Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Kilifi, Kenya.
PLoS One. 2010 Dec 16;5(12):e15569. doi: 10.1371/journal.pone.0015569.
Febrile malaria is the most common clinical manifestation of P. falciparum infection, and is often the primary endpoint in clinical trials and epidemiological studies. Subjective and objective fevers are both used to define the endpoint, but have not been carefully compared, and the relative incidence of clinical malaria by active and passive case detection is unknown.
We analyzed data from cohorts under active and passive surveillance, including 19,462 presentations with fever and 5,551 blood tests for asymptomatic parasitaemia. A logistic regression model was used to calculate Malaria Attributable Fractions (MAFs) for various case definitions. Incidences of febrile malaria by active and passive surveillance were compared in a subset of children matched for age and location.
Active surveillance identified three times the incidence of clinical malaria as passive surveillance in a subset of children matched for age and location. Objective fever (temperature≥37.5°C) gave consistently higher MAFs than case definitions based on subjective fever.
The endpoints from active and passive surveillance have high specificity, but the incidence of endpoints is lower on passive surveillance. Subjective fever had low specificity and should not be used in primary endpoint. Passive surveillance will reduce the power of clinical trials but may cost-effectively deliver acceptable sensitivity in studies of large populations.
发热性疟疾是恶性疟原虫感染最常见的临床表现，通常也是临床试验和流行病学研究中的主要终点。主观发热和客观发热均可用于定义终点，但尚未进行仔细比较，主动和被动病例检测的临床疟疾相对发病率也未知。
我们分析了主动和被动监测队列的数据，包括 19462 例发热就诊和 5551 例无症状疟原虫血症血检。采用逻辑回归模型计算各种病例定义的疟疾归因分数（MAF）。在年龄和地点匹配的儿童亚组中比较了主动和被动监测的发热性疟疾发病率。
在年龄和地点匹配的儿童亚组中，主动监测发现的临床疟疾发病率是被动监测的三倍。客观发热（体温≥37.5°C）比基于主观发热的病例定义始终给出更高的 MAF。
主动和被动监测的终点具有高特异性，但被动监测的终点发病率较低。主观发热特异性低，不应作为主要终点。被动监测会降低临床试验的效力，但在大规模人群研究中可能以可接受的敏感性提供成本效益。
