Third International Conference for Improving Use of Medicines ICIUM 2011

1. Third International Conference for Improving Use of Medicines ICIUM 2011 Antalya, Turkey, November 14-18th, 2011 Hesham El-Sayed, Abdul-Majeed Ahmed, Suzan Gad Faculty of Medicine Suez Canal University, Egypt Effectiveness of Oral Zinc Supplementation in the Treatment of Acute Watery DiarrheaINCLEN Childnet Zinc Effectiveness for Diarrhea (IC-ZED) Group

2. Study Rationale & Problem statement • Oral rehydration solution (ORS) has been successfully used around the world, and has been responsible for reduction of diarrheal deaths in the last 2 decades • In spite of the success of ORS in prevention of dehydration, there is demand for medicines that can reduce the duration and severity of diarrhea • Zinc has been shown to be efficacious in reducing duration of diarrhea and associated mortality

3. Study Objectives • To determine the effectiveness of oral zinc supplementation in the treatment of acute watery diarrhea. • To assess adherence to zinc therapy • To evaluate the impact of zinc therapy on the duration of diarrheal episodes, the use of ORS, and the usage of antibiotics and/or “antidiarrheal” medicines

4. Study Area & Population • Ismailia governorate, Egypt, with population of one million inhabitants • Four primary health care centers • Children presenting to the outpatient clinics of participating centers Other study sites: (Brazil, Ethiopia, India & Philippines) Ismailia

5. Inclusion Criteria • Children aged 2 to 59 months. • Patients resenting to the study centers with diarrhea, defined as three or more loose or watery motions per day, and of less than 7 days duration • Patients who are able to drink and do not have persistent vomiting • Informed consent by a legal guardian

6. Exclusion Criteria • Severe malnutrition (weight for height z score [WHZ] -3 SD) • Patients on IMCI-WHO Plan B or C management of dehydration • Patient suffering from dysentery • Currently using antimicrobial drugs or having other conditions requiring antimicrobials • Mothers reported positive for HIV • Not residing in catchment area

7. Study Design Randomized, controlled effectiveness trial

8. Study Maneuver • Block randomization procedure was used using block of size 8 • Recruited patients received either zinc and ORS or ORS alone • Both groups received instructions for the use of ORS, those randomized to the zinc group also received zinc tablets along with culturally appropriate message for zinc usage • Zinc (Nutriset; manufactured by Rodael, Malaunay, France) as well as ORS was provided by WHO • Zinc was supplemented as dispersible 10-mg tablets, mothers given instructions for dissolving it in water or breast milk, and administered for 14 days

9. Design of the Zinc Logo Each tablet contains: 10 mg Zinc Sulphate. The tablet should be dissolved intablespoon of water. يحتوى كل قرص على: 10 ملجم سلفات الزنك يذاب القرص فى ملعقة مائدة من الماء أولبن الأم منظمة الصحة العالمية HYDROZINC هيدروزنك

10. Patient Assessment and Follow-Up • Baseline characteristics were recorded for eligible children • All caretakers were trained to recognize the signs of worsening illness, as outlined in the WHO diarrhea manual, and advised to report to the hospital immediately if any of these signs developed • Caregivers were asked to come for two follow-up visits, the first between days 3 and 5 and the second between days 15 and 17, bringing with them any unused ORS packets and zinc tablets • A project nurse visited the homes of the patients if the child was not brought to the hospital on the expected day for follow-up visits

11. Outcome Measures • ORS use on first follow-up visit in last 24 hours • Adherence to zinc tablets (consumption of greater than 80% of the doses) • Use of antimicrobial / antidiarrheal drugs • Duration of diarrheal episodes • Frequencies of adverse effects of zinc therapy • Treatment failures, defined as one or more of the following after institution of therapy: dehydration, need for intravenous fluids, hospitalization, death

12. Study Results

13. Study Participants • 412 children aged 2-59 months were enrolled in the study; 219 males (53.2%) and 193 females (46.8%) • Mean age of the recruited children was 17.0 + 12.6 months • 222 children received zinc+ORS therapy and 190 were controls and received ORS alone; 11 lost to follow up by day 15 (8 Zinc+ORS & 3 ORS)

14. Study Groups & Sex Distribution of the Recruited Egyptian Children

15. Baseline Characteristics of Recruited Children

16. Study Results • The study showed high adherence to zinc therapy, as 73% of the children consumed more than 80% of the zinc tablets • Zinc supplementation caused significant reduction in the duration of diarrheal episodes, of about 24%, in the zinc-treated group • Significant reduction in the use of antidiarrheals and/or antibiotics use rate in the zinc study group compared to controls (7.7% vs. 20.5%) • Frequency of ORS use during diarrheal episodes was similar in the 2 study groups

17. Comparison of Clinical Outcome of Zinc+ORS Vs ORS group * P ˂0.05

18. Conclusions • Oral zinc supplementation, in under-5 children suffering from acute watery diarrhea, is efficacious in reducing the duration of diarrheal episodes and in reducing the maluse of “antidiarrheals” and antibiotics, with no decrease in the frequency of ORS use. • Children showed good adherence & acceptance to zinc therapy without considerable side effects

19. AcknowledgementThe study was supported by grant fromUSAID-CHR, Washington (via INCLEN Trust) Johns Hopkins University& WHO Technical support