Evidence map›Paper›PMID 22271863›Full record

ArticleAntimicrobial agents and chemotherapy2012

Significant reduction of brain cysts caused by Toxoplasma gondii after treatment with spiramycin coadministered with metronidazole in a mouse model of chronic toxoplasmosis.

Wai Kit Chew, Ignacio Segarra, Stephen Ambu, Joon Wah Mak

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 11% 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

39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
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  6. Transient Adaptation ofInternational journal of molecular sciences · 2024
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  10. The apicoplast is important for the viability and persistence ofProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  11. Spiramycin DisarmsAntibiotics (Basel, Switzerland) · 2023
    Article
  12. Article
  13. Article
  14. Remarkable histopathological improvement of experimental toxoplasmosis after receiving spiramycin-chitosan nanoparticles formulation.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2022
    Article
  15. Effect of spiramycin versus aminoguanidine and their combined use in experimental toxoplasmosis.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2021
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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 at 1 institution in 1 country.

Wai Kit ChewDepartment of Human Biology, School of Medicine, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia.
Ignacio Segarra
Stephen Ambu
Joon Wah Mak
International Medical University · MY

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Toxoplasma gondii is a parasite that generates latent cysts in the brain; reactivation of these cysts may lead to fatal toxoplasmic encephalitis, for which treatment remains unsuccessful. We assessed spiramycin pharmacokinetics coadministered with metronidazole, the eradication of brain cysts and the in vitro reactivation. Male BALB/c mice were fed 1,000 tachyzoites orally to develop chronic toxoplasmosis. Four weeks later, infected mice underwent different treatments: (i) infected untreated mice (n = 9), which received vehicle only; (ii) a spiramycin-only group (n = 9), 400 mg/kg daily for 7 days; (iii) a metronidazole-only group (n = 9), 500 mg/kg daily for 7 days; and (iv) a combination group (n = 9), which received both spiramycin (400 mg/kg) and metronidazole (500 mg/kg) daily for 7 days. An uninfected control group (n = 10) was administered vehicle only. After treatment, the brain cysts were counted, brain homogenates were cultured in confluent Vero cells, and cysts and tachyzoites were counted after 1 week. Separately, pharmacokinetic profiles (plasma and brain) were assessed after a single dose of spiramycin (400 mg/kg), metronidazole (500 mg/kg), or both. Metronidazole treatment increased the brain spiramycin area under the concentration-time curve from 0 h to ∞ (AUC(0-∞)) by 67% without affecting its plasma disposition. Metronidazole plasma and brain AUC(0-∞) values were reduced 9 and 62%, respectively, after spiramycin coadministration. Enhanced spiramycin brain exposure after coadministration reduced brain cysts 15-fold (79 ± 23 for the combination treatment versus 1,198 ± 153 for the untreated control group [P < 0.05]) and 10-fold versus the spiramycin-only group (768 ± 125). Metronidazole alone showed no effect (1,028 ± 149). Tachyzoites were absent in the brain. Spiramycin reduced in vitro reactivation. Metronidazole increased spiramycin brain penetration, causing a significant reduction of T. gondii brain cysts, with potential clinical translatability for chronic toxoplasmosis treatment.

Indexed as

AnimalsAntiprotozoal AgentsArea Under CurveBrainChromatography, High Pressure LiquidCystsData Interpretation, StatisticalDrug Therapy, CombinationMaleMetronidazoleMiceMice, Inbred BALB CSpiramycinToxoplasmaToxoplasmosisAntiprotozoal AgentsMetronidazoleSpiramycin

Identifiers

PMID22271863
PMCPMC3318357
OpenAlexW2091226506

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.