Performance and usability evaluation of three LDH-based malaria rapid diagnostic tests in Kédougou, Senegal

Area of Science:

• Malariology
• Diagnostic Test Development
• Parasitology

Background:

• The emergence of Plasmodium falciparum (Pf) parasites with deleted histidine-rich protein 2 and 3 (hrp2/hrp3) genes compromises the accuracy of HRP2-based malaria rapid diagnostic tests (RDTs).
• RDTs that target Pf lactate dehydrogenase (LDH) offer a potential alternative to mitigate current product limitations and enhance malaria case management.

Purpose of the Study:

• To evaluate the diagnostic performance and usability of three lactate dehydrogenase (LDH)-based RDTs in febrile patients in Kédougou, Senegal.

Main Methods:

• A cross-sectional diagnostic accuracy study was conducted involving 220 febrile patients.
• Capillary and venous blood samples were tested using HRP2-based RDTs, three LDH-based RDTs (BIOCREDIT Malaria Ag Pf [pLDH], BIOCREDIT Pf [pLDH/HRPII], BIOCREDIT Pf/Pv [pLDH/pLDH]), microscopy, and a reference PCR assay.
• RDT performance was analyzed against antigen concentration, and usability was assessed via questionnaire.

Main Results:

• Of 220 participants, 154 (70%) were Pf-positive by PCR. The BIOCREDIT Pf (pLDH/HRPII) test showed the highest sensitivity (78%) and specificity (89%).
• All tested RDTs outperformed microscopy (53% sensitivity). The HRP2 line on the BIOCREDIT Pf (pLDH/HRPII) test improved sensitivity compared to the SD BIOLINE HRP2 test, while PfLDH lines alone had lower sensitivity.
• RDT performance correlated with antigen concentration, and analytical limits of detection predicted observed sensitivity.

Conclusions:

• The best-performing Plasmodium falciparum RDT utilized both HRP2 and LDH for sensitivity.
• In areas with low rates of hrp2/hrp3 deletions, PfLDH lines alone did not fully compensate for HRP2 line performance, even with improved limits of detection.
• Analytical limits of detection of RDTs can effectively predict test performance in populations with known antigen concentrations.