Evidence map›Paper›PMID 39501325›Full record

ArticleMalaria journal2024

Emerging threat of artemisinin partial resistance markers (pfk13 mutations) in Plasmodium falciparum parasite populations in multiple geographical locations in high transmission regions of Uganda.

Bosco B Agaba, Jye Travis, David Smith, Simon P Rugera, Maria G Zalwango, Jimmy Opigo, Charles Katureebe, Ruth Mpirirwe, Dembo Bakary, Martin Antonio and 6 more

Abstract 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 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Molecules (Basel, Switzerland) · 2025
    Review
  11. Article
  12. Review
  13. Article
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

16 authors.

Bosco B AgabaThe Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine: Peter Piot Fellowship for Global Health Innovation, Epidemic Preparedness & Response, Banjul, Fajara, The Gambia. agaba1bosco2015@gmail.com.
Jye TravisQIMR Berghofer Medical Research Institute, Brisbane, Australia.
David SmithQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Simon P RugeraDepartment of Medical Laboratory Sciences, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
Maria G ZalwangoNational Malaria Control Division, Kampala, Uganda.
Jimmy OpigoNational Malaria Control Division, Kampala, Uganda.
Charles KatureebeWorld Health Organization, Country Office, Kampala, Uganda.
Ruth MpirirweMakerere University, Kampala, Uganda.
Dembo BakaryThe Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine: Peter Piot Fellowship for Global Health Innovation, Epidemic Preparedness & Response, Banjul, Fajara, The Gambia.
Martin AntonioThe Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine: Peter Piot Fellowship for Global Health Innovation, Epidemic Preparedness & Response, Banjul, Fajara, The Gambia.
Beshir KhalidLondon School of Hygiene and Tropical Medicine, London, UK.
Joseph NgonziDepartment of Medical Laboratory Sciences, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
Moses R KamyaInfectious Diseases Research Collaboration, Kampala, Uganda.
Pontiano KaleebuMedical Research Council/London School of Hygiene and Tropical Unit, Uganda Virus Research Institute, Entebbe, Uganda.
Peter PiotThe Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine: Peter Piot Fellowship for Global Health Innovation, Epidemic Preparedness & Response, Banjul, Fajara, The Gambia.
Qin ChengQIMR Berghofer Medical Research Institute, Brisbane, Australia.

Funding

US DoD Armed Forces Health Surveillance Division, Global Emerging Infections Surveillance Branch PROMIS ID P0111_22_AFWorld Health Organization 001
6 · The paper itself

Abstract

backgroundArtemisinin-based combination therapy (ACT) is currently recommended for treatment of uncomplicated malaria. However, the emergence and spread of partial artemisinin resistance threatens their effectiveness for malaria treatment in sub-Saharan Africa where the burden of malaria is highest. Early detection and reporting of validated molecular markers (pfk13 mutations) in Plasmodium falciparum is useful for tracking the emergence and spread of partial artemisinin resistance to inform containment efforts.

methodsGenomic surveillance was conducted at 50 surveillance sites across four regions of Uganda in Karamoja, Lango, Acholi and West Nile from June 2021 to August 2023. Symptomatic malaria suspected patients were recruited and screened for presence of parasites. In addition, dried blood spots (DBS) were collected for parasite genomic analysis with PCR and sequencing. Out of 563 available dried blood spots (DBS), a random subset of 240 P. falciparum mono-infections, confirmed by a multiplex PCR were selected and used for detecting the pfk13 mutations by Sanger sequencing using Big Dye Terminator method. Regional variations in the proportions of pfk13 mutations were assessed using the chi square or Fisher's exact tests while Kruskal-Wallis test was used to compare absolute parasite DNA levels between wild type and mutant parasites.

resultsOverall, 238/240 samples (99.2%) contained sufficient DNA and were successfully sequenced. Three mutations were identified within the sequenced samples; pfk13 C469Y in 32/238 (13.5%) samples, pfk13 A675V in 14/238 (5.9%) and pfk13 S522C in (1/238 (0.42%) samples across the four surveyed regions. The prevalence of pfk13 C469Y mutation was significantly higher in Karamoja region (23.3%) compared to other regions, P = 0.007. The majority of parasite isolates circulating in West Nile are of wild type (98.3), P = 0.002. Relative parasite DNA quantity did not differ in samples carrying the wild type, C469Y and A675V alleles (Kruskal-Wallis test, P = 0.6373).

conclusionDetection of validated molecular markers of artemisinin partial resistance in multiple geographical locations in this setting provides additional evidence of emerging threat of artemisinin partial resistance in Uganda. In view of these findings, periodic genomic surveillance is recommended to detect and monitor levels of pfk13 mutations in other regions in parallel with TES to assess potential implication on delayed parasite clearance and associated treatment failure in this setting. Future studies should consider identification of potential drivers of artemisinin partial resistance in the different malaria transmission settings in Uganda.

Indexed as

AntimalarialsArtemisininsDrug ResistanceMalaria, FalciparumMutationPlasmodium falciparumAdolescentAdultChildChild, PreschoolFemaleHumansMaleProtozoan ProteinsUgandaYoung AdultAntimalarialsartemisininArtemisininsProtozoan ProteinsArtemisinin resistanceEmergenceGenomic surveillancepfk13 mutationsPlasmodium falciparum

Identifiers

PMID39501325
PMCPMC11539793

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.