Malaria in urban, semi-urban and rural areas of southern of Gabon: comparison of the Pfmdr 1 and Pfcrt genotypes from symptomatic children
Authors: Lady-Charl√®ne Kouna
Jean Bernard Lekana-Douki
Bertrand Mbatchi
Rella Manego-Zoleko
Sydney Maghendji-Nzondo
Larson Boundenga
Ga√´l Mourembou
Didier Raoult
Pierre-Blaise Matsiegui
Fousseyni Toure-Ndouo
Romeo-Karl Imboumy-Limoukou
Journal: Malaria journal (2016)
Discipline: CLINICAL MEDICINE
Keywords: ACT; Children; Gabon; Haplotype; Pfcrt
Affiliations: Unit√© d'Evolution Epid√©miologie R√©sistance Parasitaire (UNEEREP), Centre International de Recherches M√©dicales de Franceville (CIRMF), B.P. 769, Franceville, Gabon., D√©partement de Biologie, Universit√© des Sciences et Techniques de Masuku, BP: 901, Franceville, Gabon., Aix Marseille Universit√©, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France., Centre de recherches M√©dicales de la Ngounie, Fougamou, Gabon., Unit√© d'Evolution Epid√©miologie R√©sistance Parasitaire (UNEEREP), Centre International de Recherches M√©dicales de Franceville (CIRMF), B.P. 769, Franceville, Gabon. ., D√©partement de Parasitologie-Mycologie M√©decine Tropicale, Facult√© de M√©decine, Universit√© des Sciences de la Sant√©, B.P. 4009, Libreville, Gabon. .

Abstract:  Background: Artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) are first- and second-line treatments for uncomplicated Plasmodium falciparum malaria in Gabon. AL remains highly efficacious, but its widespread use has led to molecular selection of the NFD haplotype on Pfmdr1 and K76 in Pfcrt. In this study, plasmodial infection characteristics and the distribution of the Pfmdr1 and Pfcrt genotypes involved in reduced efficacy of artemisinin-based combination therapy (ACT) were investigated in four Gabonese localities. Methods: A cross-sectional study was conducted in the paediatric units of rural (Lastourville and Fougamou), semi-urban (Koula-Moutou) and urban (Franceville) areas. Malaria was diagnosed with the rapid diagnostic test Optimal-IT(¬Æ) and confirmed by blood smear. Pfmdr1 codons 86, 184 and 1246 and Pfcrt codon 76 were genotyped by PCR-RFLP and sequencing. Results: Among 1129 included children, the prevalence of plasmodial infection was 79.5 % at Lastourville, 53.6 % at Fougamou, 36.1 % at Koula-Moutou, and 21.2 % at Franceville. The prevalence was significantly higher among children over 60 months of age in both semi-urban (p = 0.01) and urban (p = 0.004) areas. The prevalence of Pfmdr1 wild-type N86 differed significantly between Lastourville (57.8 %) and Koula-Moutou (45.4 %) (p = 0.039). No difference in 184F-carrying parasites was found between Lastourville (73.8 %), Fougamou (81.6 %), Koula-Moutou (83.2 %), and Franceville (80.6 %) (p = 0.240). The prevalence of wild-type D1246 was significantly different between Lastourville (94.1 %), Koula-Moutou (85.6 %) and Franceville (87.3 %) (p = 0.01). The frequency of wild-type K76 was not significantly different across the four sites: Lastourville (16.5 %), Fougamou (27.8 %), Koula-Moutou (17.4 %), and Franceville (29.4 %) (p = 0.09). The mixed genotypes were only found in Lastourville and Franceville. The NFD, YFD and NYD haplotypes were mainly Lastourville (46.6, 25.8, 14.0 %), Fougamou (45.5, 9.1, 42.4 %), Koula-Moutou (35, 6.7, 40.4 %), and Franceville (40.0, 16.0, 32.0 %). Conclusion: This study shows an increase in the prevalence of childhood plasmodial infection in Gabon according to the low socio-economic level, and a high frequency of markers associated with AL treatment failure. Close monitoring of ACT use is needed. 

Retracted: No

PubPeer comments:
 This paper is part of a set of 9 papers. According to the authors, all papers are related to the same protocol approved under the number 0023 2013 SG CNE by the National Ethics Committee of Gabon. Some of the authors are mentioned in the 9 papers. This protocol seems to cover 2 types of different objectives: -t3 papers describe a study on malaria in children. -t9 papers describe studies dedicated to characterize different new bacteria. **Study on malaria in children:** - 3 papers describe a study in hundreds of febrile and afebriles children. -tBlood samples are taken. -tThe study is performed between 2013 and 2014. **Studies to characterize different new bacteria:** 6 papers describe different protocols done on different participants. -tStools samples have been taken. No blood samples. -t4 papers describe a protocol performed on 1 child only. This is a different child for each paper. All samples have been taken on January 2015. -t1 paper describes a protocol performed on 1 adult only on January 2015 -t1 paper describes a protocol performed on 3 children in Gabon and Senegal in 2016. Can the authors explain how a unique protocol cover 2 different types of studies with 2 objectives so different? -tStudy designs are very different. -tRecruitment periods are different. -tTypes of participants are different -tTypes of sample are different, etcu2026 It seems pretty unusual that a same protocol cover -tblood samples in children to study malaria in 2013. -tand also a stool sample in 1 adult only, 2 years after. Can the authors explain the scope of the protocol Nu00b00023 2013 SG CNE and the approval process by the National Ethics Committee of Gabon for this 2 different type of design ? **Malaria in children u2013 Blood samples (2013-2014)** 1.t[Emerging infectious diseases - Possible role of Rickettsia felis in acute febrile illness among children in Gabon] 2.t[Malaria journal - Malaria in urban, semi-urban and rural areas of southern of Gabon: comparison of the Pfmdr 1 and Pfcrt genotypes from symptomatic children] 3.t[The American journal of tropical medicine and hygiene - Co-circulation of Plasmodium and bacterial DNAs in blood of febrile and afebrile children from urban and rural areas in Gabon] **Description of new bacteria u2013 Stool samples in children (or 1 adult)** 4.t[Current microbiology - Description of Gabonibacter massiliensis gen. nov., sp. nov., a new member of the family porphyromonadaceae isolated from the human gut microbiota] 5.t[New Microbes and New Infections - Taxonogenomics description of Bacillus dakarensis sp. nov., Bacillus sinesaloumensis sp. nov. and Bacillus massiliogabonensis sp. nov., three new species isolated from human stools] 6.t[New microbes and new infections - Noncontiguous finished genome sequence and description of Gabonia massiliensis gen. nov., sp. nov.] 7.t[New microbes and new infections - u201cIntestinimonas gabonensisu201d sp. nov., a new bacterium detected from a Gabonese stool specimen] 8.t[New microbes and new infections - Noncontiguous finished genome sequence and description of Kallipyga gabonensis sp. nov.] 9.t[New microbes and new infections - Discovery of a new species within Bacillus genus in a stool sample from Gabon:u201cBacillus massiliogabonensisu201d sp. nov.] ,