Development and clinical performance of high throughput loop-mediated isothermal amplification for detection of malaria

Accurate and efficient detection of sub-microscopic malaria infections is crucial for enabling rapid treatment and interruption of transmission. Commercially available malaria LAMP kits have excellent diagnostic performance, though throughput is limited by the need to prepare samples individually. H...

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Published in:	PloS one Vol. 12; no. 2; p. e0171126
Main Authors:	Perera, Rushini S, Ding, Xavier C, Tully, Frank, Oliver, James, Bright, Nigel, Bell, David, Chiodini, Peter L, Gonzalez, Iveth J, Polley, Spencer D
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 06-02-2017 Public Library of Science (PLoS)
Subjects:	Biology and Life Sciences Blood Blood coagulation tests Care and treatment Deoxyribonucleic acid Diagnosis Diagnostic systems DNA Dried Blood Spot Testing Engineering and Technology Health promotion Health services High-Throughput Screening Assays Hospitals Humans Infections Laboratories Malaria Malaria - diagnosis Malaria - parasitology Medicine and Health Sciences Microscopy Nucleic Acid Amplification Techniques Parasites Parasitology Planning Plasmodium Plasmodium - genetics Plasmodium falciparum Reproducibility of Results Research and Analysis Methods Sensitivity Sensitivity and Specificity Thermodynamic processes Tropical diseases Vector-borne diseases
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Summary:	Accurate and efficient detection of sub-microscopic malaria infections is crucial for enabling rapid treatment and interruption of transmission. Commercially available malaria LAMP kits have excellent diagnostic performance, though throughput is limited by the need to prepare samples individually. Here, we evaluate the clinical performance of a newly developed high throughput (HTP) sample processing system for use in conjunction with the Eiken malaria LAMP kit. The HTP system utilised dried blood spots (DBS) and liquid whole blood (WB), with parallel sample processing of 94 samples per run. The system was evaluated using 699 samples of known infection status pre-determined by gold standard nested PCR. The sensitivity and specificity of WB-HTP-LAMP was 98.6% (95% CI, 95.7-100), and 99.7% (95% CI, 99.2-100); sensitivity of DBS-HTP-LAMP was 97.1% (95% CI, 93.1-100), and specificity 100% against PCR. At parasite densities greater or equal to 2 parasites/μL, WB and DBS HTP-LAMP showed 100% sensitivity and specificity against PCR. At densities less than 2 p/μL, WB-HTP-LAMP sensitivity was 88.9% (95% CI, 77.1-100) and specificity was 99.7% (95% CI, 99.2-100); sensitivity and specificity of DBS-HTP-LAMP was 77.8% (95% CI, 54.3-99.5) and 100% respectively. The HTP-LAMP system is a highly sensitive diagnostic test, with the potential to allow large scale population screening in malaria elimination campaigns.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceptualization: XCD IJG SDP DB.Formal analysis: RSP SDP.Funding acquisition: IJG.Investigation: RSP.Methodology: XDC SDP FT JO NB.Project administration: IJG PLC.Resources: FT JO NB.Supervision: SDP XCD PLC.Validation: SDP PLC.Visualization: RSP.Writing – original draft: RSP.Writing – review & editing: RSP SDP XCD. Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Iveth J. Gonzalez and Xavier C. Ding are employees of FIND. Frank Tully and James Oliver are employees of 42 Technology Ltd. Nigel Bright is an employee of Porvair Sciences Ltd. David Bell is an employee of Global Good Fund, Intellectual Ventures Laboratory. All other authors declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0171126