Thymus gland size during recovery from complicated severe acute malnutrition: a prospective study of the role of probiotics

Abstract

ABSTRACTBackground: Children with severe acute malnutrition (SAM) are prone to infections due to immune dysfunction including severe thymus atrophy which recovers during nutritional rehabilitation.Aim: To investigate predictors of thymus size recovery, including probiotics during nutritional rehabilitation of children admitted with complicated SAM.Methods: In this prospective study nested in a randomized controlled trial, children 6-59 months admitted with SAM received standard care and either probiotics or placebo during hospitalization until 8 weeks post-discharge. Thymus size was measured using ultrasound at admission, discharge, 8 weeks post-discharge and among 27 community controls. Predictors of thymus size recovery were assessed using linear regression.Results: Among 388 children with SAM, mean (SD) thymus size was 1.06 cm2 (0.41), 1.24 cm2 (0.48), 2.85 cm2 (1.07) and 4.2 cm2 (0.93) at admission, discharge, follow-up and in the healthy controls respectively (p < 0.05).Probiotics did not affect thymus recovery. During both inpatient therapeutic care (ITC) and outpatient therapeutic care (OTC), thymus recovery correlated positively with anthropometry but negatively with caregiver-perceived illness severity and Haemoglobin <8 g/dl. Negative predictors of thymus recovery during ITC included grade 3 oedema (β -0.13, 95%CI -0.25; -0.01), dermatosis (β -0.21, 95%CI -0.41; -0.01), C-reactive protein (CRP) >15mg/L (β -0.13, 95%CI -0.25; -0.02) and neutrophils (β -0.01, 95%CI -0.02; -0.002). During OTC, HIV negatively predicted thymus recovery.Conclusion: Children with SAM failed to regain thymus size at 8 weeks post-discharge. Probiotics did not predict thymus recovery during nutritional rehabilitation. More research is needed to find interventions which can accelerate immune recovery.Abbreviations: ART, Antiretroviral therapy; BB-12, Bifidobacterium animalis subsp. Lactis; CRP, C-reactive protein; ITC, inpatient therapeutic care; LGG, Lactobacillus rhamnosus; MNU, Mwanamugimu Nutrition Unit; MUAC, mid-upper arm circumference; OTC, outpatient therapeutic care; PCR, Polymerised chain reaction; RUTF, ready-to-use therapeutic food; SAM, severe acute malnutrition; VAS, visual analogue score; WHO, World Health Organization; WHZ, weight-for-height score.