Recovery of children following hospitalisation for complicated severe acute malnutrition

Bwakura‐Dangarembizi, Mutsa; Dumbura, Cherlynn; Amadi, Beatrice; Chasekwa, Bernard; Ngosa, Deophine; Majo, Florence D; Sturgeon, Jonathan P; Chandwe, Kanta; Kapoma, Chanda; Bourke, Claire D.; Robertson, Ruairi C.; Nathoo, Kusum; Ntozini, Robert; Norris, Shane A.; Kelly, Paul; Prendergast, Andrew J.

doi:10.1111/mcn.13302

Cited by 17 publications

(34 citation statements)

References 35 publications

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“…The clinical importance of normalizing anti-bacterial innate immune cell function as part of rehabilitation from SAM is supported by evidence that PC1 scores during hospitalization were associated with persistent SAM status at discharge, a predictor of both mortality and persistent wasting over a year of post-discharge follow-up in HOPE-SAM (6,9). Scores for PC3 (monocyte activation), which tended to be lower in children with SAM than healthy controls, were associated with higher odds of persistent wasting within the SAM group.…”

Section: Phiri Et Al Preprintmentioning

confidence: 99%

“…In the HOPE-SAM cohort, mortality over 1 year of post- (9). Young age, SAM at discharge, non-edematous SAM at admission and cerebral palsy were also associated with hospital readmission or poor nutritional recovery after discharge (6). Symptoms of acute infection have previously been implicated in inpatient mortality among children hospitalized with SAM(3).…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

“…; https://doi.org/10.1101/2023.04. 10.23288163 doi: medRxiv preprint Phiri et al, preprint 6 Innate immune cell function was characterized in the SAM group (Table 1) using the first available venous blood sample (≥2mL) collected during their inpatient period (median time from admission to immune function assessment (time to immunoassay): 6.0 days, interquartile range (IQR): 4, 11); 38.2% of the SAM group had their first immune function assessment on the day of discharge from hospital. Clinical symptoms were recorded daily during hospitalization with 80.8% of children in the SAM group having ongoing clinical complications and 60.0% having symptoms indicative of acute infection at the time of immune function assessment (Table S2).…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

“…Children with complicated SAM experience a range of comorbidities and risk factors for adverse clinical outcomes (3,(6)(7)(8)(9), which could plausibly impact their immune function relative to healthy controls. To explore this hypothesis, we used cross-fit partialling-out lasso linear regression to estimate the effect of variables associated with mortality in the HOPE-SAM cohort (i.e.…”

Section: Anti-bacterial Innate Immune Cell Function Is Partially Shap...mentioning

confidence: 99%

“…Similarly, SAM is implicated in impaired adaptive immunity (33,59), and, although we provide some evidence for bulk differences in bacterial binding by Lin+ lymphocyte populations in children with SAM, detailed analyses of adaptive immunity was beyond our scope. Fourth, though our study is the largest of its kind and adequately-powered for our primary comparison between the SAM and healthy groups, it is increasingly apparent from clinical studies of SAM, including our own (6,9,51), that specific co-morbidities contribute to sub-conditions within current SAM diagnostic criteria (e.g. HIV-SAM, cerebral palsy-SAM, edematous/non-edematous SAM); a larger or comorbidity-focused sample size would be required to conclusively evaluate the impact of these variables on immune function.…”

Section: Phiri Et Al Preprintmentioning

confidence: 99%

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Severe acute malnutrition promotes bacterial binding over pro-inflammatory cytokine secretion by circulating innate immune cells

Phiri

Mutasa

Rukobo

et al. 2023

Preprint

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Children with severe acute malnutrition (SAM) are at high risk of infectious mortality and morbidity during and after hospital discharge. This risk persists despite nutritional and prophylactic antibiotic interventions among children with SAM, implicating persistent deficits in their immune defenses. Here we test the hypothesis that innate immune cells from children (0-59 months) hospitalized with SAM in Zambia and Zimbabwe (n=141) have distinct capacity to respond to bacteria relative to adequately-nourished healthy controls from the same communities (n=92). Neutrophils and monocytes from SAM inpatients had a higher capacity to bind E. coli but lower monocyte activation and pro-inflammatory mediator secretion in response to E. coli lipopolysaccharide (LPS) or heat-killed Salmonella typhimurium (HKST) than controls. Bacterial binding capacity differentiated children with SAM from controls after adjusting for clinical and demographic heterogeneity and normalized with duration of hospital treatment. Wasting severity, HIV status, and age group were associated with LPS and HKST-induced cytokine secretion, monocyte activation, and myeloperoxidase secretion, respectively. Bacterial binding capacity and monocyte activation during hospitalization were associated with higher odds of persistent SAM at discharge; a risk factor for subsequent mortality. Thus, SAM shifts anti-bacterial innate immune cell function, favoring bacterial containment over pro-inflammatory activation upon challenge, which contributes to persistent health deficits among hospitalized children.

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Section: Phiri Et Al Preprintmentioning

confidence: 99%

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%