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Control and Prevention of Thiamine Deficiency Disorders

Why Thiamine?

Thiamine deficiency remains a pressing public health issue. Infantile beriberi, a disease caused by thiamine deficiency, presents during the exclusive breastfeeding period and without treatment commonly results in death within hours of clinical presentation. There is also growing evidence suggesting sub-clinical thiamine deficiency may have a measurable, lasting impact on cognitive development and psychomotor functions. However, addressing the spectrum of thiamine deficiency disorders (TDD) is impeded by several gaps in knowledge. There is no accepted case definition of TDD, poor understanding of biomarkers, unknown status in large regions of the world, and important questions remain about the timing of deficiency, levels of deficiency, and the ability of prophylactic interventions to prevent or therapeutic interventions to remediate the effects of TDD in humans. This initiative will seek to address the key gaps in our knowledge of TDD and to develop a model for control of TDD in the most affected countries.

What's Next?

Over the next two years, the Academy will be engaged in a research project to reduce the global burden of thiamine deficiency. With funding from the Bill & Melinda Gates Foundation, this project will include a number of research partners around the world and fill several research gaps.

Key Knowledge Gaps

1. Limitations in assessing status.

Control and Prevention of Thiamine Deficiency Disorders

2. Lack of knowledge about prevalence, particularly in sub-Saharan Africa

Control and Prevention of Thiamine Deficiency Disorders

3. Lack of strategy to address deficiencies, particularly during lactation

Control and Prevention of Thiamine Deficiency Disorders

4. No standard approach to surveillance and prevention

5. No standard case definition

Scientific Advisory Group

Gilles Bergeron, PhD

The New York Academy of Sciences

Ken Brown, MD

Nutrition/Global Development, Bill & Melinda Gates Foundation

Tim Green, PhD

South Australian Health and Medical Institute, SAHMRI

Laurent Hiffler, MD

MSF Spain Dakar Unit-Senegal

Sengchanh Kounnavong, MD, PhD

National Institute of Public Health Lao PDR

Frank Wieringa, PhD

Institut de Recherche pour le Développment (IRD)


Funding Support



Organized By

Control and Prevention of Thiamine Deficiency Disorders

List of Useful Tools

Thiamine content of foods in key countries 

Cambodia 

Laos 

Thiamine availability based on food balance sheets (2011)

Thiamine availability below 1.2 mg/capita/day

High % of energy from low-thiamine staple crops

Analysis of thiamine biomarkers

Guidance to assess thiamine biomarkers

Analytical requirements of ThDP and ETKA

Broad-scale survey on thiamine status

Pregnant women 

Lactating mothers 

Infants

Food fortification with thiamine

Countries with existing thiamine fortification programs

Educational materials

For healthcare professionals: “Thiamine deficiency disorders: identification and treatment”

For healthcare professionals: “Infantile beriberi: clinical symptoms and case studies”

For individuals affected by or at risk of thiamine deficiency: “A guide to increase thiamine intake and prevent thiamine deficiency”.

For pregnant women and lactating mothers: “The importance of thiamine during pregnancy, breastfeeding and infancy”

List of relevant websites

Global Fortification Data Exchange

Food Fortification Initiative

Micronutrient Survey Toolkit

OpeN-Global 

Key scientific publications

Whitfield, K.C., Bourassa, M.W., Adamolekun, B., et al. (2018). Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs. Annals of the New York Academy of Sciences, 1430(1), 3-43.

Hiffler, L., Adamolekun, B., Fischer, P.R., Fattal-Vavleski, A. (2017). Thiamine content of F‐75 therapeutic milk for complicated severe acute malnutrition: time for a change? Annals of the New York Academy of Sciences, 1404(1), 20-26.

Adamolekun, B., Hiffler, L. (2017). A diagnosis and treatment gap for thiamine deficiency disorders in sub-Saharan Africa? Annals of the New York Academy of Sciences, 1408(1), 15-19.

Whitfield, K.C., Karakochuk, C.D., Kroeun, H., et al. (2017). Household consumption of thiamin-fortified fish sauce increases erythrocyte thiamin concentrations among rural Cambodian women and their children younger than 5 years of age: a randomized controlled efficacy trial. The Journal of Pediatrics, 181, 242-247.

Johnson, C. R., Fischer, P. R., Thacher, T. D., et al. (2019). Thiamin deficiency in low- and middle-income countries: Disorders, prevalences, previous interventions and current recommendationsNutrition and Health.

Control and Prevention of Thiamine Deficiency Disorders

The Academy recently convened an expert panel to estimate the global burden of thiamine deficiency and related disease risks, and to review possible intervention strategies to reduce the associated burden of disease. The panel concluded that there is a surprising lack of information on this condition, despite its likely importance as a cause of infant mortality in South East Asia and possibly in other LMIC, and its known effects on child development. Following the panel’s recommendations, this initiative aims to address the key knowledge gaps that were identified through the following projects.

Control and Prevention of Thiamine Deficiency Disorders

Supplementation

Determine the appropriate level of thiamine supplementation during lactation to provide adequate thiamine status for mothers and their infants. A dose response trial of lactating women in Cambodia will measure thiamine content in breast milk, as well as in the blood of mother and infants.

Cognitive Outcomes

There is evidence that even asymptomatic thiamine deficiency can cause long-lasting cognitive deficits. The infants enrolled in the supplementation trial will undergo neurological testing to look for cognitive differences between supplementation and placebo groups.

Fortification

Salt has been identified a good vehicle for thiamine fortification in South-East Asia. This project will measure salt consumption in Cambodia to inform the level of thiamine required to adequately fortify salt.

Biomarkers

The relationship between the two thiamine biomarkers, thiamine diphosphate and the erythrocyte transketolase assay, will be studied to assess which biomarker is best suited to identify thiamine deficiency.

African Surveys

Some neurological disorders found in Sub-Saharan Africa have similar symptoms to thiamine deficiency disorders and the increase in rice consumption has raised concern that thiamine deficiency may also be present in Africa. Pilot surveys will examine thiamine status in three populations in Africa.

Surveillance and Control Programs

Thiamine deficiency is most well known in South-East Asia and despite the efforts in the region, it remains a pervasive problem. This project will work with the countries to develop surveillance and control programs to reduce the burden thiamine deficiency through fortification, supplementation, education, behavior change and surveillance programs.

Thiamine Deficiency Disorder Case Definition

A clear case definition for TDD has not been established and creates challenges in efficiently diagnosing TDD. This program will use a case control design to establish a case definition based on cohorts of infants and children in Laos.

Control and Prevention of Thiamine Deficiency Disorders
Control and Prevention of Thiamine Deficiency Disorders

Upcoming Thiamine Workshops

Two technical workshops will be held in the region to discuss steps to be taken by each country to roll out a TDD control and prevention program in their specific context; and provide necessary knowledge and training to establish their program. Materials covered in each workshop will be sequentially organized, to facilitate the gradual development of the control program.

Workshop 1, Late 2019, Laos

The first regional workshop will be held with the four focus countries in 2019 to assess individual country situations and needs, and to introduce the Technical Reference Materials (TRMs). The focus of the discussions will be on the inputs and activities needed to enable managers to begin planning their TDD control program.

Workshop 2, Late 2020, Cambodia

The second regional workshop will be held with the same countries in 2020, using the TRMs as key resource but this time focusing on outputs, on the use of the knowledge provided by the surveillance information, and on maximizing program outcomes. As that workshop will occur in the last year of the initiative, findings from other Objectives will be available and will be incorporated in the TRMs as appropriate.