Christine F. Sizemore, Ph.D., Richard Hafner, M.D., and Anthony S. Fauci, M.D. National Institute of Allergy and Infectious Diseases National Institutes of Health
Today, more than 2 billion people worldwide are infected with the bacterium that causes TB. Although most infected people do not become ill, in 2011, an estimated 8.7 million people became sick with TB, and 1.4 million people died, according to the World Health Organization (WHO). For HIV-infected individuals, TB is a major co-infection and the leading cause of mortality, killing roughly 1 in 4 people who die of AIDS. Although the number of new cases of TB globally has been slowly declining since 2006, the complexities associated with the combined HIV and TB epidemics and continued emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) TB have made global TB control efforts extremely challenging.
But there is cause for optimism. Previous decades of complacency toward the disease have been replaced in recent years with an aggressive and focused push for TB control and reinvigorated research efforts that are now showing progress. For example, the WHO-endorsed point-of-care GeneXpert TB diagnostic test, which was developed with NIAID support, has been rolled out to more than 77 countries at an increasingly reduced cost. The test, which can detect TB bacteria and drug resistance in sputum samples in two hours, has been welcomed by health care workers accustomed to waiting a month or longer for results from standard TB tests. More must be done to make the test more widely available and affordable.
Efforts are also under way to find alternatives to existing drug regimens that typically require long courses (from six months to two years) of multiple drugs, some of which cause severe side effects. NIAID has supported various stages of development for seven investigational TB drugs that are now being evaluated in clinical trials. For example, NIAID investigators, working with researchers in South Korea, found linezolid, an antibiotic used to treat severe bacterial infections, to be effective in treating hospitalized patients with XDR-TB that had previously been unresponsive to treatment. Few patients developed resistance to the drug; however, the good news associated with the initial findings was tempered by the fact that the majority of the patients experienced significant drug-related adverse events. In late 2012, NIAID launched a Phase II trial of AZD5847 to determine the drug's bacteria-killing activity in patients newly diagnosed with drug-sensitive pulmonary TB. Additionally, we are increasing our capacity to conduct TB-related research within our existing international HIV/AIDS clinical trials networks with the intent of finding improved therapies for patients with TB as well as those who are co-infected with HIV and TB. Planning for studies to evaluate promising new TB drug combinations is being coordinated with the U.S. Centers for Disease Control and Prevention's Tuberculosis Trials Consortium, the Global Alliance for TB Drug Development, and the European and Developing Countries Clinical Trials Partnership.
As with all infectious diseases, the ultimate goal for TB control is to find a vaccine to prevent TB infection. In results announced earlier this year from a large clinical trial in Africa, a candidate vaccine given to infants who had already received the licensed TB vaccine (Bacille Calmette Guerin, or BCG) proved disappointing. However, the trial, which was the first major TB vaccine study in more than 90 years, demonstrated that such large-scale studies are possible and will help inform development of future candidate vaccines. NIAID has contributed to the identification and development of eight candidate TB vaccines that are now in various stages of human testing.
Underpinning our efforts to better fight or prevent TB is research to improve our understanding of the disease, particularly how latent, or dormant, TB turns into active disease. Novel scientific approaches in the areas of systems biology and systems immunology, high-throughput drug screening, and functional and structural genomics, can help further our understanding and potentially reveal completely unforeseen ways of detecting, treating and preventing TB. Last year, NIAID launched a major project to sequence more than 1,000 drug-sensitive and drug-resistant TB strains from human samples acquired from Russia, Uganda, Korea, South Africa, Mali, and other countries. NIAID is also part of a recently formed international consortium to sequence drug-resistant strains of TB. By analyzing TB genomes tied to specific patient histories, researchers hope to better understand genetic patterns of drug resistance, identify molecular markers and pathways for new and improved drugs and diagnostics and provide key data sets for molecular epidemiology and surveillance efforts.
Progress is being made, and the strong, committed TB partnerships and collaborations that have been formed will increase this progress. However, we must find ways to accelerate our efforts to advance the TB field if we are to make a significant global impact in bringing TB under control. World TB Day reminds us that we have daunting challenges ahead.
For more information about TB, visit NIAID's Tuberculosis website.