Diversity of clinically relevant Fusarium species complexes: preliminary analysis of from an 11-yr prospective surveillance in France

Background/Objectives.  Human infections by Fusarium spp. have varied clinical presentations depending on the immune status of the host.  Within this genus, at least six species complexes have been implicated in human and animal infections. However, little is known about the association between clinical manifestations and the presence of Fusarium species. We took advantage of the surveillance systems (semi-passive (RESOMYC) and active (RESSIF) reporting) implemented by the National Reference Center for Invasive Mycoses (NRCMA), to analyze these associations based on the characterization of 347 strains of Fusarium spp. using a polyphasic approach.

Methods. Cases were collected over an 11-year surveillance period (2005-2016) and classified as ocular (OF) or deep IFI (DIFI), and probable or proven IFI. The phylogenetic analysis of the strains was based on DNA sequence data for the elongation factor 1-α (TEF-1α) and the RNA polymerase II subunit (RPB2) regions. Antifungal susceptibility testing was performed according to EUCAST recommendations. 

Results: The 382 cases corresponded to 216 (57%) OF and 166 (43%) DIFI. Major differences between OF and DIFI concerned the proportion of male patients, the underlying immunosuppression (60% and 78% in IF, respectively), and the association to local injury (97% in OF). Among the 216 OF cases, keratitis and corneal ulcer were the main clinical forms and the wear of contact lenses was reported in 146 (68%) cases. DIFI presented predominantly as fungemia (71/166, 43%) and associated with hematological malignancies but also to solid tumors and SOTs. Localized cutaneous DIFI (49/166, 29.5%) were seen in 33 patients after local injuries or severe burns. 
For the 347 strains characterized at the NRCMA (202 OFs, 145 DIFIs), the most common species complexes (SC) were F. solani SC (n=133) F. oxysporum SC (n=91) F. fujikuroi SC (n=100) F. dimerum SC (n=19) and F. incarnatum-equiseti SC (n=4). MICs profiles for the four complexes were similar for azoles, candins and amphotericin B except for the F. dimerum SC. Most of the 100 F. fujikuroi SC were identified in DIFI (lung (n=28) and blood (n=34) localizations). On the other hand, most of the 91 F. oxysporum SC (n=76, 83.5%) were recovered from OFs. Furthermore, among the contact lens wearers with OF, F. oxysporum SC was present in 44% (64/146) while F. solani SC was more frequent in those with no report of contact lenses 56% (31/55). 

Conclusions. Our study shows the association between clinical manifestations and Fusarium complexes in a large cohort of patients. Members of the F. fujikuroi SC were significantly associated with immunocompromised patients and disseminated fusariosis, underlining the importance for accurate identification of this fungal group for epidemiological purposes. Further studies are needed to investigate the reasons for these apparent “tropisms”.

4 / Diversity of clinically relevant Fusarium species complexes: preliminary analysis of from an 11-yr prospective surveillance in France