Invasive Fungal Infections in Immunocompromised Populations

Invasive fungal infections represent a major challenge in immunocompromised individuals, including patients with haematological malignancies, solid organ or stem cell transplants, prolonged neutropenia, uncontrolled diabetes and those receiving high-dose corticosteroids or novel immunomodulatory therapies. Pathogens most commonly implicated are species of Candida, Aspergillus and the angioinvasive Mucorales, although non-Aspergillus moulds such as Fusarium and Scedosporium are increasingly recognised. These fungi penetrate host barriers, invade blood vessels and disseminate, often leading to high morbidity and mortality. Clinical presentation varies from pulmonary and sinus disease to disseminated or cutaneous forms, influenced by the underlying immune defect and geographical factors. Diagnostic delays persist because of non-specific signs, limited sensitivity of culture and imaging ambiguity. Advances in molecular diagnostics and antigen detection have improved early identification, yet access remains uneven. Antifungal therapy relies primarily on azoles, echinocandins and polyenes, but drug resistance and toxicity complicate management. Emerging strategies include immunotherapeutic adjuncts, host–pathogen interaction modulators and prophylactic regimens tailored to individual risk profiles. Global surveillance reveals shifting epidemiology driven by demographic changes, medical interventions and environmental exposures, underscoring the need for integrated prevention, rapid diagnosis and novel therapeutics to reduce the burden of these life-threatening infections.

Research from Nature Portfolio

Recent studies have demonstrated that hypoxia-inducible factor 1-alpha (HIF1α) signalling plays a dual role in pulmonary mucormycosis. In vitro and in vivo models reveal that activation of HIF1α promotes fungal invasion of airway epithelial cells while simultaneously enhancing the host’s pro-inflammatory response. Pharmacological inhibition of HIF1α reduced tissue invasion by Mucorales without increasing fungal load and conferred a survival benefit in murine infection models. These findings identify HIF1α as a central regulator of host–fungus interplay and suggest that targeted modulation of hypoxic signalling may augment standard antifungal therapy in high-risk patients.

Invasive Fungal Infections in Immunocompromised Populations publication trend

The graph below shows the total number of articles in invasive fungal infections in immunocompromised populations across all publications each year (not limited to Nature Index journals).

Technical terms

Angioinvasion: The capacity of certain fungi to invade blood vessel walls, causing thrombosis and tissue necrosis.

Hypoxia-inducible factor 1-alpha (HIF1α): A transcription factor that regulates cellular responses to low oxygen tension and modulates inflammatory pathways.

Immunocompromised host: An individual whose immune defences are impaired by disease, therapy or genetic factors, increasing susceptibility to opportunistic pathogens.

Mucormycosis: A severe angioinvasive infection caused by fungi of the order Mucorales, often affecting immunocompromised or diabetic patients.

References

1. Multiple roles for hypoxia inducible factor 1-alpha in airway epithelial cells during mucormycosis. Nature Communications (2024).
2. Global Epidemiology of Mucormycosis. Journal of Fungi (2019).
3. Epidemiology and Diagnosis of Mucormycosis: An Update. Journal of Fungi (2020).
4. Multicenter Epidemiologic Study of Coronavirus Disease–Associated Mucormycosis, India - Volume 27, Number 9—September 2021 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases (2021).
5. Invasive Non-Aspergillus Mold Infections in Transplant Recipients, United States, 2001–2006 - Volume 17, Number 10—October 2011 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases (2011).