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      Loop-mediated isothermal amplification (LAMP) for point-of-care detection of asymptomatic low-density malaria parasite carriers in Zanzibar

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          Abstract

          Background

          Asymptomatic, low parasite density malaria infections are difficult to detect with currently available point-of-care diagnostics. This study piloted a loop-mediated isothermal amplification (LAMP) kit for field-friendly, high-throughput detection of asymptomatic malaria infections during mass screening and treatment (MSAT) in Zanzibar, a malaria pre-elimination setting.

          Methods

          Screening took place in three known hotspot areas prior to the short rains in November. Finger-prick blood was taken for screening by rapid diagnostic test (RDT) and LAMP and collected on filter paper for subsequent polymerase chain reaction (PCR) analyses. LAMP results were compared to RDT and to PCR using McNemar’s test.

          Results

          Approximately 1,000 people were screened. RDT detected ten infections (1.0% (95% CI 0.3-1.6)) whilst both LAMP and PCR detected 18 (1.8% (95% CI 0.9-2.6)) infections. However, PCR identified three infections that LAMP did not detect and vice versa. LAMP testing was easy to scale-up in field conditions requiring minimal training and equipment, with results ready one to three hours after screening.

          Conclusions

          Despite lower than expected prevalence, LAMP detected a higher number of infections than the currently used diagnostic, RDT. LAMP is a field-friendly, sensitive diagnostic test that could be useful for MSAT malaria campaigns which require quick results to enable prompt treatment.

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          Most cited references12

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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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            Plasmodium falciparum gametocyte carriage in asymptomatic children in western Kenya

            Background Studies on Plasmodium falciparum gametocyte development and dynamics have almost exclusively focused on patients treated with antimalarial drugs, while the majority of parasite carriers in endemic areas are asymptomatic. This study identified factors that influence gametocytaemia in asymptomatic children in the absence and presence of pyrimethamine-sulphadoxine (SP) antimalarial treatment. Methods A cohort of 526 children (6 months – 16 years) from western Kenya was screened for asexual parasites and gametocytes and followed weekly up to four weeks. Children with an estimated parasitaemia of ≥1,000 parasites/μl were treated with SP according to national guidelines. Factors associated with gametocyte development and persistence were determined in untreated and SP-treated children with P. falciparum mono-infection. Results Gametocyte prevalence at enrolment was 33.8% in children below five years of age and decreased with age. In the absence of treatment 18.6% of the children developed gametocytaemia during follow-up; in SP-treated children this proportion was 29.8%. Age, high asexual parasite density and gametocyte presence at enrolment were predictive factors for gametocytaemia. The estimated mean duration of gametocytaemia for children below five, children from five to nine and children ten years and above was 9.4, 7.8 and 4.1 days, respectively. Conclusion This study shows that a large proportion of asymptomatic untreated children develop gametocytaemia. Gametocytaemia was particularly common in children below five years who harbor gametocytes for a longer period of time. The age-dependent duration of gametocytaemia has not been previously shown and could increase the importance of this age group for the infectious reservoir.
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              PCR and strain identification in Plasmodium falciparum.

              Anyone who has cultured Plasmodium falciparum is aware that confusion about the identity of commonly used strains, and inadvertent contamination of one strain with another have been persistent problems. These issues have been recently reviewed by Robson and colleagues. Jason Wooden, Susan Kyes and Carol Hopkins Sibley have recently adapted two methods that offer a quick, easy alternative for the identification of P. falciparum strains in the laboratory.
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                Author and article information

                Contributors
                Jackie.Cook@lshtm.ac.uk
                berit.schmidt@ki.se
                Iveth.Gonzalez@finddiagnostics.org
                dbell@intven.com
                elin.edlund.2@stud.ki.se
                maida.nassor@gmail.com
                mmwinyi@hotmail.com
                busudi@gmail.com
                Jackie.Cook@lshtm.ac.uk
                Andreas.Martensson@ki.se
                Anders.Bjorkman@ki.se
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                28 January 2015
                28 January 2015
                2015
                : 14
                : 43
                Affiliations
                [ ]Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden
                [ ]Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK
                [ ]Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland
                [ ]Global Good /Intellectual Ventures Laboratory, Bellevue, WA USA
                [ ]Zanzibar Malaria Elimination Programme, Ministry of Health, Zanzibar, Tanzania
                [ ]Global Health (IHCAR), Department of Public Health Sciences, Karolinska Institutet, SE-171 77 Stockholm, Sweden
                [ ]Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden
                Article
                573
                10.1186/s12936-015-0573-y
                4318361
                25627037
                5fd59b80-afa1-48be-86da-347f7bc5098b
                © Cook et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
                : 1 September 2014
                : 18 January 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Infectious disease & Microbiology
                lamp,low-density,malaria,zanzibar,elimination,asymptomatic,diagnostics
                Infectious disease & Microbiology
                lamp, low-density, malaria, zanzibar, elimination, asymptomatic, diagnostics

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