Persistence of Plasmodium falciparum HRP-2 antigenaemia after artemisinin combination therapy is not associated with gametocytes
Abstract Background In some settings, sensitive field diagnostic tools may be needed to achieve elimination of falciparum malaria. To this end, rapid diagnostic tests (RDTs) based on the detection of the Plasmodium falciparum protein HRP-2 are being developed with increasingly lower limits of detect...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-022-04387-0 |
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| author | Tate Oulton Almahamoudou Mahamar Koualy Sanogo Makonon Diallo Ahamadou Youssouf Sidi M. Niambele Siaka Samaké Sekouba Keita Youssouf Sinaba Adama Sacko Sekou F. Traore Kjerstin Lanke Katharine A. Collins John Bradley Chris Drakeley Will J. R. Stone Alassane Dicko |
| author_facet | Tate Oulton Almahamoudou Mahamar Koualy Sanogo Makonon Diallo Ahamadou Youssouf Sidi M. Niambele Siaka Samaké Sekouba Keita Youssouf Sinaba Adama Sacko Sekou F. Traore Kjerstin Lanke Katharine A. Collins John Bradley Chris Drakeley Will J. R. Stone Alassane Dicko |
| author_sort | Tate Oulton |
| collection | DOAJ |
| description | Abstract Background In some settings, sensitive field diagnostic tools may be needed to achieve elimination of falciparum malaria. To this end, rapid diagnostic tests (RDTs) based on the detection of the Plasmodium falciparum protein HRP-2 are being developed with increasingly lower limits of detection. However, it is currently unclear how parasite stages that are unaffected by standard drug treatments may contribute to HRP-2 detectability and potentially confound RDT results even after clearance of blood stage infection. This study assessed the detectability of HRP-2 in periods of post-treatment residual gametocytaemia. Methods A cohort of 100 P. falciparum infected, gametocyte positive individuals were treated with or without the gametocytocidal drug primaquine (PQ), alongside standard artemisinin-based combination therapy (ACT), in the context of a randomised clinical trial in Ouelessebougou, Mali. A quantitative ELISA was used to measure levels of HRP-2, and compared time to test negativity using a standard and ultra-sensitive RDT (uRDT) between residual gametocyte positive and negative groups. Results Time to test negativity was longest by uRDT, followed by ELISA and then standard RDT. No significant difference in time to negativity was found between the treatment groups with and without residual gametocytes: uRDT (HR 0.79 [95% CI 0.52–1.21], p = 0.28), RDT (HR 0.77 [95% CI 0.51–1.15], p = 0.20) or ELISA (HR 0.88 [95% CI 0.59–1.32], p = 0.53). Similarly, no difference was observed when adjusting for baseline asexual parasite density. Quantified levels of HRP-2 over time were similar between groups, with differences attributable to asexual parasite densities. Furthermore, no difference in levels of HRP-2 was found between individuals who were or were not infectious to mosquitoes (OR 1.19 [95% CI 0.98–1.46], p = 0.077). Conclusions Surviving sexual stage parasites after standard ACT treatment do not contribute to the persistence of HRP-2 antigenaemia, and appear to have little impact on RDT results. |
| first_indexed | 2024-04-13T07:21:16Z |
| format | Article |
| id | doaj.art-7bef12e0a5274c268c507fb7a406f2bb |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-04-13T07:21:16Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-7bef12e0a5274c268c507fb7a406f2bb2022-12-22T02:56:37ZengBMCMalaria Journal1475-28752022-12-0121111010.1186/s12936-022-04387-0Persistence of Plasmodium falciparum HRP-2 antigenaemia after artemisinin combination therapy is not associated with gametocytesTate Oulton0Almahamoudou Mahamar1Koualy Sanogo2Makonon Diallo3Ahamadou Youssouf4Sidi M. Niambele5Siaka Samaké6Sekouba Keita7Youssouf Sinaba8Adama Sacko9Sekou F. Traore10Kjerstin Lanke11Katharine A. Collins12John Bradley13Chris Drakeley14Will J. R. Stone15Alassane Dicko16Department of Infection Biology, London School of Hygiene & Tropical MedicineMalaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of BamakoMalaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of BamakoMalaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of BamakoMalaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of BamakoMalaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of BamakoMalaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of BamakoMalaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of BamakoMalaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of BamakoMalaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of BamakoMalaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of BamakoDepartment of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud University Medical Center, University of NijmegenDepartment of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud University Medical Center, University of NijmegenMRC International Statistics and Epidemiology Group, London School of Hygiene and Tropical MedicineDepartment of Infection Biology, London School of Hygiene & Tropical MedicineDepartment of Infection Biology, London School of Hygiene & Tropical MedicineMalaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences Techniques and Technologies of BamakoAbstract Background In some settings, sensitive field diagnostic tools may be needed to achieve elimination of falciparum malaria. To this end, rapid diagnostic tests (RDTs) based on the detection of the Plasmodium falciparum protein HRP-2 are being developed with increasingly lower limits of detection. However, it is currently unclear how parasite stages that are unaffected by standard drug treatments may contribute to HRP-2 detectability and potentially confound RDT results even after clearance of blood stage infection. This study assessed the detectability of HRP-2 in periods of post-treatment residual gametocytaemia. Methods A cohort of 100 P. falciparum infected, gametocyte positive individuals were treated with or without the gametocytocidal drug primaquine (PQ), alongside standard artemisinin-based combination therapy (ACT), in the context of a randomised clinical trial in Ouelessebougou, Mali. A quantitative ELISA was used to measure levels of HRP-2, and compared time to test negativity using a standard and ultra-sensitive RDT (uRDT) between residual gametocyte positive and negative groups. Results Time to test negativity was longest by uRDT, followed by ELISA and then standard RDT. No significant difference in time to negativity was found between the treatment groups with and without residual gametocytes: uRDT (HR 0.79 [95% CI 0.52–1.21], p = 0.28), RDT (HR 0.77 [95% CI 0.51–1.15], p = 0.20) or ELISA (HR 0.88 [95% CI 0.59–1.32], p = 0.53). Similarly, no difference was observed when adjusting for baseline asexual parasite density. Quantified levels of HRP-2 over time were similar between groups, with differences attributable to asexual parasite densities. Furthermore, no difference in levels of HRP-2 was found between individuals who were or were not infectious to mosquitoes (OR 1.19 [95% CI 0.98–1.46], p = 0.077). Conclusions Surviving sexual stage parasites after standard ACT treatment do not contribute to the persistence of HRP-2 antigenaemia, and appear to have little impact on RDT results.https://doi.org/10.1186/s12936-022-04387-0MalariaRapid diagnostic testsLateral flowUltra-sensitive RDTHRP-2Gametocytes |
| spellingShingle | Tate Oulton Almahamoudou Mahamar Koualy Sanogo Makonon Diallo Ahamadou Youssouf Sidi M. Niambele Siaka Samaké Sekouba Keita Youssouf Sinaba Adama Sacko Sekou F. Traore Kjerstin Lanke Katharine A. Collins John Bradley Chris Drakeley Will J. R. Stone Alassane Dicko Persistence of Plasmodium falciparum HRP-2 antigenaemia after artemisinin combination therapy is not associated with gametocytes Malaria Journal Malaria Rapid diagnostic tests Lateral flow Ultra-sensitive RDT HRP-2 Gametocytes |
| title | Persistence of Plasmodium falciparum HRP-2 antigenaemia after artemisinin combination therapy is not associated with gametocytes |
| title_full | Persistence of Plasmodium falciparum HRP-2 antigenaemia after artemisinin combination therapy is not associated with gametocytes |
| title_fullStr | Persistence of Plasmodium falciparum HRP-2 antigenaemia after artemisinin combination therapy is not associated with gametocytes |
| title_full_unstemmed | Persistence of Plasmodium falciparum HRP-2 antigenaemia after artemisinin combination therapy is not associated with gametocytes |
| title_short | Persistence of Plasmodium falciparum HRP-2 antigenaemia after artemisinin combination therapy is not associated with gametocytes |
| title_sort | persistence of plasmodium falciparum hrp 2 antigenaemia after artemisinin combination therapy is not associated with gametocytes |
| topic | Malaria Rapid diagnostic tests Lateral flow Ultra-sensitive RDT HRP-2 Gametocytes |
| url | https://doi.org/10.1186/s12936-022-04387-0 |
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