ORS and zinc deserve equal investment to defeat diarrheal disease

ORS and zinc deserve equal investment to defeat diarrheal disease

In a guest blog for IZiNCG, Hope Randall, Digital Communications Officer at PATH’s Defeat Diarrheal Disease (DefeatDD) Initiative asks you to get behind a proposal to add co-packaged oral rehydration solution + zinc to national essential medicines lists.

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The World Health Organization (WHO) recommends both oral rehydration solution (ORS) and zinc as the gold standard treatment for diarrhea, yet awareness of and access to both remains remarkably low. This is even truer of zinc than of ORS. 

Important nutrients like zinc, that are key for healthy growth and development, become depleted when a child has diarrhea. A vicious cycle of malnutrition and repeated infections is a common struggle for children who survive. Zinc helps ameliorate these effects in a child’s body, reducing the duration and severity of diarrhea and prevents future episodes for up to three months. Zinc also picks up where ORS leaves off, decreasing mortality or treatment failure by 40%. 

Low awareness is a key barrier to combined use of these medicines—only about a third of the children who need ORS get it—but use of zinc as a diarrhea treatment is even lower, with low awareness contributing to additional logistical barriers like facility stock-outs. And even in the rare event that the stars of awareness and availability are aligned, there is still affordability to contend with.  

Sometimes the simplest solutions are the most powerful. PATH and other global stakeholders are advocating for more countries to follow in the footsteps of Ghana, Zambia, Kenya, Senegal, and Vietnam to include co-packaged ORS + zinc into their national essential medicines lists for children. 

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Many countries include ORS and zinc in their national lists as separate medicines, which is a good beginning. But adding co-packaged ORS + zinc as a single entity to the list holds greater potential to boost awareness and uptake of the WHO-recommended combined treatment for diarrhea. 

The listing helps prioritize the co-pack in country expenditures, procurement and supply, and training of healthcare providers. Essentially, it creates an enabling environment for greater use of both medicines together, and all at a lower cost to families: in some countries, co-packaged ORS + zinc is estimated to be 46% more affordable than purchasing both medicines separately. Ultimately, that means greater healing and protection of children from the destructive impact of diarrheal infections.

And if two medicines are what it takes to protect children from the effects of diarrhea, it seems right to think of them as a non-negotiable package deal. Parents shouldn’t have to choose between them. Learn more about how to get involved.

Digging deeper into the relationship between zinc and environmental enteric dysfunction 

Digging deeper into the relationship between zinc and environmental enteric dysfunction 

Julie Long from the University of Colorado, Denver shares insights from a recently published study investigating zinc absorption from micronutrient powders (MNP) in Bangladeshi toddlers at risk of environmental enteric dysfunction.

 "Apart from contributing to the generation of knowledge, getting involved in this study was a memorable experience for me, as working with children of this age is always lots of fun and challenging at the same time. Julie, Novo and I had to spend long hours in the Clinical Trial Unit, but it never felt boring." – Dr. Prasenjit Mondal

Many young children in low-resource settings, such as Bangladesh, have malnutrition with poor growth and high rates of stunting.  Deficiencies of micronutrients are also high, including for iron and zinc.  Zinc deficiency, which causes poor growth, is prevalent in Bangladesh, with rates of nearly 50% in young children.  In recent years, there has also been increasing recognition of the role of the subclinical disorder environmental enteric dysfunction (EED) on this poor growth. EED causes gastrointestinal dysfunction, nutrient malabsorption and inflammation.   

As of current, the WHO recommends point-of-use fortification with MNP that contain 5 mg of zinc for children in setting where anemia rates are greater than 20%. It is unclear if the 5 mg of zinc in MNP is sufficient to meet the needs of children with EED and zinc deficiency, as children with both of these conditions are suspected to have higher requirements.

This question led researchers at the University of Colorado Denver and the International Centre for Diarrhoeal Disease Research, Bangladesh to collaborate on a project to answer the following:

·      How do children with EED absorb zinc and is 5 mg enough to meet their needs?

·      What dose of zinc in MNP is needed to meet the estimated requirements of children at risk for EED?

Researchers recruited toddlers at risk for EED from the peri-urban slums in Dhaka, Bangladesh. Children were randomized to receive MNP with 0, 5, 10, or 15 mg of zinc. Upon enrollment, toddlers’ gut function was measured using the lactulose:mannitol ratio (L:M). Absorbed zinc from a day’s total intake (including MNP of assigned dose) was measured, using stable zinc isotope tracers. Researchers also measured total dietary zinc and phytate, and assessed intestinal inflammation. 

Although the investigators intended to identify children with both normal and abnormal gut function, results indicated that virtually all children had evidence of gut dysfunction, i.e. consistent with EED. Zinc absorption was remarkably lower for all MNP doses. The data indicated that a MNP dose of at least 10 mg would be needed to meet requirements. This is in contrast to infants in the U.S. who were found to be able to meet zinc requirements with only ~ 3-4 mg/day.  Secondary analysis of biomarkers of intestinal and systemic inflammation were also high for most enrolled children. 

The extent to which zinc absorption was impaired for these children was greater than predicted. The results suggest that children at risk for EED and zinc deficiency likely need MNP with more than 5 mg of Zn to meet their nutritional needs to support healthier growth and development. 

Read more about IZiNCG’s ZiPT Trial, which also addresses the question of zinc dose in MNPs, here.

Read more about zinc supplementation here.

Photo credit: World Bank Photo Collection

IZiNCG Practical Tips for collecting blood in the field for assessment of plasma or serum zinc concentration

IZiNCG Practical Tips for collecting blood in the field for assessment of plasma or serum zinc concentration

The second edition of IZiNCG Practical Tips: Collecting blood in the field for assessment of plasma or serum zinc concentration is now available on our website.

The document briefly covers the following topics:

  • Precautions to prevent transmission of infectious agents when handling blood samples 

  • Practices and supplies to avoid zinc contamination of samples 

  • Tips for blood collection technique 

  • Tips for processing samples 

  • Tips for aliquoting of samples in the field laboratory 

  • Tips for sample analyses 

  • Information on reference laboratories

  • Tips for statistical analyses 

  • List of trace element-free blood collection supplies 

  • Image examples of field laboratory hoods

  • Example laboratory protocols for the analysis of plasma/serum zinc by flame atomic absorption spectrophotometry and inductively coupled plasma–optical emission spectrometry (ICP-OES) 

Please contact IZiNCG with any questions or comments regarding this brief.

Determining the risk of zinc deficiency: Assessment of dietary zinc intake - Second Edition published!

Determining the risk of zinc deficiency: Assessment of dietary zinc intake - Second Edition published!

Assessing the prevalence of inadequate dietary zinc intakes provides information on the risk of zinc deficiency in a population. 

Determining the risk of zinc deficiency: Assessment of dietary zinc intake takes you through the five main steps of assessing the adequacy of dietary zinc intake. These steps are:

  1. Determine the survey design

  2. Select a representative population sample

  3. Determine food intakes

  4. Estimate dietary intake of absorbable zinc

  5. Determine the prevalence of inadequate zinc intakes

Updates in this Second Edition of IZiNCG Technical Brief no. 3 include instructions for calculation of absorbable zinc, including a worked example, and a section on additional resources.

All of IZiNCG’s Technical Briefs are available here.

OpeN-Global: More and better data.

OpeN-Global: More and better data.

February 27, 2019: OpeN-Global, live online

OpeN-Global is a freely available, online resource aimed at supporting the objective, accurate and detailed assessment of nutritional biomarkers from populations globally. In their guest blog for IZiNCG, Drs Jessica Farebrother and Sophie Moore share what OpeN-Global is all about.

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OpeN-Global is specifically designed to support and enable work in populations from low- and middle-income countries (LMICs), but the analytical methods presented can be applied to samples from any population group. OpeN-Global additionally provides a network of experts to support the implementation of biomarker assays in laboratories globally, and to help interpret the data obtained. OpeN-Global is an open-access website that is free for all to use.

So what’s it all about?

Malnutrition, from either under- or over-nutrition, affects one in three people globally. This makes malnutrition, together with diet, the biggest risk factors for the global burden of disease - by far.

The recent 2018 Global Nutrition Report stated: “Micronutrient deficiencies are estimated to impact a significant number of people around the world, but there remains far too little information on micronutrient status and deficiencies. More essential information and surveillance need to be gathered to make substantial progress on global targets.”

What’s basically needed, are more and better data.

One of the key barriers to the development of both nutrition-specific and nutrition-sensitive programmes and policies, particularly in LMICs, is the lack of robust evidence on nutritional status in the most vulnerable groups.

Though many health and nutrition related activities in LMICs are underpinned by well-designed national surveys (e.g. the UNICEF Multiple Indicator Cluster Survey), data from the most vulnerable population groups, i.e. infants, children, adolescents, pregnant and lactating women, are often limited to anthropometry and easy-to-assay parameters e.g. haemoglobin, or single micronutrients e.g. vitamin A, iodine.

Other available information may be based on prevalence data, e.g. stunting in under 5’s to assess population risk of zinc deficiency, or household coverage of adequately iodised salt in salt fortification monitoring.

Whilst these proxy measures remain recommended strategies for population nutrition monitoring, a more accurate picture of population nutrient status can be given by biochemical data using human biomarkers.

Stunting prevalence (data) vs Plasma zinc concentration?

Household coverage of iodised salt (salt sample) vs Urinary iodine concentration?

These biochemical assays provide a real picture of nutrient status. Such assays could feature as routine, however are rarely included in demographic and health surveys in LMICs.

What are the barriers to biochemical assessment in population nutrition surveillance?

With the help of our global partner network including leading scientists based in LMICs, we uncovered some of the key barriers to assessment of biochemical samples in LMIC nutrition surveys. And funding was not the only barrier! Our kick-off workshop highlighted several key themes, including:

1. A clear need for guidance and technical support to facilitate the laboratory capabilities in many LMIC settings to support the assessment of a wider panel of nutritional biomarkers than is currently available and routinely used;

2. Excellent research infrastructure and laboratory platforms are in place in many LMIC settings, but several barriers, including staff training opportunities and technical know-how prevents full utilisation.

Support in these key areas would start a positive cycle of quality control and assurance technical accreditation, investment and increased trust – leading to better outputs. More and better data.

Supporting the generation of quality data in-country will support evidence-based policy, and transform nutritional outcomes.

Our response: OpeN-Global

We have established a global network of expertise in nutritional research methodologies. Our 37-strong global partner network of committed academic, technology and industry experts spans 20 institutions across 10 countries on 5 continents.

Through this partnership, we have created OpeN-Global a hub of resource tools to assess nutritional status in global health settings in the form of an open-access website that provides laboratory SOPs to download or signposting to published nutrition assay methods, details on quality control and accreditation, technical support, and fully-referenced general information for over 20 nutrition biomarkers, including key nutrients such as zinc and iodine, to newer technologies and -omics approaches.

And the list is growing.

Our aim: to support the objective, detailed, accurate and high-quality assessment of nutrition biomarkers used in Global Health population surveys and research.

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For more information, please contact the project lead, Dr Sophie Moore, Department of Women and Children’s Health, King’s College London on sophie.moore@kcl.ac.uk, or head to www.open-global.kcl.ac.uk from February 27th, and contact us directly from the website.

Al images taken at Medical Research Council The Gambia. Photo credits: Ian Farrell.

Written by Jessica Farebrother and Sophie Moore.

Footnotes:

1 Prevalence of stunting in children under 5 years is a recommended strategy to assess population risk of zinc deficiency. Recommendations of Biomarkers of Nutrition for Development – Zinc, and IZiNCG

2 Assessment of household coverage of iodised salt is a recommended strategy in monitoring and surveillance of relevant salt fortification strategies. Biomarkers of Nutrition for Development - Iodine, and the Iodine Global Network (www.ign.org).

Holiday Greetings!

Holiday Greetings!

It is time to look back at what has been achieved in 2018, and to thank all our supporters and contributors. We are looking forward to engaging with you in 2019!

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New IZiNCG technical brief: The value of measuring plasma or serum zinc concentrations in national surveys

New IZiNCG technical brief: The value of measuring plasma or serum zinc concentrations in national surveys

“Micronutrient deficiencies are estimated to impact a significant number of people around the world, but there remains far too little information on micronutrient status and deficiencies. More essential information and surveillance need to be gathered to make substantial progress on global targets.” 

Global Nutrition Report 2018

There is an urgent need for more and better data on the zinc status of vulnerable populations to effectively target and monitor zinc intervention programs. IZiNCG’s new Technical Brief no. 9 outlines the value of measuring plasma/serum zinc concentration in national nutrition or health-related surveys. If a population is considered at high-risk of zinc deficiency based on inadequacy of zinc in the food supply or a high prevalence of child stunting, IZiNCG recommends that plasma/serum zinc be measured in vulnerable groups.

We are pleased that plasma/serum zinc data are now included in the World Health Organization’s Vitamin and Mineral Nutrition Information System Micronutrient Database and have partnered with the Micronutrient Forum to initiate a working group to promote the inclusion of micronutrient biomarkers in large-scale surveys. 

For more information about the measurement of plasma or serum zinc concentrations, refer to previous IZiNCG Technical Briefs and Technical Documents, and the Biomarkers of Nutrition for Development (BOND) - Zinc Review.

Recent publication: A dynamic model for predicting growth in zinc-deficient stunted infants given supplemental zinc

Recent publication: A dynamic model for predicting growth in zinc-deficient stunted infants given supplemental zinc

Zinc deficiency limits infant growth and increases susceptibility to infections, which further compromises growth. Zinc supplementation improves the growth of zinc-deficient stunted infants, but the amount, frequency, and duration of zinc supplementation required to restore growth in an individual child is unknown. A dynamic model of zinc metabolism that predicts changes in weight and length of zinc-deficient, stunted infants with dietary zinc would be useful to define effective zinc supplementation regimens.

A model of zinc metabolism was developed using data on zinc kinetics, tissue zinc, and growth requirements for healthy 9 month old infants. The model suggests that frequent, smaller doses (5–10 mg Zn/d) are more effective for increasing growth in stunted, zinc-deficient 9-mo-old infants than are larger, less-frequent doses.

In the future, the model predictions of zinc supplementation need to be evaluated in homogenous groups of stunted infants with respect to age, sex, and zinc status. That information will improve predicted amounts of supplemental zinc, and it will identify the population subgroups (e.g., infants with plasma zinc and length-for-age z score below defined thresholds) most likely to respond to zinc supplementation.

The publication can be found here.

Study in progress: Reference methods for biological sample preparation and zinc analysis

Study in progress: Reference methods for biological sample preparation and zinc analysis

The accurate determination of the prevalence of zinc deficiency is essential for effective design, targeting, and evaluation of interventions. Hence, methodological knowledge gaps are important to understand and address.

The concentration of zinc in biological samples, such as plasma, serum, hair, or urine, varies considerably between populations. While part of this variation is attributable to differences in diet or inflammation – i.e. what we want to measure – part may also be due to the different methods and equipment used to process and analyze the samples. 

Instruments commonly used for zinc analysis include atomic absorption spectrometry (AAS), inductively couple plasma optical (atomic) emission spectrometry (ICP-OES / ICP-AES), and ICP mass spectrometry (ICP-MS). 

IZiNCG has earlier published reference methods for collecting plasma and serum for zinc analysis, but reference methods for sample preparation and zinc analysis have not yet been developed. 

The goals of this project are to:

a)    Establish a set of reference methods for zinc analysis, applicable to new or established laboratories using each major type of instrument; and 

b)    Develop reference data that document analytical accuracy and precision among different instruments and different types of samples under ideal conditions at multiple sites. 

The results, anticipated early-mid 2019, will be communicated as an IZiNCG technical brief following publication in a peer-reviewed scientific journal.

Participating labs:

AAS

University of Colorado Denver, USA

ETH Zurich, Switzerland

Aga Khan University, Pakistan

International Centre for Diarrhoeal Disease Research, Bangladesh

National Institute of Nutrition, Hanoi, Vietnam

ICP-OES

Children’s Hospital Oakland Research Institute, USA

ICP-MS

University of Colorado, Denver, USA

ETH Zurich, Switzerland

Oklahoma State University, USA

Which form? How much? How often?

Which form? How much? How often?

Multiple Micronutrient Powder (MNP) programs are being scaled up globally and present a golden opportunity for delivering preventive zinc to older infants and young children.