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Development of novel diagnostics for African non-falciparum malaria

非洲非恶性疟疾新型诊断方法的开发

基本信息

批准号：
10057106
负责人：
Jessica Lin
金额：
$ 18.94万
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：
2020
资助国家：
美国
起止时间：
2020-06-30 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10057106
关键词：
Address Affect Africa Africa South of the Sahara African Antigens Archives Bedside Testings Benchmarking Biological Assay Blood Care Technology Points Cause of Death Cessation of life Characteristics Clinical Clinical Sensitivity Clustered Regularly Interspaced Short Palindromic Repeats Country Democratic Republic of the Congo Dengue Virus Detection Development Devices Diagnosis Diagnostic Diagnostic tests Drops Epidemiology Evaluation Falciparum Malaria Fingers Fluorescence Generations HRP-2 protein Human Infection Laboratories Lactate Dehydrogenase Lateral Malaria Methodology Methods Modernization Mutation Nucleic Acids Parasites Pathogen detection Performance Plasmodium Plasmodium falciparum Plasmodium malariae Plasmodium ovale Plasmodium vivax Polymerase Prevalence Reaction Reporter Reporting Research Personnel Resources Ribonucleases Sampling Sensitivity and Specificity Signal Transduction Site Tanzania Technology Testing Therapeutic Time Training Translating Work World Health Organization amplification detection base cost density experience field study handheld equipment improved malaria infection mortality multiplex detection mutant new technology next generation novel novel diagnostics nucleic acid detection pathogen point of care programs recombinase trend

项目摘要

PROJECT SUMMARY While malaria deaths in Africa due to Plasmodium falciparum have fallen over the last decade, the proportion of malaria cases due to non-falciparum species is rising. Improved diagnostics are needed to respond to this changing epidemiology. Yet current “test and treat” strategies in Africa rely upon rapid diagnostic tests (RDTs) that do not reliably detect most non-falciparum infections and may be compromised by histidine-rich protein 2- (PfHRP2-) negative parasites. We propose to develop and compare novel recombinase polymerase amplification- (RPA-) and CRISPR-based diagnostic platforms that have the potential to launch the next generation of RDTs, capable of sensitive multiplexed detection of all Plasmodium species. We have already successfully adapted RPA and a new technology called SHERLOCK (Specific High Sensitivity Enzymatic Reporter Unlocking) for malaria, reaching limits of detection on par with real-time PCR. We now propose to tackle the more difficult detection of Plasmodium malariae and Plasmodium ovale. Our experience in diagnostic development and evaluation, expertise in non-falciparum and low-density malaria infections, and collaborative relationship with multiple in-country African investigators make us uniquely suited to pioneer this new technology. In Aim 1, we will develop and optimize P. malariae and P. ovale RPA and SHERLOCK assays with enhanced sensitivity and robustness, utilizing a range of strategies that have previously allowed streamlined, multiplexed detection of multiple pathogens. We will detect target nucleic acids using a multiplexed lateral flow device for RPA and simple fluorimeter for SHERLOCK. Sensitivity and specificity of the new assays will be benchmarked using a large sample bank of archived isolates from the Democratic Republic of the Congo and Tanzania. In Aim 2, we will field test the best performing RPA or SHERLOCK assays in Bagamoyo, Tanzania. We will determine their sensitivity and compare their performance to current RDTs, as well as real-time PCR. These studies will leverage promising new technology for pathogen detection to provide a low-cost platform for the study of non-falciparum malaria in low-resource settings. If successful, they will lay the groundwork for development of species-specific, sensitive RDTs capable of multiplexed detection of both P. falciparum and non-falciparum malaria in Africa.

项目总结