ArticleMalaria journal2018
Evidence for histidine-rich protein 2 immune complex formation in symptomatic patients in Southern Zambia.
Article in Malaria journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 37 citations in OpenAlex.
- Assessment of a highly sensitive rapid diagnostic test for reactive case detection of Plasmodium Falciparum infections in Myanmar.Malaria journal · 2025Article
- Histidine-rich protein (hrp) 2-based RDT false-negatives and Plasmodium falciparum hrp 2 and 3 gene deletions in low, seasonal and intense perennial transmission zones in Cameroon: a cross - sectional study.BMC infectious diseases · 2024Article
- Evolution of pfhrp2 and pfhrp3 deletions in Equatorial Guinea between the pre- and post-RDT introduction.Malaria journal · 2024Article
- Factors Affecting the Performance of HRP2-Based Malaria Rapid Diagnostic Tests.Tropical medicine and infectious disease · 2022Review
- Diagnostic performance of a 5-plex malaria immunoassay in regions co-endemic for Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae and P. ovale.Scientific reports · 2022Article
- Genetic deletions and high diversity ofFrontiers in epidemiology · 2022Article
- Genetic variation of Plasmodium falciparum histidine-rich protein 2 and 3 in Assosa zone, Ethiopia: its impact on the performance of malaria rapid diagnostic tests.Malaria journal · 2021Article
- Detection of high prevalence of Plasmodium falciparum histidine-rich protein 2/3 gene deletions in Assosa zone, Ethiopia: implication for malaria diagnosis.Malaria journal · 2021Article
- Field performance of ultrasensitive and conventional malaria rapid diagnostic tests in southern Mozambique.Malaria journal · 2020Article
- Direct Estimation of Sensitivity ofThe American journal of tropical medicine and hygiene · 2019Article
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8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundRapid diagnostic tests based on histidine-rich protein 2 (HRP2) detection are the primary tools used to detect Plasmodium falciparum malaria infections. Recent conflicting reports call into question whether α-HRP2 antibodies are present in human host circulation and if resulting immune complexes could interfere with HRP2 detection on malaria RDTs. This study sought to determine the prevalence of immune-complexed HRP2 in a low-transmission region of Southern Zambia.
methodsAn ELISA was used to quantify HRP2 in patient sample DBS extracts before and after heat-based immune complex dissociation. A pull-down assay reliant on proteins A, G, and L was developed and applied for IgG and IgM capture and subsequent immunoprecipitation of any HRP2 present in immune complexed form. A total of 104 patient samples were evaluated using both methods.
resultsImmune-complexed HRP2 was detectable in 17% (18/104) of all samples evaluated and 70% (16/23) of HRP2-positive samples. A majority of the patients with samples containing immune-complexed HRP2 had P. falciparum infections (11/18) and were also positive for free HRP2 (16/18). For 72% (13/18) of patients with immune-complexed HRP2, less than 10% of the total HRP2 present was in immune-complexed form. For the remaining samples, a large proportion (≥ 20%) of total HRP2 was complexed with α-HRP2 antibodies.
conclusionsEndogenous α-HRP2 antibodies form immune complexes with HRP2 in the symptomatic patient population of a low-transmission area in rural Southern Zambia. For the majority of patients, the percentage of HRP2 in immune complexes is low and does not affect HRP2-based malaria diagnosis. However, for some patients, a significant portion of the total HRP2 was in immune-complexed form. Future studies investigating the prevalence and proportion of immune-complexed HRP2 in asymptomatic individuals with low HRP2 levels will be required to assess whether α-HRP2 antibodies affect HRP2 detection for this portion of the transmission reservoir.
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