1. Zinc supplementation in the treatment of diarrhoeal disease
Incorporating new global recommendations into country-level policy and action
Paulo Froes, MD, MPH, PgD OH & S
UNICEF/TACRO, Health and Nutrition/Immunization Plus

2. Zinc supplementation: clinical evidence
Randomised placebo-controlled clinical trials evaluating the impact of zinc supplementation during acute and persistent diarrhoea
WHO meeting in New Delhi, India, 2001 convened to reviewh the results of all studies available

3. Zinc in acute diarrhea
Reduces duration of diarrhoea episode by up to 25%
Decrease by about 25% the proportion of episodes lasting more than seven days
It is associated with a 30% reduction in stool volume
Conclusion: significant beneficial impact on the clinical course of acute diarrhoea: reduces both severity and duration

4. Zinc in persistent diarrhoea
Zinc-supplemented children had:
24% lower probability of continuing diarrhoea
42% lower rate of treatment failure or death
Conclusion: zinc supplementation reduces the duration and severity of persistent diarrhoea

5. Zinc in bloody diarrhoea
Positive impact of the prevalence of dysentery in the month following the supplementation
Improves seroconversion to shigellaciddal antibody response and increases the proportions of circulating B lymphocytes and plasma cells and the IgA-specific immunoglobulin response
Conclusion: zinc supplementation should be given as an adjunct to antibiotic treatment of bloody diarrhoea

6. Cost-effectiveness studies
zinc supplementation significantly improved the cost-effectiveness of standard management of diarrhoea for dysenteric as well as non-dysenteric illness.
Sufficient evidence to recommend the inclusion of zinc into standard case management of both types of acute diarrhoea

7. The new WHO-UNICEF recommended policies for health professionals on the treatment of diarrhoea
Counsel mother to begin administering suitable home fluids immediately upon onset of diarrhoea in a child
Treat dehydration with new low osmolarity ORS solution (or with intravenous electrolyte solution in cases of severe dehydration)
Emphasize continued feeding or increased breastfeeding during, and increases feeding after, the diarrhoeal episode
Use antibiotics only when appropriate, i.e., in the presence of bloody diarrhoea or shigellosis, and abstain from administering anti-diarrhoeal drugs
Provide children with 20 mg per day of zinc supplementation for days (10 mg per day for infants under six months old)
Advise mothers of the need to increase fluids and continue feeding during future diarrheoal episodes

8. Zinc and Low-osmolarity ORS: effective, safe and available

9. Incorporating the new recommendations into the country’s health policy I
Identifying and obtaining commitment and support from key stakeholders:
Appropriate departments of MoH (leadership role): interprogrammatic coordination is key
Ministry of Planning and Finance
Professional Organizations: Medical and Pediatrics Associations; Nurses Association; Pharmacists Association
Private sector: Manufacturers of zinc and ORS, importers and wholesalers, private hospitals and pharmacies, drug shops, traditional healers
Collaborating partners such as NicaSalud, PATH, UNICEF, PAHO/WHO, World Bank, USAID, other NGOs

10. Incorporating the new recommendations into the country’s health policy II
Gathering clinical and scientific evidence
Endorsing the new recommendations
Revising/updating existing policies

11. Available in English, Spanish and French

12. Implementation issues: new ORS and zinc supplementation
Product issues
Supply management issues
Technical
Operational
Monitoring and evaluation

13. Product issues
Dosage
Each individual dose of zinc should contain 10 mg or 20 mg of elemental zinc
For syrups, the concentration of elemental zinc should be either 10 mg/5 ml or 20 mg/5 ml
For tablets, each tablet should contain either 10 mg of 20 mg of elemental zinc. Tablets containing 20 mg of elemental zinc should be scored.
Zinc salt used in to prepare syrups or tablets for use in the management of diarrhoea should be soluble in water:
Zinc sulphate
Zinc acetate
Zinc gluconate
Type of tablets: for use in infants and young children it is essential that the tablets be dispersible. It means that the tablets should b e completely disaggregated in about 30 seconds or less than 60 seconds in 5 ml of tap water or breast milk
Taste-masking: it is essential that the metallic taste be totally masked
Costing: it is important to keep the cost of the zinc dose as low as possible. Arbitrarly, it has been suggested that one dose of zinc not exceed US$ 0.02
Packaging: tablets and syrups should be packaged to provide a full treatment of daily doses of zinc (i.e, for syrups containing 20 mg/5 ml bottles should contain ml of syrup; for tablets, a blister should contain tablets).
Shelf life: The zinc product should have a shelf life of at least two years

14. Supply management issues I
Technical
Revision of medicine regulation
Revision of the Essential Medicines List (new ORS included in WHO EML in 2003; zinc salts included in WHO EML in 2005)
Review of Integrated Management of Childhood Illness (IMCI) guidelines (WHO/UNICEF)
Training and supervision of health professionals
Programme communication:
introduction of new treatment which providers and patients have little or no experience requires considerable planning for behaviour change strategies and capacity building at all levels
Multiple approaches to raising public awareness is recommended
Adhrerence is key with zinc treatment (10-14 days)
Instructions and job aids are strongly recommended to caregivers

15. Supply management issues II
Operational issues
Replacement of old ORS: no need to withdraw stocks. Just matter of planning introduction of new oRS in such a way that both products are not in circulation concurrently (just to prevent confusion). Existence of old ORS should not be a barrier for initiating zinc supplementation
Plan phase-in of zinc treatment: phased or immediate nationwide rollout. Phased: lower costs, ability to test implementation strategies and correct issues with materials or methods, uptake of new recommendations in the health facilities can be monitored and modelled

16. Supply management issues III
Operational issues
Forecasting of demand and quantification
Forecasting demand for zinc in the absence of good morbidity data: tentative link with procurement of ORS, e.g., one patient: two sachets of ORS and tablets of 20 mg zinc.It could underestimate true requirements if majoroity of cases makes use of home fluids instead of ORS
Forecasting demand should include team approach
Local production or international procurement?
Distribution
Stock management
Private sector distribution
Quality assurance (product efficacy, product safety – pharmacovigilance – product quality and post-marketing surveillance

17. Monitoring and Evaluation
Process indicators
% of health care staff trained in the management of diarrhoea including new ORS and day treatment with zinc
Zinc and new ORS available at the central storage facility
% of health facilities, storage facilities and private sector outlets with ORS and zinc available
% of facilities with the revised treatment guidelines
% of cases of diarrhoea in children under five prescribed of sold zinc and the new ORS
Outcome indicators
% of cases od diarrhoea in children under five treated with a course of zinc supplementation for days, in addition to ORS
Knowledge, attitudes and practices indicators
% of caregivers who are aware that zinc is an appropriate treatment for diarroeal disease
% of medical providers who believe that zinc is an effective treatment for diarrhoea in children under the age of five

18. Muito Obrigado!