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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.
The discovery of antibiotics heralded medicine's triumph over previously fatal diseases that once destroyed entire civilizations - thus earning their reputation as miracle drugs. But today, the terrifying reality of antibiotic-resistant bacteria resulting from our widespread misuse of antibiotics forewarns us that the miracle may be coming to an end. The seemingly innocent consumer who demands antibiotics to treat nonbacterial diseases such as the common cold or plays doctor by saving old prescriptions for later use is paving the way for a future of antibiotic failure. "What harm can it do?" is a popular refrain of people worldwide as they pop another antibiotic pill. Dr. Stuart Levy - the leading international expert on hazards of antibiotic misuse - reveals how this cavalier and naive attitude about the power of antibiotics can have deadly consequences. He explains that we are presently witnessing a massive evolutionary change in bacteria. This build-up of new antibiotic-resistant bacteria in individuals and the environment worldwide is an insidious and silent process. Thus, unwittingly consumers encounter resistant bacteria in their meat, poultry, fish, and vegetables. Unregulated dispensing of antibiotics in poorer countries breeds countless more resistant strains. Since bacteria recognize no geographical boundaries, resistant forms can travel the globe. If this trend continues to grow unchecked, we may someday find that all of our antibiotics are obsolete. Today doctors can no longer expect that their first choice of antibiotic for women's urinary tract infections or children's ear infections will work. Similarly, cancer therapy is rendered useless if patients are unable to fight infections that are sometimes resistant to eight to ten different drugs. In developing countries, people are now dying of previously treatable diseases that are no longer responsive to traditional antibiotics. These problems are just a harbinger of what will come if we do not act now. Dr. Levy, recognized by The New Yorker for his superb contributions to this field, is sending out an urgent message that the world cannot afford to ignore any longer. The goal of this unprecedented investigation into the dangers of antibiotic misuse is to protect the world community from resistant infections and ensure the success of antibiotics for generations to come
Probiotic microorganisms are recognised as being beneficial for human health. Prebiotics are substrates that are used preferentially by the probiotic bacteria for their growth. A great deal of interest has been generated in recent years in identifying probiotic bacteria and prebiotics, their characterization, mechanisms of action and their role in the prevention and management of human health disorders. Together they are referred to as synbiotic. This book is in response to the need for more current and global scope of probiotics and prebiotics. It contains chapters written by internationally recognized authors. The book has been planned to meet the needs of the researchers, health professionals, government regulatory agencies and industries. This book will serve as a standard reference book in this important and fast-growing area of probiotics and prebiotics in human nutrition and health.
This volume covers all aspects of the antibiotic discovery and development process through Phase II/III. The contributors, a group of highly experienced individuals in both academics and industry, include chapters on the need for new antibiotic compounds, strategies for screening for new antibiotics, sources of novel synthetic and natural antibiotics, discovery phases of lead development and optimization, and candidate compound nominations into development. Beyond discovery , the handbook will cover all of the studies to prepare for IND submission: Phase I (safety and dose ranging), progression to Phase II (efficacy), and Phase III (capturing desired initial indications). This book walks the reader through all aspects of the process, which has never been done before in a single reference. With the rise of antibiotic resistance and the increasing view that a crisis may be looming in infectious diseases, there are strong signs of renewed emphasis in antibiotic research. The purpose of the handbook is to offer a detailed overview of all aspects of the problem posed by antibiotic discovery and development.
Historically, the first observation of a transmissible lytic agent that is specifically active against a bacterium (Bacillus anthracis) was by a Russian microbiologist Nikolay Gamaleya in 1898. At that time, however, it was too early to make a connection to another discovery made by Dmitri Ivanovsky in 1892 and Martinus Beijerinck in 1898 on a non-bacterial pathogen infecting tobacco plants. Thus the viral world was discovered in two of the three domains of life, and our current understanding is that viruses represent the most abundant biological entities on the planet. The potential of bacteriophages for infection treatment have been recognized after the discoveries by Frederick Twort and Felix d’Hérelle in 1915 and 1917. Subsequent phage therapy developments, however, have been overshadowed by the remarkable success of antibiotics in infection control and treatment, and phage therapy research and development persisted mostly in the former Soviet Union countries, Russia and Georgia, as well as in France and Poland. The dramatic rise of antibiotic resistance and especially of multi-drug resistance among human and animal bacterial pathogens, however, challenged the position of antibiotics as a single most important pillar for infection control and treatment. Thus there is a renewed interest in phage therapy as a possible additive/alternative therapy, especially for the infections that resist routine antibiotic treatment. The basis for the revival of phage therapy is affected by a number of issues that need to be resolved before it can enter the arena, which is traditionally reserved for antibiotics. Probably the most important is the regulatory issue: How should phage therapy be regulated? Similarly to drugs? Then the co-evolving nature of phage-bacterial host relationship will be a major hurdle for the production of consistent phage formulae. Or should we resort to the phage products such as lysins and the corresponding engineered versions in order to have accurate and consistent delivery doses? We still have very limited knowledge about the pharmacodynamics of phage therapy. More data, obtained in animal models, are necessary to evaluate the phage therapy efficiency compared, for example, to antibiotics. Another aspect is the safety of phage therapy. How do phages interact with the immune system and to what costs, or benefits? What are the risks, in the course of phage therapy, of transduction of undesirable properties such as virulence or antibiotic resistance genes? How frequent is the development of bacterial host resistance during phage therapy? Understanding these and many other aspects of phage therapy, basic and applied, is the main subject of this Topic.
We share the Earth with more than 10,000,000,000,000,000,000,000,000,000,000 phages. Everywhere they thrive, from well-fed guts to near-boiling acidic springs, from cryoconite holes to endolithic fissures. They travel from one microbial host to the next as virions, their genetic weapons packaged inside a protective protein shell. If you could lay all of these nanoscopic phage virions side-by-side, the line-up would stretch over 42 million light years. Through their daily shenanigans they kill or collaborate with their microbial hosts to spur microbial evolution and maintain ecosystem functioning. We have learned much about them since their discovery by Frederick Twort a century ago. They also taught us that DNA, not protein, is the hereditary material, unraveled the triplet genetic code, and offered their enzymes as indispensible tools for the molecular biology revolution. More contributions will be forthcoming since the vast majority of phages await discovery. Phage genomes harbor the world's largest cache of unexplored genetic diversity, and we now have the equipment needed to go prospecting. Although there are field guides to birds, insects, wild flowers, even Bacteria, there was no such handbook to guide the phage explorer. Forest Rohwer decided to correct this oversight, for novice and expert alike, and thus was born Life in Our Phage World. A diverse collection of 30 phages are featured. Each phage is characterized by its distinctive traits, including details about its genome, habitat, lifestyle, global range, and close relatives. The beauty of its intricate virion is captured in a pen-and-ink portrait by artist Benjamin Darby. Each phage also stars in a carefully researched action story relating how that phage encounters, exploits, kills, or otherwise manipulates its host. These behaviors are imaginatively illustrated by fine artist Leah L. Pantea. Eight researchers that work closely with phages also relate their experiences as inhabitants of the phage world. Rohwer has years of first-hand experience with the phage multitudes in ecosystems ranging from coral reefs to the human lung to arctic waters. He pioneered the key metagenomic methods now widely used to catalog and characterize Earth's microbial and viral life. Despite research advances, most people, many scientists included, remain unaware of the ongoing drama in our phage world. In anticipation of 2015, the centennial of phage discovery, Forest assembled a cadre of writers, artists, scientists, and a cartographer and set them to work. The result? This alluring field guide-a feast for the imagination and a celebration of phage diversity."