Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples
Abstract Background As malaria endemic countries shift from control to elimination, the proportion of low density Plasmodium falciparum infections increases. Current field diagnostic tools, such as microscopy and rapid diagnostic tests (RDT), with detection limits of approximately 100–200 parasites/...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-03-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12936-018-2268-7 |
| _version_ | 1819078769941413888 |
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| author | Smita Das Roger B. Peck Rebecca Barney Ihn Kyung Jang Maria Kahn Meilin Zhu Gonzalo J. Domingo |
| author_facet | Smita Das Roger B. Peck Rebecca Barney Ihn Kyung Jang Maria Kahn Meilin Zhu Gonzalo J. Domingo |
| author_sort | Smita Das |
| collection | DOAJ |
| description | Abstract Background As malaria endemic countries shift from control to elimination, the proportion of low density Plasmodium falciparum infections increases. Current field diagnostic tools, such as microscopy and rapid diagnostic tests (RDT), with detection limits of approximately 100–200 parasites/µL (p/µL) and 800–1000 pg/mL histidine-rich protein 2 (HRP2), respectively, are unable to detect these infections. A novel ultra-sensitive HRP2-based Alere™ Malaria Ag P.f RDT (uRDT) was evaluated in laboratory conditions to define the test’s performance against recombinant HRP2 and native cultured parasites. Results The uRDT detected dilutions of P. falciparum recombinant GST-W2 and FliS-W2, as well as cultured W2 and ITG, diluted in whole blood down to 10–40 pg/mL HRP2, depending on the protein tested. uRDT specificity was 100% against 123 archived frozen whole blood samples. Rapid test cross-reactivity with HRP3 was investigated using pfhrp2 gene deletion strains D10 and Dd2, pfhrp3 gene deletion strain HB3, and controls pfhrp2 and pfhrp3 double deletion strain 3BD5 and pfhrp2 and pfhrp3 competent strain ITG. The commercial Standard Diagnostics, Inc. BIOLINE Malaria Ag P.f RDT (SD-RDT) and uRDT detected pfhrp2 positive strains down to 49 and 3.13 p/µL, respectively. The pfhrp2 deletion strains were detected down to 98 p/µL by both tests. Conclusion The performance of the uRDT was variable depending on the protein, but overall showed a greater than 10-fold improvement over the SD-RDT. The uRDT also exhibited excellent specificity and showed the same cross-reactivity with HRP3 as the SD-RDT. Together, the results support the uRDT as a more sensitive HRP2 test that could be a potentially effective tool in elimination campaigns. Further clinical evaluations for this purpose are merited. |
| first_indexed | 2024-12-21T19:18:22Z |
| format | Article |
| id | doaj.art-3adc3f0fca644d8c8239efc4f09c5f86 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-21T19:18:22Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-3adc3f0fca644d8c8239efc4f09c5f862022-12-21T18:53:00ZengBMCMalaria Journal1475-28752018-03-011711710.1186/s12936-018-2268-7Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samplesSmita Das0Roger B. Peck1Rebecca Barney2Ihn Kyung Jang3Maria Kahn4Meilin Zhu5Gonzalo J. Domingo6Diagnostics Program, PATHDiagnostics Program, PATHDiagnostics Program, PATHDiagnostics Program, PATHDiagnostics Program, PATHDiagnostics Program, PATHDiagnostics Program, PATHAbstract Background As malaria endemic countries shift from control to elimination, the proportion of low density Plasmodium falciparum infections increases. Current field diagnostic tools, such as microscopy and rapid diagnostic tests (RDT), with detection limits of approximately 100–200 parasites/µL (p/µL) and 800–1000 pg/mL histidine-rich protein 2 (HRP2), respectively, are unable to detect these infections. A novel ultra-sensitive HRP2-based Alere™ Malaria Ag P.f RDT (uRDT) was evaluated in laboratory conditions to define the test’s performance against recombinant HRP2 and native cultured parasites. Results The uRDT detected dilutions of P. falciparum recombinant GST-W2 and FliS-W2, as well as cultured W2 and ITG, diluted in whole blood down to 10–40 pg/mL HRP2, depending on the protein tested. uRDT specificity was 100% against 123 archived frozen whole blood samples. Rapid test cross-reactivity with HRP3 was investigated using pfhrp2 gene deletion strains D10 and Dd2, pfhrp3 gene deletion strain HB3, and controls pfhrp2 and pfhrp3 double deletion strain 3BD5 and pfhrp2 and pfhrp3 competent strain ITG. The commercial Standard Diagnostics, Inc. BIOLINE Malaria Ag P.f RDT (SD-RDT) and uRDT detected pfhrp2 positive strains down to 49 and 3.13 p/µL, respectively. The pfhrp2 deletion strains were detected down to 98 p/µL by both tests. Conclusion The performance of the uRDT was variable depending on the protein, but overall showed a greater than 10-fold improvement over the SD-RDT. The uRDT also exhibited excellent specificity and showed the same cross-reactivity with HRP3 as the SD-RDT. Together, the results support the uRDT as a more sensitive HRP2 test that could be a potentially effective tool in elimination campaigns. Further clinical evaluations for this purpose are merited.http://link.springer.com/article/10.1186/s12936-018-2268-7MalariaHistidine-rich protein 2Rapid diagnostic test |
| spellingShingle | Smita Das Roger B. Peck Rebecca Barney Ihn Kyung Jang Maria Kahn Meilin Zhu Gonzalo J. Domingo Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples Malaria Journal Malaria Histidine-rich protein 2 Rapid diagnostic test |
| title | Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples |
| title_full | Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples |
| title_fullStr | Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples |
| title_full_unstemmed | Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples |
| title_short | Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples |
| title_sort | performance of an ultra sensitive plasmodium falciparum hrp2 based rapid diagnostic test with recombinant hrp2 culture parasites and archived whole blood samples |
| topic | Malaria Histidine-rich protein 2 Rapid diagnostic test |
| url | http://link.springer.com/article/10.1186/s12936-018-2268-7 |
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