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Malaria Journal
Published in: Malaria Journal 1/2011

Open Access 01-12-2011 | Research

Prevalence of resistance associated polymorphisms in Plasmodium falciparum field isolates from southern Pakistan

Authors: Najia Karim Ghanchi, Johan Ursing, Mohammad A Beg, Maria I Veiga, Sana Jafri, Andreas Mårtensson

Published in: Malaria Journal | Issue 1/2011

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Abstract

Background

Scarce data are available on Plasmodium falciparum anti-malarial drug resistance in Pakistan. The aim of this study was, therefore, to determine the prevalence of P. falciparum resistance associated polymorphisms in field isolates from southern Pakistan.

Methods

Blood samples from 244 patients with blood-slide confirmed P. falciparum mono-infections were collected between 2005-2007. Single nucleotide polymorphisms in the P. falciparum chloroquine resistance transporter (pfcrt K76T), multi drug resistance (pfmdr1 N86Y), dihydrofolate reductase (pfdhfr A16V, N51I, C59R, S108N, I164L) and dihydropteroate synthetase (pfdhps A436S, G437A and E540K) genes and pfmdr1 gene copy numbers were determined using PCR based methods.

Results

The prevalence of pfcrt 76T and pfmdr1 86Y was 93% and 57%, respectively. The prevalence of pfdhfr double mutations 59R + 108N/51R + 108N was 92%. The pfdhfr triple mutation (51I, 59R, 108N) occurred in 3% of samples. The pfdhfr (51I, 59R, 108N) and pfdhps (437G, 540E) quintuple mutation was found in one isolate. Pfdhps 437G was observed in 51% and 540E in 1% of the isolates. One isolate had two pfmdr1 copies and carried the pfmdr1 86Y and pfcrt 76T alleles.

Conclusions

The results indicate high prevalence of in vivo resistance to chloroquine, whereas high grade resistance to sulphadoxine-pyrimethamine does not appear to be widespread among P. falciparum in southern Pakistan.
Literature
1.
Yasinzai MI, Kakarsulemankhel JK: Prevalence of human malaria infection in bordering areas of East Balochistan, adjoining with Punjab: Loralai and Musakhel. J Pak Med Assoc. 2009, 59: 132-135.PubMed
2.
Rab MA, Freeman TW, Durrani N, de Poerck D, Rowland MW: Resistance of Plasmodium falciparum malaria to chloroquine is widespread in eastern Afghanistan. Ann Trop Med Parasitol. 2001, 95: 41-46. 10.1080/00034980020035906.CrossRefPubMed
3.
Hozhabri S, Akhtar S, Rahbar MH, Luby SP: Prevalence of Plasmodium slide positivity among the children treated for malaria, Jhangara, Sindh. J Pak Med Assoc. 2000, 50: 401-405.PubMed
4.
Durrani AB, Durrani IU, Abbas N, Jabeen M: Epidemiology of cerebral malaria and its mortality. J Pak Med Assoc. 1997, 47: 213-215.PubMed
5.
Rana MS, Tanveer A: Chloroquine resistance and Plasmodium falciparum in Punjab, Pakistan during 2000-2001. Southeast Asian J Trop Med Public Health. 2004, 35: 288-291.PubMed
6.
Fox E, Khaliq AA, Sarwar M, Strickland GT: Chloroquine-resistant Plasmodium falciparum: now in Pakistani Punjab. Lancet. 1985, 1: 1432-1435. 10.1016/S0140-6736(85)91855-0.CrossRefPubMed
7.
Shah I, Rowland M, Mehmood P, Mujahid C, Razique F, Hewitt S, Durrani N: Chloroquine resistance in Pakistan and the upsurge of falciparum malaria in Pakistani and Afghan refugee populations. Ann Trop Med Parasitol. 1997, 91: 591-602. 10.1080/00034989760680.CrossRefPubMed
8.
Robinson DS, Hadley-Brown M, Ejele OA, Robinson PS: Chloroquine-resistant malaria in Pakistan. Lancet. 1984, 2: 987-10.1016/S0140-6736(84)91207-8.CrossRefPubMed
9.
10.
Rowland M, Durrani N, Hewitt S, Sondorp E: Resistance of falciparum malaria to chloroquine and sulfadoxine-pyrimethamine in Afghan refugee settlements in western Pakistan: surveys by the general health services using a simplified in vivo test. Trop Med Int Health. 1997, 2: 1049-1056. 10.1046/j.1365-3156.1997.d01-185.x.CrossRefPubMed
11.
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
12.
Mendez F, Munoz A, Carrasquilla G, Jurado D, Arevalo-Herrera M, Cortese JF, Plowe CV: Determinants of treatment response to sulfadoxine-pyrimethamine and subsequent transmission potential in falciparum malaria. Am J Epidemiol. 2002, 156: 230-238. 10.1093/aje/kwf030.CrossRefPubMed
13.
Plowe CV, Cortese JF, Djimde A, Nwanyanwu OC, Watkins WM, Winstanley PA, Estrada-Franco JG, Mollinedo RE, Avila JC, Cespedes JL, Carter D, Doumbo OK: Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. J Infect Dis. 1997, 176: 1590-1596. 10.1086/514159.CrossRefPubMed
14.
Gregson A, Plowe CV: Mechanisms of resistance of malaria parasites to antifolates. Pharmacol Rev. 2005, 57: 117-145. 10.1124/pr.57.1.4.CrossRefPubMed
15.
Triglia T, Wang P, Sims PF, Hyde JE, Cowman AF: Allelic exchange at the endogenous genomic locus in Plasmodium falciparum proves the role of dihydropteroate synthase in sulfadoxine-resistant malaria. EMBO J. 1998, 17: 3807-3815. 10.1093/emboj/17.14.3807.PubMedCentralCrossRefPubMed
16.
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. 10.1016/S1097-2765(05)00077-8.PubMedCentralCrossRefPubMed
17.
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
18.
Sisowath C, Petersen I, Veiga MI, Martensson A, Premji Z, Bjorkman A, Fidock DA, Gil JP: In vivo selection of Plasmodium falciparum parasites carrying the chloroquine-susceptible pfcrt K76 allele after treatment with artemether-lumefantrine in Africa. J Infect Dis. 2009, 199: 750-757. 10.1086/596738.PubMedCentralCrossRefPubMed
19.
Sisowath C, Ferreira PE, Bustamante LY, Dahlstrom S, Martensson A, Bjorkman A, Krishna S, Gil JP: The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa. Trop Med Int Health. 2007, 12: 736-742. 10.1111/j.1365-3156.2007.01843.x.CrossRefPubMed
20.
Mwai L, Kiara SM, Abdirahman A, Pole L, Rippert A, Diriye A, Bull P, Marsh K, Borrmann S, Nzila A: In vitro activities of piperaquine, lumefantrine, and dihydroartemisinin in Kenyan Plasmodium falciparum isolates and polymorphisms in pfcrt and pfmdr1. Antimicrob Agents Chemother. 2009, 53: 5069-5073. 10.1128/AAC.00638-09.PubMedCentralCrossRefPubMed
21.
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. 10.1086/320195.CrossRefPubMed
22.
Ursing J, Kofoed PE, Rodrigues A, Rombo L, Gil JP: Plasmodium falciparum genotypes associated with chloroquine and amodiaquine resistance in Guinea-Bissau. Am J Trop Med Hyg. 2007, 76: 844-848.PubMed
23.
Picot S, Olliaro P, de Monbrison F, Bienvenu AL, Price RN, Ringwald P: A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria. Malar J. 2009, 8: 89-10.1186/1475-2875-8-89.PubMedCentralCrossRefPubMed
24.
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. 10.1086/427997.CrossRefPubMed
25.
Duraisingh MT, Roper C, Walliker D, Warhurst DC: Increased sensitivity to the antimalarials mefloquine and artemisinin is conferred by mutations in the pfmdr1 gene of Plasmodium falciparum. Mol Microbiol. 2000, 36: 955-961. 10.1046/j.1365-2958.2000.01914.x.CrossRefPubMed
26.
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. 10.1016/S0140-6736(04)16767-6.PubMedCentralCrossRefPubMed
27.
28.
29.
Veiga MI, Ferreira PE, Bjorkman A, Gil JP: Multiplex PCR-RFLP methods for pfcrt, pfmdr1 and pfdhfr mutations in Plasmodium falciparum. Mol Cell Probes. 2006, 20: 100-104. 10.1016/j.mcp.2005.10.003.CrossRefPubMed
30.
Ndiaye D, Daily JP, Sarr O, Ndir O, Gaye O, Mboup S, Wirth DF: Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase genes in Senegal. Trop Med Int Health. 2005, 10: 1176-1179. 10.1111/j.1365-3156.2005.01506.x.PubMedCentralCrossRefPubMed
31.
Ursing J, Zakeri S, Gil JP, Bjorkman A: Quinoline resistance associated polymorphisms in the pfcrt, pfmdr1 and pfmrp genes of Plasmodium falciparum in Iran. Acta Trop. 2006, 97: 352-356. 10.1016/j.actatropica.2006.01.002.CrossRefPubMed
32.
Vinayak S, Biswas S, Dev V, Kumar A, Ansari MA, Sharma YD: Prevalence of the K76T mutation in the pfcrt gene of Plasmodium falciparum among chloroquine responders in India. Acta Trop. 2003, 87: 287-293. 10.1016/S0001-706X(03)00021-4.CrossRefPubMed
33.
WHO: Division of communicable disease control newsletter. 2005, 6: 1-4.
34.
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
35.
Ahmed A, Bararia D, Vinayak S, Yameen M, Biswas S, Dev V, Kumar A, Ansari MA, Sharma YD: Plasmodium falciparum isolates in India exhibit a progressive increase in mutations associated with sulfadoxine-pyrimethamine resistance. Antimicrob Agents Chemother. 2004, 48: 879-889. 10.1128/AAC.48.3.879-889.2004.PubMedCentralCrossRefPubMed
36.
Zakeri S, Afsharpad M, Raeisi A, Djadid ND: Prevalence of mutations associated with antimalarial drugs in Plasmodium falciparum isolates prior to the introduction of sulphadoxine-pyrimethamine as first-line treatment in Iran. Malar J. 2007, 6: 148-10.1186/1475-2875-6-148.PubMedCentralCrossRefPubMed
37.
Nair S, Williams JT, Brockman A, Paiphun L, Mayxay M, Newton PN, Guthmann JP, Smithuis FM, Hien TT, White NJ, Nosten F, Anderson TJ: A selective sweep driven by pyrimethamine treatment in southeast asian malaria parasites. Mol Biol Evol. 2003, 20: 1526-1536. 10.1093/molbev/msg162.CrossRefPubMed
38.
Roper C, Pearce R, Bredenkamp B, Gumede J, Drakeley C, Mosha F, Chandramohan D, Sharp B: Antifolate antimalarial resistance in southeast Africa: a population-based analysis. Lancet. 2003, 361: 1174-1181. 10.1016/S0140-6736(03)12951-0.CrossRefPubMed
39.
Lumb V, Das MK, Singh N, Dev V, Wajihullah , Sharma YD: Characteristics of genetic hitchhiking around dihydrofolate reductase gene associated with pyrimethamine resistance in Plasmodium falciparum isolates from India. Antimicrob Agents Chemother. 2009, 53: 5173-5180. 10.1128/AAC.00045-09.PubMedCentralCrossRefPubMed
40.
Mita T: Origins and spread of pfdhfr mutant alleles in Plasmodium falciparum. Acta Trop. 2009, 114: 166-170. 10.1016/j.actatropica.2009.07.008.CrossRefPubMed
Metadata
Title
Prevalence of resistance associated polymorphisms in Plasmodium falciparum field isolates from southern Pakistan
Authors
Najia Karim Ghanchi
Johan Ursing
Mohammad A Beg
Maria I Veiga
Sana Jafri
Andreas Mårtensson
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2011
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-10-18

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