How long do rapid diagnostic tests remain positive after anti-malarial treatment?

Abstract

BackgroundRapid diagnostic tests (RDTs) are increasingly becoming a paradigm for both clinical diagnosis of malaria infections and for estimating community parasite prevalence in household malaria indicator surveys in malaria-endemic countries. The antigens detected by RDTs are known to persist in the blood after treatment with anti-malarials, but reports on the duration of persistence (and the effect this has on RDT positivity) of these antigens post-treatment have been variable.MethodsIn this review, published studies on the persistence of positivity of RDTs post-treatment are collated, and a bespoke Bayesian survival model is fit to estimate the number of days RDTs remain positive after treatment.ResultsHalf of RDTs that detect the antigen histidine-rich protein II (HRP2) are still positive 15 (5–32) days post-treatment, 13 days longer than RDTs that detect the antigen Plasmodium lactate dehydrogenase, and that 5% of HRP2 RDTs are still positive 36 (21–61) days after treatment. The duration of persistent positivity for combination RDTs that detect both antigens falls between that for HRP2- or pLDH-only RDTs, with half of RDTs remaining positive at 7 (2–20) days post-treatment. This study shows that children display persistent RDT positivity for longer after treatment than adults, and that persistent positivity is more common when an individual is treated with artemisinin combination therapy than when treated with other anti-malarials.ConclusionsRDTs remain positive for a highly variable amount of time after treatment with anti-malarials, and the duration of positivity is highly dependent on the type of RDT used for diagnosis. Additionally, age and treatment both impact the duration of persistence of RDT positivity. The results presented here suggest that caution should be taken when using RDT-derived diagnostic outcomes from cross-sectional data where individuals have had a recent history of anti-malarial treatment.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2371-9) contains supplementary material, which is available to authorized users.

Octopi: Open configurable high-throughput imaging platform for infectious disease diagnosis in the field

“…In the same year, 276 million RDTs were sold and more than 208 million patients were tested by microscopy, whereas estimated needs for testing was well over 1 billion [22]. While RDT is easy to use, it cannot quantify parasitemia, stays positive post treatment for up to a month [23] and can create false negative due to HRP2/3 gene deletions [24, 25]. Manual microscopy, on the other hand, is labor intensive and in practice the performance is often compromised.…”

Operational Coverage and Timeliness of Reactive Case Detection for Malaria Elimination in Zanzibar, Tanzania

“…In other scenarios, albeit imperfect, conducting an histidine-rich protein 2-based test several days after treatment would still allow the retrospective confirmation of a significant proportion of cases. 18 Many private HFs were first included in the MCN system in 2016; thus, performance of the system may improve over time in these facilities as they gain more experience using it for reporting. Such performance improvements have been noted over time in other malaria rapid electronic reporting systems in Africa.…”

A Case of False-negative Malaria Rapid Diagnostic Test Induced by Treatment with Doxycycline

“…Most RDTs detect parasite histidine-rich protein 2 (pHRP-2) and pLDH from Plasmodium falciparum and Plasmodium spp., respectively. While the pHRP-2 antigen can be detected up to 40 days post-antibiotics treatment [4], the pLDH antigen has very short half-life of less than 2 days, and the median time on treatment for this test to become negative was reported as just 2 days [5]. Even though RDTs show good correlation with PBS results and can be used for evaluation of the treatment response and follow-up, low blood levels of pLDH can lead to false-negative results [1,6].…”