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Malaria Journal
Published in: Malaria Journal 1/2013

Open Access 01-12-2013 | Research

Selection of pfdhfr/pfdhps alleles and declining artesunate/sulphadoxine-pyrimethamine efficacy against Plasmodium falciparum eight years after deployment in eastern Sudan

Authors: Nahla B Gadalla, Tajeldin M Abdallah, Sharanjeet Atwal, Colin J Sutherland, Ishag Adam

Published in: Malaria Journal | Issue 1/2013

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Abstract

Background

Artesunate/sulphadoxine-pyrimethamine (AS/SP) has been the first-line treatment for falciparum malaria in Sudan since 2004. The impact of this combination on anti-malarial resistance-associated molecular markers has not been investigated. In this study, an evaluation of the efficacy and prevalence of drug resistance alleles (pfcrt, pfmdr1, pfdhfr and pfdhps) eight years after the adoption of AS/SP in eastern Sudan is reported.

Methods

A 28-day follow-up efficacy trial of AS/SP was conducted in eastern Sudan during the 2012 transmission season. Blood smears were collected from patients on days 0, 1, 2, 3, 7, 14, 21 and 28. Blood spots on filter paper were obtained pre-treatment and on the day the patient was parasite positive by microscopy. Genotyping of alleles was performed by qPCR (pfcrt 72–76 and pfmdr1 copy number) and direct sequencing of pfmdr1, pfdhfr and pfdhps.

Results

Sixty-three patients out of 68 (93%) completed the 28-day follow-up, adequate clinical, and parasitological response occurred in 90.5% and 85.3% of the patients in the per-protocol and intent-to-treat analyses, respectively. PCR corrected per-protocol efficacy was 93.7%. The enrolment prevalence of pfcrt-CVMNK was 30.2% and pfmdr1-N86 was 40.3%. The pfmdr1 haplotype NFD occurred in 32.8% of pre-treatment samples and was significantly higher than previous reports (Fisher’s exact p = 0.0001). The pfdhfr-51I/108N combination occurred in all sequenced isolates and 59R was observed in a single individual. pfdhps substitutions 436A, 437G, 540E, 581G and 613S were observed at 7.8, 77.3, 76.9%, 33.8% and 0.0%, respectively. Treatment failures were associated with the pfdhps haplotype SGEGA at these five codons (OR 7.3; 95% CI 0.65 - 368; p = 0.048).

Conclusion

The decrease of CQR associated genotypes reflects the formal policy of complete removal of CQ in Sudan. However, the frequency of markers associated with SP failure is increasing in this study area and may be contributing to the treatment efficacy falling below 90%. Further monitoring of AS/SP efficacy and of post-treatment selection of pfdhfr and pfdhps alleles in vivo is required to inform future treatment guidelines.
Appendix
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Literature
1.
WHO: World Malaria Report 2011. 2011, Geneva: World Health Organization
2.
Feachem RG, Phillips AA, Hwang J, Cotter C, Wielgosz B, Greenwood BM, Sabot O, Rodriguez MH, Abeyasinghe RR, Ghebreyesus TA, Snow RW: Shrinking the malaria map: progress and prospects. Lancet. 2010, 376: 1566-1578.PubMedCentralCrossRefPubMed
3.
WHO: World Malaria Report 2012. 2012, Geneva: World Health Organization
4.
Omer AH: Response of Plasmodium falciparum in Sudan to oral chloroquine. Am J Trop Med Hyg. 1978, 27: 853-857.PubMed
5.
Bayoumi RA, Babiker HA, Ibrahim SM, Ghalib HW, Saeed BO, Khider S, Elwasila M, Karim EA: Chloroquine-resistant Plasmodium falciparum in eastern Sudan. Acta Trop. 1989, 46: 157-165.CrossRefPubMed
6.
Ibrahim ME, Awad-el-Kariem FM, el Hassan IM, el Mubarak ER: A case of Plasmodium falciparum malaria sensitive to chloroquine but resistant to pyrimethamine/sulfadoxine in Sennar, Sudan. Trans R Soc Trop Med Hyg. 1991, 85: 446-CrossRefPubMed
7.
Gadalla NB, Elzaki SE, Mukhtar E, Warhurst DC, El-Sayed B, Sutherland CJ: Dynamics of pfcrt alleles CVMNK and CVIET in chloroquine-treated Sudanese patients infected with Plasmodium falciparum. Malar J. 2010, 9: 74-PubMedCentralCrossRefPubMed
8.
9.
Malik EM, Mohamed TA, Elmardi KA, Mowien RM, Elhassan AH, Elamin SB, Mannan AA, Ahmed ES: From chloroquine to artemisinin-based combination therapy: the Sudanese experience. Malar J. 2006, 5: 65-PubMedCentralCrossRefPubMed
10.
Adam I, Ibrahim MH, Ae IA, Elbashir MI: Efficacy of sulfadoxin pyrimethamine for uncomplicated Plasmodium falciparum malaria in a small sample of Sudanese children. East Mediterr Health J. 2004, 10: 309–-314.PubMed
11.
Mugittu K, Abdulla S, Falk N, Masanja H, Felger I, Mshinda H, Beck HP, Genton B: Efficacy of sulfadoxine-pyrimethamine in Tanzania after two years as first-line drug for uncomplicated malaria: assessment protocol and implication for treatment policy strategies. Malar J. 2005, 4: 55-PubMedCentralCrossRefPubMed
12.
Naidoo I, Roper C: Following the path of most resistance: dhps K540E dispersal in African Plasmodium falciparum. Trends Parasitol. 2010, 26: 447-456.CrossRefPubMed
13.
Sridaran S, McClintock SK, Syphard LM, Herman KM, Barnwell JW, Udhayakumar V: Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutant genotype frequencies in African Plasmodium falciparum parasite populations. Malar J. 2010, 9: 247-PubMedCentralCrossRefPubMed
14.
Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ: Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009, 361: 455-467.PubMedCentralCrossRefPubMed
15.
Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM: Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008, 359: 2619-2620.CrossRefPubMed
16.
Djimde A, Doumbo OK, Steketee RW, Plowe CV: Application of a molecular marker for surveillance of chloroquine-resistant falciparum malaria. Lancet. 2001, 358: 890-891.CrossRefPubMed
17.
Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LM, Sidhu AB, Naude B, Deitsch KW, Su XZ, Wootton JC, Roepe PD, Wellems TE: Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell. 2000, 6: 861-871.PubMedCentralCrossRefPubMed
18.
Abdel-Muhsin AM, Mackinnon MJ, Ali E, el Nassir BA, Suleiman S, Ahmed S, Walliker D, Babiker HA: Evolution of drug-resistance genes in Plasmodium falciparum in an area of seasonal malaria transmission in Eastern Sudan. J Infect Dis. 2004, 189: 1239-1244.CrossRefPubMed
19.
Babiker HA, Pringle SJ, Abdel-Muhsin A, Mackinnon M, Hunt P, Walliker D: High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance gene pfmdr1. J Infect Dis. 2001, 183: 1535-1538.CrossRefPubMed
20.
A-Elbasit IE, Khalil IF, Elbashir MI, Masuadi EM, Bygbjerg IC, Alifrangis M, Giha HA: High frequency of Plasmodium falciparum CICNI/SGEAA and CVIET haplotypes without association with resistance to sulfadoxine/pyrimethamine and chloroquine combination in the Daraweesh area, in Sudan. Eur J Clin Microbiol Infect Dis. 2008, 27: 725-732.CrossRefPubMed
21.
Tagelsir N, Ibrahim Z, Medani A, Salih O, Hamad A, Giha H, El-Agib A, Khan B, Saeed N, Ibrahim M: High frequency of Plasmodium falciparum PfCRT K76T and PfpghN86Y in patients clearing infection after chloroquine treatment in the Sudan. Acta Trop. 2006, 97: 19-25.CrossRefPubMed
22.
Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, Djimde AA, Kouriba B, Taylor TE, Plowe CV: Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis. 2003, 187: 1870-1875.CrossRefPubMed
23.
Mita T, Kaneko A, Lum JK, Bwijo B, Takechi M, Zungu IL, Tsukahara T, Tanabe K, Kobayakawa T, Bjorkman A: Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi. Am J Trop Med Hyg. 2003, 68: 413-415.PubMed
24.
Mang'era CM, Mbai FN, Omedo IA, Mireji PO, Omar SA: Changes in genotypes of Plasmodium falciparum human malaria parasite following withdrawal of chloroquine in Tiwi, Kenya. Acta Trop. 2012, 123: 202-207.CrossRefPubMed
25.
Mwai L, Ochong E, Abdirahman A, Kiara SM, Ward S, Kokwaro G, Sasi P, Marsh K, Borrmann S, Mackinnon M, Nzila A: Chloroquine resistance before and after its withdrawal in Kenya. Malar J. 2009, 8: 106-PubMedCentralCrossRefPubMed
26.
Ndiaye M, Faye B, Tine R, Ndiaye JL, Lo A, Abiola A, Dieng Y, Ndiaye D, Hallett R, Alifrangis M, Gaye O: Assessment of the molecular marker of Plasmodium falciparum chloroquine resistance (Pfcrt) in Senegal after several years of chloroquine withdrawal. Am J Trop Med Hyg. 2012, 87: 640-645.PubMedCentralCrossRefPubMed
27.
Alifrangis M, Lusingu JP, Mmbando B, Dalgaard MB, Vestergaard LS, Ishengoma D, Khalil IF, Theander TG, Lemnge MM, Bygbjerg IC: Five-year surveillance of molecular markers of Plasmodium falciparum antimalarial drug resistance in Korogwe District, Tanzania: accumulation of the 581G mutation in the P. falciparum dihydropteroate synthase gene. Am J Trop Med Hyg. 2009, 80: 523-527.PubMed
28.
Kamugisha E, Bujila I, Lahdo M, Pello-Esso S, Minde M, Kongola G, Naiwumbwe H, Kiwuwa S, Kaddumukasa M, Kironde F, Swedberg G: Large differences in prevalence of Pfcrt and Pfmdr1 mutations between Mwanza, Tanzania and Iganga, Uganda-a reflection of differences in policies regarding withdrawal of chloroquine?. Acta Trop. 2011, 121: 148-151.CrossRefPubMed
29.
Thomsen TT, Madsen LB, Hansson HH, Tomas EV, Charlwood D, Bygbjerg IC, Alifrangis M: Rapid selection of Plasmodium falciparum chloroquine resistance transporter gene and multidrug resistance gene-1 haplotypes associated with past chloroquine and present artemether-lumefantrine use in Inhambane District, southern Mozambique. Am J Trop Med Hyg. 2013, 88: 536-541.PubMedCentralCrossRefPubMed
30.
Gadalla NB, Adam I, Elzaki SE, Bashir S, Mukhtar I, Oguike M, Gadalla A, Mansour F, Warhurst D, El-Sayed BB, Sutherland CJ: Increased pfmdr1 copy number and sequence polymorphisms in Plasmodium falciparum isolates from Sudanese malaria patients treated with artemether-lumefantrine. Antimicrob Agents Chemother. 2011, 55: 5408-5411.PubMedCentralCrossRefPubMed
31.
Dokomajilar C, Nsobya SL, Greenhouse B, Rosenthal PJ, Dorsey G: Selection of Plasmodium falciparum pfmdr1 alleles following therapy with artemether-lumefantrine in an area of Uganda where malaria is highly endemic. Antimicrob Agents Chemother. 2006, 50: 1893-1895.PubMedCentralCrossRefPubMed
32.
Sisowath C, Stromberg J, Martensson A, Msellem M, Obondo C, Bjorkman A, Gil JP: In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis. 2005, 191: 1014-1017.CrossRefPubMed
33.
Thomsen TT, Ishengoma DS, Mmbando BP, Lusingu JP, Vestergaard LS, Theander TG, Lemnge MM, Bygbjerg IC, Alifrangis M: Prevalence of single nucleotide polymorphisms in the Plasmodium falciparum multidrug resistance gene (Pfmdr-1) in Korogwe District in Tanzania before and after introduction of artemisinin-based combination therapy. Am J Trop Med Hyg. 2011, 85: 979-983.PubMedCentralCrossRefPubMed
34.
Humphreys GS, Merinopoulos I, Ahmed J, Whitty CJ, Mutabingwa TK, Sutherland CJ, Hallett RL: Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria. Antimicrob Agents Chemother. 2007, 51: 991-997.PubMedCentralCrossRefPubMed
35.
Malmberg M, Ferreira PE, Tarning J, Ursing J, Ngasala B, Bjorkman A, Martensson A, Gil JP: Plasmodium falciparum drug resistance phenotype as assessed by patient antimalarial drug levels and its association with pfmdr1 polymorphisms. J Infect Dis. 2013, 207: 842-847.PubMedCentralCrossRefPubMed
36.
Vinayak S, Alam MT, Sem R, Shah NK, Susanti AI, Lim P, Muth S, Maguire JD, Rogers WO, Fandeur T, Barnwell JW, Escalante AA, Wongsrichanalai C, Ariey F, Meshnick SR, Udhayakumar V: Multiple genetic backgrounds of the amplified Plasmodium falciparum multidrug resistance (pfmdr1) gene and selective sweep of 184F mutation in Cambodia. J Infect Dis. 2010, 201: 1551-1560.PubMedCentralCrossRefPubMed
37.
Price RN, Uhlemann AC, van Vugt M, Brockman A, Hutagalung R, Nair S, Nash D, Singhasivanon P, Anderson TJ, Krishna S, White NJ, Nosten F: Molecular and pharmacological determinants of the therapeutic response to artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria. Clin Infect Dis. 2006, 42: 1570-1577.PubMedCentralCrossRefPubMed
38.
Holmgren G, Bjorkman A, Gil JP: Amodiaquine resistance is not related to rare findings of pfmdr1 gene amplifications in Kenya. Trop Med Int Health. 2006, 11: 1808-1812.CrossRefPubMed
39.
Ngasala BE, Malmberg M, Carlsson AM, Ferreira PE, Petzold MG, Blessborn D, Bergqvist Y, Gil JP, Premji Z, Bjorkman A, Martensson A: Efficacy and effectiveness of artemether-lumefantrine after initial and repeated treatment in children <5 years of age with acute uncomplicated Plasmodium falciparum malaria in rural Tanzania: a randomized trial. Clin Infect Dis. 2011, 52: 873-882.CrossRefPubMed
40.
Cowman AF, Morry MJ, Biggs BA, Cross GA, Foote SJ: Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum. Proc Natl Acad Sci USA. 1988, 85: 9109-9113.PubMedCentralCrossRefPubMed
41.
Snewin VA, England SM, Sims PF, Hyde JE: Characterisation of the dihydrofolate reductase-thymidylate synthetase gene from human malaria parasites highly resistant to pyrimethamine. Gene. 1989, 76: 41-52.CrossRefPubMed
42.
Peterson DS, Walliker D, Wellems TE: Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci USA. 1988, 85: 9114-9118.PubMedCentralCrossRefPubMed
43.
Sirawaraporn W, Yongkiettrakul S, Sirawaraporn R, Yuthavong Y, Santi DV: Plasmodium falciparum: asparagine mutant at residue 108 of dihydrofolate reductase is an optimal antifolate-resistant single mutant. Exp Parasitol. 1997, 87: 245-252.CrossRefPubMed
44.
Triglia T, Menting JG, Wilson C, Cowman AF: Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum. Proc Natl Acad Sci USA. 1997, 94: 13944-13949.PubMedCentralCrossRefPubMed
45.
Himeidan YE, Elbashir MI, El Rayah el A, Adam I: Epidemiology of malaria in New Halfa, an irrigated area in eastern Sudan. East Mediterr Health J. 2005, 11: 499-504.PubMed
46.
WHO: Methods for surveillance of antimalarial drug efficacy. 2009, Geneva: World Health Organization
47.
Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE: Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg. 1995, 52: 565-568.PubMed
48.
Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Coulibaly D, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV: A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med. 2001, 344: 257-263.CrossRefPubMed
49.
Pearce RJ, Drakeley C, Chandramohan D, Mosha F, Roper C: Molecular determination of point mutation haplotypes in the dihydrofolate reductase and dihydropteroate synthase of Plasmodium falciparum in three districts of northern Tanzania. Antimicrob Agents Chemother. 2003, 47: 1347-1354.PubMedCentralCrossRefPubMed
50.
Price RN, Uhlemann AC, Brockman A, McGready R, Ashley E, Phaipun L, Patel R, Laing K, Looareesuwan S, White NJ, Nosten F, Krishna S: Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet. 2004, 364: 438-447.PubMedCentralCrossRefPubMed
51.
Snounou G, Zhu X, Siripoon N, Jarra W, Thaithong S, Brown KN, Viriyakosol S: Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand. Trans R Soc Trop Med Hyg. 1999, 93: 369-374.CrossRefPubMed
52.
Osman ME, Mockenhaupt FP, Bienzle U, Elbashir MI, Giha HA: Field-based evidence for linkage of mutations associated with chloroquine (pfcrt/pfmdr1) and sulfadoxine-pyrimethamine (pfdhfr/pfdhps) resistance and for the fitness cost of multiple mutations in P. falciparum. Infect Genet Evol. 2007, 7: 52-59.CrossRefPubMed
53.
Menegon M, Talha AA, Severini C, Elbushra SM, Mohamedani AA, Malik EM, Mohamed TA, Wernsdorfer WH, Majori G, Nour BY: Frequency distribution of antimalarial drug resistance alleles among Plasmodium falciparum isolates from Gezira State, central Sudan, and Gedarif State, eastern Sudan. Am J Trop Med Hyg. 2010, 83: 250-257.PubMedCentralCrossRefPubMed
54.
Khalil I, Alifrangis M, Ronn AM, Gabar HA, Jelinek T, Satti GM, Bygbjerg IC: Pyrimethamine/sulfadoxine combination in the treatment of uncomplicated falciparum malaria: relation between dihydropteroate synthase/dihydrofolate reductase genotypes, sulfadoxine plasma levels, and treatment outcome. Am J Trop Med Hyg. 2002, 67: 225-229.PubMed
55.
Adam I, IE AE, Idris SM, Malik EM, Elbashir MI: A comparison of the efficacy of artesunate plus sulfadoxine-pyrimethamine with that of sulfadoxine-pyrimethamine alone, in the treatment of uncomplicated, Plasmodium falciparum malaria in eastern Sudan. Ann Trop Med Parasitol. 2005, 99: 449-455.CrossRefPubMed
56.
Mohamed AO, Eltaib EH, Ahmed OA, Elamin SB, Malik EM: The efficacies of artesunate-sulfadoxine-pyrimethamine and artemether-lumefantrine in the treatment of uncomplicated, Plasmodium falciparum malaria, in an area of low transmission in central Sudan. Ann Trop Med Parasitol. 2006, 100: 5-10.CrossRefPubMed
57.
Mukhtar EA, Gadalla NB, El-Zaki SE, Mukhtar I, Mansour FA, Babiker A, El-Sayed BB: A comparative study on the efficacy of artesunate plus sulphadoxine/pyrimethamine versus artemether-lumefantrine in eastern Sudan. Malar J. 2007, 6: 92-PubMedCentralCrossRefPubMed
58.
A-Elbasit I, Elbashir MI, Khalil IF, Alifrangis M, Giha HA: The efficacy of sulfadoxine-pyrimethamine alone and in combination with chloroquine for malaria treatment in rural Eastern Sudan: the interrelation between resistance, age and gametocytogenesis. Trop Med Int Health. 2006, 11: 604-612.CrossRefPubMed
59.
Giha HA: Artemisinin derivatives for treatment of uncomplicated Plasmodium falciparum malaria in Sudan: too early for too much hope. Parasitol Res. 2009, 106: 549-552.CrossRefPubMed
60.
Elamin SB, Malik EM, Abdelgadir T, Khamiss AH, Mohammed MM, Ahmed ES, Adam I: Artesunate plus sulfadoxine-pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in Sudan. Malar J. 2005, 4: 41-PubMedCentralCrossRefPubMed
61.
Salah MT, Mohammed MM, Himeidan YE, Malik EM, Elbashir MI, Adam I: A randomized comparison of sulphadoxine-pyrimethamine and combination of sulphadoxine pyrimethamine with chloroquine in the treatment of uncomplicated falciparum malaria in Eastern Sudan. Saudi Med J. 2005, 26: 147-148.PubMed
62.
Van den Broek I, Amsalu R, Balasegaram M, Hepple P, Alemu E, Hussein el B, Al-Faith M, Montgomery J, Checchi F: Efficacy of two artemisinin combination therapies for uncomplicated falciparum malaria in children under 5 years, Malakal, Upper Nile, Sudan. Malar J. 2005, 4: 14-PubMedCentralCrossRefPubMed
63.
Borrmann S, Sasi P, Mwai L, Bashraheil M, Abdallah A, Muriithi S, Fruhauf H, Schaub B, Pfeil J, Peshu J, Hanpithakpong W, Rippert A, Juma E, Tsofa B, Mosobo M, Lowe B, Osier F, Fegan G, Lindegårdh N, Nzila A, Peshu N, Mackinnon M, Marsh K: Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast. PLoS One. 2011, 6: e26005-PubMedCentralCrossRefPubMed
64.
Maiga AW, Fofana B, Sagara I, Dembele D, Dara A, Traore OB, Toure S, Sanogo K, Dama S, Sidibe B, Kone A, Thera MA, Plowe CV, Doumbo OK, Djimde AA: No evidence of delayed parasite clearance after oral artesunate treatment of uncomplicated falciparum malaria in Mali. Am J Trop Med Hyg. 2012, 87: 23-28.PubMedCentralCrossRefPubMed
65.
Al-Hamidhi S, Mahdy M, Al-Hashami Z, Al-Farsi H, Al-mekhlafi A, Idris M, Beja-Pereira A, Babiker H: Genetic diversity of Plasmodium falciparum and distribution of drug resistance haplotypes in Yemen. Malar J. 2013, 12: 244-PubMedCentralCrossRefPubMed
66.
Khalil IF, Ronn AM, Alifrangis M, Gabar HA, Jelinek T, Satti GM, Bygbjerg IC: Response of Plasmodium falciparum to cotrimoxazole therapy: relationship with plasma drug concentrations and dihydrofolate reductase and dihydropteroate synthase genotypes. Am J Trop Med Hyg. 2005, 73: 174-177.PubMed
67.
Hamour S, Melaku Y, Keus K, Wambugu J, Atkin S, Montgomery J, Ford N, Hook C, Checchi F: Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine-pyrimethamine and artesunate plus amodiaquine combinations. Trans R Soc Trop Med Hyg. 2005, 99: 548-554.CrossRefPubMed
68.
McCollum AM, Basco LK, Tahar R, Udhayakumar V, Escalante AA: Hitchhiking and selective sweeps of Plasmodium falciparum sulfadoxine and pyrimethamine resistance alleles in a population from central Africa. Antimicrob Agents Chemother. 2008, 52: 4089-4097.PubMedCentralCrossRefPubMed
69.
McCollum AM, Schneider KA, Griffing SM, Zhou Z, Kariuki S, Ter-Kuile F, Shi YP, Slutsker L, Lal AA, Udhayakumar V, Escalante AA: Differences in selective pressure on dhps and dhfr drug resistant mutations in western Kenya. Malar J. 2012, 11: 77-PubMedCentralCrossRefPubMed
70.
Abdallah TM, Ali AA, Bakri M, Gasim GI, Musa IR, Adam I: Efficacy of artemether-lumefantrine as a treatment for uncomplicated Plasmodium vivax malaria in eastern Sudan. Malar J. 2012, 11: 404-PubMedCentralCrossRefPubMed
71.
Pearce RJ, Pota H, Evehe MS, Bâ e-H, Mombo-Ngoma G, Malisa AL, Ord R, Inojosa W, Matondo A, Diallo DA, Mbacham W, van den Broek IV, Swarthout TD, Getachew A, Dejene S, Grobusch MP, Njie F, Dunyo S, Kweku M, Kweku M, Owusu-Agyei S, Chandramohan D, Bonnet M, Guthmann JP, Clarke S, Barnes KI, Streat E, Katokele ST, Uusiku P, Agboghoroma CO, Elegba OY, Cissé B, A-Elbasit IE, Giha HA, Kachur SP, Lynch C, Rwakimari JB, Chanda P, Hawela M, Sharp B, Naidoo I, Roper C: Multiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria. PLoS Med. 2009, 6: e1000055-PubMedCentralCrossRefPubMed
Metadata
Title
Selection of pfdhfr/pfdhps alleles and declining artesunate/sulphadoxine-pyrimethamine efficacy against Plasmodium falciparum eight years after deployment in eastern Sudan
Authors
Nahla B Gadalla
Tajeldin M Abdallah
Sharanjeet Atwal
Colin J Sutherland
Ishag Adam
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2013
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-12-255

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Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

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Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

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