Evidence map›Paper›PMID 31780741›Full record

ArticleScientific reports2019

Amplicon deep sequencing improves Plasmodium falciparum genotyping in clinical trials of antimalarial drugs.

Maria Gruenberg, Anita Lerch, Hans-Peter Beck, Ingrid Felger

Abstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing 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

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

  1. Pooled it
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  16. Health science reports · 2024
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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

4 authors.

Maria GruenbergSwiss Tropical and Public Health Institute, Basel, Switzerland.
Anita LerchSwiss Tropical and Public Health Institute, Basel, Switzerland.ORCID http://orcid.org/0000-0003-3062-5901
Hans-Peter BeckSwiss Tropical and Public Health Institute, Basel, Switzerland.ORCID http://orcid.org/0000-0001-8326-4834
Ingrid FelgerSwiss Tropical and Public Health Institute, Basel, Switzerland. ingrid.felger@unibas.ch.ORCID http://orcid.org/0000-0003-1255-2606

Funding

Understanding, tracking and eliminating malaria transmission in the Asia - Pacific RegionU19AI129392 · NIAID · WALTER AND ELIZA HALL INST MEDICAL RES · PI Ivo J Mueller, Leanne Robinson · 2017 to 2026
$7.1M
NIAID NIH HHS U19 AI129392
6 · The paper itself

Abstract

Clinical trials monitoring malaria drug resistance require genotyping of recurrent Plasmodium falciparum parasites to distinguish between treatment failure and new infection occurring during the trial follow up period. Because trial participants usually harbour multi-clonal P. falciparum infections, deep amplicon sequencing (AmpSeq) was employed to improve sensitivity and reliability of minority clone detection. Paired samples from 32 drug trial participants were Illumina deep-sequenced for five molecular markers. Reads were analysed by custom-made software HaplotypR and trial outcomes compared to results from the previous standard genotyping method based on length-polymorphic markers. Diversity of AmpSeq markers in pre-treatment samples was comparable or higher than length-polymorphic markers. AmpSeq was highly reproducible with consistent quantification of co-infecting parasite clones within a host. Outcomes of the three best-performing markers, cpmp, cpp and ama1-D3, agreed in 26/32 (81%) of patients. Discordance between the three markers performed per sample was much lower by AmpSeq (six patients) compared to length-polymorphic markers (eleven patients). Using AmpSeq for discrimination of recrudescence and new infection in antimalarial drug trials provides highly reproducible and robust characterization of clone dynamics during trial follow-up. AmpSeq overcomes limitations inherent to length-polymorphic markers. Regulatory clinical trials of antimalarial drugs will greatly benefit from this unbiased typing method.

Indexed as

GenotypeAntimalarialsDNA, ProtozoanDrug ResistanceGenotyping TechniquesHaplotypesHigh-Throughput Nucleotide SequencingHumansMalaria, FalciparumPlasmodium falciparumPolymerase Chain ReactionPolymorphism, Single NucleotideReproducibility of ResultsAntimalarialsDNA, Protozoan

Identifiers

PMID31780741
PMCPMC6883076

What OpenQuestion holds

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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.