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Molecular surveillance of Plasmodium falciparum drug resistance in the Republic of Congo: four and nine years after the introduction of artemisinin-based combination therapy.

Abstract Resistance to anti-malarial drugs hinders efforts on malaria elimination and eradication. Following the global spread of chloroquine-resistant parasites, the Republic of Congo adopted artemisinin-based combination therapy (ACT) in 2006 as a first-line treatment for uncomplicated malaria. To assess the impacts after implementation of ACT, a molecular surveillance for anti-malarial drug resistance was conducted in Congo 4 and 9 years after the introduction of ACT.
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Authors

Mayor MeshTerms
Keywords

ACT

Anti-malarial resistance

Malaria

Pfatp6

Pfcrt

Pfk13

Pfmdr1

Plasmodium falciparum

Republic of Congo

Journal Title malaria journal
Publication Year Start




PMID- 28420403
OWN - NLM
STAT- In-Process
DA  - 20170419
LR  - 20170423
IS  - 1475-2875 (Electronic)
IS  - 1475-2875 (Linking)
VI  - 16
IP  - 1
DP  - 2017 Apr 19
TI  - Molecular surveillance of Plasmodium falciparum drug resistance in the Republic
      of Congo: four and nine years after the introduction of artemisinin-based
      combination therapy.
PG  - 155
LID - 10.1186/s12936-017-1816-x [doi]
AB  - BACKGROUND: Resistance to anti-malarial drugs hinders efforts on malaria
      elimination and eradication. Following the global spread of chloroquine-resistant
      parasites, the Republic of Congo adopted artemisinin-based combination therapy
      (ACT) in 2006 as a first-line treatment for uncomplicated malaria. To assess the 
      impacts after implementation of ACT, a molecular surveillance for anti-malarial
      drug resistance was conducted in Congo 4 and 9 years after the introduction of
      ACT. METHODS: Blood samples of 431 febrile children aged 1-10 years were utilized
      from two previous studies conducted in 2010 (N = 311) and 2015 (N = 120). All
      samples were screened for malaria parasites using nested PCR. Direct sequencing
      was used to determine the frequency distribution of genetic variants in the
      anti-malarial drug-resistant Plasmodium falciparum genes (Pfcrt, Pfmdr1, Pfatp6, 
      Pfk13) in malaria-positive isolates. RESULTS: One-hundred and nineteen (N = 70
      from 2010 and N = 49 from 2015) samples were positive for P. falciparum. A
      relative decrease in the proportion of chloroquine-resistant haplotype (CVIET)
      from 100% in 2005, 1 year before the introduction and implementation of ACT in
      2006, to 98% in 2010 to 71% in 2015 was observed. Regarding the multidrug
      transporter gene, a considerable reduction in the frequency of the mutations N86Y
      (from 73 to 27%) and D1246Y (from 22 to 0%) was observed. However, the prevalence
      of the Y184F mutation remained stable (49% in 2010 compared to 54% in 2015).
      Isolates carrying the Pfatp6 H243Y was 25% in 2010 and this frequency was reduced
      to null in 2015. None of the parasites harboured the Pfk13 mutations associated
      with prolonged artemisinin clearance in Southeast Asia. Nevertheless, 13 new
      Pfk13 variants are reported among the investigated isolates. CONCLUSION: The
      implementation of ACT has led to the decline in prevalence of
      chloroquine-resistant parasites in the Republic of Congo. However, the constant
      prevalence of the PfMDR1 Y184F mutation, associated with lumefantrine
      susceptibility, indicate a selective drug pressure still exists. Taken together, 
      this study could serve as the basis for epidemiological studies monitoring the
      distribution of molecular markers of artemisinin resistance in the Republic of
      Congo.
FAU - Koukouikila-Koussounda, Felix
AU  - Koukouikila-Koussounda F
AD  - Fondation Congolaise pour la Recherche Medicale (FCRM), Brazzaville, Republic of 
      Congo.
FAU - Jeyaraj, Sankarganesh
AU  - Jeyaraj S
AD  - Institute of Tropical Medicine, University of Tubingen, Tubingen, Germany.
FAU - Nguetse, Christian N
AU  - Nguetse CN
AD  - Institute of Tropical Medicine, University of Tubingen, Tubingen, Germany.
FAU - Nkonganyi, Charles Nchotebah
AU  - Nkonganyi CN
AD  - Institute of Tropical Medicine, University of Tubingen, Tubingen, Germany.
FAU - Kokou, Kossiwa Clarisse
AU  - Kokou KC
AD  - Institute of Tropical Medicine, University of Tubingen, Tubingen, Germany.
FAU - Etoka-Beka, Mandingha K
AU  - Etoka-Beka MK
AD  - Fondation Congolaise pour la Recherche Medicale (FCRM), Brazzaville, Republic of 
      Congo.
FAU - Ntoumi, Francine
AU  - Ntoumi F
AD  - Fondation Congolaise pour la Recherche Medicale (FCRM), Brazzaville, Republic of 
      Congo.
AD  - Institute of Tropical Medicine, University of Tubingen, Tubingen, Germany.
FAU - Velavan, Thirumalaisamy P
AU  - Velavan TP
AD  - Fondation Congolaise pour la Recherche Medicale (FCRM), Brazzaville, Republic of 
      Congo. [email protected]
AD  - Institute of Tropical Medicine, University of Tubingen, Tubingen, Germany.
      [email protected]
AD  - Duy Tan University, Da Nang, Vietnam. [email protected]
AD  - Vietnamese-German Centre for Medical Research, Hanoi, Vietnam.
      [email protected]
LA  - eng
PT  - Journal Article
DEP - 20170419
PL  - England
TA  - Malar J
JT  - Malaria journal
JID - 101139802
PMC - PMC5395861
OTO - NOTNLM
OT  - ACT
OT  - Anti-malarial resistance
OT  - Malaria
OT  - Pfatp6
OT  - Pfcrt
OT  - Pfk13
OT  - Pfmdr1
OT  - Plasmodium falciparum
OT  - Republic of Congo
EDAT- 2017/04/20 06:00
MHDA- 2017/04/20 06:00
CRDT- 2017/04/20 06:00
PHST- 2017/02/16 [received]
PHST- 2017/04/09 [accepted]
AID - 10.1186/s12936-017-1816-x [doi]
AID - 10.1186/s12936-017-1816-x [pii]
PST - epublish
SO  - Malar J. 2017 Apr 19;16(1):155. doi: 10.1186/s12936-017-1816-x.

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