Factors associated with nutrition intervention adherence: Evidence from a cluster-randomised controlled trial in Kenya.

Nutrition experts point to the importance of a multipronged approach to address high stunting rates in rural areas. This can include nutrition-specific and -sensitive interventions, such as the provision of micronutrient powder, eggs, and chlorine, and nutrition training to improve feeding practices. In 2018, an agricultural nongovernmental organisation initiated a multipronged approach as part of a randomised trial. However, adherence to a programme with so many components can be challenging for participants. The aim of this study is to understand which factors are associated with high adherence in complex multifaceted nutrition-sensitive agricultural programmes. We used a mixed method approach in which we used bivariate and multivariable analyses to estimate the relationship between child and caregiver demographic factors with product adherence. We analyzed data from six focus groups and 120 feedback sessions on barriers to product adherence. We found that the age and sex of the child did not influence product adherence, but caregivers were more likely to adhere to all products if they were not the child's biological mother (most often grandmothers) (0.28 higher adherence score; p < 0.001) and if caregivers were older (0.34 higher adherence score, p < 0.001). A higher monthly training attendance, combining product distribution and interactive training, predicted stronger product adherence. Participants noted that adherence was supported by the early demonstration of positive results, regular reminders, interactive trainings, and the encouragement of family members. These findings underscore the importance of combining product distribution with training and include potentially targeting grandmothers and other caregivers who may demonstrate higher product adherence.

Risk factors of stunting and wasting in Somali pre-school age children: results from the 2019 Somalia micronutrient survey.

BACKGROUND: Stunting and wasting in children less than 5 years of age are two key indicators of child malnutrition. Reducing their prevalence is a priority of the global public health community and for Somalia, a country suffering complex humanitarian emergencies such as drought, flooding, conflict and large-scale displacements. METHODS: Data from the nationally representative cross-sectional Somalia Micronutrient Survey (SMS 2019) on 1947 children were analyzed to assess the prevalence and potential risk factors of stunting and wasting. Bivariate and multivariable analyses were conducted separately for children 0-5 months and 6-59 months, and population attributable fractions were calculated using adjusted risk ratios produced by Poisson regression models. RESULTS: Among the 1947 children, the prevalence of stunting and wasting were 17.2% (95% CI: 15.0, 19.6) and 11.0% (95% CI: 9.3, 12.9), respectively. Among children 6-59 months of age, those residing in severely food insecure households had a higher risk of stunting (adjusted risk ratio [aRR] 1.47; CI: 1.12, 1.93) compared to those in food secure households. This risk of stunting was also higher in children with inflammation (aRR 1.75; CI: 1.35, 2.25) and iron deficiency (ID) (aRR 2.09; CI: 1.58, 2.80). For wasting, a dose-response relationship was found with household wealth, with the risk of wasting increasing significantly as the household wealth quintile decreased. On the other hand, the risk of wasting was lower in iron-deficient children (aRR 0.69; CI: 0.49, 0.98) than in iron-replete children. Among children 0-5 months of age no variables remained statistically significantly associated with stunting in the multivariable analysis. Wasting, however, was more common in children with recent diarrhea (aRR 3.51; CI: 1.68, 7.36). CONCLUSIONS: Nutritional status of children in Somalia may be improved by prevention of diarrhea and other infections and improvements in household food security.

Effect of parboiling conditions on zinc and iron retention in biofortified and non-biofortified milled rice.

BACKGROUND: Zinc-biofortified rice could contribute to zinc intake in deficient populations, but processing it into parboiled rice could affect this potential benefit. Zinc and iron true retention (TR) in milled rice produced under conditions resembling household and commercial parboiled methods was evaluated. Zinc and iron TR in milled rice obtained from biofortified and non-biofortified rice subjected to different soaking temperatures during parboiling was also evaluated. RESULTS: Conditions resembling commercial parboiling methods resulted in 52.2-59.7% zinc TR and 55.4-79.1% iron TR, whereas those used for household parboiling resulted in 70.7-79.6% zinc TR and 78.2-119.8% iron TR. Zinc TR in milled (8-16% bran removal) biofortified and non-biofortified parboiled rice was 50.6-66.8% when soaking rough rice at 20 °C and 29.9-56.0% when soaking rough rice at 65 °C; both had lower zinc TR than non-parboiled rice (58.0-80.6%). Iron TR was generally similar between milled non-parboiled and parboiled rice (26.2-67.6%) and between parboiled biofortified and non-biofortified milled rice. CONCLUSION: Parboiling conditions used to obtain milled rice targeted for own household consumption resulted in higher zinc and iron TR compared to parboiling conditions used for milled rice targeted for markets. More zinc from the inner endosperm moved towards the outer layers at high soaking temperature, resulting in lower zinc TR for milled parboiled rice soaked in hotter water. Parboiled rice soaked at temperatures used in households could provide more zinc to diets compared to rice soaked in hotter water commonly used in large rice mills, especially when rice is extensively milled. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Measurement of long-term iron absorption and loss during iron supplementation using a stable isotope of iron (57 Fe).

We report the first measurements of long-term iron absorption and loss during iron supplementation in African children using a stable isotope of iron (57 Fe). After uniform labelling of body iron with 57 Fe, iron absorption is proportional to the rate of decrease in the 57 Fe tracer concentration, while iron loss is proportional to the rate of decrease in the 57 Fe tracer amount. Anaemic Gambian toddlers were given 2 mg 57 Fe orally to equilibrate with total body iron over 8-11 months. After assignment to the positive control arm of the HIGH study, 22 toddlers consumed a micronutrient powder containing 12 mg iron for 12 weeks followed by 12 weeks without iron supplementation. Their daily iron absorption increased 3·8-fold during the iron supplementation period compared to the control period [median (interquartile range, IQR): 1·00 (0·82; 1·28) mg/day vs. 0·26 (0·22; 0·35) mg/day; P = 0·001]. Unexpectedly, during the supplementation period, daily iron loss also increased by 3·4-fold [0·75 (0·55; 0·87) mg/day vs. 0·22 (0·19; 0·29) mg/day; P = 0·005]. Consequently, most (~72%) of the absorbed iron was lost during supplementation. Long-term studies of iron absorption and loss are a promising and accurate method for assessing and quantifying long-term iron balance and may provide a reference method for evaluating iron intervention programs in vulnerable population groups. This study was registered as ISRCTN 0720906.

Risk factors for anaemia among Ghanaian women and children vary by population group and climate zone.

Anaemia has serious effects on human health and has multifactorial aetiologies. This study aimed to determine putative risk factors for anaemia in children 6-59 months and 15- to 49-year-old non-pregnant women living in Ghana. Data from a nationally representative cross-sectional survey were analysed for associations between anaemia and various anaemia risk factors. National and stratum-specific multivariable regressions were constructed separately for children and women to calculate the adjusted prevalence ratio (aPR) for anaemia of variables found to be statistically significantly associated with anaemia in bivariate analysis. Nationally, the aPR for anaemia was greater in children with iron deficiency (ID; aPR 2.20; 95% confidence interval [CI]: 1.88, 2.59), malaria parasitaemia (aPR 1.96; 95% CI: 1.65, 2.32), inflammation (aPR 1.26; 95% CI: 1.08, 1.46), vitamin A deficiency (VAD; aPR 1.38; 95% CI: 1.19, 1.60) and stunting (aPR 1.26; 95% CI: 1.09, 1.46). In women, ID (aPR 4.33; 95% CI: 3.42, 5.49), VAD (aPR 1.61; 95% CI: 1.24, 2.09) and inflammation (aPR 1.59; 95% CI: 1.20, 2.11) were associated with anaemia, whereas overweight and obese women had lower prevalence of anaemia (aPR 0.74; 95% CI: 0.56, 0.97). ID was associated with child anaemia in the Northern and Middle belts, but not in the Southern Belt; conversely, inflammation was associated with anaemia in both children and women in the Southern and Middle belts, but not in the Northern Belt. Anaemia control programmes should be region specific and aim at the prevention of ID, malaria and other drivers of inflammation as they are the main predictors of anaemia in Ghanaian children and women.

Iron Absorption from Iron-Biofortified Sweetpotato Is Higher Than Regular Sweetpotato in Malawian Women while Iron Absorption from Regular and Iron-Biofortified Potatoes Is High in Peruvian Women.

BACKGROUND: Sweetpotato and potato are fast-maturing staple crops and widely consumed in low- and middle-income countries. Conventional breeding to biofortify these crops with iron could improve iron intakes. To our knowledge, iron absorption from sweetpotato and potato has not been assessed. OBJECTIVE: The aim was to assess iron absorption from regular and iron-biofortified orange-fleshed sweetpotato in Malawi and yellow-fleshed potato and iron-biofortified purple-fleshed potato in Peru. METHODS: We conducted 2 randomized, multiple-meal studies in generally healthy, iron-depleted women of reproductive age. Malawian women (n = 24) received 400 g regular or biofortified sweetpotato test meals and Peruvian women (n = 35) received 500 g regular or biofortified potato test meals. Women consumed the meals at breakfast for 2 wk and were then crossed over to the other variety. We labeled the test meals with 57Fe or 58Fe and measured cumulative erythrocyte incorporation of the labels 14 d after completion of each test-meal sequence to calculate iron absorption. Iron absorption was compared by paired-sample t tests. RESULTS: The regular and biofortified orange-fleshed sweetpotato test meals contained 0.55 and 0.97 mg Fe/100 g. Geometric mean (95% CI) fractional iron absorption (FIA) was 5.82% (3.79%, 8.95%) and 6.02% (4.51%, 8.05%), respectively (P = 0.81), resulting in 1.9-fold higher total iron absorption (TIA) from biofortified sweetpotato (P < 0.001). The regular and biofortified potato test meals contained 0.33 and 0.69 mg Fe/100 g. FIA was 28.4% (23.5%, 34.2%) from the regular yellow-fleshed and 13.3% (10.6%, 16.6%) from the biofortified purple-fleshed potato meals, respectively (P < 0.001), resulting in no significant difference in TIA (P = 0.88). CONCLUSIONS: FIA from regular yellow-fleshed potato was remarkably high, at 28%. Iron absorbed from both potato test meals covered 33% of the daily absorbed iron requirement for women of reproductive age, while the biofortified orange-fleshed sweetpotato test meal covered 18% of this requirement. High polyphenol concentrations were likely the major inhibitors of iron absorption. These trials were registered at www.clinicaltrials.gov as NCT03840031 (Malawi) and NCT04216030 (Peru).

Zinc Absorption From Agronomically Biofortified Wheat Is Similar to Post-Harvest Fortified Wheat and Is a Substantial Source of Bioavailable Zinc in Humans.

BACKGROUND: Limited data exist on human zinc absorption from wheat biofortified via foliar (FBW) or root (hydroponically fortified wheat, HBW) zinc application. Stable isotope labels added at point of consumption (extrinsic labeling) might not reflect absorption from native zinc obtained by intrinsic labeling. OBJECTIVES: We measured fractional and total zinc absorption (FAZ, TAZ) in FBW and HBW wheat, compared with control wheat (CW) and fortified wheat (FW). The effect of labeling method was assessed in HBW (study 1), and the effect of milling extraction rate (EXR, 80% and 100%) in FBW (studies 2 and 3). METHODS: Generally healthy adults (n = 71, age: 18-45 y, body mass index: 18.5-25 kg/m2) were allocated to 1 of the studies, in which they served as their own controls. In study 1, men and women consumed wheat porridges colabeled intrinsically and extrinsically with 67Zn and 70Zn. In studies 2 and 3, women consumed wheat flatbreads (chapatis) labeled extrinsically. Zinc absorption was measured with the oral to intravenous tracer ratio method with a 4-wk wash-out period between meals. Data were analyzed with linear mixed models. RESULTS: In study 1 there were no differences in zinc absorption from extrinsic versus intrinsic labels in either FW or HBW. Similarly, FAZ and TAZ from FW and HBW did not differ. TAZ was 70-76% higher in FW and HBW compared with CW (P < 0.01). In studies 2 and 3, TAZ from FW and FBW did not differ but was 20-48% higher compared with CW (P < 0.001). Extraction rate had no effect on TAZ. CONCLUSIONS: Colabeling demonstrates that extrinsic zinc isotopic labels can be used to accurately quantify zinc absorption from wheat in humans. Biofortification through foliar zinc application, root zinc application, or fortification provides higher TAZ compared with unfortified wheat. In biofortified wheat, extraction rate (100-80%) has a limited impact on total zinc absorption. These studies were registered on clinicaltrials.gov (NCT01775319).

Enhancement of cytokine-driven NK cell IFN-γ production after vaccination of HCMV infected Africans.

Human cytomegalovirus (HCMV) infection drives the phenotypic and functional differentiation of NK cells, thereby influencing the responses of these cells after vaccination. NK cell functional differentiation is particularly advanced in African populations with universal exposure to HCMV. To investigate the impact of advanced differentiation on vaccine-induced responses, we studied NK-cell function before and after vaccination with Trivalent Influenza Vaccine (TIV) or diphtheria, tetanus, pertussis, inactivated poliovirus vaccine (DTPiP) in Africans with universal, lifelong HCMV exposure. In contrast to populations with lower prevalence of HCMV infection, no significant enhancement of NK-cell responses (IFN-γ, CD107a, CD25) occurred after in vitro re-stimulation of post-vaccination NK cells with TIV or DTPiP antigens compared to pre-vaccination baseline cells. However, both vaccinations resulted in higher frequencies of NK cells producing IFN-γ in response to exogenous IL-12 with IL-18, which persisted for up to 6 months. Enhanced cytokine responsiveness was restricted to less differentiated NK cells, with increased frequencies of IFN-γ+ cells observed within CD56bright CD57- , CD56dim CD57- NKG2C- and CD56dim CD57- NKG2C+ NK-cell subsets. These data suggest a common mechanism whereby different vaccines enhance NK cell IFN-γ function in HCMV infected donors and raise the potential for further exploitation of NK cell "pre-activation" to improve vaccine effectiveness.

Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia.

The prenatal environment can alter an individual's developmental trajectory with long-lasting effects on health. Animal models demonstrate that the impact of the early life environment extends to subsequent generations, but there is a paucity of data from human populations on intergenerational transmission of environmentally induced phenotypes. Here we investigated the association of parental exposure to energy and nutrient restriction in utero on their children's growth in rural Gambia. In a Gambian cohort with infants born between 1972 and 2011, we used multiple regression to test whether parental season of birth predicted offspring birth weight (n = 2097) or length (n = 1172), height-for-age z score (HAZ), weight-for-height z score (WHZ), and weight-for-age z score (WAZ) at 2 yr of age (n = 923). We found that maternal exposure to seasonal energy restriction in utero was associated with reduced offspring birth length (crude:-4.2 mm, P = 0.005; adjusted: -4.0 mm, P = 0.02). In contrast, paternal birth season predicted offspring HAZ at 24 mo (crude: -0.21, P = 0.005; adjusted: -0.22, P = 0.004) but had no discernible impact at birth. Our results indicate that periods of nutritional restriction in a parent's fetal life can have intergenerational consequences in human populations. Fetal growth appears to be under matriline influence, and postnatal growth appears to be under patriline intergenerational influences.-Eriksen, K. G., Radford, E. J., Silver, M. J., Fulford, A. J. C., Wegmüller, R., Prentice, A. M. Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia.

Serum Hepcidin Concentrations Decline during Pregnancy and May Identify Iron Deficiency: Analysis of a Longitudinal Pregnancy Cohort in The Gambia.

Background: Antenatal anemia is a risk factor for adverse maternal and fetal outcomes and is prevalent in sub-Saharan Africa. Less than half of antenatal anemia is considered responsive to iron; identifying women in need of iron may help target interventions. Iron absorption is governed by the iron-regulatory hormone hepcidin.Objective: We sought to characterize changes in hepcidin and its associations with indexes of iron stores, erythropoiesis, and inflammation at weeks 14, 20, and 30 of gestation and to assess hepcidin's diagnostic potential as an index of iron deficiency.Methods: We measured hemoglobin and serum hepcidin, ferritin, soluble transferrin receptor (sTfR), and C-reactive protein (CRP) at 14, 20, and 30 wk of gestation in a cohort of 395 Gambian women recruited to a randomized controlled trial. Associations with hepcidin were measured by using linear regression, and hepcidin's diagnostic test accuracy [area under the receiver operating characteristic curve (AUCROC), sensitivity, specificity, cutoffs] for iron deficiency at each time point was analyzed.Results: The prevalence of anemia increased from 34.6% at 14 wk of gestation to 50.0% at 20 wk. Hepcidin concentrations declined between study enrollment and 20 wk, whereas ferritin declined between 20 and 30 wk of gestation. The variations in hepcidin explained by ferritin, sTfR, and CRP declined over pregnancy. The AUCROC values for hepcidin to detect iron deficiency (defined as ferritin <15 µg/L) were 0.86, 0.83, and 0.84 at 14, 20, and 30 wk, respectively. Hepcidin was superior to hemoglobin and sTfR as an indicator of iron deficiency.Conclusions: In Gambian pregnant women, hepcidin appears to be a useful diagnostic test for iron deficiency and may enable the identification of cases for whom iron would be beneficial. Hepcidin suppression in the second trimester suggests a window for optimal timing for antenatal iron interventions. Hemoglobin does not effectively identify iron deficiency in pregnancy. This trial was registered at www.isrctn.com as ISRCTN49285450.

Coxiella burnetii (Q fever) prevalence in associated populations of humans and small ruminants in The Gambia.

OBJECTIVES: To simultaneously estimate the prevalence of antibodies against Coxiella burnetii (Q fever) among adults and small ruminants, and C. burnetii shedding prevalence among small ruminants in households in the Kiang West district of The Gambia, and to assess associated risk factors. METHODS: Sera of 599 adults and 615 small ruminants from 125 compounds within 12 villages were tested for antibodies against C. burnetii using ELISA. Vaginal swabs and milk samples of 155 small ruminants were tested using PCR to investigate shedding of C. burnetii. RESULTS: A total of 3.8-9.7% of adults, depending on ELISA test cut-off, and 24.9% of small ruminants in Kiang West were seropositive. Having at least one seropositive animal in one's compound was a risk factor for human seropositivity (OR: 3.35, 95% CI: 1.09-14.44). A grazing area within a village was a risk factor for seropositivity in small ruminants (OR: 2.07, 95% CI: 1.26-3.50); others were having lambed (OR: 2.75, 95% CI: 1.37-5.76) and older age of the animals (OR: 2.75, 95% CI: 1.37-5.76 for 1-3 years and OR 5.84, 95% CI: 3.10-11.64 for >3 years); 57.4% of sampled small ruminants were shedding C. burnetii. CONCLUSION: Coxiella burnetii infection is endemic among both humans and small ruminants in this area of The Gambia. Human and animal exposure to C. burnetii were related at compound level. Further research into the clinical relevance of C. burnetii infection in West Africa is needed.

Natural history of chronic HBV infection in West Africa: a longitudinal population-based study from The Gambia.

BACKGROUND: The natural history of chronic HBV infection in sub-Saharan Africa is unknown. Data are required to inform WHO guidelines that are currently based on studies in Europe and Asia. METHODS: Between 1974 and 2008, serosurveys were repeated in two Gambian villages, and an open cohort of treatment-naive chronic HBV carriers was recruited. Participants were followed to estimate the rates of hepatitis B e (HBeAg) and surface antigen (HBsAg) clearance and incidence of hepatocellular carcinoma (HCC). In 2012-2013, a comprehensive liver assessment was conducted to estimate the prevalence of severe liver disease. RESULTS: 405 chronic carriers (95% genotype E), recruited at a median age of 10.8 years, were followed for a median length of 28.4 years. Annually, 7.4% (95% CI 6.3% to 8.8%) cleared HBeAg and 1.0% (0.8% to 1.2%) cleared HBsAg. The incidence of HCC was 55.5/100 000 carrier-years (95% CI 24.9 to 123.5). In the 2012-2013 survey (n=301), 5.5% (95% CI 3.4% to 9.0%) had significant liver fibrosis. HBV genotype A (versus E), chronic aflatoxin B1 exposure and an HBsAg-positive mother, a proxy for mother-to-infant transmission, were risk factors for liver fibrosis. A small proportion (16.0%) of chronic carriers were infected via mother-to-infant transmission; however, this population represented a large proportion (63.0%) of the cases requiring antiviral therapy. CONCLUSIONS: The incidence of HCC among chronic HBV carriers in West Africa was higher than that in Europe but lower than rates in East Asia. High risk of severe liver disease among the few who are infected by their mothers underlines the importance of interrupting perinatal transmission in sub-Saharan Africa.

Zinc Absorption by Adults Is Similar from Intrinsically Labeled Zinc-Biofortified Rice and from Rice Fortified with Labeled Zinc Sulfate.

BACKGROUND: Biofortification of staple food crops is a promising strategy to combat zinc deficiency, and it is of particular interest for rice and crops that are not consumed as flours and therefore not suitable for postharvest fortification. Because zinc absorption is decreased by phytic acid (PA) and perhaps other dietary components, it is important to measure the absorption of zinc from a biofortified crop before determining its efficacy. OBJECTIVE: In this study, we compared the zinc absorption from zinc-biofortified rice (hydroponically enriched with (70)Zn) with that from a control rice of the same variety fortified with (70)ZnSO4 at point of use to reach the same total zinc content of 1.1 mg/meal. Both rice meals had a PA:Zn molar ratio of 12. METHODS: Fractional absorption of zinc (FAZ) was measured with the use of the double-isotope tracer ratio method in 16 apparently healthy adults [18-45 y old; BMI (in kg/m(2)) 19-25] who consumed 2 single meals at 4-wk intervals in random order in a crossover design. RESULTS: The FAZ from the biofortified rice (mean ± SD: 25.1 ± 8.7%) did not differ significantly from that of the point-of-use fortified rice (mean ± SD: 20.8 ± 7.1%) (P = 0.08). CONCLUSIONS: These results suggest that the native zinc accumulated in the biofortified rice was readily released from the rice matrix and that its absorption by adults was influenced by PA and other food components in a similar way to the inorganic zinc compound added to the rice at point of use. Moreover, rice biofortification is likely to be as good as postharvest zinc fortification as an intervention strategy to combat zinc deficiency. This trial was registered at clinicaltrials.gov as NCT01633450.

A double blind randomised controlled trial comparing standard dose of iron supplementation for pregnant women with two screen-and-treat approaches using hepcidin as a biomarker for ready and safe to receive iron.

BACKGROUND: Until recently, WHO recommended daily iron supplementation for all pregnant women (60 mg/d iron combined with 400ug/d folic acid) where anaemia rates exceeded 40 %. Recent studies indicate that this may pose a risk to pregnant women. Therefore, there is a need to explore screen-and-treat options to minimise iron exposure during pregnancy using an overall lower dosage of iron that would achieve equivalent results as being currently recommended by the WHO. However, there is a lack of agreement on how to best assess iron deficiency when infections are prevalent. Here, we test the use of hepcidin a peptide hormone and key regulator of iron metabolism, as a potential index for 'safe and ready to receive' iron. DESIGN/METHODS: This is a 3-arm randomised-controlled proof-of-concept trial. We will test the hypothesis that a screen-and-treat approach to iron supplementation using a pre-determined hepcidin cut-off value of <2.5 ng/ml will achieve similar efficacy in preventing iron deficiency and anaemia at a lower iron dose and hence will improve safety. A sample of 462 pregnant women in rural Gambia will be randomly assigned to receive: a) UNU/UNICEF/WHO international multiple micronutrient preparation (UNIMMAP) containing 60 mg/d iron (reference arm); b) UNIMMAP containing 60 mg/d iron but based on a weekly hepcidin screening indicating if iron can be given for the next 7 days or not; c) or UNIMMAP containing 30 mg/d iron as in (b) for 12 weeks in rural Gambia. The study will test if the screen-and-treat approach is non-inferior to the reference arm using the primary endpoint of haemoglobin levels at a non-inferiority margin of 0.5 g/dl. Secondary outcomes of adverse effects, compliance and the impact of iron supplementation on susceptibility to infections will also be assessed. DISCUSSION: This trial is expected to contribute towards minimising the exposure of pregnant women to iron that may not be needed and therefore potentially harmful. If the evidence in this study shows that the overall lower dosage of iron is non-inferior to 60 mg/day iron, this may help decrease side-effects, improve compliance and increase safety. The potential for the use of hepcidin for a simple point-of-care (PoC) diagnostic for when it is most safe and effective to give iron may improve maternal health outcomes. TRIAL REGISTRATION: ISRCTN21955180.

Efficacy and safety of hepcidin-based screen-and-treat approaches using two different doses versus a standard universal approach of iron supplementation in young children in rural Gambia: a double-blind randomised controlled trial.

BACKGROUND: Iron deficiency prevalence rates frequently exceed 50 % in young children in low-income countries. The World Health Organization (WHO) recommended universal supplementation of young children where anaemia rates are >40 %. However, large randomized trials have revealed that provision of iron to young children caused serious adverse effects because iron powerfully promotes microbial growth. Hepcidin - the master regulator of iron metabolism that integrates signals of infection and iron deficiency - offers the possibility of new solutions to diagnose and combat global iron deficiency. We aim to evaluate a hepcidin-screening-based iron supplementation intervention using hepcidin cut-offs designed to indicate that an individual requires iron, is safe to receive it and will absorb it. METHODS: The study is a proof-of-concept, three-arm, double blind, randomised controlled, prospective, parallel-group non-inferiority trial. Children will be randomised to receive, for a duration of 12 weeks, one of three multiple micronutrient powders (MNP) containing: A) 12 mg iron daily; B) 12 mg or 0 mg iron daily based on a weekly hepcidin screening indicating if iron can be given for the next seven days or not; C) 6 mg or 0 mg iron daily based on a weekly hepcidin screening indicating if iron can be given for the next seven days or not. The inclusion criteria are age 6-23 months, haemoglobin (Hb) concentration between 7 and 11 g/dL, z-scores for Height-for-Age, Weight-for-Age and Weight-for-Height > -3 SD and free of malaria. Hb concentration at 12 weeks will be used to test whether the screen-and-treat approaches are non-inferior to universal supplementation. Safety will be assessed using caregiver reports of infections, in vitro bacterial and P. falciparum growth assays and by determining the changes in the gut microbiota during the study period. DISCUSSION: A screen-and-treat approach using hepcidin has the potential to make iron administration safer in areas with widespread infections. If this proof-of-concept study shows promising results the development of a point-of-care diagnostic test will be the next step. TRIAL REGISTRATION: ISRCTN07210906 , 07/16/2014.

Salmonella Infections in The Gambia, 2005-2015.

BACKGROUND: There are large data gaps in the epidemiology of diseases caused by Salmonella enterica in West Africa. Regional surveillance of Salmonella infections is necessary, especially with the emergence and spread of multidrug-resistant clones. METHODS: Data on Salmonella isolated from various clinical specimens from patients from across The Gambia were collected and analyzed retrospectively from 2005 to April 2015. Antibiotic sensitivity testing of Salmonella isolates was performed by disk diffusion method. Serotyping and serogrouping of Salmonella isolates was performed using standard microbiology techniques. RESULTS: Two hundred three Salmonella isolates were isolated from 190 patients: 52% (106/203) from blood and 39% (79/203) from stool specimens. Salmonella was also isolated from urine, aspirates, cerebrospinal fluid, wounds, and abscesses. The prevalence of Salmonella in blood cultures was 0.8% (106/13,905). Of the serotyped salmonellae, 14% (21/152) were Salmonella enterica serovar Typhi, whereas 86% (131/152) were serovars other than Typhi (nontyphoidal Salmonella). Of the 102 typed NTS isolates, 40% (41) were Salmonella enterica serovar Typhimurium, 10% (10) were Salmonella enterica serovar Enteritidis, and 3% (3) were Salmonella enterica serovar Arizonae. Overall, 70% (142/203) of the salmonellae were pansusceptible. Multidrug resistance was found in 4% (9/203) of the isolates, 3 of which were Salmonella Enteritidis. CONCLUSIONS: Salmonellae are associated with a wide spectrum of invasive and noninvasive infections across all ages in The Gambia. There is evidence of multidrug resistance in salmonellae that warrants vigilant monitoring and surveillance.

The effect of iron-fortified complementary food and intermittent preventive treatment of malaria on anaemia in 12- to 36-month-old children: a cluster-randomised controlled trial.

BACKGROUND: Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children. METHODS: A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Côte d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed-effect models were used for the comparison of the five study groups, and a 2 × 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4). RESULTS: After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 × 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb <11.0 g/dl) was 82.1 %. After 9 months, IPT decreased the odds of anaemia (odds ratio [OR], 0.46 [95 % CI 0.23-0.91]; P = 0.023), whereas iron-fortified CF did not (OR, 0.85 [95 % CI 0.43-1.68]; P = 0.68), although ID (plasma ferritin <30 µg/l) was decreased markedly in children receiving iron fortified CF (OR, 0.19 [95 % CI 0.09-0.40]; P < 0.001). CONCLUSIONS: IPT alone only modestly decreased anaemia, but neither IPT nor iron fortified CF significantly improved Hb concentration after 9 months. Additionally, IPT did not augment the effect of the iron fortified CF. CF fortified with highly bioavailable iron improved iron status but not Hb concentration, despite three-monthly IPT of malaria. Thus, further research is necessary to develop effective combination strategies to prevent and treat anaemia in malaria endemic regions. TRIAL REGISTRATION: http://www.clinicaltrials.gov ; identifier NCT01634945; registered on July 3, 2012.

Zinc absorption by young adults from supplemental zinc citrate is comparable with that from zinc gluconate and higher than from zinc oxide.

The water-soluble zinc salts gluconate, sulfate, and acetate are commonly used as supplements in tablet or syrup form to prevent zinc deficiency and to treat diarrhea in children in combination with oral rehydration. Zinc citrate is an alternative compound with high zinc content, slightly soluble in water, which has better sensory properties in syrups but no absorption data in humans. We used the double-isotope tracer method with (67)Zn and (70)Zn to measure zinc absorption from zinc citrate given as supplements containing 10 mg of zinc to 15 healthy adults without food and compared absorption with that from zinc gluconate and zinc oxide (insoluble in water) using a randomized, double-masked, 3-way crossover design. Median (IQR) fractional absorption of zinc from zinc citrate was 61.3% (56.6-71.0) and was not different from that from zinc gluconate with 60.9% (50.6-71.7). Absorption from zinc oxide at 49.9% (40.9-57.7) was significantly lower than from both other supplements (P < 0.01). Three participants had little or no absorption from zinc oxide. We conclude that zinc citrate, given as a supplement without food, is as well absorbed by healthy adults as zinc gluconate and may thus be a useful alternative for preventing zinc deficiency and treating diarrhea. The more insoluble zinc oxide is less well absorbed when given as a supplement without food and may be minimally absorbed by some individuals. This trial was registered at clinicaltrials.gov as NCT01576627.

Influence of phytase, EDTA, and polyphenols on zinc absorption in adults from porridges fortified with zinc sulfate or zinc oxide.

Fortification of cereal staples with zinc is recommended to combat zinc deficiency. To optimize zinc absorption, strategies are needed to overcome the inhibitory effect of phytic acid (PA) and perhaps polyphenols. Five zinc absorption studies were conducted in young adults consuming maize or sorghum porridges fortified with 2 mg zinc as zinc sulfate (ZnSO4) or zinc oxide (ZnO) and containing combinations of PA or polyphenols as potential inhibitors and EDTA and phytase as potential enhancers. Fractional absorption of zinc (FAZ) was measured by using the double isotopic tracer ratio method. Adding phytase to the maize porridge immediately before consumption or using phytase for dephytinization during meal preparation both increased FAZ by >80% (both P < 0.001). Adding Na2EDTA at an EDTA:zinc molar ratio of 1:1 increased FAZ from maize porridge fortified with ZnSO4 by 30% (P = 0.01) but had no influence at higher EDTA ratios or on absorption from ZnO. FAZ was slightly higher from ZnSO4 than from ZnO (P = 0.02). Sorghum polyphenols had no effect on FAZ from dephytinized sorghum porridges but decreased FAZ by 20% from PA-rich sorghum porridges (P < 0.02). The combined inhibitory effect of polyphenols and PA was overcome by EDTA. In conclusion, ZnSO4 was better absorbed than ZnO, phytase used to degrade PA during digestion or during food preparation substantially increased zinc absorption from zinc-fortified cereals, EDTA at a 1:1 molar ratio modestly enhanced zinc absorption from ZnSO4-fortified cereals but not ZnO-fortified cereals, and sorghum polyphenols inhibited zinc absorption in the presence, but not absence, of PA. This trial was registered at clinicaltrials.gov as NCT01210794.

Triple-fortified rice containing vitamin A reduced marginal vitamin A deficiency and increased vitamin A liver stores in school-aged Thai children.

Vitamin A (VA)-fortified rice is a potential intervention strategy to prevent VA deficiency in at-risk populations. Hot-extruded, triple-fortified rice grains with added VA, zinc, and iron were produced by hot extrusion technology and their ability to improve VA status was tested in Thai schoolchildren. The fortification levels were 10 mg of iron, 9 mg of zinc, and 1.05 mg of VA/g extruded rice. A paired stable isotope dilution technique with labeled ¹³C2-retinyl acetate (¹³C-RID) was used to quantify VA pool size at the beginning and end of the feeding period. Fifty healthy schoolchildren with a serum retinol (SR) concentration of >0.7 µmol/L were randomly assigned to 2 groups to receive either triple-fortified rice (n = 25) or natural rice (n = 25) for 2 mo as part of the daily school meal. The fortified grains, mixed 1:50 with regular rice, were estimated to provide an extra 890 µg of VA/d, 5 d/wk. ¹³C2-retinyl acetate (1.0 µmol) was administered orally to each child before and at the end of the feeding period to estimate total body reserves (TBRs) of VA, which increased significantly (P < 0.05) in the intervention group from 153 ± 66 µmol retinol at baseline to 269 ± 148 µmol retinol after 2 mo of feeding. There was no change in the TBRs of VA in the control group (108 ± 67 vs. 124 ± 89 µmol retinol) (P = 0.22). Serum retinol remained unchanged in both groups. We conclude that VA-fortified, hot-extruded rice is an efficacious vehicle to provide additional VA to at-risk populations, and that the efficacy of VA-fortified foods can be usefully monitored by the ¹³C-RID measurement of TBRs of VA but not by changes in SR concentration.