Evidence map›Paper›PMID 38461239›Full record

ArticleMalaria journal2024

Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021.

Catherine Bakari, Celine I Mandara, Rashid A Madebe, Misago D Seth, Billy Ngasala, Erasmus Kamugisha, Maimuna Ahmed, Filbert Francis, Samwel Bushukatale, Mercy Chiduo and 25 more

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
9.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Emergence of chloroquine-sensitiveEmerging microbes & infections · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Malaria: past, present, and future.Signal transduction and targeted therapy · 2025
    Review
  14. Review
  15. Article
  16. Article
  17. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors at 16 institutions in 6 countries.

Catherine BakariNational Institute for Medical Research, Dar Es Salaam, Tanzania.
Celine I MandaraNational Institute for Medical Research, Dar Es Salaam, Tanzania.
Rashid A MadebeNational Institute for Medical Research, Dar Es Salaam, Tanzania.
Misago D SethNational Institute for Medical Research, Dar Es Salaam, Tanzania.
Billy NgasalaDepartment of Parasitology, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania.
Erasmus KamugishaCatholic University of Health and Allied Sciences, Bugando Medical Centre, Mwanza, Tanzania.
Maimuna AhmedCatholic University of Health and Allied Sciences, Bugando Medical Centre, Mwanza, Tanzania.
Filbert FrancisNational Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania.
Samwel BushukataleDepartment of Parasitology, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania.
Mercy ChiduoNational Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania.
Twilumba MakeneDepartment of Parasitology, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania.
Abdunoor M KabanywanyiIfakara Health Institute, Dar Es Salaam Office, Dar Es Salaam, Tanzania.
Muhidin K MahendeIfakara Health Institute, Dar Es Salaam Office, Dar Es Salaam, Tanzania.
Reginald A KavisheKilimanjaro Christian Medical Centre, Moshi, Tanzania.
Florida MuroKilimanjaro Christian Medical Centre, Moshi, Tanzania.
Sigsbert MkudeNational Malaria Control Program, Dodoma, Tanzania.
Renata MandikeNational Malaria Control Program, Dodoma, Tanzania.
Fabrizio MolteniSwiss Tropical and Public Health Institute, Basel, Switzerland.
Frank ChackyNational Malaria Control Program, Dodoma, Tanzania.
Dunstan R BishangaIfakara Health Institute, Dar Es Salaam Office, Dar Es Salaam, Tanzania.
Ritha J A NjauMalariologist and Public Health Specialist, Dar Es Salaam, Tanzania.
Marian WarsameUniversity of Gothenburg, Gothenburg, Sweden.
Bilali KabulaPMI/Okoa Maisha Dhibiti Malaria, RTI International, Dar Es Salaam, Tanzania.
Ssanyu S NyinondiPMI/Okoa Maisha Dhibiti Malaria, RTI International, Dar Es Salaam, Tanzania.
Naomi W LucchiMalaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA.
Eldin TalundzicMalaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA.
Meera VenkatesanU.S. President's Malaria Initiative, USAID, Washington, DC, USA.
Leah F MoriartyMalaria Branch, U.S. President's Malaria Initiative, US Centers for Disease Control and Prevention, Atlanta, GA, USA.
Naomi SerbantezU.S. President's Malaria Initiative, USAID, Dar Es Salaam, Tanzania.
Chonge KitojoU.S. President's Malaria Initiative, USAID, Dar Es Salaam, Tanzania.
Erik J ReavesU.S. President's Malaria Initiative, US Centers for Disease Control and Prevention, Dar Es Salaam, Tanzania.
Eric S HalseyMalaria Branch, U.S. President's Malaria Initiative, US Centers for Disease Control and Prevention, Atlanta, GA, USA.
Ally MohamedNational Malaria Control Program, Dodoma, Tanzania.
Venkatachalam UdhayakumarMalaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA.
Deus S IshengomaNational Institute for Medical Research, Dar Es Salaam, Tanzania. deusishe@yahoo.com.
National Institute for Medical Research · TZAfrican Malaria Network Trust · TZCenters for Disease Control and Prevention · USMuhimbili University of Health and Allied Sciences · TZIfakara Health Institute · TZKilimanjaro Christian Medical Centre · TZPlan International Tanzania · TZAssociation of Maternal and Child Health Programs · USBugando Medical Centre · TZCatholic University of Health and Allied Sciences · TZGeorgia Mental Health Consumer Network · USMonash University · AUSwiss Tropical and Public Health Institute · CHUnited States Agency for International Development · USUniversity of Gothenburg · SEU.S. President's Malaria Initiative · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTherapeutic 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.

methodsA 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).

resultsSequencing 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%.

conclusionThis 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.

Indexed as

AntimalarialsArtemisininsMalaria, FalciparumArtemetherArtemether, Lumefantrine Drug CombinationATP-Binding Cassette, Sub-Family C ProteinsBiomarkersCarubicinDrug ResistanceHumansLumefantrinePlasmodium falciparumProtozoan ProteinsTanzaniaAntimalarialsArtemetherArtemether, Lumefantrine Drug CombinationArtemisininsATP-Binding Cassette, Sub-Family C ProteinsBiomarkersCarubicinLumefantrineN-formyl-13-dihydrocarminomycinProtozoan ProteinsMalariaMolecular markersPlasmodium falciparumPlasmodium falciparum kelch 13 (k13)Plasmodium falciparum multidrug resistance 1 (pfmdr1)TanzaniaTherapeutic efficacy studies

Identifiers

PMID38461239
PMCPMC10924419
OpenAlexW4392623311

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.