NIAID Now | March 24, 2020
Despite more than 100 years of dedicated research, tuberculosis (TB) is still the world’s leading cause of death from a single infectious disease. Since Dr. Robert Koch’s 1882 discovery of Mycobacterium tuberculosis (Mtb), the bacterium that causes TB, as many as one billion people have died of TB disease. To mark World TB Day this year, we at the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, again join the world’s public health organizations in declaring that “It’s Time” to consign tuberculosis to the history books by conducting the research needed to end this disease.
Tuberculosis primarily affects the lungs and is transmitted through the air. Symptoms of active TB disease include cough, fever, weight loss and night sweats. Although active TB can be lethal, the bacterial infection can also lie inactive as “latent TB,” causing no symptoms for weeks, months, or even years after initial infection. People with latent TB infection cannot transmit the bacteria to others. However, they have a 5-to-10 percent lifetime risk of developing active TB. Individuals with compromised immune systems, such as those with untreated HIV, receiving immunosuppressive therapy, with diabetes, smokers, and the malnourished are especially prone to develop active TB. The U.S. Centers for Disease Control and Prevention (CDC) estimate that as many as 13 million people in the United States have latent TB infection. According to the World Health Organization (WHO), around one-quarter of the world’s population has latent TB, and in 2018 alone,10 million people became sick with TB, and 1.5 million people died of TB disease.
Consequently, global health leaders have prioritized the search for TB vaccines, treatments and cures. Following the United Nations General Assembly High-Level Meeting on Ending TB in September 2018, NIAID released its Strategic Plan for Tuberculosis Research, which outlines NIAID’s priorities for continuing the fight against TB. The plan emphasizes the need for using cutting-edge technologies to better understand how the bacterium functions. The plan also prioritizes research to better understand how TB remains latent or progresses to active disease, as well as the many complex elements that impact transmission, TB disease severity, and treatment outcomes. This research may lead to new tools for healthcare providers to diagnose, treat or prevent TB.
Drug-sensitive TB treatment involves a course of antibiotics given for at least six months. Treatment may last for 24 months if the bacteria are resistant to multiple antibiotics, known as multi-drug resistant TB (MDR-TB). These long treatment courses may lead to poor adherence, can be expensive, and often cause toxic side effects. Extremely drug-resistant TB (XDR-TB) is even more difficult to treat, leaving some patients with few to no options for a cure. NIAID’s TB research program is focused on finding better prevention and treatment regimens that may include both new and older drugs and can be completed in less time. For instance, a Phase 3 clinical study examined the effect of different antibiotic regimens on both adults and adolescents living with HIV, who are at an increased risk for TB. The study demonstrated that a one-month course of two antibiotics worked as well as a nine-month regimen of a single drug to prevent TB disease.
In addition, in June 2019, NIAID partnered with NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, to launch a large TB prevention trial in 12 countries. The trial will test two oral drug regimens for preventing active TB in adults, teens, and children who live with adults who have multidrug-resistant TB. Also in 2019, a new anti-TB drug was added to the treatment toolbox when the United States Food and Drug Administration (FDA) approved pretomanid, a drug which received preclinical development support from NIAID, for use together with two other drugs for the treatment of MDR- and XDR-TB. Based on the success of this drug regimen in recent clinical trials, the World Health Organization (WHO) issued a Rapid Communication for use of this drug regimen under certain conditions, for treatment of XDR-TB. NIAID continues to help advance other drug candidates and regimens.
On a global scale, a broadly effective TB vaccine, which could prevent infection or active disease, could have a sizable impact on TB cases worldwide. An available TB vaccine was first developed in 1921—the Bacillus Calmette-Guerin (or BCG) vaccine—but only protects children and infants from disseminated TB disease and death. This protection does not extend to adults with pulmonary TB, the most common form of the disease. Thus, improving this vaccine and developing new vaccines remains a priority for NIAID. An innovative NIAID-supported study in macaques, published earlier this year, demonstrated that the BCG vaccine administered intravenously instead of via a standard skin injection, was significantly better for preventing disease following challenge with virulent Mtb.
Moreover, NIAID is supporting research into new candidate TB vaccines. Last year, ground-breaking results from a Phase 2b clinical trial demonstrated that GlaxoSmithKline’s candidate TB vaccine, M72/AS01E, significantly reduced the incidence of pulmonary TB disease in HIV-negative adults with latent TB infection. NIAID supported early studies of this vaccine candidate. To further advance the development of potential TB vaccines, NIAID established three Immune Mechanisms of Protection Against Mycobacterium tuberculosis (IMPAc-TB) Centers in 2019. Multi-disciplinary research teams in these Centers will elucidate the immune responses needed to prevent initial TB infection, establishment of latent TB infection, and transition of latent infection to active TB disease. Findings from animal and human studies conducted at these Centers will inform the development of additional novel TB vaccine candidates.
Each World TB Day, we mark the scientific advances of recent years—advances which have resulted in significant real-world impacts. Between 2000 and 2017 alone, the world saw a 2 percent annual decline in TB incidence worldwide, and the WHO calculates that roughly 54 million lives were saved through TB diagnosis and treatment. However, these successes are not enough. Today, we stand with the global health community to defy the challenges posed by TB and renew our commitment to ending this disease.