Skip to main content
Top
Published in: Malaria Journal 1/2006

Open Access 01-12-2006 | Research

Molecular monitoring of Plasmodium falciparum resistance to artemisinin in Tanzania

Authors: Kefas Mugittu, Blaise Genton, Hassan Mshinda, Hans Peter Beck

Published in: Malaria Journal | Issue 1/2006

Login to get access

Abstract

Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria, such as sub-Saharan Africa. However, their long-term usefulness in these high transmission areas remains unclear. It has been suggested that documentation of the S769N PfATPase6 mutations may indicate an emergence of artemisinin resistance of Plasmodium falciparum in the field. The present study assessed PfATPase6 mutations (S769N and A623E) in 615 asymptomatic P. falciparum infections in Tanzania but no mutant genotype was detected. This observation suggests that resistance to artemisinin has not yet been selected in Tanzania, supporting the Ministry of Health's decision to adopt artemether+lumefantrine as first-line malaria treatment. The findings recommend further studies to assess PfATPase6 mutations in sentinel sites and verify their usefulness in monitoring emergency of ACT resistance.
Literature
1.
go back to reference The East African Network for Monitoring Antimalarial Treatment (EANMAT): The efficacy of antimalarial monotherapies, sulfadoxine-pyrimethamine and amodiaquine in East Africa: implication for sub-regional policy. Trop Med Int Health. 2003, 8: 860-867. 10.1046/j.1360-2276.2003.01114.x.CrossRef The East African Network for Monitoring Antimalarial Treatment (EANMAT): The efficacy of antimalarial monotherapies, sulfadoxine-pyrimethamine and amodiaquine in East Africa: implication for sub-regional policy. Trop Med Int Health. 2003, 8: 860-867. 10.1046/j.1360-2276.2003.01114.x.CrossRef
2.
go back to reference Talisuna AO, Bloland P, D'Alessandro U: History, dynamics, and public health importance of malaria parasite resistance. Clin Microbiol Rev. 2004, 17: 235-254. 10.1128/CMR.17.1.235-254.2004.PubMedCentralCrossRefPubMed Talisuna AO, Bloland P, D'Alessandro U: History, dynamics, and public health importance of malaria parasite resistance. Clin Microbiol Rev. 2004, 17: 235-254. 10.1128/CMR.17.1.235-254.2004.PubMedCentralCrossRefPubMed
4.
go back to reference Arrow J, Panosian CB, Gelband H, (Eds): Saving lives, buying time: Economics of malaria drugs in an age of resistance. 2004, Washington DC, USA: National Academy Press Arrow J, Panosian CB, Gelband H, (Eds): Saving lives, buying time: Economics of malaria drugs in an age of resistance. 2004, Washington DC, USA: National Academy Press
5.
go back to reference Mugittu K, Ndejembi M, Malisa A, Lemnge M, Premji Z, Mwita A, Nkya W, Kataraihya J, Abdulla S, Beck HP, Mshinda H: Therapeutic efficacy of sulfadoxine-pyrimethamine and prevalence of resistance markers in Tanzania prior to revision of malaria treatment policy: Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase mutations in monitoring in vivo resistance. Am J Trop Med Hyg. 2004, 71: 696-702.PubMed Mugittu K, Ndejembi M, Malisa A, Lemnge M, Premji Z, Mwita A, Nkya W, Kataraihya J, Abdulla S, Beck HP, Mshinda H: Therapeutic efficacy of sulfadoxine-pyrimethamine and prevalence of resistance markers in Tanzania prior to revision of malaria treatment policy: Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase mutations in monitoring in vivo resistance. Am J Trop Med Hyg. 2004, 71: 696-702.PubMed
6.
go back to reference Duffy PE, Sibley CH: Are we losing artemisinin combination therapy already?. Lancet. 2005, 366: 1960-1963. 10.1016/S0140-6736(05)67768-9.CrossRef Duffy PE, Sibley CH: Are we losing artemisinin combination therapy already?. Lancet. 2005, 366: 1960-1963. 10.1016/S0140-6736(05)67768-9.CrossRef
7.
go back to reference Eckstein-Ludwig U, Webb RJ, Van Goethem ID, East JM, Lee AG, Kimura M, O'Neill PM, Bray PG, Ward SA, Krishna S: Artemisinins target the SERCA of Plasmodium falciparum. Nature. 2003, 424: 957-961. 10.1038/nature01813.CrossRefPubMed Eckstein-Ludwig U, Webb RJ, Van Goethem ID, East JM, Lee AG, Kimura M, O'Neill PM, Bray PG, Ward SA, Krishna S: Artemisinins target the SERCA of Plasmodium falciparum. Nature. 2003, 424: 957-961. 10.1038/nature01813.CrossRefPubMed
8.
go back to reference Uhlemann AC, Cameron A, Eckstein-Ludwig U, Fischbarg J, Iserovich P, Zuniga FA, East M, Lee A, Brady L, Haynes RK, Krishna S: A single amino acid residue can determine the sensitivity of SERCAs to artemisinins. Nat Struct Mol Biol. 2005, 12: 628-629. 10.1038/nsmb947.CrossRefPubMed Uhlemann AC, Cameron A, Eckstein-Ludwig U, Fischbarg J, Iserovich P, Zuniga FA, East M, Lee A, Brady L, Haynes RK, Krishna S: A single amino acid residue can determine the sensitivity of SERCAs to artemisinins. Nat Struct Mol Biol. 2005, 12: 628-629. 10.1038/nsmb947.CrossRefPubMed
9.
go back to reference Jambou R, Legrand E, Niang M, Khim N, Lim P, Volney B, Ekala MT, Bouchier C, Esterre P, Fandeur T, Mercereau-Puijalon OS: Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet. 2005, 366: 1960-1963. 10.1016/S0140-6736(05)67787-2.CrossRefPubMed Jambou R, Legrand E, Niang M, Khim N, Lim P, Volney B, Ekala MT, Bouchier C, Esterre P, Fandeur T, Mercereau-Puijalon OS: Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet. 2005, 366: 1960-1963. 10.1016/S0140-6736(05)67787-2.CrossRefPubMed
10.
go back to reference Kachur SP, Black C, Abdulla S, Goodman C: Putting the genie back in the bottle? Availability and presentation of oral artemisinin compounds at retail pharmacies in urban Dar-es-Salaam. Malar J. 2006, 5: 25-10.1186/1475-2875-5-25.PubMedCentralCrossRefPubMed Kachur SP, Black C, Abdulla S, Goodman C: Putting the genie back in the bottle? Availability and presentation of oral artemisinin compounds at retail pharmacies in urban Dar-es-Salaam. Malar J. 2006, 5: 25-10.1186/1475-2875-5-25.PubMedCentralCrossRefPubMed
11.
go back to reference Falade C, Makanga M, Premji Z, Ortmann CE, Stockmeyer M, de Palacios PI: Efficacy and safety of artemether-lumefantrine (Coartem) tablets (six-dose regimen) in African infants and children with acute, uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg. 2005, 99: 459-467. 10.1016/j.trstmh.2004.09.013.CrossRefPubMed Falade C, Makanga M, Premji Z, Ortmann CE, Stockmeyer M, de Palacios PI: Efficacy and safety of artemether-lumefantrine (Coartem) tablets (six-dose regimen) in African infants and children with acute, uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg. 2005, 99: 459-467. 10.1016/j.trstmh.2004.09.013.CrossRefPubMed
12.
go back to reference Price RN, Cassar C, Brockman A, Duraisingh M, van Vugt M, White NJ, Nosten F, Krishna S: The pfmdr1 gene is associated with a multidrug-resistant phenotype in Plasmodium falciparum from the western border of Thailand. Antimicrob Agents Chemother. 1999, 43 (12): 2943-9.PubMedCentralPubMed Price RN, Cassar C, Brockman A, Duraisingh M, van Vugt M, White NJ, Nosten F, Krishna S: The pfmdr1 gene is associated with a multidrug-resistant phenotype in Plasmodium falciparum from the western border of Thailand. Antimicrob Agents Chemother. 1999, 43 (12): 2943-9.PubMedCentralPubMed
13.
go back to reference Duraisingh MT, Cowman AF: Contribution of the pfmdr1 gene to antimalarial drug-resistance. Acta Trop. 2005, 94 (3): 181-90.CrossRefPubMed Duraisingh MT, Cowman AF: Contribution of the pfmdr1 gene to antimalarial drug-resistance. Acta Trop. 2005, 94 (3): 181-90.CrossRefPubMed
14.
go back to reference Afonso A, Hunt P, Cheesman S, Alves AC, Cunha CV, do Rosario V, Cravo P: Malaria parasites can develop stable resistance to artemisinin but lack mutations in candidate genes atp6 (encoding the sarcoplasmic and endoplasmic reticulum Ca2+ ATPase), tctp, mdr1, and cg10. Antimicrob Agents Chemother. 2006, 50: 480-489. 10.1128/AAC.50.2.480-489.2006.PubMedCentralCrossRefPubMed Afonso A, Hunt P, Cheesman S, Alves AC, Cunha CV, do Rosario V, Cravo P: Malaria parasites can develop stable resistance to artemisinin but lack mutations in candidate genes atp6 (encoding the sarcoplasmic and endoplasmic reticulum Ca2+ ATPase), tctp, mdr1, and cg10. Antimicrob Agents Chemother. 2006, 50: 480-489. 10.1128/AAC.50.2.480-489.2006.PubMedCentralCrossRefPubMed
Metadata
Title
Molecular monitoring of Plasmodium falciparum resistance to artemisinin in Tanzania
Authors
Kefas Mugittu
Blaise Genton
Hassan Mshinda
Hans Peter Beck
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2006
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-5-126

Other articles of this Issue 1/2006

Malaria Journal 1/2006 Go to the issue