Reducing malaria misdiagnosis: the importance of correctly interpreting ParaCheck Pf® "faint test bands" in a low transmission area of Tanzania

Background: Although malaria rapid diagnostic tests (RDTs) have been extensively evaluated since their introduction in the early 1990's, sensitivity and specificity vary widely limiting successful integration into clinical practice. This paper reviews specific issues surrounding RDT use in field settings and presents results of research investigating how to interpret "faint test bands" on ParaCheck Pf (R) in areas of low transmission in order to reduce malaria misdiagnosis. Methods: A multi-phase cross-sectional study was conducted at a remote hospital in the northern Tanzanian highlands. Capillary blood samples were taken from consenting participants (n = 319) for blood smear and ParaCheck Pf (R) testing. Primary outcome variables were sensitivity, specificity and proportion misdiagnosed by ParaCheck Pf (R) and local microscopy. ParaCheck Pf (R) "faint bands" were classified as both true positives or true negatives during evaluation to determine appropriate clinical interpretation. Multivariate logistic regression adjusted for age and gender was conducted to determine odds of misdiagnosis for local microscopy and ParaCheck Pf (R). Results: Overall, 23.71% of all ParaCheck Pf (R) tests resulted in a "faint band" and 94.20% corresponded with true negatives. When ParaCheck Pf (R) "faint bands" were classified as positive, specificity was 75.5% (95% CI = 70.3% 80.6%) as compared to 98.9% (95% CI = 97.0% - 99.8%) when classified as negative. The odds of misdiagnosis by local microscopy for those > 5 years as compared to those <= 5 years are 0.370 (95% CI = 0.1733 - 0.7915, p = 0.010). In contrast, even when ParaCheck Pf (R) faint bands are considered positive, the odds of misdiagnosis by ParaCheck Pf (R) for those > 5 years as compared to those <= 5 years are 0.837 (95% CI = 0.459 - 1.547, p = 0.5383). Conclusions: We provide compelling evidence that in areas of low transmission, "faint bands" should be considered a negative test when used to inform clinical decision-making. Correct interpretation of RDT test bands in a clinical setting plays a central role in successful malaria surveillance, appropriate patient management and most importantly reducing misdiagnosis.