Editor’s Note (6/6/23): Public health laboratories in the U.S. and Mexico have now detected the fungus Fusarium solani from cerebrospinal fluid in some patients affected by the fungal meningitis outbreak described in this article. As of June 1, the U.S. Centers for Disease Control and Prevention reports three deaths linked to fungal meningitis associated with surgeries that required epidural anesthesia at clinics in Matamoros, Mexico. One hundred and eighty-five additional patients are still under evaluation.
Certain fungal illnesses are notoriously dangerous and difficult to treat, and now a small pocket of suspected cases of fungal meningitis, a disease that affects the brain and spinal cord, is raising alarm in Texas. State and national health officials released an alert last week about the infections—all of which were in U.S. residents who had recently received surgery in the Mexican city of Matamoros, which borders on Brownsville, Tex. The infections have led to severe illness and hospitalization. One person has died.
The state’s public health investigation has so far found infections in at least five people. All are female Texas residents in their 30s to their 50s, and all had undergone surgeries in Matamoros that involved an epidural: an anesthetic injection around the spinal column. The surgeries were all cosmetic procedures, such as liposuction.
According to the Centers for Disease Control and Prevention, fungal meningitis outbreaks are rare—but they are known to sometimes occur after medical and surgical procedures. The recent alert from the Texas Department of State Health Services (DSHS) said the travelers began to develop symptoms around three days to six weeks after the surgeries. The state health officials and the CDC recommend that anyone who had an epidural during a procedure in Matamoros after January 1 of this year should monitor themselves for symptoms and consider checking in with a health care provider. “Meningitis, especially when caused by bacteria or fungus, can be a life-threatening illness unless treated promptly,” said DSHS Commissioner Jennifer Shuford in the alert.
“This is a really devastating disease,” says Jessica Brown, an associate professor of microbiology and immunology, who studies a meningitis-causing fungus called Cryptococcus neoformans at the University of Utah. “It’s tragic, and I hope the patients recover.”
The exact species behind the cases hasn’t been identified, and health officials in the Mexican state of Tamaulipas, where Matamoros is located, are investigating the situation. Two surgical clinics the travelers went to have been ordered to suspend activities.
Scientific American spoke further with Brown about what causes fungal meningitis, how outbreaks happen, how the infection is diagnosed and treated and why infectious fungi are important pathogens to monitor.
[An edited transcript of the interview follows.]
What is fungal meningitis?
Fungal meningitis is an infection of the central nervous system. It’s historically referred to as fungal meningitis but usually isn’t just of the meninges [layers of thin tissue surrounding the brain]. It’s often a meningoencephalitis—which is a serious inflammation and swelling of both the brain and the meninges. So you’ll see holes in the brain that you would get in encephalitis, as well as a meningeal infection.
What causes the disease?
Fungal meningitis can be caused by Candida species, as well as Aspergillus species. Coccidioides, the soil fungus that causes valley fever, can definitely cause meningitis. There are two other fungi that will sometimes cause meningitis: Blastomyces, a fungus that lives in moist soil and decaying wood, and Histoplasma, which is found in soil, as well as in bird and bat droppings. Blastomyces has been in the news recently because there’s a paper mill in Michigan that had a big Blastomyces outbreak. The most common cause of fungal meningitis is Cryptococcus neoformans. Cryptococcus species are thought to be found pretty much everywhere; it’s commonly associated with pigeon guano and soils.
Candida typically resides naturally in the body and on the skin. The others are environmental organisms—things we’re exposed to on a regular basis in the environment but that are capable of first establishing a lung infection and then spreading to the brain in severe cases. Fungal infections of environmental origin are not transmitted person to person. [Editor’s Note: Some fungi that cause superficial infections can pass from person to person, such as oral thrush, athlete’s foot and ringworm. Candida species also spread easily between people, often in hospitals and long-term care facilities.]
If you are looking at medical contamination, where you’re getting medicine directly injected into the spine, then anything goes. Once you get across those barriers [that usually protect the central nervous system and brain], a lot of things grow disturbingly well. There was an outbreak a few years ago when a compounding pharmacy had [a fungal] contamination, and some of their medicines were spinal injections. So things were infected before they got to the clinics where the individual patients were treated. It’s rare. It obviously means that there needs to be good inspections of such facilities. So probably something similar [could have happened with the recent cases].
I’d be careful not to condemn any one region’s health care products [and would] just emphasize the need for oversight. It’s sort of tragic that people are seeking medical care outside the U.S. and in some ways can be a sign of the problems of paying for health care here and how expensive things can be.
How is fungal meningitis diagnosed and treated?
Bacterial meningitis and viral meningitis are classically diagnosed by what’s called a Brudzinski’s sign. There’s a reflex that ties different parts of movements along the spinal column together that aren’t normally linked. So if you bend the neck, because the meninges are inflamed, the knees will also bend. Cryptococcal meningitis often does not have Brudzinski’s signs, so it can be hard to diagnose. Patients will often come in with an extremely severe headache, maybe nausea, vomiting, fever and light sensitivity, but they often don’t have those classic meningitis signs.*
There are very good diagnostic tests. You take a little bit of cerebrospinal fluid from a spinal tap and run it on a lateral flow assay—it’s very similar to a COVID test. But that’s if the doctors know to look. If they’re not looking for it, then it’s very easy to miss because it just seems like a severe headache, a fever—very generic symptoms. It can be a devastating diagnosis to miss, because without treatment, it is pretty much uniformly fatal. Treatment is an IV drug called amphotericin B, followed by usually at least a year of oral antifungals at various different dosages. The treatment is universal [across fungal species] because we really don’t have very good antifungal drugs.
How do fungal species such as C. neoformans infect the brain?
It’s very hard for things to get into the central nervous system, but when a fungus bypasses that, there aren’t a lot of barriers to prevent the growth. When people inhale a fungal cellular spore from the environment, its ability to survive is really quite impressive.
The fungus has to escape the lungs and get across the blood-brain barrier into a place that’s very tightly controlled. Then once it’s there, it has to grow further under oxygen and nutrient limitations. C. neoformans particularly grows very well on inositol, which is a [six-carbon] sugar found in cerebrospinal fluid. So once it gets into the central nervous system, there isn’t a whole lot to stop it. Fungi are pretty impressive masters of being able to adapt to these different environments and still grow in them.
One of the things we’ve been working on is studying the changes in cell shape, what’s called morphology. The cell will change into different sizes and shapes that allow it to enter these organs more easily. And we’re trying to figure out how. So there are all sorts of interesting shape-shifting and changes in [gene regulation] that are important for these environmental adaptations.
Who is at high risk of developing severe disease from fungal infections?
Globally, fungal infections in general kill around 1.6 million people per year. Fungal infections hit our very vulnerable patients. A lot of fungal infections in the U.S. are in patients who are on cancer chemotherapy that depletes their immune system. Solid organ transplant patients are also very vulnerable. Candida meningitis is a huge problem for premature babies. [Editor’s Note: Cryptococcal meningitis is also one of the leading causes of death in people with HIV/AIDS.] These are patients who are already undergoing stressful medical treatments and then get absolutely devastating fungal infections. It increases health care costs because you have these very costly and difficult-to-treat secondary infections. It dramatically affects patient quality of life because, in most cases, you’re on these drugs for a year.
Endemic fungi, such as Coccidioides, Blastomyces and Histoplasma, tend to hit people who are economically vulnerable. They’re patients who already cannot afford, say, a year off of work to treat their fungal infection. Construction workers, gardeners and people who work outdoors for a living are most vulnerable [because of higher potential exposure], but they’re also economically vulnerable. It’s easy to ignore overlooked people in society, but that doesn’t mean that these things don’t affect all of us. And if we really care about everyone’s well-being, we need to keep in mind that these diseases are a problem.
*Editor’s Note (5/23/23): This paragraph was edited after posting to correct the name of Brudzinski’s sign.
