Each year, about 150 children in the Netherlands are diagnosed with leukemia. During and after intensive treatment, their immune system is weakened, making them extra vulnerable to infections. Sometimes a fever develops and antibiotics do not help. Then a fungal infection is a possible cause. Such an infection is a serious complication that can delay or interrupt treatment.
Laura Rotte, pediatric oncologist in training and researcher in the Tissing Group at the Princess Máxima Center, sees the consequences of this in her work: 'To find out whether a fungus is active, children now often have to undergo a lung lavage under anesthesia. Unfortunately, it is not always possible to determine precisely in the fluid from the lung lavage whether and which fungus is present.'
Fungal DNA as a clue
In collaboration with UMC Utrecht, the researchers investigated whether cell-free fungal DNA in the fluid obtained from lung lavage as well as blood could be used for diagnosis. Researcher Emmy Wesdorp, who worked at the Center for Molecular Medicine at UMC Utrecht during the study and is now a bioinformatician in the Tytgat group at the Máxima, explains: 'We use advanced techniques to read out millions of DNA fragments. Only a fraction of them are from fungi. It's like looking for dozens of white shreds in a full paper container of blue confetti.'
The research group of Oncode investigator Prof. Dr. Jeroen de Ridder at the Center for Molecular Medicine at UMC Utrecht developed a method to detect cell-free fungal DNA in samples. By comparing this DNA with large databases, the researchers were able to determine whether a fungal infection was present, and if so, which fungus caused it. In an initial test group of seven children suspected of having a fungal infection, Aspergillus fumigatus was found in both lung lavage fluid and blood. In five of them, fungal DNA was also detected in the blood. This could be a much less stressful method than the usual lung flush for children.
The researchers published the results in npj Genomic Medicine.
Future application in the clinic
According to Prof. Dr. Louis Bont, pediatrician-infectiologist at the WKZ and clinical scientist affiliated with the Tissing Group at the Máxima Center, where he is responsible for infectious disease research, the test is very promising: 'In the future, this may enable us to make better informed choices for targeted fungal treatment. That will help prevent unnecessary medication with its side effects and damage to organs. And that in turn improves the quality of life of children with cancer.'
The researchers hope to expand the test to other types of fungi in the future. 'Our goal is a diagnostic test that is broadly applicable and low impact for children,' says Rotte. Wesdorp adds: ‘We are at the beginning, but this research shows that it can work.’