Queensland University of Technology, Brisbane, QLD, Australia.
The CDC Foundation, Atlanta, GA, USA.
Malar J. 2020 Nov 4;19(1):392. doi: 10.1186/s12936-020-03460-w.
Malaria rapid diagnostic tests (RDTs) have greatly improved access to diagnosis in endemic countries. Most RDTs detect Plasmodium falciparum histidine-rich protein 2 (HRP2), but their sensitivity is seriously threatened by the emergence of pfhrp2-deleted parasites. RDTs detecting P. falciparum or pan-lactate dehydrogenase (Pf- or pan-LDH) provide alternatives. The objective of this study was to systematically assess the performance of malaria RDTs against well-characterized pfhrp2-deleted P. falciparum parasites.
Thirty-two RDTs were tested against 100 wild-type clinical isolates (200 parasites/µL), and 40 samples from 10 culture-adapted and clinical isolates of pfhrp2-deleted parasites. Wild-type and pfhrp2-deleted parasites had comparable Pf-LDH concentrations. Pf-LDH-detecting RDTs were also tested against 18 clinical isolates at higher density (2,000 parasites/µL) lacking both pfhrp2 and pfhrp3.
RDT positivity against pfhrp2-deleted parasites was highest (> 94%) for the two pan-LDH-only RDTs. The positivity rate for the nine Pf-LDH-detecting RDTs varied widely, with similar median positivity between double-deleted (pfhrp2/3 negative; 63.9%) and single-deleted (pfhrp2-negative/pfhrp3-positive; 59.1%) parasites, both lower than against wild-type P. falciparum (93.8%). Median positivity for HRP2-detecting RDTs against 22 single-deleted parasites was 69.9 and 35.2% for HRP2-only and HRP2-combination RDTs, respectively, compared to 96.0 and 92.5% for wild-type parasites. Eight of nine Pf-LDH RDTs detected all clinical, double-deleted samples at 2,000 parasites/µL.
The pan-LDH-only RDTs evaluated performed well. Performance of Pf-LDH-detecting RDTs against wild-type P. falciparum does not necessarily predict performance against pfhrp2-deleted parasites. Furthermore, many, but not all HRP2-based RDTs, detect pfhrp2-negative/pfhrp3-positive samples, with implications for the HRP2-based RDT screening approach for detection and surveillance of HRP2-negative parasites.
疟疾快速诊断检测（RDT）极大地提高了在流行地区进行诊断的可及性。大多数 RDT 检测恶性疟原虫高变区 2 型（PfHRP2），但 PfHRP2 缺失寄生虫的出现严重威胁了其敏感性。检测恶性疟原虫或全乳酸脱氢酶（Pf-LDH）的 RDT 提供了替代方案。本研究旨在系统评估针对经充分特征描述的 PfHRP2 缺失恶性疟原虫寄生虫的疟疾 RDT 的性能。
32 种 RDT 对 100 种野生型临床分离株（200 个寄生虫/µL）和 40 种来自 10 种培养适应和临床分离株的 PfHRP2 缺失寄生虫的样本进行了检测。野生型和 PfHRP2 缺失寄生虫的 Pf-LDH 浓度相当。Pf-LDH 检测 RDT 也对缺乏 PfHRP2 和 PfHRP3 的 18 种临床分离株在更高密度（2000 个寄生虫/µL）进行了检测。
PfHRP2 缺失寄生虫的 RDT 阳性率（>94%）最高，对于两种全-LDH 仅 RDT 而言。9 种 Pf-LDH 检测 RDT 的阳性率差异很大，双缺失（PfHRP2/3 阴性；63.9%）和单缺失（PfHRP2 阴性/PfHRP3 阳性；59.1%）寄生虫的中位阳性率均低于野生型恶性疟原虫（93.8%）。在 2000 个寄生虫/µL时，22 种单缺失寄生虫中，HRP2 检测 RDT 对 22 种单缺失寄生虫的中位阳性率分别为 69.9%和 35.2%，而 HRP2 组合 RDT 的中位阳性率分别为 96.0%和 92.5%。在 2000 个寄生虫/µL时，8 种 Pf-LDH RDT 可检测到所有临床双缺失样本。
评估的全-LDH 仅 RDT 表现良好。Pf-LDH 检测 RDT 对野生型恶性疟原虫的性能不一定能预测对 PfHRP2 缺失寄生虫的性能。此外，许多（但不是全部）基于 HRP2 的 RDT 检测到 PfHRP2 阴性/PfHRP3 阳性样本，这对基于 HRP2 的 RDT 筛查方法检测和监测 PfHRP2 阴性寄生虫具有影响。
