Effectiveness of Zinc in the prevention and treatment of childhood - PowerPoint PPT Presentation

Effectiveness of Zinc in the prevention and treatment of childhood diarrhea Zulfiqar A. Bhutta Aga Khan University

Effect of zinc supplementation on diarrhea incidence (n = 33 comparisons; 16,665 children) Zinc supplementation produced a 20% reduction in overall diarrhea incidence RR = 0.80 (0.61,0.87) p=0.0004 Heterogeneity: age (+); nutritional status (-); serum ferritin (+)

Effect of zinc supplementation on incidence of ALRI (n = 16 comparisons; 12,376 children) Zinc supplementation produced a 15% reduction in overall incidence of ALRI RR = 0.85 (0.75, 0.97) p=0.017 Heterogeneity: nutritional status (-); quality of dx (+)

Trials on the Therapeutic Effect of Zinc on Acute Diarrhea • Countries: Australia, Bangladesh (4), Brazil, India (6), Indonesia, Nepal, Turkey, Multi-country • Age groups: 1-60 mo • Dose of zinc: ≈20 mg/d (range 5 -45 mg/d) • About 25% reduction in episode duration (p < 0.05) Source: Lukacik et al., Pediatrics 2007

Therapeutic Effects of Zinc Supplementation on Acute Diarrheal Severity Source: Lukacik, et al., Pediatrics 2007

Therapeutic Effects of Zinc Supplements in Diarrhea, Pneumonia, and Malaria • 3 trials in pneumonia • 1 trial in measles • Multi-center trial in malaria • 16 trials in acute diarrhea • 6 trials in persistent diarrhea

Zinc in the Treatment of Pneumonia, Measles or Malaria Location Outcome India Faster recovery from pneumonia (p<0.05) Bangladesh Faster recovery from severe pneumonia (p<0.05) India No difference in recovery from severe pneumonia India No effect on measles Ecuador, Ghana, Tanzania, No effect on malaria Uganda, Zambia

Optimal management of diarrhea • Joint statement (WHO & UNICEF) in May 2004 • Recommend for all cases of acute diarrhea 1. Low osmolarity ORS 2. Oral zinc sulfate 20 mg daily for 14 days 3. Antibiotics in dysentery 4. Continued feeding • No country has as yet implemented this strategy at scale

Community-based Trial of Zinc Supplementation During Diarrhea in Bangladesh • 30 health worker areas randomized • 8,070 3-59 mo. old children, 11,880 child-years • ORS alone vs. ORS and 20 mg/d zinc • Duration of episodes: RH 0.77 (0.69, 0.86) • Diarrhea hospitalization: RR 0.81 (0.65, 1.00) • Mortality: RR 0.49 (0.25, 0.94) Source: Baqui et al., BMJ, 2003

Community-based Trial of Zinc Supplementation during diarrhea in India • 6 Primary health care center areas allocated to intervention (90,000) and control (90,000) • ORS alone vs. ORS and 20 mg/d zinc • Hospitalizations – Diarrhea: OR 0.69 (0.50, 0.95) – ALRI: OR 0.29 (0.15, 0.54) – Total: OR 0.41 (0.29, 0.57) Source: Bhandari et al., Pediatrics, 2007

Diarrhea Management Effectiveness Trial • District Matiari – 859 villages – 45,756 households – 304,868 population • Cluster randomized trial (16 clusters) of diarrhea package – Feeding advice – Zinc and low osmolality ORS – Delivery through public & private sector staff & outlets

Lady Health Workers & General Practitioners/Pharmacies delivered a package of care for diarrhea

Trainings

Treatment Received (Control) ORS ZINCOL IV Drips Anti-biotics Anti-diarrheal 60 56.8 54.6 53.1 50 46.1 40 32 30 30 29.5 29.5 27.3 25.6 23.7 22.7 20 10 5.1 4.5 3.2 3 0 0 0 0 0 Surveillance-1 Surveillance-2 Surveillance-3 Surveillance-4

Treatment Received (Intervention) ORS ZINCOL IV Drips Anti-biotics Anti-diarrheal 70 65.2 64 62.2 60 53.2 51.7 50 50.4 40 31.4 30 28.9 28.9 27 26.6 24.2 20 15.2 15.2 11.2 10.6 10 4.8 4.7 4.1 3.7 0 Surveillance-1 Surveillance-2 Surveillance-3 Surveillance-4

Hospitalization for diarrhea (%) All children % 2 Interv. 1.8 Control 1.6 1.5 1.4 1.4 1.2 1.2 1 1 1 0.8 0.6 0.4 0.4 0.2 0.2 0.1 0 Surveillance-1 Surveillance-2 Surveillance-3 Surveillance-4 Bhutta et al (2008)

Scaling up Diarrhea Prevention & Treatment

Utilization of Zinc for Diarrhea 120 100 80 60 Intervention Control 40 20 0 Baseline Dec - Feb Mar - May Jun - Aug

Utilization of ORS in Diarrhea 100 90 80 70 60 50 Intervention Control 40 30 20 10 0 Baseline Dec - Feb Mar - May Jun - Aug

Utilization of Antibiotics in Diarrhea 50 45 40 35 30 25 Intervention Control 20 15 10 5 0 Baseline Dec - Feb Mar - May Jun - Aug

Diarrhea Rates (Previous two weeks) 14 12 10 8 Percentag Intervention e 6 Control 4 2 0 Baseline Dec - Feb Mar - May Jun - Aug

Hospitalization Interventio Indicators Control n Hospitalization 77 (0.9%) 75 (1.1 %) Mean days of 2.6 4.7 hospitalization

Conclusions (1) • Increasing evidence of the benefits of zinc in human health and disease • Large parts of the world, especially in developing countries are at risk of significant zinc deficiency and poor dietary intake • Mechanism of preventive effects probably restoring immune competence • Mechanisms of diarrhea treatment effect could be anti- secretory, immune or mucosal function

Conclusions (2) • Zinc in therapy in children – consistent effects on diarrhea, possible effects on pneumonia • Global scale-up of zinc for treatment of diarrhea is underway • Zinc in prevention in children – consistent effects on diarrhea, acute lower respiratory infections, and mortality, possible effects on malaria • Preventative use of zinc for children (supplements/fortification) needs more attention