Engineered catalytic biofilms for continuous large scale production of n-octanol and (S)-styrene oxide.

This study evaluates the technical feasibility of biofilm-based biotransformations at an industrial scale by theoretically designing a process employing membrane fiber modules as being used in the chemical industry and compares the respective process parameters to classical stirred-tank studies. To our knowledge, catalytic biofilm processes for fine chemicals production have so far not been reported on a technical scale. As model reactions, we applied the previously studied asymmetric styrene epoxidation employing Pseudomonas sp. strain VLB120ΔC biofilms and the here-described selective alkane hydroxylation. Using the non-heme iron containing alkane hydroxylase system (AlkBGT) from P. putida Gpo1 in the recombinant P. putida PpS81 pBT10 biofilm, we were able to continuously produce 1-octanol from octane with a maximal productivity of 1.3 g L ⁻¹(aq) day⁻¹ in a single tube micro reactor. For a possible industrial application, a cylindrical membrane fiber module packed with 84,000 polypropylene fibers is proposed. Based on the here presented calculations, 59 membrane fiber modules (of 0.9 m diameter and 2 m length) would be feasible to realize a production process of 1,000 tons/year for styrene oxide. Moreover, the product yield on carbon can at least be doubled and over 400-fold less biomass waste would be generated compared to classical stirred-tank reactor processes. For the octanol process, instead, further intensification in biological activity and/or surface membrane enlargement is required to reach production scale. By taking into consideration challenges such as biomass growth control and maintaining a constant biological activity, this study shows that a biofilm process at an industrial scale for the production of fine chemicals is a sustainable alternative in terms of product yield and biomass waste production.

Characterization of a biofilm membrane reactor and its prospects for fine chemical synthesis.

Biofilms are known to be robust biocatalysts. Conventionally, they have been mainly applied for wastewater treatment, however recent reports about their employment for chemical synthesis are increasingly attracting attention. Engineered Pseudomonas sp. strain VLB120 Delta C biofilm growing in a tubular membrane reactor was utilized for the continuous production of (S)-styrene oxide. A biofilm specific morphotype appeared in the effluent during cultivation, accounting for 60-80% of the total biofilm irrespective of inoculation conditions but with similar specific activities as the original morphotype. Mass transfer of the substrate styrene and the product styrene oxide was found to be dependent on the flow rate but was not limiting the epoxidation rate. Oxygen was identified as one of the main parameters influencing the biotransformation rate. Productivity was linearly dependent on the specific membrane area and on the tube wall thickness. On average volumetric productivities of 24 g L(aq) (-1) day(-1) with a maximum of 70 g L(aq) (-1) day(-1) and biomass concentrations of 45 g (BDW) L(aq) (-1) have been achieved over long continuous process periods (>or=50 days) without reactor downtimes.

Efficacy of daily and weekly multiple micronutrient food-like tablets for the correction of iodine deficiency in Indonesian males aged 6-12 mo.

BACKGROUND: Infants are highly vulnerable to iodine deficiency, and little data exist on the effect of multiple micronutrient supplementation on their iodine status. OBJECTIVE: We aimed to compare the efficacy of daily and weekly multiple micronutrient food-like tablets (foodLETs) on increasing iodine status among infants. DESIGN: In a double-blind, placebo-controlled trial, 133 Indonesian males aged 6-12 mo were randomly assigned to 1 of 4 groups: a daily multiple-micronutrient foodLET providing the Recommended Nutrient Intake (RNI)(DMM), a weekly multiple-micronutrient foodLET providing twice the RNI (WMM), a daily 10-mg Fe foodLET (DI), or placebo. Urinary iodine (UI) concentrations were measured at baseline and at 23 wk. RESULTS: At baseline, the average UI concentration (1.37 micromol/L) was within the normal range, and 30.8% of subjects had iodine deficiency (UI < 0.79 micromol/L). At 23 wk, the DMM group had the highest increment in UI; however, after adjustment for initial UI, the changes in UI were not significantly different between the 4 groups (P = 0.39). Initial UI correlated inversely with the changes in UI (P < 0.001). The DMM group had the greatest reduction and increment in the proportion of iodine-deficient infants and in infants with iodine excess, respectively; however, no significant difference was found in these proportions (P = 0.13 and P = 0.42) between the 4 groups. CONCLUSION: Daily consumption of a multiple-micronutrient foodLET providing the RNI during infancy may be one strategy to improve iodine status.

Effect of daily or weekly multiple-micronutrient and iron foodlike tablets on body iron stores of Indonesian infants aged 6-12 mo: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: There is still uncertainty about the best procedure to alleviate iron deficiency. Additionally more reliable methods are needed to assess the effect of iron intervention. OBJECTIVE: We examined the efficacy of daily iron (10 mg), daily and weekly multiple-micronutrient supplementation (10 and 20 mg Fe, respectively) in improving body iron stores of Indonesian infants. DESIGN: Infants aged 6-12 mo were randomly allocated to 1 of 4 groups: daily multiple-micronutrients (DMM) foodlike tablets (foodLETs), weekly multiple-micronutrient (WMM) foodLETs, daily iron (DI) foodLETs, or daily placebo. Hemoglobin, ferritin, transferrin receptors, and C-reactive protein data were obtained at baseline and 23 wk. RESULTS: Body iron estimated from the ratio of transferrin receptors to ferritin was analyzed for 244 infants. At baseline, mean iron stores (0.5 +/- 4.1 mg/kg) did not differ among the groups, and 45.5% infants had deficits in tissue iron (body iron < 0). At week 23, the group DI had the highest increment in mean body iron (4.0 mg/kg), followed by the DMM group (2.3 mg/kg; P < 0.001 for both). The iron stores in the WMM group did not change, whereas the mean body iron declined in the daily placebo group (-2.2 mg/kg; P < 0.001). Compared with the daily placebo group, the DMM group gained 4.55 mg Fe/kg, the DI group gained 6.23 mg Fe/kg (both P < 0.001), and the WMM group gained 2.54 mg Fe/kg (P = 0.001). CONCLUSIONS: When compliance can be ensured, DI and DMM foodLETs are efficacious in improving and WMM is efficacious in maintaining iron stores among Indonesian infants.

Efficacy of oral iodized peanut oil is greater than that of iodized poppy seed oil among Indonesian schoolchildren.

BACKGROUND: Oral iodized poppy seed oil is an appropriate measure for controlling iodine deficiency in areas where iodized salt is not yet available. However, a more effective and cheaper iodized oil preparation is needed. OBJECTIVE: The aim of this study was to compare the efficacy of iodized peanut oil with that of iodized poppy seed oil. DESIGN: Schoolchildren aged 8-10 y were supplemented with a single oral dose of iodized peanut oil (P200, P400, or P800 mg I), iodized poppy seed oil (PS400 mg I), or peanut oil (placebo). The concentration of urinary iodine (UI) was measured at 0, 4, 12, 25, and 50 wk, whereas thyroid volume and serum thyrotropin and free thyroxine concentrations were measured at 0, 25, and 50 wk. RESULTS: UI was higher in all treatment groups than in the placebo group, except at baseline. UI in the P200 group was not significantly different from that in the PS400 group at all times of measurement. In a comparison of preparations supplying 400 mg I conducted by using a mathematical model, iodine retention from the peanut oil preparation was 3 times that from the poppy seed oil, and the protection period for peanut oil was twice as long as that for the poppy seed oil (P < 0.001 for both). The reduction in thyroid volume was greater in the treatment groups than in the placebo group (P < 0.001). No significant differences in serum hormone concentrations were observed between groups before or after treatment. CONCLUSION: Iodized peanut oil is more efficacious in controlling iodine deficiency than is iodized poppy seed oil containing the same amount of iodine.

Baseline evaluation of nutritional status and government feeding programs in Chiclayo, Peru.

BACKGROUND: Because of the rapid growth of the urban population in Peru, food and nutrition insecurity will occur increasingly in this population. For appropriate policy setting and programming, the food and nutrition situation of the urban poor requires better understanding. OBJECTIVE: To gain information about the nature, magnitude, severity, and causes of the nutritional problems of the population in low-income areas of the city of Chiclayo, Peru. METHODS: A cross-sectional nutrition survey was conducted in 1,604 households, covering children under 5 years of age and their parents. RESULTS: The prevalence rates of stunting, wasting, overweight. and anemia in children were 15.4%, 1.3%, 4.6%, and 65.7%, respectively; one third of adults were overweight, and one tenth were obese; 2.1% of the mothers were underweight; and 34.3% of mothers and 12.2% of fathers had anemia. Governmental feeding programs did not address these problems adequately. CONCLUSIONS: Interventions must have adequate targeting; address appropriate responses at the household, community, and national levels; and reduce stunting, obesity, and iron-deficiency anemia.

We know much about what to do but little about how to do it: experiences with a weekly multimicronutrient supplementation campaign.

BACKGROUND: Global population growth is concentrated in urban areas, but there is little understanding of how to implement the necessary interventions to control food and nutrition insecurity. In the urban area of Peru, food insecurity is characterized mainly by micronutrient deficiencies and not by energy deficiency. OBJECTIVE: To increase the effectiveness and cost-effectiveness of weekly multimicronutrient supplementation programs in poor urban communities. METHODS: A series of operational studies were conducted of preventive weekly multimicronutrient supplementation to reduce micronutrient-deficiency anemia in a population consisting of 8,081 children under 5 years of age and 20,082 women and adolescent girls of reproductive age (12 through 44 years). RESULTS: This is one of a series of papers that describe in as much detail as possible the experiences of a multimicronutrient intervention program for poor urban mothers and their young children and summarizes the lessons learned for consideration of future programming. CONCLUSIONS: This paper shows that such programs can achieve a high compliance with good training of program staff involvement of the community, education and motivation of beneficiaries, adequate supplies, and careful monitoring.

Costs of the multimicronutrient supplementation program in Chiclayo, Peru.

BACKGROUND: There is little information on the cost parameters of weekly multimicronutrient supplementation programs. OBJECTIVE: To assess the cost parameters and cost-effectiveness of a weekly multimicronutrient supplementation program in an urban population of Peru. METHODS: Data from the Integrated Food Security Program (Programa Integrado de Seguridad Alimentaria [PISA]), which distributed capsules and foodlets to women and adolescent girls and to children under five, were extrapolated to a population of 100,000 inhabitants. RESULTS: The annual cost per community member was US$1.51. The cost-effectiveness ratio was US$0.12 per 1% of prevented anemia per community member. CONCLUSIONS: These costs are in the upper margin of iron supplementation alone. They will decrease notably when weekly multimicronutrient supplementation programs are integrated into health packages and participation by women increases. Focusing on micronutrient deficiencies would prevent these problems, and food-distribution programs would be effectively targeted to food-deficient populations.

Protective effect of multimicronutrient supplementation against anemia among children, women, and adolescent girls in lower-income areas of Chiclayo, Peru.

BACKGROUND: The Integrated Food Security Program (Programa Integrado de Seguridad Alimentaria [PISA]) implemented a campaign to promote weekly multimicronutrient supplementation among women and adolescent girls of childbearing age and children under 5 years of age. OBJECTIVES: To assess the impact of the campaign on the growth of children and on anemia among children and among women and adolescent girls of childbearing age. METHODS: Weekly multimicronutrient supplementation was provided for 8 weeks. Weights, heights, and hemoglobin concentrations were assessed at the beginning and end of the campaign. RESULTS AND CONCLUSIONS: Although supplementation did not significantly increase the hemoglobin concentrations of children (p = .80) or women and adolescent girls (p = .65) in the intervention group, the hemoglobin concentrations of the comparison groups were significantly lower after 8 weeks (p = .001 for children and p = .03 for women and adolescent girls). Furthermore, the percentage of anemic children in the comparison group increased significantly (p <.001), and the final value was significantly higher than that for the intervention group (p = .004). There were no significant effects of weekly multimicronutrient supplementation on the growth of children, but the study was too short to reliably determine any effects on growth.

Lessons learned from the scaling-up of a weekly multimicronutrient supplementation program in the integrated food security program (PISA).

BACKGROUND: Weekly multimicronutrient supplementation was initiated as an appropriate intervention to protect poor urban populations from anemia. OBJECTIVE: To identify the lessons learned from the Integrated Food Security Program (Programa Integrado de Seguridad Alimentaria [PISA]) weekly multimicronutrient supplementation program implemented in poor urban populations of Chiclayo, Peru. METHODS: Data were collected from a 12-week program in which multimicronutrient supplements were provided weekly to women and adolescent girls 12 through 44 years of age and children under 5 years of age. A baseline survey was first conducted. Within the weekly multimicronutrient supplementation program, information was collected on supplement distribution, compliance, biological effectiveness, and cost. RESULTS: Supplementation, fortification, and dietary strategies can be integrated synergistically within a micronutrient intervention program. CONCLUSIONS: To ensure high cost-effectiveness of a weekly multimicronutrient supplementation program, the following conditions need to be met: the program should be implemented twice a year for 4 months; the program should be simultaneously implemented at the household (micro), community (meso), and national (macro) levels; there should be governmental participation from health and other sectors; and there should be community and private sector participation. Weekly multimicronutrient supplementation programs are cost effective options in urban areas with populations at low risk of energy deficiency and high risk of micronutrient deficiencies.

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.

[Burden of mothers and fathers of persons with schizophrenia]. / Die Belastung von Müttern und Vätern von Schizophreniekranken.

OBJECTIVE: Most studies about the burden of schizophrenia carers included only one care-giving relative, usually the patients' mothers. The present study intended to analyse differences of the level of burden between mothers and fathers of the same patients. METHODS: 101 mothers and 101 fathers of the same patients suffering from schizophrenia were included into this study. They were assessed by means of the "Involvement Evaluation Questionnaire" and the "Carers' Needs Assessment for Schizophrenia". RESULTS: Mothers showed significantly higher scores than fathers regarding the subscores "Tensions" and "Urging". Multiple linear regression analyses showed positive associations between the frequency of mothers' as well as fathers' unmet needs and dimensions of caregiver involvement. CONCLUSION: Unmet needs among mothers and fathers have negative effects on their burden. The differences between mothers and fathers indicate the importance of considering the carer's gender in clinical work.

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.

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.

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.

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.

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.

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.

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.