The Impact of Malnutrition on Immune Responses to Tuberculosis (TBMAM)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tuberculosis; Malnutrition, Child
• Intervention / Treatment: Dietary supplement: Ready to Use supplementary food (RUSF)

Detailed Description

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

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• India
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600 008
      • Institute of Child Health
    • Chennai, Tamil Nadu, India, 600001
      • Government Stanley Medical College and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 5 years (Child)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

HIV negative, BCG vaccinated

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MAM children with TB disease	Dietary supplement: Ready to Use supplementary food (RUSF); Children with malnutrition will be given RUSF
Wellnourished children with TB disease
MAM children with latent TB infection	Dietary supplement: Ready to Use supplementary food (RUSF); Children with malnutrition will be given RUSF
Well-nourished children with latent TB infection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tuberculosis Research Centre, India
• Collaborators: London School of Hygiene and Tropical Medicine; Queen Mary University of London; Stanley Medical College; Institute of Child Health, Madras Medical College, Chennai; Kanchi Kamakoti Childs Trust Hospital, Chennai, India; DBT, India
• Investigators: Principal Investigator: Aishwarya Venkataraman, MRCPCH, ICMR-NIRT

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: September 9, 2021
• First Submitted That Met QC Criteria: September 9, 2021
• First Posted (Actual): September 16, 2021

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 26, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: malnutrition; immunology; moderate acute malnutrition
• Additional Relevant MeSH Terms: Infections; Nutrition Disorders; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Malnutrition; Child Nutrition Disorders
• Other Study ID Numbers: 2019037

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be shared according to ICMR rules and regulations after appropriate approvals

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No