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      Submicroscopic and Asymptomatic Plasmodium Parasitaemia Associated with Significant Risk of Anaemia in Papua, Indonesia

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          Abstract

          Submicroscopic Plasmodium infections are an important parasite reservoir, but their clinical relevance is poorly defined. A cross-sectional household survey was conducted in southern Papua, Indonesia, using cluster random sampling. Data were recorded using a standardized questionnaire. Blood samples were collected for haemoglobin measurement. Plasmodium parasitaemia was determined by blood film microscopy and PCR. Between April and July 2013, 800 households and 2,830 individuals were surveyed. Peripheral parasitaemia was detected in 37.7% (968/2,567) of individuals, 36.8% (357) of whom were identified by blood film examination. Overall the prevalence of P. falciparum parasitaemia was 15.4% (396/2567) and that of P. vivax 18.3% (471/2567). In parasitaemic individuals, submicroscopic infection was significantly more likely in adults (adjusted odds ratio (AOR): 3.82 [95%CI: 2.49–5.86], p<0.001) compared to children, females (AOR = 1.41 [1.07–1.86], p = 0.013), individuals not sleeping under a bednet (AOR = 1.4 [1.0–1.8], p = 0.035), and being afebrile (AOR = 3.2 [1.49–6.93], p = 0.003). The risk of anaemia (according to WHO guidelines) was 32.8% and significantly increased in those with asymptomatic parasitaemia (AOR 2.9 [95% 2.1–4.0], p = 0.007), and submicroscopic P. falciparum infections (AOR 2.5 [95% 1.7–3.6], p = 0.002). Asymptomatic and submicroscopic infections in this area co-endemic for P. falciparum and P. vivax constitute two thirds of detectable parasitaemia and are associated with a high risk of anaemia. Novel public health strategies are needed to detect and eliminate these parasite reservoirs, for the benefit both of the patient and the community.

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          Most cited references28

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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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            The changing epidemiology of malaria elimination: new strategies for new challenges.

            Malaria-eliminating countries achieved remarkable success in reducing their malaria burdens between 2000 and 2010. As a result, the epidemiology of malaria in these settings has become more complex. Malaria is increasingly imported, caused by Plasmodium vivax in settings outside sub-Saharan Africa, and clustered in small geographical areas or clustered demographically into subpopulations, which are often predominantly adult men, with shared social, behavioural, and geographical risk characteristics. The shift in the populations most at risk of malaria raises important questions for malaria-eliminating countries, since traditional control interventions are likely to be less effective. Approaches to elimination need to be aligned with these changes through the development and adoption of novel strategies and methods. Knowledge of the changing epidemiological trends of malaria in the eliminating countries will ensure improved targeting of interventions to continue to shrink the malaria map. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              A genus- and species-specific nested polymerase chain reaction malaria detection assay for epidemiologic studies.

              A nested polymerase chain reaction (PCR) assay that uses Plasmodium genus-specific primers for the initial PCR (nest 1) amplification and either genus- or species-specific primers for the nest 2 amplifications was tested on laboratory and field samples. With in vitro cultured Plasmodium falciparum-infected blood samples, it was capable of detecting six parasites/microl of blood using DNA prepared from 25-microl blood spots on filter paper. The assay was evaluated on fingerprick blood samples collected on filter paper from 129 individuals living in a malaria-endemic area in Malaysia. Malaria prevalence by genus-specific nested PCR was 35.6% (46 of 129) compared with 28.7% (37 of 129) by microscopy. The nested PCR detected seven more malaria samples than microscopy in the first round of microscopic examination, malaria in three microscopically negative samples, six double infections identified as single infections by microscopy and one triple infection identified as a double infection by microscopy. The nested PCR assay described is a sensitive technique for collecting accurate malaria epidemiologic data. When coupled with simple blood spot sampling, it is particularly useful for screening communities in remote regions of the world.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                27 October 2016
                2016
                : 11
                : 10
                : e0165340
                Affiliations
                [1 ]Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia
                [2 ]Mimika District Health Authority, Timika, Papua, Indonesia
                [3 ]Timika Malaria Research Programme, Papuan Health and Community Development Foundation, Timika, Papua, Indonesia
                [4 ]Maternal and Child Health and Reproductive Health, Department of Public Health, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
                [5 ]Eijkman Institute for Molecular Biology, Jakarta, Indonesia
                [6 ]Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
                [7 ]Division of Medicine, Christchurch Hospital, Christchurch, New Zealand
                [8 ]Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
                Ehime Daigaku, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: RNP JRP JM RN SA.

                • Formal analysis: ZP RNP NMD JS JM SA.

                • Investigation: ZP IH RAU YKT AK SK GW.

                • Writing – original draft: ZP RNP JM SA.

                • Writing – review & editing: ZP FHB IH LT RAU YKT EK DL AK GW SK JAS SA NMD RN NMA JRP JM RNP.

                Author information
                http://orcid.org/0000-0003-2000-2874
                Article
                PONE-D-16-29787
                10.1371/journal.pone.0165340
                5082812
                27788243
                d156d38c-6e19-42f7-9cc7-b612d5d8650f
                © 2016 Pava et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 July 2016
                : 10 October 2016
                Page count
                Figures: 4, Tables: 4, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 091625
                Award Recipient :
                Funded by: COLCIENCIAS
                Award ID: 512-2010
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1037304
                Award Recipient :
                The study was supported by the Wellcome Trust (Senior Fellowship in Clinical Science awarded to RNP - 091625) and Fellowships to: JRP (Wellcome Trust - 099875), JM (The Swiss National Science Foundation - - PA00P3-139723/1), ZP (Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología Francisco José de Caldas, Colciencias - 512-2010) and NMA (National Health and Medical Research Council (NHMRC) of Australia – 1042072). The Timika Research Facility and Papuan Health and Community Development Foundation were supported by DFAT (Australian Department of Foreign Affairs and Trade) and the NHMRC (Program Grant 1037304).
                Categories
                Research Article
                Biology and Life Sciences
                Parasitology
                Parasite Groups
                Apicomplexa
                Plasmodium
                Medicine and Health Sciences
                Parasitic Diseases
                Biology and Life Sciences
                Organisms
                Protozoans
                Parasitic Protozoans
                Malarial Parasites
                Medicine and Health Sciences
                Hematology
                Anemia
                Medicine and Health Sciences
                Parasitic Diseases
                Malaria
                Medicine and Health Sciences
                Tropical Diseases
                Malaria
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Fevers
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Fevers
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Pregnancy
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Pregnancy
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Custom metadata
                All relevant data are within the paper and its Supporting Information files. The data used in this paper were collected from a household survey, with IP owned by the coauthors of this paper affiliated to the Papuan Health and Community Development Foundation and Menzies School of Health Research. Further details can be obtained from the corresponding author at rprice@ 123456menzies.edu.au . The authors confirm that the data included within the paper and its Supporting Information files constitute the minimal dataset necessary to replicate the study's findings.

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