Increase in Streptococcus pneumoniae serotype 3 associated parapneumonic pleural effusion/empyema after the introduction of PCV13 in Germany

IntroductionPediatric pneumococcal pneumonia complicated by parapneumonic pleural effusion/empyema (PPE/PE) remains a major concern despite general immunization with pneumococcal conjugate vaccines (PCVs).MethodsIn a nationwide pediatric hospital surveillance study in Germany we identified 584 children <18 years of age with bacteriologically confirmed PPE/PE from October 2010 to June 2018. Streptococcus pneumoniae was identified by culture and/or PCR of blood samples and/or pleural fluid and serotyped.ResultsS. pneumoniae was identified in 256 of 584 (43.8%) children by culture (n = 122) and/or PCR (n = 207). The following pneumococcal serotypes were detected in 114 children: serotype 3 (42.1%), 1 (25.4%), 7F (12.3%), 19A (7.9%), other PCV13 serotypes (4.4%) and non-PCV13 serotypes (7.9%). Between October 2010 and June 2014 serotype 1 (38.1%) and serotype 3 (25.4%) were most prevalent, whereas between July 2014 and June 2018 serotype 3 (62.7%) and non-PCV13 serotypes (15.7%) were dominant. Compared to children with other pneumococcal serotypes, children with serotype 3 associated PPE/PE were younger (median 3.2 years [IQR 2.1–4.3 years] vs. median 5.6 years [IQR 3.8–8.2 years]; p < 0.001) and more frequently admitted to intensive care (43 [89.6%] vs. 48 [73.8%]; p = 0.04). Seventy-six of 114 (66.7%) children with pneumococcal PPE/PE had been vaccinated with pneumococcal vaccines. Thirty-nine of 76 (51.3%) had received a vaccine covering the serotype detected. Thirty of these 39 breakthrough cases were age-appropriately vaccinated with PCV13 and considered vaccine failures, including 26 children with serotype 3, three children with serotype 19A and one child with serotype 1.ConclusionFollowing the introduction of PCV13 in general childhood vaccination we observed a strong emergence of serotype 3 associated PPE/PE in the German pediatric population, including a considerable number of younger children with serotype 3 vaccine breakthrough cases and failures. Future PCVs should not only cover newly emerging serotypes, but also include a more effective component against serotype 3.     

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

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Additional bedtime H2‐receptor antagonist for the control of nocturnal gastric acid breakthrough: A Cochrane systematic review

OBJECTIVES: To assess the effectiveness and safety of additional bedtime H₂‐receptor antagonists (H₂RAs) in suppressing nocturnal gastric acid breakthrough (NAB) via a systematic review. METHODS: Eligible trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, 2004), MEDLINE (January 1966–June 2004), EMBASE (January 1980–June 2004) and CINAHL (January 1982–June 2004). Additional hand‐searching was conducted on the proceedings of correlated conferences, eight important Chinese journals and references of all included trials. All randomized controlled trials evaluating H₂RAs for the control of NAB were eligible for inclusion. The systematic review was conducted using methods recommended by The Cochrane Collaboration. RESULTS: Only two randomized crossover studies, comprising 32 participants, met the inclusion criteria. Because the design, dosage and duration of the treatments were different between the studies, it was not possible to conduct meta‐analysis. There were no consistent conclusions found between the two included studies in evaluating H₂RAs for the control of NAB. CONCLUSIONS: No implications for practice at this stage can be concluded. Appropriately designed large‐scale randomized controlled trials with long‐term follow up are needed to determine the effects of additional bedtime H₂RAs in suppressing NAB.     

Characteristics of antibody responses in tick-borne encephalitis vaccination breakthroughs

Tick-borne encephalitis (TBE) virus is an important human pathogenic flavivirus that is endemic in Europe and Asia. The disease can be effectively prevented by inactivated vaccines and vaccination breakthroughs (VBTs) are rare. We investigated the characteristics of antibody responses in such VBTs in comparison to those in unvaccinated TBE patients. In contrast to the unvaccinated controls, most of the VBTs displayed a delayed IgM antibody response and had high avidity and strongly neutralizing antibodies already in the first sample taken upon hospitalization. The antibody profile of these patients therefore had the characteristics of an anamnestic immune response. In the VBTs analyzed, immunological priming and memory were apparently not sufficient or fast enough to prevent the disease.     

Favorable efficacy of long-term lamivudine therapy in patients with chronic hepatitis B: an 8-year follow-up study

The long-term efficacy of lamivudine therapy in patients with hepatitis B virus (HBV) infection is still not clear. In this study, 20 non-cirrhotic Japanese patients infected with HBV received lamivudine therapy for more than 1 year and were followed for a median period of 8.5 years (range, 6.7-8.7 years). The rates of HBe antigen (HbeAg) negative, HBV-DNA undetectable, and alanine aminotransferase (ALT) normal level at the start of lamivudine were 55%, 25%, and 20% and 85%, 80%, and were 80%, respectively, at the last visit, including patients who received additional treatment. The values at the last visit tended to and were significantly higher than those at the start. The values improved at the last visit regardless of the emergence of YMDD motif mutant and continuation of lamivudine. YMDD mutant and biochemical relapse with mutant virus (breakthrough hepatitis) appeared in 65% and 45% during follow-up, respectively, but severe breakthrough hepatitis occurred in only 5%. Furthermore, 80% of patients who received additional treatment for breakthrough hepatitis, regardless of continuation of lamivudine, were ALT normal level at the last visit, in contrast to 25% untreated. HBsAg clearance occurred in two patients of the discontinuous lamivudine group with non-vertical transmission, who were relatively young. One was infected with HBV genotype C with breakthrough hepatitis and the other had no YMDD mutant and was infected with genotype D, a rare type in Japan. None developed cirrhosis or hepatocellular carcinoma (HCC) during follow-up. Our results suggest that long-term lamivudine therapy improves long-term prognosis, especially when additional treatment for breakthrough hepatitis is used.     

奥美拉唑联合雷尼替丁治疗十二指肠溃疡的抑酸疗效分析

目的:比较奥美拉唑(omeprazole,OME)不同剂量及联合雷尼替丁(ranitidine,RAN)治疗十二指肠球部溃疡(duodenal uncler,DU)活动期患者的抑酸效果,特别是对夜间酸突破(noctumal acid breakthrough,NAB)现象的控制,并探讨幽门螺杆菌(helicobacter pylori,HP)对抑酸疗效的影响.方法:病例选自经本院胃镜确诊为十二指肠球部溃疡活动期患者74例,随机分配入4个治疗组:A组,13例,OME 20 mg每天1次;B组,37例,OME 20 mg每天2次;C组,11例,OME 40 mg静脉推注,每12 h 1次;D组,13例,B方案联合RAN 150 mg睡前口服.在第5天对入组病人进行24 h胃内pH监测.结果:4组胃内24 h及夜间平均pH值、中位pH值、pH＜4所占的时段百分比及NAB发生率(A组76.9%,B组24.3%,C组18.2%,D组7.7%)差异有显著性,其中,A组与B、C、D 3组差异有显著性(P＜0.001);B、C、D 3组比较差异无显著性(P＞0.05);同一治疗组内HP阳性者24 h及夜间平均pH值、中位pH值均高于阴性者,pH＜4所占的时段百分比低于阴性者.HP阳性者NAB发生率低于阴性组(13.7%vs44.1%,P＜0.05),而在4个治疗组内仅有A组内HP阳性者NAB发生率低于阴性者,其余3组HP感染与否对NAB发生率无影响.结论:OME抑酸疗效具有剂量依赖效应,联用RAN有减少NAB的趋势.HP感染者应用OME抑酸效果较好.     

人文科学方法论视野下美学的困境与出路

美学的学科化建设，要求形成独有的研究方法和价值评判系统。摆脱中国美学在理论形态上的失语失范，应从根本上抛却传统实用理性的学术史观，展开特定时期或领域的历史情境重构；避免西方美学发展过程中的各种偏差和错位，须在源头上舍弃研究中僵固的概念分析及逻辑归纳方法，对具体文本或问题进行整体文化解读。在当代学术视野和人文科学方法论背景下，历史情境重构和整体文化解读，将为美学脱离学科困境、形成理论突破，提供新的探究维度和思想生长点。因为说到底，美学研究的演变历来与方法的转变息息相关。     

Hepatitis B therapies and antiviral resistance detection and management

Hepatitis B virus (HBV) infection is an important health problem and a major cause of chronic hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Durable viral suppression has been documented to lower the risk of hepatocellular carcinoma and disease progression. Treatment of chronic HBV infection remains a major clinical challenge because long-term use with approved oral antiviral agents is associated with drug resistance. Antiviral resistance can result in poor clinical outcomes; therefore first-line therapy with the most potent agent(s) is recommended to lower the risk. Early detection of resistance is paramount to possibly reduce the risk of liver-related morbidity and mortality. It is important that clinicians monitor for therapeutic efficacy and resistance, so as to optimize the management of chronic HBV.