Researchers reported Tuesday in the journal mBio that methamphetamine made it easier for the fungus Cryptococcus neoformans to colonize the lungs of mice, accelerating disease progression and leading to quicker death. The drug modified the fungus' structure, making it more effective at causing disease.
More than 12 million Americans have abused methamphetamine at least once, and an estimated 353,000 people use it regularly, according to a 2010 study published in the Annual Review of Public Health. The U.S. Department of Justice’s National Drug Threat Assessment reported an increase in meth use in 2011, especially among the young.
Although C. neoformans is usually harmless to healthy individuals, meth abuse has been shown to make people more vulnerable to infections that can endanger their health, said study author Luis Martinez, an infectious disease researcher at the Albert Einstein College of Medicine in New York City.
C. neoformans enters the body through the respiratory tract and then colonizes the lungs before migrating to the brain. Once there, it eventually causes meningoencephalitis -- inflammation of the brain and its surrounding membranes. Although antifungal drugs exist, there’s no way to treat cryptococcosis once meningoencephalitis sets in, Martinez said. At that point, death is inevitable.
Martinez and his research team have found that meth weakens the blood-brain barrier that seals the central nervous system from foreign invaders. That facilitates infection by the fungus.
Despite the large body of research examining how drugs like meth affect behavior, little is known about how they affect immunity. Since C. neoformans colonizes the lungs before traveling to the brain, the researchers set out to investigate how meth impacts infection in both of these regions.
Martinez and his colleagues periodically injected five mice with meth over the course of three weeks and then exposed them to C. neoformans. They kept five other mice meth-free to serve as controls. Nine days after infection, all the meth-treated mice were dead, while about half of the control mice were still alive. The researchers repeated the experiment twice and got similar results.
The lungs of mice exposed to meth contained large numbers of C. neoformans cells grouped in complex arrangements, which fungal cells can form to protect themselves from immune attack. The lungs of the control mice had few fungal cells. The researchers also found that meth seemed to cause the fungal cells to change their outer structure in order to escape detection by the immune system.
Exactly how the fungus enters the brain remains a mystery. Martinez thinks that the fungal cells squeeze one at a time through the cracks that meth creates in the blood-brain barrier. It’s also possible that they hide in the brain’s white blood cells and hitch a ride across, he added.
HIV may have something to do with it, too, Martinez said. Meth users are prone to contracting HIV, which increases their risk for other infections — like cryptococcosis — that usually don’t affect healthy individuals, he said.
Kirsten Nielsen, a microbiologist at North Carolina State University who was not part of the study, said more studies need to be done to see whether meth has similar effects in humans. The new findings may spur these research efforts, she said.
“We see a lot of cryptococcosis in AIDS or other immunocompromised patients, so understanding how drug use promotes a disease is very important,” she said.