1. The XN-30 Haematology Analyser for Rapid Sensitive Detection of Malaria: A Diagnostic Accuracy Study
- Author
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Robert W. Sauerwein, Jan F. Jacobs, Andre J. van der Ven Prof, Halidou Tinto, Basile Kam, Quirijn de Mast, Annelies Post, Natacha Herssens, Palpouguini Lompo, Joel Dofinissery Bognini, Wouter A. van der Heijden, Berenger Kaboré, Salou Diallo, Isaie J. Reuling, Teun Bousema, and Kjerstin Lanke
- Subjects
medicine.medical_specialty ,Hematology ,business.industry ,Febrile illness ,Diagnostic accuracy ,Malaria parasitaemia ,medicine.disease ,Institutional review board ,Internal medicine ,parasitic diseases ,Tropical medicine ,Medicine ,business ,Parasite density ,Malaria - Abstract
Background: Accurate and timely diagnosis of malaria is essential for disease management and surveillance. Microscopy and malaria rapid diagnostic tests (RDTs) are standard malaria diagnostics, but both methods have significant limitations. The novel automated haematology analyser XN-30 provides standard complete blood counts (CBC) as well as quantification of malaria parasitaemia at the price of an RDT. This study assessed the accuracy of XN-30 for malaria detection in a Controlled Human Malaria Infection (CHMI) study and subsequently in a phase-3 diagnostic accuracy study in Burkina Faso. Methods: Sixteen healthy malaria-naive CHMI participants were challenged according to standardized protocols by exposure to five laboratory reared Plasmodium falciparum-infected mosquitoes and sampled daily for XN-30, blood smear microscopy, RDT and qPCR analyses (NCT02836002). The blinded diagnostic accuracy study included 908 patients aged >3 months, presenting with acute febrile illness (NCT02669823). XN-30, microscopy and RDTs (HRP-2/pLDH) were performed on site, qPCR was done in retrospect. Microscopy was used as reference standard, results were corrected for qPCR confirmed submicroscopic cases. RDT results were compared to XN-30 for both microscopic and qPCR confirmed cases. Findings: All CHMI participants became parasitaemic by qPCR and XN-30 with a strong correlation for parasite density (R2=0·91). In the field study, the sensitivity and specificity of XN-30 compared to microscopy were 98.7% and 99.4% respectively (PPV 98·7%, NPV 99·4%, AUC=0·99). Three microscopy confirmed cases were not detected by XN-30. However, XN-30 detected 24 of 119 (20.2%) qPCR confirmed submicroscopic cases. The sensitivity and specificity of XN-30 to diagnose microscopic cases were higher than that of HRP-2 and pLDH RDTs. Interpretation: XN-30 is a novel rapid automated malaria diagnostic outperforming standard microscopy and RDT's at a similar price. Since it simultaneously provides haemocytometric data and allows high-throughput testing, XN-30 is an attractive diagnostic tool for malaria management and control. Funding Statement: The CHMI study was funded by PATH MVI. Sysmex Corporation provided the analyzer and reagents. The diagnostic accuracy study was funded by Sysmex Corporation. The funding sources were involved in the study design, but not in data collection, analysis and interpretation, or the preparation of the report. Declaration of Interests: AvV and QdM have a non-restricted research grant from SYSMEX, which funded the current study. None of the other authors had any conflict of interest. Ethics Approval Statement: The studies were performed in accordance with the declaration of Helsinki and GCLP guidelines. The CHMI study was approved by the central committee for research involving human subjects (CCMO) of the Netherlands (NL56659.091.16), and the Western Institutional Review Board (WIRB) in the USA. The diagnostic study was approved by the national ethical committee of Burkina Faso (ref 2015-01-006), the internal review board of IRSS (ref A03-2016/CEIRES) the ethical committee of the university hospital of Antwerp (ref 15/47/492) and the institutional review board of the Institute of Tropical Medicine Antwerp (ref 1029/15).
- Published
- 2018