Randomized controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitemia

Richard J. Maude, Kamolrat Silamut, Katherine Plewes, Prakaykaew Charunwatthana, May Ho, M. Abul Faiz, Ridwanur Rahman, Md Amir Hossain, Mahtab U. Hassan, Emran Bin Yunus, Gofranul Hoque, Faridul Islam, Aniruddha Ghose, Josh Hanson, Joel Schlatter, Rachel Lacey, Alison Eastaugh, Joel Tarning, Sue J. Lee, Nicholas J. WhiteKesinee Chotivanich, Nicholas P.J. Day, Arjen M. Dondorp

    Research output: Contribution to journalArticle

    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. 
    Original languageEnglish
    Pages (from-to)120-129
    Number of pages10
    JournalJournal of Infectious Diseases
    Volume209
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2014

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