Department of Immunology & Infection, London School of Hygiene and Tropical Medicine, London W1CE 7HT, UK.
Malar J. 2013 Jan 17;12:21. doi: 10.1186/1475-2875-12-21.
As malaria transmission intensity approaches zero, measuring it becomes progressively more difficult and inefficient because parasite-positive individuals are hard to detect. This situation may arise shortly before achieving local elimination, or during surveillance post-elimination to prevent reintroduction. Antibody responses against the parasite last longer than the infections themselves. This "footprint" of infection may thus be used for assessing transmission intensity. A statistical approach is presented for measuring the seroconversion rate (SCR), a correlate of the force of infection, from individual-level longitudinal data on antibody titres in an area of low Plasmodium falciparum transmission.
Blood samples were collected from 160 Indonesian schoolchildren every month for six months. Titres of antibodies against AMA-1 and MSP-1(19) antigens of P. falciparum were measured using ELISA. The distribution of antibody titres among seronegative and -positive individuals, respectively, was estimated by comparing the titres from the study data (a mixture of both seropositive and -negative individuals) with titres from a (unexposed) negative control group of Indonesian individuals. Two Markov-Chain models for the transition of individuals between serological states were fitted to individual anti-PfAMA-1 or anti-PfMSP-1 titre time series using Bayesian Markov-Chain-Monte-Carlo (MCMC). This yielded estimates of SCR as well as of the duration of seropositivity.
A posterior median SCR of 0.02 (Pf AMA-1) and 0.09 (PfMSP-1) person(-1) year(-1) was estimated, with credible intervals ranging from 1E-4 to 0.2 person(-1) year(-1). This level of transmission intensity is at the lower range of what can reliably be measured with the present study size. A Bayesian test for seroconversion of an individual between two observations is presented and used to identify the subjects who have most likely experienced an infection. Furthermore, the theoretical limits of measuring transmission intensity, and how these depend on duration and size of a study as well as on transmission intensity itself, is illustrated.
This analysis shows that it is possible to measure SCR's from individual-level longitudinal data on antibody titres. In addition, individual seroconversion events can be identified, which can be useful in assessing interruption of transmission. Analyses of further serological datasets using the present method are required to improve and validate it. This includes measurement of the duration of antibody responses, how it depends on host age or cumulative exposure, or on the particular antigen used.
随着疟疾传播强度接近零，测量传播强度变得越来越困难和低效，因为寄生虫阳性个体难以检测。这种情况可能出现在即将实现本地消除之前，或者在消除后进行监测以防止重新引入。针对寄生虫的抗体反应持续时间长于感染本身。因此，这种感染的“痕迹”可用于评估传播强度。本文提出了一种统计方法，用于从低疟原虫传播地区的个体纵向抗体滴度数据中测量血清转化率 (SCR)，血清转化率是感染强度的一个相关指标。
从 160 名印度尼西亚学童中每月采集一次血液样本，共采集 6 个月。使用 ELISA 测量针对疟原虫 AMA-1 和 MSP-1(19)抗原的抗体滴度。通过将研究数据（混合了血清阳性和阴性个体）中的滴度与来自印度尼西亚未暴露阴性对照组的滴度进行比较，分别估计血清阴性和阳性个体的抗体滴度分布。使用贝叶斯马尔可夫链蒙特卡罗 (MCMC) 对个体抗 PfAMA-1 或抗 PfMSP-1 时间序列的两种血清状态转换的马尔可夫链模型进行拟合。这得出了 SCR 以及血清阳性持续时间的估计值。
估计血清转化率的后验中位数分别为 0.02（PfAMA-1）和 0.09（PfMSP-1）人(-1)年(-1)，可信区间范围从 1E-4 到 0.2 人(-1)年(-1)。这种传播强度水平处于目前研究规模可以可靠测量的下限。本文还提出了一种用于个体在两次观察之间血清转化的贝叶斯检验，并用于识别最有可能感染的受试者。此外，还说明了测量传播强度的理论极限，以及这些极限如何取决于研究的持续时间和规模以及传播强度本身。
这项分析表明，从个体纵向抗体滴度数据中测量血清转化率是可能的。此外，可以识别个体血清转化事件，这对于评估传播中断可能有用。需要使用当前方法分析更多的血清数据集，以改进和验证该方法。这包括测量抗体反应的持续时间，它如何取决于宿主年龄或累积暴露量，或取决于使用的特定抗原。
