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Persistent ICT Malaria P.f/P.v Panmalarial and HRP2 Antigen Reactivity after Treatment of Plasmodium falciparum Malaria Is Associated with Gametocytemia and Results in False-Positive Diagnoses of Plasmodium vivax in Convalescence
Open accessAbstract
A problem with rapid Plasmodium falciparum -specific antigen histidine-rich protein 2 (HRP2) detection tests for malaria is the persistence of antigen in blood after the disappearance of asexual-stage parasitemia and clinical symptoms, resulting in false-positive (FP) test results following treatment. The ICT P.f/P.v immunochromatographic test detects both HRP2 and a panmalarial antigen (PMA) found in both P. falciparum and Plasmodium vivax . To examine posttreatment antigen persistence with this test and whether persistent sexual-stage forms (gametocytes) are a cause of FP tests after treatment, we compared serial antigen test results with microscopy results from patients symptomatic with P. falciparum malaria in Indonesia for 28 days following treatment with chloroquine (CQ; n = 66), sulfadoxine-pyrimethamine (SP; n = 36), and artesunate plus sulfadoxine-pyrimethamine (ART + SP; n = 15). Persistent FP antigenemia following SP treatment occurred in 29% (HRP2) and 42% (PMA) of the patients on day 7 and in 10% (HRP2) and 23% (PMA) on day 14. The high rates of persistent HRP2 and PMA antigenemia following CQ and SP treatment were strongly associated with the presence of gametocytemia, with the proportion with gametocytes on day 7 posttreatment being significantly greater in those with FP results than in those with true-negative PMA and HRP2 results. Gametocyte frequency on day 14 post-SP treatment was also greater in those with FP PMA results. Following SP treatment, PMA persisted longer than HRP2, giving an FP diagnosis of P. vivax in up to 16% of patients on day 14, with all FP P. vivax diagnoses having gametocytemia. In contrast, PMA was rapidly cleared following ART + SP treatment in association with rapid clearance of gametocytemia. Gametocytes appear to be an important cause of persistent posttreatment panmalarial antigenemia in areas of endemicity and may also contribute in part to persistent HRP2 antigenemia following treatment.
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“An important weakness of RDT-HRP2 tests is the prolonged half-life of the antigen. HRP-2 can be identified in plasma samples several weeks after parasite clearance, and therefore cannot be used to distinguish current from recent infection [23–25].”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [24]
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“These shortcomings hinder the use of existing RDT for managing malaria, and also for monitoring treatment efficacy [23–25].”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [24]
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Research works printed but not linked: 2
- Tjitra E. Suprianto S. Dyer M. Currie B. Anstey N. Evaluation of the therapeutic efficacy of chloroquine and sulfadoxine-pyrimethamine in uncomplicated falciparum malaria in Eastern Indonesia: high rates of chloroquine treatment failure with poor hematological recovery.Am. J. Trop. Med. Hyg.61 (Suppl.)1999S286S287 (Abstract.)
- Tjitra E. Suprianto S. Dyer M. Currie B. Anstey N. Utility of the ICT Malaria P.f/P.v immunochromatographic test in diagnosing/predicting treatment outcome following treatment of uncomplicated falciparum malaria in Eastern Indonesia.Am. J. Trop. Med. Hyg.61 (Suppl.)1999S472
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“Similarly, low parasite densities may contribute to discordance, since PfLDH, an enzyme linked to active parasite metabolism, generally has a lower sensitivity relative to HRP2-based RDT [45].”
Metadata
- Authors
- Tjitra, E., Suprianto, S., McBroom, J., Currie, B. J., & Anstey, N. M.
- Affiliations
- Menzies School of Health Research (AU)
- <!--label omitted: 3-->Directorate General of Communicable Disease Control and Environmental Health,3 Jakarta, Indonesia, and
- Venue
- Journal of Clinical Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2001-03
- Volume
- 39
- Issue
- 3
- Pages
- 1025-1031
- ISSN
- 0095-1137 (ISSN-L)
- 1098-660X
- PMC
- PMC87868
- OpenAlex
- W1997483009
- Cited by
- 113
- References
- 22
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 5 · 2020: 1 · 2019: 6 · 2018: 5 · 2017: 6 · 2015: 5 · 2014: 5 · 2013: 11 · 2012: 9
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Clinical Microbiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CDU eSpace Institutional Repository (Charles Darwin University) (submittedVersion)
- Griffith Research Online (submittedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Physical Sciences › Engineering › Biomedical Engineering › Biosensors and Analytical Detection
- Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
- Keywords
- falciparum malaria, Plasmodium vivax, HRP2 antigen, false-positive diagnosis, gametocytaemia, rapid diagnostic tests, sulfadoxine-pyrimethamine, chloroquine, convalescence
- MeSH terms
- Adult, Animals, Antigens, Protozoan, Antimalarials, Child, Child, Preschool, Convalescence, False Positive Reactions, Humans, Immunologic Tests, Microscopy, Plasmodium falciparum, Plasmodium vivax, Malaria, Falciparum, Malaria, Vivax
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