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Meta-Analysis
. 2011 Oct 17:4:201.
doi: 10.1186/1756-3305年4月20日1.

Efficacy of praziquantel and artemisinin derivatives for the treatment and prevention of human schistosomiasis: a systematic review and meta-analysis

Affiliations
Meta-Analysis

Efficacy of praziquantel and artemisinin derivatives for the treatment and prevention of human schistosomiasis: a systematic review and meta-analysis

Rong Liu et al. Parasit Vectors. .

Abstract

Background: Praziquantel has been used as first-line drug for chemotherapy of schistosomiasis since 1984. Besides praziquantel, artemether and artesunate have also been used for the control of this infectious disease since late 1990s. In this article, we conducted a systematic review and meta-analysis to evaluate the antischistosomal efficacy of different medication strategies including monotherapy or combination therapies of these drugs.

Results: A number of 52 trials from 38 articles published in peer-reviewed journals before July 2011 were selected for analysis after searching the following literature databases: the Cochrane Library, PubMed/Medline, ISI Web of Science, Chinese Biomedicine Literature Database, and China National Knowledge Infrastructure. Our meta-analyses showed that a dosage of 30-60 mg/kg praziquantel compared with placebo produced a protection rate of about 76% (95% CI: 67%-83%) for treating human schistosomiasis, which varied from 70% to 76% with no significant differences among the subspecies S. haematobium, S. japonicum or S. mansoni. Protection rates were higher when praziquantel doses were elevated, as concluded from the nRCTs results: the protection rate of praziquantel at 40 mg/kg was 52% (95% CI: 49%-55%), and it increased to 91% (95% CI: 88%-92%) when the dosages were elevated to 60/80/100 mg/kg divided two or more doses. Multiple doses of artemether or artesunate over 1- or 2-week intervals resulted in protection rates of 65% to 97% for preventing schistosomiasis, and increased doses and shorter medication intervals improved their efficacies. Praziquantel and artemisinin derivatives (artemether or artesunate) in combination resulted in a higher protection rate of 84% (95% CI: 64%-91%) than praziquantel monotherapy for treatment. praziquantel and artesunate in combination had a great protection rate of 96% (95% CI: 78%-99%) for preventing schistosomes infection.

Conclusions: According to the results, praziquantel remains effective in schistosomiasis treatment, and multiple doses would improve its efficacy; meanwhile, praziquantel is also a good drug for preventing acute schistosomiasis morbidity. It's better to use multiple doses of artemether or artesunate with 1- or 2-week intervals for prevention against schistosome infection. Praziquantel and artemether or artesunate in combination perform better in treatment than praziquantel monotherapy, and they are especially suitable for treating the patients with repeated exposure to infected water.

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Figures

Figure 1
Figure 1
Flow diagram showing the articles selection process for present meta-analyses of the efficacy of PZQ and ART (AM and AS) administrated alone or in combination for human schistosomiasis treatment or prevention. Individual searches don't add up to 351 because some articles could be found simultaneously in multiple literature databases.
Figure 2
Figure 2
Forest plots showing the efficacy of PZQ (30-60 mg/kg) for schistosomiasis treatment (RCTs). n/N = number examined as positive outcome (or not cured) over number of participants who were examined. Sub-groups with trials with patients infected by different Schistosoma species (01: S. haematobium, 02: S. mansoni, and 03: S. japonicum) were separately combined. The P value of each test for heterogeneity was ≥0.05, thus the fixed-effect model was used to combine trial-specific RRs of each sub-group and the total pooled RR, and its 95% CI were calculated by combing all sub-groups. No statistically significant difference among pooled RRs of sub-groups about different species was observed.
Figure 3
Figure 3
Forest plots showing the efficacy of AM using 6 mg/kg for preventing schistosome infection (RCTs). The trials were stratified into sub-groups based on dosages and Schistosoma species. (01) 4-7 doses by 15-day intervals for preventing S. japonicum infection (pooled RR was synthesized by the fixed-effect model); (02) 2-3 doses by 15-day intervals for preventing S. japonicum infection of short term exposure; (03) 8-13 doses by 15-day intervals for preventing S. japonicum infection (pooled RR was synthesized by random-effect model); (04) 6-7 doses by 3-week intervals for preventing S. mansoni infection; (05) 6-7 doses by 1-month intervals for preventing schistosome infection - S. haematobium and S. japonicum (pooled RR was synthesized by the fixed-effect model).
Figure 4
Figure 4
Forest plots showing the efficacy of AS using 6 mg/kg for preventing S. japonicum infection (RCTs). The trials were stratified into sub-groups based on different dosages and time intervals between every two adjacent doses. (01) 8 doses by 1-week intervals; (02) 3 doses by 1-week intervals; (03) 8-14 doses by 2-week intervals; (04) 3-5 doses by 2-week intervals. The P values of test for heterogeneity of subgroups 01, 03 and 04 were >0.05 each, thus the pooled RRs were synthesized by the fixed-effect model.
Figure 5
Figure 5
Forest plots showing the efficacy of PZQ and ARTs (AM or AS) in combination for schistosomiasis treatment. (01) PZQ and AS in combination for treating against S. haematobium or S. japonicum; (02) PZQ and AM in combination for treating against S. japonicum. The pooled RR of 0.61 (95% CI: 0.39-0.96) was determined by combing the two subgroups as the P value of overall heterogeneity test was 0.62.
Figure 6
Figure 6
Funnel plot and Egger's publication bias test for RCTs of PZQ's efficacy on schistosomiasis treatment. The pooled log-RR for these trials is shown with a dashed vertical line, and the dashed slash lines distributed in both sides are the cutoff values of 95% CI of pooled log RR. The Egger's publication bias test showed that no publication bias exists (P = 0.96).
Figure 7
Figure 7
Funnel plot and Egger's publication bias test for RCTs (2-7 doses by 15-day intervals) of AM's efficacy on preventing S. japonicum infection. There is one point (representing one trial) outside the cutoff values of 95% CI of pooled log RR. The Egger's publication bias test showed that no publication bias exists (P = 0.53).
Figure 8
Figure 8
Funnel plot and Egger's publication bias test for RCTs (8-13 doses in 15-day intervals) of AM's efficacy on preventing S. japonicum infection. There are two points (represented two trials) distributing outside the cutoff values of 95% CI of pooled log RR. The Egger's publication bias test showed that a publication bias may exist (P = 0.01).
Figure 9
Figure 9
Funnel plot and Egger's publication bias test for RCTs of AS's efficacy on preventing S. japonicum infection. The Egger's publication bias test showed that no publication bias exists (P = 0.18).

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