Low prevalence of Plasmodium falciparum parasites lacking pfhrp2/3 genes among asymptomatic and symptomatic school-age children in Kinshasa, Democratic Republic of Congo.

Low prevalence of Plasmodium falciparum parasites lacking pfhrp2/3 genes among asymptomatic and symptomatic school-age children in Kinshasa, Democratic Republic of Congo.
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DOI:
10.1186/s12936-022-04153-2
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发表时间:
2022-04-19
期刊:
影响因子:
3
通讯作者:
Yamamoto, Taro
Yamamoto, Taro
中科院分区:
医学3区
文献类型:
--
作者:
Nundu, Sabin S.;Arima, Hiroaki;Simpson, Shirley, V;Chitama, Ben-Yeddy Abel;Munyeku, Yannick Bazitama;Muyembe, Jean-Jacques;Mita, Toshihiro;Ahuka, Steve;Culleton, Richard;Yamamoto, Taro

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丧失诊断检测的效力可能导致疟疾病例得不到治疗或治疗不当,从而影响病例管理和控制。疟疾诊断越来越依赖快速诊断测试(RDTs),其中最广泛使用的是针对恶性疟原虫富组氨酸蛋白2 (PfHRP2)的快速诊断测试。有许多报道称,在某些种群中,该基因在恶性疟原虫中缺失,使它们无法通过PfHRP2 rdt检测到。本研究的目的是鉴定从刚果民主共和国金沙萨无症状和有症状学龄儿童中分离的缺乏恶性疟原虫组氨酸富蛋白2和3基因(pfhrp2/3)的恶性疟原虫。使用2019年10月至11月期间从6-14岁学龄儿童中收集并在Whatman 903™滤纸上发现的血液样本,评估了基于pfhrp3的rdt与显微镜和PCR相比的性能。然后用PCR方法鉴定缺乏pfhrp2/3基因的寄生虫分离物。266例无症状疟疾携带者镜检阳性49%,PfHRP2_RDT阳性65%,pfldh-qPCR阳性70%。与PCR相比,RDTs的灵敏度和特异性分别为80%和70%,与显微镜相比,RDTs的灵敏度和特异性分别为92%和60%。在有症状的疟疾携带者(N = 196)中,显微镜检查、基于pfhrp2的RDT检测、pfldh-qPCR检测和阳性分别占62%、67%和87%。与PCR相比,RDTs的灵敏度和特异性分别为75%和88%,而与显微镜相比,RDTs的灵敏度和特异性分别为93%和77%。在有足够DNA进行pfhrp2/3扩增的173份样本中,pfhrp2和pfhrp3的缺失率分别为2%和1%。3个(4%)样本在无症状寄生虫携带者中存在pfhrp2基因缺失,1个(1%)样本在有症状的RDT阳性亚组中缺乏pfhrp3基因。RDT阴性亚组未发现缺乏pfhrp2/3基因的寄生虫。恶性疟原虫富组氨酸蛋白2/3基因缺失在调查人群中并不常见,不会导致诊断失败。鼓励使用严格的PCR方法来鉴定pfhrp2/3基因缺失,以尽量减少对其患病率的高估。在线版本包含补充材料,可在10.1186/s12936-022-04153-2获得。
Loss of efficacy of diagnostic tests may lead to untreated or mistreated malaria cases, compromising case management and control. There is an increasing reliance on rapid diagnostic tests (RDTs) for malaria diagnosis, with the most widely used of these targeting the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). There are numerous reports of the deletion of this gene in P. falciparum parasites in some populations, rendering them undetectable by PfHRP2 RDTs. The aim of this study was to identify P. falciparum parasites lacking the P. falciparum histidine rich protein 2 and 3 genes (pfhrp2/3) isolated from asymptomatic and symptomatic school-age children in Kinshasa, Democratic Republic of Congo. The performance of PfHRP2-based RDTs in comparison to microscopy and PCR was assessed using blood samples collected and spotted on Whatman 903™ filter papers between October and November 2019 from school-age children aged 6–14 years. PCR was then used to identify parasite isolates lacking pfhrp2/3 genes. Among asymptomatic malaria carriers (N = 266), 49%, 65%, and 70% were microscopy, PfHRP2_RDT, and pfldh-qPCR positive, respectively. The sensitivity and specificity of RDTs compared to PCR were 80% and 70% while the sensitivity and specificity of RDTs compared to microscopy were 92% and 60%, respectively. Among symptomatic malaria carriers (N = 196), 62%, 67%, and 87% were microscopy, PfHRP2-based RDT, pfldh-qPCR and positive, respectively. The sensitivity and specificity of RDTs compared to PCR were 75% and 88%, whereas the sensitivity and specificity of RDTs compared to microscopy were 93% and 77%, respectively. Of 173 samples with sufficient DNA for PCR amplification of pfhrp2/3, deletions of pfhrp2 and pfhrp3 were identified in 2% and 1%, respectively. Three (4%) of samples harboured deletions of the pfhrp2 gene in asymptomatic parasite carriers and one (1%) isolate lacked the pfhrp3 gene among symptomatic parasite carriers in the RDT positive subgroup. No parasites lacking the pfhrp2/3 genes were found in the RDT negative subgroup. Plasmodium falciparum histidine-rich protein 2/3 gene deletions are uncommon in the surveyed population, and do not result in diagnostic failure. The use of rigorous PCR methods to identify pfhrp2/3 gene deletions is encouraged in order to minimize the overestimation of their prevalence. The online version contains supplementary material available at 10.1186/s12936-022-04153-2.
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