Antibody signatures of asymptomatic Plasmodium falciparum malaria infections measured from dried blood spots.

Antibody signatures of asymptomatic Plasmodium falciparum malaria infections measured from dried blood spots.
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DOI:
10.1186/s12936-021-03915-8
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发表时间:
2021-09-23
期刊:
影响因子:
3
通讯作者:
Plowe CV
Plowe CV
中科院分区:
医学3区
文献类型:
--
作者:
Markwalter CF;Nyunt MH;Han ZY;Henao R;Jain A;Taghavian O;Felgner PL;Han KT;Nyunt MM;Plowe CV

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在蛋白质微阵列上筛选疟疾特异性抗体反应可以帮助识别介导预防疟疾感染、疾病和传播的免疫因子,以及过去接触疟原虫和蚊子媒介的标记。大多数疟疾蛋白微阵列工作都使用血清作为样品基质,需要及时的实验室处理和连续的冷链,从而限制了在偏远地区的应用。干血斑 (DBS) 的生物危害极小,不需要立即进行实验室处理,并且在室温下运输时稳定,使其成为血清的潜在替代品。本研究的目的是评估 DBS 作为抗体分析来源的可行性,并使用 DBS 识别缅甸疟疾流行地区低密度恶性疟原虫感染的血清学特征。在填充有恶性疟原虫抗原片段的蛋白质微阵列上对来自缅甸 Ingapu 镇一项横断面研究的匹配 DBS 和血清样本进行了探测。比较两个样品基质中的信号和趋势。然后使用来自缅甸疟疾流行地区的 DBS 样本进行病例对照研究,并使用正则化逻辑回归模型来识别超灵敏 PCR 阳性恶性疟原虫感染的抗体特征。从 DBS 中回收了大约 30% 的血清 IgG 活性。尽管抗体活性丧失,但两个样品基质之间的抗原和群体趋势非常匹配。对 18 种蛋白片段的反应与无症状恶性疟原虫感染的几率相关,尽管其诊断特征不高(敏感性 58%,特异性 85%,阴性预测值 88%,阳性预测值 52%)。 DBS 可以可靠地检测、量化和分析疟疾特异性抗体反应,从而为无法进行血清收集、运输和储存的人群进行血清学研究打开了大门。虽然抗体特征的测试特征不足以进行个体诊断,但血清学测试可能有助于识别无症状、低密度疟疾感染的暴露情况,特别是如果血清监测策略针对先前暴露程度较低的个体作为人群暴露的哨兵。在线版本包含可在 10.1186/s12936-021-03915-8 获取的补充材料。
Screening malaria-specific antibody responses on protein microarrays can help identify immune factors that mediate protection against malaria infection, disease, and transmission, as well as markers of past exposure to both malaria parasites and mosquito vectors. Most malaria protein microarray work has used serum as the sample matrix, requiring prompt laboratory processing and a continuous cold chain, thus limiting applications in remote locations. Dried blood spots (DBS) pose minimal biohazard, do not require immediate laboratory processing, and are stable at room temperature for transport, making them potentially superior alternatives to serum. The goals of this study were to assess the viability of DBS as a source for antibody profiling and to use DBS to identify serological signatures of low-density Plasmodium falciparum infections in malaria-endemic regions of Myanmar. Matched DBS and serum samples from a cross-sectional study in Ingapu Township, Myanmar were probed on protein microarrays populated with P. falciparum antigen fragments. Signal and trends in both sample matrices were compared. A case-control study was then performed using banked DBS samples from malaria-endemic regions of Myanmar, and a regularized logistic regression model was used to identify antibody signatures of ultrasensitive PCR-positive P. falciparum infections. Approximately 30% of serum IgG activity was recovered from DBS. Despite this loss of antibody activity, antigen and population trends were well-matched between the two sample matrices. Responses to 18 protein fragments were associated with the odds of asymptomatic P. falciparum infection, albeit with modest diagnostic characteristics (sensitivity 58%, specificity 85%, negative predictive value 88%, and positive predictive value 52%). Malaria-specific antibody responses can be reliably detected, quantified, and analysed from DBS, opening the door to serological studies in populations where serum collection, transport, and storage would otherwise be impossible. While test characteristics of antibody signatures were insufficient for individual diagnosis, serological testing may be useful for identifying exposure to asymptomatic, low-density malaria infections, particularly if sero-surveillance strategies target individuals with low previous exposure as sentinels for population exposure. The online version contains supplementary material available at 10.1186/s12936-021-03915-8.
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