An Alternative Oat-Containing, Ready-To-Use, Therapeutic Food Does Not Alter Intestinal Permeability or the 16S Ribosomal RNA Fecal Microbiome Configuration Among Children With Severe Malnutrition in Sierra Leone: A Randomized Controlled Trial.

BACKGROUND: Previously, a novel oat ready-to-use therapeutic food (o-RUTF) resulted in improved recovery from severe acute malnutrition (SAM) when compared to a standard RUTF (s-RUTF). The o-RUTF contained 18% oat, while the s-RUTF has no cereal ingredients. OBJECTIVES: We determined the effects of o-RUTF on intestinal permeability, as measured by lactulose permeability, and the 16S ribosomal RNA (rRNA) fecal microbiome configuration of children with SAM. METHODS: This was a prospective, randomized, double-blinded, controlled clinical trial. Sierra Leonean children aged 6-59 mo with SAM, defined by a midupper arm circumference < 11.5 cm, were randomized to receive o-RUTF or s-RUTF. All children received 7 d of amoxicillin per guidelines. Lactulose permeability testing and fecal 16S rRNA sequencing were performed at baseline and after 4 wk of therapy. The change in lactulose permeability was the primary outcome, while the fecal 16S rRNA configuration at 4 wk was a secondary outcome. RESULTS: Of the 129 children enrolled, lactulose permeability testing was completed by 100 at baseline and 82 at week 4. After 4 wk of therapeutic feeding, there were no differences in lactulose permeability between the o-RUTF and s-RUTF groups (P = 0.84), and over half of children had increased lactulose permeability (50% s-RUTF compared with 58% o-RUTF, mean difference = -7.5%; 95% CI: -29.2, 15.2; P = 0.50). After 4 wk of feeding, there were no differences in the 16S rRNA configurations between the o-RUTF and s-RUTF groups (Permanova, 999 permutations; P = 0.648; pseudo-F = 0.581), nor were there differences in α or ß diversity. CONCLUSIONS: Despite remarkably different compositions of o-RUTF and s-RUTF, no differences were identified in lactulose permeability or the fecal 16S rRNA configuration among children with SAM receiving these foods. These results suggest that the o-RUTF exerts its beneficial effects through mechanisms other than reducing intestinal permeability or altering the fecal 16S configuration. This trial was registered at clinicaltrials.gov as NCT04334538.

The impact on key indicators of reproductive and child health after changes in program modalities in Sierra Leone, 2019.

BACKGROUND AND AIMS: In 2018, the transition to routine vitamin A supplementation (VAS) was integrated with caregivers' preparation of nutritious complementary food from local produce and confidential counseling and provision of modern contraceptives. In 2019, funding for complementary food ceased and Community Health Workers (CHWs) were trained to track defaulters, while national efforts to improve Health Management Information Systems, supply chains and reduce teenage pregnancies were intensified. We report on key indicators after these changes and in comparison, to those previously published. METHODS: The same Lot Quality Assurance Sampling methodology was used in both assessments: 19 villages were randomly selected in each of five lots in each of three districts then caregivers of children 6-59 months age randomly selected and interviewed. RESULTS: Coverage of VAS, Albendazole, and Pentavalent 3 before and after these changes was over 80%, 75%, and 80% respectively, equitable by sex, age, caregiver's religion, and educational status. Comparison with 2018 found more lots failed to reach 80% VAS by verbal affirmation (10 vs 2), and coverage in one district (Bo) had dropped (77.5% vs 92.3%). Fewer caregivers were aware that VAS should be taken every 6 months (27% vs 50%), that complementary feeding should start at 6 months (63% vs 77%) or were providing minimal dietary diversity (27% vs 45%). There was an increase in caregivers using modern contraception (45% vs 35%), obtaining information about contraception from a friend (14% vs 9%), while fewer thought country rope/herbs (traditional contraceptives) were "effective" (11% vs 21%) and stockouts of contraceptives at health facilities had dropped (24% vs 55%). Stipends for CHWs cost approximately $750 K vs complementary food: $112 K. CONCLUSION: Overall coverage for VAS, Albendazole, and Pentavalent remained effective but VAS had dropped significantly in one district. Complementary feeding practices had declined. Awareness, uptake, and contraceptives supply chains had improved.

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.

Treating high-risk moderate acute malnutrition using therapeutic food compared with nutrition counseling (Hi-MAM Study): a cluster-randomized controlled trial.

BACKGROUND: There is a lack of consensus on what is the most appropriate treatment of moderate acute malnutrition (MAM). OBJECTIVES: We aimed to determine if provision of ready-to-use-therapeutic food (RUTF) and antibiotics to "high-risk" MAM (HR-MAM) children in addition to nutritional counseling would result in higher recovery and less deterioration than nutrition counseling alone. METHODS: At the 11 intervention clinics, HR-MAM children were given RUTF and amoxicillin along with standard nutrition counseling, for 2-12 wk. All others received 6 wk of nutrition counseling alone. HR-MAM was defined as midupper arm circumference (MUAC) <11.9 cm, weight-for-age z score (WAZ) <-3.5, mother not the main caregiver, or a child <2 y old not being breastfed. Outcomes were compared using intention-to-treat analysis. RESULTS: Analysis included 573 children at the intervention sites and 714 children at the control sites. Of the intervention group, 317 (55%) were classified as HR-MAM. Short-term recovery was greater at the intervention sites [48% compared with 39% at week 12; risk difference (rd): 0.08; 95% CI: 0.03, 0.13]. The intervention group had lower risk of deteriorating to severe acute malnutrition (SAM) (18% compared with 24%; rd: -0.07; 95% CI: -0.11, -0.04), lower risk of dying (1.8% compared with 3.1%; rd: -0.02; 95% CI: -0.03, -0.00), and greater gains in MUAC and weight than did children at the control sites. However, by 24 wk, the risk of SAM was similar between the 2 arms (31% compared with 34%; rd: -0.03; 95% CI: -0.09, 0.02). Control group data identified recent illness, MUAC <12.0 cm, WAZ <-3, dropping anthropometry, age <12 mo, being a twin, and a history of previous SAM as risk factors for deterioration. CONCLUSIONS: Provision of RUTF and antibiotics to HR-MAM children improved short-term recovery and reduced short-term risk of deterioration. However, recovery rates were still suboptimal and differences were not sustained by 6 mo post enrollment.This trial was registered at clinicaltrials.gov as NCT03647150.

Routine vitamin A supplementation and other high impact interventions in Sierra Leone.

In 2017, transition to routine vitamin A supplementation (VAS) commenced as an integrated reproductive and child health service including vaccinations, Albendazole for deworming, complementary feeding demonstrations, 'quality' family planning counselling and provision of modern contraceptives. After 10 months, a lot quality assurance sampling survey evaluated coverage of these interventions. Each of three districts was divided into five supervision areas (lots), and 19 villages were randomly selected in each lot proportional to population size. Households were randomly selected, and a questionnaire was administered to a caregiver of a child 6-11, 12-23 and 24-59 months in each village. Overall, caregivers of 855 children were interviewed, and 19 questionnaires were completed for each age group (6-11, 12-23 and 24-59 months) in each of the five lots in each district. All lots in one district passed the threshold of 80% for VAS and 75% coverage for Albendazole, and two lots failed for either VAS/Albendazole in the other two districts. Overall, weighted VAS coverage for children 6-59 months was 86.9%, and weighted Albendazole coverage for children 12-59 months was 80.9%. Most caregivers (77.2%) knew that complementary feeding should be introduced at 6 months, 44.9% were providing three or more (of six) food groups, 84.9% were aware of family planning and 37.5% were using a modern contraceptive. Integration of reproductive and child health services appears to be a suitable platform for routine VAS and Albendazole whilst improving complementary feeding practices and access to family planning.

Treatment of severe acute malnutrition with oat or standard ready-to-use therapeutic food: a triple-blind, randomised controlled clinical trial.

OBJECTIVE: We hypothesised that an alternative RUTF (ready-to-use therapeutic food) made with oats (oat-RUTF) would be non-inferior to standard RUTF (s-RUTF). DESIGN: This was a randomised, triple-blind, controlled, clinical non-inferiority trial comparing oat-RUTF to s-RUTF in rural Sierra Leone. Children aged 6-59 months with severe acute malnutrition (SAM) were randomised to oat-RUTF or s-RUTF. s-RUTF was composed of milk powder, sugar, peanut paste and vegetable oil, with a hydrogenated vegetable oil additive. Oat-RUTF contained oats and no hydrogenated vegetable oil additives. The primary outcome was graduation, an increase in anthropometric measurements such that the child was not acutely malnourished. Secondary outcomes were rates of growth, time to graduation and presence of adverse events. Intention to treat analyses was used. RESULTS: Of the 1406 children were enrolled, graduation was attained in 404/721 (56%) children receiving oat-RUTF and 311/685 (45%) receiving s-RUTF (difference 10.6%, 95% CI 5.4% to 15.8%). Death, hospitalisation or remaining with SAM was seen in 87/721 (12%) receiving oat-RUTF and in 125/685 (18%) receiving s-RUTF (difference 6.2%, 95% CI 2.3 to 10.0, p=0.001). Time to graduation was less for children receiving oat RUTF; 3.9±1.8 versus 4.5±1.8 visits, respectively (p<0.001). Rates of weight in the oat-RUTF group were greater than in the s-RUTF group; 3.4±2.7 versus 2.5±2.3 g/kg/d, p<0.001. CONCLUSION: Oat-RUTF is superior to s-RUTF in the treatment of SAM in Sierra Leone. We speculate that might be because of beneficial bioactive components or the absence of hydrogenated vegetable oil in oat-RUTF. TRIAL REGISTRATION NUMBER: NCT03407326.

Integrating Vitamin A Supplementation at 6 months into the Expanded Program of Immunization in Sierra Leone.

Since 2004, twice-yearly mass vitamin A supplementation (VAS) has equitably reached over 85% of children 6-59 months old in Sierra Leone. However infants who turn 6 months after the event may wait until they are 11 months old to receive their first dose. The effectiveness of integrating VAS at 6 months into the Expanded Program of Immunization (EPI) in a revised child health card was studied. Health facilities matched according to staff cadre and work load were assigned to provide either a 'mini package' of VAS and infant and young child feeding (IYCF), a 'full package' of VAS, IYCF and family planning (FP), or 'child health card' only. 400 neonates were enrolled into each group, caregivers given the new child health card and followed until they were 12 months old. More infants in the full: 74.5% and mini: 71.7% group received VAS between 6 and 7 months of age compared with the new CH card only group: 60.2% (p = 0.002, p < 0.001 respectively). FP commodities were provided to 44.5% of caregivers in the full compared with <2.5% in the mini and new child health card only groups (p < 0.0001). Integration of VAS within the EPI schedule achieved >60% coverage for infants between 6 and 7 months of age. Provision of FP and/or IYCF further improved coverage. Funding was provided by the Canadian Department of Foreign Affairs, Trade and Development who had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

High coverage of vitamin A supplementation and measles vaccination during an integrated Maternal and Child Health Week in Sierra Leone.

BACKGROUND: In May 2012, the twice-yearly Maternal and Child Health Week (MCHW) integrated vitamin A supplementation (VAS) and supplementary measles vaccination to reach all children 6-59 months in Sierra Leone. Following the MCHW, a post event coverage survey was conducted to validate VAS coverage and assess adverse events following immunization. METHODS: Using the WHO Expanded Program on Immunization sampling methodology, 30 clusters were randomly selected using population proportionate to size sampling. Fourteen caregivers of children 6-59 months were interviewed per cluster for precision of ±5%. Responses were collected via mobile phones using EpiSurveyor. RESULTS: Overall VAS and measles coverage was 91.9% and 91.6%, respectively, with no significant differences by age group, sex, religion or occupation. Major reasons given for not receiving VAS and measles vaccination were not knowing about the MCHW or being out of the area. Significantly more mild adverse events (fever, pain at injection site) were reported via the post event coverage survey (29.1%) than MCHW (0.01%) (p<0.0001). CONCLUSION: The MCHW reached >90% of children in Sierra Leone with equitable coverage. Increased reporting of mild adverse events during the survey may be attributed to delayed onset after measles vaccination and/or direct inquiry from enumerators. Even mild adverse events following immunization requires strengthened reporting during and after vaccination campaigns.

High and equitable mass vitamin A supplementation coverage in Sierra Leone: a post-event coverage survey.

BACKGROUND: In Sierra Leone, children ages 6-59 months receive twice-yearly vitamin A supplementation (VAS) through Maternal and Child Health Week (MCHW) events. VAS coverage in 2011 was calculated using government tally sheets of vitamin A capsule distribution and outdated population projections from the 2004 census. We conducted a national post-event coverage (PEC) survey to validate coverage and inform strategies to reach universal coverage of VAS in Sierra Leone. METHODOLOGY: Immediately following the November 2011 MCHW event, we conducted a national PEC survey by interviewing caregivers with children ages 6-59 months using a randomized 30X30 cluster design (N = 900). We also interviewed one health worker and one community health worker in each cluster to determine their knowledge about VAS (N = 60). RESULTS: VAS coverage was 91.8% among children ages 6-59 months, which was lower than the 105.1% reported through tally sheets. Coverage was high and equitable among all districts and between age groups (98.5% for infants ages 6-11 months and 90.5% for children ages 12-59 months). Major reasons for not receiving VAS were that the child was out of the area (42.4%), the household was not visited by community health workers (28.0%), and the caretaker was not aware of the event (11.9%). CONCLUSION: Twice-yearly delivery of VAS through MCHW events achieved consistently high and equitable coverage in Sierra Leone. Universal coverage may be achieved through continued focus on communication and targeted outreach to hard-to-reach areas during the MCHWs.