Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    Temporal changes in Plasmodium falciparum anti-malarial drug sensitivity in vitro and resistance-associated genetic mutations in isolates from Papua New Guinea

    246401_246401.pdf (828.1Kb)
    Access Status
    Open access
    Authors
    Koleala, T.
    Karl, S.
    Laman, M.
    Moore, Brioni
    Benjamin, J.
    Barnadas, C.
    Robinson, L.
    Kattenberg, J.
    Javati, S.
    Wong, R.
    Rosanas-Urgell, A.
    Betuela, I.
    Siba, P.
    Mueller, I.
    Davis, T.
    Date
    2015
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Koleala, T. and Karl, S. and Laman, M. and Moore, B. and Benjamin, J. and Barnadas, C. and Robinson, L. et al. 2015. Temporal changes in Plasmodium falciparum anti-malarial drug sensitivity in vitro and resistance-associated genetic mutations in isolates from Papua New Guinea. Malaria Journal. 14 (1).
    Source Title
    Malaria Journal
    DOI
    10.1186/s12936-015-0560-3
    School
    School of Pharmacy
    Remarks

    This open access article is distributed under the Creative Commons license https://creativecommons.org/licenses/by/4.0/

    URI
    http://hdl.handle.net/20.500.11937/16467
    Collection
    • Curtin Research Publications
    Abstract

    Background: In northern Papua New Guinea (PNG), most Plasmodium falciparum isolates proved resistant to chloroquine (CQ) in vitro between 2005 and 2007, and there was near-fixation of pfcrt K76T, pfdhfr C59R/S108N and pfmdr1 N86Y. To determine whether the subsequent introduction of artemisinin combination therapy (ACT) and reduced CQ-sulphadoxine-pyrimethamine pressure had attenuated parasite drug susceptibility and resistance-associated mutations, these parameters were re-assessed between 2011 and 2013. Methods: A validated fluorescence-based assay was used to assess growth inhibition of 52 P. falciparum isolates from children in a clinical trial in Madang Province. Responses to CQ, lumefantrine, piperaquine, naphthoquine, pyronaridine, artesunate, dihydroartemisinin, artemether were assessed. Molecular resistance markers were detected using a multiplex PCR ligase detection reaction fluorescent microsphere assay. Results: CQ resistance (in vitro concentration required for 50% parasite growth inhibition (IC50) >100 nM) was present in 19% of isolates. All piperaquine and naphthoquine IC50s were <100 nM and those for lumefantrine, pyronaridine and the artemisinin derivatives were in low nM ranges. Factor analysis of IC50s showed three groupings (lumefantrine; CQ, piperaquine, naphthoquine; pyronaridine, dihydroartemisinin, artemether, artesunate). Most isolates (96%) were monoclonal pfcrt K76T (SVMNT) mutants and most (86%) contained pfmdr1 N86Y (YYSND). No wild-type pfdhfr was found but most isolates contained wild-type (SAKAA) pfdhps. Compared with 2005-2007, the geometric mean (95% CI) CQ IC50 was lower (87 (71-107) vs 167 (141-197) nM) and there had been no change in the prevalence of pfcrt K76T or pfmdr1 mutations. There were fewer isolates of the pfdhps (SAKAA) wild-type (60 vs 100%) and pfdhfr mutations persisted. Conclusions: Reflecting less drug pressure, in vitro CQ sensitivity appears to be improving in Madang Province despite continued near-fixation of pfcrt K76T and pfmdr1 mutations. Temporal changes in IC50s for other anti-malarial drugs were inconsistent but susceptibility was preserved. Retention or increases in pfdhfr and pfdhps mutations reflect continued use of sulphadoxine-pyrimethamine in the study area including through paediatric intermittent preventive treatment. The susceptibility of local isolates to lumefantrine may be unrelated to those of other ACT partner drugs. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12610000913077.

    Related items

    Showing items related by title, author, creator and subject.

    • Population Pharmacokinetics of Artemether, Lumefantrine, and Their Respective Metabolites in Papua New Guinean Children with Uncomplicated Malaria
      Salman, S.; Page-Sharp, Madhu; Griffin, S.; Kose, K.; Siba, P.; Ilett, K.; Mueller, I.; Davis, T. (2011)
      There are sparse published data relating to the pharmacokinetic properties of artemether, lumefantrine, and their active metabolites in children, especially desbutyl-lumefantrine. We studied 13 Papua New Guinean children ...
    • Molecular characterization of Malaysian methicillin-resistant Staphylococcus aureus
      Lim, Tien Tze (2007)
      Seventy-four methicillin-resistant Staphylococcus aureus (MRSA) from two Malaysian hospitals were characterised by both phenotypic and genotypic techniques. These isolates were collected over an 18 year time period in the ...
    • A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations
      Roche, M.; Salimi, H.; Duncan, R.; Wilkinson, B.; Chikere, K.; Moore, M.; Webb, N.; Zappi, H.; Sterjovski, J.; Flynn, J.; Ellett, A.; Gray, L.; Lee, B.; Jubb, B.; Westby, M.; Ramsland, Paul; Lewin, S.; Payne, R.; Churchill, M.; Gorry, P. (2013)
      Background: The CCR5 antagonist maraviroc (MVC) inhibits human immunodeficiency virus type 1 (HIV-1) entry by altering the CCR5 extracellular loops (ECL), such that the gp120 envelope glycoproteins (Env) no longer recognize ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.