168
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker

      research-article
      , MD a , b , , Dr, PhD c , d , * , , MD f , , MD e , g , , Prof, MD b , , Prof, MD b , h , , MD i , , MD j , , MD d , l , , Prof, PhD d , m , , PhD k , l , , PhD d , l , , Prof, MD e , , MD d , l , , PhD n , , MSc n , , MSc n , , PhD k , o , , PhD k , , Prof, MD k , , MD d , l , , MD a , l , p , , Prof, MD d , l , , Prof, FRCP d , l , , Prof, MD f , l , , Prof, FRS d , l , , MD d , l
      The Lancet. Infectious Diseases
      Elsevier Science ;, The Lancet Pub. Group

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Background

          Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations.

          Methods

          We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar.

          Findings

          Overall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 different mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations.

          Interpretation

          Artemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided.

          Funding

          Wellcome Trust–Mahidol University–Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: not found

          Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study

          Summary Background Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international effort is underway to contain artemisinin-resistant Plasmodium falciparum, but containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand–Myanmar (Burma) border. Methods In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≥4% infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms. Findings 3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95% CI 2·5–2·7) in 2001, to 3·7 h (3·6–3·8) in 2010, compared with a mean of 5·5 h (5·2–5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≥6·2 h) increased from 0·6% in 2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identified, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30% between 2001 and 2004, to 66% between 2007 and 2010. Interpretation Genetically determined artemisinin resistance in P falciparum emerged along the Thailand–Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2–6 years. Funding The Wellcome Trust and National Institutes of Health.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            A new world malaria map: Plasmodium falciparum endemicity in 2010

            Background Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (PfEIR) and the basic reproductive number (PfR). Methods Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (PfPR) surveys were used in a model-based geostatistical (MBG) prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link PfPR to PfEIR and PfR and these were fitted to field data. These models were combined with the PfPR map to create new global predictions of PfEIR and PfR. All output maps included measured uncertainty. Results An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median PfEIR of less than one and a median PfR c of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both PfEIR and PfR was substantial in regions of intense transmission. Conclusions The year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The maps presented here contribute to a rational basis for control and elimination decisions and can serve as a baseline assessment as the global health community looks ahead to the next series of milestones targeted at 2015.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia

              We describe an analysis of genome variation in 825 Plasmodium falciparum samples from Asia and Africa that reveals an unusual pattern of parasite population structure at the epicentre of artemisinin resistance in western Cambodia. Within this relatively small geographical area we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and remarkably high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalogue of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in various transporter proteins and DNA mismatch repair proteins. These data provide a population genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist its elimination.
                Bookmark

                Author and article information

                Contributors
                Journal
                Lancet Infect Dis
                Lancet Infect Dis
                The Lancet. Infectious Diseases
                Elsevier Science ;, The Lancet Pub. Group
                1473-3099
                1474-4457
                1 April 2015
                April 2015
                : 15
                : 4
                : 415-421
                Affiliations
                [a ]Myanmar Oxford Clinical Research Unit, Yangon, Myanmar
                [b ]Defence Services Medical Research Centre, Naypyitaw, Myanmar
                [c ]Department of Molecular Tropical Medicine and Genetics, Mahidol University, Bangkok, Thailand
                [d ]Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
                [e ]Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
                [f ]Shoklo Malaria Research Unit, Mae Sot, Thailand
                [g ]Institute of Medicine 1, Yangon, Myanmar
                [h ]Department of Health, Ministry of Health, Naypyitaw, Myanmar
                [i ]Department of Medical Research, Upper Myanmar, Myanmar
                [j ]Department of Medical Research, Lower Myanmar, Myanmar
                [k ]WorldWide Antimalarial Resistance Network, Oxford, UK
                [l ]Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
                [m ]Dev Care Foundation, Dhaka, Bangladesh
                [n ]Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA
                [o ]School of Mathematical Sciences, Monash University, Melbourne, Australia
                [p ]Medical Action Myanmar, Yangon, Myanmar
                Author notes
                [* ]Correspondence to: Dr Mallika Imwong, Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand noi@ 123456tropmedres.ac
                Article
                S1473-3099(15)70032-0
                10.1016/S1473-3099(15)70032-0
                4374103
                25704894
                2561eb21-6d7f-4b0f-b0e9-be155dc2693d
                © 2015 Tun et al. Open Access article distributed under the terms of CC BY

                This document may be redistributed and reused, subject to certain conditions.

                History
                Categories
                Articles

                Infectious disease & Microbiology
                Infectious disease & Microbiology

                Comments

                Comment on this article

                scite_

                Similar content744

                Cited by208

                Most referenced authors929