Post-Marketing Surveillance of Adverse Events Following Immunization with Haemophilus Influenzae Type b Conjugate Vaccine - China, 2010-2021.

Introduction: The Haemophilus influenzae type b (Hib) conjugate vaccine is widely administered in China. Methods: We extracted data on Hib vaccine doses administered and adverse events following immunization (AEFI) reported between 2010 and 2021 from the Chinese National Immunization Information System (CNIIS). A descriptive analysis was conducted to examine the characteristics and incidence rates of AEFI with the Hib vaccine. Results: In China, between 2010 and 2021, a total of 52,910 AEFIs with the Hib vaccine were reported, resulting in an overall AEFI reporting rate of 38.10 per 100,000 doses. Common (typically minor) and rare (potentially serious) vaccine reactions occurred at rates of 34.71 and 2.78 per 100,000 doses, respectively. Among the common vaccine reactions, the incidences of fever (axillary temperature ≥38.6 ℃), injection site redness and swelling (>2.5 cm in diameter), and injection site induration (>2.5 cm in diameter) were 11.93, 9.69, and 3.38 per 100,000 doses, respectively. Rare vaccine reactions included anaphylactic rash, angioedema, and febrile convulsion with reported incidences of 2.42, 0.10, and 0.05 per 100,000 doses, respectively. The incidence of serious rare vaccine reactions was 0.16 per 100,000 doses. Conclusions: The reported incidence of AEFI with the Hib vaccine was low, with the occurrence of serious rare adverse reactions also being markedly low throughout the period 2010-2021 in China.

Comparison of Statistical Signal Detection Methods in Adverse Events Following Immunization - China, 2011-2015.

Introduction: The current study aims to assess the performance of data mining techniques in detecting safety signals for adverse events following immunization (AEFI) using routinely obtained data in China. Four different methods for detecting vaccine safety signals were evaluated. Methods: The AEFI data from 2011 to 2015 was collected for our study. We analyzed the data using four different methods to detect signals: the proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). Each method was evaluated at 1-3 thresholds for positivity. To assess the performance of these methods, we used the published signal rates as gold standards to determine the sensitivity and specificity. Results: The number of identified signals varied from 602 for PRR1 (with a threshold of 1) to 127 for MGPS1. When considering the common reactions as the reference standard, the sensitivity ranged from 0.9% for MGPS1/2 to 38.2% for PRR1/2, and the specificity ranged from 85.2% for PRR1 and ROR1 to 96.7% for MGPS1. When considering the rare reactions as the reference standard, PRR1, PRR2, ROR1, ROR2, and BCPNN exhibited the highest sensitivity (73.3%), while MGPS1 exhibited the highest specificity (96.9%). Discussion: For common reactions, the sensitivities were modest and the specificities were high. For rare reactions, both the sensitivities and specificities were high. Our study provides valuable insights into the selection of signal detection methods and thresholds for AEFI data in China.

Synthesis and Characterization of 6-Ti-Substituted Polyoxomolybdate with High Catalytic Activity for Sulfide Oxidation.

A 6-Ti-substituted polyoxometalate, (NH4)5Cs7Na3H2[Cs@(Ti2GeMo10O39)3]·34H2O (1), was synthesized by reacting (NH4)6Mo7O24·4H2O, GeO2, and TiOSO4 through the conventional aqueous method. Polyanion 1a is composed of three {Ti2GeMo10} segments linked by Ti-O-Ti linkages and shows a trefoil-shaped structure. Furthermore, one Cs+ cation is encapsulated in the cavity of 1a. Notably, it possesses the highest number of Ti centers among the reported polyoxomolybdates. In addition, serving as a high-efficiency heterogeneous catalyst, 1 enables the conversion of methyl phenyl sulfide within 20 min, yielding 96.4% of the corresponding sulfoxide with good recyclability.

Impact of Influenza and Pneumococcal Polysaccharide Vaccination on Economic Burden from Acute Exacerbations of Chronic Obstructive Pulmonary Disease - Hebei Province, China, November 2018 to November 2020.

What is already known on this topic?: Chronic obstructive pulmonary disease (COPD) exacerbations increase household economic burden, but there is limited evidence from prospective cohort studies in China about the impact of vaccination on economic burden. What is added by this report?: This study demonstrated the economic burden of COPD exacerbations, pneumonia, and hospitalization in COPD patients in China is substantial. Influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately or together, were significantly associated with decreased economic burden. What are the implications for public health practice?: Our study supports evidence on recommendations that COPD patients in China are offered both influenza vaccine and PPSV23.

Soil legacy effects of plants and drought on aboveground insects in native and range-expanding plant communities.

Soils contain biotic and abiotic legacies of previous conditions that may influence plant community biomass and associated aboveground biodiversity. However, little is known about the relative strengths and interactions of the various belowground legacies on aboveground plant-insect interactions. We used an outdoor mesocosm experiment to investigate the belowground legacy effects of range-expanding versus native plants, extreme drought and their interactions on plants, aphids and pollinators. We show that plant biomass was influenced more strongly by the previous plant community than by the previous summer drought. Plant communities consisted of four congeneric pairs of natives and range expanders, and their responses were not unanimous. Legacy effects affected the abundance of aphids more strongly than pollinators. We conclude that legacies can be contained as soil 'memories' that influence aboveground plant community interactions in the next growing season. These soil-borne 'memories' can be altered by climate warming-induced plant range shifts and extreme drought.

Effectiveness of influenza and pneumococcal vaccines on chronic obstructive pulmonary disease exacerbations.

BACKGROUND AND OBJECTIVE: Single-study evidence of separate and combined effectiveness of influenza and pneumococcal vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To fill this gap, we studied the effectiveness of trivalent seasonal influenza vaccine (TIV) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately and together, at preventing adverse COPD outcomes. METHODS: Our study used a self-controlled, before-and-after cohort design to assess the effectiveness of TIV and PPSV23 in COPD patients. Patients were recruited from hospitals in Tangshan City, Hebei Province, China. Subjects self-selected into one of the three vaccination schedules: TIV group, PPSV23 group and TIV&PPSV23 group. We used a physician-completed, medical record-verified questionnaire to obtain data on acute exacerbations of COPD (AECOPD), pneumonia and related hospitalization. Vaccine effectiveness was determined by comparing COPD outcomes before and after vaccination, controlling for potential confounding using Cox regression. RESULTS: We recruited 474 COPD patients, of whom 109 received TIV, 69 received PPSV23 and 296 received TIV and PPSV23. Overall effectiveness for preventing AECOPD, pneumonia and related hospitalization were respectively 70%, 59% and 58% in the TIV group; 54%, 53% and 46% in the PPSV23 group; and 72%, 73% and 69% in the TIV&PPSV23 group. The vaccine effectiveness without COVID-19 non-pharmaceutical intervention period were 84%, 77% and 88% in the TIV group; 63%, 74% and 66% in the PPSV23 group; and 82%, 83% and 91% in the TIV&PPSV23 group. CONCLUSION: Influenza vaccination and PPSV23 vaccination, separately and together, can effectively reduce the risk of AECOPD, pneumonia and related hospitalization. Effectiveness for preventing AECOPD was the greatest.

Organic-inorganic one-dimensional hybrid aggregates constructed from aromatic-bisphosphonate-functionalized polyoxomolybdates.

Five novel lanthanide-substituted polyoxomolybdates (NH4)5Na3H2[{Ln(H2O)7}2{Mo5O15(1,4-O3PCH2C6H4CH2PO3)}4]·nH2O [Ln = Tb3+ (1), Ho3+ (2), Er3+ (3), Tm3+ (4), Yb3+ (5); n = 33, 32, 41, 30, 47] have been prepared in a conventional aqueous solution reaction of ammonium molybdate with Ln3+ ions and p-xylyenediphosphonic acid. Crystal structure analyses reveal that 1-5 are isomorphic. The prominent architecture characteristic is that their structural units consist of a tetrameric cyclic-shaped [{Mo5O15(1,4-O3PCH2C6H4CH2PO3)}4]16- segment stabilized by two [Ln(H2O)7]3+ cations, which are connected to propagate one-dimensional chain by Ln3+ ions. As is known, compounds 1-5 stand for the first Ln-substituted aromatic-bisphosphonate-functionalized polyoxomolybdates. The solid-state photoluminescence measurement of 1 has been performed at ambient temperature, and it displayed the characteristic emissions of Tb ions based on its 4f-4f transitions. In addition, the magnetic properties of 1-5 compounds show that they all exhibit anti-ferromagnetic interactions.

Immunogenicity and safety of inactivated enterovirus A71 vaccines in children aged 6-35 months in China: a non-inferiority, randomised controlled trial.

BACKGROUND: China's three inactivated enterovirus A71 (EV-A71) vaccines are the first and currently world's only EV-A71 vaccines approved by a national regulatory authority and used to prevent EV-A71 associated diseases. The three vaccines vary by vaccine strain, manufacturing cell substrate, and antigen dose, but no head-to-head comparisons of these vaccines have been done. We compared immunogenicity of the vaccines in children 6-35 months old. METHODS: We recruited healthy children aged 6-35 months who lived in a study site county into a multicentre, open-label, non-inferiority, three-group, randomised controlled trial that was conducted in five counties in China. Enrolled children were randomly assigned (1:1:1) to receive two doses of one of the three EV-A71 vaccines. The primary outcome was the proportion of children with EV-A71 neutralizing antibody seroconversion 4 weeks after the second dose; a secondary outcome was adverse events in the 4 weeks after each dose. Analyses of immunogenicity included all children who completed the study (per-protocol analysis). Safety analysis included all children completed safety follow-up after at least one. We used a 10% margin to establish non-inferiority. This trial was registered on a World Health Organization platform: Chinese Clinical Trial Registry (ChiCTR1900026663). FINDINGS: 1631 children were assessed for eligibility between Nov 4 and Nov 20, 2019. Of 1500 (92%) enrolled children, 500 were assigned to vaccine group A, B, or C; 483 in group A,484 in group B, and 487 in group C completed the study. Before dose one, the seropositive rates in groups A, B, and C were 9.7%, 7.2%, and 7.0%. Four weeks after the second dose, seroconversion rates of groups A, B, and C were 98.8%, 99.4% and 99.8% - mutually non-inferior in all two-group comparisons. There were no serious adverse events in any group and no evidence of a difference among the three groups in the incidence of local adverse event or systemic adverse event. Fever was the most common adverse event. All children with reported adverse events recovered. INTERPRETATION: Non-inferior and high seroconversion rates and equivalent safety of three EV-A71 vaccines supports use any of these vaccines to prevent EV-A71-associated diseases. These results may be useful for regulators, vaccine policy makers, and immunization programmes in China and in countries where EV-A71 is endemic.

Assembly of a Hexameric Cluster of Polyoxomolybdotriphosphonate Builts from [Zn(H2O){TeMo6O21}{N(CH2PO3)3}]6- Subunits and Its Optical and Catalytic Properties.

The crown-shaped organotriphosphonate-modified 36-molybdenum cluster (NH4)18Na7H11[Zn(H2O)TeMo6O21{N(CH2PO3)3}]6·23H2O (1) has been synthesized, which is the largest zinc-containing organophosphonate-based polyoxometalate to date. Compound 1 was prepared in buffer solution (pH 5.5) with heptamolybdate and amino trimethylene phosphonic acid (ATMP) as the organic ligand. The polyanion constructed from a hexmeric assembly of [Zn(H2O){TeMo6O21}{N(CH2PO3)3}]6- subunits has been fully investigated by a few characterization methods. In this work, we discovered that 1 exhibited reversible photochromism and it changed from white to reddish brown upon UV irradiation. In addition, compound 1, as a catalyst, can oxidize sulfides to sulfoxides, showing a high yield/conversion and a good selectivity.

Immunogenicity of 23-Valent Pneumococcal Polysaccharide Vaccine in Patients with Chronic Obstructive Pulmonary Disease - Hebei Province, China, September-December, 2019.

WHAT IS ALREADY KNOWN ON THIS TOPIC?: The global burden of chronic obstructive pulmonary disease (COPD) is serious. Pneumococcal infection is associated with acute exacerbations of COPD (AECOPD). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for COPD patients to decrease AECOPD due to pneumococcus, but evidence on the immunogenicity of PPSV23 in COPD patients is limited. WHAT IS ADDED BY THIS REPORT?: This study showed good immunogenicity of one dose of PPSV23 in COPD patients. Antibody levels against all 23 vaccine serotypes were assessed before and four weeks after vaccination of COPD patients with one dose of PPSV23. The percent of COPD patients who had two-fold increases in pneumococcal antibody levels following vaccination ranged from 65.2% (serotype 3) to 94.4% (serotype 2). There were statistically significant differences in immunogenicity by serotype. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: This study supports current recommendations for PPSV23 vaccination of COPD patients in China to provide protection from pneumococcal diseases.

Organophosphonate-Functionalized Telluromolybdate Containing a [TeMo10O37]10- Building Block and Its Catalytic Efficiency for Knoevenagel Condensation.

A novel organodiphosphonate-based telluromolybdate cluster, (NH4)6Na3H13[TeMo10O37(CoMo2O6L)4]·11H2O [1; L = (O3P)2C(O)(CH2)3NH2], has been successfully synthesized by a simple one-pot aqueous reaction. Intriguingly, the [TeMo10O37]10- subunit with tetrahedral geometry of TeO4 is observed in the organophosphonate-functionalized polyoxometalates for the first time. Compound 1 was prepared in a buffer solution (pH = 5.5) with alendronic acid (Ale) and (NH4)6Mo7O24·4H2O as raw materials. The polyanion [TeMo10O37(CoMo2O6L)4]22- was constructed from four {Mo2O6L} subunits encapsulating an interesting Te-Mo heterometal subunit [TeMo10O37]10- through four CoO6 octahedra and has been fully characterized by routine techniques. In addition, compound 1, as a heterogeneous catalyst, shows good conversion (92%) and high selectivity (99%) for Knoevenagel condensation reaction.

Immunogenicity of trivalent seasonal influenza vaccine in patients with chronic obstructive pulmonary disease.

Objective: Current evidence on the immunogenicity of influenza vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To address this need for additional knowledge, we conducted a study on the immunogenicity of trivalent seasonal influenza vaccine (TIV) in COPD patients.Methods: We recruited patients from respiratory outpatient clinics of three hospitals in Tangshan, Hebei province who had stable confirmed COPD, were less than 80 y old, and reported not having had influenza or receiving TIV during the study season prior to enrollment. Patients who had a history of allergy to any TIV component or were classified as having very severe COPD were excluded from the study. Eligible and consenting participants were given one dose of TIV after obtaining a baseline blood sample. A second blood sample was obtained 5 weeks later. We used hemagglutination inhibition (HI) assays to measure antibody responses. We considered seropositive to be an HI titer ≥1:10. We considered seroprotection to be an HI titer ≥1:40 and seroconversion to be either a change from seronegative to a post-vaccination titer of ≥1:40 or a fourfold rise in antibody titer among baseline seropositive subjects. Each subject was followed for 1 month to assess the frequency and type of adverse events.Results: Eighty-eight subjects completed our study; the median age was 64 y; most (62.5%) had moderately severe COPD; 48.9% of the subjects had comorbid conditions in addition to COPD. Post-vaccination seropositive rates for influenza H1N1, H3N2, and B were all 100%; corresponding seroprotection rates were 96.6%, 93.2%, and 98.9%; seroconversion rates were 81.8%, 87.5%, and 75.0%. There were no statistical differences in seroconversion (P = .10) and seroprotection (P = .30) among the three types of influenza virus. Geometric mean titers (1:) of HI antibodies to H1N1, H3N2, and B were 18.8 (95% CI: 14.0-25.1), 12.2 (95% CI: 9.6-15.4), and 31.8 (95% CI: 26.1-38.8) at baseline, and 267.0 (95% CI: 213.8-333.4), 190.3 (95% CI: 151.7-238.6), and 201.1 (95% CI: 166.5-242.8) after vaccination.Conclusion: The immunogenicity of one dose of influenza vaccine was excellent in COPD patients. Our study supports recommending influenza vaccination for COPD patients to provide protection from influenza and its complications.

Risk factors for pertussis among children hospitalized for pertussis during 2016-2017,in Guizhou Province of China:a case-control study / 《全球健康杂志（英文）》

Aim:Pertussis is a respiratory tract infection,the vaccine for which was introduced in the Expanded Programme on Immunization (EPI) in Guizhou Province of China (hereafter referred as Guizhou) in the 1980s.This vaccine rapidly decreased incidence rates of pertussis in the province,however,despite the wide high coverage of the diphtheria,tetanus and acellular pertussis (DTaP) combined vaccine,there has been a resurgence of pertussis since 2014.Even with this recent increase in disease transmission,risk factors for pertussis infection have not been evaluated in Guizhou.We aimed to provide information on pertussis risk factors and insight on designing targeted pertussis control policies and measures through this study.Methods:A 1∶2 matched retrospective case-control study was conducted between 2016 and 2017,involving infants and children younger than 6 years old and parents of the participants.The enrolled cases included clinical and laboratory confirmed pertussis cases according to the WHO-recommended pertussis definition.Controls were selected from children in the same neighborhood who were not diagnosed with pertussis prior to our investigation and did not exhibit any clinical manifestations of pertussis.Results:The household size[Matched odds ratio (ORm) =1.4,95％ confidence interval (CI):1.1-1.7]and house-hold members with antecedent cough (ORm =3.6,95％ CI:1.8-7.2) were significantly associated with their child's pertussis onset.The parents' occupations were significantly associated with their child's pertussis onset(ORm =9.4,95％ CI:1.6-54.8,for mother side;ORm =4.5,95％ CI:1.2-16.5,for father side),when they worked in the business and/or service industry.Having family members with a history of cough was an independent risk factor for pertussis[Adjusted odds ratio (AOR) =43.6,95％ CI:2.7-694.0].Besides,the parents' demographic characteristics and DTaP doses were not found to be independent factors.Conclusion:Household exposure is an important risk factor for pertussis infection in infants and young children and should therefore be considered as a major factor during formulation of pertussis control policies and measures.

Active Vaccine Safety Surveillance: Global Trends and Challenges in China.

Importance. The great success in vaccine-preventable diseases has been accompanied by vaccine safety concerns. This has caused vaccine hesitancy to be the top 10 in threats to global health. The comprehensive understanding of adverse events following immunization should be entirely based on clinical trials and postapproval surveillance. It has increasingly been recognized worldwide that the active surveillance of vaccine safety should be an essential part of immunization programs due to its complementary advantages to passive surveillance and clinical trials.Highlights. In the present study, the framework of vaccine safety surveillance was summarized to illustrate the importance of active surveillance and address vaccine hesitancy or safety concerns. Then, the global progress of active surveillance systems was reviewed, mainly focusing on population-based or hospital-based active surveillance. With these successful paradigms, the practical and reliable ways to create robust and similar systems in China were discussed and presented from the perspective of available databases, methodology challenges, policy supports, and ethical considerations.Conclusion. In the inevitable trend of the global vaccine safety ecosystem, the establishment of an active surveillance system for vaccine safety in China is urgent and feasible. This process can be accelerated with the consensus and cooperation of regulatory departments, research institutions, and data owners.

Two media-reported vaccine events in China from 2013 to 2016: Impact on confidence and vaccine utilization.

BACKGROUND: China media reported infant deaths following hepatitis B vaccination in late 2013, leading to temporary suspension of hepatitis B vaccine (HepB Event) until the deaths were shown to be coincidental and the vaccine was of standard, good quality. In 2016, a criminal ring in Shandong province that had been purchasing, improperly storing, and reselling Category 2 vaccines (private-sector) to 60 (of 200,000) clinics for 5 years, was exposed, publicized, and prosecuted, and the potential health and epidemiological impacts were investigated to determine whether revaccination was necessary (Shandong Vaccine Event). METHODS: We assessed parental confidence in vaccines through 9 telephone surveys in 6 and 11 provinces before, during, and after the two events. Provider confidence was assessed through in-person interviews following each event. Vaccine utilization was assessed using Immunization Information Management System data from township clinics. RESULTS: In the early stages of each event, approximately 30% of parents indicated vaccine hesitancy and 18% said they would refuse routine immunization. Five and nine months after each event, hesitancy and refusal decreased, but not to pre-event levels. During the Shandong Vaccine Event, 49·1% of parents indicated refusal to use Category 2 vaccines; six months later, the rate was 32·8%. Use of HepB decreased by 21% during the first 2 weeks of the HepB Event and by 12·6% during the first 4 weeks of Shandong Vaccine Event, but returned to baseline in less than 3 months. Use of Category 2 vaccine decreased by 49·5% in the first 3 weeks of the Shandong Vaccine Event and by 28·7% 6 months later. After the Shandong Vaccine Event, 64% of clinicians held high confidence in routine immunization, lower than at baseline. CONCLUSIONS: The two events caused mistrust, loss of confidence, and decreases in use of vaccines by parents and providers. In addition to ensuring immunization program integrity, effective communications and ongoing monitoring of vaccine use and confidence should be included to restore confidence and trust in vaccines.

[Preparation of macrocycle antibiotic chiral stationary phases by wrapping with a net in high performance liquid chromatography].

Vancomycin and teicoplanin are glycopeptide macrocyclic antibiotics with three-dimensional ring structures and multiple chiral centers. They are commonly used chiral recognition materials in enantioseparation by high-performance liquid chromatography. In this study, six chiral stationary phases wrapped with a net on silica gels were prepared by interfacial polymerization using vancomycin and teicoplanin as chiral selectors, piperazine as a monomer, 4,4'-diphenylmethane diisocyanate (MDI), 1,6-hexamethylene diisocyanate (HDI), and 2,4-toluene diisocyanate (TDI) as crosslinker. The fabricated chiral columns were used for enantioseparations. Compared to the crosslinked and commercial columns composed of vancomycin and teicoplanin, the columns wrapped with a net exhibited complementarity for the optical resolutions.