Population-based genomic study of Plasmodium vivax malaria in seven Brazilian states and across South America

Amy Ibrahim; Emilia Manko; Jamille G. Dombrowski; Mónica Campos; Ernest Diez Benavente; Debbie Nolder; Colin J. Sutherland; Francois Nosten; Diana Fernandez; Gabriel Vélez-Tobón; Alberto Tobón Castaño; Anna Caroline C. Aguiar; Dhelio Batista Pereira; Simone da Silva Santos; Martha Suarez-Mutis; Silvia Maria Di Santi; Andrea Regina de Souza Baptista; Ricardo Luiz Dantas Machado; Claudio R.F. Marinho; Taane G. Clark; Susana Campino

doi:10.1016/j.lana.2022.100420

Population-based genomic study of Plasmodium vivax malaria in seven Brazilian states and across South America

Amy Ibrahim, Emilia Manko, Jamille G. Dombrowski, Mónica Campos, Ernest Diez Benavente, Debbie Nolder, Colin J. Sutherland, Francois Nosten, Diana Fernandez, Gabriel Vélez-Tobón, Alberto Tobón Castaño, Anna Caroline C. Aguiar, Dhelio Batista Pereira, Simone da Silva Santos, Martha Suarez-Mutis, Silvia Maria Di Santi, Andrea Regina de Souza Baptista, Ricardo Luiz Dantas Machado, Claudio R.F. Marinho, Taane G. Clark^*Susana Campino^*

^*Corresponding author for this work

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

Abstract

Background: Brazil is a unique and understudied setting for malaria, with complex foci of transmission associated with human and environmental conditions. An understanding of the population genomic diversity of P. vivax parasites across Brazil can support malaria control strategies. Methods: Through whole genome sequencing of P. vivax isolates across 7 Brazilian states, we use population genomic approaches to compare genetic diversity within country (n = 123), continent (6 countries, n = 315) and globally (26 countries, n = 885). Findings: We confirm that South American isolates are distinct, have more ancestral populations than the other global regions, with differentiating mutations in genes under selective pressure linked to antimalarial drugs (pvmdr1, pvdhfr-ts) and mosquito vectors (pvcrmp3, pvP45/48, pvP47). We demonstrate Brazil as a distinct parasite population, with signals of selection including ABC transporter (PvABCI3) and PHIST exported proteins. Interpretation: Brazil has a complex population structure, with evidence of P. simium infections and Amazonian parasites separating into multiple clusters. Overall, our work provides the first Brazil-wide analysis of P. vivax population structure and identifies important mutations, which can inform future research and control measures. Funding: AI is funded by an MRC LiD PhD studentship. TGC is funded by the Medical Research Council (Grant no. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1). SC is funded by Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1) and Bloomsbury SET (ref. CCF17-7779). FN is funded by The Shloklo Malaria Research Unit - part of the Mahidol Oxford Research Unit, supported by the Wellcome Trust (Grant no. 220211). ARSB is funded by São Paulo Research Foundation - FAPESP (Grant no. 2002/09546–1). RLDM is funded by Brazilian National Council for Scientific and Technological Development - CNPq (Grant no. 302353/2003–8 and 471605/2011–5); CRFM is funded by FAPESP (Grant no. 2020/06747–4) and CNPq (Grant no. 302917/2019–5 and 408636/2018–1); JGD is funded by FAPESP fellowships (2016/13465–0 and 2019/12068–5) and CNPq (Grant no. 409216/2018–6).

Original language	English
Article number	100420
Journal	The Lancet Regional Health - Americas
Volume	18
DOIs	https://doi.org/10.1016/j.lana.2022.100420
Publication status	Published - Feb 2023
Externally published	Yes

Keywords

Brazil
Drug resistance
Genomics
Malaria
Non-falciparum malaria
Plasmodium
Plasmodium vivax
Population genetics
South America
Vector-borne diseases
Whole genome sequencing

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10.1016/j.lana.2022.100420Licence: CC BY

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Ibrahim, A., Manko, E., Dombrowski, J. G., Campos, M., Benavente, E. D., Nolder, D., Sutherland, C. J., Nosten, F., Fernandez, D., Vélez-Tobón, G., Castaño, A. T., Aguiar, A. C. C., Pereira, D. B., da Silva Santos, S., Suarez-Mutis, M., Di Santi, S. M., Regina de Souza Baptista, A., Dantas Machado, R. L., Marinho, C. R. F., ... Campino, S. (2023). Population-based genomic study of Plasmodium vivax malaria in seven Brazilian states and across South America. The Lancet Regional Health - Americas, 18, Article 100420. https://doi.org/10.1016/j.lana.2022.100420

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title = "Population-based genomic study of Plasmodium vivax malaria in seven Brazilian states and across South America",

abstract = "Background: Brazil is a unique and understudied setting for malaria, with complex foci of transmission associated with human and environmental conditions. An understanding of the population genomic diversity of P. vivax parasites across Brazil can support malaria control strategies. Methods: Through whole genome sequencing of P. vivax isolates across 7 Brazilian states, we use population genomic approaches to compare genetic diversity within country (n = 123), continent (6 countries, n = 315) and globally (26 countries, n = 885). Findings: We confirm that South American isolates are distinct, have more ancestral populations than the other global regions, with differentiating mutations in genes under selective pressure linked to antimalarial drugs (pvmdr1, pvdhfr-ts) and mosquito vectors (pvcrmp3, pvP45/48, pvP47). We demonstrate Brazil as a distinct parasite population, with signals of selection including ABC transporter (PvABCI3) and PHIST exported proteins. Interpretation: Brazil has a complex population structure, with evidence of P. simium infections and Amazonian parasites separating into multiple clusters. Overall, our work provides the first Brazil-wide analysis of P. vivax population structure and identifies important mutations, which can inform future research and control measures. Funding: AI is funded by an MRC LiD PhD studentship. TGC is funded by the Medical Research Council (Grant no. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1). SC is funded by Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1) and Bloomsbury SET (ref. CCF17-7779). FN is funded by The Shloklo Malaria Research Unit - part of the Mahidol Oxford Research Unit, supported by the Wellcome Trust (Grant no. 220211). ARSB is funded by S{\~a}o Paulo Research Foundation - FAPESP (Grant no. 2002/09546–1). RLDM is funded by Brazilian National Council for Scientific and Technological Development - CNPq (Grant no. 302353/2003–8 and 471605/2011–5); CRFM is funded by FAPESP (Grant no. 2020/06747–4) and CNPq (Grant no. 302917/2019–5 and 408636/2018–1); JGD is funded by FAPESP fellowships (2016/13465–0 and 2019/12068–5) and CNPq (Grant no. 409216/2018–6).",

keywords = "Brazil, Drug resistance, Genomics, Malaria, Non-falciparum malaria, Plasmodium, Plasmodium vivax, Population genetics, South America, Vector-borne diseases, Whole genome sequencing",

author = "Amy Ibrahim and Emilia Manko and Dombrowski, {Jamille G.} and M{\'o}nica Campos and Benavente, {Ernest Diez} and Debbie Nolder and Sutherland, {Colin J.} and Francois Nosten and Diana Fernandez and Gabriel V{\'e}lez-Tob{\'o}n and Casta{\~n}o, {Alberto Tob{\'o}n} and Aguiar, {Anna Caroline C.} and Pereira, {Dhelio Batista} and {da Silva Santos}, Simone and Martha Suarez-Mutis and {Di Santi}, {Silvia Maria} and {Regina de Souza Baptista}, Andrea and {Dantas Machado}, {Ricardo Luiz} and Marinho, {Claudio R.F.} and Clark, {Taane G.} and Susana Campino",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2023",

month = feb,

doi = "10.1016/j.lana.2022.100420",

language = "English",

volume = "18",

}

Ibrahim, A, Manko, E, Dombrowski, JG, Campos, M, Benavente, ED, Nolder, D, Sutherland, CJ, Nosten, F, Fernandez, D, Vélez-Tobón, G, Castaño, AT, Aguiar, ACC, Pereira, DB, da Silva Santos, S, Suarez-Mutis, M, Di Santi, SM, Regina de Souza Baptista, A, Dantas Machado, RL, Marinho, CRF, Clark, TG & Campino, S 2023, 'Population-based genomic study of Plasmodium vivax malaria in seven Brazilian states and across South America', The Lancet Regional Health - Americas, vol. 18, 100420. https://doi.org/10.1016/j.lana.2022.100420

TY - JOUR

T1 - Population-based genomic study of Plasmodium vivax malaria in seven Brazilian states and across South America

AU - Ibrahim, Amy

AU - Manko, Emilia

AU - Dombrowski, Jamille G.

AU - Campos, Mónica

AU - Benavente, Ernest Diez

AU - Nolder, Debbie

AU - Sutherland, Colin J.

AU - Nosten, Francois

AU - Fernandez, Diana

AU - Vélez-Tobón, Gabriel

AU - Castaño, Alberto Tobón

AU - Aguiar, Anna Caroline C.

AU - Pereira, Dhelio Batista

AU - da Silva Santos, Simone

AU - Suarez-Mutis, Martha

AU - Di Santi, Silvia Maria

AU - Regina de Souza Baptista, Andrea

AU - Dantas Machado, Ricardo Luiz

AU - Marinho, Claudio R.F.

AU - Clark, Taane G.

AU - Campino, Susana

PY - 2023/2

Y1 - 2023/2

N2 - Background: Brazil is a unique and understudied setting for malaria, with complex foci of transmission associated with human and environmental conditions. An understanding of the population genomic diversity of P. vivax parasites across Brazil can support malaria control strategies. Methods: Through whole genome sequencing of P. vivax isolates across 7 Brazilian states, we use population genomic approaches to compare genetic diversity within country (n = 123), continent (6 countries, n = 315) and globally (26 countries, n = 885). Findings: We confirm that South American isolates are distinct, have more ancestral populations than the other global regions, with differentiating mutations in genes under selective pressure linked to antimalarial drugs (pvmdr1, pvdhfr-ts) and mosquito vectors (pvcrmp3, pvP45/48, pvP47). We demonstrate Brazil as a distinct parasite population, with signals of selection including ABC transporter (PvABCI3) and PHIST exported proteins. Interpretation: Brazil has a complex population structure, with evidence of P. simium infections and Amazonian parasites separating into multiple clusters. Overall, our work provides the first Brazil-wide analysis of P. vivax population structure and identifies important mutations, which can inform future research and control measures. Funding: AI is funded by an MRC LiD PhD studentship. TGC is funded by the Medical Research Council (Grant no. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1). SC is funded by Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1) and Bloomsbury SET (ref. CCF17-7779). FN is funded by The Shloklo Malaria Research Unit - part of the Mahidol Oxford Research Unit, supported by the Wellcome Trust (Grant no. 220211). ARSB is funded by São Paulo Research Foundation - FAPESP (Grant no. 2002/09546–1). RLDM is funded by Brazilian National Council for Scientific and Technological Development - CNPq (Grant no. 302353/2003–8 and 471605/2011–5); CRFM is funded by FAPESP (Grant no. 2020/06747–4) and CNPq (Grant no. 302917/2019–5 and 408636/2018–1); JGD is funded by FAPESP fellowships (2016/13465–0 and 2019/12068–5) and CNPq (Grant no. 409216/2018–6).

AB - Background: Brazil is a unique and understudied setting for malaria, with complex foci of transmission associated with human and environmental conditions. An understanding of the population genomic diversity of P. vivax parasites across Brazil can support malaria control strategies. Methods: Through whole genome sequencing of P. vivax isolates across 7 Brazilian states, we use population genomic approaches to compare genetic diversity within country (n = 123), continent (6 countries, n = 315) and globally (26 countries, n = 885). Findings: We confirm that South American isolates are distinct, have more ancestral populations than the other global regions, with differentiating mutations in genes under selective pressure linked to antimalarial drugs (pvmdr1, pvdhfr-ts) and mosquito vectors (pvcrmp3, pvP45/48, pvP47). We demonstrate Brazil as a distinct parasite population, with signals of selection including ABC transporter (PvABCI3) and PHIST exported proteins. Interpretation: Brazil has a complex population structure, with evidence of P. simium infections and Amazonian parasites separating into multiple clusters. Overall, our work provides the first Brazil-wide analysis of P. vivax population structure and identifies important mutations, which can inform future research and control measures. Funding: AI is funded by an MRC LiD PhD studentship. TGC is funded by the Medical Research Council (Grant no. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1). SC is funded by Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1) and Bloomsbury SET (ref. CCF17-7779). FN is funded by The Shloklo Malaria Research Unit - part of the Mahidol Oxford Research Unit, supported by the Wellcome Trust (Grant no. 220211). ARSB is funded by São Paulo Research Foundation - FAPESP (Grant no. 2002/09546–1). RLDM is funded by Brazilian National Council for Scientific and Technological Development - CNPq (Grant no. 302353/2003–8 and 471605/2011–5); CRFM is funded by FAPESP (Grant no. 2020/06747–4) and CNPq (Grant no. 302917/2019–5 and 408636/2018–1); JGD is funded by FAPESP fellowships (2016/13465–0 and 2019/12068–5) and CNPq (Grant no. 409216/2018–6).

KW - Brazil

KW - Drug resistance

KW - Genomics

KW - Malaria

KW - Non-falciparum malaria

KW - Plasmodium

KW - Plasmodium vivax

KW - Population genetics

KW - South America

KW - Vector-borne diseases

KW - Whole genome sequencing

UR - http://www.scopus.com/inward/record.url?scp=85145423606&partnerID=8YFLogxK

U2 - 10.1016/j.lana.2022.100420

DO - 10.1016/j.lana.2022.100420

M3 - Article

AN - SCOPUS:85145423606

VL - 18

JO - The Lancet Regional Health - Americas

JF - The Lancet Regional Health - Americas

M1 - 100420

ER -

Population-based genomic study of Plasmodium vivax malaria in seven Brazilian states and across South America

Abstract

Keywords

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