Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola
Tóm tắt
Drug resistance in Plasmodium
falciparum has posed an obstacle to effective treatment and challenges many malaria control programmes in endemic areas. In Angola, until 2003, chloroquine (CQ) was used as first-line therapy for uncomplicated malaria. It was replaced initially by amodiaquine and, in 2006, by artemisinin-based combination therapy (ACT) with artemether-lumefantrine (AL, Coartem®). Efficacy study of ACT, conducted in Angola between 2004 and 2005, showed a baseline efficacy of ≈99 %. 103 malaria patients were enrolled according to WHO proceedings. Patients were followed up with clinical and parasitological evaluations for 28 days, parasite density and identification was evaluated by microscopy, the pfmsp2 were genotyped by nested-PCR, to distinguish parasite recrudescence from new infections; the polymorphisms at codons 86 and 1246 of pfmdr1 gene, and 769 of pfatp6 gene were assessed by PCR–RFLP and sequencing for pfk13-propeller genotype. The cure rate was 91.3 %. The obtained results showed that from 103 patients, 12.6 % (n = 13) still had parasitaemia 1 day after the treatment was finished. On day 0, of the 94 evaluated samples, wild-type alleles were identified in 73.4 % (n = 69) for pfmdr1 N86Y position and only one sample carried the mutant allele (Y) for pfmdr1 1246; 14 % of these samples showed increased pfmdr1 copy number; 100 % (n = 21) had wild-type allele of k13 gene in all the studied positions. These results showed changes in parasite profile susceptibility to AL in comparison to the baseline data from 2002 to 2004 and on the genotyping characteristics; the clinical outcome after treatment with AL did not link a particular genotype with treatment failure; observed changes do not provide sufficient evidence for a treatment policy change, but they suggest that a carefully monitoring is needed in this area.
Tài liệu tham khảo
United Nations: The Millennium Development Goals Report 2014. United Nations 2014.
WHO: World malaria report 2014. Geneva: World Health Organization, 2014.
WHO: Global report on Antimalarial Drug Efficacy and Drug Resistance: 2000–2010. Geneva, World Health Organization, 2010.
WHO. Global plan for artemisinin resistance containment. Geneva: World Health Organization, 2011:93.
ICF International PNC malaria A: Inquérito de Indicadores de Malária em Angola. 2011, 1.
Guthmann JP, Cohuet S, Rigutto C, Fortes F, Saraiva N, Kiguli J, et al. High efficacy of two artemisinin-based combinations (artesunate + amodiaquine and artemether + lumefantrine) in Caala, Central Angola. Am J Trop Med Hyg. 2006;75:143–5.
Guthmann J-P, Ampuero J, Fortes F, van Overmeir C, Gaboulaud V, Tobback S, et al. Antimalarial efficacy of chloroquine, amodiaquine, sulfadoxine-pyrimethamine, and the combinations of amodiaquine + artesunate and sulfadoxine-pyrimethamine + artesunate in Huambo and Bie provinces, central Angola. Trans R Soc Trop Med Hyg. 2005;99:485–92.
WHO. Guidelines for the treatment of malaria. Geneva: World Health Organization, 2010. p. 194.
WHO. Guidelines for treatment of malaria. 3rd edition. Geneva: World Health Organization, 2015.
Hien TT, Thuy-Nhien NT, Phu NH, Boni MF, Thanh NV, Nha-Ca NT, et al. In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam. Malar J. 2012;11:355.
WHO. Emergency Response to artemisinin resistance in the greater Mekong Subregion. Geneva: World Health Organization. 2013. p. 32.
Kamugisha E, Jing S, Minde M, Kataraihya J, Kongola G, Kironde F, et al. Efficacy of artemether-lumefantrine in treatment of malaria among under-fives and prevalence of drug resistance markers in Igombe-Mwanza, north-western Tanzania. Malar J. 2012;11:58.
Sisowath C, Ferreira PE, Bustamante LY, Dahlström S, Mårtensson A, Björkman A, et al. The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa. Trop Med Int Health. 2007;12:736–42.
Labadie-Bracho M, Adhin MR. Increased pfmdr1 copy number in Plasmodium falciparum isolates from Suriname. Trop Med Int Health. 2013;18:796–9.
Chavchich M, Gerena L, Peters J, Chen N, Cheng Q, Kyle DE. Role of pfmdr1 amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum. Antimicrob Agents Chemother. 2010;54:2455–64.
Tanabe K, Zakeri S, Palacpac NMQ, Afsharpad M, Randrianarivelojosia M, Kaneko A, et al. Spontaneous mutations in the plasmodium falciparum sarcoplasmic/endoplasmic reticulum Ca2+ -ATPase (PfATP6) gene among geographically widespread parasite populations unexposed to artemisinin-based combination therapies. Antimicrob Agents Chemother. 2011;55:94–100.
Jambou R, Martinelli A, Pinto J, Gribaldo S, Legrand E, Niang M, et al. Geographic structuring of the Plasmodium falciparum sarco(endo)plasmic reticulum Ca2+ ATPase (PfSERCA) gene diversity. PLoS One. 2010;5:e9424.
Isozumi R, Uemura H, Kimata I, Ichinose Y, Logedi J, Omar AH, et al. Novel mutations in K13 propeller gene of artemisinin-resistant Plasmodium falciparum. Emerg Infect Dis. 2015;21:490–2.
Straimer J, Gnadig NF, Witkowski B, Amaratunga C, Duru V, Ramadani AP, et al. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science. 2014;347:428–31.
Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois A-C, Khim N, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2013;505:50–5.
WHO. Methods for surveillance of antimalarial drug efficacy. Geneva: World Health Organization, 2009; p. 90.
Bailey JW, Williams J, Bain BJ, Parker-Williams J, Chiodini PL, Guideline: the laboratory diagnosis of malaria. Br J Haematol. 2012;163:573–80.
Choi E-H, Lee SK, Ihm C, Sohn Y-H. Rapid DNA extraction from dried blood spots on filter paper: potential applications in biobanking. Osong Public Health Res Perspect. 2014;5:351–7.
McCabe ER. Utility of PCR for DNA analysis from dried blood spots on filter paper blotters. PCR Methods Appl. 1991;1:99–106.
Fortes F, Dimbu R, Figueiredo P, Neto Z, do Rosário VE, Lopes D. Evaluation of prevalence’s of pfdhfr and pfdhps mutations in Angola. Malar J. 2011;10:22.
Hue NT, Chan NDH, Phong PT, Linh NTT, Giang ND. Extraction of human genomic DNA from dried blood spots and hair roots. Int J Biosci Biochem Bioinform. 2012;2:21–6.
Snounou G, Viriyakosol S, Jarra W, Thaithong S, Brown KN. Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections. Mol Biochem Parasitol. 1993;58:283–92.
Singh B, Bobogare A, Cox-Singh J, Snounou G, Abdullah MS, Rahman HA, et al. A genus- and species-specific nested polymerase chain reaction malaria detection assay for epidemiologic studies. Am J Trop Med Hyg. 1999;60:687–92.
Rouse P, Mkulama MA, Thuma PE, Mharakurwa S. Distinction of Plasmodium falciparum recrudescence and re-infection by MSP2 genotyping: a caution about unstandardized classification criteria. Malar J. 2008;7:185.
Mugittu K, Adjuik M, Snounou G, Ntoumi F, Taylor W, Mshinda H, et al. Molecular genotyping to distinguish between recrudescents and new infections in treatment trials of Plasmodium falciparum malaria conducted in Sub-Saharan Africa: adjustment of parasitological outcomes and assessment of genotyping effectiveness. Trop Med Int Health. 2006;11:1350–9.
Eshetu T, Berens-Riha N, Fekadu S, Tadesse Z, Gürkov R, Hölscher M, et al. Different mutation patterns of Plasmodium falciparum among patients in Jimma University Hospital, Ethiopia. Malar J. 2010;9:226.
Figueiredo P, Benchimol C, Lopes D, Bernardino L, do Rosario VE, Varandas L et al. Prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in Luanda, Angola. Malar J 2008; 7:236.
Wallace RB: Principles of gene manipulation. An introduction to genetic engineering. Studies in Microbiology. Volume 33; 1981.
Ferreira ID, Do Rosário VE, Cravo PVL. Real-time quantitative PCR with SYBR Green I detection for estimating copy numbers of nine drug resistance candidate genes in Plasmodium falciparum. Malar J. 2006;5:1.
Mens PF, Sawa P, van Amsterdam SM, Versteeg I, Omar SA, Schallig HDFH, et al. A randomized trial to monitor the efficacy and effectiveness by QT-NASBA of artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment and transmission control of uncomplicated Plasmodium falciparum malaria in western Kenya. Malar J. 2008;7:237.
Adjei GO, Kurtzhals JA, Rodrigues OP, Alifrangis M, Hoegberg LC, Kitcher ED, et al. Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with 1 year follow-up. Malar J. 2008;7:127.
Espié E, Lima A, Atua B, Dhorda M, Flévaud L, Sompwe EM, et al. Efficacy of fixed-dose combination artesunate-amodiaquine versus artemether-lumefantrine for uncomplicated childhood Plasmodium falciparum malaria in Democratic Republic of Congo: a randomized non-inferiority trial. Malar J. 2012;11:174.
Mita T, Tanabe K. Evolution of Plasmodium falciparum drug resistance: implications for the development and containment of artemisinin resistance. Jpn J Infect Dis. 2012;65:465–75.
Plucinski MM, Talundzic E, Morton L, Dimbu PR, Macaia AP, Fortes F, et al. Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for treatment of uncomplicated malaria in children in Zaire and Uíge Provinces, angola. Antimicrob Agents Chemother. 2015;59:437–43.
Tine RCK, Faye B, Sylla K, Ndiaye JL, Ndiaye M, Sow D, et al. Efficacy and tolerability of a new formulation of artesunate-mefloquine for the treatment of uncomplicated malaria in adult in Senegal: open randomized trial. Malar J. 2012;11:416.
Venkatesan M, Gadalla NB, Stepniewska K, Dahal P, Nsanzabana C, Moriera C, et al. Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine. Am J Trop Med Hyg. 2014;91:833–43.
Fançony C, Gamboa D, Sebastião Y, Hallett R, Sutherland C, Sousa-Figueiredo JC, et al. Various pfcrt and pfmdr1 genotypes of Plasmodium falciparum cocirculate with P. malariae, P. ovale spp., and P. vivax in Northern Angola. Antimicrob Agents Chemother. 2012;56:5271–7.
Menegon M, Pearce RJ, Inojosa WO, Pisani V, Abel PM, Matondo A, et al. Monitoring for multidrug-resistant Plasmodium falciparum isolates and analysis of pyrimethamine resistance evolution in Uige province, Angola. Trop Med Int Health. 2009;14:1251–7.
Sisowath C, Strömberg J, Mårtensson A, Msellem M, Obondo C, Björkman A, et al. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis. 2005;191:1014–7.
Conrad MD, LeClair N, Arinaitwe E, Wanzira H, Kakuru A, Bigira V, et al. Comparative impacts over 5 years of artemisinin-based combination therapies on Plasmodium falciparum polymorphisms that modulate drug sensitivity in Ugandan children. J Infect Dis. 2014;210:344–53.
Mobula L, Lilley B, Tshefu AK, Rosenthal PJ. Resistance-mediating polymorphisms in Plasmodium falciparum infections in Kinshasa, Democratic Republic of the Congo. Am J Trop Med Hyg. 2009;80:555–8.
Price RN, Cassar C, Brockman A, Duraisingh M, van Vugt M, White NJ, et al. The pfmdr1 gene is associated with a multidrug-resistant phenotype in Plasmodium falciparum from the western border of Thailand. Antimicrob Agents Chemother. 1999;43:2943–9.
Escobar C, Pateira S, Lobo E, Lobo L, Teodosio R, Dias F, et al. Polymorphisms in Plasmodium falciparum K13-Propeller in Angola and Mozambique after the Introduction of the ACTs. PLoS One. 2015;10:e0119215.
Witkowski B, Nicolau M-L, Soh PN, Iriart X, Menard S, Alvarez M, et al. Plasmodium falciparum isolates with increased pfmdr1 copy number circulate in West Africa. Antimicrob Agents Chemother. 2010;54:3049–51.
Menard S, Morlais I, Tahar R, Sayang C, Mayengue PI, Iriart X, et al. Molecular monitoring of Plasmodium falciparum drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: implications for the future. Malar J. 2012;11:113.
Vaughan-Williams CH, Raman J, Raswiswi E, Immelman E, Reichel H, Gate K, et al. Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study. Malar J. 2012;11:434.