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      Focused Screening and Treatment (FSAT): A PCR-Based Strategy to Detect Malaria Parasite Carriers and Contain Drug Resistant P. falciparum, Pailin, Cambodia

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          Abstract

          Recent studies have shown that Plasmodium falciparum malaria parasites in Pailin province, along the border between Thailand and Cambodia, have become resistant to artemisinin derivatives. To better define the epidemiology of P. falciparum populations and to assess the risk of the possible spread of these parasites outside Pailin, a new epidemiological tool named “Focused Screening and Treatment” (FSAT), based on active molecular detection of asymptomatic parasite carriers was introduced in 2010. Cross-sectional malariometric surveys using PCR were carried out in 20 out of 109 villages in Pailin province. Individuals detected as P. falciparum carriers were treated with atovaquone-proguanil combination plus a single dose of primaquine if the patient was non-G6PD deficient. Interviews were conducted to elicit history of cross-border travel that might contribute to the spread of artemisinin-resistant parasites. After directly observed treatment, patients were followed up and re-examined on day 7 and day 28. Among 6931 individuals screened, prevalence of P. falciparum carriers was less than 1%, of whom 96% were asymptomatic. Only 1.6% of the individuals had a travel history or plans to go outside Cambodia, with none of those tested being positive for P. falciparum. Retrospective analysis, using 2010 routine surveillance data, showed significant differences in the prevalence of asymptomatic carriers discovered by FSAT between villages classified as “high risk” and “low risk” based on malaria incidence data. All positive individuals treated and followed-up until day 28 were cured. No mutant-type allele related to atovaquone resistance was found. FSAT is a potentially useful tool to detect, treat and track clusters of asymptomatic carriers of P. falciparum along with providing valuable epidemiological information regarding cross-border movements of potential malaria parasite carriers and parasite gene flow.

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          Estimation of average heterozygosity and genetic distance from a small number of individuals.

          M Nei (1978)
          The magnitudes of the systematic biases involved in sample heterozygosity and sample genetic distances are evaluated, and formulae for obtaining unbiased estimates of average heterozygosity and genetic distance are developed. It is also shown that the number of individuals to be used for estimating average heterozygosity can be very small if a large number of loci are studied and the average heterozygosity is low. The number of individuals to be used for estimating genetic distance can also be very small if the genetic distance is large and the average heterozygosity of the two species compared is low.
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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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              Artemisinin resistance: current status and scenarios for containment.

              Artemisinin combination therapies are the first-line treatments for uncomplicated Plasmodium falciparum malaria in most malaria-endemic countries. Recently, partial artemisinin-resistant P. falciparum malaria has emerged on the Cambodia-Thailand border. Exposure of the parasite population to artemisinin monotherapies in subtherapeutic doses for over 30 years, and the availability of substandard artemisinins, have probably been the main driving force in the selection of the resistant phenotype in the region. A multifaceted containment programme has recently been launched, including early diagnosis and appropriate treatment, decreasing drug pressure, optimising vector control, targeting the mobile population, strengthening management and surveillance systems, and operational research. Mathematical modelling can be a useful tool to evaluate possible strategies for containment.
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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, USA )
                1932-6203
                2012
                1 October 2012
                : 7
                : 10
                : e45797
                Affiliations
                [1 ]World Health Organization, Global Malaria Programme, Geneva, Switzerland
                [2 ]National Center for Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia
                [3 ]Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia
                [4 ]World Health Organization, Phnom Penh, Cambodia
                [5 ]World Health Organization, Regional Office for the Western Pacific, Manilla, Philippines
                [6 ]Malaria Consortium, Phnom Penh, Cambodia
                [7 ]Unité d'Immunologie Moléculaire des Parasites, Institut Pasteur, Paris, France
                [8 ]Malaria Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom
                Johns Hopkins University, United States of America
                Author notes

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

                Conceived and designed the experiments: SH NH SB EMC MMT SM FA S. Yeung SD RDN DM. Performed the experiments: SN S. Kim NK SS AT S. Kheng S. Yok ST SR BW CC CY. Analyzed the data: SH MMT SM S. Yeung RDN DM. Contributed reagents/materials/analysis tools: SN S. Kim NK SS AT S. Kheng S. Yok ST SR BW CC NC US. Wrote the paper: SH SN MMT SM S. Yeung RDN DM.

                Article
                PONE-D-12-17313
                10.1371/journal.pone.0045797
                3462177
                23049687
                782b836d-ee5b-49cd-865c-b1ed4f6fd9d7
                Copyright @ 2012

                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
                : 16 June 2012
                : 24 August 2012
                Page count
                Pages: 12
                Funding
                The funding of this operational research was provided by the Bill & Melinda Gates Foundation (Grant No 48821.01) and WHO under the title: “A strategy for the containment of artemisinin tolerant malaria parasites in SE Asia”. Didier Ménard was supported by the French Ministry of Foreign Affairs during this work. Shunmay Yeung was the ARC programme was operational research coordinator during the early planning stages of this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Microbiology
                Parasitology
                Parasite Evolution
                Microbial Control
                Microbial Ecology
                Molecular Cell Biology
                Nucleic Acids
                DNA
                DNA amplification
                Population Biology
                Epidemiology
                Environmental Epidemiology
                Epidemiological Methods
                Genetic Epidemiology
                Infectious Disease Epidemiology
                Spatial Epidemiology

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                Uncategorized

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