期刊
MALARIA JOURNAL
卷 17, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12936-018-2400-8
关键词
Plasmodium falciparum; Histidine-rich protein 2; HRP2; Malaria diagnosis; Antibodies; Immune complexes
资金
- PATH: Diagnostics for malaria elimination toward eradication [1758-00-06-00]
- National Institute of Health/Fogarty International Center [D43 TW009348]
- Vanderbilt University through Laboratories for Innovation in Global Health Technologies
- National Science Foundation Graduate Research Fellowship [1445197]
Background: Rapid 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 alpha-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. Methods: An 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. Results: Immune-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 alpha-HRP2 antibodies. Conclusions: Endogenous alpha-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 alpha-HRP2 antibodies affect HRP2 detection for this portion of the transmission reservoir.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据