Increasing research and development of antifungals and improving public health policies to address the threat of invasive fungal diseases (IFDs) are proposed in the list of priority fungal pathogens recently released by WHO (WHO FPPL).
“Countries are encouraged to follow a step-by-step approach, starting with strengthening their laboratory and fungal disease surveillance capacities, and ensuring equitable access to existing quality treatments and diagnostics, globally,” urged Haileyesus Getahun, MD, MPH, PhD, WHO Director, Antimicrobial Resistance (AMR) Global Coordinating Division, in a announcement.
Getahun and his colleagues in the AMR Division developed the document to help address multiple challenges, including the toxicity and cost of existing antifungal drugs, and this particular expertise is needed to administer them effectively and with consideration for common drug interactions. .
“Furthermore, affordable access to quality medicines and diagnostic tests is unequally distributed. This is particularly acute in low-resource settings, where the disease burden is highest,” say Getahun and colleagues. “As a result, many fungal infections go undiagnosed and untreated. The causative pathogens are rarely microbiologically confirmed, and in most settings surveillance data is poor or absent.”
Their first recommendation is to use the FPPL (“as the first global effort to systematically prioritize fungal pathogens”) to focus action on priority targets. The document then identifies 3 main areas for action: improved surveillance, targeted support for R&D and innovation, and strengthened public health interventions.
State-of-the-art monitoring testing tools, such as matrix-assisted laser desorption/ionization (MALDI-TOF) mass spectrometry systems and real-time PCR, as well as antifungal therapy monitoring are currently recognized as too expensive for d other than high-income settings. The FPPL however calls for increased access to mycology laboratories using microscopy and cultures; and diagnostic tools such as CT and MRI imaging, and advanced bronchoscopy sampling and CT-guided biopsy.
Large-scale susceptibility data collection with clinical data linkage is considered essential for developing clinical endpoints for target pathogens. which in 2019 expanded its original scope of bacterial infections to include fungi.
Research and development for fungal infections is estimated in the FPPL to receive 1.5% of all infectious disease research funding. The consequence, he says, is a weak evidence base, with most treatment guidelines informed by limited evidence and expert opinion.
“Addressing the problems posed by IFD will require increased research funding, targeted to key priorities, new antifungal drugs, and improved diagnostics,” Getahun and colleagues say.
Among the proposed R&D axes:
- Focus on innovative antifungal agents in new chemical classes and new modes of action, with no cross-resistance with other antimicrobial classes and minimal drug interaction
- Improve existing therapies by characterizing optimal use, including determination of pharmacokinetics/pharmacodynamics and antifungal therapy monitoring
- Develop rapid diagnostic tests and point-of-care tests for priority pathogens
- Improve the effectiveness, efficiency and quality of fungal identification and susceptibility testing
Getahun and his colleagues argue that public health interventions must be built on the basis of surveillance and R&D, according to the priorities identified. “An in-depth and granular understanding of the dynamics of disease burden – incidence, prevalence, mortality and morbidity – and AMR prevalence for these priority pathogens will facilitate rational interventions,” they state.
They acknowledge, however, that health workers in many regions are unfamiliar with fungal infections; with resulting low clinical suspicion, misdiagnosis, incorrect or delayed treatment, and poor patient outcomes.
“To address this problem, fungal infections must be integrated beyond specialized training programs into early and ongoing medical and public health education,” Getahun and colleagues recommend.