A major category of drivers involves changes in the environment and the interface between humans, animals, and the natural world, which is a core concept of the "One Health" approach.

• Zoonotic Spillover: Around 75% of infectious diseases in humans result from a zoonotic spillover event, where a pathogen breaches biological barriers between species.
  • Encroachment on Animal Habitats: Urbanisation, deforestation, and habitat fragmentation disrupt natural ecosystems and change wildlife behaviour, forcing animals closer to human settlements and increasing chances of zoonotic contact. Human encroachment on natural habitats raises the risk of zoonotic events.
  • Climate Change and Global Warming: Climate change is a significant driver that alters animal migration patterns, vector habitats, and disease seasonality. For example, warmer temperatures have expanded the range of disease-carrying mosquitoes. Global warming is also believed to have contributed to the emergence of certain pathogens like Candida auris (C. auris), as fungi adapt to higher temperatures.
  • "Mixing Vessels" and Animal Husbandry: Intensive animal farming, where animals are confined, serves as a breeding ground for viral mutations. Live animal markets and wet markets also function as "mixing vessels" where diverse species are kept in crowded, unsanitary conditions, facilitating interspecies transmission and viral recombination. Intensive livestock husbandry, global trade, and increasing human population density all heighten the risk of emerging infectious diseases of zoonotic origin.
  • Wildlife exploitation and trade: Global trade in wildlife also creates new pathways for pathogens to spread. The illegal wildlife trade has widespread effects on species, ecosystems, and human health.

2. Pathogen Evolution and Biological Characteristics

The innate biology of pathogens influences their potential to cause pandemics and develop drug resistance.

• Viral Mutation: RNA viruses, such as coronaviruses and influenza, are particularly susceptible to mutations because of their less stable genetics and high error rates during replication. These mutations can increase transmissibility, evade immune responses, or broaden host ranges. Viruses that mutate frequently and transmit between humans and animals are most likely to cause rapid and widespread outbreaks.
• Host Range Expansion and Recombination: A pathogen’s ability to infect multiple species (host range) increases spillover risk. Viruses often jump from wildlife reservoirs to intermediate hosts, where they can mutate and recombine with other viruses, resulting in new strains that are highly infectious to humans.
• Respiratory Transmission: Viruses that spread through the respiratory system (via droplets or aerosols, as seen with influenza and coronaviruses) are most likely to cause a pandemic because they spread easily from person to person and can travel and persist in the air.
• Asymptomatic Spread: Diseases with large numbers of asymptomatic carriers that contribute to transmission create particular challenges for public health strategies. The rapid global dissemination of COVID-19, for example, was driven by asymptomatic transmission.

3. Human Activity and Failures in Public Health Systems (AMR Drivers)

The emergence and spread of antimicrobial resistance (AMR), the “invisible crisis”, are greatly accelerated by human activities and systemic failures.

• Misuse and overuse of antimicrobials (selection pressure):this is the main driver behind the development and spread of AMR across all sectors (human medicine, animal health, agriculture, and crops).
  • Inappropriate Prescribing: This includes doctors prescribing antibiotics for viral infections ("just in case") or patients poorly adhering to therapy regimens.
  • Agriculture and Livestock: Antibiotics are often misused to boost growth or prevent disease in healthy animals and crops, particularly in large-scale animal production.
  • Drug Availability: The widespread presence of substandard and falsified antimicrobials, coupled with inadequate regulation permitting over-the-counter sales, exacerbates the problem.
• Poor Sanitation and Hygiene (WASH): Inadequate access to clean water, sanitation, and hygiene (WASH) in healthcare facilities, farms, schools, households, and communities increases the burden of infectious disease and promotes the spread of drug-resistant pathogens. Infections spread more rapidly in poor living conditions due to lack of sanitation facilities, which increases the demand for antibiotics.
• Environmental Contamination and Pollution:The environment serves as a reservoir where resistance genes develop and disseminate. This process is propelled by the release of antimicrobials and resistant microorganisms into waste from healthcare facilities, pharmaceutical production, commercial farming, and fish farming.
  • Biocides/Disinfectants: The extensive use and release of biocides and disinfectants (such as Quaternary Ammonium Compounds or QACs, especially heightened during the COVID-19 pandemic) into the environment can encourage antibiotic resistance. QAC exposure can lead to cross-resistance (where a single resistance trait withstands multiple agents) and co-selection (where resistance genes are linked together) by increasing the expression of multi-drug efflux pump genes.
  • Wastewater Treatment Plants (WWTPs): WWTPs act as reservoirs for resistance development, hosting selective stressors like QACs and antibiotics, resistance donors, and resistance recipients. Even sub-inhibitory levels of chemicals in WWTPs can promote the dissemination of resistance genes.
• Vectors (Insects, Rodents, and Pets): Insects such as houseflies and cockroaches, rodents like rats and mice, and pets serve as reservoirs and vectors that spread AMR to humans, often moving between contaminated and unpolluted environments. They transmit AMR through direct contact, contamination of human food and water, and horizontal gene transfer.
• Global Mobility: International connectivity, population movement, and global travel and trade speed up the spread of both viral and bacterial resistance worldwide.

In summary, the emergence of disease results from a microbial world that is constantly evolving, meeting a human world that is rapidly transforming the planet's landscape, creating an environment rich in selection pressures (antibiotics, biocides, pollution) and pathways for swift global dissemination (human mobility, poor sanitation).

One helpful way to understand the relationship between human activities and microbial adaptation is to view antibiotic use as accelerating a microbial arms race. While bacteria naturally develop resistance over billions of years, widespread human misuse of antibiotics creates a vast, random selective pressure, pushing bacteria to quickly activate and exchange resistance genes, turning ancient survival mechanisms into immediate global dangers.

That is an excellent and focused question, especially as we prepare for future infectious threats. Based on the latest categorisation efforts documented in the sources, one pathogen frequently highlighted in the Critical Priority tier, particularly because of its nature as a multidrug-resistant (MDR) fungus and its high public health risk, is Candida auris (C. auris).

Here is an explanation of why C. auris is regarded as a critical priority pathogen on various public health and R&D lists.

1. Critical Priority Classifications

• WHO Fungal Priority Pathogens List (FPPL): The World Health Organization (WHO) has classified Candida auris as a "critical priority" fungal pathogen on its FPPL, which was developed to guide research, development, and public health action.
• CDC Urgent Threat: The U.S. Centers for Disease Control and Prevention (CDC) classifies C. auris as a public health threat that requires urgent and vigorous action. The CDC director even described it as a "catastrophic threat" in April 2017.
• Rapid Spread and Increase: The pathogen has gained widespread attention due to its multidrug resistance, high transmissibility, and quick emergence. The number of reported clinical cases of C. auris has increased nearly fivefold from 2019 to 2022 in the U.S.

2. Key Characteristics that Define its Critical Status

The critical status of C. auris arises from a combination of virulence factors, drug resistance, and environmental persistence.

A. Multidrug Resistance and Limited Treatment

C. auris is a multidrug-resistant yeast. Its resistance is highly concerning because fungi already have limited treatment options, typically relying on only three classes of antifungals.

• Broad Resistance: C. auris is often resistant to at least one kind of antifungal drug. Most isolates are resistant to fluconazole (an azole antifungal).
• Pan-Resistance: Some strains of C. auris are resistant to all three existing classes of antifungals (azoles, polyenes, and echinocandins), rendering them "pan-drug-resistant" and nearly impossible to treat.
• Decline in Antifungal Effectiveness: The number of isolates resistant to echinocandins (the preferred treatment for most C. auris infections) tripled in 2021.
• Misidentification: C. auris is often hard to identify and can be mistaken by commonly used laboratory methods, resulting in improper patient management and treatment delays.

B. Persistence in Healthcare Settings

C. auris poses a significant threat in healthcare environments, directly contributing to the kind of infection tsunami you warned about.

• Hospital Outbreaks: They cause prolonged and hard-to-manage outbreaks in hospitals and long-term care homes. This is worsened by the COVID-19 pandemic diverting resources away from fighting and monitoring the fungus, resulting in outbreaks and further spread due to poor infection control practices.
• Environmental Survival: Unlike other Candida species, C. auris can remain in the healthcare environment for weeks on inanimate surfaces, requiring specialised cleaning and disinfection protocols. It can also withstand many common hospital disinfectants. This environmental resilience facilitates transmission.
• Contagiousness: It spreads easily among severely ill patients and has a high potential for outbreaks in healthcare settings.

C. Mortality and Patient Risk

C. auris is especially dangerous because it causes severe illness in vulnerable populations, such as critically ill patients.

• High Mortality: Invasive infections such as bloodstream infections (BSI) caused by C. auris have high mortality rates, ranging from 30% to 70% in adults.

Candida auris symbolises the "tsunami of infections" because it signifies the catastrophic convergence of pathogen fitness (thermotolerant, persistent) and systemic failure (multidrug resistance, difficulty diagnosing) in the delicate hospital environment where the most vulnerable patients are treated.

That is an excellent question. The idea of "prototype pathogens" plays a crucial role in the modern, proactive approach being embraced by global health organisations to prepare for the next pandemic, rather than simply responding to the previous one.

The purpose of prototype pathogens is to act as models for research and development (R&D) to speed up the development of medical countermeasures (MCMs) for emerging and unknown threats.

Here are the specific purposes and roles of prototype pathogens, drawn from the sources:

1. Enabling Proactive Countermeasure Development

The main aim of identifying prototype pathogens is to ensure preparedness for novel or poorly understood threats.

• Model Development: Prototype pathogens are proposed to be used as a model to develop diagnostic tests, treatments, and/or vaccines.
• Family-Focused Strategy: This approach recognises that pathogens within the same viral family are closely related. By concentrating R&D on a specific prototype pathogen, the resulting medical countermeasures (MCMs) can potentially be adapted for use against other emerging pathogens within that family. This enhances the ability to respond to agents like "Disease X"—a hypothetical, unknown pathogen.
• Promoting Basic Research: Prototypes also help to advance research on lesser-known viruses. This proactive research is essential because MCMs are based on decades of fundamental research, and previous R&D on existing viruses will speed up the development of MCMS when new, related viruses appear.

2. Context within the New Priority List

The updated World Health Organization (WHO) R&D plan prioritises threats across entire viral families, rather than focusing on individual pathogens, marking a novel approach compared to the lists established in 2017 and 2018.

• Number of Prototypes: The latest list includes 30 prototype pathogens across 22 families, considered to be of high or medium risk (meaning they contain at least one priority pathogen).
• Targeted Countermeasures: The strategy highlights the importance of developing MCMs for known threats (the primary pathogens) as well as for potentially similar ones (the prototype pathogens).

In essence, designating a virus as a prototype pathogen is a strategic investment. It functions like developing a foundational toolkit against a known enemy type so that when a highly mutated or entirely new member of that enemy family appears, you are not starting the fight from scratch. Instead of waiting for the inevitable emergence of a new threat (Pathogen X), resources are directed toward building platform technologies and libraries that can rapidly be adapted within the desired "100 Days Mission" framework.