Zinc supplementation for four months does not affect plasma copper concentration in infants.

AIM: The aim of the present study, which was undertaken as a sub-study within a randomized controlled trial of zinc supplementation, was to evaluate the effect of prolonged zinc supplementation on copper status as assessed by hematological markers. METHODS: Plasma copper and zinc were estimated at baseline and after 120 d of supplementation in a randomly selected infant subset (115) of the children. Of these, 61 children were in a zinc group (Z) getting 10 mg of elemental zinc, and 54 were in a control group (C) getting supplement without zinc. RESULTS: Baseline plasma zinc was comparable in the two groups; post-supplementation zinc was significantly higher (Z 93.0 +/- 3.6 vs C 60.6 +/- 8.0) in the zinc supplementation group. There was no significant difference in the mean/median copper levels between the zinc and control groups. The percentage of children with plasma copper <100 microg/dl was also not significantly different between groups (baseline Z 14.8%, C 11.1%; post-supplementation Z 18.0%, C 11.1%). There were no differences between the zinc and control groups after 120 d of supplementation in hemoglobin (Hgb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), or number of lymphocytes or granulocytes. CONCLUSION: Zinc supplementation of 10 mg/d for 4 mo in this study did not affect copper status, as assessed by plasma copper concentration and hematological parameters, diagnostics of copper deficiency.

Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide.

Treatment of leukemia by myeloablative conditioning and transplantation of major histocompatibility complex (MHC)-mismatched stem cells is generally avoided because of the high risk of graft rejection or lethal graft-versus-host disease (GVHD). This study shows that MHC-incompatible cells can engraft stably after nonmyeloablative conditioning with immunosuppressive chemotherapy and low-dose total body irradiation (TBI). Long-term mixed hematopoietic chimerism, clonal deletion of donor-reactive T cells, and bidirectional cytotoxic T-cell tolerance were achieved by transplanting MHC-mismatched marrow cells into recipients conditioned with pretransplantation fludarabine or cyclophosphamide (Cy), 50 to 200 cGy TBI on day -1, and Cy 200 mg/kg intraperitoneally on day 3. In this model, long-term donor chimerism was proportional to the dose of TBI or donor marrow cells. Pretransplantation fludarabine and posttransplantation Cy were both required for alloengraftment, but the drugs had additional effects. For example, fludarabine sensitized host stem cells to the toxicity of TBI, because animals conditioned with both agents had higher chimerism than animals conditioned with TBI alone (P <.05). Also, posttransplantation Cy attenuated lethal and nonlethal GVH reactions, because F(1) recipients of host-reactive, parental spleen cells survived longer (P <.05) and had lower donor cell chimerism (P <.01) if they received posttransplantation Cy than if they did not. Finally, delayed infusions of donor lymphocytes into mixed chimeras prolonged survival after leukemia challenge (P <.0001) without causing lethal GVHD. These results indicate that stable engraftment of MHC-incompatible cells can be induced after fludarabine-based, nonmyeloablative conditioning and that it serves as a platform for adoptive immunotherapy with donor lymphocyte infusions.

Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial.

BACKGROUND: Increased acute lower respiratory infection incidence, severity, and mortality are associated with malnutrition, and reduced immunological competence may be a mechanism for this association. Because zinc deficiency results in impaired immunocompetence and zinc supplementation improves immune status, we hypothesized that zinc deficiency is associated with increased incidence and severity of acute lower respiratory infection. METHODS: We evaluated the effect of daily supplementation with 10 mg of elemental zinc on the incidence and prevalence of acute lower respiratory infection in a double-blind, randomized, controlled trial in 609 children (zinc, n = 298; control, n = 311) 6 to 35 months of age. Supplementation and morbidity surveillance were done for 6 months. RESULTS: After 120 days of supplementation, the percentage of children with plasma zinc concentrations <60 microg/dL decreased from 35.6% to 11.6% in the zinc group, whereas in the control group it increased from 36.8% to 43.6%. Zinc-supplemented children had 0.19 acute lower respiratory infection episodes/child/year compared with 0.35 episodes/child/year in the control children. After correction for correlation of data using generalized estimating equation regression methods, there was a reduction of 45% (95% confidence interval, 10% to 67%) in the incidence of acute lower respiratory infections in zinc-supplemented children. CONCLUSIONS: A dietary zinc supplement resulted in a significant reduction in respiratory morbidity in preschool children. These findings suggest that interventions to improve zinc intake will improve the health and survival of children in developing countries.

Efficacy of zinc supplementation in reducing the incidence and prevalence of acute diarrhea--a community-based, double-blind, controlled trial.

A community-based, double-blind, randomized trial was conducted in a population of low socioeconomic status in urban India to determine whether daily zinc supplementation reduces the incidence and prevalence of acute diarrhea, especially in those with zinc deficiency. Children 6-35 mo of age were randomly assigned to zinc (n = 286) and control (n = 293) groups and received a supplement daily for 6 mo. Zinc gluconate (10 mg elemental Zn) was given, with both zinc and control groups also receiving multivitamins. The primary outcome measures determined by home visits every fifth day and physician examinations were the number of acute diarrheal episodes (incidence) and total diarrheal days (prevalence). Zinc supplementation had no effect in children 6-11 mo old. In children aged > 11 mo there was significantly less diarrhea in the zinc group. In boys > 11 mo old, supplementation resulted in a 26% (95% CI: 13%, 38%) lower diarrheal incidence and a 35% (95% CI: 20%, 50%) lower prevalence. In zinc-supplemented girls > 11 mo of age, the incidence was 17% (95% CI: 2%, 30%) lower and the prevalence was 19% (95% CI: 4%, 47%) lower. Overall, zinc supplementation resulted in a 17% (95% CI: 1%, 30%) lower diarrheal incidence in children with plasma zinc concentrations < 9.18 mumol/L at enrollment and a 33% (95% CI: 6%, 52%) lower incidence in children with concentrations < 50 mumol/L. In conclusion, zinc supplementation had a significant effect on acute diarrheal morbidity in children > 11 mo old and in children with low plasma zinc concentrations.

Effect of zinc supplementation on cell-mediated immunity and lymphocyte subsets in preschool children.

OBJECTIVE: In a zinc supplementation trial (with a significant impact on diarrheal morbidity), to evaluate effect of zinc supplementation on cellular immune status before and after 120 days of supplementation. DESIGN: A double blind, randomized controlled trial with immune assessment at baseline and after 120 days on supplement. SETTING: Community based study in an urban slum population. SUBJECTS: Randomly selected children (zinc 38, control 48), had a Multitest CMI skin test at both times. In 66 children (zinc 22, control 34), proportions of CD3, CD4, CD8, CD16, CD20 cells and the CD/CD8 ratio were also estimated using a whole blood lysis method and flowcytometry. INTERVENTION: Zinc gluconate to provide elemental zinc 10 mg daily and 20 mg during diarrhea. MAIN OUTCOME RESULTS: Regarding CMI, the percentage of anergic or hypoergic children (using induration score) decreased from 67% to 47% in the zinc group, while in the control group it remained unchanged (73% vs 71%) (p = 0.05). The percentage of children deteriorating between first and second tests was significantly lower in the zinc group (13% vs 33%, p = 0.03). Regarding lymphocyte subsets, the zinc group had a significantly higher rise in the geometric means of CD3 (25%, p = 0.02), CD4 (64% p = 0.001), and CD4/CD8 ratio (73% p = 0.004) with no difference in CD8 and CD20. The rise in CD4 was significantly higher in the zinc as compared to the control group; the ratio of geometric means was 1.45 (95% CI, 1.03-2.01). CONCLUSION: Zinc supplementation improves cellular immune status, which may have been one of the mechanisms for observed impact of zinc supplementation on diarrheal morbidity.

Zinc supplementation reduces the incidence of persistent diarrhea and dysentery among low socioeconomic children in India.

Persistent diarrhea (PD) and dysentery (DD) account for most diarrhea-associated deaths among children in developing countries. Zinc deficiency can cause stunting and impaired immune function, both of which are risk factors for these diarrheal illnesses. We investigated the effect of zinc supplementation on the incidence of PD and DD in a community-based, double-blind randomized trial in children 6-35 mo of age. Increase over baseline in plasma zinc concentrations in the supplemented group compared with a control group (3.61 vs. 0.009 mumol.L-1), indicated successful supplementation. The overall reductions in the zinc supplemented group of 21% in the incidence of PD (95% CI -6 to 42%) and 14% in the incidence of dysentery (95% CI -15 to 36%) were not significant. There was a significant interaction of treatment effect with baseline plasma zinc concentration and age for PD and with gender for DD. In the zinc-supplemented group compared with the control group, the incidence of PD was reduced by 73% (P < 0.05; 95% CI 34 to 91%) in children with a baseline zinc < 7.65 mumol.L-1 and by 49% (P < 0.05; 95%CI 24 to 66%) in children > 11 mo of age. Zinc supplementation resulted in a 38% (P < 0.05 95%CI 8 to 59%) reduction in the incidence of DD in boys. There was no effect on PD among children 6-11 mo old or on DD in girls. In conclusion, zinc supplementation had a significant impact on the incidence of persistent diarrhea in children > 1 y old and in children with low plasma zinc, as well as on dysentery in boys. These findings may have important implications for reducing diarrhea-related morbidity and mortality.

Zinc supplementation in young children with acute diarrhea in India.

BACKGROUND: In developing countries the duration and severity of diarrheal illnesses are greatest among infants and young children with malnutrition and impaired immune status, both factors that may be associated with zinc deficiency. In children with severe zinc deficiency, diarrhea is common and responds quickly to zinc supplementation. METHODS: To evaluate the effects of daily supplementation with 20 mg of elemental zinc on the duration and severity of acute diarrhea, we conducted a double-blind, randomized, controlled trial involving 937 children, 6 to 35 months of age, in New Delhi, India. All the children also received oral rehydration therapy and vitamin supplements. RESULTS: Among the children who received zinc supplementation, there was a 23 percent reduction (95 percent confidence interval, 12 percent to 32 percent) in the risk of continued diarrhea. Estimates of the likelihood of recovery according to the day of zinc supplementation revealed a reduction of 7 percent (95 percent confidence interval, -9 percent to +22 percent) in the risk of continued diarrhea during days 1 through 3 and a reduction of 38 percent (95 percent confidence interval, 27 percent to 48 percent) after day 3. When zinc supplementation was initiated within three days of the onset of diarrhea, there was a 39 percent reduction (95 percent confidence interval, 7 percent to 61 percent) in the proportion of episodes lasting more than seven days. In the zinc-supplementation group there was a decrease of 39 percent (95 percent confidence interval, 6 percent to 70 percent) in the mean number of watery stools per day (P = 0.02) and a decrease of 21 percent (95 percent confidence interval, 10 percent to 31 percent) in the number of days with watery diarrhea. The reductions in the duration and severity of diarrhea were greater in children with stunted growth than in those with normal growth. CONCLUSION: For infants and young children with acute diarrhea, zinc supplementation results in clinically important reductions in the duration and severity of diarrhea.