There is a “critical lack” of medicines and diagnostic tools for invasive fungal diseases, according to the World Health Organization (WHO), which released its first analysis of antifungals on Tuesday.

Invasive fungal diseases are on the rise, particularly in immune-compromised people – yet they get little attention or resources, asserts the global body.

Common infections such as candida (which causes oral and vaginal thrush) are growing increasingly resistant to treatment, but there are not enough medicines in the pipeline to combat this.

Several current anti-fungal treatments cause serious side effects, frequent drug-drug interactions, and treatment requires prolonged hospital stays. 

“Invasive fungal infections threaten the lives of the most vulnerable but countries lack the treatments needed to save lives,” said Dr Yukiko Nakatani, WHO interim Assistant Director-General for Antimicrobial Resistance. 

“Not only is the pipeline of new antifungal drugs and diagnostics insufficient, but there is a void in fungal testing in low- and middle-income countries, even in district hospitals,” added Nakatani.

“This diagnostic gap means the cause of people’s suffering remains unknown, making it difficult to get them the right treatments.”

Only four new drugs in a decade

In the past decade, only four new antifungal drugs have been approved by regulatory authorities across the United States, the European Union and China. 

Nine antifungal medicines are in clinical development against the most health-threatening fungi identified in the WHO’s fungal priority pathogens list (FPPL), according to the WHO analysis, which conducted a rigorous evaluation of antifungal agents in clinical and preclinical development with the assistance of an expert advisory group on the R&D of novel antifungal treatments.

Only three of the nine are in phase 3 trials, which means “few approvals are expected within the next decade”, according to the WHO. 

“Children are particularly underserved with few clinical trials exploring paediatric dosing and age-appropriate formulations,” the global body notes.

Critical priority pathogens

Many of the fungi in the critical priority pathogen (CPP) category of the WHO’s FPPL are deadly, with mortality rates reaching as high as 88%.

This critical group includes Cryptococcus neoformans (which causes cryptococcal meningitis); Candida auris (causes infections, including in wounds and blood); Aspergillus fumigatus (causes aspergillosis, a lung infection) and Candida albicans (thrush). 

These infections disproportionately affect those with weakened immune systems, including people undergoing cancer chemotherapy, living with HIV, and who have had organ transplants.

Candida auris is particularly drug-resistant and often acquired by vulnerable people in hospitals.

The nine new antifungals all target the critical group – and most target more than one of these fungal infections. 

Aspergillus fumigatus is targeted by the highest number of antifungal candidates, followed by Candida albicans and Candida auris. Cryptococcus neoformans gets the least attention.

There are 22 drugs in pre-clinical development, but this is “insufficient” given the dropout rates, risks and challenges associated with earlier development stages, says the WHO.

Diagnostic challenges

Current tests for fungal priority pathogens “rely on well-equipped laboratories and trained staff, which means that most people in low- and middle-income countries (LMICs) do not benefit from them”, according to the WHO’s diagnostics analysis. 

In addition, these tests “work only for a limited range of fungi, are insufficiently accurate and take a long time to obtain results”. Health workers often lack knowledge about fungal infections.

WHO recommends investing in global surveillance, expanding financial incentives for drug discovery and development, funding basic research to help identify new and unexploited targets on fungi for medicines, and investigating treatments that work by enhancing patients’ immune responses.

It also urges the development of “faster, more accurate, cheaper and easier” tests for a broad range of fungal priority pathogens.

Image Credits: Science Media Centre, WHO.