Department of Public Health, University of Otago, Wellington, New Zealand.
School of Medical Sciences, University of Auckland, Auckland, New Zealand.
BMC Infect Dis. 2019 Jul 17;19(1):633. doi: 10.1186/s12879-019-4126-9.
Group A Streptococcal (GAS) infections cause the autoimmune disease acute rheumatic fever (ARF), which can progress to chronic rheumatic heart disease (RHD). Treating pharyngitis caused by GAS with antibiotics is important in preventing ARF. However, it is difficult to distinguish these infections from GAS carriers. There is growing evidence for GAS skin infections as a cause of ARF. This study will identify the incidence of true GAS pharyngitis and serological responses to GAS skin infections. The effectiveness of antibiotics for these conditions will be explored, and modifiable risk factors. Serum antibody titres indicating the upper limits of normal (ULN for ASO/ADB antibodies) will be established alongside carriage rates in asymptomatic children.
This is a prospective disease incidence study, with an associated case-control study. The study population includes 1000 children (5-14 years) from Auckland, New Zealand, 800 of whom have visited their healthcare professional, resulting in a throat or skin swab for GAS, and 200 who are asymptomatic. The conditions of interest are GAS throat swab positive pharyngitis (n = 200); GAS carriage (n = 200); GAS negative throat swab (n = 200); GAS skin infections (n = 200); and asymptomatic controls (n = 200). All participants, except asymptomatic controls, will have acute and convalescent serological testing for ASO/ADB titres (collected < 9 days, and 2-4 weeks following symptom onset, respectively), alongside viral PCR from throat swabs. Asymptomatic controls will have ASO/ADB titres measured in one blood specimen and a throat swab for microbial culture. Caregivers of children will be interviewed using a questionnaire and any GAS isolates identified will be emm typed. The persistence of GAS antibodies will also be investigated.
Findings from this study will fill critical gaps in scientific knowledge to better understand the pathophysiology of ARF, improve clinical management of GAS infections, and design more effective ARF prevention programmes. In particular it will measure the incidence of true, serologically confirmed GAS pharyngitis; assess the immune response to GAS skin infections and its role as a cause of ARF; examine the effectiveness of oral antibiotics for treating GAS pharyngitis and carriage; and identify whether risk factors for GAS infections might provide intervention points for reducing ARF.
A 组链球菌（GAS）感染可导致自身免疫性疾病急性风湿热（ARF），进而发展为慢性风湿性心脏病（RHD）。用抗生素治疗 GAS 引起的咽炎对于预防 ARF 很重要。然而，从 GAS 携带者中区分这些感染具有一定难度。越来越多的证据表明 GAS 皮肤感染是 ARF 的病因之一。本研究旨在确定真正的 GAS 咽炎的发病率以及 GAS 皮肤感染的血清学反应。我们还将探索抗生素治疗这些疾病的有效性以及可改变的危险因素。同时，我们还将建立无症状儿童的血清抗体滴度（抗链球菌溶血素 O/抗脱氧核糖核酸酶 B 抗体的上限正常值，ULN）以及携带率。
这是一项前瞻性疾病发病率研究，同时也进行一项相关的病例对照研究。研究人群包括来自新西兰奥克兰的 1000 名 5-14 岁儿童，其中 800 名曾因咽喉或皮肤拭子检查发现 GAS 而就诊，200 名无症状。本研究的关注条件为 GAS 咽拭子阳性咽炎（n=200）；GAS 携带（n=200）；GAS 阴性咽拭子（n=200）；GAS 皮肤感染（n=200）；以及无症状对照（n=200）。除无症状对照组外，所有参与者均将在急性和恢复期进行抗链球菌溶血素 O/抗脱氧核糖核酸酶 B 抗体滴度的血清学检测（分别在症状发作后<9 天和 2-4 周采集），同时采集咽喉拭子进行病毒 PCR 检测。无症状对照组仅采集一份血样检测 ASO/ADB 滴度，并进行咽喉拭子微生物培养。将对儿童的看护者进行问卷调查，对任何 GAS 分离株进行emm 型鉴定。还将对 GAS 抗体的持续性进行调查。
本研究的结果将填补科学知识的关键空白，以更好地了解 ARF 的病理生理学，改善 GAS 感染的临床管理，并设计更有效的 ARF 预防计划。特别是，本研究将测量真正的、血清学确认的 GAS 咽炎的发病率；评估 GAS 皮肤感染的免疫反应及其作为 ARF 病因的作用；检查口服抗生素治疗 GAS 咽炎和携带的效果；并确定 GAS 感染的危险因素是否可能为减少 ARF 提供干预点。
