A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria
Identifieur interne : 007C59 ( Main/Exploration ); précédent : 007C58; suivant : 007C60A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria
Auteurs : Stéphane Picot [France] ; Piero Olliaro [Suisse, Royaume-Uni] ; Frédérique De Monbrison [France] ; Anne-Lise Bienvenu [France] ; Ric N. Price [Australie] ; Pascal RingwaldSource :
- Malaria Journal [ 1475-2875 ] ; 2009.
Abstract
An assessment of the correlation between anti-malarial treatment outcome and molecular markers would improve the early detection and monitoring of drug resistance by
Clinical studies of non-severe malaria reporting on target genetic markers (SNPs for
92 studies were eligible among the selection from computerized search, with information on
When applying the selection procedure for comparative analysis, few studies fulfilled all inclusion criteria compared to the large number of papers identified, but heterogeneity was limited. Genetic molecular markers were related to an increased risk of therapeutic failure. Guidelines are discussed and a checklist for further studies is proposed.
Url:
DOI: 10.1186/1475-2875-8-89
PubMed: 19413906
PubMed Central: 2681474
Affiliations:
- Australie, France, Royaume-Uni, Suisse
- Angleterre, Auvergne-Rhône-Alpes, Oxfordshire, Rhône-Alpes
- Lyon, Oxford
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Le document en format XML
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Price</name><affiliation wicri:level="1"><nlm:aff id="I4">International Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>International Health Division, Menzies School of Health Research and Charles Darwin University, Darwin</wicri:regionArea><wicri:noRegion>Darwin</wicri:noRegion></affiliation></author><author><name sortKey="Ringwald, Pascal" sort="Ringwald, Pascal" uniqKey="Ringwald P" first="Pascal" last="Ringwald">Pascal Ringwald</name><affiliation><nlm:aff id="I5">Global Malaria Programme, World Health Organization, Geneva Switzerland</nlm:aff><wicri:noCountry code="subfield">Geneva Switzerland</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19413906</idno><idno type="pmc">2681474</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681474</idno><idno 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molecular markers of parasite resistance and treatment outcome in falciparum malaria</title><author><name sortKey="Picot, Stephane" sort="Picot, Stephane" uniqKey="Picot S" first="Stéphane" last="Picot">Stéphane Picot</name><affiliation wicri:level="3"><nlm:aff id="I1">Malaria Research Unit, EA 4170, University Lyon 1, Faculty of Medicine, 8 Avenue Rockefeller, 69373 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Malaria Research Unit, EA 4170, University Lyon 1, Faculty of Medicine, 8 Avenue Rockefeller, 69373 Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Olliaro, Piero" sort="Olliaro, Piero" uniqKey="Olliaro P" first="Piero" last="Olliaro">Piero Olliaro</name><affiliation wicri:level="1"><nlm:aff id="I2">UNICEF/UNDP/WB/WHO Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>UNICEF/UNDP/WB/WHO Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="I3">Centre for Vaccinology & Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Vaccinology & Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="De Monbrison, Frederique" sort="De Monbrison, Frederique" uniqKey="De Monbrison F" first="Frédérique" last="De Monbrison">Frédérique De Monbrison</name><affiliation wicri:level="3"><nlm:aff id="I1">Malaria Research Unit, EA 4170, University Lyon 1, Faculty of Medicine, 8 Avenue Rockefeller, 69373 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Malaria Research Unit, EA 4170, University Lyon 1, Faculty of Medicine, 8 Avenue Rockefeller, 69373 Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Bienvenu, Anne Lise" sort="Bienvenu, Anne Lise" uniqKey="Bienvenu A" first="Anne-Lise" last="Bienvenu">Anne-Lise Bienvenu</name><affiliation wicri:level="3"><nlm:aff id="I1">Malaria Research Unit, EA 4170, University Lyon 1, Faculty of Medicine, 8 Avenue Rockefeller, 69373 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Malaria Research Unit, EA 4170, University Lyon 1, Faculty of Medicine, 8 Avenue Rockefeller, 69373 Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Price, Ric N" sort="Price, Ric N" uniqKey="Price R" first="Ric N" last="Price">Ric N. Price</name><affiliation wicri:level="1"><nlm:aff id="I4">International Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>International Health Division, Menzies School of Health Research and Charles Darwin University, Darwin</wicri:regionArea><wicri:noRegion>Darwin</wicri:noRegion></affiliation></author><author><name sortKey="Ringwald, Pascal" sort="Ringwald, Pascal" uniqKey="Ringwald P" first="Pascal" last="Ringwald">Pascal Ringwald</name><affiliation><nlm:aff id="I5">Global Malaria Programme, World Health Organization, Geneva Switzerland</nlm:aff><wicri:noCountry code="subfield">Geneva Switzerland</wicri:noCountry></affiliation></author></analytic><series><title level="j">Malaria Journal</title><idno type="eISSN">1475-2875</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>An assessment of the correlation between anti-malarial treatment outcome and molecular markers would improve the early detection and monitoring of drug resistance by <italic>Plasmodium falciparum</italic>. The purpose of this systematic review was to determine the risk of treatment failure associated with specific polymorphisms in the parasite genome or gene copy number.</p></sec><sec sec-type="methods"><title>Methods</title><p>Clinical studies of non-severe malaria reporting on target genetic markers (SNPs for <italic>pfmdr1</italic>, <italic>pfcrt</italic>, <italic>dhfr</italic>, <italic>dhps</italic>, gene copy number for <italic>pfmdr1</italic>) providing complete information on inclusion criteria, outcome, follow up and genotyping, were included. Three investigators independently extracted data from articles. Results were stratified by gene, codon, drug and duration of follow-up. For each study and aggregate data the random effect odds ratio (OR) with 95%CIs was estimated and presented as Forest plots. An OR with a lower 95<sup>th </sup>confidence interval > 1 was considered consistent with a failure being associated to a given gene mutation.</p></sec><sec><title>Results</title><p>92 studies were eligible among the selection from computerized search, with information on <italic>pfcrt </italic>(25/159 studies), <italic>pfmdr1 </italic>(29/236 studies), <italic>dhfr </italic>(18/373 studies), <italic>dhps </italic>(20/195 studies). The risk of therapeutic failure after chloroquine was increased by the presence of <italic>pfcrt </italic>K76T (Day 28, OR = 7.2 [95%CI: 4.5–11.5]), <italic>pfmdr1 </italic>N86Y was associated with both chloroquine (Day 28, OR = 1.8 [95%CI: 1.3–2.4]) and amodiaquine failures (OR = 5.4 [95%CI: 2.6–11.3, p < 0.001]). For sulphadoxine-pyrimethamine the <italic>dhfr </italic>single (S108N) (Day 28, OR = 3.5 [95%CI: 1.9–6.3]) and triple mutants (S108N, N51I, C59R) (Day 28, OR = 3.1 [95%CI: 2.0–4.9]) and <italic>dhfr</italic>-<italic>dhps </italic>quintuple mutants (Day 28, OR = 5.2 [95%CI: 3.2–8.8]) also increased the risk of treatment failure. Increased <italic>pfmdr1 </italic>copy number was correlated with treatment failure following mefloquine (OR = 8.6 [95%CI: 3.3–22.9]).</p></sec><sec><title>Conclusion</title><p>When applying the selection procedure for comparative analysis, few studies fulfilled all inclusion criteria compared to the large number of papers identified, but heterogeneity was limited. Genetic molecular markers were related to an increased risk of therapeutic failure. Guidelines are discussed and a checklist for further studies is proposed.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Royaume-Uni</li><li>Suisse</li></country><region><li>Angleterre</li><li>Auvergne-Rhône-Alpes</li><li>Oxfordshire</li><li>Rhône-Alpes</li></region><settlement><li>Lyon</li><li>Oxford</li></settlement></list><tree><noCountry><name sortKey="Ringwald, Pascal" sort="Ringwald, Pascal" uniqKey="Ringwald P" first="Pascal" last="Ringwald">Pascal Ringwald</name></noCountry><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Picot, Stephane" sort="Picot, Stephane" uniqKey="Picot S" first="Stéphane" last="Picot">Stéphane Picot</name></region><name sortKey="Bienvenu, Anne Lise" sort="Bienvenu, Anne Lise" uniqKey="Bienvenu A" first="Anne-Lise" last="Bienvenu">Anne-Lise Bienvenu</name><name sortKey="De Monbrison, Frederique" sort="De Monbrison, Frederique" uniqKey="De Monbrison F" first="Frédérique" last="De Monbrison">Frédérique De Monbrison</name></country><country name="Suisse"><noRegion><name sortKey="Olliaro, Piero" sort="Olliaro, Piero" uniqKey="Olliaro P" first="Piero" last="Olliaro">Piero Olliaro</name></noRegion></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Olliaro, Piero" sort="Olliaro, Piero" uniqKey="Olliaro P" first="Piero" last="Olliaro">Piero Olliaro</name></region></country><country name="Australie"><noRegion><name sortKey="Price, Ric N" sort="Price, Ric N" uniqKey="Price R" first="Ric N" last="Price">Ric N. 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