Background and Methods: To identify recent trends in the frequency of zygomycosis in autopsy cases, we conducted epidemiological analysis every four years from 1989 to 2009 using national data reported in the “Annual of Pathological Autopsy Cases in Japan.” Results: 153,615 cases were autopsied, of which 6622 (4.3%) were found to have had mycosis. Among these, there were 243 cases (3.7%) of zygomycosis, which was the fourth most predominant causative agent of mycoses among the monopathogen mycoses. Of the complicated mycoses, zygomycosis accounted for 56 cases. A total of 299 cases with zygomycoses were observed. The frequency of zygomycosis appeared to be generally stable over the twenty-year period from 1989 to 2009, at around 4% of autopsy cases having mycosis. Younger patients tended to have severe and complicated infections that were characteristic of zygomycosis, compared with non-zygomycosis. The pulmonary and gastrointestinal (GI) systems were the most common foci in our analysis, reflecting the severity of zygomycosis in these sites. Hematological disease was the most frequent underlying disease, but there was a peak of neonatal infections in 2009, which was the first time that this was observed in our studies. Conclusion: These results of the epidemiological analysis of autopsy cases with mycosis demonstrate that clinicians should promptly recognize and treat zygomycosis.
The risk of invasive fungal infections (IFIs) is extremely high in patients with hematological malignancies due to the prolonged and profound neutropenia and immunosuppression after chemotherapy and hematopoietic stem cell transplantation. There has been increasing interest in mucormycosis despite its relatively uncommon occurrence, because occasional breakthrough infections have been observed under anti-Aspergillus prophylaxis. The aggressive nature of mucormycosis easily leads to high mortality because of delays in diagnosis and incorrect treatment decisions, which are due in part to lack of adjunctive diagnostic tools and having similar clinical and radiological features with invasive aspergillosis. The only currently available antifungals against Mucorales in Japan are amphotericin B formulations. Thus, comprehensive therapeutic strategies, including surgery, should be considered to achieve a successful outcome.
Feline sporotrichosis has been reported in Malaysia since the 1990’s. Since then, studies have revealed that clinical clade D, Sporothrix schenckii sensu stricto, of a single clonal strain is the most common cause of this disease in Malaysia. The prevalence of a single clonal strain from a clinical clade was never before reported in Asia in a specific geographical niche. This raises the possibility of a process of purifying selection and subsequent clonal proliferation. While agricultural practices may serve as the selective pressure, direct causality has yet to be established. Studies into the thermo-tolerability of the Malaysian clonal strain of S. schenckii sensu stricto revealed that a small minority of clinical isolates have the capacity to grow at 37℃, while the majority displayed low susceptibility to commonly used antifungals in clinical practice, such as itraconazole (ITZ) and terbinafine (TRB). Despite unestablished breakpoints, suspected resistance (MIC > 4 mg/mL) towards amphotericin B (AMB) and fluconazole (FLC) was recorded in the isolates. This explains the often lack of clinical response in feline patients treated with recommended doses of antifungals, including ITZ. Coupled with the potential zoonotic transmission to clients and veterinarians, protracted treatment period, and subsequent cost of treatment, prognosis of feline sporotrichosis is often regarded to be poor. The use of a higher dose of ITZ has been reported, and an adoption of this high-dose treatment regime is reported in this manuscript, with complete cure achieved in cases of recalcitrant and/or unresponsive feline sporotrichosis, which would otherwise be euthanized.
Morphology and molecular characteristics of Microsporum gypseum clinical isolates obtained from the fur of a normal rabbit (n=1) and the soil from 10 different rabbit hutches in six elementary schools (n=10) were examined. Isolates were also identified by sequence analysis of the internal transcribed spacer (ITS) region. All 11 isolates demonstrated homology with the Arthroderma fulvum ITS sequence. Furthermore, PCR analysis for the presence of mating type genes detected positivity for MAT1-1 (n=10) and MAT1-2 (n=1). However, no mating reaction was detected between A. fulvum reference strains and the clinical isolates.
A lysozyme-chitosan conjugate preparation (LYZOX), produced from egg white lysozyme and chitosan by Maillard reaction, is a commercial product developed as a cosmetic ingredient or food additive. Effects of LYZOX on in vitro growth of Candida albicans were examined. C. albicans cells were treated with LYZOX for 3 hrs, and then washed and cultured for an additional 16 hrs in modified RPMI1640 medium. Mycelial growth of C. albicans was clearly inhibited by more than 100 μg/ml of LYZOX in a concentration-dependent manner. On the other hand, corresponding concentration of chitosan or lysozyme or their mixture only scarcely showed clear inhibitory effect. Similarly, anti-Candida activity of the combination of LYZOX and decanoic acid, a middle-chain fatty acid, was also examined. Inhibitory activity of this combination against mycelial growth of C. albicans was very potent and appeared synergistic, since fractionated inhibitory concentration (FIC) index for 70% growth inhibition was calculated to be 0.20. Oral application of this combination improved the symptoms of Candida-infected-tongue in an experimental murine candidiasis model. On the basis of these results, the possible application of LYZOX as a new functional product with anti-candida activity was discussed.
Masao Ota was a Professor of Dermatology at Tokyo Imperial University. He is known to dermatologists around the world as the researcher who identified Nevus of Ota. He is also known for his research on Hansen’s Disease. He was critical of the forced isolation policy and the sterilization law. He dreamt of developing chemotherapeutic measures and dedicated himself to cultivating Mycobacterium leprae. Among his accomplishments, those in the area of medical mycology are particularly remarkable. His discovery of Microsporum ferrugineum, his proposal for Trichophytia pompholyciformis, and his work on Ota-Langeron taxonomy based on the findings on fungus colonies are highly regarded and earned him the Ordre Royale de la Legion D’honneur. His accomplishments in the field of mycology are numerous; he has published a total of 39 research papers mostly in foreign languages. He was a leading world-class medical mycologist of his day. This review introduces some of his accomplishments and some episodes in his life. Furthermore, Masao Ota had a detailed knowledge of art and culture. Under the pseudonym of Kinoshita Mokutaro, he wrote poems, plays, and novels. He was also a painter. Particularly, his paintings in botany during his later years were published in the book “One Hundred Flower Sketches” after his death. Ota said, “The consequence of both science and art is global and humanitarian.” He was one of the greatest men of culture in his time.
Fungal taxonomy has been reconstructed on the basis of genome information, and new nomenclatural rules have been enacted from 2013. It has been proposed that Cryptococcus neoformans and Cryptococcus gattii be reclassified into two species (C. neoformans and Cryptococcus deneoformans) and five species (C. gattii, Cryptococcus bacillisporus, Cryptococcus deuterogattii, Cryptococcus tetragattii, and Cryptococcus decagattii), respectively. The genus Trichosporon has been reclassified into five genera. Trichosporon asahii, which is the causative agent of trichosporonosis, has been retained in the genus Trichosporon, while Trichosporon cutaneum has been transferred into a new genus, Cutaneotrichosporon.
Cryptococcus neoformans is a yeast-type opportunistic fungal pathogen with a capsule structure consisting of polysaccharides, such as glucuronoxylomannan and galactoxylomannan, and infects the lungs via an air-borne route. Most healthy individuals undergo asymptomatic infection with granulomatous lesions in the lungs caused by C. neoformans. However, immunocompromised hosts with severely impaired cellular immunity, such as those with acquired immune deficiency syndrome (AIDS), often suffer from disseminated infection into the central nervous system, leading to life-threatening meningoencephalitis. The recognition of pathogen-associated molecular patterns (PAMPs) by macrophages and dendritic cells plays an important role as the first line of host defense in the elimination of pathogens. Recently, numerous pattern recognition receptors (PRRs) that recognize these PAMPs have been identified. Also, the involvement of these PRRs, such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and C-type lectin receptors (CLRs), in cryptococcal infection has been analyzed. In particular, TLR9, NLR family pyrin domain-containing 3 (NLRP3), Dectin-2, mannose receptor (MR), and DC-SIGN have been found to recognize the DNA, cell wall components, intracellular polysaccharides, and mannoproteins, respectively. Future studies are expected to promote elucidation of the mechanisms of host immune response to C. neoformans, which will lead to the development of new vaccines and therapies for cryptococcal infection.
Real-time test results are necessary for early diagnosis and in determining treatment orientation in medical practice. Point of Care Testing (POCT) is a testing system that provides beneficial and helpful information for diagnosis and treatment through real-time testing at the bedside. Therefore, POCT has high utility value in the field of infectious diseases as a rapid test that provides, within the consultation hours, useful information for initial treatment. Infectious disease rapid test kits are commercially available for a wide variety of prophlogistic pathogen targets, including bacterial, viral, fungal, protozoal, and other disease agents. One of these kits is immunochromatography assay (ICA), a measuring method used as POCT that is easy to operate, wherein even physicians and nurses can conduct the test. Serodiagnostic method has been adjunctively used in medical practice in Japan for early clinical diagnosis of deep mycosis as a means to determine treatments. However, this method is complicated and is considered a full-scale clinical examination; therefore, it is not included in the category of POCT. Recently, Loop-Mediated Isothermal Amplification (LAMP) method has been tested as a POCT for diagnosis of fungal infection in the US. Development of a laboratory procedure using simple and highly accurate POCT for early diagnosis of deep mycosis is expected in the near future.