Parasitic infections are the most prevalent of human diseases, and researchers continue to face the challenge of designing drugs to successfully counteract them. Chemotherapeutic Targets in Parasites analyzes the critical metabolic reactions and structural features essential for parasite survival, and advocates the latest molecular strategies with which to identify effective antiparasitic agents. An introduction to the early development of parasite chemotherapy is followed by an overview of biophysical techniques and genomic and proteomic analysis. Several chapters are devoted to specific types of chemotherapeutic agents and their targets in malaria, trypanosomes, leishmania and amitochondrial protists. Chapters on helminths include metabolic, neuromuscular, microtubular and tegumental targets. Emphasized throughout is the design of more selective and less toxic drugs than in the past. This book will be especially relevant to medical and clinical researchers and to graduate students in parasitology, pharmacology, medicine, microbiology, and biochemistry.
This manual focuses on how and when a set of low-cost or free drugs should be used in developing countries to control a set of diseases caused by worm infections. Preventive chemotherapy in this context means using drugs that are effective against a broad range of worm infections to simultaneously treat the four most common diseases caused by worms: river blindness (onchocerciasis), elephantiasis (lymphatic filariasis), schistosomiasis, and soil-transmitted helminthiasis. Significant opportunities also exist to integrate these efforts with the prevention and control of diseases such as trachoma. The new approach provides a critical first step in combining treatment regimens for diseases which, although different in themselves, require common resources and delivery strategies for control or elimination.
The dreaded protozoal diseases caused by a number of Kinetoplastid parasites threaten mankind, as therapeutic tools for the treatment of most parasitic diseases are extremely limited. Development of commercially available vaccines is still far from reality, though research and trial programs continue. This book covers current research into drug therapeutics for the conditions caused by the parasites, which if viewed globally, pose an increasing threat to human health and welfare.
The study of parasitic organisms at the molecular level has yielded fascinating new insights of great medical, social, and economical importance, and has pointed the way for the treatment and prevention of the diseases they cause. Biochemistry and Molecular Biology of Parasites presents an up-to-date account of this modern scientific discipline in a manner that allows and encourages the reader to place the biochemistry and molecular biology of these organisms in their biological context. The chapters are cross-referenced and grouped in an arrangement that provides a fully integrated whole, and permits the reader to create a composite of the biochemical function of these organisms.Individual chapter includes those devoted to metabolism, in both aerobic and anaerobic protozoa; antioxidant mechanisms; parasite surfaces; organelles; invasion mechanisms; and chemotherapy. The helminths are discussed not only from the point of view of their cellular biochemistry and metabolism, but also with respect to both their integrated functions such as neurochemistry, structure and functions of surfaces, and reproduction. Written by expert investigators, this book will be of interest to all experienced researchers, graduate students, and to the newcomer eager to become familiar with the biochemistry and molecular biology of parasites.
This handbook is the first dealing with the discovery of drugs directed against apicomplexan parasites. Amongst others, this group of endoparasites includes the causative agents of Malaria, Toxoplasmosis, and Babesiosis, the latter occurring mainly in animals. Written by renowned scientific experts from academia and industry, the book focuses on currentdrug development approaches for all apicomplexan diseases making it appealing to a large audience, ranging from research labs in academia to the human and veterinarian pharmaceutical industry. This work is the second volume of the new book series 'Drug Discovery in Infectious Diseases', edited by Prof. Dr Paul M. Selzer.
A panel of leading academic and pharmaceutical investigators takes stock of the remarkable work that has been accomplished to date with proteasome inhibitors in cancer, and examines emerging therapeutic possibilities. The topics range from a discussion of the chemistry and cell biology of the proteasome and the rationale for proteasome inhibitors in cancer to a review of current clinical trials underway. The discussion of rationales for testing proteasome inhibitors in cancer models covers the role of the proteasome in NF-kB activation, the combining of conventional chemotherapy and radiation with proteasome inhibition, notably PS-341, new proteasome methods of inhibiting viral maturation, and the role of protesome inhibition in the treatment of AIDS. The authors also document the development of bortezomib (VelcadeTM) in Phase I clinical trials and in a multicentered Phase II clinical trials in patients with relapsed and refractory myeloma.
For more than 50 years, low-cost antimalarial drugs silently saved millions of lives and cured billions of debilitating infections. Today, however, these drugs no longer work against the deadliest form of malaria that exists throughout the world. Malaria deaths in sub-Saharan Africaâ€"currently just over one million per yearâ€"are rising because of increased resistance to the old, inexpensive drugs. Although effective new drugs called "artemisinins" are available, they are unaffordable for the majority of the affected population, even at a cost of one dollar per course. Saving Lives, Buying Time: Economics of Malaria Drugs in an Age of Resistance examines the history of malaria treatments, provides an overview of the current drug crisis, and offers recommendations on maximizing access to and effectiveness of antimalarial drugs. The book finds that most people in endemic countries will not have access to currently effective combination treatments, which should include an artemisinin, without financing from the global community. Without funding for effective treatment, malaria mortality could double over the next 10 to 20 years and transmission will intensify.
Human African Trypaniosomiasis (HAT) or sleeping sickness is an old disease to be now considered as reemergent. HAT is endemic in 36 sub-Saharan African countries, in areas where tsetse flies are found. The public health importance of HAT is underestimated, but the disease causes severe social disruption in many rural areas. Along the past fifteen years, numerous studies were made, and now, the mechanisms involved in the disease pathogenesis and in the characteristics of sleep-wake disruption become to be better understood. But, since 50 years, when current drugs were introduced, problems regarding HAT chemotherapy have not been solved. Nevertheless, in-depth studies about trypanosome metabolism have permitted to discover new drug targets. Written by specialists who are very experienced in their respective fields, the contributions provide an indispensable tool for practitioners and scientists.
Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death. This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities. The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the: Nature, clinical manifestations, diagnosis, and epidemiology of malaria. Biology of the malaria parasite and its vector. Prospects for developing malaria vaccines and improved treatments. Economic, social, and behavioral factors in malaria control.
One of the top four contributors to the global burden of disease is diarrheal infections. Intestinal parasites are major causes of morbidity and mortality associated with diarrheal diseases in both the developed and developing world. Amebiasis is responsible for 50 million cases of invasive disease and 70,000 deaths annually in the world. Giardiasis has an estimated worldwide prevalence of 280 million cases annually. In developed countries, Giardia lamblia infects about 2% of adults and 6-8% of children. The prevalence of G. lamblia infection is generally higher in developing countries, ranging from 3% to 90%. Furthermore, giardial infections contribute substantially to the 2.5 million annual deaths from diarrheal disease. In Asia, Africa, and Latin America, about 500,000 new giardiasis cases are reported each year. Cryptosporidium accounts for 20% and 9% of diarrheal episodes in children in developing and developed countries, respectively. Infection with Cryptosporidium can be chronic and especially debilitating in immunosuppressed individuals and malnourished children. A recent study to measure disease burden, based on disability-adjusted life years (DALYs), found that cryptosporidiosis and amebiasis produce about 10.6 million DALYs. This exceeds the DALYs of any helminth infection currently being targeted by the World Health Organization for preventive chemotherapy. Because of its link with poverty, Giardia and Cryptosporidium were included in the WHO Neglected Diseases Initiative in 2004. E. histolytica, G. lamblia, and C. parvum have been listed by the National Institutes of Health (NIH) as category B priority biodefense pathogens due to low infectious dose and potential for dissemination through compromised food and water supplies in the United States. Despite the prevalence of amebiasis, giardiasis, and cryptosporidiosis there are no vaccines or prophylactic drugs. The first-line drugs for invasive amebiasis and giardiasis chemotherapy are nitroimidazoles, with the prototype, metronidazole, being the most common drug used worldwide. Metronidazole has been shown to be both mutagenic in a microbiological system and carcinogenic to rodents, and frequently causes gastrointestinal side effects. In spite of the efficacy of nitroimidazole drugs, treatment failures in giardiasis occur in up to 20% of cases. Clinical resistance of G. lamblia to metronidazole is proven and cross resistance is a concern with all commonly used antigiardial drugs. Nitazoxanide, the only FDA-approved drug for the treatment of cryptosporidiosis, is effective in the treatment of immunocompetent patients and partially effective for immunosuppressed patients. Therefore, it is critical to search for more effective drugs to treat amebiasis, giardiasis, and cryptosporidiosis. This Research Topic for Frontiers in Microbiology will explore the recent progress in drug development for parasitic diarrheal diseases. This includes an understanding of drug resistance mechanisms. We would also welcome submissions on the drug development for other diarrheal parasites. We hope that this research topic will include a comprehensive survey of various attempts by the parasitology research community to create effective drugs for these diseases.
