Diagnostic Performance of Conventional and Ultrasensitive Rapid Diagnostic Tests for Malaria in Febrile Outpatients in Tanzania

Abstract Background A novel ultrasensitive malaria rapid diagnostic test (us-RDT) has been developed for improved active Plasmodium falciparum infection detection. The usefulness of this us-RDT in clinical diagnosis and fever management has not been evaluated. Methods Diagnostic performance of us-RDT was compared retrospectively to that of conventional RDT (co-RDT) in 3000 children and 515 adults presenting with fever to Tanzanian outpatient clinics. The parasite density was measured by an ultrasensitive qPCR (us-qPCR), and the HRP2 concentration was measured by an enzyme-linked immunosorbent assay. Results us-RDT identified few additional P. falciparum–positive patients as compared to co-RDT (276 vs 265 parasite-positive patients detected), with only a marginally greater sensitivity (75% vs 73%), using us-qPCR as the gold standard (357 parasite-positive patients detected). The specificity of both RDTs was >99%. Five of 11 additional patients testing positive by us-RDT had negative results by us-qPCR. The HRP2 concentration was above the limit of detection for co-RDT (>3653 pg of HRP2 per mL of blood) in almost all infections (99% [236 of 239]) with a parasite density >100 parasites per µL of blood. At parasite densities 793 pg/mL) and co-RDT in 29 (25%) and 24 (20%) of 118 patients, respectively. Conclusion There is neither an advantage nor a risk of using us-RDT, rather than co-RDT, for clinical malaria diagnosis. In febrile patients, only a small proportion of infections are characterized by a parasite density or an HRP2 concentration in the range where use of us-RDT would confer a meaningful advantage over co-RDT. Ultrasensitive rapid diagnostic tests (RDTs) for malaria, designed for Plasmodium falciparum elimination campaigns, may be used off label in clinical practice. The diagnostic performances of ultrasensitive and conventional RDTs were similar in febrile Tanzanian outpatients, which is explained by the underlying HRP2 concentration and parasite density distributions.