Differing growth responses to nutritional supplements in neighboring health districts of Burkina Faso are likely due to benefits of small-quantity lipid-based nutrient supplements (LNS).

BACKGROUND: Of two community-based trials among young children in neighboring health districts of Burkina Faso, one found that small-quantity lipid-based nutrient supplements (LNS) increased child growth compared with a non-intervention control group, but zinc supplementation did not in the second study. OBJECTIVES: We explored whether the disparate growth outcomes were associated with differences in intervention components, household demographic variables, and/or children's morbidity. METHODS: Children in the LNS study received 20g LNS daily containing different amounts of zinc (LNS). Children in the zinc supplementation study received different zinc supplementation regimens (Z-Suppl). Children in both studies were visited weekly for morbidity surveillance. Free malaria and diarrhea treatment was provided by the field worker in the LNS study, and by a village-based community-health worker in the zinc study. Anthropometric assessments were repeated every 13-16 weeks. For the present analyses, study intervals of the two studies were matched by child age and month of enrollment. The changes in length-for-age z-score (LAZ) per interval were compared between LNS and Z-Suppl groups using mixed model ANOVA or ANCOVA. Covariates were added to the model in blocks, and adjusted differences between group means were estimated. RESULTS: Mean ages at enrollment of LNS (n = 1716) and Z-Suppl (n = 1720) were 9.4±0.4 and 10.1±2.7 months, respectively. The age-adjusted change in mean LAZ per interval declined less with LNS (-0.07±0.44) versus Z-Suppl (-0.21±0.43; p<0.0001). There was a significant group by interval interaction with the greatest difference found in 9-12 month old children (p<0.0001). Adjusting for demographic characteristics and morbidity did not reduce the observed differences by type of intervention, even though the morbidity burden was greater in the LNS group. CONCLUSIONS: Greater average physical growth in children who received LNS could not be explained by known cross-trial differences in baseline characteristics or morbidity burden, implying that the observed difference in growth response was partly due to LNS.

Factors Affecting the Validity of Coverage Survey Reports of Receipt of Vitamin A Supplements During Child Health Days in Southwestern Burkina Faso.

BACKGROUND: Assessment of high-dose vitamin A supplementation (VAS) coverage often relies on postevent coverage (PEC) surveys, but the validity of these methods has rarely been evaluated. OBJECTIVES: To assess reported VAS coverage and factors associated with missed coverage and to investigate the reliability of the results. METHODS: During a cross-sectional survey, 10 454 caregivers of children <27 months old were asked whether their child had received VAS in the past 6 months. During a 48-week longitudinal study of 6232 children 6 to 30 months old, caregivers were asked every 4 weeks if their child had received VAS in the past 4 weeks. RESULTS: The cross-sectional study showed that 94.4% (95% confidence interval [CI]: 93.8%, 94.9%) of eligible children 6 to 26 months of age reportedly received VAS in the previous 6 months, as did 85.8% (CI: 84.5%, 87.2%) of ineligible, 0 to 5 months old children. The longitudinal study showed that 81.6% of children surveyed within 4 weeks following a VAS campaign reportedly received VAS during the campaign and 13.4% of caregivers incorrectly reported receiving VAS when no campaign had actually occurred. False-positive reporting was more likely when oral polio vaccine (OPV) was distributed during the reporting period (20.6% vs 5.4%; P < .001). Showing a photo of OPV during the interview reduced the odds ratio (OR) of false-positive reports (OR = 0.7 [0.6-0.8]). CONCLUSIONS: The PEC surveys should include children outside the target age to assess targeting efficiency, and pictures of both VAS and oral vaccines distributed during the same period should be shown during interviews to enhance reporting accuracy.

Comparison of Preventive and Therapeutic Zinc Supplementation in Young Children in Burkina Faso: A Cluster-Randomized, Community-Based Trial.

BACKGROUND: The WHO and UNICEF recommend therapeutic zinc supplementation (TZS) for the treatment of diarrhea. In zinc-deficient populations, preventive zinc supplementation might provide greater benefits for reducing diarrhea and malaria incidence and increasing growth and plasma zinc (pZn) concentration. If effective, intermittent preventive zinc supplementation (IPZS) would cost less than daily preventive zinc supplementation (DPZS). OBJECTIVE: We assessed the effects of IPZS, DPZS, and TZS in children on the primary outcomes of diarrhea incidence, malaria incidence, growth, and pZn concentration compared with nonsupplemented control groups. METHODS: Rural Burkinabe children (n = 7641; 6-30 mo old) in 36 clusters were randomly assigned to 1 of 5 treatment groups for 16, 32, or 48 wk: 1) IPZS (10 mg Zn/d for 10 d every 16 wk); 2) DPZS (7 mg Zn/d); 3) TZS (20 mg Zn/d for 10 d for diarrhea); 4) morbidity surveillance control (MSC); or 5) nonintervention control (NIC). Supplemented groups remained masked until completion of primary analyses with mixed models. RESULTS: At baseline, stunting (28.6%) and low pZn concentration (<65 µg/dL; 43.5%) were common. After 48 wk, mean ± SE pZn increased more (P = 0.008) in the DPZS group (3.9 ± 1.3 µg/dL) than in the TZS (-0.5 ± 1.2 µg/dL) and NIC (-1.2 ± 0.9 µg/dL) groups. All supplemented groups had a moderately lower incidence of reported diarrhea (0.48-0.49 compared with 0.57 episodes/100 d, P = 0.001) and reported fever (1.1-1.2 compared with 1.5 episodes/100d, P < 0.001) and gained slightly less length (3.15-3.20 compared with 3.36 cm/16 wk, P < 0.001) than the MSC group, but did not differ from each other. Prevalence of diarrhea and incidences of confirmed fever and malaria were not different across study groups. CONCLUSIONS: The preventive and TZS groups had reduced diarrhea incidence, but it is uncertain whether this resulted from a functional response to zinc or reporting bias. The comparison should be re-examined in populations known to respond to zinc supplementation. This trial was registered at www.clinicaltrials.gov as NCT00944359.

Asymptomatic malaria infection affects the interpretation of biomarkers of iron and vitamin A status, even after adjusting for systemic inflammation, but does not affect plasma zinc concentrations among young children in Burkina Faso.

BACKGROUND: Biomarkers of iron [plasma ferritin (pF)], vitamin A [retinol binding protein (RBP)], and zinc status [plasma zinc (pZn)] are affected by the acute phase response, independent of micronutrient status. OBJECTIVE: The objective of these analyses was to assess how asymptomatic malaria infection affects the interpretation of these biomarkers after adjustment for elevated acute phase proteins (APPs). METHODS: Soluble transferrin receptor (sTfR), pF, RBP, and pZn concentrations were measured among 451 asymptomatic children aged 6-23 mo in Burkina Faso and adjusted for elevated APP (C-reactive protein ≥5 mg/L and/or α-1-acid-glycoprotein ≥1 g/L) based on a 4-group categorical model. Plasma histidine-rich protein II (HRP2) concentrations ≥0.75 µg/L were considered indicative of current or recent malaria parasitemia. RESULTS: Of the children in the study, 57.4% had at least 1 elevated APP, and 48.5% had elevated HRP2. After adjusting for APP, children with elevated HRP2 had higher pF (23.5 ± 1.5 µg/L vs. 11.1 ± 0.8 µg/L; P < 0.001) and lower RBP (0.79 ± 0.01 µmol/L vs. 0.92 ± 0.01 µmol/L; P < 0.001) than those without, but there were no differences in pZn among those with and without elevated HRP2 (64.9 ± 12.7 µg/dL vs. 64.9 ± 11.1 µg/dL; P = 0.98). Children with elevated HRP2 had higher sTfR than those without (17.6 ± 0.5 mg/L vs. 12.3 ± 0.4 mg/L; P < 0.0001). After adjusting for HRP2, along with APP, the estimated prevalence of iron deficiency (pF < 12 µg/L) increased from 38.7% to 50.6% and vitamin A deficiency (RBP < 0.84 µmol/L) decreased from 33.4% to 27.7%. CONCLUSIONS: Asymptomatic malaria is associated with indicators of micronutrient status, even after adjusting for APP. Adjusting indicators of iron and vitamin A status based only on APP may inaccurately estimate the prevalence of micronutrient deficiencies in settings with a high prevalence of malaria and inflammation. This trial was registered at clinicaltrials.gov as NCT00944853.

Associations between intestinal mucosal function and changes in plasma zinc concentration following zinc supplementation.

OBJECTIVES: Subclinical environmental enteropathy is associated with malabsorption of fats, carbohydrates, and vitamins A, B12, and folate; however, little information is available on mineral absorption. We therefore investigated the relation between intestinal mucosal function (measured by the lactulose:mannitol permeability test and plasma citrulline concentration), and zinc (Zn) absorption, as estimated by the change in plasma Zn concentration (PZC) following short-term Zn or placebo supplementation. METHODS: We conducted a randomized, partially masked, placebo-controlled trial among 282 apparently healthy children 6 to 23 months of age in Burkina Faso. After completing baseline intestinal function tests, participants received either 5 mg Zn, as zinc sulfate, or placebo, daily for 21 days. RESULTS: At baseline, mean ± standard deviation PZC was 62.9 ± 11.9 µg/dL; median (interquartile range) urinary lactulose:mannitol (L:M) recovery ratio and plasma citrulline concentrations were 0.04 (0.03-0.07) and 11.4 (9.0-15.6) µmol/L, respectively. Change in PZC was significantly greater in the Zn-supplemented versus placebo group (15.6 ± 13.3 vs 0.02 ± 10.9 µg/dL; P < 0.0001), and was negatively associated with initial urinary L:M recovery ratio (-1.1 µg/dL per 50% increase in urinary L:M recovery ratio; P = 0.014); this latter relation did not differ between supplementation groups (P = 0.26). Baseline plasma citrulline concentration was not associated with change in PZC. CONCLUSIONS: Although altered intestinal permeability may reduce dietary Zn absorption, it likely does not undermine the efficacy of Zn supplementation, given the large increases in PZC following short-term Zn supplementation observed in this study, even among those with increased urinary L:M recovery ratios.

Caregiver recognition of childhood diarrhea, care seeking behaviors and home treatment practices in rural Burkina Faso: a cross-sectional survey.

INTRODUCTION: To design effective national diarrhea control programs, including oral rehydration solution (ORS) and therapeutic zinc supplementation, information is needed on local perceptions of illness, external care seeking behaviors, and home treatment practices. METHODS: A cross-sectional, community-based household survey was conducted in the Orodara Health District, Burkina Faso. Caregivers of 10,490 children <27 months were interviewed to assess child diarrhea prevalence and related care practices. Characteristics of households, caregivers, children, and reported illnesses were compared for those caregivers who did or did not recognize the presence of diarrhea, as defined according to clinical criteria (≥ 3 liquid or semi-liquid stools/day). Multiple logistic regression models were used to examine factors associated with illness recognition and treatment. RESULTS: Clinically defined diarrhea was present in 7.6% (95% CI: 7.1-8.1%) of children during the 24 hours preceding the survey but recognized by only 55% of caregivers. Over half (55%) of the caregivers of 1,067 children with a clinically defined diarrhea episode in the past 14 days sought care outside the home; 78% of those seeking care attended a public sector clinic. Care was sought and treatment provided more frequently for children with fever, vomiting, anorexia, longer illness duration, and those living closer to the health center; and care was sought more frequently for male children. 80% of children with recent diarrhea received some form of treatment; only 24% received ORS, whereas 14% received antibiotics. Zinc was not yet available in the study area. CONCLUSIONS: Caregivers frequently fail to recognize children's diarrhea, especially among younger infants and when illness signs are less severe. Treatment practices do not correspond with international recommendations in most cases, even when caregivers consult with formal health services. Child caregivers need additional assistance to recognize diarrhea correctly, and both caregivers and health care providers need updated training on current diarrhea treatment recommendations.

Short-term zinc supplementation with dispersible tablets or zinc sulfate solution yields similar positive effects on plasma zinc concentration of young children in Burkina Faso: a randomized controlled trial.

OBJECTIVE: To assess zinc absorption from dispersible tablets by investigating the effects of short-term zinc supplementation, provided either as zinc (Zn) sulfate dispersible tablets or solution, on changes in plasma Zn concentration in young children. STUDY DESIGN: We conducted a randomized, partially-masked, placebo-controlled trial in 451 children 6 to 23 months of age in Burkina Faso, randomly assigned to receive a dispersible tablet containing 5 mg Zn, a Zn solution containing 5 mg Zn/5 mL, or a placebo solution, daily for 3 weeks. The main outcome measure was change in plasma zinc concentration after supplementation compared with baseline. RESULTS: The mean plus or minus SD change in plasma Zn concentration (µg/dL) was significantly greater in both Zn supplemented groups (tablets: 16.9±13.1µg/dL, liquid: 16.6±14.2 µg/dL), compared with the placebo group (0.2±10.9 µg/dL; P<.001, ANOVA). In both Zn supplemented groups, but not in the placebo group, change in plasma Zn concentration was progressively less with increasing age in months (-0.79 µg/dL/mo and -1.15 µg/dL/mo, respectively; P<.001); this effect did not differ in the Zn supplemented groups (P=.18). CONCLUSIONS: Short-term supplementation results in a large increase in plasma Zn concentration, regardless of whether the additional Zn is provided as a dispersible tablet or solution.

Major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children in Burkina Faso: a randomized double blind trial.

BACKGROUND: Vitamin A and zinc are crucial for normal immune function, and may play a synergistic role for reducing the risk of infection including malaria caused by Plasmodium falciparum. METHODS: A randomized, double-blind, placebo-controlled trial of a single dose of 200 000 IU of vitamin A with daily zinc supplementation was done in children of Sourkoudougou village, Burkina Faso. Children aged from 6 to 72 months were randomized to receive a single dose of 200 000 IU of vitamin A plus 10 mg elemental zinc, six days a week (n = 74) or placebo (n = 74) for a period of six months. Cross-sectional surveys were conducted at the beginning and the end of the study, and children were evaluated daily for fever. Microscopic examination of blood smear was done in the case of fever (temperature > or =37.5 degrees C) for malaria parasite detection. RESULTS: At the end of the study we observed a significant decrease in the prevalence malaria in the supplemented group (34%) compared to the placebo group (3.5%) (p < 0.001). Malaria episodes were lower in the supplemented group (p = 0.029), with a 30.2% reduction of malaria cases (p = 0.025). Time to first malaria episode was longer in the supplemented group (p = 0.015). The supplemented group also had 22% fewer fever episodes than the placebo group (p = 0.030). CONCLUSION: These results suggest that combined vitamin A plus zinc supplementation reduces the risk of fever and clinical malaria episodes among children, and thus may play a key role in malaria control strategies for children in Africa.