Assessing an aflatoxin exposure biomarker: Exploring the interchangeability and correlation between venous and capillary blood samples.

Exposure to dietary aflatoxins has been recognized as a potential threat to child nutrition and growth, in addition to being a known carcinogen. The ability to accurately assess concentration of aflatoxin in the blood of at-risk individuals is therefore very important to inform public health policies and on-the-ground programs around the world. Venous blood is frequently used to quantify biomarkers of exposure such as AFB1-lysine adducts. However, venous blood collection methods are invasive, requiring highly trained staff, which makes this method challenging to implement, especially in resource-limited settings. In contrast, capillary blood collection by fingerprick is less invasive and has the potential for application in point-of-need monitoring. The aim of this exploratory study was to investigate the correlation and interchangeability of capillary and venous human blood samples in the quantification of AFB1-lysine adduct concentration. A total of 72 venous and capillary blood samples were collected from 36 women of reproductive age (16-49 years) in northern Uganda. All sample specimens were analyzed using high-performance liquid chromatography with fluorescence detection. Regression analysis and Bland-Altman analysis were performed to compare AFB1-lysine concentrations between venous and capillary sample pairs. Bland-Altman analysis of albumin-normalized AFB1-lysine data-bias was -0.023 pg/mg-albumin and the 95% limits of agreement were 0.51 to -0.56 pg/mg-albumin for log-transformed data. There was a positive correlation between albumin-normalized venous and capillary AFB1-lysine concentrations with r of 0.71 (p < .0001). A lack of any accepted clinical cutoff for aflatoxin exposure makes definition of an 'acceptable' limit for statistical analysis and comparison of methods challenging. Our data suggests a positive correlation between albumin-normalized AFB1-lysine concentrations in venous and capillary sample pairs, but relatively weak agreement and interchangeability based on Bland-Altman analysis.

The One Nutrition in Complex Environments (ONCE) study protocol: a cluster-randomized multi-level multi-sectoral intervention to improve nutrition in Uganda.

OBJECTIVE: To implement and measure the effects of a multi-level multi-sectoral social behavior change (SBC) intervention in Agago District of Northern Uganda and to determine the potential for scale-up. INTERVENTION: Compare the Nutrition Impact and Positive Practice (NIPP) approach to a NIPP+ approach. The NIPP approach involves nutrition education and SBC, whereas the NIPP+ adds agricultural inputs, training, and tools to support improved farm and water quality practices. The intervention effect will be measured through lower levels of aflatoxin in grain, lower water contamination, and improved knowledge on nutrition and health. DESIGN: This is a three-arm cluster-randomized controlled superiority trial (cRCT). The study arms include the following: group 1: NIPP; group 2: NIPP+, and group 3: control. Groups 1 and 2 will receive a 12-week intervention (NIPP or NIPP+) with active monitoring and longitudinal follow-up at 2, 6, and 12 months post-intervention. Additionally, an in-depth process and performance evaluation of each intervention arm will be undertaken using quantitative and qualitative methods. A total of 60 clusters from 5 subcounties of the Agago district will be randomly selected, and 15 households per cluster will be recruited using specific inclusion/exclusion criteria for a total of 900 households (300/arm). Respondents for the qualitative portion will be purposely selected. ANALYSIS: We will collect data from all participants at 3 time points: baseline, endline, and 12 months post-intervention. The analysis will utilize intent-to-treat (ITT) using the initial randomization of the treatment arms to determine the overall impact of having the NIPP vs. NIPP+ vs. control. Mixed effects models will be used to determine the role of time-variant and invariant individual household, and community characteristics, as well as measures of exposure and integration on key outcome indicators. A difference-in-difference analysis (baseline/endline, baseline/12 months post-intervention, endline/12 months post-intervention) will also be used to triangulate findings. TRIAL REGISTRATION: NCT04209569 . One Nutrition in Complex Environments (ONCE) Registered 24 December 2019.

Host Fecal mRNAs Predicted Environmental Enteric Dysfunction among Children with Moderate Acute Malnutrition in Sierra Leone.

Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM among children 6 to 59 months in Sierra Leone. EED was assessed at enrollment using the L:M test and 15 host fecal mRNA transcripts on 522 children. Recovery from MAM was defined as achieving mid-upper arm circumference ≥ 12.5 cm within 12 weeks of supplementation. Random forest classification models were used to examine prediction of presence and severity of EED by host fecal mRNA transcripts. Logistic regression was used to test for effect modification by L:M test variables including % lactulose excreted (%L). Eight host fecal mRNA transcripts (AQP9, REG3A, IFI30, DECR1, BIRC3, SELL, PIK3AP1, DEFA6) identified EED (%L ≥ 0.2) and severe EED (%L ≥ 0.45) with high sensitivity and specificity. The L:M test variables did not modify the effect of SNFs on recovery from MAM. In this study, we found host fecal mRNA transcripts that could be biomarkers of EED but did not find EED to modify the effect of SNFs on MAM treatment.

Effectiveness and cost-effectiveness of 4 supplementary foods for treating moderate acute malnutrition: results from a cluster-randomized intervention trial in Sierra Leone.

BACKGROUND: Moderate acute malnutrition (MAM) affects 33 million children annually. Investments in formulations of corn-soy blended flours and lipid-based nutrient supplements have effectively improved MAM recovery rates. Information costs and cost-effectiveness differences are still needed. OBJECTIVES: We assessed recovery and sustained recovery rates of MAM children receiving a supplementary food: ready-to-use supplementary food (RUSF), corn soy whey blend with fortified vegetable oil (CSWB w/oil), or Super Cereal Plus with amylase (SC + A) compared to Corn Soy Blend Plus with fortified vegetable oil (CSB+ w/oil). We also estimated differences in costs and cost effectiveness of each supplement. METHODS: In Sierra Leone, we randomly assigned 29 health centers to provide a supplement containing 550 kcal/d for ∼12 wk to 2691 children with MAM aged 6-59 mo. We calculated cost per enrollee, cost per child who recovered, and cost per child who sustained recovery each from 2 perspectives: program perspective and caregiver perspective, combined. RESULTS: Of 2653 MAM children (98.6%) with complete data, 1676 children (63%) recovered. There were no significant differences in the odds of recovery compared to CSB+ w/oil [0.83 (95% CI: 0.64-1.08) for CSWB w/oil, 1.01 (95% CI: 0.78-1.3) for SC + A, 1.05 (95% CI: 0.82-1.34) for RUSF]. The odds of sustaining recovery were significantly lower for RUSF (0.7; 95% CI 0.49-0.99) but not CSWB w/oil or SC + A [1.08 (95% CI: 0.73-1.6) and 0.96 (95% CI: 0.67-1.4), respectively] when compared to CSB+ w/oil. Costs per enrollee [US dollars (USD)/child] ranged from $105/child in RUSF to $112/child in SC + A and costs per recovered child (USD/child) ranged from $163/child in RUSF to $179/child in CSWB w/oil, with overlapping uncertainty ranges. Costs were highest per sustained recovery (USD/child), ranging from $214/child with the CSB+ w/oil to $226/child with the SC + A, with overlapping uncertainty ranges. CONCLUSIONS: The 4 supplements performed similarly across recovery (but not sustained recovery) and costed measures. Analyses of posttreatment outcomes are necessary to estimate the full cost of MAM treatment. This trial was registered at clinicaltrials.gov as NCT03146897.