HRP2-deleted P. falciparum parasites cause false-negative RDTs

Plasmodium falciparum parasites with deletions in the hrp2 and hrp3 genes produce no HRP2 antigen, causing HRP2-based rapid diagnostic tests (RDTs) to return false negatives. This matters because RDTs are the backbone of malaria diagnosis in sub-Saharan Africa, where microscopy is unavailable or unreliable at most peripheral health facilities. When an RDT returns a false negative, a clinician sends a malaria-positive patient home without treatment. That patient's uncomplicated malaria can progress to severe malaria (cerebral malaria, severe anemia, organ failure) within 24-48 hours, especially in children under 5. Meanwhile, the patient becomes an undetected reservoir, sustaining transmission in the community. The problem persists because HRP2 deletion confers a survival advantage to the parasite under diagnostic pressure: parasites that evade detection avoid treatment, reproduce, and spread. In Eritrea and Peru, HRP2-deleted strains became so prevalent that HRP2-based RDTs had to be abandoned entirely. Surveillance for hrp2/hrp3 deletions requires PCR-based molecular testing, which is expensive and unavailable in the rural clinics where RDTs are most relied upon, creating a blind spot in the very places most at risk.