1. Global Burden of Childhood Diarrhea and Pneumonia Christa L. Fischer Walker 1, Igor Rudan 2, Li Liu 1, Harish Nair 2, Evropi Theodoratou 2, Zulfiqar Bhutta 3, Katherine L. O’Brien 1, Harry Campbell 2, Robert E. Black 1 1 Johns Hopkins Bloomberg School of Public Health 2 University of Edinburgh 3 Aga Khan University

2. A comprehensive epidemiology review Morbidity and mortality from childhood diarrhoea and pneumonia are falling, but action is needed globally and at country level to accelerate the reduction We sought to compare and contrast the burden of disease for diarrhea and pneumonia among children < 5 years of age We conducted 24 separate literature reviews to span the full epidemiologic spectrum of disease including: incidence, severe episodes, mortality, sequelae, age and sex distribution, etiology and risk factors for diarrhoea and pneumonia among children < 5 years of age

3. Regional burden of severe diarrhoea and pneumonia episodes among children aged 0-4 years in 2010 Diarrhoea 36.1 million episodes Pneumonia 14.1 million episodes AFRICA

4. Regional burden of diarrhoea and pneumonia mortality among children aged 0-4 years in 2011 Diarrhoea 711,800 deaths Pneumonia 1,256,800 deaths Africa

5. Distribution of cases of, and deaths from diarrhoea and pneumonia in children age 0-4 yrs

6. Annual rates of change in diarrhea-specific and pneumonia-specific mortality, 2000 - 2010

7. Diarrhoea and the risk of long-term sequelae A single episode of diarrhoea is typically self-limiting with ORS and zinc for treatment In low-income settings, multiple diarrhoea episodes per year can increase odds of stunting such that the proportion of stunting attributable to 5 episodes of diarrhoea in the first 2 years of life is 25% Additional rare sequelae include: Guillain Barré Syndrome, Reactive arthritis, Hemolytic Uremic Syndrome

8. Pneumonia and the risk of long-term sequelae The risk of at least one long-term major sequela from pneumonia is 5.5% (95% CI: 2.8- 8.3) in non-severe pneumonia and 13.6% (95% CI: 6.2-21.1) in hospitalized severe pneumonia Sequelae include: reduction in lung volume and bronchiectasis (0.9% of severe cases) The risk of sequelae is higher among children < 2 years of age (13.4%, 95% CI: 4.5-22.3)

9. Vaccine-preventable causes of diarrhoea severe morbidity and mortality Rotavirus is estimated to cause 28% of severe diarrhoea, resulting in 9.9 million severe episodes and more than 193,000 deaths Vibrio cholerae accounts for 1% of severe diarrhoea resulting in an estimated 456,000 severe episodes and 11,700 deaths Estimates are based on data collected over more than 20 years and thus do not account for yearly variation as a result of epidemics or recent widespread vaccination campaigns in selected countries * Number of episodes correlates to 2011 estimates; number of deaths correlates to 2010 estimates

10. Vaccine-preventable causes of pneumonia severe morbidity and mortality Streptococcus pneumoniae is the most common vaccine-preventable pathogen and accounts for 18.3% of severe episodes (2.6 million) and 32.7% of deaths (411,000) Haemophilus influenzae type B accounts for 4.1% of severe episodes (574,000) and 15.7% of deaths (197,000) Influenza virus led to 982,000 episodes (7%) and 137,000 deaths (10.9%) * Number of episodes correlates to 2011 estimates; number of deaths correlates to 2010 estimates

11. Nutritional Risk Factors and Increased Risk of Mortality Lack of breastfeeding during the first 2 yeas of life increases the risk of diarrhoea morbidity and mortality and pneumonia mortality Diarrhea MortalityPneumonia Mortality Lack of exclusive breastfeeding (0- 5 mos) Partially breastfed RR = 4.62 (1.81 – 11.76) Not breastfed RR=10.52 (2.79-39.6) Partially breastfed RR = 2.50 (1.03-6.04) Not breastfed RR = 14.97 (0.7-332.7) Lack of any breastfeeding (6- 23 mos) RR=2.18 (1.14-4.16)

12. Nutritional Risk Factors and Increased Risk of Mortality Underweight, stunting, and wasting increase the risk of mortality from both diarrhoea and pneumonia with the risk increasing as the degree of undernutrition increases Vitamin A deficiency increases the risk of mortality from diarrhoea (RR =1.47) by increasing the risk of severe disease Zinc deficiency increases the risk of diarrhoea incidence (RR=1.15) and severe pneumonia and may increases risk of both diarrhoea and pneumonia mortality Stunting DiarrhoeaPneumonia Stunted -2 to <-1 HAZ -3 to <-2 HAZ <-3 HAZ OR = 1.2 (0.9 – 1.7) OR= 1.6 (1.1-2.5) OR = 4.6 (2.7-8.1) OR = 1 (0.6 – 1.6) OR= 1.3 (0.9-2.1) OR = 3.2 (1.5-6.7)

13. Key Messages and Discussion Diarrhoea and pneumonia remain the leading infectious causes of death in children younger than 5 years, and together caused an estimated 2 million deaths, in 2011. 72% of deaths associated with diarrhoea and 81% of those associated with pneumonia happen in the first 2 years of life, suggesting that an increased emphasis on prevention and treatment in neonates and children younger than 2 years is crucial The global burden of incidence and severe disease for both diarrhoea and pneumonia is highest in southeast Asia and Africa.

14. Key Messages and Discussion Nearly 1/3 of episodes of severe diarrhoea are preventable by vaccination (i.e., against rotavirus and cholera). At least 1/3 of severe episodes and 2/3 of deaths are caused by vaccine-preventable pneumonias (Streptococcus pneumoniae, Haemophilus influenzae, and the influenza virus). Nearly ¾ of diarrhoea and pneumonia mortality are concentrated in 15 high-burden countries yet data sources from these countries are scant Undernutrition is a key shared risk factor for morbidity and mortality associated with diarrhoea and pneumonia