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In its most recent tally, the U.S. Centers for Disease Control and Prevention (CDC) confirms 105 cases of rare fungal meningitis and eight deaths in patients who received epidural steroid injections to treat back pain.
The CDC reports that the illness has been seen in nine states — Florida, Indiana, Maryland, Michigan, Minnesota, North Carolina, Ohio, Tennessee and Virginia — stemming from three contaminated lots of methylprednisolone acetate injections produced by New England Compounding Center (NECC).
Federal health investigators and state officials are looking closely at the Framingham, Mass., facility where NECC made more than 17,000 potentially tainted steroid injections — which are believed to have been tainted with two types of fungus, Aspergillus and Exserohilum, during manufacturing — and shipped them to 75 clinics in 23 states. NECC has since recalled all of its products.
(MORE: Meningitis Outbreak Grows, Highlighting Dangers of Compounding Pharmacies)
The CDC estimates that about 13,000 patients may have been exposed to the contaminated steroid injections, and clinics are continuing to reach out to all patients who may have been affected. In Ohio, health officials are even mobilizing sheriff’s offices to locate people who may have been exposed, Reuters reports. “If that means knocking on doors, then that’s what they will do,” Beth Bickford, executive director at the Association of Ohio Health Commissioners, said in a statement.
The CDC expects to see additional infections, but says that far fewer than the number of people exposed to the contaminated injections will become ill.
“Since we are still unfortunately in the early days of this investigation, it is anticipated that new cases will come to light over the next several weeks,” says Dr. William Schaffner, chairman of the department of preventive medicine at Vanderbilt University Medical Center. “This is an ongoing story and there may be new twists of which we are of the moment unaware. There will probably be new information every day in the foreseeable future.”
Here are the five things you should know about fungal meningitis and how it’s treated:
1. How is fungal meningitis typically contracted?
First, patients should be aware that fungal meningitis is extremely rare and not contagious. A variety of fungi may cause meningitis; spores can be inhaled in the environment, from infected soil, or sometimes in a hospital setting. Meningitis develops when the fungus spreads through the blood to the spinal cord. Although anyone can get fungal meningitis, patients with weakened immune systems like those with AIDS or cancer are at higher risk, according to the CDC. Steroid drugs, such as those used by the patients who were infected in the current outbreak, can also reduce immunity, as can drugs taken after organ transplants and medications that treat rheumatoid arthritis and other autoimmune conditions. In general, epidural injections are considered safe and complications are rare.
2. What are the symptoms?
Meningitis is an inflammation of the brain and spinal cord lining, and fungal meningitis occurs when the membranes protecting the brain and spinal cord become infected with fungus. Symptoms of fungal meningitis include fever, headache, stiff neck, nausea and vomiting, sensitivity to light, weakness and numbness. Patients who may have received the contaminated injections should also look out for increasing pain as well as redness and swelling at the injection site. If the infection continues long enough without treatment, it may impact consciousness causing patients to lapse into a coma state, says Schaffner.
Aspergillus-related meningitis can also impact patient’s blood vessels, causing clots and bleeding as well as trouble speaking and maintaining stability. Schaffner warns these symptoms can often be mistaken as side effects of a small stroke. “This is the sort of information we are getting out to both patients and doctors. This way patients who have had these inoculations and appear as though they had a stroke can get tested for this fungal meningitis,” he says.
(MORE: Doctors Say Steroid Shots for Spine Are Usually Safe)
3. How is fungal meningitis diagnosed?
If fungal meningitis is suspected, the most secure diagnosis is made with a lumbar puncture or spinal tap. The cerebrospinal fluid surrounding the brain and spinal cord is withdrawn and the examined under the microscope by the physician. The fluid is also sent to a laboratory where the fungus is isolated and grown. “This procedure can be done safely and efficiently with very little discomfort,” says Schaffner.
4. How is the infection treated?
The infection is treated with antifungal medications administered in a hospital through an IV. Although bacterial meningitis can be treated within a week, fungal meningitis can take much longer, sometime longer than a month. “We have fewer antifungal drugs available and because this whole instance of fungal meningitis is so unusual, there is very little clinical experience,” says Schaffner. The two drugs used to treat fungal meningitis, amphotericin B and voriconazole, can also cause serious side effects like liver and kidney damage and must be monitored meticulously by physicians.
5. How is it different from bacterial or viral meningitis?
Bacterial and viral meningitis are more common than fungal meningitis. The bacteria and viruses that cause these other types of meningitis can be contagious, but they will not necessarily cause meningitis in those who are exposed or infected.
Symptoms of fungal meningitis present themselves much more slowly than those of bacterial meningitis. “Symptoms of bacterial meningitis come on quite suddenly and very prominently,” says Schaffner. “ they kind of just ease on for the most part. The onset is not as dramatic and they become gradually more severe.”
Both Schaffner and the CDC recommend that any individual who received the injectable steroids and are experiencing symptoms to alert their doctor as soon as possible. Early diagnosis is crucial for the most effective treatment.
Q&A: Facts About the Meningitis Outbreak
How many people are at risk in this outbreak?
The investigation indicates that there were over 17,000 vials of this potentially contaminated medication produced. There may be some variability from vial to vial within each batch. It has been estimated that something like 13,000 people were exposed to this medication; some of it hadn’t been used yet by the time the alert went out, and some people received more than one dose. That’s very large. If there is a silver lining in this dark cloud, it’s that the proportion of people who received this medication who are actually getting sick is rather low. It looks to be less than 5 percent.
What are the symptoms?
The symptoms are insidious. They begin slowly and not very dramatically: fever and chills, headache and a stiff neck from the inflammation. People lose their appetite, feel ill, can be nauseated and can vomit. But there’s something else that’s subtle: It seems these fungi have the capacity to invade little blood vessels in and around the brain, cause bleeding and produce symptoms that mimic a stroke—difficulty speaking, loss of balance and trouble walking. Those symptoms can occur even without fever, so physicians have to learn that patients who present with stroke symptoms may actually be part of this.
Membranes protect the brain and spinal column from harmful particles that might be circulating in the blood. How does the fungus get past the blood–brain barrier?
The fungi were inoculated adjacent to this barrier but it is still a bit of a mystery how they were able to translocate from outside the membranes into and beyond the membranes.
There are a couple of theories. One is that the fungi begin to multiply in a secluded space, then they kind of eat their way through the membranes. Another hypothesis is: Could the inoculation have nicked the membrane and provided a microscopic mode of access? Practitioners who perform these procedures say this happens very rarely, but it remains to be seen.
People who die of the infection will receive postmortem examinations—autopsies. Careful study will help us understand what happened in this circumstance and how to prevent this from happening in the future.
What treatment options are available?
There are two major drugs, called amphotericin B and voriconazole. Both of those drugs are effective if we get in early. They are given intravenously initially, and then we hope we can transition to oral variations. They have substantial side effects, and we have to walk a kind of tightrope to treat the patient without damaging the kidneys or the liver.
This is all new territory for all of us, so we will learn as we go how completely we can treat these patients and how quickly or slowly it takes them to get better. We know that it is much slower than the treatment of bacterial meningitis.
Could you get fungal meningitis from an injection in locations other than adjacent to the spinal cord—the knee or shoulder, for example?
We know that some of these steroid vials were injected into the knees and shoulders and other joints for people who had painful inflammation in those joints. We anticipate that in the course of this outbreak we will discover people who developed infections in those joints. But those infections would not then cause meningitis.
How could the fungus have contaminated the medication?
All pharmaceutical manufacturers should adhere to good manufacturing practices and guidelines. We don’t know what went wrong, but certainly some of those practices were likely not adhered to and that opened the door for contamination. We’ll have to wait and see what the investigation tells us.
Are epidural steroid injections safe from other facilities?
Yes. Steroid preparations from other manufacturers are safe, and they can continue to be used. If you received an injection from one of those, you need not worry.
Do you think this outbreak should prompt a change in how compounding facilities are overseen?
I think these compounding pharmacies have fallen into a gap within our regulatory framework. I daresay we will see congressional hearings that address that. My own thought is that the Food and Drug Administration needs to be given explicit authority, and it needs to be given the appropriate resources so it can do the job. I think the whole role of these compounding facilities in our society and our medical care system will come under close examination.
How much longer will this outbreak last? When do we know it has run its course?
Sadly, we will see more cases. The incubation interval—the interval between the exposure, the inoculation and the onset of symptoms—can be quite prolonged. We initially thought it might extend as long as a month. But just recently it has been suggested that it can go beyond that—two months, maybe even three months. As the outbreak evolves and we gather new information, we’ll get a better idea, but for the next several weeks we will continue to see, unfortunately, new patients identified and needing therapy.
Fungal meningitis is rare, however the most common cause is Cryptococcus spp. infection, but many other fungi may occasionally cause meningitis.
Fungal meningitis is not transmitted from person to person. The fungi are usually inhaled and then spread by the blood to the central nervous system; fungi may also be directly inserted into the central nervous system by medical techniques or enter from an infected site near the central nervous system to cause meningitis.
Fungal meningitis is rare and usually the result of spread of a fungus through blood to the spinal cord. Although anyone can get fungal meningitis, people with weakened immune systems, like those with HIV infection or cancer, are at higher risk.
The most common cause of fungal meningitis for people with weakened immune systems is Cryptococcus. This disease is one of the most common causes of adult meningitis in Africa.
You may also get fungal meningitis after taking medications that weaken your immune system. Examples of these medications include steroids (such as prednisone), medications given after organ transplantation, or anti-TNF medications, which are sometimes given for treatment of rheumatoid arthritis or other autoimmune conditions.
Different types of fungus are transmitted in several ways. Cryptococcus is thought to be acquired through inhaling soil contaminated with bird droppings, and Histoplasma is found in environments with heavy contamination of bird or bat droppings. Blastomyces is thought to exist in soil rich in decaying organic matter. Coccidioides is found in the soil of endemic areas. When these environments are disturbed, the fungal spores can be inhaled. Meningitis results from the fungal infection spreading to the spinal cord. Candida is usually acquired in a hospital setting.
Fungal meningitis is treated with long courses of high dose antifungal medications, usually given through an IV line in the hospital. The length of treatment depends on the status of the immune system and the type of fungus that caused the infection. For people with immune systems that do not function well because of other conditions, like AIDS, diabetes or cancer treatment is often longer.
No specific activities are known to cause fungal meningitis. Avoid soil and other environments that are likely to contain fungus. People with weakened immune systems (for example, those with HIV infection) should try to avoid bird droppings and avoid digging and dusty activities, particularly if they live in a geographic region where fungi like Histoplasma, Coccidioides, or Blastomyces species exist. HIV-infected people cannot completely avoid exposure.
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But they may be slow to develop and mild.
“The speed at which people get sick is very different,” says Benjamin Park, MD, medical officer at the Mycotic Diseases Branch of the CDC.
Unlike bacterial and viral forms of meningitis, which tend to develop within hours, fungal meningitis “creeps up on you,” Park says.
“People who have gotten infected, they’ve had somewhat milder symptoms than you would expect,” says Park.
Park says nearly everyone who has gotten sick has had a headache, for example, but the headache wasn’t the worst-kind-you’ve-ever-had-in-your-life variety, as often comes with bacterial or viral meningitis.
In a few cases, Schaffner says, the first indication that anything was wrong was a stroke. “Patients can present with difficulty speaking, difficulty with their sense of balance or walking,” he says.
How long does it take to get sick?
“There’s a big range,” Park says. “We’ve had people who’ve gotten sick less than a week after their injection, and we’ve had people that have gotten sick, the longest now is up to 42 days,” he says.
“It’s important for people to stay vigilant for symptoms because we don’t know enough to reassure people that they’re safe,” says Park.
I’ve had a “meningitis” vaccine. Will that protect me?
The meningococcal vaccine protects against bacteria that cause meningitis and other meningococcal disease. It doesn’t protect against fungal infection.
How is fungal meningitis diagnosed?
Doctors insert a needle into the lower part of the back to collect a fluid sample. The test is called a lumbar puncture. The fluid is sent to a lab, where technicians culture it to see if fungus will grow.
It’s difficult to get fungus to grow under laboratory conditions, however, and yesterday the CDC said that some people who get meningitis will test negative for fungus.
In those cases, Schaffner says, doctors look for other signs of an infection in the spinal fluid to make the diagnosis.
“There would be an elevated number of white blood cells. The protein concentration would be high and the glucose, or sugar concentration, would be low. So that would indicate that the patient would have inflammation of those membranes surrounding the brain, and we would know that something is wrong, and we would treat the patient for meningitis,” he says.
Fungal Meningitis Overview
In early September 2012, three batches of improperly purified methylprednisolone acetate were distributed from the New England Compounding Center (NECC) in Framingham, Massachusetts, to 23 states across America. Over the past three months these nonsterile steroid vials have caused a nationwide outbreak of fungal meningitis and joint infections that have infected 438 people in 19 states, and killed 32 people as of November 9, 2012. The NECC issued a recall for the three tainted lots of steroid injections on September 26th and the CDC estimates that there was an estimated 42-day risk period that ended on November 7, 2012. Although the risk period has ended, this outbreak provides a unique opportunity to review some of the signs, symptoms, and recommended treatment related to fungal meningitis.
The signs and symptoms of fungal meningitis are identical to other forms of meningitis. Predominant symptoms include fever, headache, stiff neck, nausea, vomiting, photophobia, and altered mental status. Unlike viral or bacterial meningitis, fungal meningitis is not contagious and can only cause infection if the fungus enters the bloodstream and directly accesses the central nervous system, or if there is an infected site near the CNS. Historically, fungal meningitis has primarily been found to infect immunocompromised individuals; however, there are specific species of fungus that are found in particular environments.
|Common Fungal Meningitis Causes|
|Cryptococcus neoformans||Thought to be acquired through inhaling soil contaminated with bird droppings; AIDS and immune suppression|
|Coccidioides immitis||Found in the soil of endemic areas, particularly in Southwestern US and parts of Central and South America; increased virulence in dark-skinned races|
|Candida sp.||Hospital settings; IV drug abuse; post-surgery; prolonged intravenous therapy; disseminated candidiasis|
|Histoplasma capsulatum||Found in environments with heavy contamination of bird or bat droppings, particularly in the Midwest near the Ohio and Mississippi Rivers; AIDS; mucosal lesions|
|Blastomyces dermatitidis||Thought to exist in soil rich in decaying organic matter in the Midwestern and southeastern USA; usually systemic infection; abscesses; draining sinus; ulcers|
|Aspergillus sp.||Sinusitis; granulocytopenia or immunosuppression|
|Sporothrix schenckii||Traumatic inoculation; IV drug use; ulcerated skin lesion|
|Exserohilum rostratum||Predominant species found in 2012 fungal meningitis outbreak|
Adapted from Table 382-2 Infectious Causes of Chronic Meningitis
Fungal meningitis is treated with long courses of high dose IV antifungal medications. The length of treatment depends on the patient’s immune status and the type of fungal species causing the infection. Longer courses of treatment are required for individuals with comorbid conditions such as AIDS, HIV, diabetes, cancer, etc. The CDC currently recommends that infections of Exserohilum rostratum be treated with IV Voriconazole or Liposomal Amphotericin B.
The prognosis for fungal meningitis includes high mortality rates, frequent treatment complications, and neurologic sequelae. Patients should be monitored closely and counseled regarding the importance of adherence to antifungal maintenance therapy because of the high incidence of relapse if treatment is discontinued
She had a history of pain, the 51-year-old woman who showed up at a Maryland emergency room with a headache so bad it made her face hurt. Within 10 days she was dead, one of the first victims of an outbreak of fungal meningitis that has killed at least 20 people and made nearly 260 sick.
The case is the first to be described in medical detail, and shows that doctors need to act quickly if someone shows up with symptoms after having been given an injection that may have been contaminated with fungus.
She’d been treated for neck pain and a chronic condition called fibromyalgia that is defined by aches and pains all over the body and general weakness and fatigue. She had decided to try a new treatment, an injection in her neck of a steroid to help stop the pain there. It works in some patients – studies show it provides relief about half the time.
It should have been an in-and-out procedure. The steroid injections are considered very safe. The woman had no risk factors, Dr. Jennifer Lyons of the Howard Hughes Medical Institute and Johns Hopkins University in Baltimore reported. “She had not received injections previously, had no history of immune compromise or trauma, and was not taking any long-term medications,” they wrote in the report published in the Annals of Internal Medicine.
A week later, she developed the severe headache – so bad it drove her to the ER. Now, of course, doctors know that anyone who has had a steroid injection and shows up with symptoms like a severe headache should be checked for infection. But this woman was one of the first affected, before word got out.
Headaches are a common side-effect of any injection to the spinal cord. The ER staff did a CT scan to make sure she wasn’t having a stroke or perhaps suffering from a brain tumor and she was sent home.
But she was back the next day, suffering from double vision and nausea. She was dizzy and off-balance – all classic symptoms of meningitis. But she didn’t have a fever and her blood looked normal: no evidence of the immune system reaction seen when meningitis is caused by bacteria or viruses. An MRI didn’t show anything amiss.
All this time, the fungus must have been spreading through the patient’s brain and spine. (She hasn’t been identified in the report to protect her privacy and that of her family). State and federal investigators have found three different types of mold in samples of steroid taken from the New England Compounding Center in Massachusetts and from spinal fluid taken from some of the victims.
Mass. pharmacy responsible for meningitis outbreak autoplay autoplay
Fungal meningitis is rare, and most of the cases have been caused by a mold called Exhiloserum that had never been known to cause meningitis before. Doctors have reported that the mold seems to grow very slowly and cause very subtle symptoms at first.
The Centers for Disease Control and Prevention believes that quick treatment will help, and with the Food and Drug Administration has put out a call for doctors to proactively check with patients who have been treated with any product from NECC – especially injections.
In the case of the 51-year-old woman, the steroid injection mainlined mold right into the fluid that bathes the brain and the spine.
Her doctors didn’t suspect this, although they did an MRI and checked for viruses or bacteria. As she deteriorated, losing her ability to speak and breathe on her own, they dosed her with antivirals and antibiotics, as well as steroids. When they first checked her spinal fluid, it didn’t look that bad. Now doctors know that even small signs of inflammation might mean a patient is infected with these particular molds, and they should start immediate treatment with antifungals.
When she continued to worsen, mystified doctors transferred the patient to Johns Hopkins, where Lyons and a large team of colleagues took over.
There tested her for herpes, shingles, Epstein-Barr virus, West Nile and another virus called cytomegalovirus. They even checked for fungus – a type of yeast called cryptococcus and one called histoplasma that is found in animal droppings and that can cause an alarming type of pneumonia. Negative. It would not have occurred to them to test for a black mold more commonly known for infecting grains, and the tests probably would not have shown it, anyway.
By now the infection was showing up in her brain, and there was swelling at the place on her neck where she had been injected. By the ninth day she was in a coma and they started an antifungal drug, liposomal amphotericin B. But she was brain-dead the next day. Finally, tests revealed the Exserohilum black mold that had killed her.
An autopsy showed it had ravaged her brainstem and eaten into blood vessels and her spinal cord.
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Meningitis caused by ‘black mould’, Exserohilum rostratum
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The black mould, Exserohilum rostratum (ex-sir-oh-HY-lum ross-TRAH-tum), which has caused meningitis in people who were treated with tainted shots for back pain is proving to be difficult to treat.
Exserohilum rostratum an emerging causal agent for meningitis, is a common mould that can be found in soil and thrives in warm, humid climates. Although it has been associated with sinusitis and skin infections and, in some cases, it can cause inflammation of the eyes, bones, and heart, it has never before been observed as a cause of meningitis.
Meningitis, an inflammation of the membranes surrounding the brain and spinal cord is usually caused by bacteria and it is very unusual to see it in patients with normal immune systems. Fungal meningitis caused by Exserohilum rostratum is uncommon.
The fungus is common in dirt and grasses — people routinely come into contact with it without getting sick — but it has never before been identified as the cause of meningitis. The fungus-related meningitis presents differently than typical disease. Patients with the usual form of meningitis (bacterial or viral) get very ill quickly and usually develop fever, headache, and neck stiffness.
Meningitis caused by Exserohilum rostratum develops slowly, and patients may not develop all the classic signs and symptoms of meningitis. If a patient exposed to the fungus-containing steroids develops a headache, fever, or stiff neck, then a lumbar puncture (taking some fluid out of the spinal canal) should be performed to establish the diagnosis of fungal meningitis.
Unlike bacterial or viral meningitis, fungal meningitis is not contagious, which means it is not transmitted from person to person. Fungal meningitis can develop after a fungus spreads through the bloodstream from somewhere else in the body, as a result of the fungus being introduced directly into the central nervous system, or from an infected body site infection next to the central nervous system.
Fungal meningitis is treated with long courses of high dose antifungal medications, usually given through an IV line in the hospital. The length of treatment depends on the status of the immune system and the type of fungus that caused the infection. For people with immune systems that do not function well because of other conditions, like AIDS, diabetes, or cancer, treatment is often longer.
For more details from CTV News, .
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Article expanded and edited by Dr. Jackson Kung’u, PhD.
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People who received tainted steroid shots made by a specialty pharmacy in Massachusetts have been told to stay on guard for months to detect meningitis symptoms. According to the CDC, the biggest risk for getting sick seems to be within 42 days of receiving one of the implicated back injections.
“We know the farther out you are from receiving an injection, the lower your risk becomes for developing meningitis or other infections,” said CDC’s Dr. Tom Chiller. “We want to emphasize that.”
Fungus-caused meningitis is extremely rare, especially in healthy people. Unlike other more common bacterial and viral forms of meningitis, fungal meningitis grows very slowly and it’s hard to diagnose. The main culprit of this outbreak is a black mold commonly found in dirt and grasses.
Black mold is treatable with a drug name voriconazole, which features fewer side effects than the older treatment initially recommended when the outbreak began.
Medical experts are being asked to carefully monitor patients during treatment.
Based on reporting by the Associated Press.
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