Case Studies

Tuberculosis vignettes

Vignette 1:
Tuberculosis (TB) is a contagious and deadly, but treatable bacterial disease. Over 2 billion people world wide are infected with the TB bacteria. According to the World Health Organization, a new person becomes infected every second, with most cases in the world’s poorest countries. The mainstay of TB treatment is an antibacterial agent, isoniazid. Although treatment of TB is effective, it is not always available in many countries. The lack of effective treatment leads to nearly 2 million deaths per year. If not treated appropriately, each person with TB will infect 10 to 15 more people each year.

Vignette 2:
Isoniazid, a medication for the immediate and chronic treatment of TB, is broken down by the liver and eliminated from the body. The major mechanism of isoniazid breaking down is through an enzyme called N-acetyltransferase 2 (NAT2). Although all people have an NAT2 enzyme, genetic differences we get from our parents lead to variable levels of function. Individuals with the slow form of the NAT2 enzyme are called “slow acetylators.” Individuals with a rapid form of the NAT2 enzyme are termed “fast acetylators”.

Vignette 3:
The ratio of slow and fast NAT2 differs across the globe. For example, most of the Egyptian population (92%) have the slow form and don’t break down isoniazid as efficiently. Slow acetylators allow higher levels of isoniazid in the body for a longer time and increase the risk of liver damage when taking isoniazid. In contrast, more than half of the population in Colombia (51%) break down isoniazid quickly and are fast acetylators. Fast acetylators break down isoniazid and are less likely to develop liver problems when taking isoniazid. The prevelance of slow NAT2 in a population will change the way we can monitor to catch any liver damage early.