Beriberi Treatment:
What a medical student can teach us all
Philip Fischer, M.D., and Samuel Porter
Global Missions Health Conference
November 9th, 2012
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Prey Veng Province, Cambodia
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Debbie Coats, FNP
• Svay Chrum Health Clinic
• Previously-healthy infants presenting with
tachypnea, tachycardia, hepatomegaly, and no
fever.
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Beriberi – a significant killer
• Verbal autopsy study in Prey Veng, Cambodia1
• 45% of infants who died in their first year of
life had signs and symptoms of beriberi
• Respiratory distress, dysphonia, irritability,
vomiting
• Karen Refugees
• Record infant mortality (>20%)
• Majority were dying of beriberi2
• Reports from all over SE Asia2
1: Kauffman, G., D. Coats, et al. (2011). "Thiamine deficiency in ill children." The American Journal of
Clinical Nutrition 94(2): 616-617; author reply 617.
2: Luxemburger, C., N. J. White, et al. (2003). "Beri-beri: the major cause of infant mortality in Karen
refugees." Transactions of the Royal Society of Tropical Medicine and Hygiene 97(2): 251-255.
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“I cannot, I cannot”
• 1870  Marked increase in
beriberi incidence in SE Asia3
• Polished rice
• Christiaan Eijkman
• “White rice can be
poisonous!” (1896)3
• The “anti-beriberi” factor
• Gerrit Grijns
• Suggested dietary
deficiency (1901)4
3: "Christiaan Eijkman, Beriberi and Vitamin B1". Nobelprize.org. 11 Oct 2012
http://www.nobelprize.org/educational/medicine/vitamin_b1/eijkman.html
4:Lanska, DJ. “Chapter 30: Historical aspects of the major neurological vitamin deficiency disorders: the water-soluble B vitamins”, In: Michael
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J. Aminoff, François Boller and Dick F. Swaab, Editor(s), Handbook of Clinical Neurology, Elsevier, 2009, 95, p 445-476,
slide-5
On a molecular level …
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Beriberi in infants
• Thiamine-deficient mother due to polished rice
• Breast-fed infant does not get enough thiamine
Picture of Rice Mill (from Dr. Fischer)
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Japanese Occupation of Singapore
• First observational study in infants 5
• 1947, Archives of Disease in Children
• 139 cases, 55 % died
5: Haridas G. “Infantile beri-beri in Singapore during the latter part of the Japanese
occupation.” Arch Dis Child. 1947 Mar;22(109):23-33.
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What does beriberi in infants look like?5,6,7
• Previously healthy, 2-4 months old
• Vomiting, irritability over a few days but no fever
• Respiratory distress, tachycardia
• Hepatomegaly
• Dysphonia, hoarseness
• Cyanosis and grunting
• Cold extremities, mottled skin
• Death within a few days
5:Haridas G. “Infantile beri-beri in Singapore during the latter part of the Japanese occupation.” Arch Dis Child. 1947 Mar;22(109):23-33.
6:Thanangkul, O. and J. Whitaker (1966). "Childhood thiamin deficiency in Northern Thailand." American Journal of Clinical Nutrition 18: 275-277.
7: Luxemburger, C., N. J. White, et al. (2003). "Beri-beri: the major cause of infant mortality in Karen refugees." Transactions of the Royal Society of
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Tropical Medicine and Hygiene 97(2): 251-255.
How do we treat it?
• Replace the thiamine: 50 mg IM.
• Signs and symptoms resolve within hours.
• “Infantile beriberi is a readily-preventable
disease that nearly disappeared in the first half
of the 20th century.”2
• And yet, it remains “an important cause of
infant mortality in rural areas of [southeast
Asia].”2
2: Luxemburger, C., N. J. White, et al. (2003). "Beri-beri: the major cause of infant mortality
in Karen refugees." Transactions of the Royal Society of Tropical Medicine and Hygiene
97(2): 251-255.
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Back to Prey Veng Province …
• Do these infants have beriberi?
• Why are they so young? (1-2 months)
• Could there be an environmental or dietary
exacerbation of thiamine deficiency?
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Medical Student #1: Kelsey Shelton-Dodge
Blood draw
Blood draw
Survey
Survey
Blood draw
27 healthy
controls
(Cambodia)
& mothers
20 healthy
controls
(USA) &
mothers
27 beriberi
cases &
mothers
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Results
Thiamine:
Low
NO
difference
Thiamine:
Low
Thiamine:
Normal
27 healthy
controls
(Cambodia)
& mothers
20 healthy
controls
(USA) &
mothers
=
in
thiamine
levels
27 beriberi
cases &
mothers
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Results (cont.)
• No association between environmental and
dietary factors and thiamine levels
• Symptoms of beriberi resolved quickly after
treatment, but hepatomegly and vital signs were
slower to resolve
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Implications
• If all the Cambodian infants are thiaminedeficient, why do only some get beriberi?
• If clinical criteria don’t correlate to thiaminelevels, how are we going to diagnose beriberi?
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Medical Student #2: Liz Keating
Blood draw
Clinical &
Lab
Variables
50 infants presenting
with tachypnea
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Results
• No clinical or lab data correlates to thiamine
levels
• Even infants not treated with thiamine had
improved thiamine levels at discharge.
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Implications
• How do we diagnose beriberi?
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What about response to thiamine treatment
as a diagnostic criteria? Well …
• Acute infection could be simply running its
course, and would have resolved even without
thiamine administration.
• Thiamine deficiency may predispose infants to
more severe infections, and repletion helps
them overcome the infection.
• Lima ICU study (Brazil)8
• Mayxay Malaria study (Laos)9
8: Lima, L. F., H. P. Leite, et al. (2011). "Low blood thiamine concentrations in children upon admission to the intensive care unit: risk factors and
prognostic significance." The American Journal of Clinical Nutrition 93(1): 57-61.
9: Mayxay, M., A. M. Taylor, et al. (2007). "Thiamin deficiency and uncomplicated falciparum malaria in Laos." Tropical Medicine & International
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Health : TM & IH 12(3): 363-369.
Medical Student #3: Sam Porter
• Beriberi will show right-sided heart failure10,11
• What do hearts of Debbie’s sick kids vs.
apparently healthy infants look like?
• How do sick kids’ hearts change after thiamine
administration?
• At what thiamine level do we start seeing
cardiac dysfunction?
• N-type Pro-BNP12
10: Khowsathit, P., B. Pongpanich, et al. (1990). "Cardiac beri-beri. Report of a case with an echocardiographic study." Japanese Heart Journal 31(2): 265-269.
11:Rao, S. N. and G. R. Chandak (2010). "Cardiac beriberi: often a missed diagnosis." Journal of Tropical Pediatrics 56(4): 284-285.
12: Lowenthal, A., B. V. Camacho, et al. (2012). "Usefulness of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide as biomarkers for heart failure in
young children with single ventricle congenital heart disease." The American Journal of Cardiology 109(6): 866-872.
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Methods
Blood draw:
Day 0 & 2
Blood draw:
Day 0
Echocardiogram:
Echocardiogram:
Day 0, 1 & 2
Day 0
20 beriberi
cases
45 healthy
controls
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Working with a team
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Fitting into the culture (not vice versa)
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The Protocol
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Preliminary results
Beriberi: short axis
Healthy control:
short axis
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Preliminary results (cont)
Beriberi: 4
chamber w/
Doppler
Healthy control: 4
chamber w/
Doppler
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Preliminary results (cont)
Beriberi: Day 0
Short-axis
Beriberi 24 hours
after thiamine
treatment
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Preliminary results (cont)
Beriberi: Day 0
4 Chamber
Beriberi 24 hours
after thiamine
treatment
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Demographic Data of Beriberi Cases
• 20 beriberi cases
• 60% male, 40% female
• Mean age: 10.8 weeks (std. dev: 7.7)
• Age range: 3 – 31 weeks
• 30% pure beriberi, 70% mixed
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The questions continue …
• How do we predict which thiamine-deficient
children will succumb to beriberi?
• How do we improve thiamine levels on a
population scale?
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Summary
• Beriberi in infants presents as heart failure and
respiratory distress, and is caused by thiaminedeficiency
• In SE Asia, mothers are thiamine-deficient due to staple
diet of polished rice, and their infants do not get enough
thiamine from their breast-milk
• Thiamine deficiency is extremely common among
infants and mothers in Prey Veng Province, Cambodia,
in both apparently-healthy and sick populations
• Thiamine deficiency is not related to environmental
factors
• There may be a relationship between thiamine levels
and infectious disease, thus making beriberi difficult to
diagnose
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Clinician?
Teacher?
Researcher?
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Heal the sick. Advance the science.
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Grants
This project was supported by CTSA Grant
Number UL1 TR000135 from the National
Center for Advancing Translational Science
(NCATS), the Benjamin H. Kean Traveling
Fellowship in Tropical Medicine from the
American Society of Tropical Medicine &
Hygiene (ASTMH), and the Hubert Trust
Scholarship from Baptist Medical Dental
Fellowship (BMDF). Its contents are solely the
responsibility of the authors and do not
necessarily represent the official views of the
NIH, ASTMH, or BMDF.
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References
1: Kauffman, G., D. Coats, et al. (2011). "Thiamine deficiency in ill children." The American Journal
of Clinical Nutrition 94(2): 616-617; author reply 617.
2: Luxemburger, C., N. J. White, et al. (2003). "Beri-beri: the major cause of infant mortality in Karen
refugees." Transactions of the Royal Society of Tropical Medicine and Hygiene 97(2): 251-255.
3: "Christiaan Eijkman, Beriberi and Vitamin B1". Nobelprize.org. 11 Oct 2012
http://www.nobelprize.org/educational/medicine/vitamin_b1/eijkman.html
4:Lanska, DJ. “Chapter 30: Historical aspects of the major neurological vitamin deficiency disorders:
the water-soluble B vitamins”, In: Michael J. Aminoff, François Boller and Dick F. Swaab,
Editor(s), Handbook of Clinical Neurology, Elsevier, 2009, 95, p 445-476,
5: Haridas G. “Infantile beri-beri in Singapore during the latter part of the Japanese
occupation.” Arch Dis Child. 1947 Mar;22(109):23-33.
6:Thanangkul, O. and J. Whitaker (1966). "Childhood thiamin deficiency in Northern Thailand."
American Journal of Clinical Nutrition 18: 275-277.
7: Luxemburger, C., N. J. White, et al. (2003). "Beri-beri: the major cause of infant mortality in Karen
refugees." Transactions of the Royal Society of Tropical Medicine and Hygiene 97(2): 251-255.
8: Lima, L. F., H. P. Leite, et al. (2011). "Low blood thiamine concentrations in children upon
admission to the intensive care unit: risk factors and prognostic significance." The American
Journal of Clinical Nutrition 93(1): 57-61.
9: Mayxay, M., A. M. Taylor, et al. (2007). "Thiamin deficiency and uncomplicated falciparum malaria
in Laos." Tropical Medicine & International Health : TM & IH 12(3): 363-369.
10: Khowsathit, P., B. Pongpanich, et al. (1990). "Cardiac beri-beri. Report of a case with an
echocardiographic study." Japanese Heart Journal 31(2): 265-269.
11:Rao, S. N. and G. R. Chandak (2010). "Cardiac beriberi: often a missed diagnosis." Journal of
Tropical Pediatrics 56(4): 284-285.
12: Lowenthal, A., B. V. Camacho, et al. (2012). "Usefulness of B-type natriuretic peptide and Nterminal pro-B-type natriuretic peptide as biomarkers for heart failure in young children with
single ventricle congenital heart disease." The American Journal of Cardiology 109(6): 866-872.
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Questions?
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