Four of these patients have died as of June 7, 2023. Both clinics were shuttered by Mexican health officials on May 13, but the combination of a possible long incubation period and a high mortality rate has the Centers for Disease Control and Prevention (CDC) greatly concerned.
“If you had epidural anesthesia in Matamoros, Mexico, at River Side Surgical Center or Clinica K-3 from Jan. 1 to May 13, 2023, you are at risk for fungal meningitis. Go to the nearest emergency room as soon as possible to be evaluated for fungal meningitis, even if you do not currently have symptoms,” the CDC emphasized.1
All exposed patients should receive a spinal tap to test for fungal meningitis. Magnetic resonance imaging of the brain is not required for patients with normal lumbar puncture test results, the CDC noted. As of June 9, 2023, 207 U.S. patients were identified in various stages of investigation after receiving epidural anesthesia at the two clinics. According to the CDC, the cases are broken down into the following categories:
• Persons under investigation (179 cases): Those with no symptoms or symptoms are unknown, and those with spinal tap results pending or unknown.
• Suspected cases (14 patients): Those with symptoms consistent with meningitis, but spinal tap results are pending or unknown.
• Probable cases (10 patients): Spinal tap results suggest meningitis, but the fungus is not isolated.
• Confirmed cases (four patients): Fungus detected from samples.
• Deaths (four patients): These include two probable cases and two confirmed cases.
Compounding the situation, before the outbreak was recognized, one of the early deaths was an organ donor, said CDC mycotic diseases branch epidemiologist Dallas Smith, PharmD, at an advisory committee briefing.
“There have been five recipients of organs from this patient,” he said. “All have been notified and are under evaluation. We are working with transplant centers and other partners to properly manage these patients.”
Overall, about 10% of the cases are in men. The primary population at risk is women from more than 20 states who underwent cosmetic procedures, including liposuction and breast augmentation, at the two clinics. Mexican public officials are trying to determine if any other surgical clinics are involved. Most of the patients live in Texas, but there were cases under investigation in the distant points of Alaska and Puerto Rico.
Alert Clinician Sounds Alarm
The investigation began after an astute clinician in Texas notified the CDC on May 8, 2023, of two unusual meningitis cases with a history of cosmetic procedures. Fungal meningitis infections typically have symptoms that include headaches and neck pain resulting from inflammation of the brain and spinal cord.
These patients are not considered infectious but are at risk of stroke and other severe outcomes after infection sets in. Thus, the earlier medical treatment can begin, the better the chance of survival.
A similar outbreak that occurred in Durango, Mexico, in November 2022 had a striking mortality rate of almost 50%, with 39 of 80 cases dying. While that outbreak primarily involved Mexican citizens, the current outbreak, including the U.S. patients, appears to be caused by the same fungal pathogen: Fusarium solani species complex.
“The outbreak that we’re experiencing now is pretty similar, and it has the capacity to have this high mortality rate and just devastate families and communities,” Smith said. “We are not sure if these two outbreaks are linked, but the fact that the same organism is likely causing this fungal meningitis makes us worried about a high mortality rate. That’s why it’s so important to get patients in early.”
Although it has not been officially solved, the Durango outbreak last year also raised the issue of contaminated multidose vials. There have been press reports of Mexican officials detaining an unidentified physician who brought his own anesthetic vials to different hospitals.2
“[One] hypothesis we have is poor infection control practices,” Smith said. “Oftentimes, in Mexico, at these clinics, anesthesiologists bring their own medications and prepare them on site.”
The actual anesthesia medication is in widespread use in Mexico and does not appear to be the source of infections in the absence of other outbreaks. However, the other critical agent used in epidural spine injections — morphine — is another story.
“There’s a [morphine] shortage currently in Mexico, and there could be the potential for a ‘black market’ that could contaminate medicines,” Smith said. “There was an open vial of morphine that our colleagues in Mexico were testing, but I don't think they have results back.”
Ideally, Use Multidose Vial on One Patient
Again, the other prevailing theory is that multidose vials procured by anesthesiologists become contaminated and they are continually used. Over the years, dozens of outbreaks of various etiology have been traced to contamination and needle reentry into a multidose vial. (See “Multidose Vials Linked to HCV Spread in Clinic.”)
“If multidose vials must be used for more than one patient, they should only be kept and accessed in a dedicated clean medication preparation area (e.g., nurses’ station), away from immediate patient treatment areas,” the CDC states in its standing recommendation on this issue.3 “This is to prevent inadvertent contamination of the vial through direct or indirect contact with potentially contaminated surfaces or equipment that could then lead to infections in subsequent patients.”
The World Health Organization (WHO) — which is closely following the situation because cases also occurred in Canada and Colombia — emphasized this warning regarding the source of the unsolved outbreak: “Processes used for the storage, transport, and preparation of sharps, syringes, and vials should be examined to ensure sterility prior to use in local healthcare facilities. Use of multidose vials should be avoided.”4
Each year, more than 1 million people from the United States travel to other countries for medical procedures, the WHO reported.
“These medical tourists commonly travel to Mexico, Canada, and countries in Central America, South America, and the Caribbean.”
In investigating the current outbreak, the CDC interviewed 10 female patients (mean age 33 years) who live in Arizona, Tennessee, and Texas. “We found that 100% of these patients had liposuction procedures in the clinics in Mexico under epidural aesthesia,” Smith said. “Forty percent [also] had breast augmentation and 30% had Brazilian butt lifts.”
This gluteal fat grafting procedure involves transfer of body fat from patient “problem areas,” such as the thighs, into the buttocks. It has been associated with a high mortality rate if the transferred fat gets into the bloodstream and must be done with great care, the American Society of Plastic Surgeons warns.5 The surgical group also reports a post-pandemic boom in cosmetic surgery — driven by women age 45 years and younger — which increases the risk of more of these outbreaks.
In investigating, the CDC found that “recruiters” for the two clinics had reached out to U.S. patients with information on the procedures available.
“We’re working with them to figure out how we can raise awareness and identify more people who have been exposed during this time period,” Smith said.
Fungal ‘Signals’
As of this report, the CDC did not have a definitive isolate identifying F. solani species complex as the causative agent. However, the CDC and two U.S. research labs have detected “fungal signals” consistent with F. solani in the cerebral spinal fluid (CSF) of case patients.
A definitive isolate would allow genomic sequences to see if there is any link between the outbreak in Durango last year and the current outbreak in Matamoros. “You can do a bit of sequencing of the little region you get from a positive PCR (polymerase chain reaction), but we probably need an isolate to really understand if these two outbreaks are related,” said Luis Ostrosky-Zeichner, MD, chairman of the Mycoses Study Group, which worked with the CDC to develop interim recommendations on the testing and treatment of cases.
“Aggressive, dual antifungal treatment (liposomal amphotericin B and voriconazole) is recommended because of the high case fatality rate seen during previous outbreaks of fungal meningitis involving Fusarium,” the guidelines state.6 “Antifungal therapy should be started as soon as possible after collection of CSF.”
The recommendation came with the caveat that optimal therapy for these infections has not been established. The course of care varies between patients and may be complex and prolonged, the committee noted.
“Expert consultation is particularly important because overall clinical experience with these infections is highly limited,” the guidelines state. “Providers should contact their local health department if they have patients presenting for care. They can also contact the CDC ([email protected]). Public health officials can reach out to the CDC to connect clinicians with experts in fungal meningitis management.”
The guidance is based, in large part, on previous outbreaks of fungal meningitis, including one in 2012 in the United States that resulted in 61 deaths and 749 infections in 20 states.7 The infections were associated with injection of a contaminated glucocorticoid medication from a single compounding pharmacy in Framingham, MA.
“You may recall that, over a decade ago now, we had the largest outbreak ever recorded from a nosocomial source that indeed was a fungal meningitis due to spinal steroid injections for the most part in people [with] back pain and other conditions,” said Tom Chiller, MD, chief of the CDC mycotic diseases branch. “That was a fungus called Exserohilum rostratum, predominantly — a completely new fungus for us to deal with in the central nervous system. We learned a lot during that process. Patients did well once we got them identified and evaluated with a lumbar puncture to understand whether they had meningitis. Successful treatment was really indicated by the rapidity in which we were able to diagnose them.”
The CDC is emphasizing the following clinical advice for patients while the outbreak is ongoing:
• Starting treatment right away if you are found to have fungal meningitis greatly increases the likelihood of survival.
• Fungal meningitis infections are not contagious and are not spread from person to person.
• Cancel any elective procedure that involves an epidural injection of an anesthetic in Matamoros, Mexico — and any travel associated with such a procedure — until there is evidence that there no longer is a risk for infection at these clinics.
• Share information about this outbreak and reach out to any friends or family members who may have had procedures at River Side Surgical Center or Clinica K-3 from Jan. 1 to May 13, 2023.
REFERENCES
- Centers for Disease Control and Prevention. Fungal meningitis outbreak associated with procedures performed under epidural anesthesia in Matamoros, Mexico. Updated June 9, 2023. https://www.cdc.gov/hai/outbreaks/meningitis-epidural-anesthesia.html
- Diaz L. Doctor accused of spreading deadly meningitis arrested in Mexico. Reuters. Published Feb. 7, 2023. https://www.nasdaq.com/articles/doctor-accused-of-spreading-deadly-meningitis-arrested-in-mexico
- Centers for Disease Control and Prevention. Questions about multi-dose vials. Last reviewed June 20, 2019. https://www.cdc.gov/injectionsafety/providers/provider_faqs_multivials.html
- World Health Organization. Outbreak of suspected fungal meningitis associated with surgical procedures performed under spinal anaesthesia — the United States of America and Mexico. Published June 1, 2023. https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON470
- Clark K. Seven things you need to know about a Brazilian butt lift. American Society of Plastic Surgeons. Published March 28, 2022. https://www.plasticsurgery.org/news/articles/seven-things-you-need-to-know-about-a-brazilian-butt-lift
- Centers for Disease Control and Prevention Mycoses Study Group. Interim recommendations for diagnosis and management of fungal meningitis associated with epidural anesthesia administered in Matamoros, Mexico. Updated June 7, 2023. https://funguseducationhub.org/wp-content/uploads/2023/06/interim-recommendations-Matamoros-FM-outbreak-6_09_23.pdf
- Smith RM, Schaefer MK, Kainer MA, et al. Fungal infections associated with contaminated methylprednisolone injections. N Engl J Med 2013;369:1598-1609.
Infection control lapses, including the contamination of multidose vials of anesthetic, are suspected in a fungal meningitis outbreak that exposed about 200 American patients who received epidural injections this year in the border town of Matamoros, Mexico.
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