Kerkhof Karen, Sluydts Vincent, Willen Laura, Kim Saorin, Canier Lydie, Heng Somony, Tsuboi Takafumi, Sochantha Tho, Sovannaroth Siv, Ménard Didier, Coosemans Marc, Durnez Lies
Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Malar J. 2016 Nov 4;15(1):529. doi: 10.1186/s12936-016-1576-z.
Serological markers for exposure to different Plasmodium species have recently been used in multiplex immunoassays based on the Luminex technology. However, interpretation of the assay results requires consideration of the half-life of specific antibodies against these markers. Therefore, the aim of the present study was to document the half-life of malaria specific serological makers, as well as assessing the sensitivity of these markers to pick up recent changes in malaria exposure.
A recently developed multiplex immunoassay was used to measure the intensity of antibody (Ab) responses against 19 different Plasmodium specific antigens, covering different human malaria parasites and two vector saliva antigens. Therefore, 8439 blood samples from five cross-sectional surveys in Ratanakiri, Cambodia, were analysed. These involve a random selection from two selected surveys, and an additional set of blood samples of individuals that were randomly re-sampled three, four or five times. A generalized estimating equation model and linear regression models were fitted on log transformed antibody intensity data.
Results showed that most (17/21) Ab-responses are higher in PCR positive than PCR negative individuals. Furthermore, these antibody-responses follow the same upward trend within each age group. Estimation of the half-lives showed differences between serological markers that reflect short- (seasonal) and long-term (year round) transmission trends. Ab levels declined significantly together with a decrease of PCR prevalence in a group of malaria endemic villages.
For Plasmodium falciparum, antibodies against LSA3.RE, GLURP and Pf.GLURP.R2 are most likely to be a reflexion of recent (range from 6 to 8 months) exposure in the Mekong Subregion. PvEBP is the only Plasmodium vivax Ag responding reasonably well, in spite of an estimated Ab half-life of more than 1 year. The use of Ab intensity data rather dichotomizing the continuous Ab-titre data (positive vs negative) will lead to an improved approach for serological surveillance.
近期，基于Luminex技术的多重免疫测定法已开始使用针对不同疟原虫种类的血清学标志物。然而，对检测结果的解读需要考虑针对这些标志物的特异性抗体的半衰期。因此，本研究的目的是记录疟疾特异性血清学标志物的半衰期，并评估这些标志物检测近期疟疾暴露变化的敏感性。
采用一种最新开发的多重免疫测定法，测量针对19种不同疟原虫特异性抗原的抗体（Ab）反应强度，这些抗原涵盖了不同的人类疟原虫和两种媒介唾液抗原。因此，对柬埔寨腊塔纳基里省五次横断面调查的8439份血样进行了分析。这些样本包括从两次选定调查中随机抽取的样本，以及另外一组被随机重新采样三次、四次或五次的个体血样。对经对数转换的抗体强度数据拟合广义估计方程模型和线性回归模型。
结果显示，大多数（17/21）抗体反应在PCR阳性个体中高于PCR阴性个体。此外，这些抗体反应在每个年龄组内呈现相同的上升趋势。半衰期估计显示，反映短期（季节性）和长期（全年）传播趋势的血清学标志物之间存在差异。在一组疟疾流行村庄中，随着PCR患病率的下降，抗体水平也显著下降。
对于恶性疟原虫，针对LSA3.RE、GLURP和Pf.GLURP.R2的抗体最有可能反映湄公河次区域近期（6至8个月）的暴露情况。尽管估计抗体半衰期超过1年，但间日疟病毒红细胞结合蛋白（PvEBP）是间日疟原虫唯一反应较好的抗原。使用抗体强度数据而非将连续的抗体滴度数据二分法（阳性与阴性）将为血清学监测带来改进的方法。
