlos Henrique; Montenegro, Renan Magalhães; Wand-Del-Rey de Oliveira, Maria Leide; Heukelbach, Jorg

    2015-10-01

    Leprosy is a public health problem and a neglected condition of morbidity and mortality in several countries of the world. We analysed time trends and spatiotemporal patterns of leprosy-related mortality in Brazil. We performed a nationwide population-based study using secondary mortality data. We included all deaths that occurred in Brazil between 2000 and 2011, in which leprosy was mentioned in any field of death certificates. Leprosy was identified in 7732/12 491 280 deaths (0.1%). Average annual age-adjusted mortality rate was 0.43 deaths/100 000 inhabitants (95% CI 0.40-0.46). The burden of leprosy deaths was higher among males, elderly, black race/colour and in leprosy-endemic regions. Lepromatous leprosy was the most common clinical form mentioned. Mortality rates showed a significant nationwide decrease over the period (annual percent change [APC]: -2.8%; 95% CI -4.2 to -2.4). We observed decreasing mortality rates in the South, Southeast and Central-West regions, while the rates remained stable in North and Northeast regions. Spatial and spatiotemporal high-risk clusters for leprosy-related deaths were distributed mainly in highly endemic and socio-economically deprived regions. Leprosy is a neglected cause of death in Brazil since the disease is preventable, and a cost-effective treatment is available. Sustainable control measures should include appropriate management and systematic monitoring of leprosy-related complications, such as severe leprosy reactions and adverse effects to multidrug therapy. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Scrub Typhus: An Emerging Neglected Tropical Disease in Nepal.

    Science.gov (United States)

    Upadhyaya, B P; Shakya, G; Adhikari, S; Rijal, N; Acharya, J; Maharjan, L; Marasini, B R

    2016-05-01

    Scrub typhus is a neglected tropical disease and is under reported from Nepal. The objective of this study was to investigate the sero-epidemiology of scrub typhus in patients suffering from acute febrile illness. A total of 434 specimens collected from July to November 2015 at National Public Health Laboratory (NPHL) were investigated for detection of immunoglobulin M (IgM) antibody to Orientiatsutsugamushi.The Scrub Typhus Detect TM kit (InBios, USA) was used to detect the antibodies to O.tsutsugamushi in human serum. Randomly selected 10% positive specimens were used for confirmation by dot- enzyme-linked immunosorbent assay and indirect immunofluorescence assay. Of the total, 175 (40.3%) were positive for IgM antibodies to O. tsutsugamushi. Positive results of scrub typhus were highest among female in 11-20 year followed by males in 41-50 years age group. The IgM antibodies to O. tsutusugamushi were positive in specimens of various geographical regions including 30 districts of Nepal. Positive cases were found in various ecological regions of Nepal. Scrub typhus is one of the neglected tropical diseases in Nepal. Patients with acute febrile illness should be investigated for scrub typhus with high priority. There is an urgent need of reliable and affordable diagnostic tests at all level of health facilities of Nepal. Surveillance and public health awareness about the disease transmission and preventive measures needs to be initiated.

  6. Ebola outbreak in West Africa: a neglected tropical disease

    Directory of Open Access Journals (Sweden)

    Alcides Troncoso

    2015-04-01

    Full Text Available Neglected tropical diseases (NTDs are remediable injustices of our times. Poverty is the starting point, and the ultimate outcome, of NTD. Ebola is just one of many NTDs that badly need attention. Ebola exacerbates West Africa's poverty crisis. The virus spreading in Guinea, Liberia and Sierra Leone has led to food shortages and neglect of other devastating tropical illnesses. A health crisis that was ignored for months until it was out of control is now beginning to get the attention required, if not the resources. So far, the world´s nations have contributed far less than the $ 1 billion. The U.N. estimates would need to control the epidemic before it becomes endemic. Past outbreaks of Ebola have flared up in remote, forested communities, disconnected from much of the outside world. But the outbreak in West Africa has not slowed yet, and it worsens there the chances of it spreading to other countries. Ebola draws attention to NTD. Ebola is not only a health emergency, but also it´s a poverty crisis. The current Global Ebola crisis presents a multitude of challenges in terms of our capacity to respond; the future is even less predictable. Ebola outbreak represents inequity in health as the occurrence of health differences considered unnecessary, avoidable, unfair, and unjust, thus adding a moral and ethical dimension to health inequalities. Health equity does not refer only to the fairness in the distribution of health or the provision of health care; rather, it is linked with the larger issues of fairness and justice in social arrangements.

  7. First Universities Allied for Essential Medicines (UAEM) Neglected Diseases and Innovation Symposium

    OpenAIRE

    Musselwhite, Laura W.; Maciag, Karolina; Lankowski, Alex; Gretes, Michael C.; Wellems, Thomas E.; Tavera, Gloria; Goulding, Rebecca E.; Guillen, Ethan

    2012-01-01

    Universities Allied for Essential Medicines organized its first Neglected Diseases and Innovation Symposium to address expanding roles of public sector research institutions in innovation in research and development of biomedical technologies for treatment of diseases, particularly neglected tropical diseases. Universities and other public research institutions are increasingly integrated into the pharmaceutical innovation system. Academic entities now routinely undertake robust high-throughp...

  8. Social stigma towards neglected tropical diseases: a systematic review.

    Science.gov (United States)

    Hofstraat, Karlijn; van Brakel, Wim H

    2016-03-01

    People affected by neglected tropical diseases (NTDs) are frequently the target of social stigmatization. To date not much attention has been given to stigma in relation to NTDs. The objective of this review is to identify the extent of social stigma and the similarities and differences in the causes, manifestations, impact of stigma and interventions used between the NTDs. A systematic review was conducted in Pubmed, ScienceDirect, PsycINFO and Web of Knowledge. The search encompassed 17 NTDs, including podoconiosis, but not leprosy as this NTD has recently been reviewed. However, leprosy was included in the discussion. The 52 selected articles provided evidence on stigma related to lymphatic filariasis (LF), podoconiosis, Buruli ulcer, onchocerciasis, schistosomiasis, leishmaniasis, Chagas disease, trachoma, soil-transmitted helminthiasis (STH) and human African trypanosomiasis. The similarities predominated in stigma related to the various NTDs; only minimal differences in stigma reasons and measures were found. These similarities suggest that joint approaches to reduce stigmatization may be feasible. Lessons from leprosy and other stigmatized health conditions can be used to plan such joint approaches. Further research will be necessary to study the efficacy of joint interventions and to investigate stigma related to NTDs for which no evidence is available yet. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Drug induced lung disease

    International Nuclear Information System (INIS)

    Schaefer-Prokop, Cornelia; Eisenhuber, Edith

    2010-01-01

    There is an ever increasing number of drugs that can cause lung disease. Imaging plays an important role in the diagnosis, since the clinical symptoms are mostly nonspecific. Various HRCT patterns can be correlated - though with overlaps - to lung changes caused by certain groups of drugs. Alternative diagnosis such as infection, edema or underlying lung disease has to be excluded by clinical-radiological means. Herefore is profound knowledge of the correlations of drug effects and imaging findings essential. History of drug exposure, suitable radiological findings and response to treatment (corticosteroids and stop of medication) mostly provide the base for the diagnosis. (orig.)

  10. NEOFLAVONOIDS WITH IMPLICATIONS IN NEGLECTED DISEASES: AN TECNOLOGICA FORECASTING

    Directory of Open Access Journals (Sweden)

    George Laylson Da Silva Oliveira

    2014-09-01

    Full Text Available The present work aimed to make a technological forecasting about the neoflavonoids and its implications in treatment of neglected diseases (NDs. Thus, this research was carried out through a comprehensive and systematic bibliographic search in articles and patents. The articles were searched in the database of the Periodical of CAPES, Science Direct, Scopus, Pub Med, Web of Science and ACS Publications. The patent research was performed in bases of the INPI, EPO, WIPO, USPTO and SIPO. According to the results obtained, it was possible to observe that the neoflavonoids may be a new source of medications for the treatment of NDs, since were found studies that attributed activity for the treatment of malaria, trypanosomiasis and leishmaniasis. Large part of published documents was in the form of scientific articles and a small part in the form of deposit of record of patent applications. In this way, this work can serve as an incentive of technological innovation for the development of new research involving neoflavonoids, seen that the record number of deposits of patent applications is still relatively insufficient to meet the current demand for technological and scientific innovation with relation to NDs.

  11. A Neglected Population: Drug-Using Women and Women's Methods of HIV/STI Prevention

    Science.gov (United States)

    Gollub, Erica L.

    2008-01-01

    Women drug users are at extremely high risk of HIV and sexually transmitted infections (STIs) from sexual transmission, but remain seriously neglected in intervention research promoting women-initiated methods of HIV/STI prevention. Sparse available data indicate a high interest and enthusiasm for women-initiated methods among these women.…

  12. Toward an open-access global database for mapping, control, and surveillance of neglected tropical diseases

    DEFF Research Database (Denmark)

    Hürlimann, Eveline; Schur, Nadine; Boutsika, Konstantina

    2011-01-01

    After many years of general neglect, interest has grown and efforts came under way for the mapping, control, surveillance, and eventual elimination of neglected tropical diseases (NTDs). Disease risk estimates are a key feature to target control interventions, and serve as a benchmark...

  13. Implementing preventive chemotherapy through an integrated National Neglected Tropical Disease Control Program in Mali.

    Directory of Open Access Journals (Sweden)

    Massitan Dembélé

    Full Text Available BACKGROUND: Mali is endemic for all five targeted major neglected tropical diseases (NTDs. As one of the five 'fast-track' countries supported with the United States Agency for International Development (USAID funds, Mali started to integrate the activities of existing disease-specific national control programs on these diseases in 2007. The ultimate objectives are to eliminate lymphatic filariasis, onchocerciasis and trachoma as public health problems and to reduce morbidity caused by schistosomiasis and soil-transmitted helminthiasis through regular treatment to eligible populations, and the specific objectives were to achieve 80% program coverage and 100% geographical coverage yearly. The paper reports on the implementation of the integrated mass drug administration and the lessons learned. METHODOLOGY/PRINCIPAL FINDINGS: The integrated control program was led by the Ministry of Health and coordinated by the national NTD Control Program. The drug packages were designed according to the disease endemicity in each district and delivered through various platforms to eligible populations involving the primary health care system. Treatment data were recorded and reported by the community drug distributors. After a pilot implementation of integrated drug delivery in three regions in 2007, the treatment for all five targeted NTDs was steadily scaled up to 100% geographical coverage by 2009, and program coverage has since been maintained at a high level: over 85% for lymphatic filariasis, over 90% for onchocerciasis and soil-transmitted helminthiasis, around 90% in school-age children for schistosomiasis, and 76-97% for trachoma. Around 10 million people have received one or more drug packages each year since 2009. No severe cases of adverse effects were reported. CONCLUSIONS/SIGNIFICANCE: Mali has scaled up the drug treatment to national coverage through integrated drug delivery involving the primary health care system. The successes and lessons

  14. Neglected tropical diseases: now more than just 'other diseases'--the post-2015 agenda.

    Science.gov (United States)

    Molyneux, David H

    2014-09-01

    Neglected tropical diseases (NTDs) have become recognised as important health problems facing at least a billion people in the low-income countries and the poorest communities in middle-income countries. WHO plays a leading role in developing strategies to address these diseases, pharmaceutical companies provide drug donations to treat or control the NTDs and many partners from different constituencies have become increasingly committed to their control or elimination. This review looks to the post-2015 agenda and emphasises that despite the progress made over recent years, if the targets established are to be achieved, then not only will additional financial resources be required to up-scale treatments and increase access, but increased applied and operational research will be necessary to address problems and human capacity in NTD skills will need to be strengthened. Continuing advocacy for the relevance of control or elimination of NTDs must be placed in the context of universal health coverage and access to donated essential medicines for the poor as a right. The evidence that investment in NTD interventions are cost-effective and impact not only on health, but also to enhance socio-economic development, must be refined and promulgated. The global burden of disease attributable to NTDs requires reassessment to appropriately define the true burden, while the potential for unexpected events, political, climatic, environmental as well as biological, have the potential to reduce future progress towards the agreed post-2015 targets. NTD progress towards the WHO Roadmap targets and the fulfilment of the World Health Assembly Resolution 66.12 of 2013 demand continued commitment from all partner constituencies when challenges emerge. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. [Neglected infectious diseases: an ongoing challenge for public health and equity in Peru].

    Science.gov (United States)

    Cabezas-Sánchez, César

    2014-04-01

    Neglected Infectious Diseases (NID) affect more than one billion people worldwide, and are associated with poverty, geographic isolation of populations, social stigma, lack of precise data on estimates on both the global and local burden of disease (underreporting of the diseases), inadequate financial and political resources to effective control measures, lack of lobbying on behalf of the most vulnerable population, as well as scarce drug and diagnostic methods development. In this article we describe the relationship between NID, poverty and inequality, we propose a new concept of disease in the tropics, expanding the list of diseases that share characteristics with NID in the Peruvian context, discuss the limited availability of drugs and diagnostic tests to properly deal with these diseases, as well as highlight the contributions by the Peruvian National Institute of Health, and as final thoughts, we state that the solution for the prevention and control of NID must include an integrated approach, including the social determinants of health in the context of the fight against poverty and inequality.

  16. The role of nutrition in integrated programs to control neglected tropical diseases

    Directory of Open Access Journals (Sweden)

    Hall Andrew

    2012-04-01

    Full Text Available Abstract There are strong and direct relationships between undernutrition and the disease caused by infectious organisms, including the diverse pathogens labeled as neglected tropical diseases (NTDs. Undernutrition increases the risk of infection, the severity of disease and the risk that children will die, while the physical damage, loss of appetite, and host responses during chronic infection can contribute substantially to undernutrition. These relationships are often synergistic. This opinion article examines the role of nutrition in controlling NTDs and makes the point that mass drug treatment - the major strategy currently proposed to control several diseases - is crucial to controlling disease and transmission, but is only the start of the process of physical recovery. Without adequate energy and nutrients to repair damaged tissues or recover lost growth and development, the benefits of treatment may not be evident quickly; the effects of control programs may be not appreciated by beneficiaries; while vulnerability to reinfection and disease may not be reduced. There is substantial potential for nutritional interventions to be added to large-scale programs to deliver drug treatments and thereby contribute, within a broad strategy of public health interventions and behavior change activities, to controlling and preventing NTDs in populations, and to restoring their health.

  17. Illegal Drugs and Heart Disease

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Illegal Drugs and Heart Disease Updated:May 3,2018 Most illegal drugs can ... www.dea.gov/druginfo/factsheets.shtml Alcohol and Heart Disease Caffeine and Heart Disease Tobacco and Heart Disease ...

  18. Illicit drug exposure in patients evaluated for alleged child abuse and neglect.

    Science.gov (United States)

    Oral, Resmiye; Bayman, Levent; Assad, Abraham; Wibbenmeyer, Lucy; Buhrow, Jakob; Austin, Andrea; Bayman, Emine O

    2011-06-01

    Substantiation of drug exposure in cases with alleged maltreatment is important to provide proper treatment and services to these children and their families. A study performed at University of Iowa Hospitals and Clinics showed that 30% of pediatric patients with burn injuries, which were due to child maltreatment, were also exposed to illicit drugs. The children presenting to the University of Iowa Hospitals and Clinics with alleged maltreatment have been tested for illicit substances since 2004. The objective of this study was to analyze the presence of illicit drug exposure in the pediatric subpopulation admitted to pediatric inpatient and outpatient units for an evaluation for abuse/neglect. The study design is a retrospective chart review. Using hospital databases, every pediatric chart with a child abuse/neglect allegation was retrieved. The association between risk factors and clinical presentation and illicit drug test result was assessed. Excel and SAS were used for statistical analysis. Institutional review board approval was obtained to conduct this study. Six hundred sixty-five charts met study inclusion criteria for child abuse/neglect allegation. Of those, 232 cases were tested for illicit drugs between 2004 and 2008 per the testing protocol. Thirty-four cases (14.7%) tested positive on a drug test. Positive test rates based on clinical presentation were 28.6% (18/63) in neglect cases, 16.1% (5/31) in cases with soft tissue injuries, 14.3% (4/28) in burn injuries, 10.0% (2/20) in cases with sexual abuse, 7.1% (2/28) in cases with fractures, and 4.8% (3/62) in abusive head trauma cases. There were long-term abuse findings in 129 children (55.6%). Logistic regression analysis revealed that positive drug testing was most significantly associated with clinical symptoms suggesting physical abuse or neglect versus sexual abuse (odds ratio [OR] = 6.70; 95% confidence interval [CI], 1.26-35.49; P = 0.026), no or public health insurance versus those with

  19. A controlled evaluation of family behavior therapy in concurrent child neglect and drug abuse.

    Science.gov (United States)

    Donohue, Brad; Azrin, Nathan H; Bradshaw, Kelsey; Van Hasselt, Vincent B; Cross, Chad L; Urgelles, Jessica; Romero, Valerie; Hill, Heather H; Allen, Daniel N

    2014-08-01

    Approximately 50% of child protective service (CPS) referrals abuse drugs; yet, existing treatment studies in this population have been limited to case examinations. Therefore, a family-based behavioral therapy was evaluated in mothers referred from CPS for child neglect and drug abuse utilizing a controlled experimental design. Seventy-two mothers evidencing drug abuse or dependence and child neglect were randomly assigned to family behavior therapy (FBT) or treatment as usual (TAU). Participants were assessed at baseline, 6 months, and 10 months postrandomization. As hypothesized, intent-to-treat repeated measures analyses revealed mothers referred for child neglect not due to their children being exposed to illicit drugs demonstrated better outcomes in child maltreatment potential from baseline to 6- and 10-month postrandomization assessments when assigned to FBT, as compared with TAU mothers and FBT mothers who were referred due to child drug exposure. Similar results occurred for hard drug use from baseline to 6 and 10 months postrandomization. However, TAU mothers referred due to child drug exposure were also found to decrease their hard drug use more than TAU mothers of non-drug-exposed children and FBT mothers of drug-exposed children at 6 and 10 months postrandomization. Although effect sizes for mothers assigned to FBT were slightly larger for marijuana use than TAU (medium vs. large), these differences were not statistically significant. Specific to secondary outcomes, mothers in FBT, relative to TAU, increased time employed from baseline to 6 and 10 months postrandomization. Mothers in FBT, compared to TAU, also decreased HIV risk from baseline to 6 months postrandomization. There were no differences in outcome between FBT and TAU for number of days children were in CPS custody and alcohol intoxication, although FBT mothers demonstrated marginal decreases (p = .058) in incarceration from baseline to 6 months postrandomization relative to TAU mothers

  20. Exploring innovative ways to conduct coverage surveys for neglected tropical diseases in Malawi, Mali, and Uganda.

    Science.gov (United States)

    Woodhall, Dana M; Mkwanda, Square; Dembele, Massitan; Lwanga, Harriet; Drexler, Naomi; Dubray, Christine; Harris, Jennifer; Worrell, Caitlin; Mathieu, Els

    2014-04-01

    Currently, a 30-cluster survey to monitor drug coverage after mass drug administration for neglected tropical diseases is the most common methodology used by control programs. We investigated alternative survey methodologies that could potentially provide an estimation of drug coverage. Three alternative survey methods (market, village chief, and religious leader) were conducted and compared to the 30-cluster method in Malawi, Mali, and Uganda. In Malawi, drug coverage for the 30-cluster, market, village chief, and religious leader methods were 66.8% (95% CI 60.3-73.4), 74.3%, 76.3%, and 77.8%, respectively. In Mali, results for round 1 were 62.6% (95% CI 54.4-70.7), 56.1%, 74.8%, and 83.2%, and 57.2% (95% CI 49.0-65.4), 54.5%, 72.2%, and 73.3%, respectively, for round 2. Uganda survey results were 65.7% (59.4-72.0), 43.7%, 67.2%, and 77.6% respectively. Further research is needed to test different coverage survey methodologies to determine which survey methods are the most scientifically rigorous and resource efficient. Published by Elsevier B.V.

  1. Sexual and reproductive issues and inflammatory bowel disease: a neglected topic in men.

    Science.gov (United States)

    Allocca, Mariangela; Gilardi, Daniela; Fiorino, Gionata; Furfaro, Federica; Peyrin-Biroulet, Laurent; Danese, Silvio

    2018-03-01

    There has been considerable literature on sexual issues in women with inflammatory bowel disease (IBD), but relatively little attention has been paid to these aspects in men. To review the available literature and to provide the best management of sexual and reproductive issues in male patients with IBD. The scientific literature on sexual and reproductive issues in men with IBD was reviewed. Several factors, including surgical and medication treatments, disease activity, lifestyle, and psychological factors, may play a role in the development of infertility and sexual dysfunction and may negatively impact pregnancy outcomes. Proctocolectomy with ileal pouch-anal anastomosis increases the risk of erectile and ejaculatory dysfunction by up to 26%. A treatment with sildenafil can be effective. Sperm banking should be advised to young men with IBD before surgery. Both sulfasalazine and methotrexate may be responsible for reversible sexual dysfunction and infertility. Furthermore, sulfasalazine should be switched to mesalazine at least 4 months before conception because of a higher risk of congenital malformations in pregnancies fathered by men treated with this drug. Psychotropic drugs, frequently used in IBD, may cause sexual dysfunction up to 80%. Last but not the least, voluntary childlessness occurs frequently, mainly because of concerns about medication safety in pregnancy and fear of transmitting disease. Accurate counseling, and where necessary, psychological support can decrease any misperceptions and fears. Close collaboration between the gastroenterologist and the patient is recommended for the best management of these relevant, neglected aspects in men with IBD.

  2. Elimination of neglected diseases in latin america and the Caribbean: a mapping of selected diseases.

    Directory of Open Access Journals (Sweden)

    Maria Cristina Schneider

    2011-02-01

    Full Text Available In Latin America and the Caribbean, around 195 million people live in poverty, a situation that increases the burden of some infectious diseases. Neglected diseases, in particular, are often restricted to poor, marginalized sections of the population. Tools exist to combat these diseases, making it imperative to work towards their elimination. In 2009, the Pan American Health Organization (PAHO received a mandate to support the countries in the Region in eliminating neglected diseases and other poverty-related infections. The objective of this study is to analyze the presence of selected diseases using geo-processing techniques. Five diseases with information available at the first sub-national level (states were mapped, showing the presence of the disease ("hotspots" and overlap of diseases ("major hotspots". In the 45 countries/territories (approximately 570 states of the Region, there is: lymphatic filariasis in four countries (29 states, onchocerciasis in six countries (25 states, schistosomiasis in four countries (39 states, trachoma in three countries (29 states, and human rabies transmitted by dogs in ten countries (20 states. Of the 108 states with one or more of the selected diseases, 36 states present the diseases in overlapping areas ("major hotspots". Additional information about soil-transmitted helminths was included. The analysis suggests a majority of the selected diseases are not widespread and can be considered part of an unfinished agenda with elimination as a goal. Integrated plans and a comprehensive approach, ensuring access to existing diagnostic and treatment methods, and establishing a multi-sectoral agenda that addresses social determinants, including access to adequate water and sanitation, are required. Future studies can include additional diseases, socio-economic and environmental variables.

  3. Elimination of neglected diseases in latin america and the Caribbean: a mapping of selected diseases.

    Science.gov (United States)

    Schneider, Maria Cristina; Aguilera, Ximena Paz; Barbosa da Silva Junior, Jarbas; Ault, Steven Kenyon; Najera, Patricia; Martinez, Julio; Requejo, Raquel; Nicholls, Ruben Santiago; Yadon, Zaida; Silva, Juan Carlos; Leanes, Luis Fernando; Periago, Mirta Roses

    2011-02-15

    In Latin America and the Caribbean, around 195 million people live in poverty, a situation that increases the burden of some infectious diseases. Neglected diseases, in particular, are often restricted to poor, marginalized sections of the population. Tools exist to combat these diseases, making it imperative to work towards their elimination. In 2009, the Pan American Health Organization (PAHO) received a mandate to support the countries in the Region in eliminating neglected diseases and other poverty-related infections. The objective of this study is to analyze the presence of selected diseases using geo-processing techniques. Five diseases with information available at the first sub-national level (states) were mapped, showing the presence of the disease ("hotspots") and overlap of diseases ("major hotspots"). In the 45 countries/territories (approximately 570 states) of the Region, there is: lymphatic filariasis in four countries (29 states), onchocerciasis in six countries (25 states), schistosomiasis in four countries (39 states), trachoma in three countries (29 states), and human rabies transmitted by dogs in ten countries (20 states). Of the 108 states with one or more of the selected diseases, 36 states present the diseases in overlapping areas ("major hotspots"). Additional information about soil-transmitted helminths was included. The analysis suggests a majority of the selected diseases are not widespread and can be considered part of an unfinished agenda with elimination as a goal. Integrated plans and a comprehensive approach, ensuring access to existing diagnostic and treatment methods, and establishing a multi-sectoral agenda that addresses social determinants, including access to adequate water and sanitation, are required. Future studies can include additional diseases, socio-economic and environmental variables.

  4. Social sciences research in neglected tropical diseases 3: Investment in social science research in neglected diseases of poverty: a case study of Bill and Melinda Gates Foundation.

    Science.gov (United States)

    Pokhrel, Subhash; Reidpath, Daniel; Allotey, Pascale

    2011-01-06

    The level of funding provides a good proxy for the level of commitment or prioritisation given to a particular issue. While the need for research relevant to social, economic, cultural and behavioural aspects of neglected tropical diseases (NTD) control has been acknowledged, there is limited data on the level of funding that supports NTD social science research. A case study was carried out in which the spending of a major independent funder, the Bill and Melinda Gates Foundation (BMGF) - was analysed. A total of 67 projects funded between October 1998 and November 2008 were identified from the BMGF database. With the help of keywords within the titles of 67 grantees, they were categorised as social science or non-social science research based on available definition of social science. A descriptive analysis was conducted. Of 67 projects analysed, 26 projects (39%) were social science related while 41 projects (61%) were basic science or other translational research including drug development. A total of US$ 697 million was spent to fund the projects, of which 35% ((US$ 241 million) went to social science research. Although the level of funding for social science research has generally been lower than that for non-social science research over 10 year period, social science research attracted more funding in 2004 and 2008. The evidence presented in this case study indicates that funding on NTD social science research compared to basic and translational research is not as low as it is perceived to be. However, as there is the acute need for improved delivery and utilisation of current NTD drugs/technologies, informed by research from social science approaches, funding priorities need to reflect the need to invest significantly more in NTD social science research.

  5. Social sciences research in neglected tropical diseases 3: Investment in social science research in neglected diseases of poverty: a case study of Bill and Melinda Gates Foundation

    Directory of Open Access Journals (Sweden)

    Reidpath Daniel

    2011-01-01

    Full Text Available Abstract Background The level of funding provides a good proxy for the level of commitment or prioritisation given to a particular issue. While the need for research relevant to social, economic, cultural and behavioural aspects of neglected tropical diseases (NTD control has been acknowledged, there is limited data on the level of funding that supports NTD social science research. Method A case study was carried out in which the spending of a major independent funder, the Bill and Melinda Gates Foundation (BMGF - was analysed. A total of 67 projects funded between October 1998 and November 2008 were identified from the BMGF database. With the help of keywords within the titles of 67 grantees, they were categorised as social science or non-social science research based on available definition of social science. A descriptive analysis was conducted. Results Of 67 projects analysed, 26 projects (39% were social science related while 41 projects (61% were basic science or other translational research including drug development. A total of US$ 697 million was spent to fund the projects, of which 35% ((US$ 241 million went to social science research. Although the level of funding for social science research has generally been lower than that for non-social science research over 10 year period, social science research attracted more funding in 2004 and 2008. Conclusion The evidence presented in this case study indicates that funding on NTD social science research compared to basic and translational research is not as low as it is perceived to be. However, as there is the acute need for improved delivery and utilisation of current NTD drugs/technologies, informed by research from social science approaches, funding priorities need to reflect the need to invest significantly more in NTD social science research.

  6. Incentives for Starting Small Companies Focused on Rare and Neglected Diseases.

    Science.gov (United States)

    Ekins, Sean; Wood, Jill

    2016-04-01

    Starting biotech or pharmaceutical companies is traditionally thought to be based around a scientist, their technology platform or a clinical candidate spun out from another company. Between us we have taken a different approach and formed two small early stage companies after initially leveraging the perspective of a parent with a child with a life-threatening rare disease. Phoenix Nest ( http://www.phoenixnestbiotech.com/ ) was co-founded to work on treatments for Sanfilippo syndrome a devastating neurodegenerative lysosomal storage disorder. In the space of just over 3 years we have built up collaborations with leading scientists in academia and industry and been awarded multiple NIH small business grants. The second company, Collaborations Pharmaceuticals Inc. ( http://www.collaborationspharma.com/ ) was founded to address some of the other 7000 or so rare diseases as well as neglected infectious diseases. The Rare Pediatric Disease Priority Review Voucher is likely the most important incentive for companies working on rare diseases with very small populations. This may also be partially responsible for the recent acquisitions of rare disease companies with late stage candidates. Lessons learned in the process of starting our companies are that rare disease parents or patients can readily partner with a scientist and fund research through NIH grants rather than venture capital or angel investors initially. This process may be slow so patience and perseverance is key. We would encourage other pharmaceutical scientists to meet rare disease parents, patients or advocates and work with them to further the science on their diseases and create a source of future drugs.

  7. Podoconiosis - non-filarial geochemical elephantiasis - a neglected tropical disease?

    Science.gov (United States)

    Nenoff, Pietro; Simon, Jan Christoph; Muylowa, Grace K; Davey, Gail

    2010-01-01

    Podoconiosis or mossy foot is a form of non-filarial lymphedema. This geochemical elephantiasis is a disabling condition caused by the passage of microparticles of silica and aluminum silicates through the skin of people walking barefoot in areas with a high content of soil of volcanic origin. Podoconiosis is widespread in tropical Africa, Central America and North India, yet it remains a neglected and under-researched condition. The disabling effects of podoconiosis cause great hardship to patients. It adversely affects the economic (reduced productivity and absenteeism), social (marriage, education, etc.) and psychological (social stigma) well-being of those affected. Podoconiosis can be prevented; the main primary preventive measure is protective footwear. Secondary measures include a strict hygiene regimen and compression therapy, which can reverse initial lesions. Tertiary approaches include surgical management, such as shaving operations to reduce hyperplastic and verrucous elephantiasis.

  8. Demographic, socioeconomic and environmental changes affecting circulation of neglected tropical diseases in Egypt.

    Science.gov (United States)

    Abou-El-Naga, Iman F

    2015-11-01

    Egypt has been plagued by many neglected tropical diseases since Pharaonic time. These diseases are Schistosomiasis, soil-transmitted helminthiasis, lymphatic filariasis, leishmaniasis and fascioliasis beside the epidermal parasitic skin diseases. Indeed, theses diseases still persist as public health problem in the country by the influence of demographic, socioeconomic and environmental obstacles. This study seeks for understanding the contribution of each factor in each obstacle in neglected tropical diseases perpetuation which in turn could help the governorate in planning integrated control strategies. It was found that poverty, unregulated urbanization and inadequate sanitation are important socioeconomic factors that have great effect on the transmission dynamics of the diseases. The environmental factors which affect the epidemiology of these diseases in the country are scarcity of water, construction of dams, land reclamation for agriculture beside the climate factors. Unfortunately, the panic increase in the population growth rate minimizes the efforts done by the governorate to elevate the public health services. These conditions also affect the transmission of epidermal parasitic skin diseases including scabies, head lice and hookworm-related cutaneous larva migrans. The control programs and the recommendations to combat the diseases were discussed. The present study showed that the ecological factors affecting each neglected tropical disease in Egypt are somewhat similar which makes it worthy to develop an integrated control approaches aiming at improving the leading factors of neglected tropical diseases circulation in the country. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  9. Exploring gender dimensions of treatment programmes for neglected tropical diseases in Uganda.

    Directory of Open Access Journals (Sweden)

    Heather Rilkoff

    Full Text Available Gender remains a recognized but relatively unexamined aspect of the potential challenges for treatment programmes for Neglected Tropical Diseases (NTDs. We sought to explore the role of gender in access to treatment in the Uganda National Neglected Tropical Disease Control Programme.Quantitative and qualitative data was collected in eight villages in Buyende and Kamuli districts, Eastern Uganda. Quantitative data on the number of persons treated by age and gender was identified from treatment registers in each village. Qualitative data was collected through semi-structured interviews with sub-county supervisors, participant observation and from focus group discussions with community leaders, community medicine distributors (CMDs, men, women who were pregnant or breastfeeding at the time of mass-treatment, and adolescent males and females. Findings include the following: (i treatment registers are often incomplete making it difficult to obtain accurate estimates of the number of persons treated; (ii males face more barriers to accessing treatment than women due to occupational roles which keep them away from households or villages for long periods, and males may be more distrustful of treatment; (iii CMDs may be unaware of which medicines are safe for pregnant and breastfeeding women, resulting in women missing beneficial treatments.Findings highlight the need to improve community-level training in drug distribution which should include gender-specific issues and guidelines for treating pregnant and breastfeeding women. Accurate age and sex disaggregated measures of the number of community members who swallow the medicines are also needed to ensure proper monitoring and evaluation of treatment programmes.

  10. Poverty-related and neglected diseases – an economic and epidemiological analysis of poverty relatedness and neglect in research and development

    Science.gov (United States)

    von Philipsborn, Peter; Steinbeis, Fridolin; Bender, Max E.; Regmi, Sadie; Tinnemann, Peter

    2015-01-01

    Background Economic growth in low- and middle-income countries (LMIC) has raised interest in how disease burden patterns are related to economic development. Meanwhile, poverty-related diseases are considered to be neglected in terms of research and development (R&D). Objectives Developing intuitive and meaningful metrics to measure how different diseases are related to poverty and neglected in the current R&D system. Design We measured how diseases are related to economic development with the income relation factor (IRF), defined by the ratio of disability-adjusted life-years (DALYs) per 100,000 inhabitants in LMIC versus that in high-income countries. We calculated the IRF for 291 diseases and injuries and 67 risk factors included in the Global Burden of Disease Study 2010. We measured neglect in R&D with the neglect factor (NF), defined by the ratio of disease burden in DALYs (as percentage of the total global disease burden) and R&D expenditure (as percentage of total global health-related R&D expenditure) for 26 diseases. Results The disease burden varies considerably with the level of economic development, shown by the IRF (median: 1.38; interquartile range (IQR): 0.79–6.3). Comparison of IRFs from 1990 to 2010 highlights general patterns of the global epidemiological transition. The 26 poverty-related diseases included in our analysis of neglect in R&D are responsible for 13.8% of the global disease burden, but receive only 1.34% of global health-related R&D expenditure. Within this group, the NF varies considerably (median: 19; IQR: 6–52). Conclusions The IRF is an intuitive and meaningful metric to highlight shifts in global disease burden patterns. A large shortfall exists in global R&D spending for poverty-related and neglected diseases, with strong variations between diseases. PMID:25623607

  11. Neglect of a Neglected Disease in Italy: The Challenge of Access-to-Care for Chagas Disease in Bergamo Area.

    Directory of Open Access Journals (Sweden)

    Ernestina Carla Repetto

    2015-09-01

    Full Text Available Chagas disease (CD represents a growing problem in Europe; Italy is one of the most affected countries but there is no national framework for CD and access-to-care is challenging. In 2012 Médecins Sans Frontières (MSF started an intervention in Bergamo province, where many people of Latin American origin (PLAO are resident. A new model-of-care for CD, initiated by Centre for Tropical Diseases of Sacro Cuore Hospital, Negrar (CTD, the NGO OIKOS and the Bolivian community since 2009 in the same area, was endorsed. Hereby, we aim to describe the prevalence of CD and the treatment management outcomes among PLAO screened from 1st June 2012 to 30th June 2013.Retrospective cohort study using routine program data. Screening sessions were done in Bergamo at OIKOS outpatient service and serological confirmation, staging and treatment for CD was offered at the CTD. MSF provided health education on CD, awareness generation prior to screening days, pre-test and post-test counselling through cultural mediators of Latin American origin.Of 1305 PLAO screened, 223(17% had CD. Among 210 patients eligible for treatment, 102(49% were lost-to-follow-up before treatment. The median delay from diagnosis to treatment was 4 months (range 0.7-16.6 months. Among 108 started on treatment, 63(58% completed treatment, 36(33% interrupted treatment, (33 for drug side-effects, two for patients decision and one due to pregnancy, 6(6% were lost-to-follow-up and 3(3% were on treatment at study censuring.In this first study focusing on process of care for CD in Italy, less than 30% of patients completed treatment with drop-outs along the cascade of care. There is an urgent need to involve affected communities and local regional health authorities to take part to this model-of-care, adapting it to the local epidemiology. The Italian health authorities should take steps in advocating for a change in the current paradigm.

  12. ADVANZ – control of neglected zoonotic diseases using one health and ecohealth approaches

    DEFF Research Database (Denmark)

    Saarnak, Christopher; Mukaratirwa, S.; Johansen, Maria Vang

    , echinococcosis, and taeniasis/cysticercosis. Five other diseases have also been declared neglected, i.e. brucellosis, bovine tuberculosis, anthrax, human African trypanosomiasis, and leishmaniasis. The best strategic approach to transmission control and management of these diseases involves integrated One Health...

  13. How soil scientists help combat podoconiosis, a neglected tropical disease

    NARCIS (Netherlands)

    Visser, Benjamin Jelle

    2014-01-01

    Podoconiosis or "endemic non-filarial elephantiasis" is a tropical disease caused by prolonged exposure of bare feet to irritant alkaline clay soils of volcanic origin [1]. The name of the disease is derived from the Greek words for foot: podos, and dust: konos. Small mineral particles from irritant

  14. Asymmetries of poverty: why global burden of disease valuations underestimate the burden of neglected tropical diseases.

    Directory of Open Access Journals (Sweden)

    Charles H King

    2008-03-01

    Full Text Available The disability-adjusted life year (DALY initially appeared attractive as a health metric in the Global Burden of Disease (GBD program, as it purports to be a comprehensive health assessment that encompassed premature mortality, morbidity, impairment, and disability. It was originally thought that the DALY would be useful in policy settings, reflecting normative valuations as a standardized unit of ill health. However, the design of the DALY and its use in policy estimates contain inherent flaws that result in systematic undervaluation of the importance of chronic diseases, such as many of the neglected tropical diseases (NTDs, in world health. The conceptual design of the DALY comes out of a perspective largely focused on the individual risk rather than the ecology of disease, thus failing to acknowledge the implications of context on the burden of disease for the poor. It is nonrepresentative of the impact of poverty on disability, which results in the significant underestimation of disability weights for chronic diseases such as the NTDs. Finally, the application of the DALY in policy estimates does not account for the nonlinear effects of poverty in the cost-utility analysis of disease control, effectively discounting the utility of comprehensively treating NTDs. The present DALY framework needs to be substantially revised if the GBD is to become a valid and useful system for determining health priorities.

  15. Development of Novel Therapeutics for Neglected Tropical Disease Leishmaniasis

    Science.gov (United States)

    2016-10-01

    Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704...PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) US Naval Medical Research Unit No. Six Venezuela Av. Block 36 Bellavista, Callao-Peru Asociacion Benefica...leading drug candidates identified in the previous experiments. Site 2: Naval Medical Research Unit No. Six (NAMRU-6), Venezuela Avenue block 36

  16. How Soil Scientists Help Combat Podoconiosis, A Neglected Tropical Disease

    Directory of Open Access Journals (Sweden)

    Benjamin Jelle Visser

    2014-05-01

    Full Text Available Podoconiosis or “endemic non-filarial elephantiasis” is a tropical disease caused by prolonged exposure of bare feet to irritant alkaline clay soils of volcanic origin [1]. The name of the disease is derived from the Greek words for foot: podos, and dust: konos. Small mineral particles from irritant soils penetrate the skin and provoke an inflammatory response leading to fibrosis and blockage of lymphatic vessels, causing lymphoedema [2]. Patients suffer from disabling physical effects, but also stigma [1]. The disease can simply be prevented by avoiding contact with irritant soils (wearing shoes but this is still an unaffordable “luxury” for many people. Podoconiosis is unique because it is a completely preventable non-communicable tropical disease [1]. In the past few years, podoconiosis has received increased advocacy and is now step by step appearing on the agenda of medical researchers as well as politicians.  [...

  17. Neglected Tropical Diseases (NTD) service availability at health ...

    African Journals Online (AJOL)

    user

    treatable through systematic case finding and management. This study was conducted ... total of 873 health facilities were assessed for this analysis. All Hospitals, selected ... disease, Cysticercosis and taeniasis, Dengue fever,. Dracunculiasis ...

  18. Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable!

    Science.gov (United States)

    Pinho, Rosa T; Waghabi, Mariana C; Cardillo, Fabíola; Mengel, José; Antas, Paulo R Z

    2016-01-01

    Biomarkers or biosignature profiles have become accessible over time in population-based studies for Chagas disease. Thus, the identification of consistent and reliable indicators of the diagnosis and prognosis of patients with heart failure might facilitate the prioritization of therapeutic management to those with the highest chance of contracting this disease. The purpose of this paper is to review the recent state and the upcoming trends in biomarkers for human Chagas disease. As an emerging concept, we propose a classification of biomarkers based on plasmatic-, phenotype-, antigenic-, genetic-, and management-related candidates. The available data revisited here reveal the lessons learned thus far and the existing challenges that still lie ahead to enable biomarkers to be employed consistently in risk evaluation for this disease. There is a strong need for biomarker validation, particularly for biomarkers that are specific to the clinical forms of Chagas disease. The current failure to achieve the eradication of the transmission of this disease has produced determination to solve this validation issue. Finally, it would be strategic to develop a wide variety of biomarkers and to test them in both preclinical and clinical trials.

  19. [Podoconiosis, a society and medical community neglected disease].

    Science.gov (United States)

    Prieto-Pérez, Laura; Soriano Cea, Juan José; Górgolas Hernández-Mora, Miguel

    2015-11-20

    Podoconiosis, mossy foot or endemic non-filarial elephantiasis, is a geochemical disease that causes lower limb lymphedema; it is directly related to walking barefoot over soils of volcanic origin, in areas with a high pluviometric annual index. It has a specific geographical distribution, affecting around 5% population in areas where it is endemic. It is debilitating and disfiguring disease, which frequently leads to social margination. Podoconiosis is totally preventable and, once a diagnosis is established, it may improve with simple therapeutic measures. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  20. ADVANZ - Neglected zoonotc disease control through a One Health approach

    DEFF Research Database (Denmark)

    Saarnak, Christopher; Johansen, Maria Vang; Mukaratirwa, Samson

    2013-01-01

    As quoted in the Lancet in December 2012, endemic and enzootic zoonoses cause about a billion cases of illness and millions of death in people every year. Of these zoonoses, the diseases such as anthrax, bovine tuberculosis, brucellosis, cysticercosis, echinococcosis (hydatid disease) and rabies...... domesticated (livestock or companion) or wild animals to people. ADVANZ is One Health NZD project, funded by the European Commission through its 7th framework program. The session will describe and discuss the initiative, which main aim is to persuade decision makers and empower stakeholders at local, regional...

  1. Tick-borne encephalitis: a disease neglected by travel medicine.

    Science.gov (United States)

    Haditsch, Martin; Kunze, Ursula

    2013-01-01

    Tick-borne encephalitis (TBE) is a vector-borne disease that is primarily transmitted to humans by infected ticks and causes infection of the central nervous system. Clinical presentations range from meningitis to encephalitis with or without myelitis, and infection may result in death or long-term neurological sequelae. TBE is endemic in regions of at least 27 European as well as in some Asian countries. Infection and disease, however, can be averted successfully by tick-bite prevention and active vaccination. The risk of infection has shifted from daily life and occupational exposure to leisure-time activities, including travelling. Outdoor activities during the tick season with contact with nature increase the risk of tick bites. Although the number of travel-associated cases is unknown, it is certainly under-estimated because there is hardly any awareness of TBE in non-endemic countries. Therefore, the majority of cases remain undiagnosed, also because of the lack of diagnostic serology, as there is no routine screening for TBE in non-endemic regions. Because of the increasing number of travellers from TBE non-endemic to endemic regions, and in view of the fact that TBE was included in the list of notifiable diseases in the European Union in September 2012, this disease needs to become an important issue in travel medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Sickle cell disease in Sierra Leone: a neglected problem | Roberts ...

    African Journals Online (AJOL)

    Eleven (2.4%) were Sickle Cell-HbC disease, median age 14 years. Patients demonstrated many of the typical features of SCD. The most common reason for hospital admission was bone pain crisis associated with an infection, followed by severe anemia. Aseptic necrosis of the femoral head, leg ulcers, septic osteomyelitis ...

  3. Measuring the burden of neglected tropical diseases: the global burden of disease framework.

    Directory of Open Access Journals (Sweden)

    Colin D Mathers

    2007-11-01

    Full Text Available Reliable, comparable information about the main causes of disease and injury in populations, and how these are changing, is a critical input for debates about priorities in the health sector. Traditional sources of information about the descriptive epidemiology of diseases, injuries, and risk factors are generally incomplete, fragmented, and of uncertain reliability and comparability. The Global Burden of Disease (GBD study has provided a conceptual and methodological framework to quantify and compare the health of populations using a summary measure of both mortality and disability, the disability-adjusted life year (DALY.This paper describes key features of the Global Burden of Disease analytic approach, which provides a standardized measurement framework to permit comparisons across diseases and injuries, as well as risk factors, and a systematic approach to the evaluation of data. The paper describes the evolution of the GBD, starting from the first study for the year 1990, summarizes the methodological improvements incorporated into GBD revisions for the years 2000-2004 carried out by the World Health Organization, and examines priorities and issues for the next major GBD study, funded by the Bill & Melinda Gates Foundation, and commencing in 2007.The paper presents an overview of summary results from the Global Burden of Disease study 2002, with a particular focus on the neglected tropical diseases, and also an overview of the comparative risk assessment for 26 global risk factors. Taken together, trypanosomiasis, Chagas disease, schistosomiasis, leishmaniasis, lymphatic filariasis, onchocerciasis, intestinal nematode infections, Japanese encephalitis, dengue, and leprosy accounted for an estimated 177,000 deaths worldwide in 2002, mostly in sub-Saharan Africa, and about 20 million DALYs, or 1.3% of the global burden of disease and injuries. Further research is currently underway to revise and update these estimates.

  4. Buerger's Disease and Anaesthesia: The Neglected Cardiac Angle

    Directory of Open Access Journals (Sweden)

    Shagun Bhatia Shah

    2015-08-01

    Full Text Available Distal limb amputations and respiratory complications are common in patients with Buerger’s disease. Nicotine in cigarette is arrhythmogenic as it blocks cardiac potassium channels. Preoperative Holter ECG monitoring may be useful if preoperative electrocardiogram is normal. If the patient is undergoing major surgery, preservative free lignocaine & amiodarone infusions and a cardioverter defibrillator should be available for the intraoperative cardiac rhythm disturbances.

  5. Impact of environmental factors on neglected emerging arboviral diseases.

    Directory of Open Access Journals (Sweden)

    Camila Lorenz

    2017-09-01

    Full Text Available Brazil is a tropical country that is largely covered by rainforests and other natural ecosystems, which provide ideal conditions for the existence of many arboviruses. However, few analyses have examined the associations between environmental factors and arboviral diseases. Thus, based on the hypothesis of correlation between environment and epidemiology, the proposals of this study were (1 to obtain the probability of occurrence of Oropouche, Mayaro, Saint Louis and Rocio fevers in Brazil based on environmental conditions corresponding to the periods of occurrence of the outbreaks; (2 to describe the macroclimatic scenario in Brazil in the last 50 years, evaluating if there was any detectable tendency to increase temperatures and (3 to model future expansion of those arboviruses in Brazil based on future temperature projections.Our model assessed seven environmental factors (annual rainfall, annual temperature, elevation, seasonality of temperature, seasonality of precipitation, thermal amplitude, and daytime temperature variation for their association with the occurrence of outbreaks in the last 50 years. Our results suggest that various environmental factors distinctly influence the distribution of each arbovirus, with temperature being the central determinant of disease distribution in all high-risk areas. These areas are subject to change, since the average temperature of some areas has increased significantly over the time.This is the first spatio-temporal study of the Oropouche, Mayaro, Saint Louis, and Rocio arboviruses, and our results indicate that they may become increasingly important public health problems in Brazil. Thus, next studies and control programs should include these diseases and also take into consideration key environmental elements.

  6. Mesoamerican nephropathy: a neglected tropical disease with an infectious etiology?

    Science.gov (United States)

    Murray, Kristy O; Fischer, Rebecca S B; Chavarria, Denis; Duttmann, Christiane; Garcia, Melissa N; Gorchakov, Rodion; Hotez, Peter J; Jiron, William; Leibler, Jessica H; Lopez, Job E; Mandayam, Sreedhar; Marin, Alejandro; Sheleby, Jessica

    2015-10-01

    An outbreak of unexplained and severe kidney disease, "Mesoamerican Nephropathy," in mostly young, male sugar cane workers emerged in Central America in the late 1990's. As a result, an estimated 20,000 individuals have died, to date. Unfortunately, and with great consequence to human life, the etiology of the outbreak has yet to be identified. The sugarcane fields in Chichigalpa, Chinandega, Nicaragua, have been involved in the outbreak, and during our initial investigation, we interviewed case patients who experienced fever, nausea and vomiting, arthralgia, myalgia, headache, neck and back pain, weakness, and paresthesia at the onset of acute kidney disease. We also observed a heavy infestation of rodents, particularly of Sigmodon species, in the sugarcane fields. We hypothesize that infectious pathogens are being shed through the urine and feces of these rodents, and workers are exposed to these pathogens during the process of cultivating and harvesting sugarcane. In this paper, we will discuss the epidemic in the Chichigalpa area, potential pathogens responsible for Mesoamerican Nephropathy, and steps needed in order to diagnose, treat, and prevent future cases from occurring. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  7. Congenital Toxoplasmosis: A Plea for a Neglected Disease

    Directory of Open Access Journals (Sweden)

    Martine Wallon

    2018-02-01

    Full Text Available Maternal infection by Toxoplasma gondii during pregnancy may have serious consequences for the fetus, ranging from miscarriage, central nervous system involvement, retinochoroiditis, or subclinical infection at birth with a risk of late onset of ocular diseases. As infection in pregnant women is usually symptomless, the diagnosis relies only on serological tests. Some countries like France and Austria have organized a regular serological testing of pregnant women, some others have no prenatal program of surveillance. Reasons for these discrepant attitudes are many and debatable. Among them are the efficacy of antenatal treatment and cost-effectiveness of such a program. A significant body of data demonstrated that rapid onset of treatment after maternal infection reduces the risk and severity of fetal infection. Recent cost-effectiveness studies support regular screening. This lack of consensus put both pregnant women and care providers in a difficult situation. Another reason why congenital toxoplasmosis is disregarded in some countries is the lack of precise information about its impact on the population. Precise estimations on the burden of the disease can be achieved by systematic screening that will avoid bias or underreporting of cases and provide a clear view of its outcome.

  8. Congenital Toxoplasmosis: A Plea for a Neglected Disease.

    Science.gov (United States)

    Wallon, Martine; Peyron, François

    2018-02-23

    Maternal infection by Toxoplasma gondii during pregnancy may have serious consequences for the fetus, ranging from miscarriage, central nervous system involvement, retinochoroiditis, or subclinical infection at birth with a risk of late onset of ocular diseases. As infection in pregnant women is usually symptomless, the diagnosis relies only on serological tests. Some countries like France and Austria have organized a regular serological testing of pregnant women, some others have no prenatal program of surveillance. Reasons for these discrepant attitudes are many and debatable. Among them are the efficacy of antenatal treatment and cost-effectiveness of such a program. A significant body of data demonstrated that rapid onset of treatment after maternal infection reduces the risk and severity of fetal infection. Recent cost-effectiveness studies support regular screening. This lack of consensus put both pregnant women and care providers in a difficult situation. Another reason why congenital toxoplasmosis is disregarded in some countries is the lack of precise information about its impact on the population. Precise estimations on the burden of the disease can be achieved by systematic screening that will avoid bias or underreporting of cases and provide a clear view of its outcome.

  9. Seven challenges for modelling indirect transmission: Vector-borne diseases, macroparasites and neglected tropical diseases

    Directory of Open Access Journals (Sweden)

    T. Déirdre Hollingsworth

    2015-03-01

    Full Text Available Many of the challenges which face modellers of directly transmitted pathogens also arise when modelling the epidemiology of pathogens with indirect transmission – whether through environmental stages, vectors, intermediate hosts or multiple hosts. In particular, understanding the roles of different hosts, how to measure contact and infection patterns, heterogeneities in contact rates, and the dynamics close to elimination are all relevant challenges, regardless of the mode of transmission. However, there remain a number of challenges that are specific and unique to modelling vector-borne diseases and macroparasites. Moreover, many of the neglected tropical diseases which are currently targeted for control and elimination are vector-borne, macroparasitic, or both, and so this article includes challenges which will assist in accelerating the control of these high-burden diseases. Here, we discuss the challenges of indirect measures of infection in humans, whether through vectors or transmission life stages and in estimating the contribution of different host groups to transmission. We also discuss the issues of “evolution-proof” interventions against vector-borne disease.

  10. Seven challenges for modelling indirect transmission: vector-borne diseases, macroparasites and neglected tropical diseases.

    Science.gov (United States)

    Hollingsworth, T Déirdre; Pulliam, Juliet R C; Funk, Sebastian; Truscott, James E; Isham, Valerie; Lloyd, Alun L

    2015-03-01

    Many of the challenges which face modellers of directly transmitted pathogens also arise when modelling the epidemiology of pathogens with indirect transmission--whether through environmental stages, vectors, intermediate hosts or multiple hosts. In particular, understanding the roles of different hosts, how to measure contact and infection patterns, heterogeneities in contact rates, and the dynamics close to elimination are all relevant challenges, regardless of the mode of transmission. However, there remain a number of challenges that are specific and unique to modelling vector-borne diseases and macroparasites. Moreover, many of the neglected tropical diseases which are currently targeted for control and elimination are vector-borne, macroparasitic, or both, and so this article includes challenges which will assist in accelerating the control of these high-burden diseases. Here, we discuss the challenges of indirect measures of infection in humans, whether through vectors or transmission life stages and in estimating the contribution of different host groups to transmission. We also discuss the issues of "evolution-proof" interventions against vector-borne disease. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Neglected Tropical Diseases and the Millennium Development Goals-why the "other diseases" matter: reality versus rhetoric

    Directory of Open Access Journals (Sweden)

    Molyneux David H

    2011-12-01

    Full Text Available Abstract Since 2004 there has been an increased recognition of the importance of Neglected Tropical Diseases (NTDs as impediments to development. These diseases are caused by a variety of infectious agents - viruses, bacteria and parasites - which cause a diversity of clinical conditions throughout the tropics. The World Health Organisation (WHO has defined seventeen of these conditions as core NTDs. The objectives for the control, elimination or eradication of these conditions have been defined in World Health Assembly resolutions whilst the strategies for the control or elimination of individual diseases have been defined in various WHO documents. Since 2005 there has been a drive for the expanded control of these diseases through an integrated approach of mass drug administration referred to as Preventive Chemotherapy via community-based distribution systems and through schools. This has been made possible by donations from major pharmaceutical companies of quality and efficacious drugs which have a proven track record of safety. As a result of the increased commitment of endemic countries, bilateral donors and non-governmental development organisations, there has been a considerable expansion of mass drug administration. In particular, programmes targeting lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminth infections have expanded to treat 887. 8 million people in 2009. There has been significant progress towards guinea worm eradication, and the control of leprosy and human African trypanosomiasis. This paper responds to what the authors believe are inappropriate criticisms of these programmes and counters accusations of the motives of partners made in recently published papers. We provide a detailed response and update the information on the numbers of global treatments undertaken for NTDs and list the success stories to date. The paper acknowledges that in undertaking any health programme in

  12. Controlling Neglected Tropical Diseases (NTDs) in Haiti: Implementation Strategies and Evidence of Their Success.

    Science.gov (United States)

    Lemoine, Jean Frantz; Desormeaux, Anne Marie; Monestime, Franck; Fayette, Carl Renad; Desir, Luccene; Direny, Abdel Nasser; Carciunoiu, Sarah; Miller, Lior; Knipes, Alaine; Lammie, Patrick; Smith, Penelope; Stockton, Melissa; Trofimovich, Lily; Bhandari, Kalpana; Reithinger, Richard; Crowley, Kathryn; Ottesen, Eric; Baker, Margaret

    2016-10-01

    Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti's neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented. These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a "directly observed treatment" strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies. The evidence that these strategies were effective lies in both the high treatment coverage obtained- 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH-and the significant reduction in burden of infection- 45 communes having reached the target threshold for stopping treatment for LF. By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti's very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control. These efforts, as described, have not only helped establish the global portfolio of "best practices" for NTD control but

  13. Controlling Neglected Tropical Diseases (NTDs in Haiti: Implementation Strategies and Evidence of Their Success.

    Directory of Open Access Journals (Sweden)

    Jean Frantz Lemoine

    2016-10-01

    Full Text Available Lymphatic filariasis (LF and soil-transmitted helminths (STH have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti's neglected tropical disease (NTD program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented. These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a "directly observed treatment" strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies. The evidence that these strategies were effective lies in both the high treatment coverage obtained- 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH-and the significant reduction in burden of infection- 45 communes having reached the target threshold for stopping treatment for LF. By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti's very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control. These efforts, as described, have not only helped establish the global portfolio of "best practices" for

  14. Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases

    Science.gov (United States)

    Gaschignard, Jean; Grant, Audrey Virginia; Thuc, Nguyen Van; Orlova, Marianna; Cobat, Aurélie; Huong, Nguyen Thu; Ba, Nguyen Ngoc; Thai, Vu Hong; Abel, Laurent; Schurr, Erwin; Alcaïs, Alexandre

    2016-01-01

    After sustained exposure to Mycobacterium leprae, only a subset of exposed individuals develops clinical leprosy. Moreover, leprosy patients show a wide spectrum of clinical manifestations that extend from the paucibacillary (PB) to the multibacillary (MB) form of the disease. This “polarization” of leprosy has long been a major focus of investigation for immunologists because of the different immune response in these two forms. But while leprosy per se has been shown to be under tight human genetic control, few epidemiological or genetic studies have focused on leprosy subtypes. Using PubMed, we collected available data in English on the epidemiology of leprosy polarization and the possible role of human genetics in its pathophysiology until September 2015. At the genetic level, we assembled a list of 28 genes from the literature that are associated with leprosy subtypes or implicated in the polarization process. Our bibliographical search revealed that improved study designs are needed to identify genes associated with leprosy polarization. Future investigations should not be restricted to a subanalysis of leprosy per se studies but should instead contrast MB to PB individuals. We show the latter approach to be the most powerful design for the identification of genetic polarization determinants. Finally, we bring to light the important resource represented by the nine-banded armadillo model, a unique animal model for leprosy. PMID:27219008

  15. Neglected tropical diseases in sub-saharan Africa: review of their prevalence, distribution, and disease burden.

    Directory of Open Access Journals (Sweden)

    Peter J Hotez

    Full Text Available The neglected tropical diseases (NTDs are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA, and together produce a burden of disease that may be equivalent to up to one-half of SSA's malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA's poorest people, including 40-50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases, accounting for 93% of the world's number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46-51 million cases and onchocerciasis (37 million cases are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region's agricultural productivity. There is a dearth of information on Africa's non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases. However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa's NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur.

  16. Neglected tropical diseases in sub-saharan Africa: review of their prevalence, distribution, and disease burden.

    Science.gov (United States)

    Hotez, Peter J; Kamath, Aruna

    2009-08-25

    The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA's malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA's poorest people, including 40-50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world's number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46-51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region's agricultural productivity. There is a dearth of information on Africa's non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa's NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur.

  17. The road to elimination: an overview of neglected infectious diseases in latin america and the caribbean

    OpenAIRE

    Kenyon Ault, Steven; Unidad de Enfermedades Desatendidas, Tropicales y Transmitidas por Vectores, Departamento de Enfermedades Transmisibles y Análisis de Salud, Organización Panamericana de la Salud. Washington DC, EE. UU. Licenciado en Ciencias, Máster en Ciencias, Especialista registrado en Salud Ambiental.; Catalá Pascual, Laura; Unidad de Enfermedades Desatendidas, Tropicales y Transmitidas por Vectores, Departamento de Enfermedades Transmisibles y Análisis de Salud, Organización Panamericana de la Salud. Washington DC, EE. UU. Doctor en Medicina, especialista en Salud Pública y Medicina Preventiva, Máster en Salud Pública.; Grados-Zavala, Maria Elena; Unidad de Enfermedades Desatendidas, Tropicales y Transmitidas por Vectores, Departamento de Enfermedades Transmisibles y Análisis de Salud, Organización Panamericana de la Salud. Washington DC, EE. UU. Bachiller en Administración de Empresas y Bachiller en Economía.; Gonzálvez García, Guillermo; Departamento de Enfermedades Transmisibles y Análisis de Salud, Organización Panamericana de la Salud. Lima, Perú. Doctor en Medicina, Máster en Salud Pública; Castellanos, Luis Gerardo; Unidad de Enfermedades Desatendidas, Tropicales y Transmitidas por Vectores, Departamento de Enfermedades Transmisibles y Análisis de Salud, Organización Panamericana de la Salud. Washington DC, EE. UU.

    2014-01-01

    Neglected infectious diseases (NID) affect mainly isolated populations living in isolation and in poor socioeconomic conditions. These diseases, by their chronic and silent nature, often affect communities with a weak political voice. This translates into very little attention or political priority; which is reflected in minimal and insufficient preventive measures, monitoring and control. However, there is evidence this situation is changing favorably in some countries of the Americas. In re...

  18. Neglected Diseases

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  19. Neglected diseases and ethnic minorities in the Western Pacific Region exploring the links.

    Science.gov (United States)

    Schratz, Alexander; Pineda, Martha Fernanda; Reforma, Liberty G; Fox, Nicole M; Le Anh, Tuan; Tommaso Cavalli-Sforza, L; Henderson, Mackenzie K; Mendoza, Raymond; Utzinger, Jürg; Ehrenberg, John P; Tee, Ah Sian

    2010-01-01

    Ethnic minority groups (EMGs) are often subject to exclusion, marginalization and poverty. These characteristics render them particularly vulnerable to neglected diseases, a diverse group of diseases that comprise bacteria, ecto-parasites, fungi, helminths and viruses. Despite the health policy relevance, only little is known of the epidemiological profile of neglected diseases among EMGs. We reviewed country data from Australia, Cambodia, Lao People's Democratic Republic, Malaysia, the Philippines and Vietnam and found several overlaps between regions with high proportions of EMG population and high prevalence rates of neglected diseases (infections with soil-transmitted helminths, filarial worms, schistosomes, food-borne trematodes and cestodes). While the links are not always clearly evident and it is impossible to establish correlations among highly aggregated data without control variables-such as environmental factors-there appear indeed to be important linkages between EMGs, socio-economic status and prevalence of neglected diseases. Some determinants under consideration are lack of access to health care and general health status, poverty and social marginalization, as well as education and literacy. Further research is needed to deepen the understanding of these linkages and to determine their public health and socio-economic significance. In particular, there is a need for more data from all countries in the Western Pacific Region that is disaggregated below the provincial level. Selected case studies that incorporate other control variables-such as risk factors from the physical environment-might be useful to inform policy makers about the feasibility of prevention and control interventions that are targeted at high-risk EMGs.

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

    Science.gov (United States)

    Akinsolu, Folahanmi Tomiwa; de Paiva, Vitor Nobre; Souza, Samuel Santos; Varga, Orsolya

    2017-11-14

    "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. 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

  1. Diseases Neglected by the Media in Espírito Santo, Brazil in 2011–2012

    Science.gov (United States)

    Vasconcellos-Silva, Paulo Roberto; Oliveira, Adauto Emmerich

    2016-01-01

    Background The aims of the present study were to identify and analyse the Diseases Neglected by the Media (DNMs) via a comparison between the most important health issues to the population of Espírito Santo, Brazil, from the epidemiological perspective (health value) and their effective coverage by the print media, and to analyse the DNMs considering the perspective of key journalists involved in the dissemination of health topics in the state media. Methodology Morbidity and mortality data were collected from official documents and from Health Information Systems. In parallel, the diseases reported in the two major newspapers of Espírito Santo in 2011–2012 were identified from 10,771 news articles. Concomitantly, eight interviews were conducted with reporters from the two newspapers to understand the journalists’ reasons for the coverage or neglect of certain health/disease topics. Principal Findings Quantitatively, the DNMs identified diseases associated with poverty, including tuberculosis, leprosy, schistosomiasis, leishmaniasis, and trachoma. Apart from these, diseases with outbreaks in the period evaluated, including whooping cough and meningitis, some cancers, respiratory diseases, ischaemic heart disease, and stroke, were also seldom addressed by the media. In contrast, dengue fever, acquired immune deficiency syndrome (AIDS), diabetes, breast cancer, prostate cancer, tracheal cancer, and bronchial and lung cancers were broadly covered in the period analysed, corroborating the tradition of media disclosure of these diseases. Qualitatively, the DNMs included rare diseases, such as amyotrophic lateral sclerosis (ALS), leishmaniasis, Down syndrome, and verminoses. The reasons for the neglect of these topics by the media included the political and economic interests of the newspapers, their editorial line, and the organizational routine of the newsrooms. Conclusions Media visibility acts as a strategy for legitimising priorities and contextualizing

  2. Diseases Neglected by the Media in Espírito Santo, Brazil in 2011-2012.

    Science.gov (United States)

    Cavaca, Aline Guio; Emerich, Tatiana Breder; Vasconcellos-Silva, Paulo Roberto; dos Santos-Neto, Edson Theodoro; Oliveira, Adauto Emmerich

    2016-04-01

    The aims of the present study were to identify and analyse the Diseases Neglected by the Media (DNMs) via a comparison between the most important health issues to the population of Espírito Santo, Brazil, from the epidemiological perspective (health value) and their effective coverage by the print media, and to analyse the DNMs considering the perspective of key journalists involved in the dissemination of health topics in the state media. Morbidity and mortality data were collected from official documents and from Health Information Systems. In parallel, the diseases reported in the two major newspapers of Espírito Santo in 2011-2012 were identified from 10,771 news articles. Concomitantly, eight interviews were conducted with reporters from the two newspapers to understand the journalists' reasons for the coverage or neglect of certain health/disease topics. Quantitatively, the DNMs identified diseases associated with poverty, including tuberculosis, leprosy, schistosomiasis, leishmaniasis, and trachoma. Apart from these, diseases with outbreaks in the period evaluated, including whooping cough and meningitis, some cancers, respiratory diseases, ischaemic heart disease, and stroke, were also seldom addressed by the media. In contrast, dengue fever, acquired immune deficiency syndrome (AIDS), diabetes, breast cancer, prostate cancer, tracheal cancer, and bronchial and lung cancers were broadly covered in the period analysed, corroborating the tradition of media disclosure of these diseases. Qualitatively, the DNMs included rare diseases, such as amyotrophic lateral sclerosis (ALS), leishmaniasis, Down syndrome, and verminoses. The reasons for the neglect of these topics by the media included the political and economic interests of the newspapers, their editorial line, and the organizational routine of the newsrooms. Media visibility acts as a strategy for legitimising priorities and contextualizing various realities. Therefore, we propose that the health

  3. Neglected tropical diseases in Brazil Doenças tropicais negligenciadas no Brasil

    Directory of Open Access Journals (Sweden)

    José Angelo L. Lindoso

    2009-10-01

    Full Text Available Poverty is intrinsically related to the incidence of Neglected Tropical Diseases (NTDs. The main countries that have the lowest human development indices (HDI and the highest burdens of NTDs are located in tropical and subtropical regions of the world. Among these countries is Brazil, which is ranked 70th in HDI. Nine out of the ten NTDs established by the World Health Organization (WHO are present in Brazil. Leishmaniasis, tuberculosis, dengue fever and leprosy are present over almost the entire Brazilian territory. More than 90% of malaria cases occur in the Northern region of the country, and lymphatic filariasis and onchocerciasis occur in outbreaks in a particular region. The North and Northeast regions of Brazil have the lowest HDIs and the highest rates of NTDs. These diseases are considered neglected because there is not important investment in projects for the development of new drugs and vaccines and existing programs to control these diseases are not sufficient. Another problem related to NTDs is co-infection with HIV, which favors the occurrence of severe clinical manifestations and therapeutic failure. In this article, we describe the status of the main NTDs currently occurring in Brazil and relate them to the HDI and poverty.A pobreza está intrinsicamente relacionada com a ocorrência de doenças tropicais negligenciadas (DTNs. Os principais países com os menores índices de desenvolvimento humano (IDH e a maior carga de DTNs estão nas regiões tropicais e subtropicais do globo terrestre. O Brasil é o 70º país no ranking do IDH e concentra nove das 10 principais doenças tropicais consideradas negligenciadas pela OMS. Leishmanioses, tuberculose, dengue e hanseníase ocorrem em quase todo o território do Brasil. Mais de 90% dos casos de malária ocorrem na região norte e há surtos de filariose linfática e oncocercose. As regiões norte e nordeste apresentam o menor IDH e concentram o maior número das DTNs. Essas doen

  4. Neglected tropical diseases among the Association of Southeast Asian Nations (ASEAN: overview and update.

    Directory of Open Access Journals (Sweden)

    Peter J Hotez

    2015-04-01

    Full Text Available The ten member states of the Association of Southeast Asian Nations (ASEAN constitute an economic powerhouse, yet these countries also harbor a mostly hidden burden of poverty and neglected tropical diseases (NTDs. Almost 200 million people live in extreme poverty in ASEAN countries, mostly in the low or lower middle-income countries of Indonesia, the Philippines, Myanmar, Viet Nam, and Cambodia, and many of them are affected by at least one NTD. However, NTDs are prevalent even among upper middle-income ASEAN countries such as Malaysia and Thailand, especially among the indigenous populations. The three major intestinal helminth infections are the most common NTDs; each helminthiasis is associated with approximately 100 million infections in the region. In addition, more than 10 million people suffer from either liver or intestinal fluke infections, as well as schistosomiasis and lymphatic filariasis (LF. Intestinal protozoan infections are widespread, while leishmaniasis has emerged in Thailand, and zoonotic malaria (Plasmodium knowlesi infection causes severe morbidity in Malaysia. Melioidosis has emerged as an important bacterial NTD, as have selected rickettsial infections, and leptospirosis. Leprosy, yaws, and trachoma are still endemic in focal areas. Almost 70 million cases of dengue fever occur annually in ASEAN countries, such that this arboviral infection is now one of the most common and economically important NTDs in the region. A number of other arboviral and zoonotic viral infections have also emerged, including Japanese encephalitis; tick-borne viral infections; Nipah virus, a zoonosis present in fruit bats; and enterovirus 71 infection. There are urgent needs to expand surveillance activities in ASEAN countries, as well as to ensure mass drug administration is provided to populations at risk for intestinal helminth and fluke infections, LF, trachoma, and yaws. An ASEAN Network for Drugs, Diagnostics, Vaccines, and Traditional

  5. Neglected tropical diseases among the Association of Southeast Asian Nations (ASEAN): overview and update.

    Science.gov (United States)

    Hotez, Peter J; Bottazzi, Maria Elena; Strych, Ulrich; Chang, Li-Yen; Lim, Yvonne A L; Goodenow, Maureen M; AbuBakar, Sazaly

    2015-04-01

    The ten member states of the Association of Southeast Asian Nations (ASEAN) constitute an economic powerhouse, yet these countries also harbor a mostly hidden burden of poverty and neglected tropical diseases (NTDs). Almost 200 million people live in extreme poverty in ASEAN countries, mostly in the low or lower middle-income countries of Indonesia, the Philippines, Myanmar, Viet Nam, and Cambodia, and many of them are affected by at least one NTD. However, NTDs are prevalent even among upper middle-income ASEAN countries such as Malaysia and Thailand, especially among the indigenous populations. The three major intestinal helminth infections are the most common NTDs; each helminthiasis is associated with approximately 100 million infections in the region. In addition, more than 10 million people suffer from either liver or intestinal fluke infections, as well as schistosomiasis and lymphatic filariasis (LF). Intestinal protozoan infections are widespread, while leishmaniasis has emerged in Thailand, and zoonotic malaria (Plasmodium knowlesi infection) causes severe morbidity in Malaysia. Melioidosis has emerged as an important bacterial NTD, as have selected rickettsial infections, and leptospirosis. Leprosy, yaws, and trachoma are still endemic in focal areas. Almost 70 million cases of dengue fever occur annually in ASEAN countries, such that this arboviral infection is now one of the most common and economically important NTDs in the region. A number of other arboviral and zoonotic viral infections have also emerged, including Japanese encephalitis; tick-borne viral infections; Nipah virus, a zoonosis present in fruit bats; and enterovirus 71 infection. There are urgent needs to expand surveillance activities in ASEAN countries, as well as to ensure mass drug administration is provided to populations at risk for intestinal helminth and fluke infections, LF, trachoma, and yaws. An ASEAN Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines

  6. Lyme disease and post-treatment Lyme disease syndrome: the neglected disease in our own backyard.

    Science.gov (United States)

    Crowder, L A; Yedlin, V A; Weinstein, E R; Kortte, K B; Aucott, J N

    2014-09-01

    A survey was developed to assess experience and opinions about Lyme disease and post-treatment Lyme disease syndrome (PTLDS) among faculties in public health. No previous surveys of public health faculties have been found in the literature. This is a cross sectional study of public health school faculty members designed to measure knowledge and experience with Lyme disease and PTLDS using an internet survey instrument. Participants were recruited using all the publicly available e-mail addresses of faculty members in all the 50 accredited Schools of Public Health in the United States. A 15% response rate was seen for the survey. 50% of respondents were from Lyme endemic states. Less than 5% of faculty members consider themselves expert in Lyme or PTLDS. Many faculty members had known someone with Lyme disease or PTLDS, but few had been diagnosed themselves. Most believe that PTLDS can be severe and chronic, is not easy to treat, and does not resolve on its own, but were uncertain about its aetiology. Most respondents also felt that the incidence of Lyme disease will increase and that more education is needed. The need for further understanding and communication presents an opportunity for public health research and education in Lyme disease and the sequelae of PTLDS. Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  7. Threats from emerging and re-emerging neglected tropical diseases (NTDs).

    Science.gov (United States)

    Mackey, Tim K; Liang, Bryan A

    2012-01-01

    Neglected tropical diseases impact over 1 billion of the world's poorest populations and require special attention. However, within the NTDs recognized by the World Health Organization, some are also dually categorized as emerging and re-emerging infectious diseases requiring more detailed examination on potential global health risks. We reviewed the 17 NTDs classified by the WHO to determine if those NTDs were also categorized by the US Centers for Disease Control and Prevention as emerging and re-emerging infectious diseases (''EReNTDs''). We then identified common characteristics and risks associated with EReNTDs. Identified EReNTDs of dengue, rabies, Chagas Disease, and cysticercosis disproportionately impact resource-poor settings with poor social determinants of health, spread through globalization, are impacted by vector control, lack available treatments, and threaten global health security. This traditionally neglected subset of diseases requires urgent attention and unique incentive structures to encourage investment in innovation and coordination. Multi-sectorial efforts and targeted public-private partnerships would spur needed R&D for effective and accessible EReNTD treatments, improvement of social determinants of health, crucial low-income country development, and health system strengthening efforts. Utilization of One Health principles is essential for enhancing knowledge to efficaciously address public health aspects of these EReNTDs globally.

  8. Threats from emerging and re-emerging neglected tropical diseases (NTDs

    Directory of Open Access Journals (Sweden)

    Tim K. Mackey

    2012-08-01

    Full Text Available Background: Neglected tropical diseases impact over 1 billion of the world's poorest populations and require special attention. However, within the NTDs recognized by the World Health Organization, some are also dually categorized as emerging and re-emerging infectious diseases requiring more detailed examination on potential global health risks. Methods: We reviewed the 17 NTDs classified by the WHO to determine if those NTDs were also categorized by the US Centers for Disease Control and Prevention as emerging and re-emerging infectious diseases (‘‘EReNTDs’’. We then identified common characteristics and risks associated with EReNTDs. Results: Identified EReNTDs of dengue, rabies, Chagas Disease, and cysticercosis disproportionately impact resource-poor settings with poor social determinants of health, spread through globalization, are impacted by vector control, lack available treatments, and threaten global health security. This traditionally neglected subset of diseases requires urgent attention and unique incentive structures to encourage investment in innovation and coordination. Discussion: Multi-sectorial efforts and targeted public–private partnerships would spur needed R&D for effective and accessible EReNTD treatments, improvement of social determinants of health, crucial low-income country development, and health system strengthening efforts. Utilization of One Health principles is essential for enhancing knowledge to efficaciously address public health aspects of these EReNTDs globally.

  9. Model for product development of vaccines against neglected tropical diseases: a vaccine against human hookworm.

    Science.gov (United States)

    Bottazzi, Maria Elena; Brown, Ami Shah

    2008-12-01

    This article provides an overview of the advances in product development and technology transfer of the vaccine against human hookworm, with particular emphasis on the lessons learned and the challenges of developing a vaccine in the nonprofit sector. The comprehensive approach to vaccine development established by the Human Hookworm Vaccine Initiative (HHVI) identifies key operational and technical aspects that are essential for a successful partnership with a developing country vaccine manufacturer. This article also highlights the importance of a global access roadmap to guide the vaccine development program. The advancement of new products for the control of neglected tropical diseases portends great challenges for global access, including aspects related to vaccine design, product development and manufacture, vaccine introduction and distribution, financing, knowledge dissemination and intellectual property management. With only three vaccines for neglected tropical diseases in clinical trials - hookworm, leishmaniasis and schistosomiasis - we are at the nascent stages of developing vaccines for neglected populations. Product development public-private partnerships, such as the HHVI, continue to show great promise on this front and will eventually provide significant control tools for achieving millennium development goals related to poverty reduction, as well as child and maternal health.

  10. A business plan to help the 'global South' in its fight against neglected diseases.

    Science.gov (United States)

    Frew, Sarah E; Liu, Victor Y; Singer, Peter A

    2009-01-01

    Although neglected tropical diseases (NTDs) threaten the health of those living in the developing world, innovation directed toward addressing NTDs is comparatively meager. Health biotechnology firms in rapidly growing economies in the global South are developing and selling vaccines, diagnostics, and therapeutics for these diseases to local markets. In this paper we identify a pipeline of sixty-two NTD products from seventy-eight "Southern" companies. We also propose creation of a Global Health Accelerator-a new nonprofit organization whose mission would be to support and help grow this Southern source of affordable innovation for NTDs.

  11. Drawing attention to a neglected injecting-related harm: a systematic review of AA amyloidosis among people who inject drugs.

    Science.gov (United States)

    Harris, Magdalena; Brathwaite, Rachel; Scott, Jenny; Gilchrist, Gail; Ciccarone, Dan; Hope, Vivian; McGowan, Catherine R

    2018-04-26

    Chronic skin and soft tissue infections (SSTI) among people who inject drugs (PWID) can lead to AA amyloidosis: a serious, yet neglected, multi-organ disease. We aim to synthesize findings on the epidemiology, risk factors, clinical outcomes, screening recommendations and challenges to treatment for AA amyloidosis among PWID. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched the following bibliographic databases in July 2017: CINAHL Plus, Embase, Global Health, MEDLINE, PsycEXTRA, PsycINFO and SCOPUS. Studies were included if they investigated AA amyloidosis in PWID. Studies were not restricted to location, study type, year or language of publication. Study heterogeneity precluded meta-analysis; we present a narrative review of the literature. Thirty-seven papers from eight countries met inclusion criteria. A total of 781 PWID are reported on, of whom 177 had AA amyloidosis. Where disease causality is established, it is attributed to chronic inflammation caused by injecting-related SSTIs. Most (88.7%) PWID with AA amyloidosis had SSTIs. The proportion of PWID with AA amyloidosis at post-mortem ranged from 1.6% (Germany) to 22.5% (Serbia). Biopsy studies reported from 5.26% (Portugal) to 50% (Germany) of AA amyloidosis in PWID with suspected or known kidney disease. Following diagnosis, the typical trajectory for PWID with AA amyloidosis was rapid deterioration of renal function requiring haemodialysis. Treatment difficulties, end-stage renal failure and premature death from sepsis were observed. Good outcomes, including reversibility of AA amyloidosis, are attributed to rapid treatment of the underlining inflammation and injecting cessation. Notably, given the population in question, no studies were published in addiction or harm reduction journals; most (92%) appeared in specialist nephrology and medical journals. There is strong evidence of an association between skin

  12. Disease-modifying drugs in Alzheimer's disease

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    Ghezzi L

    2013-12-01

    Full Text Available Laura Ghezzi, Elio Scarpini, Daniela Galimberti Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy Abstract: Alzheimer's disease (AD is an age-dependent neurodegenerative disorder and the most common cause of dementia. The early stages of AD are characterized by short-term memory loss. Once the disease progresses, patients experience difficulties in sense of direction, oral communication, calculation, ability to learn, and cognitive thinking. The median duration of the disease is 10 years. The pathology is characterized by deposition of amyloid beta peptide (so-called senile plaques and tau protein in the form of neurofibrillary tangles. Currently, two classes of drugs are licensed by the European Medicines Agency for the treatment of AD, ie, acetylcholinesterase inhibitors for mild to moderate AD, and memantine, an N-methyl-D-aspartate receptor antagonist, for moderate and severe AD. Treatment with acetylcholinesterase inhibitors or memantine aims at slowing progression and controlling symptoms, whereas drugs under development are intended to modify the pathologic steps leading to AD. Herein, we review the clinical features, pharmacologic properties, and cost-effectiveness of the available acetylcholinesterase inhibitors and memantine, and focus on disease-modifying drugs aiming to interfere with the amyloid beta peptide, including vaccination, passive immunization, and tau deposition. Keywords: Alzheimer's disease, acetylcholinesterase inhibitors, memantine, disease-modifying drugs, diagnosis, treatment

  13. Heterocyclic N-oxides - A Promising Class of Agents Against Tuberculosis, Malaria and Neglected Tropical Diseases.

    Science.gov (United States)

    Dos Santos Fernandes, Guilherme Felipe; Pavan, Aline Renata; Dos Santos, Jean Leandro

    2018-04-17

    Heterocyclic N-oxides have emerged as promising agents against a number of diseases and disorders, especially infectious diseases. This review analyzes the emergence and development of this scaffold in the medicinal chemistry, focusing mainly on the discovery of new heterocyclic N-oxide compounds with potent activity against tuberculosis, malaria and neglected tropical diseases (i.e. leishmaniasis and Chagas disease). A number of heterocyclic N-oxide are described herein, nevertheless, the following chemical classes deserve to be highlighted due to the large number of reports in the literature about their promising pharmacological effects: furoxan, benzofuroxan, quinoxaline 1,4-di-N-oxide, indolone N-oxide and benzimidazole N-oxide. In order to describe those most promising compounds, we included in this review only those most biologically active heterocyclic N-oxide published since 2000. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Brucellosis as a neglected disease in a neglected population: a seroepidemiological study of migratory nomads in the Fars province of Iran.

    Science.gov (United States)

    Honarvar, B; Moghadami, M; Lankarani, K B; Davarpanah, M A; Ataolahi, M; Farbod, A; Eskandari, E; Panahi, M; Ghorbani, A; Zahiri, Z; Tabrizi, R; Pourjafar, M; Heidari, S M M

    2017-02-01

    This study assessed the seroprevalence of brucellosis and its risk factors in migratory nomads in the Fars province of Iran. Active brucellosis was defined as the combination of clinical symptoms, including fever, chills, night sweats, headache, low back pain, arthralgia, or myalgia, and positive laboratory testing, including either a serum agglutination test (SAT) ⩾1:80 with a 2-mercaptoethanol (2-ME) test ⩾1:40, or a SAT brucellosis was detected in 54 cases, indicating a prevalence of 10% (95% confidence interval 8-12). In conclusion, we determined that brucellosis is a prevalent yet neglected disease in this nomadic population. Brucellosis control is not possible as long as these high-risk populations remain neglected.

  15. Evidence connecting old, new and neglected glucose-lowering drugs to bile acid-induced GLP-1 secretion

    DEFF Research Database (Denmark)

    Kårhus, Martin L; Brønden, Andreas; Sonne, David P

    2017-01-01

    Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have...... current evidence connecting established glucose-lowering drugs to bile acid-induced GLP-1 secretion and discusses whether bile acid-induced GLP-1 secretion may constitute a new basis for understanding how metformin, inhibitors of the apical sodium-dependent bile acids transporter, and bile acid...... sequestrants - old, new and neglected glucose-lowering drugs - improve glucose metabolism....

  16. Toward an open-access global database for mapping, control, and surveillance of neglected tropical diseases.

    Directory of Open Access Journals (Sweden)

    Eveline Hürlimann

    2011-12-01

    Full Text Available BACKGROUND: After many years of general neglect, interest has grown and efforts came under way for the mapping, control, surveillance, and eventual elimination of neglected tropical diseases (NTDs. Disease risk estimates are a key feature to target control interventions, and serve as a benchmark for monitoring and evaluation. What is currently missing is a georeferenced global database for NTDs providing open-access to the available survey data that is constantly updated and can be utilized by researchers and disease control managers to support other relevant stakeholders. We describe the steps taken toward the development of such a database that can be employed for spatial disease risk modeling and control of NTDs. METHODOLOGY: With an emphasis on schistosomiasis in Africa, we systematically searched the literature (peer-reviewed journals and 'grey literature', contacted Ministries of Health and research institutions in schistosomiasis-endemic countries for location-specific prevalence data and survey details (e.g., study population, year of survey and diagnostic techniques. The data were extracted, georeferenced, and stored in a MySQL database with a web interface allowing free database access and data management. PRINCIPAL FINDINGS: At the beginning of 2011, our database contained more than 12,000 georeferenced schistosomiasis survey locations from 35 African countries available under http://www.gntd.org. Currently, the database is expanded to a global repository, including a host of other NTDs, e.g. soil-transmitted helminthiasis and leishmaniasis. CONCLUSIONS: An open-access, spatially explicit NTD database offers unique opportunities for disease risk modeling, targeting control interventions, disease monitoring, and surveillance. Moreover, it allows for detailed geostatistical analyses of disease distribution in space and time. With an initial focus on schistosomiasis in Africa, we demonstrate the proof-of-concept that the establishment

  17. Toward an Open-Access Global Database for Mapping, Control, and Surveillance of Neglected Tropical Diseases

    Science.gov (United States)

    Hürlimann, Eveline; Schur, Nadine; Boutsika, Konstantina; Stensgaard, Anna-Sofie; Laserna de Himpsl, Maiti; Ziegelbauer, Kathrin; Laizer, Nassor; Camenzind, Lukas; Di Pasquale, Aurelio; Ekpo, Uwem F.; Simoonga, Christopher; Mushinge, Gabriel; Saarnak, Christopher F. L.; Utzinger, Jürg; Kristensen, Thomas K.; Vounatsou, Penelope

    2011-01-01

    Background After many years of general neglect, interest has grown and efforts came under way for the mapping, control, surveillance, and eventual elimination of neglected tropical diseases (NTDs). Disease risk estimates are a key feature to target control interventions, and serve as a benchmark for monitoring and evaluation. What is currently missing is a georeferenced global database for NTDs providing open-access to the available survey data that is constantly updated and can be utilized by researchers and disease control managers to support other relevant stakeholders. We describe the steps taken toward the development of such a database that can be employed for spatial disease risk modeling and control of NTDs. Methodology With an emphasis on schistosomiasis in Africa, we systematically searched the literature (peer-reviewed journals and ‘grey literature’), contacted Ministries of Health and research institutions in schistosomiasis-endemic countries for location-specific prevalence data and survey details (e.g., study population, year of survey and diagnostic techniques). The data were extracted, georeferenced, and stored in a MySQL database with a web interface allowing free database access and data management. Principal Findings At the beginning of 2011, our database contained more than 12,000 georeferenced schistosomiasis survey locations from 35 African countries available under http://www.gntd.org. Currently, the database is expanded to a global repository, including a host of other NTDs, e.g. soil-transmitted helminthiasis and leishmaniasis. Conclusions An open-access, spatially explicit NTD database offers unique opportunities for disease risk modeling, targeting control interventions, disease monitoring, and surveillance. Moreover, it allows for detailed geostatistical analyses of disease distribution in space and time. With an initial focus on schistosomiasis in Africa, we demonstrate the proof-of-concept that the establishment and running of a

  18. Drugs Approved for Gestational Trophoblastic Disease

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for gestational trophoblastic disease. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  19. A Prospective Examination of the Path from Child Abuse and Neglect to Illicit Drug Use in Middle Adulthood: The Potential Mediating Role of Four Risk Factors

    Science.gov (United States)

    Wilson, Helen W.; Widom, Cathy Spatz

    2009-01-01

    This study examines prostitution, homelessness, delinquency and crime, and school problems as potential mediators of the relationship between childhood abuse and neglect (CAN) and illicit drug use in middle adulthood. Children with documented cases of physical and sexual abuse and neglect (ages 0-11) during 1967-1971 were matched with…

  20. The German government's global health strategy--a strategy also to support research and development for neglected diseases?

    Science.gov (United States)

    Fehr, Angela; Razum, Oliver

    2014-01-01

    Neglected tropical infectious diseases as well as rare diseases are characterized by structural research and development (R&D) deficits. The market fails for these disease groups. Consequently, to meet public health and individual patient needs, political decision makers have to develop strategies at national and international levels to make up for this R&D deficit. The German government recently published its first global health strategy. The strategy underlines the German government's commitment to strengthening global health governance. We find, however, that the strategy lacks behind the international public health endeavors for neglected diseases. It fails to make reference to the ongoing debate on a global health agreement. Neither does it outline a comprehensive national strategy to promote R&D into neglected diseases, which would integrate existing R&D activities in Germany and link up to the international debate on sustainable, needs-based R&D and affordable access. This despite the fact that only recently, in a consensus-building process, a National Plan of Action for rare diseases was successfully developed in Germany which could serve as a blueprint for a similar course of action for neglected diseases. We recommend that, without delay, a structured process be initiated in Germany to explore all options to promote R&D for neglected diseases, including a global health agreement.

  1. The German government's global health strategy – a strategy also to support research and development for neglected diseases?

    Directory of Open Access Journals (Sweden)

    Angela Fehr

    2014-07-01

    Full Text Available Neglected tropical infectious diseases as well as rare diseases are characterized by structural research and development (R&D deficits. The market fails for these disease groups. Consequently, to meet public health and individual patient needs, political decision makers have to develop strategies at national and international levels to make up for this R&D deficit. The German government recently published its first global health strategy. The strategy underlines the German government's commitment to strengthening global health governance. We find, however, that the strategy lacks behind the international public health endeavors for neglected diseases. It fails to make reference to the ongoing debate on a global health agreement. Neither does it outline a comprehensive national strategy to promote R&D into neglected diseases, which would integrate existing R&D activities in Germany and link up to the international debate on sustainable, needs-based R&D and affordable access. This despite the fact that only recently, in a consensus-building process, a National Plan of Action for rare diseases was successfully developed in Germany which could serve as a blueprint for a similar course of action for neglected diseases. We recommend that, without delay, a structured process be initiated in Germany to explore all options to promote R&D for neglected diseases, including a global health agreement.

  2. Re-imagining the future of diagnosis of Neglected Tropical Diseases

    Directory of Open Access Journals (Sweden)

    Rosanna W. Peeling

    Full Text Available Neglected Tropical Diseases (NTDs affect an estimated 1 billion people in 149 countries. The World Health Organization (WHO prioritised 17 NTDs for control and elimination by 2020 and defined a Road Map to help countries reach these goals. Improved diagnostics for NTDs are essential for guiding treatment strategies at different thresholds of control, interruption of transmission, elimination and post-elimination surveillance. While substantial progress has been made in the last decade with chemotherapy, the same cannot be said of diagnostics, largely due to the perceived lack of a commercially viable market for NTD diagnostics.New sample in-answer out nucleic acid amplification technologies that can be performed at the point-of-care offer improved performance over current technologies and the potential to test for multiple pathogens using a single specimen. Finding commonalities for different NTDs in terms of geographic overlap, sentinel populations and treatment strategy will allow NTD programs to leverage these innovations to build cost-effective multiplex surveillance platforms. Connectivity solutions linking data from diagnostic laboratories and POC test readers/devices provide opportunities for automated surveillance systems to make health systems more efficient, improving patient outcomes and assessing impact of interventions in real time. New models of public–private product development partnerships are critical in leveraging diagnostic innovation in other priority area for better diagnosis, control and elimination of NTDs. Keywords: Neglected tropical diseases, Diagnostics, Control, Elimination, Surveillance

  3. Global aspirations, local realities: the role of social science research in controlling neglected tropical diseases.

    Science.gov (United States)

    Bardosh, Kevin

    2014-01-01

    Neglected Tropical Diseases (NTDs) are both drivers and manifestations of poverty and social inequality. Increased advocacy efforts since the mid-2000s have led to ambitious new control and elimination targets set for 2020 by the World Health Organisation. While these global aspirations represent significant policy momentum, there are multifaceted challenges in controlling infectious diseases in resource-poor local contexts that need to be acknowledged, understood and engaged. However a number of recent publications have emphasised the "neglected" status of applied social science research on NTDs. In light of the 2020 targets, this paper explores the social science/NTD literature and unpacks some of the ways in which social inquiry can help support effective and sustainable interventions. Five priority areas are discussed, including on policy processes, health systems capacity, compliance and resistance to interventions, education and behaviour change, and community participation. The paper shows that despite the multifaceted value of having anthropological and sociological perspectives integrated into NTD programmes, contemporary efforts underutilise this potential. This is reflective of the dominance of top-down information flows and technocratic approaches in global health. To counter this tendency, social research needs to be more than an afterthought; integrating social inquiry into the planning, monitoring and evaluating process will help ensure that flexibility and adaptability to local realities are built into interventions. More emphasis on social science perspectives can also help link NTD control to broader social determinants of health, especially important given the major social and economic inequalities that continue to underpin transmission in endemic countries.

  4. Disease ecology, health and the environment: a framework to account for ecological and socio-economic drivers in the control of neglected tropical diseases.

    Science.gov (United States)

    Garchitorena, A; Sokolow, S H; Roche, B; Ngonghala, C N; Jocque, M; Lund, A; Barry, M; Mordecai, E A; Daily, G C; Jones, J H; Andrews, J R; Bendavid, E; Luby, S P; LaBeaud, A D; Seetah, K; Guégan, J F; Bonds, M H; De Leo, G A

    2017-06-05

    Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'. © 2017 The Author(s).

  5. Uncommon and Neglected Venezuelan Viral Diseases: Etiologic Agents, Physiopathological, Clinical and Epidemiological Characteristics

    Directory of Open Access Journals (Sweden)

    Juan C. Gabaldon-Figueira

    2015-10-01

    Full Text Available Abstract (english Viral infectious diseases are common in Venezuela, influenza, dengue, yellow fever, HIV infection, viral Hepatitis, chikungunya fever and many others represent public health problems in the country and therefore, have been well documented. However, other rarer and even unique or lethal viral illnesses present in Venezuela are usually poorly understood or even unknown. This review described Venezuelan Hemorrhagic Fever, Venezuelan Equine Encephalitis, Hantavirus Infections and Mayaro fever, named as neglected diseases, emphasizing the etiologic agents and their most relevant pathogenic mechanisms, clinical and epidemiological characteristics. Although there is not an official report about the re-emergence of these diseases, falling living standards and unsanitary conditions, together with limited accessibility to hygiene products and medical supplies, put us on alert about the re-emergence of these neglected diseases. Resumen (español Las enfermedades infecciosas virales son comunes en Venezuela, influenza, dengue, fiebre amarilla, infección por VIH, hepatitis viral, fiebre chikungunya y muchas otras representan problemas de salud pública en el país y por lo tanto, han sido bien documentadas. Sin embargo, otras enfermedades virales más raras e incluso únicas y letales presentes en Venezuela son generalmente poco estudiadas y hasta desconocidas. Esta revisión describe alguna de estas enfermedades olvidadas tales como la fiebre hemorrágica venezolana, la encefalitis equina venezolana, las infecciones por hantavirus y la fiebre de Mayaro, haciendo hincapié en los agentes etiológicos y en sus mecanismos patogénicos más relevantes, características clínicas y epidemiológicas. Aunque no hay informes oficiales sobre el resurgimiento de estas enfermedades, la caída de los niveles de vida y las condiciones insalubres, junto con el acceso limitado a los productos de higiene y suministros médicos, debe alertar sobre el

  6. Bibliometric study of research and development for neglected diseases in the BRICS.

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    Bai, Jing; Li, Wei; Huang, Yang-Mu; Guo, Yan

    2016-09-06

    Large numbers of people are suffering from a group of diseases that mainly affect developing countries, as there are no available or affordable products for prevention or treatment. Research and development (R&D) for these diseases is still a low priority on the health agenda. Brazil, Russia, India, China and South Africa (BRICS) are quickly growing economies and having more and more positive impact on global health. Additionally, their R&D capacity is believed to be enhanced through decades of investment in education and life science research. The BRICS, as a group of emerging and developing countries, are expected to make greater contributions to solving the problem that mainly affects the entire developing countries community. However, there has been little research to provide a macroscopic overview of BRICS' effort in R&D for neglected diseases. The aim of this study is to investigate scientific production in BRICS countries in this area and their main research hotspots. Global relevant literature was searched without time limits through PubMed and high yield countries were identified using GoPubMed. Literature up to the end of 2013 from the BRICS was obtained and high frequency words were extracted and clustered using Bibliography Item Co-occurrence Mining System 2.0 (BICOMS) and Graphical Clustering Toolkit 1.0 (gCLUTO). In total, 32, 47, 51, 31 and 44 high frequency words from Brazil, Russia, India, China and South Africa respectively were extracted for clustering analysis. The clustering indicated that eight diseases were research hotspots in BRICS countries. India had the most extensive hotspots and Brazil came in second. The other three countries shared common research foci: helminthiasis, Human Immunodeficiency Virus infection and Acquired Immune Deficiency Syndrome (HIV/AIDS) and tuberculosis. Developed countries still make the majority of contributions to R&D on neglected diseases, but BRICS countries are playing a growing role. Instead of the "big

  7. Epidemiology of Tropical Neglected Diseases in Ecuador in the Last 20 Years

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    Cartelle Gestal, Monica; Holban, Alina Maria; Escalante, Santiago; Cevallos, Marcelo

    2015-01-01

    Background Tropical and zoonotic diseases are major problems in developing countries like Ecuador. Poorly designed houses, the high proportion of isolated indigenous population and under developed infrastructure represent a fertile environment for vectors to proliferate. Control campaigns in Ecuador over the years have had varying success, depending on the disease and vectors targeted. Aims In our study we analyse the current situation of some neglected diseases in Ecuador and the efficiency of the control campaigns (by measuring changes in numbers of cases reported) that the Ecuadorian government has been running to limit the spread of these infectious and parasitic diseases. Results Our study reveals that Brucellosis, Chagas Disease, Rabies and Onchocerciasis have been controlled, but small outbreaks are still detected in endemic areas. Leptospirosis and Echinococcosis have been increasing steadily in recent years in Ecuador since the first records. The same increase has been reported world-wide also. Better diagnosis has resulted in a higher number of cases being identified, particularly with regard to the linking of outdoor activities and contact with farm animals as contributing vectors. Improvements in diagnosis are due to regular professional training, implementation of automatized systems, establishing diagnosis protocols and the creation of an epidemiological vigilance network that acts as soon as a case is reported. Conclusion Control campaigns performed in Ecuador have been successful in recent years, although natural phenomena limit their efficiency. Leptospirosis and Echinococcosis infections remain a growing problem in Ecuador as it is worldwide. PMID:26394405

  8. Epidemiology of Tropical Neglected Diseases in Ecuador in the Last 20 Years.

    Science.gov (United States)

    Cartelle Gestal, Monica; Holban, Alina Maria; Escalante, Santiago; Cevallos, Marcelo

    2015-01-01

    Tropical and zoonotic diseases are major problems in developing countries like Ecuador. Poorly designed houses, the high proportion of isolated indigenous population and under developed infrastructure represent a fertile environment for vectors to proliferate. Control campaigns in Ecuador over the years have had varying success, depending on the disease and vectors targeted. In our study we analyse the current situation of some neglected diseases in Ecuador and the efficiency of the control campaigns (by measuring changes in numbers of cases reported) that the Ecuadorian government has been running to limit the spread of these infectious and parasitic diseases. Our study reveals that Brucellosis, Chagas Disease, Rabies and Onchocerciasis have been controlled, but small outbreaks are still detected in endemic areas. Leptospirosis and Echinococcosis have been increasing steadily in recent years in Ecuador since the first records. The same increase has been reported world-wide also. Better diagnosis has resulted in a higher number of cases being identified, particularly with regard to the linking of outdoor activities and contact with farm animals as contributing vectors. Improvements in diagnosis are due to regular professional training, implementation of automatized systems, establishing diagnosis protocols and the creation of an epidemiological vigilance network that acts as soon as a case is reported. Control campaigns performed in Ecuador have been successful in recent years, although natural phenomena limit their efficiency. Leptospirosis and Echinococcosis infections remain a growing problem in Ecuador as it is worldwide.

  9. Mining SNPs in extracellular vesicular transcriptome of Trypanosoma cruzi: a step closer to early diagnosis of neglected Chagas disease.

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    Gaur, Pallavi; Chaturvedi, Anoop

    2016-01-01

    One of the newest and strongest members of intercellular communicators, the Extracellular vesicles (EVs) and their enclosed RNAs; Extracellular RNAs (exRNAs) have been acknowledged as putative biomarkers and therapeutic targets for various diseases. Although a very deep insight has not been possible into the physiology of these vesicles, they are believed to be involved in cell-to-cell communication and host-pathogen interactions. EVs might be significantly helpful in discovering biomarkers for possible target identification as well as prognostics, diagnostics and developing vaccines. In recent studies, highly bioactive EVs have drawn attention of parasitologists for being able to communicate between different cells and having likeliness of reflecting both source and target environments. Next-generation sequencing (NGS) has eased the way to have a deeper insight into these vesicles and their roles in various diseases. This article arises from bioinformatics-based analysis and predictive data mining of transcriptomic (RNA-Seq) data of EVs, derived from different life stages of Trypanosoma cruzi ; a causing agent of neglected Chagas disease. Variants (Single Nucleotide Polymorphisms (SNPs)) were mined from Extracellular vesicular transcriptomic data and functionally analyzed using different bioinformatics based approaches. Functional analysis showed the association of these variants with various important factors like Trans-Sialidase (TS), Alpha Tubulin, P-Type H+-ATPase, etc. which, in turn, are associated with disease in different ways. Some of the 'candidate SNPs' were found to be stage-specific, which strengthens the probability of finding stage-specific biomarkers. These results may lead to a better understanding of Chagas disease, and improved knowledge may provide further development of the biomarkers for prognosis, diagnosis and drug development for treating Chagas disease.

  10. Mining SNPs in extracellular vesicular transcriptome of Trypanosoma cruzi: a step closer to early diagnosis of neglected Chagas disease

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    Pallavi Gaur

    2016-11-01

    Full Text Available One of the newest and strongest members of intercellular communicators, the Extracellular vesicles (EVs and their enclosed RNAs; Extracellular RNAs (exRNAs have been acknowledged as putative biomarkers and therapeutic targets for various diseases. Although a very deep insight has not been possible into the physiology of these vesicles, they are believed to be involved in cell-to-cell communication and host-pathogen interactions. EVs might be significantly helpful in discovering biomarkers for possible target identification as well as prognostics, diagnostics and developing vaccines. In recent studies, highly bioactive EVs have drawn attention of parasitologists for being able to communicate between different cells and having likeliness of reflecting both source and target environments. Next-generation sequencing (NGS has eased the way to have a deeper insight into these vesicles and their roles in various diseases. This article arises from bioinformatics-based analysis and predictive data mining of transcriptomic (RNA-Seq data of EVs, derived from different life stages of Trypanosoma cruzi; a causing agent of neglected Chagas disease. Variants (Single Nucleotide Polymorphisms (SNPs were mined from Extracellular vesicular transcriptomic data and functionally analyzed using different bioinformatics based approaches. Functional analysis showed the association of these variants with various important factors like Trans-Sialidase (TS, Alpha Tubulin, P-Type H+-ATPase, etc. which, in turn, are associated with disease in different ways. Some of the ‘candidate SNPs’ were found to be stage-specific, which strengthens the probability of finding stage-specific biomarkers. These results may lead to a better understanding of Chagas disease, and improved knowledge may provide further development of the biomarkers for prognosis, diagnosis and drug development for treating Chagas disease.

  11. The potential of positive deviance approach for the sustainable control of neglected tropical diseases.

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    Ong, Ken Ing Cherng; Araki, Hitomi; Kano, Shigeyuki; Jimba, Masamine

    2016-01-01

    Neglected tropical diseases (NTDs) have gained much attention in recent years due to the support from various agencies. However, the main approach to combat NTDs has been to cure rather than to prevent. As many NTD infections are closely linked with human behaviors such as hygienic practices and tradition, behavior change is also very crucial to prevent relapse or reinfection. Therefore, we would like to suggest a potential new approach-the positive deviance approach-to tackle NTDs by focusing on the preventive phase. What makes this approach unique is that the solution comes from the affected population themselves and not from the expert outsiders. Preventive chemotherapy that relies on outside aid has serious sustainability issues as reinfection is also high after the aid program has ended. Learning from the success story in Vietnam on preventing childhood malnutrition, the positive deviance approach could end the spread of NTDs once and for all by making full use of the available local solutions.

  12. Leaving no one behind: a neglected tropical disease indicator and tracers for the Sustainable Development Goals.

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    Fitzpatrick, Christopher; Engels, Dirk

    2016-03-01

    The Sustainable Development Goals (SDGs) have emerged as a global pledge to 'leave no one behind'. Under SDG 3, 'Ensure healthy lives and promote wellbeing for all', target 3.3 extends the Millennium Development Goals (MDGs) beyond HIV, TB and malaria to 'end the epidemic' of neglected tropical diseases (NTDs) by 2030. Other targets are also relevant to NTDs, especially 3.8 (Universal Health Coverage), 6.1 (water) and 6.2 (sanitation). This commentary summarises the proposed NTD indicator (3.3) and tracers (3.8 and 6.1/6.2). These will help ensure that the world's poorest and most marginalized people are prioritized at every step on the path towards SDG targets. © The author 2016. The World Health Organization has granted Oxford University Press permission for the reproduction of this article..

  13. Drug and xenobiotic biotransformation in the blood-brain barrier: A neglected issue.

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    José A.G. Agúndez

    2014-10-01

    Full Text Available Drug biotransformation is a crucial mechanism for facilitating the elimination of chemicals from the organism and for decreasing their pharmacological activity. Published evidence suggests that brain drug metabolism may play a role in the development of adverse drug reactions and in the clinical response to drugs and xenobiotics. The blood-brain barrier (BBB has been regarded mainly as a physical barrier for drugs and xenobiotics, and little attention has been paid to BBB as a drug-metabolizing barrier. The presence of drug metabolizing enzymes in the BBB is likely to have functional implications because local metabolism may inactivate drugs or may modify the drug's ability to cross the BBB, thus modifying the drug response and the risk of developing adverse drug reactions. In this perspective paper, we discuss the expression of relevant xenobiotic metabolizing enzymes in the brain and in the BBB, and we cover current advances and future directions on the potential role of these BBB drug-metabolizing enzymes as modifiers of drug response.

  14. Interactions between Global Health Initiatives and country health systems: the case of a neglected tropical diseases control program in Mali.

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    Cavalli, Anna; Bamba, Sory I; Traore, Mamadou N; Boelaert, Marleen; Coulibaly, Youssouf; Polman, Katja; Pirard, Marjan; Van Dormael, Monique

    2010-08-17

    Recently, a number of Global Health Initiatives (GHI) have been created to address single disease issues in low-income countries, such as poliomyelitis, trachoma, neonatal tetanus, etc.. Empirical evidence on the effects of such GHIs on local health systems remains scarce. This paper explores positive and negative effects of the Integrated Neglected Tropical Disease (NTD) Control Initiative, consisting in mass preventive chemotherapy for five targeted NTDs, on Mali's health system where it was first implemented in 2007. Campaign processes and interactions with the health system were assessed through participant observation in two rural districts (8 health centres each). Information was complemented by interviews with key informants, website search and literature review. Preliminary results were validated during feedback sessions with Malian authorities from national, regional and district levels. We present positive and negative effects of the NTD campaign on the health system using the WHO framework of analysis based on six interrelated elements: health service delivery, health workforce, health information system, drug procurement system, financing and governance. At point of delivery, campaign-related workload severely interfered with routine care delivery which was cut down or totally interrupted during the campaign, as nurses were absent from their health centre for campaign-related activities. Only 2 of the 16 health centres, characterized by a qualified, stable and motivated workforce, were able to keep routine services running and to use the campaign as an opportunity for quality improvement. Increased workload was compensated by allowances, which significantly improved staff income, but also contributed to divert attention away from core routine activities. While the campaign increased the availability of NTD drugs at country level, parallel systems for drug supply and evaluation requested extra efforts burdening local health systems. The campaign budget

  15. Interactions between Global Health Initiatives and country health systems: the case of a neglected tropical diseases control program in Mali.

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    Anna Cavalli

    Full Text Available BACKGROUND: Recently, a number of Global Health Initiatives (GHI have been created to address single disease issues in low-income countries, such as poliomyelitis, trachoma, neonatal tetanus, etc.. Empirical evidence on the effects of such GHIs on local health systems remains scarce. This paper explores positive and negative effects of the Integrated Neglected Tropical Disease (NTD Control Initiative, consisting in mass preventive chemotherapy for five targeted NTDs, on Mali's health system where it was first implemented in 2007. METHODS AND FINDINGS: Campaign processes and interactions with the health system were assessed through participant observation in two rural districts (8 health centres each. Information was complemented by interviews with key informants, website search and literature review. Preliminary results were validated during feedback sessions with Malian authorities from national, regional and district levels. We present positive and negative effects of the NTD campaign on the health system using the WHO framework of analysis based on six interrelated elements: health service delivery, health workforce, health information system, drug procurement system, financing and governance. At point of delivery, campaign-related workload severely interfered with routine care delivery which was cut down or totally interrupted during the campaign, as nurses were absent from their health centre for campaign-related activities. Only 2 of the 16 health centres, characterized by a qualified, stable and motivated workforce, were able to keep routine services running and to use the campaign as an opportunity for quality improvement. Increased workload was compensated by allowances, which significantly improved staff income, but also contributed to divert attention away from core routine activities. While the campaign increased the availability of NTD drugs at country level, parallel systems for drug supply and evaluation requested extra efforts

  16. Can Neglected Tropical Diseases Compromise Human Wellbeing in Sex-, Age-, and Trait-Specific Ways?

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    David C Geary

    2016-04-01

    Full Text Available Traits that facilitate competition for reproductive resources or that influence mate choice have evolved to signal resilience to infectious disease and other stressors. As a result, the dynamics of competition and choice can, in theory, be used to generate predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species, including humans. These dynamics and associated vulnerabilities are reviewed for nonhuman species, focusing on traits that are compromised by exposure to parasites. Using the same approach, sex-, age-, and trait-specific vulnerabilities to parasitic disease are illustrated for children's and adolescent's physical growth and fitness. Suggestions are then provided for widening the assessment of human vulnerabilities to include age-appropriate measures of behavioral (e.g., children's play and cognitive (e.g., language fluency traits. These are traits that are likely to be compromised by infection in age- and sex-specific ways. Inclusion of these types of measures in studies of neglected tropic diseases has the potential to provide a more nuanced understanding of how these diseases undermine human wellbeing and may provide a useful means to study the efficacy of associated treatments.

  17. Search for Antiprotozoal Activity in Herbal Medicinal Preparations; New Natural Leads against Neglected Tropical Diseases

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    Núria Llurba Montesino

    2015-08-01

    Full Text Available Sleeping sickness, Chagas disease, Leishmaniasis, and Malaria are infectious diseases caused by unicellular eukaryotic parasites (“protozoans”. The three first mentioned are classified as Neglected Tropical Diseases (NTDs by the World Health Organization and together threaten more than one billion lives worldwide. Due to the lack of research interest and the high increase of resistance against the existing treatments, the search for effective and safe new therapies is urgently required. In view of the large tradition of natural products as sources against infectious diseases [1,2], the aim of the present study is to investigate the potential of legally approved and marketed herbal medicinal products (HMPs as antiprotozoal agents. Fifty-eight extracts from 53 HMPs on the German market were tested by a Multiple-Target-Screening (MTS against parasites of the genera Leishmania, Trypanosoma, and Plasmodium. Sixteen HMPs showed in vitro activity against at least one of the pathogens (IC50 < 10 µg/mL. Six extracts from preparations of Salvia, Valeriana, Hypericum, Silybum, Arnica, and Curcuma exhibited high activity (IC50 < 2.5 µg/mL. They were analytically characterized by UHPLC/ESI-QqTOF-MSMS and the activity-guided fractionation of the extracts with the aim to isolate and identify the active compounds is in progress.

  18. Dynamics of socioeconomic risk factors for neglected tropical diseases and malaria in an armed conflict.

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    Thomas Fürst

    Full Text Available BACKGROUND: Armed conflict and war are among the leading causes of disability and premature death, and there is a growing share of civilians killed or injured during armed conflicts. A major part of the civilian suffering stems from indirect effects or collateral impact such as changing risk profiles for infectious diseases. We focused on rural communities in the western part of Côte d'Ivoire, where fighting took place during the Ivorian civil war in 2002/2003, and assessed the dynamics of socioeconomic risk factors for neglected tropical diseases (NTDs and malaria. METHODOLOGY: The same standardized and pre-tested questionnaires were administered to the heads of 182 randomly selected households in 25 villages in the region of Man, western Côte d'Ivoire, shortly before and after the 2002/2003 armed conflict. PRINCIPAL FINDINGS: There was no difference in crowding as measured by the number of individuals per sleeping room, but the inadequate sanitation infrastructure prior to the conflict further worsened, and the availability and use of protective measures against mosquito bites and accessibility to health care infrastructure deteriorated. Although the direct causal chain between these findings and the conflict are incomplete, partially explained by the very nature of working in conflict areas, the timing and procedures of the survey, other sources and anecdotal evidence point toward a relationship between an increased risk of suffering from NTDs and malaria and armed conflict. CONCLUSION: New research is needed to deepen our understanding of the often diffuse and neglected indirect effects of armed conflict and war, which may be worse than the more obvious, direct effects.

  19. Disregard of neurological impairments associated with neglected tropical diseases in Africa

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    Emmanuel Quansah

    2016-06-01

    Full Text Available Neglected tropical diseases (NTDs affect people in the bottom billion poorest in the world. These diseases are concentrated in rural areas, conflict zones and urban slums in Africa and other tropical areas. While the World Health Organization recognizes seventeen priority NTDs, the list of conditions present in Africa and elsewhere that are eligible to be classified as NTDs is much longer. Although NTDs are generally marginalized, their associated neurological burden has been almost completely disregarded. However, reports indicate that trichuriasis, schistosomiasis and hookworm infection, among others, cause impairments in memory and cognition, negatively affecting school attendance rates and educational performance particularly among children, as well as agricultural productivity among adults. Consequently, the neurological impairments have substantial influence on education and economic productivity, thus aggravating and perpetuating poverty in affected societies. However, inadequate research, policy and public health attention has been paid to the neurological burdens associated with NTDs. In order to appropriately address these burdens, we recommend the development of policy interventions that focus on the following areas: (i the introduction of training programs to develop the capacity of scientists and clinicians in research, diagnostic and treatment approaches (ii the establishment of competitive research grant schemes to fund cutting-edge research into these neurological impairments, and (iii the development of public health interventions to improve community awareness of the NTD-associated neurological problems, possibly enhancing disease prevention and expediting treatment.

  20. Rare diseases and orphan drugs

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    Domenica Taruscio

    2011-01-01

    Full Text Available According to the Regulation (EC N. 141/2000 of the European Parliament and of the Council, rare diseases are life-threatening or chronically debilitating conditions, affecting no more than 5 in 10 000 persons in the European Community. It is estimated that between 6000 to 8000 distinct rare diseases affect up to 6% of the total EU population. Therefore, these conditions can be considered rare if taken individually but they affect a significant proportion of the European population when considered as a single group. Several initiatives have been undertaken at international, European and national level to tackle public health as well as research issues related to the prevention, diagnosis, treatment and surveillance of these diseases. The development of innovative and effective medical products for their diagnosis and treatment is frequently hampered by several factors, including the limited knowledge of their natural history, the difficulties in setting up clinical studies due to the limited numbers of patients affected by a specific disease, the weak interest of sponsors due to the restricted market opportunities. Therefore, incentives and other facilitations have been adopted in many parts of the world, including in the EU, in order to facilitate the development and commercialization of diagnostic tools and treatments devoted to rare diseases. This paper illustrates mainly the European initiatives and will discuss the problematic and controversial aspects surrounding orphan drugs. Finally, activities and measures adopted in Italy are presented.

  1. Neglected tropical diseases in Brazilian children and adolescents: data analysis from 2009 to 2013.

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    Brandão, Eduardo; Romero, Sebastián; da Silva, Maria Almerice Lopes; Santos, Fred Luciano Neves

    2017-11-03

    Neglected tropical diseases (NTDs) prevail in conditions of poverty and contribute to the maintenance of social inequality. Out of the NTDs prioritized by the Brazilian Ministry of Health, four parasitic infections require mandatory notification: acute Chagas disease, leishmaniasis, malaria, and schistosomiasis. Data on the behaviour of these NTDs in the young population are currently limited. This study seeks to analyse the epidemiological aspects of these parasitic infections in children and adolescents in Brazil. A retrospective exploratory ecological study was conducted. A spatial analysis of the cases reported between 2009 and 2013 in individuals aged between 0 and 19 years that were notified through the Health Notification Aggravation Information System (SINAN) was performed. In total, 64,567 cases of cutaneous and visceral leishmaniasis, malaria, schistosomiasis, and acute Chagas disease were recorded in the SINAN database, representing a rate of 20.15 cases per 100,000 inhabitants. The average age of the cases was 12.2 years and 62.32% were male. Four hundred and three deaths related to these obligatorily reported parasites were recorded, indicating a case fatality rate of 0.62%. Visceral leishmaniasis and acute Chagas disease had the highest rates of lethality. A heterogeneous spatial distribution of the studied parasites was observed. The number of cases and the lethality rate described in this study show that these diseases still represent a serious problem for public health in Brazil. This points to the need to encourage new research and the reformulation of social, economic, and public health policies aimed at ensuring better health and living conditions for all individuals, especially those among the populations considered vulnerable, as is the case of the young.

  2. Zika virus infection and once again the risk from other neglected diseases.

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    Porrino, Pedro

    2016-07-01

    Since the first cases of Zika were identified and reported in Brazil, the magnitude and consequences of the outbreak in the Americas have increased tremendously, leading the World Health Organization to consider Zika and its link with clusters of microcephaly a Public Health Emergency of International Concern. Only a previous large outbreak in French Polynesia was known and no neurological anomalies have been reported. Differences in African and Asian lineage and differences in genetic evolution of the Zika virus may possibly provide an explanation for the development of the recent outbreaks and their variable presentation. However, the similar clinical presentation between Zika and other diseases like Dengue and Chikungunya can support that Zika has been circulating and spreading inadvertently. This hypothesis gains strength when rates of laboratory confirmation diagnosis for Dengue are observed in Brazil and Colombia, two of the most affected countries by Zika virus (ZIKV) infection.The lack of attention and resources on neglected diseases supposes a huge risk that new lethal pathogens camouflage themselves to spread into large areas and populations. © The Author(s) 2016.

  3. Socio-ecological dynamics and challenges to the governance of Neglected Tropical Disease control.

    Science.gov (United States)

    Michael, Edwin; Madon, Shirin

    2017-02-06

    The current global attempts to control the so-called "Neglected Tropical Diseases (NTDs)" have the potential to significantly reduce the morbidity suffered by some of the world's poorest communities. However, the governance of these control programmes is driven by a managerial rationality that assumes predictability of proposed interventions, and which thus primarily seeks to improve the cost-effectiveness of implementation by measuring performance in terms of pre-determined outputs. Here, we argue that this approach has reinforced the narrow normal-science model for controlling parasitic diseases, and in doing so fails to address the complex dynamics, uncertainty and socio-ecological context-specificity that invariably underlie parasite transmission. We suggest that a new governance approach is required that draws on a combination of non-equilibrium thinking about the operation of complex, adaptive, systems from the natural sciences and constructivist social science perspectives that view the accumulation of scientific knowledge as contingent on historical interests and norms, if more effective control approaches sufficiently sensitive to local disease contexts are to be devised, applied and managed. At the core of this approach is an emphasis on the need for a process that assists with the inclusion of diverse perspectives, social learning and deliberation, and a reflexive approach to addressing system complexity and incertitude, while balancing this flexibility with stability-focused structures. We derive and discuss a possible governance framework and outline an organizational structure that could be used to effectively deal with the complexity of accomplishing global NTD control. We also point to examples of complexity-based management structures that have been used in parasite control previously, which could serve as practical templates for developing similar governance structures to better manage global NTD control. Our results hold important wider

  4. The field-testing of a novel integrated mapping protocol for neglected tropical diseases.

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    Sonia Pelletreau

    2011-11-01

    Full Text Available BACKGROUND: Vertical control and elimination programs focused on specific neglected tropical diseases (NTDs can achieve notable success by reducing the prevalence and intensity of infection. However, many NTD-endemic countries have not been able to launch or scale-up programs because they lack the necessary baseline data for planning and advocacy. Each NTD program has its own mapping guidelines to collect missing data. Where geographic overlap among NTDs exists, an integrated mapping approach could result in significant resource savings. We developed and field-tested an innovative integrated NTD mapping protocol (Integrated Threshold Mapping (ITM Methodology for lymphatic filariasis (LF, trachoma, schistosomiasis and soil-transmitted helminths (STH. METHODOLOGY/PRINCIPAL FINDINGS: The protocol is designed to be resource-efficient, and its specific purpose is to determine whether a threshold to trigger public health interventions in an implementation unit has been attained. The protocol relies on World Health Organization (WHO recommended indicators in the disease-specific age groups. For each disease, the sampling frame was the district, but for schistosomiasis, the sub-district rather than the ecological zone was used. We tested the protocol by comparing it to current WHO mapping methodologies for each of the targeted diseases in one district each in Mali and Senegal. Results were compared in terms of public health intervention, and feasibility, including cost. In this study, the ITM methodology reached the same conclusions as the WHO methodologies regarding the initiation of public health interventions for trachoma, LF and STH, but resulted in more targeted intervention recommendations for schistosomiasis. ITM was practical, feasible and demonstrated an overall cost saving compared with the standard, non-integrated, WHO methodologies. CONCLUSIONS/SIGNIFICANCE: This integrated mapping tool could facilitate the implementation of much

  5. Emerging and Reemerging Neglected Tropical Diseases: a Review of Key Characteristics, Risk Factors, and the Policy and Innovation Environment

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    Liang, Bryan A.; Cuomo, Raphael; Hafen, Ryan; Brouwer, Kimberly C.; Lee, Daniel E.

    2014-01-01

    SUMMARY In global health, critical challenges have arisen from infectious diseases, including the emergence and reemergence of old and new infectious diseases. Emergence and reemergence are accelerated by rapid human development, including numerous changes in demographics, populations, and the environment. This has also led to zoonoses in the changing human-animal ecosystem, which are impacted by a growing globalized society where pathogens do not recognize geopolitical borders. Within this context, neglected tropical infectious diseases have historically lacked adequate attention in international public health efforts, leading to insufficient prevention and treatment options. This subset of 17 infectious tropical diseases disproportionately impacts the world's poorest, represents a significant and underappreciated global disease burden, and is a major barrier to development efforts to alleviate poverty and improve human health. Neglected tropical diseases that are also categorized as emerging or reemerging infectious diseases are an even more serious threat and have not been adequately examined or discussed in terms of their unique risk characteristics. This review sets out to identify emerging and reemerging neglected tropical diseases and explore the policy and innovation environment that could hamper or enable control efforts. Through this examination, we hope to raise awareness and guide potential approaches to addressing this global health concern. PMID:25278579

  6. Therapeutic Drug Monitoring in Rheumatic Diseases

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    NG Hoi-Yan Alexandra

    2016-12-01

    Full Text Available The ultimate goal of treating rheumatic disease is to achieve rapid suppression of inflammation, while at the same time minimizing the toxicities from rheumatic drugs. Different patients have different individual pharmacokinetics that can affect the drug level. Moreover, different factors, such as renal function, age or even different underlying diseases, can affect the drug level. Therefore, giving the same dosage of drugs to different patients may result in different drug levels. This article will review the usefulness of therapeutic drug monitoring in maximizing drug efficacy, while reducing the risk of toxicities in Hydroxychloroquine, Mycophenolate Mofetil, Tacrolimus and Tumor Necrosis Factor inhibitors (TNF Inhibitors.

  7. The burden of neglected tropical diseases in Ethiopia, and opportunities for integrated control and elimination

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    Deribe Kebede

    2012-10-01

    Full Text Available Abstract Background Neglected tropical diseases (NTDs are a group of chronic parasitic diseases and related conditions that are the most common diseases among the 2·7 billion people globally living on less than US$2 per day. In response to the growing challenge of NTDs, Ethiopia is preparing to launch a NTD Master Plan. The purpose of this review is to underscore the burden of NTDs in Ethiopia, highlight the state of current interventions, and suggest ways forward. Results This review indicates that NTDs are significant public health problems in Ethiopia. From the analysis reported here, Ethiopia stands out for having the largest number of NTD cases following Nigeria and the Democratic Republic of Congo. Ethiopia is estimated to have the highest burden of trachoma, podoconiosis and cutaneous leishmaniasis in sub-Saharan Africa (SSA, the second highest burden in terms of ascariasis, leprosy and visceral leishmaniasis, and the third highest burden of hookworm. Infections such as schistosomiasis, trichuriasis, lymphatic filariasis and rabies are also common. A third of Ethiopians are infected with ascariasis, one quarter is infected with trichuriasis and one in eight Ethiopians lives with hookworm or is infected with trachoma. However, despite these high burdens of infection, the control of most NTDs in Ethiopia is in its infancy. In terms of NTD control achievements, Ethiopia reached the leprosy elimination target of 1 case/10,000 population in 1999. No cases of human African trypanosomiasis have been reported since 1984. Guinea worm eradication is in its final phase. The Onchocerciasis Control Program has been making steady progress since 2001. A national blindness survey was conducted in 2006 and the trachoma program has kicked off in some regions. Lymphatic Filariasis, podoconiosis and rabies mapping are underway. Conclusion Ethiopia bears a significant burden of NTDs compared to other SSA countries. To achieve success in integrated control of

  8. "English Disease": Historical Notes on Rickets, the Bone-Lung Link and Child Neglect Issues.

    Science.gov (United States)

    Zhang, Mingyong; Shen, Fan; Petryk, Anna; Tang, Jingfeng; Chen, Xingzhen; Sergi, Consolato

    2016-11-15

    Nutritional or classical rickets (here labeled as "rickets") is a worldwide disease involving mostly infants and young children having inadequate sunlight exposure, often associated with a low dietary intake of Vitamin D. Rickets targets all layers of society independently of economic status with historical information spanning more than two millennia. Vitamin D is critical for the absorption of calcium and prevention of rickets in children as well as osteomalacia in adults. The initial and misleading paradigm of the 19th and 20th centuries that rickets may have been the consequence of infection has been, indeed, reversed following the identification of the Vitamin D molecule's important role in the function of the immune system. Although traditionally considered limited to osteopathology, Vitamin D deficiency is now known to be linked to infection, inflammation, and carcinogenesis. In this review, we consider the key historical (Whistler, pre-Whistler and post-Whistler descriptors) and social facts around rickets; highlight the osteo-pathological features of rickets and the pathology of the upper and lower respiratory tract, stressing the fact that lungs remain the main secondary organ affected by Vitamin D deficiency; and emphasize the public health role in identifying the cases of child neglect or abuse based on the evaluation of the costochondral region.

  9. How to deal with neglected tropical diseases in the light of an African ethic.

    Science.gov (United States)

    Metz, Thaddeus

    2017-11-07

    Many countries in Africa, and more generally those in the Global South with tropical areas, are plagued by illnesses that the wealthier parts of the world (mainly 'the West') neither suffer from nor put systematic effort into preventing, treating or curing. What does an ethic with a recognizably African pedigree entail for the ways various agents ought to respond to such neglected diseases? As many readers will know, a characteristically African ethic prescribes weighty duties to aid on the part of those in a position to do so, and it therefore entails that there should have been much more contribution from the Western, 'developed' world. However, what else does it prescribe, say, on the part of sub-Saharan governments and the African Union, and are they in fact doing it? I particularly seek to answer these questions here, by using the 2013-16 Ebola crisis in West Africa to illustrate what should have happened but what by and large did not. © 2017 John Wiley & Sons Ltd.

  10. Immunotherapy and immunochemotherapy in visceral leishmaniasis: promising treatments for this neglected disease

    Directory of Open Access Journals (Sweden)

    Bruno Mendes Roatt

    2014-06-01

    Full Text Available Leishmaniasis has several clinical forms: self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; and visceral leishmaniasis, which is fatal if left untreated. The epidemiology and clinical features of VL vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. HIV infection, augments the severity of VL increasing the risk of developing active disease by 100 to 2320 times. An effective vaccine for humans is not yet available. Resistance to chemotherapy is a growing problem in many regions, and the costs associated with drug identification and development, make commercial production for leishmaniasis, unattractive. The toxicity of currently drugs, their long treatment course, and limited efficacy are significant concerns. For cutaneous disease, many studies have shown promising results with immunotherapy/immunochemotherapy, aimed to modulate and activate the immune response to obtain a therapeutic cure. Nowadays, the focus of many groups centers on treating canine VL by using vaccines and immunomodulators with or without chemotherapy. In human disease, the use of cytokines like Interferon-γ associated with pentavalent antimonials demonstrated promising results in patients that did not respond to conventional treatment. In mice, immunomodulation based on monoclonal antibodies to remove endogenous immunosuppressive cytokines (interleukin-10 or block their receptors, antigen-pulsed syngeneic dendritic cells, or biological products like Pam3Cys (TLR ligand has already been shown as a prospective treatment of the disease. This review addresses VL treatment, particularly immunotherapy and/or immunochemotherapy as an alternative to conventional drug treatment in experimental models, canine VL, and human disease.

  11. Neglected Parasitic Infections: Toxocariasis

    Centers for Disease Control (CDC) Podcasts

    This podcast is an overview of the Clinician Outreach and Communication Activity (COCA) Call: Neglected Parasitic Infections in the United States. Neglected Parasitic Infections are a group of diseases that afflict vulnerable populations and are often not well studied or diagnosed. A subject matter expert from CDC's Division of Parasitic Diseases and Malaria describes the epidemiology, diagnosis, and treatment of toxocariasis.

  12. The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases.

    Directory of Open Access Journals (Sweden)

    William K Redekop

    2017-01-01

    Full Text Available Lymphatic filariasis (LF, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH and trachoma represent the five most prevalent neglected tropical diseases (NTDs. They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA-also named Preventive Chemotherapy (PCT. The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments.Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010. Sensitivity analyses were used to assess the influence of changes in input parameters.The economic benefit from productivity gain was estimated to be I$251 billion in 2011-2020 and I$313 billion in 2021-2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss.Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large uncertainty, these benefits far exceed the

  13. The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases.

    Science.gov (United States)

    Redekop, William K; Lenk, Edeltraud J; Luyendijk, Marianne; Fitzpatrick, Christopher; Niessen, Louis; Stolk, Wilma A; Tediosi, Fabrizio; Rijnsburger, Adriana J; Bakker, Roel; Hontelez, Jan A C; Richardus, Jan H; Jacobson, Julie; de Vlas, Sake J; Severens, Johan L

    2017-01-01

    Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)-also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010). Sensitivity analyses were used to assess the influence of changes in input parameters. The economic benefit from productivity gain was estimated to be I$251 billion in 2011-2020 and I$313 billion in 2021-2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss. Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large uncertainty, these benefits far exceed the investment

  14. Drug development for airway diseases: looking forward

    NARCIS (Netherlands)

    Holgate, Stephen; Agusti, Alvar; Strieter, Robert M.; Anderson, Gary P.; Fogel, Robert; Bel, Elisabeth; Martin, Thomas R.; Reiss, Theodore F.

    2015-01-01

    Advancing drug development for airway diseases beyond the established mechanisms and symptomatic therapies requires redefining the classifications of airway diseases, considering systemic manifestations, developing new tools and encouraging collaborations

  15. The monetary value of human lives lost due to neglected tropical diseases in Africa.

    Science.gov (United States)

    Kirigia, Joses Muthuri; Mburugu, Gitonga N

    2017-12-18

    Neglected tropical diseases (NTDs) are an important cause of death and disability in Africa. This study estimates the monetary value of human lives lost due to NTDs in the continent in 2015. The lost output or human capital approach was used to evaluate the years of life lost due to premature deaths from NTDs among 10 high/upper-middle-income (Group 1), 17 middle-income (Group 2) and 27 low-income (Group 3) countries in Africa. The future losses were discounted to their present values at a 3% discount rate. The model was re-analysed using 5% and 10% discount rates to assess the impact on the estimated total value of human lives lost. The estimated value of 67 860 human lives lost in 2015 due to NTDs was Int$ 5 112 472 607. Out of that, 14.6% was borne by Group 1, 57.7% by Group 2 and 27.7% by Group 3 countries. The mean value of human life lost per NTD death was Int$ 231 278, Int$ 109 771 and Int$ 37 489 for Group 1, Group 2 and Group 3 countries, respectively. The estimated value of human lives lost in 2015 due to NTDs was equivalent to 0.1% of the cumulative gross domestic product of the 53 continental African countries. Even though NTDs are not a major cause of death, they impact negatively on the productivity of those affected throughout their life-course. Thus, the case for investing in NTDs control should also be influenced by the value of NTD morbidity, availability of effective donated medicines, human rights arguments, and need to achieve the NTD-related target 3.3 of the United Nations Sustainable Development Goal 3 (on health) by 2030.

  16. Building local research and development capacity for the prevention and cure of neglected diseases: the case of India.

    Science.gov (United States)

    Kettler, H E; Modi, R

    2001-01-01

    This paper examines the proposal to build research and development (R&D) capabilities for dealing with neglected infectious and tropical diseases in countries where they are endemic, as a potentially cost- and time-effective way to fill the gap between the supply of and need for new medicines. With reference to the situation in India, we consider the competencies and incentives needed by companies so that their strategy can be shifted from reverse engineering of existing products to investment in R&D for new products. This requires complex reforms, of which the intellectual property rights agreement is only one. We also consider whether Indian companies capable of conducting research and development are likely to target neglected diseases. Patterns of patenting and of R&D, together with evidence from interviews we have conducted, suggest that Indian companies, like multinational corporations, are likely to target global diseases because of the prospect of much greater returns. Further studies are required on how Indian companies would respond to push and pull incentives originally designed to persuade multinational corporations to do more R&D on neglected diseases.

  17. 76 FR 52958 - Draft Guidance for Industry on Neglected Tropical Diseases of the Developing World: Developing...

    Science.gov (United States)

    2011-08-24

    ...: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry... guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug... FURTHER INFORMATION CONTACT: Joseph G. Toerner, Center for Drug Evaluation and Research, Food and Drug...

  18. R&D investments for neglected diseases can be sensitive to the economic goal of pharmaceutical companies.

    Science.gov (United States)

    Dimitri, Nicola

    2012-08-01

    A fundamental problem with neglected diseases is how to induce pharmaceutical companies to invest resources for developing effective treatments. A recent debate focused on the role of economic incentives represented by monetary transfers to the firms. In this article I focus on the economic goals of pharmaceutical companies, as determinants for R&D effort. In particular, within a stylized framework, the work compares expected profit and expected productivity maximization, arguing that the former in general induces higher R&D investments than the latter. Therefore, as it is currently the case, when pharmaceutical firms focus on productivity, appropriate economic incentives might be needed for them to invest in R&D for neglected diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. The cross-cutting contribution of the end of neglected tropical diseases to the sustainable development goals.

    Science.gov (United States)

    Bangert, Mathieu; Molyneux, David H; Lindsay, Steve W; Fitzpatrick, Christopher; Engels, Dirk

    2017-04-04

    The Sustainable Development Goals (SDGs) call for an integrated response, the kind that has defined Neglected Tropical Diseases (NTDs) efforts in the past decade.NTD interventions have the greatest relevance for SDG3, the health goal, where the focus on equity, and its commitment to reaching people in need of health services, wherever they may live and whatever their circumstances, is fundamentally aligned with the target of Universal Health Coverage. NTD interventions, however, also affect and are affected by many of the other development areas covered under the 2030 Agenda. Strategies such as mass drug administration or the programmatic integration of NTD and WASH activities (SDG6) are driven by effective global partnerships (SDG17). Intervention against the NTDs can also have an impact on poverty (SDG1) and hunger (SDG2), can improve education (SDG4), work and economic growth (SDG8), thereby reducing inequalities (SDG10). The community-led distribution of donated medicines to more than 1 billion people reinforces women's empowerment (SDG5), logistics infrastructure (SDG9) and non-discrimination against disability (SDG16). Interventions to curb mosquito-borne NTDs contribute to the goals of urban sustainability (SDG11) and resilience to climate change (SDG13), while the safe use of insecticides supports the goal of sustainable ecosystems (SDG15). Although indirectly, interventions to control water- and animal-related NTDs can facilitate the goals of small-scale fishing (SDG14) and sustainable hydroelectricity and biofuels (SDG7).NTDs proliferate in less developed areas in countries across the income spectrum, areas where large numbers of people have little or no access to adequate health care, clean water, sanitation, housing, education, transport and information. This scoping review assesses how in this context, ending the epidemic of the NTDs can impact and improve our prospects of attaining the SDGs.

  20. Neglected tropical diseases of the Middle East and North Africa: review of their prevalence, distribution, and opportunities for control.

    Directory of Open Access Journals (Sweden)

    Peter J Hotez

    Full Text Available The neglected tropical diseases (NTDs are highly endemic but patchily distributed among the 20 countries and almost 400 million people of the Middle East and North Africa (MENA region, and disproportionately affect an estimated 65 million people living on less than US$2 per day. Egypt has the largest number of people living in poverty of any MENA nation, while Yemen has the highest prevalence of people living in poverty. These two nations stand out for having suffered the highest rates of many NTDs, including the soil-transmitted nematode infections, filarial infections, schistosomiasis, fascioliasis, leprosy, and trachoma, although they should be recognized for recent measures aimed at NTD control. Leishmaniasis, especially cutaneous leishmaniasis, is endemic in Syria, Iran, Iraq, Libya, Morocco, and elsewhere in the region. Both zoonotic (Leishmania major and anthroponotic (Leishmania tropica forms are endemic in MENA in rural arid regions and urban regions, respectively. Other endemic zoonotic NTDs include cystic echinococcosis, fascioliasis, and brucellosis. Dengue is endemic in Saudi Arabia, where Rift Valley fever and Alkhurma hemorrhagic fever have also emerged. Great strides have been made towards elimination of several endemic NTDs, including lymphatic filariasis in Egypt and Yemen; schistosomiasis in Iran, Morocco, and Oman; and trachoma in Morocco, Algeria, Iran, Libya, Oman, Saudi Arabia, Tunisia, and the United Arab Emirates. A particularly noteworthy achievement is the long battle waged against schistosomiasis in Egypt, where prevalence has been brought down by regular praziquantel treatment. Conflict and human and animal migrations are key social determinants in preventing the control or elimination of NTDs in the MENA, while local political will, strengthened international and intersectoral cooperative efforts for surveillance, mass drug administration, and vaccination are essential for elimination.

  1. Historical Perspective and Risk of Multiple Neglected Tropical Diseases in Coastal Tanzania: Compositional and Contextual Determinants of Disease Risk.

    Science.gov (United States)

    Armah, Frederick Ato; Quansah, Reginald; Luginaah, Isaac; Chuenpagdee, Ratana; Hambati, Herbert; Campbell, Gwyn

    2015-01-01

    In the past decade, research on neglected tropical diseases (NTDs) has intensified in response to the need to enhance community participation in health delivery, establish monitoring and surveillance systems, and integrate existing disease-specific treatment programs to control overlapping NTD burdens and detrimental effects. In this paper, we evaluated the geographical distribution of NTDs in coastal Tanzania. We also assessed the collective (compositional and contextual) factors that currently determine risks to multiple NTDs using a cross sectional survey of 1253 individuals in coastal Tanzania. The results show that the effect size in decreasing order of magnitude for non-binary predictors of NTD risks is as follows: NTD comorbidities > poverty > educational attainment > self-reported household quality of life > ethnicity. The multivariate analysis explained 95% of the variance in the relationship between NTD risks and the theoretically-relevant covariates. Compositional (biosocial and sociocultural) factors explained more variance at the neighbourhood level than at the regional level, whereas contextual factors, such as access to health services and household quality, in districts explained a large proportion of variance at the regional level but individually had modest statistical significance, demonstrating the complex interactions between compositional and contextual factors in generating NTD risks. NTD risks were inequitably distributed over geographic space, which has several important policy implications. First, it suggests that localities of high burden of NTDs are likely to diminish within statistical averages at higher (regional or national) levels. Second, it indicates that curative or preventive interventions will become more efficient provided they can be focused on the localities, particularly as populations in these localities are likely to be burdened by several NTDs simultaneously, further increasing the imperative of multi-disease

  2. Historical Perspective and Risk of Multiple Neglected Tropical Diseases in Coastal Tanzania: Compositional and Contextual Determinants of Disease Risk.

    Directory of Open Access Journals (Sweden)

    Frederick Ato Armah

    Full Text Available In the past decade, research on neglected tropical diseases (NTDs has intensified in response to the need to enhance community participation in health delivery, establish monitoring and surveillance systems, and integrate existing disease-specific treatment programs to control overlapping NTD burdens and detrimental effects. In this paper, we evaluated the geographical distribution of NTDs in coastal Tanzania.We also assessed the collective (compositional and contextual factors that currently determine risks to multiple NTDs using a cross sectional survey of 1253 individuals in coastal Tanzania. The results show that the effect size in decreasing order of magnitude for non-binary predictors of NTD risks is as follows: NTD comorbidities > poverty > educational attainment > self-reported household quality of life > ethnicity. The multivariate analysis explained 95% of the variance in the relationship between NTD risks and the theoretically-relevant covariates. Compositional (biosocial and sociocultural factors explained more variance at the neighbourhood level than at the regional level, whereas contextual factors, such as access to health services and household quality, in districts explained a large proportion of variance at the regional level but individually had modest statistical significance, demonstrating the complex interactions between compositional and contextual factors in generating NTD risks.NTD risks were inequitably distributed over geographic space, which has several important policy implications. First, it suggests that localities of high burden of NTDs are likely to diminish within statistical averages at higher (regional or national levels. Second, it indicates that curative or preventive interventions will become more efficient provided they can be focused on the localities, particularly as populations in these localities are likely to be burdened by several NTDs simultaneously, further increasing the imperative of multi-disease

  3. Sexually transmitted diseases among adults who had been abused and neglected as children: a 30-year prospective study.

    Science.gov (United States)

    Wilson, Helen W; Widom, Cathy S

    2009-04-01

    We examined associations between childhood abuse and neglect and the risk in adulthood for sexually transmitted diseases. In a prospective cohort design, we matched children aged 0 to 11 years with documented cases of abuse or neglect during 1967 to 1971 with a control group of children who had not been maltreated (754 participants in all) and followed them into adulthood. Information about lifetime history of sexually transmitted diseases was collected as part of a medical status examination when participants were approximately 41 years old. Childhood sexual abuse increased risk for any sexually transmitted disease (odds ratio [OR] = 1.94; 95% confidence interval [CI] = 1.00, 3.77; P = .05) and more than 1 type of sexually transmitted disease (OR = 3.33; 95% CI = 1.33, 8.22; P = .01). Physical abuse increased risk for more than 1 type of sexually transmitted disease (OR = 3.61; 95% CI = 1.39, 9.38; P = .009). Our results provided the first prospective evidence that child physical and sexual abuse increases risk for sexually transmitted diseases. Early screening and interventions are needed to identify and prevent sexually transmitted diseases among child abuse victims.

  4. Anemia in inflammatory bowel disease: A neglected issue with relevant effects

    Science.gov (United States)

    Guagnozzi, Danila; Lucendo, Alfredo J

    2014-01-01

    Anemia, a common complication associated with inflammatory bowel disease (IBD), is frequently overlooked in the management of IBD patients. Unfortunately, it represents one of the major causes of both decreased quality of life and increased hospital admissions among this population. Anemia in IBD is pathogenically complex, with several factors contributing to its development. While iron deficiency is the most common cause, vitamin B12 and folic acid deficiencies, along with the effects of pro-inflammatory cytokines, hemolysis, drug therapies, and myelosuppression, have also been identified as the underlying etiology in a number of patients. Each of these etiological factors thus needs to be identified and corrected in order to effectively manage anemia in IBD. Because the diagnosis of anemia in IBD often presents a challenge, combinations of several hematimetric and biochemical parameters should be used. Recent studies underscore the importance of determining the ferritin index and hepcidin levels in order to distinguish between iron deficiency anemia, anemia due to chronic disease, or mixed anemia in IBD patients. With regard to treatment, the newly introduced intravenous iron formulations have several advantages over orally-administered iron compounds in treating iron deficiency in IBD. In special situations, erythropoietin supplementation and biological therapies should be considered. In conclusion, the management of anemia is a complex aspect of treating IBD patients, one that significantly influences the prognosis of the disease. As a consequence, its correction should be considered a specific, first-line therapeutic goal in the management of these patients. PMID:24707137

  5. Canada's neglected tropical disease research network: who's in the core-who's on the periphery?

    Directory of Open Access Journals (Sweden)

    Kaye Phillips

    Full Text Available This study designed and applied accessible yet systematic methods to generate baseline information about the patterns and structure of Canada's neglected tropical disease (NTD research network; a network that, until recently, was formed and functioned on the periphery of strategic Canadian research funding.MULTIPLE METHODS WERE USED TO CONDUCT THIS STUDY, INCLUDING: (1 a systematic bibliometric procedure to capture archival NTD publications and co-authorship data; (2 a country-level "core-periphery" network analysis to measure and map the structure of Canada's NTD co-authorship network including its size, density, cliques, and centralization; and (3 a statistical analysis to test the correlation between the position of countries in Canada's NTD network ("k-core measure" and the quantity and quality of research produced.Over the past sixty years (1950-2010, Canadian researchers have contributed to 1,079 NTD publications, specializing in Leishmania, African sleeping sickness, and leprosy. Of this work, 70% of all first authors and co-authors (n = 4,145 have been Canadian. Since the 1990s, however, a network of international co-authorship activity has been emerging, with representation of researchers from 62 different countries; largely researchers from OECD countries (e.g. United States and United Kingdom and some non-OECD countries (e.g. Brazil and Iran. Canada has a core-periphery NTD international research structure, with a densely connected group of OECD countries and some African nations, such as Uganda and Kenya. Sitting predominantly on the periphery of this research network is a cluster of 16 non-OECD nations that fall within the lowest GDP percentile of the network.The publication specialties, composition, and position of NTD researchers within Canada's NTD country network provide evidence that while Canadian researchers currently remain the overall gatekeepers of the NTD research they generate; there is opportunity to leverage

  6. Pediatric Neglected Tropical Diseases in a Major Metropolitan Children's Hospital in the United States, 2004-2013.

    Science.gov (United States)

    Sweet, Leigh R; Palazzi, Debra L

    2016-12-01

    We conducted a retrospective study of neglected tropical diseases (NTDs) diagnosed at Texas Children's Hospital between 2004 and 2013. Forty-three patients with an NTD were identified; 47% had never traveled outside of the United States. The results of this study highlight the importance of physician awareness of NTDs in children in the United States. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Drugs of abuse and Parkinson's disease.

    Science.gov (United States)

    Mursaleen, Leah R; Stamford, Jonathan A

    2016-01-04

    The term "drug of abuse" is highly contextual. What constitutes a drug of abuse for one population of patients does not for another. It is therefore important to examine the needs of the patient population to properly assess the status of drugs of abuse. The focus of this article is on the bidirectional relationship between patients and drug abuse. In this paper we will introduce the dopaminergic systems of the brain in Parkinson's and the influence of antiparkinsonian drugs upon them before discussing this synergy of condition and medication as fertile ground for drug abuse. We will then examine the relationship between drugs of abuse and Parkinson's, both beneficial and deleterious. In summary we will draw the different strands together and speculate on the future merit of current drugs of abuse as treatments for Parkinson's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Sara Tomczyk

    Full Text Available The control of neglected tropical diseases (NTDs has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs.We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM, leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR estimates and corresponding 95% confidence intervals (CIs were calculated as a measure of intervention effect, using random effects meta-analyses.Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29, CLM (OR=0.24; 95% CI: 0.06-0.96, tungiasis (OR=0.42; 95% CI: 0.26-0.70, hookworm infection (OR=0.48; 95

  9. Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis.

    Science.gov (United States)

    Tomczyk, Sara; Deribe, Kebede; Brooker, Simon J; Clark, Hannah; Rafique, Khizar; Knopp, Stefanie; Utzinger, Jürg; Davey, Gail

    2014-01-01

    The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0

  10. Financing drug discovery for orphan diseases

    OpenAIRE

    Fagnan, David Erik; Gromatzky, Austin A.; Stein, Roger Mark; Fernandez, Jose-Maria; Lo, Andrew W.

    2014-01-01

    Recently proposed ‘megafund’ financing methods for funding translational medicine and drug development require billions of dollars in capital per megafund to de-risk the drug discovery process enough to issue long-term bonds. Here, we demonstrate that the same financing methods can be applied to orphan drug development but, because of the unique nature of orphan diseases and therapeutics (lower development costs, faster FDA approval times, lower failure rates and lower correlation of failures...

  11. A prospective examination of the path from child abuse and neglect to illicit drug use in middle adulthood: the potential mediating role of four risk factors.

    Science.gov (United States)

    Wilson, Helen W; Widom, Cathy Spatz

    2009-03-01

    This study examines prostitution, homelessness, delinquency and crime, and school problems as potential mediators of the relationship between childhood abuse and neglect (CAN) and illicit drug use in middle adulthood. Children with documented cases of physical and sexual abuse and neglect (ages 0-11) during 1967-1971 were matched with non-maltreated children and followed into middle adulthood (approximate age 39). Mediators were assessed in young adulthood (approximate age 29) through in-person interviews between 1989 and 1995 and official arrest records through 1994 (N = 1,196). Drug use was assessed via self-reports of past year use of marijuana, psychedelics, cocaine, and/or heroin during 2000-2002 (N = 896). Latent variable structural equation modeling (SEM) was used to test: (1) a four-factor model with separate pathways from CAN to illicit drug use through each of the mediating risk factors and (2) a second-order model with a single mediating risk factor comprised of prostitution, homelessness, delinquency and crime, and poor school performance. Analyses were performed separately for women and men, controlling for race/ethnicity and early drug use. In the four-factor model for both men and women, CAN was significantly related to each of the mediators, but no paths from the mediators to drug use were significant. For women, the second-order risk factor mediated the relationship between CAN and illicit drug use in middle adulthood. For men, neither child abuse and neglect nor the second-order risk factor predicted drug use in middle adulthood. These results suggest that for women, the path from CAN to middle adulthood drug use is part of a general "problem behavior syndrome" evident earlier in life.

  12. Epidemiological assessment of neglected diseases in children: lymphatic filariasis and soil-transmitted helminthiasis

    Directory of Open Access Journals (Sweden)

    Ana M. Aguiar-Santos

    2013-05-01

    intestinal em três amostras de fezes, analisadas pelo método de Hoffmann, Pons e Janer. A investigação filarial foi feita com teste antigênico pela técnica de imunocromatográfica rápida (ICT e pesquisa de microfilárias, utilizando filtração em membrana de policarbonato. Para análise de dados utilizou-se a estatística descritiva através do programa EpiInfo versão 7. Resultados: A prevalência de filariose por ICT foi de 13,8% e por microfilaremia de 1,2%, enquanto a de parasitoses intestinais foi 64,2%. A concomitância do diagnóstico filarial e de parasitoses intestinais foi de 9,4% e, 31,5% eram isentos de ambas as parasitoses. Entre os indivíduos com parasitoses intestinais, 55% eram monoparasitados e 45% poliparasitados. A presença de geohelmintos ocorreu em 72,5% dos parasitados. No grupo com infecção filarial a ocorrência de geohelmintíase foi de 54,5%. Conclusões: O diagnóstico simultâneo de infecção filarial e parasitose intestinal, bem como a elevada frequência de geohelmintos justificam uma reavaliação da estratégia terapêutica do tratamento coletivo no programa de filariose no Brasil. Keywords: Filariasis, Helminthiasis, Neglected diseases, Intestinal parasitic, Prevention and control, Palavras-chave: Filariose linfática, Helmintíase, Doenças negligenciadas, Enteropatias parasitárias, Prevenção e controle

  13. Emerging drugs for coeliac disease.

    Science.gov (United States)

    Mooney, Peter D; Hadjivassiliou, Marios; Sanders, David S

    2014-12-01

    Coeliac disease is an autoimmune gluten sensitive enteropathy and is now known to affect 1% of the adult population. A gluten-free diet (GFD) should be curative; however, up to 30% of patients have persistent symptoms and many patients find the diet difficult to fully adhere to. Currently, there are no licensed therapeutic options for patients with coeliac disease outside of a GFD. This review will outline the case for alternative treatments and discuss the potential therapeutic targets. The products in the most advanced stage of development will be discussed in detail. There is clearly an unmet need for alternatives to a GFD for the treatment of coeliac disease. Oral glutenase supplements to improve the degradation of gluten into non-toxic peptides appear to be the most likely to provide a breakthrough in the treatment of coeliac disease; however, other modalities such as a therapeutic vaccine or zonulin inhibitors to reduce intestinal permeability have shown promising results.

  14. Mitochondrial Drugs for Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Xiongwei Zhu

    2009-12-01

    Full Text Available Therapeutic strategies for Alzheimer disease (AD have yet to offer a diseasemodifying effect to stop the debilitating progression of neurodegeneration and cognitive decline. Rather, treatments thus far are limited to agents that slow disease progression without halting it, and although much work towards a cure is underway, a greater understanding of disease etiology is certainly necessary for any such achievement. Mitochondria, as the centers of cellular metabolic activity and the primary generators of reactive oxidative species in the cell, received particular attention especially given that mitochondrial defects are known to contribute to cellular damage. Furthermore, as oxidative stress has come to the forefront of AD as a causal theory, and as mitochondrial damage is known to precede much of the hallmark pathologies of AD, it seems increasingly apparent that this metabolic organelle is ultimately responsible for much, if not all of disease pathogenesis. In this review, we review the role of neuronal mitochondria in the pathogenesis of AD and critically assess treatment strategies that utilize this upstream access point as a method for disease prevention. We suspect that, with a revived focus on mitochondrial repair and protection, an effective and realistic therapeutic agent can be successfully developed.

  15. Financing drug discovery for orphan diseases.

    Science.gov (United States)

    Fagnan, David E; Gromatzky, Austin A; Stein, Roger M; Fernandez, Jose-Maria; Lo, Andrew W

    2014-05-01

    Recently proposed 'megafund' financing methods for funding translational medicine and drug development require billions of dollars in capital per megafund to de-risk the drug discovery process enough to issue long-term bonds. Here, we demonstrate that the same financing methods can be applied to orphan drug development but, because of the unique nature of orphan diseases and therapeutics (lower development costs, faster FDA approval times, lower failure rates and lower correlation of failures among disease targets) the amount of capital needed to de-risk such portfolios is much lower in this field. Numerical simulations suggest that an orphan disease megafund of only US$575 million can yield double-digit expected rates of return with only 10-20 projects in the portfolio. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Drug dosing in chronic kidney disease.

    Science.gov (United States)

    Gabardi, Steven; Abramson, Stuart

    2005-05-01

    Patients with chronic kidney disease (CKD) are at high risk for adverse drug reactions and drug-drug interactions. Drug dosing in these patients often proves to be a difficult task. Renal dysfunction-induced changes in human pathophysiology regularly results may alter medication pharmacodynamics and handling. Several pharmacokinetic parameters are adversely affected by CKD, secondary to a reduced oral absorption and glomerular filtration; altered tubular secretion; and reabsorption and changes in intestinal, hepatic, and renal metabolism. In general, drug dosing can be accomplished by multiple methods; however, the most common recommendations are often to reduce the dose or expand the dosing interval, or use both methods simultaneously. Some medications need to be avoided all together in CKD either because of lack of efficacy or increased risk of toxicity. Nevertheless, specific recommendations are available for dosing of certain medications and are an important resource, because most are based on clinical or pharmacokinetic trials.

  17. Open-source approaches for the repurposing of existing or failed candidate drugs: learning from and applying the lessons across diseases.

    Science.gov (United States)

    Allarakhia, Minna

    2013-01-01

    Repurposing has the objective of targeting existing drugs and failed, abandoned, or yet-to-be-pursued clinical candidates to new disease areas. The open-source model permits for the sharing of data, resources, compounds, clinical molecules, small libraries, and screening platforms to cost-effectively advance old drugs and/or candidates into clinical re-development. Clearly, at the core of drug-repurposing activities is collaboration, in many cases progressing beyond the open sharing of resources, technology, and intellectual property, to the sharing of facilities and joint program development to foster drug-repurposing human-capacity development. A variety of initiatives under way for drug repurposing, including those targeting rare and neglected diseases, are discussed in this review and provide insight into the stakeholders engaged in drug-repurposing discovery, the models of collaboration used, the intellectual property-management policies crafted, and human capacity developed. In the case of neglected tropical diseases, it is suggested that the development of human capital be a central aspect of drug-repurposing programs. Open-source models can support human-capital development through collaborative data generation, open compound access, open and collaborative screening, preclinical and possibly clinical studies. Given the urgency of drug development for neglected tropical diseases, the review suggests elements from current repurposing programs be extended to the neglected tropical diseases arena.

  18. How to (or not to integrate vertical programmes for the control of major neglected tropical diseases in sub-Saharan Africa.

    Directory of Open Access Journals (Sweden)

    Narcis B Kabatereine

    Full Text Available Combining the delivery of multiple health interventions has the potential to minimize costs and expand intervention coverage. Integration of mass drug administration is therefore being encouraged for delivery of preventive chemotherapy (PCT to control onchocerciasis, lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma in sub-Saharan Africa, as there is considerable geographical overlap of these neglected tropical diseases (NTDs. With only a handful of countries having embarked on integrated NTD control, experience on how to develop and implement an efficient integrated programme is limited. Historically, national and global programmes were focused on the control of only one disease, usually through a comprehensive approach that involved several interventions including PCT. Overcoming the resulting disease-specific structures and thinking, and ensuring that the integrated programme is embedded within the existing health structures, pose considerable challenges to policy makers and implementers wishing to embark on integrated NTD control. By sharing experiences from Uganda, Tanzania, Southern Sudan, and Mozambique, this symposium article aims to outlines key challenges and solutions to assist countries in establishing efficient integrated NTD programmes.

  19. RRR for NNN-a rapid research response for the Neglected Tropical Disease NGDO Network: a novel framework to challenges faced by the global programs targeting neglected tropical diseases.

    Science.gov (United States)

    Toledo, Chelsea E; Jacobson, Julie; Wainwright, Emily C; Ottesen, Eric A; Lammie, Patrick J

    2016-03-01

    While global programs targeting the control or elimination of five of the neglected tropical diseases (NTDs)-lymphatic filariasis, onchocerciasis, soil-transmitted helminthiasis, schistosomiasis and trachoma-are well underway, they still face many operational challenges. Because of the urgency of 2020 program targets, the Bill & Melinda Gates Foundation and the U.S. Agency for International Development devised a novel rapid research response (RRR) framework to engage national programs, researchers, implementers and WHO in a Coalition for Operational Research on NTDs. After 2 years, this effort has succeeded as an important basis for the research response to programmatic challenges facing NTD programs. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

  20. Neglected Parasitic Infections: Toxocariasis

    Centers for Disease Control (CDC) Podcasts

    2012-01-05

    This podcast is an overview of the Clinician Outreach and Communication Activity (COCA) Call: Neglected Parasitic Infections in the United States. Neglected Parasitic Infections are a group of diseases that afflict vulnerable populations and are often not well studied or diagnosed. A subject matter expert from CDC's Division of Parasitic Diseases and Malaria describes the epidemiology, diagnosis, and treatment of toxocariasis.  Created: 1/5/2012 by Center for Global Health, Division of Parasitic Diseases and Malaria (DPDM); Emergency Risk Communication Branch (ERCB)/Joint Information Center (JIC), Office of Public Health Preparedness and Response (OPHPR).   Date Released: 1/9/2012.

  1. Recombinant snakebite antivenoms: A cost-competitive solution to a neglected tropical disease?

    DEFF Research Database (Denmark)

    Laustsen, Andreas Hougaard; Johansen, Kristoffer H.; Engmark, Mikael

    2017-01-01

    of treatment for a snakebite envenoming with a recombinant antivenom is estimated to be in the range USD 60-250 for the Final Drug Product. One of the effective antivenoms (SAIMR Snake Polyvalent Antivenom from the South African Vaccine Producers) currently on the market has been reported to have a wholesale...

  2. Seroprevalence of five neglected parasitic diseases among immigrants accessing five infectious and tropical diseases units in Italy: a cross-sectional study.

    Science.gov (United States)

    Martelli, G; Di Girolamo, C; Zammarchi, L; Angheben, A; Morandi, M; Tais, S; Degani, M; El Hamad, I; Caligaris, S; Ciannameo, A; Grilli, E; Urbinati, L; Monteiro, G B; Scarcella, C; Petrosillo, N; Digaetano, M; Rabbi, L; Bazzanini, N; Cacciatore, F; Marta, B L; Moro, M L; Bartoloni, A; Viale, P; Verucchi, G

    2017-05-01

    This multicentre cross-sectional study aims to estimate the prevalence of five neglected tropical diseases (Chagas disease, filariasis, schistosomiasis, strongyloidiasis and toxocariasis) among immigrants accessing health care facilities in five Italian cities (Bologna, Brescia, Florence, Rome, Verona). Individuals underwent a different set of serological tests, according to country of origin and presence of eosinophilia. Seropositive patients were treated and further followed up. A total of 930 adult immigrants were enrolled: 477 men (51.3%), 445 women (47.9%), eight transgender (0.8%); median age was 37.81 years (range 18-80 years). Most of them had come from the African continent (405/930, 43.5%), the rest from East Europe, South America and Asia, and 9.6% (89/930) were diagnosed with at least one of the infections under study. Seroprevalence of each specific infection varied from 3.9% (7/180) for Chagas disease to 9.7% (11/113) for toxocariasis. Seropositive people were more likely to be 35-40 years old and male, and to come from South East Asia, sub-Saharan Africa or South America. The results of our study confirm that neglected tropical diseases represent a substantial health problem among immigrants and highlight the need to address this emerging public health issue. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  3. Emerging drugs for gastroesophageal reflux disease

    NARCIS (Netherlands)

    Boeckxstaens, G. E.

    2009-01-01

    Proton pump inhibitors (PPIs) are very effective and safe drugs for the treatment of erosive and non-erosive gastroesophageal reflux disease (GERD). Nevertheless, a significant proportion of GERD patients (30 - 40%) continue to suffer from symptoms during PPI treatment, which has stimulated the

  4. Meningococcal disease and future drug targets

    DEFF Research Database (Denmark)

    Gammelgaard, L K; Colding, H; Hartzen, S H

    2011-01-01

    recent data and current knowledge on molecular mechanisms of meningococcal disease and explains how host immune responses ultimately may aggravate neuropathology and the clinical prognosis. Within this context, particular importance is paid to the endotoxic components that provide potential drug targets...... for novel neuroprotective adjuvants, which are needed in order to improve the clinical management of meningoencephalitis and patient prognosis....

  5. The global burden of childhood coeliac disease: a neglected component of diarrhoeal mortality?

    Directory of Open Access Journals (Sweden)

    Peter Byass

    Full Text Available OBJECTIVES: Coeliac disease has emerged as an increasingly recognised public health problem over the last half-century, and is now coming to be seen as a global phenomenon, despite a profound lack of globally representative epidemiological data. Since children with coeliac disease commonly present with chronic diarrhoea and malnutrition, diagnosis is often overlooked, particularly in poorer settings where children often fail to thrive and water-borne infectious diarrhoeas are common. This is the first attempt to make global estimates of the burden of coeliac disease in childhood. METHODS: We built a relatively crude model of childhood coeliac disease, incorporating estimates of population prevalence, probability of non-diagnosis, and likelihood of mortality among the undiagnosed across all countries from 1970 to 2010, based around the few available data. All our assumptions are stated in the paper and the model is available as a supplementary file. FINDINGS: Our model suggests that in 2010 there were around 2.2 million children under 5 years of age living with coeliac disease. Among these children there could be 42,000 deaths related to coeliac disease annually. In 2008, deaths related to coeliac disease probably accounted for approximately 4% of all childhood diarrhoeal mortality. CONCLUSIONS: Although coeliac disease may only account for a small proportion of diarrhoeal mortality, these deaths are not preventable by applying normal diarrhoea treatment guidelines, which may even involve gluten-based food supplements. As other causes of diarrhoeal mortality decline, coeliac disease will become a proportionately increasing problem unless consideration is given to trying gluten-free diets for children with chronic diarrhoea and malnutrition.

  6. The Potential Use of Natural and Structural Analogues of Antimicrobial Peptides in the Fight against Neglected Tropical Diseases

    Directory of Open Access Journals (Sweden)

    Lewies Angélique

    2015-08-01

    Full Text Available Recently, research into the development of new antimicrobial agents has been driven by the increase in resistance to traditional antibiotics and Emerging Infectious Diseases. Antimicrobial peptides (AMPs are promising candidates as alternatives to current antibiotics in the treatment and prevention of microbial infections. AMPs are produced by all known living species, displaying direct antimicrobial killing activity and playing an important role in innate immunity. To date, more than 2000 AMPs have been discovered and many of these exhibit broad-spectrum antibacterial, antiviral and anti-parasitic activity. Neglected tropical diseases (NTDs are caused by a variety of pathogens and are particularly wide-spread in low-income and developing regions of the world. Alternative, cost effective treatments are desperately needed to effectively battle these medically diverse diseases. AMPs have been shown to be effective against a variety of NTDs, including African trypanosomes, leishmaniosis and Chagas disease, trachoma and leprosy. In this review, the potential of selected AMPs to successfully treat a variety of NTD infections will be critically evaluated.

  7. Neglect and not forgetting produces shameful diseases such as yellow fever

    Directory of Open Access Journals (Sweden)

    Salim Mattar V

    2017-05-01

    Full Text Available Yellow fever (YF is a disease caused by a flavivirus that bears its name, is a disease with haemorrhagic manifestations and high lethality that compromises the central nervous system. YF has two cycles; one in the jungle and another urban, epizootics precede outbreaks before migrating to urban areas. The vectors are the mosquitoes Aedes aegypti, Aedes albopictus, Haemogogus janthinomys and Sabethes sp, which have a wide geographical distribution in Colombia and South America.

  8. A Practical Green Synthesis and Biological Evaluation of Benzimidazoles Against Two Neglected Tropical Diseases: Chagas and Leishmaniasis.

    Science.gov (United States)

    Bandyopadhyay, Debashis; Samano, Selina; Villalobos-Rocha, Juan Carlos; Sanchez-Torres, Luvia Enid; Nogueda-Torres, Benjamin; Rivera, Gildardo; Banik, Bimal K

    2017-01-01

    Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Two very common neglected tropical diseases are Chagas' disease and leishmaniasis. Chagas' disease is a severe health problem, mainly in Latin America, causing approximately 50000 deaths a year and millions of people are infected. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. On the other hand, Leishmaniasis represents complex diseases with an important clinical and epidemiological diversity. It is endemic in 88 countries 72 of which are developing countries and it has been estimated that are 12 million people infected and 350 million are in areas with infection risk. On this basis, research on organic compounds that can be used against these two diseases is an important target. A very simple, green, and efficient protocol is developed in which bismuth nitrate pentahydrate is employed as a Lewis acid catalyst in aqueous media under microwave irradiation for the synthesis of various 2-aryl substituted benzimidazoles from aldehydes and o-phenylenediamine. Other salient features of this protocol include milder conditions, atom-economy, easy extraction, and no wastes. Nine 1H-benzimidazole derivatives (1-9) with substituents at positions 2 and 5 were synthesized and the structure of the compounds was elucidated by spectroscopic methods. The compounds were screened to identify whether they posses pharmacological activity against Chagas' disease and leishmaniasis. Compound 8 showed better activity than the control Nifurtimox against INC-5 Trypanosoma cruzi strain whereas compounds 3 and 9 have demonstrated potent leshmanicidal activity. A systematic green synthetic procedure and in vitro biological evaluation of nine 1H-benzimidazoles are described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Impacts of neglected tropical disease on incidence and progression of HIV/AIDS, tuberculosis, and malaria: scientific links

    Directory of Open Access Journals (Sweden)

    G.G. Simon

    2016-01-01

    Full Text Available The neglected tropical diseases (NTDs are the most common infections of humans in Sub-Saharan Africa. Virtually all of the population living below the World Bank poverty figure is affected by one or more NTDs. New evidence indicates a high degree of geographic overlap between the highest-prevalence NTDs (soil-transmitted helminths, schistosomiasis, onchocerciasis, lymphatic filariasis, and trachoma and malaria and HIV, exhibiting a high degree of co-infection. Recent research suggests that NTDs can affect HIV and AIDS, tuberculosis (TB, and malaria disease progression. A combination of immunological, epidemiological, and clinical factors can contribute to these interactions and add to a worsening prognosis for people affected by HIV/AIDS, TB, and malaria. Together these results point to the impacts of the highest-prevalence NTDs on the health outcomes of malaria, HIV/AIDS, and TB and present new opportunities to design innovative public health interventions and strategies for these ‘big three’ diseases. This analysis describes the current findings of research and what research is still needed to strengthen the knowledge base of the impacts NTDs have on the big three.

  10. Arthropod borne diseases in Italy: from a neglected matter to an emerging health problem

    Directory of Open Access Journals (Sweden)

    Roberto Romi

    2010-12-01

    Full Text Available In medical entomology, "Arthropod Borne Diseases", or "Vector Borne Diseases" (VBD are intended as a group of human and animal infections caused by different pathogen organisms (protozoa, helminthes, bacteria and viruses transmitted by the bite of a bloodsucking insect or arachnid. It is commonly known that the infectious diseases transmitted by Arthropods are mainly affecting tropical and subtropical countries, nevertheless some of them were or are still common also in the northern hemisphere, where they are usually maintained under control. VBD still represent some of the most important public health problems in the endemic areas but are becoming source of concern for developed countries too. Since the last decades of the past century, a number of VBD has been spreading geographically, being recorded for the first time in areas outside their original range. This phenomenon is strictly related to the peculiar epidemiological characteristics of these diseases, that are considered the most susceptible to climatic, environmental and socioeconomic changes. This article is a short overview of the VBD endemic and emerging in Italy. The possibility that some exotic vectors and/or pathogens could be introduced and become established in Italy is also discussed.

  11. Caprine brucellosis: A historically neglected disease with significant impact on public health

    Science.gov (United States)

    Arenas-Gamboa, Angela M.; Maurizio, Estefanía

    2017-01-01

    Caprine brucellosis is a chronic infectious disease caused by the gram-negative cocci-bacillus Brucella melitensis. Middle- to late-term abortion, stillbirths, and the delivery of weak offspring are the characteristic clinical signs of the disease that is associated with an extensive negative impact in a flock’s productivity. B. melitensis is also the most virulent Brucella species for humans, responsible for a severely debilitating and disabling illness that results in high morbidity with intermittent fever, chills, sweats, weakness, myalgia, abortion, osteoarticular complications, endocarditis, depression, anorexia, and low mortality. Historical observations indicate that goats have been the hosts of B. melitensis for centuries; but around 1905, the Greek physician Themistokles Zammit was able to build the epidemiological link between “Malta fever” and the consumption of goat milk. While the disease has been successfully managed in most industrialized countries, it remains a significant burden on goat and human health in the Mediterranean region, the Middle East, Central and Southeast Asia (including India and China), sub-Saharan Africa, and certain areas in Latin America, where approximately 3.5 billion people live at risk. In this review, we describe a historical evolution of the disease, highlight the current worldwide distribution, and estimate (by simple formula) the approximate costs of brucellosis outbreaks to meat- and milk-producing farms and the economic losses associated with the disease in humans. Successful control leading to eradication of caprine brucellosis in the developing world will require a coordinated Global One Health approach involving active involvement of human and animal health efforts to enhance public health and improve livestock productivity. PMID:28817647

  12. Compensation for environmental asbestos-related diseases in South Africa: a neglected issue

    Directory of Open Access Journals (Sweden)

    Ntombizodwa Ndlovu

    2013-01-01

    Full Text Available Background: Environmentally acquired asbestos-related diseases (ARDs are of concern globally. In South Africa, there is widespread contamination of the environment due to historical asbestos mining operations that were poorly regulated. Although the law makes provision for the compensation of occupationally acquired ARDs, compensation for environmentally acquired ARDs is only available through the Asbestos Relief Trust (ART and Kgalagadi Relief Trust, both of which are administered by the ART. This study assessed ARDs and compensation outcomes of environmental claims submitted to the Trusts. Methods: The personal details, medical diagnoses, and exposure information of all environmental claims considered by the Trusts from their inception in 2003 to April 2010 were used to calculate the numbers and proportions of ARDs and compensation awards. Results: There were 146 environmental claimants of whom 35 (23.9% had fibrotic pleural disease, 1 (0.7% had lung cancer, and 77 (52.7% had malignant mesothelioma. 53 (36.3% claimants were compensated: 20 with fibrotic pleural disease and 33 with mesothelioma. Of the 93 (63.7% claimants who were not compensated, 33 had no ARDs, 18 had fibrotic pleural disease, 1 had lung cancer, and 44 had mesothelioma. In addition to having ARDs, those that were compensated had qualifying domestic (33; 62.2% or neighbourhood (20; 37.8% exposures to asbestos. Most of the claimants who were not compensated had ARDs but their exposures did not meet the Trusts’ exposure criteria. Conclusions: This study demonstrates the environmental impact of asbestos mining on the burden of ARDs. Mesothelioma was the most common disease diagnosed, but most cases were not compensated. This highlights that there is little redress for individuals with environmentally acquired ARDs in South Africa. To stop this ARD epidemic, there is a need for the rehabilitation of abandoned asbestos mines and the environment. These issues may not be unique to

  13. Compensation for environmental asbestos-related diseases in South Africa: a neglected issue.

    Science.gov (United States)

    Ndlovu, Ntombizodwa; Naude, Jim teWater; Murray, Jill

    2013-01-24

    Environmentally acquired asbestos-related diseases (ARDs) are of concern globally. In South Africa, there is widespread contamination of the environment due to historical asbestos mining operations that were poorly regulated. Although the law makes provision for the compensation of occupationally acquired ARDs, compensation for environmentally acquired ARDs is only available through the Asbestos Relief Trust (ART) and Kgalagadi Relief Trust, both of which are administered by the ART. This study assessed ARDs and compensation outcomes of environmental claims submitted to the Trusts. The personal details, medical diagnoses, and exposure information of all environmental claims considered by the Trusts from their inception in 2003 to April 2010 were used to calculate the numbers and proportions of ARDs and compensation awards. There were 146 environmental claimants of whom 35 (23.9%) had fibrotic pleural disease, 1 (0.7%) had lung cancer, and 77 (52.7%) had malignant mesothelioma. 53 (36.3%) claimants were compensated: 20 with fibrotic pleural disease and 33 with mesothelioma. Of the 93 (63.7%) claimants who were not compensated, 33 had no ARDs, 18 had fibrotic pleural disease, 1 had lung cancer, and 44 had mesothelioma. In addition to having ARDs, those that were compensated had qualifying domestic (33; 62.2%) or neighbourhood (20; 37.8%) exposures to asbestos. Most of the claimants who were not compensated had ARDs but their exposures did not meet the Trusts' exposure criteria. This study demonstrates the environmental impact of asbestos mining on the burden of ARDs. Mesothelioma was the most common disease diagnosed, but most cases were not compensated. This highlights that there is little redress for individuals with environmentally acquired ARDs in South Africa. To stop this ARD epidemic, there is a need for the rehabilitation of abandoned asbestos mines and the environment. These issues may not be unique to South Africa as many countries continue to mine and use

  14. The Role of Nurses and Community Health Workers in Confronting Neglected Tropical Diseases in Sub-Saharan Africa: A Systematic Review.

    Science.gov (United States)

    Corley, Andrew G; Thornton, Clifton P; Glass, Nancy E

    2016-09-01

    Neglected tropical diseases produce an enormous burden on many of the poorest and most disenfranchised populations in sub-Saharan Africa. Similar to other developing areas throughout the world, this region's dearth of skilled health providers renders Western-style primary care efforts to address such diseases unrealistic. Consequently, many countries rely on their corps of nurses and community health workers to engage with underserved and hard-to-reach populations in order provide interventions against these maladies. This article attempts to cull together recent literature on the impact that nurses and community health workers have had on neglected tropical diseases. A review of the literature was conducted to assess the role nurses and community health workers play in the primary, secondary, and tertiary prevention of neglected tropical diseases in sub-Saharan Africa. Articles published between January 2005 and December 2015 were reviewed in order to capture the full scope of nurses' and community health workers' responsibilities for neglected tropical disease control within their respective countries' health systems. A total of 59 articles were identified that fit all inclusion criteria. Successful disease control requires deep and meaningful engagement with local communities. Expanding the role of nurses and community health workers will be required if sub-Saharan African countries are to meet neglected tropical disease treatment goals and eliminate the possibility future disease transmission. Horizontal or multidisease control programs can create complimentary interactions between their different control activities as well as reduce costs through improved program efficiencies-benefits that vertical programs are not able to attain.

  15. Hit and lead criteria in drug discovery for infectious diseases of the developing world.

    Science.gov (United States)

    Katsuno, Kei; Burrows, Jeremy N; Duncan, Ken; Hooft van Huijsduijnen, Rob; Kaneko, Takushi; Kita, Kiyoshi; Mowbray, Charles E; Schmatz, Dennis; Warner, Peter; Slingsby, B T

    2015-11-01

    Reducing the burden of infectious diseases that affect people in the developing world requires sustained collaborative drug discovery efforts. The quality of the chemical starting points for such projects is a key factor in improving the likelihood of clinical success, and so it is important to set clear go/no-go criteria for the progression of hit and lead compounds. With this in mind, the Japanese Global Health Innovative Technology (GHIT) Fund convened with experts from the Medicines for Malaria Venture, the Drugs for Neglected Diseases initiative and the TB Alliance, together with representatives from the Bill &Melinda Gates Foundation, to set disease-specific criteria for hits and leads for malaria, tuberculosis, visceral leishmaniasis and Chagas disease. Here, we present the agreed criteria and discuss the underlying rationale.

  16. Firewood, smoke and respiratory diseases in developing countries-The neglected role of outdoor cooking.

    Directory of Open Access Journals (Sweden)

    Jörg Langbein

    Full Text Available Smoke from cooking in the kitchen is one of the world's leading causes of premature child death, claiming the lives of 500,000 children under five annually. This study analyses the role of outdoor cooking and the prevalence of respiratory diseases among children under five years by means of probit regressions using information from 41 surveys conducted in 30 developing countries from Asia, Africa and Latin America. I find that outdoor cooking reduces respiratory diseases among young children aged 0-4 by around 9 percent, an effect that reaches 13 percent among children aged 0-1. The results suggest that simple behavioral interventions, such as promoting outdoor cooking, can have a substantial impact on health hazards.

  17. Firewood, smoke and respiratory diseases in developing countries-The neglected role of outdoor cooking.

    Science.gov (United States)

    Langbein, Jörg

    2017-01-01

    Smoke from cooking in the kitchen is one of the world's leading causes of premature child death, claiming the lives of 500,000 children under five annually. This study analyses the role of outdoor cooking and the prevalence of respiratory diseases among children under five years by means of probit regressions using information from 41 surveys conducted in 30 developing countries from Asia, Africa and Latin America. I find that outdoor cooking reduces respiratory diseases among young children aged 0-4 by around 9 percent, an effect that reaches 13 percent among children aged 0-1. The results suggest that simple behavioral interventions, such as promoting outdoor cooking, can have a substantial impact on health hazards.

  18. Firewood, smoke and respiratory diseases in developing countries—The neglected role of outdoor cooking

    Science.gov (United States)

    2017-01-01

    Smoke from cooking in the kitchen is one of the world’s leading causes of premature child death, claiming the lives of 500,000 children under five annually. This study analyses the role of outdoor cooking and the prevalence of respiratory diseases among children under five years by means of probit regressions using information from 41 surveys conducted in 30 developing countries from Asia, Africa and Latin America. I find that outdoor cooking reduces respiratory diseases among young children aged 0-4 by around 9 percent, an effect that reaches 13 percent among children aged 0-1. The results suggest that simple behavioral interventions, such as promoting outdoor cooking, can have a substantial impact on health hazards. PMID:28658290

  19. Data base management system for lymphatic filariasis--a neglected tropical disease.

    Science.gov (United States)

    Upadhyayula, Suryanaryana Murty; Mutheneni, Srinivasa Rao; Kadiri, Madhusudhan Rao; Kumaraswamy, Sriram; Nelaturu, Sarat Chandra Babu

    2012-01-01

    Researchers working in the area of Public Health are being confronted with large volumes of data on various aspects of entomology and epidemiology. To obtain the relevant information out of these data requires particular database management system. In this paper, we have described about the usages of our developed database on lymphatic filariasis. This database application is developed using Model View Controller (MVC) architecture, with MySQL as database and a web based interface. We have collected and incorporated the data on filariasis in the database from Karimnagar, Chittoor, East and West Godavari districts of Andhra Pradesh, India. The importance of this database is to store the collected data, retrieve the information and produce various combinational reports on filarial aspects which in turn will help the public health officials to understand the burden of disease in a particular locality. This information is likely to have an imperative role on decision making for effective control of filarial disease and integrated vector management operations.

  20. Nutritional status and eating disorders: neglected risks factor for nontuberculous mycobacterial lung disease?

    Science.gov (United States)

    Portillo, Karina; Morera, Josep

    2012-01-01

    Nontuberculous mycobacterial lung disease (NTMLD) in immunocompetent patients is an increasingly important epidemiologic concern. However, risk factors associated with susceptibility to NTMLD are not completely known. A prevalence of NTMLD appears to be rising, mainly in some populations such as middle-aged or elderly thin women, (a group including those with Lady Windermere syndrome) with neither remarkable history of respiratory disease nor smoking habit. Right middle lobe (RML) and lingula are often involved. Various predisposing factors and genetic defects have been described as possible causes of development of NTMLD, namely: voluntary suppression of cough, RML anatomical factors, menopause and mutations in cystic fibrosis transmembrane conductance regulator (CFTR). Malnutrition is also an important and common risk factor associated with other mycobacterial disease like tuberculosis (TB) and its probable association with NTMLD as have been pointed out for some authors. However, a real description of all nutritional aspects and eating habits of patients prior to NTMLD diagnosis is lacking. We hypothesized that malnutrition and eating disorders like anorexia nervosa could be risk factors that may promoting NTMLD. From a clinical viewpoint, if this hypothesis proves to be correct, eating habits and nutritional aspects should be taken into account in the diagnosis process of suspected NTMLD, since they are easily identifiable and treatable conditions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Interpretations of education about gene-environment influences on health in rural Ethiopia: the context of a neglected tropical disease.

    Science.gov (United States)

    Tora, Abebayehu; Ayode, Desta; Tadele, Getnet; Farrell, David; Davey, Gail; McBride, Colleen M

    2016-07-01

    Misunderstandings of the role of genetics in disease development are associated with stigmatizing behaviors and fatalistic attitudes about prevention. This report describes an evaluation of community understanding of an educational module about genetic and environmental influences on the development of podoconiosis, a neglected tropical disease endemic in highland Ethiopia. A qualitative process assessment was conducted as part of a large prospective intervention trial in August 2013, in Wolaita Zone, southern Ethiopia. Sixty five participants were purposively selected from 600 households randomized to receive the inherited susceptibility module. The educational module used pictorial representations and oral explanations of the interaction of inherited sensitivity and soil exposure and was delivered by lay health educators in participants' homes. Data were collected using semi-structured individual interviews (IDIs) or focus group discussions (FGDs). Qualitative analyses showed that most participants improved their understanding of inherited soil sensitivity and susceptibility to podoconiosis. Participants linked their new understanding to decreased stigma-related attitudes. The module also corrected misconceptions that the condition was contagious, again diminishing stigmatizing attitudes. Lastly, these improvements in understanding increased the perceived value of foot protection. Taken together, these improvements support the acceptability, feasibility and potential benefits of implementing gene-environment education in low and middle income countries. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

  2. Data base management system for lymphatic filariasis--a neglected tropical disease.

    Directory of Open Access Journals (Sweden)

    Suryanaryana Murty Upadhyayula

    Full Text Available BACKGROUND: Researchers working in the area of Public Health are being confronted with large volumes of data on various aspects of entomology and epidemiology. To obtain the relevant information out of these data requires particular database management system. In this paper, we have described about the usages of our developed database on lymphatic filariasis. METHODS: This database application is developed using Model View Controller (MVC architecture, with MySQL as database and a web based interface. We have collected and incorporated the data on filariasis in the database from Karimnagar, Chittoor, East and West Godavari districts of Andhra Pradesh, India. CONCLUSION: The importance of this database is to store the collected data, retrieve the information and produce various combinational reports on filarial aspects which in turn will help the public health officials to understand the burden of disease in a particular locality. This information is likely to have an imperative role on decision making for effective control of filarial disease and integrated vector management operations.

  3. Ethiopia and its steps to mobilize resources to achieve 2020 elimination and control goals for neglected tropical diseases webs joined can tie a lion.

    Science.gov (United States)

    Mengitsu, Belete; Shafi, Oumer; Kebede, Biruck; Kebede, Fikreab; Worku, Dagemlidet T; Herero, Merce; French, Michael; Kebede, Biruk; Mackenzie, Charles; Martindale, Sarah; Kebede, Zeyede; Hirpa, Tigist; Frawley, Hannah; Crowley, Kathryn; O'Neil, Maggie; McPherson, Scott

    2016-03-01

    In June 2013, at the launch of its National Neglected Tropical Disease (NTD) Master Plan, the Ethiopian government pledged to achieve WHO NTD elimination and control targets by 2020. With an estimated 80 million people living in areas where one or more NTDs are endemic, this goal presented an enormous challenge for the Federal Ministry of Health. However, as of September 2015, the Federal Ministry of Health has managed to mobilize support to implement mass drug administration in 84% of the trachoma endemic districts and 100% of the endemic districts for onchocerciasis, lymphatic filariasis, soil-transmitted helminthes and schistosomiasis. The national program still is facing large gaps in its podoconiosis and leishmaniasis programs, and it faces significant other challenges to stay on track for 2020 targets. However, this unprecedented scale-up in support was achieved through significant government investment in NTD interventions and creative coordination between donors and implementing partners, which may provide valuable lessons for other national NTD programs trying to achieve nationwide coverage. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Elimination of neglected tropical diseases in the South-East Asia Region of the World Health Organization.

    Science.gov (United States)

    Narain, Jai P; Dash, A P; Parnell, B; Bhattacharya, S K; Barua, S; Bhatia, R; Savioli, L

    2010-03-01

    The neglected tropical diseases (NTDs), which affect the very poor, pose a major public health problem in the South-East Asia Region of the World Health Organization (WHO). Although more than a dozen NTDs affect the region, over the past five years four of them in particular - leprosy, lymphatic filariasis, visceral leishmaniasis (kala-azar) and yaws - have been targeted for elimination. These four were selected for a number of reasons. First, they affect the WHO South-East Asia Region disproportionately. For example, every year around 67% of all new leprosy cases and 60% of all new cases of visceral leishmaniasis worldwide occur in countries of the region, where as many as 850 million inhabitants are at risk of contracting lymphatic filariasis. In addition, several epidemiological, technological and historical factors that are unique to the region make each of these four diseases amenable to elimination. Safe and effective tools and interventions to achieve these targets are available and concerted efforts to scale them up, singly or in an integrated manner, are likely to lead to success. The World Health Assembly and the WHO Regional Committee, through a series of resolutions, have already expressed regional and global commitments for the elimination of these diseases as public health problems. Such action is expected to have a quick and dramatic impact on poverty reduction and to contribute to the achievement of the Millennium Development Goals. This paper reviews the policy rationale for disease control in the WHO South-East Asia Region, the progress made so far, the lessons learnt along the way, and the remaining challenges and opportunities.

  5. Advance market commitments for vaccines against neglected diseases: estimating costs and effectiveness.

    Science.gov (United States)

    Berndt, Ernst R; Glennerster, Rachel; Kremer, Michael R; Lee, Jean; Levine, Ruth; Weizsäcker, Georg; Williams, Heidi

    2007-05-01

    The G8 is considering committing to purchase vaccines against diseases concentrated in low-income countries (if and when desirable vaccines are developed) as a way to spur research and development on vaccines for these diseases. Under such an 'advance market commitment,' one or more sponsors would commit to a minimum price to be paid per person immunized for an eligible product, up to a certain number of individuals immunized. For additional purchases, the price would eventually drop to close to marginal cost. If no suitable product were developed, no payments would be made. We estimate the offer size which would make revenues similar to the revenues realized from investments in typical existing commercial pharmaceutical products, as well as the degree to which various model contracts and assumptions would affect the cost-effectiveness of such a commitment. We make adjustments for lower marketing costs under an advance market commitment and the risk that a developer may have to share the market with subsequent developers. We also show how this second risk could be reduced, and money saved, by introducing a superiority clause to a commitment. Under conservative assumptions, we document that a commitment comparable in value to sales earned by the average of a sample of recently launched commercial products (adjusted for lower marketing costs) would be a highly cost-effective way to address HIV/AIDS, malaria, and tuberculosis. Sensitivity analyses suggest most characteristics of a hypothetical vaccine would have little effect on the cost-effectiveness, but that the duration of protection conferred by a vaccine strongly affects potential cost-effectiveness. Readers can conduct their own sensitivity analyses employing a web-based spreadsheet tool. Copyright (c) 2006 John Wiley & Sons, Ltd.

  6. Advanced and controlled drug delivery systems in clinical disease management

    NARCIS (Netherlands)

    Brouwers, JRBJ

    1996-01-01

    Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted. Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative

  7. The neglected tropical diseases of Latin America and the Caribbean: a review of disease burden and distribution and a roadmap for control and elimination.

    Directory of Open Access Journals (Sweden)

    Peter J Hotez

    Full Text Available The neglected tropical diseases (NTDs represent some of the most common infections of the poorest people living in the Latin American and Caribbean region (LAC. Because they primarily afflict the disenfranchised poor as well as selected indigenous populations and people of African descent, the NTDs in LAC are largely forgotten diseases even though their collective disease burden may exceed better known conditions such as of HIV/AIDS, tuberculosis, or malaria. Based on their prevalence and healthy life years lost from disability, hookworm infection, other soil-transmitted helminth infections, and Chagas disease are the most important NTDs in LAC, followed by dengue, schistosomiasis, leishmaniasis, trachoma, leprosy, and lymphatic filariasis. On the other hand, for some important NTDs, such as leptospirosis and cysticercosis, complete disease burden estimates are not available. The NTDs in LAC geographically concentrate in 11 different sub-regions, each with a distinctive human and environmental ecology. In the coming years, schistosomiasis could be eliminated in the Caribbean and transmission of lymphatic filariasis and onchocerciasis could be eliminated in Latin America. However, the highest disease burden NTDs, such as Chagas disease, soil-transmitted helminth infections, and hookworm and schistosomiasis co-infections, may first require scale-up of existing resources or the development of new control tools in order to achieve control or elimination. Ultimately, the roadmap for the control and elimination of the more widespread NTDs will require an inter-sectoral approach that bridges public health, social services, and environmental interventions.

  8. Dietary sodium restriction: a neglected therapeutic opportunity in chronic kidney disease

    Science.gov (United States)

    Humalda, Jelmer K.; Navis, Gerjan

    2014-01-01

    Purpose of review Restriction of dietary sodium is recommended at a population level as well as for groups at high cardiovascular risk, and chronic kidney disease (CKD). This review addresses recent evidence for the protective effect of dietary sodium restriction in CKD patients specifically. Recent findings Sodium intake in CKD populations is generally high, and often above population average. Recent data demonstrated that moderately lower sodium intake in CKD patients is associated with substantially better long-term outcome of renin–angiotensin–aldosterone system (RAAS)-blockade, in diabetic and nondiabetic CKD, related to better effects of RAAS-blockade on proteinuria, independent of blood pressure. This is in line with better short-term efficacy of RAAS-blockade during moderate sodium restriction in diabetic and nondiabetic CKD. This effect of sodium restriction is likely mediated by its effects on volume status. Sustainable sodium restriction can be achieved by approaches on the basis of behavioral sciences. Summary Moderate restriction of dietary sodium can substantially improve the protective effects of RAAS-blockade in CKD, by specific renal effects apparent from proteinuria reduction. The latter precludes straightforward extrapolation of data from nonrenal populations to CKD. Concerns regarding the adverse effects of a very low sodium intake should not distract from the protective effects of moderate sodium restriction. Prospective studies should assess the efficacy and sustainability of different strategies to target high sodium intake in CKD, along with measures at population level. Video abstract http://links.lww.com/CONH/A14 PMID:25222815

  9. [International cooperation with the neglected tropical disease Buruli ulcer in Togo].

    Science.gov (United States)

    Niiyama, Tomoki

    2013-12-01

    The objectives of this paper are to grasp the current status of an endemic disease, known as Buruli ulcer (BU), in the Republic of Togo and the expansion of international assistance in the field. By adopting the explicit support model, this paper also compares the obtained research results with those of the Republic of Ghana and Benin, to clarify the primary functions played among respective governments, WHO, and NGO. Under the auspices of the WHO Global Buruli Ulcer Initiative (GBUI, 1998-), National Buruli Ulcer Control Programme (NBUCP) in the Togo was initiated in 1999. However, due to the shortage of national budget and politico-economic instabilities of the nation, the actual implementation of NBUCP proved to be problematic. It was after 2007 that the programme began to move forward with the interventions of NGOs like DAHW and Handicap International. Currently, major players involved in the implementation of the policies provided by the GBUI are WHO, NGOs and the targeted governments. In other words, the organizations involved in BU treatment work together by fulfilling their functions. Unlike the neighboring countries, the Togolese government encountered much difficulty in materializing its national programme. Largely due to the political instability and the severe shortage of national budget, stronger assistances from NGOs were required at various levels of the national health measures from formulating to implementing the programme. As the programmes in Togo and Ghana/Benin expanded over the years, the respective support model revealed to be unique and different. In Ghana and Benin, intimate cooperation among WHO, government and NGOs has been established. In Togo, strengthening of collaboration among the three players is expected.

  10. Using Co-authorship Networks to Map and Analyse Global Neglected Tropical Disease Research with an Affiliation to Germany.

    Directory of Open Access Journals (Sweden)

    Max Ernst Bender

    2015-12-01

    Full Text Available Research on Neglected Tropical Diseases (NTDs has increased in recent decades, and significant need-gaps in diagnostic and treatment tools remain. Analysing bibliometric data from published research is a powerful method for revealing research efforts, partnerships and expertise. We aim to identify and map NTD research networks in Germany and their partners abroad to enable an informed and transparent evaluation of German contributions to NTD research.A SCOPUS database search for articles with German author affiliations that were published between 2002 and 2012 was conducted for kinetoplastid and helminth diseases. Open-access tools were used for data cleaning and scientometrics (OpenRefine, geocoding (OpenStreetMaps and to create (Table2Net, visualise and analyse co-authorship networks (Gephi. From 26,833 publications from around the world that addressed 11 diseases, we identified 1,187 (4.4% with at least one German author affiliation, and we processed 972 publications for the five most published-about diseases. Of those, we extracted 4,007 individual authors and 863 research institutions to construct co-author networks. The majority of co-authors outside Germany were from high-income countries and Brazil. Collaborations with partners on the African continent remain scattered. NTD research within Germany was distributed among 220 research institutions. We identified strong performers on an individual level by using classic parameters (number of publications, h-index and social network analysis parameters (betweenness centrality. The research network characteristics varied strongly between diseases.The share of NTD publications with German affiliations is approximately half of its share in other fields of medical research. This finding underlines the need to identify barriers and expand Germany's otherwise strong research activities towards NTDs. A geospatial analysis of research collaborations with partners abroad can support decisions to

  11. Addressing the neglected tropical disease podoconiosis in Northern Ethiopia: lessons learned from a new community podoconiosis program.

    Directory of Open Access Journals (Sweden)

    Sara Tomczyk

    Full Text Available BACKGROUND: Despite its great public health importance, few control initiatives addressing podoconiosis (non-filarial elephantiasis, a geochemical neglected tropical disease exist. In June 2010, the first podoconiosis program in Northern Ethiopia, consisting of prevention, awareness, and care and support activities, began in Debre Markos, Northern Ethiopia. This study aims to document and disseminate the lessons learned from a new community podoconiosis program in Debre Markos. METHODS/PRINCIPAL FINDINGS: We used a content analysis approach to examine and evaluate data from a series of sources. These sources include conducted interview transcripts, a focus group discussion transcript and secondary sources including monitoring and evaluation field reports, observation notes, and research obtained from a literature review. Themes were identified and grouped into matrix tables. Overall, sixteen program steps were identified and grouped into 6 domains: Initial preparation, training and sensitization, foundation building, treatment activity implementation, awareness, and follow-up. Emphasis is placed on the need for baseline data, effective training, local leadership, experience-sharing, mass-awareness, cross-cutting sector issues (i.e., water and waste management, and integration with government health systems. Related successes and challenges are also described, as are stakeholder roles and misconceptions and socio-cultural challenges affecting the program start-up. Many of the identified successes and challenges are relevant to the aim of the podoconiosis program to be sustainable and community-led. CONCLUSIONS/SIGNIFICANCE: Much of this information has already been used to improve the Debre Markos program. We also anticipate that the domains and steps identified will be useful in guiding new programs in other settings where podoconiosis is highly prevalent. We hope to encourage partnerships and collaboration among podoconiosis stakeholders in

  12. Addressing the Neglected Tropical Disease Podoconiosis in Northern Ethiopia: Lessons Learned from a New Community Podoconiosis Program

    Science.gov (United States)

    Tomczyk, Sara; Tamiru, Abreham; Davey, Gail

    2012-01-01

    Background Despite its great public health importance, few control initiatives addressing podoconiosis (non-filarial elephantiasis, a geochemical neglected tropical disease) exist. In June 2010, the first podoconiosis program in Northern Ethiopia, consisting of prevention, awareness, and care and support activities, began in Debre Markos, Northern Ethiopia. This study aims to document and disseminate the lessons learned from a new community podoconiosis program in Debre Markos. Methods/Principal Findings We used a content analysis approach to examine and evaluate data from a series of sources. These sources include conducted interview transcripts, a focus group discussion transcript and secondary sources including monitoring and evaluation field reports, observation notes, and research obtained from a literature review. Themes were identified and grouped into matrix tables. Overall, sixteen program steps were identified and grouped into 6 domains: Initial preparation, training and sensitization, foundation building, treatment activity implementation, awareness, and follow-up. Emphasis is placed on the need for baseline data, effective training, local leadership, experience-sharing, mass-awareness, cross-cutting sector issues (i.e., water and waste management), and integration with government health systems. Related successes and challenges are also described, as are stakeholder roles and misconceptions and socio-cultural challenges affecting the program start-up. Many of the identified successes and challenges are relevant to the aim of the podoconiosis program to be sustainable and community-led. Conclusions/Significance Much of this information has already been used to improve the Debre Markos program. We also anticipate that the domains and steps identified will be useful in guiding new programs in other settings where podoconiosis is highly prevalent. We hope to encourage partnerships and collaboration among podoconiosis stakeholders in future growth and

  13. Incorporating a Healthy Living Curriculum within Family Behavior Therapy: A Clinical Case Example in a Woman with a History of Domestic Violence, Child Neglect, Drug Abuse, and Obesity

    Directory of Open Access Journals (Sweden)

    Holly B. LaPota

    2014-01-01

    Full Text Available Women reported to child protective service agencies frequently report problems that significantly interfere with the health and well-being of their children and themselves. Behavioral treatment programs appear to be effective in managing these co-existing problems, such as domestic violence and substance abuse. However, evidence-supported interventions are rarely exemplified in complicated clinical cases, especially within child welfare settings. Therefore, in this case example, we describe the process of adapting an evidence-supported treatment to assist in managing significant co-existing health-related problems in a mother who was referred due to child neglect and drug abuse. At the conclusion of therapy, the participant reported improvements in perceived family relationships, illicit drug use, child maltreatment potential, whereas other health-related outcomes were mixed. Most improvements were maintained at 4-month follow-up. Issues relevant to implementing evidence-based treatments within community contexts are discussed, including methods of increasing the likelihood of valid outcome assessment, managing treatment integrity, and adjusting standardized treatments to accommodate co-occurring problems. This research was supported by a grant from the National Institute on Drug Abuse (1R01DA020548-01A1 awarded to Brad Donohue. The authors wish to thank Sally K. Miller, PhD, APN, FAANP and Associate Professor, UNLV School of Nursing for her work in completing the initial in-home health evaluation/physical for the current project.

  14. Genome-wide identification of microRNA targets in the neglected disease pathogens of the genus Echinococcus.

    Science.gov (United States)

    Macchiaroli, Natalia; Maldonado, Lucas L; Zarowiecki, Magdalena; Cucher, Marcela; Gismondi, María Inés; Kamenetzky, Laura; Rosenzvit, Mara Cecilia

    2017-06-01

    MicroRNAs (miRNAs), a class of small non-coding RNAs, are key regulators of gene expression at post-transcriptional level and play essential roles in biological processes such as development. MiRNAs silence target mRNAs by binding to complementary sequences in the 3'untranslated regions (3'UTRs). The parasitic helminths of the genus Echinococcus are the causative agents of echinococcosis, a zoonotic neglected disease. In previous work, we performed a comprehensive identification and characterization of Echinococcus miRNAs. However, current knowledge about their targets is limited. Since target prediction algorithms rely on complementarity between 3'UTRs and miRNA sequences, a major limitation is the lack of accurate sequence information of 3'UTR for most species including parasitic helminths. We performed RNA-seq and developed a pipeline that integrates the transcriptomic data with available genomic data of this parasite in order to identify 3'UTRs of Echinococcus canadensis. The high confidence set of 3'UTRs obtained allowed the prediction of miRNA targets in Echinococcus through a bioinformatic approach. We performed for the first time a comparative analysis of miRNA targets in Echinococcus and Taenia. We found that many evolutionarily conserved target sites in Echinococcus and Taenia may be functional and under selective pressure. Signaling pathways such as MAPK and Wnt were among the most represented pathways indicating miRNA roles in parasite growth and development. Genome-wide identification and characterization of miRNA target genes in Echinococcus provide valuable information to guide experimental studies in order to understand miRNA functions in the parasites biology. miRNAs involved in essential functions, especially those being absent in the host or showing sequence divergence with respect to host orthologs, might be considered as novel therapeutic targets for echinococcosis control. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Integrated Healthcare Delivery: A Qualitative Research Approach to Identifying and Harmonizing Perspectives of Integrated Neglected Tropical Disease Programs.

    Directory of Open Access Journals (Sweden)

    Arianna Rubin Means

    2016-10-01

    Full Text Available While some evidence supports the beneficial effects of integrating neglected tropical disease (NTD programs to optimize coverage and reduce costs, there is minimal information regarding when or how to effectively operationalize program integration. The lack of systematic analyses of integration experiences and of integration processes may act as an impediment to achieving more effective NTD programming. We aimed to learn about the experiences of NTD stakeholders and their perceptions of integration.We evaluated differences in the definitions, roles, perceived effectiveness, and implementation experiences of integrated NTD programs among a variety of NTD stakeholder groups, including multilateral organizations, funding partners, implementation partners, national Ministry of Health (MOH teams, district MOH teams, volunteer rural health workers, and community members participating in NTD campaigns. Semi-structured key informant interviews were conducted. Coding of themes involved a mix of applying in-vivo open coding and a priori thematic coding from a start list.In total, 41 interviews were conducted. Salient themes varied by stakeholder, however dominant themes on integration included: significant variations in definitions, differential effectiveness of specific integrated NTD activities, community member perceptions of NTD programs, the influence of funders, perceived facilitators, perceived barriers, and the effects of integration on health system strength. In general, stakeholder groups provided unique perspectives, rather than contrarian points of view, on the same topics. The stakeholders identified more advantages to integration than disadvantages, however there are a number of both unique facilitators and challenges to integration from the perspective of each stakeholder group.Qualitative data suggest several structural, process, and technical opportunities that could be addressed to promote more effective and efficient integrated NTD

  16. Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

    Science.gov (United States)

    Hanlon, J T; Perera, S; Newman, A B; Thorpe, J M; Donohue, J M; Simonsick, E M; Shorr, R I; Bauer, D C; Marcum, Z A

    2017-04-01

    There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults. This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use. Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2

  17. R&D in Vaccines Targeting Neglected Diseases: An Exploratory Case Study Considering Funding for Preventive Tuberculosis Vaccine Development from 2007 to 2014.

    Science.gov (United States)

    Costa Barbosa Bessa, Theolis; Santos de Aragão, Erika; Medeiros Guimarães, Jane Mary; de Araújo Almeida, Bethânia

    2017-01-01

    Based on an exploratory case study regarding the types of institutions funding the research and development to obtain new tuberculosis vaccines, this article intends to provoke discussion regarding the provision of new vaccines targeting neglected disease. Although our findings and discussion are mainly relevant to the case presented here, some aspects are more generally applicable, especially regarding the dynamics of development in vaccines to prevent neglected diseases. Taking into account the dynamics of innovation currently seen at work in the vaccine sector, a highly concentrated market dominated by few multinational pharmaceutical companies, we feel that global PDP models can play an important role throughout the vaccine development cycle. In addition, the authors call attention to issues surrounding the coordination of actors and resources in the research, development, manufacturing, and distribution processes of vaccine products arising from PDP involvement.

  18. [Non steroidal anti-inflammatory drugs and rheumatic diseases].

    Science.gov (United States)

    Cossermelli, W; Pastor, E H

    1995-01-01

    Nonsteroidal anti-inflammatory drugs (NSAID) comprise an important class of medicaments that reduced the symptoms of inflamation in rheumatic disease. This article emphasizes similarities and class characteristics of the NSAID, mechanisms of action, and drug-interactions.

  19. A two-pronged approach in leishmaniasis drug development in ...

    African Journals Online (AJOL)

    Nancy Kamau

    Trouiller P; Olliaro P; Torreele E;. Orbinski J; Laing R and Ford N. Drug development for neglected diseases: a deficient market and a public-health policy failure. Lancet. 2002; 359: 2188–94. 9. Nwaka S and Ridley RG. Virtual drug discovery and development for neglected diseases through public-private partnerships.

  20. Immunity against HIV/AIDS, malaria, and tuberculosis during co-infections with neglected infectious diseases: recommendations for the European Union research priorities.

    Directory of Open Access Journals (Sweden)

    Diana Boraschi

    2008-06-01

    Full Text Available Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB have received most of the world's attention. However, in rural and impoverished urban areas, a number of infectious diseases remain neglected and cause massive suffering. It has been calculated that a group of 13 neglected infectious diseases affects over one billion people, corresponding to a sixth of the world's population. These diseases include infections with different types of worms and parasites, cholera, and sleeping sickness, and can cause significant mortality and severe disabilities in low-income countries. For most of these diseases, vaccines are either not available, poorly effective, or too expensive. Moreover, these neglected diseases often occur in individuals who are also affected by HIV/AIDS, malaria, or TB, making the problem even more serious and indicating that co-infections are the rule rather than the exception in many geographical areas. To address the importance of combating co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9-11, 2007. The message coming from these scientists is that the only possibility for winning the fight against infections in low-income countries is by studying, in the most global way possible, the complex interaction between different infections and conditions of malnourishment. The new scientific and technical tools of the post-genomic era can allow us to reach this goal. However, a concomitant effort in improving education and social conditions will be needed to make the scientific findings effective.

  1. Systematic evaluation of drug-disease relationships to identify leads for novel drug uses.

    Science.gov (United States)

    Chiang, A P; Butte, A J

    2009-11-01

    Drug repositioning refers to the discovery of alternative uses for drugs--uses that are different from that for which the drugs were originally intended. One challenge in this effort lies in choosing the indication for which a drug of interest could be prospectively tested. We systematically evaluated a drug treatment-based view of diseases in order to address this challenge. Suggestions for novel drug uses were generated using a "guilt by association" approach. When compared with a control group of drug uses, the suggested novel drug uses generated by this approach were significantly enriched with respect to previous and ongoing clinical trials.

  2. Issues surrounding orphan disease and orphan drug policies in Europe.

    Science.gov (United States)

    Denis, Alain; Mergaert, Lut; Fostier, Christel; Cleemput, Irina; Simoens, Steven

    2010-01-01

    An orphan disease is a disease with a very low prevalence. Although there are 5000-7000 orphan diseases, only 50 orphan drugs (i.e. drugs developed to treat orphan diseases) were marketed in the EU by the end of 2008. In 2000, the EU implemented policies specifically designed to stimulate the development of orphan drugs. While decisions on orphan designation and the marketing authorization of orphan drugs are made at the EU level, decisions on drug reimbursement are made at the member state level. The specific features of orphan diseases and orphan drugs make them a high-priority issue for policy makers. The aim of this article is to identify and discuss several issues surrounding orphan disease and drug policies in Europe. The present system of orphan designation allows for drugs for non-orphan diseases to be designated as orphan drugs. The economic factors underlying orphan designation can be questioned in some cases, as a low prevalence of a certain indication does not equal a low return on investment for the drug across its indications. High-quality evidence about the clinical added value of orphan drugs is rarely available at the time of marketing authorization, due to the low number of patients. A balance must be struck between ethical and economic concerns. To this effect, there is a need to initiate a societal dialogue on this issue, to clarify what society wants and accepts in terms of ethical and economic consequences. The growing budgetary impact of orphan drugs puts pressure on drug expenditure. Indications can be extended for an orphan drug and the total prevalence across indications is not considered. Finally, cooperation needs to be fostered in the EU, particularly through a standardized approach to the creation and use of registries. These issues require further attention from researchers, policy makers, health professionals, patients, pharmaceutical companies and other stakeholders with a view to optimizing orphan disease and drug policies in

  3. Orphan diseases: state of the drug discovery art.

    Science.gov (United States)

    Volmar, Claude-Henry; Wahlestedt, Claes; Brothers, Shaun P

    2017-06-01

    Since 1983 more than 300 drugs have been developed and approved for orphan diseases. However, considering the development of novel diagnosis tools, the number of rare diseases vastly outpaces therapeutic discovery. Academic centers and nonprofit institutes are now at the forefront of rare disease R&D, partnering with pharmaceutical companies when academic researchers discover novel drugs or targets for specific diseases, thus reducing the failure risk and cost for pharmaceutical companies. Considerable progress has occurred in the art of orphan drug discovery, and a symbiotic relationship now exists between pharmaceutical industry, academia, and philanthropists that provides a useful framework for orphan disease therapeutic discovery. Here, the current state-of-the-art of drug discovery for orphan diseases is reviewed. Current technological approaches and challenges for drug discovery are considered, some of which can present somewhat unique challenges and opportunities in orphan diseases, including the potential for personalized medicine, gene therapy, and phenotypic screening.

  4. The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.

    Directory of Open Access Journals (Sweden)

    Becky L Rivoire

    Full Text Available True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3-10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan and MLCwA (M. leprae cell wall antigens. In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial.

  5. The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.

    Science.gov (United States)

    Rivoire, Becky L; TerLouw, Stephen; Groathouse, Nathan A; Brennan, Patrick J

    2014-01-01

    True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3-10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M. leprae cell wall antigens). In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial.

  6. Skin disease prevalence study in schoolchildren in rural Côte d'Ivoire: Implications for integration of neglected skin diseases (skin NTDs).

    Science.gov (United States)

    Yotsu, Rie Roselyne; Kouadio, Kouamé; Vagamon, Bamba; N'guessan, Konan; Akpa, Amari Jules; Yao, Aubin; Aké, Julien; Abbet Abbet, Rigobert; Tchamba Agbor Agbor, Barbine; Bedimo, Roger; Ishii, Norihisa; Fuller, L Claire; Hay, Roderick; Mitjà, Oriol; Drechsler, Henning; Asiedu, Kingsley

    2018-05-01

    Early detection of several skin-related neglected tropical diseases (skin NTDs)-including leprosy, Buruli ulcer, yaws, and scabies- may be achieved through school surveys, but such an approach has seldom been tested systematically on a large scale in endemic countries. Additionally, a better understanding of the spectrum of skin diseases and the at-risk populations to be encountered during such surveys is necessary to facilitate the process. We performed a school skin survey for selected NTDs and the spectrum of skin diseases, among primary schoolchildren aged 5 to 15 in Côte d'Ivoire, West Africa. This 2-phase survey took place in 49 schools from 16 villages in the Adzopé health district from November 2015 to January 2016. The first phase involved a rapid visual examination of the skin by local community healthcare workers (village nurses) to identify any skin abnormality. In a second phase, a specialized medical team including dermatologists performed a total skin examination of all screened students with any skin lesion and provided treatment where necessary. Of a total of 13,019 children, 3,504 screened positive for skin lesions and were listed for the next stage examination. The medical team examined 1,138 of these children. The overall prevalence of skin diseases was 25.6% (95% CI: 24.3-26.9%). The predominant diagnoses were fungal infections (n = 858, prevalence: 22.3%), followed by inflammatory skin diseases (n = 265, prevalence: 6.9%). Skin diseases were more common in boys and in children living along the main road with heavy traffic. One case of multi-bacillary type leprosy was detected early, along with 36 cases of scabies. Our survey was met with very good community acceptance. We carried out the first large-scale integrated, two-phase pediatric multi-skin NTD survey in rural Côte d'Ivoire, effectively reaching a large population. We found a high prevalence of skin diseases in children, but only limited number of skin NTDs. With the lessons learned

  7. Applying genetics in inflammatory disease drug discovery

    DEFF Research Database (Denmark)

    Folkersen, Lasse; Biswas, Shameek; Frederiksen, Klaus Stensgaard

    2015-01-01

    , with several notable exceptions, the journey from a small-effect genetic variant to a functional drug has proven arduous, and few examples of actual contributions to drug discovery exist. Here, we discuss novel approaches of overcoming this hurdle by using instead public genetics resources as a pragmatic guide...... alongside existing drug discovery methods. Our aim is to evaluate human genetic confidence as a rationale for drug target selection....

  8. The Pan American Health Organization’s role and perspectives on the mapping and modeling of the neglected tropical diseases in Latin America and the Caribbean: an overview

    Directory of Open Access Journals (Sweden)

    Steven K. Ault

    2012-09-01

    Full Text Available The Pan American Health Organization (PAHO, which functions as the regional office for the Americas of the World Health Organization, is committed to provide technical cooperation to countries to update the epidemiological information available for mapping and modelling of the neglected tropical diseases (NTDs, a set of diseases mainly caused by parasites affecting people living in low socioeconomic and favourable environmental conditions. This communication discusses PAHO’s role and perspectives in the use of mapping and modelling of these diseases with a view to promote its use in the development and implementation of integrated, inter-programmatic and inter-sectoral plans for the prevention, control or elimination of the NTDs and other infectious diseases related to poverty.

  9. The Pan American Health Organization's role and perspectives on the mapping and modeling of the neglected tropical diseases in Latin America and the Caribbean: an overview.

    Science.gov (United States)

    Ault, Steven K; Nicholls, Ruben Santiago; Saboya, Martha IdaIí

    2012-09-01

    The Pan American Health Organization (PAHO), which functions as the regional office for the Americas of the World Health Organization, is committed to provide technical cooperation to countries to update the epidemiological information available for mapping and modelling of the neglected tropical diseases (NTDs), a set of diseases mainly caused by parasites affecting people living in low socioeconomic and favourable environmental conditions. This communication discusses PAHO's role and perspectives in the use of mapping and modelling of these diseases with a view to promote its use in the development and implementation of integrated, inter-programmatic and inter-sectoral plans for the prevention, control or elimination of the NTDs and other infectious diseases related to poverty.

  10. Developmental Growth Trajectories of Self-Esteem in Adolescence: Associations with Child Neglect and Drug Use and Abuse in Young Adulthood.

    Science.gov (United States)

    Oshri, Assaf; Carlson, Matthew W; Kwon, Josephine A; Zeichner, Amos; Wickrama, Kandauda K A S

    2017-01-01

    Neglectful rearing is linked with young adults' substance use and abuse, though the developmental mechanisms that underlie this association are unclear. The present study examines links between self-esteem growth during adolescence, childhood supervisory versus physical neglect severity, and substance use and abuse in young adulthood. A sample of youth was obtained from the Add Health study (N = 8738; 55.4 %-Female; 20 %-African American, 14.7 %-Hispanic). Growth mixture modeling analyses supported declining, ascending, and stable high self-esteem trajectories. The declining and ascending trajectories reported greater neglect and alcohol abuse (but not use) as well as cannabis use and abuse. The findings suggest that compromised development of self-esteem underlies associations between neglect and substance use and abuse. Preventive interventions may benefit from targeting self-esteem among neglected youth.

  11. Pharmacogenomics to Revive Drug Development in Cardiovascular Disease.

    Science.gov (United States)

    Dubé, Marie-Pierre; de Denus, Simon; Tardif, Jean-Claude

    2016-02-01

    Investment in cardiovascular drug development is on the decline as large cardiovascular outcomes trials require considerable investments in time, efforts and financial resources. Pharmacogenomics has the potential to help revive the cardiovascular drug development pipeline by providing new and better drug targets at an earlier stage and by enabling more efficient outcomes trials. This article will review some of the recent developments highlighting the value of pharmacogenomics for drug development. We discuss how genetic biomarkers can enable the conduct of more efficient clinical outcomes trials by enriching patient populations for good responders to the medication. In addition, we assess past drug development programs which support the added value of selecting drug targets that have established genetic evidence supporting the targeted mechanism of disease. Finally, we discuss how pharmacogenomics can provide valuable evidence linking a drug target to clinically relevant outcomes, enabling novel drug discovery and drug repositioning opportunities.

  12. Integration of water, sanitation, and hygiene for the prevention and control of neglected tropical diseases: a rationale for inter-sectoral collaboration.

    Directory of Open Access Journals (Sweden)

    Matthew C Freeman

    Full Text Available Improvements of water, sanitation, and hygiene (WASH infrastructure and appropriate health-seeking behavior are necessary for achieving sustained control, elimination, or eradication of many neglected tropical diseases (NTDs. Indeed, the global strategies to fight NTDs include provision of WASH, but few programs have specific WASH targets and approaches. Collaboration between disease control programs and stakeholders in WASH is a critical next step. A group of stakeholders from the NTD control, child health, and WASH sectors convened in late 2012 to discuss opportunities for, and barriers to, collaboration. The group agreed on a common vision, namely "Disease-free communities that have adequate and equitable access to water and sanitation, and that practice good hygiene." Four key areas of collaboration were identified, including (i advocacy, policy, and communication; (ii capacity building and training; (iii mapping, data collection, and monitoring; and (iv research. We discuss strategic opportunities and ways forward for enhanced collaboration between the WASH and the NTD sectors.

  13. Integration of water, sanitation, and hygiene for the prevention and control of neglected tropical diseases: a rationale for inter-sectoral collaboration.

    Science.gov (United States)

    Freeman, Matthew C; Ogden, Stephanie; Jacobson, Julie; Abbott, Daniel; Addiss, David G; Amnie, Asrat G; Beckwith, Colin; Cairncross, Sandy; Callejas, Rafael; Colford, Jack M; Emerson, Paul M; Fenwick, Alan; Fishman, Rebecca; Gallo, Kerry; Grimes, Jack; Karapetyan, Gagik; Keene, Brooks; Lammie, Patrick J; Macarthur, Chad; Lochery, Peter; Petach, Helen; Platt, Jennifer; Prabasi, Sarina; Rosenboom, Jan Willem; Roy, Sharon; Saywell, Darren; Schechtman, Lisa; Tantri, Anupama; Velleman, Yael; Utzinger, Jürg

    2013-01-01

    Improvements of water, sanitation, and hygiene (WASH) infrastructure and appropriate health-seeking behavior are necessary for achieving sustained control, elimination, or eradication of many neglected tropical diseases (NTDs). Indeed, the global strategies to fight NTDs include provision of WASH, but few programs have specific WASH targets and approaches. Collaboration between disease control programs and stakeholders in WASH is a critical next step. A group of stakeholders from the NTD control, child health, and WASH sectors convened in late 2012 to discuss opportunities for, and barriers to, collaboration. The group agreed on a common vision, namely "Disease-free communities that have adequate and equitable access to water and sanitation, and that practice good hygiene." Four key areas of collaboration were identified, including (i) advocacy, policy, and communication; (ii) capacity building and training; (iii) mapping, data collection, and monitoring; and (iv) research. We discuss strategic opportunities and ways forward for enhanced collaboration between the WASH and the NTD sectors.

  14. Public acceptance of drug use for non-disease conditions

    DEFF Research Database (Denmark)

    Møldrup, Claus; Hansen, Rikke Rie

    2006-01-01

    OBJECTIVE: This article deals with the issue of ordinary healthy people using drugs to improve or enhance non-disease conditions. The objective is to illuminate the extent of public acceptance of this practice. RESEARCH DESIGN AND METHODS: The results are based on two studies: a classically...... of drugs for non-disease conditions. Men in particular look favourably on the use of drugs by healthy individuals. People with less education find this type of drug use unacceptable to a greater extent than those with more education, who are more positive. If we look at political affiliation, a pattern...

  15. Drug therapy for gastrointestinal and liver diseases

    National Research Council Canada - National Science Library

    Ballinger, Anne; Farthing, M. J. G. (Michael J. G.)

    2001-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Peptic ulcer disease Erik AJ Rauws, Guido NJ Tytgat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Emesis Gareth J Sanger, Paul LR Andrews...

  16. Seroepidemiology of Human Brucellosis Among Blood Donors in Southern Ethiopia: Calling Attention to a Neglected Zoonotic Disease.

    Science.gov (United States)

    Workalemahu, Bereket; Sewunet, Tsegaye; Astatkie, Ayalew

    2017-01-11

    Human brucellosis is neglected in southern Ethiopia. Although traditional food processing practices and animal husbandry which increase the risk of brucellosis are common, it has not been properly studied yet. This study was conducted to determine the seroepidemiology of brucellosis among apparently healthy individuals in southern Ethiopia. In the study, blood samples were collected to screen for serum agglutinins reactive to stained antigen of Brucella abortus Standard tube titration was performed for reactive serum to determine the titer of the agglutinin. A structured questionnaire was used to collect data on possible risk factors for brucellosis. The seroprevalence of human brucellosis in this study was found to be 10.6% (95% confidence interval = 7.0, 14.0). Possession of domestic ruminant animals, contact with ruminant animals, and husbandry practices at home were associated with seropositivity. The higher seroprevalence of human brucellosis in the study area needs attention and additional confirmatory investigation. © The American Society of Tropical Medicine and Hygiene.

  17. Could visual neglect induce amblyopia?

    Science.gov (United States)

    Bier, J C; Vokaer, M; Fery, P; Garbusinski, J; Van Campenhoudt, G; Blecic, S A; Bartholomé, E J

    2004-12-01

    Oculomotor nerve disease is a common cause of diplopia. When strabismus is present, absence of diplopia has to induce the research of either uncovering of visual fields or monocular suppression, amblyopia or blindness. We describe the case of a 41-year-old woman presenting with right oculomotor paresis and left object-centred visual neglect due to a right fronto-parietal haemorrhage expanding to the right peri-mesencephalic cisterna caused by the rupture of a right middle cerebral artery aneurysm. She never complained of diplopia despite binocular vision and progressive recovery of strabismus, excluding uncovering of visual fields. Since all other causes were excluded in this case, we hypothesise that the absence of diplopia was due to the object-centred visual neglect. Partial internal right oculomotor paresis causes an ocular deviation in abduction; the image being perceived deviated contralaterally to the left. Thus, in our case, the neglect of the left image is equivalent to a right monocular functional blindness. However, bell cancellation test clearly worsened when assessed in left monocular vision confirming that eye patching can worsen attentional visual neglect. In conclusion, our case argues for the possibility of a functional monocular blindness induced by visual neglect. We think that in presence of strabismus, absence of diplopia should induce the search for hemispatial visual neglect when supratentorial lesions are suspected.

  18. Can Patients with Cardiovascular Disease Take Nonsteroidal Antiinflammatory Drugs?

    Science.gov (United States)

    ... of the American Heart Association Cardiology Patient Page Can Patients With Cardiovascular Disease Take Nonsteroidal Antiinflammatory Drugs? ... It also does not upset the gastrointestinal tract. Can People With CVD Take an NSAID? If you ...

  19. Electrochemical studies of ropinirole, an anti-Parkinson's disease drug

    Indian Academy of Sciences (India)

    The oxidation behaviour of a potent anti-Parkinson's disease drug ropinirole hydrochloride was investigated over a wide pH range in aqueous solution at glassy carbon electrode using cyclic and square-wave voltammetry. The oxidation of drug is a pH dependent irreversible process and occurs in two steps.

  20. [Neglect of Children--a neglected problem].

    Science.gov (United States)

    Lucas, Steven; Jernbro, Carolina

    2014-11-18

    Although neglect is the most common form of child maltreatment in the home, it has received relatively little attention in both research and medical practice. Up to one in six children in the western world experience physical or psychological neglect during their upbringing. Severe neglect is associated with anatomical and physiological changes in the brain that in turn are coupled to cognitive impairment, impulsivity, and disturbances in concentration and social behavior. Reducing the risk of neglect requires the provision of preventive interventions at the individual and societal level, both universally and targeted to parents and children in need of special support. Health care services can play a key role in the prevention and early detection of neglect in childhood.

  1. Europe's neglected infections of poverty.

    Science.gov (United States)

    Hotez, Peter J; Gurwith, Meredith

    2011-09-01

    To review the prevalence, incidence, and geographic distribution of the major neglected infections of poverty in Europe as a basis for future policy recommendations. We reviewed the literature from 1999 to 2010 for neglected tropical diseases listed by PLoS Neglected Tropical Diseases (http://www.plosntds.org/static/scope.action) and the geographic regions and countries of (continental) Europe. Reference lists of identified articles and reviews were also hand searched, as were World Health Organization databases. In Eastern Europe, the soil-transmitted helminth infections (especially ascariasis, trichuriasis, and toxocariasis), giardiasis, and toxoplasmosis remain endemic. High incidence rates of selected food-borne helminthiases including trichinellosis, opisthorchiasis, taeniasis, and echinococcosis also occur, while brucellosis and leptospirosis represent important bacterial zoonoses. Turmoil and economic collapse following the war in the Balkans, the fall of Communism, and Europe's recent recession have helped to promote their high prevalence and incidence rates. In Southern Europe, vector-borne zoonoses have emerged, including leishmaniasis and Chagas disease, and key arboviral infections. Additional vulnerable populations include the Roma, orphans destined for international adoption, and some immigrant groups. Among the policy recommendations are increased efforts to determine the prevalence, incidence, and geographic distribution of Europe's neglected infections, epidemiological studies to understand the ecology and mechanisms of disease transmission, and research and development for new control tools. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Pharmacological approaches for Alzheimer's disease: neurotransmitter as drug targets.

    Science.gov (United States)

    Prakash, Atish; Kalra, Jaspreet; Mani, Vasudevan; Ramasamy, Kalavathy; Majeed, Abu Bakar Abdul

    2015-01-01

    Alzheimer's disease (AD) is the most common CNS disorder occurring worldwide. There is neither proven effective prevention for AD nor a cure for patients with this disorder. Hence, there is an urgent need to develop safer and more efficacious drugs to help combat the tremendous increase in disease progression. The present review is an attempt at discussing the treatment strategies and drugs under clinical trials governing the modulation of neurotransmitter. Therefore, looking at neurotransmitter abnormalities, there is an urge for developing the pharmacological approaches aimed at correcting those abnormalities and dysfunctioning. In addition, this review also discusses the drugs that are in Phase III trials for the treatment of AD. Despite advances in treatment strategies aimed at correcting neurotransmitter abnormalities, there exists a need for the development of drug therapies focusing on the attempts to remove the pathogenomic protein deposits, thus combating the disease progression.

  3. Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

    Science.gov (United States)

    Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

    2016-01-01

    Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

  4. Identifying gaps in research prioritization: The global burden of neglected tropical diseases as reflected in the Cochrane database of systematic reviews

    Directory of Open Access Journals (Sweden)

    Soumyadeep Bhaumik

    2015-01-01

    Full Text Available Background: Neglected tropical diseases (NTDs impact disadvantaged populations in resource-scarce settings. Availability of synthesized evidence is paramount to end this disparity. The aim of the study was to determine whether NTD systematic reviews or protocols in the Cochrane Database of Systematic Reviews (CDSR reflect disease burden. Methods: Two authors independently searched the CDSR for reviews/protocols regarding the NTDs diseases. Each review or protocol was classified to a single NTD category. Any discrepancy was solved by consensus with third author. NTD systematic review or protocol from CDSR were matched with disability-adjusted life year (DALY metrics from the Global Burden of Disease 2010 Study. Spearman′s rank correlation coefficient and associated P values were used to assess for correlation between the number of systematic reviews and protocols and the %2010 DALY associated with each NTD. Results: Overall, there was poor correlation between CDSR representation and DALYs. Yellow fever, echinococcus, onchocerciasis, and schistosomiasis representation was well-aligned with DALY. Leprosy, trachoma, dengue, leishmaniasis, and Chagas disease representation was greater, while cysticercosis, human African trypanosomiasis, ascariasis, lymphatic filariasis, and hookworm representation was lower than DALY. Three of the 18 NTDs had reviews/protocols of diagnostic test accuracy. Conclusions: Our results indicate the need for increased prioritization of systematic reviews on NTDs, particularly diagnostic test accuracy reviews.

  5. From research on rare diseases to new orphan drug development

    NARCIS (Netherlands)

    Heemstra, H.E.

    2010-01-01

    Rare diseases have a prevalence of lower than 5 in 10,000 inhabitants and are life-threatening or chronically debilitating. It is estimated that worldwide more than 5000 rare diseases exist, which account for over 55 million patients in the EU and the US together. However, the development of drugs

  6. Serotonergic Drugs and Valvular Heart Disease

    Science.gov (United States)

    Rothman, Richard B.; Baumann, Michael H.

    2009-01-01

    Background The serotonin (5-HT) releasers (±)-fenfluramine and (+)-fenfluramine were withdrawn from clinical use due to increased risk of valvular heart disease. One prevailing hypothesis (i.e., the “5-HT hypothesis”) suggests that fenfluramine-induced increases in plasma 5-HT underlie the disease. Objective Here we critically evaluate the possible mechanisms responsible for fenfluramine-associated valve disease. Methods Findings from in vitro and in vivo experiments performed in our laboratory are reviewed. The data are integrated with existing literature to address the validity of the 5-HT hypothesis and suggest alternative explanations. Conclusions The overwhelming majority of evidence refutes the 5-HT hypothesis. A more likely cause of fenfluramine-induced valvulopathy is activation of 5-HT2B receptors on heart valves by the metabolite norfenfluramine. Future serotonergic medications should be designed to lack 5-HT2B agonist activity. PMID:19505264

  7. Multimodal drugs and their future for Alzheimer's and Parkinson's disease.

    Science.gov (United States)

    Van der Schyf, Cornelis J; Geldenhuys, Werner J

    2011-01-01

    This chapter discusses the rationale for developing multimodal or multifunctional drugs (also called designed multiple ligands or DMLs) aimed at disease-modifying treatment strategies for the most common neurodegenerative diseases Alzheimer's and Parkinson's disease (AD and PD). Both the prevalence and incidence of AD and PD have seen consistent and dramatic increases, a disconcerting phenomenon which, ironically, has been attributed to extended life expectancy brought about by better health care globally. In spite of these statistics, the development and introduction to the clinic of new therapies proven to prevent or delay the onset of AD and PD have been disappointing. Evidence has accumulated to suggest that the etiopathology of these diseases is extremely complex, with an array of potential drug targets located within a number of deleterious biochemical pathways. Therefore, in these diseases, it is unlikely that the complex pathoetiological cascade leading to disease initiation or progression will be mitigated by any one drug acting on a single pathway or target. The pursuit of novel DMLs may offer far better outcomes. Although certainly not the only, and perhaps not even the best, approach but farthest along the drug development pipeline in the DML paradigm are drugs that combine inhibition of monoamine oxidase with associated etiological targets unique to either AD or PD. These compounds will constitute the major focus of this chapter, which will also explore radically new paradigms that seek to combine cognitive enhancers with proneurogenesis compounds. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Recovery of personal neglect.

    Science.gov (United States)

    Iosa, Marco; Guariglia, Cecilia; Matano, Alessandro; Paolucci, Stefano; Pizzamiglio, Luigi

    2016-12-01

    Extrapersonal unilateral spatial neglect after stroke is associated to a poor rehabilitation outcome. Minor attention has been paid to the recovery of personal neglect, to its relationship with the recovery of extrapersonal neglect and of independency in activities of daily living. The present study aims at evaluating whether there is an association between recovery of extrapersonal and personal neglect. The secondary aim was to investigate if personal neglect may affect the effectiveness of neurorehabilitation in patients with subacute stroke. Observational study. Neurorehabilitation Hospital in Rome, Italy, inpatients. A sample of 49 patients with unilateral spatial neglect resulting from right ischemic cerebral infarction was enrolled in this study, divided into three subgroups according to the presence and the degree of personal neglect, and evaluated pre and postneurorehabilitation. Personal neglect was evaluated using Zoccolotti and Judica's Scale, extrapersonal neglect using Letter Cancellation Test, Barrage Test, Sentence Reading Test and Wundt-Jastrow Area Illusion Test. Barthel Index (BI), Rivermead Mobility Index, and Canadian Neurological Scale were also administered. Results showed the following: 1) recovery of personal neglect was not significantly correlated with that of extrapersonal neglect, despite both the disorders were ameliorated after a "non-specific" rehabilitation treatment; 2) personal neglect per se was not an additional negative prognostic factor in the rehabilitation findings. Our results suggested that the recoveries of the two types of neglect are independent from each other, and that the presence of personal neglect does not imply significant additional problems to the functional outcomes. Our study highlighted the need of novel tools to assess the presence and to improve the recovery of personal neglect.

  9. Structural genomics of infectious disease drug targets: the SSGCID

    International Nuclear Information System (INIS)

    Stacy, Robin; Begley, Darren W.; Phan, Isabelle; Staker, Bart L.; Van Voorhis, Wesley C.; Varani, Gabriele; Buchko, Garry W.; Stewart, Lance J.; Myler, Peter J.

    2011-01-01

    An introduction and overview of the focus, goals and overall mission of the Seattle Structural Genomics Center for Infectious Disease (SSGCID) is given. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium of researchers at Seattle BioMed, Emerald BioStructures, the University of Washington and Pacific Northwest National Laboratory that was established to apply structural genomics approaches to drug targets from infectious disease organisms. The SSGCID is currently funded over a five-year period by the National Institute of Allergy and Infectious Diseases (NIAID) to determine the three-dimensional structures of 400 proteins from a variety of Category A, B and C pathogens. Target selection engages the infectious disease research and drug-therapy communities to identify drug targets, essential enzymes, virulence factors and vaccine candidates of biomedical relevance to combat infectious diseases. The protein-expression systems, purified proteins, ligand screens and three-dimensional structures produced by SSGCID constitute a valuable resource for drug-discovery research, all of which is made freely available to the greater scientific community. This issue of Acta Crystallographica Section F, entirely devoted to the work of the SSGCID, covers the details of the high-throughput pipeline and presents a series of structures from a broad array of pathogenic organisms. Here, a background is provided on the structural genomics of infectious disease, the essential components of the SSGCID pipeline are discussed and a survey of progress to date is presented

  10. Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease

    Directory of Open Access Journals (Sweden)

    Liane Rabinowich

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI. The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis.

  11. The Impact of Disease and Drugs on Hip Fracture Risk.

    Science.gov (United States)

    Leavy, Breiffni; Michaëlsson, Karl; Åberg, Anna Cristina; Melhus, Håkan; Byberg, Liisa

    2017-01-01

    We report the risks of a comprehensive range of disease and drug categories on hip fracture occurrence using a strict population-based cohort design. Participants included the source population of a Swedish county, aged ≥50 years (n = 117,494) including all incident hip fractures during 1 year (n = 477). The outcome was hospitalization for hip fracture (ICD-10 codes S72.0-S72.2) during 1 year (2009-2010). Exposures included: prevalence of (1) inpatient diseases [International Classification of Diseases (ICD) codes A00-T98 in the National Patient Register 1987-2010] and (2) prescribed drugs dispensed in 2010 or the year prior to fracture. We present age- and sex-standardized risk ratios (RRs), risk differences (RDs) and population attributable risks (PARs) of disease and drug categories in relation to hip fracture risk. All disease categories were associated with increased risk of hip fracture. Largest risk ratios and differences were for mental and behavioral disorders, diseases of the blood and previous fracture (RRs between 2.44 and 3.00; RDs (per 1000 person-years) between 5.0 and 6.9). For specific drugs, strongest associations were seen for antiparkinson (RR 2.32 [95 % CI 1.48-1.65]; RD 5.2 [1.1-9.4]) and antidepressive drugs (RR 1.90 [1.55-2.32]; RD 3.1 [2.0-4.3]). Being prescribed ≥10 drugs during 1 year incurred an increased risk of hip fracture, whereas prescription of cardiovascular drugs or ≤5 drugs did not appear to increase risk. Diseases inferring the greatest PARs included: cardiovascular diseases PAR 22 % (95 % CI 14-29) and previous injuries (PAR 21 % [95 % CI 16-25]; for specific drugs, antidepressants posed the greatest risk (PAR 16 % [95 % CI 12.0-19.3]).

  12. Structural Genomics and Drug Discovery for Infectious Diseases

    International Nuclear Information System (INIS)

    Anderson, W.F.

    2009-01-01

    The application of structural genomics methods and approaches to proteins from organisms causing infectious diseases is making available the three dimensional structures of many proteins that are potential drug targets and laying the groundwork for structure aided drug discovery efforts. There are a number of structural genomics projects with a focus on pathogens that have been initiated worldwide. The Center for Structural Genomics of Infectious Diseases (CSGID) was recently established to apply state-of-the-art high throughput structural biology technologies to the characterization of proteins from the National Institute for Allergy and Infectious Diseases (NIAID) category A-C pathogens and organisms causing emerging, or re-emerging infectious diseases. The target selection process emphasizes potential biomedical benefits. Selected proteins include known drug targets and their homologs, essential enzymes, virulence factors and vaccine candidates. The Center also provides a structure determination service for the infectious disease scientific community. The ultimate goal is to generate a library of structures that are available to the scientific community and can serve as a starting point for further research and structure aided drug discovery for infectious diseases. To achieve this goal, the CSGID will determine protein crystal structures of 400 proteins and protein-ligand complexes using proven, rapid, highly integrated, and cost-effective methods for such determination, primarily by X-ray crystallography. High throughput crystallographic structure determination is greatly aided by frequent, convenient access to high-performance beamlines at third-generation synchrotron X-ray sources.

  13. In silico studies in drug research against neurodegenerative diseases.

    Science.gov (United States)

    Makhouri, Farahnaz Rezaei; Ghasemi, Jahan B

    2017-08-22

    Neurodegenerative diseases such as Alzheimer's disease (AD), progressive neurodegenerative forms of Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis, spinal cerebellar ataxias, and spinal and bulbar muscular atrophy are described by slow and selective dysfunction and degeneration of neurons and axons in the central nervous system (CNS). Computer-aided or in silico design methods have matured into powerful tools for reducing the number of ligands that should be screened in experimental assays. In the present review, the authors provide a basic background about neurodegenerative diseases and in silico techniques in the drug research. Furthermore, they review the various in silico studies reported against various targets in neurodegenerative diseases, including homology modeling, molecular docking, virtual high-throughput screening, quantitative structure activity relationship (QSAR), hologram quantitative structure activity relationship (HQSAR), 3D pharmacophore mapping, proteochemometrics modeling (PCM), fingerprints, fragment-based drug discovery, Monte Carlo simulation, molecular dynamic (MD) simulation, quantum-mechanical methods for drug design, support vector machines, and machine learning approaches. Neurodegenerative diseases have a multifactorial pathoetiological origin, so scientists have become persuaded that a multi-target therapeutic strategy aimed at the simultaneous targeting of multiple proteins (and therefore etiologies) involved in the development of a disease is recommended in future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Noncommunicable diseases among urban refugees and asylum-seekers in developing countries: a neglected health care need

    Science.gov (United States)

    2014-01-01

    With the increasing trend in refugee urbanisation, growing numbers of refugees are diagnosed with chronic noncommunicable diseases (NCDs). However, with few exceptions, the local and international communities prioritise communicable diseases. The aim of this study is to review the literature to determine the prevalence and distribution of chronic NCDs among urban refugees living in developing countries, to report refugee access to health care for NCDs and to compare the prevalence of NCDs among urban refugees with the prevalence in their home countries. Major search engines and refugee agency websites were systematically searched between June and July 2012 for articles and reports on NCD prevalence among urban refugees. Most studies were conducted in the Middle East and indicated a high prevalence of NCDs among urban refugees in this region, but in general, the prevalence varied by refugees’ region or country of origin. Hypertension, musculoskeletal disease, diabetes and chronic respiratory disease were the major diseases observed. In general, most urban refugees in developing countries have adequate access to primary health care services. Further investigations are needed to document the burden of NCDs among urban refugees and to identify their need for health care in developing countries. PMID:24708876

  15. Cardiovascular disease among people with drug use disorders

    DEFF Research Database (Denmark)

    Thylstrup, Birgitte; Clausen, Thomas; Hesse, Morten

    2015-01-01

    Objectives To present the prevalence and incidence of cardiovascular disease (CVD) in a national cohort of patients seeking treatment for drug use disorders (DUD). Methods This is a longitudinal record linkage study of consecutive DUD treatment admissions between 2000 and 2006 from Denmark. Results...... treatment (SHR = 1.15, p = 0.022). The use of amphetamines was negatively associated with the risk of CVD within this cohort (SHR = 0.75, p = 0.001). Conclusions Patients injecting drugs using prescribed methadone were at elevated risk for cardiovascular disease and should be monitored for CVD. Opioid...... medications should be evaluated in terms of their cardiovascular sequelae....

  16. Emerging analgesic drugs for Parkinson's disease.

    Science.gov (United States)

    Perez-Lloret, Santiago; Rey, María Verónica; Dellapina, Estelle; Pellaprat, Jean; Brefel-Courbon, Christine; Rascol, Olivier

    2012-06-01

    Pain affects between 40 and 85% of Parkinson's disease (PD) patients. It is a frequently disabling and overlooked feature, which can significantly reduce health-related quality of life. Unfortunately, there are no universally recommended treatments for this condition. Evidence about the efficacy and safety of available analgesic treatments is summarized in this review. Potential targets for upcoming therapies are then discussed in light of what is currently known about the physiopathology of pain in PD. Protocols for efficacy and safety assessment of novel analgesic therapies are discussed. Finally, critical aspects of study protocol design such as patient selection or outcomes to be evaluated are discussed. Preliminary results indicate that duloxetine, cranial electrotherapy stimulation, rotigotine, subthalamic or pallidum nuclei stimulation or lesion or levodopa could be effective for treating pain in PD. Similarly, some case reports indicate that repetitive transcranial magnetic stimulation (rTMS) or apomorphine could be effective for relieving painful off-period dystonia. Clinical trials with rTMS or oxycodone/naloxone prolonged-release tablets for neuropathic pain or botulinum toxin for off-period dystonia are underway. Success of clinical trials about analgesic strategies in PD will depend on the selection of the right PD population to be treated, according to the type of pain, and the proper selection of study outcomes and follow-up of international recommendations.

  17. Co-authorship network analysis: a powerful tool for strategic planning of research, development and capacity building programs on neglected diseases.

    Directory of Open Access Journals (Sweden)

    Carlos Medicis Morel

    Full Text Available BACKGROUND: New approaches and tools were needed to support the strategic planning, implementation and management of a Program launched by the Brazilian Government to fund research, development and capacity building on neglected tropical diseases with strong focus on the North, Northeast and Center-West regions of the country where these diseases are prevalent. METHODOLOGY/PRINCIPAL FINDINGS: Based on demographic, epidemiological and burden of disease data, seven diseases were selected by the Ministry of Health as targets of the initiative. Publications on these diseases by Brazilian researchers were retrieved from international databases, analyzed and processed with text-mining tools in order to standardize author- and institution's names and addresses. Co-authorship networks based on these publications were assembled, visualized and analyzed with social network analysis software packages. Network visualization and analysis generated new information, allowing better design and strategic planning of the Program, enabling decision makers to characterize network components by area of work, identify institutions as well as authors playing major roles as central hubs or located at critical network cut-points and readily detect authors or institutions participating in large international scientific collaborating networks. CONCLUSIONS/SIGNIFICANCE: Traditional criteria used to monitor and evaluate research proposals or R&D Programs, such as researchers' productivity and impact factor of scientific publications, are of limited value when addressing research areas of low productivity or involving institutions from endemic regions where human resources are limited. Network analysis was found to generate new and valuable information relevant to the strategic planning, implementation and monitoring of the Program. It afforded a more proactive role of the funding agencies in relation to public health and equity goals, to scientific capacity building

  18. Co-authorship Network Analysis: A Powerful Tool for Strategic Planning of Research, Development and Capacity Building Programs on Neglected Diseases

    Science.gov (United States)

    Morel, Carlos Medicis; Serruya, Suzanne Jacob; Penna, Gerson Oliveira; Guimarães, Reinaldo

    2009-01-01

    Background New approaches and tools were needed to support the strategic planning, implementation and management of a Program launched by the Brazilian Government to fund research, development and capacity building on neglected tropical diseases with strong focus on the North, Northeast and Center-West regions of the country where these diseases are prevalent. Methodology/Principal Findings Based on demographic, epidemiological and burden of disease data, seven diseases were selected by the Ministry of Health as targets of the initiative. Publications on these diseases by Brazilian researchers were retrieved from international databases, analyzed and processed with text-mining tools in order to standardize author- and institution's names and addresses. Co-authorship networks based on these publications were assembled, visualized and analyzed with social network analysis software packages. Network visualization and analysis generated new information, allowing better design and strategic planning of the Program, enabling decision makers to characterize network components by area of work, identify institutions as well as authors playing major roles as central hubs or located at critical network cut-points and readily detect authors or institutions participating in large international scientific collaborating networks. Conclusions/Significance Traditional criteria used to monitor and evaluate research proposals or R&D Programs, such as researchers' productivity and impact factor of scientific publications, are of limited value when addressing research areas of low productivity or involving institutions from endemic regions where human resources are limited. Network analysis was found to generate new and valuable information relevant to the strategic planning, implementation and monitoring of the Program. It afforded a more proactive role of the funding agencies in relation to public health and equity goals, to scientific capacity building objectives and a more

  19. A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Qi Chen

    Full Text Available Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD, the focus is the amyloid beta peptide (Aß that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model.

  20. Extent of Integration of Priority Interventions into General Health Systems: A Case Study of Neglected Tropical Diseases Programme in the Western Region of Ghana.

    Science.gov (United States)

    Mensah, Ernest O; Aikins, Moses K; Gyapong, Margaret; Anto, Francis; Bockarie, Moses J; Gyapong, John O

    2016-05-01

    The global health system has a large arsenal of interventions, medical products and technologies to address current global health challenges. However, identifying the most effective and efficient strategies to deliver these resources to where they are most needed has been a challenge. Targeted and integrated interventions have been the main delivery strategies. However, the health system discourse increasingly favours integrated strategies in the context of functionally merging targeted interventions with multifunctional health care delivery systems with a focus on strengthening country health systems to deliver needed interventions. Neglected Tropical Diseases (NTD) have been identified to promote and perpetuate poverty hence there has been global effort to combat these diseases. The Neglected Tropical Diseases Programme (NTDP) in Ghana has a national programme team and office, however, it depends on the multifunctional health delivery system at the regional and district level to implement interventions. The NTDP seeks further health system integration to accelerate achievement of coverage targets. The study estimated the extent of integration of the NTDP at the national, regional and district levels to provide evidence to guide further integration. The research design was a descriptive case study that interviewed key persons involved in the programme at the three levels of the health system as well as extensive document review. Integration was assessed on two planes-across health system functions-stewardship and governance, financing, planning, service delivery, monitoring and evaluation and demand generation; and across three administrative levels of the health system-national, regional and district. A composite measure of integration designated Cumulative Integration Index (CII) with a range of 0.00-1.00 was used to estimate extent of integration at the three levels of the health system. Service delivery was most integrated while financing and planning were

  1. Chronotherapeutic drug delivery systems: an approach to circadian rhythms diseases.

    Science.gov (United States)

    Sunil, S A; Srikanth, M V; Rao, N Sreenivasa; Uhumwangho, M U; Latha, K; Murthy, K V Ramana

    2011-11-01

    The purpose of writing this review on chronotherapeutic drug delivery systems (ChrDDs) is to review the literatures with special focus on ChrDDs and the various dosage forms, techniques that are used to target the circadian rhythms (CR) of various diseases. Many functions of the human body vary considerably in a day. ChrDDs refers to a treatment method in which in vivo drug availability is timed to match circadian rhythms of disease in order to optimize therapeutic outcomes and minimize side effects. Several techniques have been developed but not many dosage forms for all the diseases are available in the market. ChrDDs are gaining importance in the field of pharmaceutical technology as these systems reduce dosing frequency, toxicity and deliver the drug that matches the CR of that particular disease when the symptoms are maximum to worse. Finally, the ultimate benefit goes to the patient due the compliance and convenience of the dosage form. Some diseases that follow circadian rhythms include cardiovascular diseases, asthma, arthritis, ulcers, diabetes etc. ChrDDs in the market were also discussed and the current technologies used to formulate were also stated. These technologies include Contin® , Chronotopic®, Pulsincaps®, Ceform®, Timerx®, Oros®, Codas®, Diffucaps®, Egalet®, Tablet in capsule device, Core-in-cup tablet technology. A coated drug-core tablet matrix, A bi-layered tablet, Multiparticulate-based chronotherapeutic drug delivery systems, Chronoset and Controlled release microchips.

  2. Gender and images of heart disease in Scandinavian drug advertising.

    Science.gov (United States)

    Riska, Elianne; Heikell, Thomas

    2007-01-01

    This study examines the construction of the "heart disease candidate" in advertisements for cardiovascular drugs in Scandinavian medical journals. All advertisements for cardiovascular drugs (n = 603) in Scandinavian medical journals (Denmark, Finland, Norway, and Sweden) in 2005 were collected. Only advertisements that portray users (n = 289, 48% of the advertisements) were analyzed. The results show that coronary candidacy is constructed as a male condition in half of the advertisements for cardiovascular drugs. The advertisements suggest a gendering of heart disease: men are the major victims of heart failure and cardiac insufficiency, and women are in need of cholesterol-lowering drugs. The cardiovascular drug advertisements portray a restoration of men's hyperactive agency, valorized by means of sporty images, by drawing on masculinity as a fixed trait and behavior. Hypercholesterolemia as a woman's disease reproduces the tyranny of slimness for women: Only women's stoutness is medicalized, and there are no pictures of heavy men. The findings point to the public health implications of gendered images of coronary candidacy in medical advertising.

  3. ADVANZ: Establishing a Pan-African platform for neglected zoonotic disease control through a One Health approach

    DEFF Research Database (Denmark)

    Saarnak, Christopher; Johansen, Maria Vang; Mukaratirwa, Samson

    2014-01-01

    levels towards a coordinated fight against NZDs. ADVANZ is establishing an African platform to share experiences in the prevention and control of NZDs. The platform will compile and package existing knowledge or data on NZDs and generate evidence-based algorithms for improving surveillance and control...... with the ultimate aim of eliminating and eradicating these diseases. The platform will serve as a forum for African and international stakeholders, as well as existing One Health and NZD networks and harness and consolidate their efforts in the control and prevention of NZDs. The platform had its first meeting...

  4. Biosurfactants produced by Scheffersomyces stipitis cultured in sugarcane bagasse hydrolysate as new green larvicides for the control of Aedes aegypti, a vector of neglected tropical diseases.

    Science.gov (United States)

    Franco Marcelino, Paulo Ricardo; da Silva, Vinícius Luiz; Rodrigues Philippini, Rafael; Von Zuben, Cláudio José; Contiero, Jonas; Dos Santos, Júlio César; da Silva, Silvio Silvério

    2017-01-01

    Biosurfactants are microbial metabolites with possible applications in various industrial sectors that are considered ecofriendly molecules. In recent years, some studies identified these compounds as alternatives for the elimination of vectors of tropical diseases, such as Aedes aegypti. The major bottlenecks of biosurfactant industrial production have been the use of conventional raw materials that increase production costs as well as opportunistic or pathogenic bacteria, which restrict the application of these biomolecules. The present study shows the potential of hemicellulosic sugarcane bagasse hydrolysate as a raw material for the production of a crystalline glycolipidic BS by Scheffersomyces stipitis NRRL Y-7124, which resulted in an emulsifying index (EI24) of 70 ± 3.4% and a superficial tension of 52 ± 2.9 mN.m-1. Additionally, a possible new application of these compounds as biolarvicides, mainly against A. aegypti, was evaluated. At a concentration of 800 mg.L-1, the produced biosurfactant caused destruction to the larval exoskeletons 12 h after application and presented an letal concentration (LC50) of 660 mg.L-1. Thus, a new alternative for biosurfactant production using vegetal biomass as raw material within the concept of biorefineries was proposed, and the potential of the crystalline glycolipidic biosurfactant in larvicidal formulations against neglected tropical disease vectors was demonstrated.

  5. Biosurfactants produced by Scheffersomyces stipitis cultured in sugarcane bagasse hydrolysate as new green larvicides for the control of Aedes aegypti, a vector of neglected tropical diseases.

    Directory of Open Access Journals (Sweden)

    Paulo Ricardo Franco Marcelino

    Full Text Available Biosurfactants are microbial metabolites with possible applications in various industrial sectors that are considered ecofriendly molecules. In recent years, some studies identified these compounds as alternatives for the elimination of vectors of tropical diseases, such as Aedes aegypti. The major bottlenecks of biosurfactant industrial production have been the use of conventional raw materials that increase production costs as well as opportunistic or pathogenic bacteria, which restrict the application of these biomolecules. The present study shows the potential of hemicellulosic sugarcane bagasse hydrolysate as a raw material for the production of a crystalline glycolipidic BS by Scheffersomyces stipitis NRRL Y-7124, which resulted in an emulsifying index (EI24 of 70 ± 3.4% and a superficial tension of 52 ± 2.9 mN.m-1. Additionally, a possible new application of these compounds as biolarvicides, mainly against A. aegypti, was evaluated. At a concentration of 800 mg.L-1, the produced biosurfactant caused destruction to the larval exoskeletons 12 h after application and presented an letal concentration (LC50 of 660 mg.L-1. Thus, a new alternative for biosurfactant production using vegetal biomass as raw material within the concept of biorefineries was proposed, and the potential of the crystalline glycolipidic biosurfactant in larvicidal formulations against neglected tropical disease vectors was demonstrated.

  6. Altered neural responses to heat pain in drug-naive patients with Parkinson disease.

    Science.gov (United States)

    Forkmann, Katarina; Grashorn, Wiebke; Schmidt, Katharina; Fründt, Odette; Buhmann, Carsten; Bingel, Ulrike

    2017-08-01

    Pain is a frequent but still neglected nonmotor symptom of Parkinson disease (PD). However, neural mechanisms underlying pain in PD are poorly understood. Here, we explored whether the high prevalence of pain in PD might be related to dysfunctional descending pain control. Using functional magnetic resonance imaging we explored neural responses during the anticipation and processing of heat pain in 21 PD patients (Hoehn and Yahr I-III) and 23 healthy controls (HC). Parkinson disease patients were naive to dopaminergic medication to avoid confounding drug effects. Fifteen heat pain stimuli were applied to the participants' forearm. Intensity and unpleasantness ratings were provided for each stimulus. Subjective pain perception was comparable for PD patients and HC. Neural processing, however, differed between groups: PD patients showed lower activity in several descending pain modulation regions (dorsal anterior cingulate cortex [dACC], subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex [DLPFC]) and lower functional connectivity between dACC and DLPFC during pain anticipation. Parkinson disease symptom severity was negatively correlated with dACC-DLPFC connectivity indicating impaired functional coupling of pain modulatory regions with disease progression. During pain perception PD patients showed higher midcingulate cortex activity compared with HC, which also scaled with PD severity. Interestingly, dACC-DLPFC connectivity during pain anticipation was negatively associated with midcingulate cortex activity during the receipt of pain in PD patients. This study indicates altered neural processing during the anticipation and receipt of experimental pain in drug-naive PD patients. It provides first evidence for a progressive decline in descending pain modulation in PD, which might be related to the high prevalence of pain in later stages of PD.

  7. Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening.

    Science.gov (United States)

    Marcellin, Patrick; Kutala, Blaise K

    2018-02-01

    CLDs represent an important, and certainly underestimated, global public health problem. CLDs are highly prevalent and silent, related to different, sometimes associated causes. The distribution of the causes of these diseases is slowly changing, and within the next decade, the proportion of virus-induced CLDs will certainly decrease significantly while the proportion of NASH will increase. There is an urgent need for effective global actions including education, prevention and early diagnosis to manage and treat CLDs, thus preventing cirrhosis-related morbidity and mortality. Our role is to increase the awareness of the public, healthcare professionals and public health authorities to encourage active policies for early management that will decrease the short- and long-term public health burden of these diseases. Because necroinflammation is the key mechanism in the progression of CLDs, it should be detected early. Thus, large-scale screening for CLDs is needed. ALT levels are an easy and inexpensive marker of liver necroinflammation and could be the first-line tool in this process. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Targeting cysteine proteases in trypanosomatid disease drug discovery.

    Science.gov (United States)

    Ferreira, Leonardo G; Andricopulo, Adriano D

    2017-12-01

    Chagas disease and human African trypanosomiasis are endemic conditions in Latin America and Africa, respectively, for which no effective and safe therapy is available. Efforts in drug discovery have focused on several enzymes from these protozoans, among which cysteine proteases have been validated as molecular targets for pharmacological intervention. These enzymes are expressed during the entire life cycle of trypanosomatid parasites and are essential to many biological processes, including infectivity to the human host. As a result of advances in the knowledge of the structural aspects of cysteine proteases and their role in disease physiopathology, inhibition of these enzymes by small molecules has been demonstrated to be a worthwhile approach to trypanosomatid drug research. This review provides an update on drug discovery strategies targeting the cysteine peptidases cruzain from Trypanosoma cruzi and rhodesain and cathepsin B from Trypanosoma brucei. Given that current chemotherapy for Chagas disease and human African trypanosomiasis has several drawbacks, cysteine proteases will continue to be actively pursued as valuable molecular targets in trypanosomatid disease drug discovery efforts. Copyright © 2017. Published by Elsevier Inc.

  9. [Guideline for the treatment of Graves' disease with antithyroid drug].

    Science.gov (United States)

    Nakamura, Hirotoshi

    2006-12-01

    We have published "Guideline for the Treatment of Graves' Disease with Antithyroid Drug in Japan 2006" in the middle of May from the Japan Thyroid Association. The background, working process, composition, aim and significance of this guideline are described. The most remarkable feature of this guideline is "evidence based".

  10. Neglected tropical diseases: prevalence and risk factors for schistosomiasis and soil-transmitted helminthiasis in a region of Minas Gerais State, Brazil.

    Science.gov (United States)

    Couto, Luzivalda D; Tibiriça, Sandra H C; Pinheiro, Izabella O; Mitterofhe, Adalberto; Lima, Adilson C; Castro, Milton F; Gonçalves, Murilo; Silva, Marcio R; Guimarães, Ricardo J P S; Rosa, Florence M; Coimbra, Elaine S

    2014-06-01

    Among the neglected tropical diseases (NTDs), schistosomiasis and the three main soil-transmitted helminthiases (STHs), i.e., ascariasis, trichuriasis and hookworm infection, represent the most common infections in developing countries. In Brazil, there is a lack of epidemiological data in many parts of the country, which favors the unawareness of the real situation concerning these diseases. Due to this, we investigated the occurrence of schistosomiasis and STHs in a region of Minas Gerais State, Brazil. One stool sample was collected from 503 individuals, whose ages ranged from 0.1 to 91.2 years, and screened using both the Kato-Katz and the Formol-Ether methods. In parallel, a malacological survey was carried out in the main water bodies of the district, and Biomphalaria susceptibility assays and kernel-based techniques were also performed. No individual was found infected with Ascaris lumbricoides or hookworm. Schistosoma mansoni was the most common parasite found (1.6%). The prevalence was higher in males and the chance of acquiring the disease increased by 43.35 times with contact with a body of water. None of the Biomphalaria tenagophila and B. glabrata specimens were found naturally infected, but B. glabrata was highly susceptible to infection with Schistosoma mansoni. Using kernel-based techniques, clusters of Biomphalaria were found near the households where the infected individuals lived. Schistosomiasis was the most prevalent parasitic infection found. Our findings show that the occurrence of this disease has been underestimated by the local health care service, and highlight the importance of epidemiological surveillance in areas of low prevalence for schistosomiasis. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Addictive drugs and their relationship with infectious diseases.

    Science.gov (United States)

    Friedman, Herman; Pross, Susan; Klein, Thomas W

    2006-08-01

    The use of drugs of abuse, both recreationally and medicinally, may be related to serious public health concerns. There is a relationship between addictive drugs of abuse such as alcohol and nicotine in cigarette smoke, as well as illegal drugs such as opiates, cocaine and marijuana, and increased susceptibility to infections. The nature and mechanisms of immunomodulation induced by such drugs of abuse are described in this review. The effects of opiates and marijuana, using animal models as well as in vitro studies with immune cells from experimental animals and humans, have shown that immunomodulation induced by these drugs is mainly receptor-mediated, either directly by interaction with specific receptors on immune cells or indirectly by reaction with similar receptors on cells of the nervous system. Similar studies also show that cocaine and nicotine have marked immunomodulatory effects, which are mainly receptor-mediated. Both cocaine, an illegal drug, and nicotine, a widely used legal addictive component of cigarettes, are markedly immunomodulatory and increase susceptibility to infection. The nature and mechanism of immunomodulation induced by alcohol, the most widely used addictive substance of abuse, are similar but immunomodulatory effects, although not receptor-mediated. The many research studies on the effects of these drugs on immunity and increased susceptibility to infectious diseases, including AIDS, are providing a better understanding of the complex interactions between immunity, infections and substance abuse.

  12. Surveillance of gastrointestinal disease in France using drug sales data.

    Science.gov (United States)

    Pivette, Mathilde; Mueller, Judith E; Crépey, Pascal; Bar-Hen, Avner

    2014-09-01

    Drug sales data have increasingly been used for disease surveillance during recent years. Our objective was to assess the value of drug sales data as an operational early detection tool for gastroenteritis epidemics at national and regional level in France. For the period 2008-2013, we compared temporal trends of drug sales for the treatment of gastroenteritis with trends of cases reported by a Sentinel Network of general practitioners. We benchmarked detection models to select the one with the best sensitivity, false alert proportion and timeliness, and developed a prospective framework to assess the operational performance of the system. Drug sales data allowed the detection of seasonal gastrointestinal epidemics occurring in winter with a distinction between prescribed and non-prescribed drugs. Sales of non-prescribed drugs allowed epidemic detection on average 2.25 weeks earlier than Sentinel data. These results confirm the value of drug sales data for real-time monitoring of gastroenteritis epidemic activity. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Drug development in Parkinson's disease: from emerging molecules to innovative drug delivery systems.

    Science.gov (United States)

    Garbayo, E; Ansorena, E; Blanco-Prieto, M J

    2013-11-01

    Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Epidemiology, Virology, and Pathogenesis of the Zika Virus: From Neglected Tropical Disease to a Focal Point of International Attention.

    Science.gov (United States)

    Schirmer, David A; Kawwass, Jennifer Fay

    2016-09-01

    Over the past year, the Zika virus, an arthropod-borne Flavivirus , has transitioned from a relatively unknown tropical disease to the cause of a public health emergency. The Zika virus is transmitted by the Aedes species of mosquito as well as by sexual intercourse. Although the symptoms of acute Zika virus infection are usually mild and self-limited, it causes fetal microcephaly in pregnant women, and is associated with an increased risk of Guillain-Barré syndrome. The risk of microcephaly from Zika virus infection is estimated to be highest in women who are infected during the first trimester of pregnancy. The Zika virus has been shown to have significant neurotrophism in vivo and in vitro , although further study is needed to characterize its mechanisms of pathogenesis. Zika virus has previously caused two known outbreaks in the Pacific region prior to the current epidemic in South and Central America, and the current epidemic has affected at least 440,000 to 1,300,000 people. The population of the vector for the current epidemic, Aedes aegypti , varies seasonally in the United States, however there have been few documented cases of local spread of the Zika infection in the United States and it is unclear whether epidemic spread of Zika will occur within the United States. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Drug therapy in patients with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Müller Thomas

    2012-05-01

    Full Text Available Abstract Parkinson`s disease (PD is a progressive, disabling neurodegenerative disorder with onset of motor and non-motor features. Both reduce quality of life of PD patients and cause caregiver burden. This review aims to provide a survey of possible therapeutic options for treatment of motor and non motor symptoms of PD and to discuss their relation to each other. MAO-B-Inhibitors, NMDA antagonists, dopamine agonists and levodopa with its various application modes mainly improve the dopamine associated motor symptoms in PD. This armentarium of PD drugs only partially influences the onset and occurrence of non motor symptoms. These PD features predominantly result from non dopaminergic neurodegeneration. Autonomic features, such as seborrhea, hyperhidrosis, orthostatic syndrome, salivation, bladder dysfunction, gastrointestinal disturbances, and neuropsychiatric symptoms, such as depression, sleep disorders, psychosis, cognitive dysfunction with impaired execution and impulse control may appear. Drug therapy of these non motor symptoms complicates long-term PD drug therapy due to possible occurrence of drug interactions, - side effects, and altered pharmacokinetic behaviour of applied compounds. Dopamine substituting compounds themselves may contribute to onset of these non motor symptoms. This complicates the differentiation from the disease process itself and influences therapeutic options, which are often limited because of additional morbidity with necessary concomitant drug therapy.

  16. The use of herbs against neglected diseases: Evaluation of in vitro leishmanicidal and trypanocidal activity of Stryphnodendron rotundifolium Mart

    Directory of Open Access Journals (Sweden)

    Vivianne C.S. Vandesmet

    2017-09-01

    Full Text Available The evaluation of the leishmanicidal and trypanocidal activity of the hydroalcoholic extract of the bark of Stryphnodendron rotundifolium Mart. (EHCSR was carried out to find an alternative treatment for parasitic diseases. EHCSR was prepared and used at four different concentrations (1000, 500, 250, 125 μg/mL in in vitro assays for activity against Leishmania promastigotes using the species Leishmania brasiliensis and Leishmania infantum and for trypanocidal activity using the epimastigotes of Trypanosoma cruzi. We also tested EHCSR for cytotoxicity against adhered cultured Murine J774 fibroblasts. The tests were performed in triplicate, and the percent mortality of parasites, IC50 and percent toxicity were determined. With regard to anti-leishmania activity against L. infantum, there was a mean mortality of 45% at all concentrations, and against L. brasiliensis, a substantial effect was seen at 1000 μg/mL with 56.38% mortality, where the IC50 values were 1338.76 and 987.35 μg/mL, respectively. Trypanocidal activity was notably high at 1000 μg/mL extract with 82.31% mortality of epimastigotes. Cytotoxicity at the highest extract concentrations of 500 and 1000 μg/mL was respectively 75.12% and 94.14%, with IC50 = 190.24 μg/mL. Despite that the extract has anti-parasitic activity, its substantial cytotoxicity against fibroblasts cells makes its systemic use nonviable as a therapeutic alternative.

  17. Improving drug delivery technology for treating neurodegenerative diseases.

    Science.gov (United States)

    Choonara, Yahya E; Kumar, Pradeep; Modi, Girish; Pillay, Viness

    2016-07-01

    Neurodegenerative diseases (NDs) represent intricate challenges for efficient uptake and transport of drugs to the brain mainly due to the restrictive blood-brain barrier (BBB). NDs are characterized by the loss of neuronal subtypes as sporadic and/or familial and several mechanisms of neurodegeneration have been identified. This review attempts to recap, organize and concisely evaluate the advanced drug delivery systems designed for treating common NDs. It highlights key research gaps and opinionates on new neurotherapies to overcome the BBB as an addition to the current treatments of countering oxidative stress, inflammation and apoptotic mechanisms. Current treatments do not fully address the biological, drug and therapeutic factors faced. This has led to the development of vogue treatments such as nose-to-brain technologies, bio-engineered systems, fusion protein chaperones, stem cells, gene therapy, use of natural compounds, neuroprotectants and even vaccines. However, failure of these treatments is mainly due to the BBB and non-specific delivery in the brain. In order to increase neuroavailability various advanced drug delivery systems provide promising alternatives that are able to augment the treatment of Alzheimer's disease and Parkinson's disease. However, much work is still required in this field beyond the preclinical testing phase.

  18. New drugs for the treatment of dry eye disease

    OpenAIRE

    Ridder, III, William; Karsolia,Apoorva

    2015-01-01

    William H Ridder III, Apoorva Karsolia Southern California College of Optometry, Marshall B Ketchum University, Fullerton, CA, USA Abstract: Dry eye disease (DED) is one of the most commonly encountered conditions for eye care practitioners. The prevalence of DED can be as high as 30% of the population. In the past decade, only one drug has been approved for the treatment of DED by the US Food and Drug Administration (FDA) in the USA (ie, Restasis® by Allergan, Inc.). The total annua...

  19. Spatial co-distribution of neglected tropical diseases in the East African Great Lakes region: revisiting the justification for integrated control

    Science.gov (United States)

    Clements, Archie C. A.; Deville, Marie-Alice; Ndayishimiye, Onésime; Brooker, Simon; Fenwick, Alan

    2010-01-01

    Summary OBJECTIVE To determine spatial patterns of co-endemicity of schistosomiasis mansoni and the soil-transmitted helminths (STHs) Ascaris lumbricoides, Trichuris trichiura and hookworm in the Great Lakes region of East Africa, to help plan integrated neglected tropical disease programmes in this region. METHOD Parasitological surveys were conducted in Uganda, Tanzania, Kenya and Burundi in 28 213 children in 404 schools. Bayesian geostatistical models were used to interpolate prevalence of these infections across the study area. Interpolated prevalence maps were overlaid to determine areas of co-endemicity. RESULTS In the Great Lakes region, prevalence was 18.1% for Schistosoma mansoni, 50.0% for hookworm, 6.8% for A. lumbricoides and 6.8% for T. trichiura. Hookworm infection was ubiquitous, whereas S. mansoni, A. lumbricoides and T. trichiura were highly focal. Most areas were endemic (prevalence ≥10%) or hyperendemic (prevalence ≥50%) for one or more STHs, whereas endemic areas for schistosomiasis mansoni were restricted to foci adjacent large perennial water bodies. CONCLUSION Because of the ubiquity of hookworm, treatment programmes are required for STH throughout the region but efficient schistosomiasis control should only be targeted at limited high-risk areas. Therefore, integration of schistosomiasis with STH control is only indicated in limited foci in East Africa. PMID:20409287

  20. [The trend of developing new disease-modifying drugs in Alzheimer's disease].

    Science.gov (United States)

    Arai, Hiroyuki; Furukawa, Katsutoshi; Tomita, Naoki; Ishiki, Aiko; Okamura, Nobuyuki; Kudo, Yukitsuka

    2016-03-01

    Development of symptomatic treatment of Alzheimer s disease by cholinesterase inhibitors like donepezil was successful. However, it is a disappointment that development of disease-modifying drugs such as anti-amyloid drug based on amyloid-cascade theory has been interrupted or unsuccessful. Therefore, we have to be more cautious regarding inclusion criteria for clinical trials of new drugs. We agree that potentially curative drugs should be started before symptoms begin as a preemptive therapy or prevention trial. The concept of personalized medicine also is important when ApoE4-related amyloid reducing therapy is considered. Unfortunately, Japanese-ADNI has suffered a setback since 2014. However, Ministry of Health, Labour and Welfare gave a final remark that there was nothing wrong in the data managing process in the J-ADNI data center. We should pay more attention to worldwide challenges of speeding up new drug development.

  1. A kernel for open source drug discovery in tropical diseases.

    Science.gov (United States)

    Ortí, Leticia; Carbajo, Rodrigo J; Pieper, Ursula; Eswar, Narayanan; Maurer, Stephen M; Rai, Arti K; Taylor, Ginger; Todd, Matthew H; Pineda-Lucena, Antonio; Sali, Andrej; Marti-Renom, Marc A

    2009-01-01

    Conventional patent-based drug development incentives work badly for the developing world, where commercial markets are usually small to non-existent. For this reason, the past decade has seen extensive experimentation with alternative R&D institutions ranging from private-public partnerships to development prizes. Despite extensive discussion, however, one of the most promising avenues-open source drug discovery-has remained elusive. We argue that the stumbling block has been the absence of a critical mass of preexisting work that volunteers can improve through a series of granular contributions. Historically, open source software collaborations have almost never succeeded without such "kernels". HERE, WE USE A COMPUTATIONAL PIPELINE FOR: (i) comparative structure modeling of target proteins, (ii) predicting the localization of ligand binding sites on their surfaces, and (iii) assessing the similarity of the predicted ligands to known drugs. Our kernel currently contains 143 and 297 protein targets from ten pathogen genomes that are predicted to bind a known drug or a molecule similar to a known drug, respectively. The kernel provides a source of potential drug targets and drug candidates around which an online open source community can nucleate. Using NMR spectroscopy, we have experimentally tested our predictions for two of these targets, confirming one and invalidating the other. The TDI kernel, which is being offered under the Creative Commons attribution share-alike license for free and unrestricted use, can be accessed on the World Wide Web at http://www.tropicaldisease.org. We hope that the kernel will facilitate collaborative efforts towards the discovery of new drugs against parasites that cause tropical diseases.

  2. Drugs and drug delivery systems targeting amyloid-β in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Morgan Robinson

    2015-07-01

    Full Text Available Alzheimer's disease (AD is a devastating neurodegenerative disorder with no cure and limited treatment solutions that are unable to target any of the suspected causes. Increasing evidence suggests that one of the causes of neurodegeneration is the overproduction of amyloid beta (Aβ and the inability of Aβ peptides to be cleared from the brain, resulting in self-aggregation to form toxic oligomers, fibrils and plaques. One of the potential treatment options is to target Aβ and prevent self-aggregation to allow for a natural clearing of the brain. In this paper, we review the drugs and drug delivery systems that target Aβ in relation to Alzheimer's disease. Many attempts have been made to use anti-Aβ targeting molecules capable of targeting Aβ (with much success in vitro and in vivo animal models, but the major obstacle to this technique is the challenge posed by the blood brain barrier (BBB. This highly selective barrier protects the brain from toxic molecules and pathogens and prevents the delivery of most drugs. Therefore novel Aβ aggregation inhibitor drugs will require well thought-out drug delivery systems to deliver sufficient concentrations to the brain.

  3. Elder Abuse and Neglect

    Directory of Open Access Journals (Sweden)

    Muge Gulen

    2013-06-01

    Full Text Available Abuse and neglect are preventable societal problems that influence elderly individuals physically, spiritually and socially. Elder abuse is neglected for many years and is a growing problem all over the world. The aim of this article is to review the evaluation of elderly individuals who are exposed to abuse and neglect with systematic detailed history and physical examination and to describe individual, familial, and social measures that should be taken to prevent these abuses. [Archives Medical Review Journal 2013; 22(3.000: 393-407

  4. The basics of preclinical drug development for neurodegenerative disease indications.

    Science.gov (United States)

    Steinmetz, Karen L; Spack, Edward G

    2009-06-12

    Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonization. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and

  5. The basics of preclinical drug development for neurodegenerative disease indications

    Directory of Open Access Journals (Sweden)

    Spack Edward G

    2009-06-01

    Full Text Available Abstract Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA Good Laboratory Practices and international guidelines, including the International Conference on Harmonisation. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s. Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot

  6. The Impact of Disease and Drugs on Hip Fracture Risk

    OpenAIRE

    Leavy, Breiffni; Michaëlsson, Karl; Åberg, Anna Cristina; Melhus, Håkan; Byberg, Liisa

    2017-01-01

    We report the risks of a comprehensive range of disease and drug categories on hip fracture occurrence using a strict population-based cohort design. Participants included the source population of a Swedish county, aged ?50?years (n?=?117,494) including all incident hip fractures during 1?year (n?=?477). The outcome was hospitalization for hip fracture (ICD-10 codes S72.0?S72.2) during 1?year (2009?2010). Exposures included: prevalence of (1) inpatient diseases [International Classification o...

  7. Drug-induced Liver Disease in Patients with Diabetes Mellitus

    OpenAIRE

    Iryna, Klyarytskaya; Helen, Maksymova; Elena, Stilidi

    2016-01-01

    The study presented here was accomplished to assess the course of drug-induced liver diseases in patient’s rheumatoid arthritis receiving long-term methotrexate therapy. Diabetes mellitus was revealed as the most significant risk factor. The combination of diabetes mellitus with other risk factors (female sex) resulted in increased hepatic fibrosis, degree of hepatic encephalopathy and reduction of hepatic functions. The effectiveness and safety of ursodeoxycholic acid and cytolytic type-with...

  8. Current advances in transdermal delivery of drugs for alzheimer's disease

    OpenAIRE

    Thuy Trang Nguyen; Vo Van Giau; Tuong Kha Vo

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the...

  9. Be careful for neglected diseases

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-19

    Oct 19, 2009 ... Application of E-infinity theory to biology, Chaos Soliton. Fract. 28: 285-289. He JH (2008). Fatalness of virus depends upon its cell fractal geometry,. Chaos Soliton Fract. 38: 1390-1393. West GB, Brown JH, Enquist BJ (1999). The fourth dimension of life: fractal geometry and allometric scaling of organisms, ...

  10. Non-steroidal anti-inflammatory drug use and the risk of Parkinson's disease

    DEFF Research Database (Denmark)

    Manthripragada, Angelika D; Schernhammer, Eva S; Qiu, Jiaheng

    2011-01-01

    Experimental evidence supports a preventative role for non-steroidal anti-inflammatory drugs (NSAIDs) in Parkinson's disease (PD).......Experimental evidence supports a preventative role for non-steroidal anti-inflammatory drugs (NSAIDs) in Parkinson's disease (PD)....

  11. Bibliometric Assessment of European and Sub-Saharan African Research Output on Poverty-Related and Neglected Infectious Diseases from 2003 to 2011.

    Science.gov (United States)

    Breugelmans, J Gabrielle; Makanga, Michael M; Cardoso, Ana Lúcia V; Mathewson, Sophie B; Sheridan-Jones, Bethan R; Gurney, Karen A; Mgone, Charles S

    2015-08-01

    The European & Developing Countries Clinical Trials Partnership (EDCTP) is a partnership of European and sub-Saharan African countries that aims to accelerate the development of medical interventions against poverty-related diseases (PRDs). A bibliometric analysis was conducted to 1) measure research output from European and African researchers on PRDs, 2) describe collaboration patterns, and 3) assess the citation impact of clinical research funded by EDCTP. Disease-specific research publications were identified in Thomson Reuters Web of Science using search terms in titles, abstracts and keywords. Publication data, including citation counts, were extracted for 2003-2011. Analyses including output, share of global papers, normalised citation impact (NCI), and geographical distribution are presented. Data are presented as five-year moving averages. European EDCTP member countries accounted for ~33% of global research output in PRDs and sub-Saharan African countries for ~10% (2007-2011). Both regions contributed more to the global research output in malaria (43.4% and 22.2%, respectively). The overall number of PRD papers from sub-Saharan Africa increased markedly (>47%) since 2003, particularly for HIV/AIDS (102%) and tuberculosis (TB) (81%), and principally involving Southern and East Africa. For 2007-2011, European and sub-Saharan African research collaboration on PRDs was highly cited compared with the world average (NCI in brackets): HIV/AIDS 1.62 (NCI: 1.16), TB 2.11 (NCI: 1.06), malaria 1.81 (NCI: 1.22), and neglected infectious diseases 1.34 (NCI: 0.97). The NCI of EDCTP-funded papers for 2003-2011 was exceptionally high for HIV/AIDS (3.24), TB (4.08) and HIV/TB co-infection (5.10) compared with global research benchmarks (1.14, 1.05 and 1.35, respectively). The volume and citation impact of papers from sub-Saharan Africa has increased since 2003, as has collaborative research between Europe and sub-Saharan Africa. >90% of publications from EDCTP

  12. Bibliometric Assessment of European and Sub-Saharan African Research Output on Poverty-Related and Neglected Infectious Diseases from 2003 to 2011

    Science.gov (United States)

    Gurney, Karen A.; Mgone, Charles S.

    2015-01-01

    Background The European & Developing Countries Clinical Trials Partnership (EDCTP) is a partnership of European and sub-Saharan African countries that aims to accelerate the development of medical interventions against poverty-related diseases (PRDs). A bibliometric analysis was conducted to 1) measure research output from European and African researchers on PRDs, 2) describe collaboration patterns, and 3) assess the citation impact of clinical research funded by EDCTP. Methodology/Principal Findings Disease-specific research publications were identified in Thomson Reuters Web of Science using search terms in titles, abstracts and keywords. Publication data, including citation counts, were extracted for 2003–2011. Analyses including output, share of global papers, normalised citation impact (NCI), and geographical distribution are presented. Data are presented as five-year moving averages. European EDCTP member countries accounted for ~33% of global research output in PRDs and sub-Saharan African countries for ~10% (2007–2011). Both regions contributed more to the global research output in malaria (43.4% and 22.2%, respectively). The overall number of PRD papers from sub-Saharan Africa increased markedly (>47%) since 2003, particularly for HIV/AIDS (102%) and tuberculosis (TB) (81%), and principally involving Southern and East Africa. For 2007–2011, European and sub-Saharan African research collaboration on PRDs was highly cited compared with the world average (NCI in brackets): HIV/AIDS 1.62 (NCI: 1.16), TB 2.11 (NCI: 1.06), malaria 1.81 (NCI: 1.22), and neglected infectious diseases 1.34 (NCI: 0.97). The NCI of EDCTP-funded papers for 2003–2011 was exceptionally high for HIV/AIDS (3.24), TB (4.08) and HIV/TB co-infection (5.10) compared with global research benchmarks (1.14, 1.05 and 1.35, respectively). Conclusions The volume and citation impact of papers from sub-Saharan Africa has increased since 2003, as has collaborative research between Europe and

  13. Bibliometric Assessment of European and Sub-Saharan African Research Output on Poverty-Related and Neglected Infectious Diseases from 2003 to 2011.

    Directory of Open Access Journals (Sweden)

    J Gabrielle Breugelmans

    2015-08-01

    Full Text Available The European & Developing Countries Clinical Trials Partnership (EDCTP is a partnership of European and sub-Saharan African countries that aims to accelerate the development of medical interventions against poverty-related diseases (PRDs. A bibliometric analysis was conducted to 1 measure research output from European and African researchers on PRDs, 2 describe collaboration patterns, and 3 assess the citation impact of clinical research funded by EDCTP.Disease-specific research publications were identified in Thomson Reuters Web of Science using search terms in titles, abstracts and keywords. Publication data, including citation counts, were extracted for 2003-2011. Analyses including output, share of global papers, normalised citation impact (NCI, and geographical distribution are presented. Data are presented as five-year moving averages. European EDCTP member countries accounted for ~33% of global research output in PRDs and sub-Saharan African countries for ~10% (2007-2011. Both regions contributed more to the global research output in malaria (43.4% and 22.2%, respectively. The overall number of PRD papers from sub-Saharan Africa increased markedly (>47% since 2003, particularly for HIV/AIDS (102% and tuberculosis (TB (81%, and principally involving Southern and East Africa. For 2007-2011, European and sub-Saharan African research collaboration on PRDs was highly cited compared with the world average (NCI in brackets: HIV/AIDS 1.62 (NCI: 1.16, TB 2.11 (NCI: 1.06, malaria 1.81 (NCI: 1.22, and neglected infectious diseases 1.34 (NCI: 0.97. The NCI of EDCTP-funded papers for 2003-2011 was exceptionally high for HIV/AIDS (3.24, TB (4.08 and HIV/TB co-infection (5.10 compared with global research benchmarks (1.14, 1.05 and 1.35, respectively.The volume and citation impact of papers from sub-Saharan Africa has increased since 2003, as has collaborative research between Europe and sub-Saharan Africa. >90% of publications from EDCTP

  14. Macrophage models of Gaucher disease for evaluating disease pathogenesis and candidate drugs.

    Science.gov (United States)

    Aflaki, Elma; Stubblefield, Barbara K; Maniwang, Emerson; Lopez, Grisel; Moaven, Nima; Goldin, Ehud; Marugan, Juan; Patnaik, Samarjit; Dutra, Amalia; Southall, Noel; Zheng, Wei; Tayebi, Nahid; Sidransky, Ellen

    2014-06-11

    Gaucher disease is caused by an inherited deficiency of glucocerebrosidase that manifests with storage of glycolipids in lysosomes, particularly in macrophages. Available cell lines modeling Gaucher disease do not demonstrate lysosomal storage of glycolipids; therefore, we set out to develop two macrophage models of Gaucher disease that exhibit appropriate substrate accumulation. We used these cellular models both to investigate altered macrophage biology in Gaucher disease and to evaluate candidate drugs for its treatment. We generated and characterized monocyte-derived macrophages from 20 patients carrying different Gaucher disease mutations. In addition, we created induced pluripotent stem cell (iPSC)-derived macrophages from five fibroblast lines taken from patients with type 1 or type 2 Gaucher disease. Macrophages derived from patient monocytes or iPSCs showed reduced glucocerebrosidase activity and increased storage of glucocerebroside and glucosylsphingosine in lysosomes. These macrophages showed efficient phagocytosis of bacteria but reduced production of intracellular reactive oxygen species and impaired chemotaxis. The disease phenotype was reversed with a noninhibitory small-molecule chaperone drug that enhanced glucocerebrosidase activity in the macrophages, reduced glycolipid storage, and normalized chemotaxis and production of reactive oxygen species. Macrophages differentiated from patient monocytes or patient-derived iPSCs provide cellular models that can be used to investigate disease pathogenesis and facilitate drug development. Copyright © 2014, American Association for the Advancement of Science.

  15. Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine

    Science.gov (United States)

    Brelsford, Jill B.; Plieskatt, Jordan L.; Yakovleva, Anna; Jariwala, Amar; Keegan, Brian P.; Peng, Jin; Xia, Pengjun; Li, Guangzhao; Campbell, Doreen; Periago, Maria Victoria; Correa-Oliveira, Rodrigo; Bottazzi, Maria Elena; Hotez, Peter J.

    2017-01-01

    A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus), so conventional methods for measuring relative potency are not relevant for this investigational product. Herein, we describe a novel relative potency testing program and report for the first time on the clinical lot of this NTD vaccine during its first 60 months of storage at 2–8°C. We also describe the development of a complementary functional assay that measures the ability of IgG from animals or humans immunized with Na-GST-1/Alhydrogel to neutralize this important hookworm enzyme. While 90% inhibition of the catalytic activity of Na-GST-1 was achieved in animals immunized with Na-GST-1/Alhydrogel, lower levels of inhibition were observed in immunized humans. Moreover, anti-Na-GST-1 antibodies from volunteers in non-hookworm endemic areas were better able to inhibit catalytic activity than anti-Na-GST-1 antibodies from volunteers resident in hookworm endemic areas. The results described herein provide the critical tools for the product development of NTD vaccines. PMID:28192438

  16. Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine.

    Directory of Open Access Journals (Sweden)

    Jill B Brelsford

    2017-02-01

    Full Text Available A new generation of vaccines for the neglected tropical diseases (NTDs have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus, so conventional methods for measuring relative potency are not relevant for this investigational product. Herein, we describe a novel relative potency testing program and report for the first time on the clinical lot of this NTD vaccine during its first 60 months of storage at 2-8°C. We also describe the development of a complementary functional assay that measures the ability of IgG from animals or humans immunized with Na-GST-1/Alhydrogel to neutralize this important hookworm enzyme. While 90% inhibition of the catalytic activity of Na-GST-1 was achieved in animals immunized with Na-GST-1/Alhydrogel, lower levels of inhibition were observed in immunized humans. Moreover, anti-Na-GST-1 antibodies from volunteers in non-hookworm endemic areas were better able to inhibit catalytic activity than anti-Na-GST-1 antibodies from volunteers resident in hookworm endemic areas. The results described herein provide the critical tools for the product development of NTD vaccines.

  17. Drug targets in the cytokine universe for autoimmune disease.

    Science.gov (United States)

    Liu, Xuebin; Fang, Lei; Guo, Taylor B; Mei, Hongkang; Zhang, Jingwu Z

    2013-03-01

    In autoimmune disease, a network of diverse cytokines is produced in association with disease susceptibility to constitute the 'cytokine milieu' that drives chronic inflammation. It remains elusive how cytokines interact in such a complex network to sustain inflammation in autoimmune disease. This has presented huge challenges for successful drug discovery because it has been difficult to predict how individual cytokine-targeted therapy would work. Here, we combine the principles of Chinese Taoism philosophy and modern bioinformatics tools to dissect multiple layers of arbitrary cytokine interactions into discernible interfaces and connectivity maps to predict movements in the cytokine network. The key principles presented here have important implications in our understanding of cytokine interactions and development of effective cytokine-targeted therapies for autoimmune disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. 78 FR 21613 - Prescription Drug User Fee Act Patient-Focused Drug Development; Announcement of Disease Areas...

    Science.gov (United States)

    2013-04-11

    ... Availability. SUMMARY: The Food and Drug Administration (FDA) is announcing the selection of disease areas to... selection criteria, which were published in the September 24, 2012, Federal Register notice: Disease areas... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0967...

  19. Current advances in transdermal delivery of drugs for Alzheimer's disease

    Science.gov (United States)

    Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients. PMID:28706327

  20. Print advertisements for Alzheimer's disease drugs: informational and transformational features.

    Science.gov (United States)

    Gooblar, Jonathan; Carpenter, Brian D

    2013-06-01

    We examined print advertisements for Alzheimer's disease drugs published in journals and magazines between January 2008 and February 2012, using an informational versus transformational theoretical framework to identify objective and persuasive features. In 29 unique advertisements, we used qualitative methods to code and interpret identifying information, charts, benefit and side effect language, and persuasive appeals embedded in graphics and narratives. Most elements contained a mixture of informational and transformational features. Charts were used infrequently, but when they did appear the accompanying text often exaggerated the data. Benefit statements covered an array of symptoms, drug properties, and caregiver issues. Side effect statements often used positive persuasive appeals. Graphics and narrative features emphasized positive emotions and outcomes. We found subtle and sophisticated attempts both to educate and to persuade readers. It is important for consumers and prescribing physicians to read print advertisements critically so that they can make informed treatment choices.

  1. Current advances in transdermal delivery of drugs for Alzheimer's disease.

    Science.gov (United States)

    Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients.

  2. Anti-thyroid drugs in pediatric Graves′ disease

    Directory of Open Access Journals (Sweden)

    Mathew John

    2015-01-01

    Full Text Available Graves′ disease is the most common cause of hyperthyroidism in children. Most children and adolescents are treated with anti-thyroid drugs as the initial modality. Studies have used Methimazole, Carbimazole and Propylthiouracil (PTU either as titration regimes or as block and replacement regimes. The various studies of anti-thyroid drug (ATD treatment of Graves′ disease in pediatric patients differ in terms of the regimes, remission rate, duration of therapy for adequate remission, follow up and adverse effects of ATD. Various studies show that lower thyroid hormone levels, prolonged duration of treatment, lower levels of TSH receptor antibodies, smaller goiter and increased age of child predicted higher chance of remission after ATD. A variable number of patients experience minor and major adverse effects limiting initial and long term treatment with ATD. The adverse effects of various ATD seem to more in children compared to that of adults. In view of liver injury including hepatocellular failure need of liver transplantation associated with PTU, the use has been restricted in children. The rate of persistent remission with ATD following discontinuation is about 30%. Radioactive iodine therapy is gaining more acceptance in older children with Graves′s disease in view of the limitations of ATD. For individual patients, risk-benefit ratio of ATD should be weighed against benefits of radioactive iodine therapy and patient preferences.

  3. Computer-Aided Drug Design Applied to Marine Drug Discovery: Meridianins as Alzheimer's Disease Therapeutic Agents.

    Science.gov (United States)

    Llorach-Pares, Laura; Nonell-Canals, Alfons; Sanchez-Martinez, Melchor; Avila, Conxita

    2017-11-27

    Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity found in meridianins A-G, a group of marine indole alkaloids isolated from the marine tunicate Aplidium , against various protein kinases involved in Alzheimer's disease (AD), a neurodegenerative pathology characterized by the presence of neurofibrillary tangles (NFT). Balance splitting between tau kinase and phosphate activities caused tau hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition of specific kinases involved in its phosphorylation pathway could be one of the key strategies to reverse tau hyperphosphorylation and would represent an approach to develop drugs to palliate AD symptoms. Meridianins bind to the adenosine triphosphate (ATP) binding site of certain protein kinases, acting as ATP competitive inhibitors. These compounds show very promising scaffolds to design new drugs against AD, which could act over tau protein kinases Glycogen synthetase kinase-3 Beta (GSK3β) and Casein kinase 1 delta (CK1δ, CK1D or KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to highlight the role of CADD techniques in marine drug discovery and to provide precise information regarding the binding mode and strength of meridianins against several protein kinases that could help in the future development of anti-AD drugs.

  4. Socioeconomic benefit to individuals of achieving 2020 targets for four neglected tropical diseases controlled/eliminated by innovative and intensified disease management: Human African trypanosomiasis, leprosy, visceral leishmaniasis, Chagas disease.

    Science.gov (United States)

    Lenk, Edeltraud J; Redekop, William K; Luyendijk, Marianne; Fitzpatrick, Christopher; Niessen, Louis; Stolk, Wilma A; Tediosi, Fabrizio; Rijnsburger, Adriana J; Bakker, Roel; Hontelez, Jan A C; Richardus, Jan H; Jacobson, Julie; Le Rutte, Epke A; de Vlas, Sake J; Severens, Johan L

    2018-03-01

    The control or elimination of neglected tropical diseases (NTDs) has targets defined by the WHO for 2020, reinforced by the 2012 London Declaration. We estimated the economic impact to individuals of meeting these targets for human African trypanosomiasis, leprosy, visceral leishmaniasis and Chagas disease, NTDs controlled or eliminated by innovative and intensified disease management (IDM). A systematic literature review identified information on productivity loss and out-of-pocket payments (OPPs) related to these NTDs, which were combined with projections of the number of people suffering from each NTD, country and year for 2011-2020 and 2021-2030. The ideal scenario in which the WHO's 2020 targets are met was compared with a counterfactual scenario that assumed the situation of 1990 stayed unaltered. Economic benefit equaled the difference between the two scenarios. Values are reported in 2005 US$, purchasing power parity-adjusted, discounted at 3% per annum from 2010. Probabilistic sensitivity analyses were used to quantify the degree of uncertainty around the base-case impact estimate. The total global productivity gained for the four IDM-NTDs was I$ 23.1 (I$ 15.9 -I$ 34.0) billion in 2011-2020 and I$ 35.9 (I$ 25.0 -I$ 51.9) billion in 2021-2030 (2.5th and 97.5th percentiles in brackets), corresponding to US$ 10.7 billion (US$ 7.4 -US$ 15.7) and US$ 16.6 billion (US$ 11.6 -US$ 24.0). Reduction in OPPs was I$ 14 billion (US$ 6.7 billion) and I$ 18 billion (US$ 10.4 billion) for the same periods. We faced important limitations to our work, such as finding no OPPs for leprosy. We had to combine limited data from various sources, heterogeneous background, and of variable quality. Nevertheless, based on conservative assumptions and subsequent uncertainty analyses, we estimate that the benefits of achieving the targets are considerable. Under plausible scenarios, the economic benefits far exceed the necessary investments by endemic country governments and their

  5. Empathy and child neglect: a theoretical model.

    Science.gov (United States)

    De Paul, Joaquín; Guibert, María

    2008-11-01

    To present an explanatory theory-based model of child neglect. This model does not address neglectful behaviors of parents with mental retardation, alcohol or drug abuse, or severe mental health problems. In this model parental behavior aimed to satisfy a child's need is considered a helping behavior and, as a consequence, child neglect is considered as a specific type of non-helping behavior. The central hypothesis of the theoretical model presented here suggests that neglectful parents cannot develop the helping response set to care for their children because the observation of a child's signal of need does not lead to the experience of emotions that motivate helping or because the parents experience these emotions, but specific cognitions modify the motivation to help. The present theoretical model suggests that different typologies of neglectful parents could be developed based on different reasons that parents might not to experience emotions that motivate helping behaviors. The model can be helpful to promote new empirical studies about the etiology of different groups of neglectful families.

  6. Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery.

    Science.gov (United States)

    Jang, Jiho; Yoo, Jeong-Eun; Lee, Jeong-Ah; Lee, Dongjin R; Kim, Ji Young; Huh, Yong Jun; Kim, Dae-Sung; Park, Chul-Yong; Hwang, Dong-Youn; Kim, Han-Soo; Kang, Hoon-Chul; Kim, Dong-Wook

    2012-03-31

    The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.

  7. Neglected simultaneous bilateral femoral neck fractures secondary to narcotic drug abuse treated by bilateral one-staged hemiarthroplasty: a case report

    Directory of Open Access Journals (Sweden)

    Vahedi Ehsan

    2010-06-01

    Full Text Available Abstract Simultaneous bilateral femoral neck fractures are extremely rare and associated with various conditions. Up to now Most cases had correlations with major trauma, repetitive minor trauma, seizure, parathyroid or renal dysfunction, anti-epileptic medications, seizure, etc. A 28-year-old addict man referred to us with a 10-year history of narcotic drug abuse and history of 8 months bilateral groin pain. He admitted with displaced bilateral femoral neck fracture. Because of long duration of this condition and osteonecrosis revealed on bone scan, one-staged bilateral hip hemiarthroplasty was done. A good function was noted after surgery to 4-month follow up. Up to now, have not be founded in the literature that a case of bilateral femoral neck fracture associated with narcotic drug abuse. Because of negative effects of opium or smoking on bone tissues, a simple bone pain should aware us about the risk of stress or fatigue fracture.

  8. Cognitive enhancers (Nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. Disease-modifying drugs. Update 2014.

    Science.gov (United States)

    Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas

    2014-01-01

    Scientists working in the field of Alzheimer's disease and, in particular, cognitive enhancers, are very productive. The review "Drugs interacting with Targets other than Receptors or Enzymes. Disease-modifying Drugs" was accepted in October 2012. In the last 20 months, new targets for the potential treatment of Alzheimer's disease were identified. Enormous progress was realized in the pharmacological characterization of natural products with cognitive enhancing properties. This review covers the evolution of research in this field through May 2014.

  9. Drugs in development for Parkinson's disease: an update.

    Science.gov (United States)

    Johnston, Tom H; Brotchie, Jonathan M

    2006-01-01

    The current development of emerging pharmacological treatments for Parkinson's disease (PD), front preclinical to launch, is summarized. Advances over the past year are highlighted, including the significant progress of several drugs through various stages of development. Several agents have been discontinued from development, either because of adverse effects or lack of clinical efficacy. The methyl-esterified form of L-DOPA (melevodopa) and the monoamine oxidase type B inhibitor rasagiline have both been launched. With regard to the monoamine re-uptake inhibitors, many changes have been witnessed, with new agents reaching preclinical development and pre-existing ones being discontinued or having no development reported. Of the dopamine agonists, many continue to progress successfully through clinical trials. Others have struggled to demonstrate a significant advantage over currently available treatments and have been discontinued. The field of non-dopaminergic treatments remains dynamic. The alpha2 adrenergic receptor antagonists and the adenosine A2A receptor antagonists remain in clinical trials. Trials of the neuronal' synchronization modulator levetiracetam are at an advanced stage, and there has also been a new addition to the class (ie, seletracetam). There has been a change in the landscape of neuroprotective agents that modulate disease progression. Candidates from the classes of growth factors and glyceraldehyde-3-phosphate dehydrogenase inhibitors have been discontinued, or no development has been reported, and the mixed lineage kinase inhibitor CEP-1347 has been discontinued for PD treatment. Other drugs in this field, such as neuroimmunophilins, estrogens and alpha-synuclein oligomerization inhibitors, remain in development.

  10. Bile Acid Signaling in Metabolic Disease and Drug Therapy

    Science.gov (United States)

    Li, Tiangang

    2014-01-01

    Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid–activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein–coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver. PMID:25073467

  11. DR2DI: a powerful computational tool for predicting novel drug-disease associations

    Science.gov (United States)

    Lu, Lu; Yu, Hua

    2018-05-01

    Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

  12. DR2DI: a powerful computational tool for predicting novel drug-disease associations

    Science.gov (United States)

    Lu, Lu; Yu, Hua

    2018-04-01

    Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

  13. Health Technology Assessment Of Orphan Drugs : The example of Pompe disease

    NARCIS (Netherlands)

    T.A. Kanters (Tim A.)

    2016-01-01

    markdownabstractIn recent decades, the development of orphan drugs, i.e. drugs for rare diseases, is stimulated by regulations in various countries. However, the generally high prices of orphan drugs confront policy makers with difficult reimbursement decisions. The orphan disease investigated in

  14. Micro RNA, A Review: Pharmacogenomic drug targets for complex diseases

    Directory of Open Access Journals (Sweden)

    Sandhya Bawa

    2010-01-01

    Full Text Available

    Micro RNAs (miRNAs are non-coding RNAs that can regulate gene expression to target several mRNAs in a gene regulatory network. MiRNA related Single Nucleotide Polymorphisms (S.N.P.s represent a newly identified type of genetic variability that can be of influence to the risk of certain human diseases and also affect how drugs can be activated and metabolized by patients. This will help in personalized medicines which are used for administrating the correct dosage of drug and drug efficacy. miRNA deregulated expression has been extensively described in a variety of diseases such as Cancer, Obesity , Diabetes, Schizophrenia and control and self renewal of stem cells. MiRNA can function as oncogenes and/or tumor suppressors. MiRNAs may act as key regulators of processes as diverse as early development, cell proliferation and cell death, apoptosis and fat metabolism and cell differentiation .miRNA expression have shown their role in brain development chronic lymphocytic leukemia, colonic adeno carcinoma, Burkiff’s lymphoma and viral infection. These show their links with viral disease, neurodevelopment and cancer. It has been shown that they play a key role in melanoma metastasis. These may be

  15. PML and rheumatology: the contribution of disease and drugs.

    LENUS (Irish Health Repository)

    Molloy, Eamonn S

    2011-11-01

    Progressive multifocal leukoencephalopathy (PML), a rare, typically fatal, opportunistic infection caused by the JC virus, is becoming relevant to physicians in multiple specialties, including those who prescribe biologic agents for the treatment of autoimmune disorders. Reports of PML have led to US Food and Drug Administration alerts and warning letters regarding four immunosuppressive agents in recent years (natalizumab, rituximab, efalizumab, and mycophenolate mofetil). Consequently, informed clinical decision-making requires understanding the risk of PML associated with these therapies. An estimate of the relative frequency of PML associated with specific rheumatic conditions has been generated. Systemic lupus erythematosus appears to be associated with susceptibility to PML that cannot be fully explained by the intensity of immunosuppressive therapy. Further, the use of rituximab in patients with rheumatic disease has raised concerns. However, definitive attribution of cause is precluded by the limitations of the currently available data. All patients with rheumatic disease, regardless of the intensity of their current immunosuppressive therapy, should be considered potentially at risk of PML. With an evolving understanding of a greater clinical heterogeneity of PML, advances in diagnostic methods, and significant implications for therapy, PML should be considered in the differential diagnosis of neurologic manifestations of rheumatic diseases.

  16. Electrochemical studies of ropinirole, an anti-Parkinson's disease drug

    Indian Academy of Sciences (India)

    trochemical techniques have application to drug-protein. ∗. For correspondence ... drug bioavailability and toxicity tests. ... analysis ranging from the assay of drugs in bulk form, ... stability-indicating assays.13,14 Separation and quantifi-.

  17. Sirtuins: Novel targets for metabolic disease in drug development

    International Nuclear Information System (INIS)

    Jiang Weijian

    2008-01-01

    Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases such as type 2 diabetes. SIRT1, an NAD + -dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produces beneficial effects on glucose homeostasis and insulin sensitivity. Activation of SIRT1 leads to enhanced activity of multiple proteins, including peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) and FOXO which helps to mediate some of the in vitro and in vivo effects of sirtuins. Resveratrol, a polyphenolic SIRT1 activator, mimics the effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance. In this review, we summarize recent research advances in unveiling the molecular mechanisms that underpin sirtuin as therapeutic candidates and discuss the possibility of using resveratrol as potential drug for treatment of diabetes

  18. Child dental neglect: is it a neglected area in the UK?

    Science.gov (United States)

    Sarri, G; Marcenes, W

    2012-08-01

    This commentary focuses on the condition of dental neglect (DN) in children in the UK. It is divided into three sections: the first section defines DN in children and its consequences, the second section discusses who may be responsible for dental diseases in children as a result of neglect and the third section proposes a holistic approach to address DN in children in the UK.

  19. Novel insights in the rehabilitation of neglect.

    Directory of Open Access Journals (Sweden)

    Luciano eFasotti

    2013-11-01

    Full Text Available Visuospatial neglect due to right hemisphere damage, usually a stroke, is a major cause of disability, impairing the ability to perform a whole range of everyday life activities. Conventional and long-established methods for the rehabilitation of neglect like visual scanning training, optokinetic stimulation or limb activation training have produced positive results, with varying degrees of generalisation to (untrained tasks lasting from several minutes up to various months after training. Nevertheless, some promising novel approaches to the remediation of left visuo-spatial neglect have emerged in the last decade. These new therapy methods can be broadly classified into 4 categories. First, non-invasive brain stimulation techniques by means of transcranial magnetic stimulation (TMS or transcranial direct current stimulation (tDCS, after a period of mainly diagnostic utilization, are increasingly applied as neurorehabilitative tools. Second, two classes of drugs, dopaminergic and noradrenergic, have been investigated for their potential effectiveness in rehabilitating neglect. Third, prism adaptation treatment has been shown to improve several neglect symptoms consistently, sometimes during longer periods of time. Finally, virtual reality technologies hold new opportunities for the development of effective training techniques for neglect. They provide realistic, rich and highly controllable training environments. In this paper the degree of effectiveness and the evidence gathered to support the therapeutic claims of these new approaches is reviewed and discussed. The conclusion is that for all these approaches there still is insufficient unbiased evidence to support their effectiveness. Further neglect rehabilitation research should focus on the maintenance of therapy results over time, on a more functional evaluation of treatment effects, on the design and execution of true replication studies and on the exploration of optimal combinations of

  20. Antithyroid Drug Therapy for Graves' Disease and Implications for Recurrence

    Science.gov (United States)

    Fu, Jing; Xu, Yuan

    2017-01-01

    Graves' disease (GD) is the most common cause of hyperthyroidism worldwide. Current therapeutic options for GD include antithyroid drugs (ATD), radioactive iodine, and thyroidectomy. ATD treatment is generally well accepted by patients and clinicians due to some advantages including normalizing thyroid function in a short time, hardly causing hypothyroidism, and ameliorating immune disorder while avoiding radiation exposure and invasive procedures. However, the relatively high recurrence rate is a major concern for ATD treatment, which is associated with multiple influencing factors like clinical characteristics, treatment strategies, and genetic and environmental factors. Of these influencing factors, some are modifiable but some are nonmodifiable. The recurrence risk can be reduced by adjusting the modifiable factors as much as possible. The titration regimen for 12–18 months is the optimal strategy of ATD. Levothyroxine administration after successful ATD treatment was not recommended. The addition of immunosuppressive drugs might be helpful to decrease the recurrence rate of GD patients after ATD withdrawal, whereas further studies are needed to address the safety and efficacy. This paper reviewed the current knowledge of ATD treatment and mainly focused on influencing factors for recurrence in GD patients with ATD treatment. PMID:28529524

    1. Prevalence of infectious diseases and drug abuse among Bangladeshi workers.

      Science.gov (United States)

      Rumi, M A; Siddiqui, M A; Salam, M A; Iqbal, M R; Azam, M G; Chowdhury, A K; Khan AYM; Hasan, K N; Hassan, M S

      2000-09-01

      Individuals seeking jobs abroad need health fitness certificates before entering into those countries. Medical screening of 43,213 Bangladeshi job seekers (M/F: 42,290/923) was carried out in our reference center during the period August, 1994 to May, 1996. Albeit male predominance, they represented middle and lower middle socio-economic class of the population from all over the country. All were young adults (age: 27.05+/-3.56 years; mean+/-SD) applying for job visas to different Asian countries. Physical examination and laboratory investigations including markers for several infectious diseases and drugs of abuse were carried out as required by countries recruiting the workers. Serological tests revealed that 1,884 (4.4%) of individuals were positive for hepatitis B surface antigen (HBsAg), 737 (1.7%) for Treponema pallidum hemagglutination (TPHA) and only 83 (0.2%) for antibody to human immunodeficiency virus (anti-HIV). However, we could not confirm any case of infection with HIV. Chest X-ray suggestive of pulmonary tuberculosis was found in 162 (0.4%) and on blood film, malarial parasites could be observed only in 4 cases. Their urine analysis revealed the presence of opiates or cannabinoids in 471 (1.1%) individuals. HBsAg-positive cases (p = 0.003) and abuse of opiates (p = 0.024) or cannabinoids (p = 0.002) were significantly higher among males. TPHA reactivity and chest X-ray suggestive of tuberculosis were found to be higher among opiates (p = 0.002 and 0.027) and cannabinoids (p = 0.000 for both) abused as well as with increasing age (p = 0.000). These results may represent a cross-sectional view of the prevalence of different infectious diseases and abuse of drugs among the young adult population of Bangladesh.

    2. Predicting relapse of Graves' disease following treatment with antithyroid drugs

      Science.gov (United States)

      LIU, LIN; LU, HONGWEN; LIU, YANG; LIU, CHANGSHAN; XUN, CHU

      2016-01-01

      The aim of the present study was to monitor long term antithyroid drug treatments and to identify prognostic factors for Graves' disease (GD). A total of 306 patients with GD who were referred to the Endocrinology Clinic at Weifang People's Hospital (Weifang, China) between August 2005 and June 2009 and treated with methimazole were included in the present study. Following treatment, patients were divided into non-remission, including recurrence and constant treatment subgroups, and remission groups. Various prognosis factors were analyzed and compared, including: Patient age, gender, size of thyroid prior to and following treatment, thyroid hormone levels, disease relapse, hypothyroidism and drug side-effects, and states of thyrotropin suppression were observed at 3, 6 and 12 months post-treatment. Sixty-five patients (21.2%) were male, and 241 patients (78.8%) were female. The mean age was 42±11 years, and the follow-up was 31.5±6.8 months. Following long-term treatment, 141 patients (46%) demonstrated remission of hyperthyroidism with a mean duration of 18.7±1.9 months. The average age at diagnosis was 45.6±10.3 years in the remission group, as compared with 36.4±8.8 years in the non-remission group (t=3.152; P=0.002). Free thyroxine (FT)3 levels were demonstrated to be 25.2±8.9 and 18.7±9.4 pmol/l in the non-remission and remission groups, respectively (t=3.326, P=0.001). The FT3/FT4 ratio and thyrotrophin receptor antibody (TRAb) levels were both significantly higher in the non-remission group (t=3.331, 3.389, P=0.001), as compared with the remission group. Logistic regression analysis demonstrated that elevated thyroid size, FT3/FT4 ratio and TRAb at diagnosis were associated with poor outcomes. The ratio of continued thyrotropin suppression in the recurrent subgroup was significantly increased, as compared with the remission group (P=0.001), as thyroid function reached euthyroid state at 3, 6 and 12 months post-treatment. Patients with GD exhibiting

    3. Preventing Child Abuse and Neglect

      Science.gov (United States)

      ... Wellness Courts Cultural Competence Diverse Populations and Communities Domestic Violence Human Trafficking Laws & Policies Service Array Statistics ... Home Topics Preventing Child Abuse & Neglect Preventing Child Abuse & Neglect Resources on child abuse prevention, protecting children ...

    4. The management of neglected trauma

      African Journals Online (AJOL)

      more patients could be treated in the peripheral hospitals. .... most of the inovement from Perkins exercises will occur at the fracture site .... neglected femoral neck fracture in the elderly. ... The best treatment of neglected trauma is prevention.

    5. A global framework for action to improve the primary care response to chronic non-communicable diseases: a solution to a neglected problem

      Directory of Open Access Journals (Sweden)

      Zachariah Rony

      2009-09-01

      Full Text Available Abstract Background Although in developing countries the burden of morbidity and mortality due to infectious diseases has often overshadowed that due to chronic non-communicable diseases (NCDs, there is evidence now of a shift of attention to NCDs. Discussion Decreasing the chronic NCD burden requires a two-pronged approach: implementation of the multisectoral policies aimed at decreasing population-level risks for NCDs, and effective and affordable delivery of primary care interventions for patients with chronic NCDs. The primary care response to common NCDs is often unstructured and inadequate. We therefore propose a programmatic, standardized approach to the delivery of primary care interventions for patients with NCDs, with a focus on hypertension, diabetes mellitus, chronic airflow obstruction, and obesity. The benefits of this approach will extend to patients with related conditions, e.g. those with chronic kidney disease caused by hypertension or diabetes. This framework for a "public health approach" is informed by experience of scaling up interventions for chronic infectious diseases (tuberculosis and HIV. The lessons learned from progress in rolling out these interventions include the importance of gaining political commitment, developing a robust strategy, delivering standardised interventions, and ensuring rigorous monitoring and evaluation of progress towards defined targets. The goal of the framework is to reduce the burden of morbidity, disability and premature mortality related to NCDs through a primary care strategy which has three elements: 1 identify and address modifiable risk factors, 2 screen for common NCDs and 3 and diagnose, treat and follow-up patients with common NCDs using standard protocols. The proposed framework for NCDs borrows the same elements as those developed for tuberculosis control, comprising a goal, strategy and targets for NCD control, a package of interventions for quality care, key operations for

    6. Drug-induced interstitial lung diseases. Often forgotten

      International Nuclear Information System (INIS)

      Poschenrieder, F.; Stroszczynski, C.; Hamer, O.W.

      2014-01-01

      Drug-induced interstitial lung diseases (DILD) are probably more common than diagnosed. Due to their potential reversibility, increased vigilance towards DILD is appropriate also from the radiologist's point of view, particularly as these diseases regularly exhibit radiological correlates in high-resolution computed tomography (HRCT) of the lungs. Based on personal experience typical relatively common manifestations of DILD are diffuse alveolar damage (DAD), eosinophilic pneumonia (EP), hypersensitivity pneumonitis (HP), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). These patterns are presented based on case studies, whereby emphasis is placed on the clinical context. This is to highlight the relevance of interdisciplinary communication and discussion in the diagnostic field of DILD as it is a diagnosis of exclusion or of probability in most cases. Helpful differential diagnostic indications for the presence of DILD, such as an accompanying eosinophilia or increased attenuation of pulmonary consolidations in amiodarone-induced pneumopathy are mentioned and the freely available online database http://www.pneumotox.com is presented. (orig.) [de

    7. Respirable antisense oligonucleotides: a new drug class for respiratory disease

      Directory of Open Access Journals (Sweden)

      Tanaka Makoto

      2000-12-01

      Full Text Available Abstract Respirable antisense oligonucleotides (RASONs, which attenuate specific disease-associated mRNAs, represent a new class of respiratory therapeutics with considerable potential. RASONs overcome previous obstacles that have impeded the development of antisense therapeutics targeting diseases in other organ systems. RASONs are delivered directly to the target tissue via inhalation; their uptake seems to be enhanced by cationic properties inherent in pulmonary surfactant, and, because of the markedly different target properties of mRNA and proteins, they can have very long durations of effect compared with traditional drugs targeting the protein of the same gene. RASONs contain chemical modifications that decrease their degradation by cellular nucleases. However, total insensitivity to nucleases is probably not an optimal design criterion for RASONs, because moderate nuclease sensitivity can prevent their systemic delivery, decreasing the potential for systemic toxicity. EPI-2010 is a 21-mer phosphorothioate RASON that attenuates bronchoconstriction, inflammation and surfactant depletion in preclinical models of human asthma, has a duration of effect of seven days, and seems to undergo minimal systemic delivery.

    8. Orphan drugs, orphan diseases. The first decade of orphan drug legislation in the EU.

      Science.gov (United States)

      Joppi, Roberta; Bertele', Vittorio; Garattini, Silvio

      2013-04-01

      To assess the methodological quality of Orphan Medicinal Product (OMP) dossiers and discuss possible reasons for the small number of products licensed. Information about orphan drug designation, approval, refusal or withdrawal was obtained from the website of the European Medicines Agency and from the European Public Assessment Reports. From 2000 up to 2010, 80.9 % of the 845 candidate orphan drug designations received a positive opinion from the European Medicines Agency (EMA)'s Committee on Orphan Medicinal Products. Of the 108 OMP marketing authorizations applied for, 63 were granted. Randomised clinical trials were done for 38 OMPs and placebo was used as comparator for nearly half the licensed drugs. One third of the OMPs were tested in trials involving fewer than 100 patients and more than half in trials with 100-200 cases. The clinical trials lasted less than one year for 42.9 % of the approved OMPs. Although there may have been some small improvements over time in the methods for developing OMPs, in our opinion, the number of patients studied, the use of placebo as control, the type of outcome measure and the follow-up have often been inadequate. The present system should be changed to find better ways of fostering the development of effective and sustainable treatments for patients with orphan diseases. Public funds supporting independent clinical research on OMPs could bridge the gap between designation and approval. More stringent criteria to assess OMPs' efficacy and cost/effectiveness would improve the clinical value and the affordability of products allowed onto the market.

    9. Large-scale computational drug repositioning to find treatments for rare diseases.

      Science.gov (United States)

      Govindaraj, Rajiv Gandhi; Naderi, Misagh; Singha, Manali; Lemoine, Jeffrey; Brylinski, Michal

      2018-01-01

      Rare, or orphan, diseases are conditions afflicting a small subset of people in a population. Although these disorders collectively pose significant health care problems, drug companies require government incentives to develop drugs for rare diseases due to extremely limited individual markets. Computer-aided drug repositioning, i.e., finding new indications for existing drugs, is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Structure-based matching of drug-binding pockets is among the most promising computational techniques to inform drug repositioning. In order to find new targets for known drugs ultimately leading to drug repositioning, we recently developed e MatchSite, a new computer program to compare drug-binding sites. In this study, e MatchSite is combined with virtual screening to systematically explore opportunities to reposition known drugs to proteins associated with rare diseases. The effectiveness of this integrated approach is demonstrated for a kinase inhibitor, which is a confirmed candidate for repositioning to synapsin Ia. The resulting dataset comprises 31,142 putative drug-target complexes linked to 980 orphan diseases. The modeling accuracy is evaluated against the structural data recently released for tyrosine-protein kinase HCK. To illustrate how potential therapeutics for rare diseases can be identified, we discuss a possibility to repurpose a steroidal aromatase inhibitor to treat Niemann-Pick disease type C. Overall, the exhaustive exploration of the drug repositioning space exposes new opportunities to combat orphan diseases with existing drugs. DrugBank/Orphanet repositioning data are freely available to research community at https://osf.io/qdjup/.

    10. Regulation of drug-metabolizing enzymes in infectious and inflammatory disease: implications for biologics-small molecule drug interactions.

      Science.gov (United States)

      Mallick, Pankajini; Taneja, Guncha; Moorthy, Bhagavatula; Ghose, Romi

      2017-06-01

      Drug-metabolizing enzymes (DMEs) are primarily down-regulated during infectious and inflammatory diseases, leading to disruption in the metabolism of small molecule drugs (smds), which are increasingly being prescribed therapeutically in combination with biologics for a number of chronic diseases. The biologics may exert pro- or anti-inflammatory effect, which may in turn affect the expression/activity of DMEs. Thus, patients with infectious/inflammatory diseases undergoing biologic/smd treatment can have complex changes in DMEs due to combined effects of the disease and treatment. Areas covered: We will discuss clinical biologics-SMD interaction and regulation of DMEs during infection and inflammatory diseases. Mechanistic studies will be discussed and consequences on biologic-small molecule combination therapy on disease outcome due to changes in drug metabolism will be highlighted. Expert opinion: The involvement of immunomodulatory mediators in biologic-SMDs is well known. Regulatory guidelines recommend appropriate in vitro or in vivo assessments for possible interactions. The role of cytokines in biologic-SMDs has been documented. However, the mechanisms of drug-drug interactions is much more complex, and is probably multi-factorial. Studies aimed at understanding the mechanism by which biologics effect the DMEs during inflammation/infection are clinically important.

    11. Orphan drugs for rare diseases: is it time to revisit their special market access status?

      Science.gov (United States)

      Simoens, Steven; Cassiman, David; Dooms, Marc; Picavet, Eline

      2012-07-30

      Orphan drugs are intended for diseases with a very low prevalence, and many countries have implemented legislation to support market access of orphan drugs. We argue that it is time to revisit the special market access status of orphan drugs. Indeed, evidence suggests that there is no societal preference for treating rare diseases. Although society appears to assign a greater value to severity of disease, this criterion is equally relevant to many common diseases. Furthermore, the criterion of equity in access to treatment, which underpins orphan drug legislation, puts more value on health improvement in rare diseases than in common diseases and implies that population health is not maximized. Finally, incentives for the development, pricing and reimbursement of orphan drugs have created market failures, including monopolistic prices and the artificial creation of rare diseases. We argue that, instead of awarding special market access status to orphan drugs, there is scope to optimize research and development (R&D) of orphan drugs and to control prices of orphan drugs by means of, for example, patent auctions, advance purchase commitments, pay-as-you-go schemes and dose-modification studies. Governments should consider carefully the right incentive strategy for R&D of orphan drugs in rare diseases.

    12. Drug induced exocytosis of glycogen in Pompe disease.

      Science.gov (United States)

      Turner, Christopher T; Fuller, Maria; Hopwood, John J; Meikle, Peter J; Brooks, Doug A

      2016-10-28

      Pompe disease is caused by a deficiency in the lysosomal enzyme α-glucosidase, and this leads to glycogen accumulation in the autolysosomes of patient cells. Glycogen storage material is exocytosed at a basal rate in cultured Pompe cells, with one study showing up to 80% is released under specific culture conditions. Critically, exocytosis induction may reduce glycogen storage in Pompe patients, providing the basis for a therapeutic strategy whereby stored glycogen is redirected to an extracellular location and subsequently degraded by circulating amylases. The focus of the current study was to identify compounds capable of inducing rapid glycogen exocytosis in cultured Pompe cells. Here, calcimycin, lysophosphatidylcholine and α-l-iduronidase each significantly increased glycogen exocytosis compared to vehicle-treated controls. The most effective compound, calcimycin, induced exocytosis through a Ca 2+ -dependent mechanism, although was unable to release a pool of vesicular glycogen larger than the calcimycin-induced exocytic pore. There was reduced glycogen release from Pompe compared to unaffected cells, primarily due to increased granule size in Pompe cells. Drug induced exocytosis therefore shows promise as a therapeutic approach for Pompe patients but strategies are required to enhance the release of large molecular weight glycogen granules. Copyright © 2016. Published by Elsevier Inc.

    13. Strongyloidiasis--the most neglected of the neglected tropical diseases?

      DEFF Research Database (Denmark)

      Olsen, A.; L., van Lieshout; Marti, H.

      2009-01-01

      Soil-transmitted helminths of the genus Strongyloides (S. fuelleborni and the more prevalent S. stercoralis) are currently believed to infect an estimated 30-100 million people worldwide. The health consequences of S. stercoralis infections range from asymptomatic light infections to chronic symp...

    14. [Development of anti-Alzheimer's disease drug based on beta-amyloid hypothesis].

      Science.gov (United States)

      Sugimoto, Hachiro

      2010-04-01

      Currently, there are five anti-Alzheimer's disease drugs approved. These are tacrine, donepezil, rivastigmine, galantamine, and memantine. The mechanism of the first four drugs is acetylcholinesterase inhibition, while memantine is an NMDA-receptor antagonist. However, these drugs do not cure Alzheimer's, but are only symptomatic treatments. Therefore, a cure for Alzheimer's disease is truly needed. Alzheimer's disease is a progressive neurodegenerative disease characterized by cognitive deficits. The cause of the disease is not well understood, but research indicates that the aggregation of beta-amyloid is the fundamental cause. This theory suggests that beta-amyloid aggregation causes neurotoxicity. Therefore, development of the next anti-Alzheimer's disease drug is based on the beta-amyloid theory. We are now studying natural products, such as mulberry leaf extracts and curcumin derivatives, as potential cure for Alzheimer's disease. In this report, we describe some data about these natural products and derivatives.

    15. Disease-modifying antirheumatic drugs in pregnancy - Current status and implications for the future

      NARCIS (Netherlands)

      Vroom, Fokaline; de Walle, Hermien E. K.; van de Laar, Mart A. J. F.; Brouwers, Jacobus R. B. J.; de Jong-van den Berg, Lolkje T. W.

      2006-01-01

      Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD

    16. Muscarinic Acetylcholine Receptor Subtypes as Potential Drug Targets for the Treatment of Schizophrenia, Drug Abuse and Parkinson's Disease

      DEFF Research Database (Denmark)

      Dencker, Ditte; Thomsen, Morgane; Wörtwein, Gitta

      2011-01-01

      's disease and drug abuse. Dopaminergic systems are regulated by cholinergic, especially muscarinic, input. Not surprisingly, increasing evidence implicates muscarinic acetylcholine receptor-mediated pathways as potential targets for the treatment of these disorders classically viewed as "dopamine based...... site. Such agents may lead to the development of novel classes of drugs useful for the treatment of psychosis, drug abuse and Parkinson's disease. The present review highlights recent studies carried out using muscarinic receptor knock-out mice and new subtype-selective allosteric ligands to assess...... the roles of M(1), M(4), and M(5) receptors in various central processes that are under strong dopaminergic control. The outcome of these studies opens new perspectives for the use of novel muscarinic drugs for several severe disorders of the CNS....

    17. Nuclear track microfilters in controlled drug delivery against chronic skin disease

      International Nuclear Information System (INIS)

      Gopalani, D.; Jodha, A.S.; Saravanan, S.; Kumar, S.

      2003-01-01

      Nuclear track microfilters have been developed for transdermal therapeutic system. The transdermal therapeutic method reduces the toxicity of the drug as compared to other conventional methods. For this purpose a slow drug release system containing the nuclear track microfilter was developed. This device was applied to the patients suffering from psoriasis and cellulites diseases. The delivery of the drug to the patient was confirmed through high performance liquid chromatography. The preliminary results have shown that patients are responding to drugs with minimum toxicity

    18. Nuclear track microfilters in controlled drug delivery against chronic skin disease

      Energy Technology Data Exchange (ETDEWEB)

      Gopalani, D. E-mail: deflab@sancharnet.in; Jodha, A.S.; Saravanan, S.; Kumar, S

      2003-06-01

      Nuclear track microfilters have been developed for transdermal therapeutic system. The transdermal therapeutic method reduces the toxicity of the drug as compared to other conventional methods. For this purpose a slow drug release system containing the nuclear track microfilter was developed. This device was applied to the patients suffering from psoriasis and cellulites diseases. The delivery of the drug to the patient was confirmed through high performance liquid chromatography. The preliminary results have shown that patients are responding to drugs with minimum toxicity.

    19. Huperzine A: Is it an Effective Disease-Modifying Drug for Alzheimer's Disease?

      Science.gov (United States)

      Qian, Zhong Ming; Ke, Ya

      2014-01-01

      Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there is no cure. Huperzine A (HupA) is a natural inhibitor of acetylcholinesterase (AChE) derived from the Chinese folk medicine Huperzia serrata (Qian Ceng Ta). It is a licensed anti-AD drug in China and is available as a nutraceutical in the US. A growing body of evidence has demonstrated that HupA has multifaceted pharmacological effects. In addition to the symptomatic, cognitive-enhancing effect via inhibition of AChE, a number of recent studies have reported that this drug has "non-cholinergic" effects on AD. Most important among these is the protective effect of HupA on neurons against amyloid beta-induced oxidative injury and mitochondrial dysfunction as well as via the up-regulation of nerve growth factor and antagonizing N-methyl-d-aspartate receptors. The most recent discovery that HupA may reduce brain iron accumulation lends further support to the argument that HupA could serve as a potential disease-modifying agent for AD and also other neurodegenerative disorders by significantly slowing down the course of neuronal death.

    20. Huperzine A: Is it an Effective Disease-Modifying Drug for Alzheimer’s Disease?

      Science.gov (United States)

      Qian, Zhong Ming; Ke, Ya

      2014-01-01

      Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which there is no cure. Huperzine A (HupA) is a natural inhibitor of acetylcholinesterase (AChE) derived from the Chinese folk medicine Huperzia serrata (Qian Ceng Ta). It is a licensed anti-AD drug in China and is available as a nutraceutical in the US. A growing body of evidence has demonstrated that HupA has multifaceted pharmacological effects. In addition to the symptomatic, cognitive-enhancing effect via inhibition of AChE, a number of recent studies have reported that this drug has “non-cholinergic” effects on AD. Most important among these is the protective effect of HupA on neurons against amyloid beta-induced oxidative injury and mitochondrial dysfunction as well as via the up-regulation of nerve growth factor and antagonizing N-methyl-d-aspartate receptors. The most recent discovery that HupA may reduce brain iron accumulation lends further support to the argument that HupA could serve as a potential disease-modifying agent for AD and also other neurodegenerative disorders by significantly slowing down the course of neuronal death. PMID:25191267

    1. Huperzine A: is it an effective disease-modifying drug for Alzheimer’s disease?

      Directory of Open Access Journals (Sweden)

      Zhong Ming eQian

      2014-08-01

      Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disorder for which there is no cure. Huperzine A (HupA is a natural inhibitor of acetylcholinesterase (AChE derived from the Chinese folk medicine Huperzia serrata (Qian Ceng Ta. It is a licensed anti-AD drug in China and is available as a nutraceutical in the US. A growing body of evidence has demonstrated that HupA has multifaceted pharmacological effects. In addition to the symptomatic, cognitive-enhancing effect via inhibition of AChE, a number of recent studies have reported that this drug has non-cholinergic effects on AD. Most important among these is the protective effect of HupA on neurons against amyloid beta-induced oxidative injury and mitochondrial dysfunction as well as via the up-regulation of nerve growth factor and antagonizing N-methyl-D-aspartate receptors. The most recent discovery that HupA may reduce brain iron accumulation lends further support to the argument that HupA could serve as a potential disease-modifying agent for AD and also other neurodegenerative disorders by significantly slowing down the course of neuronal death.

    2. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery

      Directory of Open Access Journals (Sweden)

      Ji Young Yhee

      2016-09-01

      Full Text Available Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD, cystic fibrosis (CF, idiopathic pulmonary fibrosis (IPF, and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed.

    3. eRepo-ORP: Exploring the Opportunity Space to Combat Orphan Diseases with Existing Drugs.

      Science.gov (United States)

      Brylinski, Michal; Naderi, Misagh; Govindaraj, Rajiv Gandhi; Lemoine, Jeffrey

      2017-12-10

      About 7000 rare, or orphan, diseases affect more than 350 million people worldwide. Although these conditions collectively pose significant health care problems, drug companies seldom develop drugs for orphan diseases due to extremely limited individual markets. Consequently, developing new treatments for often life-threatening orphan diseases is primarily contingent on financial incentives from governments, special research grants, and private philanthropy. Computer-aided drug repositioning is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Here, we present eRepo-ORP, a comprehensive resource constructed by a large-scale repositioning of existing drugs to orphan diseases with a collection of structural bioinformatics tools, including eThread, eFindSite, and eMatchSite. Specifically, a systematic exploration of 320,856 possible links between known drugs in DrugBank and orphan proteins obtained from Orphanet reveals as many as 18,145 candidates for repurposing. In order to illustrate how potential therapeutics for rare diseases can be identified with eRepo-ORP, we discuss the repositioning of a kinase inhibitor for Ras-associated autoimmune leukoproliferative disease. The eRepo-ORP data set is available through the Open Science Framework at https://osf.io/qdjup/. Copyright © 2017. Published by Elsevier Ltd.

    4. Liver Flukes: the Malady Neglected

      Energy Technology Data Exchange (ETDEWEB)

      Lim, Jae Hoon [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

      2011-06-15

      Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts. Infection occurs through ingestion of fluke-infested, fresh-water raw fish. The most well-known species that cause human infection are Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. Adult flukes settle in the small intrahepatic bile ducts and then they live there for 20-30 years. The long-lived flukes cause long-lasting chronic inflammation of the bile ducts and this produces epithelial hyperplasia, periductal fibrosis and bile duct dilatation. The vast majority of patients are asymptomatic, but the patients with heavy infection suffer from lassitude and nonspecific abdominal complaints. The complications are stone formation, recurrent pyogenic cholangitis and cholangiocarcinoma. Approximately 35 million people are infected with liver flukes throughout the world and the exceptionally high incidence of cholangiocarcinoma in some endemic areas is closely related with a high prevalence of liver fluke infection. Considering the impact of this food-borne malady on public health and the severe possible clinical consequences, liver fluke infection should not be forgotten or neglected.

    5. Liver Flukes: the Malady Neglected

      International Nuclear Information System (INIS)

      Lim, Jae Hoon

      2011-01-01

      Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts. Infection occurs through ingestion of fluke-infested, fresh-water raw fish. The most well-known species that cause human infection are Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. Adult flukes settle in the small intrahepatic bile ducts and then they live there for 20-30 years. The long-lived flukes cause long-lasting chronic inflammation of the bile ducts and this produces epithelial hyperplasia, periductal fibrosis and bile duct dilatation. The vast majority of patients are asymptomatic, but the patients with heavy infection suffer from lassitude and nonspecific abdominal complaints. The complications are stone formation, recurrent pyogenic cholangitis and cholangiocarcinoma. Approximately 35 million people are infected with liver flukes throughout the world and the exceptionally high incidence of cholangiocarcinoma in some endemic areas is closely related with a high prevalence of liver fluke infection. Considering the impact of this food-borne malady on public health and the severe possible clinical consequences, liver fluke infection should not be forgotten or neglected.

    6. Cognitive enhancers (nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. disease-modifying drugs.

      Science.gov (United States)

      Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas

      2013-01-01

      Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 19 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease modifying drugs, meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-β and tau. For drugs, whose mechanism of action is not known, they are either classified according to structure, e.g., peptides, or their origin, e.g., natural products. The review covers the evolution of research in this field over the last 25 years.

    7. Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity

      Directory of Open Access Journals (Sweden)

      Bianca Zingales

      2014-09-01

      Full Text Available This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape.

    8. Orphan drugs: trends and issues in drug development.

      Science.gov (United States)

      Rana, Proteesh; Chawla, Shalini

      2018-04-12

      Research in rare diseases has contributed substantially toward the current understanding in the pathophysiology of the common diseases. However, medical needs of patients with rare diseases have always been neglected by the society and pharmaceutical industries based on their small numbers and unprofitability. The Orphan Drug Act (1983) was the first serious attempt to address the unmet medical needs for patients with rare diseases and to provide impetus for the pharmaceutical industry to promote orphan drug development. The process of drug development for rare diseases is no different from common diseases but involves significant cost and infrastructure. Further, certain aspect of drug research may not be feasible for the rare diseases. The drug-approving authority must exercise their scientific judgment and ensure due flexibility while evaluating data at various stages of orphan drug development. The emergence of patent cliff combined with the government incentives led the pharmaceutical industry to realize the good commercial prospects in developing an orphan drug despite the small market size. Indeed, many drugs that were given orphan designation ended up being blockbusters. The orphan drug market is projected to reach $178 billion by 2020, and the prospects of research and development in rare diseases appears to be quite promising and rewarding.

    9. Drug Hypersensitivity and Anaphylaxis in Cancer and Chronic Inflammatory Diseases: The Role of Desensitizations

      Directory of Open Access Journals (Sweden)

      Mariana Castells

      2017-11-01

      Full Text Available Drug allergy is a rising problem in the twenty-first century which affects all populations and races, children, and adults, and for which the recognition, diagnosis, management, and treatment is still not well standardized. Classical and new chemotherapy drugs, monoclonal antibodies (MoAbs, and small molecules to treat cancer and chronic inflammatory diseases are aimed at improving quality of life and life expectancy of patients, but an increasing number of reactions including anaphylaxis precludes their use in targeted populations. Women are more affected by drug allergy and up to 27% of women with ovarian and breast cancer develop carboplatin allergy after multiple cycles of treatment. Carriers of BRCA genes develop drug allergy after fewer exposures and can present with severe reactions, including anaphylaxis. Atopic patients are at increased risk for chemotherapy and MoAbs drug allergy and the current patterns of treatment with recurrent and intermittent drug exposures may favor the development of drug allergies. To overcome drug allergy, desensitization has been developed, a novel approach which provides a unique opportunity to protect against anaphylaxis and to improve clinical outcomes. There is evidence that inhibitory mechanisms blocking IgE/antigen mast cell activation are active during desensitization, enhancing safety. Whether desensitization modulates drug allergic and anaphylactic responses facilitating tolerance is currently being investigated. This review provides insight into the current knowledge of drug allergy and anaphylaxis to cancer and chronic inflammatory diseases drugs, the mechanisms of drug desensitization and its applications to personalized medicine.

    10. Definition of drug resistance of Mycobacterium tuberculosis to antituberculosis drugs in patients with multidrugresistant tuberculosis and TB with extremely drug resistant depending on the case of the disease

      Directory of Open Access Journals (Sweden)

      Kryzhanovsky D.G.

      2014-11-01

      Full Text Available There was studied the profile of drug resistance to the main (I line and reserve (II line antituberculosis drugs in patients with MDR and XDR tuberculosis, depending of the case of the disease. According to the randomized retrospective research 200 patients with MDR and XDR tuberculosis, who received treatment in the clinic of hospital Municipal institution «Dnipropetrovsk rigional clinical association «Phthisiology» Dnipropetrovsk regional Council» during the period 2010 – 2012 were involved. Data about patients contained the data on a case of the disease and the results of the test of drug sensitivity to MBT. XDR – TB was revealed in 7.5% of patients with MDR tuberculosis. In patients with MDR tuberculosis as compared with patients with XDR tuberculosis «new cases» were diagnosed in 19.5% against 18.5% (p <0.05. In patients with MDR tuberculosis and with XDR tuberculosis resistance to the antituberculosis drug more commonly developed to S - 88.5%, E - 55% and Z - 24%. The presence of MDR-TB and XDR-TB prevails in patients, who underwent previous courses of treatment with anti-TB drugs in case history as compared with patients with «new cases» of treatment. The development of resistance to anti-TB drugs depends on the availability of these drugs in the previous treatment regimens.

    11. Albumin-based drug delivery: harnessing nature to cure disease.

      Science.gov (United States)

      Larsen, Maja Thim; Kuhlmann, Matthias; Hvam, Michael Lykke; Howard, Kenneth A

      2016-01-01

      The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however, challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery enabling technologies. Albumin is a natural transport protein with multiple ligand binding sites, cellular receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by covalent conjugation, genetic fusions, association or ligand-mediated association. This review will give an overview of albumin-based products with focus on the natural biological properties and molecular interactions that can be harnessed for the design of a next-generation drug delivery platform.

    12. Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases

      Science.gov (United States)

      Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H. F.; Karla, Pradeep K.; Boddu, Sai H. S.

      2018-01-01

      Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed. PMID:29495528

    13. Studying Disease Occurrence and Drug Effects in Children: A global approach

      NARCIS (Netherlands)

      O.U. Osokogu (Osemeke)

      2017-01-01

      markdownabstractChildhood diseases result from different causes and exhibit different characteristics. The occurrence of such diseases can be estimated from electronic healthcare records but the characteristics of both the diseases and the databases should be considered. Licensed drugs have limited

    14. NSAIDs and cardiovascular drugs in neurodegenerative and cerebrovascular diseases

      NARCIS (Netherlands)

      M.D.M. Haag (Mendel)

      2009-01-01

      textabstractNeurodegenerative and cerebrovascular diseases are frequent in elderly populations and comprise primarily of dementia (mainly Alzheimer disease (AD)), Parkinson disease (PD) and stroke. The prevalence of these neurological disorders rises with older age. From 55 years to 90 years and

    15. Drug sales data analysis for outbreak detection of infectious diseases: a systematic literature review.

      Science.gov (United States)

      Pivette, Mathilde; Mueller, Judith E; Crépey, Pascal; Bar-Hen, Avner

      2014-11-18

      This systematic literature review aimed to summarize evidence for the added value of drug sales data analysis for the surveillance of infectious diseases. A search for relevant publications was conducted in Pubmed, Embase, Scopus, Cochrane Library, African Index Medicus and Lilacs databases. Retrieved studies were evaluated in terms of objectives, diseases studied, data sources, methodologies and performance for real-time surveillance. Most studies compared drug sales data to reference surveillance data using correlation measurements or indicators of outbreak detection performance (sensitivity, specificity, timeliness of the detection). We screened 3266 articles and included 27 in the review. Most studies focused on acute respiratory and gastroenteritis infections. Nineteen studies retrospectively compared drug sales data to reference clinical data, and significant correlations were observed in 17 of them. Four studies found that over-the-counter drug sales preceded clinical data in terms of incidence increase. Five studies developed and evaluated statistical algorithms for selecting drug groups to monitor specific diseases. Another three studies developed models to predict incidence increase from drug sales. Drug sales data analyses appear to be a useful tool for surveillance of gastrointestinal and respiratory disease, and OTC drugs have the potential for early outbreak detection. Their utility remains to be investigated for other diseases, in particular those poorly surveyed.

    16. Immunity against HIV/AIDS, Malaria, and Tuberculosis during Co-Infections with Neglected Infectious Diseases: Recommendations for the European Union Research Priorities.

      NARCIS (Netherlands)

      Boraschi, D.; Alemayehu, M.A.; Aseffa, A.; Chiodi, F.; Chisi, J.; Prete, G. Del; Doherty, T.M.; Elhassan, I.; Engers, H.; Gyan, B; Harandi, A.M.; Kariuki, T.; Kironde, F.; Kouriba, B.; Langhorne, J.; Laskay, T.; Medaglini, D.; Olesen, O.; Onyebujoh, P.; Palma, C.; Sauerwein, R.W.; Sibanda, E.; Steinhoff, U.; Tagliabue, A.; Thiel, A.; Vahedi, M.; Troye-Blomberg, M.

      2008-01-01

      Author SummaryInfectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB) have received most of the world's attention. However, in

    17. Development and Psychometric Evaluation of the Child Neglect Questionnaire.

      Science.gov (United States)

      Stewart, Chris; Kirisci, Levent; Long, Abigail L; Giancola, Peter R

      2015-11-01

      Neglect poses a significant risk for children throughout their development and is often linked with serious consequences that reach into adulthood. The Child Neglect Questionnaire (CNQ) fills existing gaps by incorporating multiple perspectives from both parents and the child, as well as measuring the complex phenomenon of neglect multidimensionally. Furthermore, this measure addresses the need for an instrument specifically developed for late childhood (ages 10-12), as much of the extant evidence and corresponding measures focus on young children and their mothers. A panel of three psychologists, using Cicchetti's model of child neglect as a theoretical guide, began by selecting items from an existing database. Results of exploratory and confirmatory factor analyses and item response theory demonstrated the unidimensionality of physical, emotional, educational, and supervision neglect as well as a second-order construct of child neglect. Analyses controlling for risk status due to father's substance use disorder, socioeconomic status, and child's ethnicity demonstrated that father's and mother's (parental) neglect, particularly in the child's versions, had sound concurrent and predictive validity. Concurrently, at age 10-12, the child's version of both parents' neglect correlated with their parenting behaviors evaluated by other available measures. Prospectively, from 10-12 years of age to 11-13 years of age, parental neglect predicted child's drug use frequency with coexisting psychological dysregulation, psychiatric symptoms, antisocial behavior, non-normative sexual behavior, involvement with deviant peers and leisure activities thus demonstrating sound predictive validity. Also, internal consistency and inter-rater reliability were excellent. The CNQ, particularly the child's version, may thus be useful for detecting children at high risk for parental neglect. © The Author(s) 2014.

    18. Atopic Dermatitis: Drug Delivery Approaches in Disease Management.

      Science.gov (United States)

      Lalan, Manisha; Baweja, Jitendra; Misra, Ambikanandan

      2015-01-01

      In this review, we describe the very basic of atopic dermatitis (AD), the established management strategies, and the advances in drug delivery approaches for successful therapeutic outcomes. The multifactorial pathophysiology of AD has given rise to the clinician's paradigm of topical and systemic therapy and potential combinations. However, incomplete remission of skin disorders like AD is a major challenge to be overcome. Recurrence is thought to be due to genetic and immunological etiologies and shortcomings in drug delivery. This difficulty has sparked research in nanocarrier-based delivery approaches as well as molecular biology-inspired stratagems to deal with the immunological imbalance and to address insufficiencies of delivery propositions. In this review, we assess various novel drug delivery strategies in terms of their success and utility. We present a brief compilation and assessment of management modalities to sensitize the readers to therapeutic scenario in AD.

    19. Sacro-iliac joint disease in drug abusers: The role of bone scintigraphy

      International Nuclear Information System (INIS)

      Lopez-Majano, V.; Miskew, D.B.W.; Cook County Hospital, Chicago, IL

      1980-01-01

      Bone scintigrams demonstrated increased uptake in the sacroiliac joint in twenty drug addicts with low back pain and signs of localized sepsis. The localization of the disease was decisive for the orthopedist in the aspiration of the affected joint. (orig.)

    20. 76 FR 78931 - Food and Drug Administration Rare Disease Patient Advocacy Day; Notice of Meeting

      Science.gov (United States)

      2011-12-20

      ... Administration, HHS. ACTION: Notice. The Food and Drug Administration's (FDA) Office of Orphan Products... educate the rare disease community on the FDA regulatory processes. This educational meeting will consist...

    1. Antiepileptic drugs in pregnancy and hemorrhagic disease of the newborn: An update

      OpenAIRE

      Kazmin, Aleksey; Wong, Renee C.; Sermer, Mathew; Koren, Gideon

      2010-01-01

      QUESTION What is the current evidence regarding the association between hemorrhagic disease of the newborn and maternal use of hepatic enzyme-inducing antiepileptic drugs (eg, carbamazepine, phenobarbitone, topiramate)?

    2. One For All? Hitting multiple Alzheimer’s Disease targets with one drug

      Directory of Open Access Journals (Sweden)

      Rebecca Ellen Hughes

      2016-04-01

      Full Text Available Alzheimer’s disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs. Intended as a introduction for non-experts, this review describes the key multi-target drug design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch and also the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer’s Disease are rasagiline, originally developed for the treatment of Parkinson’s Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.

    3. Non-steroidal anti-inflammatory drugs and cyclooxygenase in Alzheimer's disease

      NARCIS (Netherlands)

      Hoozemans, Jeroen J. M.; Veerhuis, Robert; Rozemuller, Annemieke J. M.; Eikelenboom, Piet

      2003-01-01

      Epidemiological studies indicate that anti-inflammatory drugs, especially the non-steroidal anti-inflammatory drugs (NSAIDs), decrease the risk of developing Alzheimer's disease (AD). Their beneficial effects may be due to interference in the chronic inflammatory reaction, that takes place in AD.

    4. [Experience of rapid drug desensitization therapy in the treatment of mycobacterial disease].

      Science.gov (United States)

      Sasaki, Yuka; Kurashima, Atsuyuki; Morimoto, Kozo; Okumura, Masao; Watanabe, Masato; Yoshiyama, Takashi; Ogata, Hideo; Gotoh, Hajime; Kudoh, Shoji; Suzuki, Hiroaki

      2014-11-01

      Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used. Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan. We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted. The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients. In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

    5. Needle-free and microneedle drug delivery in children: a case for disease-modifying antirheumatic drugs (DMARDs).

      Science.gov (United States)

      Shah, Utpal U; Roberts, Matthew; Orlu Gul, Mine; Tuleu, Catherine; Beresford, Michael W

      2011-09-15

      Parenteral routes of drug administration have poor acceptability and tolerability in children. Advances in transdermal drug delivery provide a potential alternative for improving drug administration in this patient group. Issues with parenteral delivery in children are highlighted and thus illustrate the scope for the application of needle-free and microneedle technologies. This mini-review discusses the opportunities and challenges for providing disease-modifying antirheumatic drugs (DMARDs) currently prescribed to paediatric rheumatology patients using such technologies. The aim is to raise further awareness of the need for age-appropriate formulations and drug delivery systems and stimulate exploration of these options for DMARDs, and in particular, rapidly emerging biologics on the market. The ability of needle-free and microneedle technologies to deliver monoclonal antibodies and fusion proteins still remains largely untested. Such an understanding is crucial for future drug design opportunities. The bioavailability, safety and tolerance of delivering biologics into the viable epidermis also need to be studied. Copyright © 2011 Elsevier B.V. All rights reserved.

    6. Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

      Science.gov (United States)

      Schneider, Lon S

      2014-03-01

      The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

    7. Low hanging fruit in infectious disease drug development.

      Science.gov (United States)

      Kraus, Carl N

      2008-10-01

      Cost estimates for developing new molecular entities (NME) are reaching non-sustainable levels and coupled with increasing regulatory requirements and oversight have led many pharmaceutical sponsors to divest their anti-microbial development portfolios [Projan SJ: Why is big Pharma getting out of anti-bacterial drug discovery?Curr Opin Microbiol 2003, 6:427-430] [Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE, Jr: Trends in antimicrobial drug development: implications for the future.Clin Infect Dis 2004, 38:1279-1286]. Operational issues such as study planning and execution are significant contributors to the overall cost of drug development that can benefit from the leveraging of pre-randomization data in an evidence-based approach to protocol development, site selection and patient recruitment. For non-NME products there is even greater benefit from available data resources since these data may permit smaller and shorter study programs. There are now many available open source intelligence (OSINT) resources that are being integrated into drug development programs, permitting an evidence-based or 'operational epidemiology' approach to study planning and execution.

    8. Ceramic/polymer nanocomposites with tunable drug delivery capability at specific disease sites.

      Science.gov (United States)

      Liu, Huinan; Webster, Thomas J

      2010-06-01

      Pharmaceutical agents are often used to stimulate new bone formation for the treatment of bone injuries or diseases (such as osteoporosis). However, there are several problems associated with current orthopedic drug delivery methods. First, conventional systemic administration of pharmaceutical agents may not effectively reach targeted sites and, thus, they can cause nonspecific bone formation in areas not affected by injury or disease. Second, even if intentionally delivered or implanted locally to the damaged bone tissue, these agents tend to rapidly diffuse into adjacent tissues due to weak physical bonding to their drug carriers, which limits their potential to promote prolonged bone formation in targeted areas of bone disease. Therefore, in this study, biodegradable ceramic/polymer nanocomposites were explored as novel drug carriers for orthopedic applications to prolong local drug release and, thus, improve drug effectiveness at bone disease sites. Specifically, a bone morphogenetic protein (BMP-7) derived peptide (DIF-7c) was used as a model drug in this study and was first loaded onto nanocrystalline hydroxyapatite (nano-HA) by either covalent chemical attachment or physical adsorption. These drug-carrying nano-HA particles were then dispersed into a degradable polymer (poly-lactide-co-glycolide or PLGA) matrix to create an implantable system capable of long-term drug release. The aminophase silane covalent chemical immobilization process was utilized in this study. These nanocomposite-based drug delivery systems were then characterized for drug loading efficiency and in vitro drug release. Results demonstrated that DIF-7c was successfully immobilized onto nano-HA placed in PLGA. Moreover, a greater prolonged two-phase release profile (of more than 3 months) was achieved when using aminophase silane chemical immobilization to nano-HA particles. Since previous studies have demonstrated greater in vivo bone growth on nano- compared with micron-HA particles

    9. Generic versus brand-name drugs used in cardiovascular diseases.

      Science.gov (United States)

      Manzoli, Lamberto; Flacco, Maria Elena; Boccia, Stefania; D'Andrea, Elvira; Panic, Nikola; Marzuillo, Carolina; Siliquini, Roberta; Ricciardi, Walter; Villari, Paolo; Ioannidis, John P A

      2016-04-01

      This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI -0.05; 0.08) for soft outcomes; -0.06 (-0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (-0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40-7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider

    10. Modulation and rehabilitation of spatial neglect by sensory stimulation.

      Science.gov (United States)

      Kerkhoff, Georg

      2003-01-01

      After unilateral cortical or subcortical, often parieto-temporal lesions, patients exhibit a marked neglect of their contralateral space and/or body side. These patients are severely disabled in all daily activities, have a poor rehabilitation outcome and therefore require professional treatment. Unfortunately, effective treatments for neglect are just in the process of development. The present chapter reviews three aspects related to the rehabilitation of neglect. The first part summarizes findings about spontaneous recovery in patients and experimental animals with neglect. The second part deals with techniques and studies evaluating short-term sensory modulation effects in neglect. In contrast to many other neurological syndromes spatial neglect may be modulated transiently but dramatically in its severity by sensory (optokinetic, neck proprioceptive, vestibular, attentional, somatosensory-magnetic) stimulation. In part three, current treatment approaches are summarized, with a focus on three novel techniques: repetitive optokinetic stimulation, neck vibration training and peripheral somatosensory-magnetic stimulation. Recent studies of repetitive optokinetic as well as neck vibratory treatment both indicate significantly greater as well as multimodal improvements in neglect symptomatology as compared to the standard treatment of neglect. This clear superiority might result from the partial (re)activation of a distributed, multisensory vestibular network in the lesioned hemisphere. Somatosensory-magnetic stimulation of the neglected or extinguishing hand provides another feasible, non-invasive stimulation technique. It may be particularly suited for the rehabilitation of somatosensory extinction and unawareness of the contralesional body side. Finally, pharmacological approaches for the treatment of neglect are shortly addressed. Isolated drug treatment of neglect is currently no successful rehabilitation strategy due to inconsistent results as well as possible

    11. The neglected arboviral infections in mainland China.

      Directory of Open Access Journals (Sweden)

      Xiaoyan Gao

      2010-04-01

      Full Text Available The major arboviral diseases in mainland China include Japanese encephalitis, dengue fever, Crimean-Congo hemorrhagic fever (also known as Xinjiang hemorrhagic fever, and tick-borne encephalitis. These and other newly found arbovirus infections due to Banna virus and Tahyna virus contribute to a large and relatively neglected disease burden in China. Here we briefly review the literature regarding these arboviral infections in mainland China with emphasis on their epidemiology, primary vectors, phylogenetic associations, and the prevention programs associated with these agents in China.

    12. The availability and affordability of orphan drugs for rare diseases in China.

      Science.gov (United States)

      Gong, Shiwei; Wang, Yingxiao; Pan, Xiaoyun; Zhang, Liang; Huang, Rui; Chen, Xin; Hu, Juanjuan; Xu, Yi; Jin, Si

      2016-02-27

      Orphan drugs are intended to treat, prevent or diagnose rare diseases. In recent years, China healthcare policy makers and patients have become increasingly concerned about orphan drug issues. However, very few studies have assessed the availability and affordability of orphan drugs for rare diseases in China. The aim of this study was to provide an overview of the availability and affordability of orphan drugs in China and to make suggestions to improve patient access to orphan drugs. Two components of the availability of orphan drugs were examined. Market availability was assessed by the extent to which orphan drugs were marketed in China with a comparison to orphan drugs in international markets, such as the U.S., EU and Japan. We conducted surveys and collected data from 24 tertiary public hospitals in China to measure hospital-level availability of orphan drugs. The affordability of orphan drugs was calculated using hospital dispensary prices and was expressed as days of average daily income required for the cost of a course of treatment. Affordability was also analyzed under the Chinese basic medical insurance system. Orphan drugs approved in the U.S., EU and Japan had 37.8%, 24.6% and 52.4% market availability in China, respectively. Median availability of 31 orphan drugs surveyed at the 24 tertiary public hospitals was 20.8% (very low). Within a periodic treatment course, the average treatment cost of 23 orphan drugs is approximately 4, 843. 5 USD, which equates to 505.6 days of per capita net income for an urban resident with a middle income (187.4 days for a high-income urban resident) or 1,582.8 days's income for a rural resident with a middle income (657.2 days for a high-income rural resident). Except for homoharringtonine, 22 orphan drugs for 14 rare diseases were unaffordable for the most of residents in China. With 5% out-of-pocket expenses, only three generics could be afforded by middle-income residents, whereas seven drugs for high-income urban

    13. Child neglect and emotional abuse

      Science.gov (United States)

      ... poor weight gain Emotional issues such as low self-esteem, depression, and anxiety Extreme behavior such as acting ... child was abused The success of therapy and parenting classes Alternative Names Neglect - child; Emotional abuse - child ...

    14. Symbiosis: Rich, Exciting, Neglected Topic

      Science.gov (United States)

      Rowland, Jane Thomas

      1974-01-01

      Argues that the topic of symbiosis has been greatly neglected and underemphasized in general-biology textbooks. Discusses many types and examples of symbiosis, and provides an extensive bibliography of the literature related to this topic. (JR)

    15. Orphan drugs in development for Huntington's disease: challenges and progress

      Directory of Open Access Journals (Sweden)

      Burgunder JM

      2015-02-01

      Full Text Available Jean-Marc Burgunder1–4 1Swiss Huntington’s Disease Centre, Department of Neurology, University of Bern, Bern, Switzerland; 2Department of Neurology, West China Hospital, Sichuan University, Chengdu, 3Department of Neurology, Xiangya Hospital, Central South University, Changsha, 4Department of Neurology, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Huntington’s disease is a monogenic disorder encompassing a variable phenotype with progressive cognitive, psychiatric, and movement disorders. Knowledge of the mechanisms involved in this disorder has made substantial advances since the discovery of the gene mutation. The dynamic mutation is the expansion of a CAG (cytosine-adenine-guanine repeat in the huntingtin (HTT gene, which is transcribed into an abnormal protein with an elongated polyglutamine tract. Polyglutamine HTT accumulates and is changed in its function in multifaceted ways related to the numerous roles of the normal protein. The protein is expressed in numerous areas of the brain and also in other organs. The major brain region involved in the disease process is the striatum, but it is clear that other systems are involved as well. This accumulated knowledge has now led to the development of treatment strategies based on specific molecular pathways for symptomatic and disease course-modifying treatment. The most proximal way to handle the disturbed protein is to hinder the gene transcription, translation, and/or to increase protein clearance. Other mechanisms now being approached include modulation of energy and intracellular signaling, induction of factors potentially leading to neuroprotection, as well as modulation of glial function. Several clinical trials based on these approaches are now under way, and it is becoming clear that a future disease-modifying therapy will be a combination of several approaches harmonized with symptomatic treatments. In this review, some of the most promising and

    16. Drug Repositioning: An Opportunity to Develop Novel Treatments for Alzheimer’s Disease

      Directory of Open Access Journals (Sweden)

      Clive Ballard

      2013-10-01

      Full Text Available Alzheimer’s Disease (AD is the most common cause of dementia, affecting approximately two thirds of the 35 million people worldwide with the condition. Despite this, effective treatments are lacking, and there are no drugs that elicit disease modifying effects to improve outcome. There is an urgent need to develop and evaluate more effective pharmacological treatments. Drug repositioning offers an exciting opportunity to repurpose existing licensed treatments for use in AD, with the benefit of providing a far more rapid route to the clinic than through novel drug discovery approaches. This review outlines the current most promising candidates for repositioning in AD, their supporting evidence and their progress through trials to date. Furthermore, it begins to explore the potential of new transcriptomic and microarray techniques to consider the future of drug repositioning as a viable approach to drug discovery.

    17. 78 FR 9396 - Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early...

      Science.gov (United States)

      2013-02-08

      ...] Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early Stage... ``Alzheimer's Disease: Developing Drugs for the Treatment of Early Stage Disease.'' This guidance outlines FDA... trials that are specifically focused on the treatment of patients with established Alzheimer's disease...

    18. Transporter-mediated natural product–drug interactions for the treatment of cardiovascular diseases

      Directory of Open Access Journals (Sweden)

      Weibin Zha

      2018-04-01

      Full Text Available The growing use of natural products in cardiovascular (CV patients has been greatly raising the concerns about potential natural product–CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product–CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product–drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins have been identified to be substrates and inhibitors of the solute carrier (SLC transporters and the ATP-binding cassette (ABC transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product–CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product–CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product–CV drug interactions and help public and physicians understand these type of interactions. Keywords: Cardiovascular drugs, Natural products, Drug transporters, Natural product–drug interaction, Pharmacokinetics

    19. Repurposing of Copper(II)-chelating Drugs for the Treatment of Neurodegenerative Diseases.

      Science.gov (United States)

      Lanza, Valeria; Milardi, Danilo; Di Natale, Giuseppe; Pappalardo, Giuseppe

      2018-02-12

      There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews have exhaustively described either the molecular or clinical aspects of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can also be effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) chelating molecules as potential drug candidates in neurodegeneration. Starting from the well-known harmful relationships existing between the dyshomeostasis and mis-management of metals and AD onset, we surveyed the experimental work reported in the literature, which deals with the repositioning of metal-chelating drugs in the field of neurodegenerative diseases. The reviewed papers were retrieved from common literature and their selection was limited to those describing the biomolecular aspects associated with neuroprotection. In particular, we emphasized the copper(II) coordination abilities of the selected drugs. Copper, together with zinc and iron, are known to play a key role in regulating neuronal functions. Changes in copper homeostasis are crucial for several neurodegenerative disorders. The studies included in this review may provide an overview on the current strategies aimed at repurposing copper (II) chelating drugs for the treatment of neurodegenerative disorders. Starting from the exemplary case of clioquinol repurposing, we discuss the challenge and the opportunities that repurposing of other metal-chelating drugs may provide (e.g. PBT-2, metformin and cyclodipeptides) in the treatment of neurodegenerative disease. In order to improve the success rate of drug repositioning, comprehensive studies on the molecular mechanism and therapeutic efficacy are still required. The present review upholds that drug repurposing makes significant advantages over drug discovery since

    20. Is aspirin still the drug of choice for management of patients with peripheral arterial disease?

      Science.gov (United States)

      Poredos, Pavel; Jezovnik, Mateja K

      2013-03-01

      Antiplatelet drugs represent one of the basic options for management of patients with different atherosclerotic diseases. Aspirin is the oldest and most often prescribed antiplatelet drug. The efficacy of aspirin depends on the clinical characteristics of the treated population and probably also on the type or location of atherosclerotic disease. It seems that it is most effective in coronary patients with clinically unstable disease, less effective in prevention of cerebrovascular incidents, and its efficacy is uncertain in peripheral artery disease (PAD) patients. One of the first meta-analyses (Antithrombotic Trialists' Collaboration - ATC) indicated that antiplatelet drugs also significantly reduce cardiovascular events in patients with PAD. However, only one third of the PAD patients included were treated with aspirin, while the rest received other anti-platelet drugs. The latest ATC meta-analysis of randomized control trials of aspirin therapy involving patients with diabetes and PAD demonstrated no benefit of aspirin in reducing cardiovascular events. Also in patients with preclinical PAD (pathological ankle brachial index) aspirin did not result in a significant reduction of vascular events. The new anti-platelet drugs prasugrel, ticagrelor and picotamide seem to be more effective than aspirin in PAD patients, particularly in diabetic patients with PAD. In conclusion, antiplatelet drugs are effective in prevention of cardiovascular events in different atherosclerotic diseases, including PAD. However, recent studies indicated that in PAD patients aspirin is less effective than in coronary artery disease. New anti-platelet drugs showed marginal superiority over aspirin without definite advantages. Aspirin thus remains the first line of antiplatelet drug for secondary prevention of cardiovascular events in PAD patients and clopidogrel as its effective alternative. Further, new studies on PAD patients are necessary to better define the role of anti

    1. Control of drug treatment of chronic coronary artery disease: possibilities of a regional registry

      Directory of Open Access Journals (Sweden)

      Rachkova S.A.

      2016-03-01

      Full Text Available The article describes the results of the Register of hypertension, coronary artery disease, chronic heart failure (Register of AH, CAD, HF in the Ivanovo region in 2015. The frequency of prescribing of the main groups of drugs in patients with coronary artery disease was estimated.

    2. Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease?

      DEFF Research Database (Denmark)

      Andersen, K; Launer, L J; Ott, A

      1995-01-01

      Based on reports that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk for Alzheimer's disease (AD), we studied the cross-sectional relation between NSAID use and the risk for AD in a population-based study of disease and disability in older people. After controlling...

    3. The clinical implication of drug dependency in children and adults with inflammatory bowel disease: a review

      DEFF Research Database (Denmark)

      Duricova, Dana; Pedersen, Natalia; Lenicek, Martin

      2011-01-01

      Drug dependency in adult and paediatric patients with inflammatory bowel disease (IBD) is described and the significance of this response pattern in clinical practice discussed in this review. Dependent patients maintain remission while on the treatment, but they relapse shortly after drug...... corticosteroid dependency. Infliximab dependency was described in 42-66% of children and 29% of adults with Crohn's disease. The risk of surgery 50 and 40 months after treatment start was 10% and 23% in infliximab dependent children and adults, respectively. Maintenance of infliximab in dependent patients...... was suggested to postpone if not avoid the need of surgery. Lastly, mesalazine dependency was identified in 23% of adults with Crohn's disease. These patients were characterized by mild disease course and lower surgical risk compared to non-responders to mesalazine (32 vs. 61%). Identification of drug...

    4. Review on potential phytocompounds in drug development for Parkinson disease: A pharmacoinformatic approach

      Directory of Open Access Journals (Sweden)

      S. Vijayakumar

      Full Text Available Parkinson's disease (PD is caused by human physiological function and is ranked as the second most common neurodegenerative disorder. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Currently, available pharmaceutical drugs provide only temporary relief of the disease. Phytocompounds have been identified as promising target of research in the quest for new pharmaceutical compounds as they can produce secondary metabolites with novel chemical structure. In this review the drug development of Parkinson disease has been analyzed using computational tools. Keywords: Parkinson disease, Phytocompounds, Computational methods, Drug development and design

    5. A network-based classification model for deriving novel drug-disease associations and assessing their molecular actions.

      Directory of Open Access Journals (Sweden)

      Min Oh

      Full Text Available The growing number and variety of genetic network datasets increases the feasibility of understanding how drugs and diseases are associated at the molecular level. Properly selected features of the network representations of existing drug-disease associations can be used to infer novel indications of existing drugs. To find new drug-disease associations, we generated an integrative genetic network using combinations of interactions, including protein-protein interactions and gene regulatory network datasets. Within this network, network adjacencies of drug-drug and disease-disease were quantified using a scored path between target sets of them. Furthermore, the common topological module of drugs or diseases was extracted, and thereby the distance between topological drug-module and disease (or disease-module and drug was quantified. These quantified scores were used as features for the prediction of novel drug-disease associations. Our classifiers using Random Forest, Multilayer Perceptron and C4.5 showed a high specificity and sensitivity (AUC score of 0.855, 0.828 and 0.797 respectively in predicting novel drug indications, and displayed a better performance than other methods with limited drug and disease properties. Our predictions and current clinical trials overlap significantly across the different phases of drug development. We also identified and visualized the topological modules of predicted drug indications for certain types of cancers, and for Alzheimer's disease. Within the network, those modules show potential pathways that illustrate the mechanisms of new drug indications, including propranolol as a potential anticancer agent and telmisartan as treatment for Alzheimer's disease.

    6. Drug-induced impulse control disorders in Parkinson's disease.

      Science.gov (United States)

      Reiff, J; Jost, W H

      2011-05-01

      Dopamine replacement treatment with excessive or aberrant dopamine receptor stimulation can cause behavioral disturbances in Parkinson's disease, comprising dopamine dysregulation syndrome, punding, and impulse control disorders. Common impulse control disorders are compulsive buying, pathological gambling, binge eating, hypersexuality, and compulsive reckless driving.

    7. Indigenous drugs in ischemic heart disease in patients with diabetes.

      Science.gov (United States)

      Dwivedi, Shridhar; Aggarwal, Amitesh

      2009-11-01

      India is currently facing the silent epidemic of ischemic heart disease, type 2 diabetes mellitus (T2DM), hypertension, and stroke. Both diabetes and ischemic heart disease appear in Indian people a decade earlier compared to whites. The recent evidence that certain medicinal plants possess hypoglycemic, lipid-lowering, and immunomodulating properties on account of their rich flavonoid and/or other glucose-lowering active constituents merits scientific scrutiny in this regard. The present communication aims to give a brief review of those plants that could be useful in T2DM associated with hypertension, ischemic heart disease, and/or dyslipidemia. Aegle marmelos (bael), Allium sativum (garlic), Curcuma domestica (turmeric), Eugenia jambolana (jamun), Murraya koenigii (curry leaves), Trigonella foenum graecum (fenugreek), and Terminalia arjuna (arjun) have been found to be useful in diabetes associated with ischemic heart disease. Their active biomolecules have been identified. They have also been demonstrated to be safe in long-term use. Further clinical research regarding their potency and efficacy vis-à-vis oral hypoglycemics needs to done.

    8. [Drug treatment of erection disorders in patients with cardiovascular disease

      NARCIS (Netherlands)

      Meuleman, E.J.H.; Kingma, J.H.

      2001-01-01

      Erectile dysfunction is a frequent condition in cardiovascular patients. Since the arrival of oral erection-supporting medication, patients want to know how safe sexual activity is in cardiovascular disease in general and during use of erection-supporting medication in particular. Sexual intercourse

    9. Drug Repositioning in Inflammatory Bowel Disease Based on Genetic Information

      NARCIS (Netherlands)

      Collij, Valerie; Festen, Eleonora A. M.; Alberts, Rudi; Weersma, Rinse K.

      2016-01-01

      Background:Currently, 200 genetic risk loci have been identified for inflammatory bowel disease (IBD). Although these findings have significantly advanced our insight into IBD biology, there has been little progress in translating this knowledge toward clinical practice, like more cost-efficient

    10. The effect of anticholinergic drugs on 123I-IMP SPECT in Parkinson's disease

      International Nuclear Information System (INIS)

      Mizuno, Tomoyuki; Nishiyama, Kazutoshi; Hitoshi, Seiji; Takeda, Koichi; Sakuta, Manabu

      1992-01-01

      Anticholinergic drugs may be responsible for mental deterioration in Parkinson's disease (PD). This study was thus performed to examine effects of anticholinergic drugs on the brain by using N-isopropyl-p-[I-123] iodoamphetamine SPECT. The purpose of the study was twofold: (I) to compare regional cerebral uptake of tracer during treatment with anticholinergic drugs and one month after the discontinuation of the drugs in 7 PD patients given them for 6 months or more; and (II) to compare tracer uptake in 11 PD patients administered anticholinergic drugs and 25 PD patients not administered them. Each 16 regions in the bilateral cerebral cortexes and each one region in the bilateral basal ganglia, thalamus, and cerebellum were assigned as regions of interest (ROI). The count ratio of each ROI in the cerebrum to ROI in the cerebellum was designated as regional cerebral uptake ratio (rCUR). A mean rCUR was lower during administration of anticholinergic drugs in all ROIs, except for two in Group I and one in Group II, than during the period not administered the drugs. The administration of anticholinergic drugs was sigificantly associated with decreased rCUR in 10 ROIs in Group I, and in 15 ROIs in Group II. The rCUR in the occipital, basal ganglia, and thalamus was independent of the administration of anticholinergic drugs. These results suggest that anticholinergic drugs may inhibit the cortical cholinergic system in PD patients. (N.K.)

    11. The effect of anticholinergic drugs on [sup 123]I-IMP SPECT in Parkinson's disease

      Energy Technology Data Exchange (ETDEWEB)

      Mizuno, Tomoyuki; Nishiyama, Kazutoshi; Hitoshi, Seiji; Takeda, Koichi; Sakuta, Manabu [Japan Red Cross Central Hospital, Tokyo (Japan)

      1992-04-01

      Anticholinergic drugs may be responsible for mental deterioration in Parkinson's disease (PD). This study was thus performed to examine effects of anticholinergic drugs on the brain by using N-isopropyl-p-[I-123] iodoamphetamine SPECT. The purpose of the study was twofold: (I) to compare regional cerebral uptake of tracer during treatment with anticholinergic drugs and one month after the discontinuation of the drugs in 7 PD patients given them for 6 months or more; and (II) to compare tracer uptake in 11 PD patients administered anticholinergic drugs and 25 PD patients not administered them. Each 16 regions in the bilateral cerebral cortexes and each one region in the bilateral basal ganglia, thalamus, and cerebellum were assigned as regions of interest (ROI). The count ratio of each ROI in the cerebrum to ROI in the cerebellum was designated as regional cerebral uptake ratio (rCUR). A mean rCUR was lower during administration of anticholinergic drugs in all ROIs, except for two in Group I and one in Group II, than during the period not administered the drugs. The administration of anticholinergic drugs was sigificantly associated with decreased rCUR in 10 ROIs in Group I, and in 15 ROIs in Group II. The rCUR in the occipital, basal ganglia, and thalamus was independent of the administration of anticholinergic drugs. These results suggest that anticholinergic drugs may inhibit the cortical cholinergic system in PD patients. (N.K.).

    12. Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity

      Science.gov (United States)

      Massart, Julie; Begriche, Karima; Moreau, Caroline; Fromenty, Bernard

      2017-01-01

      Background Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. Aim The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity. For this purpose, we performed a data-mining analysis using different queries including drug-induced liver injury (or DILI), drug-induced hepatotoxicity, fatty liver, nonalcoholic fatty liver disease (or NAFLD), steatosis and obesity. The main data from the collected articles are reported in this review and when available, some pathophysiological hypotheses are put forward. Relevance for patients Drugs that could pose a potential risk in obese patients include compounds belonging to different pharmacological classes such as acetaminophen, halothane, methotrexate, rosiglitazone, stavudine and tamoxifen. For some of these drugs, experimental investigations in obese rodents confirmed the clinical observations and unveiled different pathophysiological mechanisms which could explain why these pharmaceuticals are particularly hepatotoxic in obesity and NAFLD. Other drugs such as pentoxifylline, phenobarbital and omeprazole might also pose a risk but more investigations are required to determine whether this risk is significant or not. Because obese people often take several drugs for the treatment of different obesity-related diseases such as type 2 diabetes, hyperlipidemia and coronary heart disease, it is urgent to identify the main pharmaceuticals that can cause acute hepatitis on a fatty liver background or induce NAFLD worsening

    13. Nitric oxide-heat shock protein axis in menopausal hot flushes: neglected metabolic issues of chronic inflammatory diseases associated with deranged heat shock response.

      Science.gov (United States)

      Miragem, Antônio Azambuja; Homem de Bittencourt, Paulo Ivo

      2017-09-01

      Although some unequivocal underlying mechanisms of menopausal hot flushes have been demonstrated in animal models, the paucity of similar approaches in humans impedes further mechanistic outcomes. Human studies might show some as yet unexpected physiological mechanisms of metabolic adaptation that permeate the phase of decreased oestrogen levels in both symptomatic and asymptomatic women. This is particularly relevant because both the severity and time span of hot flushes are associated with increased risk of chronic inflammatory disease. On the other hand, oestrogen induces the expression of heat shock proteins of the 70 kDa family (HSP70), which are anti-inflammatory and cytoprotective protein chaperones, whose expression is modulated by different types of physiologically stressful situations, including heat stress and exercise. Therefore, lower HSP70 expression secondary to oestrogen deficiency increases cardiovascular risk and predisposes the patient to senescence-associated secretory phenotype (SASP) that culminates in chronic inflammatory diseases, such as obesities, type 2 diabetes, neuromuscular and neurodegenerative diseases. This review focuses on HSP70 and its accompanying heat shock response (HSR), which is an anti-inflammatory and antisenescent pathway whose intracellular triggering is also oestrogen-dependent via nitric oxide (NO) production. The main goal of the manuscript was to show that the vasomotor symptoms that accompany hot flushes may be a disguised clue for important neuroendocrine alterations linking oestrogen deficiency to the anti-inflammatory HSR. Results from our own group and recent evidence on hypothalamic control of central temperature guided a search on PubMed and Google Scholar websites. Oestrogen elicits rapid production of the vasodilatory gas NO, a powerful activator of HSP70 expression. Whence, part of the protective effects of oestrogen over cardiovascular and neuroendocrine systems is tied to its capacity of inducing the NO

    14. Current therapeutic molecules and targets in neurodegenerative diseases based on in silico drug design.

      Science.gov (United States)

      Sehgal, Sheikh Arslan; Hammad, Mirza A; Tahir, Rana Adnan; Akram, Hafiza Nisha; Ahmad, Faheem

      2018-03-15

      As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases. Review of literature published since 1997 against neurodegenerative diseases, utilizing as keywords: in silico, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis ALS, and Huntington's disease. Due to the costs associated with experimentation and current ethical law, performing experiments directly on living organisms has become much more difficult. In this scenario, in silico techniques have been successful and have become powerful tools in the search to cure disease. Researchers use the Computer Aided Drug Design pipeline which: 1) generates 3-dimensional structures of target proteins through homology modeling 2) achieves stabilization through molecular dynamics simulation, and 3) exploits molecular docking through large compound libraries. Next generation sequencing is continually producing enormous amounts of raw sequence data while neuroimaging is producing a multitude of raw image data. To solve such pressing problems, these new tools and algorithms are required. This review elaborates precise in silico tools and techniques for drug targets, active molecules, and molecular docking studies, together with future prospects and challenges concerning possible breakthroughs in Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, and Huntington's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

    15. Budget impact analysis of drugs for ultra-orphan non-oncological diseases in Europe.

      Science.gov (United States)

      Schlander, Michael; Adarkwah, Charles Christian; Gandjour, Afschin

      2015-02-01

      Ultra-orphan diseases (UODs) have been defined by a prevalence of less than 1 per 50,000 persons. However, little is known about budget impact of ultra-orphan drugs. For analysis, the budget impact analysis (BIA) had a time horizon of 10 years (2012-2021) and a pan-European payer's perspective, based on prevalence data for UODs for which patented drugs are available and/or for which drugs are in clinical development. A total of 18 drugs under patent protection or orphan drug designation for non-oncological UODs were identified. Furthermore, 29 ultra-orphan drugs for non-oncological diseases under development that have the potential of reaching the market by 2021 were found. Total budget impact over 10 years was estimated to be €15,660 and €4965 million for approved and pipeline ultra-orphan drugs, respectively (total: €20,625 million). The analysis does not support concerns regarding an uncontrolled growth in expenditures for drugs for UODs.

    16. Global issues in drug development for Alzheimer's disease.

      Science.gov (United States)

      Doody, Rachelle S; Cole, Patricia E; Miller, David S; Siemers, Eric; Black, Ronald; Feldman, Howard; Schindler, Rachel; Graham, Stephen; Heath, Theresa; Khachaturian, Ara S; Evans, Rebecca; Carrillo, Maria C

      2011-03-01

      The number of clinical trials for Alzheimer's disease conducted outside the United States in a broad array of countries is increasing. As the number of compounds ready for clinical testing increases, and as trials become longer and more complex, this trend is expected to grow. The cultural and ethical context of global clinical trials, potential benefits for those involved, and practical approaches to obstacles generated by these global trials were discussed at a meeting of the Alzheimer's Association Research Roundtable. Regulatory issues, including regional differences in study registration procedures, rules for collecting and reporting serious adverse events, requirements for national identity of study populations, and regulatory audits were also discussed by individuals who are knowledgeable about global clinical trials for Alzheimer's disease. Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

    17. Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease

      Directory of Open Access Journals (Sweden)

      Edward C. Lauterbach

      2013-11-01

      Full Text Available Psychotropics (antipsychotics, mood stabilizers, antidepressants, anxiolytics, etc. are commonly prescribed to treat Huntington’s disease (HD. In HD preclinical models, while no psychotropic has convincingly affected huntingtin gene, HD modifying gene, or huntingtin protein expression, psychotropic neuroprotective effects include upregulated huntingtin autophagy (lithium, histone acetylation (lithium, valproate, lamotrigine, miR-222 (lithium-plus-valproate, mitochondrial protection (haloperidol, trifluoperazine, imipramine, desipramine, nortriptyline, maprotiline, trazodone, sertraline, venlafaxine, melatonin, neurogenesis (lithium, valproate, fluoxetine, sertraline, and BDNF (lithium, valproate, sertraline and downregulated AP-1 DNA binding (lithium, p53 (lithium, huntingtin aggregation (antipsychotics, lithium, and apoptosis (trifluoperazine, loxapine, lithium, desipramine, nortriptyline, maprotiline, cyproheptadine, melatonin. In HD live mouse models, delayed disease onset (nortriptyline, melatonin, striatal preservation (haloperidol, tetrabenazine, lithium, sertraline, memory preservation (imipramine, trazodone, fluoxetine, sertraline, venlafaxine, motor improvement (tetrabenazine, lithium, valproate, imipramine, nortriptyline, trazodone, sertraline, venlafaxine, and extended survival (lithium, valproate, sertraline, melatonin have been documented. Upregulated CREB binding protein (CBP; valproate, dextromethorphan and downregulated histone deacetylase (HDAC; valproate await demonstration in HD models. Most preclinical findings await replication and their limitations are reviewed. The most promising findings involve replicated striatal neuroprotection and phenotypic disease modification in transgenic mice for tetrabenazine and for sertraline. Clinical data consist of an uncontrolled lithium case series (n = 3 suggesting non-progression and a primarily negative double-blind, placebo-controlled clinical trial of lamotrigine.

    18. FOOD NEGLECT AND INFANT DEVELOPMENT.

      Science.gov (United States)

      Helton, Jesse J; Cross, Theodore P; Vaughn, Michael G; Gochez-Kerr, Tatiana

      2018-03-01

      The impact of food insecurity on child development in the general U.S. population is well-established, yet little is known about the harm of food neglect relative to other types of maltreatment. Due to the harmful physiological impact of inadequate nutrients and the social impact of food-related stress, it was hypothesized that food neglect would be more likely to impair infant cognitive and language development than physical abuse, sexual abuse, and other forms of neglect. Families of infants (N = 1,951) investigated by Child Protective Services were studied using the second cohort of the National Survey of Child and Adolescent Well-Being (NSCAW II; NSCAW Research Group, 2002). Results from multivariable logistic regression models that controlled for likely confounding variables showed that the odds of impairment in cognition and language were significantly greater when food neglect was the most serious form of maltreatment. Considering that both food insecurity and child neglect are associated with poverty and parental mental health problems, it will be important for child welfare and mental health professionals to work collaboratively to better the health of these vulnerable children. © 2018 Michigan Association for Infant Mental Health.

    19. Harnessing motivation to alleviate neglect

      Directory of Open Access Journals (Sweden)

      Charlotte eRussell

      2013-06-01

      Full Text Available The syndrome of spatial neglect results from the combination of a number of deficits in attention, with patients demonstrating both spatially lateralised and non-lateralised impairments. Previous reports have hinted that there may be a motivational component to neglect and that modulating this might alleviate some of the debilitating symptoms. Additionally, recent work on the effects of reward on attention in healthy participants has revealed improvements across a number of paradigms. As the primary deficit in neglect has been associated with attention, this evidence for reward’s effects is potentially important. However, until very recently there have been few empirical studies addressing this potential therapeutic avenue. Here we review the growing body of evidence that attentional impairments in neglect can be reduced by motivation, for example in the form of preferred music or anticipated monetary reward, and discuss the implications of this for treatments for these patients. Crucially these effects of positive motivation are not observed in all patients with neglect, suggesting that the consequences of motivation may relate to individual lesion anatomy. Given the key role of dopaminergic systems in motivational processes, we suggest that motivational stimulation might act as a surrogate for dopaminergic stimulation. In addition, we consider the relationship between clinical post stroke apathy and lack of response to motivation.

    20. [Affordability and availability of drugs for treatment of chronic diseases in the public health care system].

      Science.gov (United States)

      Helfer, Ana Paula; Camargo, Aline Lins; Tavares, Noemia Urruth Leão; Kanavos, Panos; Bertoldi, Andréa Dâmaso

      2012-03-01

      To assess the affordability by workers of drugs used for treatment of chronic diseases, as well as the availability of the reference, similar, or generic forms of these drugs in the public health care system. We employed the methodology recommended by the World Health Organization (WHO) and Health Action International (HAI) for the standardized collection of information on selling prices in the private sector and availability in the public health care system of drugs in six cities in the state of Rio Grande do Sul, Brazil. Data were collected from November 2008 to January 2009. Affordability was estimated as the number of salary days required for a worker receiving the national minimum wage to buy, in a private pharmacy, the amount of medication required for one month of treatment. Availability was assessed by the presence of these drugs in public health care system facilities. Twenty-two public facilities and 30 private pharmacies were studied. Of 21 drugs used for the treatment of seven chronic disorders, only nine were available free of charge in the six cities. Mean availability ranged from 83.3% (São Leopoldo) to 97.6% (Caxias do Sul). Affordability ranged from 0.4 to 10.5 salary days for reference drugs, 0.2 to 8.4 salary days for similar drugs, and 0.3 to 3.8 salary days for generic drugs. The overall availability of the drugs surveyed was higher than the 80% recommended by WHO. However, some treatments were not available, or had limited availability in the public system. Concerning affordability, the number of salary days required to buy these drugs may affect the continuation of drug treatments for chronic diseases.

    1. Reward Prediction Errors in Drug Addiction and Parkinson's Disease: from Neurophysiology to Neuroimaging.

      Science.gov (United States)

      García-García, Isabel; Zeighami, Yashar; Dagher, Alain

      2017-06-01

      Surprises are important sources of learning. Cognitive scientists often refer to surprises as "reward prediction errors," a parameter that captures discrepancies between expectations and actual outcomes. Here, we integrate neurophysiological and functional magnetic resonance imaging (fMRI) results addressing the processing of reward prediction errors and how they might be altered in drug addiction and Parkinson's disease. By increasing phasic dopamine responses, drugs might accentuate prediction error signals, causing increases in fMRI activity in mesolimbic areas in response to drugs. Chronic substance dependence, by contrast, has been linked with compromised dopaminergic function, which might be associated with blunted fMRI responses to pleasant non-drug stimuli in mesocorticolimbic areas. In Parkinson's disease, dopamine replacement therapies seem to induce impairments in learning from negative outcomes. The present review provides a holistic overview of reward prediction errors across different pathologies and might inform future clinical strategies targeting impulsive/compulsive disorders.

    2. Creating New Economic Incentives for Repurposing Generic Drugs for Unsolved Diseases Using Social Finance.

      Science.gov (United States)

      Bloom, Bruce E

      2015-12-01

      Repurposing research improves patient lives by taking drugs approved for one disease and clinically testing them to create a treatment for a different disease. Repurposing drugs that are generic, inexpensive, and widely available and that can be taken in their current dosage and formulation in the new indication provide a quick, affordable, and effective way to create "new" treatments. However, generic drug repurposing often provides no profit potential, and so there is no economic incentive for industry to pursue this, and philanthropy and government funds are often insufficient. One way to create new economic incentive for the repurposing of generic drugs is through social finance. This perspective describes how social finance can create a new economic incentive by using a social impact bond, or similar financial structure, to repay for-profit investors who fund the repurposing research from the proceeds of healthcare cost reductions generated when these affordable, effective, and widely available repurposed therapies improve healthcare outcomes.

    3. Neglected locked vertical patellar dislocation

      Science.gov (United States)

      Gupta, Rakesh Kumar; Gupta, Vinay; Sangwan, Sukhbir Singh; Kamboj, Pradeep

      2012-01-01

      Patellar dislocations occurring about the vertical and horizontal axis are rare and irreducible. The neglected patellar dislocation is still rarer. We describe the clinical presentation and management of a case of neglected vertical patellar dislocation in a 6 year-old boy who sustained an external rotational strain with a laterally directed force to his knee. Initially the diagnosis was missed and 2 months later open reduction was done. The increased tension generated by the rotation of the lateral extensor retinaculum kept the patella locked in the lateral gutter even with the knee in full extension. Traumatic patellar dislocation with rotation around a vertical axis has been described earlier, but no such neglected case has been reported to the best of our knowledge. PMID:23162154

    4. Neglected locked vertical patellar dislocation

      Directory of Open Access Journals (Sweden)

      Rakesh Kumar Gupta

      2012-01-01

      Full Text Available Patellar dislocations occurring about the vertical and horizontal axis are rare and irreducible. The neglected patellar dislocation is still rarer. We describe the clinical presentation and management of a case of neglected vertical patellar dislocation in a 6 year-old boy who sustained an external rotational strain with a laterally directed force to his knee. Initially the diagnosis was missed and 2 months later open reduction was done. The increased tension generated by the rotation of the lateral extensor retinaculum kept the patella locked in the lateral gutter even with the knee in full extension. Traumatic patellar dislocation with rotation around a vertical axis has been described earlier, but no such neglected case has been reported to the best of our knowledge.

    5. Neglected Tropical Diseases: Treatment of Dermatological Manifestation of Filariasis with Combination Regimen of Albendazole, Ivermectin, and Loratadine: A Case Report from a Suburban Community in Nigeria

      Directory of Open Access Journals (Sweden)

      Osede Ignis Iribhogbe

      2017-06-01

      Full Text Available Threadlike filarial nematodes have been identified as the causative agent of filariasis. Cutaneous filariasis is caused primarily by Loa loa, Onchocerca volvulus, and Mansonella streptocerca. These parasites occupy the subcutaneous layer of the skin. However, other filarial parasites are usually associated with varying degrees of dermatological manifestations. In the present discourse, two cases of cutaneous filariasis were diagnosed in two female patients (21 and 40 years old, respectively in Remitch Clinic and Maternity located in a nonriverine community in Ekpoma, Edo State, Nigeria. In this report, patients with body mass index (BMI of 18.97 and 23.45 kg/m2, respectively, presented on two different occasions at least 6 months apart with hyperpigmented skin lesions in the upper and lower limbs, respectively. There was associated intense pruritus with no evidence of lymphadenopathy and lymphoedema. Following laboratory confirmation of filariasis, the patients were placed on a single oral dose combination of albendazole (400 mg + ivermectin (200 mcg/kg, while oral doses of loratadine 10 mg were administered daily for 5 days. Patients were carefully followed up for 6 weeks during which recession of the lesion and untoward reactions were monitored. It was observed that within 6 weeks of treatment, there was a dramatic recession of skin lesion. Adverse effect reported from use of the combination was mild. This case report revealed that cutaneous filariasis is not an uncommon presentation of filariasis infestation in Nigeria. The report also validates the safety and efficacy of the combination in the management of cutaneous manifestation of the disease.

    6. Drug repurposing by integrated literature mining and drug–gene–disease triangulation

      DEFF Research Database (Denmark)

      Sun, Peng; Guo, Jiong; Winnenburg, Rainer

      2017-01-01

      recent developments in computational drug repositioning and introduce the utilized data sources. Afterwards, we introduce a new data fusion model based on n-cluster editing as a novel multi-source triangulation strategy, which was further combined with semantic literature mining. Our evaluation suggests...... that utilizing drug–gene–disease triangulation coupled to sophisticated text analysis is a robust approach for identifying new drug candidates for repurposing....

    7. The current state of GPCR-based drug discovery to treat metabolic disease.

      Science.gov (United States)

      Sloop, Kyle W; Emmerson, Paul J; Statnick, Michael A; Willard, Francis S

      2018-02-02

      One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of GPCRs. This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer and Type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents. This report reviews the current landscape of GPCR drug discovery with emphasis on efforts aimed at developing new molecules for treating T2DM and obesity. We analyse historical efforts to generate GPCR-based drugs to treat metabolic disease in terms of causal factors leading to success and failure in this endeavour. © 2018 The British Pharmacological Society.

    8. Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.

      Science.gov (United States)

      Zha, Weibin

      2018-04-01

      The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins) have been identified to be substrates and inhibitors of the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients) are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product-CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product-CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product-CV drug interactions and help public and physicians understand these type of interactions. Copyright © 2017. Published by Elsevier B.V.

    9. Spectrophotometric determination of dopaminergic drugs used for Parkinson's disease, cabergoline and ropinirole, in pharmaceutical preparations.

      Science.gov (United States)

      Onal, Armağan; Cağlar, Sena

      2007-04-01

      Simple and reproducible spectrophotometric methods have been developed for determination of dopaminergic drugs used for Parkinson's disease, cabergoline (CAB) and ropinirole hydrochloride (ROP), in pharmaceutical preparations. The methods are based on the reactions between the studied drug substances and ion-pair agents [methyl orange (MO), bromocresol green (BCG) and bromophenol blue (BPB)] producing yellow colored ion-pair complexes in acidic buffers, after extracting in dichloromethane, which are spectrophotometrically determined at the appropriate wavelength of ion-pair complexes. Beer's law was obeyed within the concentration range from 1.0 to 35 microg ml(-1). The developed methods were applied successfully for the determination of these drugs in tablets.

    10. Tobacco, illicit drugs use and risk of cardiovascular disease in patients living with HIV.

      Science.gov (United States)

      Raposeiras-Roubín, Sergio; Abu-Assi, Emad; Iñiguez-Romo, Andrés

      2017-11-01

      There is a strong link between HIV, smoking and illicit drugs. This association could be clinically relevant as it may potentiate the risk of cardiovascular diseases (CVD). The purpose of this review is to bring readers up to date on issues concerning the cardiovascular risk associated with tobacco and illicit drugs in patients living with HIV (PLHIV), examining the studies related to this topic published in the last year. There is a strong association between smoking and atherosclerotic disease in PLHIV, reducing life expectancy secondary to CVD by up to 6 years. Illicit drugs were associated with increased risk of atherosclerotic problems but to a lesser extent than smoking. A significant association of drugs such as cocaine with subclinical coronary atherosclerosis been demonstrated. The relation of marijuana, heroin and amphetamines with atherosclerosis generates more controversy. However, those drugs are associated with cardiovascular morbidity, independently of smoking and other traditional risk factors. Tobacco and illicit drugs are linked to CVD in HIV patients. This leads to the need to create special programs to address the addiction to smoking and illicit drugs, in order to mitigate their consequences and reduce cardiovascular risk.

    11. ANALYSIS OF DISEASE MODIFYING DRUGS ADMINISTRATION FREGUENCY AND CAUSES OF THEIR WITHDRAWAL IN RHEUMATOID ARTHRITIS

      Directory of Open Access Journals (Sweden)

      E V Pavlova

      2000-01-01

      Full Text Available Aim of studdy: To assess the frequency of practical application of different basic drugs in rheumatoid arthritis (RA. Material and methods: Tlxe study was conducted basing of questionner of pts and analysis of ycases by randomized sampling among 103 consequent pts (M:F= 13:90 with reliable RA (ARA, 1987 in rheumatologic department of Clinical Hospital Nol in Ekaterinburg. 74% of pts under study demonstrated systemic manifestations: anemia (in 47 pts, lymphadenopathy (in 34, rheumatoid nodules (in 15, Sjogren s syndrome (in 4, nephropathy (in 4, vascular disturbances including Raynaud s phenomenon, capillarites (by 1 pt. Results: In the course of disease basic therapy was prescribed to 88 out of103 (85.4% pts and one and the same patient could take different basic drugs. Aminochinoline drugs prevailed, after them more frequent were immunodepressants and gold preparations. More rarely pts had sulfasalazin, cuprenil and wobenzym. In general, in 133 out of 184 cases of prescribing basic drugs they were canceled. The reason for cancellation were: prevalently absence of the drug in the pharmaceutical stores (in 48 cases averagely in 8 months of taking the drug; then they insufficient efficacy (44 cases averagely in 1.3 year. In 18 cases pts themselves stopped treatment averagely in 3.5 months of drug taking. Conclusion: In the majority of cases of basic drugs cancellation in RA the cause is their absence in sail especially on free of charge prescription. Cases ofself-cancellation of the drug demonstrate the need of explaining to pts the necessity> of long-term taking disease-modifying drugs.

    12. Commentary: improving the health of neglected populations in Latin America

      Directory of Open Access Journals (Sweden)

      Jones Danielle

      2007-01-01

      Full Text Available Abstract Neglected diseases encompass a group of pathologies that disproportionally affect resource-constrained areas of the world. In tropical and subtropical areas in Latin America, the vicious cycle of poverty, disease and underdevelopment is widespread. The burden of disease associated to neglected diseases in this region is mainly expressed through diseases such as malaria, dengue, intestinal parasitic infections, Chagas' disease, and many others. These maladies have burdened Latin America throughout centuries and have directly influenced their ability to develop and become competitive societies in the current climate of globalization. Therefore, the need for a new paradigm that integrates various public health policies, programs, and a strategy with the collaboration of all responsible sectors is long overdue. In this regard, innovative approaches are required to ensure the availability of low-cost, simple, sustainable, and locally acceptable strategies to improve the health of neglected populations to prevent, control, and potentially eliminate neglected diseases. Improving the health of these forgotten populations will place them in an environment more conducive to development and will likely contribute significantly to the achievement of the Millennium Development Goals in this area of the globe.

    13. World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients.

      Science.gov (United States)

      Kontoghiorghe, Christina N; Andreou, Nicholas; Constantinou, Katerina; Kontoghiorghes, George J

      2014-09-26

      According to global annual estimates hunger/malnutrition is the major cause of death (36 of 62 million). Cardiovascular diseases and cancer (5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis (10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countries was 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone (L1) for thalassaemia up to the stage of multicentre clinical trials. The

    14. World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients

      Science.gov (United States)

      Kontoghiorghe, Christina N; Andreou, Nicholas; Constantinou, Katerina; Kontoghiorghes, George J

      2014-01-01

      According to global annual estimates hunger/malnutrition is the major cause of death (36 of 62 million). Cardiovascular diseases and cancer (5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis (10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countries was 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone (L1) for thalassaemia up to the stage of multicentre clinical trials. The

    15. Lessons Learnt From the Implementation of Mass Drug ...

      African Journals Online (AJOL)

      schistosomiasis by 2020 taking advantage of availability. 14 of funding and donated drugs. Zambia is endemic for four of the global Preventive. Chemotherapy Neglected Tropical Diseases targeted for elimination and control, namely schistosomiasis, trachoma, lymphatic filariasis (LF) and soil transmitted helminths (STH).

    16. Remission of Grave's disease after oral anti-thyroid drug treatment.

      Science.gov (United States)

      Ishtiaq, Osama; Waseem, Sabiha; Haque, M Naeemul; Islam, Najmul; Jabbar, Abdul

      2009-11-01

      To evaluate remission rate of anti-thyroid drug treatment in patients with Grave's disease, and to study the factors associated with remission. A cross sectional study. The Endocrine Department of the Aga Khan University Hospital, Karachi from 1999 to 2000. Seventy four patients of Grave's disease were recruited who were prescribed medical treatment. Grave's disease was diagnosed in the presence of clinical and biochemical hyperthyroidism along with anti-microsomal (AMA) and anti-thyroglobulin antibodies (ATA) and thyroid scan. These patients were prescribed oral anti-thyroid drugs using titration regime and followed at 3, 6, 12 and 18 months. Patients were categorized into two groups: "remission group" and "treatment failure group" and results were compared using a chi-square test, t-test and logistic regression model with significance at p disease on initial presentation.

    17. Drugs meeting the molecular basis of diabetic kidney disease: bridging from molecular mechanism to personalized medicine.

      Science.gov (United States)

      Lambers Heerspink, Hiddo J; Oberbauer, Rainer; Perco, Paul; Heinzel, Andreas; Heinze, Georg; Mayer, Gert; Mayer, Bernd

      2015-08-01

      Diabetic kidney disease (DKD) is a complex, multifactorial disease and is associated with a high risk of renal and cardiovascular morbidity and mortality. Clinical practice guidelines for diabetes recommend essentially identical treatments for all patients without taking into account how the individual responds to the instituted therapy. Yet, individuals vary widely in how they respond to medications and therefore optimal therapy differs between individuals. Understanding the underlying molecular mechanisms of variability in drug response will help tailor optimal therapy. Polymorphisms in genes related to drug pharmacokinetics have been used to explore mechanisms of response variability in DKD, but with limited success. The complex interaction between genetic make-up and environmental factors on the abundance of proteins and metabolites renders pharmacogenomics alone insufficient to fully capture response variability. A complementary approach is to attribute drug response variability to individual variability in underlying molecular mechanisms involved in the progression of disease. The interplay of different processes (e.g. inflammation, fibrosis, angiogenesis, oxidative stress) appears to drive disease progression, but the individual contribution of each process varies. Drugs at the other hand address specific targets and thereby interfere in certain disease-associated processes. At this level, biomarkers may help to gain insight into which specific pathophysiological processes are involved in an individual followed by a rational assessment whether a specific drug's mode of action indeed targets the relevant process at hand. This article describes the conceptual background and data-driven workflow developed by the SysKid consortium aimed at improving characterization of the molecular mechanisms underlying DKD at the interference of the molecular impact of individual drugs in order to tailor optimal therapy to individual patients. © The Author 2015. Published by

    18. Disease and drug-induced arrhythmias : the example of obstructive pulmonary disease

      NARCIS (Netherlands)

      Warnier, M.J.

      2014-01-01

      Notwithstanding the clinical importance of cardiac arrhythmias, relevant information about the background risk and the exact underlying mechanisms of cardiac arrhythmias in patients with obstructive pulmonary disease (asthma and chronic obstructive pulmonary disease [COPD]) is still lacking. The

    19. Association between falls in elderly women and chronic diseases and drug use: cross sectional study

      OpenAIRE

      Lawlor, Debbie A; Patel, Rita; Ebrahim, Shah

      2003-01-01

      OBJECTIVE: To assess the associations between having had a fall and chronic diseases and drug use in elderly women. DESIGN: Cross sectional survey, using data from the British women's heart and health study. SETTING: General practices in 23 towns in Great Britain. PARTICIPANTS: 4050 women aged 60-79 years. MAIN OUTCOME MEASURE: Whether women had had falls in the previous 12 months. RESULTS: The prevalence of falling increased with increasing numbers of simultaneously occurring chronic disease...

    20. Neglected zoonotic helminths: Hymenolepis nana, Echinococcus canadensis and Ancylostoma ceylanicum.

      Science.gov (United States)

      Thompson, R C A

      2015-05-01

      The majority of helminth parasites that are considered by WHO to be the cause of 'neglected diseases' are zoonotic. In terms of their impact on human health, the role of animal reservoirs and polyparasitism are both emerging issues in understanding the epidemiology of a number of these zoonoses. As such, Hymenolepis (Rodentolepis) nana, Echinococcus canadensis and Ancylostoma ceylanicum all qualify for consideration. They have been neglected and there is increasing evidence that all three parasite infections deserve more attention in terms of their impact on public health as well as their control. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

    1. Colchicine in Pericardial Disease: from the Underlying Biology and Clinical Benefits to the Drug-Drug Interactions in Cardiovascular Medicine.

      Science.gov (United States)

      Schenone, Aldo L; Menon, Venu

      2018-06-14

      This is an in-depth review on the mechanism of action, clinical utility, and drug-drug interactions of colchicine in the management of pericardial disease. Recent evidence about therapeutic targets on pericarditis has demonstrated that NALP3 inflammasome blockade is the cornerstone in the clinical benefits of colchicine. Such benefits extend from acute and recurrent pericarditis to transient constriction and post-pericardiotomy syndrome. Despite the increased utilization of colchicine in cardiovascular medicine, safety concerns remains unsolved regarding the long-term use of colchicine in the cardiac patient. Moreover, recent evidence has demonstrated that numerous cardiovascular medications, ranging from antihypertensive medication to antiarrhythmics, are known to interact with the CYP3A4 and/or P-gp system increasing the toxicity potential of colchicine. The use of adjunctive colchicine in the management of inflammatory pericardial diseases is standard of care in current practice. It is advised that a careful medication reconciliation with emphasis on pharmacokinetic is completed before prescribing colchicine in order to avoid harmful interaction by finding an alternative regimen or adjusting colchicine dosing.

    2. Mast Cell Stabilizers as Host Modulatory Drugs to Prevent and Control Periodontal Disease

      Directory of Open Access Journals (Sweden)

      Dhoom Singh Mehta

      2011-01-01

      Full Text Available Introduction: Mast cells are among the first cells to get in-volved in periodontal inflammation. Their numbers have been shown to be in-creased in cases of gingivitis and periodontal disease. The hypothesis: Since mast cell stabilizers like sodium cromogly-cate (SCG and nedocromil sodium (NS have been used in the prophylaxis of bronchial asthma without any significant adverse effects and also the fact that drugs like SCG show significant anti-inflammatory activities, it would be logical to use mast cell stabilizers as host modulating drugs for the treatment and prevention of peri-odontal disease. Evaluation of the hypothesis: Safety and efficacy of both SCG and NS are well documented. So, it will be systemically safe to use in humans. However, oral administration SCG or delivery of the drug by means local irrigation will not be very useful because SCG may not be secreted in the gingival crevicular fluid (GCF(as in the case of oral administraion or the drug may get washed out from periodontal pocket due to the constant flow of GCF(as in the case of irrigation. A local or targeted drug delivery of mast cell stabilizers can be used in patients with periodontal disease. Role of mast cells in periodontal disease has been dealt in-depth in many studies and articles. However, limited amount of research has been done on using mast cell stabilizers in the prevention and control of periodontal diseases. More studies are needed to study the efficacy and effective-ness of mast cell stabilizers as an adjunct to phase I therapy in the control of periodontal disease.

    3. Nanotechnology-based drug delivery systems for Alzheimer's disease management: Technical, industrial, and clinical challenges.

      Science.gov (United States)

      Wen, Ming Ming; El-Salamouni, Noha S; El-Refaie, Wessam M; Hazzah, Heba A; Ali, Mai M; Tosi, Giovanni; Farid, Ragwa M; Blanco-Prieto, Maria J; Billa, Nashiru; Hanafy, Amira S

      2017-01-10

      Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes. Despite extensive research, literature screening revealed that clinical activities involving NTDDS application in research for AD are lagging compared to NTDDS for other diseases such as cancers. The industrial perspectives, processability, and cost/benefit ratio of using NTDDS for AD treatment are usually overlooked. Moreover, active and passive immunization against AD are by far the mostly studied alternative AD therapies because conventional oral drug therapy is not yielding satisfactorily results. NTDDS of approved drugs appear promising to transform this research from 'paper to clinic' and raise hope for AD sufferers and their caretakers. This review summarizes the recent studies conducted on NTDDS for AD treatment, with a primary focus on the industrial perspectives and processability. Additionally, it highlights the ongoing clinical trials for AD management. Copyright © 2016 Elsevier B.V. All rights reserved.

    4. Drug-induced diseases (DIDs: An experience of a tertiary care teaching hospital from India

      Directory of Open Access Journals (Sweden)

      Vishal R Tandon

      2015-01-01

      Full Text Available Background & objectives: Drug-induced diseases (DIDs are well known but least studied. Data on DIDs from India are not available. Hence, this retrospective cross-sectional study was undertaken using suspected adverse drug reaction (ADR data collected form Pharmacovigilance Programme of India (PvPI to evaluate profile of DIDs over two years, in a tertiary care teaching hospital from north India. Methods: The suspected ADRs in the form of DID were evaluated for drug and disease related variables and were classified in terms of causality. Results: DID rate was 38.80 per cent. Mean duration of developing DIDs was 26.05 ± 9.6 days; 25.16 per cent had more than one co-morbid condition. Geriatric population (53.99% accounted for maximum DIDs followed by adult (37.79% and paediatric (8.21%. Maximum events were probable (93.98% followed by possible (6.04%. All DIDs required intervention. Gastritis (7.43%, diarrhoea (5.92%, anaemia (4.79%, hypotension (2.77%, hepatic dysfunction (2.69%, hypertension (1.51%, myalgia (1.05%, and renal dysfunction (1.01% were some of the DIDs. Anti-tubercular treatment (ATT, anti- retroviral treatment (ART, ceftriaxone injection, steroids, non-steroidal anti-inflammatory drugs, antimicrobials and anticancer drugs were found as commonly offending drugs. Interpretation & conclusions: Our findings show that DIDs are a significant health problem in our country, which need more attention.

    5. Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease.

      Science.gov (United States)

      Baek, Jong-Suep; Choo, Chee Chong; Qian, Cheng; Tan, Nguan Soon; Shen, Zexiang; Loo, Say Chye Joachim

      2016-07-01

      Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double-emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

    6. Nanotechnology in dentistry: drug delivery systems for the control of biofilm-dependent oral diseases.

      Science.gov (United States)

      de Sousa, Francisco Fabio Oliveira; Ferraz, Camila; Rodrigues, Lidiany K Arla de Azevedo; Nojosa, Jacqueline de Santiago; Yamauti, Monica

      2014-01-01

      Dental disorders, such as caries, periodontal and endodontic diseases are major public health issues worldwide. In common, they are biofilm-dependent oral diseases, and the specific conditions of oral cavity may develop infectious foci that could affect other physiological systems. Efforts have been made to develop new treatment routes for the treatment of oral diseases, and therefore, for the prevention of some systemic illnesses. New drugs and materials have been challenged to prevent and treat these conditions, especially by means of bacteria elimination. "Recent progresses in understanding the etiology, epidemiology and microbiology of the microbial flora in those circumstances have given insight and motivated the innovation on new therapeutic approaches for the management of the oral diseases progression". Some of the greatest advances in the medical field have been based in nanosized systems, ranging from the drug release with designed nanoparticles to tissue scaffolds based on nanotechnology. These systems offer new possibilities for specific and efficient therapies, been assayed successfully in preventive/curative therapies to the oral cavity, opening new challenges and opportunities to overcome common diseases based on bacterial biofilm development. The aim of this review is to summarize the recent nanotechnological developments in the drug delivery field related to the prevention and treatment of the major biofilm-dependent oral diseases and to identify those systems, which may have higher potential for clinical use.

    7. The control of neglected zoonotic diseases

      DEFF Research Database (Denmark)

      Abela-Ridder, Bernadette; Welburn, Sue; Johansen, Maria Vang

      for Animal Health and WHO tripartite and financially supported by members of the broader international community including the Bill & Melinda Gates Foundation, the UK Department for International Development, the European Union, the International Development Research Centre and the CGIAR. WHO’s 2012 Roadmap...... the momentum generated by the NZD community over the past decade, urging the more than 100 participants – including representatives from national governments, international organizations, academia, foundations, the private sector and NGOs – to exert their influence and focus on operations, especially...... in the control of some NZDs, both at national and local levels from across three continents, were provided by many countries....

    8. Hemolytic Disease of the Fetus and Newborn due to Intravenous Drug Use.

      Science.gov (United States)

      Markham, Kara B; Scrape, Scott R; Prasad, Mona; Rossi, Karen Q; O'Shaughnessy, Richard W

      2016-03-01

      Objectives The objective is to present a pregnancy complication associated with intravenous drug use, namely, that of red blood cell alloimmunization and hemolytic disease of the fetus and newborn. Methods An observational case series is presented including women with red blood cell alloimmunization most likely secondary to intravenous drug abuse Results Five pregnancies were identified that were complicated by red blood cell alloimmunization and significant hemolytic disease of the fetus and newborn, necessitating intrauterine transfusion, an indicated preterm birth, or neonatal therapy. Conclusions As opioid abuse continues to increase in the United States, clinicians should be aware of the potential for alloimmunization to red blood cell antibodies as yet another negative outcome from intravenous drug abuse.

    9. Application of Several Multimedia Approaches to the Teaching of CNS Pharmacology: Parkinson's Disease and Antiparkinsonism Drugs.

      Science.gov (United States)

      Faulkner, Thomas P.; Sprague, Jon E.

      1996-01-01

      A multimedia approach to drug therapy for Parkinson's Disease, part of a pharmacy school central nervous system course, integrated use of lecture, textbook, video/graphic technology, the movie "Awakenings," Internet and World Wide Web, and an interactive animated movie. A followup questionnaire found generally positive student attitudes…

    10. Proposal for a new nomenclature of disease-modifying antirheumatic drugs

      NARCIS (Netherlands)

      Smolen, Josef S.; van der Heijde, Desiree; Machold, Klaus P.; Aletaha, Daniel; Landewe, Robert

      2014-01-01

      In light of the recent emergence of new therapeutics for rheumatoid arthritis, such as kinase inhibitors and biosimilars, a new nomenclature for disease-modifying antirheumatic drugs (DMARDs), which are currently often classified as synthetic (or chemical) DMARDs (sDMARDS) and biological DMARDs

    11. Drug targeting systems for inflammatory disease: one for all, all for one

      NARCIS (Netherlands)

      Crielaard, B.J.; Lammers, Twan Gerardus Gertudis Maria; Schiffelers, R.M.; Storm, Gerrit

      2012-01-01

      Abstract In various systemic disorders, structural changes in the microenvironment of diseased tissues enable both passive and active targeting of therapeutic agents to these tissues. This has led to a number of targeting approaches that enhance the accumulation of drugs in the target tissues,

    12. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

      NARCIS (Netherlands)

      Mocroft, Amanda; Kirk, Ole; Reiss, Peter; de Wit, Stephane; Sedlacek, Dalibor; Beniowski, Marek; Gatell, Jose; Phillips, Andrew N.; Ledergerber, Bruno; Lundgren, Jens D.; Losso, M.; Elias, C.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Suetnov, O.; Clumeck, N.; Poll, B.; Colebunders, R.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Rozsypal, H.; Sedlacek, D.; Nielsen, J.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A.-B. E.; Skinhøj, P.; Pedersen, C.; Oestergaard, L.; Zilmer, K.; Smidt, Jelena; Ristola, M.; Katlama, C.; Viard, J.-P.; Girard, P.-M.; Livrozet, J. M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Rockstroh, J.

      2010-01-01

      Objectives: Chronic kidney disease (CKD) in HIV-positive persons might be caused by both HIV and traditional or non-HIV-related factors. Our objective was to investigate long-term exposure to specific antiretroviral drugs and CKD. Design: A cohort study including 6843 HIV-positive persons with at

    13. Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

      NARCIS (Netherlands)

      Z. Zelinkova (Zuzana); E. Bultman (Evelien); L. Vogelaar (Lauran); C. Bouziane (Cheima); E.J. Kuipers (Ernst); C.J. van der Woude (Janneke)

      2012-01-01

      textabstractAIM: To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients. METHODS: All IBD patients attending the IBD outpatient clinic of a referral hospital were identifed through the electronic diagnosis

    14. Patients’ satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis

      Directory of Open Access Journals (Sweden)

      Caroline Vieira Spessotto

      2016-08-01

      Full Text Available ABSTRACT Objective The treatment of multiple sclerosis (MS with disease-modifying-drugs (DMDs is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients’ satisfaction with the treatment must be taken into consideration. Methods Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. Results One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability. Conclusion Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD.

    15. Bioethics of intervention and the case of drugs Bevacizumab and Ranibizumab for retinal diseases

      Directory of Open Access Journals (Sweden)

      Flávio R. L. Paranhos

      2016-10-01

      Full Text Available From the year 2000, on a class of biological drugs, the anti-VEGF proved to be quite effective in the treatment of retinal diseases, which have in its pathophysiological mechanism an important vascular proliferation component that can lead to blindness. Two of these drugs, bevacizumab and ranibizumab, are quite similar and have the same efficacy and safety. They were developed by the same laboratory and are commercialized by two major pharmaceutical companies through an agreement made between them. However, there is a big difference in the price of the drugs. The aim of this article is to present the Bioethics of intervention as grounds for choosing the cheaper drug, even if forced to do so by regulatory entities.

    16. MANAGEMENT OF ENDOCRINE DISEASE: Arguments for the prolonged use of antithyroid drugs in children with Graves' disease.

      Science.gov (United States)

      Léger, Juliane; Carel, Jean-Claude

      2017-08-01

      Graves' disease is an autoimmune disorder. It is the leading cause of hyperthyroidism, but is rare in children. Patients are initially managed with antithyroid drugs (ATDs), such as methimazole/carbimazole. A major disadvantage of treatment with ATD is the high risk of relapse, exceeding 70% of children treated for duration of 2 years, and the potential major side effects of the drug reported in exceptional cases. The major advantage of ATD treatment is that normal homeostasis of the hypothalamus-pituitary-thyroid axis may be restored, with periods of drug treatment followed by freedom from medical intervention achieved in approximately 40-50% of cases after prolonged treatment with ATD, for several years, in recent studies. Alternative ablative treatments such as radioactive iodine and, less frequently and mostly in cases of very high volume goiters or in children under the age of 5 years, thyroidectomy, performed by pediatric surgeons with extensive experience should be proposed in cases of non-compliance, intolerance to medical treatment or relapse after prolonged medical treatment. Ablative treatments are effective against hyperthyroidism, but they require the subsequent administration of levothyroxine throughout the patient's life. This review considers data relating to the prognosis for Graves' disease remission in children and explores the limitations of study designs and results; and the emerging proposal for management through the prolonged use of ATD drugs. © 2017 European Society of Endocrinology.

    17. Prescriptive Oriented Drug Analysis of Multiple Sclerosis Disease by LC-UV in Whole Human Blood.

      Science.gov (United States)

      Suneetha, A; Rajeswari, Raja K

      2016-02-01

      As a polytherapy treatment, multiple sclerosis disease demands prescriptions with more than one drug. Polytherapy is sometimes rational for drug combinations chosen to minimize adverse effects. Estimation of drugs that are concomitantly administered in polytherapy is acceptable as it shortens the analytical timepoints and also the usage of biological matrices. In clinical phase trials, the withdrawal of biofluids is a critical issue for each analysis. Estimating all the coadminsitered drugs in a single shot will be more effective and economical for pharmaceuticals. A single, simple, rapid and sensitive high-performance liquid chromatography assay method has been developed with UV detection and fully validated for the quantification of 14 drugs (at random combinations) used in the treatment of multiple sclerosis disease. The set of combinations was based on prescriptions to patients. Separations were achieved on an X-Terra MS C18 (100 × 3.9 mm, 5 µm) column. The analytes were extracted from 50 µL aliquots of whole human blood with protein precipitation using acetonitrile. All the drugs were sufficiently stable during storage for 24 h at room temperature and for 23 days at 2-8°C. The percentage recoveries of all drugs were between 90 and 115%, with RSD values <10.6%. This method has been shown to be reproducible and sensitive and can be applied to clinical samples from pharmacokinetic studies and also a useful tool in studying the drug interaction studies. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

    18. COPD - control drugs

      Science.gov (United States)

      Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

    19. Hyperglycemia, a Neglected Factor during Cancer Progression

      Directory of Open Access Journals (Sweden)

      Wanxing Duan

      2014-01-01

      Full Text Available Recent evidence from large cohort studies suggests that there exists a higher cancer incidence in people with type 2 diabetes (DM2. However, to date, the potential reasons for this association remain unclear. Hyperglycemia, the most important feature of diabetes, may be responsible for the excess glucose supply for these glucose-hungry cells, and it contributes to apoptosis resistance, oncogenesis, and tumor cell resistance to chemotherapy. Considering associations between diabetes and malignancies, the effect of hyperglycemia on cancer progression in cancer patients with abnormal blood glucose should not be neglected. In this paper, we describe the role that hyperglycemia plays in cancer progression and treatment and illustrate that hyperglycemia may contribute to a more malignant phenotype of cancer cells and lead to drug resistance. Therefore, controlling hyperglycemia may have important therapeutic implications in cancer patients.

    20. Stem cells as a novel tool for drug screening and treatment of degenerative diseases.

      Science.gov (United States)

      Zuba-Surma, Ewa K; Wojakowski, Wojciech; Madeja, Zbigniew; Ratajczak, Mariusz Z

      2012-01-01

      Degenerative diseases similarly as acute tissue injuries lead to massive cell loss and may cause organ failure of vital organs (e.g., heart, central nervous system). Therefore, they belong to a group of disorders that may significantly benefit from stem cells (SCs)-based therapies. Several stem and progenitor cell populations have already been described as valuable tools for developing therapeutic strategies in regenerative medicine. In particular, pluripotent stem cells (PSCs), including adult-tissue-derived PSCs, neonatal-tissue-derived SCs, embryonic stem cells (ESCs), and recently described induced pluripotent stem cells (iPSCs), are the focus of particular attention because of their capacity to differentiate into all the cell lineages. Although PSCs are predominantly envisioned to be applied for organ regeneration, they may be also successfully employed in drug screening and disease modeling. In particular, adult PSCs and iPSCs derived from patient tissues may not only be a source of cells for autologous therapies but also for individual customized in vitro drug testing and studies on the molecular mechanisms of disease. In this review, we will focus on the potential applications of SCs, especially PSCs i) in regenerative medicine therapies, ii) in studying mechanisms of disease, as well as iii) in drug screening and toxicology tests that are crucial in new drug development. In particular, we will discuss the application of SCs in developing new therapeutic approaches to treat degenerative diseases of the neural system and heart. The advantage of adult PSCs in all the above-mentioned settings is that they can be directly harvested from patient tissues and used not only as a safe non-immunogenic source of cells for therapy but also as tools for personalized drug screening and pharmacological therapies.

    1. Neglected rupture of the quadriceps tendon in a patient with chronic ...

      African Journals Online (AJOL)

      Neglected rupture of the quadriceps tendon in a patient with chronic renal failure ... in patients with predisposing diseases such as gout, rheumatoid arthritis and ... disease and received regular hemodialysis treatment for more than 5 years.

    2. Do payers value rarity? : An analysis of the relationship between disease rarity and orphan drug prices in Europe

      NARCIS (Netherlands)

      Medic, Goran; Korchagina, Daria; Young, Katherine Eve; Toumi, Mondher; Postma, Maarten Jacobus; Wille, Micheline; Hemels, Michiel

      2017-01-01

      Background and Objective: Orphan drugs have been a highlight of discussions due to their higher prices than non-orphan drugs. There is currently no European consensus on the method of value assessment for orphan drugs. This study assessed the relationship between the prevalence of rare diseases and

    3. Sulfoximines: a neglected opportunity in medicinal chemistry.

      Science.gov (United States)

      Lücking, Ulrich

      2013-09-02

      Innovation has frequently been described as the key to drug discovery. However, in the daily routine, medicinal chemists often tend to stick to the functional groups and structural elements they know and love. Blockbuster cancer drug Velcade (bortezomib), for example, was rejected by more than 50 companies, supposedly because of its unusual boronic acid function (as often repeated: "only a moron would put boron in a drug!"). Similarly, in the discovery process of the pan-CDK inhibitor BAY 1000394, the unconventional proposal to introduce a sulfoximine group into the lead series also led to sneers and raised eyebrows, since sulfoximines have seldom been used in medicinal chemistry. However, it was the introduction of the sulfoximine group that finally allowed the fundamental issues of the project to be overcome, culminating in the identification of the clinical sulfoximine pan-CDK inhibitor BAY 1000394. This Minireview provides an overview of a widely neglected opportunity in medicinal chemistry--the sulfoximine group. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

    4. A prospective investigation of borderline personality disorder in abused and neglected children followed up into adulthood.

      Science.gov (United States)

      Widom, Cathy Spatz; Czaja, Sally J; Paris, Joel

      2009-10-01

      Child abuse has been implicated as a risk factor for borderline personality disorder (BPD), yet few prospective longitudinal studies exist. The current study examined whether 500 individuals with documented cases of childhood physical and sexual abuse and neglect were at elevated risk of BPD in adulthood, compared to 396 demographically similar control children. Results indicated that significantly more abused and/or neglected children overall met criteria for BPD as adults, compared to controls, as did physically abused and neglected children. Having a parent with alcohol/drug problems and not being employed full-time, not being a high school graduate, and having a diagnosis of drug abuse, major depressive disorder, and posttraumatic stress disorder were predictors of BPD and mediated the relationship between childhood abuse/neglect and adult BPD. These results call attention to a heightened risk of BPD in physically abused and neglected children and the need to consider multiple pathways to BPD.

    5. Nanocarrier mediated retinal drug delivery: overcoming ocular barriers to treat posterior eye diseases.

      Science.gov (United States)

      Bisht, Rohit; Mandal, Abhirup; Jaiswal, Jagdish K; Rupenthal, Ilva D

      2018-03-01

      Effective drug delivery to the retina still remains a challenge due to ocular elimination mechanisms and complex barriers that selectively limit the entry of drugs into the eye. To overcome these barriers, frequent intravitreal injections are currently used to achieve high drug concentrations in vitreous and retina. However, these repetitive injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery could overcome some of these unmet needs and various preclinical studies conducted to date have demonstrated promising results of nanotherapies in the treatment of retinal diseases. Compared to the majority of commercially available ocular implants, the biodegradable nature of most nanoparticles (NPs) avoids the need for surgical implantation and removal after the release of the payload. In addition, the sustained drug release from NPs over an extended period of time reduces the need for frequent intravitreal injections and the risk of associated side effects. The nanometer size and highly modifiable surface properties make NPs excellent candidates for targeted ocular drug delivery. Studies have shown that nanocarriers enhance the intravitreal half-life and thus bioavailability of a number of drugs including proteins and peptides. In addition, they have shown promising results in delivering genetic material to the retinal tissues by protecting it from possible intravitreal degradation. This review covers the various challenges associated with drug delivery to the posterior segment of the eye, particularly the retina, and highlights the application of nanocarriers to overcome these challenges in context with recent advances in preclinical studies. WIREs Nanomed Nanobiotechnol 2018, 10:e1473. doi: 10.1002/wnan.1473 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants. © 2017 Wiley Periodicals

    6. Patient-derived stem cells: pathways to drug discovery for brain diseases

      Directory of Open Access Journals (Sweden)

      Alan eMackay-Sim

      2013-03-01

      Full Text Available The concept of drug discovery through stem cell biology is based on technological developments whose genesis is now coincident. The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS. The second is patient-derived stem cells for modelling the cell biology of brain diseases. HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs. HCS combines new fluorescent probes with automated microscopy and computational power to quantify the effects of compounds on cell functions. Stem cell biology has advanced greatly since the discovery of genetic reprogramming of somatic cells into induced pluripotent stem cells (iPSCs. There is now a rush of papers describing their generation from patients with various diseases of the nervous system. Although the majority of these have been genetic diseases, iPSCs have been generated from patients with complex diseases (schizophrenia and sporadic Parkinson’s disease. Some genetic diseases are also modelled in embryonic stem cells generated from blastocysts rejected during in vitro fertilisation. Neural stem cells have been isolated from post-mortem brain of Alzheimer’s patients and neural stem cells generated from biopsies of the olfactory organ of patients is another approach. These olfactory neurosphere-derived cells demonstrate robust disease-specific phenotypes in patients with schizophrenia and Parkinson’s disease. High content screening is already in use to find small molecules for the generation and differentiation of embryonic stem cells and induced pluripotent stem cells. The challenges for using stem cells for drug discovery are to develop robust stem cell culture methods that meet the rigorous requirements for repeatable, consistent quantities of defined cell types at the industrial scale necessary for high

    7. Neglected infections of poverty in the United States of America.

      Directory of Open Access Journals (Sweden)

      Peter J Hotez

      2008-06-01

      Full Text Available In the United States, there is a largely hidden burden of diseases caused by a group of chronic and debilitating parasitic, bacterial, and congenital infections known as the neglected infections of poverty. Like their neglected tropical disease counterparts in developing countries, the neglected infections of poverty in the US disproportionately affect impoverished and under-represented minority populations. The major neglected infections include the helminth infections, toxocariasis, strongyloidiasis, ascariasis, and cysticercosis; the intestinal protozoan infection trichomoniasis; some zoonotic bacterial infections, including leptospirosis; the vector-borne infections Chagas disease, leishmaniasis, trench fever, and dengue fever; and the congenital infections cytomegalovirus (CMV, toxoplasmosis, and syphilis. These diseases occur predominantly in people of color living in the Mississippi Delta and elsewhere in the American South, in disadvantaged urban areas, and in the US-Mexico borderlands, as well as in certain immigrant populations and disadvantaged white populations living in Appalachia. Preliminary disease burden estimates of the neglected infections of poverty indicate that tens of thousands, or in some cases, hundreds of thousands of poor Americans harbor these chronic infections, which represent some of the greatest health disparities in the United States. Specific policy recommendations include active surveillance (including newborn screening to ascertain accurate population-based estimates of disease burden; epidemiological studies to determine the extent of autochthonous transmission of Chagas disease and other infections; mass or targeted treatments; vector control; and research and development for new control tools including improved diagnostics and accelerated development of a vaccine to prevent congenital CMV infection and congenital toxoplasmosis.

    8. Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials

      Science.gov (United States)

      Qin, Lan

      2016-01-01

      Objective: This meta-analysis was performed to compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate and adverse events. Methods: Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed and National Knowledge Infrastructure, China, were systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs in patients with Graves' disease. Results were expressed as risk ratio with 95% confidence intervals (CIs) and weighted mean differences with 95% CIs. Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. Results: 17 RCTs involving 4024 patients met the inclusion criteria and were included. Results showed that radioiodine treatment has increased risk in new ophthalmopathy, development or worsening of ophthalmopathy and hypothyroidism. Whereas, compared with antithyroid drugs, radioiodine treatment seems to have a higher hyperthyroid cure rate, lower recurrence rate and lower incidence of adverse events. Conclusion: Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate compared with antithyroid drugs. However, it also increases the risk of ophthalmopathy and hypothyroidism. Advances in knowledge: Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we would recommend radioiodine therapy as the treatment of choice for patients with Graves' disease. PMID:27266544

    9. [Drug treatment of early-stage (de novo and "honeymoon") Parkinson disease].

      Science.gov (United States)

      Cesaro, P; Defebvre, L

      2014-04-01

      In this article, we discuss the management of motor symptoms during the early phases of Parkinson's disease, excluding that of any other clinical manifestation. We relied primarily upon recently published data and do not describe older publications relating to anticholinergic drugs or amantadine. The initial pharmacological treatment of idiopathic Parkinson's disease (IPD) is symptomatic and remains based upon dopaminergic drugs. However, the development of new drugs has broadened the range of strategic options and improved overall patient management. Announcing the diagnosis is a critical moment, as pointed out by patients' associations. Patients should be advised to maintain personal, professional, social and physical activities as long as possible. The potential benefit of early pharmacological treatment should be explained, focusing on the possible disease-modifying effect of drugs such as rasagiline. According to current guidelines, L-Dopa is preferred in patients above 65years of age, while those below 65 should be treated with dopamine agonists. Like monoamine oxidase inhibitors B (MAOI-B), synthetic dopamine agonists exhibit several advantages: easy-to-use treatment with a once-daily administration, delayed L-Dopa initiation, significant efficacy on motor symptoms (although lower than that of L-Dopa). MOAI can be prescribed in association with L-Dopa or dopamine agonists. Rasagiline also delays L-Dopa initiation, and consequently motor complications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

    10. A searchable cross-platform gene expression database reveals connections between drug treatments and disease

      Directory of Open Access Journals (Sweden)

      Williams Gareth

      2012-01-01

      Full Text Available Abstract Background Transcriptional data covering multiple platforms and species is collected and processed into a searchable platform independent expression database (SPIED. SPIED consists of over 100,000 expression fold profiles defined independently of control/treatment assignment and mapped to non-redundant gene lists. The database is thus searchable with query profiles defined over genes alone. The motivation behind SPIED is that transcriptional profiles can be quantitatively compared and ranked and thus serve as effective surrogates for comparing the underlying biological states across multiple experiments. Results Drug perturbation, cancer and neurodegenerative disease derived transcriptional profiles are shown to be effective descriptors of the underlying biology as they return related drugs and pathologies from SPIED. In the case of Alzheimer's disease there is high transcriptional overlap with other neurodegenerative conditions and rodent models of neurodegeneration and nerve injury. Combining the query signature with correlating profiles allows for the definition of a tight neurodegeneration signature that successfully highlights many neuroprotective drugs in the Broad connectivity map. Conclusions Quantitative querying of expression data from across the totality of deposited experiments is an effective way of discovering connections between different biological systems and in particular that between drug action and biological disease state. Examples in cancer and neurodegenerative conditions validate the utility of SPIED.

    11. Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening.

      Science.gov (United States)

      Sharma, Arun; Wu, Joseph C; Wu, Sean M

      2013-12-24

      Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scientists as a promising cell source for replacement therapy. However, ongoing issues such as cell immaturity, scale of production, inter-line variability, and cell purity will need to be resolved before human clinical trials can begin. Meanwhile, the use of hiPSCs