ABSTRACT
BACKGROUND: Previous studies of large-dose vitamin A supplementation on respiratory morbidity have produced conflicting results in a variety of populations. The influence of malnutrition has not been examined in the majority of these trials. We hypothesized that weekly low-dose vitamin A supplementation would prevent respiratory and diarrheal disease morbidity and that malnutrition might influence the efficacy of vitamin A supplementation. METHODS: In a randomized, double-blind, placebo-controlled field trial of 400 children, 6 to 36 months of age in a high Andean urban slum, half of the children received 10 000 IU of vitamin A weekly and half received placebo for 40 weeks. Children were visited weekly at home by physicians and assessed for acute diarrheal disease and acute respiratory infections. RESULTS: Acute diarrheal disease and acute respiratory infection did not differ globally or by severity between supplement-treated and placebo groups. However, the incidence of acute lower respiratory infection (ALRI) was significantly lower in underweight (weight-for-age z score [WAZ] <-2 SD) supplement-treated children than in underweight children on placebo (8.5 vs 22.3 per 10(3) child-weeks; rate ratio: 0.38 [95% CI: 0.17-0.85]). ALRI incidence was significantly higher in normal-weight (WAZ >-2 SD) supplement-treated children than in normal-weight children on placebo (9.8 vs 4.4 per 10(3) child-weeks; rate ratio: 2.21 [95% CI: 1.24-3.93]). By logistic regression analysis the risk of ALRI was lower in underweight supplement-treated children than in underweight children on placebo (point estimate 0.148 [95% CI: 0.034-0.634]). In contrast, risk of ALRI was higher in normal-weight supplement-treated children (WAZ >-1 SD to mean) than in normal-weight children on placebo in the same WAZ stratum (point estimate: 2.51 [95% CI: 1.24-5.05]). The risk of severe diarrhea was lower in supplement-treated children 18 to 23 months of age than in children on placebo in this age group (point estimate: 0.26 [95% CI: 0.06-1.00]). CONCLUSIONS: Weekly low-dose (10 000 IU) vitamin A supplementation in a region of subclinical deficiency protected underweight children from ALRI and paradoxically increased ALRI in normal children with body weight over -1 SD. Protection from severe diarrhea was consistent with previous trials. Additional research is warranted to delineate potential beneficial and detrimental interactions between nutritional status and vitamin A supplementation regarding ALRI.
Subject(s)
Diarrhea/prevention & control , Respiratory Tract Infections/prevention & control , Vitamin A/administration & dosage , Acute Disease , Body Weight , Child Nutrition Disorders/complications , Child, Preschool , Diarrhea/classification , Diarrhea/epidemiology , Double-Blind Method , Drug Administration Schedule , Ecuador , Female , Humans , Infant , Logistic Models , Male , Nutritional Status , Pneumonia/classification , Pneumonia/epidemiology , Pneumonia/prevention & control , Respiratory Tract Infections/classification , Respiratory Tract Infections/epidemiology , Severity of Illness Index , Vitamin A/bloodABSTRACT
OBJECTIVE: To assess the effect of zinc supplementation on respiratory tract disease, immunity and growth in malnourished children. DESIGN: A randomized double-blind placebo-controlled trial. SETTING: A day-care center in Quito, Ecuador. SUBJECTS: Fifty children (12-59 months old) recruited by height-for-age and weight-for-age deficit. INTERVENTIONS: Twenty-five children (supplemented, S group) received 10 mg/day of zinc as zinc sulfate, and 25 (nonsupplemented, NS group) received a placebo during 60 days. All were also observed during a 60-day postsupplementation period. Two children of the S group dropped out. Daily the clinical presence of cough, respiratory tract secretions, and fever, was recorded. On days 0,60 and 120, the cutaneous delayed-type hypersensitivity (DTH) to multiple antigens, and anthropometric parameters were assessed. On days 0 and 60 serum zinc levels were also measured. RESULTS: On day 60, DTH was significantly larger (20.8 +/- 7.1 vs 16.1 +/- 9.7 mm), and serum zinc levels were significantly higher (118.6 +/- 47.1 vs 83.1 +/- 24.5 micrograms/dl) in the S group than in the NS group (P <0.05 for each). The incidence of fever [relative risk (RR): 0.30, c.i. = 0.08- 0.95, P =0.02], cough (RR): 0.52, c.i. = 0.32-0.84, P = 0.004) and upper respiratory tract secretions (RR):0.72, c.i. = 0.59-0.88, P = 0.001) was lower in the S group than in the NS group at day 60. At the end of the postsupplementation observation period (day 120), the incidence of fever and upper respiratory tract secretions was the same in both the S and NS groups. The incidence of cough was higher at day 120 in the S group than in the NS group (RR): 2.28, c.i. = 1.37-3.83, P = 0.001). CONCLUSIONS: This study supports a role for zinc in immunity, and immunity to respiratory infections, while pointing out the need for larger studies.
Subject(s)
Adjuvants, Immunologic/therapeutic use , Child Nutrition Disorders/drug therapy , Growth Disorders/drug therapy , Respiratory Tract Infections/drug therapy , Sulfates/therapeutic use , Zinc Compounds/therapeutic use , Child, Preschool , Cough/drug therapy , Double-Blind Method , Ecuador , Female , Fever/diagnosis , Humans , Hypersensitivity, Delayed/drug therapy , Immunity, Cellular/drug effects , Infant , Male , Respiratory Tract Infections/immunology , Risk , Zinc SulfateABSTRACT
To determine the clinical features and outcome of shigellosis in young infants, we reviewed the hospital records of 159 infants < or = 3 months of age (including 30 neonates) and 159 children 1 to 10 years of age with shigellosis who were admitted to the Diarrhoea Treatment Centre in Dacca, Bangladesh. Infants more commonly had a history of nonbloody diarrhea (82.8% vs 42.7%; p < 0.001), moderate or severe dehydration (59.9% vs 32.1%; p < 0.001), or bacteremia (12.0% vs 5.0%; p = 0.027) and less commonly had fever (32.7% vs 58.6%; p < 0.001), abdominal tenderness (1.9% vs 12.6%; p < 0.001), or rectal prolapse (0% vs 8.3%; p = 0.001). Infections caused by Shigella boydii (20.8% vs 6.3%; p < 0.001) and Shigella sonnei (7.5% vs 1.3%; p = 0.006) were more common, and Shigella dysenteriae type 1 (9.4% vs 31.4%; p < 0.001) infections were less common in infants than in older children; the proportion of Shigella flexneri infections was equivalent in the two groups (59.1% vs 60.4%). Infants were twice as likely to die as older children (16.4% vs 8.2%; p = 0.026). Only 17 infants (14.3%) were being exclusively breast fed at the onset of their illness. In a multiple logistic regression analysis, independent predictors of death in infants were gram-negative bacteremia, ileus, decreased bowel sounds, hyponatremia, hypoproteinemia, and a lower number of erythrocytes detected on microscopic examination of stool specimens. Diarrhea management algorithms that rely only on clinical findings of dysentery to diagnose and treat shigellosis are likely to be unreliable in this high-risk age group.
PIP: Findings are reported from a study conducted to determine the clinical features and outcome of shigellosis in young infants. The authors reviewed the hospital records of 159 infants of no greater than age 3 months and those of 159 children aged 1-10 years with shigellosis who were admitted to the Diarrhea Treatment Center in Dacca, Bangladesh. 82.8% of infants had a history of nonbloody diarrhea, 59.9% moderate or severe dehydration, 12% bacteremia, 32.7% fever, 1.9% abdominal tenderness, and 0% rectal prolapse. 42.7% of children had a history of nonbloody diarrhea, 32.1% moderate or severe dehydration, 5.0% bacteremia, 58.6% fever, 12.6% abdominal tenderness, and 8.3% rectal prolapse. Infections caused by Shigella boydii and Shigella sonnei were more common in infants, while Shigella dysenteriae type 1 infections were less common in infants than in older children. There was an equivalent proportion of Shigella flexneri infections in the two groups. Infants were twice as likely to die as older children. Only 17 infants were being exclusively breastfed at the onset of their illness. Multiple logistic regression analysis identified the independent predictors of death among infants to be gram-negative bacteremia, ileus, decreased bowel sound, hyponatremia, hypoproteinemia, and a lower number of erythrocytes detected on the microscopic examination of stool specimens. Diarrhea management algorithms which rely exclusively upon clinical findings of dysentery to diagnose and treat shigellosis are likely to be unreliable in this high-risk age group.