Simultaneous zinc and vitamin A supplementation in Bangladeshi children: randomised double blind controlled trial.

OBJECTIVE: To evaluate the effect of simultaneous zinc and vitamin A supplementation on diarrhoea and acute lower respiratory infections in children. STUDY DESIGN: Randomised double blind placebo controlled trial. SETTING: Urban slums of Dhaka, Bangladesh. PARTICIPANTS AND METHODS: 800 children aged 12-35 months were randomly assigned to one of four intervention groups: 20 mg zinc once daily for 14 days; 200 000 IU vitamin A, single dose on day 14; both zinc and vitamin A; placebo. The children were followed up once a week for six months, and morbidity information was collected. RESULTS: The incidence and prevalence of diarrhoea were lower in the zinc and vitamin A groups than in the placebo group. Zinc and vitamin A interaction had a rate ratio (95% confidence interval) of 0.79 (0.66 to 0.94) for the prevalence of persistent diarrhoea and 0.80 (0.67 to 0.95) for dysentery. Incidence (1.62; 1.16 to 2.25) and prevalence (2.07; 1.76 to 2.44) of acute lower respiratory infection were significantly higher in the zinc group than in the placebo group. The interaction term had rate ratios of 0.75 (0.46 to 1.20) for incidence and 0.58 (0.46 to 0.73) for prevalence of acute lower respiratory infection. CONCLUSIONS: Combined zinc and vitamin A synergistically reduced the prevalence of persistent diarrhoea and dysentery. Zinc was associated with a significant increase in acute lower respiratory infection, but this adverse effect was reduced by the interaction between zinc and vitamin A.

Simultaneous vitamin A administration at routine immunization contact enhances antibody response to diphtheria vaccine in infants younger than six months.

A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effect of simultaneous vitamin A supplementation and diphtheria, pertussis and tetanus (DPT) vaccination on the antibody levels. Infants aged 6-17 wk (n = 56) were randomly given 15 mg oral vitamin A or placebo at the time of their DPT immunization. Three such doses were given at monthly intervals. Immunoglobulin (Ig) G antibodies to diphtheria, pertussis and tetanus were assayed on enrollment and 1 mo after the third dose. Baseline antibody concentrations to diphtheria, pertussis and tetanus did not differ between the vitamin A-supplemented and placebo-treated groups. The postdose antibody to diphtheria level was significantly greater in the vitamin A than in the placebo-treated group. The geometric mean +/- SEM antibody levels (mg/L) were 22.9 +/- 1.2 and 11.0 +/- 1.3 in the vitamin A and placebo groups, respectively (P = 0.029). The postsupplementation concentrations of antibodies to pertussis and tetanus did not differ between the two groups. These results suggest that antibody response to diphtheria vaccination was potentiated by simultaneous vitamin A administration and DPT immunization.

Predictors of serum retinol in children with shigellosis.

BACKGROUND: Low serum retinol can be useful as an indicator of depleted liver vitamin A stores, particularly in population-based studies. However, serum retinol concentrations decrease transiently during infection, independent of any changes in liver stores. The magnitude of the decrease in serum retinol is often proportional to indicators of disease severity. OBJECTIVE: We examined the relation of serum retinol in children with culture-positive shigellosis with severity of illness, anthropometric indicators of nutritional status, urinary retinol excretion, and serum concentrations of C-reactive protein, alpha1-acid glycoprotein, retinol binding protein, and transthyretin. DESIGN: This was a prospective study assessing the clinical and laboratory measurements at admission and recovery of 90 children with dysentery (66 with shigellosis) hospitalized in Bangladesh. RESULTS: Serum retinol concentrations were low at admission but were significantly greater at discharge even though no vitamin A supplements were given during the illness (0.36 +/- 0.22 compared with 1.15 +/- 0.50 micromol/L, P < 0.001). Serum retinol concentrations were lower in children with Shigella dysenteriae type 1 infection than in children with shigellosis due to less virulent strains of Shigella. Low serum retinol was independently associated with S. dysenteriae type 1, high serum C-reactive protein concentrations, and low weight-forage in multiple regression analysis. CONCLUSIONS: This study showed that shigellosis was associated with a significant, transient decrease in serum retinol concentrations of approximately 0.8 micromol/L, and that this change was significantly associated with severity of disease and poor underlying nutritional status, particularly low weight-for-age.

Adverse effects of high-dose vitamin A supplements in children hospitalized with pneumonia.

OBJECTIVE: To test the hypothesis that high-dose vitamin A supplements will enhance recovery of children hospitalized for the treatment of community-acquired pneumonia. DESIGN: We conducted a randomized, double-blind, placebo-controlled clinical trial of high-dose vitamin A supplements among children 3 months to 10 years of age (N = 95) admitted to hospital with community-acquired pneumonia in Lima, Peru. Children 1 year of age received 200 000 IU on admission and 100 000 IU the next day. RESULTS: Children receiving vitamin A (n = 48) had lower blood oxygen saturation (the mean difference on day 3 in hospital was 1.1%), higher prevalence rates of retractions (37% in the vitamin A group vs 15% in the placebo group on day 3), auscultatory evidence of consolidation (28% in the vitamin A group vs 17% in the placebo group on day 3), and were more likely to require supplemental oxygen (21% in the vitamin A group vs 8% in the placebo group on day 3) than children in the placebo group (n = 47). Adjustment for baseline severity of disease and nutritional status did not alter the association of vitamin A with increased clinical severity, although the difference in blood oxygen saturation was no longer statistically significant. No differences were seen in duration of hospitalization or in chest x-ray changes 14 days after admission. No deaths occurred, and toxicity of vitamin A was not seen. CONCLUSIONS: This study indicates that high-dose vitamin A supplements cause modest adverse effects in children recovering from pneumonia and should not be used therapeutically in such patients unless there is clinical evidence of vitamin A deficiency or concurrent measles infection.

Intra- and extracellular water dynamics on rehydration in cholera and noncholera patients.

To estimate the intra- and extracellular body water compartments during rehydration of patients with cholera and noncholera diarrhea by bioimpedance analyzer, we studied 30 patients with acute watery diarrhea. Total body water (TBW), intracellular water (ICW), and extracellular water (ECW) of severely dehydrated adult patients were measured with a dual frequency bioimpedance analyzer at different phases of rehydration. Fluid compartments between cholera and noncholera patients were compared. Cholera patients gained more TBW than noncholera patients during recovery. Unlike patients with noncholera diarrhea, the gain in cholera patients was mainly contributed by the ICW (1.5 +/- 1.6 vs 3.0 +/- 1.2 liters, respectively, P < 0.01). It was also observed that the recovery of the ICW compartment in cholera patients occurred rapidly within the first 2 hr after infusion. Differential dynamics of body water compartments in cholera compared to noncholera patients as observed in this study may contribute further to understanding the mechanism of dehydration in diarrheal disease, which might help in improving case management.

Effect of early vitamin A supplementation on cell-mediated immunity in infants younger than 6 mo.

One hundred twenty infants were randomly assigned to receive either 15 mg vitamin A or placebo with each of three DPT/OPV (diphtheria, pertussis, tetanus/oral polio vaccine) immunizations at monthly intervals. Sixty-two received vitamin A and 58 received placebo. One month after the third supplementation dose, the response to the delayed cutaneous hypersensitivity test [multitest cell-mediated immunity (CMI) skin evaluation] for tetanus, diphtheria, and tuberculin (purified protein derivative, PPD) was the same in the vitamin A and placebo infants. The number of anergic infants was 17 (27%) and 19 (33%) in the vitamin A and placebo groups, respectively. The number of positive tests among well-nourished infants was significantly higher than that in malnourished infants irrespective of supplementation (P < 0.001). Among the infants with adequate serum retinol concentrations (> 0.7 mumol/L) after supplementation, the vitamin A-supplemented infants had a significantly higher proportion of positive CMI tests than the placebo infants (chi-square test: 8.99, P = 0.008). Among the infants with low serum retinol concentrations (< 0.7 mumol/L) after supplementation, vitamin A supplementation had no effect on CMI response. These results indicate that CMI in young infants was positively affected by vitamin A supplementation only in those infants whose vitamin A status was adequate (ie, serum retinol > 0.7 mumol/L) at the time of the CMI test. CMI was consistently better in well-nourished infants irrespective of supplementation.

Acute respiratory infections prevent improvement of vitamin A status in young infants supplemented with vitamin A.

At immunization contact, 165 infants 2.5 mo old were randomly assigned to receive either 15 mg vitamin A (retinyl palmitate) or placebo. Three doses were given at monthly intervals with each diphtheria, pertussis, tetanus and oral polio (DPT/OPV) immunization dose. The diarrhea and acute respiratory infection (ARI) morbidity was similar in the vitamin A and placebo groups. However, the duration (days per child-year, mean +/- SD) of ARI was less in the vitamin A group compared with placebo group (27.6 +/- 17.1 vs. 40.8 +/- 22.7; P = 0.005). Fasting retinol concentrations were measured at entry and in 61 infants, the relative dose response (RDR) test was done 1 mo after the third dose of vitamin A. Eighty-five percent of the infants had serum retinol concentration < 0.70 mol/L at entry. After 3 mo the serum retinol levels improved significantly in both groups, and in the vitamin A-supplemented group the serum retinol concentration was significantly better than that in the placebo group (P= 0.02). However, 61% of the infants remained deficient despite vitamin A supplementation. Among vitamin A-supplemented infants only, diarrhea and ARI morbidity during the 3-mo period were compared in children with normal versus children with abnormal RDR at the end of the supplementation period. The ARI episodes were more frequent in the supplemented infants who remained vitamin A deficient at the end of the 3 mo (P = 0.027). Also, the cumulative duration (days, mean +/- SD) of fever and cough was 5.0 +/- 2.8 in the normal versus 11.2 +/- 6.0 in the deficient group (P = 0.04). The results of this study suggest that a large proportion of infants remain vitamin A deficient even after large dose vitamin A supplementation because of frequent respiratory infections, particularly those accompanied by fever.

Comparison of the modified relative dose response (MRDR) and the relative dose response (RDR) in the assessment of vitamin A status in malnourished children.

The modified-relative-dose-response (MRDR) test and the relative-dose-response (RDR) test were compared in 49 mildly to moderately malnourished Bangladeshi children. The MRDR test had a significantly lower sensitivity, detecting only 71% of children with very low serum retinol (< or = 0.35 mumol/L) and 33% of children with low serum retinol (0.355-0.70 mumol/L) compared with 100% and 80% for the RDR test, respectively. The MRDR test showed a very strong dependency on retinol-binding protein (RBP) saturation (ie, percent saturation of RBP with retinol) compared with the RDR test. Only 3 (23%) of 13 children with RBP saturation > or = 55% but low vitamin A stores were diagnosed as abnormal by the MRDR test. This suggests that when apo-RBP concentration is limiting, as it is in malnourished children, didehydroretinol, the analog used in the MRDR test cannot effectively compete with retinol for binding to apo-RBP. Under these circumstances, the MRDR test is rendered ineffective. The possibility of increasing the sensitivity of the test by using a high dose of didehydroretinol needs to be investigated.

Diet and oral premalignancy in female south Indian tobacco and betel chewers: a case-control study.

The diets of 158 tobacco/betel quid-chewing women diagnosed with oral premalignant lesions and 155 quid-chewing but lesion-free controls, frequency matched for age, tobacco/betel habits, and socioeconomic status, were assessed using a food frequency survey. Index scores generated from the food frequency survey indicated that the mean levels of consumption for foods of animal origin (p < 0.001), total vegetables and fruit (p = 0.001), vegetables alone (p = 0.006), fruits alone (p = 0.006), and green leafy vegetables (p = 0.015) were significantly lower in cases than in controls. The mean index score for cobalamin (vitamin B12) was lower in cases with a borderline significance (p = 0.05), whereas the indexes for folate and carotene were not significantly different. The analysis of index scores estimating the number of 100-g servings per week of foods of animal origin [meat, eggs, milk, curd (yogurt), fish] consumed revealed that women who ate fewer servings were more likely to have premalignant lesions than those who ate more animal foods [odds ratio (OR) 3.38, 95% confidence interval (CI) 2.07-5.54, p = 0.001]. The risk for low consumption of vegetables was not as significant as that for foods of animal origin. However, those eating low levels of vegetables and low levels of foods of animal origin were at the greatest risk for lesions (OR 5.38, 95% CI 1.72-22.17, p < 0.05). In South Indian female tobacco/betel chewers, a diet deficient in foods of animal origin appears to be a more significant risk factor for oral premalignancy than is a diet deficient in fruits and vegetables.

Effect of aluminium on mineralization of rat third molar in vitro.

Crl: COBS rat third-molar explants were cultured for 12 days in either 0.6 X 10(-2), 4 X 10(-2) or 6 X 10(-2) mM aluminium, or for 12 days with exposure to 13 X 10(-2) mM Al at different 6-day intervals. Total protein, alkaline phosphatase, calcium and phosphorous were measured to evaluate cell viability and the degree of mineralization. Al in concentrations above 4 X 10(-2) mM significantly reduced the Ca and P content of explants cultured for 12 days. Explants exposed to 13 X 10(-2) mM Al for the first 6 days had less Ca and P than those exposed for the last 6 days of culture. Haematoxylin and eosin-stained sections of explants showed no gross abnormalities.