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Chagas' disease, which results from infection with the single cell parasite Trypanosoma cruzi, is a debilitating condition that is a major problem in many parts of Latin America. Rapid technical progress is now facilitating dissection of the molecular mechanisms of disease pathogenesis, a process that will ultimately provide new strategies to alleviate the enormous public health burden associated with the infection. In this book, international experts review the buoyant status of Chagas' disease research as we enter the "post-genome" era and speculate on how the new findings will impact on drug and vaccine development. The chapters outline how progress is being made on several fronts ranging from parasite population genetics to human immunology. Researchers, physicians and students with an interest in any aspect of molecular parasitology should find this book to be a valuable reference
Polyclonal lymphocyte activation and hypergammaglobulinemia characterize the acute phase of Chagas' disease, a debilitating condition caused by Trypanosoma cruzi. Such pathogenic hyper-reactivities not only compromise specific host defense against the pathogen, but may also contribute to infection-induced chronic autoimmune responses. Characterizing parasite-derived factors driving non-specific immune responses will provide insights for parasite evasion of host specific immunity. This study shows that T. cruzi trans-sialidase (TS) is one such polyclonal activator for normal murine lymphoid and non-lymphoid cells in at least three aspects. First, TS induces aggregation of immune cells and secretion of cytokines, such as IL-6. Second, TS is a T-independent B cell mitogen, directly stimulating polyclonal B cell proliferation independent of IL-6, CD40, CD43, Toll-like receptor-4 (TLR-4), and mIg crosslinking. While TS is mitogenic to wild-type B cells, mostly CD5- B2 cells, it fails to induce any proliferation of B cells from Bruton's tyrosine kinase (Btk)-defective X-linked immune deficient (xid) mice, suggesting that Btk is involved in TS signaling. Furthermore, in vivo administration of TS is followed by polyclonal Ig secretion that peaks 4-6 days after injection, before detectable TS-specific antibodies. Third, although TS does not directly stimulate T cells, it potentiates antigen specific and nonspecific T cell responses through the activation of APC, such as macrophages and B cells. TS potentiation is observed in splenocytes deficient of CD28, ICAM-1, CD40L or CD43. However, optimal TS-potentiation requires IL-6 and Btk, as it is significantly reduced in splenocytes from IL-6 -/- and xid mice. The C-terminal tandem repeat domain (LTR), but not the N-terminal catalytic domain (CD) of TS, is the active moiety that mediates TS-induced cell aggregation, IL-6 secretion, B cell and macrophage activation. At non-mitogenic concentrations, however, LTR inhibits mouse T cell activation and blocks TS-potentiated T cell response. A working model for the actions of TS, its domains and TS receptor is proposed. The results indicate that TS is a parasite-derived factor that directly and indirectly activates both APC and T cells, disturbing host lymphocyte homeostasis and cytokine regulation. Thus, TS may drive polyclonal lymphocyte activation in acute infection, potentially contributing to the immune evasion of the parasite, as well as the autoimmune abnormality in chronic Chagas' disease.
Chagas disease is a potentially life threatening condition that was historically mainly endemic to Latin America. Over the last decade, however, the disease has spread to and is increasingly prevalent in other continents such as North America and Europe, with an estimated 7 million people infected worldwide. It is primarily transmitted by insect vectors that carry the parasite Trypanosoma cruzi, the disease agent. In areas where there is vector control and in non-endemic countries, it is mainly transmitted via congenital infection. Cardiac and gastrointestinal complications are common in untreated individuals. This book offers a comprehensive overview of Chagas disease, including its vectorial and congenital transmission, and molecular diagnosis, which is essential for screening, and developing and providing timely, effective anti-trypanosomal treatment. Written by experts working with infected patients on a daily basis, it discusses the pathogenesis of congenital, cardiac, gastrointestinal and oral Chagas disease, as well as its treatment and the pharmacological aspects of drug development in this area. Chapter "Chagas Disease Treatment Efficacy Biomarkers: Myths and Realities" is available open access under a via link.springer.com.
"The presence, or absence, of neglected tropical diseases (NTDs) can be seen as a proxy for poverty and for the success of interventions aimed at reducing poverty. Today, coverage of the public-health interventions recommended by the World Health Organization (WHO) against NTDs may be interpreted as a proxy for universal health coverage and shared prosperity - in short, a proxy for coverage against neglect. As the world's focus shifts from development to sustainable development, from poverty eradication to shared prosperity, and from disease-specific goals to universal health coverage, control of NTDs will assume an important role towards the target of achieving universal health coverage, including individual financial risk protection. Success in overcoming NTDs is a "litmus test" for universal health coverage against NTDs in endemic countries. The first WHO report on NTDs (2010) set the scene by presenting the evidence for how these interventions had produced results. The second report (2013) assessed the progress made in deploying them and detailed the obstacles to their implementation. This third report analyses for the first time the investments needed to achieve the scale up of implementation required to achieve the targets of the WHO Roadmap on NTDs and universal coverage against NTDs. INVESTING TO OVERCOME THE GLOBAL IMPACT OF NEGLECTED TROPICAL DISEASES presents an investment strategy for NTDs and analyses the specific investment case for prevention, control, elimination and eradication of 12 of the 17 NTDs. Such an analysis is justified following the adoption by the Sixty-sixth World Health Assembly in 2013 of resolution WHA6612 on neglected tropical diseases, which called for sufficient and predictable funding to achieve the Roadmap's targets and sustain control efforts. The report cautions, however, that it is wise investment and not investment alone that will yield success. The report registers progress and challenges and signals those that lie ahead. Climate change is expected to increase the spread of several vector-borne NTDs, notably dengue, transmission of which is directly influenced by temperature, rainfall, relative humidity and climate variability primarily through their effects on the vector. Investments in vector-borne diseases will avoid the potentially catastrophic expenditures associated with their control. The presence of NTDs will thereby signal an early warning system for climate-sensitive diseases. The ultimate goal is to deliver enhanced and equitable interventions to the most marginalized populations in the context of a changing public-health and investment landscape to ensure that all peoples affected by NTDs have an opportunity to lead healthier and wealthier lives."--Publisher's description.
Emerging and re-emerging pathogens pose several challenges to diagnosis, treatment, and public health surveillance, primarily because pathogen identification is a difficult and time-consuming process due to the “novel” nature of the agent. Proper identification requires a wide array of techniques, but the significance of these diagnostics is anticipated to increase with advances in newer molecular and nanobiotechnological interventions and health information technology. Human Emerging and Re-emerging Infections covers the epidemiology, pathogenesis, diagnostics, clinical features, and public health risks posed by new viral and microbial infections. The book includes detailed coverage on the molecular mechanisms of pathogenesis, development of various diagnostic tools, diagnostic assays and their limitations, key research priorities, and new technologies in infection diagnostics. Volume 1 addresses viral and parasitic infections, while volume 2 delves into bacterial and mycotic infections. Human Emerging and Re-emerging Infections is an invaluable resource for researchers in parasitologists, microbiology, Immunology, neurology and virology, as well as clinicians and students interested in understanding the current knowledge and future directions of infectious diseases.
Chagas disease causes severe socioeconomic impact and a high medical cost in Latin America. WHO and the World Bank consider Chagas disease as the fourth most transmittable disease to have a major impact on public health in Latin America: 120 million persons are potentially exposed, 16 to 18 million of whom are presently infected, causing 45,000 to 50,000 deaths per year. It has been calculated that approximately 2.4 million potential working years are lost because of incapacity and mortality due to the disease, for an annual cost estimated at 20 billion Euros. American Trypanosomiasis provides a comprehensive overview of Chagas disease and discusses the latest discoveries concerning the three elements that compose the transmission chain of the disease: The host: human and mammalian reservoirs The insect vectors: domestic and sylvatic vectors The causative parasite: Trypanosoma cruzi Informs and updates on all the latest developments in the field Contributions from leading authorities and industry experts
American trypanosomiasis, or Chagas disease, is caused by the protozoan parasite, Trypanosoma cruzi. Sixteen to eighteen million people are currently infected with this organism, and 45,000 deaths are attributed to the disease each year. Infection with T. cruzi is life-long, and 10-30% of persons who harbor the parasite chronically develop cardiac and gastrointestinal problems associated with the parasitosis. Although major progress has been made in recent years in reducing vector-borne and transfusion-associated transmission of T. cruzi, the burden of disability and death in persons chronically infected with the organism continues to be enormous. Eight to ten million persons born in countries in which Chagas disease is endemic currently reside in the United States, and epidemiologic and census data suggest that 50,000-100,000 are chronically infected with T. cruzi. The presence of these infected persons poses a risk of transmission of the parasite in the USA through blood transfusion and organ transplantation and several such cases have now been documented. American Trypanosomiasis, volume seven of World Class Parasites is written for students of tropical medicine, parasitology and public health, for researchers and practitioners alike who wish to bring themselves abreast of the status quo with respect to this disease. It is intended to supplement formal textbooks, in order to broaden and illuminate current areas of scientific and public health concern. Uniquely for T. cruzi, this book addresses parasite, vector and host biology, the pathogenesis of Chagas disease and current and prospective therapeutics and control strategies in a single volume.