接种乙型肝炎疫苗后10例婴儿死亡的疑似预防接种异常反应分析

目的分析接种乙型肝炎（乙肝）疫苗（Hepatitis B Vaccine，HepB）N发生死亡的病例，评价HepB的安全性。方法对2006年1月～2007年3月，中国疾病预防控制系统突发公共卫生事件监测报告的接种HepB后死亡的病例及其个案调查资料进行分析。结果报告的10例接种HepB后婴儿死亡病例中，2例可能为接种HepB所致急性过敏性休克，其余8例为其它疾病所致死亡，根本死因均与接种HepB无关。结论国产HepB安全性良好，存在个别因过敏反应导致死亡的病例。应进一步规范预防接种，减少疑似预防接种异常反应的发生。     

Geospatial variation in measles vaccine coverage through routine and campaign strategies in Nigeria: Analysis of recent household surveys

Measles vaccination campaigns are conducted regularly in many low- and middle-income countries to boost measles control efforts and accelerate progress towards elimination. National and sometimes first-level administrative division campaign coverage may be estimated through post-campaign coverage surveys (PCCS). However, these large-area estimates mask significant geographic inequities in coverage at more granular levels. Here, we undertake a geospatial analysis of the Nigeria 2017–18 PCCS data to produce coverage estimates at 1 × 1 km resolution and the district level using binomial spatial regression models built on a suite of geospatial covariates and implemented in a Bayesian framework via the INLA-SPDE approach. We investigate the individual and combined performance of the campaign and routine immunization (RI) by mapping various indicators of coverage for children aged 9–59 months. Additionally, we compare estimated coverage before the campaign at 1 × 1 km and the district level with predicted coverage maps produced using other surveys conducted in 2013 and 2016–17. Coverage during the campaign was generally higher and more homogeneous than RI coverage but geospatial differences in the campaign’s reach of previously unvaccinated children are shown. Persistent areas of low coverage highlight the need for improved RI performance. The results can help to guide the conduct of future campaigns, improve vaccination monitoring and measles elimination efforts. Moreover, the approaches used here can be readily extended to other countries.     

CCL3, CCL5, IL-15, IL-1Ra and VEGF compose a reliable algorithm to discriminate classes of adverse events following 17DD-YF primary vaccination according to cause-specific definitions

In the present study, a range of serum biomarkers were quantified in suspected cases of adverse events following YF immunization (YEL-AEFI) to propose a reliable laboratorial algorithm to discriminate confirmed YEL-AEFI (“A1” class) from cases with other illnesses (“C” class). Our findings demonstrated that increased levels of CXCL8, CCL2, CXCL10, IL-1β, IL-6 and TNF-α were observed in YEL-AEFI (“A1” and “C” classes) as compared to primary vaccines without YEL-AEFI [PV(day 3–28)] and reference range (RR) controls. Notably, increased levels of CCL3, CCL4, CCL2, CCL5, IL-1β, IL-15, IL-1Ra and G-CSF were found in “A1” as compared to “C” class. Venn diagrams analysis allowed the pre-selection of biomarkers for further analysis of performance indices. Data demonstrated that CCL3, CCL5, IL-15 and IL-1Ra presented high global accuracy (AUC = 1.00) to discriminate “A1” from “C”. Decision tree was proposed with a reliable algorithm to discriminate YEL-AEFI cases according to cause-specific definitions with outstanding overall accuracy (91%). CCL3, CCL5, IL-15 and IL-1Ra appears as root attributes to identify “A1” followed by VEGF as branch nodes to discriminate Wild Type YFV infection (“C(WT-YFV)”) from cases with other illnesses (“C*”). Together, these results demonstrated the applicability of serum biomarker measurements as putative parameters towards the establishment of accurate laboratorial tools for complementary differential diagnosis of YEL-AEFI cases.     

Three internal fixation methods for Danis-Weber-B distal fibular fractures: A biomechanical comparison in an osteoporotic fibula model

A common agreement for the surgical treatment of osteoporotic ankle fractures has not been defined yet although locking plates are preferred for fractures with poor bone quality. This study aims to evaluate the mechanical stability of locked and conventional plates on osteoporotic Danis-Weber-B-fibula fracture models.Fractured custom-made osteoporotic fibulae were treated with neutralization plate plus lag screw, locking plate plus lag screw, or a standalone locking plate. Load until failure was applied mimicking single-leg stance. Stiffness, failureload, and interfragmentary movements were investigated.Stiffness, failureload and axial fragment movement showed no significant differences among groups. Shear movements and fragment rotation around the shaft of the neutralization plate were on average twice as high as those of the locking plates.Although no superiority was shown for overall mechanical performance, the locking plate groups exhibited higher shear and rotational stability than the neutralization plate.     

Enhanced surveillance for adverse events following immunization during the 2019 typhoid conjugate vaccine campaign in Harare,Zimbabwe

BackgroundDuring February 25–March 4, 2019, Zimbabwe’s Ministry of Health and Child Care conducted an emergency campaign using 342,000 doses of typhoid conjugate vaccine (TCV) targeting individuals 6 months–15 years of age in eight high-risk suburbs of Harare and up to 45 years of age in one suburb of Harare. The campaign represented the first use of TCV in Africa outside of clinical trials.MethodsThree methods were used to capture adverse events during the campaign and for 42 days following the last dose administered: (1) active surveillance in two Harare hospitals, (2) national passive surveillance, and (3) a post-campaign coverage survey.ResultsThirty-nine adverse events were identified during active surveillance, including 19 seizure cases (16 were febrile), 16 hypersensitivity cases, 1 thrombocytopenia case, 1 anaphylaxis case, and two cases with two conditions. Only 21 (54%) of 39 patients were hospitalized and 38 recovered without sequelae. Attack rates per 100,000 TCV doses administered were highest for seizures (6.27) and hypersensitivity (5.02). Only 6 adverse events were reported through passive surveillance by facilities other than the two active surveillance hospitals. A total of 177 (10%) of 1,817 vaccinees surveyed reported experiencing an adverse event during the post-campaign coverage survey, of which 25 (14%) sought care.ConclusionsIn line with previous evaluations of TCV, enhanced adverse event monitoring during an emergency campaign supports the safety of TCV. The majority of reported events were minor or resulted in recovery without long-term sequelae. Attack rates for seizures and hypersensitivity were low compared with previous active surveillance studies conducted in Kenya and Burkina Faso. Strengthening adverse event monitoring in Zimbabwe and establishing background rates of conditions of interest in the general population may improve future safety monitoring during new vaccine introductions.     

Safety of AS03-adjuvanted influenza vaccines: A review of the evidence

Clinical and post-licensure data have demonstrated that AS03-adjuvanted inactivated split virion vaccines, many with reduced antigen content, are effective against influenza infection. The objective of this review is to provide a comprehensive assessment of the safety of trivalent seasonal, monovalent pre-pandemic and pandemic AS03-adjuvanted influenza vaccines, based on non-clinical, clinical and post-licensure data in various populations. Non-clinical studies on local tolerance, toxicology and safety pharmacology did not raise any safety concerns with AS03 administered alone or combined with various influenza antigens. Data from clinical trials with over 55,000 vaccinated subjects showed that AS03-adjuvanted influenza vaccines were generally well tolerated and displayed an acceptable safety profile, although the power to detect rare events was limited. Approximately 90 million doses of A/H1N1pdm09 pandemic influenza vaccines (Pandemrix and Arepanrix H1N1) were administered worldwide, which contributed post-licensure data to the collective safety data for AS03-adjuvanted influenza vaccines. An association between Pandemrix and narcolepsy was observed during the A/H1N1pdm09 pandemic, for which a role of a CD4 T cell mimicry sequence in the haemagglutinin protein of A/H1N1pdm09 cannot be excluded. Provided that future AS03-adjuvanted influenza vaccines do not contain this putative mimicry sequence, this extensive safety experience supports the further development and use of AS03-adjuvanted inactivated split virion candidate vaccines against seasonal and pandemic influenza infections.     

Acquisition rate of antibody to hepatitis B surface antigen among medical and dental students in Japan after three-dose hepatitis B vaccination

Background

Health care workers (HCWs) are at high risk of contracting blood-borne infections including hepatitis B virus (HBV) infection. In Japan, all HCWs are required to receive HB vaccination before beginning work. This study aimed to investigate the dynamics of the HB surface antibody (anti-HBs) titer after a three-dose HB vaccination in HCWs and to determine effective scheduling of HB vaccination for non-responders.

Estimation of intracranial volume: A comparative study between synthetic MRI and FSL-brain extraction tool (BET)2

Brain extraction represents an important step in numerous neuroimaging analyses. The brain extraction tool (BET)2 is a widely used deformable model-based approach for extraction of intracranial volume (ICV). The aim of this study is to estimate the ICV extraction accuracy using synthetic MR(SyMRI) method and BET2 in healthy adult participants and patients with Sturge-Weber Syndrome (SWS), including infants. 'Quantification of relaxation times and proton density by multi-echo acquisition of saturation recovery with turbo-spin-echo readout' (QRAPMASTER) with a 3.0 T magnetic resonance image (MRI) system was used for data acquisition. Statistical evaluations were performed with linear regression analysis and the Jaccard similarity coefficient (J). ICV extraction accuracy with synthetic MR method is found to be higher than BET2, for both aged healthy participants and SWS.     

A large repertoire of B cell lineages targeting one cluster of epitopes in a vaccinated rhesus macaque

The repertoire of antibodies (Abs) produced upon vaccination against a particular antigenic site is rarely studied due to the complexity of the immunogens. We received such an opportunity when one rhesus macaque was immunized six times at 0, 4, 10, 16, 32, and 143 weeks with C4-447 peptide containing the 8-mer epitope for human monoclonal Ab (mAb) 447-52D specific to the V3 region of gp120 HIV-1. Strong anti-V3 antibody responses reached 50% binding titer in serum of 10⁻⁵ at week 10 that declined to 10⁻³ by week 70. After an additional boost of C4-447 peptide at week 143, titers rebounded to 10⁻⁵ at week 146, or 2.7 years after the first immunization. Using the blood sample at week 146, we produced 41 V3-specific recombinant mAbs by single B cell isolation and cloning. Sequence analysis revealed 21B cell lineages, single and clonally related, based on immunoglobulin gene usage and CDR3s. The broad repertoire of Abs directed to a small antigenic site shows the targeting potency of a vaccine-elicited immune response in rhesus macaques.