Evidence map›Paper›PMID 20419161›Full record

Trial reportPloS one2010

Oral activated charcoal prevents experimental cerebral malaria in mice and in a randomized controlled clinical trial in man did not interfere with the pharmacokinetics of parenteral artesunate.

J Brian de Souza, Uduak Okomo, Neal D Alexander, Naveed Aziz, Benjamin M J Owens, Harparkash Kaur, Momodou Jasseh, Sant Muangnoicharoen, Percy F Sumariwalla, David C Warhurst and 7 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 18% 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

6 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Exploring adjunctive therapies for cerebral malaria.Frontiers in cellular and infection microbiology · 2024
    Review
  3. Review
  4. Article
  5. Review
  6. Review
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

17 authors at 7 institutions in 2 countries.

J Brian de SouzaDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Uduak Okomo
Neal D Alexander
Naveed Aziz
Benjamin M J Owens
Harparkash Kaur
Momodou Jasseh
Sant Muangnoicharoen
Percy F Sumariwalla
David C Warhurst
Stephen A Ward
David J Conway
Luis Ulloa
Kevin J Tracey
Brian M J Foxwell
Paul M Kaye
Michael Walther
London School of Hygiene & Tropical Medicine · GBMRC Unit the Gambia · GMImperial College London · GBLiverpool School of Tropical Medicine · GBUniversity of York · GBHull York Medical School · GBUniversity College London · GB

Funding

WHITE MATTER STRUCTURAL DEFICITS IN HIGH FUNCTIONING CHILDREN WITH AUTISM SPEM01RR018535 · NCRR · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI SCHWARTZ, GUY · 2003 to 2010
$19.5M
MACROPHAGE INACTIVATION IN SEPSIS AFTER TRAUMA OR SHOCKR01GM057226 · NIGMS · NORTH SHORE UNIVERSITY HOSPITAL · PI TRACEY, KEVIN J · 1999 to 2015
$5.5M
Cholinergic regulation of NF-kB in sepsisR01GM084125 · NIGMS · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI ULLOA, LUIS · 2008 to 2012
$1.5M
Medical Research Council G0400786Medical Research Council G0700837Medical Research Council MC_U190085853Medical Research Council MC_UP_A900_1123NCRR NIH HHS 1M01RR018535NCRR NIH HHS M01 RR018535NIGMS NIH HHS R01 GM057226NIGMS NIH HHS R01 GM084125
6 · The paper itself

Abstract

backgroundSafe, cheap and effective adjunct therapies preventing the development of, or reducing the mortality from, severe malaria could have considerable and rapid public health impact. Oral activated charcoal (oAC) is a safe and well tolerated treatment for acute poisoning, more recently shown to have significant immunomodulatory effects in man. In preparation for possible efficacy trials in human malaria, we sought to determine whether oAC would i) reduce mortality due to experimental cerebral malaria (ECM) in mice, ii) modulate immune and inflammatory responses associated with ECM, and iii) affect the pharmacokinetics of parenteral artesunate in human volunteers. METHODS/PRINCIPAL

findingsWe found that oAC provided significant protection against P. berghei ANKA-induced ECM, increasing overall survival time compared to untreated mice (p<0.0001; hazard ratio 16.4; 95% CI 6.73 to 40.1). Protection from ECM by oAC was associated with reduced numbers of splenic TNF(+) CD4(+) T cells and multifunctional IFNgamma(+)TNF(+) CD4(+) and CD8(+) T cells. Furthermore, we identified a whole blood gene expression signature (68 genes) associated with protection from ECM. To evaluate whether oAC might affect current best available anti-malarial treatment, we conducted a randomized controlled open label trial in 52 human volunteers (ISRCTN NR. 64793756), administering artesunate (AS) in the presence or absence of oAC. We demonstrated that co-administration of oAC was safe and well-tolerated. In the 26 subjects further analyzed, we found no interference with the pharmacokinetics of parenteral AS or its pharmacologically active metabolite dihydroartemisinin. CONCLUSIONS/SIGNIFICANCE: oAC protects against ECM in mice, and does not interfere with the pharmacokinetics of parenteral artesunate. If future studies succeed in establishing the efficacy of oAC in human malaria, then the characteristics of being inexpensive, well-tolerated at high doses and requiring no sophisticated storage would make oAC a relevant candidate for adjunct therapy to reduce mortality from severe malaria, or for immediate treatment of suspected severe malaria in a rural setting.

trial registrationControlled-Trials.com ISRCTN64793756.

Indexed as

Administration, OralAdultAnimalsAntimalarialsArtemisininsArtesunateCharcoalDrug Evaluation, PreclinicalDrug InteractionsFemaleHumansInfusions, ParenteralMalaria, CerebralMaleMiceMice, Inbred C57BLAntimalarialsArtemisininsArtesunateCharcoal

Identifiers

PMID20419161
PMCPMC2855344
OpenAlexW2055562373

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.