Fungal Infections Kill Millions, Yet Few Effective Treatments Are Available

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Most people think of a fungal infection as something like a yeast infection or athlete’s foot—they’re itchy and annoying but harmless and relatively easy to treat. However, there are various species of fungi lurking around the world, preying on people with weakened immune systems. Once these fungi enter the human body, they can resist standard antifungal drugs and often cause serious illness or death.

One type of fungus that’s been getting recent media attention, Candida auris, is becoming more prevalent throughout the United States and the world, with a steadily rising death toll. It’s difficult to detect through blood tests because it looks like other, more easily treatable fungal infections. Once it’s identified, treatment can be challenging because of inappropriate management from prior misidentification and the infection’s ability to evade and resist current drug treatments.

The people most vulnerable to these infections are immunocompromised patients such as diabetics, those with an organ or tissue transplant, people taking immunosuppressive medications, and anyone receiving chemotherapy. Candida auris is opportunistic, particularly in hospital settings, and can make its way into the body through invasive catheters, ventilators, or surgical treatments.

It’s also easily spread from person to person, since it can live on skin with no symptoms, and spreads easily on hospital surfaces (e.g., beds and equipment) when they’re improperly cleaned. A 2018 outbreak in an Oxford University Hospital intensive care unit in the United Kingdom was determined to be caused by multiuse equipment, including thermometers used to measure temperatures under the armpit.

Candida auris and other deadly fungal pathogens, such as Aspergillus and Pneumocystis, are responsible for at least 13 million infections and about 1.5 million deaths per year, a fatality rate similar to those of tuberculosis, HIV, malaria, and breast cancer.

Since deadly fungal infections have risen steadily over the past 50 years, with global death rates similar to those of some of the worst diseases, why haven’t scientists developed effective treatments to reduce risks for immunocompromised individuals?

The answer involves scientific and economic challenges that must be overcome.

Antifungals

There are hundreds of different antibiotics used to treat bacterial infections, and antivirals have been increasingly effective in fighting off viruses, shortening symptoms, and boosting the immune system. But developing medications to treat fungal infections can be complicated because fungi have the same type of cells as humans, so a substance created to kill fungi may mistakenly target human cells. Many antifungals are highly potent, so if they attack human cells, they can cause kidney or liver damage, particularly after prolonged use.

Another challenge is the tendency of these fungal infections to become resistant to the few available working medications. There are several reasons why these infections can build resistance to antifungal medications.

• Medication misuse: Skipping doses, stopping therapy too soon, or using a prescribed dose that is too low can enhance the ability of the fungus to resist fungal medications.
• Fungicides: Many fungicidal drugs are used to protect crops, exposing fungi to more fungicides, inevitably creating resistance. People who work closely with or ingest fungicide-treated crops may become more susceptible to antifungal resistance.
• Transmitted resistance: One person can transmit drug-resistant fungus to another, even if they’ve never used an antifungal drug.
• Prolonged treatment: Some fungal infections require prolonged treatment. The longer the fungus is exposed to an antifungal drug, the more likely it will develop resistance to the drug.
• Misidentification of fungus: When a fungus is misdiagnosed and treated with the wrong antifungal, the infecting fungus can become stronger.
• Spontaneous resistance: The fungus stops responding to a previously effective antifungal medication for no known reason.

The selection of antifungal drugs is limited and becoming less effective because fungi have a sneaky way of evolving to combat current treatments.

Prospective new medicines are in development, but they require additional studies to determine whether they are safe and effective.

Immunotherapy

Immunotherapy has been used for many years to battle cancer successfully by training the immune system to find and destroy cancer cells.

Zeeshan Afzal, a veterinarian with a background in clinical science and extensive experience with fungal disease, told The Epoch Times, “One example of immunologic therapy for invasive fungal infections is monoclonal antibodies designed to target and neutralize fungal cells specifically.”

Afzal said he believes that another potential approach is to use cytokines, molecules that signal the immune system to respond to these fungal infections. “Research is ongoing, and there have been some promising findings in this area.”

Vaccines

There are more than 25 vaccines for fungal infection available worldwide, but none can protect vulnerable, immunocompromised patients from fungal infections.

Karen Norris, who holds a doctorate in biomedical sciences and microbiology and is a member of the University of Georgia Center for Vaccines and Immunology, is working to find a vaccine to protect against the fungal pathogens responsible for more than 80 percent of fatal fungal infections.

Researchers tested the efficacy in four preclinical animal trials. They relied on different immunosuppressed models to reflect drug regimens similar to those used with at-risk human patients such as transplant recipients and cancer patients. The vaccine effectively produced protective antibodies in each model.

“Because it targets three different pathogens, the vaccine has the potential to be groundbreaking regarding invasive fungal infections,” Norris told UGA Today. Plans are underway to develop the vaccine for a phase 1 (human) safety trial.

No vaccine will be available anytime soon because human trials will likely continue for the next five years.

Economic Challenges

Fungal infections cost the health care system millions of dollars each year. According to research published in Open Forum Infectious Diseases, in 2018, there were 666,235 fungal infections diagnosed in the United States. The estimated hospitalization costs directly associated were $6.7 billion, with a total cost of $37.7 billion for all visits at which any fungal infections were diagnosed.

Ultimately, the fungal infections doubled the cost to the patient, the hospital stay, and the risk of death in patients considered at-risk.

Yet there is little talk among the media or government officials about solving this overwhelming problem in the United States and worldwide.

The most likely reason is that these costly and deadly fungal infections primarily target patients with compromised immunity. The death rate for this at-risk population is estimated at more than a million annually, but pharmaceutical companies may not have a financial incentive to fund research and development for efficacious drugs, therapies, or vaccines.

While the development of effective fungal treatments may reduce the cost of medical care, which is already nearly unsustainable in the United States, pharma companies are looking to profit. Dennis Dixon, who leads bacterial and fungal research at the National Institutes of Health, told Vox on March 24, “It’s going to take someone to develop that tough market for this to go forward.”

In Conclusion

Invasive and often deadly fungal infections continue to plague the immunocompromised across the globe. The science exists to develop better antifungal drugs, immunologic therapies, and effective vaccines. Unfortunately, antifungal drugs are expensive to develop, and patients take them for a short period of time, which means the return on investment for pharmaceutical companies is relatively poor—if it exists at all.

And there is also a pattern drug companies have seen play out after developing new antibiotics for drug-resistant bacterial infections. Often, doctors are reluctant to prescribe new antibiotics for fear of the side effects and contributing to further drug resistance, so they continue to prescribe the old drugs.

The most compelling reason for the private sector to increase funding for these therapies is the millions of lives they could save.