A rapid diagnostic test (RDT) for malaria detects Plasmodium falciparum HRP-2 antigen. A patient from an area with high P. falciparum transmission has a negative microscopy but positive HRP-2 RDT. What is the most likely explanation?

• A HRP-2 antigen persists in blood for weeks after parasite clearance ✓
• B The RDT has low specificity and is a false positive
• C The patient has P. vivax co-infection
• D P. falciparum only produces HRP-2 at the trophozoite stage, which has cleared

Explanation

HRP-2 (histidine-rich protein 2) is a soluble antigen released by P. falciparum that can persist in blood for 3–4 weeks after complete parasite clearance, yielding a positive RDT with negative microscopy — a clinically important source of false positives (in the context of treatment response). This antigen-persistence phenomenon must be remembered when interpreting RDTs post-treatment. Some P. falciparum strains in Sub-Saharan Africa now have HRP-2 gene deletions causing false-negative RDTs.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

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