Restoration of anti-bacterial innate immune cell function lags behind nutritional recovery among children convalescing from complicated severe acute malnutrition

Abstract

Abstract Children recovering from complicated severe acute malnutrition (SAM) have a high risk of infectious mortality and morbidity, which could reflect impaired anti-microbial defence. We used blood samples from a cross-sectional cohort of children under 5 years’ old admitted to hospital with SAM in Zambia and Zimbabwe (cases, n  = 125) and adequately nourished non-hospitalised children from the same communities (controls, n  = 73) to characterise anti-bacterial innate immune cell function. We did not find evidence that inpatient immune function differed between cases who experienced subsequent adverse clinical outcomes (death, readmission, SAM at 48 weeks) versus those who did not. However, pro-inflammatory cytokine (IL-6, IL-8 and TNF) responses to E. coli lipopolysaccharide and heat-killed Salmonella typhimurium were positively associated with subsequent gains in mid-upper arm circumference, an indicator of nutritional recovery. We then characterised how innate immune cell function changed during post-discharge rehabilitation in a longitudinal sub-cohort of cases who provided repeat blood samples at discharge, 12, 24 and/or 48 weeks post-discharge ( n  = 83). Relative to inpatient immune function, bacterial binding capacity declined whilst anti-bacterial pro-inflammatory cytokine secretion increased in the cases over the post-discharge follow-up period with both normalising towards control ranges. These changes were also evident in cases who had recovered to a healthy nutritional status (weight-for-height Z score ≥ −2). Collectively, our data suggest that restoration of anti-bacterial innate immune cell function following complicated SAM lags behind nutritional recovery. Thus, children who are no longer wasted may continue to have deficient anti-bacterial innate immunity months after hospital admission for SAM.