Plasmodium falciparum: In vitro activity of sulfadoxine and dapsone in field isolates from Kenya: Point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance

Edward K. Mberu; Alexis M. Nzila; Eunice Nduati; Amanda Ross; Stephanie M. Monks; Gilbert O. Kokwaro; William M. Watkins; Carol Hopkins Sibley

doi:10.1016/S0014-4894(02)00108-X

Plasmodium falciparum: In vitro activity of sulfadoxine and dapsone in field isolates from Kenya: Point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance

Edward K. Mberu
, Alexis M. Nzila
, Eunice Nduati
, Amanda Ross
, Stephanie M. Monks
, Gilbert O. Kokwaro
, William M. Watkins
, Carol Hopkins Sibley^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

We have determined the relationship between point mutations in the gene that encodes the sulfa target, dihydropteroate synthase (DHPS) and the chemosensitivity profile to sulfadoxine and dapsone in 67 isolates from Kilifi, Kenya. We assessed the presence of mutations at codons 436, 437, 540, 581, and 613 of dhps. The results showed that the dhps genotype had a strong influence on the sensitivity to sulfadoxine and dapsone, but that the correlation was far from perfect. Eleven isolates carried a wild-type dhps allele, but were resistant to sulfadoxine (IC₅₀ values >10μg/ml), and 4/28 isolates were classed as sensitive to sulfadoxine (IC₅₀ values <10μg/ml), but carried a triple mutant (436/437/613) allele of dhps. These data show that in low folate medium in vitro, the dhps genotype alone did not account completely for sulfadoxine or dapsone resistance; other factors such as the utilisation of exogenous folate must also be considered.

Original language	English
Pages (from-to)	90-96
Number of pages	7
Journal	Experimental Parasitology
Volume	101
Issue number	2-3
DOIs	https://doi.org/10.1016/S0014-4894(02)00108-X
State	Published - Jun 2002
Externally published	Yes

Bibliographical note

Funding Information:
The authors thank the Director of KEMRI for permission to carry out and publish this work. The study would have been impossible without the enthusiastic co-operation of patients and staff at Kilifi. This work was supported by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), the Wellcome Trust and KEMRI. WMW is grateful to SmithKline Beecham for financial support. EKM, AMN and WMW are grateful to the Wellcome Trust of Great Britain for personal and project support (WT grant references 42163 and 056769). CHS is supported by the UNDP/World Bank/WHO special program for Research and Training in Tropical Diseases (980369) and NIH grant AI 42321. EKM holds a training fellowship in the International Training and Research in Emerging Infectious Diseases (ITREID) program at the University of Washington, Seattle, USA.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Antifolate
Apicomplexa
DHPS
Drug resistance
Malaria

ASJC Scopus subject areas

Parasitology
Immunology
Infectious Diseases

Access to Document

10.1016/S0014-4894(02)00108-X

Cite this

Mberu, E. K., Nzila, A. M., Nduati, E., Ross, A., Monks, S. M., Kokwaro, G. O., Watkins, W. M., & Sibley, C. H. (2002). Plasmodium falciparum: In vitro activity of sulfadoxine and dapsone in field isolates from Kenya: Point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance. Experimental Parasitology, 101(2-3), 90-96. https://doi.org/10.1016/S0014-4894(02)00108-X

@article{4831859217744ce5af629913fa5e9193,

title = "Plasmodium falciparum: In vitro activity of sulfadoxine and dapsone in field isolates from Kenya: Point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance",

abstract = "We have determined the relationship between point mutations in the gene that encodes the sulfa target, dihydropteroate synthase (DHPS) and the chemosensitivity profile to sulfadoxine and dapsone in 67 isolates from Kilifi, Kenya. We assessed the presence of mutations at codons 436, 437, 540, 581, and 613 of dhps. The results showed that the dhps genotype had a strong influence on the sensitivity to sulfadoxine and dapsone, but that the correlation was far from perfect. Eleven isolates carried a wild-type dhps allele, but were resistant to sulfadoxine (IC50 values >10μg/ml), and 4/28 isolates were classed as sensitive to sulfadoxine (IC50 values <10μg/ml), but carried a triple mutant (436/437/613) allele of dhps. These data show that in low folate medium in vitro, the dhps genotype alone did not account completely for sulfadoxine or dapsone resistance; other factors such as the utilisation of exogenous folate must also be considered.",

keywords = "Antifolate, Apicomplexa, DHPS, Drug resistance, Malaria",

author = "Mberu, \{Edward K.\} and Nzila, \{Alexis M.\} and Eunice Nduati and Amanda Ross and Monks, \{Stephanie M.\} and Kokwaro, \{Gilbert O.\} and Watkins, \{William M.\} and Sibley, \{Carol Hopkins\}",

note = "Funding Information: The authors thank the Director of KEMRI for permission to carry out and publish this work. The study would have been impossible without the enthusiastic co-operation of patients and staff at Kilifi. This work was supported by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), the Wellcome Trust and KEMRI. WMW is grateful to SmithKline Beecham for financial support. EKM, AMN and WMW are grateful to the Wellcome Trust of Great Britain for personal and project support (WT grant references 42163 and 056769). CHS is supported by the UNDP/World Bank/WHO special program for Research and Training in Tropical Diseases (980369) and NIH grant AI 42321. EKM holds a training fellowship in the International Training and Research in Emerging Infectious Diseases (ITREID) program at the University of Washington, Seattle, USA.",

year = "2002",

month = jun,

doi = "10.1016/S0014-4894(02)00108-X",

language = "English",

volume = "101",

pages = "90--96",

journal = "Experimental Parasitology",

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}

Mberu, EK, Nzila, AM, Nduati, E, Ross, A, Monks, SM, Kokwaro, GO, Watkins, WM & Sibley, CH 2002, 'Plasmodium falciparum: In vitro activity of sulfadoxine and dapsone in field isolates from Kenya: Point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance', Experimental Parasitology, vol. 101, no. 2-3, pp. 90-96. https://doi.org/10.1016/S0014-4894(02)00108-X

Plasmodium falciparum: In vitro activity of sulfadoxine and dapsone in field isolates from Kenya: Point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance. / Mberu, Edward K.; Nzila, Alexis M.; Nduati, Eunice et al.
In: Experimental Parasitology, Vol. 101, No. 2-3, 06.2002, p. 90-96.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

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T2 - In vitro activity of sulfadoxine and dapsone in field isolates from Kenya: Point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance

AU - Mberu, Edward K.

AU - Nzila, Alexis M.

AU - Nduati, Eunice

AU - Ross, Amanda

AU - Monks, Stephanie M.

AU - Kokwaro, Gilbert O.

AU - Watkins, William M.

AU - Sibley, Carol Hopkins

N1 - Funding Information: The authors thank the Director of KEMRI for permission to carry out and publish this work. The study would have been impossible without the enthusiastic co-operation of patients and staff at Kilifi. This work was supported by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), the Wellcome Trust and KEMRI. WMW is grateful to SmithKline Beecham for financial support. EKM, AMN and WMW are grateful to the Wellcome Trust of Great Britain for personal and project support (WT grant references 42163 and 056769). CHS is supported by the UNDP/World Bank/WHO special program for Research and Training in Tropical Diseases (980369) and NIH grant AI 42321. EKM holds a training fellowship in the International Training and Research in Emerging Infectious Diseases (ITREID) program at the University of Washington, Seattle, USA.

PY - 2002/6

Y1 - 2002/6

N2 - We have determined the relationship between point mutations in the gene that encodes the sulfa target, dihydropteroate synthase (DHPS) and the chemosensitivity profile to sulfadoxine and dapsone in 67 isolates from Kilifi, Kenya. We assessed the presence of mutations at codons 436, 437, 540, 581, and 613 of dhps. The results showed that the dhps genotype had a strong influence on the sensitivity to sulfadoxine and dapsone, but that the correlation was far from perfect. Eleven isolates carried a wild-type dhps allele, but were resistant to sulfadoxine (IC50 values >10μg/ml), and 4/28 isolates were classed as sensitive to sulfadoxine (IC50 values <10μg/ml), but carried a triple mutant (436/437/613) allele of dhps. These data show that in low folate medium in vitro, the dhps genotype alone did not account completely for sulfadoxine or dapsone resistance; other factors such as the utilisation of exogenous folate must also be considered.

AB - We have determined the relationship between point mutations in the gene that encodes the sulfa target, dihydropteroate synthase (DHPS) and the chemosensitivity profile to sulfadoxine and dapsone in 67 isolates from Kilifi, Kenya. We assessed the presence of mutations at codons 436, 437, 540, 581, and 613 of dhps. The results showed that the dhps genotype had a strong influence on the sensitivity to sulfadoxine and dapsone, but that the correlation was far from perfect. Eleven isolates carried a wild-type dhps allele, but were resistant to sulfadoxine (IC50 values >10μg/ml), and 4/28 isolates were classed as sensitive to sulfadoxine (IC50 values <10μg/ml), but carried a triple mutant (436/437/613) allele of dhps. These data show that in low folate medium in vitro, the dhps genotype alone did not account completely for sulfadoxine or dapsone resistance; other factors such as the utilisation of exogenous folate must also be considered.

KW - Antifolate

KW - Apicomplexa

KW - DHPS

KW - Drug resistance

KW - Malaria

UR - https://www.scopus.com/pages/publications/0036628341

U2 - 10.1016/S0014-4894(02)00108-X

DO - 10.1016/S0014-4894(02)00108-X

M3 - Article

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AN - SCOPUS:0036628341

SN - 0014-4894

VL - 101

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JO - Experimental Parasitology

JF - Experimental Parasitology

IS - 2-3

ER -

Plasmodium falciparum: In vitro activity of sulfadoxine and dapsone in field isolates from Kenya: Point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance

Abstract

Bibliographical note

UN SDGs

Keywords

ASJC Scopus subject areas

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