Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe

Ole Wichmann; Nikolai Muehlberger; Tomas Jelinek; Michael Alifrangis; Gabriele Peyerl-Hoffmann; Marion Muhlen; Martin P Grobusch; Joaquim Gascon; Alberto Matteelli; Hermann Laferl; Zeno Bisoffi; Stephan Ehrhardt; Juan Cuadros; Christoph Hatz; Ida Gjorup; Paul McWhinney; Jiri Beran; Saraiva da Cunha; Marco Schulze; Herwig Kollaritsch; Peter Kern; Graham Fry; Joachim Richter; European Network on Surveillance of Imported Infectious Diseases

doi:10.1086/424469

Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe

Ole Wichmann, Nikolai Muehlberger, Tomas Jelinek, Michael Alifrangis, Gabriele Peyerl-Hoffmann, Marion Muhlen, Martin P Grobusch, Joaquim Gascon, Alberto Matteelli, Hermann Laferl, Zeno Bisoffi, Stephan Ehrhardt, Juan Cuadros, Christoph Hatz, Ida Gjorup, Paul McWhinney, Jiri Beran, Saraiva da Cunha, Marco Schulze, Herwig KollaritschPeter Kern, Graham Fry, Joachim Richter, European Network on Surveillance of Imported Infectious Diseases

52 Citations (Scopus)

Abstract

BACKGROUND: Two single-point mutations of the Plasmodium falciparum cytochrome b gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of atovaquone/proguanil (Malarone) treatment failure. However, little is known about the prevalence of codon-268 mutations and their quantitative association with treatment failure. METHODS: We set out to assess the prevalence of codon-268 mutations in P. falciparum isolates imported into Europe and to quantify their association with atovaquone/proguanil treatment failure. Isolates of P. falciparum collected by the European Network on Imported Infectious Disease Surveillance between April 2000 and August 2003 were analyzed for codon-268 mutations, by use of polymerase chain reaction-restriction fragment-length polymorphism. RESULTS: We successfully screened 504 samples for the presence of either Tyr268Ser or Tyr268Asn. One case of Ser268 and no cases of Asn268 were detected. Therefore, we can be 95% confident that the prevalence of Ser268 in the European patient pool does not exceed 0.96% and that Asn268 is less frequent than 0.77%. In 58 patients treated with atovaquone/proguanil, Tyr268Ser was present in 1 of 5 patients with treatment failure but in 0 of 53 successfully treated patients. CONCLUSIONS: Tyr268Ser seems to be a sufficient, but not a necessary, cause for atovaquone/proguanil treatment failure. The prevalence of both codon-268 mutations is currently unlikely to be >1% in the European patient pool.

Original language	English
Journal	Journal of Infectious Diseases
Volume	190
Issue number	9
Pages (from-to)	1541-6
Number of pages	5
ISSN	0022-1899
DOIs	https://doi.org/10.1086/424469
Publication status	Published - 2004

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10.1086/424469

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Wichmann, O., Muehlberger, N., Jelinek, T., Alifrangis, M., Peyerl-Hoffmann, G., Muhlen, M., Grobusch, M. P., Gascon, J., Matteelli, A., Laferl, H., Bisoffi, Z., Ehrhardt, S., Cuadros, J., Hatz, C., Gjorup, I., McWhinney, P., Beran, J., da Cunha, S., Schulze, M., ... European Network on Surveillance of Imported Infectious Diseases (2004). Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe. Journal of Infectious Diseases, 190(9), 1541-6. https://doi.org/10.1086/424469

Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe. / Wichmann, Ole; Muehlberger, Nikolai; Jelinek, Tomas et al.

In: Journal of Infectious Diseases, Vol. 190, No. 9, 2004, p. 1541-6.

Research output: Contribution to journal › Journal article › Research › peer-review

Wichmann, O, Muehlberger, N, Jelinek, T, Alifrangis, M, Peyerl-Hoffmann, G, Muhlen, M, Grobusch, MP, Gascon, J, Matteelli, A, Laferl, H, Bisoffi, Z, Ehrhardt, S, Cuadros, J, Hatz, C, Gjorup, I, McWhinney, P, Beran, J, da Cunha, S, Schulze, M, Kollaritsch, H, Kern, P, Fry, G, Richter, J & European Network on Surveillance of Imported Infectious Diseases 2004, 'Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe', Journal of Infectious Diseases, vol. 190, no. 9, pp. 1541-6. https://doi.org/10.1086/424469

@article{aaac9370a99911ddb5e9000ea68e967b,

title = "Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe",

abstract = "BACKGROUND: Two single-point mutations of the Plasmodium falciparum cytochrome b gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of atovaquone/proguanil (Malarone) treatment failure. However, little is known about the prevalence of codon-268 mutations and their quantitative association with treatment failure. METHODS: We set out to assess the prevalence of codon-268 mutations in P. falciparum isolates imported into Europe and to quantify their association with atovaquone/proguanil treatment failure. Isolates of P. falciparum collected by the European Network on Imported Infectious Disease Surveillance between April 2000 and August 2003 were analyzed for codon-268 mutations, by use of polymerase chain reaction-restriction fragment-length polymorphism. RESULTS: We successfully screened 504 samples for the presence of either Tyr268Ser or Tyr268Asn. One case of Ser268 and no cases of Asn268 were detected. Therefore, we can be 95% confident that the prevalence of Ser268 in the European patient pool does not exceed 0.96% and that Asn268 is less frequent than 0.77%. In 58 patients treated with atovaquone/proguanil, Tyr268Ser was present in 1 of 5 patients with treatment failure but in 0 of 53 successfully treated patients. CONCLUSIONS: Tyr268Ser seems to be a sufficient, but not a necessary, cause for atovaquone/proguanil treatment failure. The prevalence of both codon-268 mutations is currently unlikely to be >1% in the European patient pool.",

author = "Ole Wichmann and Nikolai Muehlberger and Tomas Jelinek and Michael Alifrangis and Gabriele Peyerl-Hoffmann and Marion Muhlen and Grobusch, {Martin P} and Joaquim Gascon and Alberto Matteelli and Hermann Laferl and Zeno Bisoffi and Stephan Ehrhardt and Juan Cuadros and Christoph Hatz and Ida Gjorup and Paul McWhinney and Jiri Beran and {da Cunha}, Saraiva and Marco Schulze and Herwig Kollaritsch and Peter Kern and Graham Fry and Joachim Richter and {European Network on Surveillance of Imported Infectious Diseases}",

note = "Keywords: Adolescent; Adult; Aged; Amino Acid Substitution; Animals; Antimalarials; Atovaquone; Chloroguanide; Codon; Cytochromes b; DNA, Protozoan; Drug Combinations; Drug Resistance; Epidemiology, Molecular; Europe; Female; Genes, Protozoan; Humans; Malaria, Falciparum; Male; Middle Aged; Mutation, Missense; Naphthoquinones; Plasmodium falciparum; Point Mutation; Polymorphism, Restriction Fragment Length; Protozoan Proteins; Treatment Failure",

year = "2004",

doi = "10.1086/424469",

language = "English",

volume = "190",

pages = "1541--6",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "9",

}

TY - JOUR

T1 - Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe

AU - Wichmann, Ole

AU - Muehlberger, Nikolai

AU - Jelinek, Tomas

AU - Alifrangis, Michael

AU - Peyerl-Hoffmann, Gabriele

AU - Muhlen, Marion

AU - Grobusch, Martin P

AU - Gascon, Joaquim

AU - Matteelli, Alberto

AU - Laferl, Hermann

AU - Bisoffi, Zeno

AU - Ehrhardt, Stephan

AU - Cuadros, Juan

AU - Hatz, Christoph

AU - Gjorup, Ida

AU - McWhinney, Paul

AU - Beran, Jiri

AU - da Cunha, Saraiva

AU - Schulze, Marco

AU - Kollaritsch, Herwig

AU - Kern, Peter

AU - Fry, Graham

AU - Richter, Joachim

AU - European Network on Surveillance of Imported Infectious Diseases

N1 - Keywords: Adolescent; Adult; Aged; Amino Acid Substitution; Animals; Antimalarials; Atovaquone; Chloroguanide; Codon; Cytochromes b; DNA, Protozoan; Drug Combinations; Drug Resistance; Epidemiology, Molecular; Europe; Female; Genes, Protozoan; Humans; Malaria, Falciparum; Male; Middle Aged; Mutation, Missense; Naphthoquinones; Plasmodium falciparum; Point Mutation; Polymorphism, Restriction Fragment Length; Protozoan Proteins; Treatment Failure

PY - 2004

Y1 - 2004

N2 - BACKGROUND: Two single-point mutations of the Plasmodium falciparum cytochrome b gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of atovaquone/proguanil (Malarone) treatment failure. However, little is known about the prevalence of codon-268 mutations and their quantitative association with treatment failure. METHODS: We set out to assess the prevalence of codon-268 mutations in P. falciparum isolates imported into Europe and to quantify their association with atovaquone/proguanil treatment failure. Isolates of P. falciparum collected by the European Network on Imported Infectious Disease Surveillance between April 2000 and August 2003 were analyzed for codon-268 mutations, by use of polymerase chain reaction-restriction fragment-length polymorphism. RESULTS: We successfully screened 504 samples for the presence of either Tyr268Ser or Tyr268Asn. One case of Ser268 and no cases of Asn268 were detected. Therefore, we can be 95% confident that the prevalence of Ser268 in the European patient pool does not exceed 0.96% and that Asn268 is less frequent than 0.77%. In 58 patients treated with atovaquone/proguanil, Tyr268Ser was present in 1 of 5 patients with treatment failure but in 0 of 53 successfully treated patients. CONCLUSIONS: Tyr268Ser seems to be a sufficient, but not a necessary, cause for atovaquone/proguanil treatment failure. The prevalence of both codon-268 mutations is currently unlikely to be >1% in the European patient pool.

AB - BACKGROUND: Two single-point mutations of the Plasmodium falciparum cytochrome b gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of atovaquone/proguanil (Malarone) treatment failure. However, little is known about the prevalence of codon-268 mutations and their quantitative association with treatment failure. METHODS: We set out to assess the prevalence of codon-268 mutations in P. falciparum isolates imported into Europe and to quantify their association with atovaquone/proguanil treatment failure. Isolates of P. falciparum collected by the European Network on Imported Infectious Disease Surveillance between April 2000 and August 2003 were analyzed for codon-268 mutations, by use of polymerase chain reaction-restriction fragment-length polymorphism. RESULTS: We successfully screened 504 samples for the presence of either Tyr268Ser or Tyr268Asn. One case of Ser268 and no cases of Asn268 were detected. Therefore, we can be 95% confident that the prevalence of Ser268 in the European patient pool does not exceed 0.96% and that Asn268 is less frequent than 0.77%. In 58 patients treated with atovaquone/proguanil, Tyr268Ser was present in 1 of 5 patients with treatment failure but in 0 of 53 successfully treated patients. CONCLUSIONS: Tyr268Ser seems to be a sufficient, but not a necessary, cause for atovaquone/proguanil treatment failure. The prevalence of both codon-268 mutations is currently unlikely to be >1% in the European patient pool.

U2 - 10.1086/424469

DO - 10.1086/424469

M3 - Journal article

C2 - 15478057

SN - 0022-1899

VL - 190

SP - 1541

EP - 1546

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 9

ER -

Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe

Abstract

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