Okai Takatsugu, Chan Chim W, Kc Achyut, Omondi Protus, Musyoka Kelvin, Kongere James, Kagaya Wataru, Okomo Gordon, Kanoi Bernard N, Kido Yasutoshi, Gitaka Jesse, Kaneko Akira
Department of Virology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
Department of Parasitology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
Trop Med Health. 2024 Dec 18;52(1):94. doi: 10.1186/s41182-024-00664-7.
Malaria rapid diagnostic tests (RDTs) targeting the Plasmodium falciparum histidine-rich protein 2 (PfHRP2) are widely used to diagnose P. falciparum infection. However, reports of P. falciparum strains lacking PfHRP2 and the structurally similar PfHRP3 have raised concerns about the utility and reliability of PfHRP2-based RDTs. This study investigated the presence of P. falciparum with pfhrp2 and/or pfhrp3 gene deletions among infected residents in the Lake Victoria region, Kenya. Four cross-sectional malaria, surveys were conducted in four sites (Suba South, Mfangano, Kibuogi, and Ngodhe) from September 2018 to January 2020. P. falciparum infections were detected using a PfHRP2-based RDT, microscopy, and PCR on 9120 finger-prick blood samples. Samples negative by RDT but positive by PCR were selected for PCR amplification of pfmsp1 and pfmsp2 to confirm the quality and quantity of P. falciparum DNA. Samples positive for both pfmsp1 and pfmsp2 were included for detection of deletions of exons 1 and 2 in pfhrp2 and pfhrp3 PCR. The multiplicity of infection (MOI) was determined as the higher allele count between pfmsp1 and pfmsp2. Logistic regression analysis was performed to analyze the association between pfhrp2 and/or pfhrp3 deletions and demographic and infection variables. Of the 445 RDT-negative and PCR-positive samples, 125 (28.1%) were analyzed for pfhrp2 and pfhrp3 deletions. Single pfhrp2 deletion, single pfhrp3 deletion, and pfhrp2/3 double deletions were detected in 13 (10.4%), 19 (15.2%), and 36 (28.8%) samples, respectively. Single pfhrp2 deletion was found in all sites while single pfhrp3 deletion was found in all sites except Kibuogi. The majority of samples with pfhrp2 and/or pfhrp3 deletions were submicroscopic (73.5%), asymptomatic (80.9%), and monoclonal (80.9%). Polyclonal infection was significantly (p = 0.022) associated with a lower odds of pfhrp2/3 double deletion, suggesting detection of intact pfhrp2/3 in mixed infections. We report the presence of P. falciparum with pfhrp2/pfhrp3 double deletions among asymptomatic and submicroscopic infections in Kenya. Our findings highlight the need for active monitoring of pfhrp2 and pfhrp3 deletions at the community level to improve malaria detection and control in the region.
针对恶性疟原虫富含组氨酸蛋白2（PfHRP2）的疟疾快速诊断检测（RDT）被广泛用于诊断恶性疟原虫感染。然而，关于缺乏PfHRP2以及结构相似的PfHRP3的恶性疟原虫菌株的报道引发了对基于PfHRP2的RDT的实用性和可靠性的担忧。本研究调查了肯尼亚维多利亚湖地区受感染居民中存在pfhrp2和/或pfhrp3基因缺失的恶性疟原虫情况。2018年9月至2020年1月在四个地点（南苏巴、姆方加诺、基布奥吉和恩戈德）进行了四项横断面疟疾调查。使用基于PfHRP2的RDT、显微镜检查和PCR对9120份手指刺血样本检测恶性疟原虫感染情况。选择RDT检测为阴性但PCR检测为阳性的样本进行pfmsp1和pfmsp2的PCR扩增，以确认恶性疟原虫DNA的质量和数量。pfmsp1和pfmsp2均为阳性的样本用于检测pfhrp2和pfhrp3 PCR中外显子1和2的缺失情况。感染复数（MOI）被确定为pfmsp1和pfmsp2之间较高的等位基因计数。进行逻辑回归分析以分析pfhrp2和/或pfhrp3缺失与人口统计学和感染变量之间的关联。在445份RDT阴性且PCR阳性的样本中，125份（28.1%）被分析了pfhrp2和pfhrp3缺失情况。分别在13份（10.4%）、19份（15.2%）和36份（28.8%）样本中检测到单个pfhrp2缺失、单个pfhrp3缺失和pfhrp2/3双重缺失。在所有地点均发现了单个pfhrp2缺失，除基布奥吉外的所有地点均发现了单个pfhrp3缺失。大多数存在pfhrp2和/或pfhrp3缺失的样本为亚显微镜下感染（73.5%）、无症状感染（80.9%）和单克隆感染（8）。多克隆感染与pfhrp2/3双重缺失的较低几率显著相关（p = 0.022），这表明在混合感染中检测到完整的pfhrp2/3。我们报告了在肯尼亚无症状和亚显微镜下感染中存在pfhrp2/pfhrp3双重缺失的恶性疟原虫。我们的研究结果强调了在社区层面积极监测pfhrp2和pfhrp3缺失情况以改善该地区疟疾检测和控制的必要性。
