Evidence map›Paper›PMID 40988035›Full record

ArticleMalaria journal2025

No evidence of molecular markers of piperaquine resistance in southeastern Nigeria.

Moses Ikegbunam, Vasileios Tzirtziganis, Miriam Rodi, Linda Anagu, Lais Pessanha de Carvalho, Juliana Inoue, Jana Held

Abstract read
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Article in Malaria journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Moses IkegbunamDepartment of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe University, Awka, Nigeria.
Vasileios TzirtziganisInstitute of Tropical Medicine, Eberhard Karls University, Tübingen, Germany.
Miriam RodiInstitute of Tropical Medicine, Eberhard Karls University, Tübingen, Germany.
Linda AnaguDepartment of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe University, Awka, Nigeria.
Lais Pessanha de CarvalhoInstitute of Tropical Medicine, Eberhard Karls University, Tübingen, Germany.
Juliana InoueInstitute of Tropical Medicine, Eberhard Karls University, Tübingen, Germany.
Jana HeldInstitute of Tropical Medicine, Eberhard Karls University, Tübingen, Germany. jana.held@uni-tuebingen.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundArtemisinin‑based combination therapy (ACT) remains the first‑line treatment for uncomplicated malaria, yet its long‑term efficacy is threatened by Plasmodium falciparum resistance to both artemisinin derivatives and partner drugs. Routine surveillance of clinical efficacy and molecular‑resistance markers is therefore essential. Piperaquine (PPQ), the partner drug in dihydroartemisinin-piperaquine (DHA‑PPQ) is already compromised in Southeast Asia, and key PPQ‑resistance mutations have begun to surface in parts of Africa. No such data are available from Nigeria. Three PPQ‑resistanceassociated singlenucleotide polymorphisms (SNPs)-T93S, H97Y and F145Ilocated in exons 2 and 3 of the P. falciparum chloroquineresistance transporter gene (pfcrt), and copy‑number variation of plasmepsin 2/3 (pfpm2/3), were retrospectively investigated using 299 archived patient isolates collected in Awka (n = 200) and Onitsha (n = 99), South‑East Nigeria (2018-2019).

methodsAllelic states at pfcrt codons 93, 97 and 145 were determined by nested PCR followed by Sanger sequencing. Pfpm2/3 copy number was quantified by real‑time qPCR, using β‑tubulin as the single‑copy reference. All assays incorporated PPQ‑resistant RF7 and wild‑type 3D7 control strains, plus no‑template controls.

resultsHigh‑quality amplification was achieved for 268 of 299 isolates (89.6%). None harboured the pfcrt T93S, H97Y or F145I mutations, and all exhibited single‑copy pfpm2 and pfpm3. Two novel exon‑2 variants (K115I and synonymous L111L) were each detected once (0.4%) and are regarded as neutral polymorphisms without known phenotypic impact.

conclusionsThe complete absence of validated PPQresistance markers indicates that piperaquine remains a viable partner drug in DHA‑PPQ for South‑East Nigeria. Nonetheless, because DHA‑PPQ is increasingly available over the counter, ongoing molecular and therapeutic‑efficacy surveillance is imperative to detect any future emergence of resistance.

Indexed as

AntimalarialsDrug ResistancePlasmodium falciparumQuinolinesDNA Copy Number VariationsGenetic MarkersHumansMalaria, FalciparumMembrane Transport ProteinsNigeriaPiperazinesPolymorphism, Single NucleotideProtozoan ProteinsRetrospective StudiesAntimalarialsGenetic MarkersMembrane Transport ProteinsPfCRT protein, Plasmodium falciparumpiperaquinePiperazinesProtozoan ProteinsQuinolinesNigeriaPfcrtPiperaquinePlasmepsin 2Plasmepsin 3Plasmodium falciparumResistanceSoutheastern Nigeria

Identifiers

PMID40988035
PMCPMC12455774

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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.