In vitro antimalarial susceptibility and molecular markers of drug resistance in Franceville, Gabon.
Identifieur interne : 001290 ( Main/Exploration ); précédent : 001289; suivant : 001291In vitro antimalarial susceptibility and molecular markers of drug resistance in Franceville, Gabon.
Auteurs : Rafika Zatra [Gabon] ; Jean Bernard Lekana-Douki [Gabon] ; Faustin Lekoulou [Gabon] ; Ulrick Bisvigou [Gabon] ; Edgard Brice Ngoungou [Gabon] ; Fousseyni S Toure Ndouo [Gabon]Source :
- BMC Infectious Diseases [ 1471-2334 ] ; 2012.
Abstract
BACKGROUND: Malaria remains a major public health problem, due largely to emergence and widespread P. falciparum drug resistance. WHO recommends artemisinine combination based therapy (ACT) to overcome P. falciparum drug resistance, but reports of declining ACT efficacy have been published. A thorough understanding of the molecular bases of P. falciparum resistance to existing drugs is therefore needed. The aims of this study were to analyze the in vitro sensitivity of P. falciparum field isolates from Franceville, Gabon, to chloroquine (CQ), mefloquine (MF), dihydroartemisinine (DHA) and monodesethylamodiaquine (MDAQ), and to investigate polymorphisms associated with drug resistance. METHODS: We conducted a cross-sectional study of 53 field isolates. Field isolates sensitivity to CQ, MF, DHA and MDAQ was assessed using the colorimetric DELI test. The Pfmdr1 codons 86 and 1246, Pfcrt (haplotype codon 72 to 76) and the PfATPAse6 codons 110 and 2694 were analysed by PCR-RFLP. Associations between drug sensitivity and parasite gene polymorphisms were evaluated with the Chi square test, and routine hematological parameters were analyzed with Fisher's exact test implemented with Epinfo software. In all statistical tests, significance was assumed at p<0.05. RESULTS: A total of 46 P. falciparum isolates were successfully cultured in vitro and their sensitivity was tested. The proportions of isolates resistant to CQ, MF and MDAQ were 43.5%, 23.4% and 56.5%, respectively. Some isolates (23.9%) had DHA IC50 values higher than 10 nM. The median IC50 values were 71.67 (interquartile range (IQR, 1-438.2), 6.59 (IQR, 0.08-96), 64.79 (IQR, 0.09-448) and 6.45 nM (IQR, 0.09-23) for CQ, MF, MDAQ and DHA, respectively. The strongest correlation between diminished DHA sensitivity and MF resistance was observed (r2=0.73), followed by correlation between diminished DHA sensitivity and CQ resistance. Cross-resistance between CQ and MF was also observed. The prevalence of the 86Y and 1246Y mutations in Pfmdr1, 76T in Pfcrt, and 110A and 2694T in PfATPase6 was respectively 42% and 17.1%, 97.8%, and 0% and 22.2%. CONCLUSION: These high levels of antimalarial drug resistance in Franceville, Gabon, call for reinforced surveillance of drug efficacy.
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DOI: 10.1186/1471-2334-12-307
Affiliations:
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type="wicri:Area/Main/Exploration">001290</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">In vitro antimalarial susceptibility and molecular markers of drug resistance in Franceville, Gabon.</title><author><name sortKey="Zatra, Rafika" sort="Zatra, Rafika" uniqKey="Zatra R" first="Rafika" last="Zatra">Rafika Zatra</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-51216" status="VALID"> <orgName>Centre International de Recherches Médicales de Franceville</orgName> <orgName type="acronym">CIRMF</orgName> <desc> <address> <addrLine>Franceville</addrLine> <country key="GA"></country> </address> </desc> <listRelation> <relation active="#struct-301226" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-301226" type="direct"><org type="institution" xml:id="struct-301226" status="VALID"> <orgName>Centre International de Recherches Médicales de Franceville</orgName> <desc> <address> <country key="GA"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>Gabon</country></affiliation></author><author><name sortKey="Lekana Douki, Jean Bernard" sort="Lekana Douki, Jean Bernard" uniqKey="Lekana Douki J" first="Jean Bernard" last="Lekana-Douki">Jean Bernard Lekana-Douki</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-51216" status="VALID"> <orgName>Centre International de Recherches Médicales de Franceville</orgName> <orgName type="acronym">CIRMF</orgName> <desc> <address> <addrLine>Franceville</addrLine> <country key="GA"></country> </address> </desc> <listRelation> <relation active="#struct-301226" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-301226" type="direct"><org type="institution" xml:id="struct-301226" status="VALID"> <orgName>Centre International de Recherches Médicales de Franceville</orgName> <desc> <address> <country key="GA"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>Gabon</country></affiliation></author><author><name sortKey="Lekoulou, Faustin" sort="Lekoulou, Faustin" uniqKey="Lekoulou F" first="Faustin" last="Lekoulou">Faustin Lekoulou</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-51216" status="VALID"> <orgName>Centre International de Recherches Médicales de Franceville</orgName> <orgName type="acronym">CIRMF</orgName> <desc> <address> <addrLine>Franceville</addrLine> <country key="GA"></country> </address> </desc> <listRelation> <relation active="#struct-301226" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-301226" type="direct"><org type="institution" xml:id="struct-301226" status="VALID"> <orgName>Centre International de Recherches Médicales de Franceville</orgName> <desc> <address> <country key="GA"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>Gabon</country></affiliation></author><author><name sortKey="Bisvigou, Ulrick" sort="Bisvigou, Ulrick" uniqKey="Bisvigou U" first="Ulrick" last="Bisvigou">Ulrick Bisvigou</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-51216" status="VALID"> <orgName>Centre International de Recherches Médicales de Franceville</orgName> <orgName type="acronym">CIRMF</orgName> <desc> <address> <addrLine>Franceville</addrLine> <country key="GA"></country> </address> </desc> <listRelation> <relation active="#struct-301226" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-301226" type="direct"><org type="institution" xml:id="struct-301226" status="VALID"> <orgName>Centre International de Recherches Médicales de Franceville</orgName> <desc> <address> <country key="GA"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>Gabon</country></affiliation></author><author><name sortKey="Ngoungou, Edgard Brice" sort="Ngoungou, Edgard Brice" uniqKey="Ngoungou E" first="Edgard Brice" last="Ngoungou">Edgard Brice Ngoungou</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-61108" status="INCOMING"> <orgName>Département de Parasitologie, Mycologie et Médecine Tropicale</orgName> <desc> <address> <addrLine>Libreville, BP 4009</addrLine> <country key="GA"></country> </address> </desc> <listRelation> <relation active="#struct-303705" type="direct"></relation> <relation active="#struct-314576" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-303705" type="direct"><org type="institution" xml:id="struct-303705" status="INCOMING"> <orgName>Faculté de Médecine</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle><tutelle active="#struct-314576" type="direct"><org type="institution" xml:id="struct-314576" status="INCOMING"> <orgName>Université de Libreville</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>Gabon</country></affiliation></author><author><name sortKey="Ndouo, Fousseyni S Toure" sort="Ndouo, Fousseyni S Toure" uniqKey="Ndouo F" first="Fousseyni S Toure" last="Ndouo">Fousseyni S Toure Ndouo</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-51216" status="VALID"> <orgName>Centre International de Recherches Médicales de Franceville</orgName> <orgName type="acronym">CIRMF</orgName> <desc> <address> <addrLine>Franceville</addrLine> <country key="GA"></country> </address> </desc> <listRelation> <relation active="#struct-301226" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-301226" type="direct"><org type="institution" xml:id="struct-301226" status="VALID"> <orgName>Centre International de Recherches Médicales de Franceville</orgName> <desc> <address> <country key="GA"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>Gabon</country></affiliation></author></analytic><idno type="DOI">10.1186/1471-2334-12-307</idno><series><title level="j">BMC Infectious Diseases</title><idno type="ISSN">1471-2334</idno><imprint><date type="datePub">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"> <p>BACKGROUND: Malaria remains a major public health problem, due largely to emergence and widespread P. falciparum drug resistance. WHO recommends artemisinine combination based therapy (ACT) to overcome P. falciparum drug resistance, but reports of declining ACT efficacy have been published. A thorough understanding of the molecular bases of P. falciparum resistance to existing drugs is therefore needed. The aims of this study were to analyze the in vitro sensitivity of P. falciparum field isolates from Franceville, Gabon, to chloroquine (CQ), mefloquine (MF), dihydroartemisinine (DHA) and monodesethylamodiaquine (MDAQ), and to investigate polymorphisms associated with drug resistance. METHODS: We conducted a cross-sectional study of 53 field isolates. Field isolates sensitivity to CQ, MF, DHA and MDAQ was assessed using the colorimetric DELI test. The Pfmdr1 codons 86 and 1246, Pfcrt (haplotype codon 72 to 76) and the PfATPAse6 codons 110 and 2694 were analysed by PCR-RFLP. Associations between drug sensitivity and parasite gene polymorphisms were evaluated with the Chi square test, and routine hematological parameters were analyzed with Fisher's exact test implemented with Epinfo software. In all statistical tests, significance was assumed at p<0.05. RESULTS: A total of 46 P. falciparum isolates were successfully cultured in vitro and their sensitivity was tested. The proportions of isolates resistant to CQ, MF and MDAQ were 43.5%, 23.4% and 56.5%, respectively. Some isolates (23.9%) had DHA IC50 values higher than 10 nM. The median IC50 values were 71.67 (interquartile range (IQR, 1-438.2), 6.59 (IQR, 0.08-96), 64.79 (IQR, 0.09-448) and 6.45 nM (IQR, 0.09-23) for CQ, MF, MDAQ and DHA, respectively. The strongest correlation between diminished DHA sensitivity and MF resistance was observed (r2=0.73), followed by correlation between diminished DHA sensitivity and CQ resistance. Cross-resistance between CQ and MF was also observed. The prevalence of the 86Y and 1246Y mutations in Pfmdr1, 76T in Pfcrt, and 110A and 2694T in PfATPase6 was respectively 42% and 17.1%, 97.8%, and 0% and 22.2%. CONCLUSION: These high levels of antimalarial drug resistance in Franceville, Gabon, call for reinforced surveillance of drug efficacy.</p> </div></front></TEI><affiliations><list><country><li>Gabon</li></country></list><tree><country name="Gabon"><noRegion><name sortKey="Zatra, Rafika" sort="Zatra, Rafika" uniqKey="Zatra R" first="Rafika" last="Zatra">Rafika Zatra</name></noRegion><name sortKey="Bisvigou, Ulrick" sort="Bisvigou, Ulrick" uniqKey="Bisvigou U" first="Ulrick" last="Bisvigou">Ulrick Bisvigou</name><name sortKey="Lekana Douki, Jean Bernard" sort="Lekana Douki, Jean Bernard" uniqKey="Lekana Douki J" first="Jean Bernard" last="Lekana-Douki">Jean Bernard Lekana-Douki</name><name sortKey="Lekoulou, Faustin" sort="Lekoulou, Faustin" uniqKey="Lekoulou F" first="Faustin" last="Lekoulou">Faustin Lekoulou</name><name sortKey="Ndouo, Fousseyni S Toure" sort="Ndouo, Fousseyni S Toure" uniqKey="Ndouo F" first="Fousseyni S Toure" last="Ndouo">Fousseyni S Toure Ndouo</name><name sortKey="Ngoungou, Edgard Brice" sort="Ngoungou, Edgard Brice" uniqKey="Ngoungou E" first="Edgard Brice" last="Ngoungou">Edgard Brice Ngoungou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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