Akira Yasuoka

Influence of Human Immunodeficiency Virus Type 1 Infection on Acute Hepatitis A Virus Infection

To assess the possible influence of human immunodeficiency virus type 1 (HIV-1) infection on the clinical course of acute hepatitis A virus (HAV) infection, 15 HIV-1-infected homosexual men and 15 non-HIV-infected age-matched subjects were compared. HAV load was higher in HIV-1-infected than in non-HIV-infected patients (P<.001). Duration of viremia in HIV-1-infected patients (median, 53 days) was significantly (P<.05) longer than in non-HIV-infected patients (median, 22 days). HIV-1-infected patients had lower elevations in alanine aminotransferase levels than did non-HIV-infected patients (P<.01) but had higher elevations in alkaline phosphatase levels than did non-HIV-infected patients (P<.001). Some HIV-1-infected patients still had HAV viremia when clinical symptoms had disappeared and alanine aminotransferase levels had returned to normal (60-90 days after the onset of symptoms). HIV-1 infection was associated with prolongation of HAV viremia, which might cause a long-lasting outbreak of HAV infection in HIV-1-infected homosexual men.

An evaluation of serodiagnostic tests in patients with candidemia : Beta-glucan, mannan, candida antigen by Cand-Tec and D-arabinitol

The serodiagnostic tests, beta‐glucan, mannan, candida antigen by Cand‐Tec, and D‐arabinitol were evaluated in 10 patients with candidemia, 14 patients with suspected fungemia, and 10 healthy persons. By blood culture or lysis centrifugation, C. albicans was isolated from 5 patients, C. parapsilosis from 4, and C. tropicalis from 1 patient; no organisms were isolated from the 14 patients with suspected fungemia or the 10 healthy subjects. Beta‐glucan was measured by the difference between two chromogenic limulus tests (Endotoxin test‐D® and Endospecy®), which was more than 60 pg/ml in 7 of 9 (78%) candidemic patients and 1 of 12 (8%) patients with suspected fungemia. Mannan was positive in 6 of 10 (60%) candidemic patients and 1 of 13 (8%) patients with suspected fungemia. Both antigens were very sensitive and highly specific for candidemia. However, the Cand‐Tec assay was less specific, because titers of more than 4 were observed in 5 of 14 (34%) patients with suspected fungemia. D‐Arabinitol was the least sensitive, because a D‐arabinitol/creatinine ratio greater than 2.0 μmol/mg was observed in only 2 of 7 (29%) candidemic patients. The titers of serodiagnostic tests decreased after successful treatment with an anti‐fungal agent. Our results show that the combined use of the assays in necessary for accurate serological diagnosis of candidemia.

Serum (1→3) β-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.

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

ABSTRACT 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

ABSTRACT 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.

Antimicrobial susceptibility and molecular characteristics of 857 methicillin-resistant Staphylococcus aureus isolates from 16 medical centers in Japan (2008–2009): nationwide survey of community-acquired and nosocomial MRSA

This study is a nationwide survey of all clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, including community-acquired MRSA (CA-MRSA), in Japan. A total of 857 MRSA clinical isolates were collected from the 16 institutions throughout Japan that participated in the survey (2008-2009). The drug susceptibility and staphylococcal cassette chromosome mec (SCCmec) typing and the presence of specific pathogenic genes were evaluated. The isolates comprised SCCmec type II (73.6%), type IV (20%), and type I (6%). The percentage of SCCmec type IV isolates was significantly higher in outpatients than in inpatients. Most of the isolated strains were sensitive to vancomycin (VCM, MIC ≤2 μg/mL), linezolid (MIC ≤4 μg/mL), and teicoplanin (MIC ≤8 μg/mL). Although most strains were sensitive to VCM, the MIC value of VCM for SCCmec type II strains was higher than that for SCCmec type IV strains. Only 4 (2.3%) of 171 SCCmec type IV strains were Panton-Valentine leukocidin (lukS/F-PV)-positive. Thus, this result indicates a unique feature of SCCmec type IV strains in Japan. The information in this study not only is important in terms of local public health but will also contribute to an understanding of epidemic clones of CA-MRSA.

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.

Environmental isolation of Cryptococcus neoformans from an endemic region of HIV-associated cryptococcosis in Thailand

We successfully isolated Cryptococcus neoformans from chicken faeces in suburban areas of Thailand. C. neoformans was isolated from 36/150 houses (24.0%) in the dry season and 6/150 (4.0%) in the rainy season. All environmental isolates were of serotype A. The high isolation rate of 24% from chicken faeces has never been reported previously. Our environmental study could probably explain the high incidence of cryptococcal meningitis in HIV patients in Thailand. Copyright

Influence of Molecular Sizes of Cryptococcus neoformans Capsular Polysaccharide on Phagocytosis

The role of capsular polysaccharides (CPS) of Cryptococcus neoformans in phagocytosis by murine alveolar macrophages was investigated in four strains of C. neoformans serotype A, YC‐11, YC‐5, YC‐27 and YC‐13. Phagocytosis rates increased markedly after adding 10% mouse serum, compared to fetal calf serum. The reverse relation between capsular thickness of C. neoformans and phagocytosis by alveolar macrophages was observed except in YC‐27, which had thin capsules and high virulence. The phagocytosis rate in mice serum was 17.3% in YC‐11 (capsule thickness 2.8‐3.5 μm), 39.8% in YC‐5 (capsule size 0.8‐1.5 μm), 20.3% in YC‐27 (capsule size 0.6‐1.1 μm), and 62.8% in YC‐13 (capsule not detected microscopically). The CPS of YC‐11, YC‐5, and YC‐27 analyzed by gel‐filtration using CL‐2B showed high molecular fractions near the void volume. However, the CPS of YC‐13 showed only low molecular fractions. The widely eluted CPS of YC‐11 was separated into 3 fractions and each fraction was added in the phagocytosis assay of YC‐13. Phagocytosis was markedly suppressed particularly by the addition of a higher molecular fraction. These results suggest that phagocytosis of C. neoformans by alveolar macrophages is influenced by the molecular sizes of the CPS.

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 manufacturers 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.