The Effect of a Deworming Intervention to Improve Early Childhood Growth and Development in Resource-poor Areas

Study Overview
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Brief Summary
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Worldwide, over 2 billion people suffer from worm infections in developing countries. These infections are especially damaging to the health of children, resulting in both short-term and lifelong disability. Older children with worm infections are more likely to be stunted, underweight, vulnerable to other illnesses and perform poorly in school compared to non-infected children. Large-scale deworming programs in school-age children are therefore recommended by the World Health Organization (WHO). WHO also recommends deworming of preschool-age children (as of 12 months of age) in these areas; however, the benefits of deworming, especially in the 12-24 month age group, have been inadequately studied. This knowledge is urgently needed as studies show that all children have a similar potential for healthy growth and development, provided that appropriate nutrition and health interventions are given in the critical window of opportunity before the age of two. Therefore, the investigators are proposing to undertake a randomized controlled trial to determine the effect of deworming program for improving growth and development in children between 12 and 24 months of age. Our results will provide solid rigorous evidence on if, when, and how often, deworming should be integrated into routine child health care packages provided by Ministries of Health in the 130 countries in the world where worm infections are endemic.

Detailed Description
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Worldwide, over 2 billion people suffer from worm infections (hookworm, Ascaris and Trichuris, collectively referred to as soil-transmitted helminths (STHs)) in developing countries. STHs contribute to the overwhelming burden of poverty and deprivation in areas where adverse health, social, economic, education and other related factors predominate. STH infection in childhood results in short-term and lifelong disability, including malnutrition (e.g. underweight, stunting and wasting), cognitive impairment and increased susceptibility to other infection, among others. Mass deworming programs in school-age children are recommended by the World Health Organization (WHO). WHO also recommends deworming of preschool children (as of 12 months of age) in endemic areas; however, the benefits of deworming on improving growth and development, especially in the 12-24 month age group, have been inadequately studied. This knowledge is crucial because, with appropriate nutrition and health interventions, all children have a similar potential for healthy growth and development, provided that such interventions occur in the critical window of opportunity before the age of two. Therefore, this double-blind randomized controlled trial will assess the benefit of deworming (mebendazole), integrated into routine child health care visits in a highly STH-endemic area (Iquitos, Peru), on the primary outcome of weight gain. Timing, frequency and impact of deworming will be considered. A total of 1760 children will be recruited at their routine 12-month check-up visit and randomly assigned to one of four intervention groups: Group 1 will receive usual care and mebendazole (single dose 500 mg) at their 12-month visit and usual care and a placebo tablet at their 18-month visit; Group 2 will receive usual care and a placebo tablet at their 12-month visit and usual care and mebendazole at their 18-month visit; Group 3 will receive usual care and mebendazole at both their 12-month and 18-month visit; and Group 4 will receive usual care and placebo at both their 12-month and 18-month visit. Usual care will consist of age-appropriate immunizations, supplements and other Peruvian Ministry of Health-recommended interventions. All children will be followed up to their 24-month visit and all will be given mebendazole at that time. Additional secondary outcomes include length gain, motor and cognitive development and STH prevalence and intensity. Improving child health is a priority area in global health research and a focus of the Millennium Development Goals. Early preschool-age children are at the most critical stage of growth and development and have been neglected in deworming programs. It is anticipated that the results will inform evidence-based policy on the provision of an integrated health package for young children in endemic areas and ultimately contribute to the reduction of health inequities in this vulnerable group.

Official Title
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Improving Early Childhood Growth and Development in Resource-poor LMICs by Incorporating Deworming in Integrated Child Health Care

Conditions
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Intestinal Diseases, Parasitic, Malnutrition

Intervention / Treatment
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* Drug: Mebendazole
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: children attending any one of the participating study health centres for their routine 12-month growth and development visit children living in or near the study area Exclusion Criteria: children who are attending the clinic for suspected STH infection children who have received deworming treatment in the six months prior to randomization parents planning to move outside of the study area within the next 12 months children under 12 months of age or 14 months of age or older children with serious congenital or chronic medical conditions and who would be considered by the attending staff not to benefit from deworming

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deworming at 12 months of age<br> | Drug: Mebendazole<br>* Single-dose 500 mg mebendazole tablet<br>* Other names: Vermox, Nemasole, Pantelmin;Other: Usual care<br>* Routine child health interventions (e.g. age-specific immunizations, supplementations, etc.)<br>* Other names: Standard of care, routine health care services;|
| Experimental: Deworming at 18 months of age<br> | Drug: Mebendazole<br>* Single-dose 500 mg mebendazole tablet<br>* Other names: Vermox, Nemasole, Pantelmin;Other: Usual care<br>* Routine child health interventions (e.g. age-specific immunizations, supplementations, etc.)<br>* Other names: Standard of care, routine health care services;|
| Experimental: Deworming at 12 and 18 months of age<br> | Drug: Mebendazole<br>* Single-dose 500 mg mebendazole tablet<br>* Other names: Vermox, Nemasole, Pantelmin;Other: Usual care<br>* Routine child health interventions (e.g. age-specific immunizations, supplementations, etc.)<br>* Other names: Standard of care, routine health care services;|
| Placebo Comparator: Usual care<br> | Other: Usual care<br>* Routine child health interventions (e.g. age-specific immunizations, supplementations, etc.)<br>* Other names: Standard of care, routine health care services;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean (± standard deviation) weight gain (kg) | Weight will be measured at baseline (12 months of age), and follow-up (18 and 24 months of age) to assess the effect of the deworming intervention on growth (in terms of weight) | from 12 to 24 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean (± standard deviation) height gain (cm) | Height will be measured at baseline (12 months of age) and at follow-up (18 and 24 months of age) to evaluate the effect of the deworming intervention on growth (in terms of height) | from 12 to 24 months of age | 
| Mean (± standard deviation) of the cognitive test score | Cognitive development will be assessed using the Bayley Scale of Infant Development. This scale provides a raw score and standardized score based on age-specific abilities. This will be measured at both baseline (12 months of age) and follow-up (at 24 months of age) to evaluate the effects of the deworming intervention on cognitive development. | from 12 to 24 months of age | 
| Soil-transmitted helminth infection (Ascaris, Trichuris or hookworm) - prevalence (%) and intensity (mean eggs per gram) | Soil-transmitted helminth (STH) infection will be assessed from stool samples provided by participants. The Kato-Katz technique will be used to provide both an estimate of prevalence of each STH (e.g. % positive for each Ascaris, Trichuris, and/or hookworm) as well as an estimate of intensity of each STH (measured as mean eggs per gram of stool). This will be measured at baseline (12 months of age) and follow-up (18 and 24 months of age) to evaluate the effect of the deworming intervention on parasite prevalence and intensity. | from 12 to 24 months of age | 
| Mean (± standard deviation) of the motor test score | Fine motor development will be assessed using the Bayley Scale of Infant Development. This scale provides a raw score and standardized score based on age-specific abilities. This will be measured at both baseline (12 months of age) and follow-up (at 24 months of age) to evaluate the effects of the deworming intervention on motor development. | from 12 to 24 months of age | 
| Mean (± standard deviation) of the language test score | Receptive and expressive language development will be assessed using the Bayley Scale of Infant Development. This scale provides a raw score and standardized score based on age-specific abilities. This will be measured at both baseline (12 months of age) and follow-up (at 24 months of age) to evaluate the effects of the deworming intervention on language development. | from 12 to 24 months of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preschool-age children, soil-transmitted helminths, growth, development, deworming