The number of AIDS patients and HIV-infected persons worldwide is increasing. By country the largest number is in the U. S. A. followed by African countries. Among European countries it is striking that the number in the U. K. is small. In Asian countries, the invasion of HIV was late so that the number is still small, but WHO estimates that the number will increase rapidly and surpass that in African countries in time.
In Japan 62% of the patients were infected through the use of blood products, 19% by heterosexual contact and 6.7% by homosexual contact. The difference, therefore, is great.
The government has implemented an AIDS Stop Action Plan aimed at preventing the spread of the infection, and is developing comprehensive and concentrated anti-AIDS measures. The Japanese Foundation for AIDS Prevention is also carrying out various undertakings around the education and dissemination of correct knowledge about AIDS and, in particular, is energetically conducting training courses in AIDS counselling for medical workers.

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The acquired immunodeficiency syndrome (AIDS) is unique among the fungal infections caused by defects of the immune system. A complex interplay exists in the host between fungal virulence factors favoring disease, and immune and non-immune host mechanisms defending against disease. Moreover, the host defenses necessary to prevent mycoses are unique for each fungus. While neutrophils are essential in the defense against aspergillosis and deep-seated candidiasis, cellular immunity appears of paramount importance in defense against histoplasmosis, cryptococcosis and mucocutaneous candidiasis.
The most severely afflicted is the domain responsible for mediating cellular immunity in AIDS. Therefore, mucocutaneous candidiasis is especially common in patients with AIDS, whereas deepseated candidiasis is more prevalent in neutropenic patients.

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The pathology of AIDS is classified into three major categories; HIV-related lesions such as lymph node lesion and HIV-encephalopathy, opportunistic infection, and secondary malignancies such as Kaposi's sarcoma and malignant lymphoma. Thirty five autopsy cases of AIDS among Japanese 33 males and two were females, were analysed. Among risk factors, 22 homosexuals, nine hemophiliacs, two heterosexuals and one blood transfusion were found. One was of unknown risk factor, and there were no intravenous drug abusers. Opportunistic infection was one of the major clinical symtoms and specifically related to the direct cause of death. Among opportunistic pathogens cytomegalovirus was the most frequent involving various organs, such as adrenals, lungs and brain. The second most frequent was Pneumocystis carinii (PC) which was found in 15 cases. Two of these 15 cases showed pneumothorax due to cystic transformation of PC pneumonia caused by interstitial infection of PC and thrombosis of the pulmonary arterial branches with PC. As a deep fungus infection, Camdida spp. was the most frequent, accounting for five cases. Candida infection was found in the oral cavity, esophagus, lungs, and urinary bladder, and one case presented systemic dissemination. Cryptococcosis, aspergillosis and nocaridiosis were found in two cases, respectively. One case of cryptococcosis was disseminated, while the other was only localized in the lung with mild foreign body giant cell reaction. Conidiophores were demonstrated histologically in one aspergillosis in a man who had been operated on for lung cancer. One case of nocardiosis showed contiguous infection of the mediastinum and pericardium from the right upper lobe, the other showed conspicuous pneumonia of the left upper lobe associated with dissemination in left lower lobe and right lung.
Each case of deep fungal infection was associated with other pathogens, and some were associated with secondary malignancies or HIV-encephalopathy. Such a complex combination of various lesions is the most typical of AIDS, causing complex and severe clinical symptoms.

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The main feature of the Acquired immune deficiency syndrome is a progressive decrease of cell-mediated immunity due to defective functioning of CD 4 positive cells. For the reason, certain mycoses have risen dramatically in frequency: namely candidiasis and cryptococcosis. We reviewed 162 autopsy cases of AIDS in both UCLA Medical Center and the West Los Angeles VA Medical Center, focussing on the fungal infection.
An important point is that oral and esophageal candidiasis were common in AIDS patients who had single organ involvement. Histology of esophageal candidiasis revealed that the necrotic debris is present on the site of mucosal erosion, and the underlying submucosa is infiltrated with acute and chronic inflammatory cells. Hyphae proliferated in the necrotic debris, but did not invade underlying tissue. On the other hand, 18 patients of generalized cryptococcosis were found to present the commonest generalized fungal infection among 162 autopsies. Most of affected patients had sufficiently wide spread cryptococcal disease, for this to be considered the cause of death. The histological characteristics of the pulmonary lesions varied from case to case, based on the population of cryptococci and reacting histiocytes. However, the typical granulomas, usually observed in patients with primary cryptococcosis, and cystic lesions, characteristic of patients with agranulocytosis or other types of immune dysfunction, were not demonstrated. The essential feature of a pulmonary lesion in AIDS patients was proliferating cryptococci and reactive histiocytes with a much lesser lymphocytic infiltration. We wish to emphasize this difference - the absence of granulomas and the minimal lymphocyte response in cryptococcal disease in AIDS patients.

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Fungal infection is one of the major opportunistic infections in patients with AIDS. Although candida is isolated most frequently, most infections are superficial and can usually be treated successfully with fluconazole. With long-term use of fluconazole, however, the emergence of fluconazole resistant C. albicans is becoming a clinical problem.

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Mycosis is a common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). To investigate their clinical presentations and courses, we reviewed the records of 82 patients with AIDS in Tokyo Metropolitan Komagome Hospital from August 1 1985 to June 30 1993. The most common fungal infection was oral candidiasis (42 cases, 51.2%). Next was internal candidiasis (13 cases, 15.9%), Cryptococcal infection was found in 7 cases (8.5%), with meningitis in 5/7 of the cryptococcosis cases. Other mycoses were rare. Candidiasis therapy was successful, but that for cryptococcal meningitis was poor. Within 7 months 4 of the 5 meningitis cases had died.

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Oral candidiasis is the fungal infection most commonly involved in HIV-infected individuals. It responds to amphotericin B syrup or fluconazole, but tends to relapse if daily application is stopped.
The incidence rate of dermatophyte infection is about 30% in HIV-infected persons, and tinea of the feet and nails is especially common. We present a case of dermatophyte infection with HIV disease in which Trichophyton rubrum was isolated.
We have not observed any HIV-infected patients with cutaneous lesions of cryptococcosis, histoplasmosis or other deep fungal infections in Tokyo Metropolitan Komagome Hospital.

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Pneumocystis carinii (P. carinii), which is one of the major pathogens in AIDS patients, is considered a fungus from results of molecular biological analysis. We made a couple of interesting observations concerned with the cross relationship between P. carinii and fungi.
First, we detected (1→3)-beta-D-glucan (beta-glucan) in sera obtained from patients with P. carinii pneumonia: Beta-glucan is one of the major components of the cyst wall of P. carinii as well as the cell wall of fungi. There are several reports of beta-glucan being detected in sera obtained from patients with deep-seated mycosis. In four of the five P. carinii pneumonia patients, the level of beta-glucan was elevated more than 300pg/ml in their sera, and the level decreased along with clinical improvement.
Second, we found a new anti-P. carinii agent which was under development as an anti-fungal drug: The cell wall of P. carinii and fungi have a similar structure with a great deal of mannan backbone. Benanomicin A has antimycotic activity by binding to mannan. We examined the anti-pneumocystis activity of benanomicin A using mice with P. carinii pneumonia. After completion of three weeks of treatment with or without 100mg/kg of benanomicin A, the mean number of cysts by high performance microscopic field in the lung was 4.9 in the treated group, and 206 in the control group. There was thus a statistical difference between the two. The result indicated that the agent had the potential to be a new anti-P. carinii drug with a new mechanism of anti-P. carinii action.

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During our studies on the efficacy of oral Itraconazole (ITZ) against Aspergillus fumigates infection in mice, we found that ITZ dispersed in a non-ionic detergent (HCO-60 vehicle), was not effective in the treatment of the infection, although amphotericin B and fluconazole solubilized in the same carrier were. Further studies revealed that the efficaciousness of ITZ in mice is mainly dependent on the solvent used as a carrier. Hydroxypropyl-β-cyclodextrin was the most beneficial carrier solvent, and polyethylene glycol was a less effective carrier.

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Antibody responses to antigenic components was analyzed by the immunoblot technique. The antigen in the cytoplasmic protein were extracted from Candida albicans type KULM 83-0300. Thirty-five sera samples from 10 autopsy cases (6 patients from Kitasato University Hospital and 4 from Nihon Medical University Nagayama Hospital) with pathologic diagnosis of candidiasis, from 17 clinical cases with clinical or cultural diagnosis of candidiasis, and from 8 healthy control subjects were used to evaluate the diagnostic value of immunologic response. The patients were classified by the degree of infiltration into two groups: severe (11 cases) and mild (16 cases), with normal controls being regarded as the third group. Sera from the severe group reacted in the area of 24-151 kilodalton (kDa) with a total of 17 bands. The mild group reacted in the area of 26-88kDa with a total of 15 bands. The normal control reacted in the area of 22-65kDa with a total of 9 bands. The severe group had higher molecular weight bands than the other two groups, and these were considered to be due to the extent of the invaded area. However, 14 of 16 (87.5%) sera from the mild group and 6 of 8 (75%) sera from the control group reacted with the 47kDa antigen, while only 4 of 11 (36.4%) sera from the severe group reacted. Prognosis of the patients whose serum did not react with it tended to be poor. Though presence of the antibody for the 47kDa antigen is generally considered useful in diagnosing invasive candidiasis, these findings implied that caution should be exercised in such cases.

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Onychomycosis patients were treated topically with bifonazole-urea cream. This cream, prepared in our hospital, was composed of 0.6% bifonazole, 40% urea and 3% carboxymethylcellulose cream. Bifonazole-urea cream was applied to the infected nails, which were then covered with occlusive dressing, left overnight, washed and then further treated by application of 1% bifonazole solution. Softened, affected lesions were removed with a nail file or nail clipper. Fifty patients, positive for mycelium by direct examination, were prescribed this treatment, with forty being followed up for twelve weeks. Twenty-six out of the forty patients (65.0%) appeared to be mycologically negative after an average of 60 days' treatment. Local irritation was observed as a side effect in only one of the 50 cases. The cream with the above-mentioned formula was found to be effective both for patients who had griseofulvin-resistant onychomycosis and those with systemic diseases who could not tolerate griseofulvin treatment. This data suggests that this formula is very useful as a topical treatment for onychomycosis.

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We report a case of bronchopulmonary aspergillosis due to Aspergillus niger found at autopsy. The patient was a 64-year-old Japanese female who died of renal failure with recurrence of uterine leiomyosarcoma. The autopsy revealed typical invasive pulmonary aspergillosis in the lower lobe of the left lung. In the upper lobe of the same lung, numerous hyphae showed mural proliferation in the bronchi and terminal portions of the respiratory tree from which the hyphae invaded the surrounding pulmonary tissue. Although the tissue was not cultured, the conidial heads histologically disclosed in the air space were characteristic of Aspergillus niger. The histological pattern of the upper lobe lesion indicated colonization like non-invasive Aspergillus infection mixed with invasive bronchopulmonary aspergillosis. This case is very important in any discussion of the pathogenesis of semi-invasive bronchopulmonary aspergillosis.

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Fourteen strains of Aspergillus fumigatus, two strains of A. flavus, three strains of A. niger, and one strain of A. candidus were isolated from sputa of patients with respiratory diseases. These Aspergillus strains were incubated for 7 days at 37°C in 0.05% yeast carbon base (YCB) agar plates containing 0.1% rose bengal and 0.05% elastin. Elastase activity of Aspergillus species, and the effect of Urinastatin on this activity were examined. Five strains of A. fumigatus, one of A. flaves, and one of A. niger showed the activity.
Elastase activity of these strains was inhibited by Urinastatin. It is suggested that the combination therapy of an enzyme inhibitor, such as Urinastatin, and an anti-fungal agent is more effective for aspergillosis than the agent alone.

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We reported earlier on culture filtrate antigens from A. fumigatus that had been incubated at 25°C for 1-10 weeks (Jpn J Med Mycol 34: 439-444, 1993). Additionally, we prepared five culture filtrate antigens from A. fumigatus ATCC26430 grown by shaking at 25°C for 11-15 weeks in Sabouraud liquid medium. We also prepared a polysaccharide antigen from the same strain by extracting mycelia and conidia. The growth of the fungi became weaker in cultures after 12 weeks, and by stopped at 14 weeks. Sixteen antigens were then employed in agar gel double diffusion (DD) tests against the sera of 18 aspergilloma patients. The results of DD showed three types (A, B, C) of precipitin pattern, with 9 patients belonging to type A, 6 to type B and 3 to type C. In all cases, precipitin lines were formed with the antigens obtained after 6-15 weeks of culture. To avoid contamination, inferior cultures and accumulation of waste, the incubation time should be as short as possible. Thus, as noted in our previous letter, we found that the antigen obtained from 6-week culture filtrates at 25°C is the most useful for demonstrating precipitin reactions against the sera of aspergilloma patients.

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