PHE Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
PHE Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Int J Infect Dis. 2021 Jul;108:137-144. doi: 10.1016/j.ijid.2021.05.008. Epub 2021 May 13.
Our objective was to systematically investigate false-negative histidine-rich protein 2 rapid diagnostic tests (HRP2-RDT) in imported Plasmodium falciparum malaria cases from travelers to the UK and the Republic of Ireland (RoI).
Five imported malaria cases in travellers returning to the UK and RoI from East Africa were reported to the PHE Malaria Reference Laboratory as negative according to histidine-rich protein (HRP2)-RDT. The cases were systematically investigated using microscopic, RDT, molecular, genomic, and in in vitro approaches.
In each case, HRP2-RDT was negative, whereas microscopy confirmed the presence of P. falciparum. Further analysis revealed that the genes encoding HRP2 and HRP3 were deleted in three of the five cases. Whole-genome sequencing in one of these isolates confirmed deletions in P. falciparum chromosomes 8 and 13. Our study produced evidence that the fourth case, which had high parasitemia at clinical presentation, was a rare example of antigen saturation ('prozone-like effect'), leading to a false negative in the HRP2-RDT, while the fifth case was due to low parasitemia.
False-negative HRP2-RDT results with P. falciparum are concerning. Our findings emphasise the necessity of supporting the interpretation of RDT results with microscopy, in conjunction with clinical observations, and sets out a systematic approach to identifying parasites carrying pfhrp2 and pfhrp3 deletions.
我们旨在系统调查从英国和爱尔兰共和国（RoI）前往旅行者中输入性恶性疟原虫疟疾病例中假阴性组氨酸丰富蛋白 2 快速诊断检测（HRP2-RDT）的情况。
向 PHE 疟疾参考实验室报告了 5 例从东非返回英国和 RoI 的旅行者中的输入性疟疾病例，这些病例根据组氨酸丰富蛋白（HRP2）-RDT 检测结果为阴性。通过显微镜检查、RDT、分子、基因组和体外方法对这些病例进行了系统调查。
在每个病例中，HRP2-RDT 均为阴性，而显微镜检查则证实存在恶性疟原虫。进一步分析显示，五个病例中有三个的 HRP2 和 HRP3 基因缺失。其中一个分离株的全基因组测序证实了恶性疟原虫染色体 8 和 13 的缺失。我们的研究提供了证据表明，第四个病例在临床出现时具有高寄生虫血症，是抗原饱和的罕见例子（“类前带效应”），导致 HRP2-RDT 出现假阴性，而第五个病例则是由于寄生虫血症低。
恶性疟原虫 HRP2-RDT 检测结果呈假阴性令人担忧。我们的研究结果强调了必须结合显微镜检查和临床观察来支持 RDT 结果的解释，并提出了一种系统的方法来识别携带 pfhrp2 和 pfhrp3 缺失的寄生虫。
