Darton Thomas C, Meiring James E, Tonks Susan, Khan Md Arifuzzaman, Khanam Farhana, Shakya Mila, Thindwa Deus, Baker Stephen, Basnyat Buddha, Clemens John D, Dougan Gordon, Dolecek Christiane, Dunstan Sarah J, Gordon Melita A, Heyderman Robert S, Holt Kathryn E, Pitzer Virginia E, Qadri Firdausi, Zaman K, Pollard Andrew J
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Department of Paediatrics, Oxford Vaccine Group,University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
BMJ Open. 2017 Jul 2;7(6):e016283. doi: 10.1136/bmjopen-2017-016283.
Invasive infections caused by serovar Typhi and Paratyphi A are estimated to account for 12-27 million febrile illness episodes worldwide annually. Determining the true burden of typhoidal infections is hindered by lack of population-based studies and adequate laboratory diagnostics.The Strategic Typhoid alliance across Africa and Asia study takes a systematic approach to measuring the age-stratified burden of clinical and subclinical disease caused by typhoidal infections at three high-incidence urban sites in Africa and Asia. We aim to explore the natural history of transmission in endemic settings, addressing key uncertainties relating to the epidemiology of enteric fever identified through mathematical models, and enabling optimisation of vaccine strategies.
METHODS/DESIGN: Using census-defined denominator populations of ≥100 000 individuals at sites in Malawi, Bangladesh and Nepal, the primary outcome is to characterise the burden of enteric fever in these populations over a 24-month period. During passive surveillance, clinical and household data, and laboratory samples will be collected from febrile individuals. In parallel, healthcare utilisation and water, sanitation and hygiene surveys will be performed to characterise healthcare-seeking behaviour and assess potential routes of transmission. The rates of both undiagnosed and subclinical exposure to typhoidal (seroincidence), identification of chronic carriage and population seroprevalence of typhoid infection will be assessed through age-stratified serosurveys performed at each site. Secondary attack rates will be estimated among household contacts of acute enteric fever cases and possible chronic carriers.
This protocol has been ethically approved by the Oxford Tropical Research Ethics Committee, the icddr,b Institutional Review Board, the Malawian National Health Sciences Research Committee and College of Medicine Research Ethics Committee and Nepal Health Research Council. The study is being conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained before study enrolment. Results will be submitted to international peer-reviewed journals and presented at international conferences.
ISRCTN 12131979.
Oxford (Oxford Tropical Research Ethics Committee 39-15).Bangladesh (icddr,b Institutional Review Board PR-15119).Malawi (National Health Sciences Research Committee 15/5/1599).Nepal (Nepal Health Research Council 306/2015).
据估计，全球每年由伤寒血清型和甲型副伤寒引起的侵袭性感染导致1200万至2700万例发热性疾病发作。由于缺乏基于人群的研究和充分的实验室诊断方法，伤寒感染的真实负担难以确定。非洲和亚洲伤寒战略联盟研究采用系统方法，在非洲和亚洲的三个高发病城市地点测量伤寒感染引起的不同年龄段临床和亚临床疾病负担。我们旨在探索流行地区的自然传播史，解决通过数学模型确定的与肠热病流行病学相关的关键不确定性问题，并优化疫苗策略。
方法/设计：在马拉维、孟加拉国和尼泊尔的研究地点，以人口普查定义的分母人群≥10万个体为对象，主要结果是描述这些人群在24个月期间的肠热病负担。在被动监测期间，将从发热个体收集临床和家庭数据以及实验室样本。同时，将进行医疗保健利用以及水、卫生和卫生设施调查，以描述就医行为并评估潜在传播途径。通过在每个地点进行的年龄分层血清学调查，评估未诊断和亚临床伤寒暴露率（血清发病率）、慢性带菌者的识别以及伤寒感染的人群血清阳性率。将估计急性肠热病病例和可能的慢性带菌者家庭接触者中的二代发病率。
本方案已获得牛津热带研究伦理委员会、孟加拉国腹泻病研究国际中心机构审查委员会、马拉维国家卫生科学研究委员会和医学院研究伦理委员会以及尼泊尔卫生研究委员会的伦理批准。本研究按照《赫尔辛基宣言》和《良好临床实践》的原则进行。在研究入组前获得了知情同意。研究结果将提交给国际同行评审期刊，并在国际会议上发表。
ISRCTN 12131979。
牛津（牛津热带研究伦理委员会39 - 15）。孟加拉国（孟加拉国腹泻病研究国际中心机构审查委员会PR - 15119）。马拉维（国家卫生科学研究委员会15/5/1599）。尼泊尔（尼泊尔卫生研究委员会306/2015）。
