The first characteristic identified in surface-linked liposomal antigens was the ability to induce antigen-specific, IgE-selective unresponsiveness. These results remained consistent even when different coupling procedures were employed for antigens with liposomes or for liposomes with different lipid components. The potential usefulness of surface-linked liposomal antigens for application to vaccine development was further investigated. During this investigation, a significant difference was observed in the recognition of liposomal antigens by antigen-presenting cells between liposomes with different lipid components, and this difference correlated closely with the adjuvant activity of liposomes. In addition to this “quantitative” difference between liposomes with differential lipid components, a “qualitative” difference (i.e., a differential ability to induce cross-presentation) was observed between liposomes with different lipid components. Therefore, by utilizing the ability to induce cross-presentation, surface-linked liposomal antigens might be used to develop virus vaccines that would induce cytotoxic T lymphocyte (CTL) responses. We have successfully developed a liposome vaccine that is capable of inducing CTL responses against internal antigens of influenza viruses and thus removing virus-infected cells in the host. This CTL-based liposomal vaccine might be applicable to the development of vaccines against influenza and other viruses that frequently undergo changes in their surface antigenic molecules.
When cumulative numbers of patients (X) and deaths (Y) associated with an influenza epidemic are plotted using the log-log scale, the plots fall on an ascending straight line generally expressed as logY = k(logX − logN0). For the 2009 H1N1 influenza pandemic, the slope k was ～0.6 for Mexico and ～2 for other countries. The two-population model was proposed to explain this phenomenon (Yoshikura H. Jpn J Infect Dis. 2012;65:279-88; Yoshikura H. Jpn J Infect Dis. 2009;62:411-2; and Yoshikura H. Jpn J Infect Dis. 2009;62:482-4). The current article reviews and analyzes previous influenza epidemics in Japan to examine whether the two-population model is applicable to them. The slope k was found to be ～2 for the Spanish flu during 1918–1920 and the Asian flu during 1957–1958, and ～1 for the Hong Kong flu and seasonal influenza prior to 1960–1961; however, k was ～0.6 for seasonal influenza after 1960–1961. This transition of the slope k of seasonal influenza plots from ～1 to ～0.6 corresponded to the shift in influenza mortality toward the older age groups and a drastic reduction in infant mortality rates due to improvements in the standard of living during the 1950s and 1960s. All the above observations could be well explained by reconstitution of the influenza epidemic based on the two-population model.
A food-borne pathogen, Listeria monocytogenes serotype 4b, has been frequently isolated from patients with listeriosis, and numerous outbreaks of listeriosis are associated with this serotype. In the present study, we performed subtyping of L. monocytogenes serotype 4b strains on the basis of genetic analyses. Thirty-four isolates of serotype 4b were classified into 8 genotypes, namely genotypes 12, 15, 16, 17, 18, 23, 24, and 25, on the basis of the sequence for the partial iap gene. Genetic analyses revealed that genotype 16 and genotypes 24 and 25 belong to epidemic clone I (ECI) and ECII, respectively, which have been frequently associated with listeriosis outbreaks in the United States and Europe. The genotype isolated most frequently from retail meats in the Tokyo metropolitan area was genotype 12 (52%), followed by genotype 16 (29%), which belongs to ECI. We suggest that ECI is a common subtype of L. monocytogenes in retail meat in the area under investigation. On the other hand, ECII isolates were confirmed to be present in retail meat in Japan but were rare.
Acute diarrhea is the most common infectious disease worldwide and its causes vary from one region to another. We aimed to analyze the spectrum and epidemiological characteristics of pathogens from 22,386 outpatients with acute diarrhea on the basis of surveillance data from Shanghai, China, during 2006–2011. The following 8 pathogens were isolated and identified using standard methods: Salmonella, Shigella, Vibrio cholerae, V. parahaemolyticus, enteropathogenic Escherichia coli, enterotoxigenic E. coli, enteroinvasive E. coli, and enterohemorrhagic E. coli. In total, 2,234 strains of pathogens were obtained and the overall isolation rate of these 8 pathogens gradually decreased from 17.1% in 2006 to 7.4% in 2011. V. parahaemolyticus was the most frequently identified pathogen, followed by Shigella and Salmonella. The isolation rate of V. parahaemolyticus notably varied by season, whereas Salmonella and Shigella infections showed little seasonal variation. Age-related variation was also observed. V. parahaemolyticus infection occurred more often in patients aged 20–40 years. S. enterica serovar Enteritidis and S. flexneri were the most common serotypes of Salmonella and Shigella, respectively. The descending trend observed in the isolation rate of pathogens from the current surveillance suggests an urgent requirement or improvement.
The age-group-specific incidence and etiological patterns of community-acquired pneumonia (CAP) have not been fully established in Japan. A 2-year prospective surveillance was conducted in Kochi city, Western Japan. All CAP patients aged ≥15 years who visited a community-based hospital were enrolled in the study. Clinical samples were examined by conventional bacterial culture and urinary antigen tests, and 6 bacterial pathogens and 16 respiratory viruses were identified from sputum samples by multiplex polymerase chain reaction assays. The age-group-specific incidence of CAP was estimated using a population-based data set of the total number of outpatients in the whole city. Ninety of the 131 enrolled patients, 68.7% were positive for respiratory pathogens. Streptococcus pneumoniae was the leading bacterial pathogen identified (28.2%). Respiratory viruses were identified in 36 patients (27.5%), and human entero–rhinovirus was the most common (13.3%) among them. The estimated overall incidence of adult CAP in Kochi was 9.6 per 1,000 person-years (PY); the estimated age group-specific incidence was 3.4, 10.7, and 42.9 per 1,000 PY for those aged 15–64, 65–74, and ≥75 years, respectively. The high incidence of CAP in these rural city of Japan, probably reflects the substantial aged population. S. pneumoniae and respiratory viruses play important roles in CAP in all age groups.
Bath water samples were collected from 116 hot springs, 197 public bathhouses, and 38 24-hour home baths in Nagano Prefecture, Japan, during the period of April 2009 to November 2011, for determining the presence and extent of contamination with Legionella and nontuberculous mycobacteria. Cultures positive for Legionella were observed in 123 of the 3,314 bath water samples examined. The distribution and abundance of Legionella and/or combined contamination with Legionella and nontuberculous mycobacteria were investigated to clarify the contamination levels. The abundance of Legionella was demonstrated to correlate considerably with the levels of combined contamination with Legionella and nontuberculous mycobacteria. Legionella spp. were obtained from 61% of the water samples from 24-hour home baths, but only from 3% of the samples from public bathhouses and hot springs. This is despite the fact that a few outbreaks of Legionnaires' disease in Nagano Prefecture as well as other regions of Japan have been traced to bath water contamination. The comparatively higher rate of contamination of the 24-hour home baths is a matter of concern. It is therefore advisable to routinely implement good maintenance of the water basins, particularly of the 24-hour home baths.
Recently, new genotypes of human adenoviruses (HAdVs) have been reported and many of them have been found to be recombinant forms of different known types of HAdV species D (HAdV-D). The objective of this study was to document the evolutionary features of a novel isolate (HAdV_Chiba_E086/2012) obtained from the eye swab of a patient with conjunctivitis in Japan. Viral DNA was extracted from the isolate to sequence the whole genome by the Sanger method and aligned with available genome sequences of HAdV-Ds. The phylogenetic trees of the nucleotide sequences of the penton base, hexon, and fiber genes and the E3 region showed that HAdV_Chiba_E086/2012 is closest to HAdV genotype 65 (HAdV-GT65), HAdV-48, HAdV-GT60 and HAdV-22 at 98%, 99%, 95% and 98% identity, respectively, suggesting that this isolate is a novel recombinant form to be designated as P65H48F60. Further phylogenetic and recombination analyses of the genome alignment of the new isolate implied that nested recombination events involving HAdV-GT59, GT65, 48, GT60, 22, and some ancestral lineages or their close relatives have shaped its genome. These results showed that HAdV_Chiba_E086/2012 is the first HAdV-48-related HAdV found in Japan, which has the most complicated evolutionary history among the known HAdVs so far.
Antibiotic susceptibility of Neisseria gonorrhoeae in Guangzhou during 2002–2011 showed that resistance to penicillin and ciprofloxacin was high, while ceftriaxone remained effective although there was a trend towards reduced sensitivity.
We report a rare case of adult varicella complicated by marked thrombocytopenia. A 49-year-old woman presented with fever and rash for 3 days. Blood examination revealed marked thrombocytopenia (2.7 × 104/μL). Varicella infection was diagnosed after elevated levels of varicella zoster virus IgM and IgG antibodies were observed 2 weeks later. In this case, thrombocytopenia was due to varicella infection, and the mechanism was estimated to be non-immunological. Because varicella infection complicated by thrombocytopenia may result in fatal bleeding, thrombocytopenia in patients with varicella warrants close attention.
We analyzed the clinical and laboratory findings of both pediatric and adult patients with oropharyngeal tularemia. We also compared the therapeutic outcomes of patients who underwent surgical drainage of lymph nodes early or late during antibiotic therapy. A total of 68 patients with oropharyngeal tularemia, including 26 children and 42 adults, were enrolled in this study. The average duration between symptom onset and hospital admission was 20.8 days (4–60 days) in the pediatric group and 32.6 days (4–90 days) in the adult group (P = 0.009). The most frequently observed clinical symptoms were sore throat (100% and 100%), fever (96.2% and 90.5%), tonsillitis (69.2% and 78.6%), and rash (15.4% and 11.9%) in the pediatric and adult groups, respectively. However, the frequencies of erythema, tenderness, and fluctuant of enlarged lymph nodes were significantly higher in the adult group than in the pediatric group (P = 0.005, P = 0.029, and P = 0.041, respectively). Treatment failure was observed in 2 (7.7%) pediatric patients and 4 (9.5%) adult patients, for a total of 6 (8.8%) treatment failures in the study group. Similar clinical findings and treatment outcomes were observed in both groups. We concluded that a combination of surgical drainage and antibiotic therapy increases treatment success for patients diagnosed with oropharyngeal tularemia.
This study represents a measles outbreak caused by the genotype D9 measles virus (MeV), which was imported by Burmese individuals. Urine and throat swab specimens were collected from suspected measles cases. Viruses were isolated, and a 634-bp target fragment of the N gene was amplified by reverse transcription-PCR and sequenced. Phylogenetic results indicated that the 6 isolates belonged to genotype D9 MeV. Through appropriate prevention and control measures, the transmission of genotype D9 MeV was interrupted. Genotype D9 MeV was isolated for the first time in Shandong and was imported by Burmese individuals.
The occurrence of severe rotavirus gastroenteritis (RVGE) in children under 3 years of age before and after the introduction of rotavirus vaccine was prospectively surveyed in three pediatric clinics in Shibata City, Niigata Prefecture, Japan, during the 2011 and 2012 RVGE epidemic seasons. In this observational study, a significantly lower occurrence of severe RVGE among severe gastroenteritis cases was observed in 2012. The incidence rate of severe RVGE among outpatients in 2012 was significantly lower than that in 2011. Despite the significant reduction in severe RVGE, the results must be interpreted with caution because the surveillance period is short and requires extension to conclude whether the reduction in the incidence of severe RVGE is a direct effect of rotavirus vaccination. Therefore, we will continue the survey to evaluate the impact of vaccination.
Quantitative PCR testing for JC virus (JCV) DNA in the cerebrospinal fluid (CSF) is one of the diagnostic standards for progressive multifocal leukoencephalopathy (PML). The present study was conducted to examine its reliability using CSF specimens that had been preserved with guanidine lysis buffers in commercial nucleic acid extraction kits under different conditions. When CSFs were mixed with guanidine buffers, JCV DNA levels were not statistically reduced even after storage for 1 month at room temperature or for 3 months at −80℃, compared with the control samples. In addition, the JCV DNA level was not decreased in a mixture of CSF and guanidine thiocyanate buffer incubated for 3 days at 56℃. These data suggest that CSF specimens mixed with commercial guanidine buffers can be stored without refrigeration, more safely handled, and directly subjected to JCV DNA testing for PML.
Laboratory diagnoses for measles were performed in a total of 97 cases in Hokkaido, Japan, during 2011–2012. Two patients were confirmed to be positive for measles virus (MV), both of whom lived in the Iburi district of Hokkaido. Molecular analysis of the nucleotide sequences of the nucleoprotein (N) gene revealed that these 2 strains had high homology with each other and belonged to the genotype D8. The onset interval of these cases and epidemiological data suggested that MV transmission had occurred between them and then terminated. Phylogenetic analysis of the N gene revealed that the strains identified in Hokkaido were classified into a cluster that contained many genotype D8 strains that were detected within a large area of Japan. Eventually, 9 cases were officially reported as measles. However, other than the abovementioned 2 cases, no genetic information regarding MV was obtained. In future, further active surveillance combined with the genetic investigation should be required in all suspected measles cases to verify the elimination status.
A rapid increase in antimicrobial resistance in Campylobacter has been posing a serious concern for human health. In this study, we aimed to demonstrate the overall trend in antimicrobial resistance among Campylobacter isolates obtained from chicken meat and offal products collected from a wide geographic area throughout Japan. Resistance to Enrofloxacin was most frequently observed, with significantly higher rate of resistance among isolates obtained from offal (55.6%) than from meat (27.3%) samples (p = 0.05). These results highlight need for a better understanding of the characteristics of Campylobacter isolates obtained from chicken meat and offal products.