WHO fungal priority pathogens list to guide research, development and public health action

Abstract

Infectious diseases are among the top causes of mortality and a leading cause of disability worldwide. Drug-resistant bacterial infections are estimated to directly cause 1.27 million deaths and to contribute to approximately 4.95 million deaths every year, with the greatest burden in resource- limited settings. Against the backdrop of this major global health threat, invasive fungal diseases (IFDs) are rising overall and particularly among immunocompromised populations. The diagnosis and treatment of IFDs are challenged by limited access to quality diagnostics and treatment as well as emergence of antifungal resistance in many settings. Despite the growing concern, fungal infections receive very little attention and resources, leading to a paucity of quality data on fungal disease distribution and antifungal resistance patterns. Consequently, it is impossible to estimate their exact burden. In 2017, WHO developed its first bacterial priority pathogens list (WHO BPPL) in the context of increasing antibacterial resistance to help galvanize global action, including the research and development (R&D) of new treatments. Inspired by the BPPL, WHO has now developed the first fungal priority pathogens list (WHO FPPL). The WHO FPPL is the first global effort to systematically prioritize fungal pathogens, considering their unmet R&D needs and perceived public health importance. The WHO FPPL aims to focus and drive further research and policy interventions to strengthen the global response to fungal infections and antifungal resistance. The development of the list followed a multicriteria decision analysis (MCDA) approach. The prioritization process focused on fungal pathogens that can cause invasive acute and subacute systemic fungal infections for which drug resistance or other treatment and management challenges exist. The pathogens included were ranked, then categorized into three priority groups (critical, high, and medium). The critical group includes Cryptococcus neoformans, Candida auris, Aspergillus fumigatus and Candida albicans. The high group includes Nakaseomyces glabrata (Candida glabrata), Histoplasma spp., eumycetoma causative agents, Mucorales, Fusarium spp., Candida tropicalis and Candida parapsilosis. Finally, pathogens in the medium group are Scedosporium spp., Lomentospora prolificans, Coccidioides spp., Pichia kudriavzeveii (Candida krusei), Cryptococcus gattii, Talaromyces marneffei, Pneumocystis jirovecii and Paracoccidioides spp. This document proposes actions and strategies for policymakers, public health professionals and other stakeholders, targeted at improving the overall response to these priority fungal pathogens, including preventing the development of antifungal drug resistance. Three primary areas for action are proposed, focusing on: (1) strengthening laboratory capacity and surveillance; (2) sustainable investments in research, development, and innovation; and (3) public health interventions. Countries are encouraged to improve their mycology diagnostic capacity to manage fungal infections and to perform surveillance. In most contexts, this might require a stepwise approach. There is a need for sustainable investments in research, development, and innovation. More investments are needed in basic mycology research, R&D of antifungal medicines and diagnostics. Innovative approaches are needed to optimize and standardize the use of current diagnostic modalities globally. In addition, public health interventions are needed to highlight the importance of fungal infections, including through incorporating fungal diseases and priority pathogens in medical (clinical) and public health training programmes and curricula at all levels of training. Similarly, collaboration across sectors is required to address the impact of antifungal use on resistance across the One Health spectrum. Finally, regional variations and national contexts need to be taken into consideration while implementing the WHO FPPL to inform priority actions.