Zinc supplementation in the treatment of diarrhoeal disease

Paulo Froes, MD, MPH, PgD OH & S

UNICEF/TACRO, Health and Nutrition/Immunization Plus

Incorporating new global recommendations into country-level policy and action

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

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

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

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

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

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 10-14 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

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

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

• Gathering clinical and scientific evidence• Endorsing the new recommendations• Revising/updating existing policies

Incorporating the new recommendations into the country’s health policy II

Available in English, Spanish and French

Implementation issues: new ORS and zinc supplementation

• Product issues

• Supply management issues– Technical– Operational

• Monitoring and evaluation

Product issues 1. 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.2. 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

3. 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

4. Taste-masking: it is essential that the metallic taste be totally masked5. 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$ 0.026. Packaging: tablets and syrups should be packaged to provide a full treatment of 10-

14 daily doses of zinc (i.e, for syrups containing 20 mg/5 ml bottles should contain 50-75 ml of syrup; for tablets, a blister should contain 10-14 tablets).

7. Shelf life: The zinc product should have a shelf life of at least two years

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

• 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

Supply management issues II

• 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 10-14 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

Supply management issues III

Monitoring and Evaluation• Process indicators

– % of health care staff trained in the management of diarrhoea including new ORS and 10-14 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 10-14 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

Muito Obrigado!