Although the first mumps vaccine was licensed more than 50 years ago, the vaccine was added to Iran's Expanded Program on Immunization in 2003. Therefore, the majority of Iranians born before 2003 are unvaccinated, and their immunity is the result of natural infection. In order to evaluate cellular responses against the mumps virus following natural infection, we investigated 90 Iranian unvaccinated adults aged 20–30 years. Mumps specific memory CD4+ and CD8+ proliferation and frequency of cytotoxic lymphocyte CD8+ CD107a were evaluated using flow cytometry. Our results showed that 33 subjects were seronegative, but 28 of them showed degranulation of CD8+ T lymphocytes and expression of CD 107a, as well as proliferation of CD4 and CD8 T cells, in response to mumps antigen stimulation. In all seropositive subjects, degranulation of cytotoxic T lymphocytes and proliferation of CD4+ and CD8+ T lymphocytes was detected. Proliferation of T cells and degranulation of CD8 T cells in seropositive subjects was higher than in seronegative subjects. We conclude that natural mumps infection and subclinical reinfection could induce good protection, but the severe complications associated with mumps infections suggest the need for mumps vaccination. Natural boosters because of the prevalence of the wild-type virus may help with maintenance of immunity in populations with high vaccine coverage.
This study aimed to investigate serologic immunity to diphtheria and tetanus in army personnel and a sample population of adult civilians in Mashhad, Iran. Army personnel (n = 180) and civilians (n = 83) who presented at Mashhad army hospital participated in this study. Diphtheria and tetanus antitoxin levels were determined by enzyme-linked immunosorbent assay. Approximately 77% and 94% of army personnel aged 18–34 years had at least basic protection against diphtheria (antitoxin level ≥0.1 IU/mL) and tetanus (antitoxin level >0.1 IU/mL), respectively. For civilians in this age group, the proportions were 76% for both diseases. Antitoxin levels waned with age. Thus, participants older than 50 years had lower immunity; this decrease in immunity was more pronounced for tetanus than for diphtheria in both army personnel and civilians. For both diseases, geometric mean antitoxin titers and the proportion of participants with at least basic protection were higher in subjects with a history of vaccination in the last 10 years (P < 0.001), higher in men than women, and in army personnel than civilians in each age group. Young army personnel and civilians (18–34 years old) had adequate immunity to diphtheria and tetanus. However, the large number of susceptible older adults (>50 years old) calls for improved booster vaccination protocols.
In Japan, the number of human immunodeficiency virus (HIV)-1 infections remains relatively low; nevertheless, the annual incidence of HIV-1 infection has not decreased. New infections remain a great concern, and an improved understanding of epidemiological trends is critical for public health. The env C2V3 and pol sequences of HIV-1 RNA from 240 early (1996–2001) and 223 more recent (2010–2012) blood donations were used to compare the distribution of virus subtypes and to generate phylogenetic trees. Subtype B was clearly predominant in both early and more recent donations (both were 88.3%), and CRF01_AE was the second most common subtype. Phylogenetic analysis revealed a peculiar epidemiological transition. Compared to early subtype B isolates from 2 major endemic areas (Tokyo and Osaka), the more recent subtype B isolates formed fewer tight clusters in phylogenetic trees (from 8 to 2 clusters in Tokyo and 5 to zero clusters in Osaka). Furthermore, mixing of HIV-1 infections between these 2 endemic areas appear to increase. Analysis of phylogenetic trees suggested that local outbreaks have become smaller in Japan; however, intermixing of viral types between these 2 areas was more evident in the more recent samples.
We investigated the prevalence of 5 enteric viruses (norovirus [NoV], sapovirus, rotavirus, astrovirus, and adenovirus) in archived stool specimens collected from 70 foodborne gastroenteritis outbreaks in Tokyo, Japan, which occurred from 1966 to 1983, and genetically characterized these viruses. NoV was detected in 48 (68.6%) outbreaks, while SaV, group C rotavirus (RVC), and astrovirus were detected in 1 (1.4%) outbreak each. Based on the partial capsid sequences, the detected NoVs were classified into the following genotypes: 9 in genogroup I (GI; GI.1-6, GI.8, GI.9, and GI.NA), 13 GII (GII.1-9, GII.13, GII.16, GII.17, and GII.22), and one in GIV. The oldest NoV outbreaks occurred in 1966. No predominant genotype was found. One strain, classified as GI. NA based on the N/S region sequence, was subsequently classified as GI.8 based on the complete VP1 sequence. Nine types of recombinant NoV sequences, including 7 unreported combinations, were identified. Further genetic characterization of NoV GII.17 and GII.4 demonstrated that the NoV GII.17 strains detected from 1970 to 1982 clustered independently from previously reported NoV GII.17 strains. Phylogenetic analysis, using the complete VP1 region and the P2 domain, demonstrated that NoV GII.4 strains collected between 1975 and 1980 clustered with archival strains collected in the USA in the mid-1970s. In contrast, a NoV GII.4 strain collected in 1983 formed an independent branch from reference strains collected in the mid-1970s to 2012.
Corynebacterium is a genus consisting of Gram-positive, rod-shaped bacteria, that is wildly distributed in nature. We report the epidemiological characterization of Corynebacterium spp. isolated from blood specimens at the Kurume University Hospital, between June 2008 and November 2011. Twenty-two strains that were likely Corynebacterium spp. were isolated from 22 hospitalized patients, of which 12 (54.5%) were identified as Corynebacterium striatum. Minimum inhibitory concentration tests were performed after biochemical and genotypic identifications. Biofilm production was detected using a 96-well microplate assay. The dissemination of C. striatum was investigated using pulsed-field gel electrophoresis (PFGE). All strains showed the tendency to be resistant to multiple drugs except vancomycin. Fourteen (82.4%) strains, including 9 C. striatum strains were capable of producing biofilms. Four distinct PFGE patterns were detected among C. striatum strains; 6 of which were identified as dominant pattern A (defined in this study) and had high biofilm production ability. During the 3-year monitoring period, these strains might have repeatedly infected the patients or could have readily colonized the hospital environments. C. striatum appeared to be a potential risk factor for bloodstream infections in hospitalized patients. More surveillance and enhanced control strategies are necessary to decrease Corynebacterium spp. infections in hospitals.
We investigated the effectiveness of the Japanese health care system for human immunodeficiency virus/acquired immunodeficiency virus (HIV/AIDS), in terms of prevention, diagnosis, access to antiretroviral treatment, and treatment outcomes. Clinical information on HIV/AIDS cases was collected via questionnaires sent to 377 registered HIV/AIDS clinics in Japan. Data on 9,040 and 14,569 cases were collected in 2009 and 2014, respectively. The percentages of cases undergoing treatment were 69.6% and 87.8% in 2009 and 2014, respectively, demonstrating an improvement in treatment coverage over the 5 years between the 2 surveys. The proportion of cases with undetectable HIV RNA in the 2014 survey was 87.7%. Thus, our survey revealed that the 2 of the United Nations AIDS Fast-Track targets, 90% treated and 90% virally suppressed, are close to being achieved. However, Japan appears to have fallen short of the upstream target of 90% diagnosed. Japan needs to radically reform its strategies for encouraging people to undergo HIV testing and to develop a system for estimating the number of people living with HIV.
Our aim was to study the epidemiology and clinical manifestations of human metapneumovirus (hMPV) infection in children in the Suzhou area, China, and to investigate the effect of thymic stromal lymphopoietin (TSLP) on wheezing in hMPV-infected children. The study included 13,533 children with respiratory tract infections who were admitted to the Children's Hospital of Soochow University between January 2009 and December 2014. Clinical data were recorded. Plasma levels of TSLP, interleukin (IL)-4, and IL-2 were compared among 35 wheezing children with single hMPV infection, 15 non-wheezing children with hMPV infection, and 35 wheezing children with other viral infections. The annual rates of hMPV infection from 2009 to 2014 were 2.33%, 6.41%, 3.29%, 3.52%, 0.23%, and 0.64%, respectively, peaking in 2010. The number of CD3−/CD16+/CD56+ cells was significantly lower in inpatients with hMPV infection than that in patients with other viral infections. Serum levels of TSLP and IL-4 in wheezing children with hMPV infection were significantly higher than the levels in the other 2 groups. hMPV is a common viral pathogen that causes respiratory infections in children in Suzhou, but annual rates have declined since 2010. Infection with hMPV may affect cell-mediated immunity. Serum TSLP levels were elevated after hMPV infection.
Variable incidence rates of rotavirus gastroenteritis hospitalizations have been reported in Japan. However, it is not known whether the observed regional differences were due to the real difference in the occurrence of severe disease or other causes. This study aimed to determine the incidence rates of rotavirus hospitalization among children aged <5 years in the Yuri district in Akita prefecture and the Nantan district in Kyoto prefecture between March 2012 and February 2013. During this period, rotavirus vaccine uptake rates were equally low in both regions. All specimens were evaluated using the standardized case definition, severity scores, and the same assays. There were 44 rotavirus cases (44%) among 101 acute gastroenteritis-related hospitalizations in the Yuri district with a catchment population of 3,853, and 18 rotavirus cases (47%) among 38 acute gastroenteritis-related hospitalizations in the Nantan district with a catchment population of 5,128. While the severity score at the time of the hospitalizations was 11 in both hospitals, the incidence rates in Akita and Kyoto were 11.7 (95% confidence interval [CI]: 8.5–15.6) and 3.9 (95% CI: 2.1–5.5) per 1,000 child-years, respectively. Thus, there was a real difference in the occurrence rate of severe rotavirus infections between the 2 regions.
A cross sectional survey was performed to investigate the epidemic of human immunodeficiency virus (HIV), hepatitis C virus (HCV), syphilis, and HIV-1 subtype infections among men who have sex with men (MSM) and to evaluate factors that were correlated with sexually transmitted infections (STIs) among 657 MSM in Zhenjiang, Jiangsu, during 2012–2013. Data on socio-demographic parameters and risky behaviors were collected, and blood samples were obtained. In this survey, the prevalence of STIs due to HIV (5.3%), HCV (0.6%), and syphilis (19.2%) were measured. Of 35 HIV-infected MSM, 1 (0.2%) and 17 (2.6%) were co-infected with HCV and syphilis. Among 33 samples with available HIV-1 genomic fragment sequences, 6.1% B, 72.7% CRF01_AE, and 21.2% CRF07_BC were identified. Multivariate logistic regression analysis showed that age > 30 years (odds ratio [OR] 2.002; 95% confidence interval [CI], 1.144–3.502) and having had STI symptoms in the past year (OR, 11.673; 95% CI, 3.092–44.078) were positively correlated with having an STI, while consistent use of a condom when having sex with male partners (OR, 0.621; 95% CI, 0.408–0.945) was significantly associated with a low STI rate. The worsening epidemic of HIV, HCV, and syphilis infections, and the prevalence of complex subtypes of HIV-1 and other risk factors suggest that effective intervention strategies should be strengthened for MSM in Zhenjiang, Jiangsu.
Although Shewanella algae has been known to have weak pathogenicity, case reports on infections with this species have been steadily increasing. S. algae and S. haliotis are difficult to distinguish from each other with conventional phenotypic methods. We reviewed the microbiological and clinical features of S. algae and S. haliotis infections at our institute. Bacterial culture and identification reports from patient samples from 2010 to 2014 were reviewed to screen the cases of Shewanella infections. In addition to conventional biochemical tests, 16S rRNA gene sequence analysis and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were performed for 19 stored bacterial isolates. Medical records were reviewed for clinical characteristics and laboratory findings. All isolates were identified as S. algae by using VITEK 2. MALDI-TOF also identified all isolates as S. algae with a 99.9 confidence value. In contrast, 16S rRNA analysis identified 10 isolates as S. algae and 9 isolates as S. haliotis. Both S. algae (60%) and S. haliotis (77%) infections were strongly associated with diseases of the hepatobiliary tract and pancreas. To distinguish between S. algae and S. haliotis, 16S rRNA gene sequence analysis seems more accurate than biochemical tests or MALDI-TOF. Patients with underlying diseases in the hepatobiliary tract and pancreas seem to be susceptible to these marine pathogens.
Subtypes of stx1 and stx2 in 45 Shiga toxin-producing Escherichia coli (STEC) strains isolated from cattle were investigated by PCR. Only subtype stx1a was detected among all the stx1-positive strains. The major stx2 subtype was stx2a followed by stx2d, stx2c, stx2b, and stx2g in decreasing order of frequency. stx2c was found in strains of serotypes O157 and O174. stx2d was found in 11 strains. These strains were confirmed by DNA sequencing to carry both the activatable tail and the END motif; all were eae-negative, and 3 contained stx2d as the only stx. stx2g was found in 2 strains in association with stx2a, estA1, and astA. In addition, 7 hybrid strains of shigatoxigenic and enterotoxigenic E. coli (STEC/ETEC) were found to harbor one or both of stx1a and stx2a (stx1a/stx2a) and estA1. Among 27 serotypes of STEC strains isolated from cattle, O157:H7 and O109:H– strains were eae-positive. Other putative adhesin genes, such as saa, iha, espP, and lpfAO113 were detected in more than 12 serotypes.
Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) is a severe pathological manifestation of dengue virus (DENV) infection. Enhanced production of cytokines in dengue patients is proposed to induce endothelial barrier instability resulting in increased vascular leakage. Tumor necrosis factor (TNF)-α is an inflammatory cytokine that activates endothelial cells and enhances vascular permeability and plasma leakage in DHF/DSS. The present study investigated the in vitro effect of TNF-α and DENV infection on the expression of adherence junction proteins, tight junction proteins, and membrane integrity of human endothelial cell lines. Immunofluorescence staining and western blot analysis demonstrated platelet endothelial cell adhesion molecule-1 (PECAM-1) reorganization and decreased levels of the tight junction protein occludin in human endothelial cells treated with TNF-α and DENV, compared to mock, DENV, or TNF-α-treated cells. Permeability assessed by FITC-dextran as a transport molecule was increased and correlated with the unusual reorganization of PECAM-1. The altered distribution of PECAM-1 and low occludin protein levels in human endothelial cells treated with TNF-α and DENV correlated with increased permeability. In conclusion, the synergistic effect of TNF-α and DENV induced permeability changes in endothelial cells. These results contribute to the understanding of the mechanisms underlying enhanced vascular permeability in DENV infection.
In the spring of 2015, we experienced a cluster of 4 sporadic cases of yersiniosis in children in Nagano prefecture, a rural area of Japan. Two patients developed appendicitis-like episodes; one had acute gastroenteritis, and the other had bacteremia associated with liver abscess. The causative agent of these infections was Yersinia enterocolitica serogroup O:8. None of the patients had an underlying illness, and all have recovered completely. The patients were neither socially nor geographically related to each other. These 4 consecutive cases suggest that Y. enterocolitica O:8 has spread substantially in the middle part of Japan, and that this virulent strain might be more common than previously reported in our country.
A 54-year-old woman receiving continuous ambulatory peritoneal dialysis was admitted, complaining of diffuse abdominal pain. Peritoneal fluid cell analysis showed that the white blood cell count was 2,990 cells/mm3, with a neutrophil count of 2,510 cells/mm3. The patient was treated empirically with intraperitoneal cefazolin and ceftazidime. After 6 days, Microbacterium species grew on a peritoneal dialysate culture that had been collected on the day of admission. We analyzed the 16S rRNA gene nucleotide sequence and identified the organism as Microbacterium paraoxydans. Based on the results of the antibiotic susceptibility test, the patient was treated with intraperitoneal vancomycin and oral clarithromycin. She recovered uneventfully without interruption of peritoneal dialysis. This is a unique case of peritoneal dialysis-related peritonitis due to M. paraoxydans.
We herein report the pulmonary histopathological findings of an autopsy case of post-pandemic season A/H1N1pdm09 infection-associated acute respiratory distress syndrome (ARDS). The lung histology predominantly exhibited findings indicative of the exudative phase of diffuse alveolar damage, with similar inflammation severity observed in all sections. Furthermore, the lung sections only showed a few A/H1N1pdm09 antigen-positive cells along with a low viral RNA copy number. The sequence of the viral hemagglutinin receptor binding site identified a preference for α-2,6 linked sialic acid, suggesting low alveolar epithelial cell infectivity. The pathological findings, in this case, differed in several aspects from those of the first autopsy case of A/H1N1pdm09 infection-associated ARDS in Japan, reported during the 2009 pandemic season. In conclusion, pathological and molecular biological examinations suggested that in the post-pandemic season A/H1N1pdm09 infection, the infection-associated ARDS was not caused by direct infection-induced damage to the alveolar epithelial cells but was rather a result of indirect sepsis-mediated endothelial cell damage.
An 87-year-old man with poorly controlled diabetic mellitus presented with fever, bedsores, and elevated hepatobiliary enzyme levels. He was diagnosed with bacteremia with acute cholangitis due to Arthrobacter species, which are Gram-positive, aerobic, catalase-positive, coryneform bacteria belonging to the family Microbacteriaceae. Doripenem and subsequencial sulbactam/ampicillin treatment were used for the acute cholangitis, and the bacteremia was treated with a 2-week course of vancomycin. The bacteremia was misidentified by the phenotyping assay (API Coryne test), but was identified as Arthrobacter creatinolyticus by 16S rRNA and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry. To our knowledge, this is the first report of a human case of A. creatinolyticus bacteremia.
Multidrug-resistant Acinetobacter baumannii (MDRAB) colonization increases the risk of bacterial spread in the hospital setting. The impact of clinical factors, including antibiotic use, on prolongation of MDRAB colonization has not been investigated. Patients with respiratory tract MDRAB detected using culture were enrolled in this study. Long-term colonizers and short-term colonizers were defined as patients whose colonization periods were >30 days or ≤30 days, respectively. Clinical data were abstracted from medical records. MDRAB was isolated in 34 patients. There were 13 long-term colonizers and 9 short-term colonizers. Twelve patients were lost to follow-up and excluded from the study. There were no significant differences in average leukocyte counts, numbers of antibiotic classes administered, duration of antibiotic use in the 30 days following colonization, or rates of central catheterization or mechanical ventilation between the 2 groups. Long-term colonizers carried Neisseria species (spp.) more frequently in the 30 days following colonization than short-term colonizers (7/13 vs 1/9, p = 0.01); however, this was not the case prior to colonization with MDRAB (5/13 vs 1/9, p = 0.33). The 90-day MDRAB colonization rates for Neisseria-negative patients and Neisseria-positive patients were 10.0% and 83.3%, respectively (P < 0.01). Prolonged MDRAB colonization in the respiratory tract was associated with Neisseria spp. co-colonization.
In Japan, both a stick-type kit and an enzyme-linked immunosorbent assay (ELISA) kit are available for the detection of antibodies to Helicobacter pylori in urine. However, the accuracy of these tests has not been fully examined in northern Japanese populations. Urine samples from 359 subjects were tested using a stick-type H. pylori-antibody detection kit (RAPIRUN), and urine samples from 201 subjects were tested using an ELISA-based test (URINELISA). The prevalence of H. pylori infection was determined by the 13C-urea breath test (UBT) and a monoclonal antibody-based stool antigen test (TPAg). Subjects were considered to have the infection if either the UBT or rapid TPAg results were positive. The percentage of positive test results for RAPIRUN and URINELISA was 54.0% and 40.8%, respectively. Sensitivity and specificity were 83.3% and 67.0%, respectively, for RAPIRUN and 86.5% and 85.8% for URINELISA. Nineteen subjects had cut-off index values of between 0.4 and 0.9 by URINELISA, and 4 of these subjects (21.1%) were found to be infected with H. pylori. The urine-based ELISA was more accurate than the rapid stick-type kit in these patients. If negative ELISA results are near the cut-off value, subjects should receive an additional test to determine whether they are infected with H. pylori.
We report the first case of cerebral cyst infection by Helicobacter cinaedi, a fastidious spiral-shaped gram-negative rod bacterium. A 70-year-old man visited Tokyo Medical University Hospital with persisting fever since 2 weeks. He underwent surgery and radiotherapy for parapharyngeal space squamous cell carcinoma 10 years ago. The radiotherapy resulted in a cerebral cyst as a side effect, and an Ommaya reservoir was inserted into the cyst. Blood culture and analysis of the brain cyst fluid revealed the presence of spiral-shaped gram-negative rod bacteria, which were identified as H. cinaedi by polymerase chain reaction. Initially, we administered clarithromycin (400 mg per day). After H. cinaedi infection was confirmed, the treatment was changed to meropenem (MEPM 6 g per day). The patient was treated for 43 days in the hospital with intravenous meropenem, and his clinical course was satisfactory. On the 44th day, he was discharged and prescribed oral minocycline (MINO 200 mg per day). After discharge, the patient's H. cinaedi infection did not recur. Our case illustrated the wide clinical spectrum of H. cinaedi as well as the effectiveness of antibiotic therapy comprising MERM and MINO for treating central nervous system infection by this organism.
We studied the antimicrobial susceptibility and prevalence of the blaTEM-1 and blaTEM-135 genes in Neisseria gonorrhoeae isolates obtained in Thailand. The isolates were tested using the disk diffusion method, and 100% of 370 isolates were found susceptible to cefixime, ceftriaxone, cefotaxime, ceftazidime, cefepime, spectinomycin, and azithromycin. Some of the isolates were resistant to penicillin (85.7%), ciprofloxacin (88.0%), ofloxacin (97.4%), or tetracycline (89.1%). Penicillinase-producing N. gonorrhoeae accounted for 83.8% of isolates, with 70.0% of these further identified as penicillinase-producing plus tetracycline resistant N. gonorrhoeae. Penicillin, tetracycline, and ciprofloxacin are not recommended for treatment because of the high prevalence (89.7%) of multidrug resistant gonococci. A study of genes controlling enzyme of beta-lactamase production (blaTEM-1 and blaTEM-135) was performed using mismatch amplification mutation assay PCR method and DNA sequencing. Beta-lactamase positive N. gonorrhoeae carried blaTEM-1 (69.6%) and blaTEM-135 (30.4%), indicating that there is a significant increase and spread of blaTEM-135 among gonococci in Thailand.
This study aimed to determine the proportion of varicella non-immune pediatric healthcare workers (HCWs) of the Pediatrics Department of King Chulalongkorn Memorial Hospital and to determine cost-effective strategies for identifying non-immune personnel. A cross-sectional study using a self-administered questionnaire to determine HCWs' histories of chickenpox or 2-dose varicella vaccination was conducted. From a total of 699 HCWs, 653 HCWs (93%), including 145 physicians (22%), 297 nurses (46%), and 211 administrative staff (32%), responded to questionnaires. There were 475 HCWs (73%) who had a history of chickenpox, 58 (9%) who had completed the 2-dose varicella vaccine schedule, and 120 (18%) whose varicella-zoster virus (VZV) immunity status was uncertain. In total, 107 HCWs (89%) were tested for VZV IgG, 90 of whom had immunity, and 17 were determined to be non-immune. After combining history and VZV IgG test results, the prevalence of non-immune HCWs was 2.6% (95%CI 1.4–3.8), with those ≤40 years of age at higher risk of non-immunity. Implementing a strategy that involves testing of only those with an unknown VZV status and vaccination for only those determined to be non-immune costs 1,801 United States dollar (USD), less than the total cost (4,601 USD) for vaccinating all HCWs with uncertain status
This study presents the results of a large-scale, one-year survey of Trichinella spp. in Japanese wild boars (Sus scrofa). We analyzed the tongues of 1,168 wild boars captured by hunters in 30 prefectures of Japan, most of which were boar habitats, from October 2014 to January 2015. The samples were digested, and the prevalence of Trichinella spp. muscle larvae was examined. Examination of pooled samples from 10 individuals (15 g per head) or 117 randomly selected samples (10% of the total number of samples) that were individually processed showed no larval infection. Thus, our data suggests that Japanese wild boars do not play a major role in the sylvatic cycle of Trichinella parasites.
The major brunt of scrub typhus is borne by developing countries like India but the disease remains neglected. The rapid progression of this infection to serious complications and associated mortality calls for improved diagnostics. The immunoglobulin (Ig)M immunofluorescence assay (IFA), with all of its limitations remains the gold standard. Of 218 suspected cases from patients enrolled in a 2-year study, 30 cases of scrub typhus were detected by IgM IFA, using a 1:64 dilution. The sensitivities of the IgM enzyme-linked immunosorbent assay, IgM rapid flow assay (RFA), and IgG RFA were found to be 97%, 87%, and 77%, respectively. Their respective specificities were 100%, 100%, and 92%, respectively. The sensitivity and specificity of a nested PCR assay targeting a gene encoding a 56-kDa protein were found to be 50% and 100%, respectively.