Routine nasogastric tube placement after gastric endoscopic full-thickness resection of tumor size ≤ 2 cm may be unnecessary: a propensity score-matching analysis.

BACKGROUND: Endoscopic full-thickness resection is a common endoscopic procedure for treating gastrointestinal submucosal tumors. Nasogastric tube placement is frequently performed after abdominal surgery, but the routine use of this approach remains controversial. The aim of this research was to explore whether nasogastric tube placement after gastric endoscopic full-thickness resection is necessary. METHODS: A retrospective study enrolled patients who underwent gastric endoscopic full-thickness resection in our hospital between January 2014 and January 2019, and all the patients had a tumor size ≤ 2 cm. The patients were divided into two groups according to whether a nasogastric tube was placed. Postprocedural adverse events and hospital stay duration were compared between the two groups using 1:1 propensity score matching. RESULTS: A total of 461 patients were enrolled in this study, including 385 patients in the nasogastric tube group (NGT group) and 76 patients in the non-nasogastric tube group (non-NGT group). After matching, the baseline characteristics of 73 patients in the NGT group and 73 patients in the non-NGT group were balanced (p > 0.05). The postprocedural fever rate in the NGT group was significantly higher than that in the non-NGT group (23.3% vs. 9.6%, p = 0.044). 6.9% (5/73) of patients experienced severe nasogastric tube-related throat discomfort. However, the duration of hospitalization stay was not different between the two groups. CONCLUSIONS: For patients with tumor size ≤ 2 cm, routine nasogastric tube placement after gastric endoscopic full-thickness resection may be unnecessary.

Genotyping and macrolide-resistant mutation of Bordetella pertussis in East and South-East Asia.

OBJECTIVES: Macrolide-resistant Bordetella pertussis (MRBP) has been emerging and prevailing in mainland China since 2011. In this study, we aimed to investigate the genotype and macrolide resistance of circulating B. pertussis in East and Southeast Asia using genetic analyses. METHODS: A total of 302 DNA extracts from clinical specimens and isolates from 2010 to 2020 were analyzed: 145 from Vietnam, 76 from Cambodia, 48 from Taiwan, and 33 from Japan. Genotypes were determined by multilocus variable-number tandem-repeat analysis (MLVA). Macrolide-resistant A2047G mutation in B. pertussis 23S rRNA was investigated using the duplex Cycleave real-time polymerase chain reaction (PCR) assay. Whole-genome sequencing was performed on two MRBP isolates that were identified for the first time in Taiwan. RESULTS: Overall, 286 DNA extracts (95%) generated a complete MLVA genotype and 283 DNA extracts (94%) yielded a complete result for the A2047G mutation analysis. The A2047G mutation was detected in 18 DNA extracts: fourteen from Vietnam, one from Cambodia, two from Taiwan, and one from Japan. Most of them (78%) showed the genotypes MT104 and MT195, which have previously been reported in Chinese MRBP isolates. Further, the Taiwanese MRBP isolates were classified into the MT104 clade of Chinese MRBP isolates. CONCLUSION: After MRBP emerged and spread in mainland China, it may have spread to East and Southeast Asia in the 2010s. Continued surveillance targeting the A2047G mutation of MRBP is needed to prevent further spread of this emerging pathogen.

Rapid and simple SNP genotyping for Bordetella pertussis epidemic strain MT27 based on a multiplexed single-base extension assay.

Multilocus variable-number tandem repeat analysis (MLVA) is widely used for genotyping of Bordetella pertussis, the causative bacteria for pertussis. However, MLVA genotyping is losing its discriminate power because prevalence of the epidemic MT27 strain (MLVA-27) is increasing worldwide. To address this, we developed a single nucleotide polymorphism (SNP) genotyping method for MT27 based on multiplexed single-base extension (SBE) assay. A total of 237 MT27 isolates collected in Japan during 1999-2018 were genotyped and classified into ten SNP genotypes (SG1 to SG10) with a Simpson's diversity index (DI) of 0.79 (95% CI 0.76-0.82). Temporal trends showed a marked increase in the genotypic diversity in the 2010s: Simpson's DI was zero in 1999-2004, 0.16 in 2005-2009, 0.83 in 2010-2014, and 0.76 in 2015-2018. This indicates that the SNP genotyping is applicable to the recently circulating MT27 strain. Additionally, almost all outbreak-associated MT27 isolates were classified into the same SNP genotypes for each outbreak. Multiplexed SBE assay allows for rapid and simple genotyping, indicating that the SNP genotyping can potentially be a useful tool for subtyping the B. pertussis MT27 strain in routine surveillance and outbreak investigations.

A novel multilocus variable-number tandem repeat analysis for Bordetella parapertussis.

Purpose. Human-adapted Bordetella parapertussis is one of the causative agents of whooping cough; however, there are currently no genotyping systems with high discriminatory power for this bacterial pathogen. We therefore aimed to develop a multilocus variable-number tandem repeat analysis (MLVA) for human-adapted B. parapertussis.Methodology. Four highly polymorphic variable number tandem repeat (VNTR) loci in the B. parapertussis genome were selected and amplified by multiplex PCR. MLVA was performed based on the number of tandem repeats at VNTR loci. The discriminatory power of MLVA was evaluated with three laboratory reference strains and 50 human isolates of B. parapertussis.Results. Multiplex PCR-based MLVA characterized 53 B. parapertussis reference strains and isolates into 25 MLVA types and the Simpson diversity index was 0.91 (95 % confidence interval, 0.86-0.97). The three reference strains exhibited different MLVA types. Thirty-one Japanese isolates, ten French isolates and three Taiwanese isolates belonged to fourteen, nine and three MLVA types, respectively. In contrast, all five Australian isolates belonged to the same type. Two Japanese isolates collected from patients with known epidemiological links had the same type.Conclusion. Our novel MLVA method has high discriminatory power for genotyping human B. parapertussis. Regarding this organism, this genotyping system is a promising tool for epidemiological surveillance and investigating outbreaks.

Successful Control of Streptococcus pneumoniae 19A Replacement With a Catch-up Primary Vaccination Program in Taiwan.

BACKGROUND: Streptococcus pneumoniae infections in Taiwan mostly occur in children aged 2-4 years. Because of a significant increase in the incidence of serotype 19A-related infections, the 13-valent pneumococcal conjugate vaccine (PCV13) was initially introduced in the national immunization program for children 2-5 years of age, prior to the national programs for infants. We have assessed the impact of such vaccination programs in reducing the incidence of invasive pneumococcal disease (IPD) in Taiwanese children. METHODS: We analyzed the national data on IPDs from the Taiwan Centers for Disease Control between 2008 and 2017. We calculated the incidence rates of IPD and incidence rate ratios (IRRs) between years for different serotypes to estimate the effectiveness of the vaccination programs. RESULTS: The national catch-up primary vaccination schedule successfully reduced the incidence rate of IPD from 17.8/100 000 in 2012 to 5.5/100 000 in 2017 among children aged 0-5 years. The IRR (2017 over 2012) was 0.31, corresponding to a 69% reduction. A modest herd effect was also observed, with a 37% reduction in the incidence of IPD in elderly people (≥70 years) from 2012 to 2017. The incidence of IPD caused by serotype 19A in children aged 0-5 years was reduced by 32.6-44.3% yearly from 2012 to 2017. In 2015, serogroup 15 outnumbered 19A, to become the leading serotypes in children 0-5 years old. CONCLUSIONS: Special catch-up vaccination programs starting from children 2-5 years of age with PCV13 have been highly effective in reducing the incidence of IPD, especially as caused by serotype 19A, in Taiwanese children.

National surveillance of invasive pneumococcal diseases in Taiwan, 2008-2012: differential temporal emergence of serotype 19A.

INTRODUCTION: Serotype replacement after the introduction of seven-valent pneumococcal conjugate vaccine (PCV7) and the future availability of multivalent PCVs prompted the listing of invasive pneumococcal disease (IPD) as a notifiable disease in Taiwan in October 2007. Here, we report the national surveillance results. METHODS: The study population comprised the whole nation of Taiwan from 2008 to 2012. Restricting to cases with viable isolates, we calculated the incidence, case fatality ratio, prevalence of serotype 19A, and percentage of vaccine preventable IPD. RESULTS: 3659 cases of IPD were identified yielding an incidence of 3.2 per 100,000 population; the highest incidence was among children aged 2-4 years (21.1 per 100,000 population). The case fatality ratio was 9.2% and the highest ratio was among adults aged ≥75 years (19.0%). The percentage of PCV7 preventable IPD decreased for all age groups, especially sharply among children aged 2-4 years, from 65.8% in 2008 to 12.9% in 2012. The prevalence of serotype 19A increased from 5.5% in 2008 to 25.3% in 2012 among all Streptococcus pneumoniae, displaying a differential temporal emergence among different age groups. Serotype 19A became the most prevalent serotype among children aged <2 years in 2009, children aged 2-4 and 5-17 years in 2010, and adults aged 18-49 years in 2012. CONCLUSIONS: The incidence of IPD fluctuated during the study period, with ongoing decrease due to PCV7 vaccine serotypes and increase due to non-vaccine serotypes. Serotype 19A became the most prevalent serotype in 2010 among all S. pneumoniae.

Global population structure and evolution of Bordetella pertussis and their relationship with vaccination.

Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343 B. pertussis strains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in which B. pertussis and the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines. IMPORTANCE Whooping cough is mainly caused by Bordetella pertussis, and current vaccines are targeted against this organism. Recently, there have been increasing outbreaks of whooping cough, even where vaccine coverage is high. Analysis of the genomes of 343 B. pertussis isolates from around the world over the last 100 years suggests that the organism has emerged within the last 500 years, consistent with historical records. We show that global transmission of new strains is very rapid and that the worldwide population of B. pertussis is evolving in response to vaccine introduction, potentially enabling vaccine escape.

Antimicrobial susceptibility testing of Bordetella pertussis in Taiwan prompted by a case of pertussis in a paediatric patient.

In Taiwan, pertussis is a notifiable disease with a low incidence in recent years, and antimicrobial susceptibility testing for the causative agent, Bordetella pertussis, has not been reported to date. In May 2007, the Centers for Disease Control, Taiwan, was informed of a 1-month-old pertussis patient who did not respond to erythromycin treatment. In this study, we report the result of antimicrobial susceptibility testing performed for the suspected erythromycin-resistant isolate, as well as for an additional 27 B. pertussis clinical isolates that represented almost all epidemiologically unrelated isolates obtained throughout Taiwan between 2003 and 2007. All isolates were fully susceptible to azithromycin, erythromycin, clarithromycin and trimethoprim/sulfamethoxazole (MIC < or =0.047 mug ml(-1)). This result demonstrates the general susceptibility of B. pertussis to antimicrobial agents in vitro in Taiwan.

An OXA-66/OXA-51-like carbapenemase and possibly an efflux pump are associated with resistance to imipenem in Acinetobacter baumannii.

We investigated the mechanisms involved in imipenem resistance in 23 clinical strains of Acinetobacter baumannii. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of a 30-kDa protein in imipenem-intermediate A. baumannii (IIAB) and imipenem-resistant A. baumannii (IRAB) strains; this protein was almost undetectable in imipenem-susceptible A. baumannii (ISAB) strains. The 30-kDa protein was identified as an OXA-51-like carbapenemase using two-dimensional gel electrophoresis and mass spectrometry. Similar to other recent findings, bla(OXA-51-like) genes were found to exist in all 23 clinical strains; however, the transcript levels of bla(OXA-51-like) in the IIAB and IRAB were higher than in the ISAB strains using reverse transcriptase PCR (RT-PCR) and real-time RT-PCR assays. This change was due to the presence of an insertion sequence, ISAba1, upstream of bla(OXA-51-like) in the IIAB and IRAB strains that was not present in the ISAB strains. The introduction of bla(OXA-66) (a bla(OXA-51)(-like) gene), identified in ISAB ab1254 and IRAB ab1266, into Escherichia coli TOP10 cells resulted in 3.95-fold and 7.90-fold elevations in resistance to imipenem, respectively. Furthermore, when ISAB ab8 and ISAB ab1254 and their in vitro-selected imipenem-resistant mutants ISAB ab8(r) and ISAB ab1254(r) were compared, the results showed no change in the bla(OXA-66)/bla(OXA-51-like) gene sequences, in expression of the gene, and in the outer membrane protein profiles. However, there was a four- to eightfold reduction in imipenem resistance upon adding carbonyl cyanide m-chlorophenylhydrazone. Taken together, these results suggest that the OXA-66/OXA-51-like carbapenemase contributes to intrinsic resistance to imipenem; however, drug export by an efflux pump may be more important and/or occur more frequently in imipenem-resistant A. baumannii. Furthermore, this is the first report of a Taiwanese strain of an OXA-66/OXA-51-like carbapenemase that confers imipenem resistance in A. baumannii.

Molecular epidemiology of group A streptococcus causing scarlet fever in northern Taiwan, 2001-2002.

In this study, 830 Streptococcus pyogenes isolates collected between 2001 and 2002 from patients with scarlet fever in northern Taiwan were analyzed by M protein gene (emm) sequence typing, pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing. A total of 21 emm types and 56 PFGE patterns were identified. The most frequent emm types were emm1 (29.2%), emm4 (24.1%), emm12 (19.0%), emm6 (15.8%), stIL103 (5.7%), and emm22 (1.9%). Antimicrobial resistance profiles were determined, and resistance to erythromycin (24.6%), clindamycin (2.0%), and chloramphenicol (1.3%) was detected. Five major emm types (emm4, emm12, emm1, emm22, and emm6) accounted for 95.6% of the erythromycin-resistant isolates. The decreased prevalence of erythromycin-resistant emm12 strains coincided with the overall decrease in erythromycin resistance from 32.1% in 2001 to 21.1% in 2002 in Taiwan. Five major clones (emm4/2000, emm12/0000, emm4/2010, emm1/1000, and emm22/8100) represented 72.1% of the erythromycin-resistant isolates. The survey of group A Streptococcus emm types, genetic diversity, and antibiotic resistance has direct relevance to current antimicrobial use policies and potential vaccine development strategies.

Epidemiological shift in the prevalence of pertussis in Taiwan: implications for pertussis vaccination.

In Taiwan, routine pertussis immunization has been implemented for more than 40 years and a low incidence of pertussis was maintained until an 80-fold increase in cases occurred in 1992. The unexpected increase emphasized the significance of pertussis. This study evaluated a total of 2452 reported cases of pertussis during 1993-2004 and surveillance data on incidence, age distribution and seasonality. The highest morbidity was in infants aged <1 year, and upward trends in the incidence of pertussis were significant for infants aged <1 year and adolescents aged 10-14 years. The highest mean number of cases was observed in August and upward trends were in colder months. This study indicates that the epidemiology of pertussis may have been changed by waning immunity in Taiwan. Increased surveillance activities, especially in older age groups, and additional booster doses of acellular pertussis vaccine for children aged 6-8 years and adolescents/young adults aged 15-20 years are necessary to control and prevent pertussis.

Molecular epidemiology of Bordetella pertussis in Taiwan, 1993-2004: suggests one possible explanation for the outbreak of pertussis in 1997.

Pertussis reemerges periodically despite high pertussis vaccination coverage in many countries. We used prn and fim3 gene sequences and pulsed-field gel electrophoresis (PFGE) to analyze the molecular epidemiology of 168 clinical isolates of Bordetella pertussis during 1993-2004, and deduced possible reasons for an outbreak in 1997 in Taiwan. In Taiwan, during 1996-1997, a shift of prn1 to prn2 was reflected in a transition of PFGE group I to group IIIa; during 2000-2001, the change from fim3A to fim3B was displayed in transition of PFGE group IIIa to group IIIb. These changes were also consistent with the two peaks of pertussis incidence in 1997 and 2000. In 1997, a larger than expected increase in the incidence of pertussis occurred and isolates were characterized by complicated pulsotypes, appearance of many new profiles and an unusual presence of prn3. Based on a high resemblance of PFGE profiles and the same virulence genes, a similar shift of circulating strains was observed in European countries as well as Taiwan; thus, the high incidence of pertussis in 1997 may be due to an international expansion of B. pertussis strains from a similar source. This study provides further elucidation of the global molecular epidemiology of B. pertussis.

Surveillance of invasive Streptococcus pneumoniae in Taiwan, 2002-2003.

A total of 522 Streptococcus pneumoniae invasive isolates from diverse sources were collected from January 2002 to December 2003 in Taiwan in order to understand the serotype distribution of invasive isolates in Taiwan. The most frequently isolated serotypes of S. pneumoniae were types 14 (18.4%), 23F (15.1%), 3 (13.8%), 19F (13.4%), 6B (8.2%), 9V (3.6%) and 4 (2.5%). The majority of cases were either under 5 years of age (24.1%) or older than 65 years (36.6%). Serotype distribution in adults aged over 14 years and children aged under 2 years was similar, except for that of type 3, which was more prevalent in adults. Penicillin-non-susceptible strains accounted for 67.7% of all strains and were the predominant strains of serotypes 23F, 19F, 6B and 14. Most strains were susceptible to cephem drug, 85.7% of isolates were susceptible to cefotaxime and 92.9% were susceptible to ceftriaxone. A total of 72.6% (379/522) of the isolates were resistant to at least two antibiotics. The 23-valent vaccine in the current commercial market would cover 87.2% of the serotypes and 100% of the penicillin-non-susceptible serotypes of S. pneumoniae in Taiwan. The coverage of 7- and 11-valent protein conjugate vaccines of the serotypes in children under 2 years of age would be 78.8 and 86.5%, respectively. These results will help to assess the adequacy of the vaccine formulations marketed in Taiwan.

Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan.

BACKGROUND: Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001-2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern. METHODS: Neisseria meningitidis isolates from patients with meningococcal disease from 1996 to 2002 were collected and characterized by serogrouping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The genetic relatedness and clonal relationship between the isolates were analyzed by using the PFGE patterns and the allelic profiles of the sequence types (STs). RESULTS: Serogroups A, B, C, W135, Y, and non-serogroupable Neisseria meningitidis were, respectively, responsible for 2%, 50%, 2%, 35%, 9%, and 2% of 158 culture-confirmed cases of meningococcal disease in 1996-2002. Among 100 N. meningitidis isolates available for PFGE and MLST analyses, 51 different PFGE patterns and 30 STs were identified with discriminatory indices of 0.95 and 0.87, respectively. Of the 30 STs, 21 were newly identified and of which 19 were found in serogroup B isolates. A total of 40 PFGE patterns were identified in 52 serogroup B isolates with the patterns distributed over several distinct clusters. In contrast, the isolates within each of the serogroups A, C, W135, and Y shared high levels of PFGE pattern similarity. Analysis of the allelic profile of the 30 STs suggested the serogroup B isolates be assigned into 5 clonally related groups/ clonal complexes and 7 unique clones. The ST-41/44 complex/Lineage 3, and the ST-3439 and ST-3200 groups represented 79% of the serogroup B meningococci. In contrast, isolates within serogroups A, serogroup W135 (and C), and serogroup Y, respectively, simply belonged to ST-7, ST-11, and ST-23 clones. CONCLUSION: Our data suggested that serogroup B isolates were derived from several distinct lineages, most of which could either be indigenous or were introduced into Taiwan a long time ago. The serogroup A, W135 (and C), and Y isolates, respectively, belonged to the ST-7, ST-11, and ST-23, and the represented clones that are currently the major circulating clones in the world and are introduced into Taiwan more recently. The emergence of serogroup A, C and Y strains contributed partly to the increase in cases of meningococcal disease in 2001-2002.

Antigenic divergence of Bordetella pertussis isolates in Taiwan.

In recent studies, antigenic divergence has been observed in Bordetella pertussis circulating isolates. We collected 80 Bordetella pertussis isolates in Taiwan from 1998 to 2004 and analyzed them using a combination of pulsed-field gel electrophoresis (PFGE) and sequencing of the ptxS1 and prn genes. The incidence of pertussis increases every 3 years, and most of the isolates prevalent since 1998 have expressed nonvaccine ptxS1A and prn2 alleles. Through PFGE analysis, all isolates could be classified into four major groups, and the incidence of these groups exhibited a correlation with the prn allele expressed by the isolates. We found that PFGE is more discriminative than gene sequencing, since it could divide the isolates expressing the prn2 allele into two groups: one group circulating from 1998 to 2001 and another group circulating from 2001 to 2004. The transition between the two groups in 2000 coincided with an outbreak of 326 cases. This research indicates that the antigenic divergence of B. pertussis circulating isolates has evolved over time in Taiwan. Such information will have implications for vaccine policy in Taiwan.