Publications by authors named "Norichika Asoh"

25 Publications

  • Page 1 of 1

Development of cycling probe based real-time PCR methodology for influenza A viruses possessing the PA/I38T amino acid substitution associated with reduced baloxavir susceptibility.

Antiviral Res 2021 04 10;188:105036. Epub 2021 Feb 10.

Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata City, Japan; Infectious Diseases Research Center of Niigata University in Myanmar, Yangon, Yangon Region, Myanmar.

Baloxavir marboxil has been used for influenza treatment since March 2018 in Japan. After baloxavir treatment, the most frequently detected substitution is Ile38Thr in polymerase acidic protein (PA/I38T), and this substitution reduces baloxavir susceptibility in influenza A viruses. To rapidly investigate the frequency of PA/I38T in influenza A (H1N1)pdm09 and A (H3N2) viruses in clinical samples, we established a rapid real-time system to detect single nucleotide polymorphisms in PA, using cycling probe real-time PCR. We designed two sets of probes that were labeled with either 6-carboxyfluorescein (FAM) or 6-carboxy-X-rhodamine (ROX) to identify PA/I38 (wild type strain) or PA/I38T, respectively. The established cycling probe real-time PCR system showed a dynamic linear range of 10 to 10 copies with high sensitivity in plasmid DNA controls. This real-time PCR system discriminated between PA/I38T and wild type viruses well. During the 2018/19 season, 377 influenza A-positive clinical samples were collected in Japan before antiviral treatment. Using our cycling probe real-time PCR system, we detected no (0/129, 0.0%) influenza A (H1N1)pdm09 viruses with PA/I38T substitutions and four A (H3N2) (4/229, 1.7%) with PA/I38T substitution prior to treatment. In addition, we found PA/I38T variant in siblings who did not received baloxavir treatment during an infection caused by A (H3N2) that afflicted the entire family. Although human-to-human transmission of PA/I38T variant may have occurred in a closed environment, the prevalence of this variant in influenza A viruses was still limited. Our cycling probe-PCR system is thus useful for antiviral surveillance of influenza A viruses possessing PA/I38T.
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http://dx.doi.org/10.1016/j.antiviral.2021.105036DOI Listing
April 2021

Corrigendum to "Impact of the pediatric 13-valent pneumococcal conjugate vaccine on serotype distribution and clinical characteristics of pneumococcal pneumonia in adults: The Japan Pneumococcal Vaccine Effectiveness Study (J-PAVE)" [Vaccine 37 (2019) 2687-2693].

Vaccine 2020 Apr 19;38(17):3404. Epub 2020 Mar 19.

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Clinical Tropical Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.vaccine.2020.03.031DOI Listing
April 2020

Effectiveness of the quadrivalent inactivated influenza vaccine in Japan during the 2015-2016 season: A test-negative case-control study comparing the results by real time PCR, virus isolation.

Vaccine X 2019 Apr 29;1:100011. Epub 2019 Jan 29.

Division of International Health, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background: We estimated influenza vaccine effectiveness (VE) in 2015-2016 season against medically attended, laboratory-confirmed influenza, when quadrivalent inactivated vaccine (IIV4) was first introduced in Japan, using test-negative case-control design. Influenza A(H1N1)pdm09 cocirculated with B/Yamagata and B/Victoria during the study period in Japan.

Method: We based our case definition on two laboratory tests, real-time reverse transcription polymerase chain reaction (RT PCR), and virus isolation and compared VEs based on these tests. In addition, VE was evaluated by rapid diagnostic test (RDT). Nasopharyngeal swabs were collected from outpatients who visited clinics with influenza-like illness (ILIs) in Hokkaido, Niigata, Gunma and Nagasaki prefectures.

Results: Among 713 children and adults enrolled in this study, 578 were influenza positive by RT PCR including, 392 influenza A and 186 influenza B, while 135 were tested negative controls. The adjusted VE by RT PCR for all ages against any influenza was low protection of 36.0% (95% confidence interval [CI], 3.1% to 58.6%), for influenza A was 30.0% (95% CI: -10.0% to 55.5%), and influenza B was moderate 50.2% (95% CI: 13.3% to 71.4%). Adjusted VE for virus isolation for A(H1N1)pdm09 was 37.1% (95% CI: 1.7% to 59.7%), Yamagata lineage 51.3% (95% CI: 6.4% to 74.7%) and Victoria lineage 21.3% (95% CI: -50.0% to 58.9%). VE was highest and protective in 0-5 years old group against any influenza and influenza A and B/Yamagata, but the protective effect was not observed for other age groups and B/Victoria. RDT demonstrated concordant results with RT PCR and virus isolation. Sequencing of hemagglutinin gene showed that all A(H1N1)pdm09 belong to clade 6B including 31 strains (88.6%), which belong to clade 6B.1 possessing S162N mutations that may alter antigenicity and affect VE for A(H1N1)pdm09.

Conclusions: IIV4 influenza vaccine during 2015-2016 was effective against A(H1N1)pdm09 and the two lineages of type B. Younger children was more protected than older children and adults by vaccination.
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http://dx.doi.org/10.1016/j.jvacx.2019.100011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668230PMC
April 2019

Impact of the pediatric 13-valent pneumococcal conjugate vaccine on serotype distribution and clinical characteristics of pneumococcal pneumonia in adults: The Japan Pneumococcal Vaccine Effectiveness Study (J-PAVE).

Vaccine 2019 05 8;37(20):2687-2693. Epub 2019 Apr 8.

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Clinical Tropical Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address:

Background: The pediatric 13-valent pneumococcal conjugate vaccine (PCV13) was included in the pediatric immunization programme in Japan in late 2013. The impact of vaccination on the serotype distribution and clinical characteristics of pneumococcal pneumonia has not been described.

Methods: The first phase of this multicentre prospective study was conducted at community-based hospitals in Japan from 2011 to 2014. The second phase was conducted from 2016 to 2017. Pneumococcal isolates and clinical data were collected from patients with community-acquired pneumonia who were ≥15 years of age. Patients were classified by pneumococcal serotype to PCV13 serotype, 23-valent pneumococcal polysaccharide vaccine (PPV23) non-PCV13 serotype, and non-vaccine serotype.

Results: A total of 484 patients were enrolled, 241 in the first phase and 243 in the second. The proportion of PCV13 serotypes decreased from 53% to 33% (p < 0.001), whereas PPV23 non-PCV13 serotypes did not change (p = 0.754). PCV13 serotypes were associated with increased risk of elevated blood urea nitrogen (adjusted odds ratio 2.49; 95% confidence interval: 1.49-4.16) and hospitalization (adjusted odds ratio 1.74; 95% confidence interval: 1.02-2.95). These associations were not observed in patients with PPV23 non-PCV13 serotypes.

Conclusions: The occurrence of pneumococcal pneumonia caused by vaccine-covered serotypes dramatically decreased following the introduction of pediatric PCV13. The PCV13 serotypes were associated with pneumonia severity.
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http://dx.doi.org/10.1016/j.vaccine.2019.04.009DOI Listing
May 2019

Six underlying health conditions strongly influence mortality based on pneumonia severity in an ageing population of Japan: a prospective cohort study.

BMC Pulm Med 2018 May 23;18(1):88. Epub 2018 May 23.

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Background: Mortality prediction of pneumonia by severity scores in patients with multiple underlying health conditions has not fully been investigated. This prospective cohort study is to identify mortality-associated underlying health conditions and to analyse their influence on severity-based pneumonia mortality prediction.

Methods: Adult patients with community-acquired pneumonia or healthcare-associated pneumonia (HCAP) who visited four community hospitals between September 2011 and January 2013 were enrolled. Candidate underlying health conditions, including demographic and clinical characteristics, were incorporated into the logistic regression models, along with CURB (confusion, elevated urea nitrogen, tachypnoea, and hypotension) score as a measure of disease severity. The areas under the receiver operating characteristic curves (AUROC) of the predictive index based on significant underlying health conditions was compared to that of CURB65 (CURB and age ≥ 65) score or Pneumonia severity index (PSI). Mortality association between disease severity and the number of underlying health conditions was analysed.

Results: In total 1772 patients were eligible for analysis, of which 140 (7.9%) died within 30 days. Six underlying health conditions were independently associated: home care (adjusted odds ratio, 5.84; 95% confidence interval, CI, 2.28-14.99), recent hospitalization (2.21; 1.36-3.60), age ≥ 85 years (2.15; 1.08-4.28), low body mass index (1.99, 1.25-3.16), neoplastic disease (1.82; 1.17-2.85), and male gender (1.78; 1.16-2.75). The predictive index based on these conditions alone had a significantly or marginally higher AUROC than that based on CURB65 score (0.78 vs 0.66, p = 0.02) or PSI (0.78 vs 0.71, p = 0.05), respectively. Compared to this index, the AUROC of the total score consisting of six underlying health conditions and CURB score (range 0-10) did not improve mortality predictions (p = 0.3). In patients with one or less underlying health conditions, the mortality was discretely associated with severe pneumonia (CURB65 ≥ 3) (risk ratio: 7.24, 95%CI: 3.08-25.13), whereas in patients with 2 or more underlying health conditions, the mortality association with severe pneumonia was not detected (risk ratio: 1.53, 95% CI: 0.94-2.50).

Conclusions: Mortality prediction based on pneumonia severity scores is highly influenced by the accumulating number of underlying health conditions in an ageing society. The validation using a different cohort is necessary to generalise the conclusion.
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http://dx.doi.org/10.1186/s12890-018-0648-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967104PMC
May 2018

Accuracy of High-Throughput Nanofluidic PCR-Based Pneumococcal Serotyping and Quantification Assays Using Sputum Samples for Diagnosing Vaccine Serotype Pneumococcal Pneumonia: Analyses by Composite Diagnostic Standards and Bayesian Latent Class Models.

J Clin Microbiol 2018 05 25;56(5). Epub 2018 Apr 25.

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan

The lack of reliable diagnostic tests for detecting vaccine serotype pneumococcal pneumonia (VTPP) remains a challenging issue in pneumococcal vaccine studies. This study assessed the performances of high-throughput nanofluidic PCR-based pneumococcal serotyping and quantification assay methods using sputum samples (the nanofluidic sputum quantitative PCR [Sp-qPCR] assay) to diagnose 13-valent pneumococcal conjugate VTPP compared with the performance of the serotype-specific urinary antigen detection (UAD) assay using urine samples. Adult pneumonia patients from Japan were enrolled in this study between September 2012 and August 2014. Sputum samples were subjected to the nanofluidic Sp-qPCR assay, quantitatively cultured, and serotyped by the Quellung reaction (SpQt). Urine samples were tested by the UAD method. The diagnostic performances of these tests were assessed using composite reference standards and Bayesian latent class models (BLCMs). Among 244 total patients, 27 (11.1%) tested positive with the UAD assay, while 16 (6.6%) and 34 (13.9%) tested positive with the SpQt and nanofluidic Sp-qPCR assays, respectively, with a cutoff value of ≥10 DNA copies/ml, which showed the maximum value of the Youden index. Using BLCMs, the estimated prevalence for VTPP was 12.9%, and the nanofluidic Sp-qPCR assay demonstrated the best performance (sensitivity, 90.2%; specificity, 96.9%), followed by UAD (sensitivity, 75.6%; specificity, 97.9%) and SpQt (sensitivity, 45.8%; specificity, 99.5%). However, when a higher cutoff value of ≥10 DNA copies/ml was applied, the performance of UAD became comparable to that of Sp-qPCR. The vaccine serotype-specific pneumococcal DNA load in sputum among UAD-positive patients was 3 logs higher than that among UAD-negative patients ( = 0.036). The nanofluidic Sp-qPCR assay may be accurate and useful for detecting VTPP among adults.
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http://dx.doi.org/10.1128/JCM.01874-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5925721PMC
May 2018

The impact of virus infections on pneumonia mortality is complex in adults: a prospective multicentre observational study.

BMC Infect Dis 2017 12 6;17(1):755. Epub 2017 Dec 6.

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.

Background: Various viruses are known to be associated with pneumonia. However, the impact of viral infections on adult pneumonia mortality remains unclear. This study aimed to clarify the effect of virus infection on pneumonia mortality among adults stratified by virus type and patient comorbidities.

Methods: This multicentre prospective study enrolled pneumonia patients aged ≥15 years from September 2011 to August 2014. Sputum samples were tested by in-house multiplex polymerase chain reaction assays to identify 13 respiratory viruses. Viral infection status and its effect on in-hospital mortality were examined by age group and comorbidity status.

Results: A total of 2617 patients were enrolled in the study and 77.8% was aged ≥65 years. 574 (21.9%) did not have comorbidities, 790 (30.2%) had chronic respiratory disease, and 1253 (47.9%) had other comorbidities. Viruses were detected in 605 (23.1%) patients. Human rhinovirus (9.8%) was the most frequently identified virus, followed by influenza A (3.9%) and respiratory syncytial virus (3.9%). Respiratory syncytial virus was more frequently identified in patients with chronic respiratory disease (4.7%) than those with other comorbidities (4.2%) and without comorbidities (2.1%) (p = 0.037). The frequencies of other viruses were almost identical between the three groups. Virus detection overall was not associated with increased mortality (adjusted risk ratio (ARR) 0.76, 95% CI 0.53-1.09). However, influenza virus A and B were associated with three-fold higher mortality in patients with chronic respiratory disease but not with other comorbidities (ARR 3.38, 95% CI 1.54-7.42). Intriguingly, paramyxoviruses were associated with dramatically lower mortality in patients with other comorbidities (ARR 0.10, 95% CI 0.01-0.70) but not with chronic respiratory disease. These effects were not affected by age group.

Conclusions: The impact of virus infections on pneumonia mortality varies by virus type and comorbidity status in adults.
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http://dx.doi.org/10.1186/s12879-017-2858-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719746PMC
December 2017

Serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal pneumonia in adults aged 65 years or older: a multicentre, prospective, test-negative design study.

Lancet Infect Dis 2017 03 24;17(3):313-321. Epub 2017 Jan 24.

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. Electronic address:

Background: The serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal pneumonia has not been established in people aged 65 years or older. We assessed the effectiveness of PPV23 in this population.

Methods: For this multicentre, prospective study, we enrolled all individuals aged 65 years or older with community-onset pneumonia who visited four study hospitals in Japan between Sept 28, 2011, and Aug 23, 2014. Streptococcus pneumoniae was isolated from sputum and blood samples, and serotyped by the capsular Quellung method. Sputum samples were further tested by PCR assay to identify pneumococcal DNA, and positive samples were examined for 50 serotypes by a nanofluidic real-time PCR assay. Urine samples were tested by a urinary antigen test. Serotype-specific vaccine effectiveness was estimated using the test-negative design.

Findings: 2621 eligible patients visited the study hospitals, of whom 585 did not have sputum samples available and were excluded from our analysis. 419 (21%) of 2036 patients were positive for pneumococcal infection (232 by sputum culture, 317 by sputum PCR, 197 by urinary antigen test, and 14 by blood culture). 522 (26%) patients were judged to be vaccinated in the analyses. Effectiveness of PPV23 was 27·4% (95% CI 3·2 to 45·6) against all pneumococcal pneumonia, 33·5% (5·6 to 53·1) against PPV23 serotypes, and 2·0% (-78·9 to 46·3) against non-PPV23 serotypes. Although no significant differences between subgroups were seen, higher protection was noted in people younger than 75 years, women, and individuals with lobar pneumonia or health-care-associated pneumonia.

Interpretation: PPV23 showed low to moderate effectiveness against vaccine serotype pneumococcal pneumonia in people aged 65 years or older. To improve the current pneumococcal vaccination programme, the variability of PPV23 effectiveness in different groups of older people must be further investigated.

Funding: Pfizer and Nagasaki University.
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http://dx.doi.org/10.1016/S1473-3099(17)30049-XDOI Listing
March 2017

The burden and etiology of community-onset pneumonia in the aging Japanese population: a multicenter prospective study.

PLoS One 2015 30;10(3):e0122247. Epub 2015 Mar 30.

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Background: The increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. This study was conducted to elucidate the burden of community-onset pneumonia (COP) and its etiologic fractions in Japan, the world's most aged society.

Methods: A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged ≥ 15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics.

Results: A total of 1,772 COP episodes out of 932,080 hospital visits were enrolled during the surveillance. The estimated overall incidence rates of adult COP, hospitalization, and in-hospital death were 16.9 (95% confidence interval, 13.6 to 20.9), 5.3 (4.5 to 6.2), and 0.7 (0.6 to 0.8) per 1,000 person-years (PY), respectively. The incidence rates sharply increased with age; the incidence in people aged ≥ 85 years was 10-fold higher than that in people aged 15-64 years. The estimated annual number of adult COP cases in the entire Japanese population was 1,880,000, and 69.4% were aged ≥ 65 years. Aspiration-associated pneumonia (630,000) was the leading etiologic category, followed by Streptococcus pneumoniae-associated pneumonia (530,000), Haemophilus influenzae-associated pneumonia (420,000), and respiratory virus-associated pneumonia (420,000), including influenza-associated pneumonia (30,000).

Conclusions: A substantial portion of the COP burden occurs among elderly members of the Japanese adult population. In addition to the introduction of effective vaccines for S. pneumoniae and influenza, multidimensional approaches are needed to reduce the pneumonia burden in an aging society.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122247PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378946PMC
March 2016

Molecular characteristics of outbreaks of nosocomial infection with influenza A/H3N2 virus variants.

Infect Control Hosp Epidemiol 2011 Mar;32(3):267-75

Division of Public Health, Department of Infectious Disease Control and International Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Objective: To describe outbreaks of nosocomial influenza infection with molecular methods and to elucidate the viral linkages among outbreak case patients including both inpatients and healthcare workers (HCWs).

Setting: A 180-bed acute and long-term care hospital in Japan.

Methods: Retrospective observational study of nosocomial outbreaks of infection with influenza A/H3N2. Together with information about onset dates and vaccination history, we obtained nasopharyngeal swab samples from individuals with cases of influenza or influenza-like illness (ILI). The hemagglutinin genes of the recovered viruses were sequenced and compared, along with those of community-circulating strains, for similarity by phylogenetic tree analysis.

Results: The outbreaks occurred from February 26 through April 3, 2007, during the 2006-2007 epidemic season, and they involved 11 patients and 13 HCWs. The 2 outbreaks involved 2 different genotypes of influenza A/H3N2 viruses. These virus variants were closely related to the influenza strains that were circulating in the community during the same epidemic season.

Conclusion: This study showed the dissemination of highly homologous influenza virus variants among inpatients and HCWs within a short period, as a result of nosocomial transmission. These strains were also similar to influenza strains that were circulating in the community.
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http://dx.doi.org/10.1086/658671DOI Listing
March 2011

Clinical and microbiological characteristics of community-acquired pneumonia among human immunodeficiency virus-infected patients in northern Thailand.

J Infect Chemother 2008 Apr 30;14(2):105-9. Epub 2008 Apr 30.

Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Human immunodeficiency virus (HIV) infections are prevalent in Thailand. However, the clinical and microbiological characteristics of community-acquired pneumonia (CAP) in such patients are not completely clear at present. In the present study, we analyzed the characteristics of CAP in 191 HIV-infected patients (192 episodes, 130 males and 61 females, mean age 32.9 years, range: 20-62) who had been admitted to Nakornping Hospital in northern Thailand between December 1996 and January 2002. The mean peripheral blood CD4 lymphocyte count was 68.5/mm3 (range: 0-791). The most common organisms detected in the blood of the subjects were as follows: Penicillium marneffei, 13, Salmonella spp., 5, Cryptococcus neoformans, 4, Staphylococcus aureus, 3, and Rhodococcus equi, 3, and the most common organisms detected in sputum included Haemophilus influenzae, 38, P. marneffei, 10, Streptococcus pneumoniae, 10, R. equi, 9, and S. aureus, 9. Life-threatening meningitis in 5 (cryptococcal in 3 and tuberculous in 2), pneumothorax in 2, and tuberculous lymphadenitis in 1 were also noted, resulting in 21 fatalities (10.9%). The mean peripheral blood CD4 lymphocyte count for cases in which the subject died was 74.8/mm3 (range: 0-340). Logistic regression analysis demonstrated that high age (odds ratio of over 40 years: 15.62) and R. equi infection (odds ratio: 8.14) are related to death of HIV-infected patients with CAP. The above findings indicate that various types of organisms, including mixed organisms, cause CAP in HIV-infected patients in northern Thailand, and high age and R. equi infection seem to be risk factors for death.
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http://dx.doi.org/10.1007/s10156-007-0577-9DOI Listing
April 2008

High prevalence of amantadine-resistance influenza a (H3N2) in six prefectures, Japan, in the 2005-2006 season.

J Med Virol 2007 Oct;79(10):1569-76

Department of Public Health, Niigata University, Graduate School of Medical and Dental Science, Niigata, Japan.

Substantial increase in amantadine-resistant influenza A (H3N2) was reported in Asia and North America in 2005. In this study the frequency and genetic characteristics of amantadine-resistant influenza A, circulated in Japan in 2005-2006 season, were investigated. Isolates were tested by amantadine susceptibility test (TCID(50)/0.2 ml method), and sequencing of the M2 gene to identify mutations that confer resistance. Additionally, the hemagglutinin (HA) and neuraminidase (NA) genes of the viruses were examined. In total, 415 influenza A isolates from six prefectures were screened, and 231 (65.3%) of 354 influenza A (H3N2) were amantadine-resistant, with a serine to asparagine (S31N) change in the M2 gene. However, none of 61 A (H1N1) isolates were resistant. In addition, genetic analyses of the HA gene showed all amantadine-resistant viruses clustered in one (named clade N), possessing specific double mutations at 193, serine to phenylalanine (S193F), and at 225, asparatic acid to asparagine (D225N), and sensitive viruses belonged to another group (clade S). The clinical presentations at the clinical visit did not differ between patients shedding clade N virus and those shedding clade S virus. None of the patients had received previous treatment with amantadine. The results indicate an unusually high prevalence and wide circulation of the amantadine-resistance influenza A (H3N2) in Japan in the 2005-2006 season. These strains had the characteristic double mutations in the HA, in addition to the M2 mutation responsive for resistance. Antiviral resistance monitoring should be intensified and maintained for rapid feedback into treatment strategies, and selection of alternative therapeutic agents.
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http://dx.doi.org/10.1002/jmv.20946DOI Listing
October 2007

Significant reduction of nosocomial pneumonia after introduction of disinfection of upper airways using povidone-iodine in geriatric wards.

Dermatology 2006 ;212 Suppl 1:98-102

Department of Internal Medicine, Tagami Hospital, Nagasaki 851-0251, Japan.

We investigated the efficacy of disinfection of the upper airway using povidone-iodine against nosocomial pneumonia in geriatric wards. Cases of nosocomial pneumonia were retrospectively analyzed between January 1991 and March 1995 in geriatric wards (190 beds). Moreover, the relationship concerning methicillin-resistant Staphylococcus aureus (MRSA) isolates between patient and environment was investigated using pulsed-field gel electrophoresis (PFGE) with the SmaI restriction enzyme. The incidence of nosocomial pneumonia decreased significantly (p < 0.05). Major causative organisms of nosocomial pneumonia were MRSA and Pseudomonas aeruginosa, which significantly decreased. PFGE studies showed that the patterns of MRSA isolates show a strong association between patient and environment. Our study indicates that disinfection of the upper airways by povidone-iodine is very important in the prevention of nosocomial pneumonia in geriatric wards.
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http://dx.doi.org/10.1159/000089206DOI Listing
June 2006

Molecular analysis of intrafamiliar transmission of Moraxella catarrhalis.

Int J Med Microbiol 2005 Jun;295(3):187-91

Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

The possible intrafamiliar transmission of Moraxella catarrhalis was evaluated in 3 pairs between children and their parents, and 8 pairs between siblings from 11 families. Of the 22 isolates, all were found producing beta-lactamase. Molecular typing by pulsed-field gel electrophoresis (PFGE) with Not I and Spe I showed that the PFGE patterns in 2 of 3 pairs between children and their parents, and 4 of 8 pairs between siblings were indistinguishable and those of the remaining pairs were different. These data indicate a possible high rate of intrafamiliar transmission of M. catarrhalis.
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http://dx.doi.org/10.1016/j.ijmm.2005.03.003DOI Listing
June 2005

Usefulness of the Japanese Respiratory Society guidelines for community pneumonia: a retrospective analysis of community-acquired pneumonia between 2000 and 2002 in a general hospital.

Respirology 2005 Mar;10(2):208-14

Department of Internal Medicine, Tagami Hospital, Tagami, Nagasaki, Japan.

Objective: The aim of this study was to investigate the causative organisms of community-acquired pneumonia (CAP) diagnosed between 2000 and 2002 and to evaluate the Japanese Respiratory Society (JRS) guidelines.

Methodology: A total of 124 cases of CAP diagnosed during the study period were analyzed, and the results were compared with those of a previous study by the authors' research group. Determination of the causative organisms of CAP was based on Gram stain, morphology of colonies, quantitative culture of sputum, identification of bacterial isolates, and serological tests.

Results: During the study period, the causative organisms were identified in 42 cases (33.8%). Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were the major causative organisms. Patients were classified into three groups based on the severity of CAP according to the JRS guidelines. The survival rates of patients with moderate and severe CAP were significantly lower than those of the mild group as evaluated by the Kaplan-Meier method (moderate vs mild, 70% vs 100%; severe vs mild, 40% vs 100%; P < 0.001 for both). Seven patients died during the study, and the risk factors were old age, bedridden status with cerebral infarction, and microaspiration, which was associated with recurrent pneumonia within 17 days.

Conclusion: This study indicates that the JRS guidelines for CAP are useful for treating patients with CAP in Japan.
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http://dx.doi.org/10.1111/j.1440-1843.2005.00664.xDOI Listing
March 2005

Molecular characterization of the transmission between the colonization of methicillin-resistant Staphylococcus aureus to human and environmental contamination in geriatric long-term care wards.

Intern Med 2005 Jan;44(1):41-5

Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki.

Objective: Transmission between human and environmental contamination from colonized methicillin-resistant Staphylococcus aureus (MRSA) remains a controversial issue. We, therefore, investigated the differences between MRSA types which colonize in humans and in the environment.

Methods: A 4-week prospective culture survey for MRSA was performed for 12 patients as well as for the environment of the room of MRSA carriers in quarantine in the geriatric long-term care ward of a 270-bed hospital.

Results: A total of 97 S. aureus strains (80 MRSA and 17 methicillin-sensitive Staphylococcus aureus [MSSA]) was isolated during the periods of September 8 to 10, 23 to 25 and October 5 to 7, 1998; 25 strains were from the respiratory tract, 4 strains from feces and 11 strains from decubitus ulcers. Fifty-seven strains were from the patients' environment. Molecular typing by pulsed-field gel electrophoresis (PFGE) with the Sma I restriction enzyme demonstrated that the predominant type of MRSA isolated from the environment changed by the minute. The patterns of 42 MRSA strains isolated from the environment were identical in 26 (61.9%), closely related in 15 (35.7%) and possibly related in 1 (2.4%) of the cases of those isolated from patients simultaneously. There was no correlation between patients and the environment with the 17 MSSA isolates.

Conclusion: Our results demonstrated that MRSA from patients can contaminate the environment, whereas MRSA from the environment might be potentially transmitted to patients via health care workers under unsatisfactory infection control.
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http://dx.doi.org/10.2169/internalmedicine.44.41DOI Listing
January 2005

[Three adult cases with Corynebacterium propinquum respiratory infections in a community hospital].

Kansenshogaku Zasshi 2004 Mar;78(3):277-82

Department of Internal Medicine, Tagami Hospital, Nagasaki.

Corynebacterium propinquum, which is included in Corynebacterium group ANF-3, exists as a commensal in the oral flora. This organism has not yet been fully recognized as a respiratory pathogen. We previously reported that the first case with respiratory infection caused by C. propinquum. On the other hand, Corynebacterium pseudodiphtheriticum is recognized as a causative organism in respiratory infections. Recently we experienced two cases with C. propinquum respiratory infections in our hospital. Three types of the onset such as a community-acquired infection, a hospital-acquired infection, and a nursing home acquired infections were observed. Our analysis indicated that gram staining of the purulent sputum is an essential tool to evaluate whether C. propinquum is a respiratory pathogen or not, because this organism is a commensal bacteria.
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http://dx.doi.org/10.11150/kansenshogakuzasshi1970.78.277DOI Listing
March 2004

[A case of rhabdomyolysis associated with Kaposi's varicelliform eruption].

Kansenshogaku Zasshi 2004 Jan;78(1):59-63

Institute of Tropical Medicine, Department of Internal Medicine, Nagasaki University.

Kaposi's varicelliform eruption is a common disease for dermatologists. In general, it is caused by Herpes simplex virus-1 (HSV-1) infection to skin which is affected by atopic dermatitis. There are some case reports which document a relationship between rhabdomyolysis and virus infection, in those cases, the major pathogenic virus of rhabdomyolysis is a influenza virus. It is exceedingly rare that rhabdomyolysis is caused by Herpes simplex virus. We introduce a case of rhabdomyolysis associated with Kaposi's varicelliform eruption induced by HSV-1. It was localized in the iliopsoas muscles. Since severe rhabdomyolysis may induce fatal acute renal failure, it is important to recognize that rhabdomyolysis can complicate Herpes simplex virus infection.
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http://dx.doi.org/10.11150/kansenshogakuzasshi1970.78.59DOI Listing
January 2004

[A retrospective analysis of community-acquired pneumonia between 2000 and 2002 in a community hospital].

Nihon Kokyuki Gakkai Zasshi 2004 Jan;42(1):68-74

Department of Internal Medicine, Tagami Hospital, Nagasaki 2-14-15, Tagami, Nagasaki-shi, Nagasaki, 851-0251, Japan.

We previously reported a hospital-based retrospective study on community-acquired pneumonia (CAP) at Tagami Hospital, which was a community hospital, between 1994 and 1997. This study was designed to clarify the etiology of CAP diagnosed between 2000 and 2002. We analyzed a total of 124 cases of CAP in our hospital during the study period, and compared the results with the previous data. Identification of the causative organisms of CAP was based on gram staining, the morphology of the colonies, quantitative culture of the sputum, and the serological tests. During the study period, we determined the causative organisms in 42 cases (33.8%). Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were the major causative organisms. The severity of the cases was classified into three groups according to the guideline for CAP, which was edited by the Japanese Respiratory Society. The survival rates in the moderate and severe groups were significantly (p < 0.001) higher than that of the mild group, as analyzed by the Kaplan-Meier method, as follows: 70% (moderate) vs 100% (mild); and 40% (severe) vs 100% (mild). In a total of 7 patients who died, we found the following risk factors: elderly male patients, bedridden status with cerebral infarction, and micro-aspiration, including recurrent pneumonia at short intervals of less than 17 days. Our study indicated that the JRS-edited guideline for CAP is a very useful tool for analyzing cases with CAP in Japan.
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January 2004

Possible high rate of transmission of nontypeable Haemophilus influenzae, including beta-lactamase-negative ampicillin-resistant strains, between children and their parents.

J Clin Microbiol 2004 Jan;42(1):362-5

Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

The possible transmission of nontypeable Haemophilus influenzae between children and their parents was evaluated in 18 pairs of subjects from 15 families. Of the 33 isolates, 31 were found to be beta-lactamase negative, including 10 beta-lactamase-negative, ampicillin (AMP)-resistant (BLNAR) strains (AMP MIC, >or=1.0 microg/ml) and 2 were beta-lactamase producing. Molecular typing by pulsed-field gel electrophoresis (PFGE) showed that 10 BLNAR isolates had 6 patterns, 23 non-BLNAR isolates had 13 patterns, and these patterns were different from each other, except for 1 pattern. As a result, the PFGE patterns in 14 of 18 pairs were indistinguishable and those in 4 pairs were different. These data indicate a possible high rate of intrafamilial transmission of nontypeable H. influenzae, including BLNAR strains, between children and their parents.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC321711PMC
http://dx.doi.org/10.1128/JCM.42.1.362-365.2004DOI Listing
January 2004

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae and molecular characterization of multidrug-resistant serotype 19F, 6B, and 23F Pneumococci in northern Thailand.

J Clin Microbiol 2003 Sep;41(9):4178-83

Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Penicillin-resistant Streptococcus pneumoniae is widely spread worldwide. Our study was undertaken to examine the susceptibility and serotypes of S. pneumoniae in northern Thailand. Ninety-three S. pneumoniae strains were isolated from 93 patients at Chiang Mai University Hospital, Chiang Mai, Thailand, from September 1999 to June 2000. The strains were isolated from sputum (n = 51), blood (n = 15), nasopharynges (n = 14), and other sources (e.g., pus, ears, ascites, and cerebrospinal fluid) (n = 13). Of the 93 isolates, 29 (31.2%) were susceptible, 24 (25.8%) showed intermediate resistance (MIC, 0.12 to 1.0 micro g/ml), and 40 (43.0%) were fully resistant (MIC, >/=2.0 micro g/ml) to penicillin G. Seven (46.7%) from blood, 5 (35.7%) from nasopharynges, 15 (29.4%) from sputum, and 2 (15.4%) from other sources were susceptible isolates. Serotyping with the use of antiserum revealed differences in the predominant types that were susceptible (6A, 11A, and 19A), intermediately resistant (6B and 23F), and fully resistant (6B, 19F, and 23F). Molecular typing by pulsed-field gel electrophoresis of multidrug-resistant pneumococci showed four patterns (A, B, C, and D) for 16 isolates of serotype 19F, with pattern B being predominant (12 isolates). This finding was different from that with the Taiwan multidrug-resistant serotype 19F clone. Eleven isolates of serotype 6B all showed pattern E, and nine isolates of serotype 23F showed two patterns (F and G), with pattern F being predominant (seven isolates). This finding was similar to that with the Spanish multidrug-resistant serotype 23F clone. Our results indicated that the resistance of pneumococci to antibiotics in northern Thailand is progressing rapidly and that effort should be intensified to prevent any spread of pandemic multidrug-resistant serotypes 19F, 6B, and 23F.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC193840PMC
http://dx.doi.org/10.1128/JCM.41.9.4178-4183.2003DOI Listing
September 2003

Possible relationship of PFGE patterns of Moraxella catarrhalis between hospital- and community-acquired respiratory infections in a community hospital.

Microbiol Immunol 2003 ;47(6):379-85

Department of Internal Medicine, Tagami Hospital, Nagasaki, Nagasaki 851-0251, Japan.

We describe a prospective study of molecular analysis of Moraxella catarrhalis isolated from a community hospital. Our study was designed to investigate the possible relationship of pulsed-field gel electrophoresis (PFGE) patterns of M. catarrhalis between hospital- and community-acquired respiratory infections. A nosocomial outbreak of M. catarrhalis was observed between September 2000 and September 2001. During the study period, 40 strains of M. catarrhalis were isolated from a total of 32 patients with respiratory infections (26 strains from 18 inpatients, and 14 strains from 14 outpatients). We compared the PFGE patterns in 40 strains of M. catarrhalis isolated from the respiratory tract of the study patients. The genomic types of M. catarrhalis were classified into three PFGE patterns (A, B, and C). Interestingly, the nosocomial outbreak of M. catarrhalis included two patterns (A and B). Of the three patterns, two patterns (A and B) were found in both inpatients and outpatients. More interestingly, two subtypes of pattern B (B1 and B4) were simultaneously found in both inpatients and outpatients. Our results indicated that PFGE with SmaI chromosomal digestion is a suitable technique to establish the inter-strain genetic relatedness of M. catarrhalis, and suggested that the outbreak of M. catarrhalis occasionally included miscellaneous PFGE patterns. The results also showed that PFGE patterns of M. catarrhalis isolates were similar between hospital- and community-acquired respiratory infections. Analysis of the subtypes suggested that there might be some association between hospital- and community-acquired respiratory infections caused by M. catarrhalis.
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http://dx.doi.org/10.1111/j.1348-0421.2003.tb03374.xDOI Listing
November 2003

Emergence of rifampin-resistant Rhodococcus equi with several types of mutations in the rpoB gene among AIDS patients in northern Thailand.

J Clin Microbiol 2003 Jun;41(6):2337-40

Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

The antimicrobial susceptibilities of 30 Rhodococcus equi isolates obtained from 30 patients between 1993 and 2001 in northern Thailand were investigated. The MICs showed a tendency toward resistance to various antibiotics but sensitivity to imipenem, minocycline, vancomycin, and teicoplanin (MICs, /=64 micro g/ml) to rifampin. PCR amplification and DNA sequencing of the rpoB gene and molecular typing by pulsed-field gel electrophoresis (PFGE) were performed for eight R. equi isolates from eight AIDS patients with pneumonia or lung abscess caused by R. equi between 1998 and 2001, including one low- and three high-level rifampin-resistant isolates. As a result, two high-level rifampin-resistant strains with PFGE pattern A had a Ser531Trp (Escherichia coli numbering) mutation, and one high-level rifampin-resistant strain with PFGE pattern B had a His526Tyr mutation, whereas one low-level rifampin-resistant strain with PFGE pattern C had a Ser509Pro mutation. Four rifampin-susceptible strains with PFGE patterns D and E showed an absence of mutation in the rpoB region. Our results indicate the presence of several types of rifampin-resistant R. equi strains among AIDS patients in northern Thailand.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC156560PMC
http://dx.doi.org/10.1128/JCM.41.6.2337-2340.2003DOI Listing
June 2003

High rate of transmission of penicillin-resistant Streptococcus pneumoniae between parents and children.

J Clin Microbiol 2002 Nov;40(11):4357-9

Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Transmission of Streptococcus pneumoniae between children and their parents was evaluated in 29 pairs from 25 families. The serotypes of 35 pneumococcal isolates from 18 (62.1%) of 29 child-parent pairs were identical. Of the 35 isolates, 23 showed intermediate resistance and 10 were fully resistant to penicillin G. PCR indicated that all 35 strains had at least one alteration in penicillin-binding protein genes pbp1a, pbp2x, and pbp2b and 33 strains had macrolide resistance genes mef(A) and/or erm(B). As a result, the PCR patterns of 16 of 18 pairs were identical. Molecular typing by pulsed-field gel electrophoresis showed that 12 pairs were indistinguishable, 3 pairs were closely related, 2 pairs were possibly related, and only one pair was different. Our data indicate the presence of a high rate of transmission of penicillin-resistant S. pneumoniae between children and their parents.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC139698PMC
http://dx.doi.org/10.1128/JCM.40.11.4357-4359.2002DOI Listing
November 2002