Evidence map›Paper›PMID 37553646›Full record

ArticleMalaria journal2023

Evolution of genetic markers for drug resistance after the introduction of dihydroartemisinin-piperaquine as first-line anti-malarial treatment for uncomplicated falciparum malaria in Indonesia.

Farindira Vesti Rahmasari, Puji Budi Setia Asih, Ismail Ekoprayitno Rozi, Suradi Wangsamuda, Rifqi Risandi, Farahana Kresno Dewayanti, Dendi Hadi Permana, Lepa Syahrani, Helen Dewi Prameswari, Herdiana H Basri and 5 more

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. The Impact ofJournal of parasitology research · 2026
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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

15 authors at 6 institutions in 3 countries.

Farindira Vesti RahmasariGraduate Programme in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
Puji Budi Setia AsihEijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, Indonesia.
Ismail Ekoprayitno RoziEijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, Indonesia.
Suradi WangsamudaEijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, Indonesia.
Rifqi RisandiEijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, Indonesia.
Farahana Kresno DewayantiEijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, Indonesia.
Dendi Hadi PermanaEijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, Indonesia.
Lepa SyahraniEijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, Indonesia.
Helen Dewi PrameswariMalaria Working Group, Ministry of Health, Jakarta, Indonesia.
Herdiana H BasriWorld Health Organization, Country Office for Indonesia, Jakarta, Indonesia.
Maria Dorina G BustosWorld Health Organization, Country Office for Thailand, Nonthaburi, Thailand.
Prakaykaew CharunwatthanaDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand.
Arjen M DondorpMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Mallika ImwongDepartment of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok, 10400, Thailand. mallika.imw@mahidol.ac.th.
Din SyafruddinEijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, Indonesia.
Eijkman Institute for Molecular Biology · IDMahidol Oxford Tropical Medicine Research Unit · THNational Research and Innovation AgencyMinistry of Health · IDMuhammadiyah University of Yogyakarta · IDWWF-Indonesia · ID

Funding

Wellcome TrustWorld Health Organization 001
6 · The paper itself

Abstract

backgroundDihydroartemisinin-piperaquine has been Indonesia's first-line anti-malarial treatment since 2008. Annual therapeutic efficacy studies (TES) done in the last 12 years showed continued high treatment efficacy in uncomplicated Plasmodium falciparum malaria. Although these studies did not show evidence for artemisinin resistance, a slight increase in Late Treatment Failure was observed over time. It is highlight to explore the evolution of genetic markers for ACT partner drug resistance since adopting DHA-PPQ.

methodsDry blood spots were identified from a mass blood survey of uncomplicated falciparum malaria patients (N = 50) in Sumba from 2010 to 2018. Analysis of genotypic profile (N = 51) and a Therapeutic Efficacy Study (TES) from Papua (N = 142) from 2020 to 2021, 42-day follow-up. PCR correction using msp1, msp2, and glurp was used to distinguish recrudescence and reinfection. Parasite DNA from DBSs was used for genotyping molecular markers for antimalaria drug resistance, including in Pfk13, pfcrt, and pfmdr1, as well as gene copy number variation in pfpm2/3 and pfmdr1.

resultsThe study revealed the absence of SNPs associated with ART resistance and several novel SNPs such as L396F, I526V, M579I and N537S (4.25%). In Sumba, the mutant haplotype SDD of pfmdr1 was found in one-third of the isolates, while only 8.9% in Papua. None of the pfcrt mutations linked to piperaquine resistance were observed, but 71% of isolates had pfcrt I356L. Amplification of the pfpm2/3 genes was in Sumba (17.02%) and Papua (13.7%), while pfmdr1 copy number prevalence was low (3.8%) in both areas. For the TES study, ten recurrences of infection were observed on days 28, 35, and 42. Late parasitological failure (LPF) was observed in 10/117 (8.5%) subjects by microscopy. PCR correction revealed that all nine cases were re-infections and one was confirmed as recrudescence.

conclusionThis study revealed that DHA-PPQ is still highly effective against P. falciparum. The genetic architecture of the parasite P. falciparum isolates during 2010-2021 revealed single copy of Pfpm2 and pfmdr1 were highly prevalent. The slight increase in DHA-PPQ LTF alerts researchers to start testing other ACTs as alternatives to DHA-PPQ for baseline data in order to get a chance of achieving malaria elimination wants by 2030.

Indexed as

AntimalarialsMalariaMalaria, FalciparumArtemisininsDNA Copy Number VariationsDrug ResistanceGenetic MarkersHumansIndonesiaPiperazinesPlasmodium falciparumProtozoan ProteinsQuinolinesAntimalarialsArtemisininsartenimolGenetic MarkerspiperaquinePiperazinesProtozoan ProteinsQuinolinesPfcrtPfk13Pfmdr1Pfpm2/3Plasmodium falciparumResistance

Identifiers

PMID37553646
PMCPMC10410932
OpenAlexW4385683918

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.