Tuberculosis causes an estimated 1.5-2 million deaths each year and rivals malaria as the most common cause of death due to a single infectious agent. Mycobacterium tuberculosis was first identified by Robert Koch in 1882, although this disease has affected humans for thousands of years. Despite decades of research on chemotherapy for the disease and the development of preventive vaccines, it remains a major public health problem and was declared a global health emergency by the World Health Organization (WHO) in 1993. Although tuberculosis is preventable and in most cases can be cured, various biological, demographic and socioeconomic factors make both prevention and treatment diffi cult. The recent resurgence in tuberculosis is attributable partly to the AIDS epidemic, while the emergence of multi-drug-resistant (MDR) and extensively drug resistant (XDR) strains also hinders efforts at disease control.
In Thailand, tuberculosis is a prominent lethal infectious disease, and is the major cause of death among AIDS patients. It is estimated that the incidence of TB in the Thai population is 135/100000, and new cases of multi-drug resistance stand at approximately 2.1% annually. Tuberculosis treatment entails short-course chemotherapy using 4-5 first-line drugs such as rifampicin, isoniazid, ethambutol, pyrazinamide and/or streptomycin. However,after nearly 30 years of use, these drugs have now become ineffective for the treatment of MDR-TB and XDR-TB. This has led to the use of more expensive, more toxic and/or less efficacious second-line drugs as therapeutic agents.
Despite many calls for the development of new anti-tubercular drugs during the past two decades, the pharmaceutical industry has, with few exceptions, shown little interest in undertaking work in this area. Drug companies neglect this disease because of the low returns from bringing a new anti-tuberculous drug onto the market. Nevertheless, new anti-tubercular drugs are needed for three main reasons: (1) to improve current treatment by shortening the total duration and/or frequency of treatment regimens, (2) to improve the treatment of MDR-TB and XDR-TB, and (3) to provide more effective treatment of latent tuberculosis infection.
In order to search for new antitubercular drugs, intensive research is being carried out in the areas of pathogenesis, latency, and resistance mechanisms. The drug discovery process encompasses basic knowledge from these areas combined with knowledge of mycobacterial genomes, and the development of high-throughput drugs screening.