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, Uganda, Zambia No effect on malaria

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 &

• utlets

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

Trainings

23.7 27.3 30 22.7 3.2 3 4.5 5.1 32 29.5 25.6 29.5 46.1 53.1 54.6 56.8 10 20 30 40 50 60 Surveillance-1 Surveillance-2 Surveillance-3 Surveillance-4

ORS ZINCOL IV Drips Anti-biotics Anti-diarrheal

Treatment Received (Control)

28.9 51.7 62.2 64

15.2 50.4 53.2 65.2

4.1 4.8 4.7 3.7 31.4 15.2 11.2 10.6 28.9 27 26.6 24.2 10 20 30 40 50 60 70 Surveillance-1 Surveillance-2 Surveillance-3 Surveillance-4

ORS ZINCOL IV Drips Anti-biotics Anti-diarrheal

Treatment Received (Intervention)

1 0.4 0.2 0.1 1.2 1 1.4 1.5 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 Surveillance-1 Surveillance-2 Surveillance-3 Surveillance-4

Interv. Control

Hospitalization for diarrhea (%) All children

%

Bhutta et al (2008)

Scaling up Diarrhea Prevention & Treatment

Utilization of Zinc for Diarrhea

20 40 60 80 100 120

Baseline Dec - Feb Mar - May Jun - Aug Intervention Control

Utilization of ORS in Diarrhea

10 20 30 40 50 60 70 80 90 100

Baseline Dec - Feb Mar - May Jun - Aug Intervention Control

Utilization of Antibiotics in Diarrhea

5 10 15 20 25 30 35 40 45 50

Baseline Dec - Feb Mar - May Jun - Aug Intervention Control

Diarrhea Rates (Previous two weeks)

Percentag e

2 4 6 8 10 12 14

Baseline Dec - Feb Mar - May Jun - Aug Intervention Control

Hospitalization

Indicators Interventio n Control

Hospitalization 77 (0.9%) 75 (1.1 %) Mean days of hospitalization 2.6 4.7

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