Leprosy, or Hansen’s disease, is a chronic infectious disease caused by the bacterium Mycobacterium leprae. It affects the skin and peripheral nerves and has been a source of social stigma for centuries. The disease’s tendency to appear in certain families raises the question of whether it is a genetic condition or purely an infection. The answer lies at the intersection of microbiology and human genetics.
How Leprosy Spreads
The bacterium Mycobacterium leprae is transmitted from person to person. The main mode of transmission is through respiratory droplets released when an infected and untreated individual coughs or sneezes. These droplets can then be inhaled by someone in close contact.
Prolonged and close contact with an untreated person is required for transmission. Casual contact, such as shaking hands, sharing meals, or sitting next to an infected person, does not spread the disease. The bacteria reproduce very slowly, and symptoms can take anywhere from one to twenty years to appear after infection.
Leprosy is not passed from a parent to a child during pregnancy. Once an individual begins multidrug therapy (MDT), they can no longer transmit the bacteria. The spread of leprosy depends on the presence of untreated individuals and conditions that facilitate close contact.
Genetic Influence on Leprosy Susceptibility
While Mycobacterium leprae is the direct cause of leprosy, exposure does not automatically lead to the disease. More than 95% of people exposed to the bacterium have a natural immunity and do not develop leprosy. This has led scientists to investigate the role of genetics in determining susceptibility, and evidence shows a person’s genetic makeup plays a significant part.
Family studies show that close relatives of people with leprosy are at a higher risk of developing the disease. This increased risk points to a shared genetic predisposition, not just shared environmental exposure. This means that genes affecting the immune system are passed down, rather than the disease itself being inherited.
Inherited genetic factors influence how the body responds to an M. leprae infection. Some genetic variations might lead to a less effective immune response, allowing the bacteria to establish themselves and cause disease. Other genetic profiles may provide a robust immune reaction that clears the bacteria, preventing symptoms. This helps explain why, within the same household, some individuals may develop leprosy while others remain healthy despite similar exposure.
Specific Genes and Immune System Links
Research has identified specific genes and gene regions associated with leprosy susceptibility, many of which are involved in the immune system. These genes help immune cells recognize and respond to invading pathogens. The Human Leukocyte Antigen (HLA) complex, for example, is a group of genes that encode proteins for distinguishing the body’s cells from foreign invaders.
Variations in the HLA gene region are linked to both susceptibility and resistance to leprosy. Certain HLA types can make it harder for the immune system to recognize M. leprae. Genome-wide studies have also associated variants in the PARK2 and LRRK2 genes with an increased risk of developing the disease.
The proteins from these genes are involved in cellular processes that manage bacteria within immune cells. For example, some genes participate in autophagy, a cellular process that can eliminate intracellular bacteria. A variation in one of these genes might impair this process, giving M. leprae a survival advantage. These links show that susceptibility is a matter of how well an individual’s immune system is genetically programmed to fight this bacterium.
Why Genetics Isn’t the Whole Story
A person’s genetic makeup is just one piece of the puzzle. The development of leprosy is a multifactorial process, depending on the interplay of several elements. While a genetic predisposition increases an individual’s risk, it does not guarantee they will get sick. Environmental and other host-related factors are also involved in determining the outcome of an exposure to M. leprae.
This multifactorial nature explains why leprosy is more common in areas with poverty and crowded living conditions. Other non-genetic factors that contribute to the outcome of an infection include:
- The intensity and duration of exposure to the bacteria.
- A person’s overall immune status, which can be influenced by nutrition and co-infections.
- Poverty, which is often linked to malnutrition and a weaker immune response.
- Crowded living conditions, which increase the likelihood of prolonged exposure.
Ultimately, whether a person develops leprosy depends on a complex interaction between the bacterium, their unique genetic profile, and their environment.