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

      research-article
      1 , 2 , , 2 , 2 , 2
      Malaria Journal
      BioMed Central
      Malaria, Fever, RDT

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          Abstract

          Background

          Rapid 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.

          Methods

          In 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.

          Results

          Half 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.

          Conclusions

          RDTs 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 material

          The online version of this article (10.1186/s12936-018-2371-9) contains supplementary material, which is available to authorized users.

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          Most cited references47

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          A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT).

          The absolute necessity for rational therapy in the face of rampant drug resistance places increasing importance on the accuracy of malaria diagnosis. Giemsa microscopy and rapid diagnostic tests (RDTs) represent the two diagnostics most likely to have the largest impact on malaria control today. These two methods, each with characteristic strengths and limitations, together represent the best hope for accurate diagnosis as a key component of successful malaria control. This review addresses the quality issues with current malaria diagnostics and presents data from recent rapid diagnostic test trials. Reduction of malaria morbidity and drug resistance intensity plus the associated economic loss of these two factors require urgent scaling up of the quality of parasite-based diagnostic methods. An investment in anti-malarial drug development or malaria vaccine development should be accompanied by a parallel commitment to improve diagnostic tools and their availability to people living in malarious areas.
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            Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies.

            The global burden of malaria has been substantially reduced over the past two decades. Future efforts to reduce malaria further will require moving beyond the treatment of clinical infections to targeting malaria transmission more broadly in the community. As such, the accurate identification of asymptomatic human infections, which can sustain a large proportion of transmission, is becoming a vital component of control and elimination programmes. We determined the relationship across common diagnostics used to measure malaria prevalence - polymerase chain reaction (PCR), rapid diagnostic test and microscopy - for the detection of Plasmodium falciparum infections in endemic populations based on a pooled analysis of cross-sectional data. We included data from more than 170,000 individuals comparing the detection by rapid diagnostic test and microscopy, and 30,000 for detection by rapid diagnostic test and PCR. The analysis showed that, on average, rapid diagnostic tests detected 41% (95% confidence interval = 26-66%) of PCR-positive infections. Data for the comparison of rapid diagnostic test to PCR detection at high transmission intensity and in adults were sparse. Prevalence measured by rapid diagnostic test and microscopy was comparable, although rapid diagnostic test detected slightly more infections than microscopy. On average, microscopy captured 87% (95% confidence interval = 74-102%) of rapid diagnostic test-positive infections. The extent to which higher rapid diagnostic test detection reflects increased sensitivity, lack of specificity or both, is unclear. Once the contribution of asymptomatic individuals to the infectious reservoir is better defined, future analyses should ideally establish optimal detection limits of new diagnostics for use in control and elimination strategies.
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              Ensuring quality and access for malaria diagnosis: how can it be achieved?

              The replacement of conventional antimalarial drugs with high-cost, artemisinin-based alternatives has created a gap in the successful management of malaria. This gap reflects an increased need for accurate disease diagnosis that cannot be met by traditional microscopy techniques. The recent introduction of rapid diagnostic tests (RDTs) has the potential to meet this need, but successful RDT implementation has been curtailed by poor product performance, inadequate methods to determine the quality of products and a lack of emphasis and capacity to deal with these issues. Economics and a desire for improved case management will result in the rapid growth of RDT use in the coming years. However, for their potential to be realized, it is crucial that high-quality RDT products that perform reliably and accurately under field conditions are made available. In achieving this goal, the shift from symptom-based diagnosis to parasite-based management of malaria can bring significant improvements to tropical fever management, rather than represent a further burden on poor, malaria-endemic populations and their overstretched health services.
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                Author and article information

                Contributors
                ursula.dalrymple@zoo.ox.ac.uk
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                8 June 2018
                8 June 2018
                2018
                : 17
                : 228
                Affiliations
                [1 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Department of Zoology, , University of Oxford, ; New Radcliffe House, Radcliffe Observatory Quarter, Woodstock Rd, Oxford, OX2 6GG UK
                [2 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Big Data Institute, University of Oxford, Li Ka Shing Centre for Health Information and Discovery, ; Old Road Campus, Oxford, OX3 7LF UK
                Article
                2371
                10.1186/s12936-018-2371-9
                5994115
                29884184
                dd6d9085-f164-49e0-9970-d63156494116
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 16 April 2018
                : 28 May 2018
                Funding
                Funded by: FundRef http://data.crossref.org/fundingdata/funder/10.13039/100000865, Bill & Melinda Gates Foundation;
                Award ID: OPP1068048
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Infectious disease & Microbiology
                malaria,fever,rdt
                Infectious disease & Microbiology
                malaria, fever, rdt

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