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Abstract
Rapid, reliable, and sensitive detection of Plasmodium infection is central to malaria control and elimination. Many Malaria Rapid Diagnostic Tests (RDTs) developed for this purpose depend upon immunoassays that can be improved by advances in bound antibody sensor technology. In a previous study, immuno-polymerase chain reaction (PCR) was shown to provide highly sensitive detection of Plasmodium falciparum lactate dehydrogenase (PfLDH) in monoclonal antibody (mAb) sandwich assays. Here, we show comparably high immunoassay sensitivity by inductively coupled plasma mass spectrometry (ICP-MS) detection of gold nanoparticles (AuNPs). Following capture of PfLDH with the primary mAb and binding of the AuNP-labeled detection mAb, ICP-MS signals from the AuNPs provided quantitative measures of recombinant PfLDH test dilutions and P. falciparum-infected erythrocytes. A detection limit of 1.5 pg/mL was achieved with the PfLDH protein. Parasitemia in cultures of P. falciparum-infected erythrocytes could be detected to a lower limit of 1.6 parasite/μl (p/μl) for early ring-stage forms and 0.3 p/μl for mixed stages including mature trophozoites and schizont-stages. These results show that ICP-MS detection of AuNPs can support highly sensitive and accurate detection of Plasmodium infection.
Highlights
Asymptomatic and submicroscopic Plasmodium infections that go undetected in endemic populations and sustain transmission through mosquitoes are a continuing impediment to malaria elimination (Wu et al, 2015)
Between the relatively low sensitivity of microscopy and the high sensitivity of nucleotide sequence detection methods, a midrange of sensitivity is offered by Rapid Diagnostic Tests (RDTs), of which some can detect as few as 10 p/ml (Hemben et al, 2018)
For the immunoassay detection of Plasmodium falciparum lactate dehydrogenase (PfLDH), capture of the protein by the primary capture monoclonal antibody (mAb) and binding of the detection mAb were as previously described for high sensitivity immuno-polymerase chain reaction (PCR) assays (Mu et al, 2017)
Summary
Asymptomatic and submicroscopic Plasmodium infections that go undetected in endemic populations and sustain transmission through mosquitoes are a continuing impediment to malaria elimination (Wu et al, 2015). Receptor-target binding can be detected in label-free formats by piezoelectric immunosensors (Sharma et al, 2011) or indicator displacement assays (Chakma et al, 2016) These methods are considered to have advantages for field applications, their sensitivity (12.0 ng/ml) needs to be improved further. For malaria parasite detection, assays with AuNPs have been developed for rapid, simple, and costeffective detection of P. falciparum infections, the estimated LOD for these assays was poor (2.4 mg/ml for PfHsp and PfHSP90; ≈1,000 p/ml for PfLDH) (Castilho Mde et al, 2011; Guirgis et al, 2012; Jeon et al, 2013). We describe the ICP-MS detection of AuNPs as a proxy for the sensitive immunoassay quantification of PfLDH, both as a purified recombinant protein and as antigen present in P. falciparum-infected erythrocytes
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