Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique
Abstract Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples colle...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-04997-7 |
| _version_ | 1797806603305484288 |
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| author | Clemente da Silva Simone Boene Debayan Datta Eduard Rovira-Vallbona Andrés Aranda-Díaz Pau Cisteró Nicholas Hathaway Sofonias Tessema Arlindo Chidimatembue Glória Matambisso Abel Nhama Eusebio Macete Arnau Pujol Lidia Nhamussua Beatriz Galatas Caterina Guinovart Sónia Enosse Eva De Carvalho Eric Rogier Mateusz M. Plucinski James Colborn Rose Zulliger Abuchahama Saifodine Pedro L. Alonso Baltazar Candrinho Bryan Greenhouse Pedro Aide Francisco Saute Alfredo Mayor |
| author_facet | Clemente da Silva Simone Boene Debayan Datta Eduard Rovira-Vallbona Andrés Aranda-Díaz Pau Cisteró Nicholas Hathaway Sofonias Tessema Arlindo Chidimatembue Glória Matambisso Abel Nhama Eusebio Macete Arnau Pujol Lidia Nhamussua Beatriz Galatas Caterina Guinovart Sónia Enosse Eva De Carvalho Eric Rogier Mateusz M. Plucinski James Colborn Rose Zulliger Abuchahama Saifodine Pedro L. Alonso Baltazar Candrinho Bryan Greenhouse Pedro Aide Francisco Saute Alfredo Mayor |
| author_sort | Clemente da Silva |
| collection | DOAJ |
| description | Abstract Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pf dhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys. |
| first_indexed | 2024-03-13T06:09:46Z |
| format | Article |
| id | doaj.art-cd6a64ec370f42ed8ea5fc749da29275 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-13T06:09:46Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-cd6a64ec370f42ed8ea5fc749da292752023-06-11T11:22:53ZengNature PortfolioCommunications Biology2399-36422023-06-016111110.1038/s42003-023-04997-7Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in MozambiqueClemente da Silva0Simone Boene1Debayan Datta2Eduard Rovira-Vallbona3Andrés Aranda-Díaz4Pau Cisteró5Nicholas Hathaway6Sofonias Tessema7Arlindo Chidimatembue8Glória Matambisso9Abel Nhama10Eusebio Macete11Arnau Pujol12Lidia Nhamussua13Beatriz Galatas14Caterina Guinovart15Sónia Enosse16Eva De Carvalho17Eric Rogier18Mateusz M. Plucinski19James Colborn20Rose Zulliger21Abuchahama Saifodine22Pedro L. Alonso23Baltazar Candrinho24Bryan Greenhouse25Pedro Aide26Francisco Saute27Alfredo Mayor28Centro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)ISGlobal, Hospital Clínic – Universitat de BarcelonaISGlobal, Hospital Clínic – Universitat de BarcelonaEPPIcenter Research Program, Division of HIV, ID, and Global Medicine, Department of Medicine, University of CaliforniaISGlobal, Hospital Clínic – Universitat de BarcelonaUniversity of Massachusetts Chan Medical SchoolEPPIcenter Research Program, Division of HIV, ID, and Global Medicine, Department of Medicine, University of CaliforniaCentro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)ISGlobal, Hospital Clínic – Universitat de BarcelonaCentro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)ISGlobal, Hospital Clínic – Universitat de BarcelonaInstituto Nacional de Saúde (INS), Ministério da SaúdeWorld Health Organization, WHO Country Office MaputoMalaria Branch, Division of Parasitic Diseases and Malaria, United States Centers for Disease Control and PreventionUnited States President’s Malaria Initiative, Malaria Branch, Division of Parasitic Diseases and Malaria, United States Centers for Disease Control and PreventionClinton Health Access InitiativeU.S. President’s Malaria Initiative, USAIDU.S. President’s Malaria Initiative, USAIDCentro de Investigação em Saúde de Manhiça (CISM)National Malaria Control Programme, Ministry of HealthEPPIcenter Research Program, Division of HIV, ID, and Global Medicine, Department of Medicine, University of CaliforniaCentro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)Abstract Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pf dhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys.https://doi.org/10.1038/s42003-023-04997-7 |
| spellingShingle | Clemente da Silva Simone Boene Debayan Datta Eduard Rovira-Vallbona Andrés Aranda-Díaz Pau Cisteró Nicholas Hathaway Sofonias Tessema Arlindo Chidimatembue Glória Matambisso Abel Nhama Eusebio Macete Arnau Pujol Lidia Nhamussua Beatriz Galatas Caterina Guinovart Sónia Enosse Eva De Carvalho Eric Rogier Mateusz M. Plucinski James Colborn Rose Zulliger Abuchahama Saifodine Pedro L. Alonso Baltazar Candrinho Bryan Greenhouse Pedro Aide Francisco Saute Alfredo Mayor Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique Communications Biology |
| title | Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique |
| title_full | Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique |
| title_fullStr | Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique |
| title_full_unstemmed | Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique |
| title_short | Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique |
| title_sort | targeted and whole genome sequencing reveal a north south divide in p falciparum drug resistance markers and genetic structure in mozambique |
| url | https://doi.org/10.1038/s42003-023-04997-7 |
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