Malaria Rapid Diagnostic Tests: One Size May Not Fit All

Anthony Moody (5) provides a comprehensive and balanced review of the expanding range of malaria rapid diagnostic tests (RDTs). However, in discussing the utility and disadvantages of RDTs, Moody and others (8) do not clearly distinguish between the different contexts in which they may be used, leaving the impression that a “one size fits all” test is needed. Some of the claimed limitations of present RDTs are not necessarily a disadvantage when compared to current microscopy-based diagnosis.

In common with most studies of RDTs, Moody emphasizes the place of microscopy as a “gold standard,” albeit noting that this standard is flawed and can be expected to detect only ≥100 parasites/μl in nonspecialized laboratories. Sensitivity is further reduced when slide staining is delayed (4). Even expert microscopy is incapable of detecting many parasitemic individuals in areas of endemicity where chronic Plasmodium falciparum infections with low, fluctuating parasite density and transient, mild symptoms are expected (3, 6). As Moody suggests, detection and treatment of such cases may not be of great clinical significance, but these cases will commonly be gametocytemic (3) and therefore perpetuate transmission. Detection of persisting antigens such as histidine-rich protein II (HRPII) may therefore offer an advantage, as transient peaks in parasite density likely to be missed by microscopy will leave a trail of circulating antigens, widening the temporal window over which peaks in parasite density can be detected by RDTs. This would explain the high frequencies of “false positive” HRPII detection recorded in remote areas (2, 7), where gold standard microscopy based on a single blood sample cannot be expected to be accurate. Moody rightly states that “a negative RDT cannot at present be accepted at face value and will need to be confirmed by microscopic examination,” but this statement could as easily be reversed.

Persistence of circulating antigen is also considered a disadvantage by Moody and others (8), as it precludes short-term treatment monitoring. This is of limited relevance to many areas of endemicity, as available resources and remoteness do not allow microscopy-based treatment monitoring at present. This limitation of RDTs would be of practical significance in such areas only if a dramatic reduction in price allows multiple tests per patient. Where clinical resistance is suspected, microscopy could still be used.

Due to difficulties in providing skilled, readily available microscopy, there is no real alternative to RDTs at present in many areas of endemicity if a blood-based diagnosis is to be made; symptom-based diagnosis must miss many infectious cases if gross overtreatment is to be avoided (1, 2). It is important to ensure that further development and deployment of RDTs is not driven solely by the needs of resource-rich customers such as the military and travel markets, aiming primarily at early detection of severe acute malaria, while neglecting the immediate need for a more accurate method of detecting and interrupting transmission in resource-poor areas. Perhaps we should be looking more closely at what needs to be achieved with RDTs and consider a range of formats tailored for specific situations.