Why fungal infections are so difficult to diagnose

Danger for intensive care patients

Most frequently overlooked cause of death: why fungal infections are so difficult to diagnose

Fungal infections are difficult to diagnose and are apparently the most frequently overlooked cause of death in intensive care patients (symbol image).

Some cases reported by mushroom expert Prof. Hans-Jürgen Tietz make you shudder. For example, that of a little boy who underwent three unnecessarily head surgeries: a doctor had arranged for the surgery to remove pus from the scalp – a large, circular wound can be seen in a documentary photo. When cortisone and antibiotics didn’t help either and a fourth operation was to take place, the parents became suspicious and took the child to a university hospital. There it turned out that the six-year-old had contracted calf lichen on his grandparents’ farm and the operations were unnecessary. After all, the fungal infection could be fought well with appropriate medication, and the parents hope that one day hair will grow on the scar again.

From the mycologist’s point of view, a case like this makes it clear that fungal pathogens are too rarely considered in medicine. “Mycology is still a stepchild of infectiology,” says Tietz, who heads the Institute for Fungal Diseases in Berlin. He believes that the field urgently needs more attention. “Fungal infections are on the rise worldwide, and that gives us great concern.” The spectrum of pathogens has changed significantly in recent years: while fungi used to be mostly linked to certain regions, many species are now found worldwide. One of the reasons for this is globalization. As a result, pathogens that used to be considered exotic can appear in family doctor’s surgeries – such as Trichophyton soudanense, a germ originating from Africa which, like calf lichen, can infect the scalp of children.

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Organisms adapt to temperature changes

Such skin fungi are annoying, sometimes also psychologically stressful, but usually not dangerous. At most, for example, the widespread athlete’s foot can cause major problems in diabetics: If it affects the skin, bacteria such as staphylococci and streptococci can enter the wounds and cause dangerous infections. In contrast, “Trichophyton rubrum”, which is behind most athlete’s foot infections, does not penetrate the body. “It can spread from the foot to the face, but never goes inwards,” explains Tietz. The fungus feels much more at home on cooler extremities, especially on cold feet, than at a temperature of 37 degrees, which prevails in the body.

Species of concern

The World Health Organization (WHO) warns against these fungal pathogens: – Cryptococcus neoformans: The pathogen occurs in soil that is contaminated with bird droppings and is inhaled. It first affects the lungs, then often the brain, skin and joints. Sick people, such as AIDS patients, are at risk. So far there have only been a few cases in Germany. – Candida auris: The yeast fungus was only discovered in 2009, but has since been observed in many countries. He is dangerous for weakened people, for example in hospitals. If it enters the body, it can lead to blood poisoning, for example. The germ is transmitted via objects such as catheters. Larger outbreaks have occurred in Great Britain and Spain. – Candida albicans: The “thrush fungus” is widespread. In about 70 percent of all people, the fungus occurs in the intestine. Most of them have no problems. However, if the yeast fungus gets into the bloodstream, weakened people, such as AIDS or intensive care patients, can become seriously ill. – Aspergillus fumigatus: The mold is common throughout the world. It can trigger allergies and infect the lungs or sinuses. The fungus is dangerous for immunocompromised people. In them, it can continue to multiply from the lungs and infect the whole body.

At such high temperatures, most mushrooms cannot grow. Therefore, our body temperature protects us from many fungal infections – but by no means from all. Some organisms have adapted: If they get into the bloodstream and infect organs, it becomes life-threatening. “Normally, however, our immune system protects us from this,” says the Würzburg microbiologist Prof. Oliver Kurzai, who heads the National Reference Center for Invasive Fungal Infections. Therefore, such infections usually only occur in immunocompromised people – such as intensive care patients or people with chronic diseases. Even among fungi that can invade the body, there are new species that are spreading. This is particularly worrying because the number of susceptible people is growing. On the one hand, thanks to medical progress, people with serious illnesses are living longer, and on the other hand, there are new groups at risk, such as patients with the lung disease COPD. How dangerous some germs can be for weakened people was shown two years ago in India, when tens of thousands of corona patients became life-threateningly ill with the “black fungus” – an infection with fungi from the Mucorales group, which only occurs very rarely in Germany.

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Last autumn, the World Health Organization (WHO) took the situation as an opportunity to publish a list of dangerous fungal species for the first time.

Some fungal pathogens are resistant to common drugs

“The biggest concern for us is Candida auris,” says Kurzai. In the meantime, the yeast fungus, which was only discovered in Japan in 2009, occurs worldwide and has partly displaced other fungi. Outbreaks are common in hospitals, where it is easily transmitted by smear infection. The big problem is that the pathogen is often resistant to common agents.

In this respect, the situation is comparable to the hospital germs known as MRSA, against which some antibiotics cannot do anything. “However, the outbreak of Candida auris develops more slowly and insidiously,” says Kurzai.

The pathogen has been found around 40 times in Germany since 2015, reports the expert. “Fortunately, there hasn’t been a major eruption so far,” says Kurzai. “But it is only a matter of time before this happens.” This time must be used to prepare laboratories and clinics as well as possible for the pathogen. The expert also calls for the introduction of a laboratory reporting requirement for Candida auris.

Reliable diagnosis is difficult

It is still unclear why the fungus has suddenly spread all over the world. One thesis says that it has adapted to higher temperatures as a result of global warming and is therefore now able to grow at human body temperature. There is no evidence of this, says Kurzai. In the case of other fungi, the connection with climate change is clearer: Sandstorms in the USA, for example, ensured that the pathogen that causes “Valley Fever”, which occurs in extremely dry soil, was able to spread widely. Unlike Candida auris, however, it is not an issue in Germany.

One of the biggest problems in fighting fungi like candida auris is detecting them early. “It is difficult to reliably diagnose such infections,” says Kurzai. Among other things, doctors from different disciplines would have to work together. First of all, however, a clinic doctor has to get the idea that it could be a fungal infection. It probably often goes undiagnosed: A review on the subject concluded that fungal infections are among the most frequently overlooked causes of death in ICU patients.

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But even if the pathogen is identified, treatment is often difficult. For example, antifungal agents from the azole group, which are also used for plant protection, often have no effect on Candida auris. Therefore, finding an effective drug can be difficult. Kurzai gives the all-clear on one point: If you are completely healthy, Candida and Co cannot harm you.

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