Objective:To evaluate age-specific measles antibody dynamics and identify population immunity gaps in Youyang County, China, approximately two decades after the introduction of a two-dose measles-containing vaccine (MCV) schedule at 8 and 18 months of age. Methods:A cross-sectional serosurvey was conducted among residents without rash in 2025. Measles-specific IgG antibodies were quantified using enzyme-linked immunosorbent assay (ELISA), with seroprevalence defined as >200 mIU/mL. Seroprevalence and geometric mean concentrations (GMCs) were analyzed across eight age strata. Results:Among 608 participants, the crude overall seroprevalence was 76.5% (IPW-adjusted rate: 81.5%), with significant age-specific variation (p < 0.001). The lowest levels were observed in infants aged <8 months (36.5, 95%CI: 26.2-47.9; GMC: 120.47 mIU/mL). Following two vaccine doses, peak immunity was achieved in children aged 18 months to <6 years (>95%; GMC: 730.99-1044.61 mIU/mL). Seroprevalence then reached a distinct nadir in adults aged 18-<40 years (65.6, 95% CI: 50.9-77.9; GMC: 330.48 mIU/mL), before rebounding in older adults aged ≥40 years (90.1-93.5%). Conclusion:This investigation revealed a distinct immunity gap, with measles adjusted seroprevalence at 36.5% (95% CI: 26.2-47.9) in infants under 8 months and 65.6% (95% CI: 50.9-77.9) in reproductive-aged adults, despite robust post-vaccination responses in young children. This serological pattern may be a common characteristic in populations that complete two-dose MCV immunization by 18 months of age and experience persistently low measles incidence.
In the early stages of pertussis,timely initiation of effective antibacterial treatment(including prophylactic medication before symptom onset)can halt disease progression.In China,where measures such as maternal immunization are currently lacking,this remains a crucial approach to preventing severe illness and death from infant pertussis.However,a clear and unified time-based standard defining this"early stage"is lacking,and few studies focus on diagnostic strategies targeting early treatment.Based on the natural disease course of pertussis and limited clinical evidence,a time criterion of within 7 days from illness onset is proposed in this article for early diagnosis of pertussis.Strategies to promote early diagnosis are discussed:raising public awareness to encourage early medical consultation for infant pertussis;enhancing clinical recognition to facilitate early suspicion and testing;emphasizing the cough history of close contacts;identifying early clinical features such as the triad of afebrile status,rhinorrhea,and cough;noting significant increases in white blood cell count and/or lymphocyte proportion in routine blood tests;prioritizing etiological methods for diagnosis or exclusion;and urging health authorities to establish coordinated active surveillance and screening mechanisms between hospitals and disease control institutions.This article aims to support clinical research,standardize early diagnosis,antimicrobial treatment,and chemoprophylaxis of pertussis,and ultimately minimize severe cases and deaths in infants.
Background Pneumococcal conjugate vaccines (PCVs) have substantially reduced vaccine-serotype disease in settings with high vaccine coverage and publicly funded immunisation programmes. In mainland China, PCV13 has remained outside the National Immunization Program, with uptake largely voluntary, paid for out of pocket, and geographically uneven. We aimed to characterise long-term changes in pneumococcal serotype distribution, antimicrobial resistance, and genomic population structure among paediatric clinical S. pneumoniae isolates, with particular focus on non-PCV13 lineages. Methods We conducted a hospital-based genomic surveillance study using archived clinical S. pneumoniae isolates recovered during routine diagnostic testing from hospitalised children at Beijing Children’s Hospital between March 2013 and March 2026. One isolate per patient was included. Serotypes were determined by Quellung reaction, antimicrobial susceptibility to 23 agents was assessed by broth microdilution, and whole-genome sequencing was used for GPSC assignment, core-genome phylogenetic analysis, and virulence-associated gene screening. Temporal trends in non-PCV13 representation were assessed using logistic regression across two-year intervals. Findings Overall, 1049 non-duplicate clinical isolates were included. PCV13 serotypes accounted for 833 isolates (79·4%), remaining above 80% in all intervals from 2013-14 to 2021-22 before declining to 59·4% in 2023-24 and 60·7% in the partial 2025-26 interval. The odds of an isolate being classified as non-PCV13 increased across successive two-year intervals (OR 1·26, 95% CI 1·17-1·36; p<0·001) and remained significant after multivariable adjustment. Under CLSI oral breakpoints, resistance to penicillin and cefuroxime was more frequent among PCV13-serotype than non-PCV13 isolates (penicillin, 86·8% vs 41·2%; cefuroxime, 89·3% vs 44·9%), although resistance among non-PCV13 isolates was heterogeneous. The increase in non-PCV13 isolates was lineage structured, with isolates concentrated within recurrent non-PCV13-associated GPSCs rather than broadly distributed across PCV13-associated lineages. Among 32 non-PCV13 GPSC152 isolates, resistance to penicillin and cefuroxime under oral breakpoints was 87·5% and 100%, respectively, and 84·4% carried a complete PI-1 gene set. Interpretation PCV13 serotypes remained predominant among paediatric clinical pneumococcal isolates in this setting of incomplete and geographically uneven PCV13 uptake, although their contribution declined in recent years as non-PCV13 isolates became more frequent. This increase was lineage structured, and some non-PCV13 lineages, particularly the 15B/15C-associated GPSC152 lineage, combined substantial antimicrobial resistance with frequent carriage of virulence-associated genes. The continued burden of PCV13 serotypes supports broader PCV implementation in China. The diversity of non-PCV13 lineages highlights the need for higher-valency and serotype-independent vaccine strategies, together with integrated serotype, antimicrobial susceptibility, and genomic-lineage surveillance.
Sepsis, marked by hyperinflammation and subsequent immunosuppression, lacks effective phase-specific therapies. Although anisodamine hydrobromide (Ani HBr) reduced 28-day mortality in our prior trial, its mechanisms remained unclear. Here, we integrated network pharmacology, machine learning, immunological profiling, molecular simulations, and single-cell transcriptomics to elucidate Ani HBr's multi-target actions. Among 30 cross-species targets, ELANE and CCL5 emerged as core regulators via protein interaction networks, survival modeling (AUC: 0.72-0.95), and statistical significance (p < 0.05). Ani HBr inhibited ELANE-driven NET formation (HR = 1.176), associated with immunosuppression and endothelial damage, while enhancing CCL5-related cytotoxic T-cell recruitment (HR = 0.810). Docking and dynamics simulations showed Ani HBr binds ELANE's catalytic cleft, suggesting direct inhibition of its enzymatic activity, and interacts stably with CCL5 at potential receptor-binding interfaces, indicating a modulatory role. Single-cell analysis revealed ELANE upregulation in CCI-phase neutrophils and widespread yet stage-specific CCL5 expression. These findings support Ani HBr as a phase-tailored agent that targets ELANE in early hyperinflammation while preserving CCL5-mediated immunity. The ELANE/CCL5 prognostic model offers a framework for precision immunotherapy in sepsis.
Objectives: China was once a country with a high incidence of pertussis, with reported incidence rates exceeding 100 per 100,000 before the introduction of the pertussis vaccine. After the widespread implementation of the pertussis vaccination program, reported cases of pertussis significantly decreased. This study aimed to investigate the serological prevalence of pertussis among school-age children during the administration of the whole-cell pertussis (wP) vaccine in China. Methods: We selected a representative random sample from different schools, with the inclusion criteria being school-age children without clinical symptoms of pertussis. A total of 368 frozen serum samples were obtained from children aged 6–<18 years at various schools in Guizhou in November 2005 and subsequently analyzed. Results: The positive rate of anti-pertussis toxin (PT) IgG antibodies (>62.5 IU/mL) were 4.9% (16/368) among school-age children. The positive rates of anti-PT IgG antibodies were 3.3%, 3.8%, 4.0%, 3.3%, and 10.8% in children aged 6–<8 y, 8–<10 y, 10–<12 y, 12–<14 y, and 14–<18 y, respectively. The increase in PT-IgG antibody levels among older children was likely due to pertussis infection in these school-age children. The positive rate of anti-PT IgG varied between different schools. The pertussis antibody levels of adolescents aged 14–<18 y were significantly higher than those of school-age children in the younger age group (6–<8 y and 8–<10 y) (p = 0.0097 and p = 0.0007, respectively). Conclusions: During the era of wP vaccine use, pertussis infections were common among school-age children, particularly in adolescents, with potential unrecognized localized or school-based outbreaks.
BACKGROUND:We analyzed the impact of non-pharmacological interventions (NPIs) and PCV13 inoculation on nasopharyngeal (NP) carriage of Staphylococcus aureus (Sa), Streptococcus pneumoniae (Sp), Moraxella catarrhalis (Mc), and Haemophilus influenzae (Hi) in healthy children under 5-years-old in Beijing, China. RESEARCH DESIGN AND METHODS:NP swabs were taken from healthy children seeking routine well-child care at the pediatric preventive health clinic. NP swabs were frozen in Tryptic Soy Broth (TSB) medium and stored at -80°C, and bacterial was detected by culture. RESULTS:From December 2019 to November 2021, 1939 children were enrolled, among whom 278 (14.3%) were found to carry Sa isolates, 115 (5.9%) Sp, 39 (2.0%) Mc, and 6 (0.3%) Hi. The carriage of Sa was highest in infants under 6 months, negatively correlated with Sp and Mc. The Sa carriage rate in infants below 6 months of age rose from 26.7% in pre-NPIs to 32.7% in post-NPIs early. The 13-valent pneumococcal conjugate vaccine (PCV13) uptake rose from 42.3% in December 2019 to 62.3% by October 2021. CONCLUSIONS:The broad application of NPIs caused a decline in Sp and Mc carriage among children under 5-years-old, accompanied by an elevation in the Sa carriage rate among infants.
Objectives:To assess the epidemiology, serotype distribution, and antimicrobial resistance of GBS among both pregnant and non-pregnant adults in Baoji, China, addressing an existing gap in current research. Methods:Based on the GBS strains identified in the clinical laboratory from 2016 to 2024, information on age, gender, specimen type, and diagnosis was collected for the corresponding adult cases, including both colonization and infection cases. GBS was identified using three methods: mass spectrometry, CAMP test and latex agglutination kit for streptococcal serotyping. Serotypes were determined by latex agglutination, and antimicrobial susceptibility was tested against 20 antimicrobials using an automated drug susceptibility system. Results:A total of 200 GBS strains were collected, in which 107 were from pregnant women, and 93 from non-pregnant adults including 34 males. Clinical pathogenic isolates were defined for 86 cases, in which the urinary tract infections were predominant (61.6%), and invasive infections were confirmed for 16 cases (18.6%). A total of 5 serotypes were identified in the present 200 strains, including serotype Ib (34.5%), V (26.0%), III (21.5%), Ia (2.0%) and VIII (1.0%). In addition, 30 strains (15.0%) were non-typeable (NT). The coverage rate of the hexavalent vaccine currently in development is 84.5%. Significant differences are observed in the proportions of serotypes Ib, III, and/or V across various age groups, pregnancy statuses, and between colonized and infectious strains. Notably, the proportion of serotype V varies markedly, with 32.3% in the 18-39 age group versus 18.9% in the 40-64 age group and 10% in the >64 age group, 36.4% in pregnant women compared to 14.0% in non-pregnant women, and 34.2% in colonized strains as opposed to 15.1% in infectious ones. All 200 GBS strains were sensitive to penicillin, and the resistance rates to erythromycin, azithromycin, levofloxacin, clindamycin, tetracycline, and chloramphenicol were 93.5%, 93.5%, 70.5%, 70.0%, 53.5%, and 13.0%, respectively. Conclusion:The present findings suggest that GBS may potentially infect and colonize adults, regardless of gender or age, in Baoji, China. Serotypes Ib, III, and V are common serotypes, but their frequency is related to the host's age group, pregnancy status, and clinical relevance. GBS isolates are still generally susceptible to penicillin.
The purpose of this study is to assess the rationale and epidemiological patterns of "pertussis-like syndrome" diagnoses. A comprehensive analysis of demographic, epidemiological, and etiological characteristics was conducted on 10,561 diagnosed "pertussis-like syndrome" cases across 33 Chinese hospitals. Post-coronavirus disease 2019 pandemic, the incidence of "pertussis-like syndrome" increased significantly. Infants under 1 year old accounted for 69.73% of these cases, and severe outcomes were particularly prevalent among younger infants. Among those admitted to the intensive care unit, 83.03% were under 6 months of age, and 75.00% of the four reported deaths occurring in infants were younger than 3 months. While infants under 1 year consistently represented over half of annual cases, their proportion declined from 82.93% in 2016 to 51.21% in 2022. In contrast, there has been a notable rise in cases among children older than 3 years. It is important to highlight that only 4.37% of cases were exclusively diagnosed as "pertussis-like syndrome," with the majority of patients presenting with comorbidities, particularly lower respiratory tract infections (93.61%). The common pathogens identified in the records included respiratory syncytial virus, Mycoplasma pneumoniae, Haemophilus influenzae, and parainfluenza virus. "Pertussis-like syndrome" exhibits a high degree of overlap with pertussis in terms of the age distribution of susceptible populations and epidemiological patterns. To improve diagnostic accuracy, we recommend strengthening laboratory testing in suspected "pertussis-like syndrome" cases to confirm or rule out pertussis. For cases with identified pathogens that are not Bordetella pertussis, a precise pathogen-specific diagnosis should be established rather than relying on the ambiguous label of "pertussis-like syndrome." IMPORTANCE This study highlights the critical importance of reevaluating the diagnosis of "pertussis-like syndrome" to improve diagnostic accuracy and patient outcomes. The global resurgence of pertussis has underscored the need for precise identification of respiratory infections, particularly in pediatric populations. Our analysis of 10,561 cases across 33 hospitals in China revealed significant overlaps between "pertussis-like syndrome" and pertussis in terms of age distribution and epidemiological patterns. Cases diagnosed as "pertussis-like syndrome" may include undetected cases of pertussis. Moreover, the broad, ambiguous label of "pertussis-like syndrome" often masks the true causative pathogens. This imprecise diagnosis hinders targeted treatment and public health surveillance. Given advancements in pathogen detection technologies, we advocate for abandoning the "pertussis-like syndrome" label in favor of precise, pathogen-specific diagnoses. This shift may enhance diagnostic clarity, optimize clinical management, and strengthen efforts to monitor and control respiratory infections globally.
OBJECTIVE:To elucidate the evolution of antigen genotype and antimicrobial resistance distribution of Bordetella pertussis (B. pertussis) from 2019 to 2023 in northern China. METHODS:Polymerase chain reaction (PCR) amplification and sequencing were utilized to identify the seven antigen genotypes (ptxA, ptxC, ptxP, prn, fim2, fim3, tcfA). E-test and Kirby-Bauer (K-B) disc diffusion were employed to determine the minimum inhibitory concentration (MIC) and zone of inhibition for B. pertussis against antimicrobial agents. Subsequently, 50 isolates were chosen for multi-locus variable-number tandem-repeat analysis (MLVA) typing and whole-genome sequencing. RESULTS:A total of 442 B. pertussis isolates were determined. The strains with high virulence harbouring ptxP3 allele surged from 13.5% (21/155) in 2019-2021 to 93.0% (267/287) in 2022-2023. Concurrently, the erythromycin resistance B. pertussis (ERBP) in ptxP3 isolates markedly rose from 42.9% (9/21) in 2019-2021 to 100% (267/267) in 2022-2023. The majority of ptxP3 isolates (76.0%,219/288) exhibited the ptxA1/ptxC1/prn2/fim2-1/fim3A/tcfA-2 genotype. Among the 442 confirmed patients, the children aged 3-14 years escalated rapidly from 13.5% in 2019 to 45.6% in 2023. The MT28 strains were responsible for 66.0% (33/50) of the tested ones, in which ERBP was prevalent at 87.9% (29/33). All the present sequenced ptxP3-ERBP strains (31/31) were clustered into the sub-lineage IVd. CONCLUSIONS:These results suggested the clonal spread of the ptxP3-ERBP lineage of B. pertussis with high virulence and macrolides resistance could be an important cause of the recent pertussis resurgence in China. Furthermore, the increased cases among pre-school and school-aged children underscore the importance of booster vaccination in this population.
Background This study assessed changes in Streptococcus pneumoniae serotype distribution and antimicrobial nonsusceptibility among hospitalized children with pneumonia in Shenzhen, China, from 2009 to 2019, under low pneumococcal conjugate vaccine (PCV) coverage.Research Design and Methods We analyzed 1,361 isolates (62 invasive, 1,299 noninvasive). Serotypes were identified by latex agglutination and Quellung reaction. Antimicrobial susceptibility was determined using E-test, and vaccination data were obtained from the local CDC.Results PCV13 serotype coverage remained high among invasive isolates (96.8%) and represented a substantial proportion of all isolates. A marked decline in serotype 19F (from 59.2% to 14.4%) and increased serotype diversity (from 14 to 26 types) were observed. Non-susceptible rates to four beta-lactam antibiotics decreased from 16.0% to 2.4%, largely due to the decline of serotype 19F. PCV vaccination rates rose to 31.1% by 2019. Non-vaccine serotypes increased over time, with some (e.g. 15B/C) showing elevated beta-lactam MICs.Conclusions Despite low vaccination rate, PCV13 serotypes remained predominant among isolates. The decline of serotype 19F and reduced beta-lactam nonsusceptibility suggest vaccine impact. Rising serotype diversity and the emergence of nonsusceptible non-vaccine types highlight the need for continued surveillance.
INTRODUCTION:This study examined group A streptococcus(GAS) carriage, emm types, and antibiotic susceptibility in children (6-13 years) in Aral, China, during the post-COVID-19 scarlet fever resurgence, providing regional insights. METHODS:The prevalence of GAS carriage was assessed in 1,835 children aged 6-13 years across two surveys at an Aral school in China during the post-COVID-19 resurgence of scarlet fever. GAS isolates were analyzed for emm types, M1UK lineage, and antimicrobial susceptibility using culture, PCR, sequencing, and automated methods. RESULTS:The first survey (885 children) showed a 1.9% isolation rate, highest in 9-year-olds (4.8%) and slightly higher in boys (2.3% vs. 1.5%, P > 0.05). The second survey (950 children) reported a 3.1% rate, peaking at 10 years (6.7%) and also higher in boys (3.5% vs. 2.6%, P > 0.05). Colonization rates were similar overall (P > 0.05), but increased significantly in children aged ≥10 years (1.1% to 3.3%, P = 0.038). No children tested positive for GAS in both sampling rounds, which meant that the two surveys identified distinct host populations colonized by the bacteria. Emm12 prevalence decreased from 76.5% to 55.2% (P > 0.05), while emm1 increased from 11.8% to 31.0% (P > 0.05), with no M1UK lineage detected. All isolates were sensitive to penicillin, linezolid, vancomycin, and levofloxacin. Among 33 co-resistant isolates, emm12 accounted for 84.8% and emm1 for 15.2%. CONCLUSION:Despite low GAS carriage rates, variations in age distribution and emm types suggest increased bacterial activity, warranting ongoing monitoring for GAS-related diseases.
Background Recent studies have suggested potential impairment of the blood-brain barrier (BBB) in depression. However, due to the limited research and variability in animal models, further investigation using diverse and stable models is necessary. Methods A male mouse model of depression was established using the chronic unpredictable mild stress (CUMS) protocol. Following model establishment, depression-like behaviors were assessed using the sucrose preference test, tail suspension test, and forced swimming test. Morphological changes in the hippocampus were examined through hematoxylin-eosin staining. BBB permeability was evaluated using the Evans blue leakage test, fluorescein sodium (NaF) leakage test, and serum S100B content assessment. Gene and protein expression levels of BBB-related proteins in the hippocampus were determined via real-time PCR, western blotting, and immunofluorescence assays. Results CUMS exposure induced depression-like behaviors, including reduced body weight gain, diminished sucrose preference, and prolonged immobility in both the tail suspension test and forced swimming test. While no significant pathological changes were observed in the hippocampus of either group, increased BBB permeability was noted in the CUMS group, as evidenced by enhanced NaF leakage into the brain parenchyma and elevated serum S100B levels. Gene expression analysis revealed downregulation of angiogenesis-related genes and tight junction proteins in the CUMS group. Additionally, protein levels of tight junction proteins Claudin-5 and ZO-1 were lower in the CUMS group compared to controls. Limitations This study is limited to a male mouse model, and the BBB in females is worth exploring in the future. Conclusions Increased BBB permeability and decreased expression of tight junction proteins Claudin5 and ZO-1 were observed in mice with CUMS-induced depression.
Background: The epidemiological data of Streptococcus pneumoniae isolates are important for the practice of treatment and prevention. This research aimed to explore the epidemiological characteristics of pediatric S. pneumoniae isolated from outpatients and inpatients. Methods: S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined by diagnostic pneumococcal antisera, and resistance against 13 antibiotics was tested by either the E-test or the disc diffusion method. The sequence types (STs) were analyzed with multilocus sequence typing (MLST). Results: The five dominant serotypes obtained from inpatients were 19F(32.9%), 19A(20.7%), 23F(10.7%), 6A(10.0%), and 14 (8.6%), while those in the outpatients were 19F (13.6%), 23F (12.9%), 6A (10.0%), 6B (10.0%), and 19A (7.9%). The coverage rates of the 7-, 10- and 13-valent pneumococcal vaccine formulations were high. The non-susceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates were 7.1%, 92.8%, 65.7%, 100%, and 85.0%, respectively, while those among the outpatient isolates were 0.7%, 50.0%, 38.6%, 96.4%, and 65.7%, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was more prevalent in inpatients. Conclusions: The pneumococcal vaccine related serotypes were still prevalent either in inpatient department or in outpatient department, which with serious antibiotic resistance. These results might be helpful for understanding the epidemiology of S. pneumoniae in Beijing. PCVs can prevent vaccine related serotypes. Therefore, universal immunization of PCVs should be implemented to prevent the spread of vaccine related serotypes of S. pneumoniae .