RDT-undetectable Malaria in the DR Congo: Epidemiology and Development of Alternatives

刚果民主共和国 RDT 检测不到的疟疾：流行病学和替代方案的开发

• 批准号: 10542646
• 负责人: Rhoel David Ramos Dinglasan
• 金额: $ 0.18万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-22 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10542646
• 关键词: Adult; Africa; Africa South of the Sahara; Algorithms; Antigens; Area; Artemisinins; Biological Assay; Biological Markers; Blood specimen; Cameroon; Characteristics; Child; Clinical; Combined Modality Therapy; Congo; Country; Cross-Sectional Studies; Data; Democratic Republic of the Congo; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disasters; Epidemiology; Evolution; Failure; Future; Gene Proteins; Genes; Genome; Genotype; Goals; HRP-2 protein; Human; Immunoassay; Individual; Infection; Intervention; Lateral; Longitudinal cohort study; Malaria; Malaria Diagnosis; Malaria Diagnostic; Methods; Microsatellite Repeats; Microscopy; Modality; Molecular; Monitor; Parasites; Plasmodium falciparum; Prevalence; Proteins; Province; Public Health; Rapid diagnostics; Reporting; Research; Resistance; Saliva; Sampling; Severities; Site; South America; Test Result; Testing; Work; base; candidate marker; circulating biomarkers; cohort; detection limit; falls; histidine-rich proteins; mortality; next generation; noninvasive diagnosis; novel; novel marker; novel strategies; point of care; programs; prospective; prototype; rapid test; tool; treatment program

ABSTRACT Malaria-related mortality is falling, due in part to the implementation of rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT) treatment programs. RDTs have become the primary modality for diagnosis of malaria globally, including in Sub-Saharan Africa. Most widely used RDTs rely on the detection of histidine-rich protein 2 (HRP2), an antigen specific to P​ lasmodium falciparum​ encoded by the ​pfhrp2​ gene. However, false-negative results have recently been reported in individuals infected with P​ . falciparum ​parasites harboring a deletion of the ​pfhrp2​ gene with or without a deletion in a related histidine-rich protein gene, pfhrp3​. These parasites have been commonly described in South America and sporadically in other regions, including Africa. Until recently, the prevalence and impact of ​pfhrp2​ deletions deletions in Africa was unknown. We recently completed a large cross-sectional survey of more than 7,000 children in the Democratic Republic of Congo (DRC), where RDTs have been the primary mode of diagnosis since 2011. We found that 6.4% of parasitemic children had false-negative RDTs due to a p​ fhrp2​ deletion. In Kinshasa province, more than 20% of infections were due to ​pfhrp2​-deleted parasites. Similar findings are being made in other parts of Sub-Saharan Africa, raising the possibility that HRP2-based RDTs are becoming ineffective. Currently, our collaborators are conducting a longitudinal cohort study in Kinshasa to evaluate the epidemiology of ​pfhrp2/3 deleted parasites. Our proposal will leverage this cohort to achieve our short-term goals to (1) understand the evolutionary drivers of these deletions in the DRC, the country in Africa with the second-highest malaria burden; and (2) to develop a simple PCR assay for ​pfhrp2/3​ deletion surveillance so that malaria control programs can implement alternative diagnostics when needed. Our long-term goal is to develop alternate biomarkers and noninvasive diagnostic tests for malaria diagnosis and test them in an area of HRP2-based RDT failure. This proposal is unique in that it will help characterize an emerging public health problem while simultaneously seeking solutions. As a result, there is a high likelihood that the results of this research will significantly impact the next generation of point of care malaria diagnostic tests.

摘要 与疟疾有关的死亡率正在下降，部分原因是实施了快速诊断测试， 青蒿素联合疗法（ACT）治疗方案。RDT已成为主要的方式 用于诊断全球疟疾，包括撒哈拉以南非洲。最广泛使用的RDT依赖于检测 富含组氨酸蛋白2（HRP 2），一种由pfhrp 2基因编码的恶性疟原虫特异性抗原。 然而，假阴性结果最近已被报道，在个人感染P。恶性疟原虫 携带pfhrp 2基因的缺失，在相关的富组氨酸蛋白基因中有或没有缺失， pfhrp3。这些寄生虫在南美洲常见，在其他地区也有零星的描述， 包括非洲。直到最近，非洲pfhrp 2缺失的患病率和影响尚不清楚。 我们最近完成了对刚果民主共和国7 000多名儿童的大型横断面调查 刚果（DRC），自2011年以来，RDTs一直是主要的诊断模式。我们发现，6.4%的 寄生虫血症儿童由于pfhrp 2缺失而具有假阴性RDT。在金沙萨省， 的感染是由于PFHRP 2缺失的寄生虫。类似的调查结果也在其他地区进行。 撒哈拉以南非洲，这增加了基于HRP 2的RDT变得无效的可能性。目前我们的 合作者正在金沙萨进行一项纵向队列研究，以评估pfhrp 2/3的流行病学 删除寄生虫。我们的建议将利用这一群体来实现我们的短期目标，以（1）了解 刚果民主共和国是非洲疟疾发病率第二高的国家， 建立pfhrp 2/3基因缺失的PCR检测方法，为疟疾防治提供科学依据 程序可以在需要时实现替代诊断。我们的长期目标是开发替代 疟疾诊断的生物标志物和非侵入性诊断测试，并在基于HRP 2的区域进行测试。 RDT故障。这项建议的独特之处在于，它将有助于描述一个新出现的公共卫生问题， 同时寻求解决方案。因此，这项研究的结果很有可能 这将对下一代疟疾诊断检测产生重大影响。

项目成果

Screening strategies and laboratory assays to support Plasmodium falciparum histidine-rich protein deletion surveillance: where we are and what is needed.

• DOI: 10.1186/s12936-022-04226-2
• 发表时间: 2022-06-24
• 期刊: MALARIA JOURNAL
• 影响因子: 3
• 作者: Beshir, Khalid B.;Parr, Jonathan B.;Cunningham, Jane;Cheng, Qin;Rogier, Eric
• 通讯作者: Rogier, Eric