Helminth infections: the great neglected tropical diseases
01 Apr 2008-Journal of Clinical Investigation (American Society for Clinical Investigation)-Vol. 118, Iss: 4, pp 1311-1321
TL;DR: New insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies, which should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.
Abstract: Helminths are parasitic worms. They are the most common infectious agents of humans in developing countries and produce a global burden of disease that exceeds better-known conditions, including malaria and tuberculosis. As we discuss here, new insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies. At the same time, our understanding of the dynamics of the transmission of helminths and the mechanisms of the Th2-type immune responses that are induced by infection with these parasitic worms has increased markedly. Ultimately, these advances in molecular and medical helminth biology should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.
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TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.
7,021 citations
University of Helsinki1, Semmelweis University2, Hungarian Academy of Sciences3, University of Szeged4, University of Palermo5, Institute of Molecular Pathology and Immunology of the University of Porto6, University of Porto7, Autonomous University of Barcelona8, Instituto de Biologia Molecular e Celular9, Ikerbasque10, Harvard University11, University of Duisburg-Essen12, Salk Institute for Biological Studies13, Paracelsus Private Medical University of Salzburg14, University of Colorado Denver15, Bilkent University16, Middle East Technical University17, Statens Serum Institut18, University of Southern Denmark19, Ghent University Hospital20, Oslo University Hospital21, University of Belgrade22, University of Ljubljana23, University of Mainz24, Finnish Red Cross25, University of Gothenburg26, Latvian Biomedical Research and Study centre27, University of Applied Sciences and Arts Northwestern Switzerland FHNW28, University of Valencia29, Centro Nacional de Investigaciones Cardiovasculares30, University of Freiburg31, Utrecht University32, Trinity College, Dublin33, Catalan Institution for Research and Advanced Studies34, University of Barcelona35, International University Of Catalonia36, Aarhus University Hospital37
TL;DR: A comprehensive overview of the current understanding of the physiological roles of EVs is provided, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia.
Abstract: In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
3,690 citations
Cites background from "Helminth infections: the great negl..."
...Together, these are responsible for a large burden of disease and socio-economic losses, as hundreds of millions of people mostly in areas of extreme poverty are infected (600)....
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...EVs in lower organisms Parasites have plagued humans throughout the world for more than 150,000 years (600)....
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TL;DR: The overall burden of Africa's neglected tropical diseases may be severely underestimated, and 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.
Abstract: 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.
1,017 citations
Baylor College of Medicine1, Institute for Health Metrics and Evaluation2, Imperial College London3, Anglia Ruskin University4, Institut de recherche pour le développement5, University of London6, Johns Hopkins University7, Texas A&M University8, University of Oklahoma Health Sciences Center9, Erasmus University Rotterdam10, International Livestock Research Institute11, Swiss Tropical and Public Health Institute12, Brandeis University13, Case Western Reserve University14, Watford General Hospital15, Stanford University16
TL;DR: The publication of the Global Burden of Disease Study 2010 and the accompanying collection of Lancet articles in December 2012 provided the most comprehensive attempt to quantify the burden of almost 300 diseases, injuries, and risk factors, including neglected tropical diseases (NTDs).
Abstract: The publication of the Global Burden of Disease Study 2010 (GBD 2010) and the accompanying collection of Lancet articles in December 2012 provided the most comprehensive attempt to quantify the burden of almost 300 diseases, injuries, and risk factors, including neglected tropical diseases (NTDs) [1]–[3]. The disability-adjusted life year (DALY), the metric used in the GBD 2010, is a tool which may be used to assess and compare the relative impact of a number of diseases locally and globally [4]–[6]. Table 1 lists the major NTDs as defined by the World Health Organization (WHO) [7] and their estimated DALYs [1]. With a few exceptions, most of the NTDs currently listed by the WHO [7] or those on the expanded list from PLOS Neglected Tropical Diseases [8] are disablers rather than killers, so the DALY estimates represent one of the few metrics available that could fully embrace the chronic effects of these infections.
Table 1
Estimated DALYs (in millions) of the NTDs from the Global Burden of Disease Study 2010.
Disease DALYs from GBD 2010 (numbers in parentheses indicate 95% confidence intervals) [1]
NTDs 26.06 (20.30–35.12)
Intestinal nematode infections 5.19 (2.98–8.81)
Hookworm disease 3.23 (1.70–5.73)
Ascariasis 1.32 (0.71–2.35)
Trichuriasis 0.64 (0.35–1.06)
Leishmaniasis 3.32 (2.18–4.90)
Schistosomiasis 3.31 (1.70–6.26)
Lymphatic filariasis 2.78 (1.8–4.00)
Food-borne trematodiases 1.88 (0.70–4.84)
Rabies 1.46 ((0.85–2.66)
Dengue 0.83 (0.34–1.41)
African trypanosomiasis 0.56 (0.08–1.77)
Chagas disease 0.55 (0.27–1.05)
Cysticercosis 0.50 (0.38–0.66)
Onchocerciasis 0.49 (0.36–0.66)
Trachoma 0.33 (0.24–0.44)
Echinococcosis 0.14 (0.07–0.29)
Yellow fever <0.001
Other NTDs * 4.72 (3.53–6.35)
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* Relapsing fevers, typhus fever, spotted fever, Q fever, other rickettsioses, other mosquito-borne viral fevers, unspecified arthropod-borne viral fever, arenaviral haemorrhagic fever, toxoplasmosis, unspecified protozoal disease, taeniasis, diphyllobothriasis and sparganosis, other cestode infections, dracunculiasis, trichinellosis, strongyloidiasis, enterobiasis, and other helminthiases.
Even DALYs, however, do not tell the complete story of the harmful effects from NTDs. Some of the specific and potential shortcomings of GBD 2010 have been highlighted elsewhere [9]. Furthermore, DALYs measure only direct health loss and, for example, do not consider the economic impact of the NTDs that results from detrimental effects on school attendance and child development, agriculture (especially from zoonotic NTDs), and overall economic productivity [10], [11]. Nor do DALYs account for direct costs of treatment, surveillance, and prevention measures. Yet, economic impact has emerged as an essential feature of the NTDs, which may trap people in a cycle of poverty and disease [10]–[12]. Additional aspects not considered by the DALY metrics are the important elements of social stigma for many of the NTDs and the spillover effects to family and community members [13], [14], loss of tourism [15], and health system overload (e.g., during dengue outbreaks). Ultimately NTD control and elimination efforts could produce social and economic benefits not necessarily reflected in the DALY metrics, especially among the most affected poor communities [11].
842 citations
TL;DR: Although there are proven strategies to control several NTDs, these diseases continue to cause a massive burden of morbidity and there is urgent need for more basic and operational research, drug and vaccine development, and greater prioritization by governments and international agencies.
Abstract: Introduction: The neglected tropical diseases (NTDs) are infectious diseases that principally impact the world’s poorest people. They have been neglected for decades, initially as part of a general disregard for the developing world, and more recently due to the intensity of focus on HIV/AIDS, tuberculosis and malaria. Sources of data: Primary research and review articles were selected for inclusion using searches of PubMed and our existing collections. Results: There have been recent notable successes in NTD control. Dracunculiasis is approaching eradication. Leprosy and onchocerciasis are in decline. There are ambitious plans to eliminate trachoma and lymphatic filariasis. Investment in NTD control has high rates of economic return. Conclusion: Although there are proven strategies to control several NTDs, these diseases continue to cause a massive burden of morbidity. There is urgent need for more basic and operational research, drug and vaccine development, and greater prioritization by governments and international agencies.
767 citations
References
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Book•
11 Jul 1991
TL;DR: This book discusses the biology of host-microparasite associations, dynamics of acquired immunity heterogeneity within the human community indirectly transmitted helminths, and the ecology and genetics of hosts and parasites.
Abstract: Part 1 Microparasites: biology of host-microparasite associations the basic model - statics static aspects of eradication and control the basic model - dynamics dynamic aspects of eradication and control beyond the basic model - empirical evidence of inhomogeneous mixing age-related transmission rates genetic heterogeneity social heterogeneity and sexually transmitted diseases spatial and other kinds of heterogeneity endemic infections in developing countries indirectly transmitted microparasites. Part 2 Macroparasites: biology of host-macroparasite associations the basic model - statics the basic model - dynamics acquired immunity heterogeneity within the human community indirectly transmitted helminths experimental epidemiology parasites, genetic variability, and drug resistance the ecology and genetics of host-parasite associations.
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01 Jan 1996
TL;DR: This is the first in a planned series of 10 volumes that will attempt to "summarize epidemiological knowledge about all major conditions and most risk factors" and use historical trends in main determinants to project mortality and disease burden forward to 2020.
Abstract: This is the first in a planned series of 10 volumes that will attempt to "summarize epidemiological knowledge about all major conditions and most risk factors;...generate assessments of numbers of deaths by cause that are consistent with the total numbers of deaths by age sex and region provided by demographers;...provide methodologies for and assessments of aggregate disease burden that combine--into the Disability-Adjusted Life Year or DALY measure--burden from premature mortality with that from living with disability; and...use historical trends in main determinants to project mortality and disease burden forward to 2020." This first volume includes chapters summarizing results from the project as a whole. (EXCERPT)
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01 Jan 1996
TL;DR: 1. Cost-Effectiveness Analysis as a Guide to Resource Allocation in Health: Roles and Limitations 2. Theoretical Foundations of Cost-effectiveness Analysis 3. Framing and Designing the Cost- Effectiveness Analysis 4. Identifying and Valuing Outcomes 5. Assessing the Effectiveness of Health Interventions
Abstract: 1 Cost-Effectiveness Analysis as a Guide to Resource Allocation in Health: Roles and Limitations 2 Theoretical Foundations of Cost-Effectiveness Analysis 3 Framing and Designing the Cost-Effectiveness Analysis 4 Identifying and Valuing Outcomes 5 Assessing the Effectiveness of Health Interventions 6 Estimating Costs in Cost-Effectiveness Analysis 7 Time Preference 8 Reflecting Uncertainty in Cost-Effectiveness Analysis 9 Reporting Cost-Effectiveness Studies and Results Appendix A: Summary of Recommendations for the Reference Case Appendix B: Cost-Effectiveness of Strategies to Prevent Neural Tube Defects Appendix C: The Cost-Effectiveness of Dietary and Pharmacologic Therapy for Cholesterol Reduction in Adults
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TL;DR: Concerns about the sustainability of periodic deworming with benzimidazole anthelmintics and the emergence of resistance have prompted efforts to develop and test new control tools.
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