Recent changes in the management of childhood diarrhea

1
Recent changes in the management of childhood
diarrhea
And the future
Shinjini Bhatnagar Centre for Diarrheal Diseases
Nutrition Research Department of Pediatrics All
India Institute of Medical Sciences, New Delhi,
India
2
Revised recommendations for use of ORS by
WHO/UNICEF (2001), Govt of India IAP (2004-07)

• 75 mEq/l of sodium and 75 mmol/l of glucose
  (osmolarity 245 mosmol/l) universal single
  solution
• Red osm ORS (Na 75 glucose 75) safe
  effective for children adults with cholera
• Adults with cholera may have asymptomatic
  hyponatremia
• post market surveillance is required

3
Why was there a need to for an improved ORS?

• A desire for an improved ORS was widely expressed
  to
• achieve
• shortening of duration of diarrhea
• decrease in stool output
• decrease in need for IV fluids
• Initial concerns about hypernatremia
• Water/sodium absorption better with lower
  osmolarity in animal perfusion studies

4
Composition of standard and reduced osmolarity
ORS solutions

• Reduced Osmolarity ORS
• Standard (mEq or mmol/L)
• ORS solution
• (mEq or mmol/L)
• Glucose 111 111 75-90 75
• Sodium 90 50 60-70 75
• Chloride 80 40 60-70 65
• Potassium 20 20 20 20
• Citrate 10 30 10 10
• Osmolarity 311 251 210-260 245
• 30 mmol/L of bicarbonate instead of 10 mmol/L of
  citrate

5
Results of meta analysis comparing low osmolarity
ORS (lt 245 mosmol/l) with WHO-ORS in children
with non cholera diarrhea
Outcome Number Reduction in of
studies odds (95 CI) Need for IV
fluids 9 39 (19, 53) Stool output 12 19
(12, 26) Vomiting 6 29 (8,
45) Reduction in geometric means
6
Can it be used in children adults with cholera ?

• Children
• Stool output at 24h was same (1 study) or 30
  less (2 studies)
• Need for IV fluids was less
• (30 red osm ORS vs. 44 with std. ORS)
• Adults
• Statistically insignificant mean reduction of
  0.5ml/kg in stool output in first 24 h

7
Is reduced osmolarity ORS safe?
Non-cholera diarrhea Children
Risk of developing hyponatremia not
significant Cholera Children Mean reduction
in serum Na (mEq/L) 0.8 (95CI 0.2 to
1.4) Adults Mean reduction in serum Na (mEq/L)
1.3 (95CI 0.3 to 2.3)
8
WHO/UNICEF Joint statement for use of zinc in
clinical management of acute diarrhea (2001)
Recommendations 20 mg per day of zinc
supplementation for 10-14 days starting as early
as possible after onset of diarrhea 10 mg per
day for infants 2-6 mo Administration Once or
twice daily
Endorsed by IAP Govt of India, 2003-2007
9

• Initial interest in zinc in acute diarrhea
  started in India
• MAMC, New Delhi
• AIIMS, New Delhi Collaborators
• Prof MK Bhan, Dr Nita Bhandari, Dr Shinjini
  Bhatnagar,
• Dr Sunil Sazawal, Dr Rajiv Bahl (AIIMS)
• Dr RE Black (Hopkins), Dr Halvor Sommerfelt, Dr
  Tor Strand (Univ of Bergen)

10
Effect of zinc supplementation in acute diarrhea
in an urban community in India

• 937 children, 6-35 mo, diarrhea lt 7 d 20 mg zinc
  daily
• reduction (95CI)
• Risk of continued diarrhea 23 (12 to 32)
• episodes gt 7d 39 (7 to
  61)
• Mean no of watery stools/d 39 (6 to 70)
• No of days with watery diarrhea 21 (10 to
  31)

Sazawal et al, N Eng J Med 1995
11
Prevalence of zinc deficiency based on plasma or
serum zinc in field trials
Site Age Prevalence ()
India 6-35 mo 36 India
6-30 mo 44 India 12-59
mo 32 Mexico 18-36 mo 68
Lima 24 mo 80
PNG 2-10 yrs 37
Ontario 5-7 yrs 21 Dev.
countries lt 5 yrs 38
12
Why is zinc deficiency so prevalent?

• Breast milk not a sufficient source gt 4-5 mo
• Low intake of complementary foods
• Low consumption of animal foods
• High fecal losses during diarrheal illness
• Limited bioavailability? phytates from cereals
• Low content of soil, of foods

13
Pooled analysis of zinc supplementation trials
on diarrhea prevention in children lt5
yearsZinc 1-2 RDA daily for 4-12 moIndia,
Mexico, PNG, Peru, Vietnam, Guatemala, Jamaica

• (95 CI) Reduction
• Diarrhea incidence 18 ( 7 to 28 )
• Diarrhea prevalence 25 ( 12 to 37 )
• Zinc Investigators Collaborative Group, J
  Pediatrics 1999

14
Zinc supplementation reduced the incidence of
severe prolonged diarrhea in young North Indian
children

• Zinc 1-2 RDA daily for 4 mo
• (95 CI) Reduction
• Stool frequency 3-5 10 (2 to 17)
• 6-9 13 (2 to 23)
• gt 10 23 (6 to 37)

Bhandari et al, Pediatr 2002
15
Zinc in Treatment of Acute Diarrhea in
Hospitalized Children
No. of subjects Studies from India, Nepal,
Bangladesh 3,600 Sazawal, New Delhi
931 Bahl, New Delhi 805 Bhatnagar,
New Delhi 266 reduction in
zinc group Cessation of diarrhea
26 Total stool output
24
Zinc given for 14d beginning during acute or
persistent diarrhea reduces diarrhea morbidity
(11 reduction in incidence and 44 reduction in
prevalence) during subsequent 2-3 mo without
further supplementation
16
How does zinc work ???
17
Possible mechanisms for benefits seen with zinc
supplementation in infectious diseases
Correction of zinc deficiency
immunoreconstitution Direct effects on the
epithelial barrier Direct immunostimulatory
effect Anti secretory effect
18
What are the implications of introducing zinc in
the programme?

• Does it affect hospitalization?
• Does it have an impact on mortality?
• Does it reduce antibiotic use?
• Does it increase use of ORS?
• Will it be consumed for 14 days?

19
Effect on mortality hospitalizations after
giving zinc (with ORS) for 14d started during
acute diarrhea
20 mg Zn/d for 14 d, Matlab, Bangladesh
Intervention Control
Child-years of f. up 5866
6015 Decreased non-injury
deaths by 50
(6-75) Decreased hospitalizations by
24 (2-41)
Baqui et al, BMJ 2002
20
Introduction of treatment of acute diarrhea with
Zinc ORS vs ORS alone in Indian rural community
through PHC workers private practioners
6 PHCs randomly allocated to intervention and
control (90,000 population each sites)
Benefits in intervention villages compared to
control villages Reduction in Diarrhea
prevalence in last 2 weeks 44 Pneumonia
prevalence in last 2 weeks 45 All cause
hospitalization in last 3 months 59 Use of
unwarranted drugs in last 1 mo 78 Use of
unwarranted injections 58 Average cost of
treatment for one diarrheal episode to family
nil vs Rs. 40
Bhandari N, Pediatrics (in press)
21
Can we mix zinc with ORS ?

• ORS fortified with 40 mg zinc/ litre does not
  decrease stool output or diarrhea duration in
  500 hospitalized children (1-35 mo) with severe
  acute diarrhea

Bhatnagar et al, in press
22
ORS Zinc experience in India till now

• 2004-2006
• Reduced osmolarity ORS introduced in the National
  Health Programme
• IAP recommendations on use of reduced osm ORS
  zinc in treatment of diarrhea disseminated to
  stake holders
• Evidence from Indian effectiveness studies
  presented to the National Task Force, GOI
• Several National Task Force meetings

23
Zinc experience in India till now

• 2006-2007
• Zinc in RCH/NRHM state PIPs
• Professional bodies (IAP, IMA) conducted several
  CME symposia on use of reduced osm ORS zinc in
  treatment of diarrhea
• NGOs (POUZN, PSP) sensitized health staff on ORS
  zinc

24
Current strategies the future

• 2008
• GOI sanctioned funds for procurement of zinc
  tablets as part of RCH kit
• Transfer of technology to Indian company (process
  of manufacturing of dispersible zinc tablets )
  initiated
• Updated diarrhea guidelines prepared shared
  with GOI
• Issues of training of health workers being
  discussed
• Several pharmaceutical companies manufacturing
  syrup and dispersible zinc tablets

25
Current strategies the future

• 2008
• UNICEF
• Communication strategy being developed
• Scaling up in 16 districts
• POUZN
• Operational research to sensitize informal
  providers through NGO semi wholesalers in 5 UP
  districts
• MI
• Developing generic scale up guides for state
  govts. To support state govts of Bihar MP in
  scale up.
• IAP other professional bodies
• To continue dissemination education to
  clinicians through CME journals
• Implementation through scaling up of in service
  pre service IMNCI

26
Zinc Treatment for Diarrhea

• More than 3,000 pediatricians now prescribing
  zinc treatment
• Fastest growing segment in diarrhea treatment
  sales increased by 82 from 905,000 in 2006 to
  1.65 million in 2007
• Increase co-prescription of ORS zinc

27
Challenges!!

• Increase ORS ( zinc) use rates
• Logistics
• Anganwari as the distribution centre
• Promote ORS through health centres,
• sub-centres, hospitals
• Communication support
• Bringing private nonformal sector on board