Evidence map›Paper›PMID 26503662›Full record

ArticleAntimicrobial agents and chemotherapy2016

Within-Host Selection of Drug Resistance in a Mouse Model of Repeated Incomplete Malaria Treatment: Comparison between Atovaquone and Pyrimethamine.

Suci Nuralitha, Josephine E Siregar, Din Syafruddin, Jessica Roelands, Jan Verhoef, Andy I M Hoepelman, Sangkot Marzuki

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.3field-weighted citation impact, top 17% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Antimalarial Activity ofJournal of pathogens · 2021
    Article
  5. Article
  6. Antimalarial Drug Resistance: A Threat to Malaria Elimination.Cold Spring Harbor perspectives in medicine · 2017
    Review
  7. Article
  8. 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

7 authors at 2 institutions in 2 countries.

Suci NuralithaEijkman Institute for Molecular Biology, Jakarta, Indonesia suci@eijkman.go.id smarzuki@eijkman.go.id.
Josephine E SiregarEijkman Institute for Molecular Biology, Jakarta, Indonesia.
Din SyafruddinEijkman Institute for Molecular Biology, Jakarta, Indonesia.
Jessica RoelandsEijkman Institute for Molecular Biology, Jakarta, Indonesia.
Jan VerhoefMedical Microbiology and Infection, University Medical Center Utrecht, Utrecht, Netherlands.
Andy I M HoepelmanInternal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, Netherlands.
Sangkot MarzukiEijkman Institute for Molecular Biology, Jakarta, Indonesia suci@eijkman.go.id smarzuki@eijkman.go.id.
Eijkman Institute for Molecular Biology · IDUniversity Medical Center Utrecht · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The evolutionary selection of malaria parasites within individual hosts is an important factor in the emergence of drug resistance but is still not well understood. We have examined the selection process for drug resistance in the mouse malaria agent Plasmodium berghei and compared the dynamics of the selection for atovaquone and pyrimethamine. Resistance to these drugs has been shown to be associated with genetic lesions in the dihydrofolate reductase gene in the case of pyrimethamine and in the mitochondrial cytochrome b gene for atovaquone. A mouse malaria model for the selection of drug resistance, based on repeated incomplete treatment (RICT) with a therapeutic dose of antimalarial drugs, was established. The number of treatment cycles for the development of stable resistance to atovaquone (2.47 ± 0.70; n = 19) was found to be significantly lower than for pyrimethamine (5.44 ± 1.46; n = 16; P < 0.0001), even when the parental P. berghei Leiden strain was cloned prior to the resistance selection. Similar results were obtained with P. berghei Edinburgh. Mutational changes underlying the resistance were identified to be S110N in dihydrofolate reductase for pyrimethamine and Y268N, Y268C, Y268S, L271V-K272R, and G280D in cytochrome b for atovaquone. These results are consistent with the rate of mitochondrial DNA mutation being higher than that in the nucleus and suggest that mutation leading to pyrimethamine resistance is not a rare event.

Indexed as

Amino Acid SubstitutionAnimalsAntimalarialsAtovaquoneCell NucleusCytochromes bDrug ResistanceGene ExpressionHost-Parasite InteractionsMalariaMiceMice, Inbred BALB CMitochondriaMutation RateParasitic Sensitivity TestsPlasmodium bergheiAntimalarialsAtovaquoneCytochromes bProtozoan ProteinsPyrimethamineTetrahydrofolate Dehydrogenase

Identifiers

PMID26503662
PMCPMC4704165
OpenAlexW1865644384

What OpenQuestion holds

Textmetadata
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.