The Role of Pfmdr1 and Pfcrt in Changing Chloroquine, Amodiaquine, Mefloquine and Lumefantrine Susceptibility in Western-Kenya P. falciparum Samples during 2008–2011
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{"title"=>"The Role of Pfmdr1 and Pfcrt in Changing Chloroquine, Amodiaquine, Mefloquine and Lumefantrine Susceptibility in Western-Kenya P. falciparum Samples during 2008-2011", "type"=>"journal", "authors"=>[{"first_name"=>"Fredrick L.", "last_name"=>"Eyase", "scopus_author_id"=>"8110714600"}, {"first_name"=>"Hoseah M.", "last_name"=>"Akala", "scopus_author_id"=>"35612411100"}, {"first_name"=>"Luiser", "last_name"=>"Ingasia", "scopus_author_id"=>"55695955700"}, {"first_name"=>"Agnes", "last_name"=>"Cheruiyot", "scopus_author_id"=>"42861216600"}, {"first_name"=>"Angela", "last_name"=>"Omondi", "scopus_author_id"=>"42861918400"}, {"first_name"=>"Charles", "last_name"=>"Okudo", "scopus_author_id"=>"55389389900"}, {"first_name"=>"Dennis", "last_name"=>"Juma", "scopus_author_id"=>"55695173600"}, {"first_name"=>"Redemptah", "last_name"=>"Yeda", "scopus_author_id"=>"55506059500"}, {"first_name"=>"Ben", "last_name"=>"Andagalu", "scopus_author_id"=>"55560463100"}, {"first_name"=>"Elizabeth", "last_name"=>"Wanja", "scopus_author_id"=>"14422648000"}, {"first_name"=>"Edwin", "last_name"=>"Kamau", "scopus_author_id"=>"8703610800"}, {"first_name"=>"David", "last_name"=>"Schnabel", "scopus_author_id"=>"15843907700"}, {"first_name"=>"Wallace", "last_name"=>"Bulimo", "scopus_author_id"=>"6505964790"}, {"first_name"=>"Norman C.", "last_name"=>"Waters", "scopus_author_id"=>"7102435784"}, {"first_name"=>"Douglas S.", "last_name"=>"Walsh", "scopus_author_id"=>"7402052368"}, {"first_name"=>"Jacob D.", "last_name"=>"Johnson", "scopus_author_id"=>"55494681400"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84877642976", "sgr"=>"84877642976", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0064299", "pmid"=>"23675533", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "pui"=>"368900165"}, "id"=>"eea66276-b887-3525-9605-748fe6334051", "abstract"=>"Single Nucleotide Polymorphisms (SNPs) in the Pfmdr1, and Pfcrt, genes of Plasmodium falciparum may confer resistance to a number of anti-malaria drugs. Pfmdr1 86Y and haplotypes at Pfcrt 72-76 have been linked to chloroquine (CQ) as well as amodiaquine (AQ) resistance. mefloquine (MQ) and lumefantrine (LU) sensitivities are linked to Pfmdr1 86Y. Additionally, Pfcrt K76 allele carrying parasites have shown tolerance to LU. We investigated the association between Pfmdr1 86/Pfcrt 72-76 and P. falciparum resistance to CQ, AQ, MQ and LU using field samples collected during 2008-2011 from malaria endemic sites in western Kenya. Genomic DNA from these samples was genotyped to examine SNPs and haplotypes in Pfmdr1 and Pfcrt respectively. Additionally, immediate ex vivo and in vitro drug sensitivity profiles were assessed using the malaria SYBR Green I fluorescence-based assay. We observed a rapid but steady percent increase in wild-type parasites with regard to both Pfmdr1 and Pfcrt between 2008 and 2011 (p<0.0001). Equally, a significant reciprocate decrease in AQ and CQ median IC50 values occurred (p<0.0001) during the same period. Thus, the data in this study point to a significantly rapid change in parasite response to AQ and CQ in the study period. This may be due to releasing of drug pressure on the parasite from reduced use of AQ in the face of increased Artemisinin (ART) Combination Therapy (ACT) administration following the intervention of the Global Fund in 2008. LU has been shown to select for 76K genotypes, thus the observed increase in 76K genotypes coupled with significant cross resistance between LU and MQ, may herald emergence of tolerance against both drugs in future.", "link"=>"http://www.mendeley.com/research/role-pfmdr1-pfcrt-changing-chloroquine-amodiaquine-mefloquine-lumefantrine-susceptibility-westernken", "reader_count"=>56, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>4, "Librarian"=>1, "Researcher"=>12, "Student > Doctoral Student"=>8, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>4, "Student > Master"=>10, "Other"=>3, "Student > Bachelor"=>2, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>4, "Librarian"=>1, "Researcher"=>12, "Student > Doctoral Student"=>8, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>4, "Student > Master"=>10, "Other"=>3, "Student > Bachelor"=>2, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>7, "Medicine and Dentistry"=>14, "Agricultural and Biological Sciences"=>29, "Chemistry"=>1, "Computer Science"=>2, "Immunology and Microbiology"=>2, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>14}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>29}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}}, "reader_count_by_country"=>{"Vietnam"=>1, "Burkina Faso"=>1, "Iran"=>1, "Tanzania"=>1, "United Kingdom"=>2, "Kenya"=>1}, "group_count"=>6}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1551482"], "description"=>"<p>A. Comparison of <i>Pfcrt</i> K76T SNP against CQ IC<sub>50</sub> stratified by year; B. Comparison of <i>Pfcrt</i> K76T SNP against AQ IC<sub>50</sub> stratified by year; C. Comparison of <i>Pfcrt</i> K76T SNP against MQ IC<sub>50</sub> stratified by year; D. Comparison of <i>Pfcrt</i> K76T SNP against LU IC<sub>50</sub> stratified by year. Median values are shown. *indicates data is significant.</p>", "links"=>[], "tags"=>["genetics", "population genetics", "Genetic polymorphism", "Gene function", "Molecular genetics", "microbiology", "Protozoology", "Parastic protozoans", "Microbial mutation", "Drugs and devices", "pharmacokinetics", "Drug metabolism", "Infectious diseases", "Parasitic diseases", "malaria", "Plasmodium falciparum", "k76t", "snp", "compared"], "article_id"=>1071712, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fredrick L. Eyase", "Hoseah M. Akala", "Luiser Ingasia", "Agnes Cheruiyot", "Angela Omondi", "Charles Okudo", "Dennis Juma", "Redemptah Yeda", "Ben Andagalu", "Elizabeth Wanja", "Edwin Kamau", "David Schnabel", "Wallace Bulimo", "Norman C. Waters", "Douglas S. Walsh", "Jacob D. Johnson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064299.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pfcrt_K76T_SNP_compared_against_drug_IC_50_in_nM_/1071712", "title"=>"<i>Pfcrt</i> K76T SNP compared against drug IC<sub>50</sub> (in nM).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-13 09:24:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1551489"], "description"=>"<p>A. Comparison of <i>Pfmdr1</i> N86Y SNP against CQ IC<sub>50</sub> stratified by year; B. Comparison of <i>Pfmdr1</i> N86Y SNP against AQ IC<sub>50</sub> stratified by year; C. Comparison of <i>Pfmdr1</i> N86Y SNP against MQ IC<sub>50</sub> stratified by year; D. Comparison of <i>Pfmdr1</i> N86Y SNP against LU IC<sub>50</sub> stratified by year. Median values are shown. *indicates data is significant.</p>", "links"=>[], "tags"=>["genetics", "population genetics", "Genetic polymorphism", "Gene function", "Molecular genetics", "microbiology", "Protozoology", "Parastic protozoans", "Microbial mutation", "Drugs and devices", "pharmacokinetics", "Drug metabolism", "Infectious diseases", "Parasitic diseases", "malaria", "Plasmodium falciparum", "n86y", "snp", "compared"], "article_id"=>1071717, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fredrick L. Eyase", "Hoseah M. Akala", "Luiser Ingasia", "Agnes Cheruiyot", "Angela Omondi", "Charles Okudo", "Dennis Juma", "Redemptah Yeda", "Ben Andagalu", "Elizabeth Wanja", "Edwin Kamau", "David Schnabel", "Wallace Bulimo", "Norman C. Waters", "Douglas S. Walsh", "Jacob D. Johnson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064299.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pfmdr1_N86Y_SNP_compared_against_drug_IC_50_s_in_nM_/1071717", "title"=>"<i>Pfmdr1</i> N86Y SNP compared against drug IC<sub>50</sub>s (in nM).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-13 09:24:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1551495"], "description"=>"<p>A. <i>Pfcrt</i> 72-76 haplotype frequency per year; B. <i>Pfmdr1</i> N86Y SNP frequency per year. Statistical significance was determined by Chi-square.</p>", "links"=>[], "tags"=>["genetics", "population genetics", "Genetic polymorphism", "Gene function", "Molecular genetics", "microbiology", "Protozoology", "Parastic protozoans", "Microbial mutation", "Drugs and devices", "pharmacokinetics", "Drug metabolism", "Infectious diseases", "Parasitic diseases", "malaria", "Plasmodium falciparum", "72-76", "haplotype", "n86y"], "article_id"=>1071720, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fredrick L. Eyase", "Hoseah M. Akala", "Luiser Ingasia", "Agnes Cheruiyot", "Angela Omondi", "Charles Okudo", "Dennis Juma", "Redemptah Yeda", "Ben Andagalu", "Elizabeth Wanja", "Edwin Kamau", "David Schnabel", "Wallace Bulimo", "Norman C. Waters", "Douglas S. Walsh", "Jacob D. Johnson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064299.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Frequency_of_Pfcrt_72_76_haplotype_and_Pfmdr1_N86Y_SNP_/1071720", "title"=>"Frequency of <i>Pfcrt</i> 72-76 haplotype and <i>Pfmdr1</i> N86Y SNP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-13 09:24:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1551496"], "description"=>"<p>Correlation was determined in Graphpad prism Version 5 based on IC<sub>50</sub> values for each pair of drugs per isolate.</p>", "links"=>[], "tags"=>["genetics", "population genetics", "Genetic polymorphism", "Gene function", "Molecular genetics", "microbiology", "Protozoology", "Parastic protozoans", "Microbial mutation", "Drugs and devices", "pharmacokinetics", "Drug metabolism", "Infectious diseases", "Parasitic diseases", "malaria", "Plasmodium falciparum", "product-moment", "mq"], "article_id"=>1071721, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fredrick L. Eyase", "Hoseah M. Akala", "Luiser Ingasia", "Agnes Cheruiyot", "Angela Omondi", "Charles Okudo", "Dennis Juma", "Redemptah Yeda", "Ben Andagalu", "Elizabeth Wanja", "Edwin Kamau", "David Schnabel", "Wallace Bulimo", "Norman C. Waters", "Douglas S. Walsh", "Jacob D. Johnson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064299.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pearson_product_moment_correlation_for_CQ_AQ_MQ_and_LU_/1071721", "title"=>"Pearson product-moment correlation for CQ, AQ, MQ and LU.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-13 09:24:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1551497"], "description"=>"<p>Medians were calculated in Graphpad prism Version 5. Statistical significance was determined using Kruskal Wallis H test. Comparisons were done using Dunns Multiple comparison test.</p>", "links"=>[], "tags"=>["genetics", "population genetics", "Genetic polymorphism", "Gene function", "Molecular genetics", "microbiology", "Protozoology", "Parastic protozoans", "Microbial mutation", "Drugs and devices", "pharmacokinetics", "Drug metabolism", "Infectious diseases", "Parasitic diseases", "malaria", "Plasmodium falciparum", "pfcrt", "86", "haplotype"], "article_id"=>1071722, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fredrick L. Eyase", "Hoseah M. Akala", "Luiser Ingasia", "Agnes Cheruiyot", "Angela Omondi", "Charles Okudo", "Dennis Juma", "Redemptah Yeda", "Ben Andagalu", "Elizabeth Wanja", "Edwin Kamau", "David Schnabel", "Wallace Bulimo", "Norman C. Waters", "Douglas S. Walsh", "Jacob D. Johnson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064299.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Combined_Pfcrt_76_Pfmdr1_86_haplotype_vs_medians_/1071722", "title"=>"Combined Pfcrt 76/Pfmdr1 86 haplotype vs. medians.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-13 09:24:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1551498"], "description"=>"<p>Medians were calculated in Graphpad prism Version 5. Statistical significance was determined using Kruskal Wallis H test.</p>", "links"=>[], "tags"=>["genetics", "population genetics", "Genetic polymorphism", "Gene function", "Molecular genetics", "microbiology", "Protozoology", "Parastic protozoans", "Microbial mutation", "Drugs and devices", "pharmacokinetics", "Drug metabolism", "Infectious diseases", "Parasitic diseases", "malaria", "Plasmodium falciparum", "lu", "mq"], "article_id"=>1071723, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fredrick L. Eyase", "Hoseah M. Akala", "Luiser Ingasia", "Agnes Cheruiyot", "Angela Omondi", "Charles Okudo", "Dennis Juma", "Redemptah Yeda", "Ben Andagalu", "Elizabeth Wanja", "Edwin Kamau", "David Schnabel", "Wallace Bulimo", "Norman C. Waters", "Douglas S. Walsh", "Jacob D. Johnson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064299.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Median_IC_50s_for_CQ_AQ_LU_and_MQ_per_Year_during_2008_8211_2011_/1071723", "title"=>"Median IC<sub>50s</sub> for CQ, AQ, LU and MQ per Year during 2008–2011.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-05-13 09:24:36"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[284, 491, 620, 738, 843, 945, 1043, 1137, 1225, 1315, 1400, 1479, 1555]}, {"subject_area"=>"/Biology and life sciences/Organisms", "average_usage"=>[281, 484, 611, 728, 835, 934, 1030, 1123, 1214, 1299, 1383, 1464]}, {"subject_area"=>"/Biology and life sciences/Parasitology", "average_usage"=>[354, 586, 723, 820, 941, 1045, 1176, 1283, 1391, 1469, 1526, 1639, 1730]}, {"subject_area"=>"/Biology and life sciences/Population biology", "average_usage"=>[269, 448, 558, 658, 744, 830, 914, 995, 1068, 1139, 1214, 1284, 1349]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Health care", "average_usage"=>[278, 463, 587, 692, 804, 897, 984, 1068, 1165, 1254, 1339, 1429, 1490]}, {"subject_area"=>"/Medicine and health sciences/Pharmacology", "average_usage"=>[265, 471, 604, 723, 827, 926, 1022, 1113, 1210, 1290, 1377, 1454, 1532]}]}
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