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.

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.

Among the many who serve in the United States Armed Forces and who are deployed to distant locations around the world, myriad health threats are encountered. In addition to those associated with the disruption of their home life and potential for combat, they may face distinctive disease threats that are specific to the locations to which they are deployed. U.S. forces have been deployed many times over the years to areas in which malaria is endemic, including in parts of Afghanistan and Iraq. Department of Defense (DoD) policy requires that antimalarial drugs be issued and regimens adhered to for deployments to malaria-endemic areas. Policies directing which should be used as first and as second-line agents have evolved over time based on new data regarding adverse events or precautions for specific underlying health conditions, areas of deployment, and other operational factors At the request of the Veterans Administration, Assessment of Long-Term Health Effects of Antimalarial Drugs When Used for Prophylaxis assesses the scientific evidence regarding the potential for long-term health effects resulting from the use of antimalarial drugs that were approved by FDA or used by U.S. service members for malaria prophylaxis, with a focus on mefloquine, tafenoquine, and other antimalarial drugs that have been used by DoD in the past 25 years. This report offers conclusions based on available evidence regarding associations of persistent or latent adverse events.

Amebiasis, a parasitic disease transmitted by the unicellular protozoan parasite Entamoeba histolytica, is the cause of at least 100,000 deaths each year. The disease is mostly prevalent in developing countries and is one of the three common causes of death from parasitic diseases. The parasite has two stages in its life cycle in the host: the infective cyst and the invasive trophozoite. In the large intestine, the parasite feeds on bacteria and on cellular debris. No vaccine against amebiasis currently exists. Although metronidazole is the drug of choice for treating amebiasis, adverse effects in patients and potential resistance to metronidazole in other protozoa exist. About nine out of 10 people who are infected with E. histolytica are asymptomatic and in those individuals who develop symptoms, bloody diarrhea (amebic colitis) and liver abscess are the most common symptoms. One possible explanation for this observation is the difference in the gut microbiota between individuals that may significantly influence the host’s immune response in amebiasis and E. histolytica's virulence. Amebiasis is characterized by acute inflammation of the intestine with release of pro-inflammatory cytokines, reactive oxygen species and reactive nitrogen species from activated cells of the host's immune system. In recent years, significant advances on the cell biology of Entamoeba infection have been achieved through the development of new genetic tools to manipulate gene expression in the parasite and through the application of Omics tools. In this Research Topic, we welcome high quality original research articles, as well as review, opinion or method articles, on amebiasis including but not limited to the regulation of gene expression, cell biology and signaling, adaptation and resistance to environmental stresses, metabolism, pathogenesis and immunity, pathogenesis and microbiome, drug discovery and drug resistance.

This book documents and presents new developments in the study of amebiasis, one of the neglected tropical diseases. Nearly 50 million people worldwide are infected with the pathogen Entamoeba histolytica, causing large-scale morbidity and mortality particularly in developing countries. This book will help clinicians for better diagnosis and management of the disease, researchers for initiating research projects on some of the poorly understood aspects of the disease and the pathogen, and students for updating their knowledge. The subjects covered range from genomics and molecular and cell biology to drug resistance and new drug development, highlighting major advances in recent years in our understanding due to rapid progress in genomic and other biomedical technologies, such as visualization of molecular processes. Most of the chapters provide recent information based on latest publications. A few chapters describe some of the critical methodological issues that will be helpful for students and researchers interested in getting into the field. The contributing authors include almost all the active researchers and clinicians from around the world. This book will be a useful primary material and a valuable source of information for anyone interested in understanding amebiasis, its diagnosis, and treatment. It will also be useful to those who are interested in learning about the biology of early branching eukaryotes and protist pathogens.

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.

"The purpose of this document is to provide comprehensible, global, evidence-based guidelines to help formulate policies and protocols for the treatment of malaria. Information is presented on the treatment of uncomplicated malaria, including disease in special groups (young children, pregnant women, people who are HIV positive, travellers from non-malaria endemic regions) and in complex emergency situations and severe malaria."--Publisher's description.

Ivermectin and abamectin, members of the avermectin family of compounds, were introduced to the market in the 1980's as a veterinary antiparasitic drug and agricultural pesticide, respectively. Their acceptance and commercial success have been remarkable; both are highly effective and in worldwide use. The efficacy of ivermectin in river blindness has expanded the interest in its use in human medicine. In response to the intense scientific and industrial interest in ivermectin and abamectin and the likelihood that they will be forerunners of an expanding family of drugs, this comprehensive monograph satisfies the need for a review and synthesis of current knowledge about the use of these substances in crop protection as well as in cattle, sheep, swine, horses, dogs, cats, birds, fish, reptiles, and in man. This overview presents chemical, biochemical, and microbiological data, as well as pharmacological, safety, and environmental aspects and covers practical use of the compounds as antiparasitic and pesticide agents, as well as the available safety data that have emerged from the clinical experience with human applications.