Nasopharyngeal carriage of Streptococcus pneumoniae among children aged 30 days to <60 months in Beijing and Shenzhen, China (2018-2021) during pneumococcal conjugate vaccine introduction and the coronavirus disease (COVID-19) pandemic.

Objectives: To describe the carriage rate, serotype distribution, and antimicrobial susceptibility patterns of Streptococcus pneumoniae (S. pneumoniae) nasopharyngeal (NP) isolates among healthy children aged 30 days to <60 months in the cities of Beijing and Shenzhen during 2018-2021. Methods: A NP swab sample was collected among four annual cohorts of healthy children at routine well-child visits. S. pneumoniae was identified by culture, optochin sensitivity and bile solubility, serotypes determined by latex agglutination and Quellung, and antimicrobial susceptibility testing performed using E-test strips. Results: S. pneumoniae NP carriage was 13.1% (645/4,911), with the highest S. pneumoniae carriage prevalence (15.3%) observed in 25 to <60 months. The carriage prevalence was 15.1% in children 13-24 months, 13.2% in children 7-12 months, and 8.2% in children 30 days to 6 months (P < 0.01). Living with siblings [20.0% vs. 9.4%: OR: 2.42 (95% CI: 2.05-2.87)] or attending day-care [31.8% vs. 11.3%: OR: 3.67 (95% CI: 2.94-4.57)] increased the risk (P < 0.01). During the period (January 2020-April 2021) of strict non-pharmaceutical interventions to prevent and control the COVID-19 pandemic, the proportion of children with S. pneumoniae colonization declined from 16.0% (94/587) to 5.8% (108/1,848) in Beijing while increasing from 14.5% (64/443) to 18.6% (379/2,033) in Shenzhen. Among S. pneumoniae isolates, 36.7% (237/645) belonged to 13-valent pneumococcal conjugate vaccine (PCV13) serotypes, 64.3% (408/645) were non-PCV13 serotypes, including 20.8% (134/645) non-serotypeable S. pneumoniae (NST). A total of 158/644 isolates (24.5%) were MDR. For the PCV13 isolates, MDR was detected in 36.3% (86/237) of isolates; in comparison, 17.6% (72/407) of non-PCV13 serotypes, including NST, were MDR (P < 0.01). S. pneumoniae NP carriage was detected in 10.7% of children with previous pneumococcal vaccination (PCV7 or PCV13 only) compared with 14.9% in children without previous pneumococcal vaccination. Conclusions: The highest S. pneumoniae carriage prevalence were found in the oldest age group (25 to <60 months) and in children living with siblings or attending day-care. Vaccination with PCV7 or PCV13 was associated with lower PCV13-serotype colonization. In Beijing, S. pneumoniae carriage significantly declined during the COVID-19 pandemic.

Non-antibiotic pharmaceutical phenylbutazone binding to MexR reduces the antibiotic susceptibility of Pseudomonas aeruginosa.

Antimicrobial resistance has been an increasingly serious threat to global public health. The contribution of non-antibiotic pharmaceuticals to the development of antibiotic resistance has been overlooked. Our study found that the anti-inflammatory drug phenylbutazone could protect P. aeruginosa against antibiotic mediated killing by binding to the efflux pump regulator MexR. In this study, antibiotic activity against P. aeruginosa alone or in combination with phenylbutazone was evaluated in vitro and in vivo. Resazurin accumulation assay, transcriptomic sequencing, and PISA assay were conducted to explore the underlying mechanism for the reduced antibiotic susceptibility caused by phenylbutazone. Then EMSA, ITC, molecular dynamic simulations, and amino acid substitutions were used to investigate the interactions between phenylbutazone and MexR. We found that phenylbutazone could reduce the susceptibility of P. aeruginosa to multiple antibiotics, including parts of ß-lactams, fluoroquinolones, tetracyclines, and macrolides. Phenylbutazone could directly bind to MexR, then promote MexR dissociating from the mexA-mexR intergenic region and de-repress the expression of MexAB-OprM efflux pump. The overexpressed MexAB-OprM pump resulted in the reduced antibiotic susceptibility. And the His41 and Arg21 residues of MexR were involved in the phenylbutazone-MexR interaction. We hope this study would imply the potential risk of antibiotic resistance caused by non-antibiotic pharmaceuticals.

Seroprevalence of B. pertussis infection and the changes of specific antibody levels in health care workers during the first two years of COVID-19 in Wuhu, China.

BACKGROUND: The reported number of pertussis cases declined after the implementation of COVID-19 prevention and control measures, however, the burden of pertussis among adults in China remains largely unknown. Additionally, the waning of natural antibody level has also rarely been assessed. METHODS: A total of 762 healthcare workers (HCWs) who had underwent the health examinations in 2021 and 2022 were included. Serum anti-PT IgG and IgA levels were determined by ELISA. Recent B. pertussis infection was defined as anti-PT IgG ≥100 IU/ml and/or anti-PT IgA ≥10 IU/ml. RESULTS: In 2021, the seroprevalence of recent B. pertussis infection was 10.1 %, and those HCWs in outpatient department had a higher percentage (18.6 %), and geometric mean concentration (GMC) (6.3 IU/ml) than those in other departments. This seroprevalence decreased to 2.4 % in 2022, although the difference remained significant. In the 77 subjects with recent B. pertussis infection in 2021, anti-PT IgG was undetectable in 18 cases the following year. Majority (68/76) of the subjects with anti-PT IgA ≥10 IU/ml in 2021 no longer had detected this antibody in 2022. Among 95 pertussis cases, approximately 60.0 % of cases reported no history of cough. Among those with a documented cough history, 36 cases with suspected pertussis courses who had never been diagnosed. Prolonged cough with nocturnal exacerbation (29/38) was the most commonly reported clinical symptom, and whoop was confirmed in six cases. Uroclepsia and syncopes during the cough attacks were reported by three and one subjects, respectively. One case presented with subconjunctival hemorrhage and tensionic purpura during the course. CONCLUSIONS: The results suggested a high prevalence of B. pertussis infection among HCWs. The presence of unrecognized adult pertussis cases and the rapid waning of antibody indicate the need to improve clinical management for suspected pertussis in adults, and to updated immunization schedule after childhood program.

[Clinical diagnosis of group A streptococcal pharyngitis and progress in the application of scoring systems]. / A族链球菌咽炎的临床诊断及评分制的应用进展.

Pharyngitis can be caused by various pathogens, including viruses and bacteria. Group A streptococcus (GAS) is the most common bacterial cause of pharyngitis. However, distinguishing GAS pharyngitis from other types of upper respiratory tract infections is challenging in clinical settings. This often leads to empirical treatments and, consequently, the overuse of antimicrobial drugs. With the advancement of antimicrobial drug management and healthcare payment reform initiatives in China, reducing unnecessary testing and prescriptions of antimicrobial drugs is imperative. To promote standardized diagnosis and treatment of GAS pharyngitis, this article reviews various international guidelines on the clinical diagnosis and differential diagnosis of GAS pharyngitis, particularly focusing on clinical scoring systems guiding laboratory testing and antimicrobial treatment decisions for GAS pharyngitis and their application recommendations, providing a reference for domestic researchers and clinical practitioners.

Detection of Bordetella spp. in children with pertussis-like illness from 2018 to 2024 in China.

OBJECTIVE: To evaluate the role of Bordetella pertussis (B. pertussis), B. parapertussis, B. holmesii, and B. bronchiseptica on pertussis resurgence in China, particularly the sharp rise since the latest winter. METHODS: Nasopharyngeal swabs collected from children with pertussis-like illness from January 2018 to March 2024 were cultured to detect B. pertussis, B. parapertussis, B. holmesii, and B. bronchiseptica, and tested for all of these except for B. bronchiseptica using a pooled real-time polymerase chain reaction (PCR) kit targeting insertion sequences ptxS1, IS481, IS1001, and hIS1001. RESULTS: Out of the collected 7732 nasopharyngeal swabs, 1531 cases tested positive for B. pertussis (19.8%, 1531/7732), and 10 cases were positive for B. parapertussis (0.1%, 10/7732). B. holmesii and B.bronchiseptica were not detected. The number of specimens and the detection rate of B. pertussis were 1709 and 26.9% (459/1709) in 2018, 1936 and 20.7% (400/1936) in 2019, which sharply declined to 308 and 11.4% (35/308) in 2020, 306 and 4.2% (13/306) in 2021, and then notably increased to 754 and 17.6% (133/754) in 2022, 1842 and 16.0% (295/1842) in 2023, 877 and 22.3% (196/877) in the first quarter of 2024. The proportion of children aged 3 to less than 6 years (preschool age) and 6 to 16 years (school age) in pertussis cases increased significantly during the study period, especially the proportion of school-aged children increased from 2.0% (9/459) in 2018 to 40.8% (80/196) in 2024. CONCLUSIONS: B. pertussis was the predominant pathogen among children with pertussis-like illness in China, with sporadic detection of B. parapertussis and no detection of B. holmesii or B.bronchiseptica. The preschool and school-age children are increasingly prevalent in B. pertussis infection cases, which may be associated with the latest rapid escalation of pertussis outbreak.

Invasive pneumococcal diseases in Chinese children: a multicentre hospital-based active surveillance from 2019 to 2021.

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

Seroprevalence of tetanus and pertussis antibodies among health care workers in Wuhu, China.

This study aimed to elucidate the seroprevalence of antibodies to tetanus and pertussis among Chinese health care workers. Blood specimens from health care workers were collected during the 2021 annual medical examination at the First People's Hospital of Wuhu. Commercial ELISA kits were employed to quantify serum IgG antibodies against tetanus toxin (anti-TT IgG) and both IgG and IgA antibodies against pertussis toxin (anti-PT IgG, anti-PT IgA). A concentration of anti-TT IgG exceeding 0.1 IU/ml was deemed seroprotective against tetanus, while concentrations of anti-PT IgG ≥ 50 IU/ml or anti-PT IgA ≥ 15 IU/ml were indicative of a prior pertussis infection. The overall seroprotective rate for anti-TT IgG stood at 10.43% (92/882), with the highest seroprotective rate (13.91%) in the 20-29 age group, followed by the 30-39 age group (10.57%), 40-49 age group (5.80%), and 50-59 age group (5.63%). Eighteen (2.04%) of the studied subjects were positive to anti-PT IgG, and the positive rate in 20-39 age group and 40-59 age group was 1.19% (8/673) and 4.78% (10/209), respectively. Thirty (3.40%) subjects displayed anti-PT IgG levels ≥100 IU/ml and/or anti-PT IgA ≥ 15 IU/ml, suggesting a recent pertussis infection within the preceding year. Over half (503/882, 57.03%) had undetectable anti-PT IgG antibodies. The majority of health care workers in China appear susceptible to tetanus and pertussis, and a significant subset has experienced pertussis infection. The implementation of booster vaccinations against these diseases for Chinese health care workers is recommended.

[Research progress on the mechanism of -lactam resistance in group A Streptococci in vivo]. / Aæ—é“¾çƒèŒä½“å† è€å—-å† é °èƒºç±»è¯ç‰©çš„æœºåˆ¶ç ”ç©¶è¿›å±•.

-lactams, including penicillin, have been used for over 80 years in the treatment of group A Streptococcus (GAS) infections. Although -lactam-resistant GAS strains have not been identified in vitro tests, clinical treatment failures have been reported since the 1950s. The mechanism underlying the clinical failure of -lactam treatment in GAS infections remains unclear. Previous research has suggested that -lactam resistance in GAS in vivo is associated with reduced drug susceptibility of strains, bacterial inoculation effects, biofilm formation, the effect of coexisting bacteria, bacterial persistence, and bacterial internalization into host cells. This article reviews the main reports on -lactam treatment failure in GAS infections and analyzes the possible mechanisms of -lactam resistance in vivo. The findings aim to contribute to future research and clinical approaches in the field.

Rapid and sensitive detection of nucleic acids using an RAA-CRISPR/Cas12b one-pot detection assay (Rcod).

Rapid, sensitive and specific methods are crucial for nucleic acid detection. CRISPR/Cas12b has recently been widely used in nucleic acid detection. However, due to its thermophagic property, DNA isothermal recombinase-aided amplification (RAA) and subsequent CRISPR/Cas12b detection require two separate reactions, which is cumbersome and inconvenient and may cause aerosol pollution. In this study, we propose an RAA-CRISPR/Cas12b one-pot detection assay (Rcod) for Bordetella pertussis detection without additional amplification product transfer steps. The time from sample processing to response time was less than 30 min using nucleic acid extraction-free method, and the sensitivity reached 0.2 copies/µL. In this system, Alicyclobacillus acidoterrestris Cas12b protein (AacCas12b) exhibited strong and specific trans-cleavage activity at a constant temperature of 37 °C, while the cis-cleavage activity was weak. This characteristic reduces the interference of AacCas12b with nucleic acids in the system. Compared with real-time PCR, our Rcod system detected B. pertussis in 221 clinical samples with a sensitivity and specificity of 97.96 % and 99.19 %, respectively, with nucleic acid extraction-free method. The rapid, sensitive and specific Rcod system provides ideas for the establishment of CRISPR-based one-step nucleic acid detection and may aid the development of reliable point-of-care nucleic acid tests. IMPORTANCE: Pertussis is an acute respiratory infection caused by B. pertussis that is highly contagious and potentially fatal, and early diagnosis is essential for the treatment of whooping cough. In this study, we found that AacCas12b has high and strongly specific trans-cleavage activity at lower temperatures. A RAA-CRISPR/Cas12b one-step detection platform (Rcod) without interference with amplification was developed. In addition, the combination of Rcod and nucleic acid extraction-free method can quickly and accurately detect the qualitative detection of B. pertussis, and the detection results are visualized, which makes the pathogen nucleic acid detection and analysis process simpler, and provides a new method for the rapid clinical diagnosis of B. pertussis.

Differences in the effects of Bordetella pertussis and respiratory syncytial virus infection on the composition of nasopharyngeal flora in neonates.

Introduction: Bordetella pertussis and respiratory syncytial virus (RSV) are important pathogens causing cough in neonates. Few studies have investigated the differences in the effects of these two specific infections on respiratory flora. The aim of this study was to explore whether infections with Bordetella pertussis and RSV have different effects on respiratory floral composition in neonates. Methods: Nasopharyngeal respiratory flora was assessed by 16S ribosomal RNA amplification and V3-V4 region sequencing. Shannon and Simpson indices were calculated to determine the α diversity and principal coordinate analysis was performed to determine the ß diversity. Results: In total, 111 hospitalized neonates were divided into the pertussis (n = 29), RSV (n = 57), and control groups (n = 25) according to the pathogens detected. The relative abundance of Bordetella was significantly higher in the pertussis group (median: 19.18%, interquartile range: 72.57%). In contrast, this species was not detected in the other two groups. In the RSV group, the relative abundance of Streptococcus (median: 77.15%, interquartile range: 45.84%) was significantly higher than those in the pertussis and control groups (both P < 0.001). The α diversity of the RSV group was significantly lower than that of the control group (P < 0.001). Moreover, no statistically significant differences in the Shannon and Simpson indices were observed between the pertussis and control groups (P = 0.101 and P = 0.202, respectively). Principal coordinate analysis revealed a large overlap between the pertussis and control groups and a significant distance between the RSV and control groups without any overlap. Discussion: Thus, the effects of infections with the two species, B. pertussis and RSV, impacted the diversity of nasopharyngeal flora differently. The principles underlying the difference in the effects of different pathogens on microbial flora require further investigation.

[Recent research on the epidemiology and preventive strategies of neonatal group B Streptococcus infection in the latest decade]. / 新生儿Bæ—é“¾çƒèŒæ„ŸæŸ“æµè¡Œç— å­¦å’Œé¢„é˜²ç­–ç•¥è¿‘åå¹´æ¥çš„ç ”ç©¶è¿›å±•.

Currently, the main strategy for preventing neonatal group B Streptococcus (GBS) infection is prenatal screening combined with intrapartum antibiotic prophylaxis, which has effectively reduced the incidence of neonatal GBS early-onset disease. However, the burden of GBS infection is still significant. The intrapartum antibiotic prophylaxis strategy has limitations such as inducing antibiotic resistance and inability to effectively prevent GBS late-onset disease. It is crucial to develop and evaluate other prevention strategies, while paying close attention to assessing penicillin allergy in pregnant women and how to prevent GBS infection in neonates with negative maternal GBS screening. In recent years, there has been some progress in GBS vaccines and related immunological research, and the use of specific vaccines is expected to significantly reduce GBS infection in neonates.