부산대학교 도서관

Background: In endemic settings, diagnosis of malaria increasingly relies on the use of rapid diagnostic tests (RDTs). False positivity of such RDTs is poorly documented, although it is especially relevant in those infections that resemble malaria, such as human African trypanosomiasis (HAT). We therefore examined specificity of malaria RDT products among patients infected with Trypanosoma brucei gambiense. Methodology/Principal Findings: Blood samples of 117 HAT patients and 117 matched non-HAT controls were prospectively collected in the Democratic Republic of the Congo. Reference malaria diagnosis was based on real-time PCR. Ten commonly used malaria RDT products were assessed including three two-band and seven three-band products, targeting HRP-2, Pf-pLDH and/or pan-pLDH antigens. Rheumatoid factor was determined in PCR negative subjects. Specificity of the 10 malaria RDT products varied between 79.5 and 100% in HAT-negative controls and between 11.3 and 98.8% in HAT patients. For seven RDT products, specificity was significantly lower in HAT patients compared to controls. False positive reactions in HAT were mainly observed for pan-pLDH test lines (specificities between 13.8 and 97.5%), but also occurred frequently for the HRP-2 test line (specificities between 67.9 and 98.8%). The Pf-pLDH test line was not affected by false-positive lines in HAT patients (specificities between 97.5 and 100%). False positivity was not associated to rheumatoid factor, detected in 7.6% of controls and 1.2% of HAT patients. Conclusions/Significance: Specificity of some malaria RDT products in HAT was surprisingly low, and constitutes a risk for misdiagnosis of a fatal but treatable infection. Our results show the importance to assess RDT specificity in non-targeted infections when evaluating diagnostic tests. Author Summary: Rapid diagnostic tests (RDT) for malaria are currently rolled-out as the backbone of parasite-based diagnosis, and their diagnostic accuracy is sufficiently high to substitute microscopy. One decade ago, attention has been given to occurrence of limited false positivity in a number of malaria RDTs, but false positivity of RDTs has remained poorly documented since then. In the last years, the number of available RDT products has dramatically increased and test performance has improved. False positivity may therefore not be perceived as a problem anymore. In this manuscript, we demonstrate that specificities of malaria rapid diagnostic tests detecting parasite antigens are seriously affected by human African trypanosomiasis (sleeping sickness), with values down to 11%. Malaria constitutes the main differential diagnosis of human African trypanosomiasis, and the false-positive results for malaria RDTs increase the risk of misdiagnosis or delayed diagnosis of human African trypanosomiasis which is a fatal but treatable infection. [ABSTRACT FROM AUTHOR]