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
World TB Day, March 24, marks the day in 1882 when German microbiologist Robert Koch announced his discovery of the bacterium that causes tuberculosis (TB). Despite the considerable progress made since that discovery, TB remains one of the world's deadliest diseases. In 2013, an estimated 9 million people became ill with TB, and 1.5 million people died, according to the World Health Organization (WHO). This airborne disease is a leading killer of women and children worldwide. TB co-infection is the major cause of death among HIV-infected people, killing roughly 1 in 4 who are co-infected. The growing problems of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB further intensify the TB crisis.
WHO's theme for World TB Day 2015, Reach, Treat, Cure Everyone, highlights the continued need to effectively diagnose, treat, and cure those afflicted with the disease-many of whom live in the world's poorest, most vulnerable communities. NIAID remains committed in its broad research efforts to gain a better understanding of the disease and to find new ways to diagnose, treat, and prevent TB.
Through innovative approaches, such as mathematical modeling and genome mapping of complex biological structures, scientists are developing a greater understanding of how Mycobacterium tuberculosis (Mtb) causes disease, as well as the various stages of Mtb infection and TB disease. With NIAID's support, scientists have sequenced the genomes of approximately 2,000 Mtb strains to gain a deeper knowledge of the bacterium's genetic diversity and patterns of drug resistance-information that will contribute to the development of new diagnostics and other rapid tests for identifying patients with MDR-TB and XDR-TB.
New diagnostics and indicators, or markers, of disease to identify patients who harbor TB bacteria but do not have symptoms is a key research focus. In this regard, NIAID recently expanded its Tuberculosis Research Units program, which integrates epidemiology, immunology, and microbiology to focus on TB latency and persistence and their connection to active TB disease. Additionally, the NIAID-supported TB Clinical Diagnostic Research Consortium is evaluating several investigational diagnostics and their impact on TB management in endemic countries. NIAID supports the development of the WHO-endorsed GeneXpert MTB/RIF TB diagnostic test, which detects Mtb and drug resistance in sputum samples within two hours. Development efforts are aimed at increasing the sensitivity of Mtb detection, expanding the drug resistance markers to detect XDR-TB, as well as using non-sputum samples to facilitate diagnosis of TB in children.
Finding new TB treatments is also a major research focus at NIH. Adherence to current therapy can be difficult given that regimens require daily medications for at least six months and potentially up to two years. Moreover, with the growing threats of MDR-TB and XDR-TB, effective new medicines to overcome drug resistance are critically needed. NIAID support has contributed to more than two-thirds of the roughly 20 investigational TB drugs and drug combinations currently in clinical testing. Additionally, NIAID scientists working as part of an innovative, collaborative public-private partnership helped to identify 3,200 promising compounds for further development. In 2014, NIAID scientists and other researchers helped to identify a new type of TB treatment, called host-directed therapy, which involves manipulating the body's response to TB bacteria rather than targeting the bacteria itself.
Controlling TB infection ultimately depends on effective prevention strategies, including a vaccine. NIAID supports basic and preclinical research on new candidate TB vaccines to prevent infection or disease, as well as to help shorten the duration of TB drug treatment regimens. Several candidate vaccines have demonstrated protective effects in animal models and are now being tested in humans. Through its HIV/AIDS clinical trials networks, NIAID also evaluates preventive TB treatments for people infected with HIV.
Last year, WHO announced the goal of completely eliminating TB by 2050. NIAID remains committed to supporting and conducting the necessary research and leveraging resources with other funding agencies and organizations to reach that target. Although the challenges ahead are daunting, our resolve to end the plague of this ancient disease is steady. With continued scientific progress, we look forward to the day when World TB Day becomes a thing of the past.
Anthony S. Fauci, M.D., is the director of NIAID. Richard Hafner, M.D., is chief of the TB Clinical Research Branch in the NIAID Division of AIDS; Christine F. Sizemore, Ph.D., is chief of the Tuberculosis and Other Mycobacterial Diseases Section in the NIAID Division of Microbiology and Infectious Diseases.