micronutrient diarrhoea malnutrition-sk roy (bangladesh)
TRANSCRIPT
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Dr.S.K.RoySenior Scientist
ICDDR,B
ASCODD XII: Yogyakrta May 25th
27th
, 2009
Micronutrient: Diarrhoea andMalnutrition
Welcome to my presentation
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Causes of death among children aged under five years
(WHO, 2004)
10 Leading causes of death in the world
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10 Leading causes of death in Low-income
Countries
Distribution of global child deaths by causeBars=uncertainty bounds. *Work in progress to establish the cause specificcontribution of being underweight to neonatal deaths, Lancet 2003 (ChildSurvival-1, Black et al)
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Risk of mortality by malnutrition after treatment of diarrhoea
140
100
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65 8575550Nutritional state (% NCHS standard)
Roy et al. 1983
Mortality /1000
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Major micronutrients related toDiarrhoea
Zinc Vitamin A Folic Acid Iron Copper
Magnesium
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Relationship among Malnutrition,Diarrhoea and Micronutrient Deficiency
Malnutrition
MicronutrientDeficiency Diarrhoea
Micronutrients deficiency causes Diarrhoea
malnutrition
Loss of-Vitamin AZincFolic AcidIronCopper
Diarrhoea (loss of water & electrolytes)AD PD
Loss ofMicronutrients
Malnutrition
Immunity
Infection
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Physiological Functions of Zinc
ZincFunctioning of insulin
Epithelial cell lining Membrane s tabilization
Wound and burn healing
Synthesis and metabolism of protein and
nucleic acidImmunity
Brain development
Calcification and mineralization of boneCalcification and mineralization of bone
Zinc Deficiency Zinc Supplementation
Mucosa
Levels of the brush borderenzymes
Enhanced cellular immunity
Level of secretary antibodies
First Line of Defense
Cellular Immunity
Humoral Immunity
Size of spleen and thymus
Functioning and production ofT-cells, B-cells andmacrophages
Production of immunoglobulins(IgA, IgM, IgG)
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Mechanism of diarrhoea in animal modelDeficient
Zn+ +
in diet
Growth Clinical abnormalaitiesIntestinal mucosa
Enterocyte population Enterocyte sizeUltrastructural abnormality
Membrane defectLateral spaceDesmosen defect
Mitochondrial disruptionLysosomal activity
Endoplasmic reticulamdefectRibosomal defect
Na+
K+
ATP ase
Reduced absorption
Increased secretion
Increased net secretion of Water and electrolytes
Diarrhoea
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Roy et al 2006
Animal model study on net transport of water and electrolytes duringAnimal model study on net transport of water and electrolytes during
inin--vivo Perfusion (Meanvivo Perfusion (Mean + + SEM)SEM)
Absorption ZD ZAL ZDR Per/cm/hr (n=5) (n=5) (n=5)
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Water ( l) 27.6+2.0** 48.5+5.8 57.7+5.2
Sodium (mmol) 3.5+1.1* 7.2+2.0 7.7+3.0
Potassium (mmol) 0.07+0.2 0.07+0.02 0.03+0.1
(Roy et al 1985)(Roy et al 1985)**p
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Water Sodium Potassium
Net secretion of water, sodium and potassium in zinc deficient, acutely repleteand ad Libitum zinc fed rats in response to cholera toxin (mean SEM)
T r a n s p o r t o
f w a
t e r
+10
0
-10
-20
-30
-40
-50
-60
-70
+2
0
- 2
- 4
-6
-8
-10
ZD
ZDR
ZAL
(Roy et al. 1985,2005)(Roy et al. 1985,2005)
Zinc in Cholera toxin induced secretionZinc in Cholera toxin induced secretion
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Vitamin A
Immunity increase Epithelial tissue Formation
Antioxidant
Develop structural protein
Embryonic development
Function of vitamin A
Host immunity
Quality of cellmembranes
Intestinal secretion/ absorption
Integrity of Mucosal surface
Number of enterocytes
Hormonal control (e.g.aldosterone, thyroid)
Mechanisms by which micronutrients deficiency may influence intestinalsecretion and absorption
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Micronutrient metabolism in diarrhoea
Zinc is excreted proportionately high with severity ofdiarrhoeaCu and Mg also excreted from diarrhoeaZinc absorption is substantially reduced duringdiarrhoea
Excretion of trace elements in stoolduring persistent diarrhoea (median, range)
Micronutrients Median (Range)
Zinc (mg/Day) 4. 5 (1.10-68.57)
Mg ( g/kg) 4673 (736- 71214)
Cu ( g/kg) 21.5 (1.53-138.2)
Roy et al 2004
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Loss of total zinc (mg) over 4 days in stool during
Persistent diarrhoea and recovery phaseDiarrhoea Recovery p value*
Rice suji+Zn (15) 35.5 11.1 5.0 3.3
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Therapeutic effect ofMicronutrients in Diarrhoea
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Zinc supplementation in children during acute diarrhoeaZinc supplementation in children during acute diarrhoea
Total stool weight (g/kg body weight)(median range)Total stool weight (g/kg body weight)(median range)
PlaceboPlacebo ZincZinc p value*p value*
All children 329 (32All children 329 (32- -1464) n=37 238 (351464) n=37 238 (35- -2416) n=372416) n=37 0.060.06
Ht/age
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Probability of recovery from cholera by zincsupplementation
Roy et al ,BMJ, 2008
Impact of zinc supplementation on period of recovery indays and weight gain in shigella dysentery
Zinc (n=28) control (n=28)Zinc (n=28) control (n=28) p value*p value*
Time (days) to recovery, 2 (1Time (days) to recovery, 2 (1- -8)8) 4 (14 (1--8 )8 ) 0.03 *0.03 *median (range)median (range)
Time (days) to disappearance 2 (1Time (days) to disappearance 2 (1- -7)7) 4 (14 (1--7 )7 ) 0.040.04of mucous from stoolof mucous from stoolmedian (range)median (range)
Body weight (kg)Body weight (kg)On admission, meanOn admission, mean SD 8.75 1.2 a 9.38 1.4 aAt discharge, meanAt discharge, mean SD 9.20 0.4 9.60 1.8p valuep value 0.0000.000 0.120.12
*Mann*Mann- -whitney U testwhitney U testaapaired tpaired t- -testtest
Roy et al. 2007
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On admission On discharge p value *
H/A
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Pooled Analysis of the Therapeutic Effect of Zinc Supplementation on Acute and PersistentDiarrhoea Recovery Continuation for >7 d, failu re, death
Trial Recovered Censored Excluded RRn n n (95%CI)
Acute Diarrhoea
Indonesia 1368 0 300.92(0.83,,1.02)
India 931 6 0 0.79(0.69,0.90)
Bangladesh 101 9 1 0.85(0.57,1.28)
Pooled multifactorial 0.85(0.78,0.92)
Pooled random effect 0.85(0.76,0.95)
Persistent Diar rhoea
Peru 164 24 87 0.82(0.60,1.12)
Bangladesh 138 52 0 0.85(0.61,1.19)
Bangladesh 55 32 1 0.45(0.26,0.78)
Pakistan 55 32 0 0.98(0.57,1.67)Pooled 0.76(0.62,0.92)
Pooled multifactorial 0.75(0.62,0.91)
Pooled random effect 0.76(0.63,0.91)
Zinc Control OR
(95% CI)47(6.4) 57(8.6) 0.72(0.48,1.07)
70(15.4) 85(17.7) 0.85(0.60,1.19)
14(24.6) 16(29.6) 0.77(0.33,1.79)
0.80(0.62,1.02)
0.78(0.56,1.09)
11(7.9) 13(9.6) 0.81(0.35,1.88)
7(7.4) 17(17.9) 0.37(0.14,0.92)
9(20.5) 22(50.0) 0.25(0.10,0.64)
16(37.2) 12(27.3) 1.58(0.64,3.91)
0.60(0.38,0.93)
0.58(0.37,0.90)
0.61(0.26,1.46)
Comparison of cumulative stool output (mg kg-body wt) of children
with persistent diarrhoea during hospitalization
Khatun et al, 2001
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1.9 (-2.23,2.55)-0.9 (-2.37,2.2)
2.2 (-4.1,8.5)2.2 (-3.8,8.2)
62.2 33.564.4 37.864.4 35
PlaceboZnZn+Cu
Duration ofdiarrhea(hours)* fromenrollment
AdjustedDifference(95% Cl)**
Difference(95% Cl)*
Mean SDInterventionOutcomevariable
Table :Zinc and copper supplementation in Diarrhoealdisease
* The difference is as compared with the placebo group
** Adjusted for following covariates: age, gender,prior duration of diarrhea, weight-for-age Z-scoreat most 2, dehydration status, receipt of medication, water safety, wealth index, type of stool,baseline serum zinc and serum copper.
Preventive effect of Micronutrientsin Diarrhoeal Disease
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Effect of supplementation with zinc or vitamin A or bothon Diarrhoea and dysentery
There was no overall effect of high-dose vitamin A supplements on the
incidence of diarrheal disease.
However, there was a significant interaction between supplementation and
age: vitamin A increasedthe incidence of diarrhea in children
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Risk Factors for micronutrients deficiency in diarrhoea andmalnutrition
a. Inadequate dietary intake(cultural/geographical/economic/ignorance)
b. Decreased bioavailabilityc. Loss of micronutrients in diarrhoea
During acute and persistent diarrhoea, large amounts of zinc and othermicronutrients are lost through stool (Roy et al 2004)Children with severe PD lost about 300 g/kg/day in stool. (Rothbaum et al.1982)AD leads to Zn & Cu depletion. ( Castillo-Duran et al. 1988)PD in children is associated with lower serum levels of Zn & Cu (Rodriguez
et al. 1985)Children with PD appear to be at high risk for developing Vitamin Adeficiency. (Natarajan et al. 1990)
Explore the potential: Research
1. ZINC suppl. In adults diarrhoea
2. Add zinc in ORS packets
Clinical : zinc to AD, PD, Shigellosis, cholera
A.To improve the content and bioavailability ofzinc
Increase intake of food with highly bioavailable zinc
Reduce phytate and inhibitors for absorption
Using germination, fermentation and soaking to reducephytic acid, a potent inhibitor of zinc absorption.
(Gibson et al.1998).
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B. Adequacy of micronutrients in diets, through dietarydiversification specially animal foods, coloured vegetables
C. Food fortification for improving the status of micronutrients
D. Genetically modified food grains for higher micronutrientcontent .