Data concerning the seasonality and geographical location of tsutsugamushi disease (TD) in Japan from 1955 to 2014 were compiled. After disappearance of “classical” TD in the mid-1960s, there was a long near-vacuum. Then, in 1975, a TD epidemic with October–December seasonality emerged in southern prefectures, and in 1979, that with May–June seasonality in northern prefectures. The current TD epidemic could be classified according to seasonality and geography into three types: a large October–December epidemic with a negligibly small May–June epidemic in the southern part of Japan, a large May–June epidemic with a mid-sized October–December epidemic on the Pacific coast of northern Japan, and a large epidemic in May–June with a negligibly small October–December epidemic on the Japan Sea coast of northern Japan. In addition, there were a few patients that were scattered throughout the year in various places in Japan. How these different epidemic patterns emerged is discussed.
Variation by country in urinary tract infection (UTI)-causative bacteria is partly due to the differences in the use of antibiotics. We compared their frequencies and antibiotic susceptibilities in the treatment of patients with UTI from 2 cities, Kobe, Japan, and Surabaya, Indonesia. We retrospectively analyzed 1,804 urine samples collected from patients with UTI in 2014 (1,251 collected in 11 months at Kobe University Hospital in Kobe and 544 collected in 2 months at Dr. Soetomo Hospital in Surabaya). Surabaya data were divided into adult and pediatric patients because a substantial number of specimens from pediatric-patients had been collected. The results indicated that Escherichia coli was the most common uropathogen (24.1% in Kobe and 39.3% in Surabaya) and was significantly resistant to ampicillin and substantially to first- and third-generation cephalosporins in Surabaya adults but not in Kobe adults (p ＜ 0.01). Enterococcus faecalis was often isolated in Kobe (14.0%), but not in Surabaya (5.3%). Klebsiella spp. were isolated at a higher rate in Surabaya pediatric patients (20.3%) than in Surabaya adults (13.6%) and Kobe adults (6.6%). The antibiotic susceptibilities of the isolates form Surabaya isolates tended to be lower than the ones from Kobe. Extended-spectrum β-lactamase-producing Gram-negative bacteria were detected at a significantly higher rate in Surabaya than in Kobe (p ＜ 0.001). These results showed that the antimicrobial resistance patterns of UTI-causative bacteria are highly variable among 2 countries, and the continuous surveillance of trends in antibiotic resistance patterns of uropathogens is necessary for the future revision of antibiotic use.
Multidrug-resistant Streptococcus pneumoniae serogroup 19, including serotypes 19A and 19F, associated with clonal complex 320/271 (CC320/271), has been previously shown to be predominant in many countries after introduction of a 7-valent pneumococcal conjugate vaccine (PCV7). However, in Japan there has been no epidemiological research focused on penicillin-nonsusceptible isolates after this event. Therefore, we aimed to characterize penicillin-nonsusceptible S. pneumoniae (PNSSP; penicillin minimum inhibitory concentration [MIC] ≥ 4.0 μg/ml) after the introduction of PCV7 in Japan. Throughout Japan, we collected 1,057 pneumococcal isolates from 2010 to 2014. We then evaluated MICs and performed serotyping, multilocus sequence typing, and sequencing of penicillin-binding protein genes in 51 isolates (penicillin MIC ≥ 2.0 μg/ml). Twenty-three isolates (2.2%) showed penicillin nonsusceptibility (penicillin MIC ≥ 4.0 μg/ml). Serotypes 19F (14 isolates, 60.9%) and 23F (4 isolates, 17.4%), which are covered by the vaccine, were predominant among PNSSP strains. Only 3 isolates belonged to nonvaccine serotype 19A. Among the PNSSP isolates, CC320/271 (16/23 strains, 69.6%) was the most prevalent clone. Moreover, CC320/271 clones showed high MIC values of a third-generation cephalosporin. Thus, we demonstrated clonal predominance of serogroup 19 CC320/271 with strong resistance to β-lactams including a third-generation cephalosporin among PNSSP isolates.
Based on the involvement of nuclear factor-κB inhibitor alpha (NFKIBA) in the NF-κ B pathway, which is closely related to host immunity, we evaluated whether NFKIBA polymorphisms are associated with the disease progression of chronic hepatitis B virus (HBV) infection. We collected blood samples from a total of 212 treatment-naïve patients with chronic HBV infection. NFKBIA polymorphisms were determined by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry. Enzyme-linked immunosorbent assays were employed to quantify the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6(IL-6). Unconditional logistic regression revealed that carriers of the TT genotype at rs2233406 had a greater risk (OR = 5.57, 95% CI = 2.14–14.52) of chronic HBV infection progression. A similar association was observed for the rs2233409 polymorphism, in which the OR for the TT genotype was 4.06 (95% CI = 1.70–9.71) compared to that for the wildtype CC genotype. Mutations at rs2233406 and rs2233409 also impact liver function parameters and cytokine levels. However, null associations were observed between these parameters and rs696 polymorphism. These findings suggest that reduced NFKBIA function leads to activation of the NF-κB pathway, and consequently causes inflammation and liver damage among patients with chronic HBV infection.
Aedes albopictus is an important vector of dengue fever and tends to live in specific area, where it may ambush blood host that it encounters. Thus, host contact frequency may affect the bite rate and risk of disease outbreak, although no studies have examined these parameters. The present study used a simple model to clarify the fundamental relationship between host availability, bite rate, and risk of dengue outbreaks in non-endemic areas. A hypothetical isolated mosquito population was divided into “ambush” and “resting” subpopulations, and human hosts were modeled as visiting the mosquito population at constant intervals. A single infectious human who visited the mosquito population only on a single occasion was responsible for mosquito infections and consequently, secondary infections among humans who subsequently visit the area after the incubation period. The results confirmed that the bite rate per host increased with decreasing host availability. The number of secondary infections among hosts exhibited a unimodal relationship with the frequency of host visits, with a maximum value at host visits every 24 h. Furthermore, when host availability was not very low, the bite rate was a good indicator of the potential risk of dengue outbreaks. Therefore, human-bait-sweep collection data may be useful for monitoring the risk of dengue outbreaks.
We investigated the prevalence and characteristics of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolates from Japanese pigs. A total of 345 pig fecal specimens were collected from 30 farms in the Aichi prefecture of Japan between June 2015 and April 2016, and 22 unique ESBL-producing E. coli were isolated from 16 samples spanning 8 farms. The ESBL types included CTX-M-15 (54.5%), CTX-M-55 (27.2%), CTX-M-3 (0.9%), and CTX-M-14 (0.9%). The predominant plasmid replicon type was IncN, and the isolates carried blaCTX-M-55. Nine sequence type (ST)s, including ST117, ST1706, ST38, and ST10, were detected in the ESBL-producers, but no B2-O25-ST131 was found. ESBL producers were highly resistant to cefotaxime, ceftiofur, and tetracycline, but were susceptible to imipenem, amikacin, and fosfomycin (FOM), although 2 ST354 isolates showed resistance to ciprofloxacin. All 11 chloramphenicol-resistant isolates, including ST117 (n = 6) and ST38 (n = 3) isolates, harbored floR, and the 2 FOM-resistant ST38 isolates harbored fosA3. Our results suggest that pigs do not act as direct reservoirs in the transmission of ESBL genes to E. coli in humans. However, ST117 E. coli carrying IncN-type plasmids mediating blaCTX-M-55 were isolated from several different farms, suggesting the potential for future spread in Japan. Therefore, plasmid sequence analyses and continuous surveillance are necessary from an epidemiological point of view and are required to better protect against ESBL-producer transmission.
This study aimed to explore the epidemiology of pathogens in children who were hospitalized with lower respiratory tract infections (LRTIs) at the Children’s Hospital of Fudan University, Shanghai, China. Children aged less than 18 years who were hospitalized with LRTIs were enrolled from January 2013 to December 2015. Respiratory specimens were collected for the detection of common respiratory viruses, atypical bacteria, and other bacteria using current laboratory diagnostic tests. The epidemiological characteristics of the respiratory pathogens were analyzed. Of the 10,123 specimens obtained from the patients, 5,966 (58.7%) were positive for at least 1 pathogen. Mycoplasma pneumoniae (M.pneumoniae) was the most commonly detected pathogen (15.7%), followed by respiratory syncytial virus (RSV) (13.9%). Co-infections were found in 11.4% of patients. Of these co-infections, viral-bacterial co-infections were the most common. The detection rates for the respiratory pathogens varied considerably by age. RSV was the most common pathogen in children aged less than 24 months. Clear seasonal peaks were observed for RSV, M. pneumoniae, parainfluenza virus, human metapneumovirus, Moraxella catarrhalis, and Haemophilus influenza infections. Our findings demonstrate specific epidemiological patterns in children with LRTIs in Shanghai, China.
To determine the infection source, route, and extent of an outbreak, it is important to subtype Shiga toxin-producing Escherichia coli (STEC) isolates belonging to the same serotype for clustering into clonally related groups. In this study, we compared 3 molecular subtyping methods—multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and multiple-locus variable-number of tandem repeat analysis (MLVA)—using O157 and non-O157 STEC isolates from Japanese beef cattle. A total of 73 STEC isolates belonging to 9 O-serogroups were analyzed. By means of 3 molecular subtyping methods, the strains were subdivided into 9 MLST sequence types (STs), 23 PFGE types, and 26 MLVA types. The STEC classification by O-serogrouping and MLST was almost identical. Furthermore, PFGE and MLVA could systematically classify STEC isolates of the same serotypes and STs. MLVA and PFGE were found to be highly efficient subtyping methods after O-serogrouping for the classification of not only O157 but also non-O157 STEC isolates in an outbreak investigation.
IL28B single nucleotide polymorphism (rs12979860) is an etiology-independent predictor of hepatitis C virus (HCV)-related hepatic fibrosis. Data mining is a method of predictive analysis which can explore tremendous volumes of information from health records to discover hidden patterns and relationships. The current study aims to evaluate and compare the prediction accuracy of scoring system like aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index versus data mining for the prediction of HCV-related advanced fibrosis. This retrospective study included 427 patients with chronic hepatitis C. We used data mining analysis to construct a decision tree by reduced error (REP) technique, followed by Auto-WEKA tool to select the best classifier out of 39 algorithms to predict advanced fibrosis. APRI and FIB-4 had sensitivity-specificity parameters of 0.523–0.831 and 0.415–0.917, respectively. REPTree algorithm was able to predict advanced fibrosis with sensitivity of 0.749, specificity of 0.729, and receiver operating characteristic (ROC) area of 0.796. Out of the 16 attributes, IL28B genotype was selected by the REPTree as the best predictor for advanced fibrosis. Using Auto-WEKA, the multilayer perceptron (MLP) neural model was selected as the best predictive algorithm with sensitivity of 0.825, specificity of 0.811, and ROC area of 0.880. Thus, MLP is better than APRI, FIB-4, and REPTree for predicting advanced fibrosis for patients with chronic hepatitis C.
Aedes aegypti and Aedes albopictus are the primary and secondary vectors, respectively, of dengue, the most important arboviral disease in the world. The aim of this study was to detect and serotype dengue viruses (DENV) in the vectors Ae. aegypti and Ae. albopictus in Surabaya, Indonesia. Between 2008 and 2015, 16,605 Aedes mosquitoes were collected in 15 sub-districts of Surabaya. Ae. aegypti was dominant (90.9%), whereas few Ae. albopictus were collected (9.1%). A total of 330 pools of adult Aedes mosquitoes were subjected to the serotyping of DENV by RT-PCR. DENV-1 (52.3%) was the most frequently detected serotype, followed by DENV-2 (40.3%), DENV-4 (4.6%), and DENV-3 (2.8%). The average minimum infection rate for Ae. aegypti in various sub-districts of Surabaya was 7.2 per 1,000 mosquitoes, while that for Ae. albopictus was 0.7 per 1,000 mosquitoes. The results showed that the predominantly circulating DENV serotype in mosquitoes continuously shifted from DENV-2 (2008) to DENV-1 (2009–2012), to DENV-2 again (2013–2014), and then back to DENV-1 (2015). The circulating DENV serotypes in mosquitoes were generally consistent with those in humans. Therefore, the surveillance of infected mosquitoes with DENV might provide an early warning sign for the risk of future dengue outbreaks.
In Japan, infectious diseases are classified into 4 types based on how contagious and severe the pathogens are, and Ebola virus disease (EVD) is categorized as a category 1 infectious disease. The National Center for Global Health and Medicine in Tokyo, Japan, is designated as a specified hospital for category 1 infectious disease patients and has experienced 4 probable cases of EVD from West Africa. Even after the outbreak in West Africa is ended, we should continue to pay attention for new EVD outbreaks. Increasing the number of infectious disease specialists with the proper knowledge of viral hemorrhagic fever, including EVD, is a common problem for infectious disease physicians working in Japan, the academic society, and the government.
We collected water and soil samples from a waterfall in Thailand to investigate the presence of potentially pathogenic Leptospira. Isolation of Leptospira from all the 17 environmental samples was successful. Based on 16S rRNA gene sequence analysis, a diverse group of Leptospira species was recovered from waterfall samples including 2 pathogenic species (Leptospira alstonii [5/17, 29%] and Leptospira kmetyi [1/17, 6%]); 1 intermediate species (Leptospira wolffii [9/17, 53%]); and 2 non-pathogenic species (Leptospira meyeri [1/17, 6%] and Leptospira idonii [1/17, 6%]). The high prevalence of pathogenic and intermediate Leptospira indicates that a waterfall may serve as a natural reservoir of possible pathogens of leptospirosis.
Streptococcus gallolyticus subsp. pasteurianus, previously recognized as S. bovis biotype II/2, is an uncommon yet important cause of invasive infection in young infants. Here, we report the first case of ventriculitis that was unexpectedly diagnosed in the course of neonatal meningitis due to S. gallolyticus subsp. pasteurianus, and we review the relevant literature. A 28-day-old male infant from Japan presented with fever, lethargy, and irritability. S. bovis was isolated from blood and the cerebrospinal fluid culture and was then identified as S. gallolyticus subsp. pasteurianus. Intravenous antibiotic therapy was initiated, which helped improve the clinical course of the disease; however, the patient presented ventriculitis-related complications diagnosed using follow-up magnetic resonance imaging (MRI) on day 12 of hospitalization. Ampicillin was administered for 21 days and discontinued after the patient showed improvement, according to MRI findings. The patient was discharged without sequelae. Ventriculitis is a rare complication of childhood meningitis due to S. gallolyticus subsp. pasteurianus. However, it may have been underdiagnosed, especially in cases with no specific manifestations similar to the present case. We suggest that MRI should be performed to screen for ventriculitis in the course of meningitis to avoid failure in treatment.
Zika virus (ZIKV) infection has been documented within Central and South America, Asia, and Africa. Here we report the isolation of virus from a patient infected with ZIKV returning to Japan from the Dominican Republic. The ZIKV strain was imaged by electron microscopy and its complete genome sequence was analyzed. Phylogenetic analysis and molecular characterization revealed that the strain was of Asian lineage, and carried 2 unique mutations in its NS5 region. These mutations are characteristic of strains that originated in the Dominican Republic and the USA in 2016.
The number of reported cases of human hepatitis E virus (HEV) infection has increased since 2012. Pigs are considered an important source of viruses causing human HEV infection. It is possible that the prevalence of HEV among pigs at slaughter age (approximately 6 months old) has increased in the last decade. Therefore, we investigated the current prevalence of HEV among pigs in Japan. Although HEV RNA was detected in rectal content samples from pigs aged from one to 5 months, no HEV RNA was detected in any samples from 6-month-old pigs. The highest viral shedding prevalence (33%) was detected among 3-month-old pigs. This study shows that there has been no change in the prevalence of HEV among pigs at the slaughter age, in the prevalence of HEV by age group on pig farms, or in the phylogenetic classification of HEV isolates in the last decade. Therefore, factors downstream of the pork production stage may be contributing to the increased number of human HEV infection cases.
We previously developed a multiplex real-time PCR assay (Rapid Foodborne Bacterial Screening 24 ver.5, [RFBS24 ver.5]) for simultaneous detection of 24 foodborne bacterial targets. Here, to overcome the discrepancy of the results from RFBS24 ver.5 and bacterial culture methods (BC), we analyzed 246 human clinical samples from 49 gastroenteritis outbreaks using RFBS24 ver.5 and evaluated the correlation between the cycle threshold (CT) value of RFBS24 ver.5 and the BC results. The results showed that the RFBS24 ver.5 was more sensitive than BC for Campylobacter jejuni and Escherichia coli harboring astA or eae, with positive predictive values (PPV) of 45.5–87.0% and a kappa coefficient (KC) of 0.60–0.92, respectively. The CTs were significantly different between BC-positive and -negative samples (p ＜ 0.01). All RFBS24 ver.5-positive samples were BC-positive under the lower confidence interval (CI) limit of 95% or 99% for the CT of the BC-negative samples. We set the 95% or 99% CI lower limit to the determination CT (d-CT) to discriminate for assured BC-positive results (d-CTs: 27.42–30.86), and subsequently the PPVs (94.7%–100.0%) and KCs (0.89–0.95) of the 3 targets were increased. Together, we concluded that the implication of a d-CT-based approach would be a valuable tool for rapid and accurate diagnoses using the RFBS24 ver.5 system.