By Dr. Chinta Sidharthan Oct 27 2022 Reviewed by Benedette Cuffari, M.Sc.
A recent report released by the World Health Organization (WHO) discusses the first WHO fungal priority pathogens list (FPPL), which ranks pathogens that cause acute systemic fungal infections, pose a serious risk of morbidity and mortality in humans, and currently present drug resistance and other management challenges.
Background
Fungal pathogens are increasingly becoming a cause for concern, especially in individuals with underlying medical conditions that weaken the immune system, such as human immunodeficiency virus (HIV), diabetes mellitus, cancer, and tuberculosis.
Patients undergoing immune-suppressive therapies, organ transplants, chemotherapy, invasive medical procedures, chronic obstructive pulmonary disease, and renal and hepatic diseases are also at increased risk of invasive fungal infections.
The incidence of aspergillosis, candidaemia, and mucormycosis have also increased in association with the coronavirus disease 2019 (COVID-19) pandemic. A further challenge in this field is the emergence of antifungal resistance due to inappropriate antifungal use. Antifungal-resistant fungi such as Candida auris persist in hospitals and require second-line antifungal treatments that are often toxic.
Only four classes of antifungals are currently in clinical use, all of which cause many adverse reactions. Furthermore, antifungal medications are often not readily available in low- and middle-income countries with greater disease burden.
About the report
The present WHO FPPL report was released to increase awareness about priority fungal pathogens for implementing better surveillance, prevention, and control measures. The FPPL could lead to augmented investments in research and development of antifungal therapies and diagnostic methods, as well as support the establishment of public health policies focused on addressing fungal diseases and antifungal resistance.
The report’s target audience includes mycologists, healthcare providers, general practitioners, pharmaceutical industries, infectious disease, and mycology research institutes, diagnostic technology development industries, academic healthcare researchers, and ministries of health worldwide.
Since fungal diseases are complex in their epidemiology, disease dynamics, global distribution, and risk factors, a multicriteria decision analysis (MCDA) approach was adopted to create the FPPL. Apart from being reproducible and updatable, the MCDA approach allows various criteria, quantitative and qualitative evidence, and the expertise of different stakeholders to be combined.
The WHO commissioned 19 systematic literature reviews to select 19 priority fungal pathogens based on ten assessment criteria. The assessment factors included mortality, annual incidence, global distribution, incidence and prevalence patterns over the last decade, duration of hospital stay required for treatment, long-term complications, antifungal resistance, diagnosis and treatment, and prevention options. The compiled data was used to produce a final ranking of the fungal pathogens.
Key findings
The MCDA prioritization process revealed that public health concerns had the most prominent role in determining the priority pathogens. Most respondents believed that antifungal resistance was the most important criterion, and top ranks were given to most antifungal-resistant pathogens.
The systematic review revealed significant gaps in knowledge about deaths and susceptibility. Moreover, the review also found that epidemiology and global distribution patterns were significantly different for various fungal pathogens.
The 19 fungal pathogens were divided into three groups based on critical, high, and medium priority. Aspergillus fumigatus, Candida albicans, Candida auris, and Cryptococcus neoformans were the critical priority pathogens.
The high-priority group comprised Candida parapsilosisi, Candida tropicalisi, eumycetoma causative agents, Fusarium spp., Histoplasma spp., Mucorales, and Nakaseomyces glabrata (Candida glabrata).
The medium priority group consisted of Coccidioides spp., Cryptococcus gattii,Lomentospora prolificans, Paracoccidioides spp., Pichia kudriavzeveii (Candida krusei),Pneumocystis jirovecii, Scedosporium spp., and Talaromyces marneffei.
Implementation of FPPL
The WHO identified three broad priority areas for action, including increased surveillance, support for research and development, and improved public health interventions. Improved surveillance would require increased access to mycology laboratories, microscopy and culture tests, diagnostic tools and facilities such as computed tomography and magnetic resonance imaging, and advanced biopsy techniques.
The research and development goals would be to design new antifungal drugs and improve existing treatments to increase their efficacy and reduce toxicity. In addition, developing new diagnostic methods to provide rapid, affordable, and accurate fungal identification and susceptibility determination would also be a priority.
Enhanced public health measures would include increased medical training, new and improved infection prevention and control measures, and expanding access to quality, affordable, and equitable antifungal treatments.
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