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New crop fungicides could increase antifungal resistance WHO requested to act

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Antifungal triazole drugs are the mainstay of treatment for fungal diseases in humans and animals, yet their effectiveness is undermined by resistance. Very similar compounds are used on many crops to reduce plant fungal disease and increase yield. Today in Amsterdam, the Global Action Fund for Fungal infections published its letter to the World Health Organisation’s Director General  encouraging a position statement on preventing future resistance by careful risk assessment of new fungicides for resistance potential.

Antimicrobial Resistance (AMR) efforts have been focused on bacteria, but for fungal diseases and especially aspergillosis, there is only one class of oral drug – the triazoles. Resistance has now been found in all continents in the environment, and is directly related to the use of triazole fungicides. Patients fail therapy and mortality increases significantly when resistance is present. The only alternative antifungals are less effective and only intravenous.

There is a new generation of oral antifungal agents in clinical development, which will combat resistance: olorofim, ibrexafungerp, APX001 and others. GAFFI argues that to minimize resistance to these agents, their environmental release should be minimal, especially preventing any use on crops or for seed protection as new fungicides. Other compounds directed against the same new molecular targets as these novel antifungals could induce resistance and therefore should not be approved for fungicide use unless they are inactive against A. fumigatus.

Dr Marc Sprenger, Director of the AMR Secretariat at WHO stated: “Antimicrobial resistance, including resistance to antifungals, is an increasingly serious threat to human health that requires action across all government sectors and society. The World Health Organization (WHO) is supporting countries to prevent and control antimicrobial resistance under the Global Action Plan on AMR. The development of potential new antimicrobials, including fungicides, is essential for tackling AMR.”

Professor David Denning, Chief Executive of GAFFI said: “Since we described triazole resistance in Aspergillus in 1995, and the gradually rising numbers of resistant isolates from 2003, we now have many untreatable patients. Hopefully new antifungals will get licensed and the world needs to learn from the unintended negative consequence of fungicide spraying and worldwide resistance emergence.”

The release of the letter came during a 2 day Workshop “Azole resistance in Aspergillus fumigatus: the next step” at the Royal Netherlands Society of Arts and Sciences (Trippenhuis) which coincides with World Aspergillosis Day on February 1st.  Link to meeting: https://congresscare.com/en/congress/azole-resistance-in-aspergillus-fumigatus-the-next-step/

GAFFI’s call also included efforts to increase research on the relationship between fungicide use and resistance, a surveillance network, extended tests of fungicides for their potential to induce clinical antifungal resistance and strenuous efforts to improve stewardship of antifungals in clinical practice.

Notes to Editors:

For more information please contact Luisa Morlano, The Goodwork Organisation on Tel: +44 (0) 20 8747 1488 or via email onluisa.m@thisisgoodwork.org

GAFFI is a charitable foundation (NGO) focused on reducing deaths and illness caused by fungal disease.  Fungal diseases are neglected worldwide by public health authorities. GAFFI efforts are directed at:

1. Identifying and publicising gaps in diagnostics and treatments for fungal diseases.
2. Consulting on how healthcare could be improved through facilitating training, encouraging companies to expand their markets and recommending improvements in infrastructure.
3. Estimating the burden of serious fungal diseases, country by country. Over 75 country estimates are complete, and many of these are published
4. Developing, implementing and evaluating countrywide diagnostic programs – Guatemala (fungal infections in AIDS) the first, Kenya the second.
5. Influencing national and international agencies to ‘adopt’ fungal diseases alongside existing programs including TB, microbiology, AMR, NTDs and incorporation of key generic antifungals onto the WHO Essential Medicines List.
6. Focusing diagnostic improvements for GAFFI’s priority diseases.

GAFFI issued a 10-year Roadmap in 2015 calling for ‘95-95 by 2025’, summarized as 95 per cent of patients with serious fungal infections are diagnosed and treated. http://www.gaffi.org/roadmap/