Time series analysis of daily reported number of new positive cases of COVID-19 in Japan from January 2020 to February 2023.

This study investigated temporal variations of the COVID-19 pandemic in Japan using a time series analysis incorporating maximum entropy method (MEM) spectral analysis, which produces power spectral densities (PSDs). This method was applied to daily data of COVID-19 cases in Japan from January 2020 to February 2023. The analyses confirmed that the PSDs for data in both the pre- and post-Tokyo Olympics periods show exponential characteristics, which are universally observed in PSDs for time series generated from nonlinear dynamical systems, including the so-called susceptible/exposed/infectious/recovered (SEIR) model, well-established as a mathematical model of temporal variations of infectious disease outbreaks. The magnitude of the gradient of exponential PSD for the pre-Olympics period was smaller than that of the post-Olympics period, because of the relatively high complex variations of the data in the pre-Olympics period caused by a deterministic, nonlinear dynamical system and/or undeterministic noise. A 3-dimensional spectral array obtained by segment time series analysis indicates that temporal changes in the periodic structures of the COVID-19 data are already observable before the commencement of the Tokyo Olympics and immediately after the introduction of mass and workplace vaccination programs. Additionally, the possibility of applying theoretical studies for measles control programs to COVID-19 is discussed.

Clonal lineages and antimicrobial resistance of nonencapsulated Streptococcus pneumoniae in the post-pneumococcal conjugate vaccine era in Japan.

OBJECTIVES: The emergence and spread of nonencapsulated Streptococcus pneumoniae (NESp) is a public health concern in the post-pneumococcal conjugate vaccine era. We analyzed the prevalence, molecular characteristics, and antimicrobial resistance of NESp responsible for noninvasive infections in northern Japan. METHODS: NESp isolates were identified using molecular and phenotypical methods among 4463 S. pneumoniae isolates from noninvasive infection cases during 4 study periods between January 2011 and January 2019. NESp isolates were analyzed for antimicrobial susceptibility, genotype, and virulence-associated genes. RESULTS: Seventy-one NESp isolates were identified (1.6% of total clinical isolates) and assigned to the null capsule clade (NCC)1 (pspK+) (94.4%) or NCC2 (aliC+/aliD+) (5.6%). The dominant sequence types (STs) were ST7502 (23.9%), ST4845 (19.7%), ST16214 (11.3%), ST11379 (9.9%), and ST7786 (7.0%). These 5 dominant STs and all 7 novel STs were related to the sporadic NESp lineage ST1106 or PMEN clone Denmark14-ST230. High non-susceptibility rates of NESp were observed for trimethoprim-sulfamethoxazole, erythromycin, and tetracycline (>92.9%), and multidrug resistance was observed in 88.7% of the NESp isolates, including all ST7502, ST4845, and ST11379 isolates. CONCLUSIONS: The study revealed that the dominant clonal groups of NESp were associated with a high prevalence of non-susceptibility to antimicrobials in northern Japan.

Associations between Meteorological Factors and Reported Mumps Cases from 1999 to 2020 in Japan.

The present study investigated associations between epidemiological mumps patterns and meteorological factors in Japan. We used mumps surveillance data and meteorological data from all 47 prefectures of Japan from 1999 to 2020. A time-series analysis incorporating spectral analysis and the least-squares method was adopted. In all power spectral densities for the 47 prefectures, spectral lines were observed at frequency positions corresponding to 1-year and 6-month cycles. Optimum least-squares fitting (LSF) curves calculated with the 1-year and 6-month cycles explained the underlying variation in the mumps data. The LSF curves reproduced bimodal and unimodal cycles that are clearly observed in northern and southern Japan, respectively. In investigating factors associated with the seasonality of mumps epidemics, we defined the contribution ratios of a 1-year cycle (Q1) and 6-month cycle (Q2) as the contributions of amplitudes of 1-year and 6-month cycles, respectively, to the entire amplitude of the time series data. Q1 and Q2 were significantly correlated with annual mean temperature. The vaccine coverage rate of a measles-mumps-rubella vaccine might not have affected the 1-year and 6-month modes of the time series data. The results of the study suggest an association between mean temperature and mumps epidemics in Japan.

Drug Resistance Determinants in Clinical Isolates of Enterococcus faecalis in Bangladesh: Identification of Oxazolidinone Resistance Gene optrA in ST59 and ST902 Lineages.

Enterococcus faecalis is one of the major causes of urinary tract infection, showing acquired resistance to various classes of antimicrobials. The objective of this study was to determine the prevalence of drug resistance and its genetic determinants for E. faecalis clinical isolates in north-central Bangladesh. Among a total of 210 E. faecalis isolates, isolated from urine, the resistance rates to erythromycin, levofloxacin, and gentamicin (high level) were 85.2, 45.7, and 11.4%, respectively, while no isolates were resistant to ampicillin, vancomycin and teicoplanin. The most prevalent resistance gene was erm(B) (97%), and any of the four genes encoding aminoglycoside modifying enzyme (AME) were detected in 99 isolates (47%). The AME gene aac(6')-Ie-aph(2")-Ia was detected in 46 isolates (21.9%) and was diverse in terms of IS256-flanking patterns, which were associated with resistance level to gentamicin. Tetracycline resistance was ascribable to tet(M) (61%) and tet(L) (38%), and mutations in the quinolone resistance-determining region of both GyrA and ParC were identified in 44% of isolates. Five isolates (2.4%) exhibited non-susceptibility to linezolide (MIC, 4 µg/mL), and harbored the oxazolidinone resistance gene optrA, which was located in a novel genetic cluster containing the phenicol exporter gene fexA. The optrA-positive isolates belonged to ST59, ST902, and ST917 (CC59), while common lineages of other multiple drug-resistant isolates were ST6, ST28, CC16, and CC116. The present study first revealed the prevalence of drug resistance determinants of E. faecalis and their genetic profiles in Bangladesh.

Latitudes mediate the association between influenza activity and meteorological factors: A nationwide modelling analysis in 45 Japanese prefectures from 2000 to 2018.

BACKGROUND: Cold and dry conditions were well-documented as a major determinant of influenza seasonality in temperate countries but the association may not be consistent when the climate in temperate areas is closer to that in sub-tropical areas. We hypothesized latitudes may mediate the association between influenza activity and meteorological factors in 45 Japanese prefectures. METHODS: We used the weekly incidence of influenza-like illness of 45 prefectures from 2000 to 2018 as a proxy for influenza activity in Japan, a temperate country lying off the east coast of Asia. A combination of generalized additive model and distributed lag nonlinear model was adopted to investigate the associations between meteorological factors (average temperature, relative humidity, total rainfall, and actual vapour pressure, a proxy for absolute humidity) and the influenza incidence. Kendall's tau b (τ) and Spearman correlation coefficient (rs) between latitude and the adjusted relative risk (ARR) of each meteorological factor were also assessed. RESULTS: A higher vapour pressure was significantly associated with a lower influenza risk but the ARR strongly weakened along with a lower latitude (τ = -0.23, p-value = 0.02; rs = -0.33, p-value = 0.03). Lower temperature and lower relatively humidity were significantly associated with higher influenza risks in over 65% and around 40% of the prefectures respectively but the strength and significance of the correlations between their ARRs and latitude were weaker than that from vapour pressure. CONCLUSION: Even though the range of latitudes in Japan is small (26°N-43°N), the relationships between meteorological factors and influenza activity were mediated by the latitude. Our study echoed absolute humidity played a more important role in relating influenza risk, but we on the other hand showed its effect on influenza activity could be hampered in a low-latitude temperate region, which have a warmer climate. These findings thus offer a high-resolution characterization of the role of meteorological factors on influenza seasonality.

Molecular Epidemiological Characterization of Staphylococcus argenteus Clinical Isolates in Japan: Identification of Three Clones (ST1223, ST2198, and ST2550) and a Novel Staphylocoagulase Genotype XV.

Staphylococcus argenteus, a novel emerging species within Staphylococcus aureus complex (SAC), has been increasingly reported worldwide. In this study, prevalence of S. argenteus among human clinical isolates, and their clonal diversity and genetic characteristics of virulence factors were investigated in Hokkaido, the northern main island of Japan. During a four-month period starting from March 2019, twenty-four S. argenteus and 4330 S. aureus isolates were recovered from clinical specimens (the ratio of S. argenteus to S. aureus :0.0055). Half of S. argenteus isolates (n = 12) belonged to MLST sequence type (ST) 2250 and its single-locus variant, with staphylocoagulase genotype (coa-) XId, while the remaining isolates were assigned to ST2198/coa-XIV (n = 6), and ST1223 with a novel coa-XV identified in this study (n = 6). All the isolates were mecA-negative, and susceptible to all the antimicrobials tested, except for an ST2198 isolate with blaZ and an ST2250 isolate with tet(L) showing resistance to ampicillin and tetracyclines, respectively. Common virulence factors in the S. argenteus isolates were staphylococcal enterotoxin (-like) genes sey, selz, sel26, and sel27 in ST2250, selx in ST2198, and enterotoxin gene cluster (egc-1: seg-sei-sem-sen-seo) in ST1223 isolates, in addition to hemolysin genes (hla, hlb, and hld) distributed universally. Elastin binding protein gene (ebpS) and MSCRAMM family adhesin SdrE gene (sdrE) detected in all the isolates showed high sequence identity among them (> 97%), while relatively lower identity to those of S. aureus (78-92%). Phylogenetically, ebpS, sdrE, selx, sey, selw, sel26, and sel27 of S. argenteus formed clusters distinct from those of S. aureus, unlike sec, selz, tst-1, and staphylokinase gene (sak). The present study revealed the prevalence of S. argenteus among clinical isolates, and presence of three distinct S. argenteus clones (ST2250; ST2198 and ST1223) harboring different virulence factors in northern Japan. ST2198 S. argenteus, a minor clone (strain BN75-like) that had been rarely reported, was first identified in Japan as human isolates.

Prevalence and Genetic Diversity of Toxin Genes in Clinical Isolates of Clostridium perfringens: Coexistence of Alpha-Toxin Variant and Binary Enterotoxin Genes (bec/cpile).

Clostridium perfringens (C. perfringens) is responsible for food-borne gastroenteritis and other infectious diseases, and toxins produced by this bacterium play a key role in pathogenesis. Although various toxins have been described for C. perfringens isolates from humans and animals, prevalence of individual toxins among clinical isolates has not yet been well explored. In the present study, a total of 798 C. perfringens clinical isolates were investigated for prevalence of eight toxin genes and their genetic diversity by PCR, nucleotide sequencing, and phylogenetic analysis. Besides the alpha-toxin gene (plc) present in all the isolates, the most common toxin gene was cpe (enterotoxin) (34.2%), followed by cpb2 (beta2 toxin) (1.4%), netB (NetB) (0.3%), and bec/cpile (binary enterotoxin BEC/CPILE) (0.1%), while beta-, epsilon-, and iota-toxin genes were not detected. Genetic analysis of toxin genes indicated a high level of conservation of plc, cpe, and netB. In contrast, cpb2 was revealed to be considerably divergent, containing at least two lineages. Alpha-toxin among 46 isolates was classified into ten sequence types, among which common types were distinct from those reported for avian isolates. A single isolate with bec/cpile harbored a plc variant containing an insertion of 834-bp sequence, suggesting its putative origin from chickens.

Clonal Diversity and Genetic Characteristics of Methicillin-Resistant Staphylococcus aureus Isolates from a Tertiary Care Hospital in Japan.

Molecular epidemiological characteristics were investigated for 1,041 isolates of methicillin-resistant Staphylococcus aureus (MRSA) collected in a tertiary care hospital in northern Japan for a 4-year period (2011-2014). Genotypes (staphylococcal cassette chromosome mec [SCCmec], sequence type, spa, coa, etc.) and the presence of drug resistance/virulence factor genes in the isolates were analyzed by multiplex/uniplex PCR, and PCR-direct sequencing as needed. Among these MRSA, predominant SCCmec type was IIa (87.2%), followed by IV (10.1%) and V (1.2%). The SCCmec IIa-MRSA belonged to coagulase genotype (coa) IIa and ST5/ST764, which are known as major health care-associated-MRSA (HA-MRSA) in Japan (New York/Japan clone) and its variant. Panton-Valentine leucocidine (PVL) genes were detected in only five isolates (0.5%) with genotypes ST8-SCCmec IVa/spa-t008/coa-IIIa (USA300 clone), ST6-SCCmec IVb, and ST59-SCCmec V (Taiwanese clone). Arginine catabolic mobile element (ACME) type I and II' were identified in three and five isolates of ST8-SCCmec IVa and ST764-SCCmec IIa MRSA, respectively. PVL-/ACME- isolates were classified into various STs/clonal complexes (CCs), with CC1, CC5, CC8, CC89, and CC121 being common. It was notable that SCCmec IVl was the most common among SCCmec IV subtypes, and was carried by almost half of coa-IIIa isolates (47%, 34/72) without PVL genes, which represented the novel ST8 MRSA clone spreading in Japan (i.e., "ST8/CA-MRSA/J"). Uncommon MRSA clones in Japan, ST72-SCCmec IV (South Korean clone), ST398 livestock-associated clone, and ST20 bovine-associated MRSA, were identified. Furthermore, we isolated PVL-negative ST8-SCCmec I/coa-IIIa and ST81-SCCmec V/coa-VIIa MRSA, which were considered presumptive novel clones. The present study revealed the genetic diversity of HA-MRSA, including potentially emerging clones of putative different origins.

Time-series analysis of geographically specific monthly number of newly registered cases of active tuberculosis in Japan.

BACKGROUND: Understanding seasonality of tuberculosis (TB) epidemics may lead to identify potentially modifiable risk factors. Studies conducted outside Japan have found seasonal variation among reported TB cases, with peaks in spring and summer and low prevalence in fall and winter. One hypothesis regarding spring or summer peaks in TB epidemics is that TB transmission likely increases in winter because of indoor crowding and poor ventilation, with development of primary TB among socially vulnerable people in spring and summer. Another plausible explanation is that vitamin D deficiency in winter depresses immunity, increasing the TB reactivation risk in these seasons. Previous studies suggest latitude-dependent factors, including reduced winter sunlight and its effect on vitamin D levels. Here, we investigated mechanisms of seasonality in TB epidemics in Japan, according to the effects of crowding and latitude. METHODS: We used time-series analysis consisting of spectral analysis and least-squares method, to analyse geographically specific monthly number of newly registered cases of all forms of active TB in all 47 prefectures of Japan during 1998-2015. RESULTS: In all power spectral densities for the 47 prefectures, spectral lines were observed at frequency positions corresponding to a 1-year cycle. The degree of this seasonality was associated with population density. We did not detect greater amplitude of seasonality at higher latitudes, suggesting that latitude-dependent factors, including reduced winter sunlight and its potential effect on vitamin D levels, do not contribute significantly to seasonality in Japan. DISCUSSION AND CONCLUSION: In districts with high population density, measures are needed to address two specific types of active infection risk in adolescents and middle-aged adults: (i) public transport use, and (ii) irregular employment with no periodic medical examinations. To control active TB epidemics, investigating periodic structures in the temporal patterns of active TB in each district and each age group is important.

Molecular characterization of Staphylococcus argenteus in Myanmar: identification of novel genotypes/clusters in staphylocoagulase, protein A, alpha-haemolysin and other virulence factors.

PURPOSE: Staphylococcus argenteus is a novel emerging species of coagulase-positive staphylococcus that is genetically closely related to Staphylococcus aureus. To elucidate the molecular differences in the virulence factors (staphylocoagulase, protein A, alpha-haemolysin, enterotoxin-like toxin and staphylokinase) between these staphylococcal species, S. argenteus that had recently been isolated in Myanmar (five nasal isolates and four clinical isolates) were analysed. METHODOLOGY: The nucleotide sequences of the virulence factors were determined by PCR and direct sequencing, followed by phylogenetic analysis by mega6 and multiple alignment by clustalw using the published sequence data for S. aureus and S. argenteus. RESULTS: Six S. argenteus isolates belonged to MLST sequence type (ST) 2250, while others belonged to ST4625, ST2198 and ST2854. The novel staphylocoagulase (coa) genotype XIV and the novel coa-XI subtype (XId) were identified in an ST2198 isolate and all other isolates, respectively. Among the S. argenteus isolates, the protein A and alpha-haemolysin genes showed high sequence identity (96-98 % and >99 %, respectively), while lower identity was observed between S. argenteus and S. aureus (88-91 % and 86 %, respectively), with both species showing phylogenetically distinct clusters. Similar findings were found for the staphylococcal enterotoxin (SE)-like toxin genes selw, selx and sely. In contrast, the staphylokinase genes were almost identical between these two species. All of the coa-XId isolates had a CRISPR/Cas locus at the site of orfX without having SCCmec, whereas an ST2198 isolate lacked this locus. CONCLUSION: The primary virulence factors (staphylocoagulase, protein A andalpha-haemolysin) as well as the SE-like toxins of S. argenteus were genetically discriminated from those of S. aureus, revealing the presence of the novel coa-type/subtype (coa-IXd, XIV) in S. argenteus.

Molecular Epidemiological Characterization of Methicillin-Susceptible and -Resistant Staphylococcus aureus Isolated from Skin and Soft Tissue Infections in Bangladesh.

Genetic background and molecular characteristics of Staphylococcus aureus collected from patients with skin and soft tissue infections were studied in the North-Central region of Bangladesh from 2015 to 2016. Among 430 clinical isolates, methicillin-resistant S. aureus (MRSA) accounted for 31% having SCCmec type IV (73%) and V (14%), and belonged mostly to coagulase (coa) genotypes IIa, IIIa, IVb, and XIa, while dominant coa type in methicillin-susceptible S. aureus (MSSA) was IIIa, followed by Va, IIa, and VIa. Panton-Valentine Leukocidin genes (pvl) were detected at higher rate in MSSA (54%) than in MRSA (24%). Based on multilocus sequence typing, pvl-positive MRSA isolates were classified into clonal complex 88 (CC88) (ST88, ST2884, ST4345), CC6 (ST6, ST4350), and CC1 (ST1, ST772), while pvl-negative MRSA into CC5, CC22, CC80, CC121, and CC672. The pvl-negative ST80 MRSA isolates had SCCmec-IVa (agr-III/coa-XIc, etd/edinB-positive, fusB-negative), indicating that they belong to the novel CC80 clade related to the European community-acquired MRSA clone. Among MSSA, genotypes ST121/spa-t645/coa-Va and ST2884 (CC88)/spa-t2393/coa-IIIa were identified in both pvl-positive and negative isolates, and all the ST772 isolates harbored pvl. All the ST121 isolates had a variant of elastin-binding protein gene (ebpS-v) with internal 180-nucleotide deletion. The present study suggested that CC88 (ST88, ST2884) and ST772 are the putative dominant lineages of pvl-positive MRSA/MSSA, while novel CC80 clade is one of the main pvl-negative MRSA lineages distributed endemically in Bangladesh.

Role of temperature in reported chickenpox cases in northern European countries: Denmark and Finland.

OBJECTIVE: In this study, we sought to explore the temperature-dependent transition of patterns of reported chickenpox cases in the northern European countries of Denmark and Finland to help determine the potential relationship with epidemiological factors of the disease. We performed time-series analysis consisting of a spectral analysis based on the maximum entropy method in the frequency domain and the nonlinear least squares method in the time domain, using the following time-series data: monthly data of reported chickenpox cases and mean temperatures in the pre-vaccination era for Denmark and Finland. The results were compared with those reported for China and Japan in our previous studies. RESULTS: Time-series data of chickenpox cases for both Denmark and Finland showed a peak each winter, resulting in a unimodal cycle. For investigating the origin of the unimodal cycle, we set the contribution ratio of the 1-year cycle, Q1, as the contribution of the amplitude of a 1-year cycle, to the entire amplitude of the time-series data. The Q1 values for both countries clearly showed a positive correlation with the annual mean temperature of each country. The mean temperature substantially influenced the incidence of chickenpox in both countries.

Prevalence and Molecular Epidemiology of Clinical Isolates of Escherichia coli and Klebsiella pneumoniae Harboring Extended-Spectrum Beta-Lactamase and Carbapenemase Genes in Bangladesh.

Spread of Gram-negative bacteria producing extended-spectrum beta-lactamases (ESBLs) and carbapenemases constitutes a growing challenge in control of bacterial infections. In this study, prevalence and genetic characteristics of Escherichia coli and Klebsiella pneumoniae harboring ESBL and/or carbapenemase genes, with other beta-lactamase/resistance genes, were investigated for a total of 375 clinical isolates in Mymensingh located in north-central Bangladesh. The major ESBL gene was blaCTX-M-1 group, which was detected in 33.9% and 51.4% of E. coli and K. pneumoniae, respectively, with CTX-M-15 gene being dominant. SHV-type beta-lactamase genes, including newly identified alleles (SHV-201 and SHV-202) were detected at higher rate in K. pneumoniae (27%). Nine isolates of E. coli (3.9%) harbored carbapenemase genes; blaNDM-1 (phylogenetic group A-sequence type 2104 (A-ST2104), B2-ST73), blaNDM-5 (A-ST167, B2-ST38/ST2659-related STs), and blaNDM-7 (B1-ST101/ST224, D-ST6682). AmpC beta-lactamase genes (blaCMY-2 and blaCMY-42) were detected in E. coli, which mostly harbored blaCTX-M-15 and plasmid-mediated quinolone resistance (PMQR) determinants (aac6'-Ib-cr, qnrB, qnrS, qepA, and oqxAB). A new CMY allele (CMY-160) belonging to CMY-2 group was identified in phylogenetic group D E. coli. Among K. pneumoniae, carbapenemase gene was detected in three isolates (2%); blaNDM-1 in ST11 and ST1322, and blaOXA-181 in ST43 isolate. As well as higher rate of aac6'-Ib-cr in K. pneumoniae (39%), PMQR gene oqxAB was also commonly found among isolates analyzed. These findings indicated spread of blaNDM genes to diverse E. coli clones and emergence of blaOXA-181 in K. pneumoniae, with increased prevalence of ESBLs represented by CTX-M-15 in Bangladesh.

Prevalence of Extended-Spectrum Beta-Lactamase and Carbapenemase Genes in Clinical Isolates of Escherichia coli in Myanmar: Dominance of blaNDM-5 and Emergence of blaOXA-181.

The increasing trend of Escherichia coli producing extended-spectrum beta-lactamases (ESBLs) and carbapenemases is a global public health concern. In this study, prevalence and molecular characteristics of E. coli harboring ESBL and carbapenemase genes were investigated for 426 isolates derived from various clinical specimens in a teaching hospital in Yangon, Myanmar, for the 1-year period beginning January 2016. A total of 157 isolates (36.9%) were ESBL producers and harbored CTX-M-1 group genes (146 isolates; blaCTX-M-15, blaCTX-M55) or CTX-M-9 group genes (11 isolates; blaCTX-M-14, blaCTX-M-27). Carbapenem resistance was detected in 35 isolates (8.2%), among which 26 isolates had carbapenemase genes encoding NDM-1 (2 isolates), NDM-4 (6 isolates), NDM-5 (14 isolates), NDM-7 (3 isolates), and OXA-181 (2 isolates). blaNDM-5 was identified in phylogenetic groups A, B1, and D isolates belonging to various genotypes (ST101, ST354, ST405, ST410, ST1196) associated with blaTEM-1, blaCTX-M-15, blaOXA-181, blaCMY-2, blaCMY-6, blaCMY-42, qnrB, qnrS, or aac6'-Ib-cr. While two isolates with blaOXA-181 belonged to phylogenetic group A-ST410, one isolate had also blaNDM-5, as well as blaCTX-M-15 and blaCMY-2, and the other harbored blaCMY-42 and aac6'-Ib-cr, showing different resistance patterns. Phylogenetic group B2 isolates examined were classified into mostly ST131 and had solely blaCTX-M-15 or blaCTX-M-27, harboring more virulence factors than other phylogenetic groups. The present study revealed high prevalence of ESBL genes represented by blaCTX-M-15 and dominance of blaNDM-5 among NDM genes, disseminating to various E. coli clones. Notably, carbapenemase gene encoding OXA-181 was first identified in Myanmar, suggesting its spread together with NDM genes.

Role of meteorological conditions in reported chickenpox cases in Wuhan and Hong Kong, China.

BACKGROUND: Chickenpox is a common contagious disease that remains an important public health issue worldwide. Over 90% of unvaccinated individuals become infected, but infection occurs at different ages in different parts of the world. Many people have been infected by 20 to 30 years of age in China, and adults and pregnant women who become infected often develop severe infection. Furthermore, a mortality rate of 2-3 per 100,000 infected persons has been reported. In this study, we explore the temperature-dependent transition of patterns of reported chickenpox cases in two large subtropical climate cities, Wuhan and Hong Kong, China, to aid in the prediction of epidemics and preparation for the effects of climatic changes on epidemiology of chickenpox in China. METHODS: We used a time series analysis comprising a spectral analysis based on the maximum entropy method in the frequency domain and the nonlinear least squares method in the time domain. Specifically, the following time series data were analyzed: data of reported chickenpox cases and meteorological data, including the mean temperature, relative humidity and total rainfall in Wuhan and Hong Kong from January 2008 to June 2015. RESULTS: The time series data of chickenpox for both Wuhan and Hong Kong have two peaks per year, one in winter and another in spring, indicating a bimodal cycle. To investigate the source of the bimodal cycle of the chickenpox data, we defined the contribution ratio of the 1-year cycle, Q 1, and the 6-month cycle, Q 2, as the contribution of the amplitude of a 1-year cycle and a 6-month cycle, respectively, to the entire amplitude of the time-series data. The Q 1 values of Wuhan and Hong Kong were positively correlated with the annual mean temperature and rainfall of each city. Conversely, the Q 2 values of Wuhan and Hong Kong were negatively correlated with the annual mean temperature and rainfall of Wuhan and Hong Kong. CONCLUSION: Our results showed that the mean temperature and rainfall have a significant influence on the incidence of chickenpox, and might be important predictors of chickenpox incidence in Wuhan and Hong Kong.

Collaborative Research on Puerperal Infections in Bangladesh.

Bangladesh is considered as a high-risk country for emerging infectious diseases because of its high population density, poverty, and unhygienic conditions. Although control efforts have primarily been focused on major infectious diseases such as diarrheal diseases, tuberculosis, malaria, and HIV infection, the prevalence and impact of many local or minor infectious diseases are still unclarified in this country. In this review, we present our recent experience and outcomes of collaborative research on puerperal infection (PI), which is a poorly defined infectious disease in Bangladesh. PI is the most common complication during the perinatal period in developing countries. We investigated the incidence of individual species of aerobic bacteria causing PIs and their drug resistance, and the genetic traits of isolates during the two-year period (2010-2012). The common species of isolates from patients with PIs were Escherichia coli, Enterococcus faecalis, Staphylococcus haemolyticus, Proteus mirabilis, Staphylococcus aureus, and Klebsiella pneumoniae. A remarkable finding was the high rates of resistance to cephalosporins among Gram-negative bacteria harboring extended-spectrum beta-lactamase genes, which were associated with carbapenem resistance in a few isolates. This study defined the importance of control of antimicrobial resistance in Bangladesh, and provided suggestions for the future direction of collaborative research on infectious diseases in Bangladesh.

Collaborative Research with Chinese, Indian, Filipino and North European Research Organizations on Infectious Disease Epidemics.

In this report, we present a short review of applications of time series analysis, which consists of spectral analysis based on the maximum entropy method in the frequency domain and the least squares method in the time domain, to the incidence data of infectious diseases. This report consists of three parts. First, we present our results obtained by collaborative research on infectious disease epidemics with Chinese, Indian, Filipino and North European research organizations. Second, we present the results obtained with the Japanese infectious disease surveillance data and the time series numerically generated from a mathematical model, called the susceptible/exposed/infectious/recovered (SEIR) model. Third, we present an application of the time series analysis to pathologic tissues to examine the usefulness of time series analysis for investigating the spatial pattern of pathologic tissue. It is anticipated that time series analysis will become a useful tool for investigating not only infectious disease surveillance data but also immunological and genetic tests.

Molecular Characterization of Methicillin-Resistant Staphylococcus aureus from Outpatients in Northern Japan: Increasing Tendency of ST5/ST764 MRSA-IIa with Arginine Catabolic Mobile Element.

Arginine catabolic mobile element (ACME) is a genomic island of staphylococcus and is considered to confer enhanced ability to survive and growth on host bacterial cells. ACME has been typically identified in Panton-Valentine Leukocidin (PVL)-positive ST8 methicillin-resistant Staphylococcus aureus (MRSA) with SCCmec type IVa (USA300 clone), and it is also found in other lineages at low frequency. Prevalence and molecular characteristics of PVL+and/or ACME+ MRSA were investigated for 624 clinical isolates collected from outpatients in northern Japan from 2013 to 2014. Both PVL genes and ACME type I were detected in nine isolates (1.4%), which were ST8-MRSA-SCCmec IVa/spa type t008/agr-I; whereas solely PVL genes were positive in two isolates, ST30-MRSA-SCCmec IV and ST59-MRSA-SCCmec V. ACME type II' (previously referred to as ACME ΔII) was detected in 36 isolates (5.8%) with SCCmec II and V (32 and 4 isolates, respectively), exhibiting an increased rate within SCCmec II-MRSA (7.1%) compared with our previous studies (0.86-4.5%, 2008-2011). ACME II'-positive MRSA strains were classified into ST5-SCCmec IIa/V or ST764-SCCmec IIa belonging to five different spa types, with t002 being dominant. They harbored mostly enterotoxin gene clusters (seg-sei-sem-sen-seo-seu) and some more enterotoxin genes (seb1, seb2, sec3, sel, sep), showing resistance to more antimicrobials than ST8-MRSA-SCCmec IVa. ACME-SCCmec composite island (CI) of the 36 ACME II'-positive MRSA was classified into five types (ii)-(vi), among which type (ii) (orfX-ΨSCCΔJ1 SCCmec I-ACME II'-SCCmec II) was dominant and subdivided into the A3 variant and the less common A2 variant. CI types (v) and (vi) were considered novel genetic organizations having speG (acetyltransferase genes for polyamines) in inserted SCC4610/SCC266-like genetic elements. The present study revealed increased prevalence and genetic diversity of the ST5/ST764-MRSA-SCCmec II with ACME II' in northern Japan.

Distribution of two distinct rotavirus B (RVB) strains in the north-central Bangladesh and evidence for reassortment event among human RVB revealed by whole genomic analysis.

Human rotavirus B (RVB), a rare cause of diarrhea in several Asian countries, has been reported to be genetically highly conserved. However, 14 RVB strains with two distinct RNA electropherotypes E1 and E2 (11 and 3 strains, respectively) were detected in adult patients with diarrhea, in Mymensingh in the north-central Bangladesh in 2014. In this study, VP7 gene sequences of all the 14 strains and nearly full-length sequences of all the 11 RNA segments of four RVB (two strains each representing E1 and E2 types) were determined and analyzed phylogenetically. For all the gene segments, sequence identities among strains with the same RNA pattern were higher (99%-100%) than those between strains with different RNA patterns (94-98%). Although all the gene segments of RVB strains were grouped into Indian-Bangladeshi lineage, VP1-3, VP6, VP7, NSP1, NSP2 and NSP5 genes of strains with E1 and E2 types were assigned to distinct sublineages S1 and S2, respectively. E1-strains clustered with Bangladeshi RVB strains reported previously (e.g., Bang117), while E2-strains with those from India (e.g., NIV-1048101), Myanmar, and Nepal. In contrast, VP4, NSP3 and NSP4 genes of both E1 and E2 RVB strains were classified into sublineage S2. These findings indicated that two genetically distinct RVB strains were simultaneously circulating in Mymensingh, Bangladesh. RVB strains with E1 electropherotype were suggested to be reassortants acquiring three gene segments (VP4, NSP3 and NSP4 genes) from the foreign RVB in the genetic background of indigenous Bangladeshi RVB represented by the strain Bang117.

Whole genomic analysis of G2P[4] human Rotaviruses in Mymensingh, north-central Bangladesh.

Rotavirus A (RVA) is a dominant causative agent of acute gastroenteritis in children worldwide. G2P[4] is one of the most common genotypes among human rotavirus (HRV) strains, and has been persistently prevalent in South Asia including Bangladesh. In the present study, whole genome sequences of a total of 16 G2P[4] HRV strains (8 strains each in 2010 and 2013) detected in Mymensingh, north-central Bangladesh were determined. These strains had typical DS-1-like genotype constellation. Most of gene segments from DS-1 genogroup exhibited high level sequence identities to each other (>98%), while slight diversity was observed for VP1, VP3, and NSP4 genes. By phylogenetic analysis, individual RNA segments were classified into one (V) or two-three lineages (V-VI or V-VII). In terms of lineages (sublineages) of 11 gene segments, the 16 Bangladeshi strains could be further classified into four clades (A-D) containing 8 lineage constellations, revealing the presence of three clades (A-C) with three lineage constellations in 2010, and a single clade (D) with four constellations in 2013. Therefore, co-existence of multiple G2P[4] HRV strains with different lineage constellations, and change in clades for the study period were demonstrated. Although amino acids in the antigenic regions on VP7 and VP4 were mostly identical to those of global G2P[4] strains after 2000, VP4 of clade D RVAs in 2013 had alanine and proline at positions 88 and 114, respectively, which are novel substitutions compared with recent global G2P[4] strains. Replacement of lineage constellations associated with unique amino acid changes in the antigenic region in VP4 suggested continuous genetic evolutionary state for emerging new G2P[4] rotavirus strains in Bangladesh.