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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的疟疾相关死亡率正在下降，部分原因是快速诊断测试（RDT）的实施和以青蒿素为基础的联合疗法（ACT）已成为主要的治疗方案。全球范围内（包括撒哈拉以南非洲地区）的疟疾诊断最广泛使用的 RDT 依赖于检测。富含组氨酸的蛋白 2 (HRP2)，这是一种由 pfhrp2 基因编码的恶性疟原虫特异性抗原。然而，最近报告了感染恶性疟原虫寄生虫的个体出现假阴性结果含有pfhrp2基因的删除，以及相关的富含组氨酸的蛋白质基因的删除或不删除， pfhrp3。这些寄生虫在南美洲和其他地区都有报道，直到最近，pfhrp2 缺失在非洲的流行率和影响尚不清楚。我们最近完成了一项针对民主共和国 7,000 多名儿童的大型横断面调查刚果（金），自 2011 年以来 RDT 一直是主要的诊断方式。我们发现 6.4% 在金沙萨省，超过 20% 的寄生虫病儿童因 p fhrp2 缺失而出现假阴性 RDT。的感染是由pfhrp2删除的寄生虫引起的，在其他地区也有类似的发现。撒哈拉以南非洲地区，增加了基于 HRP2 的 RDT 目前无效的可能性。合作者正在金沙萨进行一项纵向队列研究，以评估 pfhrp2/3 的流行病学我们的提案将利用这个群体来实现我们的短期目标：（1）了解刚果民主共和国是非洲疟疾第二严重的国家，这些缺失的进化驱动因素负担；(2) 开发一种简单的 PCR 检测方法来监测 pfhrp2/3 缺失，从而控制疟疾计划可以在需要时实施替代诊断。我们的长期目标是开发替代诊断。用于疟疾诊断的生物标志物和无创诊断测试，并在基于 HRP2 的领域进行测试 RDT 失败的提议是独特的，因为它将有助于描述新出现的公共卫生问题。因此，这项研究的结果很可能会同时寻求解决方案。显着影响下一代护理点疟疾诊断测试。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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