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    Christine Clewes

    The ability of breast-feeding infants to utilize lactose, the major carbohydrate in breast-milk, is dependent on the presence of the enzyme lactase (E.C.3.2.1.108). Lactase is located in the brush border of the small intestine and because... more
    The ability of breast-feeding infants to utilize lactose, the major carbohydrate in breast-milk, is dependent on the presence of the enzyme lactase (E.C.3.2.1.108). Lactase is located in the brush border of the small intestine and because of its exposed position it is extremely vulnerable to pathogenic damage. Breast-fed Gambian infants have poor growth associated with intestinal damage beyond 3-4 months. The aim of this study was to assess the ability of Gambian infants aged 2-15 months (N = 113) to digest lactose and to see how this varied with age, intestinal permeability, and growth performance. Lactose maldigestion was estimated by monthly measurements of urinary lactose and lactulose following an oral dose of the latter. Both urinary lactose excretion and lactulose maldigestion increased with age (p < 0.0001 ANOVA). Up to 6 months the mean urinary lactose: lactulose excretion ratio was within the quoted normal range (< 0.4). Beyond this age, mean values were hypolactasic. Lactose maldigestion was related to poor growth in both weight and length (r = -0.04, p < 0.0001, after age correction). Although a major part of this relationship was a reflection of the previously reported correlation between intestinal permeability and growth, more than 30% of the association was in addition to the permeability effect. Possible explanations are discussed. Moderate-to-severe hypolactasia does occur in breast-fed Gambian infants and is related to poorer-than-expected growth. However, this does not mean that breast milk intake should be reduced as the nutritional and immunological benefits of breast milk continue to outweigh any disadvantages.
    We report an apparently protective effect of vitamin A in infants who received iron supplements (15 mg/d) for 3 mo. Those receiving iron showed increases in hemoglobin (8 g/L), ferritin (3.7 j.ag/L), and the acute-phase protein... more
    We report an apparently protective effect of vitamin A in infants who received iron supplements (15 mg/d) for 3 mo. Those receiving iron showed increases in hemoglobin (8 g/L), ferritin (3.7 j.ag/L), and the acute-phase protein cr1-antichy-motrypsin (ACT; 0.06 g/L). In both the placebo and iron-supple-mented groups there were increases in plasma retinol, lutein, a-tocopherol, immunoglobulin A, and imniunoglobulin G. The improvement in vitamin A status could only have been from a seasonal increase in dietary sources of vitamin A, eg, breast milk and early weaning foods, and there were no obvious effects on iron utilization (hemoglobin concentrations). However, in the infants receiving iron, those whose retinol concentrations increased also showed reductions in ACT, ferritin, immunoglobulin A, and im-munoglobulin M. Vitamin A is well known for its antiinfective properties and we suggest that these observations illustrate the importance of even small increases in dietary vitamin A or d...
    L'invention concerne un bandeau collecteur d'urine destine a collecter des echantillons d'urine, notamment dans le cas des patients incapables de fournir des echantillons a ecoulement libre. Le dispositif peut incorporer des... more
    L'invention concerne un bandeau collecteur d'urine destine a collecter des echantillons d'urine, notamment dans le cas des patients incapables de fournir des echantillons a ecoulement libre. Le dispositif peut incorporer des reactifs de test, de maniere a ce que l'on puisse effectuer des tests in situ. Les reactifs peuvent etre separes de l'urine pour permettre des tests a retardement. L'invention concerne aussi un test de lactose a base d'urine servant d'indicateur d'une perturbation de l'integrite des intestins.
    Many nutrient biomarkers are altered by inflammation. We calculated adjustment factors for retinol and ferritin by using meta-analyses of studies containing the respective biomarker and 2 acute phase proteins in serum, C-reactive protein... more
    Many nutrient biomarkers are altered by inflammation. We calculated adjustment factors for retinol and ferritin by using meta-analyses of studies containing the respective biomarker and 2 acute phase proteins in serum, C-reactive protein (CRP), and a1-acid glycoprotein (AGP). With the use of CRP and AGP we identified 4 groups in each study: reference (CRP #5 mg/L, AGP#1 g/L), incubation (CRP>5 mg/L, AGP#1 g/L), early convalescence (CRP>5 mg/L, AGP>1 g/L), and late convalescence (CRP #5 mg/L, AGP>1 g/L). For each biomarker, ratios of the geometric means of the reference to each inflammation group concentration were used to calculate adjustment factors for retinol (1.13, 1.24, and 1.11) and ferritin (0.77, 0.53, and 0.75) for the incubation, early, and late convalescent groups, respectively. The application of the meta-analysis factors in more recent studies compareswell with study-specific factors. The samemethodwas used to calculate adjustment factors for soluble transfe...
    Studies in the Gambia, using the lactulose–mannitol dual-sugar intestinal permeability test (lactulose:mannitol ratio) as a non-invasive way of investigating mucosal damage, have shown that food malabsorption is significantly associated... more
    Studies in the Gambia, using the lactulose–mannitol dual-sugar intestinal permeability test (lactulose:mannitol ratio) as a non-invasive way of investigating mucosal damage, have shown that food malabsorption is significantly associated with early growth retardation. In this cross-sectional study, 210 poor urban Nepali children, 0–60 months old, were recruited and measured for height or length and weight, 167 were examined for intestinal permeability and 173 for parasite infection. Weaning and morbidity data were collected from 172 caretakers. Children were mildly stunted (mean height-for-age z-score 21·45) and underweight (mean weight-for-age z-score 21·62). The lactulose:mannitol ratio (0·26) was poorer than that of UK children (0·12), but similar to that found in Bengali children of the same age (0·24). Two stages of weaning, the onset supplementary feeding (6 months) and the cessation of breast-feeding (23 months), were shown to have differential impact. In children currently br...
    Transferrin receptor (TfR) is a biomarker for iron reported to be less affected by inflammation compared to ferritin. We examined the associations between two acute phase proteins (APP), α-1-acid glycoprotein (AGP) and C-reactive protein... more
    Transferrin receptor (TfR) is a biomarker for iron reported to be less affected by inflammation compared to ferritin. We examined the associations between two acute phase proteins (APP), α-1-acid glycoprotein (AGP) and C-reactive protein (CRP), with TfR. A multi-national database of 8,410 non-pregnant women aged 15-49 y from 6 countries (USA, Laos, Ivory Coast, Cameroon and Papua New Guinea) as part of the Biomarkers Reflecting Inflammation and Nutrition Determinants of Anemia (BRINDA) project was analyzed. Elevated TfR was defined as >8.3 mg/L, elevated CRP >5 mg/L, and elevated AGP >1 g/L. Prevalence of elevated TfR was 20.0%, ranging from 5.7% in Laos to 33.8% in Cameroon. Correlations between APP and TfR ranged from 0.01 – 0.27. Based on preliminary analyses, women with elevated AGP had a higher prevalence of elevated TfR [overall prevalence odds ratio (POR) 2.0 (95%CI: 1.6–2.5), with the strongest association in Laos where the POR was 3.1(1.5–6.7). Elevated CRP was not...
    Smoking is associated with oxidative stress and increased risks of many chronic diseases that both shorten life and impair its quality. Low concentrations of several micronutrients, especially the antioxidants vitamin C and β-carotene,... more
    Smoking is associated with oxidative stress and increased risks of many chronic diseases that both shorten life and impair its quality. Low concentrations of several micronutrients, especially the antioxidants vitamin C and β-carotene, are also associated with smoking, and there has been much interest in determining whether deficiencies in micronutrients are involved etiologically in smoking-related diseases. The objective of this review was to bring together reports on dietary intakes, biochemical indicators of micronutrient status, and results of some intervention studies on micronutrients where authors had compared outcomes in smokers and non-smokers. The micronutrients discussed are vitamins A, E, and C; the carotenoids; some of the B-vitamin group; and the minerals selenium, zinc, copper, and iron. The data were then examined to determine whether effects on the biochemical markers of micronutrient status were due to differences in dietary intakes between smokers and non-smokers...
    The accurate estimation of the prevalence of vitamin A deficiency (VAD) is important in planning and implementing interventions. Retinol-binding protein (RBP) is often used in population surveys to measure vitamin A status, but its... more
    The accurate estimation of the prevalence of vitamin A deficiency (VAD) is important in planning and implementing interventions. Retinol-binding protein (RBP) is often used in population surveys to measure vitamin A status, but its interpretation is challenging in settings where inflammation is common because RBP concentrations decrease during the acute-phase response.We aimed to assess the relation between RBP concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and to investigate adjustment algorithms to account for these effects.Cross-sectional data from 8 surveys for PSC (= 8803) and 4 surveys for WRA (= 4191) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to adjust RBP concentrations in PSC in inflammation and malaria settings...
    Iron deficiency is thought to be one of the most prevalent micronutrient deficiencies globally, but an accurate assessment in populations who are frequently exposed to infections is impeded by the inflammatory response, which causes... more
    Iron deficiency is thought to be one of the most prevalent micronutrient deficiencies globally, but an accurate assessment in populations who are frequently exposed to infections is impeded by the inflammatory response, which causes iron-biomarker alterations.We assessed the relation between soluble transferrin receptor (sTfR) concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and investigated adjustment algorithms to account for these effects.Cross-sectional data from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project from 11,913 PSC in 11 surveys and from 11,173 WRA in 7 surveys were analyzed individually and combined with the use of a meta-analysis. The following 3 adjustment approaches were compared with estimated iron-deficient erythropoiesis (sTfR concentration >8.3 mg/L):) the exclusion of individuals with C-reactive protein (CR...
    Background: In many settings, populations experience recurrent exposure to inflammatory agents that catalyze fluctuations in the concentrations of acute-phase proteins and certain micronutrient biomarkers such as C-reactive protein (CRP),... more
    Background: In many settings, populations experience recurrent exposure to inflammatory agents that catalyze fluctuations in the concentrations of acute-phase proteins and certain micronutrient biomarkers such as C-reactive protein (CRP), α-1-acid glycoprotein (AGP), ferritin, and retinol. Few data are available on the prevalence and predictors of inflammation in diverse settings.Objective: We aimed to assess the relation between inflammation (CRP concentration >5 mg/L or AGP concentration >1 g/L) and covariates, such as demographics, reported illness, and anthropometric status, in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y).Design: Cross-sectional data from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project from 29,765 PSC in 16 surveys and 25,731 WRA in 10 surveys were used to model bivariable and multivariable relations.Results: The inflammation prevalence was 6.0-40.2% in...
    The accurate estimation of vitamin A deficiency (VAD) is critical to informing programmatic and policy decisions that could have important public health implications. However, serum retinol and retinol binding protein (RBP)... more
    The accurate estimation of vitamin A deficiency (VAD) is critical to informing programmatic and policy decisions that could have important public health implications. However, serum retinol and retinol binding protein (RBP) concentrations, two biomarkers often used to estimate VAD, are temporarily altered during the acute phase response, potentially overestimating the prevalence of VAD in populations with high levels of inflammation. In 22 nationally-representative surveys, we examined (1) the association between C-reactive protein (CRP) or α1-acid glycoprotein (AGP) and retinol or RBP, and (2) how different adjustment approaches for correcting for inflammation compare with one another. In preschool age children (PSC) and school age children (SAC), the association between inflammation and retinol and RBP was largely statistically significant; using the regression approach, adjustments for inflammation decreased the estimated prevalence of VAD compared to unadjusted VAD (range: -22.1...
    Background: The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection... more
    Background: The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection and inflammation.Objective: We assessed the relation between ferritin concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and investigated adjustment algorithms to account for these effects.Design: Cross-sectional data from 15 surveys for PSC (n = 27,865) and 8 surveys for WRA (24,844), from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to estimate depleted iron stores (ferritin concentration <12 μg/L in PSC and <15 μg/L in WRA) in inflammation and malaria settings as follows: 1) increase fe...
    This paper discusses various ways in which diarrhoea may be prevented from occurring in children living in developing countries, where it is still a major cause of morbidity and mortality. Possible strategies include promotion of... more
    This paper discusses various ways in which diarrhoea may be prevented from occurring in children living in developing countries, where it is still a major cause of morbidity and mortality. Possible strategies include promotion of breastfeeding, dietary supplementation with vitamin A, zinc and iron, the prevention of protein-energy malnutrition as far as possible, and improvement in the standard of preparation and hygiene of available weaning foods, involving in particular the wider use of fermented foods.
    ABSTRACT
    ABSTRACT
    ABSTRACT
    We report an apparently protective effect of vitamin A in infants who received iron supplements (15 mg/d) for 3 mo. Those receiving iron showed increases in hemoglobin (8 g/L), ferritin (3.7 micrograms/L), and the acute-phase protein... more
    We report an apparently protective effect of vitamin A in infants who received iron supplements (15 mg/d) for 3 mo. Those receiving iron showed increases in hemoglobin (8 g/L), ferritin (3.7 micrograms/L), and the acute-phase protein alpha 1-antichymotrypsin (ACT; 0.06 g/L). In both the placebo and iron-supplemented groups there were increases in plasma retinol, lutein, alpha-tocopherol, immunoglobulin A, and immunoglobulin G. The improvement in vitamin A status could only have been from a seasonal increase in dietary sources of vitamin A, eg, breast milk and early weaning foods, and there were no obvious effects on iron utilization (hemoglobin concentrations). However, in the infants receiving iron, those whose retinol concentrations increased also showed reductions in ACT, ferritin, immunoglobulin A, and immunoglobulin M. Vitamin A is well known for its antiinfective properties and we suggest that these observations illustrate the importance of even small increases in dietary vita...
    Many nutrient biomarkers are altered by inflammation. We calculated adjustment factors for retinol and ferritin by using meta-analyses of studies containing the respective biomarker and 2 acute phase proteins in serum, C-reactive protein... more
    Many nutrient biomarkers are altered by inflammation. We calculated adjustment factors for retinol and ferritin by using meta-analyses of studies containing the respective biomarker and 2 acute phase proteins in serum, C-reactive protein (CRP), and α1-acid glycoprotein (AGP). With the use of CRP and AGP we identified 4 groups in each study: reference (CRP ≤5 mg/L, AGP ≤1 g/L), incubation (CRP >5 mg/L, AGP ≤1 g/L), early convalescence (CRP >5 mg/L, AGP >1 g/L), and late convalescence (CRP ≤5 mg/L, AGP >1 g/L). For each biomarker, ratios of the geometric means of the reference to each inflammation group concentration were used to calculate adjustment factors for retinol (1.13, 1.24, and 1.11) and ferritin (0.77, 0.53, and 0.75) for the incubation, early, and late convalescent groups, respectively. The application of the meta-analysis factors in more recent studies compares well with study-specific factors. The same method was used to calculate adjustment factors for solubl...
    The effect of helminth infestation on the nutrition, growth, and physiology of the host is still poorly understood. Anthelmintic treatment of children in developing countries has had varying success in terms of growth improvements. The... more
    The effect of helminth infestation on the nutrition, growth, and physiology of the host is still poorly understood. Anthelmintic treatment of children in developing countries has had varying success in terms of growth improvements. The objective of this study was to assess the effect of regular deworming on child growth, physiology, and biochemical status. The study was a 12-mo longitudinal intervention in 123 Bangladeshi children aged 2-5 y. Treatment (mebendazole) or placebo tablets were administered every 2 mo for 8 mo and again at 12 mo. Weight, height, midupper arm circumference, intestinal permeability, plasma albumin, alpha(1)-antichymotrypsin, and total protein concentration were assessed every 2 mo. Treatment with mebendazole reduced the prevalence of Ascaris lumbricoides from 78% to 8%, of Trichuris trichiura from 65% to 9%, and of hookworm from 4% to 0%. There was no significant difference in the growth of treated children compared with those given placebo tablets. No cha...
    In a longitudinal study of child growth and nutritional status in Bangladesh, child morbidity was recorded using health interviews with the mother. The aim of the present study was to establish whether maternal reports of child illness... more
    In a longitudinal study of child growth and nutritional status in Bangladesh, child morbidity was recorded using health interviews with the mother. The aim of the present study was to establish whether maternal reports of child illness were associated with the biochemical health status of the child. Children aged 2-5 years (n 117) took part in the study and their mothers were interviewed every fortnight by Bangladeshi fieldworkers. Maternal reports of diarrhoea were associated with significantly lower plasma albumin concentrations (P < 0.001), poorer intestinal permeability (P < 0.001), higher plasma immunoglobulin A levels (P < 0.005) and higher alpha-1-antichymotrypsin (ACT) levels (P < 0.05) compared with children reported to be healthy. Children with fever had significantly higher ACT (P < 0.001) and lower albumin (P < 0.05) levels compared with their healthy counterparts. Respiratory infections (RI) were not associated with any significant changes; however, re...
    There is controversy over whether children in developing countries can catch up on their growth rates after bouts of diarrhoea. A factor influencing catch-up growth is the extent and duration of mucosal injury. To explore the relation... more
    There is controversy over whether children in developing countries can catch up on their growth rates after bouts of diarrhoea. A factor influencing catch-up growth is the extent and duration of mucosal injury. To explore the relation between intestinal disease and growth performance, a non-invasive test of intestinal integrity, the lactulose:mannitol permeability test, was done regularly on children aged 2-15 months, whose growth was monitored over a mean of 7.5 months. The study revealed persistent abnormalities in the small bowel mucosa of 2-15 month old Gambian infants and a negative correlation between these abnormalities and growth. Up to 43% of observed growth faltering can be explained on the basis of these long-term intestinal lesions.
    Fortification of staple foods has been repeatedly recommended as an effective approach to reduce micronutrient deficiencies. With the increased number of fortification projects globally, there is a need to share practical lessons learned... more
    Fortification of staple foods has been repeatedly recommended as an effective approach to reduce micronutrient deficiencies. With the increased number of fortification projects globally, there is a need to share practical lessons learned relating to their implementation and responses to project-related and external challenges. To document the achievements, challenges, lessons learned, and management responses associated with national fortification projects in Morocco, Uzbekistan, and Vietnam. Independent end-of-project evaluations conducted for each project served as the primary data source and contain the history of and project activities undertaken for, each fortification project. Other sources, including national policy documents, project reports from the Global Alliance for Improved Nutrition (GAIN) and other stakeholders, industry assessments, and peer-reviewed articles, were used to document the current responses to challenges and future project plans. All projects had key ach...
    Gut integrity, which can be measured by the urinary lactulose:mannitol excretion test, deteriorates with the introduction of weaning foods. In The Gambia, gut integrity measured monthly over 15 months in 119 infants (aged 2-15 months) was... more
    Gut integrity, which can be measured by the urinary lactulose:mannitol excretion test, deteriorates with the introduction of weaning foods. In The Gambia, gut integrity measured monthly over 15 months in 119 infants (aged 2-15 months) was least impaired from April to June. This coincides with the time of year of maximum vitamin A (VA) intake-the mango season. Subsequently, two VA intervention studies were done in infants in India. Eighty infants attending a community health center received 16,700 IU weekly or placebo. In another study, 94 hospitalized infants were given 200, 000 IU VA or placebo: 31 received VA on admission, while the rest (32 VA, 31 placebo) received treatment on discharge. All VA-treated groups had more rapid improvement in gut integrity than the placebo groups, but no group had gut integrity normalized by Western standards. The data suggest that VA status may influence gut integrity.

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