No polymorphisms in K13-propeller gene associated with artemisinin resistance in Plasmodium falciparum isolated from Brazzaville, Republic of Congo

BMC Infectious Diseases - Tập 18 - Trang 1-6 - 2018
Pembe Issamou Mayengue1,2, Roch Fabien Niama1,2, Dezi Kouhounina Batsimba1, Alida Malonga-Massanga1, Igor Louzolo2, Nadia Claricelle Loukabou Bongolo2, Lucette Macosso2, Reyna Ibara Ottia1, Ghyslain Kimbassa Ngoma1, Louis Régis Dossou-Yovo2,3, Brice Pembet Singana1, Gabriel Ahombo1, Géril Sekangue Obili4, Simon Charles Kobawila1, Henri Joseph Parra2
1Faculté des Sciences et Techniques, Université Marien Ngouabi, Brazzaville, République du Congo
2Laboratoire National de Santé Publique, Brazzaville, République du Congo
3Ecole Normale Supérieure, Université Marien Ngouabi, Brazzaville, République du Congo
4Centre Hospitalier Universitaire de Brazzaville, Brazzaville, République du Congo

Tóm tắt

In the Republic of Congo, artemisinin-based combinations have been recommended for the treatment of uncomplicated malaria since 2006. However, the emergence of resistant parasites again these combinations in Southeast Asia is a threat for the control of this disease, especially in sub-Saharan Africa where the weight of the disease is important. Indeed, polymorphisms in Plasmodium falciparum K13-propeller gene have been involved in variations of drug sensitivity of Plasmodium falciparum to artemisinin-based combinations. The aim of the current study is to determine the prevalence of mutations of this gene in isolates collected in three health centers in Brazzaville. From May 2015 to May 2016, a total of 131, 259 and 416 samples from patients with suspected malaria were collected at the Laboratoire National de Santé Publique, Hôpital de Mfilou, and the CSI «Maman Mboualé» respectively. After DNA isolation, genotyping and sequencing of Plasmodium falciparum K13-propeller were performed in positive Plasmodium falciparum isolates identified after msp-2 gene genotyping. All 806 samples collected were msp-2 genotyped and Plasmodium falciparum infections were confirmed in 287 samples with 43, 85, 159 samples from Laboratoire National de Santé Publique, Hôpital de Mfilou, and the CSI «Maman Mboualé» respectively. Of these 287 msp-2 positives samples, K13-propeller nested PCR products were successfully obtained from 145 (50.52%) isolates and sequences were generated from 127(87.58%) nested products. None of mutations that were associated with ACTs resistance in Southeast Asia were detected on the samples from three different study sites from Brazzaville. However, one mutation type was observed at position 578, where alanine was substituted by serine (A578S) in two isolates (1.57%, 2/127), those from the Hôpital de Mfilou. No mutation was found in isolates from the two other sites. The current study shows a very limited polymorphism in the K13-propeller gene in isolates from the Republic of Congo and K13 polymorphisms associate with ACT resistance are not present in this country. However, permanent and large surveillance of resistant parasite population using K13-propeller gene is recommended.

Tài liệu tham khảo

Ministry of Health and Population. Programme Biennal de Développement Sanitaire 2015-2016. Ministère de la Santé et de la Population, Brazzaville, République du Congo. 2014. Mbongo JA, Ekouya BG, Koulimaya GC, Iloki L. Paludisme Congénital au Centre Hospitalier et Universitaire de Brazzaville : une Étude Épidémiologique de 90 Cas. Health Sci Dis. 2015;16:1–4. Ministry of Health and Population. Politique nationale de lutte contre le paludisme. Ministère de la Santé et de la Population, Brazzaville, République du Congo. 2006. Accessed 4 May 2018. Ndounga M, Tahar R, Casimiro PN, Loumouamou D, Basco LK. Clinical efficacy of artemether lumefantrine in Congolese children with acute uncomplicated falciparum malaria in Brazzaville. Malar Res Treat. 2012;2012:749479. Ndounga M, Mayengue PI, Casimiro PN, Loumouamou D, Basco LK, Ntoumi F, Brasseur P. Artesunate-amodiaquine efficacy in Congolese children with acute uncomplicated falciparum malaria in Brazzaville. Malar J. 2013;12:53. Ndounga M, Mayengue PI, Casimiro PN, Koukouikila-Koussounda F, Bitemo M, Matondo DB, Ndounga DLA, Basco LK, Ntoumi F. Artesunate–amodiaquine versus artemether-lumefantrine for the treatment of acute uncomplicated malaria in Congolese children under 10 years old living in suburban area: a randomized study. Malar J. 2015;14:423. Singana BP, Bogreau H, Matondo BD, Dossou-Yovo LR, Casimiro PN, Mbouka R, Ha Nguyen KY, Pradines B, Basco LK, Ndounga M. Malaria burden and anti-malarial drug efficacy in Owando, northern Congo. Malar J. 2016;15:16. World Health Organizaion. Malaria report. Geneva: World Health Organization; 2015. Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum. Nature. 2014;505:50–5. Conrad MD, Bigira V, Kapisi J, Muhindo M, Kamya MR, Havlir DV, et al. Polymorphisms in K13 and falcipain-2 associated with artemisinin resistance are not prevalent in Plasmodium falciparum isolated from Ugandan children. PLoS One. 2014;9:e105690. Ouattara A, Kone A, Adams M, Fofana B, Maiga AW, Hampton S, et al. Polymorphisms in the K13-propeller gene in artemisinin-susceptible Plasmodium falciparum parasites from Bougoula-Hameau and Bandiagara, Mali. Am J Trop Med Hyg. 2015;92:1202–6. Li J, Chen J, Xie D, Eyi UM, Matesa RA, Ondo Obono MM, et al. Limited artemisinin resistance-associated polymorphisms in Plasmodium falciparum K13-propeller and PfATPase6 gene isolated from Bioko Island, Equatorial Guinea. Int J Parasitol Drugs Drug Resist. 2016;6:54–9. Mita T, Culleton R, Takahashi N, Nakamura M, Tsukahara T, Hunja CW, et al. Little polymorphism at the K13 propeller locus in worldwide Plasmodium falciparum populations prior to the introduction of artemisinin combination therapies. Antimicrob Agents Chemother. 2016;60:3340–7. Koukouikila-Koussounda F, Jeyaraj S, Nguetse CN, Nkonganyi CN, Kokou KC, Etoka-Beka MK, et al. Molecular surveillance of Plasmodium falciparum drug resistance in the republic of Congo: four and nine years after the introduction of artemisinin-based combination therapy. Malar J. 2017;16:155. Ntoumi F, Vouvoungui JC, Ibara R, Landry M, Sidibé A. Malaria burden and case management in the republic of Congo: limited use and application of rapid diagnostic tests results. BMC Public Health. 2013;13:135. Schwartz D. Méthodes statistiques à l'usage des médecins et des biologistes /Troisième édition. Paris: Flammarion Médecine-sciences. 1969; ISBN-2-257-30326-1; http://www.sudoc.fr/005623065. World Health Organization. Bench aids for malaria Microscopy. Geneva. 2009; ISBN-13 9789241547864. Mayengue PI, Ndounga M, Malonga FV, Bitemo M, Ntoumi F. Genetic polymorphism of mérozoïte surface protein-1 and merozoite surface protein-2 in Plasmodium falciparum isolates from Brazzaville, republic of Congo. Malar J. 2011;10:276. Kearse M, Moir R, Wilson A, Stones-Havas S, Cheung M, Sturrock S, et al. Geneious basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics. 2012;28:1647–9. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, et al. Artemisinin resistance in Plasmodium falciparum malaria. J Trop Med. 2009;5:455–67. Straimer J, Gnadig NF, Witkowski B, Amaratunga C, Duru V, Ramadani AP, et al. Drug resistance K13-propeller mutations confer artemisinin resistance in Plasmodium alciparum clinical isolates. Science. 2015;347:428–31. Muwanguzi J, Henriques G, Sawa P, Bousema P, Colin J, Sutherland Beshir K. Lack of K13 mutations in Plasmodium falciparum persisting after artemisinin combination therapy treatment of Kenyan children. Malar J. 2016;15:36. Makaba MD, Kayembe M, Situakibanza HT, Bobanga LC, Nsibu GN, Mvumbi P, et al. Falciparum malaria molecular drug resistance in the Democratic Republic of Congo: a systematic. Malar J. 2015;14:354. Feng J, Li J, Yan H, Feng X, Xia Z. Evaluation of antimalarial resistance marker polymorphism in returned migrant workers in China. Antimicrob Agents Chemother. 2015;59:326–30. Taylor SM, Parobek CM, DeConti DK, Kayentao K, Coulibaly SO, Greenwood BM, et al. Absence of putative artemisinin resistance mutations among plasmodium falciparum in sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis. 2014;211:680–8. Conrad MD, LeClair N, Arinaitwe E, Wanzira H, Kakuru A, Bigira V, et al. Comparative impacts over 5 years of artemisininbasedcombination therapies on Plasmodium falciparum polymorphismsthat modulate drug sensitivity in Ugandan children. J Infect Dis. 2014;210:344–53.