认识风湿热和风心病的新努力—关于链球菌和人类宿主的概念

虽然对A组β溶血性链球菌与风湿热的关系已认识半个多世纪,但对这个关系的许多重要的问题尚未完全确定。开始咽喉感染和真正感染与相对无害的链球菌携带状态之间的差别尚未认识,这种微生物本身很多特性很大程度上尚是一个未知数,虽然对某些链球菌的致风湿源性有过许多报道,但准确的产生风湿源性的机制尚不清楚,也未有足够的证据来认识“抗原模仿”在发病中的作用。随着在基础实验中引入了分子技术,在过去十年中,被发现的不同链球菌类型（包括M蛋白或emm基因）的数目几乎成倍增加,使链球菌的问题更为严重,因为对于这些新描述的类型的相对重要性或流行病学知之甚少。人类对链球菌的初次或重复感染的应答问题也尚未完全解决。为什么尽管婴儿对链球菌的感染有易感性,但他们常常很少（即使有过）风湿热,这是极为重要去认识的问题,因此我们对微生物的获得性免疫的作用未能得到认识,由于目前尚未有的动物模型来研究宿主的反应阻滞了上述问题的研究。虽然有初步语据提示对风湿热的人类基因敏感性,这个问题尚未完全清楚,让广泛的前瞻性研究来证实任何目前的假设。基于目前流行病学的信息,我们非常清楚,仅仅依靠抗生素不能最终控制这种心血管疾病的流行。在以相当热情采用若干不同途径来开发A组链球菌疫苗的时候,只有到准确的发病机制更加明确,这个方法才有可能是经济有效或切实可行的,需要开展相当多的流行病学,基础和应用研究来阐明这些复杂的问题。     

A组β溶血性链球菌脂磷壁酸抗体在风湿热诊断中的意义

目的 探讨A组β溶血性链球菌（乙链菌）脂磷壁酸（LTA）抗体在风湿热诊断中的意义。方法 用从A组乙链菌中提取的LTA作为抗原，采用斑点酶联免疫吸附测定（ELISA）法检测血清中的LTA抗体。结果 ①风湿性心脏炎组LTA－IgG抗体滴度水平高于静止期风湿性心脏病组、病毒性心肌炎组、非湿性心脏瓣膜病组，其他关节炎组的滴度水平；②活动期风湿热患者LTA－IgG抗体阳性率（64％）高于对照组的阳性率；③风湿性心脏炎患者的LTA－IgG抗体阳性率与外周血淋巴细胞促凝血活性（PCA）、抗链球菌壁多糖抗体（ASP）、抗DNAse－B、血沉、C反应蛋白的阳性率相接近，高于抗链球菌溶血素O(ASO)的阳性率。结论 血清LTA抗体在判断风湿热和风湿性心脏病风湿活动有较高的敏感性和一定的特异性。     

风湿性心脏病患者风湿热复发的诊断探讨

为探讨风湿性心脏病（ＲＨＤ）患者风湿热复发（ＲＡＲＦ）的诊断，选择具２年以上病程的ＲＨＤ患者和２次超声心动图检查且本次检查显示心脏瓣膜病变比２年前有明显加重的９７例病人，认为ＲＡＲＦ的诊断条件是：在新近Ａ组链球菌感染基础上，ＲＨＤ患者具有Ｊｏｎｅｓ标准一项主要表现，或缺乏主要表现而具备次要表现五项中之两项以上者即可诊断为ＲＡＲＦ。若仅具备次要表现一项，并伴有贫血、腹痛、鼻衄、心前区隐痛等症状两项和具有ＩｇＧ、ＩｇＡ、循环免疫复合物，血清补体Ｃ＿３值增高一项以上者，若能排出其他原因，亦可认为有ＲＡＲＦ之可能性。     

A组链球菌壁多糖的抗原性及交叉反应性研究

目的 研究Ａ组β溶血性链球菌壁多糖的最具抗原性的部分,及与牛心瓣膜糖蛋白的交叉反应性。方法 设计了新的提取和纯化链球菌壁多糖抗原的技术－分子筛凝胶层析法,以双向琼脂免疫扩散法鉴定出人抗原性的部分,并测定这部分多糖与牛心瓣膜糖蛋白交叉反应性。结果 发现Ａ组链球菌壁多糖由４部分组成,分子量分别为１５０００、３７０００、６６０００、１５００００。其中人抗原笥的部分是３７０００,３７０００的多糖部分和牛心     

抗甲组溶血性链球菌壁多糖抗体在风湿热活动检测上的意义

抗甲组溶血性链球菌壁多糖抗体在风湿热活动检测上的意义彭朝权余步云陈国庆梁慧反复风湿热活动会使原有的风湿性心脏病（风心病）恶化，寻找特异性和敏感性较高的指标来反映风湿热活动，对于指导防治和改善预后具有重要意义。我们旨在探讨具有瓣膜特异性的抗甲组溶血性链...     

快速检测β溶血性A族链球菌抗原对风湿热的诊断价值

对３０例风湿热患者进行快速咽部ＧＡＢＨＳ抗原检测，咽培养及ＡＳＯ测定。咽培养３例阳性，ＡＳＯ增高１８例，而快速链检２７例阳性，其阳性率显著高于ＡＳＯ。快速链检阳性而ＡＳＯ正常的９例中，ＥＳＲ均增快，７例有二尖瓣病变，２例有主动脉病变，由此来看，是ＡＳＯ敏感性不够而非快速链检假阳性。在２０例正常儿童中，有１例快速链检阳性，显著低于风湿热组。     

应用A组乙型链球菌特异性菌膜抗原诊断风湿性心脏炎的探讨

目的　研究A组乙型溶血性链球菌菌膜抗原在外周血淋巴细胞促凝血活性试验中诊断风湿性心脏炎的特异性。方法　分别用A组乙型溶血性链球菌菌膜抗原和 1%植物血凝素(PHA)作为刺激物 ,分别测定 38名健康对照组 ,30例风湿性心脏病活动组 (风心活动组 ) ,2 0例风湿性心脏病静止组 (风心静止组 )外周血淋巴细胞促凝血活性 (procoagulantactivity ,PCA)。 结果　在特异性菌膜抗原刺激下 ,风心活动组PCA (18 1± 6 3) %显著高于风心静止组 (7 2± 1 9) %和健康对照组 (6 0± 3 0 ) % ,而后二者无统计学差异。在受PHA刺激后 ,风心活动组PCA (9 0± 2 5 ) % ,风心静止组 (6 2± 1 6 ) % ,和健康对照组 (7 5± 3 2 ) %三者差异无显著性。结论　以链球菌菌膜为促凝刺激物的PCA试验在判断风湿性心脏炎方面具有特异性 ,其特异性取决于所用的刺激原为特异性抗原。     

风湿热预防及急性链球菌咽炎诊治的专家共识

2009年1月,美国心脏病协会（AHA）与风湿热、心内膜炎及川崎病委员会发表了对风湿热预防及急性链球菌咽炎诊疗的专家共识。该共识在1995年版基础上作了更新,主要内容包括：A组β-溶血性链球菌（GAS）咽炎的诊疗新方法、风湿热二级预防新建议及证据等级水平。现对其做简要解读。1流行病学GAS咽炎是引起风湿热的主要病因,3%急性链球菌感染后咽喉疼痛未处理者可继发风湿热,     

ASP对慢性风湿性心脏病患者风湿活动的诊断价值

近年轻症和不典型风湿热病例呈逐渐上升趋势,特别是瓣膜病风湿活动的诊断难度更大。国内已有实验室将A组链球菌菌壁多糖抗体（ASP）的检测应用于典型或不典型风湿热病例的诊断试验中,但是对慢性风湿性心脏病风湿活动的诊断少见报道。2004年6月～2008年5月,我们检测了92例慢性风湿性心脏病患者的ASP,以探讨其诊断价值。     

酶免疫斑点法检测心肌抗体结合吸附试验对风湿性心脏病的诊断意义

心肌抗体(ｈｅａｒｔｒｅａｃｔｉｖｅａｎｔｉｂｏｄｙ,ＨＲＡ)的检测对风湿性心脏病具有一定的诊断意义。但是,由于其他心脏疾病(如原发性心肌病、病毒性心肌炎等)患者血清中也可检测到ＨＲＡ,因此,ＨＲＡ诊断风心病的特异性意义尚有争议。本文作者应用酶免疫斑点法检测117例各种心脏病患者血清的ＨＲＡ,并将测得的阳性血清用Ａ组链球菌膜抗原进行吸附试验,以进一步探讨其特异性价值。1　资料与方法11　病例选择111　心脏病组:①风心病35例,男21例,女14例,平均年龄(38±8)岁,均符合1992年修订的Ｊｏｎｅ′ｓ标准。②原发性心肌病19例,男11…     

Prevalence of rheumatic fever and rheumatic heart disease in Bangladeshi children

Background

Recent prevalence data on rheumatic fever (RF) and rheumatic heart disease (RHD) are lacking in Bangladeshi population.

Aim

We have done this national level cross-sectional survey to determine the prevalence of RF and RHD in Bangladeshi children.

Methods

Samples were drawn from three out of seven divisions of Bangladesh from both urban and rural areas. Trained and experienced enumerators visited households to suspect cases of RF or RHD in 5–19 years children by asking structured questions on symptoms and signs of RF and RHD (n = 56,827). Then trained doctors again took history and examined them for RF/RHD. RF was defined according to the Modified Jones Criteria 1992. Doppler echocardiography was done to confirm the diagnosis in all suspected cases of RF/RHD.

Results

A total of 36 RF cases (new and old) and 16 Doppler echocardiography confirmed RHD cases were identified. Prevalence of RF and RHD was 0.9 per 1000 (95% confidence interval: 0.7–1.2) while prevalence of RF was 0.6 per 1000 (95% CI: 0.4–0.9) and RHD 0.3 per 1000 (95% CI: 0.2–0.5).

Conclusion

Observed prevalence of RF and RHD indicates that RF/RHD is disappearing from Bangladesh. However, studies using new technology of portable echocardiographic screening are needed.     

Rheumatic fever and rheumatic heart disease in Bangladesh: A review

Rheumatic fever (RF) and rheumatic heart disease (RHD) are the most-common cardiovascular disease in young people aged <25 years, globally. They are important contributors to cardiovascular morbidity and mortality in Bangladesh. Classical risk factors, i.e. poverty, overcrowding, ignorance, and insufficient health care services were responsible for the high incidence and prevalence of these diseases over the last century. In concert with the progresses in socioeconomic indicators, advances in health sectors, improved public awareness, and antibiotic prophylaxis, acute RF came into control. However, chronic RHD continues to be prevalent, and the actual disease burden may be much higher. RHD predominantly affects the young adults, seriously incapacitates them, follows a protracted course, gets complicated because of delayed diagnosis and is sometimes maltreated. The treatment is often palliative and expensive. Large-scale epidemiological and clinical researches are needed to formulate evidence-based national policy to tackle this important public health issue in future.     

A组乙型溶血性链球菌膜蛋白抗原纯化及其在风湿性心脏炎发病中意义的探讨

目的　探讨纯化A组乙型溶血性链球菌膜蛋白抗原 (A HSMPA)的方法及其在风湿性心脏炎发病免疫过程中的意义。方法　用反胶束萃取法提纯 ,分别检测提纯前后A HSMPA的成分及抗原性 ,再以A HSMPA及粒细胞 /单核细胞集落刺激因子 (GM CSF)分别刺激风湿性心脏炎组、风湿性心脏病静止期组、急性风湿性关节炎组、自身免疫性疾病组、非风湿性心脏病组、链球菌感染相关性疾病组及健康人对照组的外周血淋巴细胞 ,检测其人类白细胞抗原DR亚型 (HLA DR)分子表达量的改变。结果　 1 提纯后的A HSMPA基本为蛋白成分 ,提纯前后抗原检测外周淋巴细胞促凝血试验结果无显著差异 ,链球菌壁多糖抗体则差异显著。 2 加入A HSMPA孵育后 ,风湿性心脏炎组HLA DR分子表达量的增加为 (19 5 5± 4 32 )× 10 -6A/cell,对照组为 (12 2 2± 6 2 9)× 10 -6A/cell,各组有显著性差异 ;而经GM CSF刺激后 ,以上各组无明显差别。 3 A HSMPA对风湿性心脏炎患者的刺激作用较GM CSF明显。 4 风湿性心脏炎患者随着症状的好转其HLA DR表达量亦减少。结论　 1 反胶束萃取法可提纯A HSMPA并保持其抗原性不变 ,且简便可靠。 2 A HSMPA与HLA DR分子表达量的改变均在风湿性心脏炎发展成为风湿性心脏病过程中起了重要作用。 3 监测A HSMPA刺激后H     

抗DNA酶B在风湿热流行病学研究中的应用

目的 探索预测某一地区风湿热（ＲＦ）流行状况简便的方法。方法 对广东２１６名在乡学龄儿童血清抗ＤＮＡ酶Ｂ和抗链球菌深血素“Ｏ”（ＡＳＯ）水平进行为期１周的动态观察;另外在５个不同地区中,各抽取１００名学龄儿童在同一季节进行抗ＤＮＡ酶Ｂ水平横贯面的调查,结果与同期风湿热／风湿性心脏病（ＲＦ／ＲＨＤ）发患病率对照研究。结果 抗ＤＮＡ酶Ｂ水平呈秋、冬、春季高,夏季低的季节性变化,与ＲＦ发病率的季节性分布规律一致（ｒ＝０．９１３,Ｐ〈０．０５）。抗ＤＮＡ酶Ｂ水平高的地区,其ＲＦ／ＲＨＤ发患病率高,反之则低（ｒ＝０．９５２,Ｐ〈０．０５）。结论 测定某一地区学龄儿童血清抗ＤＮＡ酶Ｂ水平,可作为该地区ＲＦ／ＲＨＤ流行水平的初步估测和进一步研究的参考。     

近十年风湿热的演变

目的 探讨近十年风湿热临床表现及实验室榆查的变化,为诊断及治疗提供参考.方法 收集我院风湿热患者共315例,分为2组,1985-1995年就诊的为A组,1997-2007年就诊的为B组,比较2组的临床表现及实验室检查.结果 男:女为1:2.心脏炎、多关节炎仍是最常见的症状.与A组比较,B组低热、心脏炎增加,心力衰竭减少,C反应蛋白(CRP)、抗链球菌溶血素O(ASO)阳性率下降.B组的Jones诊断标准(1992)符合率为61.4%,2002-2003年世界卫生组织(WHO)诊断标准的符合率为76.4%.提示风湿性心脏炎诊断,淋巴细胞促凝血活性(PCA)的敏感性和特异性分别为79.1%和71.4%,A组链球菌多糖抗体(ASP)的敏感性和特异性分别为70.3%和70%.B组35例随访了5～10年的患者风湿热复发率为62.8%,仅1/3进行了规范二级预防,其复发率明显低于无规范二级预防的患者.结论 近十年轻症心脏炎增加;PCA、ASP提示风湿性心脏炎价值较大;应更加注意不典型病例的诊断及加强二级预防.     

Antibody titer to group A streptococcal polysaccharide in rheumatic fever and rheumatic heart disease

Antibody to group A streptococcal polysaccharide (ASP) is the only antibody of cellular components which is now detectable in clinical practice. Streptococcal polysaccharide is known to have cross-immunity with the glycoprotein of human heart tissue, and has been discussed as a pathogenesis of rheumatic carditis and valvular heart disease. In this study, ASP titer was determined by passive hemagglutination technique in patients with rheumatic fever and rheumatic heart disease. ASP titer showed higher levels in these patients compared to control children, but there was no specificity in rheumatic carditis or rheumatic heart disease.     

A dramatic decline in university hospital admissions of acute rheumatic fever in the eastern region of Saudi Arabia

Backgrounds

Acute rheumatic fever (ARF) and its sequel, chronic valvular heart disease are the most important causes for cardiovascular morbidity and mortality worldwide and mainly in developing countries. However, the incidence of ARF has declined in developed countries during the second half of 20th century.

Material and methods

The case files of all patients admitted as new cases of ARF over ∼11 years and 8 months, both in pediatric and medical departments of a university hospital located in the eastern region of Saudi Arabia were reviewed. The demographic and clinical data and the frequency of the new cases were compared with the data that have been published by us 10 years ago from the same hospital during a similar period of time (11 years and 8 months).

Results

In the current study there was a significant decline in the frequency of admission of cases of ARF as compared to our previous study during a similar period of time, with a frequency rate of 12 cases per 100.000 hospitalizations versus 45 cases per 100.000 hospitalizations, respectively, P < 0.001. Dyspnea and chest pain as clinical features of acute rheumatic carditis (ARC) were less frequent in the current study as compared to the previous study (35% versus 44%, P = 0.02 and 10% versus 28.6%, P = 0.031). The subgroup analysis revealed also a decreased frequency of the clinical features of ARC in pediatric age group in the current study as compared to our previous study.

Conclusion

There is a significant decline in the frequency of new hospital admissions due to ARF. This decline was associated with similar decline in the frequency of the manifestations of ARC especially in pediatric age group (1–12 years).     

Once weekly azithromycin in secondary prevention of rheumatic fever

Rheumatic fever and rheumatic heart disease (RHD) are still important problems in developing countries. Secondary prophylaxis which is the most cost-effective method in preventing recurrences of rheumatic fever is fraught with problems of drug compliance. The utility of 500 mg once weekly azithromycin (AZT), an orally effective long-acting antibiotic was evaluated against oral penicillin (phenoxy methyl penicillin 250 mg twice daily) in this study. Forty-eight consecutive patients (44% males, mean age 29.4 years) with established RHD were randomised into two groups-26 patients received AZT and 22 received oral penicillin. Patients were evaluated at randomisation, at 1 month, 3 months, and 6 months, clinically, serologically and by throat swab culture. End points were absence of streptococcal colonisation, infection or fever at the end of 6 months. During the study, 4 patients (15.4%) in the AZT group developed sore throat and fever, had positive throat culture and positive serology indicating streptococcal infection. None satisfied the criteria for rheumatic fever reactivation. None in the oral penicillin group developed streptococcal infection. In conclusion, weekly 500 mg of AZT is not effective in the prevention of streptococcal throat infection compared to oral penicillin therapy in adult patients with established RHD.