Evidence map›Paper›PMID 25879757›Full record

ArticleMalaria journal2015

Assessing anti-malarial drug effects ex vivo using the haemozoin detection assay.

Maria Rebelo, Carolina Tempera, José F Fernandes, Martin P Grobusch, Thomas Hänscheid

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 20% 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

5 citing papers in PubMed, 13 citations in OpenAlex.

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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

5 authors at 2 institutions in 5 countries.

Maria RebeloInstituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av Prof Egas Moniz, Lisbon, P-1649-028, Portugal. mariarebelo@fm.ul.pt.
Carolina TemperaInstituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av Prof Egas Moniz, Lisbon, P-1649-028, Portugal. ctempera@fm.ul.pt.
José F FernandesCentre de Recherches Médicales de Lambaréné - CERMEL, Albert Schweitzer Hospital, Lambaréné, Gabon. jose.fernandes@lambarene.org.
Martin P GrobuschCentre de Recherches Médicales de Lambaréné - CERMEL, Albert Schweitzer Hospital, Lambaréné, Gabon. m.p.grobusch@amc.uva.nl.
Thomas HänscheidInstituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av Prof Egas Moniz, Lisbon, P-1649-028, Portugal. t.hanscheid@fm.ul.pt.
Albert Schweitzer Hospital · GAUniversity of Lisbon · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn vitro sensitivity assays are crucial to detect and monitor drug resistance. Plasmodium falciparum has developed resistance to almost all anti-malarial drugs. Although different in vitro drug assays are available, some of their inherent characteristics limit their application, especially in the field. A recently developed approach based on the flow cytometric detection of haemozoin (Hz) allowed reagent-free monitoring of parasite maturation and detection of drug effects in culture-adapted parasites. In this study, the set-up, performance and usefulness of this novel assay were investigated under field conditions in Gabon.

methodsAn existing flow cytometer (Cyflow Blue) was modified on site to detect light depolarization caused by Hz. Blood from malaria patients was incubated for 72 hrs with increasing concentrations of chloroquine, artesunate and artemisinin. The percentage of depolarizing red blood cells (RBC) was used as maturation indicator and measured at 24, 48 and 72 hrs of incubation to determine parasite growth and drug effects.

resultsThe flow cytometer was easily adapted on site to detect light depolarization caused by Hz. Analysis of ex vivo cultures of parasites, obtained from blood samples of malaria patients, showed four different growth profiles. In 39/46 samples, 50% inhibitory concentrations (IC50) were successfully determined. IC50 values for chloroquine were higher than 200 nM in 70% of the samples, indicating the presence of chloroquine-resistant parasites. For artesunate and artemisinin, IC50 values ranged from 0.9 to 60 nM and from 2.2 nM to 124 nM, respectively, indicating fully sensitive parasites.

conclusionFlow cytometric detection of Hz allowed the detection of drug effects in blood samples from malaria patients, without using additional reagents or complex protocols. Adjustment of the initial parasitaemia was not required, which greatly simplifies the protocol, although it may lead to different IC50 values. Further investigation of set-up conditions of the Hz assay, as well as future studies in various settings should be performed to further determine the usefulness of this assay as a tool for rapid resistance testing in malaria-endemic countries.

Indexed as

AntimalarialsArtemisininsBlood CellsChloroquineFlow CytometryHemeproteinsHumansInhibitory Concentration 50Malaria, FalciparumParasitologyPlasmodium falciparumAntimalarialsArtemisininsChloroquineHemeproteinshemozoin

Identifiers

PMID25879757
PMCPMC4393616
OpenAlexW2041847593

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.