Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials.
Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials.
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DOI：
10.3389/fimmu.2022.1003452
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
预先存在和干预的低密度疟原虫感染使疟疾临床试验的进行变得复杂。这些感染混淆了感染检测终点，并且它们的免疫学效应可能会损害预期的疫苗诱导的免疫反应。从历史上看，这些感染常常未被识别，因为在试验之前和试验期间很少进行且分析上不敏感的寄生虫学检测。分子诊断现在可以检测它们，但研究人员在安排此类测试时必须权衡成本、复杂性以及研究和实验室的人员需求。本文讨论了预先存在的和干预后的低密度疟原虫感染对疟疾疫苗试验终点的影响以及当前用于感染检测的方法。我们回顾了检测技术，直到最近，这些技术还缺乏用于检测低密度感染的经济有效的策略。讨论了最近部署的、经过现场测试、简单且具有成本效益的分子诊断策略，用于检测疟疾流行环境中干血斑 (DBS) 中预先存在的和干预性疟原虫感染，为新的临床试验设计提供信息。将敏感的分子诊断技术与方便的 DBS 收集和具有成本效益的汇集策略相结合的策略可以在即将进行的疟疾临床试验和流行病学研究中实现更彻底和信息丰富的感染监测。
Pre-existing and intervening low-density Plasmodium infections complicate the conduct of malaria clinical trials. These infections confound infection detection endpoints, and their immunological effects may detract from intended vaccine-induced immune responses. Historically, these infections were often unrecognized since infrequent and often analytically insensitive parasitological testing was performed before and during trials. Molecular diagnostics now permits their detection, but investigators must weigh the cost, complexity, and personnel demands on the study and the laboratory when scheduling such tests. This paper discusses the effect of pre-existing and intervening, low-density Plasmodium infections on malaria vaccine trial endpoints and the current methods employed for their infection detection. We review detection techniques, that until recently, provided a dearth of cost-effective strategies for detecting low density infections. A recently deployed, field-tested, simple, and cost-effective molecular diagnostic strategy for detecting pre-existing and intervening Plasmodium infections from dried blood spots (DBS) in malaria-endemic settings is discussed to inform new clinical trial designs. Strategies that combine sensitive molecular diagnostic techniques with convenient DBS collections and cost-effective pooling strategies may enable more thorough and informative infection monitoring in upcoming malaria clinical trials and epidemiological studies.
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影响因子：
8
作者：
Minassian AM;Themistocleous Y;Silk SE;Barrett JR;Kemp A;Quinkert D;Nielsen CM;Edwards NJ;Rawlinson TA;Ramos Lopez F;Roobsoong W;Ellis KJ;Cho JS;Aunin E;Otto TD;Reid AJ;Bach FA;Labbé GM;Poulton ID;Marini A;Zaric M;Mulatier M;Lopez Ramon R;Baker M;Mitton CH;Sousa JC;Rachaphaew N;Kumpitak C;Maneechai N;Suansomjit C;Piteekan T;Hou MM;Khozoee B;McHugh K;Roberts DJ;Lawrie AM;Blagborough AM;Nugent FL;Taylor IJ;Johnson KJ;Spence PJ;Sattabongkot J;Biswas S;Rayner JC;Draper SJ
通讯作者：
Draper SJ
影响因子：
3.3
作者：
Jongo, Said A.;Shekalaghe, Seif A.;Hoffman, Stephen L.
通讯作者：
Hoffman, Stephen L.
影响因子：
3
作者：
Kozycki CT;Umulisa N;Rulisa S;Mwikarago EI;Musabyimana JP;Habimana JP;Karema C;Krogstad DJ
通讯作者：
Krogstad DJ
影响因子：
4.6
作者：
Mahittikorn A;Masangkay FR;Kotepui KU;De Jesus Milanez G;Kotepui M
通讯作者：
Kotepui M
影响因子：
8
作者：
Kapulu MC;Njuguna P;Hamaluba M;Kimani D;Ngoi JM;Musembi J;Ngoto O;Otieno E;Billingsley PF;Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA) Study Team
通讯作者：
Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA) Study Team