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Review
, 2013 (2), CD000528

Drugs for Treating Schistosoma Mansoni Infection

Affiliations
Review

Drugs for Treating Schistosoma Mansoni Infection

Anthony Danso-Appiah et al. Cochrane Database Syst Rev.

Abstract

Background: Schistosoma mansoni is a parasitic infection common in the tropics and sub-tropics. Chronic and advanced disease includes abdominal pain, diarrhoea, blood in the stool, liver cirrhosis, portal hypertension, and premature death.

Objectives: To evaluate the effects of antischistosomal drugs, used alone or in combination, for treating S. mansoni infection.

Search methods: We searched MEDLINE, EMBASE and LILACS from inception to October 2012, with no language restrictions. We also searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2012) and mRCT. The reference lists of articles were reviewed and experts were contacted for unpublished studies.

Selection criteria: Randomized controlled trials of antischistosomal drugs, used alone or in combination, versus placebo, different antischistosomal drugs, or different doses of the same antischistosomal drug for treating S. mansoni infection.

Data collection and analysis: One author extracted data and assessed eligibility and risk of bias in the included studies, which were independently checked by a second author. We combined dichotomous outcomes using risk ratio (RR) and continuous data weighted mean difference (WMD); we presented both with 95% confidence intervals (CI). We assessed the quality of evidence using the GRADE approach.

Main results: Fifty-two trials enrolling 10,269 participants were included. The evidence was of moderate or low quality due to the trial methods and small numbers of included participants.Praziquantel: Compared to placebo, praziquantel 40 mg/kg probably reduces parasitological treatment failure at one month post-treatment (RR 3.13, 95% CI 1.03 to 9.53, two trials, 414 participants, moderate quality evidence). Compared to this standard dose, lower doses may be inferior (30 mg/kg: RR 1.52, 95% CI 1.15 to 2.01, three trials, 521 participants, low quality evidence; 20 mg/kg: RR 2.23, 95% CI 1.64 to 3.02, two trials, 341 participants, low quality evidence); and higher doses, up to 60 mg/kg, do not appear to show any advantage (four trials, 783 participants, moderate quality evidence).The absolute parasitological cure rate at one month with praziquantel 40 mg/kg varied substantially across studies, ranging from 52% in Senegal in 1993 to 92% in Brazil in 2006/2007. Oxamniquine: Compared to placebo, oxamniquine 40 mg/kg probably reduces parasitological treatment failure at three months (RR 8.74, 95% CI 3.74 to 20.43, two trials, 82 participants, moderate quality evidence). Lower doses than 40 mg/kg may be inferior at one month (30 mg/kg: RR 1.78, 95% CI 1.15 to 2.75, four trials, 268 participants, low quality evidence; 20 mg/kg: RR 3.78, 95% CI 2.05 to 6.99, two trials, 190 participants, low quality evidence), and higher doses, such as 60 mg/kg, do not show a consistent benefit (four trials, 317 participants, low quality evidence).These trials are now over 20 years old and only limited information was provided on the study designs and methods. Praziquantel versus oxamniquine: Only one small study directly compared praziquantel 40 mg/kg with oxamniquine 40 mg/kg and we are uncertain which treatment is more effective in reducing parasitological failure (one trial, 33 participants, very low quality evidence). A further 10 trials compared oxamniquine at 20, 30 and 60 mg/kg with praziquantel 40 mg/kg and did not show any marked differences in failure rate or percent egg reduction.Combination treatments: We are uncertain whether combining praziquantel with artesunate reduces failures compared to praziquantel alone at one month (one trial, 75 participants, very low quality evidence).Two trials also compared combinations of praziquantel and oxamniquine in different doses, but did not find statistically significant differences in failure (two trials, 87 participants). Other outcomes and analyses: In trials reporting clinical improvement evaluating lower doses (20 mg/kg and 30 mg/kg) against the standard 40 mg/kg for both praziquantel or oxamniquine, no dose effect was demonstrable in resolving abdominal pain, diarrhoea, blood in stool, hepatomegaly, and splenomegaly (follow up at one, three, six, 12, and 24 months; three trials, 655 participants).Adverse events were not well-reported but were mostly described as minor and transient.In an additional analysis of treatment failure in the treatment arm of individual studies stratified by age, failure rates with 40 mg/kg of both praziquantel and oxamniquine were higher in children.

Authors' conclusions: Praziquantel 40 mg/kg as the standard treatment for S. mansoni infection is consistent with the evidence. Oxamniquine, a largely discarded alternative, also appears effective.Further research will help find the optimal dosing regimen of both these drugs in children.Combination therapy, ideally with drugs with unrelated mechanisms of action and targeting the different developmental stages of the schistosomes in the human host should be pursued as an area for future research.

Conflict of interest statement

PLO was the lead author in three of the included trials (Olliaro 2011 BRA; Olliaro 2011 MRT; Olliaro 2011 TZA) and helped secure additional financial support from WHO. The rest of the authors have no known conflict of interest.

Figures

Figure 1
Figure 1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figure 2
Figure 2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Analysis 1.1
Analysis 1.1
Comparison 1 Praziquantel versus placebo, Outcome 1 Parasitological failure at one month.
Analysis 1.2
Analysis 1.2
Comparison 1 Praziquantel versus placebo, Outcome 2 Parasitological failure at six months.
Analysis 1.3
Analysis 1.3
Comparison 1 Praziquantel versus placebo, Outcome 3 Parasitological failure at 12 months.
Analysis 2.1
Analysis 2.1
Comparison 2 Praziquantel (lower dose) versus praziquantel 40 mg/kg, Outcome 1 Parasitological failure at one month.
Analysis 2.2
Analysis 2.2
Comparison 2 Praziquantel (lower dose) versus praziquantel 40 mg/kg, Outcome 2 Parasitological failure at three months.
Analysis 2.3
Analysis 2.3
Comparison 2 Praziquantel (lower dose) versus praziquantel 40 mg/kg, Outcome 3 Parasitological failure at six to 12 months.
Analysis 3.1
Analysis 3.1
Comparison 3 Praziquantel lower dose (20 and 30 mg/kg) versus praziquantel 40 mg/kg, Outcome 1 Resolution of abdominal pain: 20 mg/kg versus 40 mg/kg.
Analysis 3.2
Analysis 3.2
Comparison 3 Praziquantel lower dose (20 and 30 mg/kg) versus praziquantel 40 mg/kg, Outcome 2 Resolution of abdominal pain: 30 mg/kg versus 40 mg/kg.
Analysis 3.3
Analysis 3.3
Comparison 3 Praziquantel lower dose (20 and 30 mg/kg) versus praziquantel 40 mg/kg, Outcome 3 Resolution of diarrhoea: 20 mg/kg versus 40 mg/kg.
Analysis 3.4
Analysis 3.4
Comparison 3 Praziquantel lower dose (20 and 30 mg/kg) versus praziquantel 40 mg/kg, Outcome 4 Resolution of diarrhoea: 30 mg/kg versus 40 mg/kg.
Analysis 3.5
Analysis 3.5
Comparison 3 Praziquantel lower dose (20 and 30 mg/kg) versus praziquantel 40 mg/kg, Outcome 5 Resolution of blood in stool: 20 mg/kg versus 40 mg/kg.
Analysis 3.6
Analysis 3.6
Comparison 3 Praziquantel lower dose (20 and 30 mg/kg) versus praziquantel 40 mg/kg, Outcome 6 Resolution of blood in stool: 30 mg/kg versus 40 mg/kg.
Analysis 3.7
Analysis 3.7
Comparison 3 Praziquantel lower dose (20 and 30 mg/kg) versus praziquantel 40 mg/kg, Outcome 7 Resolution of hepatomegaly: 20 mg/kg versus 40 mg/kg.
Analysis 3.8
Analysis 3.8
Comparison 3 Praziquantel lower dose (20 and 30 mg/kg) versus praziquantel 40 mg/kg, Outcome 8 Resolution of hepatomegaly: 30 mg/kg versus 40 mg/kg.
Analysis 3.9
Analysis 3.9
Comparison 3 Praziquantel lower dose (20 and 30 mg/kg) versus praziquantel 40 mg/kg, Outcome 9 Resolution of splenomegaly: 20 mg/kg versus 40 mg/kg.
Analysis 3.10
Analysis 3.10
Comparison 3 Praziquantel lower dose (20 and 30 mg/kg) versus praziquantel 40 mg/kg, Outcome 10 Resolution of splenomegaly: 30 mg/kg versus 40 mg/kg.
Analysis 4.1
Analysis 4.1
Comparison 4 Praziquantel (higher dose) versus praziquantel 40 mg/kg, Outcome 1 Parasitological failure at one month.
Analysis 4.2
Analysis 4.2
Comparison 4 Praziquantel (higher dose) versus praziquantel 40 mg/kg, Outcome 2 Parasitological failure at six months.
Analysis 4.3
Analysis 4.3
Comparison 4 Praziquantel (higher dose) versus praziquantel 40 mg/kg, Outcome 3 Parasitological failure at six to 12 months.
Analysis 5.1
Analysis 5.1
Comparison 5 Praziquantel 40 mg/kg divided dose versus praziquantel 40 mg/kg single dose, Outcome 1 Parasitological failure at one month.
Analysis 5.2
Analysis 5.2
Comparison 5 Praziquantel 40 mg/kg divided dose versus praziquantel 40 mg/kg single dose, Outcome 2 Parasitological failure at three months.
Analysis 5.3
Analysis 5.3
Comparison 5 Praziquantel 40 mg/kg divided dose versus praziquantel 40 mg/kg single dose, Outcome 3 Parasitological failure at six months.
Analysis 6.1
Analysis 6.1
Comparison 6 Praziquantel alternative dosing (Brazil), Outcome 1 Parasitological failure at six months.
Analysis 7.1
Analysis 7.1
Comparison 7 Oxamniquine versus placebo, Outcome 1 Parasitological failure at three to four months.
Analysis 7.2
Analysis 7.2
Comparison 7 Oxamniquine versus placebo, Outcome 2 Parasitological failure at six to 10 months.
Analysis 8.1
Analysis 8.1
Comparison 8 Oxamniquine (lower dose) versus oxamniquine 40 mg/kg, Outcome 1 Parasitological failure at one month.
Analysis 8.2
Analysis 8.2
Comparison 8 Oxamniquine (lower dose) versus oxamniquine 40 mg/kg, Outcome 2 Parasitological failure at three to four months.
Analysis 8.3
Analysis 8.3
Comparison 8 Oxamniquine (lower dose) versus oxamniquine 40 mg/kg, Outcome 3 Parasitological failure at six months.
Analysis 8.4
Analysis 8.4
Comparison 8 Oxamniquine (lower dose) versus oxamniquine 40 mg/kg, Outcome 4 Parasitological failure at 12 months.
Analysis 9.1
Analysis 9.1
Comparison 9 Oxamniquine lower dose (20 and 30 mg/kg) versus oxamniquine 40 mg/kg, Outcome 1 Resolution of abdominal pain: 20 mg/kg versus 40 mg/kg.
Analysis 9.2
Analysis 9.2
Comparison 9 Oxamniquine lower dose (20 and 30 mg/kg) versus oxamniquine 40 mg/kg, Outcome 2 Resolution of abdominal pain: 30 mg/kg versus 40 mg/kg.
Analysis 9.3
Analysis 9.3
Comparison 9 Oxamniquine lower dose (20 and 30 mg/kg) versus oxamniquine 40 mg/kg, Outcome 3 Resolution of diarrhoea: 20 mg/kg versus 40 mg/kg.
Analysis 9.4
Analysis 9.4
Comparison 9 Oxamniquine lower dose (20 and 30 mg/kg) versus oxamniquine 40 mg/kg, Outcome 4 Resolution of diarrhoea: 30 mg/kg versus 40 mg/kg.
Analysis 9.5
Analysis 9.5
Comparison 9 Oxamniquine lower dose (20 and 30 mg/kg) versus oxamniquine 40 mg/kg, Outcome 5 Resolution of blood in stool: 20 mg/kg versus 40 mg/kg.
Analysis 9.6
Analysis 9.6
Comparison 9 Oxamniquine lower dose (20 and 30 mg/kg) versus oxamniquine 40 mg/kg, Outcome 6 Resolution of blood in stool: 30 mg/kg versus 40 mg/kg.
Analysis 9.7
Analysis 9.7
Comparison 9 Oxamniquine lower dose (20 and 30 mg/kg) versus oxamniquine 40 mg/kg, Outcome 7 Resolution of hepatomegaly: 20 mg/kg versus 40 mg/kg.
Analysis 9.8
Analysis 9.8
Comparison 9 Oxamniquine lower dose (20 and 30 mg/kg) versus oxamniquine 40 mg/kg, Outcome 8 Resolution of hepatomegaly: 30 mg/kg versus 40 mg/kg.
Analysis 9.9
Analysis 9.9
Comparison 9 Oxamniquine lower dose (20 and 30 mg/kg) versus oxamniquine 40 mg/kg, Outcome 9 Resolution of splenomegaly: 20 mg/kg versus 40 mg/kg.
Analysis 9.10
Analysis 9.10
Comparison 9 Oxamniquine lower dose (20 and 30 mg/kg) versus oxamniquine 40 mg/kg, Outcome 10 Resolution of splenomegaly: 30 mg/kg versus 40 mg/kg.
Analysis 10.1
Analysis 10.1
Comparison 10 Oxamniquine (higher dose) versus oxamniquine 40 mg/kg, Outcome 1 Parasitological failure at one month.
Analysis 10.2
Analysis 10.2
Comparison 10 Oxamniquine (higher dose) versus oxamniquine 40 mg/kg, Outcome 2 Parasitological failure at three to four months.
Analysis 10.3
Analysis 10.3
Comparison 10 Oxamniquine (higher dose) versus oxamniquine 40 mg/kg, Outcome 3 Parasitological failure at six months.
Analysis 11.1
Analysis 11.1
Comparison 11 Oxamniquine (lower dose) 15 to 20 mg/kg versus oxamniquine 30 mg/kg, Outcome 1 Parasitological failure.
Analysis 12.1
Analysis 12.1
Comparison 12 Oxamniquine (higher dose) versus oxamniquine 30 mg/kg, Outcome 1 Parasitological failure at one month.
Analysis 12.2
Analysis 12.2
Comparison 12 Oxamniquine (higher dose) versus oxamniquine 30 mg/kg, Outcome 2 Parasitological failure at three to four months.
Analysis 12.3
Analysis 12.3
Comparison 12 Oxamniquine (higher dose) versus oxamniquine 30 mg/kg, Outcome 3 Parasitological failure at six months.
Analysis 13.1
Analysis 13.1
Comparison 13 Oxamniquine versus praziquantel, Outcome 1 Parasitological failure at one month.
Analysis 13.2
Analysis 13.2
Comparison 13 Oxamniquine versus praziquantel, Outcome 2 Parasitological failure at three months.
Analysis 13.3
Analysis 13.3
Comparison 13 Oxamniquine versus praziquantel, Outcome 3 Parasitological failure at six months.
Analysis 13.4
Analysis 13.4
Comparison 13 Oxamniquine versus praziquantel, Outcome 4 Parasitological failure at 12 months.
Analysis 14.1
Analysis 14.1
Comparison 14 Myrrh (Mirazid) 300 mg once daily for three days versus praziquantel 40 mg/kg, Outcome 1 Parasitological failure at three to six weeks.
Analysis 15.1
Analysis 15.1
Comparison 15 Praziquantel (40 mg/kg) plus artesunate (12 mg/kg total dose) versus praziquantel (40 mg/kg), Outcome 1 Parasitological failure at one month.
Analysis 15.2
Analysis 15.2
Comparison 15 Praziquantel (40 mg/kg) plus artesunate (12 mg/kg total dose) versus praziquantel (40 mg/kg), Outcome 2 Parasitological failure at three months.
Analysis 15.3
Analysis 15.3
Comparison 15 Praziquantel (40 mg/kg) plus artesunate (12 mg/kg total dose) versus praziquantel (40 mg/kg), Outcome 3 Parasitological failure at six months.
Analysis 16.1
Analysis 16.1
Comparison 16 Praziquantel (20 mg/kg) plus oxamniquine (7.5 mg/kg) versus praziquantel (40 mg/kg), Outcome 1 Parasitological failure at three months.
Analysis 16.2
Analysis 16.2
Comparison 16 Praziquantel (20 mg/kg) plus oxamniquine (7.5 mg/kg) versus praziquantel (40 mg/kg), Outcome 2 Parasitological failure at six months.
Analysis 16.3
Analysis 16.3
Comparison 16 Praziquantel (20 mg/kg) plus oxamniquine (7.5 mg/kg) versus praziquantel (40 mg/kg), Outcome 3 Parasitological failure at 12 months.
Analysis 17.1
Analysis 17.1
Comparison 17 Praziquantel (8 mg/kg) plus oxamniquine (4 mg/kg) versus praziquantel (20 mg/kg) plus oxamniquine (10 mg/kg), Outcome 1 Parasitological failure at one month.
Analysis 17.2
Analysis 17.2
Comparison 17 Praziquantel (8 mg/kg) plus oxamniquine (4 mg/kg) versus praziquantel (20 mg/kg) plus oxamniquine (10 mg/kg), Outcome 2 Parasitological failure at three months.
Analysis 17.3
Analysis 17.3
Comparison 17 Praziquantel (8 mg/kg) plus oxamniquine (4 mg/kg) versus praziquantel (20 mg/kg) plus oxamniquine (10 mg/kg), Outcome 3 Parasitological failure at six months.
Analysis 18.1
Analysis 18.1
Comparison 18 Praziquantel (15 mg/kg) plus oxamniquine (7.5 mg/kg) versus praziquantel (20 mg/kg) plus oxamniquine (10 mg/kg), Outcome 1 Parasitological failure at one month.
Analysis 18.2
Analysis 18.2
Comparison 18 Praziquantel (15 mg/kg) plus oxamniquine (7.5 mg/kg) versus praziquantel (20 mg/kg) plus oxamniquine (10 mg/kg), Outcome 2 Parasitological failure at three months.
Analysis 18.3
Analysis 18.3
Comparison 18 Praziquantel (15 mg/kg) plus oxamniquine (7.5 mg/kg) versus praziquantel (20 mg/kg) plus oxamniquine (10 mg/kg), Outcome 3 Parasitological failure at six months.

Update of

  • Interventions for Treating Schistosomiasis Mansoni
    H Saconato et al. Cochrane Database Syst Rev (2), CD000528. PMID 10796552. - Review
    IPraziquantel and oxamniquine both appear to be effective for the treatment of Schistosomiasis mansoni, although lower doses of oxamniquine (less than 30 milligrams per k …

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