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Randomized Controlled Trial of Levamisole Hydrochloride as Adjunctive Therapy in Severe Falciparum Malaria with High Parasitemia

Maude, Richard J., Silamut, Kamolrat, Plewes, Katherine, Charunwatthana, Prakaykaew, Ho, May, Faiz, Abul, Rahman, Ridwanur, Hossain, Md Amir, Hassan, Mahtab U., Bin Yunus, Emran, Hoque, Gofranul, Islam, Faridul, Ghose, Aniruddha, Hanson, Josh, Schlatter, Joel, Lacey, Rachel, Eastaugh, Alison, Tarning, Joel, Lee, Sue J., White, Nicholas J., Chotivanich, Kesinee, Day, Nicholas P. J. and Dondorp, Arjen M. (2014). Randomized Controlled Trial of Levamisole Hydrochloride as Adjunctive Therapy in Severe Falciparum Malaria with High Parasitemia. The Journal of Infectious Diseases,209(1):120-129.

Document type: Journal Article
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IRMA ID cmartelxPUB158
Title Randomized Controlled Trial of Levamisole Hydrochloride as Adjunctive Therapy in Severe Falciparum Malaria with High Parasitemia
Author Maude, Richard J.
Silamut, Kamolrat
Plewes, Katherine
Charunwatthana, Prakaykaew
Ho, May
Faiz, Abul
Rahman, Ridwanur
Hossain, Md Amir
Hassan, Mahtab U.
Bin Yunus, Emran
Hoque, Gofranul
Islam, Faridul
Ghose, Aniruddha
Hanson, Josh
Schlatter, Joel
Lacey, Rachel
Eastaugh, Alison
Tarning, Joel
Lee, Sue J.
White, Nicholas J.
Chotivanich, Kesinee
Day, Nicholas P. J.
Dondorp, Arjen M.
Journal Name The Journal of Infectious Diseases
Publication Date 2014
Volume Number 209
Issue Number 1
ISSN 0022-1899   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-84891363760
Start Page 120
End Page 129
Total Pages 10
Place of Publication United States of America
Publisher Oxford University Press
HERDC Category C1 - Journal Article (DIISR)
Abstract Background: Cytoadherence and sequestration of erythrocytes containing mature stages of Plasmodium falciparum are central to the pathogenesis of severe malaria. The oral anthelminthic drug levamisole inhibits cytoadherence in vitro and reduces sequestration of late-stage parasites in uncomplicated falciparum malaria treated with quinine.

Methods:
Fifty-six adult patients with severe malaria and high parasitemia admitted to a referral hospital in Bangladesh were randomized to receive a single dose of levamisole hydrochloride (150 mg) or no adjuvant to antimalarial treatment with intravenous artesunate.

Results:
Circulating late-stage parasites measured as the median area under the parasite clearance curves were 2150 (interquartile range [IQR], 0–28 025) parasites/µL × hour in patients treated with levamisole and 5489 (IQR, 192–25 848) parasites/µL × hour in controls (P = .25). The “sequestration ratios” at 6 and 12 hours for all parasite stages and changes in microvascular blood flow did not differ between treatment groups (all P > .40). The median time to normalization of plasma lactate (<2 mmol/L) was 24 (IQR, 12–30) hours with levamisole vs 28 (IQR, 12–36) hours without levamisole (P = .15).

Conclusions:
There was no benefit of a single-dose of levamisole hydrochloride as adjuvant to intravenous artesunate in the treatment of adults with severe falciparum malaria. Rapid parasite killing by intravenous artesunate might obscure the effects of levamisole.
Keywords Malaria
Severe
Falciparum
Seqestration
Artesunate
Levamisole
DOI http://dx.doi.org/10.1093/infdis/jit410   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited
Description for Link Link to CC Attribution 3.0 License
URL https://creativecommons.org/licenses/by/3.0/au


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