New evidence on intervention efficacy & effectiveness Betty Kirkwood London School of Hygiene & Tropical Medicine

Is there any major new evidence concerning interventions to improve newborn and child survival that adds to or changes our current thinking? Shams Arifeen Ann Ashworth Hill Rajiv Bahl Zulfiqar Bhutta Bob Black Jennifer Bryce Sandy Cairncross Daniel Chandramohan Anthony Costello Simon Cousens Gary Darmstadt Joy Lawn Jo Lines Jose Martines Liz Mason Saul Morris Kim Mulholland David Osrin Vinod Paul Igor Rudan Nancy Terreri Ricardo Uauy Cesar Victora Peter Winch Thanks to

Evidence-based Interventions Lancet Bellagio Child Survival Series interventions –15 preventive (9 child, 6 newborn) –8 case-management (6 child, 2 newborn) Lancet Neonatal Series additional “cost-effective” interventions

that significantly changes our assessment about the potential impact or delivery of any of the 31 interventions? for new intervention(s) to be added? about effective delivery strategies? Is there new evidence:

NEW evidence re 31 interventions: Remodel: lives saved Updated coverage data All 31 interventions Two thirds of child deaths could be saved see POSTER

NEW evidence re 31 interventions: ANTIBIOTICS FOR PNEUMONIA  Current guidelines  Non-severe pneumonia: treat at home with oral antibiotics  Severe pneumonia: admit & give parenteral antibiotics  Oral amoxycillin as effective as injectable penicillin: multi-centre trial  Potential benefits include decreases in:  Risk of needle-borne infections  Need for referral or admission  Administration costs  Costs to the family Addo-Yobo et al for the Amoxicillin Penicillin Pneumonia International Study (APPIS) Group, Lancet 2004; 364: 1141–48

POSTERS 20 & 21 NEW evidence re 31 interventions: EARLY INITIATION OF BREASTFEEDING Various measures taken to address potential reverse causality BF initiatedAdj OR Day 1, 1st hour1 Day 1, later1.45 Day Day After Day Day 1 vs Later2.40 Ghana: Risk of Neonatal Mortality after 1 st day

NEW evidence re 31 interventions: EARLY INITIATION OF BREASTFEEDING 60 priority countries Two intervention models: A: A: BF initiated within 1st hour B: B: BF initiated within 1st day (but not necessarily 1st hour)

NEW evidence re 31 interventions: Reduction compared to Controls Intervention GroupPneumoniaDiarrhoea Antibacterial Soap45% (26%-64%)50% (37%-64%) Plain Soap50% (34%-65%)53% (41%-65%) HANDWASHING  Meta-analysis 11 studies: 37% reduction in diarrhoea (CI 23-48%) (Fewtrell et al, Lancet Inf Dis 2005; 5: 42-52)  A randomised controlled trial of handwashing on child health in Karachi, Pakistan Luby et al, Lancet 2005; 366: 225–33

New intervention to add? ISSUE: 10 million children severely malnourished, High risk of mortality Usual recommendation: refer to hospital or specialised treatment unit Coverage low CONSULTATION (WHO, UNICEF, SCF; Geneva Nov 2005): Community based approach with RUTF feasible & effective –Very low case fatality rate –Only a small proportion of severely malnourised children needed to be referred to hospital Potential to save 100,000’s child deaths YES: STRONG EVIDENCEYES: STRONG EVIDENCE SEVERE MALNUTRITION RUTF (highly fortified Ready to Use Therapeutic Foods) for community-based management of SEVERE MALNUTRITION

CHAP trial, Zambia:  RCT, 541 Children aged 1-14 with clinical signs of HIV  Primary outcomes: Mortality & adverse events  DSMC recommended trial should be stopped early  43% lower mortality in cotrimoxazole group (CI 23-57%, P=0.0002) Chintu et al, Lancet 2004; 364: New intervention to add? Cotrimoxazole prophylaxis for children with clinical signs of HIV

New intervention to add?  A single cleansing of newborn skin as soon as possible after delivery (median 6 h): –28% reduction in mortality among LBW infants  Cleansing umbilical cord with 4% chlorhexidine on days 0,1,2,3,5,7,9: –24% reduction in overall neonatal mortality (Lancet in press) Chlorhexidine Cleansing: Nepal POSTERS 39 & 41 Courtesy Darmstadt & colleagues

New VACCINES to add? TO CONSIDER:  Pneumococcal conjugate vaccine (3 doses): The Gambia: 16% reduction in mortality (CI 3-28%) Cutts et al, The Lancet 2005; 365: Issues: Affordability, Availability, Composition NOT YET:  Rotavirus:  High efficacy LA/US  Trials needed in less developed countries  Malaria RTS,S/AS02A vaccine: The Gambia: 58% reduction in severe malaria (CI %) Alonso et al, Lancet 2004; 364: 1411–20

NEW evidence re effective delivery WOMEN’S GROUPS: Makwanpur Effect of a participatory intervention with women’s groups on birth outcomes in Nepal: cluster RCT (Manandhar et al, Lancet 2004) 0·70 [95% CI 0·53–0·94]) 12 pairs >6000 deliveries

NEW evidence re effective delivery NEWBORN CARE HOME VISITS: Shivgarh Mortality rate/ 1000 livebirths Control Area Intervention Area 1 Intervention Area 2 Perinatal Early neonatal Neonatal Shivgarh (India): Impact of 4 home visits by CHWs to PROMOTE ESSENTIAL NEWBORN CARE* through Community Mobilization & Behavior Change Communications * As defined in Lancet Neonatal Survival Series paper 2: Lancet 2005;365: POSTER

NEW evidence re effective delivery COMPLEMENTARY FEEDING PERU: Educational intervention delivered through health services RCT: Government health facilities (6 intervention, 6 control) Aim of intervention: enhance quality & coverage of existing nutrition education & introduce accrediation system Evaluation: Birth cohort, 187 infants OR 3.04 (CI )

Intervention to reconsider? Zanzibar: Pemba RCT (IFA, IFA+zinc, Zinc, Placebo)  IFA arms stopped because adverse effects –Adverse events: 12% higher, CI=2 to 23%, P=0.02 –Deaths: 15% higher, CI=-7 to 41%, P=0.19  “Current guidelines for universal IFA supplementation should be reconsidered” Sazawal et al, Lancet in press PROPHYLACTIC IRON SUPPLEMENTS IN MALARIA ENDEMIC AREAS

Coming soon  Impact of routine zinc supplements on child mortality  RESULTS from 2 trials in Pemba & Nepal  Next 6 months

NEW evidence: IMPLICATIONS NEW evidence: IMPLICATIONS  ADD IMMEDIATELY  RUTF for severely malnourished children  Oral amoxycillin for pneumonia  Cotrimoxazole prophylaxis for HIV+ children  Indicator for handwashing  CONSIDER  Newborn skin/cord cleansing  Pneumococcal vaccine  GET MORE EVIDENCE  Early initiation of BF & neonatal mortality  IF Ghana findings replicated, ADD to list

NEW evidence: IMPLICATIONS NEW evidence: IMPLICATIONS  Reconsider Iron Guidelines  EVALUATING INTERVENTIONS IS ESSENTIAL, as is monitoring outcomes after implementation  Evidence supports increased emphasis on community-based involvement  NEED: Evidence on scaling up