Proceedings of a Workshop Series

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This activity was supported by contracts and awards between the National Academy of Sciences and American Society of Tropical Medicine and Hygiene, Burroughs Wellcome Fund, Centers of Disease Control and Prevention (Contract No. 75D30121F00095), EcoHealth Alliance, ExxonMobil Foundation, Infectious Diseases Society of America, Johnson & Johnson (Contract No. C2021020002), Merck & Co., Inc., National Institute of Allergy and Infectious Diseases (Contract No. HHSN263201800029I, Task No. HHSN26300011), New Venture Fund (Contract No. NVF-NGDF-NAT10-Subgrant-017387-2022-04-01), Sanofi Pasteur, U.S. Agency for International Development (Grant No. 7200AA18GR00003), Uniformed Services University of Health Sciences (Award No. 5R13FD006897-03), U.S. Food and Drug Administration (Award No. 5R13FD006897-03), U.S. Department of Veterans Affairs (Contract No. 36C24518D0171). Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-69767-5
International Standard Book Number-10: 0-309-69767-0
Digital Object Identifier: https://doi.org/10.17226/26833

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2023. The role of plant agricultural practices on development of antimicrobial resistant fungi affecting human health: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/26833.

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PLANNING COMMITTEE ON THE ROLE OF PLANT AGRICULTURAL PRACTICES ON DEVELOPMENT OF ANTIMICROBIAL RESISTANT FUNGI AFFECTING HUMAN HEALTH¹

SALLY MILLER (Co-chair), Distinguished Professor of Food, Agricultural and Environmental Sciences in Plant Pathology, The Ohio State University

PAIGE WATERMAN (Co-chair), Professor of Medicine and Vice Chair of Clinical Research, Uniformed Services University of the Health Sciences

MARIN BREWER, Associate Professor, University of Georgia

TOM CHILLER, Chief, Mycotic Diseases Branch, U.S. Centers for Disease Control and Prevention

JULIUS FAJARDO, Senior Plant Pathologist, Office of Pest Management Policy, Office of Chief Economist, U.S. Department of Agriculture

SUSAN JENNINGS, Senior Advisor for Public Health, Office of Pesticide Programs, U.S. Environmental Protection Agency

RAMANAN LAXMINARAYAN, Director, One Health Trust

JEFFREY LEJEUNE, Food Safety Officer, Food Systems and Food Safety Division, Food and Agriculture Organization of the United Nations

MERVALIN MORANT, Program Manager, Food, Agriculture and Veterinary Defense, U.S. Department of Homeland Security

PHILIP TAYLOR, Training Manager and Global Plant Clinic Coordinator, CABI

Forum on Microbial Threats Staff

ELIZABETH ASHBY, Associate Program Officer

CLAIRE BIFFL, Research Assistant

CHARLES MINICUCCI, Research Assistant (until January 2023)

JUSTIN HAMMERBERG, Senior Program Assistant (until November 2022)

JULIE LIAO, Director, Forum on Microbial Threats

JULIE PAVLIN, Senior Board Director, Board on Global Health

___________________

¹ The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.

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FORUM ON MICROBIAL THREATS¹

PETER DASZAK (Chair), President, EcoHealth Alliance

KENT E. KESTER (Vice Chair), Vice President of Translational Medicine, International AIDS Vaccine Initiative

EMILY ABRAHAM, Director, External Affairs and Policy, Global Public Health at Johnson & Johnson

KEVIN ANDERSON, retired

CHRISTOPHER BRADEN, Acting Director, National Center for Emerging Zoonotic Infectious Diseases, U.S. Centers for Disease Control and Prevention

DANIEL BAUSCH, President, American Society of Tropical Medicine and Hygiene and Senior Director, Emerging Threats & Global Health Security, FIND

CRISTINA CASSETTI, Deputy Division Director, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases

ANDREW CLEMENTS, Senior Scientific Advisor, Emerging Threats Division, U.S. Agency for International Development

MALICK DIARA, Public Health Manager, Corporate Medicine and Occupational Health Department, ExxonMobil

SCOTT F. DOWELL, Deputy Director for Surveillance and Epidemiology, Bill & Melinda Gates Foundation

MARCOS A. ESPINAL, Assistant Director, Pan American Health Organization

EVA HARRIS, Professor, Division of Infectious Diseases and Vaccinology, and Director, Center for Global Public Health, University of California, Berkeley School of Public Health

JON H. HEINRICHS, Associate Vice President and R&D New Targets, Franchise Head in Portfolio Strategy and Execution, Sanofi Pasteur

ELIZABETH D. HERMSEN, Lead, Global Antimicrobial Resistance & Antimicrobial Stewardship Medical Affairs, Pfizer

MARK G. KORTEPETER, Vice President for Research and Professor of Preventive Medicine and Medicine, Uniformed Services University of the Health Sciences

MICHAEL MAIR, Acting Assistant Commissioner for Counterterrorism Policy and Acting Director, Office of the Chief Scientist, U.S. Food and Drug Administration

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¹ The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.

JONNA A. K. MAZET, Vice Provost—Grand Challenges; Chancellor’s Leadership Professor of Epidemiology & Disease Ecology, University of California, Davis

VICTORIA McGOVERN, Senior Program Officer, Burroughs Wellcome Fund

SALLY A. MILLER, Distinguished Professor of Food, Agricultural and Environmental Sciences in Plant Pathology, The Ohio State University College of Food, Agriculture, and Environmental Sciences

SUERIE MOON, Director of Research, Global Health Centre; Visiting Lecturer, graduate Institute of International and Development Studies; Adjunct Lecturer, Harvard T.H. Chan School of Public Health

RAFAEL OBREGÓN, Country Representative, UNICEF Paraguay

KUMANAN RASANATHAN, Unit Head for Equity and Health, Department of Social Determinants of Health, World Health Organization

GARY A. ROSELLE, Executive Director, National Infectious Disease Services Program, Veterans Health Administration, U.S. Department of Veterans Affairs

PETER A. SANDS, Executive Director, The Global Fund to Fight AIDS, Tuberculosis & Malaria

THOMAS W. SCOTT, Distinguished Professor, Department of Entomology and Nematology, University of California, Davis

MATTHEW ZAHN, Deputy Health Officer, Orange County Health Care Agency

National Academies of Sciences, Engineering, and Medicine Staff

ELIZABETH ASHBY, Associate Program Officer

CLAIRE BIFFL, Research Assistant

CHARLES MINICUCCI, Research Assistant (until January 2023)

JUSTIN HAMMERBERG, Senior Program Assistant (until November 2022)

JULIE LIAO, Director, Forum on Microbial Threats

JULIE PAVLIN, Senior Board Director, Board on Global Health

Reviewers

This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.

We thank the following individuals for their review of this proceedings:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by HUGH H. TILSON, University of North Carolina. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.

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Contents

BOXES AND FIGURES

ACRONYMS AND ABBREVIATIONS

1 INTRODUCTION

Workshop Objectives

Organization of the Proceedings of the Workshop

2 FUNGAL PATHOGENS IN PLANT AND HUMAN HEALTH

Antifungal Drug Uses in Human Medicine

Agricultural Chemical Use Statistical Program

Quadripartite Alliance Joint Activities on Antimicrobial Resistance

Discussion

3 FUNGAL DISEASES, ANTIFUNGAL RESISTANCE, AND HUMAN HEALTH

Impact of Invasive Fungal Diseases and Antifungal Drug Resistance on Human Health

Global Incidence and Prevalence of Aspergillosis and Introduction to Azole Resistance

The Emerging Threat of Antifungal-Resistant Candida Species

Current Research on Pathogenesis and Host Immunity Toward Treatment Options

Discussion

4 FUNGICIDE RESISTANCE IN PLANT PROTECTION USE

Genetics and Mechanisms of Fungicide Resistance

Azole-resistant Aspergillus fumigatus in Agronomic Settings: Hotspots and Coldspots

Discussion

Reflections on Day One

5 ROLE OF FUNGICIDE USE IN FOOD SAFETY AND SECURITY

Role of Azole Fungicides in Safeguarding Food Safety and Security

Azole Use for Food Safety and Security

Discussion

6 DIMENSIONS OF FUNGICIDE REGULATIONS, USE MANAGEMENT, AND RISK ASSESSMENT

Use of Fungicides in Low- and Middle-Income Countries

U.S. Fungicide Regulation and Registration

Organisation for Economic Co-operation and Development Pesticides Programme

Occupational Exposure to Environmental Resistant Fungi and Possible Implications in Human Health

Discussion

7 INNOVATIONS IN ANTIMICROBIAL RESISTANCE SURVEILLANCE TOOLS AND TECHNOLOGIES

Aspergillus fumigatus Azole Resistance Survey by Air Sampling Through a Community Science Approach

Innovation in Data Collection Tools for Surveillance and Mitigation: Crop and Environment Simulation Tools

Impact Network Analysis for Guiding Surveillance and Mitigation

Discussion

Reflections on Day Two

8 ONE HEALTH APPROACH TO ANTIMICROBIAL RESISTANCE AND PATHOGEN SURVEILLANCE

One Health Approach to Antimicrobial Resistance Surveillance and Mitigation Measures

Genomic Surveillance and Epidemiology

Diagnostics, Resistance Testing, and Surveillance Capabilities in Health Care and Agricultural Systems

International One Health Approach to Antimicrobial Resistance and Pathogen Surveillance

One Health Aspects of Circularity

Discussion

9 ANTIFUNGAL DRUG DEVELOPMENT AND STEWARDSHIP IN HEALTH CARE

New Antifungal Drugs in Development

Antifungal Research and Development: Challenges and Need for Incentives

Discussion

10 INTEGRATED PLANT DISEASE MANAGEMENT

Precision Application Technologies and Stakeholder Communication

Finding Needles in Haystacks: Disease Monitoring and Risk Assessment

Mitigation Measures in Compost Hotspots

Discussion

Reflections on Day Three

REFERENCES

APPENDIX A

APPENDIX B

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Boxes and Figures

BOXES

2-1 Strategic Framework for Collaboration on Antimicrobial Resistance

3-1 Hypothetical Case Study of Healthcare-Associated Candida Infection

FIGURES

2-1 Drivers of antimicrobial resistance

4-1 Resistance occurs to all classes of drugs used against plant and animal fungal infections

5-1 Comparative effect of fungicide seed treatment versus no treatment on peanut plant sprouting

6-1 Regional breakdown of azole fungicide use based on Plantwise data analysis

6-2 Occupational exposure versus development of fungal disease

6-3 Clinical implications of resistant Aspergillus spores

7-1 Mitigation and management strategies across the fungal pathogen life cycle

7-2 Example of modeling antimicrobial resistance

8-1 Managing resistance selection in A. fumigatus

8-2 Multifungicide-resistant environmental and clinical isolates in a single clade of A. fumigatus

9-1 Estimated cases per year and estimated mortality of fungal diseases worldwide

10-1 Pathogen life cycle

Acronyms and Abbreviations

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