Immune recovery of malnourished children takes longer than nutritional recovery: implications for treatment and discharge

Chevalier, Philippe; Sevilla, Ricardo; Sejas, Edgar; Zalles, Lourdes; Belmonte, Guadalupe; Parent, Gérard

doi:10.1093/tropej/44.5.304

Cited by 35 publications

(28 citation statements)

References 11 publications

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“…Approximately 50% of all relapses occurred within the first 3 mo of discharge from an SFP; presumably, the underlying physiologic and social factors that led to the acute malnutrition in the first place may not have been fully reversed by the time of SFP discharge, which left the child susceptible to relapse. Previous studies have shown that the immune function is often compromised during acute malnutrition (10,25,26), and these deficiencies may linger beyond traditional anthropometric recovery (27). However, in our population, we did not find abnormal serum complement C3 concentrations at the time of recovery, thereby indicating normal function in at least this single immunologic cascade.…”

Section: Discussioncontrasting

confidence: 58%

Effect of a package of health and nutrition services on sustained recovery in children after moderate acute malnutrition and factors related to sustaining recovery: a cluster-randomized trial

Stobaugh

Bollinger

Adams

et al. 2017

The American Journal of Clinical Nutrition

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Background: Children who recover from moderate acute malnutrition (MAM) have high rates of relapse in the year after nutritional recovery. Interventions to decrease these adverse outcomes are needed to maximize the overall effectiveness of supplemental feeding programs (SFPs). Objective: We evaluated the effectiveness of a package of health and nutrition interventions on improving the proportion of children who sustained recovery for 1 y after MAM treatment. We further explored factors related to sustained recovery. Design: We conducted a cluster-randomized clinical effectiveness trial involving rural Malawian children aged 6-62 mo who were enrolled on discharge from an SFP for MAM. We enrolled 718 children at 10 control sites and 769 children at 11 intervention sites. In addition to routine health and nutrition counseling, the intervention group received a package of health and nutrition interventions that consisted of a lipid nutrient supplement, deworming medication, zinc supplementation, a bed net, and malaria chemoprophylaxis. A survival analysis was used to determine the effectiveness of the intervention as well as to identify factors associated with sustained recovery. Results: Of 1383 children who returned for the full 12-mo followup period, 407 children (56%) and 347 children (53%) sustained recovery in the intervention and control groups, respectively. There was no significant difference in relapse-free survival curves between the treatment and control groups (P = 0.380; log-rank test). The risk factors for relapse or death after initial recovery were a smaller midupper arm circumference on SFP admission (P = 0.01) and discharge (P , 0.001), a lower weight-for-height z score on discharge (P , 0.01), and the receipt of ready-to-use supplementary food as opposed to ready-to-use therapeutic food during treatment (P , 0.05). Conclusion: The provision of a package of health and nutrition services in addition to traditional SFP treatment has no significant effect on improving sustained recovery in children after treatment of MAM. This trial was registered at clinicaltrials.gov as NCT02351687.Am J Clin Nutr 2017;106:657-66.

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Section: Discussioncontrasting

confidence: 58%

Effect of a package of health and nutrition services on sustained recovery in children after moderate acute malnutrition and factors related to sustaining recovery: a cluster-randomized trial

Stobaugh

Bollinger

Adams

et al. 2017

The American Journal of Clinical Nutrition

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“…Five of these studied children with severe malnutrition and found severe thymic atrophy [91] [167]–[170], reversible with nutritional rehabilitation, although thymic size did not reach normal levels as fast as anthropometric recovery [91] [170]. Thymic size was also measured by ultrasound in cohorts of children to determine patterns of thymic growth [159] [171], in a vaccination trial in Guinea Bissau [172] and in a pre-natal nutritional supplementation trial in Bangladesh [171].…”

Section: Resultsmentioning

confidence: 99%

The Immune System in Children with Malnutrition—A Systematic Review

et al. 2014

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BackgroundMalnourished children have increased risk of dying, with most deaths caused by infectious diseases. One mechanism behind this may be impaired immune function. However, this immune deficiency of malnutrition has not previously been systematically reviewed.ObjectivesTo review the scientific literature about immune function in children with malnutrition.MethodsA systematic literature search was done in PubMed, and additional articles identified in reference lists and by correspondence with experts in the field. The inclusion criteria were studies investigating immune parameters in children aged 1–60 months, in relation to malnutrition, defined as wasting, underweight, stunting, or oedematous malnutrition.ResultsThe literature search yielded 3402 articles, of which 245 met the inclusion criteria. Most were published between 1970 and 1990, and only 33 after 2003. Malnutrition is associated with impaired gut-barrier function, reduced exocrine secretion of protective substances, and low levels of plasma complement. Lymphatic tissue, particularly the thymus, undergoes atrophy, and delayed-type hypersensitivity responses are reduced. Levels of antibodies produced after vaccination are reduced in severely malnourished children, but intact in moderate malnutrition. Cytokine patterns are skewed towards a Th2-response. Other immune parameters seem intact or elevated: leukocyte and lymphocyte counts are unaffected, and levels of immunoglobulins, particularly immunoglobulin A, are high. The acute phase response appears intact, and sometimes present in the absence of clinical infection. Limitations to the studies include their observational and often cross-sectional design and frequent confounding by infections in the children studied.ConclusionThe immunological alterations associated with malnutrition in children may contribute to increased mortality. However, the underlying mechanisms are still inadequately understood, as well as why different types of malnutrition are associated with different immunological alterations. Better designed prospective studies are needed, based on current understanding of immunology and with state-of-the-art methods.

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“…This could be because the children’s nutritional status was still poorer that the healthy controls, or because immunological recovery may take longer than anthropometric recovery, as previously suggested [39]. …”

Section: Discussionmentioning

confidence: 99%

Correlates of thymus size and changes during treatment of children with severe acute malnutrition: a cohort study

et al. 2017

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BackgroundThe impairment of immune functions associated with malnutrition may be one reason for the high mortality in children with severe acute malnutrition (SAM), and thymus atrophy has been proposed as a marker of this immunodeficiency. The aim of this study was to identify nutritional and clinical correlates of thymus size in children with SAM, and predictors of change in thymus size with nutritional rehabilitation.MethodsIn an observational study among children aged 6–59 months admitted with SAM in Uganda, we measured thymus area by ultrasound on hospital admission to treatment with F75 and F100, on hospital discharge and after 8 weeks of nutritional rehabilitation with ready-to-use therapeutic food, as well as in well-nourished healthy children. We investigated anthropometric, clinical, biochemical and treatment-related correlates of area and growth of the thymus.ResultsEighty-five children with SAM with a median age of 16.5 months were included. On admission 27% of the children had a thymus undetectable by ultrasound. Median thymus area was 1.3 cm2 in malnourished children, and 3.5 cm2 in healthy children (p < 0.001). Most anthropometric z-scores, hemoglobin and plasma phosphate correlated positively with thymus area. Thymus area correlated negatively with caretaker-reported severity of illness, plasma α-1 acid glycoprotein, and C-reactive protein >5 mg/L. At follow-up after 8 weeks, median thymus area had increased to 2.5 cm2 (p < 0.001). Increase in thymus area during treatment was associated with simultaneous increase in mid-upper-arm circumference, with 0.29 cm2 higher increase in thymus area per cm larger increment in MUAC (p = 0.03). Children whose F-75 had partially been replaced by rice porridge during their hospital admission had less increase in thymus area after 8 weeks.ConclusionMalnutrition and inflammation are associated with thymus atrophy, and thymus area seems positively associated with plasma phosphate. Substituting therapeutic formula with unfortified rice porridge with the aim of alleviating diarrhea may impair regain of thymus size with nutritional rehabilitation. This calls for research into possible effects of phosphate status on thymus size and other immunological markers.Trial registrationThe study is based on data from the FeedSAM study, ISRCTN55092738.

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Immune recovery of malnourished children takes longer than nutritional recovery: implications for treatment and discharge

Cited by 35 publications

References 11 publications

Effect of a package of health and nutrition services on sustained recovery in children after moderate acute malnutrition and factors related to sustaining recovery: a cluster-randomized trial

Effect of a package of health and nutrition services on sustained recovery in children after moderate acute malnutrition and factors related to sustaining recovery: a cluster-randomized trial

The Immune System in Children with Malnutrition—A Systematic Review

Correlates of thymus size and changes during treatment of children with severe acute malnutrition: a cohort study

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