Plasmodium falciparum malaria detected by HRP-2 antigenemia before microscopic- and PCR-positive conversion

We describe a case of relapsed Plasmodium falciparum malaria detected by rapid diagnostic testing (RDT) 19 days before microscopic- or PCR-positive conversion. Three malaria tests gave discrepant results; the malaria smear and polymerase chain reaction (PCR) tests were both negative, while malaria RDT with a commercial kit to detect malarial antigens, including histidine-rich protein 2 (HRP-2), was repeatedly positive for P. falciparum. About 3 weeks after the onset of symptoms, the patient was hospitalized because of a high fever. Blood and urine cultures and malaria smears were all negative, and a subsequent bone marrow study was performed to evaluate fever of unknown origin. Unexpectedly, 19 days after the positive RDT result, malaria parasites were detected by microscopy in the bone marrow and peripheral blood. The malaria PCR result also became positive for P. falciparum on the same day. This case report shows that a positive RDT result discordant with microscopy and PCR should not be viewed as a failure of RDT, but must be evaluated carefully to rule out infection at a low parasite density. In such unusual cases, frequent follow-up tests with multiple methods are recommended for an accurate diagnosis. The RDT may achieve earlier detection than methods targeting parasitemia in some patients with malaria.