Meth Use Linked to Deadly Fungal Infection

Fran Lowry

August 02, 2013

Methamphetamine use may make individuals more prone to cryptococcosis, a deadly fungal infection affecting the lungs, and ultimately the central nervous system, new research shows.

An animal study conducted by investigators at Long Island University Post in Brookville, New York, and Albert Einstein College of Medicine in New York City found that methamphetamine injections significantly enhanced colonization of the lungs by Cryptococcus neoformans and hastened progression of the infection and time to death in mice.

"This drug of abuse stimulates colonization and biofilm formation in the lungs, followed by dissemination of the fungus to the central nervous system," the authors, led by Luis R. Martinez, PhD, write.

The study was published online July 30 in mBio.

Accelerated Time to Death

Cryptococcosis is caused by the encapsulated fungus C neoformans, the most common cause of fungal meningitis in patients with AIDS.

C neoformans is usually harmless in healthy individuals, but methamphetamine causes chinks in the blood-brain barrier that can permit the fungus to invade the central nervous system, where it causes a deadly brain infection.

There is a large body of research examining how drugs such as methamphetamine affect behavior, but little is known about how they affect immunity, Dr. Martinez said.

Dr. Luis Martinez

"Since C neoformans is an encapsulated opportunistic pathogen and colonizes the lungs before traveling to the brain, we investigated how methamphetamine, or meth, impacts infection in both of these regions," he said.

To study this effect, the researchers injected mice with doses of methamphetamine over a period of 3 weeks. They then exposed the mice to the C neoformans fungus.

Methamphetamine significantly accelerated the speed with which the infected mice died. Nine days after infection, 100% of methamphetamine-injected mice were dead, compared with 50% of the control mice.

When the researchers examined lung tissue in methamphetamine-treated and control mice using fluorescent microscopy, they found that methamphetamine enhanced the interaction of C neoformans with epithelial cells in the lining of the lung.

Seven days after exposure to the fungus, the lungs of methamphetamine-treated mice showed large numbers of fungi surrounded by vast amounts of gooey polysaccharide in a biofilm substance.

The methamphetamine-treated mice also showed low numbers of inflammatory cells early in the course of infection and breathed faster than control mice, which is a sign of respiratory distress.

"When C neoformans senses meth, it basically modifies the polysaccharide in the capsule," Dr. Martinez said. "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."

He added that understanding how drug use promotes a disease is very important.

Another Negative Consequence

Commenting on the findings for Medscape Medical News, Gaya Dowling, PhD, branch chief, Science Policy Branch at the National Institute on Drug Abuse (NIDA), Bethesda, Maryland, said that they are important for all healthcare professionals but particularly addiction psychiatrists, enabling them to understand the myriad consequences of methamphetamine abuse "so they can communicate these risks to their patients."

Methamphetamine is a highly addictive stimulant drug that causes significant consequences psychologically, medically, and socially for those who abuse it, said Dr. Dowling.

"Abusing the drug can cause memory loss, aggression, psychotic behavior, damage to the cardiovascular system, malnutrition, and severe dental problems. Methamphetamine abuse also contributes to increased transmission and progression of infectious diseases, such as HIV/AIDS," Dr. Gaya said.

"This new study furthers this body of research to show how meth can also impact opportunistic infections associated with HIV, such as Cryptococcus neoformans, the most common cause of fungal meningitis in patients with AIDS. Meth enhances the actions of C neoformans in lung tissue, ultimately leading to chronic lung infection. Once established, the fungal infection within the lung serves as a reservoir for further fungal assault, including penetration of the blood-brain barrier and infection of the brain. Clinicians must inform their patients that meth use and abuse will increase their risk of serious, life-threatening infections."

Dr. Martinez and Dr. Dowling report no relevant financial relationships.

MBio. Published online July 30, 2013. Full article

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