1. Malnutrition-associated inpatient and post-discharge child deaths Tickell KD, Walson JL, Denno DM

2. Inpatient management of malnutrition Food systems Nutrient deficiency Malnutrition & complications Infection WASH Prevention Treatment

3. Severe acute malnutrition with complications (SAM-C) Severe Acute Malnutrition: ≤ 3 SD WFH, MUAC <115 mm, Bilateral edema With medical complications or no appetite Inpatient treatment Without complications Outpatient treatment

4. SAM-C case fatality WHO indicates <10% 1 Sub-Saharan centers of excellence: 15 - 25% 2,3,4 Blantyre, Malawi: 42% at 1 year 5 Severe Acute Malnutrition: ≤ 3 SD WFH, MUAC <115 mm, Bilateral edema With medical complications or no appetite Inpatient treatment Without complications Outpatient treatment

5. Importance of SAM-C guidelines Opportunity We estimate that 100,000/year child deaths averted if 10% target reached Highly accessible population – rapid impact is possible Directly attributable to SAM-C 6 12.2% of diarrhea deaths 12.3% of measles deaths 8.7% of pneumonia deaths

6. 1)Ancestry tracing guideline –2013 WHO update –2003 & 1999 WHO SAM guideline –1981 WHO PEM guideline –Text books: F. Savage-King (1992) “Nutrition in Developing Countries” M. King (1969) “Medical Care in Developing Countries” Methods

7. Results : Only 1/4 based on RCT evidence

8. Areas of guidance Feeding & fluids Infection management Discharge & follow-up care

9. Feeding & fluids ReSoMal, unless cholera High dose vit A: measles, eye signs RUTF for diarrhea Shock/Severe dehydration: IV HS Darrow’s or Ringer’s + 5% Dextrose No Fe until rehabilitation Folic acid, Zn, Cu RCT Observational Indirect <6 mo: breastfeed or relactate F75 -> RUTF: stabilized F100->rapid wgt gain King (1969) WHO (2013) WHO (1999) WHO (2003) WHO PEM (1981) Savage King (1992) Low dose vit A Cholera: standard ORS Monitor every 5-10 mins if on IV Transfusion: unimproved shock/anemia No transfusions after 24 hrs

10. Feeding & fluids ReSoMal, unless cholera High dose vit A: measles, eye signs RUTF for diarrhea Shock/Severe dehydration: IV HS Darrow’s or Ringer’s + 5% Dextrose No Fe until rehabilitation Folic acid, Zn, Cu RCT Observational Indirect <6 mo: breastfeed or relactate F75 -> RUTF: stabilized F100->rapid wgt gain King (1969) WHO (2013) WHO (1999) WHO (2003) WHO PEM (1981) Savage King (1992) Low dose vit A Cholera: standard ORS Monitor every 5-10 mins if on IV Transfusion: unimproved shock/anemia No transfusions after 24 hrs

11. Infection Ampicillin & gentamicin on admission ART when stable if HIV+ Measles vaccine if not immunized Conscious & hypoglycemic: IV + oral dose glucose Unconcious & hypoglycemic: IV + oral dose HIV+ & >24 months: ART based on CD4 HIV+ & <24 months: ART for life RCT Observational Indirect Zn for diarrhea HIV+ no difference for zn & vit A HIV+ no difference for feeding < 6mo same ABX as older King (1969) WHO (2013) WHO (1999) WHO (2003) WHO PEM (1981) Savage King (1992)

12. Infection Ampicillin & gentamicin on admission ART when stable if HIV+ Measles vaccine if not immunized Conscious & hypoglycemic: IV + oral dose glucose Unconcious & hypoglycemic: IV + oral dose HIV+ & >24 months: ART based on CD4 HIV+ & <24 months: ART for life RCT Observational Indirect Zn for diarrhea HIV+ no difference for zn & vit A HIV+ no difference for feeding < 6mo same ABX as older King (1969) WHO (2013) WHO (1999) WHO (2003) WHO PEM (1981) Savage King (1992)

13. Discharge & follow-up care Do not use %weight gain Follow-up care d/c: WHZ >-2 & no edema x 2 weeks Provide emotional and sensory support Hospital d/c: no complications, alert, appetite not anthropometry 5g/kg/day RCT Observational Indirect Assess progress using the anthropometric measure which qualified the child for admission If edema only complication normal anthropmetirc used for F/U King (1969) WHO (2013) WHO (1999) WHO (2003) WHO PEM (1981) Savage King (1992)

14. WHO 2013 update: “Major research gaps were identified in each of the sections covered.” Two key populations: 7 “No randomized controlled trials in HIV-infected children with SAM were identified that directly addressed any of the prioritized questions.” “No studies were found in the peer-reviewed literature that reported outcomes when WHO therapeutic feeding recommendations…are applied to SAM infants who are less than 6 months of age.”

15. Weak evidence & high mortality 42% of SAM inpatients die within 1 year o 62% of HIV+ children died o 67% of infants died Post-discharge mortality o 44% of deaths Queen Elizabeth hospital: “the biggest and one of the best” (The Guardian 2005) Data from Kerac, et al 2014 5

16. Timing of deaths No data on causes of death

17. Guidelines Useful clinical tool & synthesis of evidence/opinion Evidence Weak or non-existent for most elements Systematic search of trials registries Limited potential for impact SAM-C Underlying cause: We don’t know why these children die

18. Beyond SAM-C No guidelines for MAM 34% of diarrhea deaths attributable to MAM 32% of pneumonia deaths attributable to MAM 6 No guidelines for stunting 45% of diarrhea deaths attributable to stunting 43% of pneumonia deaths attributable to stunting 6

19. Judd Walson Co-director Donna Denno Investigator Kirk Tickell Coordinator Bangladesh Pakistan Kenya Malawi Uganda Next steps: The CHAIN network Jay Berkley Director

20. Opportunities for intervention Hospital & post-discharge Intervene on modifiable pathways to death

21. References 1: WHO. Guidelines for the Inpatient Management of Severely Malnourished Children. Geneva: WHO, 2003. 2: Personal communication between Kirk Tickell and Jay Berkley (12/8/14) 3: Fergusson, P. "HIV Prevalence and Mortality Among Children Undergoing Treatment for Severe Acute Malnutrition in Sub-Saharan Africa: a Systematic Review and Meta-analysis.” R Soc Tropl Med (2009) 103, 541—548 4: Personal communication between Donna Denno and Maurice Kelly (6/6/14) 5: Kerac, MH. Et al. "Follow-Up of Post-Discharge Growth and Mortality After Treatment for Severe Acute Malnutrition (FuSAM Study): a Prospective Cohort Study." PLOS One 9.6 (2014): E96030. 7: Black RE, et al. (2013) Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet, Aug 3; 382: 427-51. 7: WHO. Updates on the Management of Severe Acute Malnutrition in Infants and Children. Geneva: WHO, 2013.