Rising threat of antifungal resistance

The World Antimicrobial Resistance (AMR) Awareness Week was celebrated from Nov 18–24, with the theme “Educate. Advocate. Act Now”, had a limited impact on community awareness and behavioral change toward rational antimicrobial use.

When bacteria, fungi, viruses, and parasites evolve over time and lose their ability to respond to medications, it’s known as AMR, which makes infections more difficult to treat and increases the risk of disease transmission, severe illness, and death. Designated as a ‘silent pandemic’ AMR has claimed three lives per minute, totaling around 36m deaths since 1990. Without urgent policy interventions, and preventative actions, the current projection indicates an alarming rise to 1.9m deaths annually by 2050. 

The economic impact is equally staggering, with the World Bank’s 2017 projection estimating that AMR could cost up to $1trn globally by mid-century and force an additional 28m into extreme poverty by 2050, with 93 percent of them residing in low-income countries. AMR was associated with 23,200 fatalities and attributed to 6,400 additional deaths in Nepal in 2019. The country ranks 52nd globally and 2nd in South Asia for age-standardized AMR mortality rates per 100,000 population.

AMR includes not only bacterial infections and antibiotic misuse but also resistance to antifungal medications, crucial for treating life-threatening infections in immunocompromised individuals. Fungal illnesses are prevalent in Nepal, especially among those with chronic conditions like diabetes, HIV, cancer, lung disease, and tuberculosis. 

A 2015 study estimated 1.87 percent Nepali population suffers from serious fungal infections annually, with conditions such as invasive aspergillosis and cryptococcal meningitis being prevalent among HIV/AIDS patients. Another 2020 research in Bhaktapur found that one-third diabetic patients had fungal infections, caused by Candida and Aspergillus species, resistance to fluconazole and ketoconazole, both broad-spectrum azole antifungals. This underscores the urgent need for improved diagnosis and treatment strategies to tackle antifungal resistance in Nepal.

Antifungal resistance affects both human and animal, with escalating antifungal use in veterinary and agriculture contributing to resistant strains. This dual threat compromises treatments, impacts livestock productivity, undermines food security and economics. Studies highlight widespread fungal contamination in food, feed, and livestock, emphasizing the urgent need for awareness, surveillance, rational use, stewardship and containment strategies to safeguard public health and agricultural productivity.

Aflatoxin contamination is a significant concern in Nepal, particularly in maize, rice, and animal feed. A 2005 study by Koirala and team observed high aflatoxin in staple foods, posing health risks like liver damage and immune suppression. Another 2024 research by Agriculture and Forestry University revealed very high levels of aflatoxin contamination in the dairy milk in Kathmandu, presenting a serious public health issue. Resistant fungal infections in livestock have reduced milk production and caused health issues.

The aquaculture sector in Nepal is also affected by fungal pathogens, which contribute to fish morbidity and mortality, threatening the livelihoods of small-scale farmers, as highlighted by Shrestha and team in 2020 through research at four fish farms. Similarly, a 2009 study by Aryal and Karki from Nepal Agriculture Research Council found a high prevalence of aflatoxins in poultry feed, further impacting the rural economy.

Climate change exacerbates the fungal threat by promoting fungal growth and aflatoxin production through erratic rainfall and seasonal variation. Poor air quality increases airborne fungi, worsening respiratory and skin infections, particularly in immunocompromised individuals. Shifting monsoon patterns and poor storage practices raise contamination risks, especially in crops like rice straw used for animal feed. Droughts enhance spore release from Coccidioides, while flooding spreads spores. Climate change also enables fungi to spread into new areas and adapt to higher temperatures, increasing the prevalence of pathogens like Candida auris.

The diagnostic approach to antifungal resistance in Nepal involves several key components. Precise fungal pathogen diagnosis is crucial for effective treatment, with traditional methods like laboratory culture and morphological identification being time-consuming and error-prone. Recent studies emphasize the need for rapid diagnostic tests to identify resistant strains for targeted treatment. Leveraging facilities developed during the Covid-19 pandemic, such as PCR, Next-generation sequencing (NGS) and serological tests, could enable robust, faster, precise diagnoses. 

The WHO’s AWaRe framework, which categorizes antifungals into Access for common infections, Watch for broader-spectrum requiring monitoring, and Reserve for last-resort options, can guide prescribing practices to contain resistance. Implementing this framework can optimize antifungal prescribing while reducing resistance. Nepal can adapt this framework to suit local healthcare needs, incorporating more accessible, user-friendly methods. 

However, patterns of antifungals use reveal concerning trends, with practitioners relying on broad-spectrum antifungals without proper diagnostics, leading to overuse and resistance. Additionally, antifungals used as growth promoters in livestock fosters resistance in animal pathogens, posing risks to human health via zoonotic transmission.

Antifungal resistance in Nepal is driven by several challenges such as limited awareness, inadequate surveillance, poor stewardship and weak healthcare infrastructure. Addressing this, the government must establish robust monitoring systems for antifungal resistance in food and feed, supported by regulatory frameworks to protect public health. Evidence-based education and training programs for healthcare providers, veterinarians, and farmers are essential to promote rational antifungal use and raise community awareness about contamination risks. Integrating fungal infections into livestock insurance and providing essential antifungal medications free of charge can improve accessibility.

Strengthening collaboration among the Department of Livestock Services, ‘One Health’ stakeholders and local governments is vital for enhancing prevention, diagnosis, and treatment capabilities. Implementing standard treatment guidelines and rational use policies can help mitigate overuse. Cross-sectoral collaboration among agricultural experts, veterinarians, and public health officials is vital. Paired with community campaigns, it can drive behavioral change toward responsible antifungal practices. Research institutions should prioritize studying local resistance mechanisms and innovating new solutions. Adopting the ‘One Health’ approach provides a framework for integrated interventions across human, animal, agricultural and environmental sectors, essential for effectively combating the escalating threat of antifungal resistance.

The authors are researchers at the Nexus Institute of Research and Innovation specializing in AMR