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: 10475414
• 负责人: Rhoel David Ramos Dinglasan
• 金额: $ 4.76万
• 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 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10475414
• 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; 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