Randomized controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitemia.
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.
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Richard J
RJ
Maude
Kamolrat
K
Silamut
Katherine
K
Plewes
Prakaykaew
P
Charunwatthana
May
M
Ho
M
M
Abul Faiz
Ridwanur
R
Rahman
Md Amir
MA
Hossain
Mahtab U
MU
Hassan
Emran
E
Bin Yunus
Gofranul
G
Hoque
Faridul
F
Islam
Aniruddha
A
Ghose
Josh
J
Hanson
Joel
J
Schlatter
Rachel
R
Lacey
Alison
A
Eastaugh
Joel
J
Tarning
Sue J
SJ
Lee
Nicholas J
NJ
White
Kesinee
K
Chotivanich
Nicholas P J
NP
Day
Arjen M
AM
Dondorp
D000328:Adult; D000962:Antimalarials / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D019344:Lactic Acid / Q000097:blood; D007978:Levamisole / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000378:metabolism / Q000469:parasitology; D008297:Male; D055806:Microvessels / Q000187:drug effects; D008875:Middle Aged; D018512:Parasitemia / Q000188:drug therapy* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000737:chemistry / Q000302:isolation & purification; D012039:Regional Blood Flow
D000962:Antimalarials; D007978:Levamisole; D019344:Lactic Acid
artesunate; falciparum; levamisole; malaria; sequestration; severe