Abstract
BackgroundAlthough rapid diagnostic tests (RDTs) have practical advantages over light microscopy (LM) and good sensitivity in severe falciparum malaria in Africa, their utility where severe non-falciparum malaria occurs is unknown. LM, RDTs and polymerase chain reaction (PCR)-based methods have limitations, and thus conventional comparative malaria diagnostic studies employ imperfect gold standards. We assessed whether, using Bayesian latent class models (LCMs) which do not require a reference method, RDTs could safely direct initial anti-infective therapy in severe ill children from an area of hyperendemic transmission of both Plasmodium falciparum and P. vivax. Methods and FindingsWe studied 797 Papua New Guinean children hospitalized with well-characterized severe illness for whom LM, RDT and nested PCR (nPCR) results were available. For any severe malaria, the estimated prevalence was 47.5% with RDTs exhibiting similar sensitivity and negative predictive value (NPV) to nPCR (≥96.0%). LM was the least sensitive test (87.4%) and had the lowest NPV (89.7%), but had the highest specificity (99.1%) and positive predictive value (98.9%). For severe falciparum malaria (prevalence 42.9%), the findings were similar. For non-falciparum severe malaria (prevalence 6.9%), no test had the WHO-recommended sensitivity and specificity of >95% and >90%, respectively. RDTs were the least sensitive (69.6%) and had the lowest NPV (96.7%).ConclusionsRDTs appear a valuable point-of-care test that is at least equivalent to LM in diagnosing severe falciparum malaria in this epidemiologic situation. None of the tests had the required sensitivity/specificity for severe non-falciparum malaria but the number of false-negative RDTs in this group was small.
Highlights
The World Health Organization (WHO) advocates treatment of malaria based on universal access to light microscopy of blood smears (LM) and/or antigen-based rapid diagnostic tests (RDTs) [1]
When LM and RDTs have been compared with more sensitive polymerase chain reaction (PCR)-based methods, RDTs often outperform LM for the detection of P. falciparum [6,7] but not P. vivax [8]
Rather than assume that either LM or PCR was the gold standard, we developed a Bayesian latent class models (LCMs) to determine the diagnostic performance of each test in the absence of a gold standard
Summary
The World Health Organization (WHO) advocates treatment of malaria based on universal access to light microscopy of blood smears (LM) and/or antigen-based rapid diagnostic tests (RDTs) [1]. LM has been the conventional reference method but requires trained technicians and good quality smears, and has limited sensitivity for low parasite densities and mixed Plasmodium species [2]. When LM and RDTs have been compared with more sensitive polymerase chain reaction (PCR)-based methods, RDTs often outperform LM for the detection of P. falciparum [6,7] but not P. vivax [8]. In studies of malaria diagnostic modalities, the comparators can only ever be as good as, but never better than, an imperfect gold standard. Rapid diagnostic tests (RDTs) have practical advantages over light microscopy (LM) and good sensitivity in severe falciparum malaria in Africa, their utility where severe non-falciparum malaria occurs is unknown. LM, RDTs and polymerase chain reaction (PCR)-based methods have limitations, and conventional comparative malaria diagnostic studies employ imperfect gold standards. We assessed whether, using Bayesian latent class models (LCMs) which do not require a reference method, RDTs could safely direct initial anti-infective therapy in severe ill children from an area of hyperendemic transmission of both Plasmodium falciparum and P. vivax
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