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Abstract The emergence of antimicrobial resistance (AMR) caused by the excess use of antimicrobials has come to be recognized as a global threat to public health. There is a ‘tragedy of the commons’ type social dilemma behind this excess use of antimicrobials, which should be recognized by all stakeholders. To address this global threat, we thus surveyed eight countries/areas to determine whether people recognize this dilemma and showed that although more than half of the population pays little, if any, attention to it, almost 20% recognize this social dilemma, and 15–30% of those have a positive attitude toward solving that dilemma. We suspect that increasing individual awareness of this social dilemma contributes to decreasing the frequency of AMR emergencies.

Plain English summary Periodontal disease is known to cause many complications. For instance, pregnant women with periodontal disease are at increased risk of preterm birth and delivering low-birth-weight infants. However, the importance of oral care during pregnancy is not an important consideration in rural Africa, where preterm birth rates and low-birth-weight rates are particularly high. Moreover, even the oral hygiene status of pregnant women has not been assessed in such areas. In this study, we focused on the amount of periodontal bacteria that cause periodontal disease and investigated the relationship between the amount of bacteria and birth outcomes. Our findings indicate that tooth brushing guidance for pregnant women and improved access to dental clinics in rural Africa may contribute to reduced rates of preterm birth and low birth weight.

Mycobacterium avium subsp. hominissuis (MAH) is one of the most prevalent mycobacteria causing non-tuberculous mycobacterial disease in humans and animals. Of note, MAH is a major cause of mycobacterial granulomatous mesenteric lymphadenitis outbreaks in pig populations. To determine the precise source of infection of MAH in a pig farm and to clarify the epidemiological relationship among pig, human and environmental MAH lineages, we collected 50 MAH isolates from pigs reared in Japan and determined draft genome sequences of 30 isolates. A variable number of tandem repeat analysis revealed that most pig MAH isolates in Japan were closely related to North American, European and Russian human isolates but not to those from East Asian human and their residential environments. Historical recombination analysis revealed that most pig isolates could be classified into SC2/4 and SC3, which contain MAH isolated from pig, European human and environmental isolates. Half of the isolates in SC2/4 had many recombination events with MAH lineages isolated from humans in East Asia. To our surprise, four isolates belonged to a new lineage (SC5) in the global MAH population. Members of SC5 had few footprints of inter-lineage recombination in the genome, and carried 80 unique genes, most of which were located on lineage specific-genomic islands. Using unique genetic features, we were able to trace the putative transmission route via their host pigs. Together, we clarify the possibility of species-specificity of MAH in addition to local adaptation. Our results highlight two transmission routes of MAH, one exposure on pig farms from the environment and the other via pig movement. Moreover, our study also warns that the evolution of MAH in pigs is influenced by MAH from patients and their residential environments, even if the MAH are genetically distinct.

Abstract Background Facing a global epidemic of new infectious diseases such as COVID-19, non-pharmaceutical interventions (NPIs), which reduce transmission rates without medical actions, are being implemented around the world to mitigate spreads. One of the problems in assessing the effects of NPIs is that different NPIs have been implemented at different times based on the situation of each country; therefore, few assumptions can be shared about how the introduction of policies affects the patient population. Mathematical models can contribute to further understanding these phenomena by obtaining analytical solutions as well as numerical simulations. Methods and results In this study, an NPI was introduced into the SIR model for a conceptual study of infectious diseases under the condition that the transmission rate was reduced to a fixed value only once within a finite time duration, and its effect was analyzed numerically and theoretically. It was analytically shown that the maximum fraction of infected individuals and the final size could be larger if the intervention starts too early. The analytical results also suggested that more individuals may be infected at the peak of the second wave with a stronger intervention. Conclusions This study provides quantitative relationship between the strength of a one-shot intervention and the reduction in the number of patients with no approximation. This suggests the importance of the strength and time of NPIs, although detailed studies are necessary for the implementation of NPIs in complicated real-world environments as the model used in this study is based on various simplifications.

Abstract Background Tibetan highlanders have adapted to hypoxic environments through the development of unique mechanisms that suppress an increase in hemoglobin (Hb) concentration even in high-altitude areas. Hb concentrations generally decrease with increasing age. However, in the highlands, chronic altitude sickness is known to occur in the elderly population. To investigate how aging in a hypoxic environment affects Hb levels in Tibetan highlanders, we focused on the Mustang people, who live above 3500 m. We tried to clarify the pure relationship between aging and Hb levels in a hypoxic environment. Results We found that the Hb concentration increased with increasing age in females but not in males. Multivariate analysis showed that age, pulse pressure, the poverty index, and vascular diameter were strongly correlated with the Hb concentration. Conclusions We found unique Hb dynamics among female Tibetan highlanders. As seen in these Hb dynamics, there may be sex-based differences in the adaptive mechanism in Tibetan highlanders.

Stochastic consensus algorithms are considered for multi-agent systems over noisy unbalanced directed networks. The graph which represents a communication network of the system is assumed to contain a directed spanning tree, that is, a given digraph is weakly connected. Then two types of stochastic consensus are investigated, where one is for the agent states themselves and the other is for the time averages of the agent states. The convergence of the algorithms is investigated, which gives a stopping rule, i.e., an explicit relation between the number of iterations and the closeness of the agreement.

Abstract While large scale mobility data has become a popular tool to monitor the mobility patterns during the COVID-19 pandemic, the impacts of non-compulsory measures in Tokyo, Japan on human mobility patterns has been under-studied. Here, we analyze the temporal changes in human mobility behavior, social contact rates, and their correlations with the transmissibility of COVID-19, using mobility data collected from more than 200K anonymized mobile phone users in Tokyo. The analysis concludes that by April 15th (1 week into state of emergency), human mobility behavior decreased by around 50%, resulting in a 70% reduction of social contacts in Tokyo, showing the strong relationships with non-compulsory measures. Furthermore, the reduction in data-driven human mobility metrics showed correlation with the decrease in estimated effective reproduction number of COVID-19 in Tokyo. Such empirical insights could inform policy makers on deciding sufficient levels of mobility reduction to contain the disease.

Mycobacterium avium subsp. hominissuis (MAH) is one of the most important agents causing non-tuberculosis mycobacterial infection in humans and pigs. There have been advances in genome analysis of MAH from human isolates, but studies of isolates from pigs are limited despite its potential source of infection to human. Here, we obtained 30 draft genome sequences of MAH from pigs reared in Japan. The 30 draft genomes were 4,848,678–5,620,788 bp in length, comprising 4652–5388 coding genes and 46–75 (median: 47) tRNAs. All isolates had restriction modification-associated genes and 185–222 predicted virulence genes. Two isolates had tRNA arrays and one isolate had a clustered regularly interspaced short palindromic repeat (CRISPR) region. Our results will be useful for evaluation of the ecology of MAH by providing a foundation for genome-based epidemiological studies.

ABSTRACT Amikacin and colistin are effective against carbapenem-resistant Klebsiella pneumoniae. In 2017, we successively isolated three carbapenem-resistant K. pneumoniae isolates (ST967) from a patient with chronic renal failure in Japan. The first (SMKP01, sputum, day 0) and second (SMKP02, blood, day 14) strains were resistant to most antimicrobials tested but still susceptible to amikacin (MICs of 4 and 0.5 mg/liter, respectively) and colistin (MIC of 0.5 mg/liter for both). The third strain (SMKP03, blood, day 51) was not susceptible to amikacin (MIC, 32 mg/liter), and its MIC for colistin varied (0.5 to 8 mg/liter). Whole-genome sequencing of SMKP01 revealed that 17 of 20 antimicrobial resistance genes, including qnrB91 (a novel qnrB2 variant) and aac(6′)-Ib-cr, were located on an 86.9-kb IncFII-IncQ plasmid. The qnrB91 conferred greater fluoroquinolone resistance than qnrB2. SMKP03 aac(6′)-Ib-cr that possessed a gene mutation that resulted in an R102W substitution, namely, aac(6′)-Ib-D179Y, made a greater contribution to amikacin resistance than did aac(6′)-Ib-cr. SMKP03 harbored a nonsense mutation in mutS, which encodes a DNA repair enzyme. Introduction of this mutation into SMKP01 (SMKP01mutSA307T) resulted in a dramatic increase (>58-fold) in the frequency of spontaneous amikacin-resistant mutants relative to SMKP01, and the substantial mutants possessed aac(6′)-Ib-D179Y. SMKP01mutSA307T exhibited an unstable MIC for colistin (0.5 to 8 mg/liter). The results demonstrate that a disruptive mutation in MutS, arising during the clinical course of an infection, created a platform for the acquisition of amikacin nonsusceptibility and colistin heteroresistance in multidrug-resistant K. pneumoniae, mediated by the elevated frequency of spontaneous mutations. IMPORTANCE The emergence of multidrug resistance in pathogens such as Klebsiella pneumoniae is of great clinical concern. Antimicrobial resistance sometimes arises during the course of an infection. Although many studies have reported the emergence of antimicrobial resistance and novel antimicrobial resistance genes in the clinical isolates, the identity of the bacterial factor(s) that generate this emergence is still unclear. We report that a disruptive mutation in MutS, arising during the clinical course of an infection, created a context for the acquisition of colistin resistance and the emergence of a novel variant of the amikacin resistance gene in multidrug-resistant K. pneumoniae via an increase in the frequency of spontaneous mutation. This observation is important for understanding how K. pneumoniae develops multidrug resistance during infection and could potentially lead to new antimicrobial treatments for high-risk pathological microbes.

In 2016, disseminated tuberculosis caused by Mycobacterium caprae was diagnosed in a captive Borneo elephant in Japan. The bacterium was initially identified from clinical isolates. An isolate collected during a relapse showed isoniazid monoresistance and a codon 315 katG mutation.

Abstract Background Epidemiology of noncommunicable diseases (NCDs) such as obesity and diabetes mellitus (DM) are influenced by multiple hosts and environmental factors. This study aims to investigate the prevalence of NCDs and determine their risk factors among the adults residing in an isolated village situated at a rural highland of Nepal. Methods A cross-sectional survey was conducted in a village located at 3570 m. Each 188 randomly selected participants of age ≥ 18 years old answered a questionnaire and took a full physical exam that included biomedical measurements of glycosylated hemoglobin (HbA1c). Results The prevalence of intermediate hyperglycemia and DM was 31.6% and 4.6% respectively, and the prevalence of hypoxemia (SpO2

Synchronous and asynchronous algorithms are presented for distributed minimax optimization. The objective here is to realize the minimization of the maximum of component functions over the standard multi-agent network, where each node of the network knows its own function and it exchanges its decision variable with its neighbors. In fact, the proposed algorithms are standard consensus and gossip based subgradient methods, while the original minimax optimization is recast as minimization of the sum of component functions by using a p-norm approximation. A scalable step size depending on the approximation ratio p is also presented in order to avoid slow convergence. Numerical examples illustrate that the algorithms with this step size work well even in the high approximation ratios.

A chance constrained AC optimal power flow is to find the optimal economic operation plan whose probability satisfying AC power flow equations and various inequality constraints on operating limits of the power system is greater than a specified probability level. Even if a constraint condition for each uncertain power supply value is convex with respect to decision variables, the chance constrained problem is not convex in general. Thus, it is difficult to solve the problem within reasonable computational time. Employment of randomization techniques for this issue is proposed in this paper. A main advantage of the framework leads to a solution with a theoretical guarantee. Its sample complexities are of polynomial order for parameters of a given accuracy. The efficiency of this algorithm is demonstrated by applying it to the Japanese power system models.

Opinion formation is investigated over signed gossip networks, where asymptotic and transient opinion behaviors are analyzed in detail. The network is modeled by a connected signed graph, where each edge of the graph has positive or negative weight, i.e., these edges represent friendly or hostile relationship. Interactions each of which occurs between two persons chosen randomly follow an asynchronous procedure. Then it is shown that their opinions always converge in mean square and converge almost surely. A convergence time is defined as the smallest time such that it takes for the values of nodes to get within a given neighborhood of the consensus value with high probability, regardless of initial state. An upper bound and a lower bound of the convergence time of the gossip algorithm are given in terms of a structure of the given network.

In many countries with low to moderate tuberculosis (TB) incidence, cases have shifted to elderly persons. It is unclear, however, whether these cases are associated with recent Mycobacterium tuberculosis transmission or represent reactivation of past disease. During 2009–2015, we performed a population-based TB investigation in Yamagata Prefecture, Japan, using in-depth contact tracing and 24-loci variable-number tandem-repeat typing optimized for Beijing family M. tuberculosis strains. We analyzed 494 strains, of which 387 (78.3%) were derived from elderly patients. Recent transmission with an epidemiologic link was confirmed in 22 clusters (70 cases). In 17 (77.3%) clusters, the source patient was elderly; 11 (64.7%) of the 17 clusters occurred in a hospital or nursing home. In this setting, the increase in TB cases was associated with M. tuberculosis transmissions from elderly persons. Prevention of transmission in places where elderly persons gather will be an effective strategy for decreasing TB incidence among predominantly elderly populations.

Elucidation of the structure of human sexual networks is not only an interesting topic in the area of social networks but also an important clue for understanding the spreading risk of sexually transmitted infections (STIs). Some previous studies have indicated that sexual networks are scale free, while others have suggested that they are not. We conducted a Web-based survey on sexual contact in Japan to collect data on cumulative (total) heterosexual partners and the number of recent (in the last three or previous three months) heterosexual partners. To determine whether the number of heterosexual contacts in Japan has a power-law tail, we used maximum likelihood fitting methods and Kolmogorov-Smirnov tests. For confirmation, we also used the Akaike information criterion (AIC) and the Bayesian information criterion (BIC). Our results indicate that the distributions of the number of sexual partners in Japan have power-law tails.

Carnivore protoparvovirus 1 (CPPV-1) is widespread among free-living carnivores, and CPPV-1 infection may directly or indirectly impact on the population of endangered carnivore species. In this study, we used molecular screening of viral capsid protein 2 (VP2) from 2015 to 2017, to assess the prevalence of CPPV-1 infection in 9 live-trapped (LT) and 17 vehicle collision (VC)-affected free-living leopard cats (Prionailurus bengalensis chinensis). In addition, we conducted the phylogenetic analysis to evaluate the possible transmission of CPPV-1 between domestic carnivores and leopard cats. We identified the circulation of feline parvovirus and variants of canine parvovirus (CPV), including CPV-2a, CPV-2b, and CPV-2c, in the free-living leopard cat population. The partial sequences of different variants of VP2 obtained from the leopard cats were identical with those obtained from the domestic dogs and cats in Taiwan. Our result suggested that CPPV-1 was currently transmitted between domestic carnivores and leopard cats in Taiwan. A plan of conservation measures based on vaccination program for domestic carnivores, strict controls on populations of free-living dogs and cats and limiting road development only to low-risk areas for leopard cats should be encouraged.

The rhythm of automatic cyclic movements such as walking is known to be generated by a rhythm generator called CPG in the spinal cord. The measurement of rhythm characteristics in walking is considered to be important for analyzing human bipedal walking and adaptive walking on irregular terrain. In particular, the soles that contact the terrain surface perform flexible movements similar to the movement of the fins of a lungfish, which is considered to be the predecessor of land animals. The sole movements are believed to be a basic movement acquired during prehistoric times. The detailed rhythm pattern of sole motion is considered to be important. We developed a method for measuring electrification without installing device on a subject's body and footwear for stabilizing the electrification of the human body. We measured the rhythm pattern of 20 subjects including 4 infants when walking by using this system and the corresponding equipment. Therefore, we confirmed the commonality of the correlative rhythm patterns of 20 subjects. Further, with regard to an individual subject, the reproducibility of a rhythm pattern with strong correlation coefficient > 0.93 ± 0.5 (mean ± SD) concerning rhythms of trials that are differently conducted on adult subjects could be confirmed.

For a method for detecting the human body, such factors that no blind corner should exist, subjects other than human beings will not be erroneously detected. In this paper, a new method for detecting a human body wherein attention is focused on the human characteristics of walking will be studied. It had been known that a human body is electrified by walking, thus forming an electrical field around the human body. It was considered from walking waveforms in which human walking was reflected that a human body could be detected more advantageously. The measuring method is not affected by vibrations, etc. In addition, detection is possible with a simple electrode, which is advantageous in terms of cost. In this study, electrification on the human body in which components of actions of both feet are superimposed will be measured at a remote place, under an assumed living environment, and by using an algorithm that remotely detects walking characteristics based on the waveforms in which movements of both feet are reflected. Walking of 10 subjects including infants was actually measured, and a system, which is capable of detecting the number of steps at an accuracy of approximately 99.4% was shown.

Mycobacterium tuberculosis transmission routes can be estimated from genotypic analysis of clinical isolates from patients. In Japan, still a middle-incidence country of TB, a unique genotype strain designated as 'M-strain' has been isolated nationwide recently. To ascertain the history of the wide spread of the strain, 10 clinical isolates from different areas were subjected to genome-wide analysis based on deep sequencers. Results show that all isolates possessed common mutations to those of referential strains. The greatest number of accumulated single nucleotide variants (SNVs) from the oldest coalescence was 13 nucleotides, indicating high clonality of these isolates. When an SNV common to the isolates was used as a surrogate marker of the clone, authentic clonal isolates with variation in a reliable subset of variable number of tandem repeat (VNTR) genotyping method can be selected successfully from clinical isolates populations of M. tuberculosis. When the authentic clones can also be assigned to sub-clonal groups by SNVs derived from the genomic comparison, they are classifiable into three sub-clonal groups with a bias of geographical origins. Feedback from genomic analysis of clinical isolates of M. tuberculosis to genotypic markers will be an efficient strategy for the big data in various settings for public health actions against TB.

Beijing family strains of Mycobacterium tuberculosis have attracted worldwide attention because of their wide geographical distribution and global emergence. Peru, which has a historical relationship with East Asia, is considered to be a hotspot for Beijing family strains in South America. We aimed to unveil the genetic diversity and transmission characteristics of the Beijing strains in Peru. A total of 200 Beijing family strains were identified from 2140 M. tuberculosis isolates obtained in Lima, Peru, between December 2008 and January 2010. Of them, 198 strains were classified into sublineages, on the basis of 10 sets of single nucleotide polymorphisms (SNPs). They were also subjected to variable number tandem-repeat (VNTR) typing using an international standard set of 15 loci (15-MIRU-VNTR) plus 9 additional loci optimized for Beijing strains. An additional 70 Beijing family strains, isolated between 1999 and 2006 in Lima, were also analyzed in order to make a longitudinal comparison. The Beijing family was the third largest spoligotyping clade in Peru. Its population structure, by SNP typing, was characterized by a high frequency of Sequence Type 10 (ST10), which belongs to a modern subfamily of Beijing strains (178/198, 89.9%). Twelve strains belonged to the ancient subfamily (ST3 [n=3], ST25 [n=1], ST19 [n=8]). Overall, the polymorphic information content for each of the 24 loci values was low. The 24 loci VNTR showed a high clustering rate (80.3%) and a high recent transmission index (RTI(n-1)=0.707). These strongly suggest the active and on-going transmission of Beijing family strains in the survey area. Notably, 1 VNTR genotype was found to account for 43.9% of the strains. Comparisons with data from East Asia suggested the genotype emerged as a uniquely endemic clone in Peru. A longitudinal comparison revealed the genotype was present in Lima by 1999.

Infection and transmission of multidrug-resistant Mycobacterium tuberculosis (MDR-Mtb) and extensively drug-resistant M. tuberculosis (XDR-Mtb) is a serious health problem. We analyzed a total of 1,110 Mtb isolates in Osaka Prefecture and neighboring areas from April 2000 to March 2009. A total of 89 MDR-Mtb were identified, 36 (48.5%) of which were determined to be XDR-Mtb. Among the 89 MDR-Mtb isolates, 24 (27.0%) phylogenetically distributed into six clusters based on mycobacterial interspersed repetitive units-various number of tandem repeats (MIRU-VNTR) typing. Among these six clusters, the MIRU-VNTR patterns of four (OM-V02, OM-V03, OM-V04, and OM-V06) were only found for MDR-Mtb. Further analysis revealed that all isolates belonging to OM-V02 and OM-V03, and two isolates from OM-V04 were clonal. Importantly such genotypes were not observed for drug-sensitive isolates. These suggest that few but transmissible clones can transmit after acquiring multidrug resistance and colonize even in a country with a developed, well-organized healthcare system.