Antimicrobial resistance (AMR) has long been a recognised global health crisis, but the focus has primarily been on bacterial infections. Despite their increasing prevalence and treatment resistance, fungal infections have been under-represented in public health efforts. The World Health Organisation (WHO) took a significant step in 2022 by releasing the Fungal Priority Pathogen List (FPPL), aiming to draw attention to the critical issue of antifungal resistance (AFR). The rapid rise of AFR is not only a public health concern but also a potential threat to global food security due to the overlap in the use of antifungal agents in both agriculture and medicine. This article delves into the causes, implications, and potential solutions to this silent pandemic.
The Complexity of Fungal Resistance
Developing antifungal drugs is significantly more challenging than antibiotics because fungi share greater biological similarities with human cells than bacteria do. This makes it challenging to target fungal cells without causing harm to human cells. As a result, there are currently only four main classes of systemic antifungal drugs: azoles, polyenes, echinocandins, and allylamines. However, resistance to these drugs, especially azoles and echinocandins, is increasing rapidly. This resistance has led to the emergence of multidrug-resistant strains like Candida auris, Aspergillus fumigatus, and Trichophyton indotineae, which are increasingly difficult to treat with existing drugs.
One key factor contributing to this resistance is the widespread use of fungicides in agriculture, which often have mechanisms of action similar to medical antifungals. For instance, azoles are extensively used to protect crops from fungal infections. However, this agricultural use has led to cross-resistance in human pathogens such as Aspergillus fumigatus. As food security becomes a growing concern with climate change and increasing population pressure, the question arises: how can we balance the need for effective fungicides in agriculture with the growing threat of AFR?
The Impact of AFR on Global Health
Fungal infections currently affect approximately 6.5 million people annually, contributing to an estimated 3.8 million deaths globally. While bacterial resistance has garnered much attention, the threat posed by fungal pathogens remains largely under-recognised. Invasive fungal infections often occur in immunocompromised patients, such as those undergoing chemotherapy, organ transplants, or suffering from HIV/AIDS. These populations are particularly vulnerable to drug-resistant fungal infections, which can be fatal if not treated effectively.
The difficulty in diagnosing fungal infections further complicates their treatment. In many low- and middle-income countries, where the burden of fungal infections is highest, diagnostic tools such as mass spectrometry or molecular testing are either unavailable or unaffordable. This delay in diagnosis often leads to inappropriate treatment, contributing to the rise of resistance. Moreover, antifungal susceptibility testing, which is essential for determining the most effective treatment, is not widely accessible. The lack of adequate diagnostic capabilities exacerbates the spread of resistant fungal strains, leading to a vicious cycle of misdiagnosis and ineffective treatment.
Agricultural Practices and Cross-Resistance
The use of antifungals in agriculture has a direct impact on the development of drug-resistant fungal strains. The fungicides used to protect crops often have mechanisms of action similar to those used in human medicine. As a result, fungal pathogens exposed to these agricultural fungicides can develop resistance that also applies to medical antifungals. This phenomenon is particularly concerning with Aspergillus fumigatus, a common environmental fungus that can cause life-threatening infections in immunocompromised individuals. The widespread use of azoles in agriculture has led to the emergence of azole-resistant strains of A. fumigatus, which are now found in clinical settings, making infections more challenging to treat.
The agrochemical industry, driven by the need to protect crops from fungal diseases, has developed fungicides with similar modes of action to those used in medicine. This has led to cross-resistance in critical priority pathogens, such as A. fumigatus. Efforts to curb the use of medically important antifungals in agriculture have been implemented in some countries. For example, India's government has banned the use of certain antibiotics and antifungals for plant protection. However, a global, coordinated effort is needed to address this issue comprehensively, as the continued use of these chemicals poses a long-term risk to both food security and human health.
Conclusion
Antifungal resistance is a growing threat that requires immediate global attention. The rise of drug-resistant fungal pathogens, fuelled by both medical and agricultural practices, threatens to undo decades of progress in managing fungal infections. The complexity of fungal biology, the limited number of antifungal drug classes, and the challenges of diagnosing infections all contribute to the difficulty of combating this silent pandemic. As the world faces increasing pressure on food security and public health, stakeholders from both agriculture and medicine must come together to develop sustainable solutions. Collaborative efforts, improved diagnostic capabilities, and a more judicious use of antifungals in agriculture and medicine are crucial to preventing a future where fungal infections become untreatable.
Source: The Lancet
Image Credit: iStock
