Interventions for treating schistosomiasis mansoni

  • Review
  • Intervention

Authors


Abstract

Background

Schistosoma mansoni is a parasite carried by freshwater snails. S. mansoni infects the intestine, liver and spleen and can be fatal.

Objectives

To assess the effects of oxamniquine and praziquantel for treating S. mansoni infection.

Search methods

We searched the Cochrane Infectious Diseases Group specialized trials register (September 2005), CENTRAL (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to September 2005), EMBASE (1980 to September 2005), LILACS (September 2005), and reference lists of articles. The Revista da Sociedade Brasileira de Medicina Tropical and Brazilian Tropical Medicine Congress abstracts were hand searched

Selection criteria

Randomised and quasi-randomised trials comparing oxamniquine and/or praziquantel with placebo for the treatment of S. mansoni.

Data collection and analysis

Two reviewers independently assessed trial quality and extracted data.

Main results

Thirteen trials met the inclusion criteria. Oxamniquine and praziquantel are effective in curing S. mansoni infection when compared to placebo. In Africa, 15 mg/kg oxamniquine is less effective than 40 mg/kg praziquantel in people older than 14 years (OR 0.23, 95% CI 0.09 to 0.60), but no difference was shown using 30 mg/kg oxamniquine (OR 2.88, 95% CI 0.69 to 11.96). In Brazil, 15 to 19 mg/kg oxamniquine is as effective as 50 to 70 mg/kg praziquantel in people older than 14 years (OR 0.61, 95% CI 0.26 to 1.46). Both drugs appear safe. No difference in reinfection rate between zinc supplementation and placebo has been shown.

Authors' conclusions

Oxamniquine and praziquantel both appear to be effective for treatment of S. mansoni, although lower doses of oxamniquine (less than 30 mg/kg) may not be as effective in some areas.

Plain language summary

Interventions for treating schistosomiasis mansoni

Schistosoma mansoni is a parasite that infects the intestine, liver and spleen and can be fatal. People become infected when they come in contact with contaminated water. The review found that the drugs oxamniquine and praziquantel are both effective for curing the infection. Evidence from one trial shows that zinc supplements do not help to prevent re-infection. A small number of patients given oxamniquine have suffered seizures which could mean that this drug is less safe.

Background

People become infected with Schistosoma mansoni when they come in contact with water contaminated with the parasite that is carried by freshwater snails. The disease occurs in the tropics, including countries in South America, the Caribbean, Africa, and the eastern Mediterranean (WHO 1993). Infection usually occurs in recognised geographical areas, and sometimes 80% of inhabitants in a village may be infected (Elliott 1996).

The life cycle of S. mansoni is complicated. It has two hosts. A particular species of snail (Biomphalaria genus) release larvae (called cercariae) into surrounding fresh water. The larvae swim seeking a host, attracted by body heat in the water. Larvae can survive up to 48 hours in water, but their infectiousness drops after four hours of leaving the snail.

The oral sucker of the larvae attaches to human skin. Enzymes assist the parasite to migrate through the epidermis into the blood stream. From here, the worms migrate along the pulmonary capillaries to enter the left side of the heart. Schistosomula - the parasite with a protective shell - are carried with the arterial blood flow through the aorta to the mesenteric arteries, splanchnic capillaries and portal veins. As schistosomula mature in the blood vessels of the liver, they pair with the opposite sex. The female is carried by the male worm, migrating against the blood flow to the mesenteric veins where the female worms lay hundreds to thousands of eggs per day (Elliott 1996).

Schistosomiasis infects the intestine, liver, and spleen. It can cause bloody diarrhoea, bloody stools, and abdominal pain (Gryseels 1992; WHO 1993). Infection of the liver and spleen causes liver fibrosis and portal hypertension that are generally irreversible in the late stages and kill patients, sometimes as a result of haemorrhage from varices (WHO 1993). Liver failure may also occur, especially when S. mansoni infection is associated with viral hepatitis (Pereira 1994).

Diagnosis of infection is by direct microscopy for parasite eggs in the stool or rectal mucosa (Rabello 1992a; Rabello 1992b). Quantitative methods are recommended for epidemiological purposes because it is possible to estimate the worm burden and to evaluate the impact of control programmes (WHO 1985). Among the quantitative methods of stool examination, the Kato/Katz technique is preferable because it has the greatest capacity to concentrate eggs (Costa 1984), and the estimate of intensity of infection remains constant for periods of days and months (Rabello 1992a; Rabello 1992b).

Currently, doctors use either oxamniquine or praziquantel for treatment, both given by mouth, although food appears to retard absorption of oxamniquine and limits the concentration achieved in plasma (Tracy 1996). Lower doses of oxamniquine are given in South America, the Caribbean islands, and West Africa from where the New World parasites were introduced; a single dose of 15 mg/kg for adult patients and 20 mg/kg for children. In other countries of Africa and the Arabian Peninsula, higher doses are given, the total dose varying from 30 mg/kg to 60 mg/kg (Foster 1987). Differences in the susceptibility of parasites to the drug seem to account for the variation in dosage (Tracy 1996).

Development of drug-resistant parasites, poor drug absorption or malabsorption, and immunosuppressed host status all contribute toward the reduced efficacy of schistosomicidal drugs. Moreover, susceptibility to schistosomicides is related to the sex and age of the parasites. Adult male S. mansoni are more sensitive than are the female worms, and immature worms are more resistant to oxamniquine and praziquantel than adult worms (Brindley 1994).

As the morbidity of S. mansoni infection is associated with worm burden, chemotherapy plays an important role in the strategy of control and in the reduction and prevention of morbidity. Periodic treatment has been established as a central component of schistosomiasis control. Several useful approaches for community-based chemotherapy have been developed (WHO 1993). These include:

1. Mass treatment: treatment of the entire population without regard to individual infection status.

2. Selective population treatment: treatment of infected persons identified by a diagnostic survey of the entire population.

3. Selective group treatment: treatment of all, or infected members, of a high-risk age or occupational group.

4. Phased treatment: use of the above strategies in a sequence of progressively greater selectivity.

High prevalence areas may justify treatment of entire populations without further individual diagnosis. If there is some impact on infection, programmes can move to a selective approach (WHO 1993). However, programmes have not always had the impact that was expected. Environmental change is required to reduce exposure, and chemotherapeutic programmes are hampered by reinfection (WHO 1993).

As there was no systematic review evaluating the effectiveness of oxamniquine and praziquantel in the treatment of S. mansoni infection, we decided to review the effectiveness of these two drugs, and seek information on comparative effectiveness. We also analysed the role of zinc supplementation in the prevention of S. mansoni reinfection.

Objectives

1. To evaluate whether oxamniquine and praziquantel are effective for treating Schistosoma mansoni infection.

2. To compare the effectiveness of oxamniquine and praziquantel for treating S. mansoni infection.

3. To evaluate whether zinc supplementation is effective in preventing reinfection with S. mansoni.

Effectiveness was evaluated in terms of parasitic cure and clinical improvement, and tolerability by adverse effects.

Methods

Criteria for considering studies for this review

Types of studies

All randomised or pseudo-randomised (individual or group) controlled clinical trials of oxamniquine and/or praziquantel.

Randomised or pseudo-randomised controlled trials comparing zinc supplementation with placebo.

Types of participants

Any adults or children with Schistosoma mansoni diagnosed by positive stool examination for viable eggs.

Types of interventions

  • Oxamniquine or praziquantel versus placebo

  • Oxamniquine versus praziquantel

  • Zinc supplementation versus placebo

Types of outcome measures

Parasitic outcomes
  • Cure (primary outcome): absence of viable eggs of S. mansoni in the stool or biopsy of the rectal mucosa.

  • Reinfection: presence of viable eggs of S. mansoni in successfully treated individuals.

Clinical outcomes
  • Diarrhoea

  • Bloody diarrhoea

  • Abdominal pain

  • Spleen and liver size reductions measured by ultrasound or physical examination

Tolerability outcomes
Adverse clinical events
  • Neurological: headache, seizures, sleepiness, dizziness

  • Gastrointestinal: nausea, vomiting, diarrhoea, abdominal pain

  • Systemic side effects: skin rash, fever, myalgia (muscle pain), asthenia (weakness).

Adverse biochemical changes

The time interval from the start of drug use to the development of biochemical abnormalities was estimated in the assessment of drug toxicity. The laboratory tests analysed include:

  • Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase to evaluate hepatotoxicity. Only elevation twice the upper limit of normal was considered in the evaluation of possible drug-induced liver disease in the analysis.

  • Serum creatinine to evaluate nephrotoxicity.

Search methods for identification of studies

The trials register of the Cochrane Infectious Diseases Group was searched for trials (published or in progress) up to April 2003. The topic search terms used were: Schistosoma mansoni, schistosomiasis, bilharziasis, esquistossomose, schistosomicides, praziquantel, oxamniquine, and zinc supplementation.

The reviewers searched the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (Issue 3, 2005). This contains mainly reference information to randomized controlled trials and controlled clinical trials in health care.

The following databases were also searched: MEDLINE (1966 to September 2005); EMBASE (1980 to September 2005); and LILACS (September 2005), using the search terms in combination with the search strategy developed by the Cochrane Collaboration and detailed in the Cochrane Reviewers' Handbook (Clarke 2003). Specific search terms used: Schistosoma mansoni, schistosomiasis, bilharziasis, esquistossomose, schistosomicides, praziquantel, oxamniquine and zinc supplementation.

The bibliographic references of books and review articles relating to schistosomiasis and tropical diseases were searched in order to find randomised controlled trials not already identified by electronic searching.

In addition, the Revista da Sociedade Brasileira de Medicina Tropical and Brazilian Tropical Medicine Congress' abstracts were hand-searched.

Data collection and analysis

The main reviewer applied inclusion criteria to all potential studies. Independently, a second reviewer applied the same inclusion criteria. If there was disagreement a third person was asked for an opinion in order to reach consensus. Methodological quality was assessed by both reviewers using the standard approach of the Infectious Diseases Group (see module editorial information for details). Pre-specified trial characteristics were extracted from each included study by the first reviewer and checked by the second.

Studies were excluded if they reported more than 20% drop-out or were duplicate publications of a study already included.

Results

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification.

Thirteen randomised controlled trials met the inclusion criteria. Six studies were carried out in Brazil and seven in Africa. The follow-up period varied between one and 12 months. In six studies follow-up was longer than one month. These studies were analysed separately because, in this instance, the probability of underestimated results is greater since the rate of reinfection may be high.

Six studies examined only children younger than 15 years old. Two other studies included only individuals older than 14 years. Five studies evaluated both children and adults. Different dose schedules of oxamniquine and praziquantel were compared according to age. The schedules also varied according to geographic area, and the African studies used higher doses than the studies carried out in Brazil.

Stool examination, according to Kato or Kato/Katz methods, was the assessment method used in 10 studies. The number of stool samples varied between one and three, but the results of each sample were not always reported. In Cunha 1986, stool examination was performed according to the Hoffman, Pons & Janer, and Kato/Katz methods, and a rectal mucosa biopsy was also done.

Two trials compared oxamniquine with placebo (Ayele 1986; de Jonge 1991). Comparison between praziquantel and placebo was performed in three trials (de Jonge 1991; Jaoko 1996; Sukwa 1993); however, the Jaoko trial only evaluated side effects.

The trial by de Jonge 1991 was carried out in individuals with mixed Schistosoma mansoni and S. haematobium infections. This study evaluated the effects of oxamniquine and praziquantel (and metrifonate) by measuring the serum level of circulating anodic antigens and comparing cure rate based on stool examination.

Clinical improvement through physical examination was evaluated in only one trial (Sukwa 1993) in which school children were allocated to receive praziquantel or placebo. Physical examination was performed at the time of enrolment, then at six months and 12 months after the treatment. The cure rate, however, was not provided.

Friis 1997 evaluated the rate of reinfection with S. mansoni after zinc supplementation in children.

Risk of bias in included studies

The included studies did not provide clear descriptions of allocation concealment or randomisation methods.

Six studies used double-blind methods. In two trials the outcome measurement was blinded, but there was no indication if the patients were blinded. Double-blind method was not described in five trials.

The drop-out rate was variable. In most of the included studies, the loss to follow-up was more than 10%. Three trials were excluded from the efficacy analysis because the loss was more than 20% after three months of follow-up. These studies were included in the analysis of tolerance outcomes because these were recorded one to seven days after treatment when drop-out was minimal.

Effects of interventions

Any drug versus placebo

Two trials compared oxamniquine (60 mg/kg) with placebo (Ayele 1986; de Jonge 1991), showing the drug to be more effective for parasitological cure (61/93 versus 0/61; OR 17.68, 95% CI 9.02 to 34.64). The de Jonge trial included patients with mixed Schistosoma mansoni and S. haematobium infections.

One trial comparing praziquantel (40 mg/kg) with placebo reported on parasitic outcome (de Jonge 1991). As mentioned above, infections in this trial were mixed S. mansoni and S. haematobium. Cure of S. mansoni was higher with praziquantel than in the placebo group (31/48 v 0/21; OR 13.10, 95% CI 4.71 to 36.44). Only Sukwa 1993 was included in the analysis of clinical improvement. It was not possible to conclude whether praziquantel was more effective than placebo in the reduction of morbidity when the control cure was achieved after six months or 12 months.

Oxamniquine versus praziquantel

Parasitological cure after one month

Comparison between oxamniquine at a dose of 15 mg/kg and praziquantel at a dose of 40 mg/kg was reported in Taddese 1988. Praziquantel was given to one treatment group as a single dose and to another group as two doses of 20 mg/kg. Praziquantel showed a higher cure rate than oxamniquine, in single dose (OR 0.23, 95% CI 0.08 to 0.66) or split dose (OR 0.34, 95% CI 0.12 to 0.94) and overall (OR 0.23, 95% CI 0.09 to 0.60). When the dose of oxamniquine was increased to 30 mg/kg no difference was shown between oxamniquine and praziquantel in single dose (OR 2.80, 95% CI 0.38 to 20.52) or split dose (OR 4.07, 95% CI 0.79 to 21.04) or overall (OR 2.88, 95% CI 0.69 to 11.96).

One trial compared oxamniquine 20 mg/kg with praziquantel 40 mg/kg in an area where the cure rate with praziquantel is low (Stelma 1997). Parasitological cure was higher in the group using oxamniquine than in the praziquantel group and the difference was statistically significant (OR 4.22, 95% CI 2.16 to 8.23).

Only one trial compared oxamniquine 60 mg/kg with praziquantel 40 mg/kg in mixed S. mansoni and S. haematobium infections (de Jonge 1991). No statistically significant difference was shown (OR 0.54, 95% CI 0.24 to 1.17).

Parasitological cure, follow-up greater than two months

In adults (Taddese 1988), oxamniquine 15 mg/kg was less effective than praziquantel 40 mg/kg (overall OR 0.46, 95% CI 0.26 to 0.81; praziquantel single dose OR 0.58, 95% CI 0.31 to 1.07; praziquantel split dose OR 0.40, 95% CI 0.21 to 0.76). After three months or more, no difference was shown between oxamniquine 30 mg/kg and praziquantel 40 mg/kg single dose (OR 2.02, 95% CI 0.97 to 4.23) or split dose (OR 1.39, 95% CI 0.63 to 3.09) or overall (OR 1.65, 95%CI 0.87 to 3.14).

Higher dose praziquantel (50-70 mg/kg) did not result in a higher cure rate, at greater than two months follow-up in two studies, than oxamniquine 15-19 mg/kg, in individuals older than 14 years. Single dose praziquantel OR 0.61, 95% CI 0.26 to 1.46 (Cunha 1986; Fernandes 1986); split dose praziquantel OR 0.54, 95% CI 0.15 to 1.90 (Fernandes 1986).

No trials were found to allow us to explore differences between praziquantel and oxamniquine in children.

Tolerability

Adverse clinical events

There were several adverse clinical effects reported, but no deaths, after administration of oxamniquine or praziquantel. The most serious side effect reported was seizure, and this was observed in two patients using oxamniquine out of a total of 372 patients evaluated (Taddese 1988; Rezende 1985). Other neurological side effects were commonly reported with both drugs. No statistical difference was shown in incidence of headache, dizziness or sleepiness in individuals taking oxamniquine or praziquantel.

Diarrhoea and abdominal pain were less frequently reported as side effects in oxamniquine-treated patients: diarrhoea 38/544 (7%) patients compared to 74/536 (14%) praziquantel-treated patients (OR 0.48, 95% CI 0.32 to 0.71); abdominal pain 15/571 (20%) compared to 240/563 (42%) praziquantel-treated patients (OR 0.34, 95% CI 0.26 to 0.44). No difference in vomiting or nausea was shown.

Other systemic side effects, such as asthenia and skin rash, were less frequent and similar with the two treatments. Myalgia did occur with oxamniquine (7/352) but was not reported with praziquantel (0/327). Fever was reported with praziquantel treatment (4/267) but not with oxamniquine (0/272).

Only one trial (Jaoko 1996) compared side effects between praziquantel and placebo. Headache, dizziness, nausea, abdominal pain, and fever were reported more frequently in the group using praziquantel. Bloody diarrhoea was reported in one praziquantel patient, as was urticaria.

Adverse biochemical changes

No abnormality suggesting nephrotoxicity or hepatotoxicity was observed after administration of oxamniquine or praziquantel in terms of development of biochemical abnormalities reported in one study (Silva 1986). Both drugs appeared to be safe.

Zinc supplementation

Only one included trial (Friis 1997) compared zinc supplementation with placebo to prevent reinfection with S. mansoni. No statistical difference in the incidence of reinfection was shown in 261 patients (OR 0.82, 95% CI 0.47 to 1.41).

Discussion

The methodological quality of the included studies was poor. None clearly described concealment of allocation or randomisation procedures. Few studies were double blind and loss to follow-up was as high as 20%. Follow-up time of more than six weeks does not appear appropriate (Stelma 1997) because the probability of underestimation of treatment effect may occur as the reinfection rate could be high after this period.

An important question is the ideal dose for a patient's age, and whether different doses are required in different geographic areas. Lack of data precluded exploring these questions.

Compared with placebo, oxamniquine (60 mg/kg) has been shown in one study to be effective in curing Schistosoma mansoni infection (88% of evaluated patients cured versus 2% given placebo). The same dose of oxamniquine in one other study, and 40 mg/kg praziquantel, was also more effective than placebo in curing S. mansoni infection in patients with mixed S. mansoni and S. haematobium infections (49% cure rate with oxamniquine, 64% with praziquantel, versus 0% with placebo).

Comparing the two drugs, praziquantel at a dose of 40 mg/kg was more effective than oxamniquine at a dose of 15 mg/kg in individuals older than 14 years, but when the dose of oxamniquine was increased to 30 mg/kg or more no statistical difference has been shown between the two drugs.

Both praziquantel and oxamniquine appear to be similarly safe, except that two oxamniquine-treated patients had seizures which could suggest that oxamniquine might be less safe.

The available evidence from one trial (261 patients) suggests that zinc supplementation is not more effective than placebo in preventing reinfection with S. mansoni.

Authors' conclusions

Implications for practice

1. Oxamniquine and praziquantel are effective treatments for Schistosoma mansoni infection. No compelling evidence shows a difference between the two drugs. However, oxamniquine at a dose of 15 mg/kg is less effective than 40 mg/kg praziquantel.

2. In mixed Schistosoma mansoni and S. haematobium infections no difference has been shown between 60 mg/kg oxamniquine and 40 mg/kg praziquantel.

3. It is not possible to conclude whether oxamniquine or praziquantel has an effect on morbidity caused by infection.

4. Oxamniquine might be less safe than praziquantel based on two patients who had seizures.

5. There is no evidence from randomised trials that zinc supplementation is effective to prevent reinfection with S. mansoni.

Implications for research

1. A systematic review of observational studies, including case reports, is required to document potential toxicity and tolerability of the two drugs.

2. A good randomised trial is needed to examine clinical effectiveness in terms of morbidity outcomes.

3. Further work to explore varying effectiveness with geographic area may be useful.

Acknowledgements

We thank Iain Chalmers and Paul Garner for their support.

Data and analyses

Download statistical data

Comparison 1. Oxamniquine versus placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Parasitological cure2 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
1.1 Oxamniquine 60mg/kg2154Peto Odds Ratio (Peto, Fixed, 95% CI)17.68 [9.02, 34.64]
Analysis 1.1.

Comparison 1 Oxamniquine versus placebo, Outcome 1 Parasitological cure.

Comparison 2. Praziquantel versus placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Parasitological cure1 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
1.1 Praziquantel 40mg/kg versus placebo169Peto Odds Ratio (Peto, Fixed, 95% CI)13.10 [4.71, 36.44]
2 Clinical improvement after 6 months1 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
2.1 Diarrhoea1101Peto Odds Ratio (Peto, Fixed, 95% CI)1.15 [0.52, 2.52]
2.2 Bloody diarrhoea150Peto Odds Ratio (Peto, Fixed, 95% CI)0.80 [0.26, 2.52]
2.3 Abdominal pain00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.4 Hepatomegaly1168Peto Odds Ratio (Peto, Fixed, 95% CI)1.12 [0.61, 2.04]
2.5 Splenomegaly159Peto Odds Ratio (Peto, Fixed, 95% CI)0.85 [0.30, 2.43]
3 Clinical improvement after 12 months1 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
3.1 Diarrhoea1101Peto Odds Ratio (Peto, Fixed, 95% CI)0.70 [0.25, 1.99]
3.2 Bloody diarrhoea150Peto Odds Ratio (Peto, Fixed, 95% CI)0.92 [0.06, 15.20]
3.3 Hepatomegaly1168Peto Odds Ratio (Peto, Fixed, 95% CI)1.07 [0.57, 2.04]
3.4 Splenomegaly159Peto Odds Ratio (Peto, Fixed, 95% CI)2.27 [0.80, 6.41]
4 Clinical side effects1 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
4.1 Headache1436Peto Odds Ratio (Peto, Fixed, 95% CI)4.43 [2.77, 7.10]
4.2 Dizziness1436Peto Odds Ratio (Peto, Fixed, 95% CI)2.03 [0.94, 4.39]
4.3 Nausea1436Peto Odds Ratio (Peto, Fixed, 95% CI)3.11 [1.55, 6.26]
4.4 Bloody diarrhoea1436Peto Odds Ratio (Peto, Fixed, 95% CI)3.91 [0.05, 329.60]
4.5 Abdominal pain1436Peto Odds Ratio (Peto, Fixed, 95% CI)2.68 [1.68, 4.26]
4.6 Fever1436Peto Odds Ratio (Peto, Fixed, 95% CI)2.38 [1.00, 5.66]
4.7 Urticaria1436Peto Odds Ratio (Peto, Fixed, 95% CI)3.91 [0.05, 329.60]
Analysis 2.1.

Comparison 2 Praziquantel versus placebo, Outcome 1 Parasitological cure.

Analysis 2.2.

Comparison 2 Praziquantel versus placebo, Outcome 2 Clinical improvement after 6 months.

Analysis 2.3.

Comparison 2 Praziquantel versus placebo, Outcome 3 Clinical improvement after 12 months.

Analysis 2.4.

Comparison 2 Praziquantel versus placebo, Outcome 4 Clinical side effects.

Comparison 3. Oxamniquine versus Praziquantel
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Parasitological cure after 1 month3 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
1.1 Oxamniquine 15mg/kg versus Praziquantel 40mg/kg1100Peto Odds Ratio (Peto, Fixed, 95% CI)0.23 [0.08, 0.66]
1.2 Oxamniquine 15mg/kg vs Praziquantel 2 x 20mg/kg1100Peto Odds Ratio (Peto, Fixed, 95% CI)0.34 [0.12, 0.94]
1.3 Oxamniquine 20mg/kg vs Praziquantel 40mg/kg1138Peto Odds Ratio (Peto, Fixed, 95% CI)4.22 [2.16, 8.23]
1.4 Oxamniquine 30mg/kg vs Praziquantel 40mg/kg1100Peto Odds Ratio (Peto, Fixed, 95% CI)2.80 [0.38, 20.52]
1.5 Oxamniquine 30mg/kg vs Praziquantel 2 x 20mg/kg1100Peto Odds Ratio (Peto, Fixed, 95% CI)4.07 [0.79, 21.04]
1.6 Oxamniquine 60mg/kg vs Praziquantel 40mg/kg1101Peto Odds Ratio (Peto, Fixed, 95% CI)0.54 [0.24, 1.17]
2 Parasitological cure, follow-up >2 months3 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
2.1 Oxamniquine 15mg/kg versus Praziquantel 40mg/kg1200Peto Odds Ratio (Peto, Fixed, 95% CI)0.58 [0.31, 1.07]
2.2 Oxamniquine 15mg/kg vs Praziquantel 2 x 20mg/kg1200Peto Odds Ratio (Peto, Fixed, 95% CI)0.40 [0.21, 0.76]
2.3 Oxamniquine 15-19 mg/kg vs Praziquantel 50-70mg/kg2134Peto Odds Ratio (Peto, Fixed, 95% CI)0.61 [0.26, 1.46]
2.4 Oxamniquine 15-19mg/kg vs Praziquantel 50-70mg/kg (two doses)180Peto Odds Ratio (Peto, Fixed, 95% CI)0.54 [0.15, 1.90]
3 Parasitological cure, follow-up 3 months or more1 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
3.1 Oxamniquine 30mg/kg vs Praziquantel 40mg/kg1200Peto Odds Ratio (Peto, Fixed, 95% CI)2.02 [0.97, 4.23]
3.2 Oxamniquine 30mg/kg vs Praziquantel 2 x 20mg/kg1200Peto Odds Ratio (Peto, Fixed, 95% CI)1.39 [0.63, 3.09]
4 Clinical side effects7 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
4.1 Any side effect4829Peto Odds Ratio (Peto, Fixed, 95% CI)0.92 [0.67, 1.26]
4.2 Neurological: Seizures2739Peto Odds Ratio (Peto, Fixed, 95% CI)7.32 [0.46, 117.06]
4.3 Neurological: Headache71254Peto Odds Ratio (Peto, Fixed, 95% CI)1.26 [0.88, 1.82]
4.4 Neurological: Dizziness71254Peto Odds Ratio (Peto, Fixed, 95% CI)1.23 [0.97, 1.56]
4.5 Neurological: Sleepiness5953Peto Odds Ratio (Peto, Fixed, 95% CI)0.96 [0.67, 1.40]
4.6 Gastro-intestinal: Nausea5953Peto Odds Ratio (Peto, Fixed, 95% CI)0.94 [0.63, 1.41]
4.7 Gastro-intestinal: Vomiting51080Peto Odds Ratio (Peto, Fixed, 95% CI)1.08 [0.67, 1.76]
4.8 Gastro-intestinal: Diarrhoea51080Peto Odds Ratio (Peto, Fixed, 95% CI)0.48 [0.32, 0.71]
4.9 Gastro-intestinal: Abdominal pain61134Peto Odds Ratio (Peto, Fixed, 95% CI)0.34 [0.26, 0.44]
4.10 Other systemic: Myalgia2659Peto Odds Ratio (Peto, Fixed, 95% CI)7.47 [1.68, 33.11]
4.11 Other systemic: Asthenia3779Peto Odds Ratio (Peto, Fixed, 95% CI)0.89 [0.47, 1.67]
4.12 Other systemic: Fever1539Peto Odds Ratio (Peto, Fixed, 95% CI)0.13 [0.02, 0.94]
4.13 Other systemic: Skin rash3713Peto Odds Ratio (Peto, Fixed, 95% CI)0.36 [0.05, 2.59]
5 Biochemical side effects1 Mean Difference (IV, Fixed, 95% CI)Subtotals only
5.1 Hepatotoxicity: ALT1120Mean Difference (IV, Fixed, 95% CI)-3.83 [-8.21, 0.55]
5.2 Hepatotoxicity: AST1120Mean Difference (IV, Fixed, 95% CI)-0.48 [-2.29, 1.33]
5.3 Hepatotoxicity: Gamma-glutamyl transpeptidase1120Mean Difference (IV, Fixed, 95% CI)-3.02 [-13.22, 7.18]
Analysis 3.1.

Comparison 3 Oxamniquine versus Praziquantel, Outcome 1 Parasitological cure after 1 month.

Analysis 3.2.

Comparison 3 Oxamniquine versus Praziquantel, Outcome 2 Parasitological cure, follow-up >2 months.

Analysis 3.3.

Comparison 3 Oxamniquine versus Praziquantel, Outcome 3 Parasitological cure, follow-up 3 months or more.

Analysis 3.4.

Comparison 3 Oxamniquine versus Praziquantel, Outcome 4 Clinical side effects.

Analysis 3.5.

Comparison 3 Oxamniquine versus Praziquantel, Outcome 5 Biochemical side effects.

Comparison 4. Zinc supplementation versus placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Reinfection rate1 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
Analysis 4.1.

Comparison 4 Zinc supplementation versus placebo, Outcome 1 Reinfection rate.

What's new

DateEventDescription
24 September 2008AmendedConverted to new review format.

History

Protocol first published: Issue 4, 1997
Review first published: Issue 1, 1998

DateEventDescription
5 September 2005New search has been performedNew studies sought but none found.
11 May 2000AmendedEdited text, including abstract, and added a 'Plain language summary' (previously called 'Synopsis').
26 May 1999AmendedModified title, added two trials (Jaoko 1996; Friis 1997), and excluded some studies.

Declarations of interest

We certify that we have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of the review (e.g. employment, consultancy, stock ownership, honoraria, expert testimony).

Sources of support

Internal sources

  • Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil.

  • Federal University of Rio Grande do Norte, Brazil.

External sources

  • Department for International Development, UK.

  • European Commission (Directorate General XII), Belgium.

  • International Clinical Epidemiology Network, USA.

  • Liverpool School of Tropical Medicine, UK.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ayele 1986

Methods

Random allocation, but the method of randomisation not clearly described

Blinded outcome measurement (stool examination), but blinding patients is not described

Participantsn=162 patients children below 15 years of age
Interventions1. Oxamniquine 15 mg/kg twice daily for two days (total 60 mg/kg)
2. Oxamniquine 20 mg/kg twice daily for one day (total 40 mg/kg)
3. Oxamniquine 15 mg/kg twice daily for one day (total 30 mg/kg)
4. Placebo
OutcomesStool examinations according Kato to evaluate parasitic cure or improvement after 4 months of the treatment
NotesSetting: Ethiopia

Branchini 1982

Methods

Random allocation, but method of randomisation unspecified

Double blind

Participantsn=101 patients, age varied from 10 to 65 years, mean age 29.7 years
Interventions1. Oxamniquine an average dose of 13.8 mg/kg
2. Praziquantel an average dose of 45.4 mg/kg
Outcomes

Stool examinations according Kato/Katz to evaluate parasitic cure or improvement after 4 months of the treatment

Clinical and biochemical tolerance

Notes

Setting: Brazil

Follow-up: 6 months

Drop-out in the end of the study higher than 20%

Not included in the efficacy analysis

Cunha 1986

Methods

Random allocation, but method of randomisation unspecified

Double blind

Participantsn=54 patients between 15 and 55 years of age. Intestinal and hepatointestinal forms were present in 54% and 46 % of the individuals, respectively
Interventions1. Oxamniquine an average dose of 18 mg/kg
2. Praziquantel an average dose of 65 mg/kg
Outcomes

Stool examinations according Kato/Katz and spontaneous sedimentation methods;

Rectal mucosa biopsy

Tolerance: clinical

Notes

Setting: Brazil

Parasitological control at the end of 1, 2, 4 and 6 months, but they present analysis of the 6th month

Drop-out 14.81%

de Jonge 1991

Methods

Random allocation, but the method of randomisation not clearly described

Double blind method not described

Participantsn=160 children with mixed Schistosoma haematobium and Schistosoma mansoni infections
InterventionsThe patients were divided in four groups:
1. Metrifonate 20 mg/kg: 38 patients
2. Oxamniquine 60 mg/kg single dose: 53 patients
3. Praziquantel 40 mg/kg single dose: 48 patients
4. Placebo: 21 patients
Outcomes

Stool examinations using Kato method

Urine examination

Blood samples to determine circulating anodic antigen

Notes

Setting: Sudan

Follow-up: 1 and 5 months after treatment

Drop-out: 14.4% after 1 month, and 18.8% after 5 months

Fernandes 1986

Methods

Random allocation, but the method of randomisation not clearly described

Double blind method not described

Participantsn=120 patients with egg counts in the range 112-1296 eggs/g of S. mansoni in the stool
Interventions1. Oxamniquine: 15 mg/kg single dose
2. Praziquantel: 70 mg/kg in a single dose
3. Praziquantel: 35 mg/kg twice daily
Outcomes

Stool examinations according Kato/Katz

Clinical improvement

Notes

Setting: Brazil

Parasitological control after 2, 4 and 6 months

Friis 1997

Methods

Random allocation by "simple randomization"

Details of the allocation concealment is not described

Double blind

Participantsn=313 children with Schistosoma mansoni and/or Schistoma haematobium infections
Interventions

Supplementation with zinc sulphate (30 or 50 mg according to weight of children)

Placebo with identical-looking of zinc sulphate tablets

OutcomesSchistoma mansoni and Schistosoma haematobium reinfections
Notes

Setting: Zimbabwe

Parasitological examination was done 6 weeks and 3, 6, and 12 months after treatment

Compliance rate was 47% among children in whom reinfections could be assessed

Drop-out rate: 17%

Jaoko 1996

MethodsRandom allocation but allocation concealment is not described. Double blind is not mentioned
Participantsn=320 children with Schistosoma mansoni infection
Interventions1. Praziquantel: 40 mg/kg
2. Placebo
OutcomesPrevalence of side effects
NotesSetting: Kenya

Katz 1982

Methods

Random allocation, but method of randomisation unspecified

Double blind

Participantsn=120 children with active Schistosoma mansoni living in two endemic areas
Interventions

Oxamniquine 20 mg/kg single dose

Praziquantel 65 mg/kg single dose

Outcomes

Three consecutive daily stool examinations according Kato/Katz method

Clinial and laboratorial tolerance

Notes

Setting: Brazil

Follow-up: 6 months

Drop-out rate higher than 20%

Not included in the efficacy analysis

Rezende 1985

Methods

Random allocation, but randomisation method is not described.

Double blind

Participantsn=539 adults and children, no previous anti-schistosomiasis treatment
Interventions1. Oxamniquine an average dose of 16 mg/kg
2. Praziquantel an average dose of 55 mg/kg
Outcomes

Three consecutive daily stool examinations according to Kato/Katz method

Clinical and biochemical side effects

Notes

Setting: Brazil

Follow-up of six months

Silva 1986

Methods

Random allocation, but the method of randomisation not clearly described

Double blind method

Participantsn= 120 patients selected by three pre-treatment egg counts according to Kato/Katz method. Only intestinal and hepatointestinal forms were included
Interventions1. Oxamniquine 15 mg/kg single dose
2. Praziquantel 55 mg/kg single dose
Outcomes

Stool examinations according Kato/Katz method

Rectal mucosa biopsy with negative stool examination in the 6th month

Side effects

Notes

Setting: Brazil

Follow-up: 10 months

Drop-out: 21.7%

Not included in the efficacy analysis

Stelma 1997

Methods

Random allocation, but allocation concealment is not descibed

Double blind method is not described

Participants

n=138 patients

The participants were prestratified by age, intensity of infection, and history of previous praziquantel treatment

Interventions1. Praziquantel 40 mg/kg
2. Oxamniquine 20 mg/kg
OutcomesParasitological cure after 6 weeks according stool examinations by Kato method
Notes

Setting: Senegal

The study were performed in a area where cure rate with praziquantel is low

Follow-up: 6 weeks

Drop-out: no mention

Sukwa 1993

Methods

Random allocation, but the method of randomisation not clearly described

Blinded outcome measurement (physical examination), but blinding patients is not described

Participants

n=377 children

All eligible children received a initial dose of 40 mg/kg of praziquantel. After initial treatment, 190 children were retreated with praziquantel at six month follow-up, irrespective of Schistosoma mansoni infection status; and 187 children received placebo at the same time

Interventions1. Praziquantel 40 mg/kg
2. Placebo
OutcomesPhysical examination to evaluate clinical improvement
Notes

Setting: Zambia

Follow-up: 12 months

Drop-out less than 10%

Taddese 1988

Methods

Random allocation, but the method of randomisation not clearly described

Double blind method not described

Participantsn=200 individuals with a geometric mean egg excretion rate of at least 50 eggs/g of faeces aged from 17-52 years
Interventions1. Oxamniquine 15 mg/kg single dose
2. Oxamniquine 30 mg/kg twice
3. Praziquantel 40 mg/kg single dose
4. Praziquantel 40 mg/kg twice
Outcomes

Stool examinations according Kato/Katz were performed 1, 3 and 6 months after treatment

Spleen and liver size

Notes

Setting: Ethiopia

Drop-out: 9%

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Abu-Ely-Azeed 1993The study is a randomised double-blind controlled trial evaluating the effectiveness and safety of 1% niclosamide skin lotion in the prevention of the penetration of Schistosoma mansoni cercariae.
Barakat 1995This is not a randomised controlled trial. The study design is a cross-sectional.
Bella 1982The study compares different dosages of oltipraz. There was no description of randomisation method.
Coutinho 1983Randomised study comparing two different dosages of praziquantel, however, there was no comparison between praziquantel and oxamniquine or placebo.
Coutinho 1984Randomised study comparing two different dosages of praziquantel, however, there was no comparison between praziquantel and oxamniquine or placebo.
Creasey 1986This is a randomised controlled trial, but the comparison was between a combination of oxamniquine plus praziquantel with placebo.
Cunha 1982Compares different doses of oxamniquine, however, there was no comparison between oxamniquine and praziquantel or placebo, and the authors did not describe the allocation method, and there was no description whether random method had been used.
Cunha 1987Randomised study comparing two different dosages of praziquantel, however, there was no comparison between praziquantel and oxamniquine or placebo.
Cury 1986The study is not a randomised controlled trial comparing oxamniquine with placebo, and the drop-out rate was 61.6%.
De Clerq 1997This is not randomised controlled trial.
El Tayeb 1988This is a randomised controlled trial, but the comparison was between praziquantel and oltipraz, and there was no comparison between praziquantel and oxamniquine or placebo.
Emanuel 1983aRandomised study comparing different doses of praziquantel, however, there was no comparison between praziquantel and oxamniquine or placebo.
Emanuel 1983bThe study is not a randomised controlled trial.
Gryseels 1989Three villages were evaluated. Residents of two villages received different regimens of oxamniquine and residents of the other received two different regimens of praziquantel, and the study compared the prevalence and morbidity in each village. They did not compare praziquantel with oxamniquine in each village.
Guiniady 1994Does not meet inclusion criteria. This study evaluated the pharmacokinetics of praziquantel and did not compare praziquantel with placebo or oxamniquine. There was no description of random allocation method.
Guisse 1997Randomised study comparing two different dosages of praziquantel, however, there was no comparison between praziquantel and oxamniquine or placebo.
Guyatt 1998This is a decision analysis. The study analyses the interaction between drug efficacy and drug price of different brands of praziquantel in determining the cost-effectiveness of treatment of schistosomiasis mansoni. This is not a randomised controlled trial.
Igail 1985The study is a randomised controlled trial comparing different doses of oltipraz in the treatment of Schistosoma mansoni infection. Praziquantel or oxamniquine were not evaluated.
Kardman 1983Randomised study comparing two different regimens of praziquantel, a single dose of 40 mg/kg body-weight, and a divided dose 2 x 20 mg/kg body-weight. However, there was no comparison between praziquantel and oxamniquine or placebo.
Kardman 1985Randomised study comparing two different regimens of praziquantel, a single dose of 40 mg/kg body-weight, and a divided dose 2 x 20 mg/kg body-weight. However, there was no comparison between praziquantel and oxamniquine or placebo.
Katz 1979The study compares different doses of praziquantel, however, there was no comparison between praziquantel and oxamniquine or placebo. Furthermore, the authors did not describe the allocation method, and there was no description whether a random method had been used.
Katz 1983The study compares praziquantel with oxamniquine, but the authors did not describe the allocation method, and there was no description whether a random method had been used.
Katz 1991The study compare praziquantel with oxamniquine, but the authors did not describe the allocation method, and there was no description whether a random method had been used.
Kilpatrick 1982This is a randomised controlled trial, but the comparison was between oxamniquine and niridazole; there was no comparison between oxamniquine and praziquantel or placebo.
Lapierre 1983This study do not appear to be a randomised controlled trial, and there was no description of how the treatment was allocated.
Lieshout 1994The study compares praziquantel 60 mg/kg of body weight (Group 1) with praziquantel 40mg/kg of body weight (Group 2), but the authors did not describe if the patients were randomly allocated.
McMahon 1981Randomised study comparing different doses of praziquantel, however, there was no comparison between praziquantel and oxamniquine or placebo.
Mohamed-Ali 1991Randomised study comparing different doses of praziquantel, however, there was no comparison between praziquantel and oxamniquine or placebo.
Nozais 1979Randomised study comparing two different doses of oxamniquine, however, there was no comparison between praziquantel and praziquantel or placebo.
Nozais 1980The study evaluated oxamniquine in dose of 15-20 mg/kg, however, there was no comparison between praziquantel or placebo. It is a descriptive study. There was no description of randomisation method.
Odongo-Aginya 1996This is not randomised controlled trial. All of the people infected with Schistosoma mansoni were treated with praziquantel 40 mg/kg of body weight.
Omer 1981Randomised study comparing different doses of praziquantel, however, there was no comparison between praziquantel and oxamniquine or placebo.
Pedroso 1987The study compared oxamniquine with placebo in pulmonary Schistosoma mansoni. However, the authors did not describe the allocation method, and there was no description whether random method had been used.
Picquet 1998This is not a randomised controlled trial.
Polderman 1988This study did not appear to be a randomised controlled trial, and there was no description of how the treatment was allocated.
Prata 1982Randomised study comparing three different doses of praziquantel. However, there was no comparison between praziquantel and oxamniquine or placebo.
Rahim 1988Randomised study comparing three different doses of oxamniquine, however, there was no comparison between oxamniquine and praziquantel or placebo.
Rees 1975This is a randomised controlled trial, but the comparison was between oxamniquine and hycanthone; there was no comparison between oxamniquine and praziquantel or placebo.
Rouquayrol 1976This is a randomised controlled trial, but the comparison was between oxamniquine and hycanthone; there was no comparison between oxamniquine and praziquantel or placebo.
Rugemalila 1984Drop-out rate higher than 20%, and the study did not evaluated cure rate.
Saladin 1983This study is not a randomised controlled trial.
Santos 1986Randomised controlled trial comparing oxamniquine with placebo, but the drop-out rate was higher than 20%.
Schwerdtfeger 1992Randomised study comparing two different doses of praziquantel, however, there was no comparison between praziquantel and oxamniquine or placebo.
Shafei 1979This study is not randomised controlled trial.
Strickland 1982The authors wrote that two subjects were randomly chosen in each group of six to receive placebo or oxamniquine, but they did not clearly state the allocation method, nor was it possible to determine whether the study was randomised.
Taylor 1988Randomised study comparing four different doses of praziquantel, however, there was no comparison between praziquantel and oxamniquine or placebo. One group did not receive praziquantel, but the author did not say if this group received placebo or not.
Teesdale 1984Drop-out rate higher than 20 per cent.
Zwingenberger 1987This study is a randomised controlled trial, but the comparison was between a low-dose combination of oxamniquine plus praziquantel against oxamniquine or praziquantel alone, and the drop-out rate was more than 20%.

Characteristics of studies awaiting assessment [ordered by study ID]

Butterworth 1991

Methods
Participants
Interventions
Outcomes
Notes

Lambertucci 1982

Methods
Participants
Interventions
Outcomes
Notes

Ancillary