ChloroquineV1, France, Analysis, bibRecord, 000142

Molecular epidemiology of drug-resistant Plasmodium falciparum in Benguela province, Angola

Identifieur interne : 000142 ( France/Analysis ); précédent : 000141; suivant : 000143

Molecular epidemiology of drug-resistant Plasmodium falciparum in Benguela province, Angola

Auteurs : Vincent Foumane Ngane [Cameroun] ; Joseph Allico Djaman [Côte d'Ivoire] ; Cécile Culeux [France] ; Nathalie Piette [France] ; Pierre Carnevale [Angola] ; Patrick Besnard [Angola] ; Filomeno Fortes [Angola] ; Leonardo K. Basco [France] ; Rachida Tahar [France]

Source :

Malaria Journal [ 1475-2875 ] ; 2015-03-14.

RBID : Hal:hal-01217921

English descriptors

mix :
- AMODIAQUINE, Antifolate drugs, CHLOROQUINE, Drug resistance, GENE, LUANDA, LUMEFANTRINE, MALARIA, Molecular markers, NORTHERN ANGOLA, PFCRT, PFDHPS MUTATIONS, Plasmodium falciparum, SULFADOXINE-PYRIMETHAMINE.

Abstract

Background: The malaria situation has been worsening in Angola, partly due to armed conflict until the recent past and drug-resistant Plasmodium falciparum. Malaria transmission is heterogeneous within the country, and data on drug-resistant malaria in different parts of the country are incomplete. The aim of the present study was to evaluate resistance to 4-aminoquinolines and antifolate drugs in P. falciparum isolates collected in Benguela province, central Angola, using molecular markers. Methods: Fingerprick capillary blood was collected from asymptomatic children aged less than 15 years old during a household survey in and around Balombo town in 2010–2011. Samples were screened for P. falciparum by nested PCR. Molecular markers (P. falciparum dihydrofolate reductase [pfdhfr], P. falciparum dihydropteroate synthase [pfdhps], P. falciparum chloroquine resistance transporter [pfcrt], and P. falciparum multidrug-resistance gene 1 [pfmdr1]) were sequenced to determine the key codons associated with drug resistance. Results: A total of 60 blood samples were positive for P. falciparum. Most isolates with successful PCR amplification had mutant pfdhfr alleles, with either double mutant AICNI (69%) or triple mutant AIRNI (21%) haplotypes. A16V, S108T, and I164L substitutions were not found. Many of the isolates were carriers of either SGKAA (60%) or AGKAA (27%) pfdhps haplotype. K540E substitution was absent. There were only two pfcrt haplotypes: wild-type CVMNK (11%) and mutant CVIET (89%). Wild-type pfmdr1 NYSND haplotype was found in 19% of the isolates, whereas single mutant pfmdr1 YYSND and NFSND haplotypes occurred in 48% and 11%, respectively. Double mutant pfmdr1 haplotypes (YFSND and YYSNY) occurred rarely. Conclusions: The results suggest that the high prevalence of mutant pfcrt CVIET haplotype is in agreement with low clinical efficacy of chloroquine observed in earlier studies and that the double pfdhfr mutant AICNI and single pfdhps mutant SGKAA are currently the predominant haplotypes associated with antifolate resistance in Benguela province. The hallmark of clinical resistance observed in East Africa, i.e. triple pfdhfr mutant haplotype (AIRNI) and double pfdhps mutant haplotype (SGEAA), was absent. These molecular findings need to be further evaluated in parallel with clinical studies, in particular with the efficacy of intermittent preventive treatment using sulphadoxine-pyrimethamine in pregnant women and artesunate-amodiaquine for uncomplicated malaria.

Url:

https://hal-amu.archives-ouvertes.fr/hal-01217921

DOI: 10.1186/s12936-015-0634-2

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Hal, to step Corpus: 000163
to stream Hal, to step Curation: 000163
to stream Hal, to step Checkpoint: 000099
to stream Main, to step Merge: 000E53
to stream Main, to step Curation: 000E52
to stream Main, to step Exploration: 000E52
to stream France, to step Extraction: 000142

Links to Exploration step

Hal:hal-01217921

Le document en format XML

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<country>France</country>
</affiliation>
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<author><name sortKey="Carnevale, Pierre" sort="Carnevale, Pierre" uniqKey="Carnevale P" first="Pierre" last="Carnevale">Pierre Carnevale</name>
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          <desc>            <address>              <country key="FR"></country>
            </address>
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</tutelle>
</tutelles>
</hal:affiliation>
<country>Angola</country>
</affiliation>
</author>
<author><name sortKey="Besnard, Patrick" sort="Besnard, Patrick" uniqKey="Besnard P" first="Patrick" last="Besnard">Patrick Besnard</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-439701" status="INCOMING">          <orgName>Malaria Control Programme</orgName>
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          <desc>            <address>              <country key="FR"></country>
            </address>
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</tutelles>
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<country>Angola</country>
</affiliation>
</author>
<author><name sortKey="Fortes, Filomeno" sort="Fortes, Filomeno" uniqKey="Fortes F" first="Filomeno" last="Fortes">Filomeno Fortes</name>
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          <desc>            <address>              <country key="AO"></country>
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</tutelles>
</hal:affiliation>
<country>Angola</country>
</affiliation>
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<author><name sortKey="Basco, Leonardo K" sort="Basco, Leonardo K" uniqKey="Basco L" first="Leonardo K" last="Basco">Leonardo K. Basco</name>
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          <idno type="RNSR">200817431S</idno>
          <orgName>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes</orgName>
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            <ref type="url">http://www.mediterranee-infection.com/</ref>
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<country>France</country>
<placeName><settlement type="city">Marseille</settlement>
<region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region>
</placeName>
<orgName type="university">Université d'Aix-Marseille</orgName>
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</author>
<author><name sortKey="Tahar, Rachida" sort="Tahar, Rachida" uniqKey="Tahar R" first="Rachida" last="Tahar">Rachida Tahar</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-134260" status="OLD">          <idno type="IdRef">180320637</idno>
          <idno type="ISNI">0000 0004 0508 7272 </idno>
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          <orgName>Mère et enfant face aux infections tropicales</orgName>
          <orgName type="acronym">MERIT - UMR_D 216</orgName>
          <date type="start">2014-01-01</date>
          <date type="end">2019-12-31</date>
          <desc>            <address>              <addrLine>Faculté de pharmacie - Laboratoire de parasitologie4 avenue de l'Observatoire 75270 Paris cedex 6</addrLine>
              <country key="FR"></country>
            </address>
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          <orgName type="acronym">IRD</orgName>
          <desc>            <address>              <addrLine>SiègeLe Sextant 44, bd de DunkerqueCS 9000913572 Marseille cedex 02</addrLine>
              <country key="FR"></country>
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            <ref type="url">http://www.ird.fr/</ref>
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<tutelle name="UMR_D 216" active="#struct-301664" type="direct"><org type="institution" xml:id="struct-301664" status="OLD">          <idno type="IdRef">026404788</idno>
          <idno type="ISNI">0000 0001 2188 0914 </idno>
          <orgName>Université Paris Descartes - Paris 5</orgName>
          <orgName type="acronym">UPD5</orgName>
          <date type="start">1971-01-01</date>
          <date type="end">2019-12-31</date>
          <desc>            <address>              <addrLine>12, rue de l'École de Médecine - 75270 Paris cedex 06</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.parisdescartes.fr/</ref>
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        </org>
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<country>France</country>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.1186/s12936-015-0634-2</idno>
<series><title level="j">Malaria Journal</title>
<idno type="ISSN">1475-2875</idno>
<imprint><date type="datePub">2015-03-14</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>AMODIAQUINE</term>
<term>Antifolate drugs</term>
<term>CHLOROQUINE</term>
<term>Drug resistance</term>
<term>GENE</term>
<term>LUANDA</term>
<term>LUMEFANTRINE</term>
<term>MALARIA</term>
<term>Molecular markers</term>
<term>NORTHERN ANGOLA</term>
<term>PFCRT</term>
<term>PFDHPS MUTATIONS</term>
<term>Plasmodium falciparum</term>
<term>SULFADOXINE-PYRIMETHAMINE</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en">              <p>Background: The malaria situation has been worsening in Angola, partly due to armed conflict until the recent past and drug-resistant Plasmodium falciparum. Malaria transmission is heterogeneous within the country, and data on drug-resistant malaria in different parts of the country are incomplete. The aim of the present study was to evaluate resistance to 4-aminoquinolines and antifolate drugs in P. falciparum isolates collected in Benguela province, central Angola, using molecular markers. Methods: Fingerprick capillary blood was collected from asymptomatic children aged less than 15 years old during a household survey in and around Balombo town in 2010–2011. Samples were screened for P. falciparum by nested PCR. Molecular markers (P. falciparum dihydrofolate reductase [pfdhfr], P. falciparum dihydropteroate synthase [pfdhps], P. falciparum chloroquine resistance transporter [pfcrt], and P. falciparum multidrug-resistance gene 1 [pfmdr1]) were sequenced to determine the key codons associated with drug resistance. Results: A total of 60 blood samples were positive for P. falciparum. Most isolates with successful PCR amplification had mutant pfdhfr alleles, with either double mutant AICNI (69%) or triple mutant AIRNI (21%) haplotypes. A16V, S108T, and I164L substitutions were not found. Many of the isolates were carriers of either SGKAA (60%) or AGKAA (27%) pfdhps haplotype. K540E substitution was absent. There were only two pfcrt haplotypes: wild-type CVMNK (11%) and mutant CVIET (89%). Wild-type pfmdr1 NYSND haplotype was found in 19% of the isolates, whereas single mutant pfmdr1 YYSND and NFSND haplotypes occurred in 48% and 11%, respectively. Double mutant pfmdr1 haplotypes (YFSND and YYSNY) occurred rarely. Conclusions: The results suggest that the high prevalence of mutant pfcrt CVIET haplotype is in agreement with low clinical efficacy of chloroquine observed in earlier studies and that the double pfdhfr mutant AICNI and single pfdhps mutant SGKAA are currently the predominant haplotypes associated with antifolate resistance in Benguela province. The hallmark of clinical resistance observed in East Africa, i.e. triple pfdhfr mutant haplotype (AIRNI) and double pfdhps mutant haplotype (SGEAA), was absent. These molecular findings need to be further evaluated in parallel with clinical studies, in particular with the efficacy of intermittent preventive treatment using sulphadoxine-pyrimethamine in pregnant women and artesunate-amodiaquine for uncomplicated malaria.</p>
            </div>
</front>
</TEI>
<affiliations><list><country><li>Angola</li>
<li>Cameroun</li>
<li>Côte d'Ivoire</li>
<li>France</li>
</country>
<region><li>Provence-Alpes-Côte d'Azur</li>
</region>
<settlement><li>Marseille</li>
</settlement>
<orgName><li>Université d'Aix-Marseille</li>
</orgName>
</list>
<tree><country name="Cameroun"><noRegion><name sortKey="Foumane Ngane, Vincent" sort="Foumane Ngane, Vincent" uniqKey="Foumane Ngane V" first="Vincent" last="Foumane Ngane">Vincent Foumane Ngane</name>
</noRegion>
</country>
<country name="Côte d'Ivoire"><noRegion><name sortKey="Djaman, Joseph Allico" sort="Djaman, Joseph Allico" uniqKey="Djaman J" first="Joseph Allico" last="Djaman">Joseph Allico Djaman</name>
</noRegion>
</country>
<country name="France"><noRegion><name sortKey="Culeux, Cecile" sort="Culeux, Cecile" uniqKey="Culeux C" first="Cécile" last="Culeux">Cécile Culeux</name>
</noRegion>
<name sortKey="Basco, Leonardo K" sort="Basco, Leonardo K" uniqKey="Basco L" first="Leonardo K" last="Basco">Leonardo K. Basco</name>
<name sortKey="Piette, Nathalie" sort="Piette, Nathalie" uniqKey="Piette N" first="Nathalie" last="Piette">Nathalie Piette</name>
<name sortKey="Tahar, Rachida" sort="Tahar, Rachida" uniqKey="Tahar R" first="Rachida" last="Tahar">Rachida Tahar</name>
</country>
<country name="Angola"><noRegion><name sortKey="Carnevale, Pierre" sort="Carnevale, Pierre" uniqKey="Carnevale P" first="Pierre" last="Carnevale">Pierre Carnevale</name>
</noRegion>
<name sortKey="Besnard, Patrick" sort="Besnard, Patrick" uniqKey="Besnard P" first="Patrick" last="Besnard">Patrick Besnard</name>
<name sortKey="Fortes, Filomeno" sort="Fortes, Filomeno" uniqKey="Fortes F" first="Filomeno" last="Fortes">Filomeno Fortes</name>
</country>
</tree>
</affiliations>
</record>

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Molecular epidemiology of drug-resistant Plasmodium falciparum in Benguela province, Angola

Molecular epidemiology of drug-resistant Plasmodium falciparum in Benguela province, Angola

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