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Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin and school performance

  1. David C Taylor-Robinson1,*,
  2. Nicola Maayan2,
  3. Karla Soares-Weiser2,
  4. Sarah Donegan1,
  5. Paul Garner1

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 11 JUL 2012

Assessed as up-to-date: 31 MAY 2012

DOI: 10.1002/14651858.CD000371.pub4

How to Cite

Taylor-Robinson DC, Maayan N, Soares-Weiser K, Donegan S, Garner P. Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin and school performance. Cochrane Database of Systematic Reviews 2012, Issue 7. Art. No.: CD000371. DOI: 10.1002/14651858.CD000371.pub4.

Author Information

  1. 1

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

  2. 2

    Enhance Reviews Ltd, Wantage, UK

*David C Taylor-Robinson, International Health Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, Merseyside, L3 5QA, UK. David.Taylor-Robinson@liverpool.ac.uk.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 11 JUL 2012

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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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

 
Summary of findings for the main comparison. Multiple dose deworming drugs for treating soil-transmitted intestinal worms in children: effects on nutrition and school performance (outcomes measured more 1 year)

Multiple dose deworming drugs for treating soil-transmitted intestinal worms in children: effects on nutrition and school performance (outcomes measured more 1 year)

Patient or population: Children
Settings: Communities living in areas endemic for intestinal helminths
Intervention: Multiple dose deworming drugs

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of randomized units
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlMultiple dose deworming drugs

Weight (kg)
Follow-up: 1.5 to 3 years
See comment1347
(5 studies)
⊕⊝⊝⊝
very low1,2,3
One study Awasthi 2008 (Cluster) showed a very large effect of 0.980 kg average difference in weight gain - with all the others with small average non significant differences of less than 0.2 kg

302 clusters and 1045 individually randomized participants

Height (cm)
Follow-up: 1.5 to 2 years
The mean height (cm) in the intervention groups was
0.26 lower
(0.84 lower to 0.31 higher)
1219
(3 studies)
⊕⊝⊝⊝
very low3,4
174 clusters and 1045 individually randomized participants

Haemoglobin (g/dL)
Follow-up: 14 months to 2 years
The mean haemoglobin (g/dL) in the intervention groups was
0.02 lower
(0.3 lower to 0.27 higher)
1365
(2 studies)
⊕⊝⊝⊝
very low3,5

Formal tests of cognition
Follow-up: 2 years
See commentSee commentNot estimable(2 studies)⊕⊝⊝⊝
very low6
Two trials reported on formal tests of intellectual development but not in a form that could be added to the meta-analysis.7

School attendance

Follow-up: 2 years
The mean attendance (%) in the intervention group was
5 higher

(-0.5 lower to 10.5 higher)
1 study⊕⊝⊝⊝

very low8
50 clusters

DeathUnable to report result as trial unpublished91 study

(one million children)

*The basis for the assumed risk (eg the median control group risk across studies) is provided in 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;

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 Awasthi 2000 and Awasthi 2008 (Cluster) have a high risk of bias for sequence generation and allocation concealment. Alderman 2006 (Cluster) and Awasthi 2008 (Cluster) have a high risk of bias for blinding. Alderman 2006 (Cluster) has a high risk of bias for incomplete outcome reporting.
2 A high level of heterogeneity was found for this outcome.
3 The 95% CIs around the pooled effect estimate include both significant benefit and harm of intervention.
4 Awasthi 2000 and Awasthi 2008 (Cluster) have a high risk of bias for sequence generation and allocation concealment. Awasthi 2008 (Cluster) has a high risk of bias for blinding.
5 Awasthi 2000 and Kirwan 2010 have a high risk of bias for sequence generation and allocation concealment.
6Awasthi 2000 and Hall 2006 (Cluster) did not fully report data for this outcome. Awasthi 2000has a high risk of bias for sequence generation and allocation concealment.
7 Awasthi 2000, with a follow-up of two years, reported that there was no difference in development between treatment groups in terms of proportion with "normal" development. Hall 2006 (Cluster), with a follow-up of two years, reported that there were no statistically significant differences in the results of formal tests of intellectual development at the start or end of the study.
8Miguel 2004 (Cluster) has a high risk of bias for sequence generation, allocation concealment, blinding, incomplete outcome data and baseline imbalance.
9DEVTA (unpublished) remains unpublished despite completion in 2005.

 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Description of the condition

The three soil-transmitted helminth (STH) infections, ascariasis (roundworm), trichuriasis (whipworm), and hookworm, are the main intestinal helminth infections in humans (Bethony 2006; de Silva 2003b). Specialists estimate that each type of infection causes between 600–800 million cases worldwide each year (Hotez 2009, de Silva 2003b), with more than a quarter of the world's population infected with one or more of the soil-transmitted intestinal worms (Chan 1997). Estimates from 2003 suggest that global prevalence of STH infections is declining, with marked improvement in the Americas and Asia, but a static picture in sub-Saharan Africa (de Silva 2003b). STH infections particularly affect children living in poverty, where inadequate sanitation, overcrowding, low levels of education, and lack of access to health care make them particularly susceptible (Bethony 2006, de Silva 2003b). In 1993, the World Bank ranked soil-transmitted helminth infection as a greater cause of ill health in children aged 5 to 15 years than any other infection (World Bank 1993), but there has been considerable variation in the quoted estimates of global burden (de Silva 2003b), which are currently being updated.

Policy makers are concerned that the long-term effects of worm infestation impair childhood nutritional status, school performance, and long-term cognitive development (Bethony 2006). It is thought that iron status may mediate these effects, since hookworm and whipworm disease are associated with iron-deficiency anaemia (Crompton 2000; de Silva 2003a), and a fall in blood haemoglobin levels is associated with increasing intensity of infection (Crompton 2003). Furthermore, hookworm-induced iron-deficiency anaemia has been associated with decreased physical activity and worker productivity (Crompton 2003).

Worms are associated with malnutrition, impaired growth, and poor school performance. Roundworms obtain their nutrition from gastrointestinal contents. The association with malnutrition is possibly mediated through impaired fat digestion, reduced vitamin absorption (particularly vitamin A), and temporary lactose intolerance (WHO 2002). Whipworm infection has been associated with malnutrition, although the precise mechanism for this is unclear (Cappello 2004). Some suggest that the effects on nutrition are through appetite suppression, increased nutrient loss, and decreased nutrient absorption and utilization (Stephenson 2000; de Silva 2003a).

Roundworm, hookworm, and whipworm disease have all been associated with impaired growth in school children (de Silva 2003a). Observational studies have reported an association between worm infection and lower scores on tests of school performance (Sakti 1999; Kvalsvig 2003). In a multiple-regression model based on cross-sectional data, Sakti 1999 found that hookworm infection was associated with worse scores in six out of 14 cognitive tests in Indonesian school children. Severe whipworm (Trichuris dysentery syndrome) was associated with low IQ, school achievement, and cognitive function after a four-year follow up of a specific group of Jamaican children with severe infection (Callender 1998).

While these associations would suggest potential benefits of deworming, the associations could equally be caused by the confounding factor of poverty. Even with adjustment for known confounding factors, residual confounding could be a problem. Furthermore, the causal link between chronic infection and impaired childhood development is extrapolated from the recorded improvement in these features after deworming (Bethony 2006). Hence, reliable randomized controlled trials are required to assess whether policies are effective. These can examine the effectiveness of treating worm infection in an individual, as evidence of efficacy, and treatment in schools or communities, as evidence of the effectiveness of programmes. The latter studies are ideally cluster-RCTs, and thus able to detect any externalities (benefits to other children) accruing as a result of reduced transmission.

 

Description of the intervention

Public health interventions to tackle worm infection include those that improve sanitation and hygiene, or those that administer drug therapy to populations or targeted groups in the community, often coupled with health education. The work of the Rockefeller Sanitary Commission in the early 1900s led to the recognition that sanitary reform was needed alongside chemotherapeutic approaches to have an effect on worm prevalence (Horton 2003). In Japan, worms virtually disappeared over a 20-year period after the Second World War; this has been credited to an integrated programme of sanitary reform combined with screening and treatment of positive cases (Savioli 2002; Horton 2003). A similar experience occurred in Korea (Savioli 2002). The current global decline in worm prevalence has been credited to economic development and deworming programmes (de Silva 2003b). The impact of the chemotherapeutic element is difficult to assess. In countries where an improvement in sanitation and hygiene has occurred as a component of economic growth, a parallel decline in the prevalence of geohelminths has occurred: for example, in Italy, between 1965 and 1980, the trichuriasis prevalence dropped from 65% to less than 5% without control activity (Savioli 2002).

 The World Health Organization (WHO) policy outlines three categories of public health drug treatment policies (WHO 2002):

  • Selective: individual deworming based on a diagnosis of infection.

  • Targeted: group deworming where a (risk) group is treated without prior diagnosis.

  • Universal: population deworming in which the whole community is treated irrespective of infection status.

The WHO and others promote targeted treatment. They do not recommend individual screening since the cost is four to 10 times that of the treatment itself. The policy's aim appears to be to control morbidity by reducing the intensity of infection in the most vulnerable populations. The strategy is to target drug treatment at groups: pre-school-age children (between one and five years); school-age children (between six and 15 years); and women of childbearing age. The strategy requires a population survey for prevalence and intensity of infection to determine the population worm burden. This determines the recommended frequency of treatment, updated in a WHO field manual in 2006: once per year for low-risk communities with 20 to 50% prevalence, or twice per year for high-risk communities with >50% prevalence (WHO 2006b).

The policy promotes the use of schools, maternal and child health clinics, and vaccination campaigns to reach at-risk groups. The WHO advocate school-based programmes in particular, as it is easy to deliver medicines through teaching staff, with estimated costs varying from US$ 0.05 to 0.65 per child per year for annual dosing (Savioli 2002; WHO 2002). In areas with a high prevalence, the current policy recommends treatment three times per year (WHO 2006b), based on modelling and reinfection prevalence studies. Following drug treatment worm populations tend to return rapidly to pretreatment levels; in less than a year for roundworm and whipworm (Anderson 1991). Anderson 1991 suggests that to control morbidity in areas of endemic infection, targeted treatment should be repeated every three to four months for roundworm and whipworm, with longer intervals acceptable for longer-lived species such as hookworm. The WHO recommends monitoring with a range of impact indicators, including prevalence and intensity, incidence, morbidity and mortality (WHO 2010). The control programme is intended to reduce the worm burden in the 10% to 15% of children who are most heavily infected in a particular population and to keep it low through repeated treatments.

It is also argued that treating individuals in communities reduces transmission in the community as a whole (Anderson 1991), and that this can lead to health and schooling benefits for the whole population, including those who have not received deworming treatment (Bundy 2009). These 'spill over' effects, or externalities, are not captured in individually randomized control trials, since any benefit in the control group reduces the overall treatment effect. A cluster design is therefore required to identify these additional putative effects.

 

How the intervention might work

It is argued that deworming programmes improve nutrition, haemoglobin, and cognition. As a result of these benefits, children are thought to have increased physical well being, with improved intellect, and are better able to attend school. As a result, performance at school is enhanced, and mortality is reduced; over the long-term this benefits society as a whole, and reduces poverty (Figure 1) (WHO 2005).

 FigureFigure 1.

In this review, the primary outcomes sought are the main effects (increased haemoglobin, nutrition, and improved cognition); measurable aspects of the mediating pathways (school attendance and physical well being); and measurable aspects of impact (mortality and school performance; Figure 1 ).

Clinical observation of treating children heavily infected with worms indicated weight gain was sometimes marked, and so in this review we include community studies that measure effects after a single dose of deworming drugs ('efficacy' measures in the individual), as well as studies of multiple doses with follow-up under a year (showing early benefits) and studies with follow-up beyond a year. The latter studies are likely to detect externalities and potential long term benefits.

 

Why it is important to do this review

The intended impacts of deworming programmes – to reduce mortality, and increase children's long term economic productivity – are clearly worthwhile goals and are heavily promoted by advocates in the field such as the WHO (Montresor 2002; WHO 2002; WHO 2006b), and the World Bank (World 2011). Furthermore, deworming with albendazole was recently endorsed in the 2012 Copenhagen consensus statement, as the 4th highest ranking solution to address 'big issues facing the planet' in terms of cost and benefit (Copenhagen Consensus Center 2012). The widely-cited cost-effectiveness estimates from the Disease Control Priorities in Developing Countries (DCP2) report (Jamison 2006) state that deworming for STH infections was one of the most cost-effective interventions for global health. The reliability of these estimates, however, has been questioned recently by the organization GiveWell, which suggests they have been overstated by a factor of about 100 (GiveWell 2011).

Advocates point to the favourable cost-effectiveness estimates for deworming programmes, with a focus on the putative effect on schooling outcomes, and productivity (Deworm the World 2012). The evidential basis for this draws on a range of study designs, including historical econometric studies such as Bleakely 2004, which analysed the Rockefeller Sanitary Commission's campaign to eradicate hookworm in the American South. This showed an association between areas with higher levels of hookworm infection prior to the campaign and greater increases in school attendance and literacy after the intervention, and an association with income gains in the longer-term. Another influential study is Miguel 2004 (Cluster), which is included in this review.

Current policies have become even more challenging to assess, as global specialists conflate the evidence on different helminths. Some advocates describe the benefits of treating all helminths, including schistosomiasis, filariasis, and STH infections. For example, the WHO states that deworming treatment against schistosomes and STH infections helps (1) eradicate extreme poverty and hunger; (2) achieve universal primary education; (3) promote gender equality and empower women; (4) reduce child mortality and improve maternal health; and (5) combat HIV/AIDS, malaria, and other diseases (WHO 2005). The evidence for the benefit of treating populations with schistosomiasis is fairly clear (Danso-Appiah 2008), as the infection has a very substantive effect on health. However, this does not mean that a different drug treating a different helminth species is equally effective.

Despite the lack of rigour in considering the evidence for separate components of these policies, they are moving forward globally with large scale purchases of drugs. The current Neglected Tropical Disease (NTD) policy focus has been on addressing 'polyparasitism' by treating the parasites that cause ascariasis, trichuriasis, hookworm, lymphatic filariasis, onchocerciasis, schistosomiasis, and trachoma with ivermectin, albendazole, azithromycin, and praziquantel (Hotez 2009). These four drugs are donated by pharmaceutical companies, and the 'overlapping specificity' would mean multiple pathogens would be targeted (Hotez 2006b). Thus, mass drug administration for NTDs is promoted as "one of the lowest cost and cost-efficient mechanisms for both improving maternal child health and lifting the bottom billion out of poverty" (Hotez 2011b). Significant resources are being invested in this agenda, with the UK Department for International Development committing £50 million in 2008, and the US government (USG) committing US$65 million in 2010 as part of the US Global Health Initiative (GHI) (Hotez 2011a).

Given the amount of investment of public money in these programmes, it is important to be clear whether mass or targeted drug administration is able to contribute to health and development in such a substantive way – not least because if it does then major investment is justified. Indeed, international donors and developed country governments and tax payers are contributing to the efforts to tackle STH infections in the belief that they will improve the health of children in the way that the WHO claim (WHO 2005).

Thus this review of reliable evidence from controlled trials will help delineate whether there is an impact of these drugs in populations with STH infections (ascariasis, trichuriasis, and hookworm).

 
History of this review

In 2007, we systematically reviewed the reliable evidence from controlled trials about the effects of anthelminth drugs for STH infection on child growth and cognition (Taylor-Robinson 2007). This systematic review demonstrated uncertainty around the assumed benefit and concluded that deworming may be effective in relation to weight gain in the short-term in some areas, but not in others; the potential long-term impact on weight was unclear. For school performance, data were very limited, and no convincing treatment effect was demonstrated.

New trials have been recently published, and other unpublished studies have been made available to us. In this review update, we have reapplied the inclusion criteria, repeated data extraction, added new trials, added haemoglobin as a primary outcome, restructured the analysis, and used GRADE to assess the quality of the evidence. We were also able to:

  • combine trials with nutritional outcomes as change and end values in the same meta-analysis, as this has been shown to be valid.
  • stratify the analysis by endemicity of worms, as the policy question is whether deworming should be given in all areas, or only high prevalence areas.

In addition, following correspondence with the authors of a large study that measured schooling as an outcome, we have included this in the current edition (Miguel 2004 (Cluster)).

Unfortunately, we have been unable to include a trial of over a million children completed in 2005 (DEVTA (unpublished).This is despite our best efforts in trying to elicit public disclosure of the results.

This Cochrane Review does not cover deworming and pregnancy, which is covered elsewhere (Haider 2009).

 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

In deworming programmes for soil-transmitted intestinal worms (nematode geohelminths) in children, to summarise the effects on nutritional indicators, haemoglobin, cognition, school attendance; and the impacts on school performance and mortality.

 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomized and quasi-randomized controlled trials (RCTs). We included cluster-RCTs, provided more than two clusters were allocated to each treatment arm.

 

Types of participants

Children aged 16 years or less in community studies. We excluded trials of sick children or children being treated for malnutrition.

 

Types of interventions

 

Intervention

Deworming drugs for geohelminth worms, administered at any location (including health facilities, schools, and communities). We included studies examining effects after a single dose, and after multiple doses.

The deworming drugs we included are those included in the WHO Model List of Essential Medicines for deworming drugs of geohelminths (WHO 2006a). This includes albendazole, levamisole, mebendazole, pyrantel, and ivermectin. Other drugs used are nitazoxanide, piperazine, tetrachlorethylene, and thiabendazole.

We included studies that provided health education to the intervention arm alone. Studies that provided other additional interventions (eg growth monitoring, micronutrient supplementation, malaria chemoprevention, or other drugs) were included when the additional intervention was given to both the control and intervention arm.

 

Control

Placebo or no treatment.

 

Types of outcome measures

 

Primary

  • Weight.
  • Haemoglobin.
  • Psychometric tests of cognition.

 

Secondary

  • Other nutritional indicators:
    • Height.
    • Mid-upper arm circumference.
    • Skin fold thickness (eg tricep and subscapular skin fold).
    • Body mass index.
  • Measures of physical well being (eg Harvard Step Test).
  • School attendance:
    • Days present at school.
    • Number of children dropping out.
  • School performance (measured by examination results).
  • Death.

 

Adverse events

  • Serious adverse events (death, life-threatening events, or events leading to hospitalisation).
  • Other adverse events.

 

Search methods for identification of studies

The authors along with the Cochrane Infectious Diseases Group Information Specialist attempted to identify all relevant trials regardless of language or publication status (published, unpublished, in press, and in progress).

The Information Specialist searched the following databases using the search terms and strategy described in  Table 1: Cochrane Infectious Diseases Group Specialized Register (15 February 2012); Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (2011, Issue 4); MEDLINE (2000 to 15 February 2012); EMBASE (2000 to 15 February 2012); and LILACS (2000 to 15 February 2012). The metaRegister of Controlled Trials (mRCT) was also searched using 'helminth* OR anthelminth*' (15 February 2012).

We also searched the same databases for the effect of administration of deworming drugs on haemoglobin, using the search terms listed in  Table 2. This additional search was conducted in February 2012.

In addition, we drew on existing reviews of the topic and we checked the citations of all the trials identified by the above methods. We also re-appraised the studies identified in the previous versions of this review (Dickson 2000a; Taylor-Robinson 2007).

 

Data collection and analysis

 

Selection of studies

David Taylor-Robinson (DTR) checked the results of the search for potentially relevant trials and retrieved full articles as required. DTR and Paul Garner (PG) independently assessed the trial eligibility using an eligibility form based on the inclusion criteria; where there was uncertainty, all five authors participated in the decision about inclusion. We checked that trials with multiple publications were managed as one study. We recorded reasons for the exclusion of studies and we contacted authors of unpublished studies for information on when they intended to publish their results.

 

Data extraction and management

DTR, Nicola Maayan (NM), Sarah Donegan (SD), and Karla Soares-Weiser (KSW) independently extracted data using data extraction forms. PG extracted and cross-checked the data from a selection of papers. We resolved any differences in opinion by discussion. Where methods, data, or analyses were unclear or missing, we contacted authors for further details.

For each treatment group of each trial, we extracted the number of patients randomized. For each outcome of interest, we extracted the number of participants analysed in each treatment group of each trial.

 

RCTs that randomize individuals

For dichotomous outcomes, we planned to extract the number of patients with the event. For continuous outcomes, we aimed to extract means and standard deviations. Where these data were not reported, we extracted medians and ranges or any other summary statistics. Where change from baseline results were presented alongside results purely based on the end value, we only extracted the change from baseline results.

 

RCTs that randomize clusters

For each cluster-RCT, we extracted the cluster unit, the number of clusters in the trial, the average size of clusters, and the unit of randomization (eg household or institution). Where possible, we extracted the statistical methods used to analyse the trial along with details describing whether these methods adjusted for clustering or other covariates. When reported, estimates of the intra-cluster correlation coefficient (ICC) for each outcome were extracted.

Where a cluster-RCT adjusted for clustering in their analysis, we extracted the cluster adjusted results. When the trial did not account for clustering in their analysis, we extracted the same data as for trials that randomize individuals.

 

Assessment of risk of bias in included studies

DTR, PG, NM, SD, and KSW independently assessed the risk of bias (Higgins 2011b). Differences were resolved by discussion. On occasion, we corresponded with trial investigators when methods were unclear.

For RCTs that randomized individuals we addressed six components: sequence generation; allocation concealment; blinding; incomplete outcome data; selective outcome reporting; and other biases. For RCTS randomized by cluster, we addressed additional components: recruitment bias; baseline imbalance; loss of clusters; incorrect analysis; compatibility with RCTs randomized by individual. For each component, we placed judgments of low, high, or unclear/unknown risk of bias as described in Appendix 1. We displayed the results in risk of bias tables, a risk of bias summary, and a risk of bias graph.

 

Measures of treatment effect

Continuous data (means and standard deviations) were summarised using the mean differences. We planned to use the risk ratio to compare the treatment and control groups for dichotomous outcomes. All treatment effects were presented with 95% Confidence Intervals (CIs).

 

Unit of analysis issues

For a particular cluster-RCT when the analyses had not been adjusted for clustering, we attempted to adjust the results for clustering by estimating the design effect calculated as 1+(m-1)*ICC where m is the average cluster size and ICC is the intra-cluster correlation coefficient. To make the adjustment, we estimated a treatment effect that did not adjust for clustering and then multiplied the standard errors of the estimate by the square root of the design effect. When the true ICC was unknown, we estimated it from other included cluster-RCTs.

 

Dealing with missing data

We aimed to conduct a complete-case analysis in this review, such that all patients with a recorded outcome were included in the analysis.

 

Assessment of heterogeneity

We inspected the forest plots to detect overlapping CIs, applied the Chi2 test with a P value of 0.10 used to indicate statistical significance, and also implemented the I2 statistic with values of 30 to 60%, 59 to 90%, and 75 to 100% used to denote moderate, substantial, and considerable levels of heterogeneity, respectively.

 

Assessment of reporting biases

We decided not to construct funnel plots to look for evidence of publication bias because there were a limited number of trials in each analysis.

 

Data synthesis

KSW, NM, DTR, and SD analysed data with Review Manager 5. The analysis was structured into five sections:

Screened for infection: included trials that only included children who were identified as infected

  • after a single dose;
  • after multiple doses (outcomes measured in the first year).

Target population treated: included trials that included screened and unscreened children

  • after a single dose;
  • after multiple doses (outcomes measured in the first year);
  • after multiple doses (outcomes measured after the first year).

In the analyses of the target population, we stratified the analysis into three categories based on prevalence and intensity: High prevalence or high intensity areas (referred to as 'high prevalence'); moderate prevalence and low intensity (referred to as 'moderate prevalence'); and low prevalence with low intensity (referred to as 'low prevalence'). We used the WHO technical guidelines classification (WHO 2002;  Table 3), rather than the simplified prevalence based field guide categories that are now used to determine treatment frequency (WHO 2006b;  Table 3). In trials where information on intensity was not provided, we estimated the community category on the basis of quoted prevalence; it is possible that the community category has been underestimated in these trials (as per  Table 3).

Cluster-RCTs that adjusted for clustering and RCTs that randomized individuals were combined using meta-analysis. We presented results of cluster-RCTs that were not adjusted for clustering in an additional table. We used a fixed-effect meta-analysis when the assessments of heterogeneity did not reveal heterogeneity. In the presence of heterogeneity, random-effects meta-analysis was used.

For continuous data, we combined change from baseline results with end value results providing they were from distinct trials (Cochrane Collaboration 2002; Higgins 2011a). Labels on the meta-analyses indicate when end values were used.

We presented data that could not be meta-analysed in additional tables and reported on in these each section, under a heading, 'other data'.

 

Subgroup analysis and investigation of heterogeneity

In the presence of statistically significant heterogeneity, we planned to explore the following potential sources using subgroup analyses: age group (< five years versus ≥ five years); manufacturer; treatment setting (community, school, health post, hospital). We did not carry out these analyses because there were too few studies in the analyses.

 

Sensitivity analysis

We carried out sensitivity analyses including only those trials with a low risk of bias regarding allocation concealment.

 

Summary of findings table

We interpreted results using a summary of findings (SOF) table, which provides key information about the quality of evidence for the included studies in the comparison, the magnitude of effect of the interventions examined, and the sum of available data on the main outcomes. Data were imported from Review Manager 5 using the GRADE profiler (GRADE 2004). We selected the primary outcomes for the review in the SOF, and added height, school attendance, and death for multiple dose comparisons. Thus, our SOF table included:

  • Weight (kg)
  • Height (cm) (for Comparison 4: Multiple dose, outcomes measured > 1 year only)
  • Haemoglobin (g/dL)
  • Psychometric tests of cognition.
  • School attendance (for Comparison 4: Multiple dose, outcomes measured < 1 year only; and Comparison 5: Multiple dose, outcomes measured > 1 year only)
  • Death (for Comparison 5: Multiple dose, outcomes measured > 1 year only): awaiting publication (DEVTA (unpublished).

In addition, physical fitness was measured in two studies after one dose of deworming medicine, and this measure was also included in the SOF table for this comparison only.

 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Description of studies

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

We identified 42 trials reported in 53 articles that met the inclusion criteria (see Characteristics of included studies); this includes one study of one million children, completed in 2005, for which we are unable to report outcomes because it has not yet been published (DEVTA (unpublished)). A second study, completed in 2006, has never been published, but we were able to use the data from the manuscript supplied by the authors (Hall 2006 (Cluster)).

For Alderman 2006 (Cluster), the authors did not adjust the CIs to take into account clustering for the primary outcome. For this review, we used the corrected values supplied by the author.

Thirty-eight trials were excluded (see Characteristics of excluded studies), and two trials are ongoing (see Characteristics of ongoing studies).

 

Location

The included trials were undertaken in 23 different countries: Bangladesh (four trials); Ethiopia (two trials); Haiti (two trials); India (five trials); Indonesia (two trials); Jamaica (two trials); Kenya (five trials); South Africa (two trials); Vietnam (three trials); Zanzibar (two trials); Benin, Botswana, Cameroon, Guatemala, Java, Malaysia, Nigeria, Philippines, Sierra Leone, Tanzania, Uganda, Zaire (one trial in each); China, Philippines and Kenya (one multicentre trial).

 

Population

Children were recruited from school populations in 20 trials, communities in 16 trials, and in health facilities or by health workers in six trials. One of these recruited children on discharge from hospital (Donnen 1998). Olds 1999 also included adolescents 17 to 19 years, but the participants were predominantly under 16 years old.

Thirty-five trials were based on mass targeted treatment of an unscreened population. Fourteen trials were conducted in populations where worms were of high prevalence or intensity (community category 1), 10 in populations with moderate prevalence and low intensity (category 2), and 11 in populations with low prevalence and low intensity (category 3). Seven trials studied children that were screened and selected on the basis of their having high worm loads (Freij 1979a; Freij 1979a; Kvalsvig 1991a; Nokes 1992; Adams 1994; Simeon 1995; Sarkar 2002), and the purpose of three of these trials was to measure cognitive outcomes (Kvalsvig 1991a; Nokes 1992; Simeon 1995). Stephenson 1993 also studied an infected subgroup of the larger unscreened study population for cognitive and haemoglobin outcomes.

 

Interventions

 

Albendazole studies

 

Other anthelminths

 

Control groups

Placebo or no treatment was used as a control in the majority of studies (see Characteristics of included studies). Others used vitamin A (Donnen 1998), vitamin C (Beach 1999; Fox 2005), or calcium powder (Awasthi 2000).

There were 13 trials where both the treatment and control group received nutritional supplementation: multi-nutrient (Kruger 1996, Nga 2009, Solon 2003); vitamin B (Sur 2005); iron (Dossa 2001, Le Huong 2007, Palupi 1997, Stoltzfus 2001); vitamin A (Awasthi 2001 (Cluster); Awasthi 2008 (Cluster); Hall 2006 (Cluster);  DEVTA (unpublished)); or child health package (Alderman 2006 (Cluster)).

 

Study design

Eight trials were cluster randomized (Alderman 2006 (Cluster); Awasthi 2008 (Cluster); Awasthi 2001 (Cluster); DEVTA (unpublished); Hall 2006 (Cluster); Rousham 1994 (Cluster); Stoltzfus 1997 (Cluster)), one was a study with quasi-random allocation of the 75 clusters (Miguel 2004 (Cluster)). The rest used the individual as the unit of randomization.

Five out of the eight cluster-RCTs used an appropriate method to take clustering into account. Awasthi 2001 (Cluster) and Awasthi 2008 (Cluster) used urban slums as the unit of randomization (50 and 124 respectively), and DEVTA (unpublished) used 72 rural administrative blocks. These three trials were analysed at the cluster level (mean of cluster mean values and associated standard deviations). Stoltzfus 1997 (Cluster) randomized 12 schools and adjusted for within-school correlations using generalized estimating equations. Miguel 2004 (Cluster) adjust for clustering in their regression estimates, and present robust standard errors.

We encountered problems with the adjustment in the three remaining cluster-RCTs:

  • Alderman 2006 (Cluster) had not adjusted the primary outcome for clustering in this study of 48 parishes containing 27,955 children in total. The authors upon request sent us the adjusted values which we have used in the analysis.
  • Hall 2006 (Cluster) had 80 units of randomization (schools) containing 2659 children in total, and had not adjusted for clustering. We used the ICC calculated from the Alderman data to adjust the primary weight outcome for inclusion in meta-analysis. As the average cluster size for Hall 2006 (Cluster) (ie 33 children) differed somewhat from that of Alderman 2006 (Cluster) (ie 582 children), the true ICC for Hall 2006 (Cluster) may be different to that of Alderman 2006 (Cluster), therefore the adjusted result for weight is merely an approximation.
  • Rousham 1994 (Cluster) had 13 units of randomization (villages) containing 1476 children in total and had also not adjusted for clustering, but no outcomes from this study were suitable for meta-analysis.

Four trials had a factorial design. DEVTA (unpublished) randomized clusters to usual care, six-monthly vitamin A, six-monthly 400 mg albendazole, and both vitamin A and albendazole. Kruger 1996 randomized individual participants to albendazole or placebo, and, also, three of the five schools in the trial received soup fortified with vitamins and iron, and two received unfortified soup. Le Huong 2007 randomized individual participants to iron-fortified noodles and mebendazole, noodles without iron fortification and mebendazole, iron-fortified noodles and placebo, noodles without iron fortification and placebo, and iron supplementation and mebendazole. Stoltzfus 2001 randomized households to iron, with random allocation of mebendazole by child, stratified by iron allocation and age grouped households; disaggregated data for each treatment allocation group was not provided for each outcome.

Follow-up periods for the trials that used a single dose ranged from one to 11 months, while the follow-up periods for trials that used multiple doses ranged from six months to 5 years.

Miguel 2004 (Cluster) included 75 schools with a total of 30,000 pupils enrolled. The intervention was a deworming package that was phased over time. The package included public health lectures, wall charts, teacher education, and health education in handwashing. In addition, a number of schools in the study were also mass treated for schistosomiasis. We previously excluded this study on the basis of confounding by schistosomiasis treatment. We received clarification from the authors that allowed inclusion of the study in this review update. The authors kindly provided data excluding 17 of the 75 schools that were mass treated for schistosomiasis. Overall, this analysis showed very similar results so we have included the data from the published paper.

In Miguel 2004 (Cluster), there were two potential quasi-randomized comparisons, one in 1998 and one in 1999. Included schools were stratified by zone, their involvement with other NGO programmes, and then listed alphabetically and every third school assigned to start the programme in 1998, to start it in 1999, or to be a control. The schools were thus divided into three groups: Group 1 schools were in the treatment group throughout; Group 2 schools were in the control group for the 1998 comparison, but in the treatment group in the 1999 comparison; Group 3 schools were in the control group throughout. Two comparisons were thus identified: Group 1 schools versus Group 2 and 3 schools in 1998; and Group 1 and 2 schools versus Group 3 schools in 1999.

The authors clarified that there were no health outcome data for Group 3 schools for 1999. This left one quasi-randomized comparison with contemporary health information in both treatment and control, which was 1998, Group 1 versus Group 2 and 3. However, results for health outcomes were presented for the 1998 comparison of Group 1 (25 schools) versus Group 2 (25 schools).

Details of the outcomes we extracted and present are:

  • Haemoglobin. This was measured in 4% of the randomized population (778/20,000). It was unclear how the sample were selected.
  • Weight and height. This was measured in an unknown sample of the 20,000 children. No sampling method was given.
  • School attendance with up to a year follow-up was calculated as the weighted average school participation rate among all pupils enrolled, comparing Group 1 to Groups 2 and 3 (1998), and Group 2 versus Group 3 (1999), with approximately 20,000 children per group. Pupils present on the day of an unannounced NGO visit were considered participants. Pupils had 3.8 observations on average per year. School attendance with follow up over one year was also reported in 1999, comparing Group 1 and Group 3. However, the authors did not give any baseline values for attendance, so it was not possible to know whether differences detected are the results of the intervention or random differences in average attendance between groups.
  • Exam performance was measured, but the authors did not provide the results by the quasi-randomized comparisons eligible for this review, and it was unclear how many children contributed to this outcome (1998 Group 1 versus Group 2 and 3; 1999 Group 1 and 2 versus Group 3).

Cognitive tests results were collected in 2000 for all three groups, but the authors did not report these results.

 

Outcome measures

 

Nutritional outcomes

Nutritional indicators were measured in 42 trials. Some trials reported absolute values, or changes in absolute values of weight and height (or other anthropometric measures). Many trials presented anthropometric data in terms of z-scores or percentiles of weight-for-age, weight-for-height, and height-for-age, and compared the trial results to an external reference. Sometimes these values were dichotomised and presented as the prevalence of underweight, stunting or wasting (defined as -2SD z-scores). The external standard was usually quoted as the National Centre for Health Statistics (NCHS) standard, but a variety of references was quoted (eg anthropometric computer packages or country standards). These data have not been used in the meta-analyses as the results were already incorporated in the values for weight and height. Furthermore, in some trials, outcome data were not reported or were incomplete and could not be used in meta-analysis. A number did not report summary outcome data for each trial arm, and the results were reported in terms of regression modelling outcomes or subgroup analyses. The results of these trials are described in  Table 4.

 

Haemoglobin

Seventeen trials measured haemoglobin. Of these, two trials did not report the measured haemoglobin results (Olds 1999; Solon 2003), two trials only measured this outcome in a subset of the participants (DEVTA (unpublished), Miguel 2004 (Cluster)) and one trial did not report results by randomized comparisons (Stephenson 1993).

 

Psychometric tests of cognition

Nine trials measured intellectual development using formal tests.

 

Measures of physical well being

Two studies (Stephenson 1989; Stephenson 1993) measured physical well being using the Harvard Step Test.

 

School attendance

Three trials measured school attendance.

 

School performance

Exam performance was measured by Miguel 2004 (Cluster).

 

Death

DEVTA (unpublished) provided data on mortality.

 

Adverse events

Two trials provided information on adverse events (Michaelsen 1985; Fox 2005).

 

Risk of bias in included studies

See Figure 2 and Figure 3 for Summaries of the risk of bias and Characteristics of included studies' for details of the risk of bias and methods used in each trial.

 FigureFigure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
 FigureFigure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

 

Generation of sequence

In the 35 individually randomized trials, the risk of bias was low in 10 trials (see Figure 2 and Figure 3), high in five, and unclear in the other trials. For the eight cluster-RCTs, the risk of bias was low in one trial (Alderman 2006 (Cluster)), high in two trials (Awasthi 2008 (Cluster); Miguel 2004 (Cluster) ) and unclear in five trials.

 

Allocation concealment

For the 35 individually randomized trials, the risk of bias was low in seven trials (Fox 2005; Garg 2002; Le Huong 2007; Nga 2009; Olds 1999; Stoltzfus 2001; Sur 2005), high in two trials (Awasthi 2000; Kirwan 2010), and unclear in the other trials.

The risk of bias was low in one of the eight cluster-RCTs (Hall 2006 (Cluster)), high in two trials (Awasthi 2008 (Cluster); Miguel 2004 (Cluster)), and unclear in the remaining five trials.

 

Blinding

Fifteen trials were double blinded (Beach 1999; Fox 2005; Goto 2009; Kirwan 2010; Le Huong 2007; Nga 2009; Olds 1999; Rousham 1994 (Cluster); Sarkar 2002; Solon 2003; Stephenson 1989; Stephenson 1993; Sur 2005; Watkins 1996; Willett 1979) and judged to be at a low risk of bias. Five trials were at high risk of bias as they did not use blinding (Alderman 2006 (Cluster); Awasthi 2008 (Cluster); Garg 2002; Lai 1995; Miguel 2004 (Cluster)). Details of blinding were unclear in the remaining 22 trials.

 

Incomplete outcome data

Twenty-four trials had a low risk of bias for incomplete outcome data (Adams 1994; Awasthi 2000; Awasthi 2001 (Cluster); Awasthi 2008 (Cluster); Beach 1999; Donnen 1998; Fox 2005; Freij 1979b; Garg 2002; Goto 2009; Greenberg 1981; Hadju 1996; Le Huong 2007; Lai 1995; Nga 2009; Palupi 1997; ; Rousham 1994 (Cluster); Sarkar 2002; Simeon 1995; Stephenson 1989; Stephenson 1993; Stoltzfus 1997 (Cluster); Sur 2005; Watkins 1996), in seven trials the risk of bias was unclear (DEVTA (unpublished); Freij 1979a; Hall 2006 (Cluster); Kloetzel 1982; Kvalsvig 1991a; Olds 1999; Solon 2003), and in the remaining trials there was a high risk of bias.

Overall, the percentage of randomized participants that were evaluable ranged from 4% to 100%, with 18 trials including 90% or more of the randomized participants (low risk cut-off). The percentage was particularly low in two of the trials measuring school performance and cognitive outcomes: 73% in Nokes 1992; and 52% in Stoltzfus 2001, and in one trial measuring haemoglobin: 26% in Kirwan 2010. In Miguel 2004 (Cluster), for haemoglobin approximately 4% (778/20,000) of eligible participants were assessed, but it is unclear how these were selected, and for nutritional outcomes the number assessed was unclear.

 

Selective outcome reporting

Thirteen trials had evidence of selective reporting and were judged to be at high risk of bias (Goto 2009; Greenberg 1981; Kirwan 2010; Koroma 1996; Nga 2009; Nokes 1992; Olds 1999; Simeon 1995; Solon 2003; Stoltzfus 1997 (Cluster); Stoltzfus 2001; Sur 2005; Willett 1979). The remaining trials did not show evidence of selective reporting.

 

Other biases

Quality of the design of the eight cluster-RCTs was judged as low risk for recruitment bias (five trials), baseline imbalance (eight trials), loss of clusters (eight trials), compatibility with RCTs that randomized individuals (one trial) and incorrect analysis (seven trials). Alderman 2006 (Cluster) did not adjust for clustering in the published trial, but gave us the adjusted data (see study design above), and we used this to adjust the analysis in Hall 2006 (Cluster).

 

Effects of interventions

See:  Summary of findings for the main comparison Multiple dose deworming drugs for treating soil-transmitted intestinal worms in children: effects on nutrition and school performance (outcomes measured more 1 year)

The effects were grouped into:

  • trials where children were screened for infection (comparisons 1 and 2);
  • trials treating whole populations (comparisons 3 to 5). Comparison 3 is after a single dose of deworming drug, comparison 4 after multiple doses with follow up for up to a year, and comparison 5 after multiple doses with follow up of one year or more.

In the trials treating whole populations, we stratified the results by community worm prevalence. Prevalence strata are detailed in  Table 3 (high prevalence or high intensity areas (referred to as 'high prevalence'); moderate prevalence and low intensity referred to as ('moderate prevalence'); and low prevalence with low intensity referred to as 'low prevalence'). Within each section, we present the results of the meta-analysis, and then report any other data from trials that we could not include in the meta-analysis.

 

Only infected children included

These trials screened for infection, and then only included children with proven infection. None of these trials provided data for the outcomes school attendance (number of children dropping out), school performance, mortality or adverse events.

 

Single dose (comparison 1)

For nutritional measures, trials measured weight (n = 3), height (n = 2), MUAC (n = 3), triceps (n = 2), subscapular (n = 1) skinfold and BMI (n = 1). The trials demonstrated weight gain (0.58 kg, 95% CI 0.40 to 0.76; 149 participants, three trials;  Analysis 1.1); and gains in MUAC, triceps and subscapular skinfold values ( Analysis 1.3;  Analysis 1.4;  Analysis 1.5). No difference in height or body mass index was detected after a single dose ( Analysis 1.2;  Analysis 1.6). Nokes 1992 did not provide data for nutritional outcomes as nine weeks was cited as too short a follow-up period to demonstrate a change ( Table 4).

For haemoglobin, the mean value was slightly higher at the end of the study with deworming (mean difference 0.37 g/dL, 95% CI 0.10 to 0.64; 108 participants, two trials;  Analysis 1.7).

For psychometric tests of cognition, two trials reported on formal tests ( Table 5). Kvalsvig 1991a did not clearly report change in cognitive scores; Nokes 1992 did not report unadjusted data, but results of multiple regression suggest an improvement in treated children in three of the 10 tests carried out (fluency, digit span forwards, digit span backwards).

 

Multiple doses (comparison 2)

Simeon 1995 gave screened children albendazole at 0, 3 and 6 months and then carried out measurements two weeks after the last dose.

For nutritional measures, the authors reported end values of body mass index, and did not demonstrate a difference (mean difference -0.20 cm, 95% CI -0.46 to 0.06; 407 participants, one trial,  Analysis 2.1). They also reported height for age z-score and did not detect a difference.

For psychometric tests of cognition, the authors measured intellectual development using a wide range achievement test in the main study, and digit spans and verbal fluency tests in subgroups. The authors reported that deworming had no effect on intellectual development scores, but did not report the data ( Table 5).

For school attendance (days present at school), deworming had no demonstrable effect on school attendance rates of children actively attending school (mean difference -2.00, 95% CI -5.49 to 1.49; 407 participants, one trial;  Analysis 2.2).

 

Whole population treated

 

Single dose (comparison 3)

No trials provided data for the outcomes school attendance, adverse events and mortality.

For nutritional measures trials were in high (n = 4), moderate (n = 2) and low (n = 3) prevalence areas. Across prevalence categories for weight, height, MUAC, and skinfold (triceps and subscapular) no effect was evident in seven trials; but a substantive effect was seen in two trials (Stephenson 1989 and 1993) for weight, MUAC, and skinfold (both triceps and subscapular) ( Analysis 3.1;  Analysis 3.3;  Analysis 3.4;  Analysis 3.5), with an average weight gain of over one kilogram in both studies. These trials were in a high prevalence area of Kenya. Stephenson 1989 also showed the gain in height was higher in the albendazole group by 6 mm over six months, but Stephenson 1993 did not detect a difference ( Analysis 3.2). The high level of heterogeneity precludes meta-analysis in the high prevalence groups, but in moderate and low prevalence areas the meta-analysis suggests no marked effect, although the CIs do not exclude a clinically important effect (3058 participants, nine trials;  Analysis 3.1).

For haemoglobin, three studies were in moderate prevalence areas, and two in low prevalence areas. No effect was demonstrable in individual studies or on meta analysis (mean difference 0.02 g/dL, 95% CI -0.05 to 0.09; 1992 participants, four trials;  Analysis 3.6).

For psychometric tests of cognition, Solon 2003 ( Table 5) measured cognitive ability using a standardized written mental-abilities test, and reported that deworming had either no effect or a negative effect on mental ability scores, but did not report the data.

For measures of physical well being, two trials in the same high prevalence area of Kenya measured performance on the Harvard Step Test (Stephenson 1989; Stephenson 1993). This indicated benefit ( Analysis 3.7; mean difference 6.00, 95% CI 4.31 to 7.69; 86 participants, two trials).

For adverse events, Fox 2005 reported none in 46 patients given albendazole. Michaelsen 1985 reported a number of adverse events with tetra-chloroethylene, a drug no longer used ( Table 4).

 
Other data

Six trials did not provide data in a form that we could use in meta-analysis. We have collated these data in  Table 4, and this information is summarized below:

  • Beach 1999 did not detect a nutritional benefit of treatment after four months for the entire study population (no figures provided).
  • Fox 2005 only reported on subgroups infected with worms.
  • Greenberg 1981 stated there was no significant difference for all measured anthropometric variables for the total group and for subgroups defined by severity of infection (no figures provided).
  • Kloetzel 1982 reported the proportion of treatment or control group that improved, deteriorated, or experienced no change, but it is not known what anthropological measures were used.
  • Koroma 1996 found significant increases in weight-for-height, weight-for-age, and height-for-age z-scores recorded in rural and urban treatment groups at six months.
  • Michaelsen 1985 found no significant difference in change in mean for haemoglobin or weight for height at five months.

 
Sensitivity analysis

In the sensitivity analysis including only trials where the risk of bias for allocation concealment was low, no significant difference between treatment and control groups in weight, height, mid-upper arm circumference, or haemoglobin was evident ( Analysis 6.1;  Analysis 6.2;  Analysis 6.3;  Analysis 6.4).

 

Multiple doses, less than a year of follow up (comparison 4).

No trials provided data for the outcomes adverse events, school attendance (number of children dropping out) and mortality.

For nutritional outcomes, studies were carried out in high (n = 2), moderate (n = 2) and low (n = 3) prevalence areas. For weight, overall there was no evidence of an effect ( Analysis 4.1), although one trial (Stephenson 1993) showed a large weight gain in the treatment group (900 g); notably this effect had been detected after a single dose (see 'single dose' section above). Overall, the meta-analysis did not demonstrate a difference in weight gain between intervention and control (mean difference 0.06 kg, 95% CI -0.17 to 0.30; 2460 participants, seven trials), but the heterogeneity was high (I2 = 80%). When the trials were stratified by community category, heterogeneity was not explained. On the other hand, no significant effect was apparent in any subgroup. For MUAC, and triceps skinfold, no effects were evident in the studies measuring this (Dossa 2001, Watkins 1996, Donnen 1998), apart from Stephenson 1993, who reported large effects for MUAC, triceps and subscapular skinfold thickness ( Analysis 3.3;  Analysis 3.4;  Analysis 3.5). No effect in height was demonstrated in any of the six trials measuring this ( Analysis 4.2).

For haemoglobin, four trials reported this, with no difference between intervention and control apparent ( Analysis 4.6).

For psychometric tests of cognition, three trials measured this. Watkins 1996 measured reading and vocabulary, and Stoltzfus 2001 measured motor and language development, and reported that no effect was demonstrated. Miguel 2004 (Cluster) measured a range of cognitive tests. The results were not reported, but the authors state that no deworming effect was demonstrated.

For school attendance (days present at school): Two trials report this (Watkins 1996; Miguel 2004 (Cluster);  Table 6  Analysis 4.7). Watkins reports attendance rates of children actively attending school, at baseline and after treatment, and no effect was demonstrated. Miguel 2004 (Cluster) reports on end value differences in attendance for girls under 13 and all boys. In 1998, between Group 1 versus Group 2 and 3: there was a difference of 9.3% in schooling attendance detected, and in 1999, Group 2 versus Group 3, a difference of 5.5% was detected. No comparable baseline values of attendance were given so it was unclear whether these reflect differences in baseline or true effects. As the two comparisons in the Miguel 2004 (Cluster) trial were not independent (the control children in 1998 become the intervention children in 1999), they could not be meta-analysed together, so we carried out two separate meta-analyses ( Analysis 4.7), the first with Miguel (1998 comparison) + Watkins; and the second with Miguel (1999 comparison) + Watkins. Neither meta-analysis demonstrated a significant effect on school attendance (using 1998 data: mean difference 4%, 95% CI -6 to 14; using 1999 data, mean difference 2%, 95% CI -4 to 8%).

For school performance: Miguel 2004 (Cluster) measured exam score performance (English, Mathematics and Science-Agriculture exams in pupils in grades 3 to 8), but did not report results by the quasi-randomized comparisons.

 
Other data

Six trials did not provide data in a form that we could use in meta-analysis. We have collated these data in  Table 4, and this information is summarized below:

  • Goto 2009 reported no significant differences in mean z-scores or prevalence of stunting, underweight or wasting between the intervention groups, and the changes between intervals (eg between weeks 0 to 12, 0 to 24, 0 to 36, 12 to 24, etc) did not differ significantly between groups.
  • Hadju 1997 reported no significant differences detected between treatment groups on basis of multivariate analyses.
  • Le Huong 2007 reported no obvious trend in nutritional variable.
  • Miguel 2004 (Cluster) demonstrated no significant effect on weight-for-age z score, height-for-age z score, and haemoglobin (only 4% of quasi-randomized participants followed up for haemoglobin outcome; the proportion followed up for nutritional outcomes is unclear).
  • Stoltzfus 2001 reported that mebendazole significantly reduced the prevalence of mild wasting malnutrition in a subgroup of children aged < 30 months.
  • Stoltzfus 1997 (Cluster) reported that in a subgroup of under 10 year olds, the twice-yearly treated group experienced significantly greater weight gain (kg) compared to control (2.38 (SE 0.08) versus 2.11 (SE 0.08), P < 0.05).
  • Willett 1979 reported no statistical difference in growth rates in terms of height and weight between the two groups.

 
Sensitivity analysis

Including only trials with low risk of bias for allocation of concealment: no significant difference between treatment and control groups was detected in weight or haemoglobin ( Analysis 7.1;  Analysis 7.2).

 

Multiple doses, follow up of one year or more (comparison 5).

No trials provided data for adverse events and school attendance (number of children dropping out).

For nutritional indicators one study (Awasthi 2008 (Cluster)) showed a very large effect of 0.98 kg average difference in weight gain – with all the others showing small average non-significant differences of less than 0.2 kg ( Analysis 5.1; 302 clusters and 1045 individually randomized participants, five trials). The high level of heterogeneity in the low prevalence group precludes meta-analysis. Of the five trials, all but one reported change in weight, and one reported end values only. For height, gain was similar in the deworming and control groups (mean difference -0.26 cm, 95% CI -0.84 to 0.31; 174 clusters and 1045 individually randomized participants, three trials;  Analysis 5.2).

For haemoglobin, deworming drugs did not increase haemoglobin compared with control (mean difference -0.02 g/dL, 95% CI -0.30 to 0.27; 1365 participants, two trials;  Analysis 5.3).

For psychometric tests of cognition, Awasthi 2000 measured developmental status using the Denver Questionnaire, and Hall 2006 (Cluster) measured mathematics and Vietnamese test scores ( Table 5). Both trials reported that they did not demonstrate an effect of deworming.

For school attendance (days present at school): (Miguel 2004 (Cluster)  Table 6;  Analysis 5.4) reported on end values for attendance rates of children (1999, Group 1 versus Group 3), and found no significant effect (mean difference 5%, 95% CI -0.5 to 10.5). No baseline values were given so there is potential for any random differences between the groups to confound the end values.

For death, data from the DEVTA trial are awaited (DEVTA (unpublished)).

 
Other data

Four trials reported narratively on results, collated in  Table 4. In summary:

  • Awasthi 2008 (Cluster) reported 23 deaths during the study, 13 of which were in the usual care arm, and 10 were in the treatment arm.
  • Lai 1995 found no difference in height or weight between treatment and control group at the end of two-year follow up.  
  • Hall 2006 (Cluster) reported no difference in final and change in height.
  • Rousham 1994 (Cluster) ANOVAS of the change in z-scores revealed no significant improvement with treatment.

 
Sensitivity analysis

Only one study had low risk of bias for allocation of concealment. In Hall 2006 (Cluster), no significant difference between treatment and control groups was detected in weight or height ( Analysis 8.1;  Analysis 8.2)

 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Summary of main results

 

1. Selective deworming

 

What is the effect of a dose of deworming drug given to children infected with worms in populations screened for intestinal helminths?

 
It probably increases weight gain

In three trials, the meta-analysis shows a mean difference 0.58 kg, 95% CI 0.40 to 0.76; 149 participants; moderate quality evidence.

 
It may increase haemoglobin levels

In two trials, the mean difference 0.37 g/dL, 95% CI 0.10 to 0.64; 108 participants, low quality evidence.

 
We don’t know whether there is an effect on cognition

Two trials reported on formal tests of intellectual development, using different outcomes. One trial did not report the outcome, and one trial reported and improvement in 3/10 tests of cognitive function in treated children: very low quality evidence.

 See Summary of findings (A),  Table 7.

 

2. Targeted deworming (one dose)

 

What is the effect of one dose of deworming drug given to all children living in an endemic area?

 
We don’t know the effect on weight gain

Deworming increased weight gain in two early trials, both carried out in the same location, but had no effect in seven trials conducted subsequently (3058 participants, nine trials; very low quality evidence).

 
It may have no effect on haemoglobin levels

In four trials, meta-analysis of haemoglobin difference was not significant (mean difference 0.02 g/dL, 95% CI -0.05 to 0.09; 1992 participants, low quality evidence).

 
We don’t know whether there is an effect on cognition

One trial reported that deworming had either no effect or a negative effect on mental ability scores, but did not report the data, very low quality evidence.

 
It may have an effect on physical well being

Two trials in the same high prevalence area of Kenya indicated benefit (Harvard Step Test mean difference 6.00, 95% CI 4.31 to 7.69; 86 participants, two trials, low quality evidence)

See Summary of findings (B),  Table 8.

 

3. Targeted deworming (multiple doses)

Eight of the 42 trials in this systematic review were cluster-RCTs and assessed multiple doses of deworming, and thus will potentially capture any population effects as a result of interrupting transmission.

 

What is the effect of multiple doses of deworming drugs to all children (follow up for up to a year)?

 
We don’t know the effect on weight gain

Deworming increased weight gain in one trial in a high prevalence location, decreased weight in one trial in a low prevalence area, but had no effect elsewhere (mean difference 0.06 kg, 95% CI -0.17 to 0.30; 2460 participants, seven trials, very low quality evidence)

 
It may have little or no effect on haemoglobin levels.

In four trials, the mean difference -0.01 g/dL, 95% CI -0.14 to 0.13; 807 participants, low quality evidence.

 
We don’t know the effect on cognition

Three trials measured formal tests of intellectual development using different outcomes. All three trials reported no effect of deworming, very low quality evidence.

 
We don’t know the effect on school attendance

In two trials, 75 clusters and 143 individually randomized participants, the mean difference 4% higher attendance; 95% CI -6 to 14, very low quality evidence.

 See Summary of findings (C),  Table 9.

 

What is the effect of multiple doses of deworming drugs to all children (follow up for over a year)?

This outcome will capture both deworming effects and any effects as a result of a potential reduction in transmission.

 
We don’t know the effect on weight gain

Deworming increased weight gain in one early trial in a low prevalence location, but had no effect in two subsequent trials in the same location, or in higher prevalence locations. Four out of five trials in this analysis were cluster-RCTs so capturing both the individual effect and any additional population level effect as a result of interrupting transmission (302 clusters and 1045 individually randomized participants, five trials, very low quality evidence)

 
We don’t know the effect on height gain

In three trials, 174 clusters and 1045 individually randomized participants, the mean difference -0.26 cm, 95% CI -0.84 to 0.31, very low quality evidence.

 
We don’t know the effect on haemoglobin levels

in two trials, no difference was detected (mean -0.02 g/dL, 95% CI -0.30 to 0.27; 1365 participants, two trials; very low quality evidence).

 
We don’t know the effect on cognition

Two trials reported on formal tests of intellectual development using different outcomes. Both trials reported no effect of deworming: very low quality evidence.

 
We don’t know the effect on school attendance

In one trial the mean difference in school attendance was 5%, 95%CI -0.5 to 10.5, very low quality evidence.

 
For mortality

A large trial of around one million children carried out in Lucknow was completed in 2005, but the results have not been published (DEVTA (unpublished).

See  Summary of findings for the main comparison.

 

Secondary outcomes

For anthropometry, results were broadly consistent with the primary outcomes.

 

Key messages

Selective deworming probably increases weight and may increase haemoglobin in children confirmed to have worms on the basis of screening.

Targeted deworming:

  • has sometimes demonstrated a substantive impact on weight gain (three trials), but in the majority of studies no effect has been shown on nutritional indicators.

  • does not appear to have an effect on haemoglobin.

  • may have an effect on physical well being.

  • has not been shown to have a definitive effect on cognition.

  • has not been shown to have a convincing effect on school attendance.

Mortality has been evaluated in a large trial completed in 2005 but this has not been published.

 

Overall completeness and applicability of evidence

Review question: The review indicates that screening and treating children infected with worms is promising, but the evidence base is small. However, when the intervention is used in the way the WHO currently recommends – targeted treatment to high risk populations – the effect is not so clear. An effect on weight was only seen in the two Stephenson trials assessing single-dose deworming in the same high prevalence school (Stephenson 1989; Stephenson 1993), where more than 90% of the children were infected with both hookworm and Trichuris, with heavy worm loads; and a cluster-RCT assessing long term multiple dosing in a low-burden community undertaken in 1995 in India (Awasthi 2008 (Cluster)). What is also interesting in the two Stephenson studies in Kenya is that effects were seen after a single dose only, and the effects in the results of 'multiple-doses, outcomes less than one year of follow-up' can be mainly attributed to the effect seen after one dose of the deworming drug.

Trials conducted subsequently, some of them large cluster-RCTs, have not demonstrated significant effects.

Completeness of the analysis: Critics of a previous version of this review (Dickson 2000a) stated that the impact must be considered stratified by the intensity of the infection (Cooper 2000; Savioli 2000). We have done this comprehensively in this edition and no clear pattern of effect has emerged. Other criticisms were that studies of short-term treatment cannot assess the long-term benefits of regular treatment (Bundy 2000). However, this analysis clearly examines long-term outcomes from trials conducted over the last 10 years.

Extrapolating evidence on selective deworming to targeted deworming: It could be argued that evidence of benefit seen in selective deworming provides an evidential base for targeted deworming, because the latter reduces costs due to diagnostic screening. However, the data on targeted deworming is limited (three small trials, n = 149); the quality of the evidence is 'moderate' for weight and 'low' for haemoglobin; and the intervention itself is different. For example, having been screened, and then told they have worms, children are more likely to comply with treatment, and alter their behaviour.

Choking: The WHO has raised concerns about the prevalence of choking in young children (aged between 1 to 3 years), with several pages of recommendations about how to administer albendazole in tablet form without children choking (http://www.who.int/wormcontrol/newsletter/PPC8_eng.pdf ) WHO 2007. Although common sense might suggest this is a rare occurrence, nevertheless some might argue there is a lack of evidence on the safety of administering deworming drugs to young children in tablet form in a community setting.

Polyparasitism: Individuals and communities are often infected with more than one helminth infection (Molyneux 2005) and the WHO is currently promoting the large-scale use of 'preventive chemotherapy'. This involves use of multiple anthelminthic drugs to treat a range of diseases, including soil-transmitted helminths, schistosomiasis, and filariasis. Engels 2009 comment on the need for a comprehensive assessment of the impact of deworming. In the absence of such evidence, there is a need to demonstrate that a drug is effective against a particular parasite and to quantify its effects on humans before combining all the drugs into a basket treatment for all helminth infections, and assuming that all components are effective.

Secular trends in worm burden: Evidence of benefit of deworming on nutrition appear to depend on three studies, all conducted more than 15 years ago, with two from the same area of Kenya where nearly all children were infected with worms and worm burdens were high. Later and much larger studies have failed to demonstrate the same effects. It may be that over time the intensity of infection has declined, and that the results from these few trials are simply not applicable to contemporary populations with lighter worm burdens.

 

Quality of the evidence

Conducting field trials to test this intervention is complex and challenging, and researchers have worked hard to generate this body of research evidence. There is now a reasonable amount of evidence from studies in a range of settings, including high, moderate, and low burden areas. There have also been five studies ( Analysis 5.1) that have assessed the long-term effects of multiple doses of deworming, four of which were cluster-RCTs. These are particularly important, because they can detect the 'real life' community level effects of treatment that include possible effects from a reduction in worm transmission (Bundy 2009).

We formally assessed the quality of the evidence using the standard GRADE methods.The quality of evidence was downgraded due to 'risk of bias', 'consistency' and 'indirectness'. For 'Risk of bias' the study designs were often wanting: only one trial out of 42 provided complete information to assure good methodological quality (Fox 2005). Allocation concealment was adequate in only eight trials (20%), and 18 trials (42%) included 90% of the randomized participants in the analysis. 'Consistency’ relates to variation (unexplained heterogeneity) between the studies, which leads to uncertainty about the pooled estimates. There was marked heterogeneity (above 80%) in the analyses of weight gain in unscreened populations, which was not explained by stratification of the results by worm prevalence. We had concerns about 'indirectness' in the context of the two Stephenson studies, which were carried out in the same school (Stephenson 1989; Stephenson 1993). Evidence from this very high worm burden population may not be applicable to other populations.

In all assessments of the formal tests of cognition, the GRADE quality of the evidence was very low. Nine trials measured intellectual development using formal tests. Only one of these trials demonstrated an effect on cognitive outcomes in 3/10 of the outcomes measured (Nokes 1992,  Table 5,  Table 6).  The trials used a range of cognitive tests, which seems to reflect the difficulty inherent in choosing appropriate cognitive performance tests since there is no accepted test battery that can be applied across cultures and settings, and, as Miguel 2004 (Cluster) points out, the mechanisms for any putative effects are unknown.

Similiarly, for school attendance, the GRADE quality of the evidence was very low. One quasi-randomized trial (Miguel 2004 (Cluster) reported an effect, which was apparent in only one of the two comparisons in up to a year of follow up, and not apparent in the one comparison after one year. Miguel 2004 (Cluster) measured attendance outcomes directly, unlike the other two trials (Simeon 1995; Watkins 1996) which measured attendance using school registers, which may be inaccurate in some settings. However, in Miguel 2004 (Cluster) , the values for school attendance were end values and not corrected for baseline. Thus random differences in baseline attendance between the two groups could have confounded any result.

 

Potential biases in the review process

Publication bias: We are uncertain about the number of unpublished trials in this area. We know of two unpublished trials.

1. Hall 2006 (Cluster) is a large trial from Vietnam, with two years follow-up and did not demonstrate a significant difference in weight gain. Clustering was not taken into account in the analysis, which artificially narrows the CIs. In this update we included the results of this trial in meta-analysis by imputing an intra-cluster correlation coefficient, calculated from the adjusted data from Alderman 2006 (Cluster).

2. (DEVTA (unpublished); the world's largest ever RCT, which includes over a million children randomized in a cluster design with mortality as the primary outcome, remains unpublished six years after completion. We have corresponded with the senior author on several occasions. We also wrote a letter to the Lancet in June 2011, asking for publication of this important study. When this letter was accepted, the authors submitted the manuscript to the Lancet within a week, and we withdrew our letter. However, at the time of writing (June 2012) the paper remains unpublished.

Statistical errors in analysis: Of the eight cluster-RCTs, three did not take adequate account of cluster randomization (Alderman 2006 (Cluster), Hall 2006 (Cluster), Rousham 1994 (Cluster). This has a substantive impact on the interpretation of the trials. For example, the significant difference between intervention and control quoted on the cover of the BMJ for Alderman 2006 (Cluster), assumed 27,995 children had been individually randomized. When we clarified this with the authors, they provided the BMJ with a correction, which showed that no significant difference was detected in weight gain between intervention and control groups; this corrected result has been used in the meta-analysis in this study.

Nutritional outcomes: The included trials reported a range of nutritional status outcomes. For meta-analysis, we did not use nutritional data expressed as z-scores or percentile scores calculated on the basis of reference standards, or dichotomised z- or percentile scores (eg proportion stunted with height-for-age z-score<-2). As these data were derived from the absolute values, we used these values for evidence of benefit. We knew the nutritional data would be captured in the absolute values and wanted to reduce selective reporting through collection of multiple variables from papers that are all derived from the same basic outcomes measured in the trial. We noted that in some trials there was a discrepancy between what was measured and what was reported; for example, Nokes 1992 recorded but did not report anthropometric data. This is a concern as it may indicate selective reporting. However, we have systematically reported all relevant outcomes not included in meta-analysis in  Table 4.

Subgroup analyses: Some trials presented data from subgroups, selected on the basis of factors such as infection status (Beach 1999, Fox 2005, Greenberg 1981), location (Koroma 1996), age (Stoltzfus 2001), frequency of treatment (Stoltzfus 1997 (Cluster)), and sex (Lai 1995). These comparisons were not randomized and have not been included in meta-analysis. Two trials, one of which one was a cluster-RCT, demonstrated improvements in nutritional outcomes in subgroup analyses (Stoltzfus 1997 (Cluster); Stoltzfus 2001). These data are reported in  Table 4.

 

Agreements and disagreements with other studies or reviews

A review and meta-analysis by Hall et al (Hall 2008), funded by the World Bank, presents evidence in favour of an effect of deworming on weight gain (mean difference 0.21 kg  95% CI 0.17 to 0.26, 11 studies). This analysis differs from our analyses of weight gain in a number of respects: it was not a protocol driven systematic review; the review excluded studies in lower prevalence areas (< 50%); pooled results were presented without exploration of significant heterogeneity; it combined trials that included both screened and unscreened children; it included trials excluded from our study on the basis of methodological quality; it included data from subgroup analyses; and included data unadjusted for cluster randomization.

The narrative review (Albonico 2008) explored the evidence for the impact of deworming on pre-school age children, and concluded that deworming has been shown to improve growth. Their analysis differed from our analyses in a number of ways: a different population was considered, although our review considers data from this subgroup; it was not a protocol driven systematic review; it included trials excluded from our review; it was a narrative summary rather than meta-analysis of data; it reported results from subgroup analyses; it reported point estimates without taking into account statistical significance; and it included data unadjusted for cluster randomization. The authors state “A few studies have failed to show any impact of deworming on growth”. This is at odds with our interpretation of the reliable randomized comparisons of nutritional outcomes in this review, which suggests that the majority of studies have failed to show an effect on nutrition.

Gulani and colleagues undertook a systematic review of the effects of deworming on haemoglobin, and reported a marginal increase in mean values that could translate into small reduction (5% to 10%) in anaemia in a population with a high prevalence of intestinal helminths (Gulani 2007). This systematic review differs from our analysis of haemoglobin in a number of respects: it included studies in adults and pregnant women; included studies excluded from our study on the basis of methodological quality.

Others advocates of deworming, such as Bundy 2009, have argued that many of the underlying trials of deworming suffer from three critical methodological problems: treatment externalities in dynamic infection systems, inadequate measurement of cognitive outcomes and school attendance, and sample attrition. We agree with these points. However, externalities will be detected by large cluster-RCTs with a year or more follow up, and there are now five trials such as this included in this review.

 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

 

Implications for practice

In examining the logic model in relation to targeted treatment (Figure 1), the evidence for the main effects is weak.

An effect on nutrition has only been demonstrated in the studies mentioned above; haemoglobin does not seem to improve; and there is no evidence for an effect on cognition. Evidence for the mediating pathways, is more sparse: there are no data on intellect, the data on physical well being are encouraging but from same studies showing substantive weight gain after a single dose of deworming drug (Stephenson 1989; Stephenson 1993); and the data on school attendance are insufficient to demonstrate an effect. Evidence of impact, in terms of school performance, is unknown; it was measured in one study but not reported by the comparison; and in terms of mortality, the data have been collected in one study, but not yet published.

In conclusion:

  • Selective deworming – screening school children for intestinal helminths, and then treating those infected – probably has some value in relation to weight and haemoglobin but the evidence base is small. The frequency of the screening and the effectiveness of subsequent doses is not known.
  • There is insufficient evidence to recommend deworming drugs in targeted community programmes. The research has not shown an effect in most studies, although clearly there was an impact on weight gain reported in some older studies. Exactly what makes the intervention effective in these and not more recent studies is not clear. There is no direct evidence from trials to show that this depends on background helminth prevalence or intensity.  
  • It is probably misleading to justify deworming on the basis of effects on school performance or attendance. There is simply insufficient reliable information to know whether this is so. 
  • The evidence of deworming externalities – in terms of impacts on nutrition, haemoglobin and cognitive function in groups of people treated over a longer period of time – has not been clearly demonstrated in the studies included, although one study in India did show a large effect on weight.
  • The WHO should review its guidelines and policies in this area, using currently recommended methods for guideline development, drawing on summaries such as this review and GRADE assessment in transparent decision making processes.
  • Guideline developers and policy makers at global, national, and local levels should be allowed to consider the evidence carefully before committing to investing existing resources in delivering these programmes. Governments funding deworming programmes should consider current evidence before committing public funds to programmes where the evidence base from RCTs is so limited.

 
Implications for research

  • Our view is that the tools exist to answer the research questions investigated in this review, particularly through cluster-RCTs. Further research will be needed, however, if policymakers want to predict when it is worthwhile to implement deworming in a community, and to determine if and when treating all schoolchildren is effective.
  • Further research is required before policymakers can be clear whether the intervention is of benefit or not on children's long-term nutrition and school performance. 
  • Further research is needed to determine the impact of deworming packages that include multiple interventions. These studies are important, but the results are more difficult to generalise to other settings since it is often not clear which component of an intervention is effective.
  • Trial authors are encouraged to present trial data in line with CONSORT guidelines (Moher 2001). 
  • Authors of cluster-RCTs should report their data adjusting for design effects. We recommend trials that use current standards of design and are planned together to allow an individual patient data meta-analysis to correct for clustering and to help explore subgroup effects. 
  • Authors of trials, whether they are small or large, should publish the results of the trials irrespective of the findings, in line with the basic principles of research integrity.

 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

The authors wish to thank all of those people who gave of their time and expertise to comment on this review. Thanks to the authors of the previous version of this Cochrane Review (Dickson 2000a; Taylor-Robinson 2007).

This document is an output from a project funded by the UK Department for International Development (DFID) for the benefit of developing countries. The views expressed are not necessarily those of DFID.

 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
Download statistical data

 
Comparison 1. Screened for infection - Single dose

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

 1 Weight (kg)3149Mean Difference (IV, Fixed, 95% CI)0.58 [0.40, 0.76]

 2 Height (cm)2136Mean Difference (IV, Fixed, 95% CI)0.10 [-0.15, 0.35]

 3 Mid-upper arm circumference (cm)3112Mean Difference (IV, Fixed, 95% CI)0.28 [0.12, 0.44]

 4 Triceps skin fold thickness (mm)268Mean Difference (IV, Fixed, 95% CI)0.77 [0.46, 1.08]

 5 Subscapular skin fold thickness (mm)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 6 Body mass index1Mean Difference (IV, Fixed, 95% CI)Subtotals only

 7 Haemoglobin (g/dL)2108Mean Difference (IV, Fixed, 95% CI)0.37 [0.10, 0.64]

 
Comparison 2. Screened for infection - Multiple dose, outcomes in the first year

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

 1 Body mass index1407Mean Difference (IV, Fixed, 95% CI)-0.20 [-0.46, 0.06]

 2 School attendance (days present at school)1Mean Difference (IV, Fixed, 95% CI)Subtotals only

 
Comparison 3. Target population treated - Single dose

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

 1 Weight (kg)9Mean Difference (IV, Random, 95% CI)Subtotals only

    1.1 High prevalence
4629Mean Difference (IV, Random, 95% CI)0.73 [-0.12, 1.57]

    1.2 Moderate prevalence
2873Mean Difference (IV, Random, 95% CI)0.11 [-0.16, 0.38]

    1.3 Low prevalence
31556Mean Difference (IV, Random, 95% CI)-0.09 [-0.22, 0.03]

 2 Height (cm)7Mean Difference (IV, Random, 95% CI)Subtotals only

    2.1 High prevalence
3566Mean Difference (IV, Random, 95% CI)0.25 [-0.10, 0.60]

    2.2 Moderate prevalence
1191Mean Difference (IV, Random, 95% CI)-0.20 [-0.47, 0.07]

    2.3 Low prevalence
31556Mean Difference (IV, Random, 95% CI)-0.26 [-0.74, 0.21]

 3 Mid-upper arm circumference (cm)5Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 High prevalence
3546Mean Difference (IV, Random, 95% CI)0.36 [0.08, 0.64]

    3.2 Moderate prevalence
1482Mean Difference (IV, Random, 95% CI)0.19 [-0.01, 0.40]

    3.3 Low prevalence
1222Mean Difference (IV, Random, 95% CI)-0.3 [-0.52, -0.08]

 4 Triceps skin fold thickness (mm)2Mean Difference (IV, Random, 95% CI)Subtotals only

    4.1 High prevalence
2339Mean Difference (IV, Random, 95% CI)1.50 [0.91, 2.08]

 5 Subscapular skin fold thickness (mm)2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    5.1 High prevalence
2339Mean Difference (IV, Fixed, 95% CI)1.29 [1.13, 1.44]

 6 Haemoglobin (g/dL)4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    6.1 Moderate prevalence
2658Mean Difference (IV, Fixed, 95% CI)0.06 [-0.06, 0.17]

    6.2 Low prevalence
21334Mean Difference (IV, Fixed, 95% CI)0.00 [-0.08, 0.08]

 7 Harvard Step Test (measure of physical well being)2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    7.1 High prevalence
286Mean Difference (IV, Fixed, 95% CI)6.0 [4.31, 7.69]

 
Comparison 4. Target population treated - Multiple dose, outcomes in the first year

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

 1 Weight (kg)7Mean Difference (IV, Random, 95% CI)Subtotals only

    1.1 High prevalence
2414Mean Difference (IV, Random, 95% CI)0.50 [-0.25, 1.25]

    1.2 Moderate prevalence
2811Mean Difference (IV, Random, 95% CI)0.03 [-0.20, 0.26]

    1.3 Low prevalence
31235Mean Difference (IV, Random, 95% CI)-0.23 [-0.60, 0.14]

 2 Height (cm)6Mean Difference (IV, Random, 95% CI)Subtotals only

    2.1 High prevalence
2415Mean Difference (IV, Random, 95% CI)0.02 [-0.15, 0.18]

    2.2 Moderate prevalence
1129Mean Difference (IV, Random, 95% CI)0.10 [-0.46, 0.66]

    2.3 Low prevalence
31235Mean Difference (IV, Random, 95% CI)-0.17 [-0.59, 0.25]

 3 Mid-upper arm circumference (cm)4Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 High prevalence
2395Mean Difference (IV, Random, 95% CI)0.24 [-0.07, 0.55]

    3.2 Moderate prevalence
1129Mean Difference (IV, Random, 95% CI)0.06 [-0.22, 0.33]

    3.3 Low prevalence
1198Mean Difference (IV, Random, 95% CI)-0.35 [-0.65, -0.05]

 4 Triceps skin fold thickness (mm)2Mean Difference (IV, Random, 95% CI)Subtotals only

    4.1 High prevalence
1188Mean Difference (IV, Random, 95% CI)1.80 [1.52, 2.08]

    4.2 Moderate prevalence
1130Mean Difference (IV, Random, 95% CI)-0.30 [-1.28, 0.68]

 5 Subscapular skin fold thickness (mm)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 High prevalence
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Haemoglobin (g/dL)4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    6.1 Moderate prevalence
2464Mean Difference (IV, Fixed, 95% CI)0.02 [-0.15, 0.19]

    6.2 Low prevalence
2343Mean Difference (IV, Fixed, 95% CI)-0.06 [-0.28, 0.17]

 7 School attendance (days present at school)2Mean Difference (Random, 95% CI)Subtotals only

    7.1 High prevalence (Miguel 1998 comparison)
2Mean Difference (Random, 95% CI)0.04 [-0.06, 0.14]

    7.2 High prevalence (Miguel 1999 comparison)
2Mean Difference (Random, 95% CI)0.02 [-0.04, 0.08]

 
Comparison 5. Target population treated - Multiple dose, outcomes after the first year

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

 1 Weight (kg)5Mean Difference (Random, 95% CI)Subtotals only

    1.1 High prevalence
1Mean Difference (Random, 95% CI)0.0 [-0.14, 0.14]

    1.2 Moderate prevalence
1Mean Difference (Random, 95% CI)0.15 [-0.02, 0.33]

    1.3 Low prevalence
3Mean Difference (Random, 95% CI)0.37 [-0.40, 1.15]

 2 Height (cm)3Mean Difference (IV, Fixed, 95% CI)Subtotals only

    2.1 Low prevalence
31219Mean Difference (IV, Fixed, 95% CI)-0.26 [-0.84, 0.31]

 3 Haemoglobin (g/dL)2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    3.1 Low prevalence
21365Mean Difference (IV, Fixed, 95% CI)-0.02 [-0.30, 0.27]

 4 School attendance (days present at school)1Mean Difference (Fixed, 95% CI)Totals not selected

    4.1 High prevalence
1Mean Difference (Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 6. Target population treated - Single dose (low risk of bias for allocation concealment)

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

 1 Weight (kg)2Mean Difference (IV, Random, 95% CI)Totals not selected

    1.1 Moderate prevalence
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    1.2 Low prevalence
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 2 Height (cm)1Mean Difference (IV, Random, 95% CI)Totals not selected

    2.3 Low prevalence
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 3 Mid-upper arm circumference (cm)1Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 Moderate prevalence
1482Mean Difference (IV, Random, 95% CI)0.19 [-0.01, 0.40]

 4 Haemoglobin (g/dL)2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    4.1 Moderate prevalence
1467Mean Difference (IV, Fixed, 95% CI)0.05 [-0.08, 0.17]

    4.2 Low prevalence
1347Mean Difference (IV, Fixed, 95% CI)0.06 [-0.24, 0.36]

 
Comparison 7. Target population treated - Multiple dose, outcomes in the first year (low risk of bias for allocation concealment)

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

 1 Weight (kg)1Mean Difference (IV, Random, 95% CI)Totals not selected

    1.1 Moderate prevalence
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 2 Haemoglobin (g/dL)1Mean Difference (IV, Fixed, 95% CI)Subtotals only

    2.1 Moderate prevalence
1326Mean Difference (IV, Fixed, 95% CI)-0.02 [-0.21, 0.16]

 
Comparison 8. Target population treated - Multiple dose, outcomes after the first year (low risk of bias for allocation concealment)

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

 1 Weight (kg)1Mean Difference (Random, 95% CI)Totals not selected

    1.1 High prevalence
1Mean Difference (Random, 95% CI)0.0 [0.0, 0.0]

 2 Height (cm)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 Low prevalence
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 

Appendices

  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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Appendix 1. Authors' judgment on risk of bias


Potential biasAuthors’ judgement

Random sequence generation (selection bias)High – not randomized or quasi-randomized

Unclear – States “randomized”, but does not report method

Low – describes method of randomization

Allocation concealment (selection bias)High – not concealed, open label trial for individually randomized, method of concealment not adequate

Unclear  – details of method not reported or insufficient details

Low – central allocation, sequentially numbered opaque sealed envelopes

Blinding (performance bias and detection bias)High – personnel, participants or outcome assessors not blinded

Unclear – no details reported, insufficient details reported

Low – personnel, participants and outcome assessors blinded

Incomplete outcome data (attrition bias)High – losses to follow-up not evenly distributed across intervention and control group, high attrition rate  (20% or more for the main outcome)

Unclear - no details reported, insufficient details reported

Low – no losses to follow-up, losses below 20% and evenly distributed across groups, intention-to-treat analysis used.

Note: for cluster RCTs, the loss relates to the clusters

Selective reporting (reporting bias)High – did not fully report measured or relevant outcomes

Unclear – not enough information reported to judge

Low – all stated outcomes reported

Other biasLow – no obvious other source of bias of concern to reviewers

High – major source of bias such as unexplained differences in baseline characteristics



 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

Last assessed as up-to-date: 31 May 2012.


DateEventDescription

31 May 2012New search has been performedSubstantive update:

  1. We added a logic framework to the background.
  2. We replaced Awasthi 1995 (unpublished data) with the published data (Awasthi 2008 (Cluster)). We received clarification on methods and results from Miguel and Kremer and included this study in the review (Miguel 2004 (Cluster)). Also, we tried to include the DEVTA (unpublished) completed in 2006 but were unable to as it remains unpublished as of May 2012.
  3. We added haemoglobin as a primary outcome and we added all trials measuring haemoglobin. We merged end values and change values to simplify the review. We reanalysed the school attendance data. In addition, we brought the sensitivity analysis in line with current best practice (by only including trials with evidence of allocation concealment).
  4. We added Summary of Findings tables. We adjusted the wording in line with our policy of using standard words to correspond to quality of the evidence.
  5. In the light of these changes, we rewrote the review entirely.

31 May 2012New citation required but conclusions have not changedReview updated, new studies added.



 

History

  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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

Protocol first published: Issue 3, 1997
Review first published: Issue 2, 1998


DateEventDescription

7 May 2008AmendedThere are two alterations to the review:

1. We have corrected an error in the discussion. The sentence that read "There was a weight gain of 2.413 kg in the treatment parishes and 2.474 kg in the control parishes at an unspecified follow-up point." now reads "There was a weight gain of 2.413 kg in the treatment parishes and 2.259 kg in the control parishes at an unspecified follow-up point."

2. We have detailed our correspondence to date with Michael Kremer and Edward Miguel in the discussion.

12 August 2007New citation required and conclusions have changed2007, Issue 4 (substantive update): author team changed; review title modified from the original title of "Anthelmintic drugs for treating worms in children: effects on growth and cognitive performance"; updated methods, reapplied the inclusion criteria, repeated data extraction, added new trials, and included additional analyses as recommended by policy specialists.

31 March 2000New citation required and conclusions have changed2000, Issue 2 (substantive update): new trials added and review updated



 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

DTR wrote the protocol, applied inclusion criteria, assessed quality, extracted data, conducted data analysis, and wrote the first draft of the review. KS-W and NM applied inclusion criteria, assessed quality, extracted data, conducted data analysis, and drafted the results of the update. SD assessed risk of bias and extracted data for a subset of the trials; and contributed to the analysis and the writing of the review. PGr provided advice at all stages of the review production, applied inclusion criteria, assessed quality, quality assured data extraction, helped construct the comparisons, and helped write the review.

 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

DTR is supported by an MRC Population Health Scientist Fellowship  (G0802448). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

This review is supported by a Department for International Development (DFID) grant aimed at ensuring the best possible systematic reviews, particularly Cochrane Reviews, are completed on topics relevant to the poor, particularly women, in low- and middle-income countries. DFID does not participate in the selection of topics, in the conduct of the review, or in the interpretation of findings.The grant provides partial salary support for PG, SD, and the funds for the contract with Enhance Reviews Ltd.

 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Internal sources

  • Liverpool School of Tropical Medicine, UK.

 

External sources

  • Department for International Development, UK.

 

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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

Not applicable.

 

Notes

  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. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

Not applicable.

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. References to ongoing studies
  24. Additional references
  25. References to other published versions of this review
Adams 1994 {published data only}
  • Adams EJ, Stephenson LS, Latham MC, Kinoti SN. Physical activity and growth of Kenyan school children with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved after treatment with albendazole. Journal of Nutrition 1994;124(8):1199-206.
Alderman 2006 (Cluster) {published data only}
  • Alderman H, Konde-Lule J, Sebuliba I, Bundy D, Hall A. Effect on weight gain of routinely giving albendazole to preschool children during child health days in Uganda: cluster randomised controlled trial. BMJ 2006;333(7559):122.
Awasthi 2000 {published and unpublished data}
  • Awasthi S, Pande VK, Fletcher RS. Effectiveness and cost-effectiveness of albendazole in improving nutritional status of pre-school children in urban slums. Indian Pediatrics 2000;37(1):19-29.
Awasthi 2001 (Cluster) {published data only}
  • Awasthi S, Pande VK. Six-monthly de-worming in infants to study effects on growth. Indian Journal of Pediatrics 2001;68(9):823-7.
Awasthi 2008 (Cluster) {published data only}
  • Awasthi S, Peto R, Fletcher R, Glick H. Controlling parasitic infection in children under five years of age: giving albendazole in conjunction with an Indian government Vitamin A supplement program. Treating parasitic infestations in children [Monograph No. 3]. Philadelphia: International Clinical Epidemiology Network (INCLEN), 1995.
  • Awasthi S, Peto R, Pande VK, Fletcher RH, Read S, Bundy DA. Effects of deworming on malnourished preschool children in India: an open-labelled, cluster-randomized trial. PLoS Neglected Tropical Diseases 2008;2(4):e223.
Beach 1999 {published data only}
  • Beach MJ, Streit TG, Addiss DG, Prospere R, Roberts JM, Lammie PJ. Assessment of combined ivermectin and albendazole for treatment of intestinal helminth and Wuchereria bancrofti infections in Haitian schoolchildren. American Journal of Tropical Medicine and Hygiene 1999;60(3):479-86.
DEVTA (unpublished) {unpublished data only}
  • Awasthi S, Peto R, Read S, Richards S, Pande V, Bundy DA and the DEVTA team. Population de-worming with 6-monthly albendazole: DEVTA, a cluster-randomised trial among 1 million preschool children in North India. [unpublished manuscript].
  • University of Oxford and the United States Agency for International Development (USAID). Deworming and Enhanced Vitamin A Supplementation DEVTA Project(The DEVTA Trial). Registered September 13, 2005; Completed October 27, 2005;Clinical Trials Register Number NCT00222547:Information obtained from ClinicalTrials.gov on February 23, 2012.
Donnen 1998 {published data only}
  • Donnen P, Brasseur D, Dramaix M, Vertongen F, Zihindula M, Muhamiriza M, et al. Vitamin A Supplemenation but not deworming improves growth of malnourished preschool children in eastern Zaire. Journal of Nutrition 1998;128(8):1320-7.
Dossa 2001 {published data only}
  • Dossa RA, Ategbo EA, de Koning FL, van Raaij JM, Hautvast JG. Impact of iron supplementation and deworming on growth performance in preschool Beninese children. European Journal of Clinical Nutrition 2001;55(4):223-8.
Fox 2005 {published data only}
  • Fox LM, Furness BW, Haser JK, Desire D, Brissau JM, Milord MD, et al. Tolerance and efficacy of combined diethylcarbamazine and albendazole for treatment of Wuchereria bancrofti and intestinal helminth infections in Haitian children. American Journal of Tropical Medicine and Hygiene 2005;73(1):115-21.
Freij 1979a {published data only}
  • Freij L, Meeuwisse GW, Berg NO, Wall S, Gebre-Medhin M. Ascariasis and malnutrition. A study in urban Ethiopian children. American Journal of Clinical Nutrition 1979;32(7):1545-53.
Freij 1979b {published data only}
  • Freij L, Meeuwisse GW, Berg NO, Wall S, Gebre-Medhin M. Ascariasis and malnutrition. A study in urban Ethiopian children. American Journal of Clinical Nutrition 1979;32(7):1545-53.
Garg 2002 {published data only}
  • Garg R, Lee LA, Beach MJ, Wamae CN, Ramakrishnan U, Deming MS. Evaluation of the Integrated Management of Childhood Illness guidelines for treatment of intestinal helminth infections among sick children aged 2-4 years in western Kenya. Transactions of the Royal Society of Tropical Medicine and Hygiene 2002;96(5):543-8.
Goto 2009 {published data only}
  • Goto R, Mascie-Taylor CG, Lunn PG. Impact of anti-Giardia and anthelminthic treatment on infant growth and intestinal permeability in rural Bangladesh: a randomised double-blind controlled study. Transactions of the Royal Society of Tropical Medicine and Hygiene 2009;103:520-9.
Greenberg 1981 {published data only}
  • Greenberg BL, Gilman RH, Shapiro H, Gilman JB, Mondal G, Maksud M, et al. Single dose piperazine therapy for Ascaris lumbricoides: an unsuccessful method of promoting growth. American Journal of Clinical Nutrition 1981;34(11):2508-16.
Hadju 1996 {published data only}
  • Hadju V, Stephenson LS, Abadi K, Mohammed HO, Bowman DD, Parker RS. Improvements in appetite and growth in helminth-infected schoolboys three and seven weeks after a single dose of pyrantel pamoate. Parasitology 1996;113(Pt 5):497-504.
Hadju 1997 {published data only}
  • Hadju V, Satriono, Abadi K, Stephenson LS. Relationship between soil-transmitted helminthiases and growth in urban slum school children in Ujung Pandang, Indonesia. International Journal of Food Sciences and Nutrition 1997;48(2):85-93.
Hall 2006 (Cluster) {unpublished data only}
  • Hall A, Nguyen Bao Khanh L, Bundy D, Quan Dung N, Hong Son T, Lansdown R. A randomized trial of six monthly deworming on the growth and educational achievements of Vietnamese school children. Unpublished manuscript.
Kirwan 2010 {published data only}
  • Kirwan P, Asaolu SO, Molloy SF, Abiona TC, Jackson AL, Holland CV. Patterns of soil-transmitted helminth infection and impact of four monthly albendazole treatments in preschool children from semi-urban communities in Nigeria: a double-blind placebo-controlled randomised trial. BMC Infectious Diseases 2009;9:20.
  • Kirwan P, Jackson AL, Asaolu SO, Molloy SF, Abiona TC, Bruce MC, et al. Impact of repeated four-monthly anthelmintic treatment on Plasmodium infection in preschool children: a double-blind placebo-controlled randomized trial. BMC Infectious Diseases 2010;10:277.
Kloetzel 1982 {published data only}
  • Kloetzel K, Merluzzi Filho TJ, Kloetzel D. Ascaris and malnutrition in a group of Brazilian children - a follow-up study. Journal of Tropical Pediatrics 1982;28(1):41-3.
Koroma 1996 {published data only}
  • Koroma MM, Williams RA, de la Haye RR, Hodges M. Effects of albendazole on growth of primary school children and the prevalence and intensity of soil-transmitted helminths in Sierra Leone. Journal of Tropical Pediatrics 1996;42(6):371-2.
Kruger 1996 {published data only}
  • Kruger M, Badenhorst CJ, Mansvelt EPG, Laubscher JA, Benade AJS. The effect of iron fortification in a school feeding scheme and anthelminthic therapy on the iron status and growth of 6-8 year old school children. Food and Nutrition Bulletin 1996;17(1):11-21.
Kvalsvig 1991a {published data only}
  • Kvalsvig JD, Cooppan RM, Connolly KJ. The effects of parasite infections on cognitive processes in children. Annals of Tropical Medicine and Parasitology 1991;85(5):551-68.
Lai 1995 {published data only}
  • Lai KP, Kaur H, Mathias RG, Ow-Yang CK. Ascaris and Trichuris do not contribute to growth retardation in primary school children. Southeast Asian Journal of Tropical Medicine and Public Health 1995;26(2):322-8.
Le Huong 2007 {published data only}
  • Le Huong T, Brouwer ID, Nguyen KC, Burema J, Kok FJ. The effect of iron fortification and de-worming on anaemia and iron status of Vietnamese schoolchildren. British Journal of Nutrition 2007;97(5):955-62.
Michaelsen 1985 {published data only}
  • Michaelsen KF. Hookworm infection in Kweneng District, Botswana. A prevalence survey and a controlled treatment trial. Transactions of the Royal Society of Tropical Medicine and Hygiene 1985;79(6):848-51.
Miguel 2004 (Cluster) {published data only}
Nga 2009 {published data only}
  • Nga TT, Winichagoon P, Dijkhuizen MA, Khan NC, Wasantwisut E, Furr H, et al. Multi-micronutrient-fortified biscuits decreased prevalence of anemia and improved micronutrient status and effectiveness of deworming in rural Vietnamese school children. Journal of Nutrition 2009;139(5):1013-21.
  • Nga TT, Winichagoon P, Dijkhuizen MA, Khan NC, Wasantwisut E, Wieringa FT. Decreased parasite load and improved cognitive outcomes caused by deworming and consumption of multi-micronutrient fortified biscuits in rural Vietnamese schoolchildren. American Journal of Tropical Medicine and Hygiene 2011;85(2):333-40.
Nokes 1992 {published data only}
  • Nokes C, Grantham-McGregor SM, Sawyer AW, Cooper ES, Bundy DA. Parasitic helminth infection and cognitive function in school children. Proceedings of The Royal Society of London. Series B: Biological sciences 1992;247(1319):77-81.
  • Nokes C, Grantham-McGregor SM, Sawyer AW, Cooper ES, Robinson BA, Bundy DA. Moderate to heavy infections of Trichuris trichiura affect cognitive function in Jamaican school children. Parasitology 1992;104(Pt 3):539-47.
Olds 1999 {published data only}
  • Olds GR, King C, Hewlett J, Olveda R, Wu G, Ouma J, et al. Double-blind placebo-controlled study of concurrent administration of albendazole and praziquantel in school children with schistosomiasis and geohelminths. The Journal of Infectious Diseases 1999;179(4):996-1003.
Palupi 1997 {published data only}
  • Palupi L, Schultink W, Achadi E, Gross R. Effective community intervention to improve hemoglobin status in preschoolers receiving once-weekly iron supplementation. American Journal of Clinical Nutrition 1997;65(4):1057-61.
Rousham 1994 (Cluster) {published data only}
  • Northrop-Clewes CA, Rousham EK, Mascie-Taylor CN, Lunn PG. Anthelmintic treatment of rural Bangladeshi children: effect on host physiology, growth, and biochemical status. American Journal of Clinical Nutrition 2001;73(1):53-60.
  • Rousham EK, Mascie-Taylor CG. An 18-month study of the effect of periodic anthelminthic treatment on the growth and nutritional status of pre-school children in Bangladesh. Annals of Human Biology 1994;21(4):315-24.
Sarkar 2002 {published data only}
  • Sarkar NR, Anwar KS, Biswas KB, Mannan MA. Effect of deworming on nutritional status of ascaris infested slum children of Dhaka, Bangladesh. Indian Pediatrics 2002;39(11):1021-6.
Simeon 1995 {published data only}
  • Gardner JM, Grantham-McGregor S, Baddeley A. Trichuris trichiura infection and cognitive function in Jamaican school children. Annals of Tropical Medicine and Parasitology 1996;90(1):55-63.
  • Simeon DT, Grantham-McGregor SM, Callender JE, Wong MS. Treatment of Trichuris trichiura infections improves growth, spelling scores and school attendance in some children. Journal of Nutrition 1995;125(7):1875-83.
  • Simeon DT, Grantham-McGregor SM, Wong MS. Trichuris trichiura infection and cognition in children: results of a randomized clinical trial. Parasitology 1995;110(Pt 4):457-64.
Solon 2003 {published data only}
  • Solon FS, Sarol JN, Bernardo ABI, Solon JA, Mehansho H, Sanchez-Fermin LE, et al. Effect of a multiple-micronutrient-fortified fruit powder beverage on the nutrition status, physical fitness, and cognitive performance of schoolchildren in the Philippines. Food and Nutrition Bulletin 2003;24(4):S129-40.
Stephenson 1989 {published data only}
  • Stephenson LS, Latham MC, Kinoti SN, Kurz KM, Brigham H. Improvements in physical fitness of Kenyan school boys infected with hookworm, Trichuris trichiura, and Ascaris lumbricoides following a single dose of albendazole. Transactions of the Royal Society of Tropical Medicine and Hygiene 1990;84(2):277-82.
  • Stephenson LS, Latham MC, Kurz KM, Kinoti SN, Brigham H. Treatment with a single dose of albendazole improves growth of Kenyan schoolchildren with hookworm, Trichuris trichiura, and Ascaris lumbricoides infections. American Journal of Tropical Medicine and Hygiene 1989;41(1):78-87.
Stephenson 1993 {published data only}
  • Stephenson LS, Latham MC, Adams EJ, Kinoti SN, Pertet A. Physical fitness, growth and appetite of Kenyan school boys with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved four months after a single dose of albendazole. Journal of Nutrition 1993;123(6):1036-46.
  • Stephenson LS, Latham MC, Adams EJ, Kinoti SN, Pertet A. Weight gain of Kenyan school children infected with hookworm, Trichuris trichiura and Ascaris lumbricoides is improved following once- or twice-yearly treatment with albendazole. Journal of Nutrition 1993;123(4):656-65.
Stoltzfus 1997 (Cluster) {published and unpublished data}
  • Stoltzfus RJ, Albonico M, Chwaya HM, Tielsch JM, Schulze KJ, Savioli L. Effects of the Zanzibar school-based deworming program on iron status of children. American Journal of Clinical Nutrition 1998;68(1):179-86.
  • Stoltzfus RJ, Albonico M, Tielsch JM, Chwaya HM, Savioli L. School-based deworming program yields small improvement in growth of Zanzibari school children after one year. Journal of Nutrition 1997;127(11):2187-93.
Stoltzfus 2001 {published data only}
  • Stoltzfus RJ, Chway HM, Montresor A, Tielsch JM, Jape JK, Albonico M, et al. Low dose daily iron supplementation improves iron status and appetite but not anemia, whereas quarterly anthelminthic treatment improves growth, appetite and anemia in Zanzibari preschool children. Journal of Nutrition 2004;134(2):348-56.
  • Stoltzfus RJ, Kvalsvig JD, Chwaya HM, Montresor A, Albonico M, Tielsch JM, et al. Effects of iron supplementation and anthelmintic treatment on motor and language development of preschool children in Zanzibar: double blind, placebo controlled study. BMJ 2001;323(7326):1389-93.
Sur 2005 {published data only}
  • Sur D, Saha DR, Manna B, Rajendran K, Bhattacharya SK. Periodic deworming with albendazole and its impact on growth status and diarrhoeal incidence among children in an urban slum of India. Transactions of the Royal Society of Tropical Medicine and Hygiene 2005;99(4):261-7.
Watkins 1996 {published data only}
Willett 1979 {published data only}

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. References to ongoing studies
  24. Additional references
  25. References to other published versions of this review
Araujo 1987 {published data only}
  • Araujo RL, Araujo MB, Machado RD, Braga AA, Leite BV, Oliveira JR. Evaluation of a program to overcome vitamin A and iron deficiencies in areas of poverty in Minas Gerais, Brazil. Archivos Latinoamericanos de Nutricion 1987;37(1):9-22.
Beasley 1999 {published data only}
Bhargava 2003 {published data only}
  • Bhargava A, Jukes M, Lambo J, Kihamia CM, Lorri W, Nokes C, et al. Anthelmintic treatment improves the hemoglobin and serum ferritin concentrations of Tanzanian schoolchildren. Food and Nutrition Bulletin 2003;24(4):332-42.
Bhutta 2009 {published data only}
  • Bhutta Z, Klemm R, Shahid F, Rizvi A, Rah JH, Christian P. Treatment response to iron and folic acid alone is the same as with multivitamins and/or anthelminthics in severely anemic 6- to 24-month-old children. The Journal of Nutrition 2009;139(8):1568-74.
Boivin 1993 {published data only}
  • Boivin MJ, Giordani B. Improvements in cognitive performance for schoolchildren in Zaire, Africa, following an iron supplement and treatment for intestinal parasites. Journal of Pediatric Psychology 1993;18(2):249-64.
Cooper 2006 {published data only}
  • Cooper PJ, Chico ME, Vaca MG, Moncayo AL, Bland JM, Mafla E, et al. Effect of albendazole treatments on the prevalence of atopy in children living in communities endemic for geohelminth parasites: a cluster-randomised trial. Lancet 2006;367(9522):1598-603.
Cowden 2000 {published data only}
Diouf 2002 {published data only}
  • Diouf S, Diagne I, Moreira C, Signate SY, Faye O, Ndiaye O, et al. Integrated treatment of iron deficiency, vitamin A deficiency and intestinal parasitic diseases: impact on Senegalese children's growth [Traitement integre de la carence en fer, de l'avitaminose A et des parasitoses intestinales: impact sur la croissance des enfants senegalais]. Archives de Pédiatrie 2002;9(1):102-3.
Evans 1986 {unpublished data only}
  • Evans J, Martin J, Mascie-Taylor CGN. The effect of periodic deworming with pyrantel pamoate on the growth and nutritional status of pre-school children in northern Bangladesh [Monograph No. 3]. London: Save the Children Fund, 1986.
Fernando 1983 {published and unpublished data}
  • Fernando MA, Balasuriya, Somaratne. Effect of Ascaris lumbricoides infestation on growth of children. Indian Pediatrics 1983;20(10):721-31.
Forrester 1998 {published data only}
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.
Gilgen 2001 {published data only}
Gupta 1982 {published data only}
  • Gupta MC, Urrutia JJ. Effect of periodic antascaris and antigiardia treatment on nutritional status of preschool children. American Journal of Clinical Nutrition 1982;36(1):79-86.
Hadidjaja 1998 {published data only}
  • Hadidjaja P, Bonang E, Suyardi MA, Abidin SA, Ismid IS, Margono SS. The effect of intervention methods on nutritional status and cognitive function of primary school children infected with Ascaris lumbricoides. American Journal of Tropical Medicine and Hygiene 1998;59(5):791-5.
Hathirat 1992 {published data only}
  • Hathirat P, Valyasevi A, Kotchabhakdi NJ, Rojroongwasinkul N, Pollitt E. Effects of an iron supplementation trial on the Fe status of Thai schoolchildren. The British Journal of Nutrition 1992;68(1):245-52.
Jalal 1998 {published data only}
  • Jalal F, Nesheim MC, Agus Z, Sanjur D, Habicht JP. Serum retinol concentrations in children are affected by food sources of beta-carotene, fat intake, and anthelmintic drug treatment. American Journal of Clinical Nutrition 1998;68(3):623-9.
Jinabhai 2001a {published data only}
  • Jinabhai CC, Taylor M, Coutsoudis A, Coovadia HM, Tomkins AM, Sullivan KR. Epidemiology of helminth infections: implications for parasite control programmes, a South African perspective. Public Health Nutrition 2001;4(6):1211-9.
Jinabhai 2001b {published data only}
  • Jinabhai CC, Taylor M, Coutsoudis A, Coovadia HM, Tomkins AM, Sullivan KR. A randomized controlled trial of the effect of antihelminthic treatment and micronutrient fortification on health status and school performance of rural primary school children. Annals of Tropical Paediatrics 2001;21(4):319-33.
Karyadi 1996 {published data only}
  • Karyadi E, Gross R, Sastroamidjojo S, Dillon D, Richards AL, Sutanto I. Anthelminithic treatment raises plasma iron levels but dose not decrease the acute-phase response in Jakarta School children. Southeast Asian Journal of Tropical Medicine and Public Health 1996;27(4):742-53.
Krubwa 1974 {published data only}
  • Krubwa F, Gatti F, Lontie M, Nguete M, Vandepitte J, Thiepont D. Quarterly administration of mebendazole to suburban school children [Administration trimestrielle de mebendazole en milieu scolaire suburbain]. Medecine Tropicale 1974;34(5):679-87.
Kvalsvig 1991b {published data only}
  • Kvalsvig JD, Cooppan RM, Connolly KJ. The effects of parasite infections on cognitive processes in children. Annals of Tropical Medicine and Parasitology 1991;85(5):551-68.
Latham 1990 {published data only}
  • Latham MC, Stephenson LS, Kurz KM, Kinoti SN. Metrifonate or praziquantel treatment improves physical fitness and appetite of Kenyan schoolboys with Schistosoma haematobium and hookworm infections. American Journal of Tropical Medicine and Hygiene 1990;43(2):170-9.
Marinho 1991 {published data only}
  • Marinho HA, Shrimpton R, Giugliano R, Burini RC. Influence of enteral parasites on the blood vitamin A levels in preschool children orally supplemented with retinol and/or zinc. European Journal of Clinical Nutrition 1991;45(11):539-44.
Mwaniki 2002 {published data only}
  • Mwaniki D, Omondi B, Muniu E, Thiong’o F, Ouma J, Magnussen P, et al. Effects on serum retinol of multi-micronutrient supplementation and multi-helminth chemotherapy: a randomised, controlled trial in Kenyan school children. European Journal of Clinial Nutrition 2002;56(7):666-73.
Pollitt 1991 {published data only}
  • Pollitt E, Wayne W, Perez-Escamilla R, Latham M, Stephenson LS. Double blind clinical trial on the effects of helminth infection on cognition. FASEB Journal 1991;5:A1081.
Rohner 2010 {published data only}
  • Rohner F, Zimmermann MB, Amon RJ, Vounatsou P, Tschannen AB, N’Goran EK, et al. In a randomized controlled trial of iron fortification, anthelmintic treatment and intermittent preventive treatment of malaria for anemia control in Ivorian children, only anthelmintic treatment shows modest benefit. Journal of Nutrition 2010;140(3):635-41. [DOI: 10.3945/jn.109.114256]
Steinmann 2008 {published data only}
  • Steinmann P, Zhou XN, Du ZW, Jiang JY, Xiao SH, Wu ZX, et al. Tribendimidine and albendazole for treating soil-transmitted helminths, Strongyloides stercoralis and Taenia spp.: open-label randomized trial. PLoS Neglected Tropical Diseases 2008;2(10):e322.
Stephenson 1980 {published data only}
  • Stephenson LS, Crompton DW, Latham MC, Schulpen TW, Nesheim MC, Jansen AA. Relationships between Ascaris infection and growth of malnourished preschool children in Kenya. American Journal of Clinical Nutrition 1980;33(5):1165-72.
Stephenson 1985 {published data only}
  • Stephenson LS, Latham MC, Kurz KM, Kinoti SN, Oduori ML, Crompton DW. Relationships of Schistosoma hematobium, hookworm and malarial infections and metrifonate treatment to hemoglobin level in Kenyan school children. American Journal of Tropical Medicine and Hygiene 1985;34(3):519-28.
Tanumihardjo 1996 {published data only}
  • Tanumihardjo SA, Permaesih D, Muherdiyantiningsih, Rustan E, Rusmil K, Fatah AC, et al. Vitamin A status of Indonesian children infected with Ascaris lumbricoides after dosing with vitamin A supplements and albendazole. Journal of Nutrition 1996;126(2):451-7.
Tanumihardjo 2004 {published data only}
  • Tanumihardjo SA, Permaesih D, Muhilal. Vitamin A status and hemoglobin concentrations are improved in Indonesian children with vitamin A and deworming interventions. European Journal of Clinical Nutrition 2004;58(9):1223-30.
Taylor 2001 {published data only}
  • Taylor M, Jinabhai CC, Couper I, Kleinschmidt I, Jogessar VB. The effect of different anthelmintic treatment regimens combined with iron supplementation on the nutritional status of schoolchildren in KwaZulu-Natal, South Africa: a randomized controlled trial. Transactions of the Royal Society of Tropical Medicine and Hygiene 2001;95(2):211-6.
Thein-Hlaing 1991 {published data only}
  • Thein-Hlaing, Thane-Toe, Than-Saw, Myat-Lay-Kyin, Myint-Lwin. A controlled chemotherapeutic intervention trial on the relationship between Ascaris lumbricoides infection and malnutrition in children. Transactions of the Royal Society of Tropical Medicine and Hygiene 1991;85(4):523-8.
Uscátegui 2009 {published data only}
  • Uscátegui RM, Correa AM, Carmona-Fonseca J. Changes in retinol, hemoglobin and ferritin concentrations in Colombian children with malaria. Biomédica: revista del Instituto Nacional de Salud 2009;29(2):270-81.
Wright 2009 {published data only}
  • Wright VJ, Ame SM, Haji HS, Weir RE, Goodman D, Pritchard DI, et al. Early exposure of infants to GI nematodes induces Th2 dominant immune responses which are unaffected by periodic anthelminthic treatment. PLoS Neglected Tropical Diseases 2009;3(5):e433.
Yang 2003 {published data only}
  • Yang WP, Shao JO, Chen YJ. Effect of chemotherapeutic regimens on soil-transmitted nematode infections in areas with low endemicity. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 2003;21(2):128.

References to ongoing studies

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. References to ongoing studies
  24. Additional references
  25. References to other published versions of this review
Alam 2006 {unpublished data only}
  • Alam MM, Principal Investigator, ICDDR, B: Centre for Health and Population Research. Relative efficacy of two regimens of ante-helminthic treatment. ClinicalTrials.gov identifier: NCT00367627.
Elliot 2007 {published data only}
  • Elliott AM, Kizza M, Quigley MA, Ndibazza J, Nampijja M, Muhangi L, et al. The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447].. Clinical Trials (London, England). 2007; 4(1):42-57; ISSN: CN-00587053.

Additional references

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. References to ongoing studies
  24. Additional references
  25. References to other published versions of this review
Albonico 2008
  • Albonico M, Allen H, Chitsulo L, Engels D, Gabrielli AF, Savioli L. Controlling soil-transmitted helminthiasis in pre-school-age children through preventive chemotherapy. PLoS Neglected Tropical Diseases 2008;2(3):e126.
Anderson 1991
  • Anderson RM, May RM. Infectious diseases of humans: dynamics and control. Oxford: Oxford University Press, 1991.
Bethony 2006
Bleakely 2004
Bundy 2000
  • Bundy D, Peto R. Treatment for intestinal helminth infection. Studies of short term treatment cannot assess long term benefits of regular treatment. BMJ (Clinical research ed.) 2000;321(7270):1225.
Bundy 2009
  • Bundy DA, Kremer M, Bleakley H, Jukes MC, Miguel E. Deworming and development: asking the right questions, asking the questions right. PLoS Neglected Tropical Diseases 2009;3(1):e362.
Callender 1998
Cappello 2004
Chan 1997
Cochrane Collaboration 2002
  • Alderson P, Green S (editors). Meta-analysis of continuous data: Deciding on a change (from baseline). The Cochrane Collaboration: Open learning material for reviewers (Available at http://www.cochrane-net.org/openlearning/html/modA1-6.htm). 2002.
Cooper 2000
Copenhagen Consensus Center 2012
  • Copenhagen Consensus Center. Copenhagen Consensus 2012. http://www.copenhagenconsensus.com/Default.aspx?ID=1626 (accessed 22nd May 2012).
Crompton 2000
Crompton 2003
  • Crompton DWT, Torlesse H, Hodges ME. Hookworm infection and iron status. In: Crompton DWT, Montresor A, Nesheim MC, Savioli L editor(s). Controlling disease due to helminth infections. Geneva: World Health Organization, 2003:23-32.
Danso-Appiah 2008
de Silva 2003a
de Silva 2003b
Deworm the World 2012
  • Deworm the World. [The Evidence For School-Based Deworming]. http://www.dewormtheworld.org/?q=node/105 (accessed 22nd May 2012).
Engels 2009
GiveWell 2011
  • GiveWell 2011. Errors in DCP2 cost-effectiveness estimate for deworming. http://blog.givewell.org/2011/09/29/errors-in-dcp2-cost-effectiveness-estimate-for-deworming/ (accessed 22nd May 2012).
GRADE 2004
  • Jan Brozek, Andrew Oxman, Holger Schunemann. GRADEpro. Version 3.2 for Windows. Jan Brozek, Andrew Oxman, Holger Schunemann, 2008.
Gulani 2007
  • Gulani A, Nagpal J, Osmond C, Sachdev HP. Effect of administration of intestinal anthelmintic drugs on haemoglobin: systematic review of randomised controlled trials. BMJ 2007;334(7603):1095.
Haider 2009
Hall 2008
Higgins 2011a
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Higgins 2011b
  • Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; Vol. 343:d5928.
Horton 2003
Hotez 2006b
  • Hotez P, Bundy D, Beegle K, Brooker S, Drake L, se Silva N, et al. Helminth infections: Soil-transmitted helminth infections and schistosomiasis. Disease control priorities in developing countries. 2nd Edition. New York: Oxford University Press, 2006:467-82.
Hotez 2009
Hotez 2011a
  • Hotez PJ. New antipoverty drugs, vaccines, and diagnostics: a research agenda for the US President's Global Health Initiative (GHI). PLoS Neglected Tropical Diseases 2011;5(5):e1133.
Hotez 2011b
  • Hotez PJ. Unleashing “Civilian Power”: A new American diplomacy through neglected tropical disease control, elimination, research, and development. PLoS Neglected Tropical Diseases 2011;5(6):e1134.
Jamison 2006
  • Jamison DT, Breman JG, Measham AR, Alleyne G, Claeson M. Evans DB, et al (editors). Disease Control Priorities in Developing Countries. 2nd Edition. New York: Oxford University Press and the World Bank, 2006.
Kvalsvig 2003
  • Kvalsvig JD. Parasites, nutrition, child development and public policy. In: Crompton DWT, Montresor A, Nesheim MC, Savioli L editor(s). Controlling disease due to helminth infections. Geneva: World Health Organization, 2003:55-65.
Lefebvre 2011
  • Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 (updated March 2011). The Cochrane Collaboration, 2011.
Moher 2001
  • Moher D, Schulz KF, Altman DG for the CONSORT Group. The CONSORT statement: Revised recommendations for improving the quality of reports of parallel group randomized trials 2001. www.consort-statement.org/Statement/revisedstatement.htm (accessed 3 August 2005).
Molyneux 2005
  • Molyneux DH, Hotez PJ, Fenwick A. "Rapid-impact interventions": How a policy of integrated control for Africa's neglected tropical diseases could benefit the poor. PLoS Medicine 2005;2(11):e336.
Montresor 2002
  • Montresor A, Crompton DWT, Gyorkos TW, Savioli L. Helminth control in school-age children: a guide for managers of control programmes. Geneva: World Health Organization, 2002.
Review Manager 5
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.1 for Windows. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
Sakti 1999
Savioli 2000
  • Savioli L, Neira M, Albonico M, Beach MJ, Chwaya HM, Crompton DW, et al. Treatment for intestinal helminth infection. Review needed to take account of all relevant evidence, not only effects on growth and cognitive performance. BMJ 2000;321(7270):1226-7.
Savioli 2002
  • Savioli L, Montresor A, Albonico M. Control strategies. In: Holland CV, Kennedy MW editor(s). The geohelminths: Ascaris, Trichuris and Hookworm. Netherlands: Kluwer Academic Publishers, 2002:25-37.
Stephenson 2000
Taylor-Robinson 2007
WHO 2002
  • WHO Expert Committee on the Control of Schistosomiasis (2001: Geneva, Switzerland). Prevention and control of schistosomiasis and soil-transmitted helminthiasis: report of a WHO expert committee. WHO technical report series no. 912. Geneva: World Health Organization, 2002.
WHO 2005
  • World Health Organization. Strategy Development and Monitoring for Parasitic Diseases and Vector Control Team. Deworming: The Millennium Development Goals. The evidence is in: deworming helps meet the Millennium Development Goals [WHO/CDS/CPE/PVC/2005.12]. Geneva: World Health Organization, 2005.
WHO 2006a
  • World Health Organization. WHO Essential Medicines Library. mednet3.who.int/emlib/ 2006 (accessed 13 June 2007).
WHO 2006b
  • WHO. Preventive chemotherapy in human helminthiasis: coordinated use of anthelminthic drugs in control interventions: a manual for health professionals and programme managers. Accessed at http://whqlibdoc.who.int/publications/2006/9241547103_eng.pdf. WHO, 2006.
WHO 2007
  • WHO. Action against worms. http://www.who.int/wormcontrol/newsletter/PPC8_eng.pdf 2007.
WHO 2010
  • WHO. Monitoring drug coverage for preventive chemotherapy. http://whqlibdoc.who.int/publications/2010/9789241599993_eng.pdf 2010.
World 2011
  • World Bank. School Deworming http://web.worldbank.org/WBSITE/EXTERNAL/TOPICS/EXTHEALTHNUTRITIONANDPOPULATION/EXTPHAAG/0,,contentMDK:20785786˜menuPK:1314819˜pagePK:64229817˜piPK:64229743˜theSitePK:672263,00.html(accessed 10th Jan 2012). 2011.
World Bank 1993
  • The World Bank. World Development Report 1993: Investing in health. Oxford: Oxford University Press, 1993.

References to other published versions of this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. References to ongoing studies
  24. Additional references
  25. References to other published versions of this review
Dickson 2000a
  • Dickson R, Awasthi S, Demellweek C, Williamson P. Anthelmintic drugs for treating worms in children: effects on growth and cognitive performance. Cochrane Database of Systematic Reviews 2000, Issue 2. [DOI: 10.1002/14651858.CD000371]
Dickson 2000b
  • Dickson R, Awasthi S, Williamson P, Demellweek C, Garner P. Effects of treatment for intestinal helminth infection on growth and cognitive performance in children: systematic review of randomised trials. BMJ 2000;320(7251):1697-701.