Diagnostic accuracy of PfHRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillance
Malaria remains a significant cause of childhood morbidity and mortality, with Plasmodium falciparum Histidine-Rich Protein 2 (PfHRP2)-based malaria rapid diagnostic tests (mRDTs) widely used in endemic regions where microscopy is sometimes not feasible. While these tests offer high sensitivity, per...
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Frontiers Media S.A.
2025-05-01
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| Online Access: | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10585/full |
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| author | Sharley A. Wasena Sharley A. Wasena Clinton O. Onyango Clinton O. Onyango Shamim W. Osata Shamim W. Osata Samuel B. Anyona Samuel B. Anyona Evans Raballah Evans Raballah Ivy Hurwitz Philip D. Seidenberg Philip D. Seidenberg Collins Ouma Collins Ouma Qiuying Cheng Kristan A. Schneider Douglas J. Perkins Douglas J. Perkins |
| author_facet | Sharley A. Wasena Sharley A. Wasena Clinton O. Onyango Clinton O. Onyango Shamim W. Osata Shamim W. Osata Samuel B. Anyona Samuel B. Anyona Evans Raballah Evans Raballah Ivy Hurwitz Philip D. Seidenberg Philip D. Seidenberg Collins Ouma Collins Ouma Qiuying Cheng Kristan A. Schneider Douglas J. Perkins Douglas J. Perkins |
| author_sort | Sharley A. Wasena |
| collection | DOAJ |
| description | Malaria remains a significant cause of childhood morbidity and mortality, with Plasmodium falciparum Histidine-Rich Protein 2 (PfHRP2)-based malaria rapid diagnostic tests (mRDTs) widely used in endemic regions where microscopy is sometimes not feasible. While these tests offer high sensitivity, persistent PfHRP2 antigenemia and gene deletions can cause false-positive and false-negative results, compromising their accuracy for malaria case management and surveillance. This study evaluated the diagnostic performance and antigen persistence of PfHRP2-mRDTs using data from a longitudinal birth cohort of 750 children followed monthly from birth to 36 months in a holoendemic region of Kenya. Malaria diagnosis was performed using both microscopy and mRDTs, with a total of 15,006 clinical events recorded from 573 children between 2017 and 2023. Data from an independent acute febrile cohort of 937 children (<5 years) followed for 14 days was analyzed to validate the findings. The mRDT showed a high sensitivity of 97.27% but a moderate specificity of 65.00% in acute febrile illness, indicating frequent false-positive results. The positive predictive value was low (35.10%), suggesting that confirmatory testing is needed, while the negative predictive value was high (98.89%), reinforcing the reliability of mRDTs in ruling out malaria. Persistent PfHRP2 antigenemia was observed, with a median antigen clearance time of 51.14 days, respectively. Higher initial parasite densities (>50,000/μL) were associated with a slower antigen decay rate (p = 0.001), highlighting the challenge of interpreting positive mRDT results after treatment. Validation using the acute febrile cohort showed that mRDT specificity exceeded 95% at initial diagnosis and follow-up. Overall, PfHRP2-based mRDTs remain valuable for frontline malaria diagnosis but are limited by antigen persistence, leading to false positives in follow-up testing. Where feasible, integration of confirmatory diagnostic methods, such as microscopy or molecular assays, could improve the performance of malaria case management and clinical decision making, particularly in high-transmission settings. |
| format | Article |
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| institution | DOAJ |
| issn | 1535-3699 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-21961d7ce8284f5e9dac3a30d1aaeee62025-08-20T03:13:11ZengFrontiers Media S.A.Experimental Biology and Medicine1535-36992025-05-0125010.3389/ebm.2025.1058510585Diagnostic accuracy of PfHRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillanceSharley A. Wasena0Sharley A. Wasena1Clinton O. Onyango2Clinton O. Onyango3Shamim W. Osata4Shamim W. Osata5Samuel B. Anyona6Samuel B. Anyona7Evans Raballah8Evans Raballah9Ivy Hurwitz10Philip D. Seidenberg11Philip D. Seidenberg12Collins Ouma13Collins Ouma14Qiuying Cheng15Kristan A. Schneider16Douglas J. Perkins17Douglas J. Perkins18University of New Mexico-Kenya Global Health Programs, Kisumu, KenyaDepartment of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, KenyaUniversity of New Mexico-Kenya Global Health Programs, Kisumu, KenyaDepartment of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, KenyaUniversity of New Mexico-Kenya Global Health Programs, Kisumu, KenyaDepartment of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, KenyaUniversity of New Mexico-Kenya Global Health Programs, Kisumu, KenyaDepartment of Medical Biochemistry, School of Medicine, Maseno University, Maseno, KenyaUniversity of New Mexico-Kenya Global Health Programs, Kisumu, KenyaDepartment of Medical Laboratory Sciences, School of Public Health, Biomedical Sciences and Technology, Masinde Muliro University of Science and Technology, Kakamega, KenyaCenter for Global Health, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, United StatesCenter for Global Health, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, United StatesDepartment of Emergency Medicine, School of Medicine, University of New Mexico, Albuquerque, NM, United StatesUniversity of New Mexico-Kenya Global Health Programs, Kisumu, KenyaDepartment of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, KenyaCenter for Global Health, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, United StatesCenter for Global Health, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, United StatesUniversity of New Mexico-Kenya Global Health Programs, Kisumu, KenyaCenter for Global Health, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, United StatesMalaria remains a significant cause of childhood morbidity and mortality, with Plasmodium falciparum Histidine-Rich Protein 2 (PfHRP2)-based malaria rapid diagnostic tests (mRDTs) widely used in endemic regions where microscopy is sometimes not feasible. While these tests offer high sensitivity, persistent PfHRP2 antigenemia and gene deletions can cause false-positive and false-negative results, compromising their accuracy for malaria case management and surveillance. This study evaluated the diagnostic performance and antigen persistence of PfHRP2-mRDTs using data from a longitudinal birth cohort of 750 children followed monthly from birth to 36 months in a holoendemic region of Kenya. Malaria diagnosis was performed using both microscopy and mRDTs, with a total of 15,006 clinical events recorded from 573 children between 2017 and 2023. Data from an independent acute febrile cohort of 937 children (<5 years) followed for 14 days was analyzed to validate the findings. The mRDT showed a high sensitivity of 97.27% but a moderate specificity of 65.00% in acute febrile illness, indicating frequent false-positive results. The positive predictive value was low (35.10%), suggesting that confirmatory testing is needed, while the negative predictive value was high (98.89%), reinforcing the reliability of mRDTs in ruling out malaria. Persistent PfHRP2 antigenemia was observed, with a median antigen clearance time of 51.14 days, respectively. Higher initial parasite densities (>50,000/μL) were associated with a slower antigen decay rate (p = 0.001), highlighting the challenge of interpreting positive mRDT results after treatment. Validation using the acute febrile cohort showed that mRDT specificity exceeded 95% at initial diagnosis and follow-up. Overall, PfHRP2-based mRDTs remain valuable for frontline malaria diagnosis but are limited by antigen persistence, leading to false positives in follow-up testing. Where feasible, integration of confirmatory diagnostic methods, such as microscopy or molecular assays, could improve the performance of malaria case management and clinical decision making, particularly in high-transmission settings.https://www.ebm-journal.org/articles/10.3389/ebm.2025.10585/fullmalaria diagnosisPlasmodium falciparumhistidine rich proteinPfHRP2mRDT |
| spellingShingle | Sharley A. Wasena Sharley A. Wasena Clinton O. Onyango Clinton O. Onyango Shamim W. Osata Shamim W. Osata Samuel B. Anyona Samuel B. Anyona Evans Raballah Evans Raballah Ivy Hurwitz Philip D. Seidenberg Philip D. Seidenberg Collins Ouma Collins Ouma Qiuying Cheng Kristan A. Schneider Douglas J. Perkins Douglas J. Perkins Diagnostic accuracy of PfHRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillance Experimental Biology and Medicine malaria diagnosis Plasmodium falciparum histidine rich protein PfHRP2 mRDT |
| title | Diagnostic accuracy of PfHRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillance |
| title_full | Diagnostic accuracy of PfHRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillance |
| title_fullStr | Diagnostic accuracy of PfHRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillance |
| title_full_unstemmed | Diagnostic accuracy of PfHRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillance |
| title_short | Diagnostic accuracy of PfHRP2-based malaria rapid diagnostic tests and antigenemia persistence in Kenyan children from a holoendemic region: implications for case management and surveillance |
| title_sort | diagnostic accuracy of pfhrp2 based malaria rapid diagnostic tests and antigenemia persistence in kenyan children from a holoendemic region implications for case management and surveillance |
| topic | malaria diagnosis Plasmodium falciparum histidine rich protein PfHRP2 mRDT |
| url | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10585/full |
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