Interventions to address deaths from childhood Pneumonia and Diarrhoea equitably : what works and at what cost? Zulfiqar A Bhutta, Jai K Das, Neff Walker, Arjumand Rizvi, Harry Campbell, Igor Rudan, Robert E Black, for The Lancet Diarrhoea and Pneumonia Interventions Study Group April 12, 2013 Lancet Launch London

In Paper 2 of this series We systematically reviewed evidence showing the effectiveness of various potential preventive and therapeutic interventions against childhood diarrhoea and pneumonia, and relevant delivery strategies We used the Lives Saved Tool model to assess the effect of scaling up 15 proven interventions on mortality due to diarrhoea and pneumonia and lives saved in 75 Countdown countries

Conceptual Framework INCREASED SUSCEPTIBILITY INCREASED SUSCEPTIBILITY EXPOSURE EXPOSURE PNEUMONIA DIARRHOEA PNEUMONIA DIARRHOEA ENVIRONMENTAL WASH*, reduce overcrowding and Household air Pollution NUTRITION Breast feeding promotion, Preventive vitamin A or zinc supplementation* VACCINES Measles, haemophilus Influenzae type B, Pneumococcal infection, Rotavirus, cholera TREATMENT Oral rehydration solution, continued feeding after diarrhoea, zinc for diarrhoea treatment, probiotic use, antibiotics and oxygen therapy for pneumonia, antibiotics for dysentery DELIVERY PLATFORMS Community based health & behavior change promotion Financial Incentives to promote care seeking Integrated Community Case Management Facility Based IMCI SURVIVAL DEATH

Review evidence base for key diarrhea and pneumonia prevention and treatment interventions Goal: To estimate the effect of selected interventions on diarrhea and pneumonia morbidity and mortality in children less than 5 years of age Methods: Conducted systematic literature review of all outcomes If data on 0-5 years was scarce, we included older children Abstracted data Applied standard methods for risk of bias assessment Applied standard set of LiST rules for estimating effect on morbidity and mortality given evidence available Methods

Interventions common to Diarrhoea and Pneumonia

Not breast feeding was associated with 165% (RR 2·65, 95% CI 1·72–4·07) increase in diarrhoea (0–5 months) 32% (1·32, 95% CI 1·06–1·63) increase in diarrhoea (6–11 months) 32% (1·32, 95% CI 1·06–1·63) increase in diarrhoea (12-23 months) 47% (1·47, 95% CI 0·67–3·25) increase in diarrhoea mortality (6–11 months) 157% (2·57, 95% CI 1·10–6·01) increase in 12–23 months BREASTFEEDING AND THE RISK FOR MORBIDITY AND MORTALITY

BREASTFEEDING EDUCATION AND EFFECTS ON BREASTFEEDING RATES Increased EBF 43% at 1 day 30% at 0–1 months 90% at 1–6 months Decreased no breastfeeding 32% at 1 day, 30% at 0–1 month 18% for 1–6 months Predominant and partial breastfeeding were not significant After 6 months increase rates of partial breastfeeding by 19%

Risk reductions for diarrhoea 48% with hand washing with soap 17% with improved water quality 36% with excreta disposal WATER, SANITATION, AND HYGIENE INTERVENTIONS

Non-significant reduction in Diarrhoea-related mortality: 18% (0·82, 95% CI 0·64–1·05) All-cause mortality: 9% (0·91, 0·82–1·01) ALRI-related mortality: 15% (0·85, 0·65–1·11) PREVENTIVE ZINC SUPPLEMENTATION

Diarrhoea specific interventions Preventive

Effectiveness against very severe rotavirus infection: 74% (95% CI 35–90%) Effectiveness against severe rotavirus infection: 61% (95% CI 38–75%) Effectiveness against hospital admission for rotavirus: 47% (95% CI 22–64%) ROTAVIRUS VACCINE

Effectiveness against cholera infection: 52% (RR 0·48, 95% CI 0·35–0·64) Increase in Vibriocidal antibodies by124% (RR 2·24, 95% CI 1·32– 3·80) Increase in risk of adverse events by 42% (RR 1·42, 95% 1·06– 1·89) CHOLERA VACCINE

Diarrhoea specific interventions Therapeutic

Reduction in: Diarrhoea mortality by 69% (95% CI 51–80%) Treatment failure by 0·2% (95% CI 0·1–0·2%) ORS and recommended home fluids

Significant reduction in: All-cause mortality by 46% (RR 0.54, 95% CI 0·32–0·88) Hospital admission by 23% (RR 0·77, 95% CI 0·69–0·85) Non-significant reduction in: Diarrhoea mortality by 66% (RR 0·34, 95% CI 0·04–1·37) Diarrhoea prevalence by 19% (RR 0·81, 95% CI 0·53–1·04) Therapeutic Zinc supplementation

In acute diarrhoea lactose –free diet significantly reduced: Duration of diarrhoea: SMD –0·36, 95% CI –0·62 to –0·10 Treatment failure: RR 0·53, 95% CI 0·40–0·70 Weight gain did not have any significant effect Feeding strategies & improved dietary management of diarrhoea

Cryptosporidiosis: Reduced clinical failure by 52% Reduction in parasitological failure by 38% Non-significant reduction in all-cause mortality Antibiotics for Shigella, Cholera and Cryptosporidiosis Shigella: Reduced clinical failure by 82% Reduced bacteriological failure by 96% Cholera: Reduced clinical failure by 63% Reduced bacteriological failure by 75%

Pneumonia specific interventions Preventive

Hib Vaccine: Severe pneumonia by 6% (RR 0·94, 95% CI 0·89–0·99) Vaccines Measles Vaccine: 85% (95% CI 83–87%) effective in prevention of disease before age 1 year Pneumococcal conjugate vaccine: 29% reduction in radiologically confirmed pneumonia 11% reduction in severe pneumonia

Pneumonia specific interventions Therapeutic

Oral or injectable antibiotics reduced: All-cause neonatal mortality by 25% (RR 0·75, 95% CI 0·64–0·89) Neonatal pneumonia mortality by 42% (0·58, 95% CI 0·41–0·82) Antibiotics for the treatment of neonatal pneumonia

Pulse oximetry together with oxygen therapy reduced severe pneumonia mortality by 35% (RR 0·65, 95% CI 0·52–0·78) Oxygen systems

Delivery Platforms Community-based promotion and case management: 160% significant increase in use of oral rehydration solution 80% increase in use of zinc in diarrhoea 13% increase in care-seeking for pneumonia 9% increase in care-seeking for diarrhoea. 75% significant decline in inappropriate use of antibiotics for diarrhoea 40% reduction in rates of treatment failure for pneumonia. Reduction of financial barriers Promote increased coverage of child health interventions Pronounced effects achieved by those that directly removed user fees for access to health services.

LiST modeling effects on mortality outcomes for 75 Countdown countries

Historic Trends Scale up- 54% of diarrhoea and 51% of pneumonia deaths in children younger than 5 years can be averted Ambitious Scale up- Eliminate almost all diarrhoea deaths, but only two-thirds of pneumonia deaths

Coverage of Interventions in 75 Countdown Countries

Additional effect of the ambitious scale-up approach on diarrhoea and pneumonia deaths averted for the 75 Countdown countries up to 2025 Specific Interventions

Impact of individual interventions on deaths due to diarrhoea and pneumonia (Sequential)

Equity Analysis

Equity analysis for Bangladesh, Ethiopia and Pakistan

Cost Analysis

The costs are based on four components: Personnel and labour Drugs and supplies Other direct costs Indirect costs Historic Trend- USD3·8 billion dollars to avert 882,274 deaths Ambitious Scale-up - USD6·715 billion dollars to avert 1,439,437 deaths An extra USD2·914 billion to save an additional 557,163 lives.

Most the interventions exist within present health systems, although their coverage and availability to poor and marginalised populations varies greatly Delivery strategies receive relative less focus Structural changes are needed to reduce environmental pollution and provide safe water and sanitation The forthcoming decade of vaccines initiative offers a unique possibility Community delivery of these interventions could also ensure equitable delivery Discussion

Interventions with maximum effect include breastfeeding, oral rehydration solution, and community case management 15 interventions delivered at scale can prevent most of diarrhea and pneumonia deaths If the interventions are scaled up by 80% in the 75 Countdown countries, they could save 95% of diarrhoeal and 67% of pneumonia deaths in children younger than 5 years by 2025 Scaling up of diarrhoea and pneumonia interventions would cost USD6·715 billion, only USD2·9 billion more than present levels of spending The cost-effectiveness of these interventions in national health systems needs urgent assessment Key messages

THANKS