Use of Capillary Blood Samples Leads to Higher Parasitemia Estimates and Higher Diagnostic Sensitivity of Microscopic and Molecular Diagnostics of Malaria Than Venous Blood Samples

[[[ Background: ]]] Diagnosis of malaria is usually based on samples of peripheral blood. However, it is unclear whether capillary (CAP) or venous (VEN) blood samples provide better diagnostic performance. Quantitative differences of parasitemia between CAP and VEN blood and diagnostic performance characteristics were investigated. [[[ Methods: ]]] Patients were recruited between September 2015 and February 2016 in Gabon. Light microscopy and quantitative polymerase chain reaction (qPCR) measured parasitemia of paired CAP and VEN samples. CAP and VEN performance characteristics using microscopy were evaluated against a qPCR gold standard. [[[ Results: ]]] Microscopy revealed a median parasitemia of 495/μL in CAP and 429/μL in VEN samples, manifesting in a 16.6% (P = .04) higher CAP parasitemia compared with VEN parasitemia. Concordantly, in qPCR -0.278 (P = .006) cycles were required for signal detection in CAP samples. CAP sensitivity of microscopy relative to the gold standard was 81.5% vs VEN sensitivity of 73.4%, while specificities were 91%. CAP and VEN sensitivities dropped to 63.3% and 45.9%, respectively, for a subpopulation of low-level parasitemias, whereas specificities were 92%. [[[ Conclusions: ]]] CAP sampling leads to higher parasitemias compared to VEN sampling and improves diagnostic sensitivity. These findings may have important implications for routine diagnostics, research, and elimination campaigns of malaria.