Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021
Abstract Background Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-03-01
|
| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-024-04896-0 |
| _version_ | 1797266939095023616 |
|---|---|
| author | Catherine Bakari Celine I. Mandara Rashid A. Madebe Misago D. Seth Billy Ngasala Erasmus Kamugisha Maimuna Ahmed Filbert Francis Samwel Bushukatale Mercy Chiduo Twilumba Makene Abdunoor M. Kabanywanyi Muhidin K. Mahende Reginald A. Kavishe Florida Muro Sigsbert Mkude Renata Mandike Fabrizio Molteni Frank Chacky Dunstan R. Bishanga Ritha J. A. Njau Marian Warsame Bilali Kabula Ssanyu S. Nyinondi Naomi W. Lucchi Eldin Talundzic Meera Venkatesan Leah F. Moriarty Naomi Serbantez Chonge Kitojo Erik J. Reaves Eric S. Halsey Ally Mohamed Venkatachalam Udhayakumar Deus S. Ishengoma |
| author_facet | Catherine Bakari Celine I. Mandara Rashid A. Madebe Misago D. Seth Billy Ngasala Erasmus Kamugisha Maimuna Ahmed Filbert Francis Samwel Bushukatale Mercy Chiduo Twilumba Makene Abdunoor M. Kabanywanyi Muhidin K. Mahende Reginald A. Kavishe Florida Muro Sigsbert Mkude Renata Mandike Fabrizio Molteni Frank Chacky Dunstan R. Bishanga Ritha J. A. Njau Marian Warsame Bilali Kabula Ssanyu S. Nyinondi Naomi W. Lucchi Eldin Talundzic Meera Venkatesan Leah F. Moriarty Naomi Serbantez Chonge Kitojo Erik J. Reaves Eric S. Halsey Ally Mohamed Venkatachalam Udhayakumar Deus S. Ishengoma |
| author_sort | Catherine Bakari |
| collection | DOAJ |
| description | Abstract Background Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021. Methods A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021. Photo-induced electron transfer polymerase chain reaction (PET-PCR) was used to confirm presence of malaria parasites before capillary sequencing, which targeted two genes: Plasmodium falciparum kelch 13 propeller domain (k13) and P. falciparum multidrug resistance 1 (pfmdr1). Results Sequencing success was ≥ 87.8%, and 1,724/1,769 (97.5%) k13 wild-type samples were detected. Thirty-seven (2.1%) samples had synonymous mutations and only eight (0.4%) had non-synonymous mutations in the k13 gene; seven of these were not validated by the WHO as molecular markers of resistance. One sample from Morogoro in 2020 had a k13 R622I mutation, which is a validated marker of artemisinin partial resistance. For pfmdr1, all except two samples carried N86 (wild-type), while mutations at Y184F increased from 33.9% in 2016 to about 60.5% in 2021, and only four samples (0.2%) had D1246Y mutations. pfmdr1 haplotypes were reported in 1,711 samples, with 985 (57.6%) NYD, 720 (42.1%) NFD, and six (0.4%) carrying minor haplotypes (three with NYY, 0.2%; YFD in two, 0.1%; and NFY in one sample, 0.1%). Between 2016 and 2021, NYD decreased from 66.1% to 45.2%, while NFD increased from 38.5% to 54.7%. Conclusion This is the first report of the R622I (k13 validated mutation) in Tanzania. N86 and D1246 were nearly fixed, while increases in Y184F mutations and NFD haplotype were observed between 2016 and 2021. Despite the reports of artemisinin partial resistance in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I suggesting that intensified surveillance is urgently needed to monitor trends of drug resistance markers and their impact on the performance of ACT. |
| first_indexed | 2024-04-25T01:08:39Z |
| format | Article |
| id | doaj.art-bbdfbdb13b094de59208ee4c4414aa68 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-04-25T01:08:39Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-bbdfbdb13b094de59208ee4c4414aa682024-03-10T12:06:24ZengBMCMalaria Journal1475-28752024-03-0123111110.1186/s12936-024-04896-0Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021Catherine Bakari0Celine I. Mandara1Rashid A. Madebe2Misago D. Seth3Billy Ngasala4Erasmus Kamugisha5Maimuna Ahmed6Filbert Francis7Samwel Bushukatale8Mercy Chiduo9Twilumba Makene10Abdunoor M. Kabanywanyi11Muhidin K. Mahende12Reginald A. Kavishe13Florida Muro14Sigsbert Mkude15Renata Mandike16Fabrizio Molteni17Frank Chacky18Dunstan R. Bishanga19Ritha J. A. Njau20Marian Warsame21Bilali Kabula22Ssanyu S. Nyinondi23Naomi W. Lucchi24Eldin Talundzic25Meera Venkatesan26Leah F. Moriarty27Naomi Serbantez28Chonge Kitojo29Erik J. Reaves30Eric S. Halsey31Ally Mohamed32Venkatachalam Udhayakumar33Deus S. Ishengoma34National Institute for Medical ResearchNational Institute for Medical ResearchNational Institute for Medical ResearchNational Institute for Medical ResearchDepartment of Parasitology, Muhimbili University of Health and Allied SciencesCatholic University of Health and Allied Sciences, Bugando Medical CentreCatholic University of Health and Allied Sciences, Bugando Medical CentreNational Institute for Medical Research, Tanga Research CentreDepartment of Parasitology, Muhimbili University of Health and Allied SciencesNational Institute for Medical Research, Tanga Research CentreDepartment of Parasitology, Muhimbili University of Health and Allied SciencesIfakara Health InstituteIfakara Health InstituteKilimanjaro Christian Medical CentreKilimanjaro Christian Medical CentreNational Malaria Control ProgramNational Malaria Control ProgramSwiss Tropical and Public Health InstituteNational Malaria Control ProgramIfakara Health InstituteMalariologist and Public Health SpecialistUniversity of GothenburgPMI/Okoa Maisha Dhibiti Malaria, RTI InternationalPMI/Okoa Maisha Dhibiti Malaria, RTI InternationalMalaria Branch, U.S. Centers for Disease Control and PreventionMalaria Branch, U.S. Centers for Disease Control and PreventionU.S. President’s Malaria Initiative, USAIDMalaria Branch, U.S. President’s Malaria Initiative, US Centers for Disease Control and PreventionU.S. President’s Malaria Initiative, USAIDU.S. President’s Malaria Initiative, USAIDU.S. President’s Malaria Initiative, US Centers for Disease Control and PreventionMalaria Branch, U.S. President’s Malaria Initiative, US Centers for Disease Control and PreventionNational Malaria Control ProgramMalaria Branch, U.S. Centers for Disease Control and PreventionNational Institute for Medical ResearchAbstract Background Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021. Methods A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021. Photo-induced electron transfer polymerase chain reaction (PET-PCR) was used to confirm presence of malaria parasites before capillary sequencing, which targeted two genes: Plasmodium falciparum kelch 13 propeller domain (k13) and P. falciparum multidrug resistance 1 (pfmdr1). Results Sequencing success was ≥ 87.8%, and 1,724/1,769 (97.5%) k13 wild-type samples were detected. Thirty-seven (2.1%) samples had synonymous mutations and only eight (0.4%) had non-synonymous mutations in the k13 gene; seven of these were not validated by the WHO as molecular markers of resistance. One sample from Morogoro in 2020 had a k13 R622I mutation, which is a validated marker of artemisinin partial resistance. For pfmdr1, all except two samples carried N86 (wild-type), while mutations at Y184F increased from 33.9% in 2016 to about 60.5% in 2021, and only four samples (0.2%) had D1246Y mutations. pfmdr1 haplotypes were reported in 1,711 samples, with 985 (57.6%) NYD, 720 (42.1%) NFD, and six (0.4%) carrying minor haplotypes (three with NYY, 0.2%; YFD in two, 0.1%; and NFY in one sample, 0.1%). Between 2016 and 2021, NYD decreased from 66.1% to 45.2%, while NFD increased from 38.5% to 54.7%. Conclusion This is the first report of the R622I (k13 validated mutation) in Tanzania. N86 and D1246 were nearly fixed, while increases in Y184F mutations and NFD haplotype were observed between 2016 and 2021. Despite the reports of artemisinin partial resistance in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I suggesting that intensified surveillance is urgently needed to monitor trends of drug resistance markers and their impact on the performance of ACT.https://doi.org/10.1186/s12936-024-04896-0MalariaMolecular markersTherapeutic efficacy studiesPlasmodium falciparum kelch 13 (k13)Plasmodium falciparum multidrug resistance 1 (pfmdr1)Plasmodium falciparum |
| spellingShingle | Catherine Bakari Celine I. Mandara Rashid A. Madebe Misago D. Seth Billy Ngasala Erasmus Kamugisha Maimuna Ahmed Filbert Francis Samwel Bushukatale Mercy Chiduo Twilumba Makene Abdunoor M. Kabanywanyi Muhidin K. Mahende Reginald A. Kavishe Florida Muro Sigsbert Mkude Renata Mandike Fabrizio Molteni Frank Chacky Dunstan R. Bishanga Ritha J. A. Njau Marian Warsame Bilali Kabula Ssanyu S. Nyinondi Naomi W. Lucchi Eldin Talundzic Meera Venkatesan Leah F. Moriarty Naomi Serbantez Chonge Kitojo Erik J. Reaves Eric S. Halsey Ally Mohamed Venkatachalam Udhayakumar Deus S. Ishengoma Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021 Malaria Journal Malaria Molecular markers Therapeutic efficacy studies Plasmodium falciparum kelch 13 (k13) Plasmodium falciparum multidrug resistance 1 (pfmdr1) Plasmodium falciparum |
| title | Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021 |
| title_full | Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021 |
| title_fullStr | Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021 |
| title_full_unstemmed | Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021 |
| title_short | Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021 |
| title_sort | trends of plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in mainland tanzania from 2016 to 2021 |
| topic | Malaria Molecular markers Therapeutic efficacy studies Plasmodium falciparum kelch 13 (k13) Plasmodium falciparum multidrug resistance 1 (pfmdr1) Plasmodium falciparum |
| url | https://doi.org/10.1186/s12936-024-04896-0 |
| work_keys_str_mv | AT catherinebakari trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT celineimandara trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT rashidamadebe trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT misagodseth trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT billyngasala trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT erasmuskamugisha trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT maimunaahmed trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT filbertfrancis trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT samwelbushukatale trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT mercychiduo trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT twilumbamakene trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT abdunoormkabanywanyi trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT muhidinkmahende trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT reginaldakavishe trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT floridamuro trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT sigsbertmkude trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT renatamandike trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT fabriziomolteni trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT frankchacky trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT dunstanrbishanga trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT rithajanjau trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT marianwarsame trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT bilalikabula trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT ssanyusnyinondi trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT naomiwlucchi trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT eldintalundzic trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT meeravenkatesan trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT leahfmoriarty trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT naomiserbantez trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT chongekitojo trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT erikjreaves trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT ericshalsey trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT allymohamed trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT venkatachalamudhayakumar trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 AT deussishengoma trendsofplasmodiumfalciparummolecularmarkersassociatedwithresistancetoartemisininsandreducedsusceptibilitytolumefantrineinmainlandtanzaniafrom2016to2021 |