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      Diagnostic performance of rapid diagnostic test, light microscopy and polymerase chain reaction during mass survey conducted in low and high malaria-endemic areas from two North-Eastern states of India

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          Abstract

          An early and accurate diagnosis followed by prompt treatment is pre-requisite for the management of any disease. Malaria diagnosis is routinely performed by microscopy and rapid diagnostic tests (RDTs) in the field settings; however, their performance may vary across regions, age and asymptomatic status. Owing to this, we assessed the diagnostic performance of conventional and advanced molecular tools for malaria detection in low and high malaria-endemic settings. We performed mass blood surveys in low and high endemic regions of two North-Eastern districts from the states of Assam and Meghalaya. A total of 3322 individuals were screened for malaria using RDT, microscopy and PCR and measures of diagnostic accuracy were estimated. Out of 3322 individuals, 649 (19.5%) were detected with malaria parasite. Asymptomatic were 86.4% (2872/3322), of which 19.4% (557/2872) had Plasmodium infection. The sensitivity and specificity of microscopy were 42.7% and 99.3%, and RDT showed 49.9% and 90.4%, respectively, considering PCR as standard. RDT (AUC: 0.65 vs 0.74; p = 0.001) and microscopy (AUC: 0.64 vs 0.76; p < 0.0001) performances were significantly lower in low compared to high endemic areas. True positive rate was lower in asymptomatics but true negative rate was found similar to symptomatic individuals. The conventional diagnostic tools (RDT and microscopy) had detected malaria in children with nearly twofold greater sensitivity than in the adults ( p < 0.05). To conclude, asymptomatics, adults and low malaria-endemic regions require major attention due to mediocre performance of conventional diagnostic tools in malaria detection.

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          Sensitivity, Specificity, and Predictive Values: Foundations, Pliabilities, and Pitfalls in Research and Practice

          Within the context of screening tests, it is important to avoid misconceptions about sensitivity, specificity, and predictive values. In this article, therefore, foundations are first established concerning these metrics along with the first of several aspects of pliability that should be recognized in relation to those metrics. Clarification is then provided about the definitions of sensitivity, specificity, and predictive values and why researchers and clinicians can misunderstand and misrepresent them. Arguments are made that sensitivity and specificity should usually be applied only in the context of describing a screening test’s attributes relative to a reference standard; that predictive values are more appropriate and informative in actual screening contexts, but that sensitivity and specificity can be used for screening decisions about individual people if they are extremely high; that predictive values need not always be high and might be used to advantage by adjusting the sensitivity and specificity of screening tests; that, in screening contexts, researchers should provide information about all four metrics and how they were derived; and that, where necessary, consumers of health research should have the skills to interpret those metrics effectively for maximum benefit to clients and the healthcare system.
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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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              A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting

              Background Many countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting. Methods During the survey, 9,491 blood samples were collected and examined by microscopy for Plasmodium species and density, with a subset also examined by polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs). The performances of these diagnostic methods were compared. Results A total of 256 samples were positive by microscopy, giving a point prevalence of 2.7%. The species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax. In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P. vivax infected subjects were febrile (≥38°C) at the time of the survey. A significant proportion of infections detected by microscopy, 40% and 65.6% for P. falciparum and P. vivax respectively, had parasite density below 100/μL. There was an age correlation for the proportion of parasite density below 100/μL for P. vivax infections, but not for P. falciparum infections. PCR detected substantially more infections than microscopy (point prevalence of 8.71%), indicating a large number of subjects had sub-microscopic parasitemia. The concordance between PCR and microscopy in detecting single species was greater for P. vivax (135/162) compared to P. falciparum (36/118). The malaria RDT detected the 12 microscopy and PCR positive P. falciparum, but failed to detect 12/13 microscopy and PCR positive P. vivax infections. Conclusion Asymptomatic malaria infections and infections with low and sub-microscopic parasite densities are highly prevalent in Temotu province where malaria transmission is low. This presents a challenge for elimination since the large proportion of the parasite reservoir will not be detected by standard active and passive case detection. Therefore effective mass screening and treatment campaigns will most likely need more sensitive assays such as a field deployable molecular based assay.
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                Author and article information

                Contributors
                neelima1.nimr@gmail.com
                Journal
                Parasitol Res
                Parasitol Res
                Parasitology Research
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0932-0113
                1432-1955
                27 March 2021
                : 1-11
                Affiliations
                [1 ]GRID grid.419641.f, ISNI 0000 0000 9285 6594, Parasite-Host Biology Group, , ICMR-National Institute of Malaria Research, ; Sector-8, Dwarka, New Delhi, 110077 India
                [2 ]ICMR-National Institute of Malaria Research Field Unit, Guwahati, Assam 781022 India
                Author notes

                Section Editor: Nawal Hijjawi

                Author information
                http://orcid.org/0000-0002-1736-368X
                Article
                7125
                10.1007/s00436-021-07125-8
                7997798
                33772349
                425df69f-b7d0-40dd-90db-0aea987cbdc0
                © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 17 December 2020
                : 15 March 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001411, Indian Council of Medical Research;
                Award ID: NER/55/2015/ECD-I
                Award Recipient :
                Categories
                Treatment and Prophylaxis - Original Paper

                Parasitology
                asymptomatic,diagnosis,endemicity,malaria,molecular method
                Parasitology
                asymptomatic, diagnosis, endemicity, malaria, molecular method

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