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Drug Development for Parasite-Induced Diarrheal Diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452484 Year: Pages: 177 DOI: 10.3389/978-2-88945-248-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2018-02-27 16:16:44
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Abstract

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.

Parasite Infections: From Experimental Models to Natural Systems

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454853 Year: Pages: 294 DOI: 10.3389/978-2-88945-485-3 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Internal medicine
Added to DOAB on : 2019-01-23 14:53:42
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Eukaryotic parasites (including parasitic protozoans, worms and arthropods) are more complex and heterogeneous organisms than pathogenic bacteria and viruses. This notion implies different evolutionary strategies of host exploitation. Typically, parasites establish long-term infections and induce relatively little mortality, as they often limit pathological changes by modulating host cells and downregulating adverse immune responses. Their pattern of distribution tends to be endemic rather than epidemic. Despite these seemingly benign traits, parasites usually cause substantial chronic morbidity, thus constituting an enormous socioeconomic burden in humans, particularly in resource poor countries, and in livestock worldwide. Parasite-induced fitness costs are an evolutionary force that can shape populations and contribute to species diversity. Therefore, a thorough understanding of parasites and parasitic diseases requires detailed knowledge of the respective biochemical, molecular and immunological aspects as well as of population genetics, epidemiology and ecology. This Research Topic (RT) bridges disciplines to connect molecular, immunological and wildlife aspects of parasitic infections. The RT puts emphases on four groups of parasites: Plasmodium, Toxoplasma, Giardia and intestinal helminths. Co-infections are also covered by the RT as they represent the most common form of parasite infections in wildlife and domestic animal populations. Within the four types of parasites the following topics are addressed: (1) Experimental models: hypothesis testing, translation and limits. (2) Critical appraisal of experimental models. (3) Natural systems: Technological advances for investigations in natural parasite-host systems and studies in natural systems. (4) The urgent need for better models and methods in natural parasite systems. Hence, the RT covers and illustrate by the means of four main parasitic infections the parasite-host system at the molecular, cellular and organismic level.

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