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WHO Ranks Risks of Invasive Fungal Infections

The World Health Organization's fungal priority pathogens list is intended to prompt research, development and policy against the increasing health threat.

A recently issued call and guide for global action against the public health threat of invasive fungal diseases (IFDs) by the World Health Organization (WHO) ranks the risks posed by 19 pathogens, including 4 deemed "critical."

"Emerging from the shadows of the bacterial antimicrobial resistance pandemic, fungal infections are growing, and are ever more resistant to treatments, becoming a public health concern wordwide," said Hanan Balkhy, MD, Assistant Director-General, Animicrobial Resistance (AMR), WHO, in an accompanying announcement.

The WHO Fungal Priority Pathogens List to Guide Research, Development and Public Health Action (WHO FPPL)was developed by members of the multinational AMR Division, overseen by Haileyesus Getahun, MD, MPH, PhD, WHO Director, Antimicrobial Resistance(AMR) Global Coordination Division.

Getahun and colleagues point out that the rise in IFDs are particularly notable among immunocompromised populations; and that diagnosis and treatment are challenged by limited access to quality diagnostics and treatment, and to the emergence of antifungal resistance.

A Wall Street Journal article citing the WHO document highlights its assessment that the present antifungal armamentarium is too limited and too toxic; with the last new class (of only 4 total) to treat severe infection approved over two decades ago. The article notes, however, the hopeful progress with fosmanogepix (Amplyx Pharmaceuticals), rezafungin (Cidara Therapeutics), olorofim (F2G Ltd); and a potentially less toxic version of amphotericin B (Matinas BioPharma).

The 4 pathogens deemed "critical" targets for improved treatments and public policy are:

  • Cryptococcus neoformans
  • Candida auris
  • Aspergillus fumigatus
  • Candidaalbicans

The next highest priority group includes:

  • Nakaseomyces glabrata (Candida glabrata)
  • Histoplasma spp.
  • eumycetoma causative agents
  • Mucorales
  • Fusarium spp.
  • Candida tropicalis
  • Candida parapsilosis

Additionally, of medium priority are:

  • Scedosporium spp.
  • Lomentospora prolificans
  • Coccidioides spp.
  • Pichia kudriavzeveii (Candida krusei)
  • Cryptococcus gattii
  • Talaromyces marneffei
  • Pneumocystis jirovecii
  • Paracoccidioides spp.

The document indicates that strong determinants of priority level were from responses to Best-Worst Scaling (BWS) global surveys regarding public health importance and unmet research and development need. Specifically, prioritizing followed from prevalence of antifungal resistance, and disease-burden related criteria (eg, mortality, annual incidence and morbidity).

"The list is focused on fungal pathogens responsible for acute, subacute systemic fungal infections for which drug resistance or other treatability and management challenges exist," Getahun and colleagues explain. "The pathogens included are all associated with serious risk of mortality and/or morbidity."

The ranking involved a weighing of factors, which were illustrated with 2 examples. Lomentospora prolificans was ranked high for the need for research and development of effective treatment options, but low in perceived public health importance due to its rarity, ranking 13th of the 19. In contrast, while Aspergillus fumigatus and Candida albicans ranked lower for unmet R&D need, they were high for public health burden, resulting in their placement in the highest "critical" group of 4 pathogens.

The document points out that some threatening pathogens are specific to particular geographical areas and populations, and do not now pose risk on a global scale. It advises then, that regions and countries contextualize the findings to inform local actions; and to protect at-risk populations (eg, cancer and immunosuppressed patients, and newborns with HIV infections).

Also acknowledged is that there were limited data on complications and sequelae of infection and duration of inpatient care for many pathogens. Expert consensus was used when data gaps were encountered, and so some findings may be subject to bias.

"Large multinational prospective cohort studies are needed to fill the gaps on burden of disease criteria," Getahun and colleagues declare. "In addition, quality surveillance data on antifungal resistance, and evidence on IPC (Infection Prevention and Control) measures are needed to better inform future iterations of the WHO FPPL."