Challenges and advances in the diagnosis of invasive Mucormycosis

Challenges and Advances in the Diagnosis of Invasive Mucormycosis

Abstract

Mucormycosis is an aggressive, angioinvasive infection caused by molds of the order Mucorales and is now listed among the high-priority WHO fungal pathogens. Angioinvasion drives vascular thrombosis and ischaemic necrosis, producing fulminant disease with mortality of roughly 40–50% overall and up to 80% in pulmonary or disseminated forms. The COVID-19 pandemic triggered a marked resurgence—tens of thousands of cases within months, chiefly in India—superimposed on the classic risk groups of uncontrolled diabetes, haematological malignancy, transplantation and corticosteroid use. Because survival depends on early liposomal amphotericin B and surgical debridement, prompt diagnosis is the key modifiable determinant of outcome.

Diagnosis remains difficult. Clinical and radiological features are nonspecific and overlap with invasive aspergillosis; the reverse halo sign on CT is suggestive but not confirmatory. Conventional microscopy, culture and histopathology are slow, require invasive biopsy, often yield negative cultures, and cannot reliably identify the genus. Critically, galactomannan and (1→3)-β-D-glucan have no diagnostic value because Mucorales lack these cell-wall components, leaving a persistent gap in non-invasive testing.

This review summarises the advances reshaping diagnosis. Foremost is molecular detection: Mucorales-specific quantitative PCR on serum, plasma and whole blood—including cell-free DNA—offers non-invasive, early diagnosis (≈85% sensitivity, ≈90% specificity), often turning positive several days before mycological confirmation, prompting proposals to add Mucorales PCR to EORTC/MSGERC consensus definitions. Complementary tools include MALDI-TOF and multiplex PCR/sequencing for species identification, metagenomic sequencing, and novel Mucorales-specific antigen lateral-flow devices with point-of-care potential. Emerging CRISPR assays, breath metabolomics, biosensors and AI-assisted imaging promise faster, cheaper platforms.

No single assay is yet sufficient: optimal diagnosis integrates clinical suspicion, imaging, histopathology, culture and molecular/antigen testing, consistent with ECMM/MSGERC guidance. Key priorities are validating and standardising molecular and antigen tests and developing affordable, rapid, non-invasive diagnostics for resource-limited settings, where the burden is greatest.

Keywords: mucormycosis; Mucorales; invasive fungal infection; diagnosis; Mucorales PCR; cell-free DNA; lateral-flow assay

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