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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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This is not the most recent version of the article. View current version (14 NOV 2012)

 
Characteristics of included studies [ordered by study ID]
Adams 1994

MethodsRandomized controlled trial

Length of follow up: 2.25 months (9 weeks)


ParticipantsNumber analysed for primary outcome: 55

Inclusion criteria: children in nursery and standard 1 classes of Mvindeni Primary School in Kwale, Kenya; > 500 eggs/g hookworm or > 1000 eggs/g Trichuris or Ascaris; pre-pubertal; > 5 years old

Exclusion criteria: severe anaemia (haemoglobin < 75 g/L)


InterventionsSingle dose versus placebo
1. Albendazole: 3 x 400 mg doses on 3 consecutive days
2. Identical placebo

Treatment strategy: screened children then randomized and treated infected children


Outcomes1. Mean weight post-treatment
2. Mean change in weight post-treatment
3. Mean height post-treatment
4. Mean change in height post-treatment
5. Mean mid-upper arm circumference
6. Mean change in mid-upper arm circumference
7. Mean triceps skinfold thickness
8. Mean change in triceps skinfold thickness
9. Mean subscapular skinfold thickness
10. Mean change in subscapular skinfold thickness
11. Mean haemoglobin post-treatment
12. Activity levels (a measure of gross motor activity of legs)
13. Self rating of appetite

Not included in review: helminth prevalence and intensity (arithmetic and geometric mean eggs/g); baseline and post-intervention values for arm muscle area and arm fat area; z-scores for weight, height, weight-for-height, mid-upper-arm circumference, triceps skinfold, subscapular, arm muscle, and arm fat area


NotesLocation: Kenya

Community category: 1

Source of funding not stated


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk“Subjects were grouped according to sex and paired according to hookworm intensity,- one of each pair was allocated at random to the albendazole-treated group or the placebo group.” Method not reported.

Allocation concealment (selection bias)Unclear riskNo details reported.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOne participant lost to follow-up in the placebo group, data for this subject were omitted from analyses. No details of reason for drop out. Inclusion of all randomized participants (number evaluable/number randomized): 98% (55/56).

Selective reporting (reporting bias)Low riskAll stated outcomes reported.

Other biasLow riskNo other obvious source of bias.

Alderman 2006 (Cluster)

MethodsCluster-randomized controlled trial

Method to adjust for clustering: multivariate regression models in Stata for table 3. Primary outcome of weight gain not adjusted for clustering in BMJ paper.

Cluster unit: parish

Average cluster size: 560

ICCs: not reported but calculated from adjusted ands unadjusted figures to be 0.01.

Length of follow up: 3 years


ParticipantsNumber analysed for primary outcome: 27,995 in 48 clusters

Age range: 1 to 7 years

Inclusion criteria: children aged 1 to 7 in 50 parishes in Uganda selected by the government on the basis that around 60% of children aged 5 to 10 years in these parishes were infected with intestinal nematodes

Exclusion criteria: sick children


InterventionsMultiple dose versus no treatment

1. Albendazole: 400 mg tablet (Zentel, GSK) every 6 months, although in the event a year elapsed between the first and second treatment round; given in conjunction with a child health package including vaccinations, vitamin A, and health promotion
2. Child health package including vaccinations, vitamin A, and health promotion

Treatment strategy: randomized and treated all children


Outcomes1. Mean change in weight post-treatment


NotesLocation: Uganda

Community category: 2

Weight gain data taking into account the effects of cluster randomization provided by the author.

Source of funding: the nutrition and early child development project, government of Uganda, the Institute of Public Health and the research committee of the World Bank.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskCoin toss “The randomization was done by a member of the research team (HA) by assigning numbers to all of the parishes and converting these to base two and then determining which of the parishes were to be in the treatment by coin flips”

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
High riskNone. “It was not possible for us to carry out a double blind trial because of the scale of the programme and because we aimed to assess the effectiveness of giving albendazole […] during standard child health days without any study specific inputs”

Incomplete outcome data (attrition bias)
All outcomes
High risk75% (27,995/37,165) of randomized participants were evaluated

Selective reporting (reporting bias)Low riskAll stated outcomes reported.

Other biasLow riskRecruitment bias: low risk

Baseline imbalance: Characteristics similar (low risk)

Loss of clusters: nil (low risk)

Incorrect analysis:primary outcome in paper not adjusted for clustering, but was subsequently corrected (low risk)

Comparability with RCTs randomizing individuals: unclear

Awasthi 2000

MethodsQuasi-randomized controlled trial

Length of follow up: 2 years


ParticipantsNumber analysed for primary outcome: 1045

Age range: 1.5 to 3.5 years

Inclusion criteria: children living in 32 randomly selected urban slums; registered with an Anganwadi worker (health worker); between 1.5 to 3.5 years of age

Exclusion criteria: none stated


InterventionsMultiple doses versus placebo

1. Albendazole powder: 600 mg every 6 months for 2 years
2. Placebo: calcium powder

Treatment strategy: randomized and treated all children


Outcomes1. Mean weight post-treatment
2. Mean change in weight post-treatment
3. Mean height post-treatment
4. Mean change in height post-treatment
5. Developmental status (Denver Questionnaire): reported as proportion with normal development

6. Haemoglobin

Not included in review: prevalence of underweight and stunting over 2 years as defined by z-scores, haemoglobin (visual colour estimation), stool examination (non-concentration method), incidence of illness, and death


NotesLocation: Lucknow, India

Community category: 3

Source of funding: International Clinical Epidemiology Network (INCLEN), Philadelphia, USA grant #2002-94-623 under the Clinical Economics Small Grants Program.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High risk32 Anganwadi centres randomly selected, and then children allocated to a serial number; those with odd or non-zero ending numbers were assigned to placebo

Allocation concealment (selection bias)High riskNot concealed

Blinding (performance bias and detection bias)
All outcomes
Unclear riskSingle blind

Incomplete outcome data (attrition bias)
All outcomes
Low risk9/610 children in the albendazole group and 7/451 in the placebo group were lost to follow-up

Inclusion of all randomized participants (number evaluable/number randomized): 98% (1045/1061)

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo other obvious source of bias

Awasthi 2001 (Cluster)

MethodsCluster-randomized controlled trial

Method to adjust for clustering: cluster used as unit of analysis.

Cluster unit: urban slums

Average cluster size: 13.5

ICCs: not reported.

Length of follow up: 1.5 years


ParticipantsNumber analysed for primary outcome: 124 slums randomized containing 1672 children

Inclusion criteria: clusters selected if they have functional community workers in slum areas of Lucknow; within each cluster, children recruited if aged between 0.5 and 1 year, on basis of survey register held by each worker of their particular area

Exclusion criteria: none stated


InterventionsMultiple doses versus placebo

1. Albendazole plus placebo: albendazole suspension (concentration not stated) (Zentel, SZB) every 6 months and 100,000 units of vitamin A every 6 months
2. Placebo: 100,000 units of vitamin A every 6 months

Treatment strategy: randomized and treated all children


Outcomes1. Mean weight post-treatment
2. Mean change in weight post-treatment
3. Mean height post-treatment
4. Mean change in height post-treatment (not used due to question over quoted standard error)

Not included in review: stool smear for Ascaris prevalence on a subsample of the group; death rates


NotesLocation: Lucknow, India

Community category: 3

Means of cluster means used in analysis. The results (weight gain) in the abstract differ from the text.

Source of funding: International Clinical Epidemiological Network (INCLEN) Inc, USA and Clinical Trials Unit (CTSU), Oxford, UK.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskCluster-randomized trial, no further details

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskIntention to treat analysis; 13.9% lost to follow-up in albendazole group and 16.2% in the placebo group. Inclusion of all randomized participants (number evaluable/number randomized): 83% (1672/2010)

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskRecruitment bias: Unclear (Not known if children shift clinics in the light of the intervention)

Baseline imbalance: Characteristics similar (low risk)

Loss of clusters: No loss reported (low risk)

Incorrect analysis: Cluster adjusted (low risk)

Comparability with RCTs randomising individuals: low ( Analysis 5.1 and  Analysis 5.2)

Awasthi 2008 (Cluster)

MethodsCluster-quasi-randomized controlled trial

Method to adjust for clustering: cluster used as unit of analysis.

Cluster unit: urban slum

Average cluster size: 74

ICCs: not reported.

Length of follow up: 2 years


ParticipantsNumber analysed for primary outcome: 3712

Age range: 1 to 4 years

Inclusion criteria: children aged 1 to 4 from 50 urban slums in Lucknow selected on the basis of geographic convenience

Exclusion criteria: none stated


InterventionsMultiple doses versus placebo

1. Albendazole plus placebo: 400 mg albendazole plus 2 mL vitamin A every 6 months
2. Placebo: 2 mL vitamin A every 6 months

Treatment strategy: randomized and treated all children


Outcomes1. Mean change in weight post-treatment
2. Mean change in height post-treatment


NotesLocation: Lucknow, India

Community category: 3

Trail carried out in 1995 and published in 2008.

Weight data taken from Awasthi 2008 published document. Height data from INCLEN 1995 monograph. Means of cluster means used in analysis; details of correspondence from previous review suggest that trial was ongoing; data for 3-year follow up are provided from R Dickson's correspondence with the author for the Dickson 2000a Cochrane Review, but the loss to follow up is very high: only 24% analysed.

Source of funding: Clinical Trial Service Unit (CTSU), University of Oxford, United Kingdom, and co-funded by the International Clinical Epidemiology Network Inc., Philadelphia, United States of America. Albendazole was donated by SmithKline Beecham (now GlaxoSmithKline).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuasi-randomized: “Random allocation was done by SA, listing the anganwadi centers of each slum area serially in alphabetical order, numbering them from 1 to 50, and then generating a single random number by computer that allocated either all odd or all even numbers to a specific intervention type.”

Allocation concealment (selection bias)High riskNot concealed

Blinding (performance bias and detection bias)
All outcomes
High riskCluster RCT with health staff and participants knowing which group they were allocated to

Incomplete outcome data (attrition bias)
All outcomes
Low risk1852/1968 children in the treatment group completed all follow-up visits; 1860/1967 children in the usual care group completed all follow-up visits. Inclusion of all randomized participants (number evaluable/number randomized): 94% (3712/3935)

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskRecruitment bias: Unclear (Not known if children shift clinics in the light of the intervention)

Baseline imbalance: Unclear

Loss of clusters: Low (none reported)

Incorrect analysis: Cluster adjusted (low risk)

Comparability with RCTs randomising individuals: unclear ( Analysis 5.1 and  Analysis 5.2)

Beach 1999

MethodsRandomized controlled trial

Length of follow up: 4 months


ParticipantsNumber analysed for primary outcome: 853

Inclusion criteria: all children attending 5 schools (grades 1 to 4)

Exclusion criteria: haematocrit < 22%


InterventionsSingle dose versus placebo

1. Albendazole: 400 mg (SmithKlineBeecham, Philadelphia or generic BeltaPharm, Milan)
2. Ivermectin: 200 to 400 µg/kg (mean 282.7 µg/kg) (Merck, West Point, PA)
3. Albendazole plus ivermectin
4. Placebo: 250 mg vitamin C

Treatment strategy: randomized and treated all children


Outcomes1. Height
2. Weight
3. Stool examination for helminth prevalence and intensity (geometric mean)
4. Haematocrit


NotesLocation: Haiti

Community category: 3

Results presented in a stratified analysis as per individual infection: disaggregated results not presented; measures of error not given in tables.

Source of funding: USAID.
Invermectin provided by Philippe Gaxotte (Merck, Inc.) and albendazole by John Horton (SmithKline Beecham)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number table

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants, provider, and assessors were blind

Incomplete outcome data (attrition bias)
All outcomes
Low risk29/229 were lost to follow-up in the placebo group and 25/244 were lost to follow-up in the albendazole group. Inclusion of all randomized participants (number evaluable/number randomized): 88.4% (853/965)

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo other obvious source of bias

DEVTA (unpublished)

MethodsCluster-randomized controlled trial

Method to adjust for clustering: cluster used as unit of analysis ('means of block-specific numbers of deaths per AWC').

Cluster unit: a block of 10,000-20,000 children

Average cluster size: 9259 approximately (under-5 population 1 million/108 clusters).

ICCs: not reported.

Length of follow up: 5 years


ParticipantsNumber analysed for primary outcome: 8338 ICDS-staffed preschool centres in 72 administrative blocks (under-5 population 1 million)

Inclusion criteria: All preschool children then aged 1-6·0 in 72 participating blocks near Lucknow that were considered to have a well-functioning ICDS system with willing district and block directors and with paid workers in most of the block’s anganwadi centres.

Exclusion criteria: severe anaemia (haemoglobin < 75 g/L)


InterventionsMultiple doses versus placebo

Factorial design in four arms:

1. Usual care – no placebo;

2. 6-monthly vitamin A [for 5 years];

3. 6-monthly 400 mg albendazole;

4. Both 6-monthly vitamin A and 6-monthly 400 mg albendazole.


Outcomes1. Mortality


NotesLocation: Lucknow, India

Community category: 3

Annually about 30 non-randomly selected preschool children were surveyed for growth, nutritional and morbidity outcomes from one randomly selected AWC per block (10,000 to 20,000 children in about 120 AWCs per block).

Source of funding: UK Medical Research Council, USAID OMNI project, World  Bank. Albendazole (Zentel) was donated by SmithKlineBeecham.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk“randomly allocated”; “Randomisation (in Oxford) was stratified in groups of 4 neighbouring blocks, where possible in the same district.”

Allocation concealment (selection bias)Unclear riskSee above

Blinding (performance bias and detection bias)
All outcomes
Unclear riskAll cause mortality is the outcome

Incomplete outcome data (attrition bias)
All outcomes
Low risk89 AWCs (2%) in the albendazole block lost to follow-up, 86 AWCs (2%) in the placebo block lost to follow-up. “Loss to follow-up is defined by having only 1-6 follow-up visits (mean only 3, as against 12 in the included AWCs), and was generally because the AWC had ceased to function.” Inclusion of all randomized participants (number evaluable/number randomized): Denominator for mortality was all children. A subset of 5165 children were assessed for other outcomes

Selective reporting (reporting bias)Low riskMortality is the single outcome for this trial

Other biasLow riskRecruitment bias: unclear.

Baseline imbalance: unclear.

Loss of clusters: unclear.

Incorrect analysis: Cluster adjusted (low risk).

Comparability with RCTs randomising individuals: unclear.

Donnen 1998

MethodsRandomized controlled trial

Length of follow up: 1 year


ParticipantsNumber analysed for primary outcome: 222

Inclusion criteria: children aged 0 to 72 months eligible on discharge from hospital where primary cause for admission is malnutrition

Exclusion criteria: none stated


InterventionsMultiple doses versus placebo and no treatment

1. Mebendazole: 500 mg at start and every 3 months
2. Placebo: 60 mg vitamin A at start and 3 months
3. No treatment

Treatment strategy: randomized and treated all children


Outcomes1. Mean weight post-treatment
2. Mean change in weight post-treatment
3. Mean height post-treatment
4. Mean change in height post-treatment
5. Mean mid-upper arm circumference
6. Mean change in mid-upper arm circumference

Not included in review: vitamin A levels; z-scores for height-for-age, weight-for-age, weight-for-height (NCHS reference); egg counts (eggs/g: Kato Katz method)


NotesLocation: Zaire

Community category: 3

Unadjusted data not provided in original paper; results of multiple-regression models presented on basis of stratifications into vitamin A status and sex; results in meta-analysis from R Dickson's correspondence with author when preparing the Dickson 2000a Cochrane Review.

Source of funding: Fonds de la Recherche Scientifique et Medicale (FRSM), contract 3.4505.94 and the David and Alice Van Buuren Foundation.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk“randomized”, no further details reported.

Allocation concealment (selection bias)Unclear riskNo details reported.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOverall, 6% of children were lost to follow-up, with approximately equal proportions from each group. During the follow- up period, 25 children died. The final sample included 311 children Inclusion of all randomized participants (number evaluable/number randomized): 86% (311/358).

Selective reporting (reporting bias)Low riskAll stated outcomes reported.

Other biasLow riskNo other obvious source of bias.

Dossa 2001

MethodsRandomized controlled trial

Length of follow up: 10 months


ParticipantsNumber analysed for primary outcome: 65

Inclusion criteria: children aged 3 to 5 years; not acutely unwell

Exclusion criteria: none stated


InterventionsMultiple doses versus placebo

1. Albendazole plus iron: 200 mg albendazole per day for 3 consecutive days repeated 1 month later plus iron
2. Placebo plus iron
3. Albendazole: 200 mg per day for 3 consecutive days repeated 1 month later plus iron placebo
4. Placebo plus placebo

Treatment strategy: randomized and treated all children


Outcomes1. Mean change in weight post-treatment
2. Mean change in height post-treatment
3. Mean change in mid-upper arm circumference
4. Mean change in triceps skinfold thickness
5. Mean haemoglobin post-treatment

Not included in review: weight-for-height z-score and height-for-age z-score at 3 and 10 months (both after 2 doses)

Measured but not reported: z-scores for weight-for-height, height for age using NCHS reference data; egg count (arithmetic and geometric mean); prevalence, intensity; food intake over 3 days in subset at end of trial (not at baseline)


NotesLocation: Benin

Community category: 2

Source of funding: The Nestle Foundation (Lausanne, Switzerland).Smithkline Beecham provided the deworming and placebo tablets.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk“Randomly assigned”, no further details provided

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear risk“Double-blind”, no further details provided

Incomplete outcome data (attrition bias)
All outcomes
High risk175/177 children finished the study, but 140 were included in the final analysis: “One child was treated for severe worm infection and 34 children received other pills during the study period (iron, vitamins/minerals or deworming pills that were not provided by our research team).” Inclusion of all randomized participants (number evaluable/number randomized): 79% (140/177)

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasHigh riskNo obvious other source of bias

Fox 2005

MethodsRandomized controlled trial

Length of follow up: 6 months


ParticipantsNumber analysed for primary outcome: 626

Inclusion criteria: children aged 5 to 11 years attending any of 12 primary schools in Haiti where no other deworming activity was taking place

Exclusion criteria: none stated


InterventionsSingle dose versus placebo:

1. Albendazole 400 mg plus placebo (250 mg vitamin C tablet)
2. 6 mg/kg diethylcarbamazine (DEC) plus placebo (250 mg vitamin C tablet)
3. Albendazole 400 mg plus single dose of 6 mg/kg diethylcarbamazine (DEC)
4. Placebo plus placebo (2 x 250 mg vitamin C tablets)

Treatment strategy: randomized and treated all children


Outcomes1. Weight: final and change in weight
2. Height: final and change in height
3. Adverse effects

Not included in review: worm intensity and prevalence; microfilarial density


NotesLocation: Haiti

Community category: 2

Weight and height outcomes are only presented for a subgroup of children infected with Trichuris

Source of funding: Emerging Infections Program of the Centers for Disease Control and Prevention and an Institutional Strengthening Grant from the World Health Organization to the Hopital Sainte Croix.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom-number table

 

Allocation concealment (selection bias)Low riskCentrally-coded allocation system broken after baseline measures taken

 

Blinding (performance bias and detection bias)
All outcomes
Low risk“Double-blind”. Laboratory personnel, measurement teams and personnel evaluating students for adverse reactions were all blinded

 

Incomplete outcome data (attrition bias)
All outcomes
Low risk626/646 participants analysed for the primary outcome. Reasons for loss to follow-up unclear

 Inclusion of all randomized participants (number evaluable/number randomized): 97% (626/646)

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo obvious other source of bias

Freij 1979a

MethodsQuasi-randomized controlled trial

Length of follow up: 28 days


ParticipantsNumber analysed for primary outcome: 13

Inclusion criteria: boys attending mother and child clinic with Ascaris on stool smear; aged 1.5 to 5 years with no history of diarrhoea for preceding 2 weeks; no fever; no respiratory symptoms; no signs of severe disease

Exclusion criteria: children diagnosed with other parasites; excluded girls to eliminate the contamination of samples with urine


InterventionsSingle dose versus placebo

1. Piperazine: 3 g single dose
2. Placebo syrup: single dose

Treatment strategy: screened children then randomized and treated infected children


Outcomes1. Weight
2. Mid-upper arm circumference
3. Triceps skinfold thickness

Not included in review: Ascaris worm count


NotesLocation: Ethiopia

Community category: unclear

The authors mention that boys were matched in pairs so that if there were drop outs they could be replaced. They do not indicate if there were any drop outs. Standard deviations calculated from individual data

Freij 1979a and Freij 1979ai were reported in the same article.

Source of funding: Semper Nutrition Fund, Stockholm; Swedish Medical Research Council.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuasi-randomized controlled trial: boys matched into pairs of equal age and nutritional status

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDescribed as double blind, no further details reported

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk100% (13/13) of enrolled participants were evaluated. The authors mention that boys were matched in pairs so that if there were drop outs they could be replaced. They do not indicate if there were any drop outs. Inclusion of all randomized participants (number evaluable/number randomized): 100% (13/13)

Selective reporting (reporting bias)Low riskAuthors had intended to measure bicep and tricep skinfolds, but staff were unable to take these measurements

Other biasLow riskNo obvious other source of bias

Freij 1979b

MethodsQuasi-randomized controlled trial

Length of follow up: 34 days


ParticipantsNumber analysed for primary outcome: 44

Inclusion criteria: 92 children 1 to 5 years from a community morbidity study


InterventionsSingle dose versus placebo

1. Piperazine: 3 g/day for 2 days
2. Placebo: for 2 days

Treatment strategy: screened children then randomized and treated infected children


Outcomes1. Mid-upper arm circumference
2. Morbidity

Not included in review: weight in % of Harvard standard; authors had intended to measure bicep and tricep skinfolds, but staff were unable to take these measurements


NotesLocation: Ethiopia

Community category: 3

Freij 1979a and Freij 1979ai were reported in the same article.

Source of funding: Semper Nutrition Fund, Stockholm; Swedish Medical Research Council.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuasi-randomized controlled trial: children matched into pairs of equal age and nutritional status

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDescribed as double blind, no further details reported

Incomplete outcome data (attrition bias)
All outcomes
Low risk100% (44/44) of enrolled participants were evaluated. Inclusion of all randomized participants (number evaluable/number randomized): 100% (44/44)

Selective reporting (reporting bias)Low riskAuthors had intended to measure bicep and tricep skinfolds, but staff were unable to take these measurements

Other biasLow riskNo obvious other source of bias

Garg 2002

MethodsRandomized controlled trial

Length of follow up: 6 months


ParticipantsNumber analysed for primary outcome: 347

Inclusion criteria: sick children 2 to 4 years old presenting to 3 government health centres in Bungamo district, without palmar pallor

Exclusion criteria: children with palmar pallor


InterventionsSingle dose versus placebo

1. Mebendazole: 500 mg (Vermox, Janssen, Belgium)
2. Placebo: sucrose starch capsule

Treatment strategy: randomized and treated all children


Outcomes1. Mean weight post-treatment
2. Mean change in weight post-treatment
3. Mean height post-treatment
4. Mean change in height post-treatment
5. Mean haemoglobin post-treatment
6. Mean change in haemoglobin post-treatment

Not included in review: z-scores for weight-for-age, height-for-age, and weight-for-height; egg count (formol-ethyl acetate concentration method) in categories of intensity


NotesLocation: Kenya

Community category: 3

Source of funding: the Centers for Disease Control and Prevention, Atlanta, USA.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated list of random numbers

Allocation concealment (selection bias)Low riskDrugs kept in envelope until after baseline assessment

Blinding (performance bias and detection bias)
All outcomes
High risk“the trial was not double-blinded” Assessors were blinded; participants unclear; provider not blinded

Incomplete outcome data (attrition bias)
All outcomes
Low risk93% (347/370) of randomized participants were evaluated, loss to follow-up balanced across groups. Inclusion of all randomized participants (number evaluable/number randomized): 93% (347/370)

Selective reporting (reporting bias)Low riskAll stated outcomes included

Other biasLow riskNo obvious other source of bias

Goto 2009

MethodsRandomized controlled trial

Length of follow up: 36 weeks


ParticipantsNumber analysed for primary outcome: 410

Inclusion criteria: infants under 11 months of age in the local area.

Exclusion criteria: Not stated.


InterventionsMultiple doses versus placebo

1. anti-Giardia (secnidazole every 4 weeks) and anthelminthic (albendazole every 12 weeks).

2. anti-Giardia treatment only (secnidazole every 4 weeks) and placebo.

3. Placebo and placebo

Treatment strategy:

Secnidazole: a 70 mg/mL suspension with about 0.5 g of sweetener was made up, and 0.5 mL per kg body weight was given by spoon. If the infant was sick immediately, secnidazole was re-administrated.

Albendazole: A 200 mg (5 mL) suspension given by spoon.


Outcomes1. Hb (g/L) (endpoint week 36)

Not included in review:

2. Height-for-age z-score (endpoint week 36)

3. Weight-for-age z-score (endpoint week 36)

4. Weight-for-height z-score (endpoint week 36)

5. Plasma albumin (g/L) (endpoint week 36)

6. IgG (g/L) (endpoint week 36)

7. Alpha-1-acid glycoprotein (g/L) (endpoint week 36)

8. Giardia-specific IgM titre (endpoint week 36)

9. Lactulose/mannitol ratio (endpoint week 36)

10. Prevalence of Giardia-specific IgM titre, % (week 0,12,24,36)

11. Prevalence of Giardia cysts, % (week 0,12,24,36)

12. Prevalence of Ascaris/Trichuris, % (week 0,12,24,36)

13. Prevalence of Intestinal mucosal damage, % (week 0,12,24,36)

14. Prevalence of Anaemia, % (week 0,12,24,36)


NotesLocation: Dhamrai Upazila, located 40km northwest of Dhaka, Bangladesh.

Community category: 3. "Prevalences and intensities of geohelminths were consistently low throughout the intervention"

Drug source: Dhaka, Bangladesh (Essential Drugs Company Ltd for secnidazole; Square Pharmaceuticals Ltd for the secnidazole placebo; Opsonin Chemical Industries Ltd for albendazole; and UniMed and UniHealthManufacturing Ltd for albendazole placebo).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer generated

Randomized on the basis of their age, sex, height-for-age, weight-for-age and weight-for-height z-scores, socio-demographic and economic data and presence of any parasitic infection

Allocation concealment (selection bias)Unclear riskUnclear whether the allocation was concealed since patients were randomized by their characteristics.

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind

"Bottles containing the two medications and placebo suspensions were labelled with different colours corresponding to the three intervention groups, but the assistants did not know the relationship between the colour codings and the contents of the bottles."

Incomplete outcome data (attrition bias)
All outcomes
Low risk394/410 (96.10%) of randomized participants were evaluated.

"A total of 16 infants were excluded from the study, as they had either moved away from the study area (n = 12), or were absent during the study period (n = 2) or the parents subsequently refused to participate (n = 2). Of the infants who completed the study (n = 394), data on 96 infants was incomplete (ie they did not provide information for all the ten z-scores and four intestinal permeabilities, serological variables and prevalences of parasite infections), and severe anaemic infants were also omitted from the study" Inclusion of all randomized participants (number evaluable/number randomized): 96% (394/410)

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo obvious other source of bias

Greenberg 1981

MethodsRandomized controlled trial

Length of follow up: 11 months


ParticipantsNumber analysed for primary outcome: 152 aged 1.5 to 8 years

Inclusion criteria: children aged 1.5 to 8 years living in Nandipara, Bangladesh; 50% entered into study; only those who provided stool sample and had anthropometric measurements taken at first visit entered

Exclusion criteria: none stated


InterventionsSingle dose versus placebo

1. Piperazine citrate: 80 mg/kg added to flavoured syrup; 2 doses in 2-week period
2. Placebo: syrup only

Treatment strategy: randomized and treated all children


Outcomes1. Cure rates
2. Reinfection rates
3. Weight-for-height
4. Height-for-age (NCHS reference)
5. Weight-for-age (graphically)
6. Other measured parameters not reported: weight; height; triceps skinfold thickness; mid-upper arm circumference; chest circumference; abdominal girth; egg counts (Dunn's method); prevalence; triceps skinfold for age; mid-upper arm circumference for age (Tanner reference charts)


NotesLocation: Bangladesh

Community category: 1

Groups stratified by intensity of Ascaris infection

Source of funding not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk“Randomly assigned”, no further details provided

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear risk“Double-blind”. Participants blinded both placebo and treatment given as a flavoured syrup, no information about provider and assessor blinding

Incomplete outcome data (attrition bias)
All outcomes
Low risk82% (152/185) of randomized participants were evaluated. Reasons for leaving the study early not reported. Inclusion of all randomized participants (number evaluable/number randomized): 82% (152/185)

Selective reporting (reporting bias)High riskNot all stated outcomes reported

Other biasLow riskNo obvious other source of bias

Hadju 1996

MethodsQuasi-randomized controlled trial

Length of follow up: 1.75 months (7 weeks)


ParticipantsNumber analysed for primary outcome: 64

Inclusion criteria: boys aged 6 to 10 years attending second grade at 3 primary schools; completed assessment and provided a stool sample; randomized by descending hookworm count (all treated)

Exclusion criteria: none stated


InterventionsSingle dose versus placebo

1. Pyrantel pamoate: 10 mg/kg
2. Placebo

Treatment strategy: randomized and treated all children


Outcomes1. Mean weight post-treatment
2. Appetite: consumption test (mL porridge) and self assessment

Not included in review: egg counts arithmetic and geometric means (Kato-Katz); weight-for-age (NCHS reference)


NotesLocation: Indonesia

Community category: 1

Large drops in geometric mean egg counts in placebo noted

Source of funding not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized: “Randomly assigned" by descending A. lubricoides egg count"

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear risk“Double-blind”. Participants blinded both placebo and treatment identical round white tablets, no information about provider and assessor blinding

Incomplete outcome data (attrition bias)
All outcomes
Low risk85% (64/75) of randomized participants were evaluated. Reasons for loss to follow-up included: moved away, refused to be examined, did not return a stool sample, absent during examination. Not clear how many lost from each treatment group. Inclusion of all randomized participants (number evaluable/number randomized): 85% (64/75)

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo obvious other source of bias.

Hadju 1997

MethodsRandomized controlled trial

Length of follow up: 12 months


ParticipantsNumber analysed for primary outcome: 330; mean age 8.3 years

Inclusion criteria: all primary school children in grades 1, 2, and 3 in 2 schools in slum areas in Indonesia; randomized according to Ascaris egg count and age

Exclusion criteria: children > 11; signs of puberty; signs of severe protein energy malnutrition


InterventionsMultiple doses versus placebo

1. Pyrantel pamoate: 10 mg/kg
2. Pyrantel pamoate: 10 mg/kg repeated at 6 months
3. Albendazole: 400 mg
4. Albendazole: 400 mg repeated at 6 months
5. Placebo

Treatment strategy: randomized and treated all children


Outcomes1. Stool (Kato-Katz) prevalence and intensity
2. Weight
3. Height
4. Mid-upper arm circumference
5. z-scores: weight-for-age, height for age, weight-for-height, and mid-upper arm circumference

Results of multivariate analysis using z-scores presented and could not be used in meta-analysis; unadjusted results not reported


NotesLocation: Indonesia

Community category: 1

Placebo group showed an unexplained drop in egg counts at the 3-month exam

Source of funding: Directorate of Higher Education, Department of Education and Culture, Government of Indonesia through Hibah Bersaing Project I & II. Albendazole and placebo provided by Smithkline Beecham Pharmaceuticals Indonesia. 


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomly assigned "by sex and egg count"

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details reported 

Incomplete outcome data (attrition bias)
All outcomes
High risk65% (330/507) of randomized participants were evaluated, number lost from each treatment group not reported. Inclusion of all randomized participants (number evaluable/number randomized): 65% (330/507)

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo obvious other source of bias

Hall 2006 (Cluster)

MethodsCluster-randomized controlled trial

Method to adjust for clustering: not adjusted (review authors adjusted using the ICC from Alderman 2006).

Cluster unit: school

Average cluster size: 33

ICCs: not reported.

Length of follow up: 2 years


ParticipantsNumber analysed for primary outcome: 80 schools randomized containing 2659 children in class 3

Mean age: 104.5 months

Inclusion criteria: children from class 3 and born in 1990 of 80/81 schools in the Red River delta of north Vietnam


InterventionsMultiple doses versus placebo

1. Albendazole (GlaxoSmithKline): 400 mg every 6 months and 200,000 IU retinol after first 6 months only
2. Retinol: 200,000 IU after first 6 months followed by inert placebo every 6 months

Treatment strategy: randomized and treated all children


OutcomesMeasured:
1. Hookworm, Trichuris, and Ascaris prevalence
2. Eggs/g faeces
3. Weight and height

4. Mathematics test score, Vietnamese test score


NotesLocation: Vietnam

Community category: 1

It is unclear what is meant by "randomization was adjusted so that there were equal numbers of schools in each district of the study group". It is also appears as if the analysis has not taken into account the effects of cluster randomization

Source of funding not reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"randomization was adjusted so that there were equal numbers of schools in each district of the study group" (unclear what this means)

Allocation concealment (selection bias)Low riskCentral allocation. “...using a list provided by the Ministry of Education”

Blinding (performance bias and detection bias)
All outcomes
Unclear riskPlacebo was used, blinding not reported

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskInsufficient reporting of attrition/exclusions. 80 schools containing 56,444 pupils randomized, and those from class 3 used in study. Inclusion of all randomized participants (number evaluable/number randomized): unclear; 80 schools containing 56,444 pupils randomized, and those from class 3 used in study

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskAlthough not adjusted for clustering, we used estimates to adjust in the review

Recruitment bias: Low (schools)

Baseline imbalance: Low (characteristics similar)

Loss of clusters: Low (no loss reported)

Incorrect analysis: not cluster adjusted (high risk)

Comparability with RCTs randomising individuals: Unclear

Kirwan 2010

MethodsRandomized controlled trial

Length of follow up: 14 months


ParticipantsNumber analysed for primary outcome: 320

Inclusion criteria: Pre-school children aged 12 to 59 months, either sex

Exclusion criteria: Severe anaemia less than 5 g/dL, severe malaria


InterventionsMultiple doses versus placebo

1. Albendazole
2. Placebo

Treatment strategy: 200 mg (one tablet) albendazole was given to children aged 1 year, 400 mg (two tablets) albendazole was given to children aged 2, 3 and 4 years. Children who were in the placebo group were given one or two (1 year) placebo (2-4 years) tablets. Treatment or placebo was given at baseline, 4, 8 and 12 months and then followed up for the last time at 14 months. Children in the placebo group were treated with albendazole at 14 months.


Outcomes1. Haemoglobin, measured at baseline and 4, 8, 12 and 14 months

Unable to use: Nutritional status and anthropometric measures, at baseline and 14 months, no data was reported for these outcomes.

Not included in review: Infection with soil-transmitted helminths, measured at baseline and 4, 8, 12 and 14 months (eggs or worms in stool sample). Incidence of malaria and malaria attacks, measured at baseline and 4, 8, 12 and 14 months. Adverse events not fully reported for albendazole treatment versus placebo.


NotesLocation: 4 semi-urban villages, Osun State, Nigeria

Community category: 3

No adverse events reported in the Albendazole treatment group. Not reported for control group.

Source of funding: Health Research Board (HRB) (Ireland). GlaxoSmithKline sponsored the drug albendazole which

was used in the study.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuasi-randomized, “During the first assessment each alternate child was assigned tablet B”

Allocation concealment (selection bias)High riskAlternation, one of the investigators “placed the albendazole and placebo tablets in containers labelled either A or B” later “The treatment coordinator [...] oversaw the allocation of treatments to the children”

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants and key personnel were blinded. “Experienced physicians […] enrolled all participants, measured all study endpoints, and were kept masked to treatment allocation of children. Field workers involved in data collection and mothers of participating children were also masked to the treatment allocation.”
“Albendazole and placebo tablets were identical”

Incomplete outcome data (attrition bias)
All outcomes
High risk320 children (out of 1228, 26.1%) complied with all the follow-up assessments and were included in the analyses. Inclusion of all randomized participants (number evaluable/number randomized): 26% (320/1228)

Selective reporting (reporting bias)High riskNutritional status and anthropometric measures not reported. Main paper states these outcomes are reported in the companion paper; no data reported for these outcomes in the companion paper

Other biasLow riskNo obvious other source of bias

Kloetzel 1982

MethodsRandomized controlled trial

Length of follow up: 10 months


ParticipantsNumber analysed for primary outcome: 337; unclear how many randomized; aged 1 to 8 years old

Inclusion criteria: enlisted from 9 rural communities in Pariquera-Acu state of Sao Paulo

Exclusion criteria: none stated


InterventionsSingle dose versus placebo

1. Mebendazole: 100 mg twice per day for 3 days
2. Placebo

Treatment strategy: randomized and treated all children


Outcomes1. Weight
2. Height
3. Head, chest, and mid-arm circumference
4. Triceps skinfold
5. Stool egg counts (Kato-Katz)


NotesLocation: Cameroon

Community category: 1

Results reported as changes in nutritional status grouped into 3 categories: improved, deteriorated, no change (unclear on basis of which parameter), and proportions compared

Source of funding: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomized", no further details provided

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDescribed as double blind, no details reported

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo details about losses to follow-up reported; “the present report only deals with those 337 that could be followed throughout the entire 10 months”. Inclusion of all randomized participants (number evaluable/number randomized): unclear (337 analysed). 

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo obvious other sources of bias

Koroma 1996

MethodsRandomized controlled trial

Length of follow up: 6 months


ParticipantsNumber analysed for primary outcome: 187

Inclusion criteria: selected (unclear how) urban and rural school primary children aged 6 to 10 years

Exclusion criteria: not stated


InterventionsSingle dose versus placebo

1. Albendazole: 400 mg
2. Placebo

Treatment strategy: randomized and treated all children


Outcomes1. Prevalence and intensity (arithmetic mean eggs/g)
2. z-scores (no reference category stated): weight-for-height, weight-for-age, and height-for-age


NotesLocation: Sierra Leone

Community category: 2

Source of funding: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomized", no further details provided

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details reported

Incomplete outcome data (attrition bias)
All outcomes
High risk76% (187/247) of randomized participants were evaluated. Reasons for loss to follow-up not reported. Inclusion of all randomized participants (number evaluable/number randomized): 76% (187/247) 

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo obvious other sources of bias

Kruger 1996

MethodsRandomized controlled trial

Length of follow up: 11 months


ParticipantsNumber analysed for primary outcome: 74 aged 6 to 8 years

Inclusion criteria: 65 pupils in first year of school randomly selected from each of 5 primary schools; schools included in a feeding scheme

Exclusion criteria: age > 9 years; current use of iron supplements; inclusion in an iron fortification trial; infection (raised white cell count)


InterventionsMultiple doses versus placebo

1. Albendazole: 2 x 200 mg repeated at 4 months, daily unfortified soup
2. Placebo: daily unfortified soup

Also: whole population
3/5 schools also allocated soup fortified with 20 mg elemental iron per day, and 100 mg vitamin C for 6 months; unclear whether this intervention was cluster randomized. All schools taking part in feeding programme providing bread, soup, and peanut butter to all pupils

Treatment strategy: randomized and treated all children


Outcomes1. Mean change in weight post-treatment
2. Mean change in height post-treatment
3. Mean change in haemoglobin post-treatment

Not included in review: other iron indices; stool egg counts (Visser filter method); z-scores for weight-for-age, height for age, and weight-for-height


NotesLocation: South Africa

Community category: 3

In the Dickson 2000a Cochrane Review, the data were combined irrespective of the possible confounding effects of iron allocation; data extracted for albendazole-iron placebo versus placebo-placebo groups only for this review

Data stratified by baseline iron stores into 2 groups that were combined for meta-analysis.

Source of funding: Fortified and unfortified soup provided by Funa Foods, Zentel and placebo provided by SmithKline Beecham Pharmaceuticals (Pty) Ltd.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Randomly assigned", no further details provided

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details reported

Incomplete outcome data (attrition bias)
All outcomes
High risk72% (179/247) of randomized participants were evaluated. Reasons for loss to follow-up not reported. Inclusion of all randomized participants (number evaluable/number randomized): 72% (179/247)

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo obvious other source of bias 

Kvalsvig 1991a

MethodsRandomized controlled trial

Length of follow up: 1 month


ParticipantsNumber analysed for primary outcome: unclear; age range unclear

Inclusion criteria: most severely infected 100 children in a primary school

Exclusion criteria: children with schistosomiasis


InterventionsSingle dose versus placebo

1. Mebendazole: 500 mg
2. Placebo

Treatment strategy: screened children then randomized and treated infected children


Outcomes1. Cognition tests: card sorting task (coloured cards; cancellation task - striking out of letter 's' in text, number done in a period)

Not included in review: height; weight at baseline; standardized using NCHS standards; stool examination (intensity index designed for this trial); no nutritional outcomes reported that can be used in the review


NotesLocation: South Africa

Community category: 1

No data used in meta-analysis since standard deviations not provided.

Source of funding: Janssen Pharmaceutica, South African Medical Research Council.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Assigned randomly", no further details provided

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear risk"A ‘blind’ procedure was adopted; the research assistant did not know whether a particular child had received drug or placebo", no further details provided

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo details reported. Inclusion of all randomized participants (number evaluable/number randomized): unclear

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo obvious other source of bias

Lai 1995

MethodsQuasi-randomized controlled trial

Length of follow up: 2 years


ParticipantsNumber analysed for primary outcome: 314

Inclusion criteria: school children aged 8 who provided a stool sample

Exclusion criteria: concurrent illness; anthelminth treatment in previous 3 months


InterventionsMultiple doses versus placebo

1. Mebendazole plus pyrantel: 100 mg mebendazole and 200 mg pyrantel every 3 months for 2 years
2. Placebo: every 3 months for 2 years

Treatment strategy: randomized and treated all children


OutcomesMeasured:
1. Hookworm, Trichuris, and Ascaris prevalence
2. Eggs/g faeces
3. Weight and height


NotesLocation: Malaysia

Community category: 1

No data used in meta-analysis since standard deviations not provided

Source of funding not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuasi-randomized: block assignment design by school, then by sex, then by presence of worms as none, light, or moderate/heavy, and then by rank order of body weight in the group; used odd and even numbers; in urban area the odd numbered children were assigned to treatment; in the peri-urban area the even numbered children were assigned to the treatment group.

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
High risk Participants were blinded; study staff new which group they were in

Incomplete outcome data (attrition bias)
All outcomes
Low risk89% (314/353) of randomized participants were evaluated

Inclusion of all randomized participants (number evaluable/number randomized): 89% (314/353)

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo obvious other sources of bias

Le Huong 2007

MethodsRandomized controlled trial

Length of follow up: 6 months


ParticipantsNumber analysed for primary outcome: 510 randomized

Inclusion criteria: Children in Grades 1–3 with Hb less than 110 g/L but not less than 70 g/L

Exclusion criteria: Haemoglobin (Hb) concentrations <70 g/L


InterventionsMultiple dose versus placebo

Factorial design

Mebendazole 500 mg at 0 and 3 months

1. iron-fortified noodles and mebendazole 500 mg;

2. noodles without iron fortificant and mebendazole 500 mg;

3. iron-fortified noodles and placebo;

4. noodles without iron fortificant and placebo; and

5. iron supplementation and mebendazole 500 mg.

Treatment strategy: children screened for anaemia then randomized and all children treated


Outcomes1. Haemoglobin - change

2. Prevalence of underweight, stunting and wasting  (defined as -2SD for weight-for-height, height-for-age and weight-for- age using WHO/NCHS reference data)

Not included in review: Ferritin; serum transferrin; worm prevalence; CRP


NotesLocation:Vietnam

Community category: 2

Source of funding: Neys-van Hoogstraten Foundation, Ellison Medical Foundation and the Ministry of Education and Training, Vietnam.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, no further details

Allocation concealment (selection bias)Low riskCentral allocation. “Randomization was carried out by a researcher [...] who did not know the children and could not introduce bias in the randomization.”

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants and key personnel blinded. “Children, teachers and researchers were blinded to the treatment.”

Placebo identical to intervention drug

Incomplete outcome data (attrition bias)
All outcomes
Low risk409/425 participants were evaluated. Reason for drop-out: refusal (n=16, intervention: 4.7%, placebo: 2.3%). Inclusion of all randomized participants (number evaluable/number randomized): 96% (409/425)

Selective reporting (reporting bias)Low riskPre-specfied outcomes reported

Other biasLow riskNo obvious other sources of bias

Michaelsen 1985

MethodsRandomized controlled trial

Length of follow up: 5 months


ParticipantsNumber analysed for primary outcome: 121 for nutritional outcomes; age range 5 to 14 years

Inclusion criteria: children from a school identified as having high prevalence of hookworm on the basis of a previous survey

Exclusion criteria: children with height above 137 cm girls and 145 cm for boys since these were the upper limits in the reference ranges


InterventionsSingle dose versus placebo

1. Tetrachloroethylene: 0.1 mL/kg (max 5 mL dose)
2. Placebo: children's cough medicine

Treatment strategy: randomized and treated all children


OutcomesMeasured:
1. Stool: prevalence in subgroup
2. Haemoglobin
3. Weight
4. Height
5. Weight-for-height (WHO reference median 1983)

Reported:
1. Stool prevalence (graph) with 95% CIs
2. Haemoglobin mean and difference (no SD)
3. Weight-for-height %, mean and difference (no SD)


NotesLocation: Botswana

Community category: 1

Source of funding not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk“Random sample of half the children” were give the treatment and the remaining the placebo. No further details reported. 

Allocation concealment (selection bias)Unclear riskNo details reported 

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details reported

Incomplete outcome data (attrition bias)
All outcomes
High risk53% (121/228) of randomized participants were evaluated. Inclusion of all randomized participants (number evaluable/number randomized): 53% (121/228)

Selective reporting (reporting bias)Low riskPre-specfied outcomes reported

Other biasLow riskNo obvious other sources of bias 

Miguel 2004 (Cluster)

MethodsCluster phased intervention, which means some comparisons were quasi-randomized.
Method to adjust for clustering: CIs adjusted for clustering in regression modelling, robust standard errors presented (confirmed in correspondence with authors).
Cluster unit: schools.
Average cluster size: 400
ICCs: not reported.
Length of follow up: one year for phased quasi-randomized comparisons for health outcomes. Two years for school attendance.


ParticipantsNumber analysed for primary outcome: For haemoglobin approximately 4% (778/20,000) - unclear how these were selected. Unclear for nutritional outcomes. Unclear for exam performance and cognitive tests.

Inclusion criteria: none explicitly stated. "Nearly all rural primary schools" in Busia district, Kenya, involved in a NGO deworming programme were studied, with a total enrolment of 30,000 pupils aged six to eighteen.Exclusion criteria: girls > 13 years old


InterventionsDeworming package of interventions including multiple doses of anthelminth versus no treatment within phased intervention

1. Albendazole 600mg (Zentel, SZB) every 6 months in 1998 intervention, and albendazole 400mg (Zentel, SZB) in 1999. In addition:

  • Worm prevention education (public health lectures, wall charts and teacher training in worm prevention. Health education on hand washing and wearing shoes to prevent worm infection.
  • Schools with schistosomiasis prevalence over 30% were mass treated with praziquantel (40mg/kg Bayer) annually. 6/25 schools treated with praziquantel in 1998, and 16/50 treated with praziquantel in 1990.


2. No treatment


Outcomes1. Weight-for-age Z score difference in end value

2. Haemoglobin difference in end value

3. Exam score performance (ICS administered English, Mathematics and Science-Agriculture exams in pupils in grades 3 to 8)

4. Cognitive tests including picture search, Raven matrix, verbal fluency, digit span, Spanish learning, and a dynamic test using syllogisms.

5. Height-for-age Z score difference in end value
6. School participation rate based on external NGO assessment at unannounced visit

Not included in review: worm prevalence and intensity, self reported sickness, worm prevention behaviours: proportion "clean" as per health worker observation, proportion wearing shoes as per health worker observation, self-reported contact with fresh-water in past week, access to home latrine, malaria/fever


NotesThis was an econometric analysis of 75 schools with a total of 30,000 pupils enrolled. The intervention was phased over time, and there were two comparisons, one in 1998 and one in 1999 if the analysis is comparative within each individual year. Schools in a deworming project 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 are divided into 3 groups: Group 1 schools are in the treatment group throughout. Group 2 schools are in the control group for the 1998 comparison, but in the treatment group in the 1999 comparison. Group 3 schools are in the control group throughout.

In the description of the intervention two comparisons are 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. However, in a personal correspondence the authors state that there is no health data for Group 3 schools for 1999. For nutritional and haemoglobin outcomes, this implies that there is one possible quasi-randomized comparison with contemporary information in both treatment and control, which is 1998, Group 1 versus Group 2 & 3. However, results for health outcomes are presented for the 1998 comparison of Group 1 (25 schools) versus Group 2 (25 schools).

Number of children followed up for nutritional outcomes in 1998 comparison is unclear.

A sub-sample of the original quasi-randomized comparison appears to have been followed up for haemoglobin and nutritional outcomes, but it is not clear how this sample was selected (table V in the paper).

For school attendance, during the study, the authors carry out a rigorous assessment of participation rate. This was then calculated as a weighted average by school. For school attendance results are presented for Group 1 versus Group 2 & 3 in 1998 (one year of treatment, multiple dose), and for Group 1 versus Group 3 in 1999 (two years of treatment, multiple dose), and for Group 2 versus Group 3 in 1999 (one year of treatment, multiple dose). Baseline data is presented for attendance at schools, recorded by school registers in a four week period prior to intervention, recording 97.3% in Group 1, and 96.3% in Group 2. However the authors state that this is not considered reliable. There are no comparable baseline values (ie measured in the same way as the outcome measurement of school attendance) to know whether baseline attendance happens to be different across groups.

Group 1 schools have an overall prevalence of 38% heavy/moderate worm infection in 1998, compared to the initial survey in control schools in 1999, where it was 52%.

Academic performance measured by Internationaal Christelijk Steunfonds Africa (ICS) exam scores in a regression analysis that included school participation during the year of the exam, and also if it was a year 1 treatment school or a year 2 treatment school. The authors did not provide the results by the quasi-randomized comparison eligible for this review (1998 Group 1 versus Group 2 & 3; 1999 Group 1 & 2 versus group 3).

The cognitive tests were carried out in all three groups of schools during 2000. The authors do not formally report the result in the paper, other than to state that they were not significant.

27/75 schools were involved in other NGO projects which consisted of financial assistance for textbook purchase and classroom construction, and teacher performance incentives. The distribution of these other interventions is not clear, but the authors state that these schools were stratified according to involvement in these other programmes.

The authors state that health education had a minimal impact on behaviour, and that any programme effect is almost certainly due to the effect of deworming drugs, rather than health education.

School participation rate was computed among all pupils enrolled in 1998. Pupils present on the day of an unannounced NGO visit were considered participant. Pupils had 3.8 observations on average per year.

Location: Kenya

Community category: 1

Source of funding: Sponsored by the World Bank and the Partnership for Child Development.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskSchools in a deworming project 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.

Allocation concealment (selection bias)High riskNot concealed (see above).

Blinding (performance bias and detection bias)
All outcomes
High riskPragmatic cluster implementation study with no blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskFor haemoglobin, weight and height the outcomes appear to have been measured on a sub-sample of the quasi-randomized population. For haemoglobin this was approximately 4% (778/20,000) - it is unclear how these were selected. The number of participants or measurements on which nutritional outcomes are based is not stated. For exam performance only regression data are given.

Selective reporting (reporting bias)Low riskOutcome data not reported for cognitive tests, though authors state: Deworming treatment effects are not significantly different than zero for any component of the cognitive exam (results available on request).

Other biasHigh riskRecruitment bias: Low (no asymmetric migration between schools)

Baseline imbalance: High (Group 1 schools have an overall prevalence of 38% heavy/moderate worm infection in 1998, compared to the initial survey in control schools in 1999, where it was 52%.)

Loss of clusters: Low (none reported)

Incorrect analysis: Low (correctly adjusted for clustering).

Comparability with RCTs randomizing individuals: high ( Analysis 4.7)

The intervention was a package including deworming drugs for soil transmitted helminths, praziquantel to treat schistosomiasis in schools with >30% prevalence, and health promotion interventions. In addition 27/75 schools were involved in other NGO projects which consisted of financial assistance for textbook purchase and classroom construction, and teacher performance incentives. The distribution of the latter interventions is not clear.

These co-interventions confound the potential effects of deworming drugs to treat STHs. However, the authors kindly provided a re-analysis of their data, with the praziquantel treated schools removed from the analysis. This represents as subgroup analysis of the original quasi-randomized comparison.

Nga 2009

MethodsRandomized controlled trial

Length of follow up: 4 months


ParticipantsNumber analysed for primary outcome: 510 randomized

Inclusion criteria: School children aged 6–8 years and written informed consent from parents/caregivers

Exclusion criteria: Haemoglobin (Hb) concentrations <80 g/L, chronic illness, congenital abnormalities, mental or severe physical handicap, severe malnutrition ([z-scores for weight-for-height (WHZ) <-3.0 SD), obesity (BMI >=25 or z-scores for WHZ >+2 SD), or receiving deworming within the previous 6 months.


InterventionsSingle dose versus placebo

1. Non-fortified biscuit plus placebo deworming-treatment (placebo);

2. Multi-micronutrient–fortified biscuit plus placebo deworming-treatment;

3. Non- fortified biscuit plus deworming treatment with albendazole(400 mg);

4. Multi-micronutrient–fortified biscuits plus deworming treatment with Albendazole (400 mg)

Treatment strategy: randomized and treated all children


Outcomes1. Haemoglobin

2. Mean mid-upper arm circumference

3. Cognitive function

4. Change in weight-for-age (WAZ), height-for-age (HAZ), and WHZ, using the EpiInfo program (version 6.0, CDC) and the National Center for Health Statistics/WHO nutritional reference data

Not included in review: Changes in zinc, iodine, and ferritin concentration; worm prevalence

Measured but not reported:

Weight and height recorded at baseline and end point but only baseline data reported. Skin fold thickness recorded at baseline and end point, but no data reported.


NotesLocation:Vietnam

Community category: 2

This study was supported by the Neys-van Hoogstraten Foundation, The Netherlands, and the Ellison Medical Foundation.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer generated. “pupils were allocated to 1 of the 4 intervention groups based on a computer generated list, matched on age (12-mo age groups) and sex, and using a block size of 8 by one of the researchers not involved in the field work”.

Allocation concealment (selection bias)Low riskCentral allocation.

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants and key personnel were blinded. “All investigators, field assistants, teachers, and children did not know the codes of the study groups.”

Placebo identical to treatment (orange chewable tablet).

Incomplete outcome data (attrition bias)
All outcomes
Low risk482/510 randomized participants were evaluated. Reasons for drop-out: moved=12, surgery=2, refusal to participate (n = 14), balanced across intervention groups. Inclusion of all randomized participants (number evaluable/number randomized): 94.5% (482/510).

Selective reporting (reporting bias)High riskThree outcomes (weight, height and skin fold thickness) not reported adequately.

Other biasLow riskNo obvious other source of bias.

Nokes 1992

MethodsRandomized controlled trial

Length of follow up: 2.25 months (9 weeks)


ParticipantsNumber analysed for primary outcome: 103; age range 9 to 12 years

Inclusion criteria: children from 3 schools in Mandeville; Trichuris egg counts > 1900, but low hookworm counts on 2 occasions before the trial separated by 3 months

Exclusion criteria: twins; severe illness; physical handicaps; neurological disorders


InterventionsSingle dose versus placebo
1. Albendazole: 400 mg daily for 3 days (SmithKlineBeecham)
2. Placebo: identical

Treatment strategy: screened children then randomized and treated infected children


OutcomesCognitive tests: digit span forwards/backwards; arithmetic and coding from Wechsler Intelligence Scale for Children; fluency and listening comprehension from the Clinical Evaluation of Language functions; and matching familiar figures test

Not included in review: stool egg counts at baseline and 10 days (prevalence and arithmetic mean); height and weight (expressed as % NCHS standard) iron status; school attendance; IQ; socioeconomic status; educational opportunity measures at baseline

Outcomes not reported: nutritional outcomes at 9 weeks cited as too short a follow-up period to demonstrate a change. School attendance only measured at baseline.


NotesLocation: Jamaica

Community category: 1

There was an infected placebo group and an "uninfected control group"

Source of funding not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk“Randomly assigned”; no further details reported

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details reported

Incomplete outcome data (attrition bias)
All outcomes
High risk73% (103/140) of randomized participants were evaluated. Inclusion of all randomized participants (number evaluable/number randomized): 73% (103/140)

Selective reporting (reporting bias)Unclear riskPyschometric tests reported; other outcomes such as nutrition not reported

Other biasLow riskNo obvious other source of bias

Olds 1999

MethodsRandomized controlled trial

Length of follow up: 6 months for randomized comparison


ParticipantsNumber analysed for primary outcome: 1518 randomized, 90% followed up at 6 months

Inclusion criteria: School age children

Exclusion criteria: Failure to submit 2 stool specimens prior to the initial treatment, known allergy to either drug, treatment with either drug within 6 months, lack of consent, and marriage or possible pregnancy.


InterventionsAlbendazole (400mg) plus praziquantel (40 mg/ kg)

Praziquantel plus an albendazole placebo

Albendazole plus a praziquantel placebo,

Both placebos.


OutcomesNo useable data.

Not included in review: Ultrasound, physical examination and history findings, duplicate stool and urine measurements of egg counts

Measured but not reported:

Weight, height, skinfold thickness (subscapular, triceps, and abdominal) and haemoglobin recorded at baseline and end point but only baseline data reported. Data for side effects not useable in review.


NotesLocation: China, Philippines and Kenya

Community category: 1

randomized comparison up to 6 months at which point all infected children were treated as needed, and followed up until one year.

There was no difference between the side effect rate from albendazole or the double placebo

Result text: “No statistically significant improvement was seen in haemoglobin after albendazole treatment. In the study population as a whole, no significant differences between treatment groups were seen in any of the growth and anthropometric measurements.”

Source of funding: Tropical Disease Research of the World Health Organization.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer generated. “Randomization lists were prepared by WHO/TDR using a randomized block design with a block size of 80”

Allocation concealment (selection bias)Low riskCentral allocation

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants, key personnel and outcome assessment was blinded. “The randomization code was not broken until after the 6-month results were tabulated and submitted to WHO”

Incomplete outcome data (attrition bias)
All outcomes
Low risk1518 participants, 90% at 6 months follow-up, 83% at one year, no further details. Inclusion of all randomized participants (number evaluable/number randomized): 90% (1366/1518)

Selective reporting (reporting bias)High riskWeight, height, skinfold thickness and haemoglobin recorded at baseline and end point but only baseline data reported

Other biasLow riskNo obvious other source of bias

Palupi 1997

MethodsRandomized controlled trial

Length of follow up: 9 weeks (2.25 months)


ParticipantsNumber analysed for primary outcome: 191

Inclusion criteria: children ages 2 to 5 years registered at village health centres

Exclusion criteria: none stated


InterventionsSingle dose versus placebo

1. Albendazole: 400 mg plus 30 mg elemental iron weekly
2. Elemental iron: 30 mg weekly

Treatment strategy: randomized and treated all children


Outcomes1. Mean change in weight post-treatment
2. Mean change in height post-treatment
3. Mean change in haemoglobin post-treatment
4. Mean haemoglobin post-treatment

Not included in review: z-scores for height-for-age, weight-for-age, and weight-for-height (NCHS reference)


NotesLocation: Java, Indonesia

Community category: 2

Source of funding: Kimia Farma Indonesia.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk“The children were randomly divided into three, equal-sized treatment groups”, no further details reported.

Allocation concealment (selection bias)Unclear riskNo details reported.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDescribed as double blind, participants were blinded, unclear whether provider and assessor were.

Incomplete outcome data (attrition bias)
All outcomes
Low risk97% (289/299) of enrolled participants were evaluated. Inclusion of all randomized participants (number evaluable/number randomized): 97% (289/299).

Selective reporting (reporting bias)Low riskPre-specfied outcomes reported.

Other biasLow riskNo obvious other source of bias.

Rousham 1994 (Cluster)

MethodsCluster-randomized controlled trial

Method to adjust for clustering: not adjusted

Cluster unit: village.

Average cluster size: 114.

ICCs: not reported.

Length of follow up: 18 months


ParticipantsNumber analysed for primary outcome: 1402

Inclusion criteria: children ages 2 to 6 years from 13 villages surrounding a mother and child health centre; subgroup living in 8 villages within waking distance of health centre analysed for additional outcomes

Exclusion criteria: none stated


InterventionsMultiple doses versus placebo

1. Mebendazole: 500 mg (Janssen) every 2 months
2. Placebo
3. Pyrantel pamoate and mebendazole: initial dose of 10 mg/kg pyrantel pamoate (Combantrin, Pfizer, UK) then mebendazole 500 mg bimonthly for 8 months (4 doses)

Treatment strategy: randomized and treated all children


Outcomes1. ANOVAs for change in z-scores for z-scores for height-for-age, weight-for-age, and weight-for-height (NCHS reference)
2. Change in mid-upper arm circumference at 6, 12, and 18 months (no SD)
3. Other outcomes measured but not reported: height; weight; stool examination for prevalence and intensity in subgroup (eggs/g: modified sedimentation technique); subgroup also analysed for intestinal permeability, albumin, alpha-1-antichymotrypsin, total protein every 2 months


NotesLocation: Bangladesh

Community category: 1

No adjustment made for cluster randomization

Source of funding: the Overseas Development Administration and the University of Cambridge Maintenance Fund


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe study was described as randomized, no further details reported

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants and field workers were blinded, unclear if assessment was blinded. "The treatment and placebo tablets were given in a double-blind manner; neither the fieldworkers nor the parents were aware of the group to which they belonged".

Incomplete outcome data (attrition bias)
All outcomes
Low risk94% (1402/1476) of enrolled participants were evaluated. Inclusion of all randomized participants (number evaluable/number randomized): 94% (1402/1476)

Selective reporting (reporting bias)Low riskNot all pre-specified outcomes reported

Other biasLow riskRecruitment bias: unclear (Not known if children shift clinics in the light of the intervention)

Baseline imbalance: low (No differences apparent)

Loss of clusters: low (none reported)

Incorrect analysis: not adjusted (high risk)

Comparability with RCTs randomizing individuals: unclear

Sarkar 2002

MethodsRandomized controlled trial

Length of follow up: 4 months (16 weeks)


ParticipantsNumber analysed for primary outcome: 81

Inclusion criteria: children ages 2 to 12 living in Mirpur slum infected with Ascaris

Exclusion criteria: none stated


InterventionsSingle dose versus placebo

1. Pyrantel pamoate: 11 mg/kg (Combantrin, Pfizer, Bangladesh)
2. Placebo

Treatment strategy: screened children then randomized and treated infected children


Outcomes1. Mean change in weight post-treatment
2. Mean weight post-treatment
3. Mean change in height post-treatment
4. Mean height post-treatment

Not included in review: median % weight-for-age, weight-for-height, and height-for-age


NotesLocation: Bangladesh

Community category: 1

Source of funding: research grant from the World Bank and was funded by the Bangladesh National Nutrition Council.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk“Random table”

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Low risk"Double-blind"; "The syrups were identical in appearance and flavor and were packaged in identical containers. Randomized patient numbers were labeled on the bottles to maintain the double blind design"

Incomplete outcome data (attrition bias)
All outcomes
Low risk94% (81/85) of randomized participants were evaluated. Inclusion of all randomized participants (number evaluable/number randomized): 94% (81/85)

Selective reporting (reporting bias)Low riskPre-specfied outcomes reported

Other biasLow riskNo obvious other source of bias

Simeon 1995

MethodsRandomized controlled trial

Length of follow up: 6.5 months (26 weeks)


ParticipantsNumber analysed for primary outcome: 392; age range 6 to 12 years

Inclusion criteria: children in grades 2 to 5 of 14 schools in Jamaica with intensities of Trichura > 1200 eggs/g

Exclusion criteria: children with mental handicaps identified by their teachers


InterventionsMultiple doses versus placebo

1. Albendazole: 800 mg (400 mg in each of 2 days), repeated at 3 months and 6 months
2. Identical placebo

Treatment strategy: screened children then randomized and treated infected children


Outcomes1. Main study (264 children)
Wide range achievement test: reading, arithmetic, and spelling subtests; school attendance from children with class registers pre- and post-intervention, height-for-age z-score, body mass index pre- and post-intervention
2. Subgroup 1 (189 infected children from original population)
Digit span; verbal fluency test; visual search; number choice; French vocabulary learning
3. Subgroup 2 (97 children from grade 5)
French learning; digit spans (forward and backward); Corsi block span; verbal fluency; picture search; silly sentences

Other outcomes measured but not reported: stool at baseline and at 8 weeks after second treatment round (Kato): prevalence and intensity, weight, height, z-scores (NCHS standard)


NotesLocation: Jamaica

Community category: 1

Source of funding: grant from the James S. McDonnell Foundation.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom-numbers table

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskParicipants blinded; unclear whether assessors were

Incomplete outcome data (attrition bias)
All outcomes
Low risk96% (392/407) of randomized participants were evaluated. Inclusion of all randomized participants (number evaluable/number randomized): 96% (392/407).

Selective reporting (reporting bias)Low riskAll stated outcomes reported

Other biasLow riskNo obvious other source of bias 

Solon 2003

MethodsRandomized controlled trial

Length of follow up: 16 weeks


ParticipantsNumber analysed for primary outcome: 808/851

Inclusion criteria: Children in grades 1-6

Exclusion criteria: Children with Haemoglobin < 8 g/dL


InterventionsSingle dose versus placebo

1. Fortified beverage (multivitamin and iron) twice per day for 16 weeks with anthelmintic therapy (Albendazole 400mg)

2. Fortified beverage with placebo anthelmintic therapy

3. Non-fortified beverage with anthelmintic therapy (400mg)

4. Non-fortified beverage with placebo anthelmintic therapy


OutcomesNo useable data.

Not included in review: Urine iodine, stool egg count

Measured but not reported: Weight, height, haemoglobin, physical fitness (Harvard step test), heart rate, cognitive ability measured by the Primary Mental Abilities Test for Filipino Children. The test measures verbal, non verbal and quantitative skills


NotesLocation: Philippines

Community category: 2

Narrative results:

No significant difference in change in weight. Deworming improved the iron status of a subgroup of moderately to severely subjects. Deworming had either no effect or a negative effect on fitness scores, and the effect on heart rate was inconclusive. Deworming had either no effect or a negative effect on mental ability scores.

Sources of support: The Nutrition Center of the Philippines, The Procter & Gamble Co.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomization at individual level, no further details.

Allocation concealment (selection bias)Unclear riskNo details reported.

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study. "Both the researchers and the study participants were blinded to the treatment assignment of each child".

"Placebo beverage and placebo anthelmintic pills were indistinguishable from their counterparts in appearance, smell and taste".

Incomplete outcome data (attrition bias)
All outcomes
Low risk808/851 (95%) enrolled participants were evaluated, no reasons for withdrawal reported. Inclusion of all randomized participants (number evaluable/number randomized): 95% (808/851).

Selective reporting (reporting bias)High riskNutritional and haemoglobin outcomes not fully reported.

Other biasLow riskNo obvious other source of bias.

Stephenson 1989

MethodsRandomized controlled trial

Length of follow up: 6 months


ParticipantsNumber analysed for primary outcome: 150

Inclusion criteria: all available children in lower grades (standards 1 and 2) in Mvindeni Primary School, Kwale district (unscreened); subgroup of 36 boys chosen; haemoglobin > 8 g/dL; willing to co-operate in physical tests; pre-pubertal

Exclusion criteria: haemoglobin < 8 g/dL.


InterventionsSingle dose versus placebo

1. Albendazole: 2 x 200 mg (SmithKline and French)
2. Placebo: identical

Treatment strategy: randomized and treated all children


Outcomes1. Mean weight post-treatment
2. Mean change in weight post-treatment
3. Mean height post-treatment
4. Mean change in height post-treatment
5. Mean mid-upper arm circumference
6. Mean change in mid-upper arm circumference
7. Mean triceps skinfold thickness
8. Mean change in triceps skinfold thickness
9. Mean subscapular skinfold thickness
10. Mean change in subscapular skinfold thickness

Not included in review: all above converted to % median for sex and age; prevalence and mean egg counts (arithmetic and geometric means); Harvard Step Test heart rates and score for subgroup


NotesLocation: Kenya

Community category: 1

Source of funding: Smith Kline & French Laboratories, Ltd., and the Edna McConnell Clark Foundation, grant 284-0120.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"allocated at random within sex", no further details reported 

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants blinded, tablets identical for treatment and placebo; "Both examinations were carried out with the same team of workers, each doing the same procedures, and were done in a blind fashion".

Incomplete outcome data (attrition bias)
All outcomes
Low risk88% (150/171) of randomized participants were evaluated, reasons for losses to follow up not reported. Inclusion of all randomized participants (number evaluable/number randomized): 88% (150/171).

Selective reporting (reporting bias)Low riskPre-specified outcomes reported

Other biasLow riskNo obvious other source of bias 

Stephenson 1993

MethodsRandomized controlled trial

Length of follow up: 3.6 months (subgroup) and 8.2 months (main study)


ParticipantsNumber analysed for primary outcome: 284

Inclusion criteria: all school children (unscreened) in grades 1 to 5 in Mvindeni Primary School

Subgroup (53 analysed) of 60 boys chosen because haemoglobin > 80 g/L, willing to cooperate in physical tests and appetite tests, pre-pubertal, infected with at least 1 of helminths (screened), hookworm < 20,000 eggs/g; hookworm or Trichuris count > 1000 eggs/g or Ascaris > 4000 eggs/g

Exclusion criteria: Severe anaemia (haemoglobin < 75 g/L)


InterventionsMultiple doses versus placebo

1. Albendazole (single dose) plus placebo: 600 mg (3 x 200 mg) SmithKline Beecham at outset, identical placebo at 3.6 months
2. Albendazole (multiple doses): single dose 600 mg repeated at 3.6 months
3. Placebo: identical placebo

Treatment strategy: randomized and treated all children (but infected children for appetite/activity outcomes)


Outcomes1. Mean weight post-treatment
2. Mean change in weight post-treatment
3. Mean height post-treatment
4. Mean change in height post-treatment
5. Mean mid-upper arm circumference
6. Mean change in mid-upper arm circumference
7. Mean triceps skinfold thickness
8. Mean change in triceps skinfold thickness
9. Mean subscapular skinfold thickness
10. Mean change in subscapular skinfold thickness
11. Mean haemoglobin post-treatment
12. Mean change in haemoglobin post treatment

Not included in review: prevalence, eggs/g: geometric and arithmetic mean; converted to percentage of median for age and sex using NCHS references; % weight-for-age, % height for age; % weight-for-height; % arm circumference for age; % triceps for age; % subscapular for age; Harvard Step Test; appetite (self-rating and snack consumed intake in kilojoules).


NotesLocation: Kwale, Kenya

Community category: 1

Source of funding: supported in part by Thrasher Research Fund and SmithKline Beecham, Ltd. 


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"at random within sex by descending hookworm egg count". 

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants blinded, tablets identical for treatment and placebo; "Both examinations were conducted by the same team, each doing the same procedures, and were done in a blind fashion".

Incomplete outcome data (attrition bias)
All outcomes
Low risk86% (284/328) of randomized participants were evaluated, reasons for losses to follow up not reported. Inclusion of all randomized participants (number evaluable/number randomized): 86% (284/328).

Selective reporting (reporting bias)Low riskPre-specified outcomes reported

Other biasLow riskNo obvious other source of bias

Stoltzfus 1997 (Cluster)

MethodsCluster-randomized controlled trial

Method to adjust for clustering: generalised estimating equations.

Cluster unit: school.

Average cluster size: 255.

ICCs: not reported.

Length of follow up: 12 months


ParticipantsNumber analysed for primary outcome: 3063; mean age 10.5 years

Inclusion criteria: children in grades 1 to 5 from 12 randomly selected schools on Pemba island; only grades 1 to 4 included in evaluation of nutritional effect

Exclusion criteria: none stated


InterventionsMultiple doses versus placebo

1. Mebendazole: 500 mg twice yearly
2. Mebendazole: 500 mg 3 times a year
3. Placebo

Treatment strategy: randomized and treated all children


Outcomes1. Weight gain
2. Height gain
3. Change in haemoglobin at 12 months

Estimates are provided from multiple regression models taking into account various baseline differences for 2 subgroups above and below 10 years old. Unadjusted outcomes not presented. (These 2 groups were combined in the Dickson 2000a Cochrane Review.)

Other outcomes measured but not reported: micronutrient status (blood) for protoporphyrin and serum ferritin; stool egg count (Kato-Katz); z-scores for height-for-age and weight-for-height; body mass index


NotesLocation: Zanzibar, Tanzania

Community category: 1

Appropriate adjustment made for cluster randomization using general estimating equation

Source of funding: Funded through cooperative agreement DAN-5116-1-00-8051-00 between The Johns Hopkins University and the Office of Health and Nutrition, United States Agency for International Development.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk3 schools randomly selected from each of the 4 districts, and then allocated.

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details reported

Incomplete outcome data (attrition bias)
All outcomes
Low risk84% (3063/3605) of randomized participants were evaluated, reasons for losses to follow up not reported. Inclusion of all randomized participants (number evaluable/number randomized): 84% (3063/3605).

Selective reporting (reporting bias)High riskNot all pre-specified outcomes reported adequately.

Other biasLow riskRecruitment bias: low (Unlikely to change schools)

Baseline imbalance: low (no differences apparent)

Loss of clusters: low (none reported)

Incorrect analysis: cluster adjusted (low risk).

Comparability with RCTs randomising individuals: unclear

Stoltzfus 2001

MethodsRandomized control trial (factorial design)

Length of follow up: 12 months


ParticipantsNumber analysed for primary outcome: 359 in mebendazole arm aged 6 to 59 months

Inclusion criteria: all children in Kengeja village, with age reported as 3 to 56 months by parents; 3 months before planned start of trial (pre-school children)

Exclusion criteria: severe anaemia (< 70 g/L)


InterventionsMultiple doses versus placebo

1. Mebendazole: 500 mg given every 3 months at home visits
2. Placebo: identical

Treatment strategy: randomized and treated all children

Both groups also received: 0.5 mL ferrous sulfate (20 mg/mL); 10 mg iron daily for 1 year or placebo as per factorial design


Outcomes1. Cognitive outcomes: motor and language development by parents reporting gross motor and language milestones using scoring system developed specifically for the trial
2. Anthropometric measures presented in a stratified manner: (< 30 months, > 30 months), and presented as proportion of children with small arm circumference, mild wasting, and stunting
3. Proportion of children with poor appetite, and proportion with severe anaemia are presented for the whole group
4. Iron indices (not disaggregated, independent of the iron randomization)

Not included in review: prevalence and egg counts (no SD/SEM); motor and language scores (results of multiple regression and correlations; raw data not reported) haemoglobin (results not reported by randomized comparisons)

Others measured but not reported: stool (Kato-Katz); weight; height; malaria film; ferritin; appetite as reported by mothers


NotesLocation: Zanzibar, Tanzania

Community category: 2

Factorial design, with households randomized to iron, random allocation of mebendazole by child, stratified by iron allocation and age grouped households. An iron with mebendazole treatment term was tested in all regression models, but it did not reach significance

Source of funding: Thrasher Research Fund between The Johns Hopkins University and the United States Agency for International Development, AL Pharma, Baltimore, MD, and Pharmamed, Malta.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized by "blocks of 4", no further details reported

Allocation concealment (selection bias)Low riskPills in bottles with unique treatment codes, assigned by 1 investigator, codes kept in sealed envelopes

Blinding (performance bias and detection bias)
All outcomes
Unclear riskParticipants and provider were blinded; unclear whether assessor was blinded

Incomplete outcome data (attrition bias)
All outcomes
High risk52% (359/684) enrolled participants were evaluated. Inclusion of all randomized participants (number evaluable/number randomized): 52% (359/684 = 52%).

Selective reporting (reporting bias)Low riskAll prespecified outcomes reported

Other biasHigh riskNo obvious other source of bias

Sur 2005

MethodsRandomized controlled trial

Length of follow up: 12 months


ParticipantsNumber analysed for primary outcome: 683

Inclusion criteria: all children aged 2 to 5 in slum area of Tiljala identified and enrolled

Exclusion criteria: major illnesses; birth defects; and unwillingness to participate


InterventionsMultiple doses versus placebo

1. Albendazole: 400 mg in a vitamin B complex base liquid; repeated at 6 months
2. Placebo: vitamin B complex base

Treatment strategy: randomized and treated all children


Outcomes1. Mean weight post-treatment (presented graphically)

Other outcomes measured but not reported: stool samples from random sample of 30% (formalin concentration technique) for prevalence of Ascaris; weight-for-age; diarrhoeal episodes


NotesLocation: India

Community category: 2

Source of funding: the Indian Council of Medical Research, New Delhi, India


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random numbers sequence

Allocation concealment (selection bias)Low riskIdentical coded bottles

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants and key personnel were blinded

Incomplete outcome data (attrition bias)
All outcomes
Low risk97% (683/702) of enrolled participants were evaluated. Inclusion of all randomized participants (number evaluable/number randomized): 97% (683/702).

Selective reporting (reporting bias)High riskIncomplete reporting of some outcomes (prevalence of Ascaris in stools; weight-for-age; diarrhoeal episodes).

Other biasLow riskNo obvious other source of bias

Watkins 1996

MethodsRandomized controlled trial

Length of follow up: 6 months


ParticipantsNumber analysed for primary outcome: 226 for nutritional outcomes, reduced for cognitive outcomes; age 7 to 12 years

Inclusion criteria: children attending grades 1 to 4 in primary schools in the Guatemala highlands

Exclusion criteria: > 12 years; deworming medicine in last year


InterventionsMultiple doses versus placebo

1. Albendazole: 2 x 200 mg at baseline and 12 weeks
2. Placebo: identical at baseline and 12 weeks

Treatment strategy: randomized and treated all children


Outcomes1. Mean weight post-treatment
2. Mean change in weight post-treatment
3. Mean height post-treatment
4. Mean change in height post-treatment
5. School performance: attendance rates of children actively attending school measured using attendance books, dropout rates
6. Mean mid-upper arm circumference
7. Mean change in mid-upper arm circumference
8. Cognitive tests: Interamerican vocabulary test, Interamerican reading test, Peabody picture vocabulary test

Not included in review: egg counts (Kato-Katz: arithmetic and geometric mean); z-scores (NCHS-CDC-WHO reference) for weight-for-age, change in weight-for-age, height, change in height, height-for-age, change in height-for-age, weight-for-height, and change in height-for-age


NotesLocation: Guatemala

Community category: 1

Source of funding: Pew Charitable Trusts, the US Agency for International Development University Development and Linkage Program, the Children’s Miracle Network Telethon, and the ARCS Foundation.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"stratified by gender and age and then randomly assigned" 

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Low risk"The children and field workers were unaware of treatment group assignment".

Incomplete outcome data (attrition bias)
All outcomes
Low risk90% (226/250) of randomized participants were evaluated. No differences were detected in treatment group assignment, initial age, anthropometry, SES, and worm status between the 228 children who remained in the study and the 18 who dropped out.” Sample size for nutritional data is smaller due to missing data. Inclusion of all randomized participants (number evaluable/number randomized): 90% (226/250).

Selective reporting (reporting bias)Low riskPre-specified outcomes reported

Other biasLow riskNo other obvious source of bias.

Willett 1979

MethodsRandomized controlled trial

Length of follow up: 12 months


ParticipantsNumber analysed for primary outcome: 268; age range 6 to 91 months

Inclusion criteria: pre-school children from Ubiri village who attended clinic and produced a stool sample

Exclusion criteria: none stated


InterventionsMultiple doses

1. Levamisole syrup: 2.5 mg/kg every 3 months
2. Flavoured sucrose syrup: every 3 months

Treatment strategy: randomized and treated all children


Outcomes1. Growth rates in both groups, and subgroup of those infected; these have been corrected for various factors using analysis of covariance (unadjusted data are not reported and the growth rates are not presented with any measure of variance)

Measured but not reported: height; length; stool egg count in subgroup (Kato method); growth rates using least square method


NotesLocation: Tanzania

Community category: 3

Source of funding: Research and Publications Committee, University of Dar es Salaam. Analysis was supported by a training grant (HL 05998-04) from the National Heart, Lung and Blood Institute, NIH, DHEW Bethesda, MD.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom-numbers table

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Low risk“children were weighed and measured as before by a person unaware of their treatment status”; placebo and treatment given as a flavoured syrup.

Incomplete outcome data (attrition bias)
All outcomes
High risk78% (268/341) of randomized participants were evaluated. Inclusion of all randomized participants (number evaluable/number randomized): 78% (268/341).

Selective reporting (reporting bias)High riskNot all pre-specified outcomes reported

Other biasLow riskNo obvious other source of bias

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Araujo 1987Not a randomized controlled trial.

Beasley 1999Treatment regimen comprised of albendazole for geohelminths and praziquantel against schistosomiasis versus placebo.

Bhargava 2003Treatment regimen comprised of albendazole for geohelminths and praziquantel against schistosomiasis versus placebo.

Bhutta 2009Population with significant comorbidity – 6-24 month old children with severe anaemia (<70 g/L). In population with severe anaemia.

Boivin 1993Factorial-designed randomized controlled trial with children allocated to deworming and iron supplementation, and in which the analysis compares the results for the levamisole and iron group against all the other groups combined. Thus the analysis is confounded by the iron co-intervention (Included in the Dickson 2000a Cochrane Review).

Cooper 2006Study of allergy with no outcomes of interest.

Cowden 2000Not a randomized controlled trial.

Diouf 2002Intervention comprised mebendazole, vitamin A, and iron supplementation and metronidazole as a combined intervention versus placebo.

Evans 1986Treatments randomized, but some placebo groups accessed treatment. Analysis was by the treatment received, and randomization was ignored. (Included in the Dickson 2000a Cochrane Review).

Fernando 19832 villages allocated to treatment or no treatment on the basis of a coin toss. Essentially a cluster-randomized trial with 2 large clusters (Included in the Dickson 2000a Cochrane Review, which reported that no conclusions could be drawn from the results due to selective reporting).

Forrester 1998Treatment regimen comprised of 3 days of albendazole versus 1 day of albendazole and 2 days of placebo versus 1 day of pyrantel and 2 days of placebo.

Friis 2003Combined treatment regimen albendazole for geohelminths and praziquantel for Schistosoma mansoni versus placebo.

Gilgen 2001Population consists of adults.

Gupta 1982Only two units of allocation for relevant comparison. Children randomly divided into 4 groups, "taking care that age distribution was similar in each group". The 4 groups were then allocated 1 of 4 different single treatment regimens; no details given.

Hadidjaja 1998Cluster-randomized controlled trial with 2 units of allocation to mebendazole and placebo. Authors stated that there were differences in environmental sanitary conditions in the clusters (Included in the Dickson 2000a Cochrane Review, but it was noted that the groups were not comparable and there was high loss to follow up).

Hathirat 1992Treatment regimen comprised of albendazole for geohelminths and iron versus placebo.

Jalal 1998No relevant outcomes.

Jinabhai 2001aTreatment regimen comprised of albendazole for geohelminths and praziquantel against schistosomiasis versus placebo.

Jinabhai 2001bTreatment regimen comprised of albendazole for geohelminths and praziquantel against schistosomiasis versus placebo.

Karyadi 1996Not a randomized controlled trial.

Krubwa 1974Not a randomized controlled trial.

Kvalsvig 1991bThe researchers were unable to collect outcome data after treatment due to major floods in the area.

Latham 1990Population with schistosomiasis treated with praziquantel.

Marinho 1991Treatment regimen comprised of mebendazole and metronidazole versus placebo.

Mwaniki 2002Treatment regimen albendazole for geohelminths and praziquantel for schistosomiasis versus placebo.

Pollitt 1991Not described as randomized; conference proceedings.

Rohner 2010Treatment regimen albendazole for geohelminths and praziquantel for schistosomiasis versus placebo.

Steinmann 2008No relevant outcomes.

Stephenson 1980Treatment consisted of levamisole with no untreated controls.

Stephenson 1985Treatment regimen metrifonate used to treat Schistosoma haematobium versus placebo

Tanumihardjo 1996No relevant outcomes.

Tanumihardjo 2004The only randomisation is the timing of the deworming medicine.

Taylor 2001Treatment regimen albendazole for geohelminths and praziquantel for Schistosoma haematobium versus placebo.

Thein-Hlaing 19913/21 intervention villages were not randomly allocated, and unclear how intervention and control villages were allocated as there was a large imbalance (8 intervention and 13 non-intervention villages).

Uscátegui 2009Study in population with malaria.

Wright 2009No relevant outcomes.

Yang 2003Did not consider nutritional or cognitive outcome measures.

 
Characteristics of ongoing studies [ordered by study ID]
Alam 2006

Trial name or title"Relative efficacy of two regimens of ante-helminthic treatment"

MethodsClinical trial

ParticipantsTotal enrolment: 200

Inclusion criteria: age 2 to 5 years; not suffering from serious chronic illness; stool test positive for soil-transmitted helminths; not taken any anthelminthic drug in previous 6 months; parents/guardian agree their child's participation

Exclusion criteria: age < 2 years and > 5 years; stool test negative for any intestinal helminth; suffering from serious chronic illness; parents/guardian not willing to give consent for their child's participation; if he/she receives any anthelminthic drug after survey but before the study interventions

Interventions1. Conventional treatment of 400 mg of albendazole in a single dose at 6-month interval
2. Intervention group: 400 mg of albendazole in a single-dose treatment at 3-month interval

OutcomesPrimary
1. To determine the relative efficacy of de-worming at every 3 months versus every 6 month single dose of albendazole treatment

Secondary
2. To compare additional morbidity information such as diarrhoeal diseases, respiratory tract infections, nutritional status and E. histolytica associated morbidity between 2 groups

Starting dateNot yet recruiting

Contact informationMohammad M Alam MBBS, Principal Investigator, ICDDR,B: Centre for Health and Population Research, masud_icddrb@yahoo.com

NotesClinicalTrials.gov identifier: NCT00367627

Sources of support: International Centre for Diarrhoeal Disease Research, Bangladesh (sponsor)

Elliot 2007

Trial name or titleThe 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].

MethodsThe trial has three randomized, double-blind, placebo-controlled interventions at two times, in two people: a pregnant woman and her child. Pregnant women are randomized to albendazole or placebo and praziquantel or placebo. At age 15 months their children are randomized to three-monthly albendazole or placebo, to continue to age five years. The proposed designation for this sequence of interventions is a 2 X 2(x2) factorial design.

ParticipantsA cohort of 2500 women has been recruited.

Interventions1. Praziquantel + albendazole
2. Praziquantel + placebo matching albendazole
3. Placebo matching praziquantel + albendazole
4. Placebo matching praziquantel + placebo matching albendazole

OutcomesThe principal outcomes are:

  • Immunological responses to BCG and tetanus immunization
  • Incidence of infection in childhood with malaria and Mycobacterium tuberculosis.
  • Incidence of infectious and atopic disease events in childhood (pneumonia, diarrhoea, malaria,measles, tuberculosis and vertical HIV transmission; atopic eczema, urticaria, allergic rhinitis and conjunctivitis, wheeze).


Secondary outcomes are anaemia, growth and development.

Starting date01/04/2003

Contact informationDr Alison Elliott, Uganda Virus Research Institute, Entebbe, Uganda

NotesAdded as of 21/03/2012:
Funding has been awarded to allow follow-up to 2016, this will allow the assessment of outcomes between ages 5 and 12 years. Additional outcome measures have been added for this age group.

 
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]

 
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.
 
Table 1. Detailed search strategies

Search setCIDG SRaCENTRALMEDLINEbEMBASEbLILACSb

1helmint*helmint*helmint*helmint$helmint*

2Ancylostoma duodenaleAncylostoma duodenaleAncylostoma duodenaleAncylostoma duodenaleAncylostoma duodenale

3Necator americanusNecator americanusNecator americanusNecator americanusNecator americanus

4AscarisAscarisAscarisAscarisAscaris

5Enterobius vermicularisEnterobius vermicularisEnterobius vermicularisEnterobius vermicularisEnterobius vermicularis

6trichuristrichuristrichuristrichuristrichuris

7Strongyloid*Strongyloid*Strongyloid*Strongyloid*Strongyloid*

8albendazolehookworm*hookworm*hookworm$1-7/OR

9mebendazoleroundworm*roundworm*roundworm$albendazole

10piperazinepinworm*pinworm*pinworm$mebendazole

11levamisolewhipworm*whipworm*whipworm$piperazine

12pyrantel1-11/OR1-11/OR1-11/ORlevamisole

13tiabendazolealbendazolealbendazolealbendazolepyrantel

14mebendazolemebendazolemebendazoletiabendazole

15piperazinepiperazinepiperazine9-14/OR

16levamisolelevamisolelevamisole8 and 15

17pyrantelpyrantelpyrantelLimit 16 to human

18tiabendazoletiabendazoletiabendazole

1913 or 14 or 15 or 16 or 17 or 1813 or 14 or 15 or 16 or 17 or 1813 or 14 or 15 or 16 or 17 or 18

2012 and 1912 and 1912 and 19

21Limit 20 to humanLimit 20 to human

 aCochrane Infectious Diseases Group Specialized Register.
bSearch terms used in combination with the search strategy for retrieving trials developed by The Cochrane Collaboration (Lefebvre 2011).
 
Table 2. Haemoglobin search strategy

1helmint*

2Ancylostoma duodenale

3Necator americanus

4Ascaris

5Enterobius vermicularis

6trichuris

7Strongyloid*

8hookworm*

9roundworm*

10pinworm*

11whipworm*

121-11/OR

13albendazole

14mebendazole

15piperazine

16levamisole

17pyrantel

18tiabendazole

1913 or 14 or 15 or 16 or 17 or 18

20haemoglobin

21hemoglobin

22anemia

23anaemia

24HB

2520 or 21 or 22 or 23 or 24

2612 and 19 and 25

27Limit 26 to human

 Search terms used in electronic databases in combination with the search strategy for retrieving trials developed by The Cochrane Collaboration (Lefebvre 2011);
 
Table 3. Community diagnosis categories and recommended treatment strategies

Community category (WHO 2002)PrevalenceaProportionbSchool intervention

1. High prevalence or high intensity> 70%> 10%Targeted treatment of school-age children 2 to 3 times per year

2. Moderate prevalence and low intensity> 50% but < 70%< 10%Targeted treatment of school-age children once per year

3. Low prevalence and low intensity< 50%< 10%Selective treatment

Category (WHO 2006b)PrevalenceaAction to be taken

High risk community> 50%Targeted treatment of pre-school and school-age children 2 or 3 times per year

Low risk community>20% but <50%Targeted treatment of pre-school and school-age children once per year

 aOf any worm infection.
bOf moderate to heavy infections.
 
Table 4. Data not included in meta-analysis

Screened for infection - single dose (outcomes measured < 1 year)

Nokes 1992
Albendazole
Growth measured but not reported: 9 weeks cited as too short a follow-up period to demonstrate a change.

Screened for infection - multiple dose (outcome measured < 1 year)

Simeon 1995
Albendazole
No significant difference in any reported outcome for whole group.
Height-for-age z-score at baseline in treatment group -0.48 (0.95) and in placebo group -0.39 (0.90). At follow up in treatment group -0.48 (0.97) and in placebo group -0.41 (0.89).
Body mass index (kg/m2) at baseline in treatment group 15.3 (1.3) and in placebo group 15.5 (1.3). At follow up in treatment group 15.6 (1.3) and in placebo group 15.8 (1.4).

Whole target population treated - single dose (outcome measured < 1 year)

Beach 1999
Albendazole
A nutritional benefit of treatment was not detectable after 4 months for the entire study population (853 participants, no figures provided).

Stratification by infection demonstrated small positive effects in the treatment group for some anthropometric outcomes. In Ascaris-infected children (51), height gain was 0.62 cm greater than placebo in the combination treatment group (P = 0.01) at 4 months. In Trichuris-infected children (158), weight gain was 0.56 kg greater than placebo in the combination treatment group (P = 0.01) at 4 months.

Fox 2005
Albendazole
No results provided for whole study population.

Results for height and weight only presented in the narrative for subgroups infected with hookworm and Ascaris: no significant anthropometric changes detected (no figures quoted). In those infected with Trichuris, weight gain was greater in the albendazole group (difference compared to placebo 0.28 kg, P = 0.038). Adverse events: no serious adverse events (albendazole 0/46 versus placebo 0/43). Myalgia and cough were reported significantly more frequently in the placebo group compared to albendazole.

Greenberg 1981
Piperazine citrate
Treatment group tended to show worse nutrition than placebo.

Comparison showed 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
Mebendazole
No significant difference was found between the groups.

Results reported as the proportion of treatment or control group that improved, deteriorated, or experienced no change. Unclear which anthropological measures were used in this categorization process. Proportions in each category were not significantly different between trial arms (improved: 51% in mebendazole group versus 49% in control; deteriorated: 35% in mebendazole group versus 33% in control; no change: 14% in mebendazole group versus 18% in control; no significance test results quoted).

Koroma 1996
Albendazole
Significant increases in weight-for-height, weight-for-age, and height-for-age z-scores recorded in rural and urban treatment groups at 6 months.
Mean increase in rural treatment group compared to placebo: weight-for-height z-score 0.28 (SE 0.17) P < 0.05; weight-for-age z-score 1.04 (SE 0.03) P < 0.05; and height-for-age z-score 0.83 (SE 0.03) P < 0.001.
Mean increase in urban treatment group compared to placebo: weight-for-height z-score 1.04 (SE 0.07) P < 0.05; weight-for-age z-score 1.02 (SE 0.09) P < 0.001; and height-for-age z-score 1.01 (SE 0.02) P <0.05.

Michaelsen 1985
Tetra-chlorethylene
No significant difference in change in mean for haemoglobin.

(tetrachloroethylene 0.22 g/100 mL versus placebo 0.09 g/100 mL; quoted as non-significant) or weight for height at 5 months (tetrachloroethylene -1.3% of WHO reference mean versus placebo -0.4%; quoted as non-significant).

Adverse events: 17% (19/119: results not given for separate trial arms) of the children suffered adverse effects (nausea and ataxia) that began one and a half hours after treatment. All symptoms disappeared within four hours. Tetrachlorethylene is not in current use as a deworming drug.

Nga 2009

Albendazole
No significant differences in weight-for-height, weight-for-age, and height-for-age z-scores and skin fold thickness at 4 months.

There was no statistically significant effect of deworming on weight, height, HAZ scores, WAZ scores, or WHZ scores. There were no statistically significant differences in skin fold thickness after four months of intervention.

Whole target population treated - multiple dose (outcome measured < 1 year)

Goto 2009
Albendazole plus secnidazole
No significant differences in mean z-scores or prevalence of stunting, underweight or wasting between the intervention groups were found, 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.
Height-for-age z-score: at baseline in treatment group -1.08 (1.02) and in control group -1.21 (1.0). At follow up in treatment group -1.59 (0.93) and in control group -1.70 (0.93).
Weight-for-age z-score: at baseline in treatment group -1.91 (1.15) and in control group -1.85 (1.14). At follow up in treatment group -2.62 (1.17) and in control group -2.59 (1.17).
Weight-for-height z-score: at baseline in treatment group -1.25 (1.18) and in control group -0.96 (1.17). At follow up in treatment group -1.55 (1.07) and in control group -1.83 (1.06).

Hadju 1997
Pyrantel pamoate
Albendazole
No significant differences detected between treatment groups on basis of multivariate analyses controlling for age, sex, and ‘times’.
Change in weight-for-age z-score: placebo 0.02; pyrantel 1 x treatment 0.03; pyrantel 2 x treatments 0.08; albendazole 1 x treatment -0.10; albendazole 2 x treatments 0.01.
Change in height-for-age z-score: placebo 0.01; pyrantel 1 x treatment 0.00; pyrantel 2 x treatments 0.04; albendazole 1 x treatment -0.07; albendazole 2 x treatments 0.01.
Change in weight-for-height z-score: placebo 0.02; pyrantel 1 x treatment 0.08; pyrantel 2 x treatments 0.05; albendazole 1 x treatment -0.07; albendazole 2 x treatments 0.03.
Change mid-arm circumference z-score: placebo -0.09; pyrantel 1 x treatment -0.11; pyrantel 2 x treatments -0.11; albendazole 1 x treatment -0.07; albendazole 2 x treatments -0.01.

Le Huong 2007
Mebendazole
No obvious trend in nutrition variable.

Anthropometric indices were calculated using WHO/NCHS reference data. Being wasted, stunted and underweight was defined by z-scores ,< - 2SD for weight-for-height, height-for-age and weight-for-age, respectively.
Percentage underweight: At baseline Fe 41·9, Fe + MEB 51·9, MEB 50·6, Placebo 45·1; after treatment Fe 33·7, Fe + MEB 46·8, MEB 38, Placebo 35·4.
Percentage stunted: At baseline Fe 30·2, Fe + MEB 31·6, MEB 41·8, Placebo 31·7; after treatment Fe 29·1, Fe + MEB 27·8, MEB 29·1, Placebo 29·3.
Percentage wasted: At baseline Fe 9·3, Fe + MEB 16·5, MEB 13·9, Placebo 12·2; after treatment Fe 5·8, Fe + MEB 17·7, MEB 13·9, Placebo 13·4.

Miguel 2004 (Cluster)No effect on nutrition or haemoglobin demonstrated

Data from published paper including praziquantel treated clusters (25 treatment schools versus 25 control schools in 1998 comparison):

It is unclear how many children were followed up for nutritional outcomes. For haemoglobin a sample of around 4% (778/20,000) of the quasi-randomized comparison of group 1 versus group 2 in 1998 was analysed. It is unclear how this group was selected.

Difference in weight-for age Z score (treatment - control): 0.00 (SE 0.04).

Difference in height-for-age Z score end value (treatment - control): 0.09 (SE 0.05).
Difference in haemoglobin (g/L) (treatment - control): 1.6 (SE 1.4).

Stoltzfus 2001
Mebendazole
Mebendazole is reported as significantly reducing the prevalence of mild wasting malnutrition in a subgroup of children aged < 30 months only

adjusted odds ratio for mebendazole 0.38 (95% CI 0.16 to 0.90) for weight-for-height z-score < -1. Mebendazole is reported as significantly reducing the prevalence of poor appetite across the whole group (adjusted odds ratio for mebendazole 0.52 (95% CI 0.30 to 0.89) for weight-for-height z-score < -1). Mebendazole had no impact on iron indices. Adjusted effect on motor scores had a tendency to favour mebendazole, but this was not significant.

Willett 1979
Levamisole
No statistical difference in nutrition in terms of height and weight differences between the 2 groups.

Growth rates presented are adjusted for a number of variables. Weight gain (kg/year) in levamisole group 2.08 versus 1.92 in placebo group (P = 0.06). Height gain (cm/year) in levamisole group 7.58 versus 7.73 in placebo group (no significance quoted).

Stoltzfus 1997 (Cluster)
Mebendazole
Weight gain: 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).

In the thrice yearly treatment group the difference was not significant (2.31 (SE 0.08) versus 2.11 (SE 0.08), no P value stated).
Height gain: in under 10 year olds the thrice-yearly treated group experienced significantly greater height gain (cm) compared to control (4.59 (SE 0.07) versus 4.29 (SE 0.07), P < 0.01). In the twice-yearly treatment group the difference in height gain was not significant (4.42 (SE 0.07) versus 4.29 (SE 0.07), no P value stated). There were no significant differences found in the subgroup of children aged over 10 years.
Haemoglobin change: deworming had no effect on haemoglobin change in an adjusted analysis presented for the whole study group (g/L): control 11.3 (SE 1.7); twice-yearly treatment group 10.3 (SE 1.7); and thrice-yearly group 12.7 (SE 1.7).

Whole target population treated - multiple dose (outcome measured > 1 year)

Awasthi 2008 (Cluster)During the study there were 23 deaths, 13 were in the usual care arm and 10 were in the treatment arm.
These data were not adjusted for cluster randomization.

Lai 1995
Mebendazole plus pyrantel
No difference in height or weight between treatment and control group at the end of 2-year follow up. Standard deviations not provided. Results stratified for males and females:
Females: change in height in treatment arm 12.2 cm versus change in height in placebo arm 12.4 cm; change in weight in treatment arm 5.6 kg versus change in weight in placebo arm 5.6 kg.
Males: change in height in treatment arm 11.8 cm versus change in height in placebo arm 11.4cm; change in weight in treatment arm 5.7 kg versus change in weight in placebo arm 4.7 kg.

Hall 2006 (Cluster)
Albendazole
Trial authors reported no difference in final and change in height.

Mid-upper arm circumference and subscapular skinfold thickness improved significantly in the control group compared to the albendazole group (7.87 versus 7.61, P = 0.005 and 1.22 versus 1.05, P = 0.005 respectively). These results do not appear to have been adjusted for cluster randomization. The results that show no effect, however, will not remain non-significant even after appropriate adjustment, though the CIs may change.

Rousham 1994 (Cluster)
Mebendazole
ANOVAS of the change in z-scores revealed no significant improvement with treatment.

Change in weight-for-age and weight-for-height z-scores were significantly worse in the treatment group. Height-for-age z-score (mebendazole 0.25 v 0.17 in placebo group, P 'non-significant'), weight-for-age z-score (mebendazole 0.03 versus 0.12 in placebo group, P < 0.05), weight-for-height z-score (mebendazole -0.25 versus -0.05 in placebo group, P < 0.001), and mid-upper arm circumference were presented (mebendazole 0.33 versus 0.23 in placebo group, P 'non-significant').

 
Table 5. Trials evaluating psychometric tests of cognition

Trial detailsOutcome measuresResults

Screened for infection - single dose (outcomes measured < 1 year)

Kvalsvig 1991a

Mebendazole versus placebo, 1 month
Card sorting task; cancellation task (number of letter 's' in text deleted in a time period).Changes in cognitive scores are not clearly reported since "the dose of mebendazole was inadequate to free children from infection".

Nokes 1992
Albendazole versus placebo

2.25 months
Digit span (forward and backward); arithmetic and coding from Wechsler Intelligence Scale for Children; fluency; listening comprehension from the Clinical Evaluation of Language functions; matching familiar figures test.Mean test scores pre- and post-intervention presented with CIs

No comment made on significance of unadjusted data.

Results of multiple regression suggest a greater improvement in treated children in 3/10 tests (fluency, digit span forwards, digit span backwards).

Screened for infection - multiple dose (outcome measured < 1 year)

Simeon 1995
Albendazole versus placebo
6.5 months
1. Main study (264 children)
Wide range achievement test: reading, arithmetic, and spelling sub tests;

2. Subgroup 1 (189 children 189 infected children from original population)
Digit span; verbal fluency test; visual search; number choice; French vocabulary learning

3. Subgroup 2 (97 children from grade 5)
French learning; digit spans (forward and backward); Corsi block span; verbal fluency; picture search; silly sentences
1. Main study: no difference in any reported outcome measure

2. Subgroup 1: no significant effect on any of the outcome measures

3. Subgroup 2: no significant improvement with treatment in any of the tests was found in multiple regression modelling

Whole target population treated - single dose (outcome measured < 1 year)

Nga 2009

Albendazole
Cognitive performance was measured using Raven's Colored Matrices and also a series of cognitive tests from Wechsler's Intelligence Scale for Children III: digit span backward and forward, block design and coding.Deworming had no significant effect on any of the cognitive tests.

Solon 2003
Albendazole versus placebo

16 weeks
Cognitive ability was measured using a standardized written mental-abilities test called the Primary Mental Abilities Test for Filipino Children (PMAT-FC). The test covers general knowledge and comprehension, verbal relationships, fundamental mathematical comprehension and skills, numerical sequencing, and ability to perceive and apply relationships based on meaningless stimuli.Deworming had either no effect or a negative effect on mental ability scores. Data was not reported.

Whole target population treated - multiple dose (outcome measured < 1 year)

Miguel 2004 (Cluster)

Deworming package including albendazole versus placebo

1 year
1. Exam score performance (measured by Internationaal Christelijk Steunfonds Africa (ICS) administered English, Mathematics and Science-Agriculture exams) in pupils in grades 3 to 8.

2. Cognitive tests including picture search, Raven matrix, verbal fluency, digit span, Spanish learning, and a dynamic test using syllogisms measured for all three school groups in 2000.
1. The authors did not provide outcomes by the quasi-randomized comparison eligible for this review (1998 Group 1 versus Group 2 & 3; 1999 Group 1&2 versus group 3). Regression modelling, adjusting for participation and treatment year presented.

2. Outcome data not reported for cognitive tests, though authors state: "Deworming treatment effects are not significantly different than zero for any component of the cognitive exam (results available on request)".

Stoltzfus 2001
Mebendazole versus placebo, 1 year
Motor and language development by parents reporting gross motor and language milestones using scoring system developed specifically for the trial.Unadjusted data not reported.
Treatment had no significant effect on motor or language development.

Watkins 1996
Albendazole versus placebo, 6 months
Interamerican vocabulary test; Interamerican reading test; Peabody picture vocabulary test.All outcome measures reported as unadjusted scores.
No difference in any of the tests found between treatment groups.

Whole target population treated - multiple dose (outcome measured > 1 year)

Awasthi 2000

Albendazole versus placebo, 2 years
Developmental status (Denver Questionnaire).No difference in development between treatment groups in terms of proportion with "normal" development.

Hall 2006 (Cluster)

Albendazole versus placebo, 2 years
Mathematics test score, Vietnamese test score.No statistically significant differences in test results at start or end of study. These results have not been adjusted for cluster randomization. They will remain non-significant, however, even after appropriate adjustment, though the CIs may change.

 
Table 6. Trials evaluating school attendance (days present at school).

Trial detailsOutcome measuresResults

Screened for infection - multiple dose (outcome measured < 1 year)

Simeon 1995
Albendazole versus placebo
6.5 months
Main study (264 children).
School attendance from children with class registers pre- and post-intervention.

 
There was no significant difference between the treatment and placebo groups at either baseline or post-test.

The mean percentage of school attendance went from 62.6 (SD 20.4) at baseline to 67.3 (SD 18.4) post-test in the treatment group, and from 66.3 (SD 20.8) to 69.3 (SD 17.5) in the placebo group.

Whole target population treated - multiple dose (outcome measured < 1 year)

Miguel 2004 (Cluster)1. School participation rate was computed among all pupils enrolled in 1998 (group 1 versus groups 2 and 3, 1998 comparison).

2. School participation rate was computed among all pupils enrolled in 1998 (group 2 versus group 3, 1999 comparison).

Pupils present on the day of an unannounced NGO visit were considered participant. Pupils had 3.8 observations on average per year. This was then calculated as a weighted average by school.
In 1998, in the intervention group, school participation in girls <13 and boys was 84.1%, and in the comparison group (groups 2 and 3) it was 73.1%, giving a difference of 9.3% (SE 3.1%).

In 1999, in the intervention group 2, school participation in girls <13 and boys was 71.7%, and in the comparison group 3 (groups 3) it was 66.3%, giving a difference of 5.5% (SE 2.8%).

However, there are no comparable baseline values to know whether baseline attendance happens to be higher in group 1 schools.

Watkins 1996
Albendazole versus placebo, 6 months
Attendance rates of children actively attending school.There was no difference in attendance between the albendazole and placebo groups before or after treatment.

Treatment group: before treatment: n = 108, mean = 0.92, SEM = 0.01; after treatment n = 123 mean = 0.88 SEM = 0.01

Placebo group: before treatment  n = 105 mean = 0.90, SEM = 0.01 and after treatment n = 120, mean = 0.89, SEM = 0.01

Whole target population treated - multiple dose (outcome measured > 1 year)

Miguel 2004 (Cluster)1. School participation rate was computed among all pupils enrolled in 1998 (Group 1 versus Group 3, 1999 comparison).

Pupils present on the day of an unannounced NGO visit were considered participant. Pupils had 3.8 observations on average per year. This was then calculated as a weighted average by school.
In the intervention group, school participations in girls <13 and boys was 71.3%, and in the comparison group (group3) it was 66.3%, giving a difference of 5% (SE 2.8%).

However, there are no comparable baseline values to know whether baseline attendance happens to be higher in Group 1 schools.

 
Table 7. SUMMARY OF FINDINGS (A). Single dose deworming drugs for treating soil-transmitted intestinal worms in children screened for infection: effects on nutrition and school performance

Single dose deworming drugs for treating soil-transmitted intestinal worms in children screened for infection: effects on nutrition and school performance

Patient or population: Children screened for infection
Settings: Communities living in areas endemic for intestinal helminths
Intervention: Single dose deworming drug

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

Assumed riskCorresponding risk

ControlSingle dose deworming drugs

Weight (kg)
Follow-up: 4 to 16 weeks
The mean weight (kg) in the intervention groups was
0.58 higher
(0.4 to 0.76 higher)
149
(3 studies)
⊕⊕⊕⊝
moderate1

Haemoglobin (g/dL)The mean haemoglobin (g/dL) in the intervention groups was
0.37 higher
(0.1 to 0.64 higher)
108
(2 studies)
⊕⊕⊝⊝
low2

Formal tests of cognitionSee commentSee commentNot estimable0
(2 studies)
⊕⊝⊝⊝
very low3
Two trials reported on formal tests of intellectual development but not in a form that could be added to the meta-analysis.4

*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 Freij 1979a has a high risk of bias for sequence generation.
2 Both Adams 1994 and Stephenson 1993 have an unclear risk of bias for sequence generation and allocation concealment. Adams 1994 also has an unclear risk of bias for blinding. Significant imprecision around the effect estimate, ranging from clinically small to large effect sizes.
3 Kvalsvig 1991a and Nokes 1992 did not fully report data for this outcome.
4 Two studies measured cognitive functioning: i) Kvalsvig 1991a, with a follow-up of one month, did not clearly report the changes in cognitive scores since "the dose of mebendazole was inadequate to free children from infection"; and ii) Nokes 1992, with a follow-up of 9 weeks, reported that results of a multiple regression suggest a greater improvement in treated children in 3/10 tests (fluency, digit span forwards, digit span backwards).
 
Table 8. SUMMARY OF FINDINGS (B). Single dose deworming drugs for treating soil-transmitted intestinal worms in children: effects on nutrition and school performance

Single dose deworming drugs for treating soil-transmitted intestinal worms in children: effects on growth and school performance

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

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

Assumed riskCorresponding risk

ControlSingle dose deworming drugs

Weight (kg)
Follow-up: 7 weeks to 1 year
See commentSee commentNot estimable3058
(9 studies)
⊕⊝⊝⊝
very low1,2
Positive effect only demonstrated in 2 trials in a single location.3

Haemoglobin (g/dL)
Follow-up: 9 weeks to 6 months
The mean haemoglobin (g/dL) in the intervention groups was
0.02 higher
(0.05 lower to 0.09 higher)
1992
(4 studies)
⊕⊕⊝⊝
low4

Formal tests of cognitionSee commentSee commentNot estimable(1 study)⊕⊝⊝⊝
very low5
One trial reported on formal tests of intellectual development but not in a form that could be added to the meta-analysis.6

Physical well being

Harvard step test
See commentThe mean difference in the intervention groups was
6.00 higher
(4.31 higher to 7.69 higher)
86

(2 studies)
⊕⊕⊝⊝
low7
Two trials reported on Harvard Step Test, mean percent increase in the intervention group was 6% higher.8

*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 has a high risk of bias for sequence generation and allocation concealment. Garg 2002 has a high risk of bias for blinding. In addition, Stephenson 1989 and Stephenson 1993 have a high prevalence of polyparasitism, and differ from the other high prevalence studies in this respect. They were conducted in the same primary school in Kenya, in a population where virtually all of the children had hookworm and Trichuris infection, and about half were also infected with Ascaris.
2 A high level of heterogeneity was found for this outcome.
3 Deworming increased weight gain in two trials in the same high prevalence school, but had no effect in seven subsequent trials.
4 Awasthi 2000, which contributes 63.1% of the weight to this outcome, has a high risk of bias for sequence generation and allocation concealment.
5 Solon 2003 did not fully report data for this outcome.
6 Solon 2003, with a follow-up of 16 weeks, reported that deworming had either no effect or a negative effect on mental ability scores, but did not report the data.
7Stephenson 1989 and Stephenson 1993 have an unclear risk of bias for sequence generation and allocation concealment. As above, both studies were conducted in the same high prevalence primary school.
8 Harvard Step Test is out of 100, and Stephenson 1989 and Stephenson 1993 have both 6% higher value in treated groups (from 74% and 76% in control groups)
 
Table 9. SUMMARY OF FINDINGS (C). Multiple dose deworming drugs for treating soil-transmitted intestinal worms in children: effects on nutrition and school performance (outcomes measured at less than one year)

Multiple dose deworming drugs for treating soil-transmitted intestinal worms in children: effects on nutrition and school performance (outcomes measured at less than one 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 participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlMultiple dose deworming drugs

Weight (kg)
Follow-up: 6 to 12 months
The mean weight (kg) in the intervention groups was
0.06 higher
(0.17 lower to 0.30 higher)
2460
(7 studies)
⊕⊝⊝⊝
very low1,2,3

Haemoglobin (g/dL)
Follow-up: 6 to 11 months
The mean haemoglobin (g/dL) in the intervention groups was
0.01 lower
(0.14 lower to 0.13 higher)
807
(4 studies)
⊕⊕⊝⊝
low3,4

Formal tests of cognitionSee commentSee commentNot estimable(3 studies)⊕⊝⊝⊝
very low5
Three trials reported on formal tests of intellectual development but not in a form that could be added to the meta-analysis.6

School attendance

Follow-up: 6 to 12 months
The mean attendance (%) in the intervention group was
4 higher
(6 lower to 14 higher))
2 studies⊕⊝⊝⊝

very low2,7
75 clusters and 143 individually randomized participants

*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 has a high risk of bias for sequence generation and allocation concealment. Dossa 2001 and Kruger 1996 have a high risk of bias for incomplete outcome data. In addition, Stephenson 1993 has a high prevalence of polyparasitism, and differs from the other high prevalence studies in this respect. They were conducted in the same primary school in Kenya, in a population where virtually all of the children had hookworm and Trichuris infection, and about half were also infected with Ascaris.
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 Dossa 2001 and Kruger 1996 have a high risk of bias for incomplete outcome data.
5 Miguel 2004 (Cluster), Stoltzfus 2001 and Watkins 1996 did not fully report data for this outcome.
6 Three studies measured intellectual development: i) Miguel 2004 (Cluster), with a follow up of 12 months, did not report unadjusted outcomes for measures of exam performance. In addition Miguel 2004 (Cluster) measured a range of cognitive tests, but no deworming effect was demonstrated. Stoltzfus 2001, with a follow-up of 12 months, found that treatment had no significant effect on motor or language development; ii) Watkins 1996, with a follow-up of six months, found no difference on any of the tests between treatment groups.
7Miguel 2004 (Cluster) has a high risk of bias for sequence generation, allocation concealment, blinding, incomplete outcome data and baseline imbalance.