Basics

Tuberculosis (TB) is a lung disease caused by the bacterium Mycobacterium tuberculosis, which is transmissible from person to person by coughing and sneezing. TB infections can be either latent (no symptoms) or active (causes disease symptoms), and only active cases are transmissible. An infection will become an active case in about 5-10% of people, although antibiotics can be used to reduce an individual’s likelihood to develop an active case. (Source: WHO)

Disease Burden

Despite the high rate of latent cases, TB is the world’s most deadly infectious disease, killing nearly 1.5 million people each year. About a quarter of the world’s population has a TB infection, and it causes 1/40th of all deaths worldwide. Untreated TB has about a 45% fatality rate in HIV-negative people. In HIV-positive people, the fatality rate is near 100%–TB and HIV reinforce each other dangerously, and the presence of HIV also makes it more difficult to treat or vaccinate against TB. This relationship between HIV and TB is particularly dangerous, as the greatest part of the TB disease burden is carried by areas of the world where HIV is also prevalent. 30 countries account for 87% of new TB cases, with India hardest-hit. (Source: WHO)

Treatment

TB can be treated with a course of antibiotics, such as isoniazid monotherapy, which, if the course is followed, can reduce the chance of a latent case of TB turning into an active case by 93%. A course of antibiotics will cure active TB 90% of the time, but active TB still leads to death 3% of the time for HIV-negative patients. In addition, isoniazid, a primary component of TB treatment, can cause liver damage which results in death between 0.02% and 0.06% of the time.

Why Are We Interested In Challenge Trials?

Given the enormous numbers of people that TB affects and the dangers of TB, developing a safe and effective TB vaccine would be a historic achievement. TB vaccine specialists advocate (1, 2, 3) for using challenge trials for TB vaccines, and human challenge models have already been successfully used in vaccine development for endemic diseases in similar regions, like cholera and malaria. A TB challenge model could more cheaply test vaccines before spending hundreds of millions or billions of dollars on large natural efficacy studies, and they could also establish which immune responses correlate to effective protection. It would be excessively dangerous to run a challenge study for TB at this point, due to the risk of TB infections becoming active and spreading TB outside of the study, but there is active research investigating ways to make a TB challenge study acceptably safe.

Current State Of The Art

There is a vaccine, BCG, but it is only about 50% effective at reducing the risk of TB, with widely varying efficacy. It was developed nearly a century ago and there is no better alternative.

There is ongoing research to develop strains of TB that would have a limited period of replication or built-in “kill switches” that would prevent community transmission and limit the severity of symptoms. The advantages of using an attenuated strain would need to be balanced against the importance of using a challenge strain that mimics a wild-type strain in order to ensure vaccine efficacy.