肺炎链球菌蛋白质疫苗研究进展

肺炎链球菌是引起肺炎、中耳炎、脑膜炎等的重要致病菌。目前投入使用的荚膜多糖疫苗有很大的局限性，因此针对其主要毒力因子的蛋白质疫苗发展很快，有望替代多糖疫苗。     

肺炎链球菌疫苗的研究进展

肺炎链球菌是引起全球所有年龄组高发病率和病死率的主要病原菌,其疫苗的研制和使用对肺炎链球菌感染的防治具有重要意义。目前临床投入使用的肺炎链球菌疫苗主要有23价荚膜多糖疫苗和7价多糖蛋白结合疫苗,两者都具有一定的效力和良好的安全性,但也存在许多局限性。其他肺炎链球菌多价多糖蛋白结合疫苗、蛋白疫苗、DNA疫苗、联合疫苗等也在研制和开发中。     

肺炎链球菌新型疫苗研究进展

肺炎链球菌是引起肺炎的主要病原体,肺炎链球菌性疾病是全球严重的公共卫生问题之一,每年约导致160万人死亡。目前,已明确的肺炎链球菌血清型高达100种,已上市的预防肺炎链球菌感染的疫苗只覆盖了部分肺炎链球菌血清型,无法预防非疫苗血清型和不可分型肺炎链球菌感染。因此,新型“通用型”肺炎链球菌疫苗的研发迫在眉睫,本综述旨在总结目前在用或在研究疫苗策略的优势和局限性,为进一步研发肺炎链球菌疫苗提供新的参考思路。     

尿肺炎链球菌抗原检测在儿童肺炎链球菌肺炎诊断中的临床意义

目的：探讨尿肺炎链球菌抗原检测在肺炎链球菌肺炎诊断中的临床意义。方法随机选择下呼吸道感染患儿300例,同时采集患儿痰标本、血标本、尿标本,对痰、血标本进行病原菌培养、鉴定,采用胶体金法检测尿肺炎链球菌抗原。结果300例患儿中,痰培养、血培养和尿肺炎链球菌抗原检测阳性率分别为10．33％（31/300）、15．67％（47/300）和19．33％（58/300）,尿肺炎链球菌抗原检测阳性率高于其他两种方法,血培养检测阳性率高于痰培养（P＜0．05）;尿肺炎球链菌抗原检测诊断肺炎链球菌肺炎的灵敏度和特异度分别为82．98％（39/47）和92．49％（234/253）。结论尿肺炎链球菌抗原检测可作为儿童肺炎链球菌肺炎的辅助诊断依据。     

肺炎链球菌耐药性进化

世界卫生组织报道,全球每年约有160万人因肺炎链球菌性疾病死亡(其中约有70~100万5岁以下儿童)。在全球疫苗可预防疾病中,肺炎链球菌疾病已成为导致5岁以下儿童死亡的首要病因。于1940年引进青霉素使得肺炎链球菌疾病的发病率和病死率急剧下降,然而,其过度使用导致青霉素耐药菌出现,多重耐药(MDR)肺炎链球菌的广泛传播已成为一个不容忽视的公共健康问题。根据肺炎链球菌荚膜多糖抗原的差异,大约可鉴别出90余种血清型,致病的血清型虽在年龄和地理位置的分布有所不同,但造成大部分婴幼儿患病的多为最常见的7种血清型,因此接种七价肺炎链球菌结合疫苗(PCV7)被认为是现今最有效、直接的预防手段。在美国,PCV7已成功减少侵袭性肺炎链球菌疾病(IPD)的发病率和相关血清型菌群的耐药性,然而这也造成了非疫苗血清型菌株的耐药性与其引起IPD发病率的增加,尤其是血清型19A[1]。新型结合疫苗的应用,特别是PCV13,对肺炎链球菌的耐药性产生了巨大的影响。     

肺炎链球菌耐药性调查

目的探讨肺炎链球菌分布,对其耐药性进行连续监测,为临床抗感染治疗提供应用依据。方法收集本院2004年5月-2005年3月入托健康儿童体检1500人,取咽拭子进行细菌培养,分离出肺炎链球菌114株,检出率7.6%。同期本院852名住院患者为对照组,取咽拭子和痰标本进行细菌培养,检出146株肺炎链球菌(其中内科患者检出20株,儿科检出122株),执行NCCLS2001年抗微生物药物敏感实验的执行标准,然后对两组进行耐药性比较。结果追踪健康儿童与住院患者分离出的肺炎链球菌,它们的同源性与耐药性基本一致,对青霉素耐药率较低(患者4.1%,健康儿童1.8%),而对苯唑西林、红霉素、林可霉素、四环素、复方新诺明有较高耐药率,而头孢菌素类药、喹诺酮类药普遍耐药率呈上升趋势。因而本地区分离肺炎链球菌以耐苯唑西林、克林霉素、大环内酯类、复方新诺明多重耐药株为主,应引起临床重视,合理使用抗生素。     

肺炎链球菌耐药性进化

世界卫生组织报道,全球每年约有160万人因肺炎链球菌性疾病死亡（其中约有70～100万5岁以下儿童）。在全球疫苗可预防疾病中,肺炎链球菌疾病已成为导致5岁以下儿童死亡的首要病因。于1940年引进青霉素使得肺炎链球菌疾病的发病率和病死率急剧下降,然而,其过度使用导致青霉素耐药菌出现,多重耐药（MDR）肺炎链球菌的广泛传播已成为一个不容忽视的公共健康问题。根据肺炎链球菌荚膜多糖抗原的差异,大约可鉴别出90余种血清型,致病的血清型虽在年龄和地理位置的分布有所不同,但造成大部分婴幼儿患病的多为最常见的7种血清型,因此接种七价肺炎链球菌结合疫苗（PCV7）被认为是现今最有效、直接的预防手段。在美国, PCV7已成功减少侵袭性肺炎链球菌疾病（IPD）的发病率和相关血清型菌群的耐药性,然而这也造成了非疫苗血清型菌株的耐药性与其引起 IPD 发病率的增加,尤其是血清型19A［1］。新型结合疫苗的应用,特别是 PCV13,对肺炎链球菌的耐药性产生了巨大的影响。     

儿童肺炎链球菌和流感嗜血杆菌疾病及其疫苗预防

肺炎链球菌(Streptococcuspneumoniae,Sp)和流感嗜血杆菌(Haemophilusinfluenzae,Hi)是儿童社区获得性感染的重要病原,能引起化脓性脑膜炎(化脑)、肺炎、败血症和急性中耳炎等感染性疾病,严重危害儿童健康。因此,在儿童人群中,预防这两种细菌感染尤显重要。已经投入应用的Sp和Hib结合疫苗已经通过临床研究,能有效预防儿童Sp和Hib疾病,降低发病率,保障儿童健康。在我国,医务和预防工作人员应共同努力,加强对Sp和Hib疾病的研究,为疫苗研制和应用提供必要和充分的依据。     

23价肺炎链球菌多糖疫苗佐治慢性支气管炎的疗效观察-附32例报告

1引言2001年2月～2002年2月,我院采用在常规治疗的基础上,应用23价肺炎链球菌多糖疫苗(纽莫法23)三角肌肌内注射治疗32例慢性支气管炎(慢支)病例,取得较好的疗效,现将结果报道如下。2资料与方法2.1一般资料2001年2月～2002年2月我院门诊和住院的慢支患者57例,全部符合慢支的诊断标准犤1犦,均有2年以上慢性咳嗽、咳痰反复发作史。随机分为治疗组32例,对照组25例。治疗组男18例,女14例,年龄48～70岁,中位年龄66岁,其中单纯型20例,喘息型12例;急性发作期23例,慢性迁延期9例。对照组男14例,女11例,年龄49～72岁,中位年龄65岁,其中单纯型16例,喘…     

基层医院肺炎患儿肺炎链球菌的分离及耐药性分析

目的了解基层医院对肺炎患儿的肺炎链球菌(SP)分离及耐药情况,为基层社区医院经验治疗儿童肺炎提供药物选择依据。方法对2011年4月至2012年3月新入院住院及门诊首诊肺炎患儿痰及咽拭子标本培养,分离SP。采用生物-梅里埃ATBExpression细菌分析仪及配套试剂确认菌株、药敏试验。结果从1656例儿童肺炎标本中分离出395株SP,分离率为23.85%。耐药率超过95%的有红霉素、复方新诺明、四环素、克林霉素共4种,青霉素、阿莫西林、头孢噻肟、氯霉素耐药率介于40%～20%,耐药率较低的喹奴普汀、左氧氟沙星、万古霉素。结论基层社区医院接诊肺炎儿童病例多,SP分离率高,菌株对常用抗菌药物耐药率高,加强细菌培养及抗菌药物使用情况的监测,对SP感染引起肺炎的治疗和抗菌药物的选择具有重要意义。     

Impact of the pneumococcal conjugate vaccine on serotype distribution and susceptibility trends of pediatric non-invasive Streptococcus pneumoniae isolates in Tokai,Japan over a 5-year period

Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in February 2010 markedly reduced the burden of invasive pneumococcal disease (IPD) and changed serotype distribution in Japan. We investigated the serotype distribution and susceptibility trends of non-invasive Streptococcus pneumoniae isolates collected from pediatric patients. A total of 564 pneumococcal isolates were collected over a 5-year period between 2008 and 2012. The coverage of PCV7 significantly decreased throughout the study period, from 49.3% in period 1 (between June 2008 and April 2009) to 23.4% in period 4 (between October 2011 and March 2012). This change was mainly due to a large decrease in the frequency of 19F (from 20.6% to 9.9%) and 6B (from 10.3% to 2.7%) and an increase in serotype 3 (from 5.1% to 13.5%) and serogroup 15 (from 4.4% to 9.0%). According to serotype replacement, the susceptible ratios of S. pneumoniae to β-lactams increased slightly while macrolide resistance remained high. The high frequency of macrolide-resistant pneumococcal isolates may continue because of the high frequency of erm(B) in replace serotypes such as serotype 3 and serogroup 15. The continuous surveillance study is essential following the introduction of a second generation 13-valent pneumococcal conjugate vaccine (PCV13).     

Pneumococcal conjugated vaccine: PHiD-CV

At the beginning of a new century, we have gained significant achievements against pneumococcal infections by using conjugated pneumococcal vaccines. In January 2009, the EMEA issued a positive opinion about, and recommended the approval of, GlaxoSmithKline’s pediatric pneumococcal candidate vaccine, which is indicated for active immunization against invasive pneumococcal disease (IPD) and acute otitis media caused by Streptococcus pneumoniae in infants and children from 6 weeks up to 2 years of age. The approved 10-valent pneumococcal vaccine (PHiD-CV) contains all serotypes in 7-valent pneumococcal conjugate vaccine (PCV-7) plus serotypes 1, 5 and 7F. Protein D from nontypeable Haemophilus influenzae is the carrier protein for eight serotypes, while tetanus and diphtheria toxins are in the carrier proteins for the remaining two serotypes. It has also been proved that PHiD-CV is immunogenic, safe and well-tolerated in children. This vaccine can be coadministered with routinely used pediatric vaccines. Noninferiority criteria of PHiD-CV compared with PCV-7 were established in shared serotypes, except for serotypes 6B and 23F, and PHiD-CV is immunogenic for additional serotypes as assessed by the percentage of subjects with antibody concentrations. PHiD-CV is also immunogenic for ten serotypes as assessed by post-primary and post-booster dose opsonophagocytic activity responses. Vaccine efficacy against IPD and other conditions should be monitored for shared serotypes and also additional serotypes during the postmarketing period. Optimal scheduling, safety and immunogenicity data in children with different risk factors for IPD, or whether it will provide herd immunity, are the questions waiting for answers in the postmarketing period. Further studies are needed to assess the potential advantages of protein D as a carrier and the potential efficacy of this new vaccine against H. influenzae. The potential public health efficacy of PHiD-CV in low-income countries, where IPD and pneumonia are a major public health problem, is a major concern.     

Pneumococcal vaccine and opsonic pneumococcal antibody

Streptococcus pneumoniae is a major human pathogen responsible for the majority of bacterial pneumonia cases as well as invasive pneumococcal diseases with high mortality and morbidity. Use of conjugate vaccines targeting the pneumococcal capsule has dramatically reduced the incidence of invasive diseases, and there are active efforts to further improve the conjugate vaccines. However, in children new pneumococcal vaccines can no longer be tested with placebo-based clinical trials because effective vaccines are currently available. Thus, vaccine studies must depend on surrogate markers of vaccine efficacy. Although traditional antibody levels (e.g., ELISA) are useful as a surrogate marker of protection, they have limitations, and a bioassay measuring the capacity of antibodies to opsonize pneumococci has been developed. This opsonophagocytosis assay (OPA) replicates the in vivo mechanism of antibody protection and should therefore better reflect protection by vaccine-induced antibodies. Technical improvements of OPA have made this bioassay rapid, multiplexed, and practical for analyzing small samples including those from children. Strong correlations between ELISA and OPA have been observed in many studies of young children. However, poor correlations have been found in some important clinical situations (such as determination of protection by cross-reactive antibodies) and populations (such as elderly adults and immunodeficient patients). In these settings, OPA has become a useful supplementary measure of pneumococcal vaccine immunogenicity. Current efforts to standardize OPA will further expand its uses.     

Pneumococcal vaccination in adults: recommendations, trends, and prospects

The US Centers for Disease Control and Prevention recommends vaccination against Streptococcus pneumoniae for all people age 65 and older and also for younger people at high risk. However, experts continue to debate the efficacy of the vaccine; most observational studies found it beneficial, while clinical trials were inconclusive as a group. Although pneumococcal vaccination may or may not protect against pneumonia or death from any cause, it does significantly decrease the risk of invasive pneumococcal disease and is worthwhile for this reason.     

Prevalence and molecular characterisation of Streptococcus pneumoniae serotype 6C in Queensland,Australia

Streptococcus pneumoniae serotype 6C was first identified in 2007, although retrospective studies have since identified serotype 6C among stored isolates dating back to 1962. We investigated the incidence and genetic diversity of serotype 6C strains isolated from Queensland patients between 2001 and 2011. Isolates were identified by Quellung reaction and antimicrobial susceptibility testing was performed. The incidence of serotype 6C among serogroup 6 Queensland invasive pneumococcal disease increased from 6.8% (2001–2004) to 39% (2005–2010) of serogroup 6 isolates (P = 0). Genetic diversity of Queensland 6C isolates was high, with molecular analysis identifying 19 sequence types by multi-locus sequence typing, and 35 types by multi-locus variable-number tandem repeat analysis.     

IL-23 and IL-17 in acute ischemic stroke: Correlation with stroke scales and prognostic value

Background and PurposeInflammation plays a crucial role in brain damage following stroke. Here, we evaluate interleukin 23 (IL-23) and interleukin 17 (IL-17) in the inflammatory process and its relations with neurological findings of patients with acute ischemic stroke (AIS).Material and MethodsFifty consecutive patients with AIS admitted to our hospital within 24 h of stroke onset were enrolled in a prospective cohort study. Serum IL-23 and IL-17 were measured in the first, third and fifth day after the stroke. Neurological stroke severity were determined with the National Institutes of Health Stroke Scale (NIHSS) and with the modified Rankin Scale (mRS) within 24 h of the acute event, on the third and fifth day after the stroke, and at the time of hospital discharge.ResultsBoth neurological scores for stroke outcome at hospital discharge were related to IL-23 protein within 24 h and on the fifth day, but with low stroke outcome predictive values. The other measurements did not show predictive capacity for stroke outcome. There was a significant increase in median serum concentrations of IL-23 on the fifth day (p < 0.001) and in IL-17 median levels on the third day compared to the first 24 h after the acute injury (p < 0.001). However, there was no correlation between IL-23 and IL-17 levels with neurological outcomes at hospital discharge or after four years.ConclusionIL-23 and IL-17 increase after stroke, but had no sufficient discriminative capacity to be of clinical use as outcome stroke predictors.     

Changing Trends of Invasive Pneumococcal Disease in the Era of Conjugate Pneumococcal Vaccination in Olmsted County: A Population-Based Study

ObjectiveTo estimate the incidence of invasive pneumococcal disease (IPD) in the pre–13-valent pneumococcal conjugate vaccine (pre-PCV13; 7-valent pneumococcal conjugate vaccine era, 2002-2010) and post-PCV13 (2011-2018) time periods.Patients and MethodsUsing the Rochester Epidemiology Project, we conducted a population-based cohort study of all IPD cases in Olmsted County, Minnesota, from January 1, 2002, to December 31, 2018.ResultsOverall, 187 cases of IPD were identified. The incidence of IPD decreased significantly from 11.1 (95% CI, 9.1 to 13.2) to 5.6 (95% CI, 4.3 to 6.9) per 100,000 person-years when the pre- and post-PCV13 periods (2002-2010 vs 2011-2018) were compared (P<.001). Of the 187 patients with IPD, 112 (59.9%) had previously received at least 1 dose of pneumococcal vaccine. Among the IPD cases in the post-PCV13 period, there was an increase in non-PCV13 serotypes, mainly 11A (from 1.0% [1 of 105] to 6.2% [4 of 64]) and 33F (from 2.9% [3 of 105] to 15.6% [10 of 64]), while PCV13/non–7-valent pneumococcal conjugate vaccine serotypes declined from 38.1% (40 of 105) to 15.6% (10 of 64). At 30 days after an IPD diagnosis, the survival rate was 88.8% (95% CI, 84.4% to 93.4%).ConclusionA marked decline in IPD incidence occurred during the post-PCV13 era. Because of the observed increase in non-PCV13 serotypes, coupled with multiple factors that impact the epidemiology of IPD, ongoing surveillance of patients with IPD, particularly due to non-PCV13 serotypes, is warranted.     

The development of 13-valent pneumococcal conjugate vaccine and its possible use in adults

Introduction: Worldwide, Streptococcus pneumoniae causes significant morbidity and mortality. The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for use in persons aged 65 years and over and in adults with certain chronic medical conditions. Pneumococcal conjugate vaccines (PCVs) have been developed for use in infants and children aged less than 5 years, and are being studied for use in adult populations.

Areas covered: The different types of pneumococcal vaccines are discussed. Studies comparing PPSV23 and PCVs, as well as the results of the widespread use of 7-valent PCV are covered. The possible extension of the use of 13-valent PCV to adults, particularly to vulnerable populations, is discussed. The MEDLINE database was used to identify relevant studies from literature published in English between January 1977 and January 2011. All studies of adults aged over 18 years were considered for the review.

Expert opinion: Elderly individuals and adults with chronic medical conditions who are at increased risk for pneumococcal disease would benefit from more effective prevention than is provided by the currently recommended PPSV23.