The Impact of Malnutrition on Immune Responses to Tuberculosis

Study Overview
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Brief Summary
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The aim of this study is to assess immune responses to Mtb in children with MAM compared to well-nourished children and to evaluate the impact of a nutrition intervention on these immune responses.

Detailed Description
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Immune dysfunction in malnourished children is poorly characterised. The aim of this study is to assess immune responses to Mycobacterium tuberculosis (Mtb) in children with moderate acute malnutrition (MAM) compared to wellnourished children and to evaluate the impact of a nutrition intervention on these immune responses. Innate and adaptive immune responses to Mtb will be characterised in four groups: 1) MAM children with TB disease; 2) Wellnourished children with TB disease; 3) MAM children with latent TB infection; 4) Well-nourished children with latent TB infection. A range of assays to compare innate, adaptive and functional immune responses to TB between groups will be performed. Whether nutritional supplementation improves immune function in MAM children remains uncertain. Hence, children in all four groups will be followed up during 6 months of TB therapy/chemoprophylaxis. MAM children will receive 12 weeks of concomitant ready-to-use supplementary food, to evaluate longitudinal changes in innate and adaptive immune function, monocyte:lymphocyte ratio and mycobacterial growth inhibition. The results of this study will provide data to understand the reasons for infection susceptibility in malnourished children and provide a proof-of-concept that nutritional rehabilitation promotes immune rehabilitation. It will also provide a proof-of concept for use of nutritional supplementation as adjust therapy in TB disease

Official Title
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The Impact of Malnutrition on Immune Responses to Tuberculosis in Indian Children

Conditions
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Malnutrition, Child, Tuberculosis

Intervention / Treatment
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* Dietary Supplement: Ready to Use supplementary food (RUSF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 12-60 months HIV-negative BCG vaccinated Moderate acute malnutrition (WHZ -2 to -3 or MUAC 115 - 125mm ± HAZ <-2) TB disease Latent TB infection Exclusion Criteria: Inclusion criteria not met Severe acute malnutrition (WHZ<-3; MUAC<115mm; bilateral oedema) Severe anaemia (Hb: <7g/dl) Chronic infection (HIV, hepatitis B or C) Chronic disease (e.g. Crohn's disease) Feeding problems (eg cerebral palsy) that prevent ingestion of RUSF Known nut allergy MDR TB disease and contacts of MDR TB adults

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 60 Months

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MAM children with TB disease<br> | Dietary Supplement: Ready to Use supplementary food (RUSF)<br>* Children with malnutrition will be given RUSF<br>|
| Wellnourished children with TB disease<br> | |
| MAM children with latent TB infection<br> | Dietary Supplement: Ready to Use supplementary food (RUSF)<br>* Children with malnutrition will be given RUSF<br>|
| Well-nourished children with latent TB infection<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IFNγ concentration | IFNγ concentration in supernatant after overnight incubation of whole blood with TB antigens | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malnutrition, moderate acute malnutrition, immunology