Wasting time for wasted children: severe child undernutrition must be resolved in non-emergency settings.
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Child, Preschool↗
Biomedical subjects
Rainer Gross
Publications and source records attributed to Rainer Gross.
Micronutrient supplementation in pregnancy.
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Albendazole↗
Zinc deficiency: what are the most appropriate interventions?
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Diet↗
The International Research on Infant Supplementation initiative.
The International Research on Infant Supplementation trials emerged as an attempt to develop a credible evidence base to guide policy decision making in this area. The fact that infant diets in developing country settings are more often deficient in multiple micronutrients rather than in single nutrients and/or energy was increasingly recognized during the 1990s. The concept of a "foodlet," a crushable hybrid between a tablet and a food that is water dispersible, was developed at the first IRIS meeting in Rio de Janeiro in 1999. Trials were performed in 4 countries: Indonesia, Peru, South Africa, and Vietnam. Four different formulations of foodlets were tested: a daily placebo supplement, a daily iron supplement, a daily multiple micronutrient supplement, and a weekly multiple micronutrient supplement with a placebo on the other 6 d. The multiple micronutrient foodlets contained adequate daily intakes of 13 micronutrients considered most likely to be inadequate in infant diets. The foodlets were produced in Peru and distributed to all 4 of the country study sites. The methods used in the efficacy trials were standardized across countries, and the trials were carried out in infants 6-11 mo of age for 6 mo. Anthropometry was measured monthly and morbidity checked daily. Blood samples were collected at baseline and at the end of the trial. The data and the biological samples collected in each country were analyzed centrally. The results of this remarkable international collaboration are encouraging and, hopefully, will spur the development of programs in this area of nutrition interventions.
Copper↗
Efficacy of a foodlet-based multiple micronutrient supplement for preventing growth faltering, anemia, and micronutrient deficiency of infants: the four country IRIS trial pooled data analysis.
Diets of infants across the world are commonly deficient in multiple micronutrients during the period of growth faltering and dietary transition from milk to solid foods. A randomized placebo controlled trial was carried out in Indonesia, Peru, South Africa, and Vietnam, using a common protocol to investigate whether improving status for multiple micronutrients prevented growth faltering and anemia during infancy. The results of the pooled data analysis of the 4 countries for growth, anemia, and micronutrient status are reported. A total of 1134 infants were randomized to 4 treatment groups, with 283 receiving a daily placebo (P), 283 receiving a weekly multiple micronutrient supplement (WMM), 280 received a daily multiple micronutrient (DMM) supplement, and 288 received daily iron (DI) supplements. The DMM group had a significantly greater weight gain, growing at an average rate of 207 g/mo compared with 192 g/mo for the WMM group, and 186 g/mo for the DI and P groups. There were no differences in height gain. DMM was also the most effective treatment for controlling anemia and iron deficiency, besides improving zinc, retinol, tocopherol, and riboflavin status. DI supplementation alone increased zinc deficiency. The prevalence of multiple micronutrient deficiencies at baseline was high, with anemia affecting the majority, and was not fully controlled even after 6 mo of supplementation. These positive results indicate the need for larger effectiveness trials to examine how to deliver supplements at the program scale and to estimate cost benefits. Consideration should also be given to increasing the dosages of micronutrients being delivered in the foodlets.
Anemia↗
Multiple micronutrient supplements improve micronutrient status and anemia but not growth and morbidity of Indonesian infants: a randomized, double-blind, placebo-controlled trial.
Multiple micronutrient deficiencies are highly prevalent in Indonesia, but the interventions are still focused on single micronutrients. This study aimed to investigate the efficacy of multiple micronutrient supplements for improving micronutrient status, anemia, growth, and morbidity of Indonesian infants. In this double-blind, placebo-controlled trial, 284 infants aged 6-12 mo were randomly allocated to 4 treatment groups for 23 wk; 260 (92%) infants completed the study. Group 1 (DMM) received one adequate intake of multiple micronutrient supplements daily (n = 66); group 2 (WMM) received 2 adequate intakes of multiple micronutrient on 1d plus 6 d of placebo (n = 60); group 3 (DI) received 10 mg of iron supplement daily (n = 69); group 4 received a placebo supplement daily (n = 65). Blood samples were collected at baseline and at posttreatment to assess anemia and micronutrient status. Anthropometric measurements were taken monthly, and morbidity was recorded daily. At baseline, 58.1% of infants were anemic, 34.2% were iron deficient, 21.3% were vitamin A deficient, and 11% were zinc deficient. The DMM and DI supplements both corrected iron deficiency, but DMM supplements were more efficacious in improving hemoglobin levels of anemic infants than the other supplements. However, anemia still persisted in one-third of DMM infants posttreatment. The DMM supplement was more efficacious than WMM or DI supplementation in improving infant status of other micronutrients, including zinc, tocopherol, and riboflavin, whereas DI exacerbated zinc deficiency. There were no significant differences in growth and morbidity among treatment groups, and growth faltering was not prevented.
Anemia↗
Efficacy of multiple micronutrient supplementation for improving anemia, micronutrient status, growth, and morbidity of Peruvian infants.
Anemia, micronutrient deficiencies, and growth faltering are still common in Peru. The study objective was to determine the efficacy of different micronutrient supplements in preventing growth failure, anemia, and micronutrient deficiencies in Peruvian infants. Three hundred and thirteen infants aged 6 to 12 mo participated in a double-blind, masked, controlled trial in which they were randomly assigned to receive either a daily dose of iron (DI), a daily dose of multiple micronutrients (DMM), a weekly dose of multiple micronutrients, or a placebo (P) for 6 mo. None of the supplements tested prevented growth faltering or the morbidities common during infancy. Anemia and plasma homocysteine concentrations fell significantly in all groups during the study, but the mean change of plasma homocysteine during the trial period was significantly smaller in the DI group than in other groups, and the increase in hemoglobin concentrations was smaller in the P group than the micronutrient treatment groups. Plasma ferritin concentrations decreased least in the groups taking daily micronutrient supplements containing iron (DI and DMM). There were no significant differences among groups in mean final values or changes in plasma zinc, retinol, tocopherol, or riboflavin. Although the DMM intervention was the most efficacious for preventing anemia, iron, and zinc deficiencies, 15%, 20%, and 50% of this group still remained anemic, zinc deficient, and iron deficient, respectively, at the end of the study. Further research thus should investigate whether higher doses of iron and zinc, together with infection control measures, are more efficacious.
Adult↗
Efficacy of multiple micronutrient supplementation for improving anemia, micronutrient status, and growth in South African infants.
Growth faltering, anemia, and multiple micronutrient deficiency are common during infancy in developing countries. This South African trial was part of a multicenter study aimed at testing the efficacy of multiple micronutrient supplementation on growth, anemia, micronutrient status, and morbidity during infancy across 4 countries. A total of 265 infants aged 6-12 mo were individually randomized to 1 of 4 intervention groups: a daily multiple micronutrient supplement (DMM), a daily placebo supplement (P); a multiple micronutrient supplement 1 d of the week and placebo supplement on the other days of the week (WMM), and a daily iron supplement (DI). For 6 mo, the blinded supplements were provided to mothers at monthly health clinic sessions, and consumption was verified during weekly household visits by community health workers, when morbidity was also checked. Weight and height of the infants were measured monthly, and blood samples were taken at the beginning and at the end for assessing the infants micronutrient status. There were no significant differences in nutritional status of the groups at baseline with 40% of infants with anemia (hemoglobin < 110 g/L), 16% vitamin A deficiency (plasma retinol < 0.7 micromol/L), 47% zinc deficiency (plasma zinc < 10.7 micromol/L), 2% underweight, and 11% stunting. There was no difference in growth or morbidity between the micronutrient supplemented groups and the P group during the 6-mo study. The DMM was the most effective intervention tested, not only for improving anemia but also for improving iron, zinc, riboflavin, and tocopherol status.
Adult↗
Milk fortified with iron or iron supplementation to improve nutritional status of pregnant women: an intervention trial from rural Vietnam.
Anemia is still the major nutritional problem among pregnant women in Southeast Asia. The objective of this study was to measure hemoglobin status and reduction of underweight in a group of pregnant women who received iron-fortified or nonfortified milk, and another group who received iron supplements (tablets) or placebo. The 44 women in the iron-fortified milk group received 15 mg of iron per day per 400 ml of milk, and 41 women received placebo. The 40 women in the iron supplement group received 60 mg of iron per day, and 43 women received nonfortified milk. During this intervention trial, all women were supervised from the 14th to the 18th week of gestation until delivery. Blood was sampled at 0, 5, 10, and 16 weeks of intervention. After the 16th week of intervention, the changes in hemoglobin (deltaHb) concentrations in both treatment groups (the iron-fortified milk and the iron tablet groups) were not significantly different (deltaHb: -0.5+/-0.9 and -0.3+/-0.9 g/L, respectively), but the changes were significantly greater in the nonfortified milk and placebo groups (deltaHb: -1.2+/-0.9 and -1.1+/-0.8 g/L, respectively; p < .01). The change in transferrin saturation (deltaTS) in the iron-fortified milk group (deltaTS: 3.4+/-12.9%) was greater than that in the placebo and nonfortified milk groups (deltaTS: -10.1+/-9.8% and -11.6+/-10.7 %, respectively) (p < .01). The weight gain of the subjects during intervention did not differ significantly in the fortified and nonfortified milk groups (delta weight: 5.0+/-2.0 and 5.8+/-2.1 kg, respectively), but was higher than in the iron tablet group (delta weight: 4.6+/-3.1 kg; p < .05) and the placebo group (delta weight: 3.8+/-2.5 kg; p < .001). Iron supplementation and fortification were seen to be effective in promoting weight gain in pregnant Vietnamese women. For women who are underweight, the administration of iron-fortified milk has additional benefits to those of supplementation, most likely due to additional energy and nutrient inputs.
Adult↗
Daily iron alone but not in combination with multimicronutrients increases plasma ferritin concentrations in indonesian infants with inflammation.
Iron deficiency is a public health problem in infancy. We assessed the efficacy of iron supplements in infants with inflammation on iron status and subsequent inflammation. This was a prospective, nested, case-control study of 6- to 12-mo-old infants participating in the International Research on Infant Supplementation study, Indonesia. Cases (n = 46) were selected on the basis of their inflammation status at baseline, C-reactive protein (>5 mg/L) or alpha-1 acid glycoprotein (>1 g/L); there were 44 controls without inflammation. Infants received 10 mg/d of elemental iron alone or in combination with multimicronutrients, or placebo. Blood samples were collected at baseline and at 6 mo for determinations of plasma ferritin, zinc, copper, retinol, beta-carotene, alpha-tocopherol, and inflammation status. Data on breast-feeding and acute respiratory infections (ARI) were collected daily. At baseline, 33% of infants had iron deficiency, and those with inflammation had lower retinol, beta-carotene, higher concentrations of copper and higher rates of ARI compared with controls. After 6 mo, compared with infants given placebo, ferritin concentration increased significantly in infants administered iron alone independently of inflammation status at baseline or at the end of the study. In those given multimicronutrients with iron, ferritin increased significantly in infants who did not have inflammation at baseline or at the end of the study compared with those given placebo. Consequently, iron alone resolved iron deficiency, whereas multimicronutrients reduced the deterioration of iron stores compared with placebo (chi(2), P < 0.05), without enhancing inflammation. Iron alone is recommended in populations in which iron deficiency is a public health problem despite the presence of inflammation in infants who are still breast-feeding.
Acute-Phase Proteins↗
Moxifloxacin and glucose homeostasis: a pooled-analysis of the evidence from clinical and postmarketing studies.
BACKGROUND: Recently, clinical data has emerged suggesting that the fluoroquinolone, gatifloxacin, can affect glucose homeostosis through an unknown mechanism. In order to explore the potential effects of moxifloxacin on glucose metabolism in humans, a pooled analysis of phase II/III clinical trials and postmarketing studies was performed and compared with results from an investigation in laboratory animals. METHODS: A pooled analysis of 30 (26 controlled, 4 uncontrolled) oral and two intravenous/oral prospective, controlled phase II/III moxifloxacin studies was performed to evaluate the frequency of hyper- and hypoglycaemic episodes and glucose-related adverse events and adverse reactions (i.e. those considered to be drug related) versus comparator antimicrobials (penicillins, cephalosporins, macrolides, doxycycline, fluoroquinolones). Similar evaluations were conducted on data pooled from five postmarketing surveillance studies. In addition, potential effects of supratherapeutic doses of moxifloxacin on blood glucose and plasma insulin levels in fed and fasted rats were assessed in comparison with those of gatifloxacin, levofloxacin and glibenclamide (glyburide). RESULTS: The phase II/III database was comprised of 14,731 patients (8474 moxifloxacin, 6257 comparator antimicrobial). There were no drug-related hypoglycaemic adverse events reported for moxifloxacin in either the oral or intravenous/oral database. Two drug-related hypoglycaemic adverse events were reported in the oral comparator group, both following administration of levofloxacin and both of mild severity; one drug-related hypoglycaemic adverse event was reported in the intravenous/oral comparator group after trovafloxacin administration. Drug-related hyperglycaemic adverse events were reported in seven (<0.1%) moxifloxacin and 1 (<0.1%) comparator-treated patients in the oral study database, none of these cases were considered serious and six of the seven moxifloxacin cases were graded as mild and required no countermeasures. There were no cases of drug-related hyperglycaemic events in any patient enrolled in the intravenous/oral studies. Coadministration of oral antidiabetic drugs with moxifloxacin or comparator antimicrobials did not change the rate of blood glucose increases or decreases in diabetic patients. Data from five moxifloxacin postmarketing studies (46 130 subjects) reported no episodes of hypoglycaemia and two non-drug-related hyperglycaemic episodes. Data from animal studies revealed that supratherapeutic doses of moxifloxacin and levofloxacin did not affect blood glucose or plasma insulin levels in both fed and fasted rats, whereas gatifloxacin decreased both blood glucose and plasma insulin in a dose-dependent manner in fed rats only. The reference compound glibenclamide increased insulin and decreased glucose levels as expected. CONCLUSIONS: Hyperglycaemic or hypoglycaemic adverse reactions were reported rarely in studies with oral or sequential intravenous/oral moxifloxacin, and incidence was comparable in moxifloxacin and comparator groups. Changes in glucose metabolism were also similar in diabetic patients treated with moxifloxacin compared with those patients without diabetes mellitus. This comprehensive analysis of the datapool for moxifloxacin phase II/III clinical trials and postmarketing studies suggests that moxifloxacin administration has no clinically relevant effect on blood glucose homeostasis.
Animals↗
Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids.
Chronic hepatitis B virus (HBV) infection is a major cause of liver disease. Only interferon-alpha and the nucleosidic inhibitors of the viral polymerase, 3TC and adefovir, are approved for therapy. However, these therapies are limited by the side effects of interferon and the substantial resistance of the virus to nucleosidic inhibitors. Potent new antiviral compounds suitable for monotherapy or combination therapy are highly desired. We describe non-nucleosidic inhibitors of HBV nucleocapsid maturation that possess in vitro and in vivo antiviral activity. These inhibitors have potential for future therapeutic regimens to combat chronic HBV infection.
Acetylcysteine↗
Introduction to the proceedings of the International Research on Infant Supplementation (IRIS) Initiative.
In 2001, students and professionals from 13 nations were hosted by UNICEF for the International Workshop on Multi-Micronutrient Deficiency Control in the Life Cycle in Lima, Peru, May 30-June 1, 2001. Workshop participants engaged in both narrow and broad discussions of ways to combat multiple micronutrient deficiencies in developing countries. Preliminary data from four common-protocol studies conducted in Peru, South Africa, Indonesia, and Vietnam were presented. Participants also discussed the immediate, preliminary, and interim issues that could guide both policy and planning of future studies of multiple micronutrient deficiency. Among the studies highlighted was the International Research on Infant Supplementation (IRIS) I trial. A review of IRIS I yielded some confirmation of the efficacy using a crushable "foodlet" (i.e., cross between food and tablet) as a supplementation vehicle, as well as concerns about potential adverse consequences of nutrient-nutrient and nutrient-nutriture interactions. Other plenary topics illustrated the practical matters of how the IRIS I logistics and operations were built, and several focused on how to best design follow-up research on infant supplementation. Finally, a series of working groups allowed for in-depth discussions on the topics of community and policy, monitoring and implementation, and research. Researchers continue to try to identify efficient and effective programs suited to the low-income settings in which infant multi-micronutrient malnutrition occurs. The papers in these proceedings elaborate on several aspects of the IRIS study, and they are published in the hope that their analysis by readers will produce wider dissemination of the details of this devastating problem.
Child Nutrition Disorders↗
Bioavailability of iron, zinc, folate, and vitamin C in the IRIS multi-micronutrient supplement: effect of combination with a milk-based cornstarch porridge.
The effect of combining a multi-micronutrient supplement with a milk-based cornstarch porridge on the bioavailability of iron, zinc, folate, and vitamin C was evaluated using the plasma curve response over time (8 hours) in healthy women. Three tests were carried out in a crossover design: S (multi-micronutrient supplement), MS (multi-micronutrient supplement plustest meal), and M (test meal). Relative bioavailability was determined as the percent ratio of the area under the curve (AUC) in MS corrected by M, and AUC in S. Compared to S, AUC in MS was smaller for iron (p < .05), for zinc (p < .01), and for folate (p < .05), but not different for vitamin C. Relative bioavailability was lower (p < .05) than 100% for iron (80%), zinc (70%), and folate (85%). The decrease in bioavailability of these nutrients when the multi-micronutrient supplement is combined with a milk-based cornstarch porridge is small. Therefore, the tested meal is a suitable vehicle for the multi-micronutrient supplement.
Adult↗
IRIS. I: a FOODlet-based multiple-micronutrient intervention in 6- to 12-month-old infants at high risk of micronutrient malnutrition in four contrasting populations: description of a multicenter field trial.
Infants in developing countries are at risk of concurrent micronutrient deficiencies, because the same causative factors may lead to deficiencies of different micronutrients. Inadequate dietary intake is considered one of the major causes of micronutrient deficiencies, especially among poor and underprivileged children in developing countries. Operational strategies and distribution systems are often duplicated when supplementation programs for single micronutrients are implemented at the same time. The International Research on Infant Supplementation (IRIS) trial was conducted in four distinct populations on three continents: Africa, Latin America, and Asia. The participating countries were South Africa, Peru, Vietnam, and Indonesia. The study had a randomized, doubleblind, placebo-controlled design. Each country aimed to enroll at least 70 infants per intervention group (65 + 5 anticipated dropouts). The micronutrient vehicle was in the form of a "foodlet" (food-like tablet) manufactured as chewable tablets, which were easy to break and dissolve, and which had the same taste, color, and flavor for all countries. Children were randomly assigned to one of four 6-month intervention groups: group 1 received a daily foodlet containing multiple micronutrients; group 2 received a daily placebo foodlet containing no micronutrients; group 3 received a weekly foodlet that contained multiple micronutrients (twice the dose of the daily foodlet) and placebo foodlets on the other days of the week; group 4 received a daily foodlet containing only 10 mg of elemental iron. The IRIS Trial aimed to examine the prevalence of multi-micronutrient deficiencies in 6- to 12-month-old infants from rural populations, and to examine the efficacy of multi-micronutrient supplementation in infants from the different countries included in the study. This paper describes the general methodology of the IRIS trial and the operational differences among the country sites.
Biomarkers↗
IRIS. III: proposal of a multicenter efficacy study using a high-energy, micronutrient-dense spread.
There is an urgent need for the development of a high-energy, micronutrient-dense food, such as a spread, for clinical and emergency nutrition. The spread to be used in the International Research on Infant Supplementation (IRIS) III trial will contain carotene-rich palm oil as a source of vitamin A and energy, and heme iron from slaughterhouse blood as an iron source. All other micronutrients shall come from a pre-mix. The product shall be designed for young children, in particular, but can be consumed by adults, as well. An efficacy study will be conducted for six months in children 6 to 12 months old.
Carotenoids↗
Multiple micronutrient deficiencies: future research needs.
There has been a rising current of calls for a moratorium on international nutritional research in favor of an investment in intervention programs, per se. The topic of multiple-micronutrient supplementation reviewed at the International Workshop on Multi-Micronutrient Deficiency Control in the Life Cycle (May 30-June 1, 2001) has confirmed once again, however, the intimate interaction between program development and a supporting agenda of applied research. The areas of research required to produce successful intervention programs include biologic availability, safety and efficacy, communications and behavior, effectiveness, cost-effectiveness (efficiency), and food and pharmaceutical technology. Attention to safety and surveillance for unintended adverse effects has acquired new relevance as we analyze the multi-center International Research on Infant Supplementation (IRIS) I studies. All professionals involved in research projects in this area must assure both the quality and reliability of investigations and adhere to the highest principles of ethical conduct of research in human studies. The fundamental principles of research design and hypothesis development, quality assurance, reliability of measurements, and sound and unbiased interpretation of findings apply to all experimental science, and must be guaranteed for this mission. Agencies, academic institutions, and industry alike must work to create a system in which researchers can uphold these standards, and realize at the same time that the area of multi-micronutrient supplementation in developing countries can be a fertile area for training future researchers.
Cost-Benefit Analysis↗
A double-blind, placebo-controlled study of vitamin A and zinc supplementation in persons with tuberculosis in Indonesia: effects on clinical response and nutritional status.
BACKGROUND: The results of cross-sectional studies indicate that micronutrient deficiencies are common in patients with tuberculosis. No published data exist on the effect of vitamin A and zinc supplementation on antituberculosis treatment. OBJECTIVE: Our goal was to investigate whether vitamin A and zinc supplementation increases the efficacy of antituberculosis treatment with respect to clinical response and nutritional status. DESIGN: In this double-blind, placebo-controlled trial, patients with newly diagnosed tuberculosis were divided into 2 groups. One group (n = 40) received 1500 retinol equivalents (5000 IU) vitamin A (as retinyl acetate) and 15 mg Zn (as zinc sulfate) daily for 6 mo (micronutrient group). The second group (n = 40) received a placebo. Both groups received the same antituberculosis treatment recommended by the World Health Organization. Clinical examinations, assessments of micronutrient status, and anthropometric measurements were carried out before and after 2 and 6 mo of antituberculosis treatment. RESULTS: At baseline, 64% of patients had a body mass index (in kg/m(2)) < 18.5, 32% had plasma retinol concentrations < 0.70 micromol/L, and 30% had plasma zinc concentrations < 10.7 micromol/L. After antituberculosis treatment, plasma zinc concentrations were not significantly different between groups. Plasma retinol concentrations were significantly higher in the micronutrient group than in the placebo group after 6 mo (P < 0.05). Sputum conversion (P < 0.05) and resolution of X-ray lesion area (P < 0.01) occurred earlier in the micronutrient group. CONCLUSION: Vitamin A and zinc supplementation improves the effect of tuberculosis medication after 2 mo of antituberculosis treatment and results in earlier sputum smear conversion.
Adolescent↗