Puspitasari Agatha Mia, Sutanto Edwin, Syauqi Khilal, Amalia Ristya, Nisa Fahira Ainun, Trianty Leily, Sidhartha Elizabeth, Kenangalem Enny, Poespoprodjo Jeanne Rini, Ahmed Rukhsana, Owusu Ewurama, Carlier Lise, Tetteh Kevin K A, Cheng Qin, Noviyanti Rintis
Exeins Health Initiative, Jakarta, Indonesia.
Indonesia International Institute of Life Sciences, Jakarta, Indonesia.
Sci Rep. 2025 Jun 4;15(1):19511. doi: 10.1038/s41598-025-02834-x.
The rising prevalence of histidine-rich protein 2 (PfHRP2) gene deletions (pfhrp2-) poses a threat to the accuracy of PfHRP2-based rapid diagnostic tests (RDTs). However, evidence of this deletion is scarce in Indonesia. We examined the prevalence of pfhrp2 and its paralogue histidine-rich protein 3 (PfHRP3) gene deletions (pfhrp3-) in blood samples collected from a study assessing three PfHRP2-based RDTs conducted between December 2022 and April 2023 in Timika, Papua. Out of 2157 symptomatic-patients enrolled, 566 P. falciparum mono-infection cases were included for pfhrp2/3 exon 2 genotyping. We detected nine samples (1.59%, 95% CI 0.73-3.00%) with pfhrp2-/pfhrp3-, of which eight were PfHRP2-RDTs positive. Of three pfhrp2- samples (0.53%, 95% CI 0.11-1.54%), one was PfHRP2-RDTs positive. In contrast, 201 samples (35.51%, 95% CI 31.57-39.61%) had pfhrp3-, five of which were pfhrp2 + but PfHRP2-RDT negative; however, four exhibited low parasitemia. Five PfHRP2-RDTs negative samples with pfhrp2 + /pfhrp3 + were sequenced alongside two pfhrp2 + with PfHRP2-RDTs positive samples. We found more repeat-type variations in pfhrp2 compared to pfhrp3. Seven unique repeat types in pfhrp2 and one unique repeat type in pfhrp3 amino acid sequences were characterized in single or multiple copies per sample. These results demonstrated the low prevalence of pfhrp2- 2.12% (95% CI 1.10-3.67%) suggesting PfHRP2-based RDTs remain suitable for malaria diagnosis in Timika, Papua, Indonesia.
富含组氨酸蛋白2（PfHRP2）基因缺失（pfhrp2-）的患病率不断上升，对基于PfHRP2的快速诊断检测（RDT）的准确性构成威胁。然而，在印度尼西亚，这种缺失的证据很少。我们在2022年12月至2023年4月于巴布亚省蒂米卡进行的一项评估三种基于PfHRP2的RDT的研究中，检测了从血液样本中采集的pfhrp2及其旁系同源物富含组氨酸蛋白3（PfHRP3）基因缺失（pfhrp3-）的患病率。在纳入的2157例有症状患者中，566例恶性疟原虫单感染病例被纳入pfhrp2/3外显子2基因分型。我们检测到9个样本（1.59%，95%CI 0.73 - 3.00%）存在pfhrp2-/pfhrp3-，其中8个样本的PfHRP2 - RDT检测呈阳性。在3个pfhrp2-样本（0.53%，95%CI 0.11 - 1.54%）中，1个样本的PfHRP2 - RDT检测呈阳性。相比之下，201个样本（35.51%，95%CI 31.57 - 39.61%）存在pfhrp3-，其中5个样本为pfhrp2+但PfHRP2 - RDT检测为阴性；然而，4个样本的疟原虫血症水平较低。对5个PfHRP2 - RDT检测为阴性且pfhrp2+/pfhrp3+的样本以及2个PfHRP2 - RDT检测为阳性且pfhrp2+的样本进行了测序。我们发现pfhrp2中的重复型变异比pfhrp3更多。在pfhrp2的氨基酸序列中鉴定出7种独特的重复类型，在pfhrp3的氨基酸序列中鉴定出1种独特的重复类型，每个样本中这些重复类型以单拷贝或多拷贝形式存在。这些结果表明pfhrp2-的患病率较低，为2.12%（95%CI 1.10 - 3.67%），这表明基于PfHRP2的RDT仍然适用于印度尼西亚巴布亚省蒂米卡的疟疾诊断。
