Department of Immunology and Parasitology, Med Biotech Laboratories, Kampala, Uganda.
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Front Immunol. 2022 Sep 20;13:1003452. doi: 10.3389/fimmu.2022.1003452. eCollection 2022.
Pre-existing and intervening low-density 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 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 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.
先前存在和介入的低密度 感染使疟疾临床试验复杂化。这些感染使感染检测终点复杂化，其免疫效应可能会削弱预期的疫苗诱导的免疫反应。历史上，由于在试验前和试验期间进行的寄生虫学检测频率低且往往分析不敏感，这些感染常常未被识别。分子诊断现在允许检测这些感染，但研究人员在安排此类检测时，必须权衡研究和实验室的成本、复杂性和人员需求。本文讨论了先前存在和介入的低密度 感染对疟疾疫苗试验终点的影响，以及目前用于感染检测的方法。我们回顾了检测技术，直到最近，这些技术为检测低密度感染提供了缺乏成本效益的策略。讨论了一种最近部署的、经过现场测试的、简单且具有成本效益的分子诊断策略，用于从疟疾流行地区的干血斑 (DBS) 中检测先前存在和介入的 感染，以告知新的临床试验设计。将敏感的分子诊断技术与方便的 DBS 采集和具有成本效益的汇集策略相结合的策略，可能使即将到来的疟疾临床试验和流行病学研究中的感染监测更加全面和有意义。
