Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi

Research output: Contribution to journalJournal articleResearchpeer-review

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Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi. / Ravenhall, Matt; Benavente, Ernest Diez; Mipando, Mwapatsa; Jensen, Anja T R; Sutherland, Colin J; Roper, Cally; Sepúlveda, Nuno; Kwiatkowski, Dominic P; Montgomery, Jacqui; Phiri, Kamija S; Terlouw, Anja; Craig, Alister; Campino, Susana; Ocholla, Harold; Clark, Taane G.

In: Malaria Journal, Vol. 15, 575, 29.11.2016.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Ravenhall, M, Benavente, ED, Mipando, M, Jensen, ATR, Sutherland, CJ, Roper, C, Sepúlveda, N, Kwiatkowski, DP, Montgomery, J, Phiri, KS, Terlouw, A, Craig, A, Campino, S, Ocholla, H & Clark, TG 2016, 'Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi', Malaria Journal, vol. 15, 575. https://doi.org/10.1186/s12936-016-1634-6

APA

Ravenhall, M., Benavente, E. D., Mipando, M., Jensen, A. T. R., Sutherland, C. J., Roper, C., Sepúlveda, N., Kwiatkowski, D. P., Montgomery, J., Phiri, K. S., Terlouw, A., Craig, A., Campino, S., Ocholla, H., & Clark, T. G. (2016). Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi. Malaria Journal, 15, [575]. https://doi.org/10.1186/s12936-016-1634-6

Vancouver

Ravenhall M, Benavente ED, Mipando M, Jensen ATR, Sutherland CJ, Roper C et al. Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi. Malaria Journal. 2016 Nov 29;15. 575. https://doi.org/10.1186/s12936-016-1634-6

Author

Ravenhall, Matt ; Benavente, Ernest Diez ; Mipando, Mwapatsa ; Jensen, Anja T R ; Sutherland, Colin J ; Roper, Cally ; Sepúlveda, Nuno ; Kwiatkowski, Dominic P ; Montgomery, Jacqui ; Phiri, Kamija S ; Terlouw, Anja ; Craig, Alister ; Campino, Susana ; Ocholla, Harold ; Clark, Taane G. / Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi. In: Malaria Journal. 2016 ; Vol. 15.

Bibtex

@article{0d9a5755ea4e40208a2fda6cc9afc26b,
title = "Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi",
abstract = "BACKGROUND: Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the Plasmodium falciparum population.METHODS: Whole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used. More than 745,000 SNPs were identified, and differences in allele frequencies between countries assessed, as well as genetic regions under positive selection determined.RESULTS: Positive selection signals were identified within dhps, dhfr and gch1, all components of the parasite folate pathway associated with SP resistance. Sitting predominantly on a dhfr triple mutation background, a novel copy number increase of ~twofold was identified in the gch1 promoter. This copy number was almost fixed (96.8% frequency) in Malawi samples, but found at less than 45% frequency in other African populations, and distinct from a whole gene duplication previously reported in Southeast Asian parasites.CONCLUSIONS: SP resistance selection pressures have been retained in the Malawian population, with known resistance dhfr mutations at fixation, complemented by a novel gch1 promoter duplication. The effects of the duplication on the fitness costs of SP variants and resistance need to be elucidated.",
author = "Matt Ravenhall and Benavente, {Ernest Diez} and Mwapatsa Mipando and Jensen, {Anja T R} and Sutherland, {Colin J} and Cally Roper and Nuno Sep{\'u}lveda and Kwiatkowski, {Dominic P} and Jacqui Montgomery and Phiri, {Kamija S} and Anja Terlouw and Alister Craig and Susana Campino and Harold Ocholla and Clark, {Taane G}",
year = "2016",
month = nov,
day = "29",
doi = "10.1186/s12936-016-1634-6",
language = "English",
volume = "15",
journal = "Malaria Journal",
issn = "1475-2875",
publisher = "BioMed Central",

}

RIS

TY - JOUR

T1 - Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi

AU - Ravenhall, Matt

AU - Benavente, Ernest Diez

AU - Mipando, Mwapatsa

AU - Jensen, Anja T R

AU - Sutherland, Colin J

AU - Roper, Cally

AU - Sepúlveda, Nuno

AU - Kwiatkowski, Dominic P

AU - Montgomery, Jacqui

AU - Phiri, Kamija S

AU - Terlouw, Anja

AU - Craig, Alister

AU - Campino, Susana

AU - Ocholla, Harold

AU - Clark, Taane G

PY - 2016/11/29

Y1 - 2016/11/29

N2 - BACKGROUND: Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the Plasmodium falciparum population.METHODS: Whole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used. More than 745,000 SNPs were identified, and differences in allele frequencies between countries assessed, as well as genetic regions under positive selection determined.RESULTS: Positive selection signals were identified within dhps, dhfr and gch1, all components of the parasite folate pathway associated with SP resistance. Sitting predominantly on a dhfr triple mutation background, a novel copy number increase of ~twofold was identified in the gch1 promoter. This copy number was almost fixed (96.8% frequency) in Malawi samples, but found at less than 45% frequency in other African populations, and distinct from a whole gene duplication previously reported in Southeast Asian parasites.CONCLUSIONS: SP resistance selection pressures have been retained in the Malawian population, with known resistance dhfr mutations at fixation, complemented by a novel gch1 promoter duplication. The effects of the duplication on the fitness costs of SP variants and resistance need to be elucidated.

AB - BACKGROUND: Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the Plasmodium falciparum population.METHODS: Whole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used. More than 745,000 SNPs were identified, and differences in allele frequencies between countries assessed, as well as genetic regions under positive selection determined.RESULTS: Positive selection signals were identified within dhps, dhfr and gch1, all components of the parasite folate pathway associated with SP resistance. Sitting predominantly on a dhfr triple mutation background, a novel copy number increase of ~twofold was identified in the gch1 promoter. This copy number was almost fixed (96.8% frequency) in Malawi samples, but found at less than 45% frequency in other African populations, and distinct from a whole gene duplication previously reported in Southeast Asian parasites.CONCLUSIONS: SP resistance selection pressures have been retained in the Malawian population, with known resistance dhfr mutations at fixation, complemented by a novel gch1 promoter duplication. The effects of the duplication on the fitness costs of SP variants and resistance need to be elucidated.

U2 - 10.1186/s12936-016-1634-6

DO - 10.1186/s12936-016-1634-6

M3 - Journal article

C2 - 27899115

VL - 15

JO - Malaria Journal

JF - Malaria Journal

SN - 1475-2875

M1 - 575

ER -

ID: 169638614