Micronutrient Diarrhoea Malnutrition-SK Roy (Bangladesh)

8/13/2019 Micronutrient Diarrhoea Malnutrition-SK Roy (Bangladesh)

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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 .

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Micronutrient Diarrhoea Malnutrition-SK Roy (Bangladesh)