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The human body is a hostile environment for Aspergillus species, which originally live outside the human body. There are lots of elimination mechanisms against Aspergillus inhaled into the human body, such as high body temperature, soluble lung components, mucociliary clearance mechanism, or responses of phagocytes. Aspergillus fumigatus, which is the primary causative agent of human infections among the human pathogenic species of Aspergillus, defend itself from the hostile human body environment by various mechanisms, such as thermotolerance, mycotoxin production, and characteristic morphological features. Here we review mechanisms of defense in Aspergillus against elimination from the human body.

Aspergillus spp. are important fungi because of the high mortality associated with aspergillosis. However, we have only three classes of anti-aspergillus drugs available; and only two drugs, itraconazole (ITCZ) and voriconazole (VRCZ), are available as oral agents in Japan. If azole-resistant Aspergillus causes chronic aspergillosis, we cannot treat such patients with oral azoles on an outpatient basis. As is the case with foreign countries, we found the existence of azole-resistant Aspergillus fumigatus in clinical settings in Japan. Resistance was attributed to mutations of the target protein (CYP51A). Additionally, we also found that long-term itraconazole treatment induced G54 substitution in CYP51A, causing itraconazole-resistance. Although there are few resistant Aspergillus strains existing in Japan now, we have to continue to find such resistant isolates, which are spreading worldwide.

We evaluated species distribution and antifungal susceptibility of Candida isolates during 2002-2008. Of 177 Candida isolates from blood, species distribution was 90 (51%) Candida albicans, 30 (17%) C. parapsilosis, 22 (12%) C. glabrata, 6 (3%) C. tropicalis and 29 (16%) other Candida spp.. Of 162 Candida isolates from vascular catheter, species distribution was 87 (54%) C. albicans, 14 (9%) C. parapsilosis, 36 (22%) C. glabrata, 5 (3%), C. tropicalis, 2 (1%) C. krusei and 18 (11%) other Candida spp.. Of 1889 Candida isolates from urine, species distribution was 1165 (62%) C. albicans, 22 (1%) C. parapsilosis, 484 (26%) C. glabrata, 83 (4%) C. tropicalis, 26 (1%) C. krusei and 109 (6%) other Candida spp.. Of 782 Candida isolates from stool, species distribution was 425 (54%) C. albicans, 3 (1%) C. parapsilosis, 103 (13%) C. glabrata, 28 (4%) C. tropicalis, 5 (1%), C. krusei and 218 (28%) other Candida spp. Both C. albicans and non-Candida spp. isolated from urine increased slightly over the past 7 years. Flucytosine, fluconazole, itraconazole and micafungin still have strong activity against Candida isolates.

Highly pathogenic avian influenza (HPA1) virus of H5N1 subtype has spread worldwide and continues to cause outbreaks in poultry and sporadic human infections since 2003. As of 9 April 2010, 493 confirmed human cases including 292 fatal cases were reported from 15 countries. Despite emergence of the pandemic A (H1N1)2009 virus, pandemic threats posed by H5N1 subtype virus still remain. H7 subtype avian influenza viruses also pose a similar threat to humans as H5N1 subtype virus. We provide here an updated overview on the human infections of HPA1 viruses in the world.

We evaluated species distribution and antifungal susceptibility of Candida isolates during 2002-2008. Of 177 Candida isolates from blood, species distribution was 90 (51%) Candida albicans, 30 (17%) C. parapsilosis, 22 (12%) C. glabrata, 6 (3%) C. tropicalis and 29 (16%) other Candida spp.. Of 162 Candida isolates from vascular catheter, species distribution was 87 (54%) C. albicans, 14 (9%) C. parapsilosis, 36 (22%) C. glabrata, 5 (3%), C. tropicalis, 2 (1%) C. krusei and 18 (11%) other Candida spp.. Of 1889 Candida isolates from urine, species distribution was 1165 (62%) C. albicans, 22 (1%) C. parapsilosis, 484 (26%) C. glabrata, 83 (4%) C. tropicalis, 26 (1%) C. krusei and 109 (6%) other Candida spp.. Of 782 Candida isolates from stool, species distribution was 425 (54%) C. albicans, 3 (1%) C. parapsilosis, 103 (13%) C. glabrata, 28 (4%) C. tropicalis, 5 (1%), C. krusei and 218 (28%) other Candida spp.. Both C. albicans and non-Candida spp. isolated from urine increased slightly over the past 7 years. Flucytosine, fluconazole, itraconazole and micafungin still have strong activity against Candida isolates.

We retrospectively analyzed the severity of community-acquired pneumonia in 293 patients. Based on the Japanese Respiratory Society (JRS) risk stratification guidelines (A-DROP), patients were classified as follows: mild, 74 (25%); moderate, 140 (48%); severe, 53 (18%); and extremely severe, 26 (9%). The mortality of each category was classified as follows: mild, 0 (0%); moderate, 4 (3%); severe, 8 (15%); and extremely severe, 8 (31%). Based on the Pneumonia Severity Index (PSI) score used in the Infectious Disease Society of America/American Thoracic Society (IDSA/ATS) consensus guidelines, patients were classified as follows: I, 36 (12%); II, 44 (15%); III, 61 (21%); IV, 92 (31%); and V, 60 (20%). The mortality of each category was classified as follows: I-III, 0 (0%); IV, 5 (25%); or V, 15 (75%). Comparisons made between patients who died within 14 days and those who survived, showed that leukocytes and CRP values were higher among the fatality group. Moreover, Alb/BUN correlated with the PSI score (r = - 0.62). We propose Alb/BUN as a new index for prognostic factor of community-acquired pneumonia.