Impact of zinc supplementation on subsequent morbidity and growth in Bangladeshi children with persistent diarrhoea.

This study was conducted to explore whether supplementation of zinc to children during persistent diarrhoea has any subsequent effect on morbidity and growth. A prospective follow-up study was conducted among children, aged 3-24 months, with persistent diarrhoea, who participated earlier in a double-blind randomized placebo-controlled trial. During persistent diarrhoea, children were randomly allocated to receive either zinc in multivitamin syrup or only multivitamin syrup for two weeks. After recovering from diarrhoea, 76 children in the multi-vitamin syrup and 78 children in the zinc plus multivitamin syrup group were followed up for subsequent morbidity and growth. Weekly morbidity and two-weekly anthropometric data were collected for the subsequent 12 weeks. Data showed that episodes and duration of diarrhoea were reduced by 38% and 44% respectively with supplementation of zinc. There was no significant difference in the incidence or duration of respiratory tract infection between the zinc-supplemented and the non-supplemented group. Improved linear growth was observed in underweight children (weight-for-age <70% of the National Center for Health Statistics standard) who received zinc compared to those who did not receive.

Cost of delivering child immunization services in urban Bangladesh: a study based on facility-level surveys.

This facility-based study estimated the costs of providing child immunization services in Dhaka, Bangladesh, from the perspective of healthcare providers. About a quarter of all immunization (EPI) delivery sites in Dhaka city were surveyed during 1999. The EPI services in urban Dhaka are delivered through a partnership of the Government of Bangladesh (GoB) and non-governmental organizations (NGOs). About 77% of the EPI delivery sites in Dhaka were under the management of NGOs, and 62% of all vaccinations were provided through these sites. The outreach facilities (both GoB and NGO) provided immunization services at a much lower cost than the permanent static facilities. The average cost per measles-vaccinated child (MVC), an indirect measure of number of children fully immunized (FIC-the number of children immunized by first year of life), was 11.61 U.S. dollars. If all the immunization doses delivered by the facilities were administered to children who were supposed to be immunized (FVC), the cost per child would have been 6.91 U.S. dollars. The wide gap between the cost per MVC and the cost per FVC implies that the cost of immunizing children can be reduced significantly through better targeting of children. The incremental cost of adding new services or interventions with current EPI was quite low, not significantly higher than the actual cost of new vaccines or drugs to be added. NGOs in Dhaka mobilized about 15,000 U.S. dollars from the local community to support the immunization activities. Involving local community with EPI activities not only will improve the sustainability of the programme but will also increase the immunization coverage.

Immune modulation after measles vaccination of 6-9 months old Bangladeshi infants.

Measles still causes high mortality in children younger than 1 year of age. Administration of high titre measles vaccines before 7 months of age led to increased overall mortality, raising questions as to the immunological effects of measles vaccine in young infants. We investigated the immune response to standard titre vaccines given to children in Bangladesh in a single dose at age 9 months, or two doses at 6 and 9 months. Of the children vaccinated at age 9 months, 95% serocoverted, compared with 70% at age 6 months. Delayed-type-hypersensitivity reactions to candida antigen were significantly reduced in both vaccine groups at 6 weeks post-vaccination, but responses to other recall antigens studied were not significantly different from controls. In both vaccine groups, peripheral blood lymphocytes isolated at 6 and 24 weeks after vaccination showed significantly higher expression of activation markers upon in vitro stimulation, and a sustained increase in IL-2 production. These findings suggest prolonged immune activation after measles vaccination at the same time as some reduction in delayed hypersensitivity responses. Further study of the clinical effects of these changes is warranted.

Increased childhood morbidity after measles is short-term in urban Bangladesh.

In a 1995-1996 cohort study in the city of Dhaka, Bangladesh, morbidity in 117 hospitalized and 137 acute measles cases compared with age-matched children without measles (unexposed) was determined by weekly interview for 6 months. Compared with unexposed children, there were higher incidences of hospitalization (adjusted rate ratio (RR) = 3.1, 95% confidence interval (CI): 1.3, 7.6) and bloody diarrhea (adjusted RR = 2.7, 95% CI: 1.4, 5.1) in hospital measles cases during the 6 weeks after recruitment. Among community cohorts, there were higher incidences of bloody diarrhea (adjusted RR = 4.1, 95% CI: 1.1, 14.6), watery diarrhea (adjusted RR = 1.6, 95% CI: 0.9, 2.7), fast breathing (adjusted RR = 3.8, 95% CI: 2.1, 6.9), and the weekly point prevalence of pneumonia (adjusted prevalence ratio = 3.1, 95% CI: 1.0, 9.8) in measles cases during the same period. All measles cases regained lost weight within about 6 weeks. The prevalence of anergy to seven recall antigens 6 weeks after recruitment was higher in both hospital (adjusted odds ratio = 2.8, 95% CI: 1.2, 6.4) and community (adjusted odds ratio = 3.1, 95% CI: 1.1, 8.9) measles cases. Morbidity increased during the first 6-8 weeks after measles, but the authors found no consistent evidence of longer-term morbidity or wasting. The results support recent findings that measles is not associated with increased delayed mortality.

Impact of zinc supplementation on subsequent growth and morbidity in Bangladeshi children with acute diarrhoea.

OBJECTIVE: To assess the impact of zinc supplementation during acute diarrhoea on subsequent growth and morbidity in malnourished young children. DESIGN: Double blind randomized controlled clinical trial SETTING: International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: Sixty-five children aged 3-24 months with acute diarrhoea for less than 3 d. INTERVENTION: Either elemental zinc (20 mg/d) in a multivitamin syrup or multivitamin syrup alone divided in three divided daily doses for a period of two weeks. Children were followed up weekly at home to assess subsequent growth and morbidity for a period of eight weeks. MAIN OUTCOME MEASURES: Gain in length and body weight and reduction in diarrhoea and respiratory tract infection. RESULTS: During the follow-up, zinc supplemented children showed significantly greater cumulative length gain (18.9 mm vs 14.5 mm, P <0.03) and comparable body weight gain than the children of the control group. Subsequent length gain was not correlated with initial height in the zinc-supplemented group (r=-0.13), P = 0.5), but was significantly correlated in the control group (r = -0.6, P < 0.0007). Zinc-supplemented and stunted children (< or = 90% length for age n = 18) experienced significantly fewer episodes of diarrhoea (0.07 vs 0.6, P < 0.05) and respiratory illness (1.0 vs 2.4, P < 0.01) compared to the control group. The underweight children (< or = 71% weight/age n = 38) receiving zinc-supplementation also had fewer episodes of diarrhoea (0.4 vs 1.0, P<0.04) and shorter duration of diarrhoeal episodes (1.0 vs 3.0d, P<0.04) compared to their counterparts in the control group. CONCLUSION: These results suggest that a short course of zinc supplementation to malnourished children during acute diarrhoea reduces growth-faltering and diarrhoeal and respiratory morbidity during subsequent two months.

Long-term supplementation with iron does not enhance growth in malnourished Bangladeshi children.

To evaluate the effect of long-term oral iron supplementation on growth, 250 children aged 6-71 mo were studied in a randomized double-blind controlled trial. The intervention group received 125 mg of ferrous gluconate (15 mg elemental iron) plus multivitamins (vitamins A, D and C); the comparison group received only multivitamins daily for 12 mo. Weight (kg) and height (cm) were measured every month. Eighty three percent of the children continued the treatment for one year. The weight increment over the 12-mo period was 1.35 +/- 0.65 kg (mean +/- SD) in the intervention group and 1.39 +/- 0.54 kg in the comparison group. The height increments were 6.01 +/- 1.47 and 6.18 +/- 1.58 cm in the intervention and comparison groups, respectively. Mean weight and height increments did not differ; in an analysis stratified according to different age and nutritional categories, they also did not differ between the two groups, indicating that long-term iron supplementation does not increase growth in children.

Impact of zinc supplementation on persistent diarrhoea in malnourished Bangladeshi children.

To evaluate the impact of zinc supplementation on the clinical recovery and body weight of children with persistent diarrhoea, a randomized, double-blind, controlled trial was conducted in 190 children with persistent diarrhoea aged between 3 and 24 months. Children were randomly allocated to receive either zinc (20 mg d(-1)) syrup with multivitamin (2 x RDA) or multivitamin alone in three divided daily doses for 2 weeks. The trial was conducted in a diarrhoeal disease hospital in Dhaka, Bangladesh. Duration until clinical recovery (d), impact on body weight and serum zinc level after 2 weeks of zinc supplementation were recorded. The duration of illness was significantly reduced (33%) with zinc supplementation among children who were underweight (< or =70% wt/age, p = 0.03). Supplemented male children also had a significant reduction (27%) in duration for recovery compared with unsupplemented children (p = 0.05). From baseline to convalescence, zinc-supplemented children maintained their serum zinc concentration (13.4 vs 13.6 micromol l(-1)), whereas unsupplemented children had a decrease in serum zinc after the 2 weeks of diarrhoea (13.6 vs 11.8 micromol l(-1),p < 0.03). The mean body weight of the children in the supplemented group was maintained (5.72 vs 5.70 kg, p = 0.62) during hospitalization, unlike that of the control group, in which there was a reduction in body weight (5.75 vs 5.67 kg, p = 0.05). Five children in the unsupplemented group and one child in the zinc-supplemented group died during the 2 weeks of supplementation (p = 0.06). Zinc supplementation in persistent diarrhoea significantly reduced the length of the recovery period in malnourished children and prevented a fall in body weight and serum zinc concentration, indicating that zinc is a beneficial therapeutic strategy in this high-risk childhood illness.

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea.

OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.

Long-term oral supplementation with iron is not harmful for young children in a poor community of Bangladesh.

The effect of long-term oral iron supplementation on morbidity due to diarrhea, dysentery and respiratory infections in 349 children, aged 2-48 mo, living in a poor community of Bangladesh, was evaluated in this double-blind study. The treatment group received 125 mg of ferrous gluconate (15 mg elemental iron) plus multivitamins and the controls received only multivitamins, daily for 15 mo. House-to-house visits were made on alternate days by trained community health workers for recording symptoms and duration of illnesses and for monitoring medicine intake. Seventy-six percent of the children continued the syrup for over 1 y. No untoward effects were noticed in either treatment group. The attack rates for diarrhea, dysentery and acute respiratory tract infections (ARI) were 3, 3 and 5 episodes per child per year, respectively. Each episode of diarrhea lasted a mean of 3 d, and those of dysentery and ARI, 5 d. The two treatment groups did not differ in the number of episodes, mean duration of each episode, or total days of illnesses due to diarrhea, dysentery and ARI. However, a 49% greater number of episodes of dysentery was observed with iron supplementation in a subset of the study children who were less than 12 mo old (P = 0.03). The results of this study suggest that long-term oral iron supplementation is not harmful for older children in a poor community. Further studies are needed to demonstrate the safety and efficacy of iron administration in young infants.

Impact of a single megadose of vitamin A at delivery on breastmilk of mothers and morbidity of their infants.

OBJECTIVES: To evaluate the effect of vitamin A supplementation 24 h after delivery on breastmilk retinol concentration. METHODS: Fifty low income women were randomly assigned to a single oral dose of 209 micromol of Vitamin A or none at delivery. Maternal serum and breastmilk retinol levels and infant morbidity and anthropometry were serially assessed. RESULTS: Mean (95% CI) serum retinol levels increased in the supplemented mothers at 2.77 (2.3, 3.2) compared to 1.15 (0.9, 1.4) micromol/l in controls (P < 0.05) and remained at a significantly higher level of 1.59 (1.4, 1.8) micromol/l compared to 1.33 (1.8, 1.5) micromol/l in the control group (P < 0.001) up to a period of three months. Breastmilk retinol concentration was also greater at 24 h after supplementation, mean (CI) 11.34 (9.0, 13.7) micromol/l, compared to 2.95 (2.3, 3.6) micromol/l in the control group (P < 0.0001), and remained higher for the next six months at 1.06 (0.9, , 1.3) micromol/l compared to 0.73 (0.6, 0.8) micromol/l in the control group (P < 0.02). Infants of the supplemented mothers had reduced mean duration of respiratory tract infection of 3.1 (2.7, 3.5) days compared to 3.7 (3.3, 4.2) days (P < 0.03) and mean incidence of febrile illness 0.1 (0.1, 0.1) compared to control infants 0.3 (0.3, 0.3) days, (P < 0.002). CONCLUSION: Vitamin A supplementation of malnourished mothers maintains higher breastmilk retinol concentration for at least six months and reduces the duration of respiratory tract infection and febrile illness in their breastfed infants.

Persistent diarrhoea: efficacy of a rice-based diet and role of nutritional status in recovery and nutrient absorption.

A diet based on rice powder, soya-bean oil, glucose, egg-white and salts was given to twenty-six patients of different nutritional status aged 4-18 months with persistent diarrhoea and twenty-five age-matched controls without diarrhoea. Clinical response was monitored during 1 week of dietary treatment and absorption of macronutrients was estimated during a 72 h balance study. Twenty-one patients (81%) recovered from diarrhoea within 7 d. There were significant relationships between nutritional indices, recovery, and absorption of total energy, fat and N. The absorption of fat, protein and carbohydrate in the better nourished controls without diarrhoea was significantly higher than in patients with persistent diarrhoea with better nutrition or malnutrition. The duration of diarrhoea was significantly longer in lighter patients (weight-for-age < 65% NCHS (1976) standard), in wasted patients (weight/height < 80% of NCHS) and those with mid upper arm circumference (MUAC) less than 110 mm. There were negative relationships between the period of recovery and the coefficient of absorption of fat (P < 0.001), total energy intake (P < 0.01) and MUAC (P < 0.05). Weight-for-age and MUAC showed most effective discriminative power for absorption of nutrients. However, the coefficients of absorption for carbohydrate were not different for any pair of nutritional groups. Absorption of all nutrients was also correlated negatively with severity of persistent diarrhoea on admission. The results of the present study indicate that a rice-based diet is highly effective in the management of persistent diarrhoea and less malnutrition aggravates nutrient malabsorption, increases duration and severity of diarrhoea and less severely malnourished patients do not absorb nutrients as well as healthy controls. Malnutrition and the initial severity of diarrhoea are significant determinants of clinical prognosis and nutrient absorption in persistent diarrhoea.

Impact of zinc supplementation on intestinal permeability in Bangladeshi children with acute diarrhoea and persistent diarrhoea syndrome.

Zinc has been shown to enhance intestinal mucosal repair in patients suffering from acrodermatitis enteropathica; but the impact on mucosal integrity during acute (AD) or persistent (PD) diarrhoea is unknown. One hundred eleven children with AD and 190 with PD aged between 3 and 24 months received, randomly and blind to the investigators, either an elemental zinc supplement of 5 mg/kg body wt/day or placebo in multivitamin syrup for 2 weeks while intestinal permeability and, biochemical and anthropometric markers were serially monitored. The permeability test was administered as an oral dose of 5 g lactulose/l g mannitol in a 20-ml solution followed by a 5-h urine collection. The ratio of the urinary probe sugars was correlated to clinical, biochemical, and microbiological parameters. At presentation, lactulose excretion was increased and mannitol excretion decreased in both AD and PD as compared with age-matched asymptomatic children. The lactulose/mannitol ratio (L/M) was higher in subjects with mucosal invasive pathogens (rotavirus and enteropathogenic Escherichia coli) compared with children excreting Vibrio cholera and enterotoxigenic E. coli. Two-week zinc supplementation significantly reduced lactulose excretion in both AD and PD, whereas the change in mannitol excretion and L/M was similar between study groups in both studies. Changes in lactulose excretion were significantly influenced by zinc supplementation in children with E. coli, Shigella sp., and Campylobacter jejuni stool isolates. The greatest reduction in total lactulose excretion was seen in supplemented children who on presentation were lighter (wt/age less than 80%), thinner (wt/ht less than 85%), and undernourished [middle upper arm circumference (MUAC) less than 12.5 cm] or with hypozincaemia (less than 14 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Persistent diarrhoea: factors affecting absorption and clinical prognosis during management with a rice-based diet.

Twenty-six persistent diarrhoea patients aged 4 to 18 months were treated with a diet prepared with rice powder, soya oil, glucose, egg white and water. Absorption of macronutrients was estimated in a 72 h balance study and clinical response was examined during one week of dietary treatment. Nutrient absorption was compared with that of 25 healthy age-matched controls treated with the same diet. Twenty-one patients (81%) recovered from diarrhoea within seven days. Absorption of nutrients was significantly reduced among the persistent diarrhoea patients. More malnourished patients had a significantly reduced absorption of nutrients except carbohydrate and an increased severity and longer duration of diarrhoea. Total gut transit time had significant association with nutrient absorption in the persistent diarrhoea patients. The period of recovery negatively correlated with coefficient of absorption and positively with initial stool weight. Failure to recover was associated with severity of diarrhoea and systemic infection. The study indicates that nutrient absorption is significantly reduced in patients with persistent diarrhoea and nutritional status, and that initial purging rate and intestinal hurry are significantly related to the prognosis and nutrient absorption.

Persistent diarrhea: total gut transit time and its relationship with nutrient absorption and clinical response.

The study was undertaken to better understand the role of total gut transit time (TGTT) on the absorption of nutrients in patients with persistent diarrhea. Twenty-six boys aged 3-18 months with persistent diarrhea and 25 age-matched healthy controls were studied. Their TGTT was measured with charcoal markers during their treatment with a diet made up with rice powder soya oil, glucose, and egg white. Coefficients of absorption of nutrients were estimated in a 72-h balance study. The median TGTTs in patients and controls were 5 and 11.6 h, respectively. Among the patients, the TGT correlated significantly with absorption of total energy (p less than 0.01), absorption of fat (p less than 0.01), stool frequency (p less than 0.01), and stool weight during the 1st 24 h (p less than 0.01). Coefficients of absorption of energy, fat, and carbohydrate were significantly different among the patients above or below the median transit time (5 h). None of these relationships was present among the healthy controls. The TGTT was negatively associated with the duration of clinical recovery. The results of this study suggested that intestinal transit time is an important factor for absorption of nutrients that may influence clinical recovery in patients with persistent diarrhea.