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Drugs for treating Schistosoma mansoni infection

  1. Anthony Danso-Appiah1,*,
  2. Piero L Olliaro2,
  3. Sarah Donegan1,
  4. David Sinclair1,
  5. Jürg Utzinger3,4

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 16 OCT 2012

DOI: 10.1002/14651858.CD000528.pub2

How to Cite

Danso-Appiah A, Olliaro PL, Donegan S, Sinclair D, Utzinger J. Drugs for treating Schistosoma mansoni infection. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD000528. DOI: 10.1002/14651858.CD000528.pub2.

Author Information

  1. 1

    Liverpool School of Tropical Medicine, International Health Group, Liverpool, UK

  2. 2

    World Health Organization, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), Geneva, Switzerland

  3. 3

    Swiss Tropical and Public Health Institute, Department of Epidemiology and Public Health, Basel, Switzerland

  4. 4

    University of Basel, Basel, Switzerland

*Anthony Danso-Appiah, International Health Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. tdappiah@yahoo.co.uk.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 28 FEB 2013

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Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

 
Summary of findings for the main comparison. Praziquantel 40 mg/kg for treating S. mansoni infection

Praziquantel 40 mg/kg for treating S. mansoni infection

Patient or population: People with S. mansoni infection
Settings: Endemic settings
Intervention: Praziquantel 40 mg/kg

OutcomesComparisonIllustrative comparative risks1 (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)

Assumed riskCorresponding risk

Praziquantel 40 mg/kgComparator

Parasitological failure

at 1 month
versus placebo22 per 10069 per 100
(23 to 100)
RR 3.13
(1.03 to 9.53)
414
(2 trials)
⊕⊕⊕⊝
moderate2,3,4

versus 20 mg/kg22 per 10050 per 100
(34 to 72)
RR 2.23
(1.64 to 3.02)
341
(2 trials)
⊕⊕⊝⊝
low4,5

versus 30 mg/kg22 per 10033 per 100
(25 to 44)
RR 1.52
(1.15 to 2.01)
521
(3 trials)
⊕⊕⊝⊝
low4,5

versus 60 mg/kg22 per 10021 per 100
(16 to 28)
RR 0.97
(0.73 to 1.29)
783
(4 trials)
⊕⊕⊕⊝
moderate6,7

versus split dose22 per 10010 per 100
(3 to 37)
RR 0.47
(0.13 to 1.69)
525
(2 trials)
⊕⊕⊝⊝
low4,8

*The basis for the assumed risk is given in the footnotes.

The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio.

GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Treatment failure with praziquantel 40 mg/kg ranged from 5% to 48% in the included studies. The risk given here is the median risk in these studies and is given for illustrative purposes.
2 No serious risk of bias. Both studies adequately concealed allocation and blinded participants and investigators. Loss to follow-up was high in one study.
3 No serious inconsistency: Both trials showed statistically significant benefits with praziquantel but the size of the effect varied. In Kenya in 1999 failure with praziquantel was 43% at one month and in Uganda in 2009 it was 18%.
4 Downgraded by 1 for indirectness: Only two trials from limited settings have evaluated this comparison.
5 Downgraded by 1 for risk of bias: These trials are more than twenty years old and do not provide an adequate description of methods to reduce the risk of bias.
6 No serious risk of bias: The three trials by Olliaro in 2010 adequately concealed allocation and blinded participants and investigators to be considered at low risk of bias.
7 Downgraded by 1 for indirectness: The trials so far do not indicate a benefit with higher doses than 40 mg/kg. However, we cannot be certain that there might not be some benefit in specific settings.
8 Downgraded by 1 for inconsistency: One trial found a significant benefit with splitting the dose and one did not. The trials were of similar size and power.

 Summary of findings 2 Oxamniquine 40 mg/kg for treating S. mansoni infection

 Summary of findings 3 Oxamniquine 40 mg/kg versus praziquantel 40 mg/kg

 Summary of findings 4 Artesunate (12 mg/kg) plus praziquantel (40 mg/kg) versus praziquantel (40 mg/kg) alone

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
 

Description of the condition

Schistosomiasis is a parasitic blood fluke infection, of which three species commonly infect humans; Schistosoma mansoni (common in the tropics and sub-tropics), S. haematobium (mostly endemic in Africa and the Middle East) and S. japonicum (endemic in the People's Republic of China and the Philippines) (Engels 2002; WHO 2002; Gryseels 2006; Steinmann 2006; Utzinger 2009). It has been estimated that 779 million people are at risk of schistosomiasis worldwide and 207 million people may be infected (Steinmann 2006). Of these, 120 million people are estimated to be symptomatic and 20 million suffer from long-term complications (Chitsulo 2000; WHO 2002; van der Werf 2003). In global burden of disease estimates, schistosomiasis causes 1.7 to 4.5 million disability-adjusted life years (DALYs) (WHO 2002; WHO 2004; Hotez 2006; Steinmann 2006; Utzinger 2009). Some suggest that this value may underestimate the true burden of schistosomiasis (WHO 2002; van der Werf 2003; King 2005; King 2007; King 2008a; King 2010).

People infected with S. mansoni excrete the fluke eggs in their faeces, and faecal contamination of freshwater allows these eggs to hatch into larvae (miracidia) which penetrate a specific freshwater snail (the intermediate host). Within the snail, the miracidia develop into cercariae (the infective larvae), which can penetrate a person’s skin upon contact with contaminated water bodies.

Following infection, the worms migrate through the human venous system, via the right chamber of the heart and the lungs, and through the mesenteric arteries and the liver via the portal vein, before finally settling in the superior mesenteric veins which drain the large intestine. Here, male and female worms mature, pair up and the female worms start to produce eggs (≂ 300 per day) (Davis 2009). An adult worm usually lives for three to five years, but some can live up to 30 years (Gryseels 2006). The eggs produced by the worms traverse the intestinal wall to be excreted in the faeces, and in the process some become trapped and initiate inflammatory reactions, which cause the underlying pathology and symptomatic illness (Richter 2003a; King 2008b). Early symptoms depend on the severity of infection (Gryseels 1987), and if treatment is not provided early, chronic illness and long-term serious disease can follow.

 

Symptoms and effects

Schistosomiasis mansoni can present as an acute or chronic illness. The acute illness, or Katayama syndrome, is caused by migrating and maturing schistosomula that may result in a systemic hypersensitivity reaction characterized by fever, feeling of general discomfort (malaise), muscle pain (myalgia), fatigue, non-productive cough, diarrhoea (with or without blood), and pain in the upper right part of the abdomen just below the rib cage. Chronic and advanced disease results from the host's immune response to schistosome eggs deposited in tissues and the granulomatous reaction evoked by the antigens they secrete and is characterized by non-specific intestinal symptoms, such as abdominal pain, diarrhoea and blood in the stool (Gryseels 1992; Gray 2011; Gryseels 2012).

Inflammatory reactions in the liver lead to hepatosplenic schistosomiasis, a key feature of chronic infection, which can manifest within a couple of months for heavy infections or many years after light infections. The chronic inflammation produces fibrotic lesions, which in turn lead to liver cirrhosis that progressively occludes the portal system giving rise to portal hypertension. The portal hypertension eventually leads to enlargement of hepatic arteries, and the associated oesophageal varices may rupture with heavy blood loss, haemorrhagic shock and death. The patient may also suffer repeated episodes of variceal bleeding – the primary cause of death in hepatic schistosomiasis (Andersson 2007). Severity of disease depends upon the intensity and duration of infection (Naus 2003), but recent evidence suggests the presence of the infection alone determines morbidity (King 2008a).

S. mansoni infection overlaps in distribution with S. haematobium in some areas of sub-Saharan Africa resulting in mixed infections (WHO 2002). Unlike S. mansoni, the main early symptoms of S. haematobium infection are blood in urine (haematuria) and painful urination (dysuria). Chronic and advanced disease is insidious and may result in structural damage to the bladder wall which may eventually lead to kidney failure.

 

Diagnosis

Definitive diagnosis of S. mansoni infection is by microscopy for parasite eggs in the stool. Quantitative methods are recommended for epidemiological purposes because they allow estimation of intensity and evaluation of the impact of control programmes not only in terms of cure rate but also egg reduction rate (WHO 1985; Doenhoff 2004; Bergquist 2009). The Kato-Katz technique (Katz 1972) is the most common quantitative technique (Booth 2003). Recently, the FLOTAC technique has been applied for the detection and quantification of S. mansoni eggs in stools with promising results and hence warranting further investigation (Glinz 2010).

Egg output can be influenced by several factors, such as day-to-day, intra-stool, and seasonal variations as well as environmental conditions (Braun-Munzinger 1992; Engels 1996; Engels 1997; Enk 2008). Therefore negative results following microscopic examination of a single stool are unreliable (de Vlas 1992; Kongs 2001; Booth 2003; Enk 2008), and measurement of prevalence and intensity of infection by egg count has shortcomings (Gryseels 1996; de Vlas 1997; Utzinger 2001a). Rectal biopsy is more sensitive than microscopy and is occasionally done when repeated stool examinations are negative for eggs. However, this method is unsuitable for use in population-based control programmes (Allan 2001).

A monoclonal antibody-based dipstick is increasingly being used for the diagnosis of the infection with promising results (Polman 2001; Legesse 2007; Legesse 2008; Caulibaly 2011). A more specific and sensitive diagnostic technique based on polymerase chain reaction (PCR) is increasingly being used in some reference laboratories in Europe (Sandoval 2006; Cnops 2012; Enk 2012). Ultrasound is used for diagnosing and assessing infection-related pathology (Hatz 1990; Mohamed-Ali 1991; Doehring-Schwerdtfeger 1992; Hatz 2001; Richter 2003b).

Clinically, intestinal schistosomiasis is diagnosed on the basis of presence of blood in stool, (bloody) diarrhoea, and abdominal pain, but these are non-sensitive and non-specific (Gryseels 1992; Utzinger 2000c; Danso-Appiah 2004) as diarrhoea or blood in stool can be due to other causes such as hookworm infection, dysentery and typhoid fever.

 

Description of the intervention

Schistosomiasis control measures implemented before the 1970s – when efficacious antischistosomal drugs were not available – focused mainly on interrupting transmission with molluscicides to kill the intermediate host snails (WHO 1985; Sturrock 2001). The 1970s marked the turning point in schistosomiasis control when efficacious drugs that can be applied in a single oral dose were discovered, shifting the control emphasis from transmission control to chemotherapy-based morbidity control (WHO 1985; Cioli 1995). A body of evidence suggests that morbidity due to schistosomiasis can be prevented and pathology reversed with available antischistosomal treatments (Mohamed-Ali 1991; Doehring-Schwerdtfeger 1992; Savioli 2004; Zhang 2007; Webster 2009; Koukounari 2010).

Mass drug administration, or treatment of infected individuals or entire 'at-risk' populations (eg school-aged children), usually without prior diagnosis - an approach termed 'preventive chemotherapy', is the control strategy currently pursued by the World Health Organization (WHO) and applied in many endemic countries (WHO 2006). Usually, praziquantel at a single 40 mg/kg oral dose is used (Fenwick 2009), but still there are uncertainties regarding this dose. An exception is Brazil where the national policy adopted since 1995 recommends a single oral dose of 60 mg/kg for children aged between two and 15 years, and 50 mg/kg for adolescents and adults (Favre 2009). The recently adopted policy for schistosomiasis control in Brazil disapproves of treatment without prior diagnosis, and therefore the preventive chemotherapy strategy is no longer applied in Brazil (Favre 2009).

Oxamniquine has also been used extensively for the control of schistosomiasis mansoni in different endemic countries, most notably Brazil, where more than 12 million doses of oxamniquine have been administered by the national schistosomiasis control programme (Katz 2008). There are uncertainties around the standard dose of oxamniquine (Foster 1987; Cioli 1995). Therefore, the WHO recommends total doses of 20 to 60 mg/kg (in divided doses of up to 20 mg/kg) (WHO 2001).

More recently, the artemisinin derivatives used in the treatment of malaria have been shown to have antischistosomal properties, particularly against the immature developing stages of the schistosome parasites (Borrmann 2001; Utzinger 2007). Praziquantel, in contrast, acts against the adult worms and the very young schistosomula just after skin penetration (Sabah 1986; Utzinger 2007).

The current emphasis of schistosomiasis control is to reduce the burden of disease in high endemicity areas and to interrupt transmission in low endemicity areas (WHO 2002). Intensity of infection is highest in school-aged children and adolescents, therefore preventive chemotherapy is targeted especially to these at-risk groups (Magnussen 2001; WHO 2002; Savioli 2004; Savioli 2009).

The efficacy of myrrh (Mirazid) in the treatment of intestinal schistosomiasis has been evaluated in Egypt (Barakat 2005 EGY; Botros 2005 EGY).

 

Why it is important to do this review

Currently, entire control and treatment programmes are based on praziquantel and there is risk of drug resistance and perhaps shortages of praziquantel. There is a need to assess alternative drugs or combinations. Still there are uncertainties around effective and safe dosage of praziquantel and standard doses of oxamniquine. There are also uncertainties about adequacy of current adult doses used in children.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

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

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomized controlled trials.

 

Types of participants

Individuals infected with S. mansoni diagnosed microscopically for the presence of S. mansoni eggs in stool using the Kato-Katz technique (Katz 1972), or any other quantitative diagnostic method, such as the quantitative oogram and FLOTAC techniques.

 

Types of interventions

The following comparisons are evaluated in this review:

  1. Antischistosomal drugs alone or in combination versus placebo;
  2. Antischistosomal drugs alone or in combination versus a different dose of the same antischistosomal drug; and
  3. Antischistosomal drugs alone or in combination versus different antischistosomal drugs alone or in combination.

Trials that allocated non-schistosomal drug or interventions in addition to the treatment and control of interest were eligible provided the same drug was allocated to both treatment and control groups.

 

Types of outcome measures

 

Primary outcomes

  • Parasitological failure, defined as treated individuals who remained positive for S. mansoni eggs in stool using the standard Kato-Katz or other quantitative techniques (follow-up: up to one month).
  • Egg reduction rate, defined as percent reduction in S. mansoni egg count after treatment (follow-up: up to 12 months).

 

Secondary outcomes

  • Parasitological failure (follow-up: greater than one month).
  • Resolution of symptoms (eg abdominal pain, diarrhoea and bloody diarrhoea).
  • Resolution of pathology (eg hepatomegaly, splenomegaly, portal fibrosis, cirrhosis of the liver or colonic polyps) measured by ultrasound, by standard international classification or other standardized methods (CWG 1992).

 

Adverse events

  • Non-serious adverse events.
  • Serious adverse events (ie any untoward medical occurrence or effect that at any dose: results in death; is life-threatening; requires hospitalisation or prolongation of existing inpatients' hospitalisation; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect).

 

Search methods for identification of studies

We attempted to identify all relevant trials regardless of language or publication status (published, unpublished, in press, under review and in progress).

 

Electronic searches

 

Databases

We searched the following databases using the search terms and strategy described in  Table 1: Cochrane Infectious Diseases Group Specialized Register (October 2012); Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (1966 to October 2012); EMBASE (1974 to October 2012); and LILACS (1982 to October 2012). We also searched the metaRegister of Controlled Trials (mRCT) in October 2012 using ’Schisto * mansoni' as the search term.

 

Searching other resources

 

Researchers and organizations

We contacted individual researchers working on antischistosomal drugs, pharmaceutical industries and experts from the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) for unpublished data and ongoing trials.

 

Reference lists

We checked the reference lists of all studies identified by the aforementioned methods for additional relevant studies.

 

Data collection and analysis

 

Selection of studies

Vittoria Lutje, the Cochrane Infectious Diseases Group (CIDG) Information Retrieval Specialist, searched the literature and retrieved studies using the search strategy outlined in  Table 1. Anthony Danso-Appiah (ADA) screened the results to identify potentially relevant trials, obtained the full trial reports and assessed the eligibility of trials for inclusion in the review using an eligibility form based on the inclusion criteria. Jürg Utzinger (JU) independently verified the eligibility assessment results.

ADA contacted the authors of potentially relevant trials for clarification if eligibility was unclear. We excluded studies that did not meet our inclusion criteria and we have detailed the reasons for exclusion in the Characteristics of excluded studies. This was verified independently by JU and Piero L. Olliaro (PLO). We resolved any discrepancies through discussion between the authors.

 

Data extraction and management

ADA extracted trial characteristics such as methods, participants, interventions and outcomes, and recorded on standard forms, which were independently verified by JU. ADA and JU resolved discrepancies through discussion, and where necessary contacted a third author (PLO). ADA contacted trial authors for clarification, or insufficient or missing data when necessary.

We extracted the number of participants randomized and the number of patients followed-up in each treatment arm. For dichotomous outcomes, we recorded the number of participants experiencing the event in each treatment group of the trial. For continuous outcomes summarized as geometric means, we extracted means and their standard deviations (SD) on the log scale. If the data were summarized as arithmetic mean, we extracted the means and their SDs. We extracted medians or ranges when they were reported to summarize the data.

For each outcome, we extracted data for each follow-up time reported in the trial report.

 

Assessment of risk of bias in included studies

ADA assessed the risk of bias of each trial using The Cochrane Collaboration's risk of bias tool (Higgins 2011) and the assessment results were verified independently by Dave Sinclair (DS). Where information in the trial report was unclear, we attempted to contact the trial authors for clarification. We assessed the risk of bias for six domains: sequence generation, allocation concealment, blinding (investigators, outcome assessors and participants), incomplete outcome data, selective outcome reporting and other sources of bias. For each domain, we made a judgment of 'low risk' of bias, 'high risk' of bias or 'unclear'. We resolved any discrepancies by discussion between the authors.

 

Measures of treatment effect

We presented dichotomous outcomes using risk ratios (RR). Mean differences (MD) were used as the measure of effect for continuous outcomes that were summarized as arithmetic means. We used geometric mean ratios for continuous outcomes that were summarized as geometric means. We presented all results with 95% confidence intervals (CI).

 

Dealing with missing data

We analysed data based on the number of patients for whom an outcome was recorded (complete case analysis).

 

Assessment of heterogeneity

We assessed heterogeneity by inspecting the forest plots for overlapping CIs and outlying data; using the Chi2 test with a P value < 0.1 to indicate statistically significant heterogeneity; and using the I2 statistic.

 

Assessment of reporting biases

We would have attempted to explore publication bias using funnel plots if there were sufficient number of trials in the comparisons.

 

Data synthesis

We used Review Manager (RevMan) to perform the statistical analyses. We stratified the analyses by: comparison; the dose of the drug; and the length of follow-up time. We used meta-analysis to combine the results across trials. When heterogeneity was detected, we used a random-effects meta-analysis approach; otherwise a fixed-effect approach was adopted. We tabulated adverse events and also data that could not be meta-analysed.

 

Subgroup analysis and investigation of heterogeneity

When heterogeneity was detected, we planned to carry out subgroup analyses to explore potential causes. Subgroupings would be as follows: patient age (children versus adults); and intensity of infection (< 500 eggs per gram of stool versus > 500 eggs per gram of stool).

We conducted a subsidiary, non-randomized comparison of failure rates in children with failure rates in adults for the same drug and same dose (mg/kg) to explore issues around dose applicability in children.

 

Sensitivity analysis

Where data were sufficient we planned to conduct sensitivity analyses to assess the robustness of the results to the risk of bias components.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
 

Description of studies

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

We identified 52 trials (10,269 participants) which met the inclusion criteria (see Characteristics of included studies). We managed one multicentre trial carried out in Brazil, Mauritania and Tanzania as three separate trials in the analysis (Olliaro 2011 BRA; Olliaro 2011 MRT; Olliaro 2011 TZA), and three papers contained multiple individual studies which we again managed separately (de Clarke 1976a ZWE; de Clarke 1976b ZWE; de Clarke 1976c ZWE; de Clarke 1976d ZWE; Katz 1979a BRA; Katz 1979b BRA; Gryseels 1989a BDI; Gryseels 1989b BDI; Gryseels 1989c BDI).

Of the 52 trials we identified, 19 evaluated praziquantel, 17 evaluated oxamniquine and 12 directly compared praziquantel with oxamniquine. In addition, two compared myrrh (mirazid) with praziquantel, and two compared different brands of praziquantel.

Three trials assessed combination therapies: including praziquantel plus oxamniquine (Creasey 1986 ZWE; Zwingenberger 1987 BRA) and praziquantel plus artesunate (De Clercq 2000 SEN).

For the two primary outcomes, 47 trials reported cure rate or failure rate, 34 trials reported egg reduction rate and 33 trials reported both outcomes. Only Sukwa 1993 ZMB reported reinfection rate.

For secondary outcomes, five trials (Rugemalila 1984 TZA; Gryseels 1989a BDI; Gryseels 1989b BDI; Gryseels 1989c BDI; Sukwa 1993 ZMB) reported clinical improvement or functional indices, but we could not include Rugemalila 1984 TZA and Sukwa 1993 ZMB in the meta-analysis because of insufficient information. Thirty-three trials reported adverse events.

In the study by de Jonge 1990 SDN, we excluded the two arms that received metrifonate and placebo respectively from the analysis. Also, we excluded one arm of the study by Ibrahim 1980 SDN involving participants who did not have S. mansoni infection and also one arm each of the trials by Rugemalila 1984 TZA and Taylor 1988 ZWE that did not receive treatment from the analysis.

The trial by Tweyongyere 2009 UGA assessing the effects of praziquantel was a nested cohort study within a larger mother and baby cohort study in which pregnant women found to be infected with S. mansoni were randomized to receive praziquantel or placebo. We obtained data on parasitological failure rate and clinical improvement from figures (Gryseels 1989a BDI; Gryseels 1989b BDI; Gryseels 1989c BDI), but it was not possible to extract egg count data.

 

Trial setting and participants

The trials were conducted in Africa (n = 36), South America (n = 15; all in Brazil) and the Middle East (n = 1). Eight trials were conducted in the late 1970s, 28 in the 1980s, seven in the 1990s and only nine since the year 2000.

Eighteen trials involved children, 12 trials recruited adults, and 22 recruited whole populations comprising children, adolescents and adults.

Seventeen trials recruited participants from the outpatient clinics, six did not specify the setting whilst one trial (Omer 1981 SDN) consisted of both participants identified in a field survey and those attending the hospital; two trials (Katz 1979a BRA; Katz 1979b BRA) involved military officers in a Barracks who became exposed to the infection during training and another trial (Ibrahim 1980 SDN) recruited university students on campus. The remaining 25 trials recruited participants through community surveys.

 

Risk of bias in included studies

For risk of bias of included studies see the Characteristics of included studies and summary of the risk of bias graph (Figure 1) and risk of bias summary (Figure 2).

 FigureFigure 1. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
 FigureFigure 2. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

 

Allocation

We considered 16 trials as low risk of bias with regard to the generation of the randomization sequence (Figure 2). In the remaining 36 trials, the methods used to generate the sequence of allocation were not described and therefore the risk of bias is unclear.

Fourteen trials adequately described allocation concealment and had a low risk of bias. One trial did not conceal allocation (Fernandes 1986 BRA); and the methods were unclear in the remaining 37 trials (Figure 2).

 

Blinding

Twenty-seven trials employed blinding and stated who was blinded. However, none described the methods of blinding. Nevertheless, the studies were considered to be at low risk of bias. One trial did not employ blinding (Fernandes 1986 BRA) and we therefore classed it at high risk of bias; whereas in 25 trials blinding was unclear (Figure 2).

 

Incomplete outcome data

We considered the risk of bias for incomplete outcome data to be low in 17 trials (Figure 2). We deemed the risk of bias to be high in 19 trials, and in the remaining 16 trials as unclear.

 

Selective reporting

All 52 trials had low risk of selective outcome reporting (Figure 2).

 

Other potential sources of bias

Overall, 42 trials were considered to be free from other biases and the level of bias was unclear in the remaining 10 trials (Figure 2).

 

Effects of interventions

See:  Summary of findings for the main comparison Praziquantel 40 mg/kg for treating S. mansoni infection;  Summary of findings 2 Oxamniquine 40 mg/kg for treating S. mansoni infection;  Summary of findings 3 Oxamniquine 40 mg/kg versus praziquantel 40 mg/kg;  Summary of findings 4 Artesunate (12 mg/kg) plus praziquantel (40 mg/kg) versus praziquantel (40 mg/kg) alone

 

Section 1. Monotherapies

 

Praziquantel

Nineteen trials, conducted in Africa, Brazil and the Arabian Penunsula, evaluated praziquantel. Four studies compared praziquantel with placebo, and 17 trials directly compared different dosing schedules of praziquantel with the standard dose of 40 mg/kg.

 

Analysis 1: Praziquantel versus placebo

 
Parasitological failure

Two trials from Kenya and Uganda used the WHO recommended dose of 40 mg/kg. Praziquantel 40 mg/kg achieved parasitological cure in 57% and 82% of the patients respectively, compared to placebo where almost all continued to excrete eggs at one to two months (RR 3.13, 95% CI 1.03 to 9.53, two trials, 414 participants,  Analysis 1.1).

In addition, one small trial from Brazil compared three different doses of praziquantel with placebo and presented outcomes at six and 12 months. All patients given 40 mg/kg and 60 mg/kg praziquantel achieved parasitological cure at six months, while two out of five patients given 20 mg/kg and almost all those given placebo continued to excrete eggs (one trial, 40 participants,  Analysis 1.2). At 12 months, reinfection was demonstrable in some of those given praziquantel ( Analysis 1.3). One further trial from Brazil gave 60 mg/kg praziquantel each day for three days and achieved 100% parasitological cure at six months compared to almost complete failure with placebo (one trial, 55 participants,  Analysis 1.2).

 
Egg reduction

None of these trials reported on percentage egg reduction.

 
Adverse events

No serious adverse events were recorded in these trials but transient dizziness and abdominal pain appeared to be more commonly reported with praziquantel than placebo (seven trials, 1255 participants,  Table 2).

 

Analyses 2 and 3: Lower doses praziquantel versus 40 mg/kg

 
Parasitological failure

Lower doses (20 mg/kg to 30 mg/kg) have been evaluated in Zimbabwe, Burundi, Sudan and Brazil. Compared to 40 mg/kg, parasitological failure at one month was more than double with the 20 mg/kg dose, and 50% higher with the 30 mg/kg dose (20 mg/kg: RR 2.23, 95% CI 1.64 to 3.02, two trials, 341 participants; 30 mg/kg: RR 1.52, 95% CI 1.15 to 2.01, three trials, 521 participants;  Analysis 2.1). Follow-up at three months ( Analysis 2.2) and at six to 12 months showed a similar pattern ( Analysis 2.3).

 
Egg reduction

In one trial from Brazil evaluating 30 mg/kg versus 40 mg/kg, geometric mean egg reductions were high in both groups, at six months (92.5% versus 97.7%, statistical significance not reported (one trial, 138 participants,  Analysis 2.4)).

 
Symptom resolution

One trial compared a lower dose of praziquantel at 20 mg/kg with 40 mg/kg and showed no difference in resolving symptoms at three, six, 12 and 24 months of follow-up: diarrhoea (one trial, 44 participants,  Analysis 3.3), blood in stool (one trial, 37 participants,  Analysis 3.5), hepatomegaly (one trial, 55 participants,  Analysis 3.7) and splenomegaly (one trial, 73 participants,  Analysis 3.9), except one study that showed that 40 mg/kg significantly improved abdominal pain at one month (RR 0.59, 95% CI 0.36 to 0.98, one trial, 169 participants,  Analysis 3.1).

Two trials compared 30 mg/kg with 40 mg/kg and did not show any difference in resolving symptoms at one, three, six, 12 and 24 months of follow-up: abdominal pain (two trials, 318 participants,  Analysis 3.2), diarrhoea (two trials, 48 participants,  Analysis 3.4), blood in stool (two trials, 82 participants,  Analysis 3.6), hepatomegaly (two trials, 109 participants,  Analysis 3.8) and splenomegaly (two trials, 122 participants,  Analysis 3.10).

 
Adverse events

In the three trials reporting adverse events, consistent differences in frequency or severity between 20, 30 and 40 mg/kg doses have not been shown (three trials, 319 participants,  Table 3).

 

Analysis 4: Higher doses praziquantel versus 40 mg/kg

 
Parasitological failure

Higher doses (50 mg/kg to 60 mg/kg) have been evaluated in Brazil (three trials), Mauritania, Senegal and Tanzania. Compared to 40 mg/kg, parasitological failure has not been shown to be improved with higher doses at one month (five trials, 783 participants,  Analysis 4.1).

 
Egg reduction

Among participants still excreting eggs, percentage egg reductions were similar in both groups at one month (four trials, 786 participants,  Analysis 4.4).

 
Adverse events

One multi-country trial reported adverse events and recorded one serious event (a seizure) with the higher dose. At the trial site in Brazil, non-severe adverse events appeared to be more common with the higher dose but this was not seen consistently at the trial sites in Mauritania or Tanzania (one trial, 653 participants, see  Table 4).

 

Analysis 5: Split dose praziquantel versus 40 mg/kg in a single dose

Splitting 40 mg/kg into divided doses given on the same day was evaluated in the 1980s in three trials in Sudan.

 
Parasitological failure

At one month, two trials did not demonstrate a statistically significant benefit with the split dose regimen compared to a single 40 mg/kg dose (two trials, 525 participants,  Analysis 5.1), but showed benefit at three months (RR 0.31, 95% CI 0.18 to 0.53, two trials, 516 participants,  Analysis 5.2).

One further small trial, only reported the outcome at six months and found no difference (one trial, 64 participants,  Analysis 5.3).

 
Egg reduction

In the only trial reporting egg count, the mean percent reduction at one month was higher with the divided dose but statistical significance was not reported (divided dose 93.2% versus single dose 86.5%, one trial, 350 participants,  Analysis 5.4).

 
Adverse events

No serious adverse events were reported in these trials. Only one trial reported the frequency of adverse events in each treatment group (Kardaman 1983 SDN). Mild abdominal pain and diarrhoea were less common when the dose was given in divided doses but vomiting was more common (one trial, 350 participants,  Table 5).

 

Analysis 6: Other praziquantel dosing regimens

Several trials from Brazil have evaluated higher praziquantel dosing regimens with 30 mg/kg to 60 mg/kg given for up to six days (see  Analysis 6.1). It is difficult to draw conclusions from these studies as the comparator dose is also a non-standard regimen, but one trial did demonstrate improved parasitological cure rates with prolonged courses given over three to six days compared to courses lasting one day.

 
Adverse events

No serious adverse events were reported in these trials, events were mainly transient dizziness and nausea (one trial, 79 participants,  Table 6).

 

Oxamniquine

Seventeen trials evaluated oxamniquine, with the most recent conducted in the 1980s. Oxamniquine has since fallen out of use in favour of praziquantel. Four trials compared oxamniquine with placebo and 12 trials directly compared different dosing schedules of oxamniquine in different geographical locations in Africa and Brazil. The most common comparator dose was 40 mg/kg.

 

Analysis 7: Oxamniquine versus placebo

 
Parasitological failure

In two trials in Brazil, 20 mg/kg was significantly superior to placebo at longer timepoints (RR 3.68, 95% CI 2.53 to 5.36, two trials, 146 participants,  Analysis 7.2). In two trials from Ethiopia, oxamniquine achieved parasitological cure rates of > 75% with 30, 40, and 60 mg/kg at three to four months, compared to placebo where almost all participants continued to excrete eggs (30 mg/kg: RR 4.34, 95% CI 2.47 to 7.65, two trials, 82 participants; 40 mg/kg: RR 8.74, 95% CI 3.74 to 20.43, two trials, 82 participants; 60 mg/kg: RR 19.38, 95% CI 5.79 to 64.79, two trials, 89 participants;  Analysis 7.1).

 
Egg reduction

Among those still excreting eggs at three to four months, two trials from Ethiopia reported significant reductions in egg numbers in those given oxamniquine (68.1% to 100%), compared to increases of 59 to 80.6% in the placebo groups (two trials, 227 participants,  Analysis 7.3).

 
Adverse events

No serious adverse events were reported in these trials. Dizziness was more commonly reported with oxamniquine than placebo but is described as transient, with most resolving within 24 hours (five trials, 425 participants,  Table 7).

 

Analyses 8 and 9: Lower doses oxamniquine versus 40 mg/kg

Lower doses of oxamniquine (20 to 30 mg/kg) have been compared to 40 mg/kg in Ethiopia (two trials), Sudan (two trials), Zimbabwe (two trials), Burundi and Malawi.

 
Parasitological failure

Compared to 40 mg/kg, both 20 mg/kg and 30 mg/kg of oxamniquine resulted in significantly more parasitological failures at one month (20 mg/kg: RR 3.78, 95% CI 2.05 to 6.99, two trials, 190 participants; 30 mg/kg: RR 1.78, 95% CI 1.15 to 2.75, four trials, 268 participants,  Analysis 8.1), and at three to four months (20 mg/kg: RR 2.28, 95% CI 1.40 to 3.71, three trials, 209 participants; 30 mg/kg: RR 1.64, 95% CI 1.10 to 2.43, seven trials, 373 participants,  Analysis 8.2).

At later time points, no statistically significant differences were shown: six months (20 mg/kg: two trials, 163 participants; 30 mg/kg: three trials, 214 participants,  Analysis 8.3) and 12 months (20 mg/kg: two trials, 144 participants; 30 mg/kg: one trial, 77 participants,  Analysis 8.4).

 
Egg reduction

Percent egg reduction was evaluated in six of these trials and both lower dose and 40 mg/kg showed a wide range of benefit at one, three and six months: lower dose (57.1% to 99%) and 40 mg/kg (42.7 to 100%) (six trials, 878 participants,  Analysis 8.5).

 
Symptom resolution

One trial compared a lower dose of 20 mg/kg oxamniquine with 40 mg/kg and did not find any difference between the two doses in resolving symptoms at one, three, six, 12 and 24 months of follow-up: abdominal pain (one trial, 95 participants,  Analysis 9.1), diarrhoea (one trial, 16 participants,  Analysis 9.3), blood in stool (one trial, 85 participants,  Analysis 9.5), hepatomegaly (one trial, 64 participants,  Analysis 9.7) and splenomegaly (one trial, 69 participants,  Analysis 9.9).

Also, 30 mg/kg did not show any difference statistically compared with 40 mg/kg in resolving symptoms at one, three, six, 12 and 24 months of follow-up: abdominal pain (one trial, 95 participants,  Analysis 9.2), diarrhoea (one trial, 15 participants,  Analysis 9.4), blood in stool (one trial, 41 participants,  Analysis 9.6), hepatomegaly (one trial, 51 participants,  Analysis 9.8) and splenomegaly (one trial, 54 participants,  Analysis 9.10).

 
Adverse events

Six trials from Ethiopia (two trials), and one trial each from Malawi, Sudan, Zambia and Zimbabwe assessed adverse events and reported no serious events. Dizziness was most commonly reported, but the event rate and severity did not differ between doses (six trials, 508 participants,  Table 8).

 

Analysis 10: Higher doses oxamniquine versus 40 mg/kg

Higher doses of oxamniquine (50 mg/kg to 60 mg/kg) have been compared to 40 mg/kg in six trials from three countries; Sudan (three trials), Ethiopia (two trials) and Zambia (one trial).

 
Parasitological failure

Higher doses of oxamniquine have not shown consistent statistically significant benefits over 40 mg/kg at one month (five trials, 349 participants,  Analysis 10.1), at three to four months (six trials, 397 participants,  Analysis 10.2), or six months (two trials, 177 participants,  Analysis 10.3).

Losses to follow-up were high in the trial investigating 50 mg/kg, reaching 76.9% at three months, and heterogeneity between the trials was significant (I2= 64% to 82%).

 
Egg reduction

Seven trials evaluated egg count and reported a wide range of percent mean reductions among those not cured at one month (86% to 100% versus 56% to 99.1%, four trials, 561 participants,  Analysis 10.4), three to four months (82% to 100% versus 42% to 100%, six trials, 791 participants,  Analysis 10.4) and six months (62.% to 100% versus 75% to 100%, four trials, 561 participants,  Analysis 10.4).

 
Adverse events

In five trials reporting adverse events, no serious events were recorded. Dizziness and nausea were most commonly reported, but these were transient and did not require additional interventions (one trial, 482 participants,  Table 9).

 

Analyses 11 and 12: Other oxamniquine dosing regimes

Nine additional trials compared 30 mg/kg oxamniquine with higher and lower doses in Ethiopia (three trials), Zimbabwe (two trials), Burundi (one trial), Nigeria (one trial), Sudan (one trial) and Zambia (one trial).

 
Lower doses versus 30 mg/kg

Compared to 30 mg/kg, parasitological failure was higher with 15 mg/kg to 20 mg/kg oxamniquine at one month (RR 1.77, 95% CI 1.14 to 2.74, two trials, 230 participants), and at three to four months (RR 2.16, 95% CI 1.40 to 3.32, four trials, 249 participants,  Analysis 11.1).

At later follow-up times, no statistically significant difference were demonstrated (six months: two trials, 179 participants; and 12 months: one trial, 95 participants,  Analysis 11.1).

 
Higher doses versus 30 mg/kg

Compared to 30 mg/kg, 60 mg/kg oxamniquine resulted in significantly fewer parasitological failures at one month (RR 0.04, 95% CI 0.01 to 0.26, two trials, 175 participants,  Analysis 12.1), at three to four months (RR 0.17, 95% CI 0.07 to 0.39, four trials, 265 participants,  Analysis 12.2) and at six months (RR 0.17, 95% CI 0.06 to 0.50, two trials, 157 participants,  Analysis 12.3).

No statistically significant differences were seen between 50 mg/kg and 30 mg/kg at one month (one trial, 36 participants,  Analysis 12.1) or at three to four months (two trials, 53 participants,  Analysis 12.2).

 

Analysis 13: Praziquantel (40 mg/kg) versus oxamniquine

Eleven trials from different geographical locations directly compared various doses of oxamniquine with praziquantel 40 mg/kg. Dosing schedules commonly applied across different locations are reported in  Table 10. The most recent trial, from Sudan, was published in 1990.

 
Parasitological failure

We did not identify statistically significant differences between oxamniquine (at doses from 10 mg/kg to 60 mg/kg) and praziquantel 40 mg/kg at one month (see  Analysis 13.1). No difference was demonstrable at three months between 25 to 30 mg/kg (three trials, 319 participants), 40 mg/kg (one trial, 18 participants) or 50 to 60 mg/kg (one trial, 14 participants,  Analysis 13.2). However, 10 to 20 mg/kg of oxamniquine did result in significantly more failures (RR 3.42, 95% CI 1.10 to 10.61, two trials, 135 participants,  Analysis 13.2).

In addition, there were no differences between oxamniquine (lower or higher dose) and praziquantel (40 mg/kg) at six months (nine trials, 1167 participants,  Analysis 13.3) or 12 months (one trial, 52 participants,  Analysis 13.4).

 
Egg reduction

Three trials from Brazil, Ethiopia and Malawi compared oxamniquine 15, 20, 30, 40, and 50 mg/kg with praziquantel 40 mg/kg and measured high percent egg reduction at one month (82.9% to 100% for oxamniquine versus 90% to 92.8% for praziquantel, two trials, 391 participants), three months (70.2% to 99.5% for oxamniquine versus 70% to 100% for praziquantel, three trials, 440 participants), six months (32.5% to 97% for oxamniquine versus 33.6% to 96.8% for praziquantel, three trials, 291 participants), and 12 months (94% for oxamniquine versus 96% for praziquantel, one trial, 91 participants,  Analysis 13.5).

 
Adverse events

In five trials reporting from Brazil, Ethiopia, Malawi, Saudi Arabia and Tanzania that assessed adverse events, only two serious adverse events were recorded (both with oxamniquine) in two trials: one from a moderate endemicity setting in Ethiopia that used 30 mg/kg in a split dose given the same day; and one trial from Saudi Arabia that used a single dose of 25 mg/kg. No further differences were observed in the number and type of adverse events between oxamniquine and praziquantel although dizziness was recorded in excess with oxamniquine and abdominal pain with praziquantel ( Table 11).

 

Analysis 14: Myrrh (Mirazid) versus praziquantel

 
Parasitological failure

Myrhh (Mirazid) was tested in two trials at a single daily dose of 300 mg for three days, and almost all failed treatment at three to six weeks (RR 4.08, 95% CI 2.87 to 5.78, 236 participants,  Analysis 14.1). Consequently, further investigation of this compound was abandoned.

 
Egg reduction rate

There were only small reductions in reported percent geometric mean egg reduction in these two studies, but they were not clinically important ( Analysis 14.2).

 
Adverse events

No trial reports adverse events.

 

Section 2. Combination therapies

 

Analysis 15: Praziquantel plus artesunate versus praziquantel alone

One trial conducted from 1999 to 2000 in a high endemicity setting in Senegal evaluated artesunate plus praziquantel versus praziquantel alone.

 
Parasitological failure

In this setting, parasitological failure at one month occurred in 50% of participants given praziquantel 40 mg/kg alone. The addition of artesunate 12 mg/kg given in a divided dose of 2.5 mg/kg daily for five days resulted in a lower failure rate at one month but this did not reach statistical significance (one trial, 75 participants,  Analysis 15.1). At three and six months no additional benefit with artesunate plus praziquantel was seen.

 
Egg reduction

Geometric mean egg reductions appear lower with combination treatment but tests of statistical significance were not reported, and the clinical relevance of this finding are unclear (one trial, 75 participants,  Analysis 15.4).

 
Adverse events

Adverse events were not reported.

 

Analysis 16: Praziquantel plus oxamniquine versus praziquantel alone

Only one trial in a high endemicity setting in Brazil published in 1987 has evaluated oxamniquine plus praziquantel versus praziquantel alone.

 
Parasitological failure

Compared to praziquantel alone (40 mg/kg in two divided doses on one day), a combination of oxamniquine (7.5 mg/kg) plus praziquantel (20 mg/kg) did not demonstrate any statistically significant benefits at three, six or 12 months follow-up (one trial, 52 participants,  Analysis 16.1).

 
Egg reduction

The combination treatment was associated with lower geometric mean egg reductions at three, six and 12 months but tests of statistical significance were not reported (one trial, 52 participants,  Analysis 16.4).

 
Adverse events

These were not reported.

 

Analysis 17: Praziquantel (8 mg/kg) plus oxamniquine (4 mg/kg) versus praziquantel (20 mg/kg) plus oxamniquine (10 mg/kg)

One small trial of schoolchildren from a high endemicity setting co-endemic for S. mansoni and S. haematobium in Zimbabwe investigated different oxamniquine and praziquantel dose combinations.

 
Parasitological failure

Children aged seven to 16 years and excreting more than 100 eggs per gram of stool were included in this trial. Statistically fewer failures were seen with the higher dose-combination at one month (RR 6.30, 95% CI 1.60 to 24.75, one trial, 28 participants,  Analysis 17.1), but not at three months (one trial, 29 participants,  Analysis 17.2) or six months (one trial, 20 participants,  Analysis 17.3).

 
Egg reduction

The percentage egg reduction also appeared to be lower in those receiving the higher dose combination but tests of statistical significance were not reported (one trial, 59 participants,  Analysis 17.4).

 
Adverse events

No serious adverse events were recorded and the incidence of non-severe events did not differ between combinations. About 70% of children reported abdominal discomfort but these were transient and had resolved by the following day ( Table 12).

 

Analysis 18: Praziquantel (15 mg/kg) plus oxamniquine (7.5 mg/kg) versus praziquantel (20 mg/kg) plus oxamniquine (10 mg/kg)

One trial in Zimbabwe investigated slightly higher oxamniquine and praziquantel dose combinations. The included children had to excrete more than 100 eggs per gram of stool.

 
Parasitological failure

A statistically significant difference was not demonstrated at one, three and six months (one trial, 48 participants,  Analysis 18.1,  Analysis 18.2,  Analysis 18.3).

 
Egg reduction rate

Percent egg reductions were high at one, three and six months (82% to 96.1% versus 66.3% to 96.6%, one trial, 59 participants,  Analysis 18.4).

 
Adverse events

No serious adverse events were recorded apart from one child who reported dizziness immediately after treatment but required no further treatment ( Table 12).

 

Section 3. Do failure rates vary in children and adults?

 

Praziquantel

A subgroup analysis conducted in two studies from Burundi raised concern that parasitological failure following 40 mg/kg may be higher in children than in adults. The frequency of parasitological treatment failure was consistently higher in children than adults at one, three, six, and 12 months, and this was also observed for doses of 20 mg/kg and 30 mg/kg (see  Table 13).

 

Oxamniquine

Similarly, a subgroup analysis of two studies from Burundi and Sudan administering oxamniquine has shown a consistent pattern of higher parasitological treatment failure in children than adults at one to 12 months (see  Table 14).

Subgroup analysis of treatment arms receiving 40 mg/kg in the other included studies was not possible given the available data.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
 

Summary of main results

Compared to placebo, praziquantel 40 mg/kg substantially reduced parasitological treatment failure at one month post-treatment (moderate quality evidence). Compared to this standard dose, lower doses of 20 mg/kg and 30 mg/kg were inferior (low quality evidence); and higher doses, up to 60 mg/kg, have not shown any advantage (moderate quality evidence).

Compared to placebo, oxamniquine 40 mg/kg substantially reduced parasitological treatment failure at three months (moderate quality evidence). Lower doses than 40 mg/kg were inferior at one month (low quality evidence), and higher doses such as 60 mg/kg have not shown a consistent benefit (low quality evidence).

Ten trials compared oxamniquine at 20, 30 and 60 mg/kg with praziquantel 40 mg/kg and did not show any convincing differences in failure rate and percent egg reduction. Only one small study directly compared praziquantel 40 mg/kg with oxamniquine 40 mg/kg and did not demonstrate a statistically significant difference in parasitological failure (very low quality evidence).

Combining praziquantel with artesunate has not been shown to have benefits in terms of failure rate compared to praziquantel alone at one month, three or six months (one trial, 75 participants, very low quality evidence). Two trials have also compared combinations of praziquantel and oxamniquine in different doses but did not find statistically significant differences in failure rate.

Compared to 40 mg/kg, no dose effect was demonstrable for clinical improvement with lower doses (20 and 30 mg/kg) of praziquantel or oxamniquine in resolving abdominal pain, diarrhoea, blood in stool, hepatomegaly, and splenomegaly at one, three, six, and 12 months, or up to two years of follow-up. Adverse events were not well reported but were mostly described as minor and transient.

 

Overall completeness and applicability of evidence

For praziquantel, the evidence presented is generally supportive of the current WHO recommended dose of 40 mg/kg to treat S. mansoni infection (WHO 2002). Parasitological cure as low as 57% has been reported in Kenya in the 1990s (Olds 1999 KEN), and 52% in Senegal in 1993 (Guisse 1997 SEN). However, higher efficacy has been seen in more recent trials; Tanzania (81%), Mauritania (95%) and Brazil (92%) in 2006/2007 (Olliaro 2011 BRA; Olliaro 2011 MRT; Olliaro 2011 TZA), and Uganda (87%) in 2003/2005 (Tweyongyere 2009 UGA). The lower cure rates from the earlier studies could be expected from the high endemicities where pre-treatment intensity of infection were very high (prevalence > 80%) compared to the recent studies (prevalence < 30%). In such situations, even at 95% efficacy, a sufficient number of surviving schistosomes would remain, causing sustained egg excretion in most of the treated participants (Danso-Appiah 2002). Furthermore, as a result of intense transmission, most treated participants might have acquired large numbers of new infections just before treatment and as immature worms are less sensitive to praziquantel most would have escaped drug action and developed into egg-laying adult worms shortly after treatment to present as failures. The high diagnostic sensitivity (mostly duplicate slides from two or more consecutive stool specimens) and lower dose of praziquantel applied in the earlier studies (except Guisse 1997 SEN) would have also contributed to the observed lower cure rates.

The results in this review appear to be generalizable elsewhere but it should be noted that these trials excluded preschool children under five years and concerns remain that this dose may be less effective in this group. This is because praziquantel works in synergy with host immune status (Sabah 1986) and this is not yet fully developed in very young children. A subgroup analysis conducted in two studies from Burundi with praziquantel at 40 mg/kg and another two studies from Burundi and Sudan with oxamniquine 40 mg/kg raises concern as parasitological failure was consistently higher in children than in adults at one to 12 months of follow-up. This trend was also observed for doses of 20 mg/kg and 30 mg/kg for both treatments, and a higher dose (60 mg/kg) for oxamniquine.

Higher doses than 40 mg/kg have been national policy in Brazil since 1995: 60 mg/kg for children and 50 mg/kg for adolescents and adults. We found little direct evidence from randomized controlled trials to support or refute this as a policy. Only a single trial from Brazil reported outcomes at one month and this failed to show a statistically significant advantage with 60 mg/kg compared to 40 mg/kg, and excluded children aged less than 10 years (Olliaro 2011 BRA). Several further trials from Brazil have evaluated higher doses and longer regimens but these only reported outcomes at six months or beyond. These do offer some limited evidence that increasing the dose of praziquantel might have parasitological benefits.

There is no justification for using lower doses, even if potentially effective in morbidity control, as sub-curative doses may eventually select for drug resistant parasites (Doenhoff 1998; Doenhoff 2008).

Praziquantel is known to be less effective on immature schistosomes than adult worms (Sabah 1986), and combination therapy (with drugs with unrelated mechanisms of action and targeting the different developmental stages of the schistosomes), has potential as a future control strategy. Potential partner drugs include oxamniquine and the artemisinin derivatives. Of these, the artemisinin derivatives have been shown to be effective against immature schistosomes in laboratory studies (Utzinger 2001; Utzinger 2002; Utzinger 2003; Utzinger 2007), and there is some indirect evidence for efficacy from non-randomized studies in urinary schistosomiasis (De Clercq 2002; Inyang-Etoh 2004; Boulanger 2007; Inyang-Etoh 2009), and from people with malaria co-infected S. haematobium (Boulanger 2007). However, to date only a single trial has directly evaluated praziquantel plus artesunate and no additional benefit was observed compared to praziquantel alone (De Clercq 2000 SEN).

For oxamniquine, there is no current consensus on the optimal dosing regimen and it has largely fallen out of use in favour of praziquantel. Although the presented data are now more than 20 years old, and suffers some methodological problems, there is sufficient evidence of its efficacy against S. mansoni to suggest that it could be reinstated as an alternate treatment to decrease the pressure on praziquantel. However, a limitation of oxamniquine is that its effect is restricted to S. mansoni as this is the only species possessing the enzyme which converts oxamniquine to its active metabolite (Cioli 1995). It is therefore unsuitable for use in areas where co-infection with S. haematobium is common.

The optimal dose of oxamniquine may also be 40 mg/kg but further studies are required to confirm this, preferably in direct comparison with praziquantel, and trials should include and evaluate the efficacy of this dose in young children.

Safety was under reported and inconsistently assessed in most of these clinical trials. Furthermore, only the few studies comparing the intervention versus placebo allow identification of potentially drug-related events. From these few studies it is therefore not possible to provide a reliable account of treatment tolerability.

 

Quality of the evidence

The quality of evidence was assessed using the GRADE methodology and displayed in summary of findings (SOF) tables for the main comparisons. The level of quality is judged on a 4-point scale. High quality evidence implies that level of confidence in the effect estimate is high and that further research is unnecessary. Moderate quality evidence implies lower confidence in the result and further research may have an important impact on the result. Low and very low quality evidence reflect increasing uncertainty in the result and a greater need for further research.

The evidence presented is generally considered to be of moderate or low quality due to concerns related to three key factors: i) the age of the trials, with the majority more than 20 years old, ii) the poor methodological reporting of many of these older trials, and iii) the number and size of the trials being small and often underpowered to reliably detect statistically significant differences. The specific reasons for downgrading the quality of the evidence are given in the footnotes to the SOF tables.

 

Potential biases in the review process

A few minor difficulties in extracting the data from the available papers should be noted but these are unlikely to have introduced major bias into this review. For three trials (Gryseels 1989a BDI; Gryseels 1989b BDI; Gryseels 1989c BDI), data on parasitological failure were obtained from figures and might not be the exact estimates. One trial (Sukwa 1993 ZMB) actually reported reinfection rate but this is included in this review because this outcome is similar to failure rate. The trial by Tweyongyere 2009 UGA was a nested cohort study within a larger mother and baby cohort study in which pregnant women found to be infected with S. mansoni were randomized to receive praziquantel or placebo. Despite representing a special population, this is not likely to affect the validity of the results.

 

Agreements and disagreements with other studies or reviews

A non-Cochrane review compared praziquantel with placebo in two studies in Brazil and showed slightly higher cure rate with praziquantel (Liu 2011). The reliability of the evidence in this review cannot be established given that the two studies that assessed this outcome involved only 25 participants.

The effects of praziquantel and artesunate in urinary schistosomiasis due to S. haematobium have been evaluated in a separate Cochrane review last published in 2008. Praziquantel was found to be effective against S. haematobium with few adverse events, and similarly to this review there was insufficient evidence for the use of artesunate monotherapy or combination therapy (Danso-Appiah 2008).

Limitations in the design and methodology in schistosomiasis trials identified during the earlier Cochrane review, and consequent future research needs have also been reported elsewhere (Danso-Appiah 2009).

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

 

Implications for practice

The available evidence supports single dose praziquantel at 40 mg/kg as the standard treatment for S. mansoni infection as recommended by the WHO.

Oxamniquine, a largely discarded alternative, appears efficacious and production and distribution should continue to ease selective pressure on praziquantel. However, its use should be limited to areas without S. haematobium co-endemicity.

 
Implications for research

Further research is necessary to find the optimal dosing regimen of praziquantel and oxamniquine in children under five years, given the observational evidence that failure rates with 40 mg/kg may be higher in this age-group.

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; for example; praziquantel plus oxamniquine, praziquantel plus mefloquine, and praziquantel plus an artemisinin derivative.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

We thank Dr. Vittoria Lujte (Information Specialist) for developing the search strategy and doing the search for studies and Christianne Esparza for retrieving hard copies of published studies. We are grateful to Dr. Harriet MacLehose (former Deputy Editor), Anne-Marie Stephani (Managing Editor), Phil Hinds (Editorial Assistant & Administrator), Reive Robbs (former CIDG Co-ordinator) and the entire International Health Group for their support during the preparation of this review. Our sincere thanks go to Dr Otavio Pieri and Prof Martin Meremikwu for critically reading this review and for providing useful comments, and to Dr Deirdre Walshe (Associate Editor) for drafting the plain language summary.

This document is funded by the UK Department for International Development (DFID) for the benefit of developing countries. . The views expressed are not necessarily those of DFID. PLO is a staff member of the WHO; the author alone is responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy, or views of WHO.

H. Saconato and A. Atallah prepared the original version of this review (Issue 3, 1999).

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
Download statistical data

 
Comparison 1. Praziquantel versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at one month2Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 40 mg/kg single dose
2414Risk Ratio (M-H, Random, 95% CI)3.13 [1.03, 9.53]

 2 Parasitological failure at six months2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    2.1 20 mg/kg single dose
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 40 mg/kg in two divided doses on the same day
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.3 60 mg/kg in 3 divided doses 3 hours apart
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.4 60 mg/kg daily for 3 days
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Parasitological failure at 12 months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    3.1 20 mg/kg single dose
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 40 mg/kg in two divided doses on the same day
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.3 60 mg/kg in 3 divided doses 3 hours apart
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. Praziquantel (lower dose) versus praziquantel 40 mg/kg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at one month3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Praziquantel 20 mg/kg versus praziquantel 40 mg/kg
2341Risk Ratio (M-H, Fixed, 95% CI)2.23 [1.64, 3.02]

    1.2 Praziquantel 30 mg/kg versus praziquantel 40 mg/kg
3521Risk Ratio (M-H, Fixed, 95% CI)1.52 [1.15, 2.01]

 2 Parasitological failure at three months3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Praziquantel 20 mg/kg versus praziquantel 40 mg/kg
2325Risk Ratio (M-H, Fixed, 95% CI)2.15 [1.66, 2.79]

    2.2 Praziquantel 30 mg/kg versus praziquantel 40 mg/kg
3508Risk Ratio (M-H, Fixed, 95% CI)1.40 [1.10, 1.77]

 3 Parasitological failure at six to 12 months6Risk Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Praziquantel 20 mg/kg versus praziquantel 40 mg/kg
3350Risk Ratio (M-H, Random, 95% CI)2.54 [1.35, 4.76]

    3.2 Praziquantel 30 mg/kg versus praziquantel 40 mg/kg
5651Risk Ratio (M-H, Random, 95% CI)1.48 [1.19, 1.85]

 4 Percent egg reductionOther dataNo numeric data

 
Comparison 3. Praziquantel lower dose (20 and 30 mg/kg) versus praziquantel 40 mg/kg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Resolution of abdominal pain: 20 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Resolution of abdominal pain: 30 mg/kg versus 40 mg/kg2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 One month
2318Risk Ratio (M-H, Fixed, 95% CI)0.78 [0.55, 1.10]

    2.2 Three months
2318Risk Ratio (M-H, Fixed, 95% CI)0.77 [0.53, 1.11]

    2.3 Six months
2318Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.52, 1.08]

    2.4 12 months
2318Risk Ratio (M-H, Fixed, 95% CI)0.59 [0.35, 1.01]

    2.5 24 months
2318Risk Ratio (M-H, Fixed, 95% CI)0.82 [0.55, 1.25]

 3 Resolution of diarrhoea: 20 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    3.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Resolution of diarrhoea: 30 mg/kg versus 40 mg/kg2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    4.1 One month
248Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.70, 1.03]

    4.2 Three months
248Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.82, 1.25]

    4.3 Six months
248Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.76, 1.22]

    4.4 12 months
248Risk Ratio (M-H, Fixed, 95% CI)1.02 [0.77, 1.37]

    4.5 24 months
248Risk Ratio (M-H, Fixed, 95% CI)0.92 [0.69, 1.23]

 5 Resolution of blood in stool: 20 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    5.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Resolution of blood in stool: 30 mg/kg versus 40 mg/kg2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    6.1 One month
280Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.89, 1.11]

    6.2 Three months
280Risk Ratio (M-H, Fixed, 95% CI)1.02 [0.91, 1.13]

    6.3 Six months
280Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.87, 1.07]

    6.4 12 months
282Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.79, 1.22]

    6.5 24 months
282Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.78, 1.40]

 7 Resolution of hepatomegaly: 20 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    7.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Resolution of hepatomegaly: 30 mg/kg versus 40 mg/kg2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    8.1 One month
2109Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.83, 1.35]

    8.2 Three months
2109Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.80, 1.27]

    8.3 Six months
2109Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.79, 1.29]

    8.4 12 months
2109Risk Ratio (M-H, Fixed, 95% CI)0.92 [0.73, 1.16]

    8.5 24 months
2109Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.69, 1.14]

 9 Resolution of splenomegaly: 20 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    9.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 10 Resolution of splenomegaly: 30 mg/kg versus 40 mg/kg2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    10.1 One month
2122Risk Ratio (M-H, Fixed, 95% CI)0.86 [0.65, 1.15]

    10.2 Three months
2122Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.66, 1.25]

    10.3 Six months
2122Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.70, 1.36]

    10.4 12 months
2122Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.76, 1.46]

    10.5 24 months
2122Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.72, 1.23]

 
Comparison 4. Praziquantel (higher dose) versus praziquantel 40 mg/kg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at one month4Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Praziquantel 60 mg/kg versus praziquantel 40 mg/kg
4783Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.73, 1.29]

 2 Parasitological failure at six months2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    2.1 Praziquantel 50 mg/kg versus praziquantel 40 mg/kg
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Praziquantel 60 mg/kg versus praziquantel 40 mg/kg
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Parasitological failure at six to 12 months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    3.1 Praziquantel 60 mg/kg versus praziquantel 40 mg/kg
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Percent egg reduction at one monthOther dataNo numeric data

 
Comparison 5. Praziquantel 40 mg/kg divided dose versus praziquantel 40 mg/kg single dose

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at one month2525Risk Ratio (M-H, Random, 95% CI)0.47 [0.13, 1.69]

 2 Parasitological failure at three months2516Risk Ratio (M-H, Random, 95% CI)0.31 [0.18, 0.53]

 3 Parasitological failure at six months1Risk Ratio (M-H, Random, 95% CI)Subtotals only

 4 Percent egg reduction at one monthOther dataNo numeric data

 
Comparison 6. Praziquantel alternative dosing (Brazil)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at six months3Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 Praziquantel 30 mg/kg x 2 daily for 2 days versus praziquantel 30 mg/kg x 2 in one day
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Praziquantel 30 mg/kg x 2 daily for 3 days versus praziquantel 30 mg/kg x 2 in one day
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Praziquantel 30 mg/kg x 1 daily for 6 days versus 30 mg/kg x 2 in one day
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.4 Praziquantel 20 mg/kg x 3, 4 hours apart versus praziquantel 50 mg/kg single dose
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.5 Praziquantel 40 mg/kg x 2, 1 hour apart versus praziquantel 50 mg/kg single dose
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Percent egg reduction at six monthsOther dataNo numeric data

 3 Percent egg reduction at six monthsOther dataNo numeric data

 4 Percent egg reduction at six monthsOther dataNo numeric data

 
Comparison 7. Oxamniquine versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at three to four months2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 30 mg/kg
282Risk Ratio (M-H, Fixed, 95% CI)4.34 [2.47, 7.65]

    1.2 40 mg/kg
282Risk Ratio (M-H, Fixed, 95% CI)8.74 [3.74, 20.43]

    1.3 60 mg/kg
289Risk Ratio (M-H, Fixed, 95% CI)19.38 [5.79, 64.79]

 2 Parasitological failure at six to 10 months2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 20 mg/kg
2146Risk Ratio (M-H, Fixed, 95% CI)3.68 [2.53, 5.36]

 3 Percent egg reduction at three to four monthsOther dataNo numeric data

    3.1 Oxamniquine (40 mg/kg) versus placebo
Other dataNo numeric data

    3.2 Oxamniquine (20 to 30 mg/kg) versus placebo
Other dataNo numeric data

    3.3 Oxamniquine (60 mg/kg) versus placebo
Other dataNo numeric data

 
Comparison 8. Oxamniquine (lower dose) versus oxamniquine 40 mg/kg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at one month5Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Oxamniquine 20 mg/kg versus oxamniquine 40 mg/kg
2190Risk Ratio (M-H, Fixed, 95% CI)3.78 [2.05, 6.99]

    1.2 Oxamniquine 30 mg/kg versus oxamniquine 40 mg/kg
4268Risk Ratio (M-H, Fixed, 95% CI)1.78 [1.15, 2.75]

 2 Parasitological failure at three to four months8Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Oxamniquine 20 mg/kg versus oxamniquine 40 mg/kg
3209Risk Ratio (M-H, Fixed, 95% CI)2.28 [1.40, 3.71]

    2.2 Oxamniquine 30 mg/kg versus oxamniquine 40 mg/kg
7373Risk Ratio (M-H, Fixed, 95% CI)1.64 [1.10, 2.43]

 3 Parasitological failure at six months4Risk Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Oxamniquine 20 mg/kg versus oxamniquine 40 mg/kg
2163Risk Ratio (M-H, Random, 95% CI)0.83 [0.48, 1.46]

    3.2 Oxamniquine 30 mg/kg versus oxamniquine 40 mg/kg
3214Risk Ratio (M-H, Random, 95% CI)1.10 [0.71, 1.69]

 4 Parasitological failure at 12 months2Risk Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 Oxamniquine 20 mg/kg versus oxamniquine 40 mg/kg
2144Risk Ratio (M-H, Random, 95% CI)0.87 [0.32, 2.36]

    4.2 Oxamniquine 30 mg/kg versus oxamniquine 40 mg/kg
177Risk Ratio (M-H, Random, 95% CI)0.94 [0.67, 1.31]

 5 Percent egg reductionOther dataNo numeric data

    5.1 One month
Other dataNo numeric data

    5.2 Three to four months
Other dataNo numeric data

    5.3 Six months
Other dataNo numeric data

 
Comparison 9. Oxamniquine lower dose (20 and 30 mg/kg) versus oxamniquine 40 mg/kg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Resolution of abdominal pain: 20 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Resolution of abdominal pain: 30 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    2.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Resolution of diarrhoea: 20 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    3.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Resolution of diarrhoea: 30 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    4.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Resolution of blood in stool: 20 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    5.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Resolution of blood in stool: 30 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    6.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Resolution of hepatomegaly: 20 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    7.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Resolution of hepatomegaly: 30 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    8.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Resolution of splenomegaly: 20 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    9.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 10 Resolution of splenomegaly: 30 mg/kg versus 40 mg/kg1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    10.1 One month
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.2 Three months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.3 Six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.4 12 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.5 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 10. Oxamniquine (higher dose) versus oxamniquine 40 mg/kg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at one month5Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Oxamniquine (50 mg/kg) versus oxamniquine (40 mg/kg)
132Risk Ratio (M-H, Random, 95% CI)0.88 [0.21, 3.73]

    1.2 Oxamniquine (60 mg/kg) versus oxamniquine (40 mg/kg)
4317Risk Ratio (M-H, Random, 95% CI)0.45 [0.09, 2.11]

 2 Parasitological failure at three to four months6Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Oxamniquine (50 mg/kg) versus oxamniquine (40 mg/kg)
116Risk Ratio (M-H, Random, 95% CI)1.11 [0.25, 4.86]

    2.2 Oxamniquine (60 mg/kg) versus oxamniquine (40 mg/kg)
5381Risk Ratio (M-H, Random, 95% CI)0.40 [0.12, 1.38]

 3 Parasitological failure at six months2Risk Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Oxamniquine (60 mg/kg) versus oxamniquine (40 mg/kg)
2177Risk Ratio (M-H, Random, 95% CI)0.61 [0.12, 3.12]

 4 Percent egg reductionOther dataNo numeric data

    4.1 One month
Other dataNo numeric data

    4.2 Three to four months
Other dataNo numeric data

    4.3 Six months
Other dataNo numeric data

 
Comparison 11. Oxamniquine (lower dose) 15 to 20 mg/kg versus oxamniquine 30 mg/kg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure4Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 One month
3230Risk Ratio (M-H, Fixed, 95% CI)1.77 [1.14, 2.74]

    1.2 Three to four months
4249Risk Ratio (M-H, Fixed, 95% CI)2.16 [1.40, 3.32]

    1.3 Six months
2179Risk Ratio (M-H, Fixed, 95% CI)1.23 [0.86, 1.75]

    1.4 6 to 12 months
195Risk Ratio (M-H, Fixed, 95% CI)1.74 [1.02, 2.96]

 
Comparison 12. Oxamniquine (higher dose) versus oxamniquine 30 mg/kg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at one month3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Oxamniquine 50 mg/kg versus oxamniquine 30 mg/kg
136Risk Ratio (M-H, Fixed, 95% CI)0.48 [0.15, 1.56]

    1.2 Oxamniquine 60 mg/kg versus oxamniquine 30 mg/kg
2175Risk Ratio (M-H, Fixed, 95% CI)0.04 [0.01, 0.26]

 2 Parasitological failure at three to four months6Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Oxamniquine 50 mg/kg versus oxamniquine 30 mg/kg
253Risk Ratio (M-H, Fixed, 95% CI)0.82 [0.44, 1.53]

    2.2 Oxamniquine 60 mg/kg versus oxamniquine 30 mg/kg
4265Risk Ratio (M-H, Fixed, 95% CI)0.17 [0.07, 0.39]

 3 Parasitological failure at six months2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 Oxamniquine (60 mg/kg) versus oxamniquine (30 mg/kg)
2157Risk Ratio (M-H, Fixed, 95% CI)0.17 [0.06, 0.50]

 
Comparison 13. Oxamniquine versus praziquantel

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at one month4Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Oxamniquine 10 to 20 mg/kg versus praziquantel 40 mg/kg
2232Risk Ratio (M-H, Random, 95% CI)1.08 [0.08, 14.47]

    1.2 Oxamniquine 30 mg/kg versus praziquantel 40 mg/kg
2136Risk Ratio (M-H, Random, 95% CI)0.71 [0.35, 1.45]

    1.3 Oxamniquine 40 mg/kg versus praziquantel 40 mg/kg
133Risk Ratio (M-H, Random, 95% CI)0.4 [0.13, 1.22]

    1.4 Oxamniquine 50 to 60 mg/kg versus praziquantel 40 mg/kg
2122Risk Ratio (M-H, Random, 95% CI)0.89 [0.16, 4.84]

 2 Parasitological failure at three months4Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Oxamniquine (10 to 20 mg/kg) versus praziquantel 40 mg/kg
2135Risk Ratio (M-H, Random, 95% CI)3.42 [1.10, 10.61]

    2.2 Oxamniquine (25 to 30 mg/kg) versus praziquantel 40 mg/kg
3319Risk Ratio (M-H, Random, 95% CI)0.92 [0.40, 2.12]

    2.3 Oxamniquine 40 mg/kg versus praziquantel 40 mg/kg
118Risk Ratio (M-H, Random, 95% CI)0.4 [0.14, 1.12]

    2.4 Oxamniquine (50 to 60 mg/kg) versus praziquantel 40 mg/kg
114Risk Ratio (M-H, Random, 95% CI)0.44 [0.13, 1.48]

 3 Parasitological failure at six months9Risk Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Oxamniquine (10 to 20 mg/kg) versus praziquantel 40 mg/kg
3197Risk Ratio (M-H, Random, 95% CI)1.10 [0.70, 1.74]

    3.2 Oxamniquine (25 to 30 mg/kg) versus praziquantel 40 mg/kg
2295Risk Ratio (M-H, Random, 95% CI)1.00 [0.22, 4.49]

    3.3 Oxamniquine (50 to 60 mg/kg) versus praziquantel 40 mg/kg
179Risk Ratio (M-H, Random, 95% CI)2.19 [1.11, 4.30]

    3.4 Oxamniquine (15 to 20 mg/kg) versus praziquantel 40 mg/kg
4596Risk Ratio (M-H, Random, 95% CI)1.12 [0.83, 1.51]

 4 Parasitological failure at 12 months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    4.1 Oxamniquine (10 to 20 mg/kg) versus praziquantel 40 mg/kg
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Percent egg reductionOther dataNo numeric data

    5.1 One month
Other dataNo numeric data

    5.2 Three months
Other dataNo numeric data

    5.3 Six months
Other dataNo numeric data

    5.4 12 months
Other dataNo numeric data

 
Comparison 14. Myrrh (Mirazid) 300 mg once daily for three days versus praziquantel 40 mg/kg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at three to six weeks2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

 2 Percent egg reduction three to six weeksOther dataNo numeric data

 
Comparison 15. Praziquantel (40 mg/kg) plus artesunate (12 mg/kg total dose) versus praziquantel (40 mg/kg)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at one month1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Parasitological failure at three months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Parasitological failure at six months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Percent egg reductionOther dataNo numeric data

    4.1 One month
Other dataNo numeric data

    4.2 Three months
Other dataNo numeric data

    4.3 Six months
Other dataNo numeric data

 
Comparison 16. Praziquantel (20 mg/kg) plus oxamniquine (7.5 mg/kg) versus praziquantel (40 mg/kg)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at three months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Parasitological failure at six months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Parasitological failure at 12 months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Percent egg reductionOther dataNo numeric data

    4.1 Three months
Other dataNo numeric data

    4.2 Six months
Other dataNo numeric data

    4.3 12 months
Other dataNo numeric data

 
Comparison 17. Praziquantel (8 mg/kg) plus oxamniquine (4 mg/kg) versus praziquantel (20 mg/kg) plus oxamniquine (10 mg/kg)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at one month1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Parasitological failure at three months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Parasitological failure at six months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Percent egg reductionOther dataNo numeric data

    4.1 One month
Other dataNo numeric data

    4.2 Three months
Other dataNo numeric data

    4.3 Six months
Other dataNo numeric data

 
Comparison 18. Praziquantel (15 mg/kg) plus oxamniquine (7.5 mg/kg) versus praziquantel (20 mg/kg) plus oxamniquine (10 mg/kg)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Parasitological failure at one month1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Parasitological failure at three months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Parasitological failure at six months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Percent egg reductionOther dataNo numeric data

    4.1 One month
Other dataNo numeric data

    4.2 Three months
Other dataNo numeric data

    4.3 Six months
Other dataNo numeric data

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

Last assessed as up-to-date: 16 October 2012.


DateEventDescription

6 November 2012New citation required and conclusions have changedThis review update has been prepared by new authors (Danso-Appiah A, Olliaro PL, Donegan S, Sinclair D and Utzinger J). Each section of the review has been rewritten and updated, including the results and conclusions.

6 November 2012New search has been performedThis is a new review with a fresh authorship team, replacing a previous version.  The previous version included 13 trials and the last search was in 2005 and only reported parasitological failure. The current version includes 52 trials, includes percentage egg reduction as an outcome, and includes new trials evaluating artesunate. All data have been re-extracted. Each section of the review has been rewritten. Results are summarized using a Summary of Findings table. Data in the intervention arm in relation to cure are explored by age.



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

ADA, JU and PLO developed the protocol. ADA selected studies, extracted data, assessed risk of bias in the included studies, analysed the data and drafted the review. JU independently verified study selection, data extraction, risk of bias assessment, results of the analysis and edited the draft review. PLO verified study selection, risk of bias assessment and edited the draft review. SD provided statistical advice and edited the methods section. DS helped restructure the review, verified risk of bias assessment and prepared the SOF tables, which were checked by ADA. ADA, JU and PLO interpreted the data, and all authors helped with revisions following the referees' comments.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

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.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
 

Internal sources

  • Liverpool School of Tropical Medicine, UK.

 

External sources

  • Department for International Development, UK.
  • The World Health Organization, Switzerland.
  • Swiss National Science Foundation (Project no PPOOB-102883, PPOOB-119129), Switzerland.

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

None

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
Abdel Rahim 1988 SDN {published data only}
  • Abdel Rahim IM, Haridi AA, Abdel-Hameed AA. Field study of different oxamniquine dose for Schistosoma mansoni in Gezira, Sudan. Journal of Tropical Medicine and Hygiene 1988;91(3):131-7.
  • Abdel-Rahim IM, Haridi AA, Abdel-Hameed AA. A field evaluation of three dose levels of oxamniquine in Gezira- Sudan. East African Medical Journal 1988;65(11):771-7.
Al Aska 1990 SAU {published data only}
  • Al-Aska AK, Al-Mofleh IA, Al-Rashed R, Hafez MA, Al-Nozha M, Abu-Aisha H, et al. Praziquantel, oxamniquine, and metrifonate in the treatment of schistosomiasis in Riyadh. Annals of Saudi Medicine 1990;10(3):296-8.
Ayele 1984 ETH {published data only}
  • Ayele T. Preliminary clinical trial of oral oxamniquine in the treatment of Schistosoma mansoni in Ethiopia. East African Medical Journal 1984;61(8):632-6.
Ayele 1986 ETH {published data only}
  • Ayele T. Preliminary clinical trial of oral oxamniquine in the treatment of Schistosoma mansoni in children in Ethiopia. East African Medical Journal 1986;63(4):291-4.
Barakat 2005 EGY {published data only}
  • Barakat R, Elmorshedy H, Fenwick A. Efficacy of myrrh in the treatment of human schistosomiasis mansoni. American Journal of Tropical Medicine and Hygiene 2005;73(2):365-7.
Botros 2005 EGY {published data only}
  • Botros S, Sayed H, El-Dusoki H, Sabry H, Rabie I, El-Ghannam M, et al. Efficacy of mirazid in comparison with praziquantel in Egyptian Schistosoma mansoni-infected school children and households. American Journal of Tropical Medicine and Hygiene 2005;72(2):119-23.
Branchini 1982 BRA {published data only}
  • Branchini ML, Pedro R J de, Dias LC, Deberaldini ER. Double-blind clinical trial comparing praziquantel with oxamniquine in the treatment of patients with schistosomiasis mansoni. Revista do Instituto de Medicina Tropical de São Paulo 1982;24(5):315-21.
Creasey 1986 ZWE {published data only}
  • Creasey AM, Taylor P, Thomas JE. Dosage trial of a combination of oxamniquine and praziquantel in the treatment of schistosomiasis in Zimbabwean schoolchildren. Central African Journal of Medicine 1986;32(7):165-7.
da Cunha 1986 BRA {published data only}
  • da Cunha AS, Pedrosa RC. Double-blind therapeutical evaluation based on the quantitative oogram technique, comparing praziquantel and oxamniquine in human Schistosomiasis mansoni. Revista do Instituto de Medicina Tropical de São Paulo 1986;28(5):337-51.
da Cunha 1987 BRA {published data only}
  • da Cunha AS, Cançado JR, de Rezende GL. Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique. Revista do Instituto de Medicina Tropical de São Paulo 1987;29(5):295-304.
da Silva 1986 BRA {published data only}
  • da Silva LC, Zeitune JM, Rosa-Eid LM, Lima DM, Antonelli RH, Christo CH, et al. Treatment of patients with schistosomiasis mansoni: a double blind clinical trial comparing praziquantel with oxamniquine. Revista do Instituto de Medicina Tropical de São Paulo 1986;28(3):174-80.
de Clarke 1976a ZWE {published data only}
  • de Clarke V, Blair DM, Weber MC, Garnett PA. Dose-finding trials of oral oxamniquine in Rhodesia. South African Medical Journal 1976;50(46):1867-71.
de Clarke 1976b ZWE {published data only}
  • de Clarke V, Blair DM, Weber MC, Garnett PA. Dose-finding trials of oral oxamniquine in Rhodesia. South African Medical Journal 1976;50(46):1867-71.
de Clarke 1976c ZWE {published data only}
  • de Clarke V, Blair DM, Weber MC, Garnett PA. Dose-finding trials of oral oxamniquine in Rhodesia. South African Medical Journal 1976;50(46):1867-71.
de Clarke 1976d ZWE {published data only}
  • de Clarke V, Blair DM, Weber MC, Garnett PA. Dose-finding trials of oral oxamniquine in Rhodesia. South African Medical Journal 1976;50(46):1867-71.
De Clercq 2000 SEN {published data only}
  • De Clercq D, Vercruysse J, Verle P, Kongs A, Diop M. What is the effect of combining artesunate and praziquantel in the treatment of Schistosoma mansoni infections?. Tropical Medicine and International Health 2000;5(10):744-6.
de Jonge 1990 SDN {published data only}
  • de Jonge N, Schommer G, Feldmeier H, Krijger FW, Dafalla AA, Bienzle U, et al. Mixed Schistosoma haematobium and S. mansoni infection: effect of different treatments on the serum level of circulating anodic antigen (CAA). Acta Tropica 1990;48(1):25-35.
  • Doehring E, Ehrich JH, Vester U, Feldmeier H, Poggensee U, Brodehl J. Proteinuria, hematuria, and leukocyturia in children with mixed urinary and intestinal schistosomiasis. Kidney International 1985;28(3):520-5.
  • Doehring E, Poggensee U, Feldmeier H. The effect of metrifonate in mixed Schistosoma haematobium and Schistosoma mansoni infections in humans. American Journal of Tropical Medicine and Hygiene 1986;35(2):323-9.
  • Feldmeier H, Gastl GA, Poggensee U, Kortmann C, Daffalla AA, Peter HH. Relationship between intensity of infection and immunomodulation in human schistosomiasis. II. NK cell activity and in vitro lymphocyte proliferation. Clinical and Experimental Immunology 1985;60(2):234-40.
  • Feldmeier H, Nogueira-Queiroz JA, Peixoto-Queiroz MA, Doehring E, Dessaint JP, de Alencar JE, et al. Detection and quantification of circulating antigen in schistosomiasis by monoclonal antibody. II. The quantification of circulating antigens in human schistosomiasis mansoni and haematobium: relationship to intensity of infection and disease status. Clinical and Experimental Immunology 1986;65(2):232-43.
Fernandes 1986 BRA {published data only}
  • Fernandes P, Oliveira CC. Efficacy of two regimes of praziquantel versus oxamniquine [Estudo comparativo da eficacia do praziquantel, em dois esquemas posologicos, e da oxaminiquina no tratamento da esquistossomose mansonica]. Folha Medica 1986;93(5-6):389-93.
Ferrari 2003 BRA {published data only}
  • Ferrari ML, Coelho PM, Antunes CM, Tavares CA, da Cunha AS. Efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infection: a controlled trial. Bulletin of the World Health Organization 2003;81(3):190-6.
Gryseels 1989a BDI {published data only}
  • Gryseels B, Nkulikyinka L. Two-year follow-up of Schistosoma mansoni infection and morbidity after treatment with different regimens of oxamniquine and praziquantel. Transactions of the Royal Society of Tropical Medicine and Hygiene 1989;83(2):219-28.
Gryseels 1989b BDI {published data only}
  • Gryseels B, Nkulikyinka L. Two-year follow-up of Schistosoma mansoni infection and morbidity after treatment with different regimens of oxamniquine and praziquantel. Transactions of the Royal Society of Tropical Medicine and Hygiene 1989;83(2):219-28.
Gryseels 1989c BDI {published data only}
  • Gryseels B, Nkulikyinka L. Two-year follow-up of Schistosoma mansoni infection and morbidity after treatment with different regimens of oxamniquine and praziquantel. Transactions of the Royal Society of Tropical Medicine and Hygiene 1989;83(2):219-28.
Guisse 1997 SEN {published data only}
  • Guisse F, Polman K, Stelma FF, Mbaye A, Talla I, Niang M, et al. Therapeutic evaluation of two different dose regimens of praziquantel in a recent Schistosoma mansoni focus in Northern Senegal. American Journal of Tropical Medicine and Hygiene 1997;56(5):511-4.
Gupta 1984 ZMB {published data only}
Homeida 1989 SDN {published data only}
  • Homeida MM, Eltom IA, Sulaiman SM, Ali HM, Bennett JL. Tolerance of two brands of praziquantel. Lancet 1989;334(8659):391.
Ibrahim 1980 SDN {published data only}
Jaoko 1996 KEN {published data only}
  • Jaoko WG, Muchemi G, Oguya FO. Praziquantel side effects during treatment of Schistosoma mansoni infected pupils in Kibwezi, Kenya. East African Medical Journal 1996;73(8):499-501.
Kardaman 1983 SDN {published data only}
  • Kardaman MW, Amin MA, Fenwick A, Cheesmond AK, Dixon HG. A field trial using praziquantel (Biltricide) to treat Schistosoma mansoni and Schistosoma haematobium infection in Gezira, Sudan. Annals of Tropical Medicine and Parasitology 1983;77(3):297-304.
Kardaman 1985 SDN {published data only}
  • Kardaman MW, Fenwick A, el Igail AB, el Tayeb M, Daffalla AA, Dixon HG. Treatment with praziquantel of schoolchildren with concurrent Schistosoma mansoni and S. haematobium infections in Gezira, Sudan. Journal of Tropical Medicine and Hygiene 1985;88(2):105-9.
Katz 1979a BRA {published data only}
Katz 1979b BRA {published data only}
Katz 1981 BRA {published data only}
  • Katz N. Clinical trials with praziquantel in schistosomiasis mansoni. Revista do Instituto de Medicina Tropical de São Paulo 1981;23(2):72-8.
Katz 1982 BRA {published data only}
  • Katz N, Rocha RS. Double-blind clinical trial comparing praziquantel with oxamniquine in schistosomiasis mansoni. Revista do Instituto de Medicina Tropical de São Paulo 1982;24(5):310-4.
Lambertucci 1982 BRA {published data only}
  • Lambertucci JR, Greco DB, Pedroso ER, da Costa Rocha MO, Salazar HM, de Lima DP. A double blind trial with oxamniquine in chronic schistosomiasis mansoni. Transactions of the Royal Society of Tropical Medicine and Hygiene 1982;76(6):751-5.
Metwally 1995 EGY {published data only}
Olds 1999 KEN {published data only}
  • Olds GR, King CH, Hewlett J, Olveda R, Wu G, Ouma J, et al. Double-blind placebo-controlled study of concurrent administration of albendazole and praziquantel in schoolchildren with schistosomiasis and geohelminths. Journal of Infectious Diseases 1999;179(4):996-1003.
Olliaro 2011 BRA {published data only}
  • Olliaro P, Vaillant M, Belizario V, Lwambo N, Ouldabdallahi M, Pieri OS, et al. A multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg versus 60 mg/kg for treating intestinal schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil. PLoS Neglected Tropical Diseases 2011;5(6):e1165.
Olliaro 2011 MRT {published data only}
  • Olliaro P, Vaillant M, Belizario V, Lwambo N, Ouldabdallahi M, Pieri OS, et al. A multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg versus 60 mg/kg for treating intestinal schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil. PLoS Neglected Tropical Diseases 2011;5(6):e1165.
Olliaro 2011 TZA {published data only}
  • Olliaro P, Vaillant M, Belizario V, Lwambo N, Ouldabdallahi M, Pieri OS, et al. A multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg versus 60 mg/kg for treating intestinal schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil. PLoS Neglected Tropical Diseases 2011;5(6):e1165.
Omer 1978 SDN {published data only}
  • Omer AH. Oxamniquine for treating Schistosoma mansoni infection in Sudan. British Medical Journal 1978;2(6131):163-5.
Omer 1981 SDN {published data only}
Queiroz 2010 BRA {published data only}
  • Queiroz LC, Drummond SC, Matos ML, Paiva MB, Batista TS, Kansaon AZ, et al. Comparative randomised trial of high and conventional doses of praziquantel in the treatment of schistosomiasis mansoni. Memorias do Instituto Oswaldo Cruz 2010;105(4):445-8.
Rezende 1985 BRA {published data only}
  • Rezende GL de. Survey on the clinical results achieved in Brazil comparing praziquantel and oxamniquine in the treatment of S. mansoni schistosomiasis. Revista do Instituto de Medicina Tropical de São Paulo 1985;27(6):328-68.
Rugemalila 1984 TZA {published data only}
  • Rugemalila JB, Asila J, Chimbe A. Randomized comparative trials of single doses of the newer antischistosomal drugs at Mwanza, Tanzania. I. Praziquantel and oxamniquine for the treatment of schistosomiasis mansoni. Journal of Tropical Medicine and Hygiene 1984;87(6):231-5.
Shafei 1979 NGA {published data only}
  • Shafei AZ. A preliminary report on the treatment of intestinal schistosomiasis with oxamniquine. Journal of Tropical Medicine and Hygiene 1979;82(1):18-20.
Stelma 1997 SEN {published data only}
  • Stelma FF, Sall S, Daff B, Sow S, Niang M, Gryseels B. Oxamniquine cures Schistosoma mansoni infection in a focus in which cure rates with praziquantel are unusually low. Journal of Infectious Diseases 1997;176(1):304-7.
Sukwa 1993 ZMB {published data only}
  • Sukwa TY. A community-based randomized trial of praziquantel to control schistosomiasis morbidity in schoolchildren in Zambia. Annals of Tropical Medicine and Parasitology 1993;87(2):185-94.
Taddese 1988 ETH {published data only}
  • Taddese K, Zein ZA. Comparison between the efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infections on a sugar estate in Ethiopia. Annals of Tropical Medicine and Parasitology 1988;82(2):175-80.
Taylor 1988 ZWE {published data only}
  • Taylor P, Murare HM, Manomano K. Efficacy of low doses of praziquantel for Schistosoma mansoni and S. haematobium. Journal of Tropical Medicine and Hygiene 1988;91(1):13-7.
Teesdale 1984 MWI {published data only}
Tweyongyere 2009 UGA {published data only}
  • Tweyongyere R, Mawa PA, Emojong NO, Mpairwe H, Jones FM, Duong T, et al. Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial. BMC Infectious Diseases 2009;9:32.
  • Tweyongyere R, Mawa PA, Ngom-Wegi S, Ndibazza J, Duong T, Vennervald BJ, et al. Effect of praziquantel treatment during pregnancy on cytokine responses to schistosome antigens: results of a randomized, placebo-controlled trial. Journal of Infectious Diseases 2008;198(12):1870-9.
Zwingenberger 1987 BRA {published data only}
  • Zwingenberger K, Queiroz JA, Poggensee U, Alencar JE, Valdegunas J, Esmeralda F, et al. Efficacy of oxamniquine, praziquantel and a combination of both drugs in schistosomiasis mansoni in Brazil. Revista do Instituto de Medicina Tropical de São Paulo 1987;29(5):305-11.

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
Abu-Elyazeed 1997 {published data only}
  • Abu-Elyazeed RR, Youssef FG, Merrell BR, El-Gamal RL, El-Khoby TA, Hassanein YA, et al. Praziquantel in the treatment of Schistosoma mansoni infection: comparison of 40 and 60 mg/kg bodyweight regimens. American Journal of Tropical Medicine and Hygiene 1997;56(4):404-7.
Adam 2008 {published data only}
  • Adam I, Elhardello OA, Elhadi MO, Abdalla E, Elmardi KA, Jansen FH. The antischistosomal efficacies of artesunate-sulfamethoxypyrazine-pyrimethamine and artemether-lumefantrine administered as treatment for uncomplicated Plasmodium falciparum malaria. Annals of Tropical Medicine and Parasitology 2008;102(1):39-44.
Almeida 2012 {published data only}
  • Almeida MCF, Lima GS, Cardoso LS, Souza RPD, Campos RA, Cruz AA, et al. The effect of antihelminthic treatment on subjects with asthma from an endemic area of schistosomiasis: A randomized, double-blinded, and placebo-controlled trial. Journal of Parasitology Research 2012;2012(296856):1-11.
Assis 1998 {published data only}
  • Assis AM, Barreto ML, Prado MS, Reis MG, Parraga IM, Blanton RE. Schistosoma mansoni infection and nutritional status in schoolchildren: a randomized, double-blind trial in northeastern Brazil. American Journal of Clinical Nutrition 1998;86(6):1247-53.
Boisier 1998 {published data only}
  • Boisier P, Ramarokoto CE, Ravaoalimalala VE, Rabarijaona L, Serieye J, Roux J, et al. Reversibility of Schistosoma mansoni-associated morbidity after yearly mass praziquantel therapy: ultrasonographic assessment. Transactions of the Royal Society of Tropical Medicine and Hygiene 1998;92(4):451-3.
Coura 1980 {published data only}
  • Coura JR, Argento CA, Conceição MJ, Lewis EM, dos Santos ML, Magalhães P. Field experiences with oral oxamniquine in the treatment of schistosomiasis mansoni. Revista do Instituto de Medicina Tropical de São Paulo 1980;22(1 Suppl 4):77-84.
De Clercq 2000b {published data only}
  • De Clercq D, Vercruysse J, Verlé P, Niasse F, Kongs A, Diop M. Efficacy of artesunate against Schistosoma mansoni infections in Richard Toll, Senegal. Transactions of the Royal Society of Tropical Medicine and Hygiene 2000;94(1):90-1.
Doehring 1992 {published data only}
  • Doehring-Schwerdtfeger E, Abdel-Rahim IM, Kardorff R, Kaiser C, Franke D, Schlake J, et al. Ultrasonographical investigation of periportal fibrosis in children with Schistosoma mansoni infection: reversibility of morbidity twenty-three months after treatment with praziquantel. American Journal of Tropical Medicine and Hygiene 1992;46(4):409-15.
Eigege 2008 {published data only}
  • Eigege A, Pede E, Miri E, Umaru J, Ogbu Pearce P, Jinadu MY, et al. Triple drug administration (TDA), with praziquantel, ivermectin and albendazole, for the prevention of three neglected tropical diseases in Nigeria. Annals of Tropical Medicine and Parasitology 2008;102(2):177-9.
el Guiniady 1994 {published data only}
  • el Guiniady MA, el Touny MA, Abdel-Bary MA, Abdel-Fatah SA, Metwally A. Clinical and pharmacokinetic study of praziquantel in Egyptian schistosomiasis patients with and without liver cell failure. American Journal of Tropical Medicine and Hygiene 1994;51(6):809-18.
el-Hawey 1991 {published data only}
  • el-Hawey AM, Massoud AM, el-Rakieby A, Royzeik MS, Nassar MO. Study of some aspects of cell mediated immune response in bilharzial children on a field level. Journal of the Egyptian Society of Parasitology 1991;21(2):411-6.
Friis 1997 {published data only}
  • Friis H, Ndhlovu P, Mduluza T, Kaondera K, Sandström B, Michaelsen KF, et al. The impact of zinc supplementation on growth and body composition: a randomized, controlled trial among rural Zimbabwean schoolchildren. European Journal of Clinical Nutrition 1997;51(1):38-45.
Friis 2003 {published data only}
  • Friis H, Mwaniki D, Omondi B, Muniu E, Thiong'o F, Ouma J, et al. Effects on haemoglobin of multi-micronutrient supplementation and multi-helminth chemotherapy: a randomized, controlled trial in Kenyan school children. European Journal of Clinical Nutrition 2003;57(4):573-9.
Gryseels 1987 {published data only}
  • Gryseels B, Nkulikyinka L, Coosemans MH. Field trials of praziquantel and oxamniquine for the treatment of schistosomiasis mansoni in Burundi. Transactions of the Royal Society of Tropical Medicine and Hygiene 1987;81(4):641-4.
Homeida 1988 {published data only}
  • Homeida M, Abdel-Gadir AF, Cheever AW, Bennett JL, Arbab BM, Ibrahium SZ, et al. Diagnosis of pathologically confirmed Symmers' periportal fibrosis by ultrasonography: a prospective blinded study. American Journal of Tropical Medicine and Hygiene 1988;38(1):86-91.
Kabatereine 2003 {published data only}
  • Kabatereine NB, Kemijumbi J, Ouma JH, Sturrock RF, Butterworth AE, Madsen H, et al. Efficacy and side effects of praziquantel treatment in a highly endemic Schistosoma mansoni focus at Lake Albert, Uganda. Transactions of the Royal Society of Tropical Medicine and Hygiene 2003;97(5):599-603.
Katz 1973 {published data only}
  • Katz N, Pellegrino J, Grinbaum E, Chaves A, Zicker F. Preliminary clinical trials with oxamniquine, a new antischistosomal agent. Revisto do Instituto de Medecina Tropical de São Paulo 1973;15(1):25-9.
Mohamed 2009 {published data only}
  • Mohamed AA, Mahgoub HM, Magzoub M, Gasim GI, Eldein WN, Ahmed AA, et al. Artesunate plus sulfadoxine/pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni in eastern Sudan. Transactions of the Royal Society of Tropical Medicine and Hygiene 2009;103(10):1062-4.
Navaratnam 2012 {published data only}
  • Navaratnam AMD, Sousa-Figueiredo JC, Stothard JR, Kabatereine NB, Fenwick A, Mutumba-Nakalembe MJ. Efficacy of praziquantel syrup versus crushed praziquantel tablets in the treatment of intestinal schistosomiasis in Ugandan preschool children, with observation on compliance and safety. Transactions of the Royal Society of Tropical Medicine and Hygiene 2012;106(7):400-7.
Obonyo 2010 {published data only}
  • Obonyo CO, Muok MO, Mwinzi NM. Efficacy of artesunate with sulfalene plus pyrimethamine versus praziquantel for treatment of Schistosoma mansoni in Kenyan children: an open-label randomised controlled trial. Lancet Infectious Diseases 2010;10(9):603-11.
Odongo-Aginya 1996 {published data only}
  • Odongo-Aginya EI, Doehring M, Lakwo TL, Etyono S, Luyinda LB, Roth J, et al. Integrated control trial of schistosomiasis at Nakiwogo fishing village near Entebbe, Uganda. East African Medical Journal 1996;73(8):495-8.
Olsen 2000 {published data only}
  • Olsen A, Nawiri J, Friis H. The impact of iron supplementation on reinfection with intestinal helminths and Schistosoma mansoni in western Kenya. Transactions of the Royal Society of Tropical Medicine and Hygiene 2000;94(5):493-99.
Olsen 2003 {published data only}
  • Olsen A, Thiong'o FW, Ouma JH, Mwaniki D, Magnussen P, Michaelsen KF, et al. Effects of multimicronutrient supplementation on helminth reinfection: a randomized, controlled trial in Kenyan schoolchildren. Transactions of the Royal Society of Tropical Medicine and Hygiene 2003;97(1):109-14.
Pitchford 1978 {published data only}
Polderman 1988 {published data only}
  • Polderman AM, Gryseels B, de Caluwe P. Cure rates and egg reduction in treatment of intestinal schistosomiasis with oxamniquine and praziquantel in Maniema, Zaire. Transactions of the Royal Society of Tropical Medicine and Hygiene 1988;82(1):115-6.
Utzinger 2000a {published data only}
Utzinger 2000b {published data only}
van Lieshout 1994 {published data only}
  • van Lieshout L, de Jonge N, el-Masry N, Mansour MM, Bassily S, Krijger FW, et al. Monitoring the efficacy of different doses of praziquantel by quantification of circulating antigens in serum and urine of schistosomiasis patients. Parasitology 1994;108(Pt 5):519-26.

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
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