Fungal Genomics & Biology
Open Access

Diagnostic and Therapeutic Gaps in Invasive Mycoses Management

Reza Iacopino^{* *}Correspondence: Reza Iacopino, Department of Life Sciences, University of Sao Paulo, Sao Paulo, Brazil, Email:

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Description

Invasive mycoses-severe fungal infections that invade deep tissues and organs-pose a growing threat to global public health, particularly among immunocompromised individuals. Despite advances in medical technology, the mortality associated with invasive fungal infections remains unacceptably high. Significant diagnostic and therapeutic gaps contribute to delayed treatment, drug resistance, and poor clinical outcomes. This article explores the major diagnostic and therapeutic shortcomings in invasive mycoses management, including limited diagnostic sensitivity, slow turnaround times, antifungal resistance, inadequate therapeutic options, and disparities in global healthcare access. Addressing these gaps requires a multifaceted approach integrating early diagnostics, targeted therapies, and public health interventions.

Invasive mycoses, caused by pathogenic fungi such as Candida, Aspergillus, Cryptococcus, and emerging species like Candida auris, are responsible for over 1.5 million deaths annually worldwide. The incidence of these infections has escalated due to an increase in immunocompromised populations-such as patients with HIV/AIDS, organ transplant recipients, cancer patients undergoing chemotherapy, and those in Intensive Care Units (ICUs). Despite clinical advancements, high mortality rates-often exceeding 50%-highlight major limitations in the current management of these infections. Early and accurate diagnosis, followed by prompt and effective therapy, is essential for survival. Unfortunately, existing diagnostic tools are slow, insensitive, or non-specific, and therapeutic options remain limited due to toxicity, resistance, and lack of novel agents.

The clinical manifestations of Invasive Fungal Infections (IFIs) are often nonspecific-fever, fatigue, or organ dysfunction-making it difficult to distinguish from bacterial or viral infections. This is especially problematic in critically ill or immunocompromised patients, where early differentiation is crucial for survival. Traditional culture-based methods remain the gold standard for fungal diagnosis but suffer from poor sensitivity and prolonged turnaround times. For example, blood cultures detect less than 50% of candidemia cases and may take days to yield results. Aspergillus species rarely grow in culture from blood or cerebrospinal fluid. Non-culture-based diagnostics such as Galactomannan (GM) and β-D-Glucan (BDG) assays have improved detection of Aspergillus and other fungi, but they lack specificity and are susceptible to false positives due to crossreactivity or concurrent bacterial infections. Moreover, their utility in pediatric and non-neutropenic patients remains controversial. Radiological imaging such as CT scans can suggest IFIs (e.g., “halo sign” in pulmonary aspergillosis), but these features are not pathognomonic. Imaging is also inaccessible in resource-limited settings and often does not detect early-stage disease. Molecular diagnostics, including PCR-based assays, Next-Generation Sequencing (NGS), and point-of-care Lateral Flow Assays (LFA), have shown promise in rapidly identifying fungal pathogens. However, these technologies are not yet widely implemented due to cost, lack of standardization, and the need for technical expertise.

Only four major classes of antifungal agents are currently available: Polyenes (e.g., amphotericin B), azoles (e.g., fluconazole, voriconazole), echinocandins (e.g., caspofungin), and flucytosine. This is in stark contrast to the arsenal of antibiotics for bacterial infections. Each antifungal class has limitations in terms of spectrum, resistance, toxicity, or pharmacokinetics. Resistance is increasingly reported among Candida, Aspergillus, and Cryptococcus species. The emergence of multidrug-resistant Candida auris is particularly alarming due to its ability to survive in hospital environments and resist multiple antifungal agents. Long-term prophylactic or empirical antifungal use further drives resistance development.

Amphotericin B, although effective, is associated with significant nephrotoxicity. Azoles interact with cytochrome P450 enzymes, leading to drug-drug interactions with immunosuppressants, anticoagulants, and chemotherapeutics. This complicates treatment in patients with comorbidities. Therapeutic Drug Monitoring (TDM) is necessary for agents like voriconazole and posaconazole to ensure efficacy and minimize toxicity. However, TDM is often unavailable in many healthcare settings. Lack of standardized dosing protocols also contributes to suboptimal outcomes. Because of diagnostic delays, antifungal therapy is often initiated empirically. Empirical treatment may miss resistant strains or unnecessarily expose patients to toxic agents. This further underscores the need for rapid, accurate diagnostics. Diagnostic and therapeutic gaps are exacerbated in Low and Middle-Income Countries (LMICs), where laboratory capacity, access to antifungals, and healthcare infrastructure are limited. This is most evident in the management of cryptococcal meningitis and histoplasmosis in sub-Saharan Africa and Latin America. The lack of fungal disease surveillance in many countries leads to underreporting and underfunding of fungal research and treatment.

Conclusion

Despite notable advancements, invasive mycoses remain underdiagnosed and undertreated worldwide. Diagnostic delays, limited antifungal options, resistance, and global disparities contribute to poor outcomes. Bridging these diagnostic and therapeutic gaps requires global collaboration, investment in diagnostic infrastructure, development of new antifungal agents, and policies to ensure equitable access to life-saving interventions. As fungal infections continue to emerge and evolve, a proactive and integrated approach is critical to improving patient survival and public health resilience.