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      Active Case Finding for Malaria: A 3-Year National Evaluation of Optimal Approaches to Detect Infections and Hotspots Through Reactive Case Detection in the Low-transmission Setting of Eswatini

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          Abstract

          Background

          Reactive case detection (RACD) is a widely practiced malaria elimination intervention whereby close contacts of index cases receive malaria testing to inform treatment and other interventions. However, the optimal diagnostic and operational approaches for this resource-intensive strategy are not clear.

          Methods

          We conducted a 3-year prospective national evaluation of RACD in Eswatini, a malaria elimination setting. Loop-mediated isothermal amplification (LAMP) was compared to traditional rapid diagnostic testing (RDT) for the improved detection of infections and for hotspots (RACD events yielding ≥1 additional infection). The potential for index case–, RACD-, and individual-level factors to improve efficiencies was also evaluated.

          Results

          Among 377 RACD events, 10 890 participants residing within 500 m of index cases were tested. Compared to RDT, LAMP provided a 3-fold and 2.3-fold higher yield to detect infections (1.7% vs 0.6%) and hotspots (29.7% vs 12.7%), respectively. Hotspot detection improved with ≥80% target population coverage and response times within 7 days. Proximity to the index case was associated with a dose-dependent increased infection risk (up to 4-fold). Individual-, index case–, and other RACD-level factors were considered but the simple approach of restricting RACD to a 200-m radius maximized yield and efficiency.

          Conclusions

          We present the first large-scale national evaluation of optimal RACD approaches from a malaria elimination setting. To inform delivery of antimalarial drugs or other interventions, RACD, when conducted, should utilize more sensitive diagnostics and clear context-specific operational parameters. Future studies of RACD’s impact on transmission may still be needed.

          Abstract

          Optimal approaches to find malaria infections and hotspots in reactive case detection are not clear. Here, molecular testing compared to standard rapid diagnostic testing and operational factors (≥80% coverage, response ≤7 days, and 200-m screening radius) maximized efficiency and yield.

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          Most cited references35

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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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            Operational strategies to achieve and maintain malaria elimination

            Summary Present elimination strategies are based on recommendations derived during the Global Malaria Eradication Program of the 1960s. However, many countries considering elimination nowadays have high intrinsic transmission potential and, without the support of a regional campaign, have to deal with the constant threat of imported cases of the disease, emphasising the need to revisit the strategies on which contemporary elimination programmes are based. To eliminate malaria, programmes need to concentrate on identification and elimination of foci of infections through both passive and active methods of case detection. This approach needs appropriate treatment of both clinical cases and asymptomatic infections, combined with targeted vector control. Draining of infectious pools entirely will not be sufficient since they could be replenished by imported malaria. Elimination will thus additionally need identification and treatment of incoming infections before they lead to transmission, or, more realistically, embarking on regional initiatives to dry up importation at its source.
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              Identification of hot spots of malaria transmission for targeted malaria control.

              Variation in the risk of malaria within populations is a frequently described but poorly understood phenomenon. This heterogeneity creates opportunities for targeted interventions but only if hot spots of malaria transmission can be easily identified. We determined spatial patterns in malaria transmission in a district in northeastern Tanzania, using malaria incidence data from a cohort study involving infants and household-level mosquito sampling data. The parasite prevalence rates and age-specific seroconversion rates (SCRs) of antibodies against Plasmodium falciparum antigens were determined in samples obtained from people attending health care facilities. Five clusters of higher malaria incidence were detected and interpreted as hot spots of transmission. These hot spots partially overlapped with clusters of higher mosquito exposure but could not be satisfactorily predicted by a probability model based on environmental factors. Small-scale local variation in malaria exposure was detected by parasite prevalence rates and SCR estimates for samples of health care facility attendees. SCR estimates were strongly associated with local malaria incidence rates and predicted hot spots of malaria transmission with 95% sensitivity and 85% specificity. Serological markers were able to detect spatial variation in malaria transmission at the microepidemiological level, and they have the potential to form an effective method for spatial targeting of malaria control efforts.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press (US )
                1058-4838
                1537-6591
                01 April 2020
                16 May 2019
                16 May 2019
                : 70
                : 7
                : 1316-1325
                Affiliations
                [1 ] Department of Pediatrics, University of Texas Southwestern Medical Center , Dallas
                [2 ] Malaria Elimination Initiative, Global Health Group
                [3 ] Department of Pediatrics, University of California , San Francisco (UCSF)
                [4 ] Clinton Health Access Initiative, Eswatini Office , Mbabane
                [5 ] Division of Prevention Science, Department of Medicine , UCSF
                [6 ] Eswatini National Malaria Programme , Manzini
                [7 ] Eswatini National Reference Laboratory , Mbabane
                [8 ] Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine , UCSF
                Author notes
                Correspondence: M. S. Hsiang, University of Texas Southwestern Medical Center, Department of Pediatrics, 5323 Harry Hines Blvd, Dallas, TX 75390 ( michelle.hsiang@ 123456UTSouthwestern.edu ).
                Article
                ciz403
                10.1093/cid/ciz403
                7318780
                31095677
                39d1122d-721a-441d-88db-c1f356771eef
                © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

                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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 January 2019
                : 15 May 2019
                : 25 July 2019
                Page count
                Pages: 10
                Funding
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Award ID: K23AI101012
                Funded by: National Institute of Allergy and Infectious Diseases, DOI 10.13039/100000060;
                Funded by: Burroughs Wellcome Fund, DOI 10.13039/100000861;
                Award ID: A120079
                Funded by: American Society of Tropical Medicine and Hygiene, DOI 10.13039/100001949;
                Funded by: Eswatini Ministry of Health;
                Funded by: Bill & Melinda Gates Foundation, DOI 10.13039/100000865;
                Award ID: A121292
                Funded by: Horchow Family Fund Scholarship;
                Award ID: 5300375400
                Funded by: Clinton Health Access Initiative;
                Funded by: Eswatini National Malaria Program;
                Funded by: Horchow Family Fund Scholarship Award;
                Award ID: 5300375400
                Categories
                Articles and Commentaries
                AcademicSubjects/MED00290

                Infectious disease & Microbiology
                malaria elimination,reactive case detection,loop-mediated isothermal amplification,eswatini,efficiency

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