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.

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.

To effectively treat patients diagnosed with drug-resistant (DR) tuberculosis (TB) and protect the population from further transmission of this infectious disease, an uninterrupted supply of quality-assured (QA), second-line anti-TB drugs (SLDs) is necessary. Patients diagnosed with multidrug-resistant tuberculosis (MDR TB)-a disease caused by strains of Mycobacterium tuberculosis (M.tb.) resistant to two primary TB drugs (isoniazid and rifampicin)-face lengthy treatment regimens of 2 years or more with daily, directly observed treatment (DOT) with SLDs that are less potent, more toxic, and more expensive than those used to treat drug-susceptible TB. From 2000 to 2009, only 0.2-0.5 percent of the estimated 5 million MDR TB cases globally were treated with drugs of known quality and in programs capable of delivering appropriate care (Keshavjee, 2012). The vast majority of MDR TB patients either died from lack of treatment or contributed to the spread of MDR TB in their communities. A strengthened global supply chain for SLDs could save lives by consistently delivering high quality medicines to more of the people who need them. This public workshop explored innovative solutions to the problem of how to get the right SLDs for MDR TB to people who critically need them. More specifically, the workshop examined current problems and potential opportunities for coordinated international efforts to ensure that a reliable and affordable supply of high-quality SLDs is available. Developing and Strengthening the Global Supply Chain for Second-Line Drugs for Multidrug-Resistant Tuberculosis: Workshop Summary covers the objectives of the workshop, which were to review: -To what extent and in what ways current mechanisms are or are not effectively accomplishing what is needed, including consideration of bottlenecks. -The advantages and disadvantages of centralization in the management of the global drug supply chain, and potential decentralized approaches to improve operations of the supply chain. -What can be learned from case studies and examples from other diseases (e.g., the Affordable Medicines Facility-malaria (AMFm) and the U.S. President's Emergency Plan for AIDS Relief [PEPFAR]) - The current allocation of responsibilities and roles of the private (including industry and nonprofit public health organizations) and public sectors, and examination of opportunities for enhancing and optimizing collaboration -Identification of potential innovative solutions to the problem

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.

Mots-clés de l'auteur: tuberculosis ; anti-TB drugs ; drug discovery and development ; drug resistance ; QcrB inhibitors ; natural product lapachol ; F420 cofactor ; benzothiazinone ; PBTZ169.

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 (TB) refers to a type of infectious disease generally caused by Mycobacterium tuberculosis. Lungs are the primary target of this disease, but it can also affect the other parts of the body. It can be treated with a combination of antibacterial medications. However, the evolution of drug-resistant tuberculosis necessitates the development of effective, novel and safe drug regimens. Drug discovery and development is a difficult, expensive and time-consuming process. One of the popular frameworks used in drug discovery is model-informed drug discovery and development (MID3). It aims to provide an informative prediction of drug efficacy and exposure in people for choosing innovative anti-tuberculosis drug combinations. This book is compiled in such a manner, that it will provide in-depth knowledge about drug discovery for treating tuberculosis. Those with an interest in this area of pharmaceutical science would find it helpful.