Background: Aspergillus flavus complex (AFC) has attracted worldwide attention for economic and
public health reasons because of its industrial use and toxigenic potential. Among the
known Aspergillus species causing human infections, AFC is the second most
common Aspergillus species in Western countries, and is as important as A. fumigatus, particularly
in fungal sinusitis, in Asia. AFC consists of two groups of species; one includes A. flavus and A.
nomius and others producing aflatoxin and causing serious problems worldwide in agricultural
commodities. The other group includes the non-aflatoxin-producing species A. oryzae and A. tamarii,
which have been used for production of traditional fermented foods in Asia. Identification of the
species has relied mainly upon the morphological characters used as taxonomic criteria. It is,
however, difficult to identify AFC species because of morphological divergence among isolates of the
same species. A single center study in Taiwan during 2000- 2009 showed that 40 (32%) of 183 AFC
clinical isolates were proven/probable invasive aspergillosis (IA). However, the prevalence and
contribution of Aspergillus nomius to IA in human is unknown.
Material/Methods: This multicenter laboratory surveillance study in Taiwan included 111 clinical
isolates of AFC from 89 patients and 5 environment isolates. Isolates were identified based on
morphological methods and sequencing the ITS1-5.8S-ITS2 region of the ribosomal DNA after PCR
amplification using the universal fungal primers (ITS1 and ITS4), Β-tubulin and calmodulin. Antifungal
susceptibility determined by YeastOne microdilution method. Cases were categorized to proven or
probable according to EORTC/MSG definition.
Results: None of environment isolates and 8 isolates collected from 8 patients were A. nomius.
Antifungal susceptibility was 0.06-0.5 mg/L for itraconazole and posaconazole, 1 mg/L for
voriconazole. 2-4 mg/L for amphotericin B. One each was colonization, superficial infection, and
indeterminate. 5 were proven/probable IA. Seven patients had risk factors associated with IA,
including steroid use, leukemia. Only one immunocompetent host with the diagnosis of otitis externa
had superficial infection due to AFC and symptom (itching and local erythema) resolved after topical
antifungal agent. The first case of IA due to A. nomius raised our attention was a 27-year-old man who
had acute myeloid leukemia status post second HLA-matched unrelated donor peripheral blood stem
cell transplantation in May 2012. Within one month, he had acute graft-versus-host reaction and
probable pulmonary aspergillosis was diagnosed based on serum galactomannan antigen was 6.5
and sputum grew AFC which was later confirmed to be mixed A. flavus and A. nomius. Despite of
continued use of oral voriconazole, breakthrough endocarditis was diagnosed in September 2012.
Surgical specimen grew A. nomius and PCR-sequencing of vegetation also confirmed this finding.
Conclusion: Although contributing only 9% in patients with AFC colonization/infection, 62% of A.
nomius cause severe infection in immunocompromised patients.
Full conference title:
- ECCMID 27th (2017)