Evidence map›Paper›PMID 27821442›Full record

ArticleAntimicrobial agents and chemotherapy2017

Critical Evaluation of Molecular Monitoring in Malaria Drug Efficacy Trials and Pitfalls of Length-Polymorphic Markers.

Camilla Messerli, Natalie E Hofmann, Hans-Peter Beck, Ingrid Felger

Abstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing 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

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

  1. Pooled it
  2. Trial
  3. Trial
  4. Efficacy of Cipargamin (KAE609) in a Randomized, Phase II Dose-Escalation Study in Adults in Sub-Saharan Africa With Uncomplicated Plasmodium falciparum Malaria.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Trial
  5. Trial
  6. Trial
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Genetic Diversity ofTropical medicine and infectious disease · 2025
    Article
  15. Article
  16. Review
  17. Genotyping and CharacterizingTropical medicine and infectious disease · 2024
    Review
  18. Article
  19. Article
  20. Genetic diversity ofFrontiers in cellular and infection microbiology · 2024
    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

4 authors.

Camilla MesserliSwiss Tropical and Public Health Institute, Basel, Switzerland.
Natalie E HofmannSwiss Tropical and Public Health Institute, Basel, Switzerland.
Hans-Peter BeckSwiss Tropical and Public Health Institute, Basel, Switzerland.ORCID 0000-0001-8326-4834
Ingrid FelgerSwiss Tropical and Public Health Institute, Basel, Switzerland ingrid.felger@unibas.ch.ORCID 0000-0003-1255-2606

Funding

TransmissionU19AI089686 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI ZIMMERMAN, PETER A. · 2010 to 2016
$9.9M
NIAID NIH HHS U19 AI089686
6 · The paper itself

Abstract

Estimation of drug efficacy in antimalarial drug trials requires parasite genotyping to distinguish new infections from treatment failures. When using length-polymorphic molecular markers, preferential amplification of short fragments can compromise detection of coinfections, potentially leading to misclassification of treatment outcome. We quantified minority clone detectability and competition among msp1, msp2, and glurp amplicons using mixtures of Plasmodium falciparum strains and investigated the impact of template competition on genotyping outcomes in 44 paired field samples. Substantial amplification bias was detected for all three markers, with shorter fragments outperforming larger fragments. The strongest template competition was observed for the marker glurp Detection of glurp fragments in multiclonal infections was severely compromised. Eight of 44 sample pairs were identified as new infections by all three markers. Ten pairs were defined as new infections based on one marker alone, seven of which were defined by the questionable marker glurp The impact of size-dependent template competition on genotyping outcomes therefore calls for necessary amendments to the current WHO recommendations for PCR correction of malaria drug trial endpoints. Accuracy of genotyping outcomes could be improved by separate amplification reactions per allelic family and basing results on markers msp1 and msp2 first, with glurp only used to resolve discordant results.

Indexed as

Antigens, ProtozoanAntimalarialsGenotypeMerozoite Surface Protein 1Plasmodium falciparumPolymerase Chain ReactionPolymorphism, GeneticProtozoan ProteinsAntigens, ProtozoanAntimalarialsglutamate-rich protein, PlasmodiumMerozoite Surface Protein 1merozoite surface protein 2, PlasmodiumProtozoan Proteinsamplification biasdrug trialgenotypingglurpmsp1msp2PCRPlasmodium falciparumtemplate competition

Identifiers

PMID27821442
PMCPMC5192142

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.