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Published in: Malaria Journal 1/2002

Open Access 01-12-2002 | Research

Molecular surveillance of drug resistance through imported isolates of Plasmodium falciparum in Europe

Authors: Tomas Jelinek, Gabriele Peyerl-Hoffmann, Nikolai Mühlberger, Ole Wichmann, Michael Wilhelm, Nadja Schmider, Martin P Grobusch, Frank von Sonnenburg, Joaquim Gascon, Hermann Laferl, Christoph Hatz, Michael Alifrangis, Gerd Burchard, Paul McWhinney, Marco Schulze, Herwig Kollaritsch, Saraiva da Cunha, Jiři Beřan, Peter Kern, Ida Gjørup, Juan Cuadros

Published in: Malaria Journal | Issue 1/2002

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Abstract

Background

Results from numerous studies point convincingly to correlations between mutations at selected genes and phenotypic resistance to antimalarials in Plasmodium falciparum isolates. In order to move molecular assays for point mutations on resistance-related genes into the realm of applied tools for surveillance, we investigated a selection of P. falciparum isolates that were imported during the year 2001 into Europe to study the prevalence of resistance-associated point mutations at relevant codons. In particular, we tested for parasites which were developing resistance to antifolates and chloroquine. The screening results were used to map the prevalence of mutations and, thus, levels of potential drug resistance in endemic areas world-wide.

Results

337 isolates have been tested so far. Prevalence of mutations that are associated with resistance to chloroquine on the pfcrt and pfmdr genes of P. falciparum was demonstrated at high levels. However, the prevalence of mutations associated with resistance to antifolates at the DHFR and DHPS genes was unexpectedly low, rarely exceeding 60% in endemic areas.

Conclusions

Constant screening of imported isolates will enable TropNetEurop to establish a screening tool for emerging resistance in endemic areas.
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Literature
1.
2.
go back to reference Ouellette M: Biochemical and molecular mechanisms of drug resistance in parasites. Trop Med Int Health. 2001, 6: 874-876. 10.1046/j.1365-3156.2001.00777.x.CrossRefPubMed Ouellette M: Biochemical and molecular mechanisms of drug resistance in parasites. Trop Med Int Health. 2001, 6: 874-876. 10.1046/j.1365-3156.2001.00777.x.CrossRefPubMed
3.
go back to reference Wellems T, Plowe C: Chloroquine-resistant malaria. J Infect Dis. 2001, 184: 770-776. 10.1086/322858.CrossRefPubMed Wellems T, Plowe C: Chloroquine-resistant malaria. J Infect Dis. 2001, 184: 770-776. 10.1086/322858.CrossRefPubMed
4.
go back to reference Curtis J, Duraisingh M, Trigg J, Mbwana H, Warhurst D, Curtis C: Direct evidence that asparagine at position 108 of the Plasmodium falciparum dihydrofolate reductase is involved in resistance to antifolate drugs in Tanzania. Trans R Soc Trop Med Hyg. 1996, 90: 678-680.CrossRefPubMed Curtis J, Duraisingh M, Trigg J, Mbwana H, Warhurst D, Curtis C: Direct evidence that asparagine at position 108 of the Plasmodium falciparum dihydrofolate reductase is involved in resistance to antifolate drugs in Tanzania. Trans R Soc Trop Med Hyg. 1996, 90: 678-680.CrossRefPubMed
5.
go back to reference Curtis J, Duraisingh M, Warhurst D: In Vivo Selection for a specific Genotype of Dihydropteroate Synthetase of Plasmodium falciparum by Pyrimethamine-Sulfadoxine but not Chlorproguanil-Dapsone Treatment. J Infect Dis. 1998, 177: 1429-1433.CrossRefPubMed Curtis J, Duraisingh M, Warhurst D: In Vivo Selection for a specific Genotype of Dihydropteroate Synthetase of Plasmodium falciparum by Pyrimethamine-Sulfadoxine but not Chlorproguanil-Dapsone Treatment. J Infect Dis. 1998, 177: 1429-1433.CrossRefPubMed
6.
go back to reference Jelinek T, Ronn AM, Lemnge MM, Curtis J, Mhina J, Duraisingh MT, Bygbjerg IC, Warhurst DC: Polymorphisms in the dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) genes of Plasmodium falciparum and in vivo resistance to sulphadoxine/pyrimethamine in isolates from Tanzania. Trop Med Int Health. 1998, 3: 605-9. 10.1046/j.1365-3156.1998.00280.x.CrossRefPubMed Jelinek T, Ronn AM, Lemnge MM, Curtis J, Mhina J, Duraisingh MT, Bygbjerg IC, Warhurst DC: Polymorphisms in the dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) genes of Plasmodium falciparum and in vivo resistance to sulphadoxine/pyrimethamine in isolates from Tanzania. Trop Med Int Health. 1998, 3: 605-9. 10.1046/j.1365-3156.1998.00280.x.CrossRefPubMed
7.
go back to reference Jelinek T, Kilian A, Curtis J, Duraisingh M, Kabagambe G, von Sonnenburg F, Warhurst D: Plasmodium falciparum: Selection of serine 108 of dihydrofolate reductase (DHFR) and alanine 581 of dihydropteroate synthetase (DHPS) during co-trimoxazole treatment of uncomplicated malaria in Ugandan children. Am J Trop Med Hyg. 1999, 61: 125-130.PubMed Jelinek T, Kilian A, Curtis J, Duraisingh M, Kabagambe G, von Sonnenburg F, Warhurst D: Plasmodium falciparum: Selection of serine 108 of dihydrofolate reductase (DHFR) and alanine 581 of dihydropteroate synthetase (DHPS) during co-trimoxazole treatment of uncomplicated malaria in Ugandan children. Am J Trop Med Hyg. 1999, 61: 125-130.PubMed
8.
go back to reference Djimde A, Doumbo O, Cortese J, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su X, Nomura T, Fidock D, Wellems T, Plowe C: A molecular marker for chloroquine-resistant falciparum malaria. New Engl J Med. 2001, 344: 257-263. 10.1056/NEJM200101253440403.CrossRefPubMed Djimde A, Doumbo O, Cortese J, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su X, Nomura T, Fidock D, Wellems T, Plowe C: A molecular marker for chloroquine-resistant falciparum malaria. New Engl J Med. 2001, 344: 257-263. 10.1056/NEJM200101253440403.CrossRefPubMed
9.
go back to reference Kublin J, Dzinjalamala F, Kamwendo D, Malkin E, Cortese J, Martino L, Mukadam R, Rogerson S, Lescano A, Molyneux M, Winstanley P, Chimpeni P, Taylor T, Plowe C: Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis. 2002, 185: 380-388. 10.1086/338566.CrossRefPubMed Kublin J, Dzinjalamala F, Kamwendo D, Malkin E, Cortese J, Martino L, Mukadam R, Rogerson S, Lescano A, Molyneux M, Winstanley P, Chimpeni P, Taylor T, Plowe C: Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis. 2002, 185: 380-388. 10.1086/338566.CrossRefPubMed
10.
go back to reference Jelinek T, Schulte C, Behrens R, Grobusch M, Coulaud J, Bisoffi Z, Matteelli A, Clerinx J, Corachán M, Puente S, Gjørup I, Harms G, Kollaritsch H, Kotlowski A, Björkmann A, Delmont J, Knobloch J, Nielsen L, Cuadros J, Hatz C, Beran J, Schmid M, Schulze M, Lopez-Velez R, Fleischer K, Kapaun A, McWhinney P, Kern P, Atougia J, Fry G, da Cunha S, Boecken G: Clinical and epidemiological characteristics among travellers and immigrants with imported Falciparum malaria in Europe: sentinel surveillance data from TropNetEurop. Clin Infect Dis. 2002, 34: 572-576. 10.1086/338235.CrossRefPubMed Jelinek T, Schulte C, Behrens R, Grobusch M, Coulaud J, Bisoffi Z, Matteelli A, Clerinx J, Corachán M, Puente S, Gjørup I, Harms G, Kollaritsch H, Kotlowski A, Björkmann A, Delmont J, Knobloch J, Nielsen L, Cuadros J, Hatz C, Beran J, Schmid M, Schulze M, Lopez-Velez R, Fleischer K, Kapaun A, McWhinney P, Kern P, Atougia J, Fry G, da Cunha S, Boecken G: Clinical and epidemiological characteristics among travellers and immigrants with imported Falciparum malaria in Europe: sentinel surveillance data from TropNetEurop. Clin Infect Dis. 2002, 34: 572-576. 10.1086/338235.CrossRefPubMed
11.
go back to reference Jelinek T, Pröll S, Hess F, von Sonnenburg F, Kabagambe K, Löscher T, Kilian AHD: Geographical differences in the sensitivity of polymerase chain reaction for detection of P. falcipar um infection in Uganda. Am J Trop Med Hyg. 1996, 55: 647-651.PubMed Jelinek T, Pröll S, Hess F, von Sonnenburg F, Kabagambe K, Löscher T, Kilian AHD: Geographical differences in the sensitivity of polymerase chain reaction for detection of P. falcipar um infection in Uganda. Am J Trop Med Hyg. 1996, 55: 647-651.PubMed
12.
go back to reference Duraisingh M, Drakeley C, Muller O, Bailey R, Snounou G, Targett G, Greenwood B, Warhurst D: Evidence for selection for the tyrosine-86 allele of the pfmdr 1 gene of Plasmodium falciparum by chloroquine and amodiaquine. Parasitology. 1997, 114: 205-211. 10.1017/S0031182096008487.CrossRefPubMed Duraisingh M, Drakeley C, Muller O, Bailey R, Snounou G, Targett G, Greenwood B, Warhurst D: Evidence for selection for the tyrosine-86 allele of the pfmdr 1 gene of Plasmodium falciparum by chloroquine and amodiaquine. Parasitology. 1997, 114: 205-211. 10.1017/S0031182096008487.CrossRefPubMed
13.
go back to reference Flüeck T, Jelinek T, Kilian A, Adagu I, Kabagambe G, von Sonnenburg F, Warhurst D: Correlation of in vivo-resistance to chloroquine and allelic polymorphisms in Plasmodium falciparum isolates from Uganda. Trop Med Int Health. 2000, 5: 174-178. 10.1046/j.1365-3156.2000.00543.x.CrossRefPubMed Flüeck T, Jelinek T, Kilian A, Adagu I, Kabagambe G, von Sonnenburg F, Warhurst D: Correlation of in vivo-resistance to chloroquine and allelic polymorphisms in Plasmodium falciparum isolates from Uganda. Trop Med Int Health. 2000, 5: 174-178. 10.1046/j.1365-3156.2000.00543.x.CrossRefPubMed
14.
go back to reference Fidock D, Nomura T, Talley A, Cooper A, Dzekunov M, Ferdig T, Ursos M, Sidhu A, Naude B, Deitsch W, Su Z, Wootton C, Roepe D, Wellems E: 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 Fidock D, Nomura T, Talley A, Cooper A, Dzekunov M, Ferdig T, Ursos M, Sidhu A, Naude B, Deitsch W, Su Z, Wootton C, Roepe D, Wellems E: 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
15.
go back to reference Duraisingh M, Curtis J, Warhurst D: Plasmodium falciparum: Detection of Polymorphisms in the Dihydrofolate Reductase and Dihydropteroate Synthetase Genes by PCR and Restriction Digestion. Exp Parasitol. 1998, 89: 1-8. 10.1006/expr.1998.4274.CrossRefPubMed Duraisingh M, Curtis J, Warhurst D: Plasmodium falciparum: Detection of Polymorphisms in the Dihydrofolate Reductase and Dihydropteroate Synthetase Genes by PCR and Restriction Digestion. Exp Parasitol. 1998, 89: 1-8. 10.1006/expr.1998.4274.CrossRefPubMed
16.
go back to reference Sanchez C, Lanzer M: Changing ideas on chloroquine in Plasmodium falciparum. Curr Opin Infect Dis. 2000, 13: 653-658.CrossRefPubMed Sanchez C, Lanzer M: Changing ideas on chloroquine in Plasmodium falciparum. Curr Opin Infect Dis. 2000, 13: 653-658.CrossRefPubMed
17.
go back to reference Wernsdorfer W: Epidemiology of drug resistance in malaria. Acta Trop. 1994, 56: 143-156. 10.1016/0001-706X(94)90060-4.CrossRefPubMed Wernsdorfer W: Epidemiology of drug resistance in malaria. Acta Trop. 1994, 56: 143-156. 10.1016/0001-706X(94)90060-4.CrossRefPubMed
Metadata
Title
Molecular surveillance of drug resistance through imported isolates of Plasmodium falciparum in Europe
Authors
Tomas Jelinek
Gabriele Peyerl-Hoffmann
Nikolai Mühlberger
Ole Wichmann
Michael Wilhelm
Nadja Schmider
Martin P Grobusch
Frank von Sonnenburg
Joaquim Gascon
Hermann Laferl
Christoph Hatz
Michael Alifrangis
Gerd Burchard
Paul McWhinney
Marco Schulze
Herwig Kollaritsch
Saraiva da Cunha
Jiři Beřan
Peter Kern
Ida Gjørup
Juan Cuadros
Publication date
01-12-2002
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2002
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-1-11

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