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Controlled release of artemisone for the treatment of experimental cerebral malaria

Overview of attention for article published in Parasites & Vectors, March 2017
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Title
Controlled release of artemisone for the treatment of experimental cerebral malaria
Published in
Parasites & Vectors, March 2017
DOI 10.1186/s13071-017-2018-7
Pubmed ID
Authors

Jacob Golenser, Viola Buchholz, Amir Bagheri, Abed Nasereddin, Ron Dzikowski, Jintao Guo, Nicholas H. Hunt, Sara Eyal, Natalia Vakruk, Andreas Greiner

Abstract

Cerebral malaria (CM) is a leading cause of malarial mortality resulting from infection by Plasmodium falciparum. Treatment commonly involves adjunctive care and injections or transfusion of artemisinins. All artemisinins that are in current use are metabolized to dihydroxyartemisinin (DHA), to which there is already some parasite resistance. We used artemisone, a derivative that does not convert to DHA, has improved pharmacokinetics and anti-plasmodial activity and is also anti-inflammatory (an advantage given the immunopathological nature of CM). We examined controlled artemisone release from biodegradable polymers in a mouse CM model. This would improve treatment by exposing the parasites for a longer period to a non-toxic drug concentration, high enough to eliminate the pathogen and prevent CM. The preparations were inserted into mice as prophylaxis, early or late treatment in the disease course. The most efficient formulation was a rigid polymer, containing 80 mg/kg artemisone, which cured all of the mice when used as early treatment and 60% of the mice when used as a very late treatment (at which stage all control mice would die of CM within 24 h). In those mice that were not completely cured, relapse followed a latent period of more than seven days. Prophylactic treatment four days prior to the infection prevented CM. We also measured the amount of artemisone released from the rigid polymers using a bioassay with cultured P. falciparum. Significant amounts of artemisone were released throughout at least ten days, in line with the in vivo prophylactic results. Overall, we demonstrate, as a proof-of-concept, a controlled-sustained release system of artemisone for treatment of CM. Mice were cured or if treated at a very late stage of the disease, depicted a delay of a week before death. This delay would enable a considerable time window for exact diagnosis and appropriate additional treatment. Identical methods could be used for other parasites that are sensitive to artemisinins (e.g. Toxoplasma gondii and Neospora caninum).

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Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 42 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 26%
Student > Master 7 17%
Student > Bachelor 4 10%
Researcher 4 10%
Other 3 7%
Other 4 10%
Unknown 9 21%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 5 12%
Medicine and Dentistry 5 12%
Chemistry 3 7%
Agricultural and Biological Sciences 3 7%
Computer Science 2 5%
Other 8 19%
Unknown 16 38%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 March 2017.
All research outputs
#6,962,517
of 9,134,189 outputs
Outputs from Parasites & Vectors
#1,914
of 2,626 outputs
Outputs of similar age
#186,649
of 254,148 outputs
Outputs of similar age from Parasites & Vectors
#111
of 152 outputs
Altmetric has tracked 9,134,189 research outputs across all sources so far. This one is in the 13th percentile – i.e., 13% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,626 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 254,148 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 152 others from the same source and published within six weeks on either side of this one. This one is in the 8th percentile – i.e., 8% of its contemporaries scored the same or lower than it.