Development Of New Antituberculosis Drugs

In the global war to control tuberculosis (TB), there are several critical battles which must be waged and won if we are to make significant progress. Broadly speaking, these battlefields may be regarded as diagnosis, treatment and prevention. Within the arena of treatment are various critical elements. Current drug regimens require 6 months to achieve predictable cures; it is essential that shorter regimens be developed to lessen non-adherence and to improve affordability. To facilitate directly-observed therapy, intermittent (less than daily) regimens have been employed. To ensure favourable outcomes, including patients with AIDS, thrice-weekly regimens are the current standard; reducing the frequency of dosing to twice- or once-weekly may offer significant advantages. Drug resistance to the current major medications, the rifamycins and isoniazid, threatens to make tuberculosis untreatable for rising numbers of patients in many regions of the world. Finding new, effective agents is essential to ensure cures for these cases and to halt transmission of multidrug-resistant tuberculosis to others. Additional issues include reducing the side effects and toxicity of anti-tuberculosis regimens and developing regimens that can be given simultaneously with anti-retroviral therapy without deleterious drug-drug interactions or unacceptable toxicity. Finally, attention must be directed to the potential utility of treating latent infection to prevent the evolution of active disease. The current vaccine Bacille Calmette-Guerin (BCG), while protecting infants and children against potentially lethal forms of TB, has done little to control the incidence of communicable adult pulmonary disease. Research is underway to develop improved vaccines, but due to the prolonged period to determine the efficacy of a TB vaccine (a minimum of 10 to 20 years) -- alternative strategies must be pursued. Furthermore, the utility of a traditional vaccine would be sorely limited by the fact that roughly two billion persons today harbour latent tuberculosis infection. This huge reservoir of future disease would not be eligible for a traditional pre-infection vaccine. "Preventive therapy" with isoniazid has been shown to reduce the subsequent risk of tuberculosis by about 70% in large, randomised placebo-controlled clinical trials. However, this strategy is limited by the requirement for extended duration of treatment (6 to 9 months), the risks of drug-induced hepatitis and rising rates of resistance to isoniazid in many regions of the world where the TB epidemic is most intense. Alternative means for the treatment of latent tuberculosis infection should be given high priority. The authors have assembled an outstanding panel of contributors to address these issues. The topics herein have great relevance both in the industrialised nations where contemporary medications and strategies appear to have exacted their maximum benefits and for the developing nations where this ancient scourge remains rampant. This book will provide an impetus for authorities and organisations devoted to the development of new drugs to address the aforementioned growing problems of TB world-wide.

Tuberculosis emerged as an epidemic in the 1600s, began to decline as sanitation improved in the 19th century, and retreated further when effective therapy was developed in the 1950s. TB was virtually forgotten until a recent resurgence in the U.S. and around the worldâ€"ominously, in forms resistant to commonly used medicines. What must the nation do to eliminate TB? The distinguished committee from the Institute of Medicine offers recommendations in the key areas of epidemiology and prevention, diagnosis and treatment, funding and organization of public initiatives, and the U.S. role worldwide. The panel also focuses on how to mobilize policy makers and the public to effective action. The book provides important background on the pathology of tuberculosis, its history and status in the U.S., and the public and private response. The committee explains how the U.S. can act with both self-interest and humanitarianism in addressing the worldwide incidence of TB.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and still represents one of the global health threats to mankind. The World Health Organization estimated more than 10 million new cases and reported more than 1.5 million deaths in 2019, thus ranking TB among the main causes of death due to a single pathogen. Standard anti-TB therapy includes four first-line antibiotics that should be administered for at least six months. However, in the case of multi- and extensively drug-resistant TB, second-line medications must be used and these frequently cause severe side effects resulting in poor compliance. Developing new anti-TB drug candidates is therefore of outmost importance. In this Special Issue dedicated to Tuberculosis Drug Discovery and Development, we present the main and latest achievements in the fields of drug and target discovery, host-directed therapy, anti-virulence drugs, and describe the development of two advanced compounds: macozinone and delpazolid. In addition, this Special Issue provides an historical perspective focused on Carlo Forlanini, the inventor of pneumothorax for TB treatment, and includes an overview of the state-of-the-art technologies which are being exploited nowadays in TB drug development. Finally, a summary of TB vaccines that are either approved or undergoing clinical trials concludes the Special Issue.

Infectious diseases are the leading cause of death globally, particularly among children and young adults. The spread of new pathogens and the threat of antimicrobial resistance pose particular challenges in combating these diseases. Major Infectious Diseases identifies feasible, cost-effective packages of interventions and strategies across delivery platforms to prevent and treat HIV/AIDS, other sexually transmitted infections, tuberculosis, malaria, adult febrile illness, viral hepatitis, and neglected tropical diseases. The volume emphasizes the need to effectively address emerging antimicrobial resistance, strengthen health systems, and increase access to care. The attainable goals are to reduce incidence, develop innovative approaches, and optimize existing tools in resource-constrained settings.

An estimated 2 billion people, one third of the global population, are infected with Mycobacterium tuberculosis, the bacterium that causes tuberculosis. Spread through the air, this infectious disease killed 1.7 million in 2009, and is the leading killer of people with HIV. Tuberculosis (TB) is also a disease of poverty-the vast majority of tuberculosis deaths occur in the developing world. Exacerbating the devastation caused by TB is the growing threat of drug-resistant forms of the disease in many parts of the world. Drug-resistant tuberculosis presents a number of significant challenges in terms of controlling its spread, diagnosing patients quickly and accurately, and using drugs to treat patients effectively. In Russia in recent decades, the rise of these strains of TB, resistant to standard antibiotic treatment, has been exacerbated by the occurrence of social, political, and economic upheavals. The Institute of Medicine (IOM) Forum on Drug Discovery, Development, and Translation, in conjunction with the Russian Academy of Medical Sciences held a workshop to discuss ways to fight the growing threat of drug-resistant TB. The New Profile of Drug-Resistant Tuberculosis in Russia: A Global and Local Perspective: Summary of a Joint Workshop presents information from experts on the nature of this threat and how it can be addressed by exploring various treatment and diagnostic options.

Tuberculosis (TB) remains one of the major infectious diseases of mankind although drugs for its treatment have been available for nearly 60 years. The standard short-course 6-month regimen used since about 1980 has helped to save millions of lives, but co-infection with HIV has had a devastating effect on the epidemic, and multidrug-resistant TB is a growing problem, particularly in communities with a high incidence of HIV. Following the declaration by the WHO in the early 1990s that TB was a ‘global health emergency’, interest in TB research and the development of new drugs has increased significantly.This volume reviews anti-TB chemotherapy with the emphasis on the actions and pharmacology of existing drugs and the development and evaluation of new agents. A close look is taken at new research regarding our existing drugs by some of the best-known specialists in the field, and historical aspects of these agents are reviewed from a modern perspective. The prospects for the introduction of new drugs and different approaches of how to assess them in adults and in children are discussed in detail. Several papers address the problems associated with drug resistance, its spread and diagnosis.Compiled by two editors from Cape Town, which has a particularly high incidence of TB and is a centre of tuberculosis research, this publication is an indispensable reference for anyone involved in the management of TB either as a researcher, clinician or administrator, and those working in drug development.

In 1957, a Streptomyces strain, the ME/83 (S.mediterranei), was isolated in the Lepetit Research Laboratories from a soil sample collected at a pine arboretum near Saint Raphael, France. This drug was the base for the chemotherapy with Streptomicine. The euphoria generated by the success of this regimen lead to the idea that TB eradication would be possible by the year 2000. Thus, any further drug development against TB was stopped. Unfortunately, the lack of an accurate administration of these drugs originated the irruption of the drug resistance in Mycobacterium tuberculosis. Once the global emergency was declared in 1993, seeking out new drugs became urgent. In this book, diverse authors focus on the development and the activity of the new drug families.