{"doi":"10.17615/0kp5-wr90","title":"Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm","abstract":"ABSTRACT Poor specificity may negatively impact rapid diagnostic test (RDT)-based diagnostic strategies for malaria. We performed real-time PCR on a subset of subjects who had undergone diagnostic testing with a multiple-antigen (histidine-rich protein 2 and pan -lactate dehydrogenase pLDH [HRP2/pLDH]) RDT and microscopy. We determined the sensitivity and specificity of the RDT in comparison to results of PCR for the detection of Plasmodium falciparum malaria. We developed and evaluated a two-step algorithm utilizing the multiple-antigen RDT to screen patients, followed by confirmatory microscopy for those individuals with HRP2-positive (HRP2 + )/pLDH-negative (pLDH − ) results. In total, dried blood spots (DBS) were collected from 276 individuals. There were 124 (44.9%) individuals with an HRP2 + /pLDH + result, 94 (34.1%) with an HRP2 + /pLDH − result, and 58 (21%) with a negative RDT result. The sensitivity and specificity of the RDT compared to results with real-time PCR were 99.4% (95% confidence interval [CI], 95.9 to 100.0%) and 46.7% (95% CI, 37.7 to 55.9%), respectively. Of the 94 HRP2 + /pLDH − results, only 32 (34.0%) and 35 (37.2%) were positive by microscopy and PCR, respectively. The sensitivity and specificity of the two-step algorithm compared to results with real-time PCR were 95.5% (95% CI, 90.5 to 98.0%) and 91.0% (95% CI, 84.1 to 95.2), respectively. HRP2 antigen bands demonstrated poor specificity for the diagnosis of malaria compared to that of real-time PCR in a high-transmission setting. The most likely explanation for this finding is the persistence of HRP2 antigenemia following treatment of an acute infection. The two-step diagnostic algorithm utilizing microscopy as a confirmatory test for indeterminate HRP2 + /pLDH − results showed significantly improved specificity with little loss of sensitivity in a high-transmission setting.","journal":"UNC Libraries","year":2020,"id":137322,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":597315,"name":"Edgar Mulogo","orcid":"0000-0003-3859-453X","position":1,"is_corresponding":false},{"id":597316,"name":"Michael Matte","orcid":"0000-0001-7034-0543","position":2,"is_corresponding":false},{"id":96894,"name":"Yap Boum","orcid":"0000-0002-6823-8539","position":3,"is_corresponding":false},{"id":597317,"name":"Moses Murungi","orcid":"0000-0002-5051-3977","position":4,"is_corresponding":false},{"id":270620,"name":"Travis Fulton","orcid":"0000-0001-9028-928X","position":5,"is_corresponding":false},{"id":428586,"name":"Ross M. Boyce","orcid":"0000-0002-9489-6324","position":6,"is_corresponding":false},{"id":597318,"name":"Moses Ntaro","orcid":"0000-0001-7944-4082","position":7,"is_corresponding":false},{"id":270632,"name":"Jonathan J. Juliano","orcid":"0000-0002-0591-0850","position":8,"is_corresponding":false},{"id":597319,"name":"Dan Nyehangane","orcid":"0000-0002-1898-4162","position":9,"is_corresponding":false},{"id":69650,"name":"Mark J. Siedner","orcid":"0000-0003-3506-842X","position":10,"is_corresponding":false},{"id":597314,"name":"R. de los Reyes","orcid":"0000-0003-0485-9552","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:16:56.001887Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}