Analytical sensitivity of current best-in-class malaria rapid diagnostic tests.
BACKGROUND
Rapid diagnostic tests (RDTs) are today the most widely used method for malaria diagnosis and are recommended, alongside microscopy, for the confirmation of suspected cases before the administration of anti-malarial treatment. The diagnostic performance of RDTs, as compared to microscopy or PCR is well described but the actual analytical sensitivity of current best-in-class tests is poorly documented. This value is however a key performance indicator and a benchmark value needed to developed new RDTs of improved sensitivity.


METHODS
Thirteen RDTs detecting either the Plasmodium falciparum histidine rich protein 2 (HRP2) or the plasmodial lactate dehydrogenase (pLDH) antigens were selected from the best performing RDTs according to the WHO-FIND product testing programme. The analytical sensitivity of these products was evaluated using a range of reference materials including P. falciparum and Plasmodium vivax whole parasite samples as well as recombinant proteins.


RESULTS
The best performing HRP2-based RDTs could detect all P. falciparum cultured samples at concentrations as low as 0.8 ng/mL of HRP2. The limit of detection of the best performing pLDH-based RDT specifically detecting P. vivax was 25 ng/mL of pLDH.


CONCLUSIONS
The analytical sensitivity of P. vivax and Pan pLDH-based RDTs appears to vary considerably from product to product, and improvement of the limit-of-detection for P. vivax detecting RDTs is needed to match the performance of HRP2 and Pf pLDH-based RDTs for P. falciparum. Different assays using different reference materials produce different values for antigen concentration in a given specimen, highlighting the need to establish universal reference assays.
ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.|Spanish Consortium for Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Alfons
A
Jimenez
Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, UK.
Roxanne R
RR
Rees-Channer
Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, UK.
Rushini
R
Perera
Departamento de Ciencias Celulares y Moleculares, Facultad de Ciencias y Filosofía & Instituto de Medicina Tropical Alexander Von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
Dionicia
D
Gamboa
Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, UK.
Peter L
PL
Chiodini
FIND, Geneva, Switzerland.
Iveth J
IJ
González
ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.|Centro de Investigação em Saúde da Manhiça (CISM), Maputo, Mozambique.
Alfredo
A
Mayor
FIND, Geneva, Switzerland. xavier.ding@finddx.org.
Xavier C
XC
Ding
D000328:Adult; D000953:Antigens, Protozoan / Q000032:analysis; D002846:Chromatography, Affinity / Q000379:methods*; D003955:Diagnostic Tests, Routine / Q000379:methods*; D006801:Humans; D008288:Malaria / Q000175:diagnosis*; D016778:Malaria, Falciparum; D016780:Malaria, Vivax; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification; D010966:Plasmodium vivax / Q000276:immunology / Q000302:isolation & purification*; D012680:Sensitivity and Specificity; D013997:Time Factors
D000953:Antigens, Protozoan
Analytical sensitivity; HRP2; Malaria rapid diagnostic test; pLDH