Kawasaki disease (KD) is an inflammatory disease that was identified by Professor Tomisaku Kawasaki in 1961. Candida albicans-derived substances, such as C. albicans water-soluble fraction (CAWS) , induce coronary arteritis similar to KD in mice. CAWS functions as a pathogen-associated molecular pattern (PAMP) by acting as a ligand for dectin-2. A gut-associated immunological system has developed specifically to segregate advantageous and detrimental stimuli, and the microbial flora has been found to markedly affect the development and severity of diseases. We herein investigated whether diet affects the onset and progression of CAWS vasculitis in mice. A standard diet, CE-2, and chemically defined diet, AIN93G, which is free of β-glucan, were used. Although all mice administered with CAWS died, the mean number of survival days was smaller in the AIN93G group because vasculitis was induced earlier than in the CE-2 group. Bacteroides, which are inflammatory flora, were enriched in the microbial flora of the AIN93G group. The results of the present study suggest that diet quality affects not only microbial flora changes, but also the progression of systemic disease.
A 73-year-old male who had been receiving immunosuppressive drugs for 15 years developed a nodule on the left buttock region. The nodule slowly grew into a 15-cm fluctuant multilocular subcutaneous cyst. Serum beta-D-glucan levels were high, and the yellow purulent fluid obtained from the cyst was positive for Trichophyton rubrum. Granuloma formation in the cyst wall and large abscesses in the central cystic area were found, and septated hyphae were observed in both tissues. The cyst was surgically removed, and followed by itraconazole treatment. Notably, the clinical manifestations closely resembled those of a huge atheroma.
Azole-resistant strains of Aspergillus fumigatus containing a tandem repeat in the cyp51A promoter and amino acid substitution(s) have been isolated in the environment worldwide; however, this type of resistant strain had never been isolated from the environment in Japan. Our previous study indicated that an azole-resistant A. fumigatus strain OKH50 containing a 34-bp tandem repeat in cyp51A promoter with L98H substitution in Cyp51A was isolated from a patient in Obihiro of Hokkaido, Japan. In this study, we collected azole-resistant Aspergillus spp. by air sampling from the environment in Japan. One Aspergillus-like colony was isolated from one of 10 sampling sites surveyed. The strain Env1 was confirmed as A. fumigatus by nucleotide sequencing and possessed a 34-bp tandem repeat in the promoter region of cyp51A with L98H substitution in Cyp51A. A. fumigatus Env1 has the identical short tandem repeat pattern with the OKH50 strain, indicating that these strains are closely related with each other. Additionally, the short tandem repeat pattern is closely related to Danish and Iranian environmental isolates, suggesting that azole-resistant strains have crossed transnational boundaries and are now present in Japan, and therefore, further analysis throughout Japan is required to determine the distribution of this type of azole-resistant A. fumigatus.
Understanding deep cutaneous fungal infection requires not only reading many case reports and checking the typical clinical images of skin lesions, but also managing the patients properly to prevent misdiagnosis. Herein, I review my recent experiences with eight typical cases of deep cutaneous infections (including protothecosis and nocardiosis) in Japan. It is very important to do the four management processes; namely, KOH direct microscopic examination, skin biopsy, fungal culture, and microscopic examination of the histopathological specimen of PAS and Grocott staining. Also, to aid in memorizing the names of important diseases, I recommend the mnemonic “AC PPPS MD” (Aspergillosis, Cryptococcosis, Phaeohyphomycosis, Protothecosis, Pseudoallescheriosis, Sporotrichosis, Mycetoma, and Dermatophytosis). Isolation of the fungus by culturing from the skin lesion is the best way to carry out quick and correct diagnosis.
In recent years, the incidence of fungal infections has been increasing, particularly among patients with immune systems compromised by human immunodeficiency virus infection, organ transplantation, and/or chemotherapy for cancer. Current therapies for treating systemic fungal infection have limited effectiveness and have created problems of adverse reactions and drug resistance. These issues therefore motivate us to develop novel antifungals. Elucidation of stress response mechanisms and virulence factors in pathogenic fungi is required in developing an effective antifungal strategy. There are actually numerous studies concerning various stress responses in several important fungal pathogens. Among these responses, we focused on stress response for iron starvation to identify potential targets for novel antifungals because iron starvation occurs in blood, where pathogenic fungi often infect. Here we show recent progress of studies on iron homeostasis in Candida species, especially focusing on Candida glabrata, and propose novel antifungal targets.
Several pathogenic fungi and cases related to Japanese medical mycologists were reviewed. Trichosporon inkin (as Sarcinomyces inkin) was reported as a pathogen of scrotal lesion by Oho in 1921, and Trichosporon asahii was isolated from generalized keratotic lesions in 1922 by Akagi in Japan. They were once included in Trichophyton beigelii, but then based on revision using DNA molecular technology, were returned to their original names. Microsporum ferrugineum was reported by Ota as a causative dermatophyte of tinea capitis in Japan and surrounding areas. It was once classified under the genus Trichophyton, but after the discovery of characteristic rough-walled macroconidia belonging to genus Microsporum, the fungus was again assigned to the original name.
Infection rate of tinea pedis is high in the elderly, wherein treatment by a dermatologist should be considered to prevent infecting their family members. About 90 percent of cases with tinea pedis is treated only using external preparations. In treating the elderly with tinea pedis using external preparation, we should take into consideration that the elderly have thinner and weaker skin compared to younger people. There are many kinds of dosage form (cream, ointments, lotion, spray, and so on) for external preparations to treat tinea pedis. Generally, liquid forms such as lotions and sprays cause stronger irritation compared to ointments and creams, thus, caution should be taken for side effects when applying them to the elderly. Contact dermatitis is the most frequent side effect of external preparations. Caution should also be taken for the type of additives used. The composition of the preparation should be checked when changing dosage forms, or when switching brand-name drugs to generic drugs. Since the adherence rate of external preparations is low, it is preferable to use those with strong antibacterial activity and only have to be applied once a day.
The incidence of oral candidiasis has increased in the elderly in recent years. Although the increase of the elderly population plays a big role in this rise of oral candidiasis, the broader recognition that elderly people have higher infection rates for oral candidiasis is considered to be also an important factor. Oral candidiasis can be categorized into three types. Pseudomembranous oral candidiasis is characterized by the appearance of white moss, erythematous oral candidiasis by the eruption of erythema, and hyperplastic oral candidiasis by mucosal hyperplasia. Miconazole has been commonly used when treating oral candidiasis. Elderly patients, however, have a tendency to develop oral candidiasis repeatedly. It is therefore critical to take measures to prevent recurrence. We recommend the use an oral moisturizer containing hinokitiol, an antifungal substance, on a regular basis, to help prevent recurrence of oral candidiasis.
The dermatophyte antigen kit uses monoclonal antibodies that react with polysaccharides present in the dermatophyte cell wall to detect dermatophyte antigens in specimens based on the principle of immunochromatography. Clinical studies showed that the kit was very useful in the diagnosis of tinea unguium but not tinea pedis. The kit was therefore further developed as an in vitro diagnostic tool for tinea unguium and was approved by the Pharmaceuticals and Medical Devices Agency of Japan. The kit’s extraction solution can extract antigens from nail specimens quickly and efficiently. When direct microscopy fails to detect fungal elements in a specimen of suspected tinea unguium, the kit can be used so that positive samples are re-examined by direct microscopy, in order to reduce the likelihood of false-negative detection. In addition, in settings where direct microscopy is unavailable, the kit can be used so that treatment for dermatophytes is withheld when results are negative. Such an approach can reduce both wasteful treatment and medical costs. It is important to note that the kit is used to complement conventional fungus testing methods and that direct microscopy must be used to confirm the final morphological diagnosis of the pathogenic fungal infection. Use of a combination of direct microscopy and this kit should improve the accuracy of diagnosis of tinea unguium.