9.6 Million Sick With Active TB; 480,000 New Cases Of Multidrug-Resistant TB; 1.5 Million Deaths. Infograhic courtesy of the CDC.
Infectious Diseases NIH Statement on World Tuberculosis Day, March 24, 2019 Statement of Alan Embry, Ph.D., Richard Hafner, M.D., and Anthony S. Fauci, M.D. National Institute of Allergy and Infectious Diseases, National Institutes of Health
Tuberculosis (TB) is the world’s leading infectious cause of death. In the 137 years since Dr. Robert Koch’s discovery of Mycobacterium tuberculosis (Mtb), the bacterium that causes TB, as many as one billion people worldwide have died of TB disease. This year’s World TB Day theme is “It’s Time” to end tuberculosis once and for all. We at the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, are committed to accelerating the cutting-edge research necessary to ending this ancient disease.
Mtb is transmitted through the air and primarily affects the lungs. According to the World Health Organization (WHO), an estimated 2 billion people are latently infected with TB, meaning they carry the infection in an inactive form but do not experience TB symptoms, such as cough, fever, weight loss and night sweats. A person with latent TB infection cannot transmit the bacteria to others. The U.S. Centers for Disease Control and Prevention (CDC) estimates that as many as 13 million people in the United States have latent TB infection. Overall, people with latent TB infection have a 5 to 15 percent lifetime risk of developing active TB disease. However, individuals with compromised immune systems, such as those with HIV, people receiving immunosuppressive therapy, diabetics, smokers and the malnourished are at increased risk of developing active TB disease. In 2017, an estimated 10 million new cases of active TB disease occurred worldwide, including 558,000 new cases of multi-drug resistant TB, and 1.6 million deaths, according to the WHO.
The huge burden of TB has, deservedly, made it a priority for global health leaders in recent years. At a September 2018 United Nations General Assembly High-Level Meeting on Ending TB, national leaders presented two goals to achieve by 2022: prevent at least 30 million people from developing active TB disease and treat 40 million people who are sick with the disease. In connection with that meeting, NIAID released its Strategic Plan for Tuberculosis Researchpdf, which builds on the institute’s existing TB research portfolio and details NIAID’s priorities for further understanding of TB and developing and applying cutting-edge tools to fight the disease. Specifically, the plan prioritizes expanding fundamental knowledge of TB using modern technologies, such as imaging and systems biology methods, to better understand how TB remains latent in some individuals but progresses to active disease in others, as well as the host and microbial factors that affect TB disease, transmission, and epidemiology. The Lancet Commission on TB, which includes 37 commissioners from 13 countries, echoed these priorities in its March 20 report (link is external) calling for increased global investment in TB research, scale up of existing interventions and reaching high-risk groups, and increased accountability among government leaders for TB outcomes.
In keeping with its strategic plan, NIAID also is working to find improved TB diagnostics; specifically, rapid, accurate inexpensive point-of-care tests. NIAID research played a key role in the development of the WHO-endorsed GeneXpert MTB/rifampicin resistance test currently used worldwide, and the institute continues to pursue other next-generation diagnostics. Additionally, NIAID supports a large-scale Mtb genome sequencing project at the Broad Institute in Cambridge, Massachusetts, to better understand genetic diversity and patterns of drug resistance, which will contribute to the development of new diagnostics and more rapid drug susceptibility tests for multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB).
Treating TB involves antibiotics that must be taken for six months or longer, often with toxic side effects. With MDR-TB, the drug regimens can require even longer periods (up to 20 months) and are costly and prone to failure. XDR-TB is even more difficult to treat, and effective treatment regimens may not exist for some patients. NIAID supports two-thirds of the current experimental TB treatments currently in clinical studies around the world. The focus is to identify both improved, shorter-duration treatment regimens and make better use of existing TB drugs for both treatment and prevention. For example, an NIAID-supported clinical trial comparing a 9-month regimen of isoniazid to a one-month regimen of rifapentine and isoniazid (link is external) for preventing active TB in HIV-infected patients demonstrated the shorter regimen worked just as well as the longer regimen. For treatment of active disease, the WHO approved in 2018 a shorter, all-oral treatment regimen for MDR-TB. Additionally, last year NIAID-funded researchers discovered through a refined analysis of TB strains collected from volunteers before TB treatment that they could accurately predict whether those volunteers would be likely to relapse after standard treatment was completed. This finding could help to improve TB treatment success rates and decrease the development of drug-resistant TB.
Finding a broadly effective, preventive TB vaccine remains a key focus of NIAID-sponsored research. The current Bacillus Calmette-Guerin (or BCG) vaccine, developed in 1921, protects children and infants from disseminated TB disease and death, but this protection does not extend to adults. Further, the vaccine must be kept refrigerated to remain effective. NIAID is conducting and supporting research involving multiple vaccine candidates. For example, a temperature-stable experimental TB vaccine called ID93 entered Phase 1 human clinical trials in January through NIAID’s support. A freeze-dried vaccine like ID93, if proven to be safe and effective, would be cheaper and easier to distribute in developing countries where a refrigerated supply chain is not guaranteed. NIAID has also contributed significant preclinical data to H56, a TB vaccine candidate (link is external) that may help the immune system target a protein produced during latent TB infection, helping to prevent the infection from becoming active. In other encouraging developments, GlaxoSmithKline’s M72/AS01E candidate TB vaccine reduced the incidence of pulmonary TB disease in HIV-negative adults with latent TB infection in Phase 2b clinical trials.
Significant progress had been made in the fight against TB, with a 2 percent annual decline in TB incidence worldwide and roughly 54 million lives saved through TB diagnosis and treatment between 2000 and 2017, according to the WHO. However, the challenges the disease presents are daunting and the rate of improvement not fast enough. It will require an intensified research effort, investment and collaboration with global partners to build on the progress to date and make TB a historical footnote. On this World TB Day, we stand with our global health partners in our firm resolve to end TB.
Anthony S. Fauci, M.D., is Director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, Maryland. Richard Hafner, M.D., is chief of the TB Clinical Research Branch in NIAID’s Division of AIDS. Alan Embry, Ph.D., is chief of the Respiratory Diseases Branch in NIAID’s Division of Microbiology and Infectious Diseases.