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.

Over the years, India has attained a prominent global position in the manufacture of Generic Drugs. This success can be attributed to its synthetic organic chemistry and chemical engineering strengths, nurtured by the timely policies of the Government of India. However, breakthrough successes in New Drug Discovery have remained elusive, despite the brilliant and sustained efforts of many Indian researchers and Pharma establishments. The Indian National Science Academy thought it appropriate to document India's New Drug Discovery Research (NDDR) journey to date. Gathering contributions from prominent researchers in the Indian Pharma Industry and Academia, this book highlights their efforts, achievements, and the status quo of Indian NDDR. .

Tuberculosis (TB) strains with drug resistance (DR-TB) are more difficult to treat than drug-susceptible ones, and threaten global progress towards the targets set by the End TB Strategy of the World Health Organization (WHO). There is thus a critical need for evidence-based policy recommendations on the treatment and care of patients with DR-TB, based on the most recent and comprehensive evidence available. In this regard, the WHO consolidated guidelines on drug-resistant tuberculosis treatment fulfil the mandate of WHO to inform health professionals in Member States on how to improve treatment and care for patients with DR-TB. Between 2011 and 2018, WHO has developed and issued evidence-based policy recommendations on the treatment and care of patients with DR-TB. These policy recommendations have been presented in several WHO documents and their associated annexes, including the WHO treatment guidelines for multidrug- and rifampicin-resistant tuberculosis, 2018 update, issued by WHO in December 2018. The policy recommendations in each of these guidelines have been developed by WHO-convened Guideline Development Groups (GDGs), using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to summarize the evidence, and formulate policy recommendations and accompanying remarks. The present Consolidated guidelines include a comprehensive set of WHO recommendations for the treatment and care of DR-TB, derived from these WHO guidelines documents. The consolidated guidelines include policy recommendations on treatment regimens for isoniazid-resistant TB (Hr-TB) and MDR/RR-TB, including longer and shorter regimens, culture monitoring of patients on treatment, the timing of antiretroviral therapy (ART) in MDR/RR-TB patients infected with the human immunodeficiency virus (HIV), use of surgery for patients receiving MDR-TB treatment, and optimal models of patient support and care.

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.

Between 2011 and 2019, WHO has developed and issued evidence-based policy recommendations on the treatment and care of patients with DR-TB. These policy recommendations have been presented in several WHO documents and their associated annexes, including the WHO Consolidated Guidelines on Drug Resistant Tuberculosis Treatment, issued by WHO in March 2019. The policy recommendations in each of these guidelines have been developed by WHO-convened Guideline Development Groups, using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to summarize the evidence, and formulate policy recommendations and accompanying remarks. The present WHO Consolidated Guidelines on Tuberculosis, Module 4: Treatment - Drug-Resistant Tuberculosis Treatment includes a comprehensive set of WHO recommendations for the treatment and care of DR-TB. The document includes two new recommendations, one on the composition of shorter regimens and one on the use of the BPaL regimen (i.e. bedaquiline, pretomanid and linezolid). In addition, the consolidated guidelines include existing recommendations on treatment regimens for isoniazid-resistant TB and MDR/RR-TB, including longer regimens, culture monitoring of patients on treatment, the timing of antiretroviral therapy (ART) in MDR/RR-TB patients infected with the human immunodeficiency virus (HIV), the use of surgery for patients receiving MDR-TB treatment, and optimal models of patient support and care. The guidelines are to be used primarily in national TB programmes, or their equivalents in Ministries of Health, and for other policy-makers and technical organizations working on TB and infectious diseases in public and private sectors and in the community.

WHO has published a global TB report every year since 1997. The main aim of the report is to provide a comprehensive and up-to-date assessment of the TB epidemic, and of progress in prevention, diagnosis and treatment of the disease, at global, regional and country levels. This is done in the context of recommended global TB strategies and targets endorsed by WHO?s Member States, broader development goals set by the United Nations (UN) and targets set in the political declaration at the first UN high-level meeting on TB (held in September 2018). The 2019 edition of the global TB report was released on 17 October 2019. The data in this report are updated annually. Please note that direct comparisons between estimates of TB disease burden in the latest report and previous reports are not appropriate. The most recent time-series of estimates are published in the 2019 global TB report.

Vital information for discovering and optimizing new drugs "Understanding the data and the experimental details that support it has always been at the heart of good science and the assumption challenging process that leads from good science to drug discovery. This book helps medicinal chemists and pharmacologists to do exactly that in the realm of enzyme inhibitors." -Paul S. Anderson, PhD This publication provides readers with a thorough understanding of enzyme-inhibitor evaluation to assist them in their efforts to discover and optimize novel drug therapies. Key topics such as competitive, noncompetitive, and uncompetitive inhibition, slow binding, tight binding, and the use of Hill coefficients to study reaction stoichiometry are all presented. Examples of key concepts are presented with an emphasis on clinical relevance and practical applications. Targeted to medicinal chemists and pharmacologists, Evaluation of Enzyme Inhibitors in Drug Discovery focuses on the questions that they need to address: * What opportunities for inhibitor interactions with enzyme targets arise from consideration of the catalytic reaction mechanism? * How are inhibitors evaluated for potency, selectivity, and mode of action? * What are the advantages and disadvantages of specific inhibition modalities with respect to efficacy in vivo? * What information do medicinal chemists and pharmacologists need from their biochemistry and enzymology colleagues to effectively pursue lead optimization? Beginning with a discussion of the advantages of enzymes as targets for drug discovery, the publication then explores the reaction mechanisms of enzyme catalysis and the types of interactions that can occur between enzymes and inhibitory molecules that lend themselves to therapeutic use. Next are discussions of mechanistic issues that must be considered when designing enzyme assays for compound library screening and for lead optimization efforts. Finally, the publication delves into special forms of inhibition that are commonly encountered in drug discovery efforts, but can be easily overlooked or misinterpreted. This publication is designed to provide students with a solid foundation in enzymology and its role in drug discovery. Medicinal chemists and pharmacologists can refer to individual chapters as specific issues arise during the course of their ongoing drug discovery efforts.

This is the eighteenth global report on tuberculosis (TB) published by WHO in a series that started in 1997. It provides a comprehensive and up-to-date assessment of the TB epidemic and progress in implementing and financing TB prevention care and control at global regional and country levels using data reported by almost 200 countries that account for over 99% of the world's TB cases. Two years before the 2015 deadline for achievement of global TB targets the 2013 report includes a special supplement that assesses progress towards the 2015 targets and the actions needed to accelerate towards or move beyond them.The report has 8 main chapters. The introductory chapter provides general background on TB as well as an explanation of global targets for TB control the WHO's Stop TB Strategy that covers the period 2006-2015 and the development of a post-2015 global TB strategy. The remaining seven chapters cover the disease burden caused by TB (incidence prevalence mortality); TB case notifications and treatment outcomes; drug resistance surveillance among TB patients and the programmatic response in detecting and providing treatment for multidrug-resistant TB; diagnostics and laboratory strengthening for TB; addressing the co-epidemics of TB and HIV; financing TB care and control; and research and development for new TB diagnostics drugs and vaccines.The four annexes of the report include a thorough explanation of methods used to estimate the burden of disease caused by TB one-page profiles for 22 high TB-burden countries and tables of data on key indicators for all countries organized by WHO region.

Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are increasingly encountered in resource-limited settings. In the context of a national response to MDR- and XDR-TB, health workers in TB clinics (in district hospitals and some accredited health centers) will need to diagnose MDR-TB, initiate second-line anti-TB drugs, and monitor MDR-TB treatment. This Field Guide was created to help health workers carry out these tasks. It is a job aid that medical officers and TB nurses are meant to use frequently during the day for quick reference. It is based on the Emergency Update 2008 of Guidelines for Programmatic Management of Drug-resistant Tuberculosis, and may be considered a companion document to these guidelines. It also draws on the experience of the international health NGO Partners In Health (PIH) in many countries. This module should be introduced to health workers in the context of a training course with a strong emphasis on TB-HIV co-management.

Some of the more recent efforts in tuberculosis (TB) and trypanosomiasis drug discovery from both Product Development Partnerships (PDPs) and academia are highlighted in this this volume. Drug discovery approaches include both target- and phenotypic whole cell screening- approaches. Regarding the latter, mechanism of action studies through target identification are also illustrated.