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For large scale screening, such as malaria screening for elimination, diagnostic assay can be a challenge, as both the throughput and cost of the assay must be considered. The requirement of nucleic acid extraction hampers the throughput of most molecular assays. Co-amplification of multiple species or multiplex identification either can result in missed diagnosis or are too costly for large-scale screening. A genus- and species-specific diagnostic assay with simplified procedure, high sensitivity and throughput is still needed. This study aimed to develop a sensitive and high-throughput approach for large-scale infectious disease screening.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We developed multi-section Capture and Ligation Probe PCR (mCLIP-PCR) for the direct detection of RNA without extraction and reverse transcription. Multiple tailed sandwich hybridization probes were used to bind at genus- and species-specific sections of the target RNA to cooperatively capture the target onto a 96-well plate. After enzymatic ligation of the bound probes, a single-stranded DNA formed at each section with distinct tail sequence at the ends. They were separately PCR-amplified with primers corresponding to tail sequences for genus or species identification. We applied the method to the active screening of <jats:italic>Plasmodium<\/jats:italic> infections of 4,580 asymptomatic dried blood spot samples collected in malaria endemic areas and compared the results with standard qPCR using linear regression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>With multi-section cooperative capture but separate amplification strategy, we accurately identified genus <jats:italic>Plasmodium<\/jats:italic> and species <jats:italic>P. falciparum<\/jats:italic> and <jats:italic>P. vivax<\/jats:italic> without RNA extraction, with favorable sensitivities among the published reports. In the active screening, our method identified all 53 positive infections including two mixed infections, and two <jats:italic>P. vivax<\/jats:italic> infections that were missed by standard qPCR.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>mCLIP-PCR provides a sensitive and high-throughput approach to large-scale infectious disease screening with low cost and labor, making it a valuable tool for malaria elimination in endemic region.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s40249-022-00948-2","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T08:04:34Z","timestamp":1646640274000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A direct, sensitive and high-throughput genus and species-specific molecular assay for large-scale malaria screening"],"prefix":"10.1186","volume":"11","author":[{"given":"Yaling","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihua","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duoquan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4049-010X","authenticated-orcid":false,"given":"Zhi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"948_CR1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.4269\/ajtmh.14-0650","volume":"93","author":"R Ehtesham","year":"2015","unstructured":"Ehtesham R, Fazaeli A, Raeisi A, Keshavarz H, Heidari A. 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All the samples were collected with written informed consents.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"25"}}