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Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/ΔNS2/Δ1313/I1314L in RSV-Seronegative Children.

RSV/Δ ns2/Δ 1313/I1314L 呼吸道合胞病毒疫苗在 RSV 血清阴性儿童中的安全性和免疫原性。

  • 影响因子:4.10
  • DOI:10.1093/infdis/jiz408
  • 作者列表:"Karron RA","Luongo C","Mateo JS","Wanionek K","Collins PL","Buchholz UJ
  • 发表时间:2020-06-16
Abstract

BACKGROUND:Respiratory syncytial virus (RSV) is the leading global cause of severe pediatric acute respiratory tract illness, and a vaccine is needed. RSV/ΔNS2/Δ1313/I1314L contains 2 attenuating elements: (1) deletion of the interferon antagonist NS2 gene and (2) deletion of codon 1313 of the RSV polymerase gene and the stabilizing missense mutation I1314L. This live vaccine candidate was temperature-sensitive, genetically stable, replication restricted, and immunogenic in nonhuman primates. METHODS:A single intranasal dose of RSV/ΔNS2/Δ1313/I1314L was evaluated in a double-blind, placebo-controlled trial (vaccine-placebo ratio, 2:1) at 106 plaque-forming units (PFU) in 15 RSV-seropositive children and at 105 and 106 PFU in 21 and 30 RSV-seronegative children, respectively. RESULTS:In RSV-seronegative children, the 105 PFU dose was overattenuated, but the 106 PFU dose was well tolerated, infectious (RSV/ΔNS2/Δ1313/I1314L replication detected in 90% of vaccinees), and immunogenic (geometric mean serum RSV plaque-reduction neutralizing antibody titer, 1:64). After the RSV season, 9 of 20 vaccinees had increases in the RSV titer that were significantly greater than those in 8 of 10 placebo recipients (1:955 vs 1:69, respectively), indicating that the vaccine primed for anamnestic responses after natural RSV exposure. CONCLUSION:Rational design yielded a genetically stable candidate RSV vaccine that is attenuated yet immunogenic in RSV-seronegative children, warranting further evaluation. CLINICAL TRIALS REGISTRATION:NCT01893554.

摘要

背景: 呼吸道合胞病毒 (RSV) 是引起小儿严重急性呼吸道疾病的主要原因,需要一种疫苗。RSV/Δ NS2/Δ 1313/I1314L 含有 2 个衰减元件 :( 1) 干扰素拮抗剂 NS2 基因的缺失和 (2) RSV 聚合酶基因密码子 1313 的缺失和稳定错义突变 I1314L。该活疫苗候选物对温度敏感,遗传稳定,复制受限,在非人灵长类动物中具有免疫原性。 方法: 在一项双盲、安慰剂对照试验 (疫苗-安慰剂比,2:1) 中评价了单次鼻内剂量的 RSV/Δ ns2/Δ 1313/I1314L 15 例 RSV 血清阳性儿童的 106 个空斑形成单位 (PFU),21 例和 30 例 RSV 血清阴性儿童的 105 和 106 PFU。 结果: 在 RSV-血清阴性儿童中,105 PFU 剂量过度衰减,但 106 PFU 剂量耐受性良好,感染性 (90% 的接种者检测到 RSV/Δ ns2/Δ 1313/I1314L 复制) 和免疫原性 (几何平均血清 RSV 空斑减少中和抗体滴度,1:64)。RSV 季节后,20 名接种者中有 9 名 RSV 滴度增加,显著高于 10 名安慰剂接受者中的 8 名 (分别为 1:955 vs 1:69),表明该疫苗为自然 RSV 暴露后的遗忘反应奠定了基础。 结论: 合理设计产生了一种遗传稳定的候选 RSV 疫苗,该疫苗在 RSV 血清阴性儿童中具有减毒但免疫原性,值得进一步评价。 临床试验注册: nct01893554。

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影响因子:1.98
发表时间:2020-01-29
DOI:10.1080/02770903.2020.1723622
作者列表:["Parlar-Chun R","Arnold K"]

METHODS:INTRODUCTION:Continuous albuterol is a mainstay in management of pediatric status asthmaticus. While the National Heart Lung and Blood Institute Asthma Guidelines suggest 0.5 mg/kg/hr as the recommended dosage, there is a paucity of evidence comparing different weight based rates on hospital outcomes. METHODS:Patients requiring continuous albuterol for asthma exacerbation from January 2015 to December 2016 were identified using ICD codes. The concentration of albuterol (5 mg/h - 20 mg/h) and the duration of treatment were used to determine total albuterol administration. After dividing by patient weight, average weight based doses were divided into equal quintiles. Unadjusted and length of stay adjusted for age, initial asthma severity score, and administration of magnesium were compared among the quintiles. The same multivariate analysis was used for duration of continuous albuterol. RESULTS:533 hospitalizations for asthma were identified of which 289 received continuous albuterol. Weight based dosage quintiles ranged from lowest (0.07 - 0.29 mg/kg/hr) to the highest (>0.76 - 3.2 mg/kg/hr). Baseline characteristics were similar aside from age, race, and magnesium administration. There was no difference in adjusted length of stay or adjusted duration of continuous albuterol therapy among the five quintiles. CONCLUSION:No optimal weight based dose of continuous albuterol was found. Further investigation is needed to see if lower amounts of continuous albuterol may be as efficacious as higher doses. This could improve cost of status asthmaticus management and limit the number of adverse events associated with high exposure to continuous albuterol.

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影响因子:2.40
发表时间:2020-02-02
来源期刊:BMC Pulmonary Medicine
DOI:10.1186/s12890-020-1056-7
作者列表:["Joon Young Choi","Jeong Uk Lim","Ho Jung Jeong","Ji Eun Lee","Chin Kook Rhee"]

METHODS:Abstract Background We investigated the association between a combination of two markers, peripheral (PEC) and bronchoalveolar lavage (BAL) eosinophil percentage (BEP), and oxygen requirements in patients with acute eosinophilic pneumonia (AEP). Methods We retrospectively reviewed the medical records of patients with AEP treated at the Armed Forces Capital Hospital between May 2012 and May 2017. We used correlation analyses to assess the association between PEC/BEP and clinical outcomes in AEP patients. Receiver operating characteristic (ROC) curve analyses were used to calculate the cut-off value for BEP that categorised patients requiring a significant oxygen supply. The BAL/blood eosinophil (BBE) score was introduced to stratify patients with peripheral eosinophilia and elevated BEP. Clinical characteristics and outcomes were compared between the different groups. Multiple logistic regression was performed for significant oxygen requirements using two different models using age, C-reactive protein (CRP), smoking duration, and BBE score (model 1) and age, CRP, BEP, and PEC (model 2). Results Among the 338 patients, 99.7% were male, and their mean age was 20.4 ± 1.4 years. Only 0.6% of patients were never smokers and the mean number of smoking days was 26.2 ± 25.4. Correlation analyses revealed that both the PaO2/FiO2 ratio and duration of oxygen supply were associated with BEP. ROC curve analyses indicated a cut-off level of 41.5%. Patients with a high BBE score had favourable outcomes in terms of hypoxemia, hospital days, intensive care unit admission, oxygen supply days, and steroid treatment days. Multiple logistic regression revealed that BEP and BBE score tended to be associated with significant oxygen requirements. Conclusions In this study, we revealed that both peripheral and BAL eosinophilia is associated with favourable outcomes in AEP patients.

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影响因子:2.41
发表时间:2020-01-22
DOI:10.1155/2020/9814916
作者列表:["Fei Zhao","Xuemei Guan","Jing Li","Liyong Liu","Jie Gong","Lihua He","Fanliang Meng","Jianzhong Zhang"]

METHODS:Background. Extensive studies have focused on the diagnosis and treatment of Mycoplasma pneumoniae infection; however, rare studies investigated the posttreatment conditions. We analyzed the carrying status of M. pneumoniae in the respiratory tract of children before and after treatment. Methods. Ninety-two children with M. pneumoniae pneumonia were included in this study. Clinical data were obtained from each patient, and pharyngeal swab sampling was performed at preliminary diagnosis and discharge. Real-time PCR and dilution quantitative culture were utilized to determine the DNA quantification and number of viable M. pneumoniae from samples collected upon preliminary diagnosis and discharge. Results. All the 92 cases showed DNA positivity upon preliminary diagnosis, serum IgM antibody was detected in 80 patients, and positivity of M. pneumoniae culture was observed in 82 cases. Upon discharge, the M. pneumoniae nucleotide and culture positivity were detected in 87 and 49 cases, respectively. The content of viable M. pneumoniae was 10–104 CCU/mL and 10–102 CCU/mL in the preliminary diagnosis samples and discharge samples, respectively. Conclusions. Real-time PCR was rapid and effective for the qualitative diagnosis of M. pneumoniae at the early stage, but it cannot be used to evaluate the prognosis of patients with M. pneumoniae infection. Quantitative analysis for M. pneumoniae DNA could not directly reflex the viable strain content.

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