Surveillance of molecular markers of Plasmodium falciparum artemisinin resistance (kelch13 mutations) in Papua New Guinea between 2016 and 2018
Plasmodium falciparum resistance to artemisinin-based combination therapy (ACT) is a global threat to malaria control and elimination efforts. Mutations in the P. falciparum kelch13 gene (Pfk13) that are associated with delayed parasite clearance have emerged on the Thai-Cambodian border since 2008....
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Elsevier
2021-08-01
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Series: | International Journal for Parasitology: Drugs and Drug Resistance |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320721000312 |
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doaj-198619d3abfe4e2bbb6d7c0403e93cc4 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dulcie Lautu-Gumal Zahra Razook Tamarah Koleala Elma Nate Samuel McEwen Diana Timbi Manuel W. Hetzel Evelyn Lavu Nakapi Tefuarani Leo Makita James Kazura Ivo Mueller William Pomat Moses Laman Leanne J. Robinson Alyssa E. Barry |
spellingShingle |
Dulcie Lautu-Gumal Zahra Razook Tamarah Koleala Elma Nate Samuel McEwen Diana Timbi Manuel W. Hetzel Evelyn Lavu Nakapi Tefuarani Leo Makita James Kazura Ivo Mueller William Pomat Moses Laman Leanne J. Robinson Alyssa E. Barry Surveillance of molecular markers of Plasmodium falciparum artemisinin resistance (kelch13 mutations) in Papua New Guinea between 2016 and 2018 International Journal for Parasitology: Drugs and Drug Resistance Plasmodium falciparum Artemisinin resistance Antimalarial drug resistance kelch13 mutations Malaria control Surveillance |
author_facet |
Dulcie Lautu-Gumal Zahra Razook Tamarah Koleala Elma Nate Samuel McEwen Diana Timbi Manuel W. Hetzel Evelyn Lavu Nakapi Tefuarani Leo Makita James Kazura Ivo Mueller William Pomat Moses Laman Leanne J. Robinson Alyssa E. Barry |
author_sort |
Dulcie Lautu-Gumal |
title |
Surveillance of molecular markers of Plasmodium falciparum artemisinin resistance (kelch13 mutations) in Papua New Guinea between 2016 and 2018 |
title_short |
Surveillance of molecular markers of Plasmodium falciparum artemisinin resistance (kelch13 mutations) in Papua New Guinea between 2016 and 2018 |
title_full |
Surveillance of molecular markers of Plasmodium falciparum artemisinin resistance (kelch13 mutations) in Papua New Guinea between 2016 and 2018 |
title_fullStr |
Surveillance of molecular markers of Plasmodium falciparum artemisinin resistance (kelch13 mutations) in Papua New Guinea between 2016 and 2018 |
title_full_unstemmed |
Surveillance of molecular markers of Plasmodium falciparum artemisinin resistance (kelch13 mutations) in Papua New Guinea between 2016 and 2018 |
title_sort |
surveillance of molecular markers of plasmodium falciparum artemisinin resistance (kelch13 mutations) in papua new guinea between 2016 and 2018 |
publisher |
Elsevier |
series |
International Journal for Parasitology: Drugs and Drug Resistance |
issn |
2211-3207 |
publishDate |
2021-08-01 |
description |
Plasmodium falciparum resistance to artemisinin-based combination therapy (ACT) is a global threat to malaria control and elimination efforts. Mutations in the P. falciparum kelch13 gene (Pfk13) that are associated with delayed parasite clearance have emerged on the Thai-Cambodian border since 2008. There is growing evidence of widespread Pfk13 mutations throughout South-East Asia and they have independently emerged in other endemic regions. In Papua New Guinea (PNG), Pfk13 “C580Y” mutant parasites with reduced in vitro sensitivity to artemisinin have been isolated in Wewak, a port town in East Sepik Province. However, the extent of any local spread of these mutant parasites in other parts of PNG is unknown. We investigated the prevalence of Pfk13 mutations in multiple malaria-endemic regions of PNG. P. falciparum isolates (n = 1152) collected between 2016 and 2018 and assessed for Pfk13 variation by sequencing. Of 663 high quality Pfk13 sequences a total of five variants were identified. They included C580Y, a mutation at a previously documented polymorphic locus: N499K, and three previously undescribed mutations: R471C, K586E and Y635C. All variants were found in single isolates, indicating that these Pfk13 mutations were rare in the areas surveyed. Notably, C580Y was absent from Maprik district, which neighbours Wewak where C580Y mutant parasites were previously identified. The single C580Y isolate was found in the port town of Lae, Morobe Province, a potential entry site for the importation of drug resistant parasites into PNG. Although sample size in this location was small (n = 5), our identification of a C580Y mutant in this second location is concerning, highlighting the urgent need for further surveillance in Lae. Other Pfk13 mutants were rare in PNG between 2016 and 2018. Continued surveillance for molecular markers of drug resistance is critically important to inform malaria control in PNG. |
topic |
Plasmodium falciparum Artemisinin resistance Antimalarial drug resistance kelch13 mutations Malaria control Surveillance |
url |
http://www.sciencedirect.com/science/article/pii/S2211320721000312 |
work_keys_str_mv |
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doaj-198619d3abfe4e2bbb6d7c0403e93cc42021-08-04T04:19:37ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072021-08-0116188193Surveillance of molecular markers of Plasmodium falciparum artemisinin resistance (kelch13 mutations) in Papua New Guinea between 2016 and 2018Dulcie Lautu-Gumal0Zahra Razook1Tamarah Koleala2Elma Nate3Samuel McEwen4Diana Timbi5Manuel W. Hetzel6Evelyn Lavu7Nakapi Tefuarani8Leo Makita9James Kazura10Ivo Mueller11William Pomat12Moses Laman13Leanne J. Robinson14Alyssa E. Barry15Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; Vector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea; Life Sciences Discipline, Burnet Institute, Melbourne, Victoria, Australia; Corresponding author. The Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, 3004, Australia.Life Sciences Discipline, Burnet Institute, Melbourne, Victoria, Australia; Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Geelong, Victoria, AustraliaVector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New GuineaVector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New GuineaLife Sciences Discipline, Burnet Institute, Melbourne, Victoria, AustraliaVector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New GuineaHealth Interventions Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, SwitzerlandPapua New Guinea Central Public Health Laboratories, Port Moresby, National Capital District, Papua New GuineaSchool of Medicine & Health Sciences, University of Papua New Guinea, Port Moresby, National Capital District, Papua New GuineaPapua New Guinea National Department of Health, Port Moresby, National Capital District, Papua New GuineaCentre for Global Health Diseases, School of Medicine, Case Western Reserve University, Cleveland, OH, USAPopulation Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; Department of Parasites and Insect Vectors, Institut Pasteur, Paris, FranceVector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New GuineaVector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New GuineaPopulation Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; Vector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea; Life Sciences Discipline, Burnet Institute, Melbourne, Victoria, Australia; School of Preventative Medicine and Public Health, Monash University, Melbourne, Victoria, AustraliaDepartment of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; Life Sciences Discipline, Burnet Institute, Melbourne, Victoria, Australia; Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Geelong, Victoria, AustraliaPlasmodium falciparum resistance to artemisinin-based combination therapy (ACT) is a global threat to malaria control and elimination efforts. Mutations in the P. falciparum kelch13 gene (Pfk13) that are associated with delayed parasite clearance have emerged on the Thai-Cambodian border since 2008. There is growing evidence of widespread Pfk13 mutations throughout South-East Asia and they have independently emerged in other endemic regions. In Papua New Guinea (PNG), Pfk13 “C580Y” mutant parasites with reduced in vitro sensitivity to artemisinin have been isolated in Wewak, a port town in East Sepik Province. However, the extent of any local spread of these mutant parasites in other parts of PNG is unknown. We investigated the prevalence of Pfk13 mutations in multiple malaria-endemic regions of PNG. P. falciparum isolates (n = 1152) collected between 2016 and 2018 and assessed for Pfk13 variation by sequencing. Of 663 high quality Pfk13 sequences a total of five variants were identified. They included C580Y, a mutation at a previously documented polymorphic locus: N499K, and three previously undescribed mutations: R471C, K586E and Y635C. All variants were found in single isolates, indicating that these Pfk13 mutations were rare in the areas surveyed. Notably, C580Y was absent from Maprik district, which neighbours Wewak where C580Y mutant parasites were previously identified. The single C580Y isolate was found in the port town of Lae, Morobe Province, a potential entry site for the importation of drug resistant parasites into PNG. Although sample size in this location was small (n = 5), our identification of a C580Y mutant in this second location is concerning, highlighting the urgent need for further surveillance in Lae. Other Pfk13 mutants were rare in PNG between 2016 and 2018. Continued surveillance for molecular markers of drug resistance is critically important to inform malaria control in PNG.http://www.sciencedirect.com/science/article/pii/S2211320721000312Plasmodium falciparumArtemisinin resistanceAntimalarial drug resistancekelch13 mutationsMalaria controlSurveillance |