M. A. Wahed

Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial

BACKGROUND Pneumonia is a leading cause of morbidity and mortality in young children. Early reversal of severity signs--chest indrawing, hypoxia, and tachypnoea--improves outcome. We postulated that zinc, an acute phase reactant, would shorten duration of severe pneumonia and time in hospital. METHODS In a double-blind placebo-controlled clinical trial in Matlab Hospital, Bangladesh, 270 children aged 2-23 months were randomised to receive elemental zinc (20 mg per day) or placebo, plus the hospitals standard antimicrobial management, until discharge. The outcomes were time to cessation of severe pneumonia (no chest indrawing, respiratory rate 50 per min or less, oxygen saturation at least 95% on room air) and discharge from hospital. Discharge was allowed when respiratory rate was 40 per minute or less for 24 consecutive hours while patients were maintained only on oral antibiotics. FINDINGS The group receiving zinc had reduced duration of severe pneumonia (relative hazard [RH]=0.70, 95% CI 0.51-0.98), including duration of chest indrawing (0.80, 0.61-1.05), respiratory rate more than 50 per min (0.74, 0.57-0.98), and hypoxia (0.79, 0.61-1.04), and overall hospital duration (0.75, 0.57-0.99). The mean reduction is equivalent to 1 hospital day for both severe pneumonia and time in hospital. All effects were greater when children with wheezing were omitted from the analysis. INTERPRETATION Adjuvant treatment with 20 mg zinc per day accelerates recovery from severe pneumonia in children, and could help reduce antimicrobial resistance by decreasing multiple antibiotic exposures, and lessen complications and deaths where second line drugs are unavailable.

A randomized controlled clinical trial of zinc, vitamin A or both in undernourished children with persistent diarrhea in Bangladesh

In a double‐blind randomized controlled clinical trial, moderately malnourished Bangladeshi children (61–75% of the median weight/age) were studied for the effect of zinc and/or vitamin A supplementation on the clinical outcome of persistent diarrhea. Children 6 mo to 2 y of age with diarrhea for more than 14 d were randomly allocated into 4 groups of 24 receiving a multivitamin syrup and (i) zinc (20 mg elemental), (ii) vitamin A, (iii) both zinc and vitamin A, or (iv) neither, in 2 doses daily for 7 d. Clinical data on recovery and on stool output, consistency and frequency were recorded for 7 d, and weight change from day 1 to day 7 was assessed. The baseline characteristics of the four study groups were comparable. The mean daily stool outputs from days 2 to 7 of therapy were significantly less in the zinc and zinc plus vitamin A groups, but not in the vitamin A group, in comparison with the control group. In children receiving zinc, the cumulative stool weight in the 7 d was 39% less than in the control group (p < 0.001) and 32% less than in the vitamin A group (p= 0.006). The cumulative stool weight in the zinc plus vitamin A group was 24% less than in the control group (p <0.001), but the 14% lower output than in the vitamin A group was not statistically different The change in body weight over the 7d study period was significantly different between the group receiving zinc and the control group (+111 g vs –90 g, p = 0.045). The rate of clinical recovery of children within 7 d was significantly greater in the zinc group (88%) compared with the control group (46%, p= 0.002) or vitamin A group (50%, p= 0 005), but not statistically different from the zinc plus vitamin A group (67%, p= 0.086).

β-Carotene losses during different methods of cooking green leafy vegetables in Bangladesh.

Abstract Green leafy vegetables containing β-carotene (provitamin A) may serve as an alternative inexpensive source of vitamin A for the majority ofthe poor people in developing countries. Previous studies showed conflicting results as to whether considerable amounts of β-carotene in vegetables are destroyed by cooking. The present study was undertaken to assess the extent of β-carotene loss in vegetables subjected to three traditional methods of cooking practiced in Bangladesh: Method I: boiling for 7–9 min, followed by frying in oil for 4–6 min in an open pot with stirring and allowing the water portion to evaporate or to be thrown away; Method II: simple boiling for 8–10 min with the lid of the pot on for most of the cooking time; and Method III: placing vegetables on the surface of partially cooked rice until cooking is done and then mashing it into a paste with condiments. Housewife volunteers (8–10) participated in the cooking experiments using each of 6 types of commonly eaten vegetables; only one type was used in Method III. A modified Holdens method which was used to measure β-carotene was statistically comparable to the conventional method of the Association of Official Analytical Chemists. The percentage loss of β-carotene for Method I was 31 to 43%; Method II, 11 to 14%; and Method III, 2.3 to 11%. The β-carotene contents of 14 types of commonly eaten green leafy vegetables in Bangladesh ranged between 5400 and 16000 μg/100 g. The cause and implication of the high loss of β-carotene by cooking Method I are discussed. Health planners of developing countries should educate people to use cooking methods similar to Methods II and III.

Vitamin a megadoses during early infancy on serum retinol concentration and acute side effects and residual effects on 6 month follow-up

We evaluated the safety and efficacy of 3 oral doses of 50000 IU vitamin A at monthly intervals in predominantly breastfed infants from poor urban Bangladesh aged 6 to 17 weeks along with DPT and oral polio vaccines in a randomised double-masked controlled trial. Ninety-seven infants received vitamin A and 103 received placebo. Initial fasting serum retinol concentrations were very low in most infants (52% <10 µg/dl and 74% <15 µg/dl) which improved in both groups but was still less than 15 µg/dl in 30% of those who received vitamin A. Nine infants in the vitamin A group and 2 in the placebo group had bulged fontanelle after the second and/or third dose (RR=4.78 95% CI 1.06-21.54 P<0.025) which resolved in 48 hours. In conclusion young infants from a deprived urban community in Bangladesh were deficient in vitamin A; a large proportion remained deficient even after three large doses of vitamin A. In spite of deficiency bulged fontanelle an apparent toxic manifestation occurred in 9.3% with this dosage schedule of vitamin A. Alternative and/or complementary approaches e.g. maternal supplementation are needed to prevent vitamin A deficiency in under 6 month infants in developing countries. (authors)

Supplementing iron and zinc: double blind, randomized evaluation of separate or combined delivery

Background/Objectives:Many children have diets deficient in both iron and zinc, but there has been some evidence of negative interactions when they are supplemented together. The optimal delivery approach would maximize clinical benefits of both nutrients. We studied the effectiveness of different iron and zinc supplement delivery approaches to improve diarrhea and anemia in a rural Bangladesh population.Study Design:Randomized, double blind, placebo-controlled factorial community trial.Results:Iron supplementation alone increased diarrhea, but adding zinc, separately or together, attenuated these harmful effects. Combined zinc and iron was as effective as iron alone for iron outcomes. All supplements were vomited <1% of the time, but combined iron and zinc were vomited significantly more than any of the other supplements. Children receiving zinc and iron (together or separately) had fewer hospitalizations. Separating delivery of iron and zinc may have some additional benefit in stunted children.Conclusions:Separate and combined administration of iron and zinc are equally effective for reducing diarrhea, hospitalizations and improving iron outcomes. There may be some benefit in separate administration in stunted children.

Effect of consumption of the nutrient-dense, freshwater small fish Amblypharyngodon mola on biochemical indicators of vitamin A status in Bangladeshi children : a randomised, controlled study of efficacy

In Bangladesh, some commonly consumed, indigenous, freshwater small fish species (eaten whole with bone, head and eyes) such as mola (Amblypharyngodon mola) are nutrient-dense, containing preformed vitamin A as retinol and especially 3,4-dehydroretinol. The objective of the present randomised, controlled efficacy study was to evaluate the effects of mola on biochemical indicators of vitamin A status. Children (n 196), aged 3-7 years, with serum retinol 0.36-0.75 micromol/l, were randomly allocated to one of three treatment groups to receive a daily test meal (6 d/week for 9 weeks) of rice and vegetable curry (no vitamin A) ad libitum and 50 g fish curry consisting of: (1) mola, 600 retinol activity equivalents (RAE) (using 40 % biological activity of 3,4-dehydroretinol isomers) (experimental group, n 66); (2) rui (Labeo rohita), a large fish (no vitamin A), with added retinyl palmitate, 600 RAE (positive control group, n 65); or (3) rui, 0 RAE (negative control group, n 65). The nutrient compositions of the dishes were analysed. After 9 weeks, no significant treatment effects were observed for serum retinol (P = 0.52) and retinol-binding protein (P = 0.81) in the experimental group compared with the negative control, whereas the positive control improved significantly (P < 0.001). The present results do not suggest conversion of the large amount of 3,4-dehydroretinol in mola curry to retinol. Further research on the functional effect of mola in humans is needed. Mola is a nutrient-dense animal-source food, rich in haem Fe, Zn and especially Ca, thus consumption of mola in Bangladesh should continue to be encouraged.

Acute-phase protein levels, diarrhoea, Trichuris trichiura and maternal education are predictors of serum retinol: a cross-sectional study of children in a Dhaka slum, Bangladesh.

The objectives of the present study were to identify predictors of serum retinol concentration as well as to assess the prevalence of low serum retinol concentration, in both the whole population after correcting for the effect of serum C-reactive protein (CRP) (using multiple categories), and the healthy subgroup. A cross-sectional study of 579 apparently healthy children, aged 3-7 years from a Dhaka slum, Bangladesh, was conducted. The effects of age, gender, serum CRP and alpha1-antichymotrypsin, reported morbidity (during the previous 2 weeks), Ascaris lumbricoides and Trichuris trichiura infections, parental education, wasting, stunting and underweight on serum retinol were estimated using multiple linear regression. The mean serum retinol concentration was 0.84 (sd 0.27) micromol/l. Elevated serum CRP levels, reported diarrhoea, reported nasal discharge and T. trichiura infection were negative predictors of serum retinol, whereas maternal education was a positive predictor. Compared with a serum CRP level of < 1 mg/l, CRP levels of 2 to < 5, 5 to < 10 and > or = 10 mg/l were associated with 0.12, 0.16 and 0.32 micromol/l lower serum retinol, respectively. The prevalence of low serum retinol (< 0.70 micromol/l) fell from 31.2 % to 15.6 % in the whole population, after correcting for the effect of CRP, and was 20.1 % in the healthy subgroup (CRP < 2 mg/l). The prevalence of low serum retinol was high but overestimated due to the effect of CRP. Interventions are needed to address low serum retinol in Bangladesh. Controlling diarrhoea, nasal discharge and T. trichiura infection and improving maternal education may be important interventions. The use of multiple categories of acute-phase proteins and cut-off values that indicate elevated levels need further research.

The Paired Deuterated Retinol Dilution Technique Can Be Used to Estimate the Daily Vitamin A Intake Required to Maintain a Targeted Whole Body Vitamin A Pool Size in Men

The estimated average requirement (EAR) for vitamin A (VA) of adult males is based on the amount of dietary VA required to maintain adequate function and provide a modest liver VA reserve (0.07 μmol/g). In the present study, the paired-deuterated retinol dilution technique was used to estimate changes in VA pool size in Bangladeshi men from low-income, urban neighborhoods who had small initial VA pool sizes (0.059 ± 0.032 mmol, or 0.047 ± 0.025 μmol/g liver; n = 16). The men were supplemented for 60 d with 1 of 8 different levels of dietary VA, ranging from 100 to 2300 μg/d (2 men/dietary VA level). VA pool size was estimated before and after the supplementation period. The mean change (plus or minus) in VA pool size in the men was plotted against their corresponding levels of daily VA intake and a regression line was fit to the data. The level of intake at which the regression line crossed the x-axis (where estimates of VA pool size remained unchanged) was used as an estimate of the EAR. A VA intake of 254-400 μg/d was sufficient to maintain a small VA pool size (0.059 ± 0.032 mmol) in the Bangladeshi men, corresponding to a VA intake of 362-571 μg/d for a 70-kg U.S. man, which is lower than their current EAR of 625 μg/d. The data suggest that the paired-deuterated retinol dilution technique could be used for estimating the EAR for VA for population subgroups for which there are currently no direct estimates.

Evaluation of an energy-dense meal liquefied with amylase of germinated wheat in children with acute watery diarrhoea: A randomized controlled clinical trial

Abstract To evaluate the role of an energy-dense diet liquefied with amylase of germinated wheat flour (ARF) in increasing the energy intake in children with acute diarrhoea and its effect on the course of diarrhoea, 95 children aged 6–23 months were randomized to receive either an ARF treated liquid porridge (test diet) or an unaltered thick porridge (control-1) or a porridge diluted with extra water (control-2). The children were rehydrated with rice-based oral rehydration solution (ORS) and intravenous acetate solution (if needed) and the study diets were offered 4 times a day for four days. In addition, they received a milk cereal mixture and breast feeding ad libitum . Intake was calculated by subtracting the left-over from the amount offered. Intake (ORS, IV, and food) and output (stool, urine, and vomiting) were summarized 8 hourly. The mean ± SD total energy intake (kJ/kg.d) from porridge in the test, control-1 and control-2 groups were 414 ± 97, 355 ± 120, and 351 ± 73 respectively (difference between mean, 95% CI: test vs control-1 = 59, 5–114 and test vs control-2 = 63, 20–106). Breastmilk intake was similar in the three groups. There was no difference in stool output, ORS intake, and duration of diarrhoea among the three groups. However, vomiting was more marked in the test and control-2 group who had increased volume intake of liquid meals compared to control-1 group. The results suggest that energy intake can be increased in children during acute diarrhoea using liquefied high energy porridge and its use did not worsen the diarrhoea.

Subclinical vitamin A deficiency in young infants from Bangladesh

Abstract In Bangladesh, the high prevalence of clinically evident vitamin A deficiency in children under 5 years has been well documented, however, little is known about the vitamin A status of children under 1 year. The relative dose response (RDR) test was carried out in 85 healthy infants (5.9±2.3 months) coming to the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) or Dhaka Shishu Hospital for routine immunization and whose parents agreed to participate in the study. Mean serum retinol [R] was 0.66±0.3 μmol/l and mean RDR value was 29.8±22.1. Fifty-six (56%) percent of the infants had serum [R] values under 0.70 μmol/l and 18% under 0.35 μmol/l. Sixty-four percent (64%) of the infants had abnormal RDR values (≥20) indicating low liver reserves of vitamin A. These results indicate that there is a high prevalence of subclinical vitamin A deficiency in Bangladeshi infants. RDR values showed a negative correlation with weight-forage. The percentage of infants with serum retinol concentration