The Immune System in Children with Malnutrition—A Systematic Review

Abstract

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.

Malnutrition and vaccination in developing countries

“…There is therefore an urgent need for further, larger studies of well-characterized cohorts of children with varying degrees of malnutrition, categorized according to current criteria, and followed longitudinally to probe immune function using modern laboratory techniques. Nevertheless, certain consistent findings from prior studies of immune function can be drawn from the literature, as comprehensively reviewed by Rytter et al [12]. The current paper will provide only a brief summary of these findings, before focusing on vaccination in the context of malnutrition.…”

“…Scrimshaw et al [9] first described a vicious cycle of infection and undernutrition, whereby infections predispose to malnutrition, through reduced intake and absorption and diversion of nutrients away from growth, while malnutrition reduces immune function and increases the risk and/or severity of infections. Various iterations of this cycle have been proposed over the years, with more recent versions recognizing that subclinical infection, enteropathy, changes in the composition and function of the gut microbiota and systemic inflammation are likely to be important in the pathogenesis of malnutrition, in addition to overt infections [10][11][12]. Children hospitalized for severe acute malnutrition are extremely sick, with physiological dysfunction such as reduced respiratory muscle mass, impaired cardiac function and electrolyte disturbance, in addition to micronutrient deficiencies, inflammation, clinical infection and mucosal barrier breakdown.…”

Causes of impaired oral vaccine efficacy in developing countries

“…It appears in various forms, including impaired growth (e.g., stunting) and deficiencies in specific micronutrients (e.g., zinc, iron and vitamin A). Several abnormalities in immune function have been linked with malnutrition, including deficits in secretory IgA, complement production, gut barrier function and T-cell memory maintenance, among others [107]. In spite of these immunological deficits, a consistent link between malnutrition and oral vaccine performance has not been found [108,109].…”

Human genetic basis of interindividual variability in the course of infection

“…Malnutrition in some ways mimics intestinal failure and has been shown to account for severe infections (38). The various types of organ failure associated with malnutrition may contribute to immunodeficiency (39). It also has been suggested that specific vitamin deficiencies favor infectious diseases.…”