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Published in: Malaria Journal 1/2011

Open Access 01-12-2011 | Research

Detection of high levels of mutations involved in anti-malarial drug resistance in Plasmodium falciparum and Plasmodium vivax at a rural hospital in southern Ethiopia

Authors: Patricia Mula, Amalia Fernández-Martínez, Aida de Lucio, Jose Manuel Ramos, Francisco Reyes, Vicenta González, Agustín Benito, Pedro Berzosa

Published in: Malaria Journal | Issue 1/2011

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Abstract

Background

In Ethiopia, malaria is caused by Plasmodium falciparum and Plasmodium vivax, and anti-malarial drug resistance is the most pressing problem confronting control of the disease. Since co-infection by both species of parasite is common and sulphadoxine-pyrimethamine (SP) has been intensively used, resistance to these drugs has appeared in both P. falciparum and P. vivax populations. This study was conducted to assess the prevalence of anti-malarial drug resistance in P. falciparum and P. vivax isolates collected at a rural hospital in southern Ethiopia.

Methods

A total of 1,147 patients with suspected malaria were studied in different months across the period 2007-2009. Plasmodium falciparum dhfr and dhps mutations and P. vivax dhfr polymorphisms associated with resistance to SP, as well as P. falciparum pfcrt and pfmdr1 mutations conferring chloroquine resistance, were assessed.

Results

PCR-based diagnosis showed that 125 of the 1147 patients had malaria. Of these, 52.8% and 37.6% of cases were due to P. falciparum and P. vivax respectively. A total of 10 cases (8%) showed co-infection by both species and two cases (1.6%) were infected by Plasmodium ovale. Pfdhfr triple mutation and pfdhfr/pfdhps quintuple mutation occurred in 90.8% (95% confidence interval [CI]: 82.2%-95.5%) and 82.9% (95% CI: 72.9%-89.7%) of P. falciparum isolates, respectively. Pfcrt T76 was observed in all cases and pfmdr1 Y86 and pfmdr1 Y1246 in 32.9% (95% CI: 23.4%-44.15%) and 17.1% (95% CI: 10.3-27.1%), respectively. The P. vivax dhfr core mutations, N117 and R58, were present in 98.2% (95% CI: 89.4-99.9%) and 91.2% (95% CI: 80.0-96.7%), respectively.

Conclusion

Current molecular data show an extraordinarily high frequency of drug-resistance mutations in both P. falciparum and P. vivax in southern Ethiopia. Urgent surveillance of the emergence and spread of resistance is thus called for. The level of resistance indicates the need for implementation of entire population access to the new first-line treatment with artemether-lumefantrine, accompanied by government monitoring to prevent the emergence of resistance to this treatment.
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Literature
1.
go back to reference WHO: World Malaria Report 2009. 2009, Geneva: World Health Organization WHO: World Malaria Report 2009. 2009, Geneva: World Health Organization
2.
go back to reference McMichael AJ, Woodruff RE, Hales S: Climate change and human health: present and future risks. Lancet. 2006, 367: 859-869. 10.1016/S0140-6736(06)68079-3.CrossRefPubMed McMichael AJ, Woodruff RE, Hales S: Climate change and human health: present and future risks. Lancet. 2006, 367: 859-869. 10.1016/S0140-6736(06)68079-3.CrossRefPubMed
3.
go back to reference WHO: World Malaria Report 2008. 2008, Geneva: World Health Organization WHO: World Malaria Report 2008. 2008, Geneva: World Health Organization
4.
go back to reference Federal Democratic Republic of Ethiopia MoH: Guideline for malaria epidemic prevention and control in Ethiopia. 2004, Addis Ababa, Ethiopia Federal Democratic Republic of Ethiopia MoH: Guideline for malaria epidemic prevention and control in Ethiopia. 2004, Addis Ababa, Ethiopia
5.
go back to reference Federal Democratic Republic of Ethiopia MoH: National Five Year Strategic Plan for Malaria Prevention and Control in Ethiopia. 2006, Addis Ababa, Ethiopia Federal Democratic Republic of Ethiopia MoH: National Five Year Strategic Plan for Malaria Prevention and Control in Ethiopia. 2006, Addis Ababa, Ethiopia
6.
go back to reference Abeku TA, van Oortmarssen GJ, Borsboom G, De Vlas SJ, Habbema JD: Spatial and temporal variations of malaria epidemic risk in Ethiopia: factors involved and implications. Acta Trop. 2003, 87: 331-340. 10.1016/S0001-706X(03)00123-2.CrossRefPubMed Abeku TA, van Oortmarssen GJ, Borsboom G, De Vlas SJ, Habbema JD: Spatial and temporal variations of malaria epidemic risk in Ethiopia: factors involved and implications. Acta Trop. 2003, 87: 331-340. 10.1016/S0001-706X(03)00123-2.CrossRefPubMed
7.
go back to reference Tulu AN: The ecology of health and disease in Ethiopia. Malaria. Edited by: Zein Ahmed Z, Kloos H. 1993, Westview Press, 341-352. Tulu AN: The ecology of health and disease in Ethiopia. Malaria. Edited by: Zein Ahmed Z, Kloos H. 1993, Westview Press, 341-352.
8.
go back to reference Jima D: The 2003 malaria situation in Ethiopia. Proceedings of the Panel Discussion on the 2003 Malaria Epidemics in Ethiopia. 2004, Addis Ababa, Ethiopia Jima D: The 2003 malaria situation in Ethiopia. Proceedings of the Panel Discussion on the 2003 Malaria Epidemics in Ethiopia. 2004, Addis Ababa, Ethiopia
9.
go back to reference Deressa W, Ali A, Enqusellassie F: Self-treatment of malaria in rural communities, Butajira, southern Ethiopia. Bull World Health Organ. 2003, 81: 261-268.PubMedCentralPubMed Deressa W, Ali A, Enqusellassie F: Self-treatment of malaria in rural communities, Butajira, southern Ethiopia. Bull World Health Organ. 2003, 81: 261-268.PubMedCentralPubMed
10.
go back to reference Zhou G, Minakawa N, Githeko AK, Yan G: Association between climate variability and malaria epidemics in the East African highlands. Proc Natl Acad Sci USA. 2004, 101: 2375-2380. 10.1073/pnas.0308714100.PubMedCentralCrossRefPubMed Zhou G, Minakawa N, Githeko AK, Yan G: Association between climate variability and malaria epidemics in the East African highlands. Proc Natl Acad Sci USA. 2004, 101: 2375-2380. 10.1073/pnas.0308714100.PubMedCentralCrossRefPubMed
11.
go back to reference Ngo T, Duraisingh M, Reed M, Hipgrave D, Biggs B, Cowman AF: Analysis of pfcrt, pfmdr1, dhfr, and dhps mutations and drug sensitivities in Plasmodium falciparum isolates from patients in Vietnam before and after treatment with artemisinin. Am J Trop Med Hyg. 2003, 68: 350-356.PubMed Ngo T, Duraisingh M, Reed M, Hipgrave D, Biggs B, Cowman AF: Analysis of pfcrt, pfmdr1, dhfr, and dhps mutations and drug sensitivities in Plasmodium falciparum isolates from patients in Vietnam before and after treatment with artemisinin. Am J Trop Med Hyg. 2003, 68: 350-356.PubMed
12.
go back to reference Wernsdorfer WH, Noedl H: Molecular markers for drug resistance in malaria: use in treatment, diagnosis and epidemiology. Curr Opin Infect Dis. 2003, 16: 553-558. 10.1097/00001432-200312000-00007.CrossRefPubMed Wernsdorfer WH, Noedl H: Molecular markers for drug resistance in malaria: use in treatment, diagnosis and epidemiology. Curr Opin Infect Dis. 2003, 16: 553-558. 10.1097/00001432-200312000-00007.CrossRefPubMed
13.
go back to reference Looareesuwan S, Buchachart K, Wilairatana P, Chalermrut K, Rattanapong Y, Amradee S, Siripiphat S, Chullawichit S, Thimasan K, Ittiverakul M, Triampon A, Walsh DS: Primaquine-tolerant vivax malaria in Thailand. Ann Trop Med Parasitol. 1997, 91: 939-943.CrossRefPubMed Looareesuwan S, Buchachart K, Wilairatana P, Chalermrut K, Rattanapong Y, Amradee S, Siripiphat S, Chullawichit S, Thimasan K, Ittiverakul M, Triampon A, Walsh DS: Primaquine-tolerant vivax malaria in Thailand. Ann Trop Med Parasitol. 1997, 91: 939-943.CrossRefPubMed
14.
go back to reference Murphy GS, Basri H, Purnomo , Andersen EM, Bangs MJ, Mount DL, Gorden J, Lal AA, Purwokusumo AR, Harjosuwarno S: Vivax malaria resistant to treatment and prophylaxis with chloroquine. Lancet. 1993, 341: 96-100. 10.1016/0140-6736(93)92568-E.CrossRefPubMed Murphy GS, Basri H, Purnomo , Andersen EM, Bangs MJ, Mount DL, Gorden J, Lal AA, Purwokusumo AR, Harjosuwarno S: Vivax malaria resistant to treatment and prophylaxis with chloroquine. Lancet. 1993, 341: 96-100. 10.1016/0140-6736(93)92568-E.CrossRefPubMed
15.
go back to reference Alam MT, Bora H, Bharti PK, Saifi MA, Das MK, Dev V, Kumar A, Singh N, Dash AP, Das B, Wajihullah , Sharma YD: Similar trends of pyrimethamine resistance-associated mutations in Plasmodium vivax and P. falciparum. Antimicrob Agents Chemother. 2007, 51: 857-863. 10.1128/AAC.01200-06.PubMedCentralCrossRefPubMed Alam MT, Bora H, Bharti PK, Saifi MA, Das MK, Dev V, Kumar A, Singh N, Dash AP, Das B, Wajihullah , Sharma YD: Similar trends of pyrimethamine resistance-associated mutations in Plasmodium vivax and P. falciparum. Antimicrob Agents Chemother. 2007, 51: 857-863. 10.1128/AAC.01200-06.PubMedCentralCrossRefPubMed
16.
go back to reference Hastings MD, Porter KM, Maguire JD, Susanti I, Kania W, Bangs MJ, Sibley CH, Baird JK: Dihydrofolate reductase mutations in Plasmodium vivax from Indonesia and therapeutic response to sulfadoxine plus pyrimethamine. J Infect Dis. 2004, 189: 744-750. 10.1086/381397.CrossRefPubMed Hastings MD, Porter KM, Maguire JD, Susanti I, Kania W, Bangs MJ, Sibley CH, Baird JK: Dihydrofolate reductase mutations in Plasmodium vivax from Indonesia and therapeutic response to sulfadoxine plus pyrimethamine. J Infect Dis. 2004, 189: 744-750. 10.1086/381397.CrossRefPubMed
17.
go back to reference Imwong M, Pukrittakayamee S, Looareesuwan S, Pasvol G, Poirreiz J, White NJ, Snounou G: Association of genetic mutations in Plasmodium vivax dhfr with resistance to sulfadoxine-pyrimethamine: geographical and clinical correlates. Antimicrob Agents Chemother. 2001, 45: 3122-3127. 10.1128/AAC.45.11.3122-3127.2001.PubMedCentralCrossRefPubMed Imwong M, Pukrittakayamee S, Looareesuwan S, Pasvol G, Poirreiz J, White NJ, Snounou G: Association of genetic mutations in Plasmodium vivax dhfr with resistance to sulfadoxine-pyrimethamine: geographical and clinical correlates. Antimicrob Agents Chemother. 2001, 45: 3122-3127. 10.1128/AAC.45.11.3122-3127.2001.PubMedCentralCrossRefPubMed
18.
go back to reference Imwong M, Pukrittayakamee S, Renia L, Letourneur F, Charlieu JP, Leartsakulpanich U, Looareesuwan S, White NJ, Snounou G: Novel point mutations in the dihydrofolate reductase gene of Plasmodium vivax: evidence for sequential selection by drug pressure. Antimicrob Agents Chemother. 2003, 47: 1514-1521. 10.1128/AAC.47.5.1514-1521.2003.PubMedCentralCrossRefPubMed Imwong M, Pukrittayakamee S, Renia L, Letourneur F, Charlieu JP, Leartsakulpanich U, Looareesuwan S, White NJ, Snounou G: Novel point mutations in the dihydrofolate reductase gene of Plasmodium vivax: evidence for sequential selection by drug pressure. Antimicrob Agents Chemother. 2003, 47: 1514-1521. 10.1128/AAC.47.5.1514-1521.2003.PubMedCentralCrossRefPubMed
19.
go back to reference de Pecoulas PE, Tahar R, Ouatas T, Mazabraud A, Basco LK: Sequence variations in the Plasmodium vivax dihydrofolate reductase-thymidylate synthase gene and their relationship with pyrimethamine resistance. Mol Biochem Parasitol. 1998, 92: 265-273. 10.1016/S0166-6851(97)00247-8.CrossRefPubMed de Pecoulas PE, Tahar R, Ouatas T, Mazabraud A, Basco LK: Sequence variations in the Plasmodium vivax dihydrofolate reductase-thymidylate synthase gene and their relationship with pyrimethamine resistance. Mol Biochem Parasitol. 1998, 92: 265-273. 10.1016/S0166-6851(97)00247-8.CrossRefPubMed
20.
go back to reference Pukrittayakamee S, Chantra A, Simpson JA, Vanijanonta S, Clemens R, Looareesuwan S, White NJ: Therapeutic responses to different antimalarial drugs in vivax malaria. Antimicrob Agents Chemother. 2000, 44: 1680-1685. 10.1128/AAC.44.6.1680-1685.2000.PubMedCentralCrossRefPubMed Pukrittayakamee S, Chantra A, Simpson JA, Vanijanonta S, Clemens R, Looareesuwan S, White NJ: Therapeutic responses to different antimalarial drugs in vivax malaria. Antimicrob Agents Chemother. 2000, 44: 1680-1685. 10.1128/AAC.44.6.1680-1685.2000.PubMedCentralCrossRefPubMed
21.
go back to reference Korsinczky M, Fischer K, Chen N, Baker J, Rieckmann K, Cheng Q: Sulfadoxine resistance in Plasmodium vivax is associated with a specific amino acid in dihydropteroate synthase at the putative sulfadoxine-binding site. Antimicrob Agents Chemother. 2004, 48: 2214-2222. 10.1128/AAC.48.6.2214-2222.2004.PubMedCentralCrossRefPubMed Korsinczky M, Fischer K, Chen N, Baker J, Rieckmann K, Cheng Q: Sulfadoxine resistance in Plasmodium vivax is associated with a specific amino acid in dihydropteroate synthase at the putative sulfadoxine-binding site. Antimicrob Agents Chemother. 2004, 48: 2214-2222. 10.1128/AAC.48.6.2214-2222.2004.PubMedCentralCrossRefPubMed
22.
go back to reference Jima D, Tesfaye G, Medhin A, Kebede A, Argaw D, Babaniyi O: Safety and efficacy of artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in Ethiopia. East Afr Med J. 2005, 82: 387-390.PubMed Jima D, Tesfaye G, Medhin A, Kebede A, Argaw D, Babaniyi O: Safety and efficacy of artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in Ethiopia. East Afr Med J. 2005, 82: 387-390.PubMed
23.
go back to reference Aponte JJ, Schellenberg D, Egan A, Breckenridge A, Carneiro I, Critchley J, Danquah I, Dodoo A, Kobbe R, Lell B, May J, Premji Z, Sanz S, Sevene E, Soulaymani-Becheikh R, Winstanley P, Adjei S, Anemana S, Chandramohan D, Issifou S, Mockenhaupt F, Owusu-Agyei S, Greenwood B, Grobusch MP, Kremsner PG, Macete E, Mshinda H, Newman RD, Slutsker L, Tanner M, Alonso P, Menendez C: Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials. Lancet. 2009, 374: 1533-1542. 10.1016/S0140-6736(09)61258-7.CrossRefPubMed Aponte JJ, Schellenberg D, Egan A, Breckenridge A, Carneiro I, Critchley J, Danquah I, Dodoo A, Kobbe R, Lell B, May J, Premji Z, Sanz S, Sevene E, Soulaymani-Becheikh R, Winstanley P, Adjei S, Anemana S, Chandramohan D, Issifou S, Mockenhaupt F, Owusu-Agyei S, Greenwood B, Grobusch MP, Kremsner PG, Macete E, Mshinda H, Newman RD, Slutsker L, Tanner M, Alonso P, Menendez C: Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials. Lancet. 2009, 374: 1533-1542. 10.1016/S0140-6736(09)61258-7.CrossRefPubMed
24.
go back to reference Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR: Epidemiology of drug-resistant malaria. Lancet Infect Dis. 2002, 2: 209-218. 10.1016/S1473-3099(02)00239-6.CrossRefPubMed Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR: Epidemiology of drug-resistant malaria. Lancet Infect Dis. 2002, 2: 209-218. 10.1016/S1473-3099(02)00239-6.CrossRefPubMed
25.
go back to reference Contreras CE, Cortese JF, Caraballo A, Plowe CV: Genetics of drug-resistant Plasmodium falciparum malaria in the Venezuelan state of Bolivar. Am J Trop Med Hyg. 2002, 67: 400-405.PubMed Contreras CE, Cortese JF, Caraballo A, Plowe CV: Genetics of drug-resistant Plasmodium falciparum malaria in the Venezuelan state of Bolivar. Am J Trop Med Hyg. 2002, 67: 400-405.PubMed
26.
go back to reference Nagesha HS, Din S, Casey GJ, Susanti AI, Fryauff DJ, Reeder JC, Cowman AF: Mutations in the pfmdr1, dhfr and dhps genes of Plasmodium falciparum are associated with in-vivo drug resistance in West Papua, Indonesia. Trans R Soc Trop Med Hyg. 2001, 95: 43-49. 10.1016/S0035-9203(01)90329-3.CrossRefPubMed Nagesha HS, Din S, Casey GJ, Susanti AI, Fryauff DJ, Reeder JC, Cowman AF: Mutations in the pfmdr1, dhfr and dhps genes of Plasmodium falciparum are associated with in-vivo drug resistance in West Papua, Indonesia. Trans R Soc Trop Med Hyg. 2001, 95: 43-49. 10.1016/S0035-9203(01)90329-3.CrossRefPubMed
27.
go back to reference Nzila AM, Mberu EK, Sulo J, Dayo H, Winstanley PA, Sibley CH, Watkins WM: Towards an understanding of the mechanism of pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: genotyping of dihydrofolate reductase and dihydropteroate synthase of Kenyan parasites. Antimicrob Agents Chemother. 2000, 44: 991-996. 10.1128/AAC.44.4.991-996.2000.PubMedCentralCrossRefPubMed Nzila AM, Mberu EK, Sulo J, Dayo H, Winstanley PA, Sibley CH, Watkins WM: Towards an understanding of the mechanism of pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: genotyping of dihydrofolate reductase and dihydropteroate synthase of Kenyan parasites. Antimicrob Agents Chemother. 2000, 44: 991-996. 10.1128/AAC.44.4.991-996.2000.PubMedCentralCrossRefPubMed
28.
go back to reference Schmider N, Peyerl-Hoffmann G, Restrepo M, Jelinek T: Short communication: point mutations in the dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum isolates from Colombia. Trop Med Int Health. 2003, 8: 129-132. 10.1046/j.1365-3156.2003.01005.x.CrossRefPubMed Schmider N, Peyerl-Hoffmann G, Restrepo M, Jelinek T: Short communication: point mutations in the dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum isolates from Colombia. Trop Med Int Health. 2003, 8: 129-132. 10.1046/j.1365-3156.2003.01005.x.CrossRefPubMed
29.
30.
go back to reference Zakeri S, Motmaen SR, Afsharpad M, Djadid ND: Molecular characterization of antifolates resistance-associated genes, (dhfr and dhps) in Plasmodium vivax isolates from the Middle East. Malar J. 2009, 8: 20-10.1186/1475-2875-8-20.PubMedCentralCrossRefPubMed Zakeri S, Motmaen SR, Afsharpad M, Djadid ND: Molecular characterization of antifolates resistance-associated genes, (dhfr and dhps) in Plasmodium vivax isolates from the Middle East. Malar J. 2009, 8: 20-10.1186/1475-2875-8-20.PubMedCentralCrossRefPubMed
31.
go back to reference Auliff A, Wilson DW, Russell B, Gao Q, Chen N, Anh lN, Maguire J, Bell D, O'Neil MT, Cheng Q: Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs. Am J Trop Med Hyg. 2006, 75: 617-621.PubMed Auliff A, Wilson DW, Russell B, Gao Q, Chen N, Anh lN, Maguire J, Bell D, O'Neil MT, Cheng Q: Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs. Am J Trop Med Hyg. 2006, 75: 617-621.PubMed
32.
go back to reference Rungsihirunrat K, Na-Bangchang K, Hawkins VN, Mungthin M, Sibley CH: Sensitivity to antifolates and genetic analysis of Plasmodium vivax isolates from Thailand. Am J Trop Med Hyg. 2007, 76: 1057-1065.PubMed Rungsihirunrat K, Na-Bangchang K, Hawkins VN, Mungthin M, Sibley CH: Sensitivity to antifolates and genetic analysis of Plasmodium vivax isolates from Thailand. Am J Trop Med Hyg. 2007, 76: 1057-1065.PubMed
33.
go back to reference Khatoon L, Baliraine FN, Bonizzoni M, Malik SA, Yan G: Prevalence of antimalarial drug resistance mutations in Plasmodium vivax and P. falciparum from a malaria-endemic area of Pakistan. Am J Trop Med Hyg. 2009, 81: 525-528.PubMedCentralPubMed Khatoon L, Baliraine FN, Bonizzoni M, Malik SA, Yan G: Prevalence of antimalarial drug resistance mutations in Plasmodium vivax and P. falciparum from a malaria-endemic area of Pakistan. Am J Trop Med Hyg. 2009, 81: 525-528.PubMedCentralPubMed
34.
go back to reference Kaur S, Prajapati SK, Kalyanaraman K, Mohmmed A, Joshi H, Chauhan VS: Plasmodium vivax dihydrofolate reductase point mutations from the Indian subcontinent. Acta Trop. 2006, 97: 174-180. 10.1016/j.actatropica.2005.10.003.CrossRefPubMed Kaur S, Prajapati SK, Kalyanaraman K, Mohmmed A, Joshi H, Chauhan VS: Plasmodium vivax dihydrofolate reductase point mutations from the Indian subcontinent. Acta Trop. 2006, 97: 174-180. 10.1016/j.actatropica.2005.10.003.CrossRefPubMed
35.
go back to reference Hawkins VN, Joshi H, Rungsihirunrat K, Na-Bangchang K, Sibley CH: Antifolates can have a role in the treatment of Plasmodium vivax. Trends Parasitol. 2007, 23: 213-222. 10.1016/j.pt.2007.03.002.CrossRefPubMed Hawkins VN, Joshi H, Rungsihirunrat K, Na-Bangchang K, Sibley CH: Antifolates can have a role in the treatment of Plasmodium vivax. Trends Parasitol. 2007, 23: 213-222. 10.1016/j.pt.2007.03.002.CrossRefPubMed
36.
go back to reference Tjitra E, Baker J, Suprianto S, Cheng Q, Anstey NM: Therapeutic efficacies of artesunate-sulfadoxine-pyrimethamine and chloroquine-sulfadoxine-pyrimethamine in vivax malaria pilot studies: relationship to Plasmodium vivax dhfr mutations. Antimicrob Agents Chemother. 2002, 46: 3947-3953. 10.1128/AAC.46.12.3947-3953.2002.PubMedCentralCrossRefPubMed Tjitra E, Baker J, Suprianto S, Cheng Q, Anstey NM: Therapeutic efficacies of artesunate-sulfadoxine-pyrimethamine and chloroquine-sulfadoxine-pyrimethamine in vivax malaria pilot studies: relationship to Plasmodium vivax dhfr mutations. Antimicrob Agents Chemother. 2002, 46: 3947-3953. 10.1128/AAC.46.12.3947-3953.2002.PubMedCentralCrossRefPubMed
37.
go back to reference Zakeri S, Afsharpad M, Ghasemi F, Raeisi A, Safi N, Butt W, Atta H, Djadid ND: Molecular surveillance of Plasmodium vivax dhfr and dhps mutations in isolates from Afghanistan. Malar J. 2010, 9: 75-10.1186/1475-2875-9-75.PubMedCentralCrossRefPubMed Zakeri S, Afsharpad M, Ghasemi F, Raeisi A, Safi N, Butt W, Atta H, Djadid ND: Molecular surveillance of Plasmodium vivax dhfr and dhps mutations in isolates from Afghanistan. Malar J. 2010, 9: 75-10.1186/1475-2875-9-75.PubMedCentralCrossRefPubMed
38.
go back to reference Rubio JM, Benito A, Roche J, Berzosa PJ, Garcia ML, Mico M, Edu M, Alvar J: Semi-nested, multiplex polymerase chain reaction for detection of human malaria parasites and evidence of Plasmodium vivax infection in Equatorial Guinea. Am J Trop Med Hyg. 1999, 60: 183-187.PubMed Rubio JM, Benito A, Roche J, Berzosa PJ, Garcia ML, Mico M, Edu M, Alvar J: Semi-nested, multiplex polymerase chain reaction for detection of human malaria parasites and evidence of Plasmodium vivax infection in Equatorial Guinea. Am J Trop Med Hyg. 1999, 60: 183-187.PubMed
40.
go back to reference Dippmann AK, Bienzle U, Harms G, Mockenhaupt FP: pfmdr1 mutations in imported African Plasmodium falciparum isolates. Trans R Soc Trop Med Hyg. 2008, 102: 1148-1150. 10.1016/j.trstmh.2008.04.001.CrossRefPubMed Dippmann AK, Bienzle U, Harms G, Mockenhaupt FP: pfmdr1 mutations in imported African Plasmodium falciparum isolates. Trans R Soc Trop Med Hyg. 2008, 102: 1148-1150. 10.1016/j.trstmh.2008.04.001.CrossRefPubMed
41.
go back to reference Newcombe RG: Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998, 17: 857-872. 10.1002/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E.CrossRefPubMed Newcombe RG: Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998, 17: 857-872. 10.1002/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E.CrossRefPubMed
42.
go back to reference Kebede F, Taffa N, Tedla T: An in-vivo study of falciparum malaria sensitivity to Chloroquine in unstable malaria endemic area of central Ethiopia. Ethiop Med J. 1999, 37: 97-109.PubMed Kebede F, Taffa N, Tedla T: An in-vivo study of falciparum malaria sensitivity to Chloroquine in unstable malaria endemic area of central Ethiopia. Ethiop Med J. 1999, 37: 97-109.PubMed
43.
go back to reference Schunk M, Kumma WP, Miranda IB, Osman ME, Roewer S, Alano A, Loscher T, Bienzle U, Mockenhaupt FP: High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in southern Ethiopia. Malar J. 2006, 5: 54-10.1186/1475-2875-5-54.PubMedCentralCrossRefPubMed Schunk M, Kumma WP, Miranda IB, Osman ME, Roewer S, Alano A, Loscher T, Bienzle U, Mockenhaupt FP: High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in southern Ethiopia. Malar J. 2006, 5: 54-10.1186/1475-2875-5-54.PubMedCentralCrossRefPubMed
44.
go back to reference Karunamoorthi K, Bekele M: Prevalence of malaria from peripheral blood smears examination: a 1-year retrospective study from the Serbo Health Center, Kersa Woreda, Ethiopia. J Infect Public Health. 2009, 2: 171-176. 10.1016/j.jiph.2009.08.005.CrossRefPubMed Karunamoorthi K, Bekele M: Prevalence of malaria from peripheral blood smears examination: a 1-year retrospective study from the Serbo Health Center, Kersa Woreda, Ethiopia. J Infect Public Health. 2009, 2: 171-176. 10.1016/j.jiph.2009.08.005.CrossRefPubMed
45.
go back to reference Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, Coulibaly D: A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med. 2001, 344: 257-263. 10.1056/NEJM200101253440403.CrossRefPubMed Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, Coulibaly D: A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med. 2001, 344: 257-263. 10.1056/NEJM200101253440403.CrossRefPubMed
46.
go back to reference Mockenhaupt FP, Ehrhardt S, Eggelte TA, Agana-Nsiire P, Stollberg K, Mathieu A, Markert M, Otchwemah RN, Bienzle U: Chloroquine-treatment failure in northern Ghana: roles of pfcrt T76 and pfmdr1 Y86. Ann Trop Med Parasitol. 2005, 99: 723-732. 10.1179/136485905X75395.CrossRefPubMed Mockenhaupt FP, Ehrhardt S, Eggelte TA, Agana-Nsiire P, Stollberg K, Mathieu A, Markert M, Otchwemah RN, Bienzle U: Chloroquine-treatment failure in northern Ghana: roles of pfcrt T76 and pfmdr1 Y86. Ann Trop Med Parasitol. 2005, 99: 723-732. 10.1179/136485905X75395.CrossRefPubMed
Metadata
Title
Detection of high levels of mutations involved in anti-malarial drug resistance in Plasmodium falciparum and Plasmodium vivax at a rural hospital in southern Ethiopia
Authors
Patricia Mula
Amalia Fernández-Martínez
Aida de Lucio
Jose Manuel Ramos
Francisco Reyes
Vicenta González
Agustín Benito
Pedro Berzosa
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2011
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-10-214

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