A blueprint for fortification planning and programming: Lessons learned from an analytical review of existing fortification frameworks.

With multiple food fortification frameworks, countries can find it challenging to determine optimal methods for planning and implementing food fortification programmes to combat vitamin and mineral deficiencies, especially without additional technical support. To address this challenge, this study aimed to review existing frameworks to determine consistencies, differences, strengths, and weaknesses across the frameworks, and based on the review findings, formulate an enhanced and streamlined fortification framework. Nineteen frameworks were ultimately examined following a comprehensive literature review and key informant interviews. Generally, the reviewed frameworks amply describe motives and methods for the determination of fortification need and feasibility, industry engagement/quality assurance and quality control, and impact evaluations/surveillance. However, there was limited inclusion or discussion throughout the reviewed frameworks around harmonization of fortification with existing micronutrient interventions; fortification policy and/or strategy; enforcement, incentives, and penalties to ensure producer compliance with industry standards; and periodic fortification programme review and reassessment. The findings were used to develop a comprehensive Fortification Blueprint that aims to provide structured guidance and a library of tools and resources to fortification programme managers and key stakeholders to ensure optimal and sustainable programme design.

Preventing birth defects, saving lives, and promoting health equity: an urgent call to action for universal mandatory food fortification with folic acid.

July 20, 2021 marked the 30th anniversary of the publication of the landmark trial by the British Medical Research Council showing unequivocally that maternal intake of folic acid (vitamin B9) starting before pregnancy prevents most cases of infant spina bifida and anencephaly-two major neural tube defects that are severe, disabling, and often fatal. Mandatory food fortification with folic acid is a safe, cost-effective, and sustainable intervention to prevent spina bifida and anencephaly. Yet few countries implement fortification with folic acid; only a quarter of all preventable spina bifida and anencephaly cases worldwide are currently avoided by food fortification. We summarise scientific evidence supporting immediate, mandatory fortification with folic acid to prevent the development of spina bifida and anencephaly. We make an urgent call to action for the World Health Assembly to pass a resolution for universal mandatory folic acid fortification. Such a resolution could accelerate the slow pace of spina bifida and anencephaly prevention globally, and will assist countries to reach their 2030 Sustainable Development Goals on child mortality and health equity. The cost of inaction is profound, and disproportionately impacts susceptible populations in low-income and middle-income countries.

Enablers and Barriers of Zinc Fortification; Experience from 10 Low- and Middle-Income Countries with Mandatory Large-Scale Food Fortification.

Adequate zinc nutrition is important for child growth, neurodevelopment, immune function, and normal pregnancy outcomes. Seventeen percent of the global population is estimated to be at risk for inadequate zinc intake. However, zinc is not included in the fortification standards of several low- and middle-income countries with mandatory fortification programs, despite data suggesting a zinc deficiency public health problem. To guide policy decisions, we investigated the factors enabling and impeding the inclusion of zinc as a fortificant by conducting in-depth interviews with 17 key informants from 10 countries. Findings revealed the decision to include zinc was influenced by guidance from international development partners and enabled by the assessment of zinc deficiency, mandatory regional food fortification standards which included zinc, the World Health Organization (WHO) guidelines for zinc fortification, and the low cost of zinc compound commonly used. Barriers included the absence of zinc from regional fortification standards, limited available data on the efficacy and effectiveness of zinc fortification, and the absence of national objectives related to the prevention of zinc deficiency. To promote zinc fortification there is a need to put the prevention of zinc deficiency higher on the international nutrition agenda and to promote large-scale food fortification as a key deficiency mitigation strategy.

Effects of Foods Fortified with Zinc, Alone or Cofortified with Multiple Micronutrients, on Health and Functional Outcomes: A Systematic Review and Meta-Analysis.

Seventeen per cent of the world's population is estimated to be at risk of inadequate zinc intake, which could in part be addressed by zinc fortification of widely consumed foods. We conducted a review of efficacy and effectiveness studies to ascertain the effect of zinc fortification [postharvest fortification of an industrially produced food or beverage; alone or with multiple micronutrients (MMN)] on a range of health outcomes. Previous reviews have required that the effect of zinc be isolated; because zinc is always cofortified with MMN in existing fortification programs, we did not impose this condition. Outcomes assessed were zinc-related biomarkers (plasma or serum, hair or urine zinc concentrations, comet assay, plasma fatty acid concentrations, and the proportion of and total zinc absorbed in the intestine from the diet), child anthropometry, morbidity, mortality, cognition, plasma or serum iron and copper concentrations, and for observational studies, a change in consumption of the food vehicle. Fifty-nine studies were included in the review; 54 in meta-analyses, totaling 73 comparisons. Zinc fortification with and without MMN increased plasma zinc concentrations (efficacy, n = 27: 4.68 µg/dL; 95% CI: 2.62-6.75; effectiveness, n = 13: 6.28 µg/dL; 95% CI: 5.03-7.77 µg/dL) and reduced the prevalence of zinc deficiency (efficacy, n = 11: OR: 0.76, 95% CI: 0.60-0.96; effectiveness, n = 10: OR: 0.45, 95% CI: 0.31-0.64). There were statistically significant increases in child weight (efficacy, n = 11: 0.43 kg, 95% CI: 0.11-0.75 kg), improvements in short-term auditory memory (efficacy, n = 3: 0.32 point, 95% CI: 0.13-0.50 point), and decreased incidence of diarrhea (efficacy, n = 3: RR: 0.79, 95% CI: 0.68-0.92) and fever (efficacy, n = 2: RR: 0.85, 95% CI: 0.74-0.97). However, these effects cannot be solely attributed to zinc. Our review found that zinc fortification with or without MMN reduced the prevalence of zinc deficiency and may provide health and functional benefits, including a reduced incidence of diarrhea.

Systematic Process Framework for Conducting Implementation Science Research in Food Fortification Programs.

Food fortification has proven to be an effective approach for preventing micronutrient deficiencies in many settings. Factors that lead to successful fortification programs are well established. However, due to the multisectoral nature of fortification and the added complexities present in many settings, the barriers to success are not always evident and the strategies to address them are not always obvious. We developed a systematic process for identifying and addressing gaps in the implementation of a food fortification program. The framework is composed of 4 phases: (1) connect program theory of change to program implementation; (2) develop an implementation research agenda; (3) conduct implementation research; and (4) analyze findings and develop/disseminate recommendations for next steps. We detail steps in each phase to help guide teams through the process. To our knowledge, this is the first attempt to outline a systematic process for applying implementation science research to food fortification. The development of this framework is intended to promote implementation research in the field of food fortification, thus improving access to and effectiveness of this key public health intervention.

The Unfinished Agenda for Food Fortification in Low- and Middle-Income Countries: Quantifying Progress, Gaps and Potential Opportunities.

Large-scale food fortification (LSFF) is a cost-effective intervention that is widely implemented, but there is scope to further increase its potential. To identify gaps and opportunities, we first accessed the Global Fortification Data Exchange (GFDx) to identify countries that could benefit from new fortification programs. Second, we aggregated Fortification Assessment Coverage Toolkit (FACT) survey data from 16 countries to ascertain LSFF coverage and gaps therein. Third, we extended our narrative review to assess current innovations. We identified 84 countries as good candidates for new LSFF programs. FACT data revealed that the potential of oil/ghee and salt fortification is not being met due mainly to low coverage of adequately fortified foods (quality). Wheat, rice and maize flour fortification have similar quality issues combined with lower coverage of the fortifiable food at population-level (< 50%). A four-pronged strategy is needed to meet the unfinished agenda: first, establish new LSFF programs where warranted; second, systems innovations informed by implementation research to address coverage and quality gaps; third, advocacy to form new partnerships and resources, particularly with the private sector; and finally, exploration of new fortificants and vehicles (e.g. bouillon cubes; salt fortified with multiple nutrients) and other innovations that can address existing challenges.

Addressing the Fortification Quality Gap: A Proposed Way Forward.

Large-scale food fortification is an effective, sustainable, and scalable intervention to address vitamin and mineral deficiencies, however, pressing gaps exist globally around ensuring the quality of fortified foods. This paper summarizes the global challenges and gaps faced in monitoring the quality of fortified foods, the guidance produced in response to these challenges, where we are today in terms of effective implementation, and what approaches and opportunities may be usefully applied to enhance the quality of fortified foods moving forward.

Review of Grain Fortification Legislation, Standards, and Monitoring Documents.

OBJECTIVE: Analyze the content of documents used to guide mandatory fortification programs for cereal grains. METHODS: Legislation, standards, and monitoring documents, which are used to mandate, provide specifications for, and confirm fortification, respectively, were collected from countries with mandatory wheat flour (n=80), maize flour (n=11), and/or rice (n=6) fortification as of January 31, 2015, yielding 97 possible country-grain combinations (e.g., Philippines-wheat flour, Philippines-rice) for the analysis. After excluding countries with limited or no documentation, 72 reviews were completed, representing 84 country-grain combinations. Based on best practices, a criteria checklist was created with 44 items that should be included in fortification documents. Two reviewers independently scored each available document set for a given country and food vehicle (a country-grain combination) using the checklist, and then reached consensus on the scoring. We calculated the percentage of country-grain combinations containing each checklist item and examined differences in scores by grain, region, and income level. RESULTS: Of the 72 country-grain combinations, the majority of documentation came from countries in the Americas (46%) and Africa (32%), and most were from upper and lower middle-income countries (73%). The majority of country-grain combinations had documentation stating the food vehicle(s) to be fortified (97%) and the micronutrients (e.g., iron) (100%), fortificants (e.g., ferrous fumarate) (88%), and fortification levels required (96%). Most (78%) stated that labeling is required to indicate a product is fortified. Many country-grain combinations described systems for external (64%) monitoring, and stated that industry is required to follow quality assurance/quality control (64%), though detailed protocols (33%) and roles and responsibilities (45%) were frequently not described. CONCLUSIONS: Most country-grain combinations have systems in place for internal, external, and import monitoring. However, documentation of other important items that would influence product compliance to national standard, such as roles and responsibilities between agencies, the cost of regulating fortification, and enforcement strategies, are often lacking. Countries with existing mandatory fortification can improve upon these items in revisions to their documentation while countries that are beginning fortification can use the checklist to assist in developing new policies and programs.

Regulatory Monitoring of Fortified Foods: Identifying Barriers and Good Practices.

While fortification of staple foods and condiments has gained enormous global traction, poor performance persists throughout many aspects of implementation, most notably around the critical element of regulatory monitoring, which is essential for ensuring foods meet national fortification standards. Where coverage of fortified foods is high, limited nutritional impact of fortification programs largely exists due to regulatory monitoring that insufficiently identifies and holds producers accountable for underfortified products. Based on quality assurance data from 20 national fortification programs in 12 countries, we estimate that less than half of the samples are adequately fortified against relevant national standards. In this paper, we outline key findings from a literature review, key informant interviews with 11 fortification experts, and semi-quantitative surveys with 39 individuals from regulatory agencies and the food fortification industry in 17 countries on the perceived effectiveness of regulatory monitoring systems and barriers to compliance against national fortification standards. Findings highlight that regulatory agencies and industry disagree on the value that enforcement mechanisms have in ensuring compliance against standards. Perceived political risk of enforcement and poorly resourced inspectorate capacity appear to adversely reinforce each other within an environment of unclear legislation to create a major hurdle for improving overall compliance of fortification programs against national standards. Budget constraints affect the ability of regulatory agencies to create a well-trained inspector cadre and improve the detection and enforcement of non-compliant and underfortified products. Recommendations to improve fortification compliance include improving technical capacity; ensuring sustained leadership, accountability, and funding in both the private and the public sectors; and removing political barriers to ensure consistent detection of underfortified products and enforcement of applicable fortification standards. Only by taking concrete steps to improve the entire regulatory system that is built on a cooperative working relationship between regulatory agencies and food producers will a nutrition strategy that uses fortification see its intended health effects.

Biomimetic affinity ligands for immunoglobulins based on the multicomponent Ugi reaction.

Affinity chromatography is the method of choice for biomolecule separation and isolation with highly specific target recognition; it is ideally suited to the purification of immunotherapeutic proteins (i.e., mAbs). Conventional affinity purification protocols are based on natural immunoglobulin (Ig)-binding proteins, which are expensive to produce, labile, unstable, and exhibit lot-to-lot variability. Biological ligands are now being replaced by cost-effective, synthetic ligands, derived from the concepts of rational design and combinatorial chemistry, aided by in silico approaches. In this chapter, we describe a new synthetic procedure for the development of affinity ligands for immunoglobulins based on the multicomponent Ugi reaction. The lead ligand developed herein is specific for the IgG-Fab fragment and mimics Protein L (PpL), an IgG-binding protein isolated from Peptostreptococcus magnus strains and usually used for the purification of antibodies and their fragments.

Building capacity in health facility management: guiding principles for skills transfer in Liberia.

BACKGROUND: Management training is fundamental to developing human resources for health. Particularly as Liberia revives its health delivery system, facility and county health team managers are central to progress. Nevertheless, such management skills are rarely prioritized in health training, and sustained capacity building in this area is limited. We describe a health management delivery program in which a north and south institution collaborated to integrate classroom and field-based training in health management and to transfer the capacity for sustained management development in Liberia. METHODS: We developed and implemented a 6-month training program in health management skills (i.e. strategic problem solving, financial management, human resource management and leadership) delivered by Yale University and Mother Patern College from Liberia, with support from the Clinton HIV/AIDS Initiative. Over three 6-month cycles, responsibility for course instruction was transferred from the north institution to the south institution. A self-administered survey was conducted of all participants completing the course to measure changes in self-rated management skills, the degree to which the course was helpful and met its stated objectives, and faculty members' responsiveness to participant needs as the transfer process occurred. RESULTS: Respondents (n=93, response rate 95.9%) reported substantial improvement in self-reported management skills, and rated the helpfulness of the course and the degree to which the course met its objectives highly. Levels of improvement and course ratings were similar over the three cohorts as the course was transferred to the south institution. We suggest a framework of five elements for implementing successful management training programs that can be transferred and sustained in resource-limited settings, including: 1) use a short-course format focusing on four key skill areas with practical tools; 2) include didactic training, on-site projects, and on-site mentoring; 3) collaborate with an in-country academic institution, willing and able to scale-up and maintain the training; 4) provide training for the in-country academic faculty; and 5) secure Ministry-level support to ensure participation. CONCLUSION: Our findings demonstrate key elements for scaling up and replicating educational initiatives that address management skills essential for long-term health systems strengthening in resource-poor settings.

Hospital quality improvement in Ethiopia: a partnership-mentoring model.

BACKGROUND AND OBJECTIVE: Quality improvement efforts are increasingly common in the United States; however, their use in developing countries is limited. We sought to evaluate the impact of a large-scale intervention on several key management indicators through hospital quality improvement efforts. DESIGN: Pre-post-descriptive study of 14 hospitals in Ethiopia. SETTING: Six regions and two city administrations in Ethiopia. PARTICIPANTS: Hospital leaders and management mentors in participating hospitals. INTERVENTION: In collaboration with the Ministry of Health and the Clinton HIV/AIDS Initiative, we implemented a countrywide quality improvement initiative in which 24 mentors with hospital administration experience were placed for 1 year in Ethiopia to work side-by-side with hospital management teams. We also provided a professional development course to enhance quality improvement skills. MAIN OUTCOME MEASURE: s) Presence of 75 key management indicators; reported management skills of hospital leaders by the mentors. RESULTS: In pre-post analysis, we found improvement in 45 of the 75 (60%) key management indicators between August 2006 and May 2007. The changes reflected a total of 105 management indicators improved across the 14 hospitals, which equates to a per-hospital mean of 7.5 (standard deviation 5.9) improvements. Reported management skills of hospital leaders improved in several management domains, although their reported confidence in these skills remained largely unchanged. CONCLUSIONS: Our findings indicate that quality improvement efforts can be effective in improving hospital management in developing countries. Longer follow-up is required to assess the sustainability of the hospital improvements accomplished.