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Update on Diarrhoea Management

What is New?

O. Fontaine, WHO – GenevaOn behalf of the Zinc task Force

A Workshop to Support the Introduction of Zinc as part of Diarrhoea Management in Indonesia

Jakarta, Indonesia

26-28 September 2006

Epidemiology

Diarrhoea Mortality

• 1980: 4.6 million child deaths from diarrhoea

• 2003: 1.8 million child deaths from diarrhoea

Black, Morris, Bryce. Lancet 2003.

Jones, Steketee, Black et al. Lancet 2003.

Diarrhoea prevalence in under-five children by socioeconomic status in

selected countries

0

5

10

15

20

25

30

Bangladesh Viet Nam Benin Tanzania

Country

Dia

rrh

oea p

revale

nce

Poorest 20%

Richest 20%

Diarrhoea Treatment Policy

Global Diarrhoea Treatment Policy

• Treatment of dehydration with ORS solution (or with an intravenous electrolyte solution in cases of severe dehydration)

• Continue feeding or increase breastfeeding during , and increase feeding after the diarrhoeal episode

• Use antibiotics only when appropriate (i.e. bloody diarrhoea) and abstain from administering anti-diarrhoeal drugs

• Advise mothers of the need to increase fluids and continue feeding during future episodes

• Provide children with 20mg per day of zinc for 10-14 days

WHO/UNICEF. Joint statement on the clinical management of acute diarrhoea. 2004.

Global Diarrhoea Treatment Policy

• Treatment of dehydration with ORS solution (or with an intravenous electrolyte solution in cases of severe dehydration)

• Continue feeding or increase breastfeeding during , and increase feeding after the diarrhoeal episode

• Use antibiotics only when appropriate (i.e. bloody diarrhoea) and abstain from administering anti-diarrhoeal drugs

• Advise mothers of the need to increase fluids and continue feeding during future episodes

• Provide children with 20mg per day of zinc for 10-14 days

WHO/UNICEF. Joint statement on the clinical management of acute diarrhoea. 2004.

Global Diarrhoea Treatment Policy

• Treatment of dehydration with ORS solution (or with an intravenous electrolyte solution in cases of severe dehydration)

• Continue feeding or increase breastfeeding during , and increase feeding after the diarrhoeal episode

• Use antibiotics only when appropriate (i.e. bloody diarrhoea) and abstain from administering anti-diarrhoeal drugs

• Advise mothers of the need to increase fluids and continue feeding during future episodes

• Provide children with 20mg per day of zinc for 10-14 days

WHO/UNICEF. Joint statement on the clinical management of acute diarrhoea. 2004.

Recent Scientific Advancesabout Zinc in the Treatment of

Diarrhoea

Zinc for the Treatment of DiarrhoeaHistory of Research

• Ongoing research from the 1990s until today

• 13 trials in acute diarrhoea

• 5 trials in persistent diarrhoea

• Age groups: 3-60 mo

• Dose of zinc: ≈ 20 mg/d (range 5-45 mg/d)

Zinc for the Treatment of DiarrhoeaResearch Findings

• 15% reduction in duration of acute diarrhoea

• 24% reduction in duration of persistent diarrhoea

• 42% reduction in treatment failure or death in persistent diarrhoea

Zinc Investigators’ Collaborative Group. AJCN 2000.

Effect of Zinc Supplementation on Duration of Acute Diarrhoea/Time to Recovery

*Bangladesh, 1999

Pooled

1*Difference in mean and 95% CI

Relative Hazards and 95% CI

*India, 1988

*India, 2000*Brazil, 2000*India, 2001

Indonesia, 1998India, 1995

Bangladesh, 1997India, 2001

India, 2001

Nepal, 2001

Bangladesh, 2001

Therapeutic Effects of Zinc on Diarrhoea Severity

CountryDiarrhoea Outcome

Percent Reduction

India Frequency 18

India Frequency 39

Bangladesh Output 28

India Output 38

Brazil Frequency 59

Additional Preventive Aspects of Zinc Treatment

• Zinc supplementation for 10-14 days has longer term effects on childhood illnesses in the 2-3 months after treatment

• 34% reduction in prevalence of diarrhoea

• 26% reduction in incidence of pneumonia

Zinc Investigators’ Collaborative Group. Pediatrics. 1999.

Preventive Effect of Zinc Supplementation on Diarrhoea Incidence in Short - Course

Supplementation Trials Bangladesh (I)

Bangladesh (II)

Pakistan

Bangladesh (III)

Pooled

0 0.25 0.5 0.75 1 1.25 1.5 1.75 2 2.25 2.5

Odds Ratio and 95% CI

Community-based Trial Demonstrates Zinc Effectiveness in

Treating Diarrhoea

• 30 health worker areas in rural Bangladesh randomized to ORS alone or ORS + zinc (20mg/d for 14 days) for diarrhoea treatment

• 11,880 child-years of observation during the 2 year study

• 23% decrease in duration of all diarrhoea episodes in zinc treatment clusters compared to control clusters (RH 0.77, 95% CI 0.69-0.86)

Baqui, Black, Arifeen. BMJ 2003.

Community-based Trial Demonstrates Longer-term Benefits of Zinc

• Zinc supplementation decreased:• Overall diarrhoea prevalence by 15% (RR

0.85, 95% CI: 0.76, 0.96)• Hospitalization from diarrhoea by 19% (RR

0.81, 95% CI: 0.65, 1.00)• ALRI prevalence by 7% (RR 0.93, 95% CI:

0.78, 1.10)• Hospitalization from ALRI by 19% (RR 0.81,

95% CI: 0.53, 1.23)

Community-based Trial Demonstrates Longer-term Benefits

of Zinc

• Decreased overall mortality by 51% (RR 0.49 95% CI: 0.25, 0.94), non-injury deaths

• Decreased antibiotic use rate from 34% in control clusters to 13% in zinc clusters (p<0.01)

• Increased ORS use from 50% in control clusters to 75% in zinc clusters (p<0.01)

Safety of Zinc Supplementation

• 9,100 children less than 5 years of age studied in 18 published clinical trials

• 11,880 child yrs of observation in 1 large community trial

• Vomiting is the only reported adverse effect– 5/7 trials report no differences between zinc and

placebo– 2 trials report slightly higher vomiting rates in zinc

supplemented children

• 4 trials show no difference in copper status after 2 weeks of zinc supplementation

Cost Effectiveness of ORS and Zinc Supplementation

• Decreases the duration and severity of the episode

• Decreases the need for expensive hospitalization

• Decreases the use of unnecessary antibiotics and other drugs

• Further cost-benefit analyses are underway• Robberstad, Strand, Sommerfelt, and Black. Bull WHO 2004.

Baqui, Black, Arifeen. J Health Pop Nutr. 2004.

ORS and Zinc

Treatment is now more effective

This is the chance to make a difference