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Beriberi Treatment: What a medical student can teach us all

Beriberi Treatment: What a medical student can teach us all. Philip Fischer, M.D., and Samuel Porter. Global Missions Health Conference November 9 th , 2012. Prey Veng Province, Cambodia. Debbie Coats, FNP. Svay Chrum Health Clinic

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Beriberi Treatment: What a medical student can teach us all

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  1. Beriberi Treatment: What a medical student can teach us all Philip Fischer, M.D., and Samuel Porter Global Missions Health Conference November 9th, 2012

  2. Prey Veng Province, Cambodia

  3. Debbie Coats, FNP Svay Chrum Health Clinic Previously-healthy infants presenting with tachypnea, tachycardia, hepatomegaly, and no fever.

  4. 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 Nutrition94(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 Hygiene97(2): 251-255.

  5. “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 J. Aminoff, François Boller and Dick F. Swaab, Editor(s), Handbook of Clinical Neurology, Elsevier, 2009, 95, p 445-476,

  6. On a molecular level …

  7. 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)

  8. 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.

  9. 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 Tropical Medicine and Hygiene97(2): 251-255.

  10. How do we treat it? Replace the thiamine: 50 mg IM. Signs and symptoms resolve within hours. “Infantile beriberi is a readily-preventabledisease 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 Hygiene97(2): 251-255.

  11. 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?

  12. Medical Student #1: Kelsey Shelton-Dodge Blood draw Blood draw Blood draw Survey Survey 27 beriberi cases & mothers 27 healthy controls (Cambodia) & mothers 20 healthy controls (USA) & mothers

  13. Results NO difference Thiamine: Low Thiamine: Low Thiamine: Normal = in thiamine levels 27 beriberi cases & mothers 27 healthy controls (Cambodia) & mothers 20 healthy controls (USA) & mothers

  14. 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

  15. Implications If all the Cambodian infants are thiamine-deficient, why do only some get beriberi? If clinical criteria don’t correlate to thiamine-levels, how are we going to diagnose beriberi?

  16. Medical Student #2: Liz Keating Clinical & Lab Variables Blood draw 50 infants presenting with tachypnea

  17. Results • No clinical or lab data correlates to thiamine levels • Even infants not treated with thiamine had improved thiamine levels at discharge.

  18. Implications How do we diagnose beriberi?

  19. 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 Nutrition93(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 & IH12(3): 363-369.

  20. 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 Journal31(2): 265-269. 11:Rao, S. N. and G. R. Chandak (2010). "Cardiac beriberi: often a missed diagnosis." Journal of Tropical Pediatrics56(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 Cardiology109(6): 866-872.

  21. Methods Blood draw: Day 0 & 2 Blood draw: Day 0 Echocardiogram: Day 0, 1 & 2 Echocardiogram: Day 0 20 beriberi cases 45 healthy controls

  22. Working with a team

  23. Fitting into the culture (not vice versa)

  24. The Protocol

  25. Preliminary results Beriberi: short axis Healthy control: short axis

  26. Preliminary results (cont) Beriberi: 4 chamber w/ Doppler Healthy control: 4 chamber w/ Doppler

  27. Preliminary results (cont) Beriberi: Day 0 Short-axis Beriberi 24 hours after thiamine treatment

  28. Preliminary results (cont) Beriberi: Day 0 4 Chamber Beriberi 24 hours after thiamine treatment

  29. 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

  30. 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?

  31. Summary Beriberi in infants presents as heart failure and respiratory distress, and is caused by thiamine-deficiency 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

  32. Clinician? Teacher? Researcher?

  33. Heal the sick. Advance the science.

  34. 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.

  35. References 1: Kauffman, G., D. Coats, et al. (2011). "Thiamine deficiency in ill children." The American Journal of Clinical Nutrition94(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 Hygiene97(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 Hygiene97(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 Nutrition93(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 & IH12(3): 363-369. 10: Khowsathit, P., B. Pongpanich, et al. (1990). "Cardiac beri-beri. Report of a case with an echocardiographic study." Japanese Heart Journal31(2): 265-269. 11:Rao, S. N. and G. R. Chandak (2010). "Cardiac beriberi: often a missed diagnosis." Journal of Tropical Pediatrics56(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 Cardiology109(6): 866-872.

  36. Questions?

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