Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan.

OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population. METHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined. RESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications. CONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.

The prevalence of opportunistic infections and malignancies in autopsied patients with human immunodeficiency virus infection in Japan.

BACKGROUND: Opportunistic infections and malignancies such as malignant lymphoma and Kaposi sarcoma are significant complications of human immunodeficiency virus (HIV) infection. However, following the introduction of antiretroviral therapy in Japan in 1997, the incidence of clinical complications has decreased. In the present study, autopsy cases of HIV infection in Japan were retrospectively investigated to reveal the prevalence of opportunistic infections and malignancies. METHODS: A total of 225 autopsy cases of HIV infection identified at 4 Japanese hospitals from 1985-2012 were retrospectively reviewed. Clinical data were collected from patient medical records. RESULTS: Mean CD4 counts of patients were 77.0 cells/µL in patients who received any antiretroviral therapy during their lives (ART (+) patients) and 39.6 cells/µL in naïve patients (ART (-) patients). Cytomegalovirus infection (142 cases, 63.1%) and pneumocystis pneumonia (66 cases, 29.3%) were the most frequent opportunistic infections, and their prevalence was significantly lower in ART (+) patients than ART (-) patients. Non-Hodgkin lymphoma and Kaposi sarcoma were observed in 30.1% and 16.2% of ART (-) patients, and 37.9% and 15.2% of ART (+) patients, respectively. Malignant lymphoma was the most frequent cause of death, followed by cytomegalovirus infection regardless of ART. Non-acquired immunodeficiency syndrome (AIDS)-defining cancers such as liver and lung cancer caused death more frequently in ART (+) patients (9.1%) than in ART (-) patients (1.5%; P = 0.026). CONCLUSIONS: The prevalence of infectious diseases and malignancies were revealed in autopsy cases of HIV infection in Japan. The prevalence of cytomegalovirus infection and pneumocystis pneumonia at autopsy were lower in ART (+) patients than ART (-) patients. Higher prevalence of non-AIDS defining malignancies among ART (+) patients than ART (-) patients suggests that onsets of various opportunistic infections and malignancies should be carefully monitored regardless of whether the patient is receiving ART.

Nationwide Longitudinal Annual Survey of HIV/AIDS Referral Hospitals in Japan From 1999 to 2021: Trend in Non-AIDS-defining Cancers Among Individuals Infected With HIV-1.

BACKGROUND: Non-AIDS-defining cancers (NADCs) in patients infected with HIV have recently attracted attention because of the improved survival of this patient population. To obtain accurate data, a longitudinal study is warranted for the nationwide surveillance of the current status and national trend of NADCs in patients infected with HIV in Japan. SETTING: An annual nationwide surveillance of NADCs in patients infected with HIV-1 in Japan from 1999 to 2021. METHODS: An annual questionnaire was sent to 378 HIV/AIDS referral hospitals across Japan to collect data (clusters of differentiation 4-positive lymphocytes, time of onset, outcomes, and antiretroviral therapy status) of patients diagnosed with any of the NADCs between 1999 and 2021. RESULTS: The response and case-capture rates for the questionnaires in 2021 were 37.8% and 81.2%, respectively. The number of reported NADC cases subsequently increased since the beginning of this study. Evaluation of the case counts of NADCs demonstrated a high incidence of lung, colorectal, gastric, and liver cancers as the top 4 cancers. Pancreatic cancer (0.63), lung cancer (0.49), and leukemia (0.49) had the highest mortality rates among the NADCs. Trends of NADCs regarding transmission routes were maintained over the years in male individuals who have sex with male individuals compared with heterosexual male individuals and female individuals. CONCLUSIONS: We demonstrated an increasing trend in the incidence of NADCs over a period of 23 years in Japan. The current data highlighted the importance of raising awareness regarding cancer management for patients infected with HIV in Japan.

Seroprevalence of Kaposi's sarcoma-associated herpesvirus among men who have sex with men in Japan.

Kaposi's sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi's sarcoma, causes malignancies frequently in patients with acquired immunodeficiency syndrome. In the United States and Europe, KSHV infection is common among men who have sex with men. However, the seroprevalence of KSHV among men who have sex with men in Japan is unknown. In the present study, the seroprevalence of KSHV was investigated among 230 men who have sex with men and 400 age- and area of residence-matched men (controls) using a mixed-antigen (KSHV-encoded K8.1, open reading frame 59, 65, and 73 proteins) enzyme-linked immunosorbent assay and an immunofluorescence assay. Among the Japanese men who have sex with men, serological assays revealed that 27 (11.7%) were seropositive for KSHV; 20 (5%) of the men in the control group were also KSHV seropositive. The seroprevalence of KSHV among men who have sex with men was significantly higher than in the control group (odds ratio = 2.52, 95% confidence intervals = 1.38-4.62, P = 0.0019, Chi-square test). Infection with the human immunodeficiency virus, Treponema pallidum, or hepatitis B and C virus did not correlate with KSHV infection. Furthermore, the association of KSHV seropositivity with specific sexual activities was not statistically significant. In conclusion, a higher KSHV seroprevalence was found among Japanese men who have sex with men than among the controls, suggesting that the circulation of KSHV infection is more efficient among men who have sex with men in Japan than among men who do not engage in such sexual activities.

Prospective randomized comparison study of piperacillin/tazobactam and meropenem for healthcare-associated pneumonia in Japan.

Healthcare-associated pneumonia (HCAP) may have a more severe course than community-acquired pneumonia (CAP); hence, it is more likely to be caused by drug-resistant bacterial pathogens and anaerobes involved in aspiration pneumonia. We compared the efficacy and safety of initial empiric therapy with piperacillin/tazobactam (PIPC/TAZ, 13.5 g/day) with that of meropenem (MEPM, 1.5 g/day) as single broad-spectrum regimens with gram-negative and anaerobic coverage in patients with HCAP in Japan. The clinical cure rate was 75.9 % (22/29 cases) in the PIPC/TAZ group and 64.3 % (18/28 cases) in the MEPM group. The clinical efficacy rate was 87.9 % (29/33 cases) in the PIPC/TAZ group and 74.2 % (23/31 cases) in the MEPM group. The bacteriological eradication rate was 94.4 % (17/18) in the PIPC/TAZ group and 87.5 % (14/16) in the MEPM group. Adverse drug reactions were seen in 22.4 % (11/49 cases) of patients in the PIPC/TAZ group and 17.4 % (8/46 cases) of patients in the MEPM group. Although not statistically different, the PIPC/TAZ group had a slightly higher efficacy rate than the MEPM group. Both treatment regimens are tolerable and might be appropriate to use as initial empiric therapy for HCAP in Japan. To investigate the differences in efficacy profiles of those two regimens, a further confirmatory study with a larger cohort as determined by a power analysis is recommended.

Correlation between triazole treatment history and susceptibility in clinically isolated Aspergillus fumigatus.

This is the first report of a detailed relationship between triazole treatment history and triazole MICs for 154 Aspergillus fumigatus clinical isolates. The duration of itraconazole dosage increased as the itraconazole MIC increased, and a positive correlation was observed (r = 0.5700, P < 0.0001). The number of itraconazole-naïve isolates dramatically decreased as the itraconazole MIC increased, particularly for MICs exceeding 2 µg/ml (0.5 µg/ml versus 2 µg/ml, P = 0.03). We also examined the relationship between cumulative itraconazole usage and the MICs of other azoles. A positive correlation existed between itraconazole dosage period and posaconazole MIC (r = 0.5237, P < 0.0001). The number of itraconazole-naïve isolates also decreased as the posaconazole MIC increased, particularly for MICs exceeding 0.5 µg/ml (0.25 µg/ml versus 0.5 µg/ml, P = 0.004). Conversely, the correlation coefficient obtained from the scattergram of itraconazole usage and voriconazole MICs was small (r = -0.2627, P = 0.001). Susceptibility to three triazole agents did not change as the duration of voriconazole exposure changed. In addition, we carried out detailed analysis, including microsatellite genotyping, for isolates obtained from patients infected with azole-resistant A. fumigatus. We confirmed the presence of acquired resistance to itraconazole and posaconazole due to a G54 substitution in the cyp51A gene for a patient with chronic pulmonary aspergillosis after oral itraconazole therapy. We should consider the possible appearance of azole-resistant A. fumigatus if itraconazole is used for extended periods.

Antifungal susceptibilities of Aspergillus fumigatus clinical isolates obtained in Nagasaki, Japan.

We investigated the triazole, amphotericin B, and micafungin susceptibilities of 196 A. fumigatus clinical isolates in Nagasaki, Japan. The percentages of non-wild-type (non-WT) isolates for which MICs of itraconazole, posaconazole, and voriconazole were above the ECV were 7.1%, 2.6%, and 4.1%, respectively. A G54 mutation in cyp51A was detected in 64.2% (9/14 isolates) and 100% (5/5 isolates) of non-WT isolates for itraconazole and posaconazole, respectively. Amphotericin B MICs of ≥2 µg/ml and micafungin minimum effective concentrations (MECs) of ≥16 µg/ml were recorded for two and one isolates, respectively.

Bronchoalveolar lavage galactomannan for the diagnosis of chronic pulmonary aspergillosis.

Diagnosing chronic pulmonary aspergillosis (CPA) is complicated, and there are limited data available regarding the identification of galactomannan (GM) in clinical specimens to assist the detection of this infection. The purpose of this study was to evaluate the detection of GM in bronchoalveolar lavage fluid (BALF) and serum and to assess its utility for diagnosing CPA. We retrospectively reviewed the diagnostic and clinical characteristics of 144 patients, with and without CPA, in Nagasaki University Hospital, Japan, whose BAL and serum specimens were examined for the presence of GM. The Platelia Aspergillus enzyme immunoassay (PA EIA) was performed according to the manufacturer's instructions. The mean values of BALF GM antigen were 4.535 (range, 0.062-14.120) and 0.430 (range, 0.062-9.285) in CPA (18) and non-CPA (126) patients, respectively. The mean values of serum GM antigen were 1.557 (range, 0.232-5.397) and 0.864 (range, 0.028-8.956) in CPA and non-CPA patients, respectively. PA EIA of BALF is superior to the test with serum, with the optimal cut-off values for BALF and serum of 0.4 and 0.7, respectively. The sensitivity and specificity of PA EIA in BALF at a cut-off of 0.4 were 77.2% and 77.0%, respectively, whereas with serum at a cut-off of 0.7, they were 66.7% and 63.5%, respectively. GM testing using BALF showed reasonable sensitivity and specificity as compared to that using serum. Thus, assessing GM levels in BALF may enhance the accuracy of diagnosing CPA.

A case of bronchial aspergillosis caused by Aspergillus udagawae and its mycological features.

Aspergillus udagawae and A. fumigatus share similar morphological features but they differ genetically. There is also an important clinical distinction as A. udagawae is less sensitive to amphotericin B than A. fumigatus. We encountered a rare case of bronchial infection due to A. udagawae that was successfully treated with voriconazole. An 82-year-old woman with diabetes mellitus complained of bloody sputum. Bronchoscopy revealed a white plugged region at the origin of the right bronchi B5. Cytological study revealed a clot composed of filamentous fungi and Aspergillus spp. was detected by culture. Molecular analysis revealed that the causative agent was A. udagawae, and voriconazole was used for the treatment. In comparison to A. fumigatus, the A. udagawae strain isolated in this case was less sensitive to amphotericin B, less virulent in immunosuppressed mice, and more sensitive to hydrogen peroxide, features that are almost identical to those of the previously reported isolates of the fungus. We should be aware of the emergence of new Aspergillus species that might pose a clinical threat.

[Anti-cytomegaloviral drugs].

Cytomegalovirus infection is often life threatening in immunocompromised patients. Three anti-CMV drugs, ganciclovir, valganciclovir and foscarnet are available in commercial basis in Japan. In addition to them, cidofovir is provided for patients with HIV by a research group supported by Ministry of Health, Labour and Welfare. Every anti-CMV drug has serious side effects, as bone marrow suppression with ganciclovir and valganciclovir, renal toxicity with foscarnet and both with cidofovir. Strict dose adjustment to the renal function and close monitoring with laboratory examinations are essential when using those drugs.

The glycosylphosphatidylinositol-linked aspartyl protease Yps1 is transcriptionally regulated by the calcineurin-Crz1 and Slt2 MAPK pathways in Candida glabrata.

In the pathogenic fungus Candida glabrata, the YPS1 gene, which encodes a glycosylphosphatidylinositol-linked aspartyl protease, is required for cell wall integrity and virulence. Although the expression of YPS1 has been studied in Saccharomyces cerevisiae, the transcriptional regulation of this gene in C. glabrata is not well understood. Here, we report that C. glabrata Yps1 is required for cell growth at elevated temperatures, and that the heat-induced expression of YPS1 is regulated predominantly by the calcineurin-Crz1 pathway and partially by the Slt2 MAPK pathway. Although a total of 11 YPS genes are present in the C. glabrata genome, the loss of transcriptional induction in a calcineurin mutant was observed only for YPS1. The results of a YPS1 promoter-lacZ reporter assay using a series of constructs with mutated promoter elements indicated that the transcription factor Crz1 binds to multiple sites in the promoter region of YPS1. To date, as none of the putative Crz1 targets in C. glabrata have been characterized using a Δcrz1 mutant, monitoring the expression of YPS1 represents an effective method for measuring the activity of the calcineurin-Crz1 signaling pathway in this fungus.

Diagnostic significance of Aspergillus species isolated from respiratory samples in an adult pneumology ward.

Although the diagnostic significance of isolating Aspergillus spp. from respiratory cultures has been studied in immunocompromised hosts with invasive pulmonary aspergillosis (IPA), little is known of such infections in immunocompetent patients with other forms of aspergillosis. In this study of adult pneumology ward patients, we examined the association between Aspergillus spp. and disease prevalence. Laboratory records from April 1998 to March 2009 were reviewed to identify patients with Aspergillus spp. in respiratory samples. Correlations between the isolated species and clinical characteristics of patients were evaluated. During the study period, 165 Aspergillus spp. isolates were detected in the respiratory cultures of 139 patients. Of these patients, 62 (45%) were colonized with Aspergillus spp. and displayed no clinical symptoms of aspergillosis, while 77 (55%) had a form of pulmonary aspergillosis, characterized as either chronic necrotizing pulmonary aspergillosis (CNPA) (48%), aspergilloma (29%), IPA (13%), or allergic bronchopulmonary aspergillosis (ABPA) (10%). The dominant species were Aspergillus fumigatus (41%), A. niger (32%), and A. versicolor (12%). A. fumigatus was most commonly isolated in patients with IPA, aspergilloma, and CNPA, whereas A. niger was the dominant species in colonized patients and those with ABPA. Isolation of an Aspergillus spp. from respiratory samples does not confirm it as the etiologic pathogen because airway colonization by Aspergillus spp. is a common feature in several chronic lung diseases. Repeated isolation of the identical Aspergillus species and detection of anti-Aspergillus antibodies and/or Aspergillus antigens in sera are needed to determine the isolate represents the etiologic agent of disease.

Clinical characteristics of seven patients with Aeromonas septicemia in a Japanese hospital.

The genus Aeromonas comprises flagellated gram-negative rods widely distributed in freshwater, estuarine and marine environments. Aeromonas species may cause a variety of illnesses in humans, such as enterocolitis and septicemia, especially in warmer tropical or subtropical environments. To recognize the characteristics of Aeromonas septicemia in Japan, we reviewed laboratory data and medical records in our hospital. During 11 years (from 2000 to 2010), Aeromonas septicemia was observed in seven patients involving six female subjects. Six patients were observed in summer or fall. The incidence of Aeromonas septicemia was about 0.07 per 1000 admissions, and two out of the seven patients died. All patients had underlying diseases such as malignancy (six patients) and choledocholithiasis (one patient). Two patients developed septicemia within two days after ingesting raw seafood. Five patients developed Aeromonas septicemia > 48 h after admission. Fever was present in all patients, and four out of the seven patients developed septic shock. All patients developed monomicrobial septicemia. A. hydrophila was isolated from five patients, and A. caviae and A. veronii biovar sobria were isolated from one patient each. Most antimicrobial agents had high activity against the isolated strains. However, a carbapenem-resistant strain appeared in one patient during treatment and led to death. Aeromonas septicemia is uncommon in temperate areas but can occur particularly in warm seasons. Immunocompromised conditions and recent ingestion of raw fish or shellfish are important characteristics of developing Aeromonas septicemia.

Nationwide surveillance of AIDS-defining illnesses among HIV patients in Japan from 1995 to 2017.

OBJECTIVES: The accurate prevalence of acquired immunodeficiency syndrome (AIDS)-defining illnesses (ADIs) in human immunodeficiency virus (HIV)-infected patients has not been well investigated. Hence, a longitudinal nationwide surveillance study analyzing the current status and national trend of opportunistic complications in HIV-infected patients in Japan is warranted. METHODS: A nationwide surveillance of opportunistic complications in HIV-infected patients from 1995 to 2017 in Japan was conducted. An annual questionnaire was sent to 383 HIV/AIDS referral hospitals across Japan to collect information (CD4+ lymphocyte count, time of onset, outcome, and antiretroviral therapy [ART] status) of patients diagnosed with any of 23 ADIs between 1995 and 2017. RESULTS: The response and case capture rates of the questionnaires in 2017 were 53% and 76%, respectively. The number of reported cases of opportunistic complications peaked in 2011 and subsequently declined. Pneumocystis pneumonia (38.7%), cytomegalovirus infection (13.6%), and candidiasis (12.8%) were associated with the cumulative incidence of ADIs between 1995 and 2017. The mortality rate in HIV-infected patients with opportunistic complications substantially decreased to 3.6% in 2017. The mortality rate was significantly higher in HIV patients who received ART within 14 days of diagnosis of complications than in those who received ART 15 days after diagnosis (13.0% vs. 3.2%, p < 0.01). CONCLUSIONS: We have demonstrated a 23-year trend of a newly diagnosed AIDS status in Japan with high accuracy. The current data reveal the importance of Pneumocystis pneumonia as a first-onset illness and that early initiation of ART results in poor outcomes in HIV patients in Japan.

[Opportunistic infections in HIV/AIDS].

The number of diagnosed AIDS and HIV infection is still increasing year by year in Japan. Therefore, reported annual number of opportunistic infections (OIs) is also increasing. Pneumocystis pneumonia, cytomegalovirus infection, candidiasis, and tuberculosis are the major OIs in Japan. Increment of malignancies such as malignant lymphoma and Kaposi's sarcoma is remarkable in recent years. Although diagnosis and treatment of OIs are almost established, some novel diagnostic tests and treatment option have developed and imploved the clinical outcome of HIV-related OIs. Anti-retroviral therapy (ART) is strongly influenced to the OI threapy in relation to the drug interaction, timing of ART and induction of immunoreconstitution syndrome. Clinicians should consider proper sequence and timing of OI therapy and ART initiation in each case.

Serum (1-->3) beta-D-glucan as a noninvasive adjunct marker for the diagnosis of Pneumocystis pneumonia in patients with AIDS.

High serum (1-->3) beta-D-glucan levels are described in patients with Pneumocystis pneumonia (PCP). We evaluated the diagnostic value of beta-D-glucan in 111 patients with AIDS who had PCP and confirmed its usefulness. However, it does not correlate with disease severity and is not suitable for monitoring response to treatment.

Sequence-based spa typing as a rapid screening method for the areal and nosocomial outbreaks of MRSA.

Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of nosocomial infection and MRSA outbreaks have become a major problem. Therefore, the rapid and accurate typing of MRSA isolates is important for epidemiological surveys and nosocomial infection control. Pulsed-field gel electrophoresis (PFGE) is considered as the gold standard technique for MRSA typing, because of its high discriminatory power, but its procedure is rather complicated and time-consuming. The spa gene encodes a cell wall component of Staphylococcus aureus protein A, and exhibits polymorphism. Sequencing the spa gene is expected superior to PFGE in speed and data interpretation. In the present study, we evaluated whether spa typing of MRSA is useful for nosocomial outbreak analysis and epidemiological investigations. We analyzed 19 nosocomial outbreak isolates from 4 separate hospitals and 26 isolates from outpatients of Toyama University Hospital. Either PFGE or spa typing revealed a single nosocomial strain that appears unique to each hospital. Indeed, spa typing confirmed the four different strains, but PFGE demonstrated only 3 strains. With the total 45 isolates, PFGE showed 16 different patterns and spa typing showed 12 patterns. Moreover, we were able to analyze the spa gene in about 2 days, from sampling to obtaining the results, whereas it took about 7 days with PFGE. In conclusion, sequence-based spa typing shows comparable sensitivities to PFGE, and is a rapid and easy handling method. The sequence-based spa typing can be used as the rapid screening test when MRSA outbreak is suspected in areas and hospitals.

Munchausen syndrome mimicking refractory subcutaneous abscess with bacteremia, diagnosed by repetitive element sequence-based polymerase chain reaction: a case report.

BACKGROUND: Rapid diagnosis and appropriate treatment of Munchausen syndrome is important not only for the patient but also for health care workers because a delay in diagnosis can worsen patients' clinical outcomes, and result in a substantial medical cost. CASE PRESENTATION: A young and previously healthy 24-year-old Japanese woman, a nurse, presented with complaints of refractory abscess on her left upper limb for 3 months. A physical examination on admission revealed low-grade fever and a subcutaneous abscess in her left forearm. Laboratory data suggested mild systemic inflammation and liver dysfunction, but no abnormalities of the immune system, including changes in the number of lymphocytes and neutrophils, neutrophil phagocytic capacity, and natural killer (NK) cell activity, were observed. A human immunodeficiency virus test was also negative. Multiple modalities, including positron emission tomography-computed tomography, failed to detect any cause and focus of infection except her left upper limb. Streptococcus mitis and Prevotella buccae were detected from the wound, but no microorganisms were detected in a blood culture. The cellulitis promptly resolved; however, exacerbation of the subcutaneous abscess with polymicrobial bacteremia repeatedly occurred unexpectedly. Because of this puzzling clinical course, the possibility of self-injury was finally suspected. Three syringes with needles, with a turbid liquid, were found in our patient's bag. Enterobacter cloacae and Enterococcus faecalis were detected in the liquid, and an analysis via repetitive element sequence-based polymerase chain reaction determined that Enterococcus faecalis in the wound and syringe contents were genetically identical. She was diagnosed as having Munchausen syndrome and treated with the collaboration of a psychiatrist. She finally confessed that she had injected her own saliva and toilet water into the drip line and wound. CONCLUSIONS: This case report is valuable in that it is the first case in which this syndrome was diagnosed by a genetic method. Munchausen syndrome should not be neglected as a possible cause of refractory and recurrent infection.

Decrease in Epstein-Barr virus-positive AIDS-related lymphoma in the era of highly active antiretroviral therapy.

Recent introduction of highly active antiretroviral therapy (HAART) is reported to have reduced the incidence of lymphoma among HIV-infected individuals. A clinicopathological study was performed on 86 AIDS-related lymphoma patients who were treated in Tokyo area from 1987 to 2005. The incidence of lymphoma detected by autopsy was 27% (53 cases/198 autopsies). Diffuse large B cell lymphoma was the most predominant histological subtype throughout the period (78%). Burkitt's lymphoma (BL) increased from 2% in the pre-HAART era (before end-1997) to 13% in the HAART era, whereas incidence of BL did not vary between HAART users and non-users. Epstein-Barr virus (EBV)-positive lymphoma decreased from 88% in the pre-HAART era to 58% in the HAART era, but did not differ significantly between HAART users (73%) and non-users (74%). Nodal involvement of lymphoma increased from 14% in the pre-HAART era to 50% in the HAART era; however, central nervous system involvement decreased from 62 to 38%. Kaposi's sarcoma-associated herpesvirus infection was rare (4%) among all cases. These data suggest that HAART might play a partial role in these changes, and the alteration in immunological backgrounds, such as EBV prevalence, is suggested as another leading cause of these changes in Japanese AIDS-related lymphoma.

[Fungal infections in HIV-infected patients].

Recent situation of HIV-related mycosis was discussed in this paper, with the analysis of 1) annual report of HIV trends in Japan by the AIDS epidemiology committee, 2) report of HIV-related opportunistic infections (OIs) collected by the AIDS-OIs research group funded by the Ministry of Health, Labour and Welfare, and 3) 17 cases of HIV-related aspergillosis collected by the author. Annual AIDS cases were increasing, and their major diseases were included with the following mycosis: pneumosystis pneumonia 35.7%, candidiasis 19.1%, and cryptococcosis 2.4%. There were two foreigner's cases of histoplasmosis and no coccidioidosis. Candidiasis was likely to be shown in Japanese patients and cryptococcosis was in foreigners. Outcome of cryptococcosis was very poor as 32.7% of patients died. There were 17 HIV-related aspergillosis, which consisted of 13 cases of lung diseases, 2 of brain lesions, and one each of sinus and stomach disease. Remarkable risk factor of HIV-related aspergillosis was decrease of CD4 cell count less than 10/microl, in addition to the usual risk factors of aspergillosis. Outcome of aspergillosis was very poor, as all treated cases died except one recent case treated with voriconazole.