Efficacy of Oral Zinc Supplementation in Radiologically Confirmed Pneumonia: Secondary Analysis of a Randomized Controlled Trial.

Objective: To evaluate the effect of zinc as an adjuvant therapy in radiologically confirmed pneumonia in children 2-24 months of age. Patients and Methods: We analyzed data of 212 children with pneumonia for whom chest X-ray films were available at enrollment and at least two radiologists agreed on the diagnosis of pneumonia. We compared the time to recovery in the two groups (n = 121, zinc group and n = 91, placebo group) using a Cox proportional hazards regression model. Results: Time to recovery was similar in both groups [median interquartile range: zinc, 84 h (64, 140 h); placebo, 85 h (65, 140 h)]. The absolute risk reduction for treatment failure was 5.2% (95% confidence interval: -4.8, 15.1) with zinc supplementation. Conclusion: There was no significant beneficial effect of zinc on the duration of recovery or risk of treatment failure in children with radiologically confirmed pneumonia.

An integrated nutrition and health program package on IYCN improves breastfeeding but not complementary feeding and nutritional status in rural northern India: A quasi-experimental randomized longitudinal study.

BACKGROUND: Undernutrition below two years of age remains a major public health problem in India. We conducted an evaluation of an integrated nutrition and health program that aimed to improve nutritional status of young children by improving breast and complementary feeding practices over that offered by the Government of India's standard nutrition and health care program. METHODS: In Uttar Pradesh state, through multi-stage cluster random sampling, 81 villages in an intervention district and 84 villages in a comparison district were selected. A cohort of 957 third trimester pregnant women identified during house-to-house surveys was enrolled and, following childbirth, mother-child dyads were followed every three months from birth to 18 months of age. The primary outcomes were improvements in weight-for-age and length-for-age z scores, with improved breastfeeding and complementary feeding practices as intermediate outcomes. FINDINGS: Optimal breastfeeding practices were higher among women in intervention than comparison areas, including initiating breastfeeding within one hour of delivery (17.4% vs. 2.7%, p<0.001), feeding colostrum (34.7% vs. 8.4%, p<0.001), avoiding pre-lacteals (19.6% vs. 2.1%, p<0.001) and exclusively breastfeeding up to 6 months (24.1% vs. 15.3%, p = 0.001). However, differences were few and mixed between study arms with respect to complementary feeding practices. The mean weight-for-age z-score was higher at 9 months (-2.1 vs. -2.4, p = 0.0026) and the prevalence of underweight status was lower at 12 months (58.5% vs. 69.3%, p = 0.047) among intervention children. The prevalence of stunting was similar between study arms at all ages. Coefficients to show the differences between the intervention and comparison districts (0.13 cm/mo) suggested significant faster linear growth among intervention district infants at earlier ages (0-5 months). INTERPRETATION: Mothers participating in the intervention district were more likely to follow optimal breast, although not complementary feeding practices. The program modestly improved linear growth in earlier age and weight gain in late infancy. Comprehensive nutrition and health interventions are complex; the implementation strategies need careful examination to improve feeding practices and thus impact growth. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, NCT00198835.

Global action plan for childhood diarrhoea: Developing research priorities: Report from a Workshop of the Programme for Global Paediatric Research.

BACKGROUND: Childhood diarrhoea remains a major public health problem responsible for the deaths of approximately 800 000 children annually, worldwide. The present study was undertaken to further define research priorities for the prevention and treatment of diarrhoea in low and middle income countries. We used the Child Health and Nutrition Research Initiative (CHNRI) process for defining research priorities. This provided a transparent, systematic method of obtaining the opinions of experts regarding research priorities in childhood diarrhoea. The present report describes the deliberations of a workshop that reviewed these research priorities by stakeholders including colleagues from: government agencies, academic institutions, major funding agencies and non-governmental organizations. METHODS: The workshop included 38 participants, divided into four groups to consider issues in the categories of description, delivery, development and discovery. Each group received 20 to 23 questions/research priorities previously identified by the CHNRI process. Deliberations and conclusions of each group were summarized in separate reports that were further discussed in a plenary session including all workshop participants. RESULTS: THE REPORTS OF THE WORKING GROUPS EMPHASIZED THE FOLLOWING FIVE KEY POINTS: 1) A common theme was the need to substantially increase the use of oral rehydration salts (ORS) and zinc in the prevention and treatment of diarrhoea. There is a need for better definitions of those factors that supported and interfered with the use of these agents; 2) There is an urgent need to determine the long-term effects of chronic and recurrent bouts of diarrhoea on the physical and intellectual development of affected children; 3) Improvements in water, sanitation and hygiene facilities are critical steps required to reduce the incidence and severity of childhood diarrhoea; 4)Risk factors enhancing the susceptibility and clinical response to diarrhoea were explored; implementation research of modifiable factors is urgently required; 5) More research is required to better understand the causes and pathophysiology of various forms of enteropathy and to define the methods and techniques necessary for their accurate study. CONCLUSIONS: The participants in this workshop determined that use of the CHNRI process had successfully defined those research priorities necessary for the study of childhood diarrhoea. The deliberations of the workshop brought these research priorities to the attention of stakeholders responsible for the implementation of the recommendations. It was concluded that the deliberations of the workshop positively supplemented the research priorities developed by the CHNRI process.

Efficacy of zinc given as an adjunct in the treatment of severe and very severe pneumonia in hospitalized children 2-24 mo of age: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Pneumonia is a leading cause of death; in India, an estimated 370,000 children die of pneumonia each year. Zinc has multiple influences on the immune response to infections. Zinc supplementation has been shown to prevent diarrhea and pneumonia in children. However, zinc's therapeutic effect on respiratory infections is less clear. OBJECTIVE: We evaluated the role of zinc as an adjunct to antibiotics in the treatment of children hospitalized for severe or very severe pneumonia. DESIGN: In this randomized, double-blind, placebo-controlled trial, we enrolled 550 children aged 2-24 mo with severe or very severe pneumonia. Within each hospital and pneumonia-severity stratum, children were randomly assigned to receive zinc (20 mg elemental zinc/d) or a placebo in addition to antibiotics and supportive care. RESULTS: The time to recovery from severe or very severe pneumonia was similar in both groups (HR: 0.98; 95% CI: 0.82, 1.17). In the stratified analysis, zinc was shown to be efficacious in reducing the time to recovery in children with very severe pneumonia (HR: 1.52; 95% CI: 1.03, 2.23); however, the effect was no longer statistically significant after adjustment for differences in severely underweight children in the 2 groups. CONCLUSIONS: This study showed no overall benefit of the addition of zinc to antibiotics in reducing the time to recovery from pneumonia but showed a possible benefit of zinc supplementation in a subgroup of children with very severe pneumonia. Additional research is needed in specific subgroups such as children with very severe pneumonia. This trial was registered at http://www.controlled-trials.com as ISRCTN48954234.

Progress and barriers for the control of diarrhoeal disease.

Discovery of intestinal sodium-glucose transport was the basis for development of oral rehydration solution, and was hailed as potentially the most important medical advance of the 20th century. Before widespread use of oral rehydration solution, treatment for diarrhoea was restricted to intravenous fluid replacement, for which patients had to go to a health-care facility to access appropriate equipment. These facilities were usually neither available nor reasonable to use in the resource-poor settings most affected by diarrhoea. Use of oral rehydration solution has stagnated, despite being effective, inexpensive, and widely available. Thus, diarrhoea continues to be a leading cause of child death with consistent mortality rates during the past 5 years. New methods for prevention, management, and treatment of diarrhoea-including an improved oral rehydration formulation, zinc supplementation, and rotavirus vaccines-make now the time to revitalise efforts to reduce diarrhoea mortality worldwide.

Cost-effectiveness of skin-barrier-enhancing emollients among preterm infants in Bangladesh.

OBJECTIVE: To evaluate the cost-effectiveness of topical emollients, sunflower seed oil (SSO) and synthetic Aquaphor, versus no treatment, in preventing mortality among hospitalized preterm infants (< 33 weeks gestation) at a tertiary hospital in Bangladesh. METHODS: Evidence from a randomized controlled efficacy trial was evaluated using standard Monte Carlo simulation. Programme costs were obtained from a retrospective review of activities. Patient costs were collected from patient records. Health outcomes were calculated as deaths averted and discounted years of life lost (YLLs) averted. Results were deemed cost-effective if they fell below a ceiling ratio based on the per capita gross national income of Bangladesh (United States dollars, US$ 470). FINDINGS: Aquaphor and SSO were both highly cost-effective relative to control, reducing neonatal mortality by 26% and 32%, respectively. SSO cost US$ 61 per death averted and US$ 2.15 per YLL averted (I$ 6.39, international dollars, per YLL averted). Aquaphor cost US$ 162 per death averted and US$ 5.74 per YLL averted (I$ 17.09 per YLL averted). Results were robust to sensitivity analysis. Aquaphor was cost-effective relative to SSO with 77% certainty: it cost an incremental US$ 26 more per patient treated, but averted 1.25 YLLs (US$ 20.74 per YLL averted). CONCLUSION: Topical therapy with SSO or Aquaphor was highly cost-effective in reducing deaths from infection among the preterm neonates studied. The choice of emollient should be made taking into account budgetary limitations and ease of supply. Further research is warranted on additional locally available emollients, use of emollients in community-based settings and generalizability to other geographic regions.

Impact of clean delivery-kit use on newborn umbilical cord and maternal puerperal infections in Egypt.

This cross-sectional cohort study explored the impact of the use of clean delivery-kit (CDK) on morbidity due to newborn umbilical cord and maternal puerperal infections. Kits were distributed from primary-care facilities, and birth attendants received training on kit-use. A nurse visited 334 women during the first week postpartum to administer a structured questionnaire and conduct a physical examination of the neonate and the mother. Results of bivariate analysis showed that neonates of mothers who used a CDK were less likely to develop cord infection (p = 0.025), and mothers who used a CDK were less likely to develop puerperal sepsis (p = 0.024). Results of multiple logistic regression analysis showed an independent association between decreased cord infection and kit-use [odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.18-0.97, p = 0.041)]. Mothers who used a CDK also had considerably lower rates of puerperal infection (OR = 0.11, 95% CI 0.01-1.06), although the statistical strength of the association was of borderline significance (p = 0.057). The use of CDK was associated with reductions in umbilical cord and puerperal infections.

Practices of rural Egyptian birth attendants during the antenatal, intrapartum and early neonatal periods.

Neonatal deaths account for almost two-thirds of infant mortality worldwide; most deaths are preventable. Two-thirds of neonatal deaths occur during the first week of life, usually at home. While previous Egyptian studies have identified provider practices contributing to maternal mortality, none has focused on neonatal care. A survey of reported practices of birth attendants was administered. Chi-square tests were used for measuring the statistical significance of inter-regional differences. In total, 217 recently-delivered mothers in rural areas of three governorates were interviewed about antenatal, intrapartum and postnatal care they received. This study identified antenatal advice of birth attendants to mothers about neonatal care and routine intrapartum and postpartum practices. While mothers usually received antenatal care from physicians, traditional birth attendants (dayas) conducted most deliveries. Advice was rare, except for breastfeeding. Routine practices included hand-washing by attendants, sterile cord-cutting, prompt wrapping of newborns, and postnatal home visits. Suboptimal practices included lack of disinfection of delivery instruments, unhygienic cord care, lack of weighing of newborns, and lack of administration of eye prophylaxis or vitamin K. One-third of complicated deliveries occurred at home, commonly attended by relatives, and the umbilical cord was frequently pulled to hasten delivery of the placenta. In facilities, mothers reported frequent use of forceps, and asphyxiated neonates were often hung upside-down during resuscitation. Consequently, high rates of birth injuries were reported. Priority areas for behaviour change and future research to improve neonatal health outcomes were identified, specific to type of provider (physician, nurse, or daya) and regional variations in practices.

Effect of skin barrier therapy on neonatal mortality rates in preterm infants in Bangladesh: a randomized, controlled, clinical trial.

OBJECTIVE: Skin barrier therapy during the neonatal period, when the skin barrier is most highly compromised and the risk of death is greatest, has been shown to have a number of potential benefits, including reduced risk of nosocomial sepsis. Topical application of emollients that augment skin barrier function was evaluated as a strategy for improving survival rates among hospitalized preterm infants in Bangladesh. METHODS: A prospective, randomized, controlled, clinical trial was conducted in the special care nursery at Dhaka Shishu (Children) Hospital, the largest tertiary care children's hospital in Bangladesh. Preterm infants (gestational age: < or = 33 weeks; N = 497) received daily topical applications of sunflower seed oil or Aquaphor ointment. Neonatal mortality rates were compared in an intent-to-treat analysis with a control group that did not receive emollient therapy. RESULTS: Treatment with sunflower seed oil resulted in a statistically significant 26% reduction in mortality rates, compared with infants not receiving topical emollient therapy. Aquaphor therapy also significantly reduced mortality rates, by 32%. CONCLUSIONS: Topical therapy with skin barrier-enhancing emollients improved survival rates among preterm hospitalized infants in Bangladesh. This study provides strong evidence for the implementation of topical therapy for high-risk preterm neonates in developing countries.

Direct detection of the multidrug resistance genome of Haemophilus influenzae in cerebrospinal fluid of children: implications for treatment of meningitis.

BACKGROUND: Multidrug resistance (MDR), specifically to ampicillin and chloramphenicol, has complicated the treatment of Haemophilus influenzae type b (Hib) meningitis. This is worsened by use of prior antibiotics, which limits identification of the causative agent by culture and increases reliance on antigen detection. OBJECTIVE: We aimed to develop a PCR assay for detecting the family of Haemophilus integrating and conjugative elements (ICEs) represented by ICEHin1056 among antibiotic resistant Hib, and then apply this directly to CSF to diagnose Hib meningitis and predict organism susceptibility, irrespective of culture results. STUDY DESIGN: Primers specific for orf 51 of ICEHin1056 were designed and multiplexed with Bex primers, specific for H. influenzae, and tested on culture positive and negative cases. RESULTS: Of 73 Hib isolates, orf 51 PCR amplicons, predicting the presence of ICEs, were found in all 33 MDR isolates while only in 1 of 33 sensitive strains. The remaining 7 ampicillin susceptible, chloramphenicol and tetracycline resistant strains did not produce a PCR product to orf 51. PCR amplification from CSF specimens of these culture positive cases produced identical results with 100% and 97% positive and negative predictive values, respectively. Multiplex PCR to detect Bex and orf 51 identified another 16 MDR Hib cases among 81 culture-negative CSF samples. CONCLUSIONS: Direct PCR for orf 51 in CSF identified resistance pattern of 51% more Hib strains than culture alone (110 versus 73). The ability to detect MDR, in culture negative Hib meningitis cases has significant implications for better directing antibiotic treatment of meningitis cases and thus for preventing disability and death.

Acceptability of massage with skin barrier-enhancing emollients in young neonates in Bangladesh.

Oil massage of newborns has been practised for generations in the Indian sub-continent; however, oils may vary from potentially beneficial, e.g. sunflower seed oil, to potentially toxic, e.g. mustard oil. The study was carried out to gain insights into oil-massage practices and acceptability of skin barrier-enhancing emollients in young, preterm Bangladeshi neonates. Preterm infants of <33 weeks gestational age were randomized to high-linoleate sunflower seed oil, Aquaphor Original Emollient Ointment, or the comparison group (usual care). A survey was administered at admission to assess routine skin-care practices prior to admission and at discharge to assess acceptability of emollient therapy during hospitalization. Oil massage was given to 83 (21%) of 405 babies before hospital admission, 86% (71/83) of whom were delivered at home. Application of oil, most commonly mustard oil (88%, 73/83), was started within one hour of birth in 51 cases (61%) and was applied all over the body (89%, 74/83) one to six (mean 2.2) times before admission. Of infants who received emollient therapy in the hospital, 42% (n=32) of mothers reported that the emollient applied in the hospital was better than that available at home, and only 29% would use the same oil (i.e. mustard oil) in the future as used previously at home. No problems resulted from use of emollient in the hospital. Topical therapy with sunflower seed oil or Aquaphor was perceived by many families to be superior to mustard oil. If caregivers and health professionals can be motivated to use inexpensive, available emollients, such as sunflower seed oil that are beneficial, emollient therapy could have substantial public-health benefit.

Infectious etiology modifies the treatment effect of zinc in severe pneumonia.

BACKGROUND: Zinc is undergoing evaluation as an inexpensive therapeutic adjuvant for severe pediatric pneumonia. OBJECTIVE: We explored the effect of etiology on the treatment effect of zinc in young children hospitalized for severe pneumonia. DESIGN: We analyzed data from a randomized, double-blind, placebo-controlled clinical trial conducted at the Christian Medical College Hospital, a teaching hospital in Tamilnadu, India. Children aged 2-23 mo (n = 299) were randomly assigned to receive a 10-mg tablet of zinc sulfate or placebo twice a day during hospitalization. The primary outcomes were length of hospitalization and time to resolution of severe pneumonia stratified by etiologic classification on the basis of serum C-reactive protein (CRP) concentrations at admission. RESULTS: CRP concentrations were available for 295 (98.7%) of the enrolled cases. Of these 295 cases, 223 (75.6%) were classified as suspected nonbacterial pneumonias (CRP concentrations 40 mg/L), the median length of hospitalization was approximately 20 h longer in the zinc-supplemented group than in the placebo group (87.3 and 68.3 h, respectively; HR: 0.56; 95% CI: 0.34, 0.93; P = 0.025). The treatment effect was not modified in the suspected nonbacterial cases of pneumonia. CONCLUSIONS: Our results suggest that the treatment effect of zinc for severe pediatric pneumonia may be modified by bacterial infection. Further studies are required to develop appropriate recommendations for the use of zinc in the treatment of severe pneumonia. This trial was registered at clinicaltrials.gov as NCT00198666.

Immunization with the heptavalent pneumococcal conjugate vaccine in Bangladeshi infants and effects of zinc supplementation.

BACKGROUND: Zinc deficiency is known to impair immunologic functions. However, the effect of zinc supplementation on immune response to polysaccharide vaccines is not known. OBJECTIVE: To determine the immunogenicity of the heptavalent Pneumococcal protein conjugate (PNC) vaccine in poor Bangladeshi infants and to assess the effect of zinc supplementation on immune response to the PNC vaccine. DESIGN: We immunized a sub-cohort of 241 infants who had previously received three doses of a Hib conjugate vaccine with three doses of the heptavalent PNC vaccine at 4 weeks intervals beginning at 18+/-1 weeks of age. The infants were supplemented with daily 5 mg zinc or placebo from 4 to 33 weeks of age. Response to each of the seven PNC serotypes were assessed at 4, 24 and 33 weeks of age. RESULTS: After three doses of PNC, at 29 weeks of age, geometric mean titres for the pneumococcal serotypes ranged from 3.68 to 13.34 microg/ml. Titres were significantly higher for infants who had received PNC compared to infants who had only received DTP-Hib. Zinc supplementation resulted in higher titres for serotype 9V (4.09 microg/ml; [95% CI: 3.27; 5.10] and 3.33 microg/ml; [95% CI: 2.79; 3.96] for zinc and placebo group, respectively; p<0.05) after three doses but had no effect on other serotypes. CONCLUSIONS: A heptavalent PNC vaccine proved to be safe and immunogenic in Bangladeshi infants. Zinc supplementation enhanced the immune response to only one of the serotypes (9V). However, there was no effect on other serotypes.

Efficacy of zinc in the treatment of severe pneumonia in hospitalized children <2 y old.

BACKGROUND: Severe pneumonia remains a leading cause of morbidity and mortality in undernourished young children in developing countries. OBJECTIVE: This study evaluated the effect of adjuvant zinc therapy on recovery from severe pneumonia by hospitalized children in southern India who were receiving standard antibiotic therapy. DESIGN: This randomized, double-blind, placebo-controlled clinical trial was conducted at the Christian Medical College Hospital, an 1800-bed teaching hospital in Tamilnadu, India. Enrollment and follow-up occurred between September 2003 and August 2004. Children aged 2-23 mo (n = 299) who were hospitalized with severe pneumonia were randomly assigned to receive 10-mg tablets of zinc sulfate or placebo twice a day during hospitalization, along with standard therapy for severe pneumonia. All clinical signs and symptoms of pneumonia were assessed and recorded at 8-h intervals. RESULTS: There were no clinical or statistically significant differences in the duration of tachypnea, hypoxia, chest indrawing, inability to feed, lethargy, severe illness, or hospitalization. Zinc supplementation was associated with a significantly longer duration of pneumonia in the hot season (P = 0.015). CONCLUSIONS: Zinc supplementation had no overall effect on the duration of hospitalization or of clinical signs associated with severe infection in young children hospitalized for severe pneumonia in southern India. This finding differs from the results of 2 previously reported trials wherein zinc supplementation was associated with a shorter period of recovery from severe pneumonia. Given the conflicting results, further research in representative settings is required to help clarify the role of zinc in the treatment of severe pneumonia.

The effect of zinc supplementation during pregnancy on immune response to Hib and BCG vaccines in Bangladesh.

An essential role for zinc in development of the fetal immune system has been documented. However, the effect of antenatal zinc supplementation on infants' postnatal immune response to vaccinations is unknown. The objective of this study was to evaluate the effect of zinc supplementation during pregnancy on immune response to the Bacillus Calmette-Guerin (BCG) vaccine and the Haemophilus influenzae type b (Hib) component of the combined diphtheria, tetanus toxoid and pertussis (DTP)-Haemophilus influenzae type-b (Hib)- conjugate vaccine in poor Bangladeshi infants. We immunized 405 infants whose mothers were supplemented daily with 30 mg elemental zinc or placebo beginning at 12-16 weeks gestation with the standard BCG vaccine at birth. A subcohort of 203 infants were in addition immunized at 1-month intervals with three doses of DTP-Hib vaccine starting at 9 weeks of age. The delayed hypersensitivity (PPD) skin test was performed in 345 infants at 24 weeks of age. Hib polysaccharide (PRP) antibodies were assessed for 91 infants at 4 and 24 weeks of age. In infants born with low birth weight (LBW) a lower proportion of negative responses to PPD skin test were observed in the zinc (66.2%) compared to placebo (78.5%) group (p = 0.07). No differences were observed in normal birth weight infants. There were no differences in proportion of infants above the protective thresholds for anti-PRP antibodies between zinc (81%) and placebo (89%) group. Geometric mean PRP antibody titres at 4 and 24 weeks of age were not different between groups. Zinc supplementation during pregnancy did not enhance immune response to Hib-conjugate vaccine but there was a suggestion of improved delayed hypersensitivity immune responses to BCG-vaccine in Bangladeshi LBW infants.

Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: randomised controlled trial.

BACKGROUND: Pneumonia and diarrhoea cause much morbidity and mortality in children younger than 5 years. Most deaths occur during infancy and in developing countries. Daily regimens of zinc have been reported to prevent acute lower respiratory tract infection and diarrhoea, and to reduce child mortality. We aimed to examine whether giving zinc weekly could prevent clinical pneumonia and diarrhoea in children younger than 2 years. METHODS: 1665 poor, urban children aged 60 days to 12 months were randomly assigned zinc (70 mg) or placebo orally once weekly for 12 months. Children were assessed every week by field research assistants. Our primary outcomes were the rate of pneumonia and diarrhoea. The rates of other respiratory tract infections were the secondary outcomes. Growth, final serum copper, and final haemoglobin were also measured. Analysis was by intention to treat. FINDINGS: 34 children were excluded before random assignment to treatment group because they had tuberculosis. 809 children were assigned zinc, and 812 placebo. After treatment assignment, 103 children in the treatment group and 44 in the control group withdrew. There were significantly fewer incidents of pneumonia in the zinc group than the control group (199 vs 286; relative risk 0.83, 95% CI 0.73-0.95), and a small but significant effect on incidence of diarrhoea (1881 cases vs 2407; 0.94, 0.88-0.99). There were two deaths in the zinc group and 14 in the placebo group (p=0.013). There were no pneumonia-related deaths in the zinc group, but ten in the placebo group (p=0.013). The zinc group had a small gain in height, but not weight at 10 months compared with the placebo group. Serum copper and haemoglobin concentrations were not adversely affected after 10 months of zinc supplementation. INTERPRETATION: 70 mg of zinc weekly reduces pneumonia and mortality in young children. However, compliance with weekly intake might be problematic outside a research programme.

Efficacy of zinc in young infants with acute watery diarrhea.

BACKGROUND: Recent studies reported that zinc significantly reduced the duration and volume of acute watery diarrhea in children aged > or = 4 mo, but there were no data specifically on infants aged < 6 mo. OBJECTIVE: This study investigated the effect of zinc on the duration of illness and the stool quantity in acute watery diarrhea of infants aged 1-6 mo by comparing a 20 mg Zn/d dose with a 5 mg Zn/d dose. DESIGN: Infants hospitalized with at least some dehydration (by World Health Organization classification) were enrolled in a double-blind, randomized, placebo-controlled trial. Infants were randomly assigned to receive 20 mg Zn (acetate)/d, 5 mg Zn/d, or placebo for the duration of illness. RESULTS: Two hundred seventy-five infants were enrolled between 20 September 1998 and 18 December 2000. Neither diarrhea duration nor mean stool volume differed between groups. There were no significant differences in fluid intake, the need for unscheduled intravenous fluid, weight gain, or vomiting rates between the groups. CONCLUSIONS: Zinc supplementation did not affect diarrhea duration or stool volume in young infants. Young infants tolerated both zinc doses. A beneficial effect on subsequent illness cannot be ruled out.

Effect of topical treatment with skin barrier-enhancing emollients on nosocomial infections in preterm infants in Bangladesh: a randomised controlled trial.

BACKGROUND: Infections and complications of prematurity are main causes of neonatal mortality. Very low birthweight premature infants have compromised skin barrier function, and are at especially high risk for serious infections and mortality. Our aim was to ascertain whether topical application of emollients to enhance skin barrier function would prevent nosocomial infections in this population. METHODS: We randomly assigned infants born before week 33 of gestation after admission to Dhaka Shishu Hospital, Bangladesh, to daily massage with sunflower seed oil (n=159) or Aquaphor (petrolatum, mineral oil, mineral wax, lanolin alcohol; n=157). We then compared incidence of nosocomial infections among infants in these two groups with an untreated control group (n=181) by an intention-to-treat analysis. FINDINGS: 20 patients in the control group, and 22 in each of the treatment groups left the hospital early, but were included in the final analysis. Overall, infants treated with sunflower seed oil were 41% less likely to develop nosocomial infections than controls (adjusted incidence rate ratio [IRR] 0.59, 95% CI 0.37-0.96, p=0.032). Aquaphor did not significantly reduce the risk of infection (0.60, 0.35-1.03, p=0.065). No adverse events were seen. INTERPRETATION: Our findings confirm that skin application of sunflower seed oil provides protection against nosocomial infections in preterm very low birthweight infants. The low cost, availability, simplicity, and effect of treatment make it an important intervention for very low birthweight infants admitted to hospital in developing countries.

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 hospital's 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.

Zinc therapy for diarrhoea increased the use of oral rehydration therapy and reduced the use of antibiotics in Bangladeshi children.

Excessive use of antibiotics for diarrhoea is a major contributing factor towards increasing rates of antimicrobial resistance in developing countries. Zinc therapy for diarrhoea has been shown to be beneficial in controlled efficacy trials, and it is of interest to determine if availability of zinc syrup for treatment of diarrhoea would satisfy the demand for a 'medicine' for diarrhoea, thus reducing the use of antibiotics, without competing with the use of oral rehydration therapy (ORT). This community-based controlled trial was conducted from November 1998 to October 2000, and all children aged 3-59 months in the study area were included. In this trial, the availability of zinc supplements, along with ORT and appropriate education programmes, was associated with significantly higher use of ORT and lower use of antibiotics.