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Lancet Reg Health Eur
Lancet Reg Health Eur
The Lancet Regional Health - Europe
2666-7762
Elsevier

S2666-7762(24)00206-0
10.1016/j.lanepe.2024.101039
101039
Comment
Contemporary diagnosis and epidemiological trends of mucormycosis: a call for action and caution
Rudramurthy Shivaprakash M. mrshivprakash@gmail.com
a∗
Muthu Valliappan b
Agarwal Ritesh b
a Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, India
b Department of Pulmonary Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, India
∗ Corresponding author. Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, 160012, India. mrshivprakash@gmail.com
21 8 2024
10 2024
21 8 2024
45 1010397 8 2024
8 8 2024
© 2024 The Author(s)
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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pmcMucormycosis, a rare but serious fungal infection, has historically been less studied than the more common mould infection, aspergillosis. However, recently mucormycosis is gaining greater global recognition,1, 2, 3 as evident by including its causative agent as one of the WHO's high-priority fungal pathogens. In this context, the surveillance study from the French mycoses network published in this issue of The Lancet Regional Health—Europe is a significant contribution to the existing literature on mucormycosis epidemiology.4 This report on 550 cases of mucormycosis, is the largest of its kind from Europe and is notable for several reasons.4

To date, studies on mucormycosis have included only proven and probable cases as defined by the EORTC/MSG guidelines.5 The current study is the first to include putative cases diagnosed solely on Mucorales PCR (in serum or bronchoalveolar lavage samples) and merits discussion.4 The study results, particularly the higher proportion of putative cases, a different epidemiology, and an increase in cases coincide with the large-scale implementation of nucleic acid amplification assays in France. Interestingly, the proportion of proven or probable cases remained stable throughout the surveillance period (2012–2022), while the cases with a positive PCR result increased from 16% in 2012 to 91% in 2022.4

Early diagnosis of mucormycosis is an unmet need, and several tests are being developed.6,7 Among these, PCR-based diagnosis is considered specific and has a lower turnaround time than conventional diagnostic tests. While the current data suggests a potential for early diagnosis and better survival in mucormycosis, there are a few important caveats. Among the putative cases (n = 158) included in the current study, 87% had haematological malignancy compared to 5% with diabetes mellitus as the underlying risk factor. Contrarily, among proven or probable cases, haematological malignancy and diabetes mellitus accounted for 55% and 20%, respectively.4 The higher rate of PCR-only diagnosis (putative cases) in haematological malignancy could be due to the serial testing with Mucorales PCR. Studies on Mucorales PCR, especially the large MODIMUCOR study, reported an excellent diagnostic performance of in-house Mucorales PCR.7 However, sera were collected twice weekly, and a median of seven samples were tested per patient for those with a positive result.7 Such a strategy of repeated screening is not practical for patients with other risk factors such as diabetes mellitus. Additionally, the current surveillance data does not report how many samples were tested per patient before achieving a diagnosis. This information is relevant considering the limited availability and cost of PCR-based diagnosis. In a recent pan-European study enrolling 383 institutions from 45 countries, the facilities for Mucorales PCR was available onsite only in 20% (range 7–29%, depending on the income of the countries) of the centres and outsourced in 27% (17–37%). The rates are likely lower in lower- and middle-income countries.8

There are other inherent challenges in employing a highly sensitive molecular test, especially the interpretation of borderline results, coinfections, environmental contamination, and differentiating colonizers from invasive infections (especially from BAL samples).9 Finally, the perils of molecular diagnosis in patient management and clinical trials encountered in other disease conditions should not be forgotten,10 and robust testing across different settings is urgently required. For instance, the current study reports a high prevalence of coinfections (24%; most commonly aspergillosis),4 making the interpretion of a single or borderline Mucorales PCR result difficult. The study population was also at risk for other infections, including invasive aspergillosis, thus complicating the interpretation of PCR results. Surely, the current data should encourage more prospective studies from different centres and in subjects with varied risk factors for mucormycosis. The role of PCR needs to be delineated before routine implementation or inclusion in clinical trials.

The authors elegantly highlight the association of different species with risk factors and sites. Apart from confirming known associations (e.g., haematological malignancy with pulmonary presentation), previously unidentified epidemiological associations have been described (e.g., Lichtheimia ramosa and L. corymbifera in cutaneo-articular disease). While the overall mortality in mucormycosis was comparable to existing data at 55.8%, the mortality in patients with underlying haematological malignancy improved from around 79% to 60% since the implementation of Mucorales PCR screening in 2015.

In conclusion, the French Mycoses network study provides important epidemiological data and lays the foundation for future studies. Crucial future research areas include investigating host–pathogen interactions driving various epidemiological associations, examining environmental and seasonal variations in causative organisms, and most importantly, exploring the role of molecular diagnosis in diverse settings of mucormycosis.

Contributors

SMR conceptualized and VM wrote the first draft, SMR and RA edited the manuscript. All the authors approved the final version.

Declaration of interests

All the authors have no conflict of interest to declare.
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