Editor’s Note (6/6/23): Public health laboratories in the US and Mexico have now discovered 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 associated with fungal meningitis associated with surgeries requiring epidural anesthesia at clinics in Matamoros, Mexico. One hundred and eighty-five additional patients are still being evaluated.
Certain fungal diseases are notoriously dangerous and difficult to treat, and now a small number of suspected cases of fungal meningitis, a disease that affects the brain and spinal cord, are raising alarm in Texas. State and national health officials issued a warning last week about the infections – all in US residents who recently had surgery in the Mexican town of Matamoros, which borders Brownsville, Tex. The infections have led to serious illness and hospitalization. One person has died.
The state’s public health investigation has found infections in at least five people so far. They are all female Texas residents in their thirties to fifties, and all had surgeries in Matamoros that involved an epidural: an anesthetic injection around the spine. The surgeries were all cosmetic procedures, such as liposuction.
According to the Centers for Disease Control and Prevention, outbreaks of fungal meningitis 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 started developing symptoms about three days to six weeks after the surgeries. State health officials and the CDC recommend anyone who has had an epidural during a procedure in Matamoros January 1 of this year should check themselves for symptoms and consider checking in with a healthcare provider. “Meningitis, especially when caused by bacteria or fungi, 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 Brownan 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 has not been identified and health officials in the Mexican state of Tamaulipas, where Matamoros is located, are investigating the situation. Two surgical clinics where the travelers went ordered to suspend operations.
Scientific American went on to talk to 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 called fungal meningitis, but it’s usually not just of the meninges [layers of thin tissue surrounding the brain]. It is often meningoencephalitis, a severe inflammation and swelling of both the brain and meninges. So you’ll see holes in the brain that you’d get in encephalitis, as well as a meningeal infection.
What causes the disease?
Fungal meningitis can be caused by Candida types, as well Aspergillus kind. Coccidioids, the soil fungus that causes valley fever, can certainly cause meningitis. There are two other fungi that sometimes cause meningitis: blastomyces, a fungus that lives in moist soil and rotting wood, and histoplasm, which is found in the soil, but also in bird and bat droppings. blastomyces has been in the news recently because there a paper mill in Michigan that had a big one blastomyces outbreak. The most common cause of fungal meningitis is Cryptococcus neoformans. Cryptococci species are thought to exist almost everywhere; it is often associated with pigeon guano and bottoms.
Candida usually occurs naturally in the body and on the skin. The others are environmental organisms – things that we are regularly exposed to in the environment, but which are capable of acquiring a lung infection first and then spreading to the brain in severe cases. Fungal infections of environmental origin are not transmitted from 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.]
When you look at medical contagion, where drugs are injected directly into the spine, anything is possible. Once you get over those barriers [that usually protect the central nervous system and brain], many things are growing alarmingly well. There was an outbreak a few years ago had a compounding pharmacy [a fungal] infection, and some of their drugs were spinal injections. So things were contaminated before they reached the clinics where the individual patients were treated. It is rare. It obviously means that proper inspections of such facilities must take place. So probably something similar [could have happened with the recent cases].
I would be careful not to condemn the healthcare products of any region [and would] just emphasize the need for supervision. It’s kind of tragic that people are seeking medical care outside of the US and in some ways it can be a sign of the difficulties 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 is called a Brudzinski’s sign. There is a reflex that connects different parts of movements along the spine that are not normally connected. 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 difficult to diagnose. Patients often come in with extremely severe headaches, perhaps nausea, vomiting, fever and light sensitivity, but often do not have those classic signs of meningitis.*
There are very good diagnostic tests. You take a little bit of cerebrospinal fluid from an epidural and run it on a lateral flow assay – it’s very similar to a COVID test. But that’s if the doctors know how to look. If they’re not looking for it, it’s very easy to miss because it only looks like a severe headache, fever – very common symptoms. It can be a devastating diagnosis to miss because without treatment it is almost always fatal. The treatment is called an IV drug amphotericin B, followed by usually at least a year of oral antifungal drugs at various doses. The treatment is universal [across fungal species] because we really don’t have very good antifungal drugs.
How fungi species such as C. neoformans infect the brain?
It’s very hard for things to get into the central nervous system, but if a fungus gets around that, there aren’t many barriers to prevent its growth. When humans inhale a cell spore from an environmental fungus, its ability to survive is really quite impressive.
The fungus has to escape from the lungs and get through the blood-brain barrier at a place that is very tightly controlled. Once there, it must continue to grow under oxygen and nutrient restrictions. C. neoformans special grows very well on inositolwhat is one [six-carbon] sugar found in cerebrospinal fluid. So once it gets into the central nervous system, there’s not much to stop it. Fungi are pretty impressive masters at 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, called morphology. The cell will change into different sizes and shapes making it easier for it to enter these organs. And we’re trying to figure out how. So there are all kinds of interesting shape changes and changes in it [gene regulation] that are important for these environmental adaptations.
Who is at high risk of developing serious illness from fungal infections?
Worldwide fungal infections in general kills about 1.6 million people a year. Fungal infections affect our very vulnerable patients. Many fungal infections in the US are in patients undergoing cancer chemotherapy that depletes their immune systems. 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 develop absolutely devastating yeast infections. It increases healthcare costs because you have these very expensive and difficult to treat secondary infections. It has a dramatic impact on the patient’s quality of life because in most cases you take these drugs for a year.
Endemic fungi, such as coccidioids, blastomyces And histoplasm, tend to affect people who are economically vulnerable. They are patients who, for example, can afford to take a year off from work to treat their fungal infection. Construction workers, gardeners and people who work outside the home are the most vulnerable [because of higher potential exposure]but they are also economically vulnerable. It’s easy to ignore overlooked people in society, but that doesn’t mean these things don’t concern us all. And if we really care about everyone’s well-being, we have 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 board.
