Molecular markers of anti-malarial drug resistance in Central, West and East African children with severe malaria
Identifieur interne : 000055 ( Main/Exploration ); précédent : 000054; suivant : 000056Molecular markers of anti-malarial drug resistance in Central, West and East African children with severe malaria
Auteurs : Christian N. Nguetse [Allemagne] ; Ayola Akim Adegnika [Allemagne, Gabon] ; Tsiri Agbenyega [Ghana] ; Bernhards R. Ogutu [Kenya] ; Sanjeev Krishna [Allemagne, Royaume-Uni] ; Peter G. Kremsner [Allemagne, Gabon] ; Thirumalaisamy P. Velavan [Allemagne, Viêt Nam]Source :
- Malaria Journal [ 1475-2875 ] ; 2017.
Abstract
The
Samples from 287 children with severe malaria [(Gabon: n = 114); (Ghana: n = 89); (Kenya: n = 84)] were genotyped for
Artemisinins are still highly efficacious in large malaria-endemic regions though declining efficacy has occurred in Southeast Asia. The return of chloroquine-sensitive strains following the removal of drug pressure is observed. However, selection of wild-type alleles in the multidrug-resistance gene and the increased gene copy number is associated with reduced lumefantrine sensitivity. This study indicates a need to constantly monitor drug resistance to artemisinin in field isolates from malaria-endemic countries.
Url:
DOI: 10.1186/s12936-017-1868-y
PubMed: 28535801
PubMed Central: 5442681
Affiliations:
- Allemagne, Gabon, Ghana, Kenya, Royaume-Uni, Viêt Nam
- Bade-Wurtemberg, District de Tübingen
- Tübingen
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Le document en format XML
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Kremsner</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Institute of Tropical Medicine,</institution><institution>University Tübingen,</institution></institution-wrap>Wilhelmstrasse 27, 72074 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Wilhelmstrasse 27, 72074 Tübingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.452268.f</institution-id><institution></institution><institution>Centre de Recherches Médicales de Lambaréné,</institution></institution-wrap>Lambaréné, Gabon</nlm:aff><country xml:lang="fr">Gabon</country><wicri:regionArea>Lambaréné</wicri:regionArea></affiliation></author><author><name sortKey="Velavan, Thirumalaisamy P" sort="Velavan, Thirumalaisamy P" uniqKey="Velavan T" first="Thirumalaisamy P." last="Velavan">Thirumalaisamy P. Velavan</name><affiliation wicri:level="3"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2190 1447</institution-id><institution-id institution-id-type="GRID">grid.10392.39</institution-id><institution>Institute of Tropical Medicine,</institution><institution>University Tübingen,</institution></institution-wrap>Wilhelmstrasse 27, 72074 Tübingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Wilhelmstrasse 27, 72074 Tübingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.452468.9</institution-id><institution></institution><institution>Fondation Congolaise pour la Recherche Médicale,</institution></institution-wrap>Brazzaville, Republic of Congo</nlm:aff><wicri:noCountry code="subfield">Republic of Congo</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff8">Vietnamese-German Center for Medical Research, Hanoi, Vietnam</nlm:aff><country xml:lang="fr">Viêt Nam</country><wicri:regionArea>Vietnamese-German Center for Medical Research, Hanoi</wicri:regionArea><wicri:noRegion>Hanoi</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff9"><institution-wrap><institution-id institution-id-type="GRID">grid.444918.4</institution-id><institution>Faculty of Medicine,</institution><institution>Duy Tan University,</institution></institution-wrap>Da Nang, Vietnam</nlm:aff><country xml:lang="fr">Viêt Nam</country><wicri:regionArea>Da Nang</wicri:regionArea></affiliation></author></analytic><series><title level="j">Malaria Journal</title><idno type="eISSN">1475-2875</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The <italic>Plasmodium falciparum</italic> multidrug resistance 1 (PfMDR1), <italic>P. falciparum</italic> Ca<sup>2+</sup>-ATPase (PfATP6) and Kelch-13 propeller domain (PfK13) loci are molecular markers of parasite susceptibility to anti-malarial drugs. Their frequency distributions were determined in the isolates collected from children with severe malaria originating from three African countries.</p></sec><sec><title>Methods</title><p>Samples from 287 children with severe malaria [(Gabon: n = 114); (Ghana: n = 89); (Kenya: n = 84)] were genotyped for <italic>pfmdr1, pfatp6</italic> and <italic>pfk13</italic> loci by DNA sequencing and assessing <italic>pfmdr1</italic> copy number variation (CNV) by real-time PCR.</p></sec><sec><title>Results</title><p><italic>Pfmdr1</italic>-N86Y mutation was detected in 48, 10 and 10% in Lambaréné, Kumasi and Kisumu, respectively. At codon 184, the prevalence of the mutation was 73% in Lambaréné, 63% in Kumasi and 49% Kisumu. The S1034C and N1042D variants were absent at all three sites, while the frequency of the D1246Y mutation was 1, 3 and 13% in Lambaréné, Kumasi and Kisumu, respectively. Isolates with two <italic>pfmdr1</italic> gene copy number predominantly harboured the N86Y wild-type allele and were mostly found in Kumasi (10%) (<italic>P</italic> < 0.0001). Among the main <italic>pfmdr1</italic> haplotypes (NFD, NYD and YFD), NYD was associated with highest parasitaemia (<italic>P</italic> = 0.04). At the <italic>pfatp6</italic> locus, H243Y and A623E mutations were observed at very low frequency at all three sites. The prevalence of the <italic>pfatp6</italic> E431K variant was 6, 18 and 17% in Lambaréné, Kumasi and Kisumu, respectively. The L263E and S769N mutations were absent in all isolates. The <italic>pfk13</italic> variants associated with artemisinin resistance in Southeast Asia were not observed. Eleven novel substitutions in the <italic>pfk13</italic> locus occurring at low frequency were observed.</p></sec><sec><title>Conclusions</title><p>Artemisinins are still highly efficacious in large malaria-endemic regions though declining efficacy has occurred in Southeast Asia. The return of chloroquine-sensitive strains following the removal of drug pressure is observed. However, selection of wild-type alleles in the multidrug-resistance gene and the increased gene copy number is associated with reduced lumefantrine sensitivity. This study indicates a need to constantly monitor drug resistance to artemisinin in field isolates from malaria-endemic countries.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Dondorp, Am" uniqKey="Dondorp A">AM Dondorp</name></author><author><name sortKey="Nosten, F" uniqKey="Nosten F">F Nosten</name></author><author><name sortKey="Yi, P" uniqKey="Yi P">P Yi</name></author><author><name sortKey="Das, D" uniqKey="Das D">D Das</name></author><author><name sortKey="Phyo, Ap" uniqKey="Phyo A">AP Phyo</name></author><author><name sortKey="Tarning, J" uniqKey="Tarning J">J Tarning</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amaratunga, C" uniqKey="Amaratunga C">C Amaratunga</name></author><author><name sortKey="Sreng, S" uniqKey="Sreng S">S Sreng</name></author><author><name sortKey="Suon, S" uniqKey="Suon S">S Suon</name></author><author><name sortKey="Phelps, 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Aseffa</name></author><author><name sortKey="Berhe, N" uniqKey="Berhe N">N Berhe</name></author><author><name sortKey="Teklehaymanot, T" uniqKey="Teklehaymanot T">T Teklehaymanot</name></author><author><name sortKey="Clouse, Rm" uniqKey="Clouse R">RM Clouse</name></author><author><name sortKey="Gebru, T" uniqKey="Gebru T">T Gebru</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Gabon</li><li>Ghana</li><li>Kenya</li><li>Royaume-Uni</li><li>Viêt Nam</li></country><region><li>Bade-Wurtemberg</li><li>District de Tübingen</li></region><settlement><li>Tübingen</li></settlement></list><tree><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Nguetse, Christian N" sort="Nguetse, Christian N" uniqKey="Nguetse C" first="Christian N." last="Nguetse">Christian N. Nguetse</name></region><name sortKey="Adegnika, Ayola Akim" sort="Adegnika, Ayola Akim" uniqKey="Adegnika A" first="Ayola Akim" last="Adegnika">Ayola Akim Adegnika</name><name sortKey="Kremsner, Peter G" sort="Kremsner, Peter G" uniqKey="Kremsner P" first="Peter G." last="Kremsner">Peter G. Kremsner</name><name sortKey="Krishna, Sanjeev" sort="Krishna, Sanjeev" uniqKey="Krishna S" first="Sanjeev" last="Krishna">Sanjeev Krishna</name><name sortKey="Velavan, Thirumalaisamy P" sort="Velavan, Thirumalaisamy P" uniqKey="Velavan T" first="Thirumalaisamy P." last="Velavan">Thirumalaisamy P. Velavan</name></country><country name="Gabon"><noRegion><name sortKey="Adegnika, Ayola Akim" sort="Adegnika, Ayola Akim" uniqKey="Adegnika A" first="Ayola Akim" last="Adegnika">Ayola Akim Adegnika</name></noRegion><name sortKey="Kremsner, Peter G" sort="Kremsner, Peter G" uniqKey="Kremsner P" first="Peter G." last="Kremsner">Peter G. Kremsner</name></country><country name="Ghana"><noRegion><name sortKey="Agbenyega, Tsiri" sort="Agbenyega, Tsiri" uniqKey="Agbenyega T" first="Tsiri" last="Agbenyega">Tsiri Agbenyega</name></noRegion><name sortKey="Agbenyega, Tsiri" sort="Agbenyega, Tsiri" uniqKey="Agbenyega T" first="Tsiri" last="Agbenyega">Tsiri Agbenyega</name></country><country name="Kenya"><noRegion><name sortKey="Ogutu, Bernhards R" sort="Ogutu, Bernhards R" uniqKey="Ogutu B" first="Bernhards R." last="Ogutu">Bernhards R. Ogutu</name></noRegion></country><country name="Royaume-Uni"><noRegion><name sortKey="Krishna, Sanjeev" sort="Krishna, Sanjeev" uniqKey="Krishna S" first="Sanjeev" last="Krishna">Sanjeev Krishna</name></noRegion></country><country name="Viêt Nam"><noRegion><name sortKey="Velavan, Thirumalaisamy P" sort="Velavan, Thirumalaisamy P" uniqKey="Velavan T" first="Thirumalaisamy P." last="Velavan">Thirumalaisamy P. Velavan</name></noRegion><name sortKey="Velavan, Thirumalaisamy P" sort="Velavan, Thirumalaisamy P" uniqKey="Velavan T" first="Thirumalaisamy P." last="Velavan">Thirumalaisamy P. Velavan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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