Antimicrobial-resistant Helicobacter pylori in Japan: Report of nationwide surveillance for 2018-2020.

BACKGROUND: Antimicrobial therapy is necessary to eradicate Helicobacter pylori infection. The emergence of antimicrobial-resistant bacteria poses a threat to continued treatment with antimicrobial agents. For those who prescribe antimicrobial therapy, it is necessary to constantly monitor the emergence of antimicrobial-resistant bacteria. METHOD: H. pylori clinical isolates were collected in Japan from August 2018 to December 2020 for antimicrobial susceptibility testing. The agar dilution method was used for the determination of the minimum inhibitory concentration (MIC) of clarithromycin (CLR), amoxicillin (AMX), metronidazole (MNZ), and sitafloxacin (STX). RESULTS: MICs for 938 H. pylori isolates were examined. The primary resistance rates of H. pylori clinical isolates for CLR, AMX, MNZ, and STX in Japan were 35.5%, 2.7%, 4.2%, and 27.6%, respectively. The primary resistance rates for CLR, AMX, and MNZ were significantly higher than those of the 2002-2005 isolates. The resistance rate for CLR was significantly higher in females (males: 30.7%, females: 41.5%, p < 0.001) and higher in the ≤29 years age group (54.8%) than in the other age groups, although there were no significant differences (p = 0.104). The MNZ resistance rate was significantly higher in the ≤29 years age group than in the other age groups (p = 0.004). The resistance rate for STX increased with age, but a significant difference was only seen between the 30-49 years age group and the ≥70 years age group (p < 0.001), and the resistance rate was significantly higher in strains isolated in the Kyushu region than in the other regions (p < 0.001). CONCLUSIONS: The primary resistance rates for CLR, AMX, and MNZ of H. pylori clinical isolates in Japan were higher than those of the 2002-2005 isolates. Continuous surveillance is needed to monitor the trends in antimicrobial-resistant H. pylori.

Isolation and characterization of Helicobacter suis from human stomach.

Helicobacter suis, a bacterial species naturally hosted by pigs, can colonize the human stomach in the context of gastric diseases such as gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Because H. suis has been successfully isolated from pigs, but not from humans, evidence linking human H. suis infection to gastric diseases has remained incomplete. In this study, we successfully in vitro cultured H. suis directly from human stomachs. Unlike Helicobacter pylori, the viability of H. suis decreases significantly on neutral pH; therefore, we achieved this using a low-pH medium for transport of gastric biopsies. Ultimately, we isolated H. suis from three patients with gastric diseases, including gastric MALT lymphoma. Successful eradication of H. suis yielded significant improvements in endoscopic and histopathological findings. Oral infection of mice with H. suis clinical isolates elicited gastric and systemic inflammatory responses; in addition, progression of gastric mucosal metaplasia was observed 4 mo postinfection. Because H. suis could be isolated from the stomachs of infected mice, our findings satisfied Koch's postulates. Although further prospective clinical studies are needed, H. suis, like H. pylori, is likely a gastric pathogen in humans. Furthermore, comparative genomic analysis of H. suis using complete genomes of clinical isolates revealed that the genome of each H. suis isolate contained highly plastic genomic regions encoding putative strain-specific virulence factors, including type IV secretion system-associated genes, and that H. suis isolates from humans and pigs were genetically very similar, suggesting possible pig-to-human transmission.

Helicobacter ailurogastricus in Patient with Multiple Refractory Gastric Ulcers, Japan.

We report the isolation of Helicobacter ailurogastricus, a Helicobacter species that infects cats and dogs, from a person with multiple refractory gastric ulcers. In addition to H. suis, which infects pigs, Helicobacter species that infect cats and dogs should be considered as potential gastric pathogens in humans.

Molecular ruler of the attachment organelle in Mycoplasma pneumoniae.

Length control is a fundamental requirement for molecular architecture. Even small wall-less bacteria have specially developed macro-molecular structures to support their survival. Mycoplasma pneumoniae, a human pathogen, forms a polar extension called an attachment organelle, which mediates cell division, cytadherence, and cell movement at host cell surface. This characteristic ultrastructure has a constant size of 250-300 nm, but its design principle remains unclear. In this study, we constructed several mutants by genetic manipulation to increase or decrease coiled-coil regions of HMW2, a major component protein of 200 kDa aligned in parallel along the cell axis. HMW2-engineered mutants produced both long and short attachment organelles, which we quantified by transmission electron microscopy and fluorescent microscopy with nano-meter precision. This simple design of HMW2 acting as a molecular ruler for the attachment organelle should provide an insight into bacterial cellular organization and its function for their parasitic lifestyles.

A Nationwide Plasmidome Surveillance in Thailand Reveals a Limited Variety of New Delhi Metallo-ß-Lactamase-Producing Carbapenem-Resistant Enterobacteriaceae Clones and Spreading Plasmids.

Despite frequent identification of plasmids carrying carbapenemase genes, the transfer of plasmids carrying carbapenemase genes is not well recognized in clinical settings because of technical limitations. To investigate the detailed mechanisms of the spread of carbapenem-resistant Enterobacteriaceae (CRE), we performed multifaceted genomic surveillance of CRE isolates in Thailand and analyzed their plasmidome. We analyzed 371 Enterobacteriaceae isolates carrying blaNDM-1 and 114 Enterobacteriaceae isolates carrying blaNDM-5 obtained from clinical samples of 473 patients in 11 representative hospitals located in six provinces in Thailand between 2012 and 2017. The complete structures of plasmids carrying blaNDM and chromosomal phylogeny were determined by combining Southern blotting hybridization analysis and our previously performed whole-genome short-read sequencing data. Dissemination of the blaNDM-5 gene among the Enterobacteriaceae isolates in Thailand was mainly owing to the nationwide clonal spread of Escherichia coli ST410 and regional clonal spreads of Escherichia coli ST361 and ST405. Analysis of blaNDM-1-carrying isolates revealed nationwide dissemination of two specific plasmids and nationwide clonal dissemination of Klebsiella pneumoniae ST16 accompanied with regional disseminations of three distinctive K. pneumoniae clones (ST231, ST14, and ST147) with different plasmids. Dissemination of CRE carrying blaNDM in Thailand is mainly based on nationwide clonal expansions of E. coli ST410 carrying blaNDM-5 and K. pneumoniae ST16 carrying blaNDM-1, nationwide dissemination of two distinctive plasmids carrying blaNDM-1, and accumulation of clonal expansions in regional areas. Although the overuse of antibiotics can promote CRE dissemination, the limited variety of transmitters highlights the importance of preventing horizontal dissemination among patients.

Establishment of a reference panel of Helicobacter pylori strains for antimicrobial susceptibility testing.

BACKGROUND: Eradication treatment for Helicobacter pylori gastritis is covered by national health insurance since 2013 in Japan. However, eradication failure due to the increase of antimicrobial resistance has become a serious problem. The present study aims to establish a reference panel of Japanese H. pylori strains for antimicrobial susceptibility testing. METHOD: A total of 28 strains were collected from 4 medical facilities in Japan. Antimicrobial susceptibility tests (ASTs) to clarithromycin (CLR), amoxicillin (AMX), and metronidazole (MNZ), were used to select standard reference strains. Complete genome sequences were also determined. RESULTS: Three H. pylori strains (JSHR3, JSHR6 and JSHR31) were selected as standard reference strains by the Japanese Society for Helicobacter Research (JSHR). The minimum inhibitory concentrations (MICs) of the antibiotics against these 3 strains by agar dilution method with Brucella-based horse-serum-containing agar medium were as follows: JSHR3 (CLR 16 µg/ml, AMX 0.032 µg/ml and MNZ 4 µg/ml), JSHR6 (CLR 0.016 µg/ml, AMX 0.032 µg/ml and MNZ 4 µg/ml), and JSHR31 (CLR 16 µg/ml, AMX 1 µg/ml and MNZ 64 µg/ml). CONCLUSIONS: A reference panel of H. pylori JSHR strains was established. The panel consisted of JSHR6, which was antibiotic-susceptible, JSHR3, which was CLR-resistant, and JSHR31, which was multi-resistant. This reference panel will be essential for standardized ASTs before the optimal drugs are selected for eradication treatment.

Association between the frequency of surgeries for video-assisted thoracic surgery and the incidence of consequent surgical site infections: a retrospective observational study based on national surveillance data.

BACKGROUND: The association between the frequency of surgeries and the incidence of surgical site infections (SSIs) has been reported for various surgeries. However, no previous study has explored this association among video-assisted thoracic surgeries (VATS). Hence, we aimed to investigate the association between the frequency of surgeries and SSI in video-assisted thoracic surgeries. METHODS: We analyzed the data of 26,878 thoracic surgeries, including 21,154 VATS, which were collected during a national surveillance in Japan between 2014 and 2018. The frequency of surgeries per hospital department was categorized into low (< 50/year), moderate (50-100/ year), and high (> 100/year). Chi-squared test or Fisher's exact test was used for discrete explanatory variables, whereas Wilcoxon's rank-sum test or Kruskal-Wallis test was used for continuous explanatory variables. Univariate analysis of the department groups was conducted to explore confounding factors associated with both SSIs and the department groups. We used a multiple logistic regression model focusing on VATS and stratified by the National Nosocomial Infections Surveillance System (NNIS) risk index. RESULTS: The rates of SSIs in the hospital groups with low, moderate, and high frequency of surgeries were 1.39, 1.05, and 1.28%, respectively. In the NNIS risk index 1 stratum, the incidence of SSIs was significantly lower in the moderate-frequency of surgeries group than that in the other groups (odds ratio [OR]: vs. low-frequency of surgeries: 2.48 [95% confidence interval [CI]: 1.20-5.13], P = 0.0143; vs. high-frequency of surgeries: 2.43 [95% CI: 1.44-4.11], P = 0.0009). In the stratum of NNIS risk indices 2 and 3, the incidence of SSI was significantly higher in the low-frequency of surgeries group (OR: 4.83, 95% CI: 1.47-15.93; P = 0.0095). CONCLUSION: The result suggests that for departments with low-frequency of surgeries, an increase in the frequency of surgeries to > 50 per department annually potentially leads to a decrease in the incidence of SSIs. This occurs through an increase in the experience of the departmental surgeons and contributes to the improvement of VATS outcomes in thoracic surgeries.

Nationwide multicenter questionnaire surveys on countermeasures against antimicrobial resistance and infections in hospitals.

BACKGROUND: The goals of the National Action Plan on Antimicrobial Resistance (AMR) of Japan include "implementing appropriate infection prevention and control" and "appropriate use of antimicrobials," which are relevant to healthcare facilities. Specifically, linking efforts between existing infection control teams and antimicrobial stewardship programs was suggested to be important. Previous studies reported that human resources, such as full-time equivalents of infection control practitioners, were related to improvements in antimicrobial stewardship. METHODS: We posted questionnaires to all teaching hospitals (n = 1017) regarding hospital countermeasures against AMR and infections. To evaluate changes over time, surveys were conducted twice (1st survey: Nov 2016, 2nd survey: Feb 2018). A latent transition analysis (LTA) was performed to identify latent statuses, which refer to underlying subgroups of hospitals, and effects of the number of members in infection control teams per bed on being in the better statuses. RESULTS: The number of valid responses was 678 (response rate, 66.7%) for the 1st survey and 559 (55.0%) for the 2nd survey. More than 99% of participating hospitals had infection control teams, with differences in activity among hospitals. Roughly 70% had their own intervention criteria for antibiotics therapies, whereas only about 60 and 50% had criteria established for the use of anti-methicillin-resistant Staphylococcus aureus antibiotics and broad-spectrum antibiotics, respectively. Only 50 and 40% of hospitals conducted surveillance of catheter-associated urinary tract infections and ventilator-associated pneumonia, respectively. Less than 50% of hospitals used maximal barrier precautions for central line catheter insertion. The LTA identified five latent statuses. The membership probability of the most favorable status in the 2nd study period was slightly increased from the 1st study period (23.6 to 25.3%). However, the increase in the least favorable status was higher (26.3 to 31.8%). Results of the LTA did not support a relationship between increasing the number of infection control practitioners per bed, which is reportedly related to improvements in antimicrobial stewardship, and being in more favorable latent statuses. CONCLUSIONS: Our results suggest the need for more comprehensive antimicrobial stewardship programs and increased surveillance activities for healthcare-associated infections to improve antimicrobial stewardship and infection control in hospitals.

Invasive Haemophilus influenzae type a infection and polyarthritis in a 72-year-old Japanese man: A case report.

Haemophilus influenzae is a small, nonmotile, non-spore-forming bacterium classified into 6 serotypes (a to f) and non-typeable strains that lack a capsule. Although H. influenzae serotype a (Hia) is prevalent in Canada, the United States, Brazil, Australia, across the African continent, and several other locations, it has not been reported in Japan thus far. Our case was of a 72-year-old Japanese man who sought medical consultation after presenting with chills, fever, and polyarthritis. Cultures of blood and synovial fluid from the left knee revealed H. influenzae infection. Diagnostic imaging showed poor contrast regions in both kidneys, fluid retention around both knee joints, the left shoulder joint, and both elbow joints. Subsequently, the patient was diagnosed with invasive H. influenzae infection accompanied by polyarthritis and renal infarction. 16S ribosomal RNA gene sequencing revealed that the bacterial strain was Hia. The patient was treated with antimicrobial agents and arthroscopic curettage. We present a case of invasive Hia infection accompanied by polyarthritis and renal infarction. To the best of our knowledge, this is the first case of Hia infection in Japan. The case is very rare considering that the disease occurred in an elderly patient who developed polyarthritis.

Limitations of Ribotyping as Genotyping Method for Corynebacterium ulcerans.

We conducted molecular typing of a Corynebacterium ulcerans isolate from a woman who died in Japan in 2016. Genomic DNA modification might have affected the isolate's ribotyping profile. Multilocus sequence typing results (sequence type 337) were more accurate. Whole-genome sequencing had greater ability to discriminate lineages at high resolution.

Macrolide-Resistant Bordetella pertussis, Vietnam, 2016-2017.

Macrolide-resistant Bordetella pertussis emerged in Vietnam during 2016-2017. Direct analyses of swab samples from 10 patients with pertussis revealed a macrolide-resistant mutation, A2047G, in the 23S rRNA. We identified the MT104 genotype of macrolide-resistant B. pertussis (which is prevalent in mainland China) and its variants in these patients.

National trend of blood-stream infection attributable deaths caused by Staphylococcus aureus and Escherichia coli in Japan.

There has been scarce evidence about deaths due to blood stream infection (BSI) in Japan so far. The main objective of this study is to understand the epidemiological trend of deaths caused by BSIs due to Staphylococcus aureus and Escherichia coli including Methicillin-resistant S. aureus (MRSA) and fluoroquinolone-resistant E. coli (FQREC) at national level. We annually estimated the number of BSI caused by S. aureus and E. coli between 2011 and 2017 across Japan using comprehensive data of bacterial culturing and drug susceptibilities collected in Japan Nosocomial Infection Surveillance (JANIS). The number of death was estimated by using BSI mortality obtained from previous studies in Japan. The number of BSI death attributable to S. aureus was estimated to 17,412 in 2011 and 17,157 in 2017, respectively, out of the whole population (126.8 million) in Japan. Among them, cases attributed to MRSA accounted for 5924 (34.0%) in 2011, and decreased to 4224 (24.6%) cases in 2017. On the other hand, the number of BSI death attributable to E. coli was estimated to 9044 in 2011 and increased to 14,016 in 2017. Among them, cases attributed to FQREC accounted for 2045 (22.6%) in 2011 and increased to 3915 (27.9%) cases in 2017. The number of BSI death attributable to MRSA has been decreasing and that attributable to FQREC has been increasing. This study provides the first annual estimate of disease burden of BSI caused by antimicrobial resistant (AMR) bacteria in Japan, and basis for formulating health policy to deal with AMR.

Novel Sequence Type in Bacillus cereus Strains Associated with Nosocomial Infections and Bacteremia, Japan.

Bacillus cereus is associated with foodborne illnesses characterized by vomiting and diarrhea. Although some B. cereus strains that cause severe extraintestinal infections and nosocomial infections are recognized as serious public health threats in healthcare settings, the genetic backgrounds of B. cereus strains causing such infections remain unknown. By conducting pulsed-field gel electrophoresis and multilocus sequence typing, we found that a novel sequence type (ST), newly registered as ST1420, was the dominant ST isolated from the cases of nosocomial infections that occurred in 3 locations in Japan in 2006, 2013, and 2016. Phylogenetic analysis showed that ST1420 strains belonged to the Cereus III lineage, which is much closer to the Anthracis lineage than to other Cereus lineages. Our results suggest that ST1420 is a prevalent ST in B. cereus strains that have caused recent nosocomial infections in Japan.

Production and characterization of recombinant P1 adhesin essential for adhesion, gliding, and antigenic variation in the human pathogenic bacterium, Mycoplasma pneumoniae.

Mycoplasma pneumoniae forms an attachment organelle at one cell pole, binds to the host cell surface, and glides via a unique mechanism. A 170-kDa protein, P1 adhesin, present on the organelle surface plays a critical role in the binding and gliding process. In this study, we obtained a recombinant P1 adhesin comprising 1476 amino acid residues, excluding the C-terminal domain of 109 amino acids that carried the transmembrane segment, that were fused to additional 17 amino acid residues carrying a hexa-histidine (6 × His) tag using an Escherichia coli expression system. The recombinant protein showed solubility, and chirality in circular dichroism (CD). The results of analytical gel filtration, ultracentrifugation, negative-staining electron microscopy, and small-angle X-ray scattering (SAXS) showed that the recombinant protein exists in a monomeric form with a uniformly folded structure. SAXS analysis suggested the presence of a compact and ellipsoidal structure rather than random or molten globule-like conformation. Structure model based on SAXS results fitted well with the corresponding structure obtained with cryo-electron tomography from a closely related species, M. genitalium. This recombinant protein may be useful for structural and functional studies as well as for the preparation of antibodies for medical applications.

Mutations in Genes Encoding Penicillin-Binding Proteins and Efflux Pumps Play a Role in ß-Lactam Resistance in Helicobacter cinaedi.

ß-Lactams are often used to treat Helicobacter cinaedi infections; however, the mechanism underlying ß-lactam resistance is unknown. In this study, we investigated ß-lactam resistance in an H. cinaedi strain, MRY12-0051 (MICs of amoxicillin [AMX] and ceftriaxone [CRO], 32 and 128 µg/ml; obtained from human feces). Based on a comparative whole-genome analysis of MRY12-0051 and the CRO-susceptible H. cinaedi strain MRY08-1234 (MICs of AMX and CRO, 1 and 4 µg/ml; obtained from human blood), we identified five mutations in genes encoding penicillin-binding proteins (PBPs), including two in pbpA, one in pbp2, and two in ftsI Transformation and penicillin binding assays indicated that CRO resistance was mainly associated with mutations in pbpA; mutations in ftsI also led to increased resistance to AMX. Knocking out cmeB and cmeD, which encode resistance-nodulation-division-type efflux pump components, in H. cinaedi type strain CCUG18818 (AMX MIC, 4 to 8 µg/ml) resulted in 8- and 64-fold decreases, respectively, in the AMX MIC. Hence, MICs of AMX in H. cinaedi become similar to those of Helicobacter pylori isolates in the absence of cmeD In conclusion, the difference in susceptibility to ß-lactams between H. pylori and H. cinaedi is explained by differences in efflux pump components. Mutations in pbpA are the primary determinant of high resistance to ß-lactams in H. cinaedi.

Distribution and Molecular Characterization of Acinetobacter baumannii International Clone II Lineage in Japan.

Multidrug-resistant (MDR) Acinetobacter spp. have been globally disseminated in association with the successful clonal lineage Acinetobacter baumannii international clone II (IC II). Because the prevalence of MDR Acinetobacter spp. in Japan remains very low, we characterized all Acinetobacter spp. (n = 866) from 76 hospitals between October 2012 and March 2013 to describe the entire molecular epidemiology of Acinetobacter spp. The most prevalent species was A. baumannii (n = 645; 74.5%), with A. baumannii IC II (n = 245) accounting for 28.3% of the total. Meropenem-resistant isolates accounted for 2.0% (n = 17) and carried ISAba1-blaOXA-23-like (n = 10), blaIMP (n = 4), or ISAba1-blaOXA-51-like (n = 3). Multilocus sequence typing of 110 representative A. baumannii isolates revealed the considerable prevalence of domestic sequence types (STs). A. baumannii IC II isolates were divided into the domestic sequence type 469 (ST469) (n = 18) and the globally disseminated STs ST208 (n = 14) and ST219 (n = 4). ST469 isolates were susceptible to more antimicrobial agents, while ST208 and ST219 overproduced the intrinsic AmpC ß-lactamase. A. baumannii IC II and some A. baumannii non-IC II STs (e.g., ST149 and ST246) were associated with fluoroquinolone resistance. This study revealed that carbapenem-susceptible A. baumannii IC II was moderately disseminated in Japan. The low prevalence of acquired carbapenemase genes and presence of domestic STs could contribute to the low prevalence of MDR A. baumannii A similar epidemiology might have appeared before the global dissemination of MDR epidemic lineages. In addition, fluoroquinolone resistance associated with A. baumannii IC II may provide insight into the significance of A. baumannii epidemic clones.

Clinical and Bacteriologic Analysis of Nontypeable Haemophilus influenzae Strains Isolated from Children with Invasive Diseases in Japan from 2008 to 2015.

Haemophilus influenzae type b (Hib) conjugate vaccines have led to dramatic reductions in Hib disease among young children worldwide. Nontypeable H. influenzae (NTHi) is now the major cause of invasive H. influenzae infections. We investigated the clinical characteristics of invasive NTHi diseases among children in Japan, to clarify the pathogenicity of isolated NTHi strains. The mortality rate was 10.7%, with deaths occurring mainly among children with underlying comorbidities. Biotypes II and III were the most common, and most strains (64.3%) had multiple amino acid substitutions at the Asp-350, Ser-357, Ser-385, and/or Met-377 sites of penicillin-binding protein 3. Two strains were ß-lactamase positive and ampicillin-clavulanate resistant. Biofilm indices varied widely, and IS1016 was detected in 10.7% of the strains tested. Moreover, there was wide variation in the characteristics of invasive NTHi strains. NTHi strains, showing great genetic diversity, are responsible for most invasive H. influenzae infections in children in the postvaccine era. Continuous monitoring of NTHi strains responsible for invasive diseases in children is important to detect changes in the epidemiology of invasive H. influenzae infections in the postvaccine era.

Development of vaccine for Clostridium difficile infection using membrane fraction of nontoxigenic Clostridium difficile.

Although standard antibiotic therapy is performed for diarrhea and pseudomembranous colitis caused by Clostridium difficile, a high recurrence rate of C. difficile infection (CDI) remains a major problem. We previously showed that a membrane fraction of nontoxigenic C. difficile (ntCDMF) was effective as a vaccine antigen by in vitro experiments. In this study, we examined whether ntCDMF had an in vivo effect in animal challenge experiments. By intrarectal immunization with ntCDMF, the number of C. difficile cells in feces of mice was decreased approximately 99% compared to the control mice. In addition, survival rate of C. difficile-challenged hamsters was increased almost 30% by immunization with ntCDMF. These results showed that ntCDMF could be a practical vaccine candidate.

Trends and patterns of national antimicrobial consumption in Japan from 2004 to 2016.

Frequent use of broad-spectrum antimicrobial classes has been reported in Japan; however, little is known about the long-term trend of national antimicrobial consumption, and that of individual agents. This study analyzed the national sales data of systemic antimicrobials from 2004 to 2016, derived from the IMS Japan Pharmaceutical Market database, to assess the consumption patterns of antimicrobial classes and agents in Japan. The number of defined daily doses per 1000 inhabitants per day (DID) was calculated for each antimicrobial agent. During the last 13 years, total antimicrobial consumption fluctuated by only 5% around the average of 14.41 DID. In 2016, the most used class was macrolides (32%), followed by cephalosporins (28%) and fluoroquinolones (19%). Oral agents comprised a large proportion (93%) of antimicrobial consumption. The most used agent, clarithromycin, accounted for 25% of all oral compounds used in 2016. The consumption of oral agents with high bioavailability, such as fluoroquinolones, amoxicillin, and sulfamethoxazole/trimethoprim increased, whereas that of cephalosporins decreased. In 2016, ceftriaxone was the most consumed parenteral agent, followed by cefazolin. The consumption of parenteral agents increased after 2009 when high-dose regimens of piperacillin/tazobactam, meropenem, and ampicillin/sulbactam were approved by the health insurance system. National antimicrobial consumption has been stable over the last 13 years. Moreover, shifts in the use of agents with high bioavailability and those approved for high-dose regimens were observed. However, the increased use of broad-spectrum agents is worrisome. A multifaceted approach is required to reduce overall antimicrobial consumption.

Significant Decrease in Pertactin-Deficient Bordetella pertussis Isolates, Japan.

Prevalence of pertactin-lacking Bordetella pertussis isolates has been observed worldwide. In Japan, however, we found that the frequency of pertactin-deficient isolates in 2014-2016 (8%) was significantly lower than the frequency in 2005-2007 (41%), 2008-2010 (35%), and 2011-2013 (25%). This reduction was closely associated with changes in genotypes.