The drug methamphetamine may make a user's brain more vulnerable to a deadly fungal infection called cryptococcosis, accoriding to a new study published in the journal mBio. Given this infection starts in the lungs, these findings in mice highlight the broad effects that methamphetamine has on the body.

"The highest uptake of the drug is in the lungs," said author Dr. Luis Martinez of Long Island University-Post and of Albert Einstein College of Medicine. "This may render the individual susceptible to infection."

Cryptococcus neoformans is fungus that is rare, but, according to the U.S. Centers for Disease Control and Prevention, still manages to kill nearly 625,000 people worldwide every year. Most healthy people never even realize that they are infected with the fungus because their immune systems are strong enough to eradicate the disease. Immunocompromised individuals, namely those with HIV/AIDS, suffer the brunt of the fungus, which starts in the lung but often moves to the brain where it causes life-threatening meningitis.

Because crystal meth is believed to impair the immune system, Martinez and his colleagues wondered if the drug could exacerbate cryptococcosis.

They found that meth accelerated the pace of the fungal infection in mice. After nine days of infection, 100 percent of mice given meth prior to the fungal infection were dead, whereas only half this number perished with fungus-alone.

Meth had two effects on the C. neoformans­-infected mice by changing the environment in both the lungs and the brain.

First, the drug made it easier for the fungus to stick to lung cells and form colonies, both grown in a dish and inside of the mice.

Cryptococcus neoformans secretes a sugary mixture in little capsules that help the fungus stick to lung cells and colonize the organ. Further investigation showed that meth changed the composition of this sugary liquid, which served as a possible explanation for the enhanced adhesions.

"When the organism senses the drug, it basically modifies the polysaccharide in the capsule," said Martinez. "This might be an explanation for the pathogenicity of the organism in the presence of the drug, but it also tells you how the organism senses the environment and that it will modify the way that it causes disease."

Greater lung colonization elevates the liklihood that C. neoformans­ will find its way into the bloodstream and eventually to the brain. But the brain is protected by a special cellular partition, called the blood-brain barrier, which makes it less susceptible to infections in the blood... that is, until meth enters the picture.

The researchers found that meth makes the blood-brain barrier more porous to C. neoformans­, which doubled the rate and size of brain infections.

"METH-induced alterations to the molecules responsible to maintain the integrity of the blood-brain barrier provide an explanation for the susceptibility of METH abuser to brain infection by HIV and other pathogens," wrote the authors.

Crystal meth is taken recreationally to induce feelings of elation, confidence, and sexual desire. Although abuse rates are dropping among the youth, there are still an estimated 13 million users.

The drug has a plethora of short-term and long-term health consequences, including elevated blood pressure, tooth decay, and loss of bone density.

This study displays the multifarious ways that meth can alter physiology in the lungs and brain. The authors are planning further investigations into the dynamics between methamphetaines, immunology, and the blood-brain barrier.

 

Source: Patel D, Desai GM, Frases S, et al. Methamphetamine Enhances Cryptococcus neoformans Pulmonary Infection and Dissemination to the Brain. mBio. 2013.