Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Malaria Journal
Published in: Malaria Journal 1/2014

Open Access 01-12-2014 | Research

Distribution of pfmdr1 polymorphisms in Plasmodium falciparum isolated from Southern Thailand

Authors: Mathirut Mungthin, Somchai Intanakom, Nantana Suwandittakul, Preeyaporn Suida, Sakultip Amsakul, Naruemon Sitthichot, Suwich Thammapalo, Saovanee Leelayoova

Published in: Malaria Journal | Issue 1/2014

Login to get access

Abstract

Background

Drug resistance in Plasmodium falciparum is a major problem in malaria control especially along the Thai-Myanmar and Thai-Cambodia borders. To date, a few molecular markers have been identified for anti-malarial resistance in P. falciparum, including the P. falciparum chloroquine resistance transporter (pfcrt) and the P. falciparum multidrug resistance 1 (pfmdr1). However no information is available regarding the distribution pattern of these gene polymorphisms in the parasites from the Thai-Malaysia border. This study was conducted to compare the distribution pattern of the pfcrt and pfmdr1 polymorphisms in the parasites from the lower southern provinces, Thai-Malaysia border and the upper southern provinces, Thai-Myanmar border. In addition, in vitro sensitivities of anti-malarial drugs including chloroquine, mefloquine, quinine, and artesunate were determined.

Methods

In all, 492 P. falciparum-positive blood samples were collected from the lower southern provinces: Songkhla, Yala and Narathiwas. From the upper southern part of Thailand, Ranong and Chumphon, 66 samples were also collected. Polymorphisms of the pfcrt and the pfmdr1 gene were determined using PCR techniques. In vitro sensitivities of anti-malarial drugs were determined using radioisotopic method.

Results

All parasites from both areas contained the pfcrt 76 T allele. The pfmdr 1 86Y allele was significantly more common in the parasites isolated from the lower southern areas. In contrast, the pfmdr1 184F allele was predominant among the parasites from the upper southern areas especially Ranong. In addition, the parasites from Ranong contained higher copy numbers than the parasites from other provinces. All adapted parasite isolates exhibited CQ-resistant phenotype. Neither QN nor MQ resistance was detected in these isolates.

Conclusion

The parasites from Thai-Malaysia border exhibited different resistant patterns compared to other areas along the international border of Thailand. This information will be useful for anti-malarial drug policy in Thailand.
Appendix
Available only for authorised users
Literature
1.
WHO: Global Report on Antimalarial Drug Efficacy and Drug Resistance 2000–2010. 2010, Geneva: World Health Organization
2.
WHO: Guidelines for the Treatment of Malaria. 2006, Geneva: World Health Organization
3.
Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, Artemisinin Resistance in Cambodia 1 (ARC1) Study Consortium: Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008, 359: 2619-2620. 10.1056/NEJMc0805011.CrossRefPubMed
4.
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. 10.1056/NEJMoa0808859.PubMedCentralCrossRefPubMed
5.
Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LM, Sidhu AB, Naudé 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
6.
Cooper RA, Ferdig MT, Su XZ, Ursos LM, Mu J, Nomura T, Fujioka H, Fidock DA, Roepe PD, Wellems TE: Alternative mutations at position 76 of the vacuolar transmembrane protein PfCRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium falciparum. Mol Pharmacol. 2002, 61: 35-42. 10.1124/mol.61.1.35.CrossRefPubMed
7.
Foote SJ, Kyle DE, Martin RK, Oduola AM, Forsyth K, Kemp DJ, Cowman AF: Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature. 1990, 345: 255-258. 10.1038/345255a0.CrossRefPubMed
8.
Reed MB, Saliba KJ, Caruana SR, Kirk K, Cowman AF: Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature. 2000, 403: 906-909. 10.1038/35002615.CrossRefPubMed
9.
Babiker HA, Pringle SJ, Abdel-Muhsin A, Mackinnon M, Hunt P, Walliker D: Highl-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
10.
Setthaudom C, Tan-ariya P, Sitthichot N, Khositnithikul R, Suwandittakul N, Leelayoova S, Mungthin M: Role of Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes on in vitro chloroquine resistance in isolates of Plasmodium falciparum from Thailand. Am J Trop Med Hyg. 2011, 85: 606-611. 10.4269/ajtmh.2011.11-0108.PubMedCentralCrossRefPubMed
11.
Wilson CM, Volkman SK, Thaithong S, Martin RK, Kyle DJ, Milhous WK, Wirth DF: Amplification of pfmdr1 associated with mefloquine and halofantrine resistance in Plasmodium falciparum from Thailand. Mol Biochem Parasitol. 1993, 57: 151-160. 10.1016/0166-6851(93)90252-S.CrossRefPubMed
12.
Cowman AF, Galatis D, Thompson JK: Selection for mefloquine resistance in Plasmodium falciparum is linked to amplification of the pfmdr1 gene and cross-resistance to halofantrine and quinine. Proc Natl Acad Sci U S A. 1994, 91: 1143-1147. 10.1073/pnas.91.3.1143.PubMedCentralCrossRefPubMed
13.
Pickard AL, Wongsrichanalai C, Purfield A, Kamwendo D, Emery K, Zalewski C, Kawamoto F, Miller RS, Meshnick SR: Resistance to antimalarials in Southeast Asia and genetic polymorphisms in pfmdr1. Antimicrob Agent Chemother. 2003, 47: 2418-2423. 10.1128/AAC.47.8.2418-2423.2003.CrossRef
14.
Nelson AL, Purfield A, McDaniel P, Uthaimongkol N, Buathong N, Sriwichai S, Miller RS, Wongsrichanalai C, Meshnick SR: Pfmdr1 genotyping and in vivo mefloquine resistance on the Thai-Myanmar border. Am J Trop Med Hyg. 2005, 72: 586-592.PubMed
15.
Duraisingh MT, Cowman AF: Contribution of the pfmdr1 gene to antimalarial drug-resistance. Acta Trop. 2005, 94: 181-190. 10.1016/j.actatropica.2005.04.008.CrossRefPubMed
16.
Duraisingh MT, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst DC: The tyrosine-86 allele of the pfmdr 1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. Mol Biochem Parasitol. 2000, 108: 12-23.CrossRef
17.
Poyomtip T, Suwandittakul N, Sitthichot N, Khositnithikul R, Tan-ariya P, Mungthin M: Polymorphisms of the pfmdr1 but not the pfnhe-1 gene is associated with in vitro quinine sensitivity in Thai isolates of Plasmodium falciparum. Malar J. 2012, 11: 7-10.1186/1475-2875-11-7.PubMedCentralCrossRefPubMed
18.
Mungthin M, Khositnithikul R, Sitthichot N, Suwandittakul N, Wattanaveeradej V, Ward SA, Na-Bangchang K: Association between the pfmdr1 gene and in vitro artemether and lumefantrine sensitivity in Thai isolates of Plasmodium falciparum. Am J Trop Med Hyg. 2010, 83: 1005-1009. 10.4269/ajtmh.2010.10-0339.PubMedCentralCrossRefPubMed
19.
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: 283-292. 10.1016/0166-6851(93)90050-8.CrossRefPubMed
20.
Trager W, Jensen JB: Human malaria parasites in continuous culture. Science. 1976, 193: 673-675. 10.1126/science.781840.CrossRefPubMed
21.
Desjardins RE, Canfield J, Haynes D, Chulay JD: Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother. 1979, 16: 710-718. 10.1128/AAC.16.6.710.PubMedCentralCrossRefPubMed
22.
Wooden J, Gould EE, Paull AT, Sibley CH: Plasmodium falciparum: a simple polymerase chain reaction method for differentiating strains. Exp Parasitol. 1992, 75: 207-212. 10.1016/0014-4894(92)90180-I.CrossRefPubMed
23.
Djimdé A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourté 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
24.
Duraisingh MT, Roper C, Walliker D, Warhurst DC: Increased sensitivity to the antimalarials mefloquine and artemisinin is conferred by mutations in the pfmdr 1 gene of Plasmodium falciparum. Mol Microbiol. 2000, 36: 955-961. 10.1046/j.1365-2958.2000.01914.x.CrossRefPubMed
25.
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 pfmdr 1 gene copy number. Lancet. 2004, 364: 438-447. 10.1016/S0140-6736(04)16767-6.PubMedCentralCrossRefPubMed
26.
Bickii J, Basco LK, Ringwald P: Assessment of three in vitro tests and an in vivo test for chloroquine resistance in Plasmodium falciparum clinical isolates. J Clin Microbiol. 1998, 36: 243-247.PubMedCentralPubMed
27.
Basco LK, Le Bras J: In vitro susceptibility of Cambodian isolates of Plasmodium falciparum to halofantrine, pyronaridine and artemisinin derivatives. Ann Trop Med Parasitol. 1994, 88: 137-144.PubMed
28.
Hatin I, Trape JF, Legros F, Bauchet J, Le Bras J: Susceptibility of Plasmodium falciparum strains to mefloquine in an urban area in Senegal. Bull World Health Org. 1992, 70: 363-367.PubMedCentralPubMed
29.
Mungthin M, Suwandittakul N, Chaijaroenkul W, Rungsrihirunrat K, Harnyuttanakorn P, Seugorn A, Na Bangchang K: The patterns of mutation and amplification of Plasmodium falciparum pfcrt and pfmdr1 genes in Thailand during the year 1988 to 2003. Parasitol Res. 2010, 107: 539-545. 10.1007/s00436-010-1887-x.CrossRefPubMed
30.
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 184 F mutation in Cambodia. J Infect Dis. 2010, 201: 1551-1560. 10.1086/651949.PubMedCentralCrossRefPubMed
31.
Phompradit P, Wisedpanichkij R, Muhamad P, Chaijaroenkul W, Na-Bangchang K: Molecular analysis of pfatp6 and pfmdr1 polymorphisms and their association with in vitro sensitivity in Plasmodium falciparum isolates from the Thai-Myanmar border. Acta Trop. 2011, 120: 130-135. 10.1016/j.actatropica.2011.07.003.CrossRefPubMed
32.
Rojanawatsirivej C, Vijaykadga S, Amklad I, Wilairatna P, Looareesuwan S: Monitoring the therapeutic efficacy of antimalarials against uncomplicated falciparum malaria in Thailand. Southeast Asian J Trop Med Public Health. 2003, 34: 536-541.PubMed
33.
Vijaykadga S, Rojanawatsirivej C, Cholpol S, Phoungmanee D, Nakavej A, Wongsrichanalai C: In vivo sensitivity monitoring of mefloquine monotherapy and artesunate-mefloquine combinations for the treatment of uncomplicated falciparum malaria in Thailand in 2003. Trop Med Int Health. 2006, 11: 211-219. 10.1111/j.1365-3156.2005.01557.x.CrossRefPubMed
34.
WHO: Malaria in the Greater Mekong Subregion: Regional and Country Profiles. 2010, Geneva: World Health Organization
35.
Pumpaibool T, Arnathau C, Durand P, Kanchanakhan N, Siripoon N, Suegorn A, Sitthi-Amorn C, Renaud F, Harnyuttanakorn P: Genetic diversity and population structure of Plasmodium falciparum in Thailand, a low transmission country. Malar J. 2009, 8: 155-10.1186/1475-2875-8-155.PubMedCentralCrossRefPubMed
36.
Atroosh WM, Al-Mekhlafi HM, Mahdy MA, Surin J: The detection of pfcrt and pfmdr1 point mutations as molecular markers of chloroquine drug resistance, Pahang, Malaysia. Malar J. 2012, 11: 251-10.1186/1475-2875-11-251.PubMedCentralCrossRefPubMed
37.
Rungsihirunrat K, Chaijareonkul W, Seugorn A, Na-Bangchang K, Thaithong S: Association between chloroquine resistance phenotypes and point mutations in pfcrt and pfmdr1 in Plasmodium falciparum isolates from Thailand. Acta Trop. 2009, 109: 37-40. 10.1016/j.actatropica.2008.09.011.CrossRefPubMed
38.
Andriantsoanirina V, Ratsimbasoa A, Bouchier C, Tichit M, Jahevitra M, Rabearimanana S, Raherinjafy R, Mercereau-Puijalon O, Durand R, Ménard D: Chloroquine clinical failures in P. falciparum malaria are associated with mutant Pfmdr-1, not Pfcrt in Madagascar. PLoS One. 2010, 5: e13281-10.1371/journal.pone.0013281.PubMedCentralCrossRefPubMed
39.
Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, Djimdé 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. 10.1086/375419.CrossRefPubMed
40.
Wang X, Mu J, Li G, Chen P, Guo X, Fu L, Chen L, Su X, Wellems TE: Decreased prevalence of the Plasmodium falciparum chloroquine resistance transporter 7 6 T marker associated with cessation of chloroquine use against P. falciparum malaria in Hainan, People's Republic of China. Am J Trop Med Hyg. 2005, 72: 410-414.PubMed
41.
Hayward R, Saliba KJ, Kirk K: Pfmdr1 mutations associated with chloroquine resistance incur a fitness cost in Plasmodium falciparum. Mol Microbiol. 2005, 55: 1285-1295. 10.1111/j.1365-2958.2004.04470.x.CrossRefPubMed
42.
Ochong E, Tumwebaze PK, Byaruhanga O, Greenhouse B, Rosenthal PJ: Fitness consequences of Plasmodium falciparum pfmdr1 polymorphisms inferred from ex vivo culture of Ugandan parasites. Antimicrob Agents Chemother. 2013, [Epub ahead of print]
43.
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. 10.1016/j.meegid.2006.03.008.CrossRefPubMed
Metadata
Title
Distribution of pfmdr1 polymorphisms in Plasmodium falciparum isolated from Southern Thailand
Authors
Mathirut Mungthin
Somchai Intanakom
Nantana Suwandittakul
Preeyaporn Suida
Sakultip Amsakul
Naruemon Sitthichot
Suwich Thammapalo
Saovanee Leelayoova
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2014
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-13-117

Other articles of this Issue 1/2014

Malaria Journal 1/2014 Go to the issue

Research

Impact of malaria related messages on insecticide-treated net (ITN) use for malaria prevention in Ghana

Research

Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceum

Research

Dramatic declines in seropositivity as determined with crude extracts of Plasmodium falciparum schizonts between 2000 and 2010 in Dielmo and Ndiop, Senegal

Commentary

The role of immunity in mosquito-induced attenuation of malaria virulence

Research

Development and optimization of the Suna trap as a tool for mosquito monitoring and control

Research

Biochemical and functional characterization of Plasmodium falciparum GTP cyclohydrolase I
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits