百日咳流行病学研究进展

百日咳主要是由百日咳杆菌、副百日咳杆菌引起的一种传染性强的急性呼吸系统疾病,人群普遍易患,小婴儿病情最重。尽管疫苗覆盖率较高,但是全球百日咳仍未完全根除。相反,过去20年,全球百日咳的发病率较之前升高,出现局部地区小流行,称百日咳再现,因此有必要对国内外百日咳发病现状做出评估,为更好地监测和控制百日咳提供依据。该文对百日咳的流行病学变化及其相关原因分析和免疫策略作一综述。     

百日咳杆菌的分子流行病学研究

目的 明确百日咳杆菌分离株的分子分型,比较不同年代分离株的型别差异.方法 共25株百日咳菌株,其中18株为2000年至2007年北京儿童医院临床分离株,7株为20世纪70年代分离株,采用脉冲场凝胶电泳(PFGE)和多位点序列分型(MLST)2种方法对菌株进行分型.结果 2000年以后菌株MIST分型均为ST2型,PFGE分型分为8种型;20世纪70年代菌株MLST分型均为ST1型,PFGE分为5种型.2000年后菌株与20世纪70年代菌株无相同的PFGE型和MLST型.结论 不同时期流行的百日咳杆菌具有不同的分子分型.     

细菌性脑膜炎的病原体及抗生素敏感性分析

目的　回顾分析我院 1 997～ 2 0 0 3年儿童细菌性脑膜炎 (菌脑 )的病原体及其抗生素敏感性。方法　分析符合菌脑临床诊断患儿脑脊液或血培养分离菌及其药敏试验结果。结果　菌脑 40 1例患儿中 97例细菌培养阳性 ,诊断阳性率 2 4 % ,最常见病原菌为金黄色葡萄球菌 (2 8% ) ,其次是肺炎链球菌 (1 9% )与大肠杆菌 (1 3 % ) ,并出现条件致病菌如微球菌。金黄色葡萄球菌分离株对青霉素不敏感 ,其中 1株对万古霉素与替考拉宁耐药 ;大肠杆菌、肠杆菌和假单胞菌均有对泰能的耐药株。结论　金黄色葡萄球菌是菌脑主要病原菌 ,临床用药须考虑当地的病原菌及其耐药问题。     

百日咳患儿血清PT-IgG水平相关因素分析

目的 探讨影响百日咳患儿血清百日咳毒素抗体(PT-IgG)水平的相关因素。方法 回顾性分析2018年4月1日至2019年7月31日住院治疗的百日咳患儿的临床资料。分析不同病程、百日咳疫苗接种剂次、发病年龄、疾病严重程度对于百日咳患儿PT-IgG水平的影响。结果 共纳入638例患儿,其中未接种组313例,男177例、女136例,中位年龄78.0(52.0～125.0)天;接种组325例,男163例、女162例,中位年龄232.0(144.0～483.0)天。未接种组患儿不同采样时病程(≤14d、15～21d、>21d)组间不同PT-IgG水平分布差异有统计学意义(P<0.01);病程>21d组PT-IgG≥80 IU/mL的比例较高。接种组患儿不同采样时病程组间不同PT-IgG水平分布差异有统计学意义(P<0.01);病程15～21d组和>21d组PT-IgG≥80 IU/mL的比例较高。不同疫苗接种剂次组之间PT-IgG水平的差异有统计学意义(P<0.01);随着疫苗接种剂次增加,PT-IgG水平逐渐增高。未接种组中,无论重症组还是普通组,不同采样时...     

百日咳致病菌株的药物敏感性和疫苗相关基因型研究

目的　了解百日咳确诊患儿的临床特征、致病菌株的毒力基因分型及抗菌药物敏感性状况。 方法　收集2015-2016年首都医科大学附属北京儿童医院细菌培养确诊的224例百日咳患儿的临床信息,采用E-test法及KB纸片法检测分离的百日咳鲍特菌对抗菌药物的敏感性,并检测菌株的23S rDNA基因耐药突变及其抗原基因型。结果　224例患儿分别来自全国14个省份,其中150例（67.0%）患儿＜6月龄,176例（78.6%）例患儿未接种或未完成全程百日咳疫苗接种。224株百日咳鲍特菌的主要抗原基因型为ptxA1/ptxC1/ptxP1/prn1/fim2-1/fim3-1/tcfA2,占90.6%（203/224）。所有红霉素耐药菌株均为ptxP1基因型,且23S rDNA基因均检测到A2047G位点突变。分离到18株ptxP3基因型高毒力株,对大环内酯类药物均敏感。全部分离株对磺胺甲基异噁唑/甲氧苄啶（SMZ）最小抑菌浓度（MIC）值分布范围为0.004～0.500 mg/L。结论　当前培养确诊的百日咳患儿以未接种疫苗的小婴儿为主,致病菌株的抗原基因型主要为ptxA1/ptxC1/ptxP1/prn1/fim2-1/fim3-1/tcfA2,该型菌株普遍对大环内酯类耐药。高毒力的ptxP3型致病菌株较少见,均对大环内酯类敏感。体外药物敏感性试验提示SMZ可用于百日咳的经验治疗。     

新生儿百日咳临床特点和致病菌耐药性分析

目的 总结新生儿百日咳的临床特点和致病株的耐药性。方法 分析7 例新生儿百日咳患儿的临床特点,采用Etest 方法和纸片扩散法检测分离株对红霉素等抗生素的敏感性。结果 7 例患儿中,6 例患儿的母亲或祖辈有持续10 d 以上的咳嗽,其中4 例患儿的家庭成员中,≥ 3 人咳嗽。患儿早期均有鼻塞、轻咳症状,5 例在病程4~7 d 出现典型痉挛性咳嗽;5 例口唇青紫,4 例有呼吸暂停,3 例有屏气发作,仅2 例有发热表现。可见程度不一的鼻扇、三凹征等呼吸困难表现。分离株中5 株在红霉素纸片周围没有形成抑菌环,Etest 检查显示红霉素、阿奇霉素、克拉霉素和克林霉素对其的最小抑菌浓度（MIC）均>256 mg/L。结论 对于有呼吸道症状,且曾与呼吸道感染患者密切接触的新生儿应警惕百日咳的可能,应详问流行病学史,并及时进行病原学检查;大环内酯类抗生素耐药菌株在百日咳病原菌中已很常见。     

儿童类百日咳综合征病原学及临床特征研究

目的　探讨类百日咳综合征的病原学及其临床特点。方法　对2016年2月至2017年12月苏州大学附属儿童医院可疑百日咳住院患儿进行痰百日咳博德特菌聚合酶链式反应（PCR）检测、细菌培养、呼吸道病毒抗原及血清肺炎支原体抗体检测。结果　共有197例患儿纳入研究,其中119例（60.4%）百日咳博德特菌PCR检测阳性,78例百日咳检测阴性的标本中,其他病原检测阳性者37例,其中鼻病毒14例（37.8%）,肺炎支原体14例（37.8%）,博卡病毒4例（10.8%）,副流感病毒3型3例（8.1%）,呼吸道合胞病毒1例（2.7%）,流感嗜血杆菌1例（2.7%）。百日咳组患儿的平均年龄、痉挛样咳嗽、鸡鸣样回声、咳后呕吐、阵发性青紫、并发症及肺部体征比较差异均无统计学意义（P＞0.05）。百日咳组男性患儿的比例（57.1% vs. 35.3%）、白细胞计数［（18.83±11.54）×109/L vs. （12.46±6.01）×109/L］、淋巴细胞计数［（10.62±8.48） ×109/L vs. （6.54±5.13×109/L］明显高于类百日咳组,差异均有统计学意义（P＜0.05）。结论　鼻病毒和肺炎支原体是引起类百日咳综合征的主要病原,白细胞和淋巴细胞计数可作为临床初步区别百日咳与类百日咳的一个指标。     

中国百日咳行动计划专家共识

自20世纪80年代以来,一些百日咳白喉破伤风联合疫苗接种率高的国家陆续发生了百日咳流行或局部暴发,被称为百日咳再现。近年来,我国一些省份也陆续出现百日咳疫情大幅回升,引起各方高度关注。为此,中华预防医学会参考"全球百日咳行动计划"工作模式,发起了"中国百日咳行动计划",并组织相关专家研究形势,分析问题。在对国内外百日咳...     

小儿百日咳51例临床分析

目的　分析近五年百日咳患儿的临床特点。方法总结分析1998年1月-2003年1月间我院51例住院百日咳患儿临床资料,从发病季节、发病区域、年龄分布、是否进行免疫接种、主要临床表现及并发症、疗程、预后等方面进行分析。结果51例百日咳患儿在发病区域、年龄分布、免疫接种等方面有着显著性差异(P<0.05)。疗程与预后方面无显著性差异(P>0.05)。发现1岁以下婴儿发病占总病例数的76.47%,发病以1岁以下婴儿为主(P<0.01),其中3月龄以内小婴儿占总病例数的35.29%。农村患儿发病高于城市患儿(P<0.01)。结论百日咳住院患儿以农村患儿及无免疫接种史或不全接种史者为主,3月龄以内小婴儿发病率有上升趋势。     

儿童百日咳临床特征及重症百日咳危险因素分析

目的　分析儿童百日咳临床特征及重症百日咳发生的危险因素,为临床诊治提供参考。方法　以首都儿科研究所中心实验室为检测中心,回顾性分析2019年1月至12月确诊的114例百日咳住院患儿病例资料。根据是否合并其他病原感染,分为单纯百日咳组73例,混合感染组41例;根据病情程度分为普通百日咳组100例,重症百日咳组14例。组间进行单因素比较,同时行二元Logistic回归分析重症百日咳的危险因素。结果　（1）百日咳好发于秋冬季共66例（62.2%）。患儿以≤6月龄为主,共79例（69.3%）。未免疫89例（78.1%）,免疫25例（21.9%）。（2）单因素分析比较得出,混合感染组较单纯百日咳组更易出现血氧下降、三凹征、发热、肺部湿啰音（P＜0.05）;重症组中有早产史、咳嗽后青紫、三凹征、发热、肺部湿啰音、肺炎和混合感染患者占比高于普通组（P＜0.05）;混合感染组、重症组较单纯百日咳组、普通组住院时间更长（P＜0.05）;重症组白细胞峰值较普通组高（P＜0.05）,Logistic回归分析显示白细胞峰值高是重症百日咳的危险因素（OR＝1.096,P＜0.05）。（3）114例确诊患儿均使用大环内酯类抗生素治疗,10例（8.8%）患儿在病程7 d内用药,33例（28.9%）在病程8～14 d用药,余均＞病程14 d用药,其中5例重症患儿＞病程21 d用药。（4）≤4月龄的重症百日咳患儿易并发肺炎、百日咳脑病、心肺衰竭等严重并发症,其中8例患儿行有创通气治疗。经积极治疗,1例患儿死亡,余均好转出院。结论　≤6月龄、未免疫的小婴儿百日咳发病多见,常需住院治疗,小月龄的百日咳患儿并发症发生率更高。合并感染、延迟用药可能会加重百日咳病情,延长住院时间。监测血白细胞峰值有助于病情程度的判断。     

Laboratory-confirmed reinfections with Bordetella pertussis

Susceptibility to infection with Bordetella pertussis re-emerges several years after pertussis vaccination. However, the duration of immunity after natural infection with B. pertussis, postulated to be lifelong, is not known. In an ongoing study, the longitudinal course of pertussis antibodies in patients who have had laboratory-confirmed pertussis is being followed using sera obtained at irregular intervals. In 4 patients a reinfection with Bordetella pertussis is described respectively 7 (patient A), 12 (patients B and C) and 3.5 (patient D) y after the first infection. It seems that the longer the interval between the infections the more severe the complaints. Conclusion: To the authors' knowledge. these are the first patients in whom symptomatic reinfection with B. pertussis has definitely been proven by laboratory confirmation of both episodes. Bordetella pertussis infection should be considered in patients with symptoms of typical or atypical whooping cough, irrespective of their vaccination status or previous whooping cough.     

Rapid,sensitive and specific diagnosis of Bordetella pertussis using the polymerase chain reaction

Use of a repetitive DNA sequence of Bordetella pertussis allowed successful detection of the organism by the polymerase chain reaction (PCR). The method was highly sensitive, being able to detect B. pertussis in specimens containing only a few cells. It was also highly specific, with no amplification of specimens containing other organisms, for example Haemophilus influenzae or Neisseria, being observed. A diagnosis could be made within 1 day. The PCR assay was also evaluated in clinical specimens. Among 47 nasopharyngeal specimens obtained from 24 patients with laboratory-confirmed pertussis, 27 were positive by PCR and 19 by culture. In particular, all three bronchial aspirates from one patient with pertussis were positive by PCR, but only one showed positive on culture. Eleven specimens from parapertussis patients and 65 specimens from patients without pertussis tested negative. It was concluded that this newly developed PCR method for the diagnosis of pertussis was more rapid and sensitive than the usual culture method. Polymerase chain reaction could have a major impact on the treatment and control of this infection and would be a useful tool for studying the pathogenesis of B. pertussis infection.     

新生儿百日咳 17 例临床分析

目的探讨新生儿百日咳的临床表现、诊断、治疗及预后。方法回顾性分析经百日咳鲍特菌聚合酶链反应确诊为百日咳的17例新生儿患者的临床资料。结果 17例患儿中,男8例、女9例,早产儿2例,发病日龄15~27 d。13例患儿有咳嗽患者接触史,4例早期有鼻塞、流涕等症状,5例有典型痉挛性咳嗽,1例咳嗽伴有鸡鸣样回声,6例咳嗽剧烈有面色通红,7例咳嗽剧烈时伴口唇发绀,2例住院前曾出现全身青紫,7例咳嗽后有吐奶,3例有发热。15例患儿外周血白细胞计数升高,为(12.57~79.63)×109/L,淋巴细胞比例为45.1%~75.2%。百日咳PCR拷贝数为7.12×10~2~1.04×10~8/m L。17例患儿均予静脉滴注红霉素治疗,均有明显好转,无死亡病例。结论对于有明确咳嗽患者接触史、出现阵发性咳嗽,外周血白细胞升高,并以淋巴细胞为主的新生儿需警惕百日咳可能,应及早行相关检查。     

Antibody levels to Bordetella pertussis in 10-yr-old children with atopy and atopic asthma

Suboptimal immune responses to vaccination have been suggested among atopic infants. The aim of this study was to assess the influence of atopy and atopic asthma on the humoral response to Bordetella pertussis vaccination. Immunoglobulin (Ig)G and IgA specific antibodies were measured by enzyme linked-immunosorbent assay in 102, 10-yr-old atopic children (66 of them also being asthmatics) and compared with 76 non-atopic and 53 non-atopic non-asthmatic controls of similar age. The levels of antibodies and the percentage of positives to B. pertussis were comparable in all groups. Children with a very high total serum immunoglobulin (Ig)E (Percentile (Pct) > 90th) showed higher (p = 0.01) IgG pertussis antibodies than children with very low serum IgE (Pct < 10th). In conclusion, we found normal pertussis antibody levels in atopic and in atopic asthmatic children in late childhood, thus overriding any possible suboptimal response during infancy.     

Recent progress in clinical and basic pertussis research

Over the last decade, substantial progress has been made in the field of pertussis research. This includes better understanding of virulence mechanisms and their influence on the pathogenicity of Bordetella pertussis, increased awareness of the broad spectrum of disease and more insight into the host's immune response to infection, improved diagnostic tools, development, evaluation, introduction and implementation of several acellular pertussis vaccines and better understanding of the epidemiology of pertussis in adolescents and adults. Conclusion The major achievements in the field of pertussis research are reviewed and discussed. They have great impact on the current and future practice of paediatric, adolescent and adult medicine. Received: 19 August 2000 and in revised form: 9 November 2000 / Accepted: 10 November 2000     

Respiratory failure caused by dual infection with Bordetella pertussis and respiratory syncytial virus

Two infants with pneumonia caused by both Bordetella pertussis and respiratory syncytial virus (RS virus) suffered respiratory failure preceded by convulsion. Detection of respiratory pathogens with polymerase chain reaction and enzyme-linked immunosorbent assay was crucial in the management of dually infected infants.     

γ T cells are decreased in the blood of children with Bordetella pertussis infection

The biological role of T cell receptor (TCR) γ bearing cells is not yet fully understood. We studied 12 children with Bordetella pertussis infection and 12 age- and sex-matched healthy controls. Patients with whooping-cough yielded significantly lower relative and absolute numbers of blood TCR-γ+ cells than normal controls (both p < 0.001). It is suggested that the depletion of circulating γ T cells in patients with Bordetella pertussis infection might be the result of the dispatch of these cells to the site of inflammation, i.e. the bronchial mucosa. Interestingly, other human lung diseases, such as allergic bronchial asthma and sarcoidosis display similar pulmonary phenotypical features.     

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??Objective??To explore the clinical characteristics of coinfections in children with pertussis. Methods??From February 2016 to September 2017??198 cases with pertussis-like symptom were tested for PCR??bacterial culture??respiratory virus antigen and serum mycoplasma pneumoniae antibody in Children’s Hospital of Soochow University. Results??Totally 198 patients were enrolled and 105 patients were B.Pertussis positive. Single infection was in 37 cases??35.2%??. Coinfections were observed in 68??64.8%?? children with pertussis??including co-infection with one pathogen in 51 cases??75.0%??. The most frequent co-infection pathogen was rhinovirus??50.9%??26 cases????followed by Mycoplasma pneumoniae??13.7%??7 cases?? and Streptococcus pneumoniae??11.8%??6 cases??. There was no statistical difference in the coinfection rate among different age groups??P = 0.08??. Pertussis coinfection with MP was increased with age. Coinfections patients were older than those with single infections???11.77±2.32?? months vs. ??6.74±8.07?? months??P = 0.017??. Fever??dyspnea??and positive signs of lung in chest imang were more common in children with mixed infections??0 vs. 10.3%??20.6% vs. 5.4%??76.5% vs. 36.4%??P??0.05??. Chest imaging showed pathy shadow in most cases. There was no significant difference in lab tests??such as white blood cell counts??neutrophil counts??C-reactive protein??CRP????course of disease prior to admission or hospital stay between patients with pertussis only and those with mixed-pathogen infections??P??0.05??. Patients older than 3 months??OR??3.0??95%CI 1.1-8.5??P??0.03?? and fever??OR??2.5??95%CI 1.1-6.7??P??0.03?? were the independent risk factors for mixed infections. Conclusion??There is a higher proportion of coinfection in hospitalized children with pertussis??most commonly co-infected with rhinovirus??followed by Mycoplasma pneumoniae and Streptococcus pneumoniae. Coinfections are found to aggravate pertussis. Fever and being older than 3 months are risk factors of mixed infection.