Conclusions

Zygomycetes are known as human pathogens for more than 100 years but have remained largely understudied partly due to the low frequency of the disease. The recent increase of incidence of zygomycosis in immunocompromised patients and the high mortality rate of the disease despite therapy have prompted many recent studies. Although very important advances have been made during the last 5 years, a better understanding of the biology of the pathogens and the epidemiology of the disease will be of particular importance in the coming years. New diagnostic tools and improved therapeutic strategies are also urgently needed.

Zygomycetes comprise very diverse genera and species. Recent molecular studies have allowed revising the taxonomy and phylogenetic relationships of these pathogens. Some species are clearly misplaced taxonomically and will probably be reassigned to different genera.

Pathophysiology of zygomycosis remains largely unknown and has been poorly explored recently. The few recent studies have focused on the role of iron in patho-genesis and on the interactions between the fungus and the endothelial cells with interesting results. A better knowledge of the biology of zygomycetes would greatly help the understanding of the pathogenesis of the disease. Very unexpected data have shown that some isolates of Rhizopus spp. harbored endosymbiont bacteria responsible for toxin production. The potential role of these bacteria and of the produced toxin as a virulence factor for humans needs to be explored in experimental models. It is sure that the recent availability of the complete genome of R. oryzae, as well as the recent development of new techniques for genetic manipulations of these fungi will considerably facilitate the analysis of putative virulence factors.

Incidence of zygomycetes infections has risen in the last two decades but reasons for emergence of the disease is still not completely understood. The role of new antifungal drugs has been suspected but increase in the incidence could also be linked to recent changes in immunosuppression regimens given to the patients. To answer these clinically relevant issues, surveillance studies on a national and international basis are needed.

In a patient with a suspected invasive filamentous fungi infection, diagnosis of zygomycosis remains very difficult. Unfortunately no major advances have been made for improving diagnosis. In particular, there is neither serological nor antigen-detection tests currently available and PCR techniques are not yet fully standardized. In contrast, very important advances have been made for identification of the strains in culture. Evaluation of intra- and interspecies variability of several DNA regions and increase of sequence data in public databases have made accurate identification to the species level possible. These new and reliable identification methods will allow to precise the respective role of each species and probably to identify new species responsible for human infections.

Zygomycosis remains a life-threatening infection and treatment efficacy is still suboptimal. Recent data obtained in several in vitro studies demonstrated that the different species exhibited different antifungal susceptibilities. Nevertheless, the clinical relevance of these differences has to be confirmed. New antifungal drugs such as posaconazole have also shown potential clinical efficacy on a limited number of patients. The exact role of these new antifungals, either alone or in combination, for the management of zygomycosis remains to be further evaluated.

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