Ursodeoxycholic acid and artesunate in the treatment of severe falciparum malaria patients with jaundice.
OBJECTIVE
Plasmodium falciparum (PF) infection can lead to severe complications. Ursodeoxycholic acid (UDCA) is increasingly used for the treatment of cholestatic liver diseases. The present study aims to determine the effects of combined UDCA and artesunate compared to placebo and artesunate on the improvement of liver tests in severe PF jaundiced patients.


METHODS
All severe PF jaundiced patients, aged > or = 15 years and diagnosed as having severe malaria according to WHO 2000 criteria, were enrolled. Patients with evidence of biliary obstruction, other cholestatic liver diseases and those who were pregnant were excluded. Patients were randomized to receive either oral UDCA or placebo for 2 weeks in additional to artesunate. All patients were admitted for at least 14 days to monitor the result of the treatment.


RESULTS
Seventy-four severe PF malaria patients with jaundice were enrolled. Both groups had similar demographic and laboratory tests, with the exception being more males in the UDCA group than in the placebo group (P = 0.04). The median of percentage change of total bilirubin and aminotransferase levels at the end of weeks 1, 2, 3 and 4 showed no difference between the two groups. Only the median of percentage change of alkaline phosphatase at the end of week one compared with the baseline values showed less increment in the UDCA group than in the placebo group (P = 0.04). No serious adverse events were seen during the 4 weeks of follow up.


CONCLUSIONS
In severe PF malaria patients with jaundice, combined therapy with UDCA and artesunate is safe, but does not significantly improve liver tests compared to placebo and artesunate.
Treeprasertsuk
Sombat
S
Department of Gastroenterology, Chulalongkorn University, Thailand. battan5410@yahoo.com
Silachamroon
Udomsak
U
Krudsood
Srivicha
S
Huntrup
Arun
A
Suwannakudt
Plengsakoon
P
Vannaphan
Suparp
S
Wilairatana
Polrat
P
D000284:Administration, Oral; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D000077332:Artesunate; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007565:Jaundice / Q000175:diagnosis / Q000188:drug therapy* / Q000469:parasitology; D008111:Liver Function Tests; D016778:Malaria, Falciparum / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D000962:Antimalarials; D037621:Artemisinins; D015415:Biomarkers; D002756:Cholagogues and Choleretics; D000077332:Artesunate; D014580:Ursodeoxycholic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin