[Developmental effects of TCIPP and TnBP on zebrafish (Danio rerio) embryos].

Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 µmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 µmol/L were measured. Results: The 50% lethal concentrations (LC50) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 µmol/L (96 hpf), 156.5 and 26.05 µmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 µmol/L) and TnBP (10 µmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.

[Progress of serogroup B meningococcal outer membrane vesicle vaccines].

This research and development of MenB meningococcal vaccines includes two technical routes: outer membrane vesicle (OMV) vaccines and recombinant protein vaccines. This article intends to review the development, production and application of MenB meningococcal OMV vaccines in order to provide a reference for the development of MenB meningococcal OMV vaccine in China.

[Serotyping methods of Streptococcus pneumonia].

More than 100 serotypes of Streptococcus pneumonia have been identified, which has been one bottleneck problem for pneumococcal disease diagnosis, surveillance, development of pneumococcal vaccine and effectiveness evaluation of pneumococcal vaccines. Three categories of approaches for pneumococcal serotyping will be discussed including phenotyping based on anti-serum, biochemical typing based on pneumococcal capsular characteristics and genotyping based on pneumococcal capsular locus sequences. We reviewed the development and applications of different serotyping of pneumococcus to provide guidance for pneumococcal disease prevention and control.

[Research progress on immunogenicity evaluation of serogroup B meningococcal vaccine].

Epidemic cerebrospinal meningitis (meningococcal meningitis) is an acute respiratory infectious disease with high mortality and serious sequelae. Meningococcal vaccine is an effective measure to prevent and control meningococcal meningitis. At present, group B meningococcal meningitis has become the main prevalent serum group in the world, including China. Meningococcal ACYW and other vaccines are mainly composed of capsular polysaccharides, while the main component of group B meningococcal vaccine is protein, including outer membrane vesicles (OMV) and recombinant protein vaccine. The methods for evaluating the immunogenicity of group B meningococcal vaccine include hSBA and alternative methods such as meningococcal antigen typing system (MATS), flow cytometric meningococcal antigen surface expression assay (MEASURE), genetic meningococcal antigen typing system (gMATS) and bexsero antigen sequence type (BAST). The evaluation of vaccine immunogenicity is the basis of vaccine development and clinical trial research, However, at present, there is no group B meningococcal vaccine in China. Therefore, in this paper, the research progress of immunogenicity evaluation of group B meningococcal vaccine has been reviewed, in order to provide technical guidance for the research and development of group B meningococcal vaccine, immunogenicity evaluation and clinical trial research in China.

[Epidemiological and Etiologic characteristics of Meningococcal meningitis in Xinjiang Uygur Autonomous Region,1960-2019].

Objective: To understand the epidemiological and etiologic characteristics of meningococcal meningitis in Xinjiang Uygur Autonomous Region (Xinjiang). Methods: The epidemiological data about the meningococcal meningitis cases in Xinjiang from 1960 to 2019 were collected from the China information system for disease control and prevention and the Center for Disease Control and Prevention of Xinjiang. The epidemiological characteristics were analyzed. Clinical specimens from suspected cases were cultured and tested by real-time PCR method. A survey on the carriage rate of Neisseria meningitides (Nm) in the healthy population was performed. The serogroups of isolates were determined by serum-agglutination and PCR methods. Multi-locus sequence typing was used for subtyping the isolates. Results: The incidence rates of meningococcal meningitis in Xinjiang from 1960 to 2019 were 0.02/100 000-81.32/100 000, with the mortality as 1.05%-20.78%. The five districts with the most cases were Kashi prefecture, Aksu prefecture, Urumqi city, Changji Hui autonomous prefecture, and Hotan prefecture. Before 1990, serogroup A (81.82%) was the commonest group for cases and contacts. After 1990, 14.00% of the cases were caused by serogroups B, C, W, and Y. There was no predominant serogroup for contacts with serogroups B, C, W, Y, and C accounting for 23.28%, 18.53%, 15.52%, 9.91% and 7.33% respectively. The general Nm carriage rate was 15.50%, with the population of 16 - 20 years age group having the highest rate (25.53%). Serogroups B (52.11%), W (20.66%), C (12.21%), and Y (9.39%) occupied 52.11%, 20.66%, 12.21% and 9.39% respectively. The commonest clonal lineages of Nm isolates were ST-4821, ST-175, and ST-5 clonal complexes, while the ST-5 and ST-4821 clonal complexes were the major ones for invasive strains. Conclusions: There appeared regional differences in the incidence rates of Xinjiang meningococcal meningitis, and the carriage rate of Nm was high. The serogroups have been changing. It is necessary to strengthen the prevention and control of meningococcal meningitis to prevent any potential outbreak.

[Systematic review on the reform of disease prevention and control system in China].

Objective: To systematically understand the reform progress of disease prevention and control system in China. Methods: The literature regarding the reform of China's disease prevention and control system was searched by using the keywords including disease prevention and control, center for disease prevention and control (CDC), disease control, reform, and system from 2003 to 2020 in China CNKI, Wanfang Data knowledge service platform, VIP information and China biomedical literature database. The language is limited to Chinese. A total of 25 studies were included to analyze the information about the organizational structure, functional orientation, financing mechanism and personnel system of China's disease prevention and control system. Results: The 25 studies described the specific changes and reform suggestions of China's disease prevention and control system, including key policies (7 studies), organizational structure transformation (4 studies), institutional function transformation (7 studies), financing mechanism transformation (5 studies), personnel system reform (2 studies), and performance-based salary system reform (4 studies). Meanwhile, the reform suggestions were concluded at the top-level design system reform (two aspects), organization structure (three aspects), functioning (four aspects), and personnel guarantee mechanism (three aspects). Conclusions: This study indicates that there is a lack of empirical evidence regarding specific reform effects and content analysis at the micro level of disease prevention and control system in China. Future study should strengthen the rigorousness of study design and focus on the quantitative impacts of reform implementation in China.

[Analysis on antimicrobial sensitivity of Neisseria meningitidis in China from 2005 to 2019].

Objective: To analyze the antimicrobial resistance characteristics of 538 Neisseria meningitidis isolated from 2005 to 2019 in China. Method: Total of 538 Neisseria meningitidis strains collected from 30 provinces in China from 2005 to 2019. Antimicrobial susceptibility test were performed based on the standards of clinical and laboratory standardization association (CLSI) including 11 recommended antibiotics. Gradient diffusion method was used to detect the antibiotic sensitivity of Neisseria meningitidis. Results: All 538 strains were sensitive to azithromycin, meropenem, chloramphenicol, rifampicin and ceftriaxone. As to other six antibiotics, the antibiotics sensitivity rates were cefotaxime (97.4%, 524 strains), ampicillin (87.7%, 472 strains), penicillin (84.8%, 456 strains), minocycline (95.2%, 512 strains), ciprofloxacin (24.9%, 134 strains) and trimethoprim/sulfamethoxazole (11.2%, 60 strains) respectively. Conclusions: Neisseria meningitidis isolated from 2005-2019 in China were all sensitive to azithromycin, meropenem, chloramphenicol, rifampicin and ceftriaxone. It should highlight Neisseria meningitidis resistant to cefotaxime, ampicillin and penicillin. Ciprofloxacin and sulfamethoxazole are not recommended as the priority choice for clinical treatment and prophylactic medication.

[The prevalence rate and influencing factors of cough in children under 5 years old in Yiwu city, Zhejiang Province in 2019].

Objectives: To investigate the prevalence of cough and its influencing factors in community children under 5 years old. Methods: From October to December 2019, we selected 3 102 community children under the age of 5 from 50 natural villages/residential communities in 14 towns/streets of Yiwu, Zhejiang Province, using multi-stage random sampling method. A face-to-face and on-site questionnaire survey was conducted among child caregivers to collect demographic data and information about children's cough in the last 1 month. Multiple logistic regression model was used to analyze children's cough and the influencing factors of different cough states. Results: Multivariate logistic regression model analysis results showed that compared with 0-1 year old, dispersed, caregivers with education level below high school, families with 1 child under 5 years old, Cough risk was higher in 1-2, 2-3, 3-4 years old, nurseries, caregivers with education level of high school or above, and families with more than 2 children under 5 years old. OR (95%CI) values were 1.52(1.19-1.92), 1.65(1.29-2.10), 1.86(1.36-2.54), 2.59(1.99-3.38), 1.48(1.26-1.74) and 1.35(1.13-1.62), respectively. Further analysis of the influencing factors of different states of cough, multivariate logistic regression model analysis results showed that preschool status, the number of children under 5 years old in the family and the education level of caregivers were the influencing factors of acute, prolonged and chronic cough. Age was only an influencing factor of acute and persistent cough. Conclusions: The disease burden of cough in children under 5 years old community was heavy, and the cough was related to children's age, education level of caregivers, number of children under 5 years old in the family and childcare status.

[Survey of antibody levels of pertussis, diphtheria and tetanus in 495 pregnant women in Nanshan District of 2019, Shenzhen].

Objective: The purpose of this study was to investigate the IgG antibody levels of whooping cough, diphtheria, and tetanus in pregnant women in Nanshan District. Methods: From January to March 2019, 495 pregnant women who met the inclusion criteria in a hospital in Nanshan District, Shenzhen were selected as the survey subjects. The enzyme-linked immunosorbent assay was used to detect serum levels of pertussis, diphtheria, and tetanus IgG antibodies and we compared the differences in antibody levels of pregnant women with different characteristics. Results: The maternal age was (29.23±4.08) years old. The geometric mean concentration of pertussis antibody was 2.589 (1.172-4.953) IU/ml, 1.01% (5 cases) of pregnant women had pertussis antibody concentration ≥ 40 IU/ml, and 75.15% (372 cases) of pregnant women had pertussis antibody concentration<5 IU/ml. The GMC value and antibody positive rate of diphtheria in pregnant women were 0.024(0.009-0.065) IU/ml and 72.53% (359 cases), respectively. The GMC value and antibody positive rate of tetanus in pregnant women were 0.014 (0.006-0.034) IU/ml and 53.74% (266 cases), respectively. There was no statistical difference in the antibody level and antibody positive rate among pregnant women of diphtheria and tetanus, respectively. Conclusion: The concentration of antibodies against pertussis, diphtheria, and tetanus in pregnant women are all at a low level, which is not enough to protect themselves from disease infection.

[Epidemiological characteristics and the development of spatiotemporal analysis models on hemorrhagic fever with renal syndrome in China].

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease of natural infectious focus caused by Hantavirus (HV) with clinical characteristics as fever, hemorrhage, hyperemia, hypotensive shock and renal damage. Through contacting the excreta or secretion of infected rats, human may get infected. The epidemiological characteristics of HFRS are significantly different in terms of population differences, geographical heterogeneity and seasonal variation, which are all closely related to the habitat of host animals and human productive activities. The reported number of HFRS is about 150 000 to 200 000 each year worldwide, and China accounted for 70%-90% of the total reported cases standing the most seriously infected country. In this study, we reviewed the epidemiological characteristics and the influencing factors of HFRS as well as the models and methods used in relevant ecological studies, in order to understand the distribution of time, regional and population and potential influencing factors on the transmission of HFRS better, so as to improve the strategies on investigation, monitoring, prevention and control of the diseases.

[Effectiveness of 23-valent pneumococcal polysaccharide vaccine on adult pneumococcal disease].

Streptococcus pneumoniae (Spn) will cause various pneumococcal diseases when host has a weak immune system. The World Health Organization ranks it as one of the 12 key pathogens causing heavy burden of disease. At present, the drug resistance of Spn is rising, and vaccination is an important and effective strategy to decrease the burden of disease. The 23-valent pneumococcal polysaccharide vaccine (PPV23) is a preventive vaccine for adults that covers 65% to 91% of Spn isolates worldwide. Accumulating evidence have confirmed the effectiveness of PPV23 in decreasing the incidence, hospitalization, mortality, and economic burden of pneumococcal diseases in adults. The burden of pneumococcal diseases in China is heavy, but the adult vaccination rate is low. Here, we review the prevalence of adult pneumococcal diseases, the preventive and protective effects and benefits of PPV23 vaccine on high-risk population, especially the elderly individuals. We hope this review can provide references and new ideas for adult PPV23 vaccination programs in China.

[Specifications for diagnosis and treatment of non-neonatal tetanus].

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Non-neonatal tetanus remains a serious public health problem, although neonatal tetanus has been eliminated in China since 2012. Non-neonatal tetanus is a potential fatal disease. In the absence of medical intervention, the mortality rate of severe cases is almost 100%. Even with vigorous treatment, the mortality rate is still 30%-50% globally. These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China, in order to improve medical quality and safety. These specifications introduce the etiology, epidemiology, pathogenesis, clinical manifestations and laboratory tests, diagnosis, differential diagnosis, grading and treatment of non-neonatal tetanus.

[Guidelines for the use of post-traumatic tetanus vaccines and passive immune preparation].

Post-traumatic tetanus is the main type of non-neonatal tetanus. To reduce the incidence and mortality rateof tetanus and guide the primary medical institutions to prevent and control tetanus after trauma, the National Immunization Planning Technical Working Group of the Chinese Center for Disease Control and Prevention has compiled this document in the reference with Position Paper by World Health Organization, and the latest research progress both at home and abroad. The guidelines focus on the basic procedures for the prevention and treatment of post-traumatic tetanus, the application of tetanus vaccines and immune preparation, and pre-exposure immunization in high-risk populations of trauma.

[Specifications for diagnosis and treatment of non-neonatal tetanus].

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Although neonatal tetanus in China has been eliminated since 2012, non-neonatal tetanus remains a serious public health problem. Non-neonatal tetanus is a potential fatal disease, and the mortality rate of severe cases is almost 100% in the absence of medical intervention. Even with vigorous treatment, the mortality rate is still 30~50% globally. In order to standardize the diagnosis and treatment of non-neonatal tetanus in China, this specification is hereby formulated. This standard includes etiology, epidemiology, pathogenesis, clinical manifestations, laboratory tests, diagnosis, differential diagnosis, classification, grading and treatment of non-neonatal tetanus.

[Guidelines for the use of post-traumatic tetanus vaccines and passive immune preparation].

Post-traumatic tetanus is the main type of non-neonatal tetanus. To reduce the incidence and mortality rate of tetanus and guide the primary medical institutions to prevent and control tetanus after trauma, National Immunization Planning Technical Working Group of the Chinese Center for Disease Control and Prevention has compiled this document in the reference with Position Paper by World Health Organization, the latest research progress from home and abroad. The guidelines focus on the basic procedures for the prevention and disposition of post-traumatic tetanus, the application of tetanus vaccines and immune preparation, and the pre-exposure immunization in high-risk populations of trauma.

[Important role of study on intrauterine transmission of HBV in prevention and control of hepatitis B].

The new research of intrauterine transmission of HBV includes intrauterine dominant infection and occult infection. Intrauterine dominant infection of HBV is the traditional intrauterine infection. Although intrauterine infection of HBV has been studied for decades, the intervention effects on HBV infection are very limited. As a result, mother to child transmission has become the main route of the transmission of HBV. With the development of science and technology, people's understand of intrauterine occult infection of HBV has been deepened, and the definition of intrauterine transmission of HBV has been further completed and expanded. The study of intrauterine occult infection of HBV will play an important role in prevention and control of hepatitis B in China through filling in a gap in the field of prevention and control of vertical transmission of HBV, exploring new research perspective and providing guideline for related decision-making.

[Epidemic situation and preventive strategy for meningococcal disease].

The incidence of meningococcal disease is generally low globally at present. The epidemics, problems and challenges of meningococcal disease were described in order to provide support for prevention and control of meningococcal disease in China, especially in the areas of disease surveillance, epidemic changes, serogroup witching, vaccines and vaccination strategies and meningococcal group B vaccine development.

[Molecular characteristics of serogroup B neisseria meningitidis, China].

Objective: To investigate the molecular characteristics of serogroup B neisseria meningitidis in China. Methods: Total of 485 (100 strains isolated from cerebrospinal fluid or blood samples of encephalomyelitis cases, and 385 strains isolated from nasopharynx of healthy carriers) Meningococcal serogroup B (MenB) strains, isolated from 29 provinces of China between 1968 and 2016, were analyzed by multilocus sequence typing (MLST) and PorA typing methods. Further, the genetic diversity of three MenB vaccine proteins, FHbp, NadA and NHBA, were analyzed. Results: The 485 study strains belonged to 270 sequence types (STs), 107 of which (representing 211 strains) could be grouped into ten clonal complexes (CC). CC4821 has been the predominant lineage in China since 2005 (28.7%, n=139). The most common PorA types of MenB strains from invasive meningococcal cases were P1.5-2,2-2 (10.0%, n=10), P1.5-1,2-2 (9.0%, n=9) and P1.5-1,10-4 (9.0%, n=9). Four hundred and twenty one strains had intact fhbp gene; variant 1, 2 and 3 accounted for 12.8% (54 strains), 85.0% (358 strains) and 2.2% (9 strains) respevtively. Ten out of 432 strains (2.3%) contained complete nadA gene. All the 172 strains for which the nhba gene was sequenced had intact gene sequence which corresponded to 68 peptide types. Conclusion: CC4821 was the predominant CC of MenB strains in China; the vaccine proteins were diverse about the sequences. The vaccine proteins should be carefully selected when developing MenB vaccines in China.

[Acute meningitis and encephalitis syndrome surveillance disease burden in four China prefectures].

Objectives: To explore acute meningitis and encephalitis syndrome (AMES) surveillance in 4 China prefectures, to understand the epidemiological features and disease burden of neisseria meningitides (Nm) meningitis, streptococcus pneumoniae (Sp) meningitis, haemophilus influenza type b (Hib) meningitis and Japanese encephalitis and provide evidence for related disease prevention and control. Methods: AMES surveillance were conducted in Jinan, Shandong Province and Yichang, Hubei Province in September 2006, and in 13 districts of Shijiazhuang, Hebei Province and Guigang City, Guangxi Zhuang Autonomous Region in April 2007. Six hospitals in each city were selected as monitoring pilot hospitals to carry out reports of suspected cases of acute meningitis and encephalitis, case investigation, blood specimens and cerebrospinal fluid specimen collection, anti-JEV IgM antibody enzyme-linked immunosorbent assay, Nm, Sp and Hib culture and polymerase chain reaction detection, etc. According to the age group, the incidence of bacterial meningitis and Japanese encephalitis in local residents <20 years old was estimated. Results: From 2006 to 2013, a total of 19 423 surveillance cases were reported in four cities, of which 11 071 (56.99%) were reported in the pilot hospitals. Of the 11 071 cases, 5 315 were tested for bacteriology and 9 180 were tested for anti-JEV IgM antibodies. Among the bacteriological tests, 176 cases were positive, including 75 cases of Nm positive, 91 cases of Sp positive and 10 cases of Hib positive. The incidence of three bacterial meningitis is estimated for people under 20 years old, with estimated incidence of Nm, Sp and Hib meningitis in children <5 years old was 0.46/100 000-0.71/100 000, 0.34/100 000-0.83/100 000 and 0.32/100 000-0.57/100 000 respectively; the estimated incidence of Nm and Sp meningitis in children aged 5-9 years was 0.59/100 000-1.14/100 000 and 0.50/100 000-1.66/100 000 respectively. In 732 cases of positive JE cases, the positive detection rates of <5 years old, 40-49 years old and ≥50 years old were 9.51% (95/999), 28.09% (66/235) and 33.85% (130/384), respectively. The estimated annual incidence rate of JE was 0.12/100 000-0.79/100 000.ratio of cases 1.19∶1. Most of cases (27.30%) were children and adolescents aged 5-14 years and those (26.84%) aged over 45 year. Conclusion: The study found that primary and secondary school students are the key population of Nm meningitis, suggesting that it is necessary to explore the enhanced immunization study of meningococcal vaccine in this population; Sp has the possibility of occurrence in all age groups; <5 years old children are the main population of Hib meningitis.