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Micronutrient Malnutrition, Infection, and Immunity in Children

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (25 April 2023) | Viewed by 21040

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Special Issue Editors

Dr. Kurt Long

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Guest Editor

Department of Epidemiology and Public Health, Swiss Tropical and Public Health, Basel, Switzerland
Interests: vitamin A; diarrhea; malnutrition; infectious disease epidemiology; child nutrition; childhood/pediatric obesity; zinc

Dr. Helen Powell

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Guest Editor

Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Interests: statistical methods; analysis; regression; public health; data management; Bayesian methods; spatial correlation; spatial misalignment; confounding

Dr. Johanna Sanchez

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Guest Editor

1. IHPME, Dalla Lana School of Public Health,155 College St Room 500, Toronto, ON M5T 3M7, Canada
2. School of Occupational and Public Health, Ryerson University, 350 Victoria St, Toronto, ON M5B 2K3, Canada
Interests: epidemiology; enteric infection; public health; WASH; child growth; maternal & child health; global health

Special Issue Information

Dear Colleagues,

The synergism between nutrition and infectious diseases substantially contributes to the childhood burden of disease in low- and middle-income countries. Clinical and population studies have addressed the spectrum of nutritional deficiencies and the multitude of infectious agents that can comprise this synergism. The papers to be included in the proposed book will examine these relationships at different scales and apply innovative analytical techniques to provide a better understanding of the causal pathways linking nutritional status and infectious disease. The first chapters will be concerned with how nutritional status either through diet or through nutritional interventions affects the gut microbiome and enteric infections among young children. The impact of children’s nutritional status on the immune response that underlies these relationships will also be addressed in these chapters. Causal associations between childhood stunting and specific enteric infections in the household environment will be examined in the next chapter using structural linear models. The association of soil-transmitted helminths and childhood malnutrition will then be explored at regional levels in Sub-Saharan Africa through spatial modeling techniques. These studies presented in these chapters will provide an overview and further understanding of the causal relationships between malnutrition and infectious diseases that can inform efforts to more systematically reduce childhood disease burden.

Dr. Kurt Long
Dr. Helen Powell
Dr. Johanna Sanchez
Guest Editors

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Keywords

micronutrient malnutrition
nutrition deficiencies
infection and infectious disease
children immunity
COVID-19
gut microbiome
diet intervention
epidemic

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Published Papers (7 papers)

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Research

16 pages, 888 KiB

Open AccessArticle

Identification of Enteric Pathogen Reservoirs and Transmission Pathways Associated with Short Childhood Stature in the Kolkata Indian Site of the Global Enteric Multicenter Study

by Kurt Z. Long, Inong R. Gunanti, Chris Stride, Johanna Sanchez, Dipika Sur, Byomkesh Manna, Thandavarayan Ramamurthy, Suman Kanungo, James P. Nataro, Helen Powell, Anna Roose, Dilruba Nasrin, Halvor Sommerfelt, Myron Levine and Karen Kotloff

Nutrients 2024, 16(16), 2733; https://doi.org/10.3390/nu16162733 - 16 Aug 2024

Cited by 1 | Viewed by 1053

Abstract

Age-stratified path analyses modeled associations between enteric pathogen reservoirs, transmission pathways and height-for-age z-scores (HAZ) to identify determinants of childhood growth in the Kolkata, India site of the Global Enteric Multicenter Study (GEMS). Models tested direct associations of potential pathogen reservoirs with HAZ at 60-day follow-up in separate moderate and severe diarrhea (MSD) case and control cohorts or indirectly when mediated by enteric infections. In the MSD cohort, rotavirus and typical EPEC (tEPEC) infections among children 0–11 months of age and ST-ETEC infections among children 12–23 months of age were associated with lower HAZ. Handwashing after defecating and before cooking reduced impaired growth through reductions in rotavirus and tEPEC infections. Water storage increased rotavirus and ST-ETEC infection risks, resulting in increased impaired growth, but was reduced with reported child feces disposal. The GII norovirus variant was inversely associated with HAZ among children 12–59 months of age in the control cohort. Reported handwashing before the handling of children reduced GII infections and impaired growth. Boiling water and the disposal of children’s feces mediated by stored water were positively associated with HAZ. The targeting of pathogen-specific reservoirs and transmission pathways may more effectively improve childhood linear growth in South Asian urban communities. Full article

(This article belongs to the Special Issue Micronutrient Malnutrition, Infection, and Immunity in Children)

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13 pages, 301 KiB

Open AccessArticle

Correlation of Cytokines with Parasitic Infections, Undernutrition and Micronutrient Deficiency among Schoolchildren in Rural Tanzania: A Cross-Sectional Study

by Emmanuel C. Mrimi, Marta S. Palmeirim, Elihaika G. Minja, Kurt Z. Long and Jennifer Keiser

Nutrients 2023, 15(8), 1916; https://doi.org/10.3390/nu15081916 - 15 Apr 2023

Cited by 4 | Viewed by 2381

Abstract

Malnutrition and parasitic infections are often interconnected in a vicious cycle. Malnutrition can lead to changes in immune response, which may affect cytokine concentrations and potentially increase susceptibility to infections. In turn, parasitic infections can exacerbate malnutrition by impairing nutrient absorption. This cross-sectional study aimed to explore this interplay. Schoolchildren aged 6–12 years living in rural Tanzania (n = 120) provided blood, stool and urine samples to determine the relationship between cytokine concentrations (interleukin 4 (IL-4), interferon gamma (IFNγ) and interleukin 17A (IL-17A)), parasitic infections, undernutrition and micronutrient deficiency adjusting for sex, age, inflammatory markers, socioeconomic status and school categories. All schoolchildren had a normal blood cell count. The concentration of IL-4 was significantly higher in schoolchildren diagnosed with stunting, Schistosoma mansoni infection, a high C-reactive protein concentration, nausea, poor housing and increasing age. The concentration of IFNγ was associated with Plasmodium falciparum and Entamoeba histolytica/Entamoeba dispar/Entamoeba moshkovskii infections, vitamin A deficiency, attending the most remote schools and low socioeconomic status. Our study confirms a potential relationship between cytokine concentrations and parasitic infections, malnutrition and low socioeconomic status. A better understanding of long-term effects of parasitic infections and malnutrition on the immune function could help in designing tailored and effective interventions. Full article

(This article belongs to the Special Issue Micronutrient Malnutrition, Infection, and Immunity in Children)

14 pages, 671 KiB

Open AccessArticle

Ready-to-Use Therapeutic Foods Fail to Improve Vitamin A and Iron Status Meaningfully during Treatment for Severe Acute Malnutrition in 6–59-Month-old Cambodian Children

by Sanne Sigh, Nanna Roos, Chamnan Chhoun, Arnaud Laillou and Frank T. Wieringa

Nutrients 2023, 15(4), 905; https://doi.org/10.3390/nu15040905 - 10 Feb 2023

Cited by 7 | Viewed by 3729

Abstract

Severe acute malnutrition (SAM) remains a global health concern. Studies on the impact of ready-to-use therapeutic foods (RUTFs) on micronutrient status during SAM treatment are almost nonexistent. The objective was to investigate the impact of RUTFs on the iron and vitamin A status of 6–59-month-old children receiving SAM treatment. Biomarkers of vitamin A status (retinol-binding protein, RBP), iron status (ferritin and soluble transferrin receptor, sTfR), and inflammation (C-reactive protein, CRP, and alpha-1 acid glycoprotein, AGP) were collected at admission and discharge (week 8) during an RUTF effectiveness trial. Vitamin A deficiency was defined as RBP <0.70 µmol/L, low body iron as body iron (BI) <0 mg/kg and deficient iron stores as ferritin <12 µg/L. Data were available for 110 and 75 children at admission and discharge, respectively. There was no significant difference in haemoglobin, ferritin, sTfR, BI or RBP concentrations between admission and discharge. At discharge, BI was 0.2 mg/kg lower, and there was a tendency towards a slightly lower RBP concentration, but the prevalence of vitamin A deficiency was low at admission and discharge (6% and 3%, respectively). The small impact of both RUTFs on improving vitamin A and iron status during SAM treatment calls for further research on the bioavailability of micronutrients to enhance the effectiveness of SAM treatment on micronutrient status. Full article

(This article belongs to the Special Issue Micronutrient Malnutrition, Infection, and Immunity in Children)

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14 pages, 7756 KiB

Open AccessArticle

The Role of Food Insecurity and Dietary Diversity on Recovery from Wasting among Hospitalized Children Aged 6–23 Months in Sub-Saharan Africa and South Asia

by Adino Tesfahun Tsegaye, Patricia B. Pavlinac, Lynnth Turyagyenda, Abdoulaye H. Diallo, Blaise S. Gnoumou, Roseline M. Bamouni, Wieger P. Voskuijl, Meta van den Heuvel, Emmie Mbale, Christina L. Lancioni, Ezekiel Mupere, John Mukisa, Christopher Lwanga, Michael Atuhairwe, Mohammod J. Chisti, Tahmeed Ahmed, Abu S.M.S.B. Shahid, Ali F. Saleem, Zaubina Kazi, Benson O. Singa, Pholona Amam, Mary Masheti, James A. Berkley, Judd L. Walson and Kirkby D. Tickell Show full author list Hide full author list

Nutrients 2022, 14(17), 3481; https://doi.org/10.3390/nu14173481 - 24 Aug 2022

Viewed by 2829

Abstract

Background: Current guidelines for the management of childhood wasting primarily focus on the provision of therapeutic foods and the treatment of medical complications. However, many children with wasting live in food-secure households, and multiple studies have demonstrated that the etiology of wasting is complex, including social, nutritional, and biological causes. We evaluated the contribution of household food insecurity, dietary diversity, and the consumption of specific food groups to the time to recovery from wasting after hospital discharge. Methods: We conducted a secondary analysis of the Childhood Acute Illness Network (CHAIN) cohort, a multicenter prospective study conducted in six low- or lower-middle-income countries. We included children aged 6–23 months with wasting (mid-upper arm circumference [MUAC] ≤ 12.5 cm) or kwashiorkor (bipedal edema) at the time of hospital discharge. The primary outcome was time to nutritional recovery, defined as a MUAC > 12.5 cm without edema. Using Cox proportional hazards models adjusted for age, sex, study site, HIV status, duration of hospitalization, enrollment MUAC, referral to a nutritional program, caregiver education, caregiver depression, the season of enrollment, residence, and household wealth status, we evaluated the role of reported food insecurity, dietary diversity, and specific food groups prior to hospitalization on time to recovery from wasting during the 6 months of posthospital discharge. Findings: Of 1286 included children, most participants (806, 63%) came from food-insecure households, including 170 (13%) with severe food insecurity, and 664 (52%) participants had insufficient dietary diversity. The median time to recovery was 96 days (18/100 child-months (95% CI: 17.0, 19.0)). Moderate (aHR 1.17 [0.96, 1.43]) and severe food insecurity (aHR 1.14 [0.88, 1.48]), and insufficient dietary diversity (aHR 1.07 [0.91, 1.25]) were not significantly associated with time to recovery. Children who had consumed legumes and nuts prior to diagnosis had a quicker recovery than those who did not (adjusted hazard ratio (aHR): 1.21 [1.01,1.44]). Consumption of dairy products (aHR 1.13 [0.96, 1.34], p = 0.14) and meat (aHR 1.11 [0.93, 1.33]), p = 0.23) were not statistically significantly associated with time to recovery. Consumption of fruits and vegetables (aHR 0.78 [0.65,0.94]) and breastfeeding (aHR 0.84 [0.71, 0.99]) before diagnosis were associated with longer time to recovery. Conclusion: Among wasted children discharged from hospital and managed in compliance with wasting guidelines, food insecurity and dietary diversity were not major determinants of recovery. Full article

(This article belongs to the Special Issue Micronutrient Malnutrition, Infection, and Immunity in Children)

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17 pages, 1443 KiB

Open AccessArticle

Hypothesis: Low Vitamin A and D Levels Worsen Clinical Outcomes When Children with Sickle Cell Disease Encounter Parvovirus B19

by Rhiannon R. Penkert, Melissa Azul, Robert E. Sealy, Bart G. Jones, Jola Dowdy, Randall T. Hayden, Li Tang, A. Catharine Ross, Jane S. Hankins and Julia L. Hurwitz

Nutrients 2022, 14(16), 3415; https://doi.org/10.3390/nu14163415 - 19 Aug 2022

Cited by 4 | Viewed by 2205

Abstract

Human parvovirus B19 causes life-threatening anemia due to transient red cell aplasia (TRCA) in individuals with sickle cell disease (SCD). Children with SCD experiencing profound anemia during TRCA often require red blood cell transfusions and hospitalization. The prevalence of vitamin deficiencies in SCD is high and deficiencies are associated with respiratory and pain symptoms, but the effects of vitamins on acute infection with parvovirus B19 remain unclear. We performed a clinical study in which 20 SCD patients hospitalized with parvovirus B19 infections (Day 0) were monitored over a 120-day time course to query relationships between vitamins A and D and clinical outcomes. There were significant negative correlations between Day 0 vitamin levels and disease consequences (e.g., red blood cell transfusion requirements, inflammatory cytokines). There were significant positive correlations (i) between Day 0 vitamins and peak virus-specific antibodies in nasal wash, and (ii) between Day 0 virus-specific serum plus nasal wash antibodies and absolute reticulocyte counts. There was a significant negative correlation between Day 0 virus-specific serum antibodies and virus loads. To explain the results, we propose circular and complex mechanisms. Low baseline vitamin levels may weaken virus-specific immune responses to permit virus amplification and reticulocyte loss; consequent damage may further reduce vitamin levels and virus-specific immunity. While the complex benefits of vitamins are not fully understood, we propose that maintenance of replete vitamin A and D levels in children with SCD will serve as prophylaxis against parvovirus B19-induced TRCA complications. Full article

(This article belongs to the Special Issue Micronutrient Malnutrition, Infection, and Immunity in Children)

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20 pages, 2212 KiB

Open AccessArticle

Putative Biomarkers of Environmental Enteric Disease Fail to Correlate in a Cross-Sectional Study in Two Study Sites in Sub-Saharan Africa

by Pascale Vonaesch, Munir Winkel, Nathalie Kapel, Alison Nestoret, Laurence Barbot-Trystram, Clément Pontoizeau, Robert Barouki, Maheninasy Rakotondrainipiana, Kaleb Kandou, Zo Andriamanantena, Lova Andrianonimiadana, Azimdine Habib, Andre Rodriguez-Pozo, Milena Hasan, Inès Vigan-Womas, Jean-Marc Collard, Jean-Chrysostome Gody, Serge Djorie, Philippe J. Sansonetti, Rindra Vatosoa Randremanana and on behalf of the Afribiota Investigators Show full author list Hide full author list

Nutrients 2022, 14(16), 3312; https://doi.org/10.3390/nu14163312 - 12 Aug 2022

Cited by 3 | Viewed by 2884

Abstract

Environmental enteric dysfunction (EED) is an elusive, inflammatory syndrome of the small intestine thought to be associated with enterocyte loss and gut leakiness and lead to stunted child growth. To date, the gold standard for diagnosis is small intestine biopsy followed by histology. Several putative biomarkers for EED have been proposed and are widely used in the field. Here, we assessed in a cross-sectional study of children aged 2–5 years for a large set of biomarkers including markers of protein exudation (duodenal and fecal alpha-1-antitrypsin (AAT)), inflammation (duodenal and fecal calprotectin, duodenal, fecal and blood immunoglobulins, blood cytokines, C-reactive protein (CRP)), gut permeability (endocab, lactulose-mannitol ratio), enterocyte mass (citrulline) and general nutritional status (branched-chain amino acids (BCAA), insulin-like growth factor) in a group of 804 children in two Sub-Saharan countries. We correlated these markers with each other and with anemia in stunted and non-stunted children. AAT and calprotectin, CRP and citrulline and citrulline and BCAA correlated with each other. Furthermore, BCAA, citrulline, ferritin, fecal calprotectin and CRP levels were correlated with hemoglobin levels. Our results show that while several of the biomarkers are associated with anemia, there is little correlation between the different biomarkers. Better biomarkers and a better definition of EED are thus urgently needed. Full article

(This article belongs to the Special Issue Micronutrient Malnutrition, Infection, and Immunity in Children)

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16 pages, 5775 KiB

Open AccessArticle

Alteration in Gut Microbiota Associated with Zinc Deficiency in School-Age Children

by Xiaohui Chen, Yu Jiang, Zhuo Wang, Youhai Chen, Shihua Tang, Shuyue Wang, Li Su, Xiaodan Huang, Danfeng Long, Liang Wang, Wei Guo and Ying Zhang

Nutrients 2022, 14(14), 2895; https://doi.org/10.3390/nu14142895 - 14 Jul 2022

Cited by 14 | Viewed by 4369

Abstract

Zinc deficiency could lead to a dynamic variation in gut microbial composition and function in animals. However, how zinc deficiency affects the gut microbiome in school-age children remains unclear. The purpose of this study was to profile the dynamic shifts in the gut microbiome of school-age children with zinc deficiency, and to determine whether such shifts are associated with dietary intake. A dietary survey, anthropometric measurements, and serum tests were performed on 177 school-age children, and 67 children were selected to explore the gut microbial community using amplicon sequencing. School-age children suffered from poor dietary diversity and insufficient food and nutrient intake, and 32% of them were zinc deficient. The inflammatory cytokines significantly increased in the zinc deficiency (ZD) group compared to that in the control (CK) group (p < 0.05). There was no difference in beta diversity, while the Shannon index was much higher in the ZD group (p < 0.05). At the genus level, Coprobacter, Acetivibrio, Paraprevotella, and Clostridium_XI were more abundant in the ZD group (p < 0.05). A functional predictive analysis showed that the metabolism of xenobiotics by cytochrome P450 was significantly depleted in the ZD group (p < 0.05). In conclusion, gut microbial diversity was affected by zinc deficiency with some specific bacteria highlighted in the ZD group, which may be used as biomarkers for further clinical diagnosis of zinc deficiency. Full article

(This article belongs to the Special Issue Micronutrient Malnutrition, Infection, and Immunity in Children)

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