Shabir A. Madhi. Progress and Challenges of Immunization Contributing Toward Attaining the MDG Goal to Reduce under-5 Childhood Mortality.

Transcription

1 Shabir A. Madhi Progress and Challenges of Immunization Contributing Toward Attaining the MDG Goal to Reduce under-5 Childhood Mortality. National Institute for Communicable Diseases & University of Witwatersrand, South Africa Respiratory and Meningeal Pathogens Research Unit, & DST/NRF: Vaccine Preventable Diseases

2 Disclosure of interest Received grants from : GSK, Pfizer, Novartis Received honoraria from: GSK, Pfizer, Novartis, Merck Investigator in clinical vaccine trials for: GSK, Wyeth/Pfizer, Novartis, Medimmune Consultant/ member of advisory boards/ lecturer for: GSK, Pfizer, Merck, Abbott

3 Overview Trends in Global under-5 childhood mortality. Recent contribution of childhood vaccines in reducing under-5 mortality. Potential of new childhood vaccines in reducing under-5 mortality. New horizons in reducing under-5/neonatal morbidity and mortality by vaccination.

4 Overview Trends in Global under-5 childhood mortality. Recent contribution of childhood vaccines in reducing under-5 mortality. Potential of new childhood vaccines in reducing under-5 mortality. New horizons in reducing under-5/neonatal morbidity and mortality by vaccination.

5 Global trends in under-5 childhood deaths, 2000 to 2010 Reduction in all-cause under-5 mortality from to million between 2000 to Liu L et al. Lancet 2012; 379:

6 Progress in reduction of potentially vaccinepreventable disease between 2000 to 2010 Cause 2000 estimates (x1000) 2010 estimates (x1000) Under-5 children Total deaths Annual Percentage reduction Pneumonia ( ) ( ) 3.1% ( %) Diarrhoea ( ) 801 ( ) 4.0% ( %) Malaria (2004) 700 ( ) 564 ( ) 4.0% ( %) Measles 477 ( ) 114 ( ) 14.6% ( %) Neonatal sepsis 412 ( ) 393 ( ) 0.7% ( %) Neonatal tetanus 146 ( ) 58 ( ) 9.5% ( %) Liu L et al. Lancet 2012; 379:

7 Regional Causes of Death In Children under-5 Years Age: Western Pacific Liu L et al. Lancet 2012; 379:

8 Overview Trends in Global and South African under-5 childhood mortality. Recent contribution of childhood vaccines in reducing under-5 mortality. Potential of new childhood vaccines in reducing under-5 mortality. New horizons in reducing under-5/neonatal morbidity and mortality by vaccination.

9 Percentage of deaths (2.5 million) from vaccine-preventable diseases (VPDs) among children <5 years worldwide, 2002 Pneumococcus 28% ( ) Other VPDs 1% (25 000) Pertussis 11% ( ) Measles 21% ( ) Over 50% of VPDs in under-5 children in 2002 due to diseases for which vaccine available since the 1930s-early 90s. MMWR; 2006: 55:511-5 &WHO. 2004: Global Immunization Data

10 Measles Containing Vaccine Coverage By WHO Region, Global Coverage At 80% In MCV coverage (%) Global AFR AMR EMR EUR SEAR WPR Source: WHO/UNICEF coverage estimates , August WHO Member States. Date of slide: 16 August 2007

11 Estimated measles deaths in 2000 and Africa Eastern Mediterranean SE-Asia India Western Pacific measles deaths in % 2% % 9% 64% 26% 2% 47% Africa Eastern Mediterranean SE-Asia India Western Pacific measles deaths in % 1 36% % % % 7% % 1 Per cent reduction in 2010 compared to % decrease in global measles deaths between 2000 to Target: 90% reduction in measles mortality by 2010 compared to Simons E et al. Lancet 2012; 379:

12 Global Estimated Measles Mortality and Measles Deaths Averted. 9.6 million measles deaths averted between 2000 compared to 2010 assuming complete absence of measles vaccine. Simons E et al. Lancet 2012; 379:

13 Percentage of children under one year age who received measles vaccine, by household wealth quintile and region, Percent Need to focus immunization efforts on reaching out to the poorest quintile, who are also disadvantaged to access to curative health services Source: UNICEF. Pneumonia and Diarrhoea. June Available:

14 Global estimates of burden of deaths due to H. influenzae type b in children younger than 5 years; 2000 Europe: ( ) Eastern Mediterranean ( ) Americas: ( ) SE Asia: ( ) Western Pacific: ( ) Africa: ( ) Hib caused 8.13 ( ) million serious illnesses worldwide in 2000 Hib caused ( ) deaths in 2000 Watts JP, et al. Lancet 2009; 374:903=11

15 Countries having Introduced Hib Vaccine in 1997 and Source: WHO/IVB database, September 2011 and IVAC VIMS Report Dec 2013

16 Proportion of countries, by income-group, that have introduced Hib conjugate vaccine into immunization programs Per cent countries in which HibCV introduced Source: UNICEF. Pneumonia and Diarrhoea. June Available: Estimate: Improved HibCV coverage by 2011 in low-income countries, particularly in Africa, possibly prevents approximately additional deaths annually.

17 Overview Trends in Global and South African under-5 childhood mortality. Recent contribution of childhood vaccines in reducing under-5 mortality. Potential of new childhood vaccines in reducing under-5 mortality. New horizons in reducing under-5/neonatal morbidity and mortality by vaccination.

18 Acceleration in Development of Vaccines

19 Global Causes of under-5 Mortality, 2010 Liu L et al. Lancet 2012; 379:

20 Treatment and preventative strategies for the prevention of childhood pneumonia and diarrhoea Source: UNICEF. Pneumonia and Diarrhoea. June Available:

21 Challenges in treatment-access for diarrhea and pneumonia contribute to high childhood mortality, in developing countries Proportion of children under age 5 with diarrhea receiving ORS Proportion of children with suspected pneumonia receive antibiotics ( ). Source: UNICEF. Pneumonia and Diarrhoea. June Available:

22 Proportion of children under-5 with suspected pneumonia taken to appropriate healthcare provider, by wealth quintile and region, Source: UNICEF. Pneumonia and Diarrhoea. June Available:

23 Overview Trends in Global and South African under-5 childhood mortality. Recent contribution of childhood vaccines in reducing under-5 mortality. Potential of new childhood vaccines in reducing under-5 mortality:: Pneumococcal Conjugate Vaccine New horizons in reducing under-5/neonatal morbidity and mortality by vaccination.

24 Death rate of pneumococcal disease in children <5 years (per 100,000) Incidence rates per Number of deaths: 447,000 Africa America Eastern Mediterranean 33,100 90% of the pneumococcal deaths associated with pneumonia Europe Southeast Asia Western Pacific 100,100 15, ,000 43,000 O Brien K et al. Lancet 2009;374;

25 Impact of 7-valent PCV on Incidence of Vaccineserotype Invasive Pneumococcal Disease Adapted from: Fitzwater SP et al. PIDJ; 2012: 31:

26 Impact of 7-valent PCV on Reduction in Incidence of all-cause pneumonia hospitalization. Adapted from: Fitzwater SP et al. PIDJ; 2012: 31:

27 PCV significantly improves child survival in The Gambia All-cause mortality was decreased by 16% (95% CI: 2 38) in children vaccinated with PCV9 over a median follow-up period of 2 years Seven deaths were prevented for every 1000 children vaccinated with PCV9 in The Gambia Cutts F et al. Lancet 2005;365:

28 Proportion of Paediatric Pneumococcal Disease Preventable by Vaccination 7-valent Assumes cross protection within serogroup 6 86% 60% 71% 62% 38% 73% 10-valent 13-valent 88% 84% 92% 89% 81% 66% 87% 73% 81% 81% 87% 86% Hausdorff et al. Clin Infect Dis 2000;30:122 40

29 Introduction of pneumococcal conjugate vaccines into national immunization programs. Percent of countries in which PCV been introduced Source: UNICEF. Pneumonia and Diarrhoea. June Available: Uptake of PCV to current DTP3 coverage levels in low income countries could potentially prevent approximately under-5 childhood deaths annually.

30 PCV Introduction into Countries by : Sixty-five percent worlds infants unlikely to be vaccinated with PCV. Sixty percent world s infants live in countries where PCV not introduced. Source: IVAC VIMS Report. Dec 2013

31 Overview Trends in Global and South African under-5 childhood mortality. Recent contribution of childhood vaccines in reducing under-5 mortality. Potential of new childhood vaccines in reducing under-5 mortality: Rotavirus vaccine New horizons in reducing under-5/neonatal morbidity and mortality by vaccination.

32 Proportional Decline in all-cause diarrhea related death greater than decline in rotavirus attributed to mortality.? Parashar UD et al. J Infect Dis; 2009: 200 (S1):S9-S15; Tate JE, et al. Lancet Infect Dis; 2012; 12: ; Black RE et al. Lancet 2010; 375: ; Bryce J et al. Lancet 2005; 365: ; Liu L et al. Lancet;

33 Improved access to drinking water may be contributing to reduction in diarrhoea morbidity and mortality. The MDG drinking water target has been met. Per cent reduction in diarrhoea morbidity, by intervention Source: UNICEF. Pneumonia and Diarrhoea. June Available:

34 Rotavirus detection rates and deaths due to diarrhoea and rotavirus by WHO child mortality group and region. Country category Very low child mortality Mean rotavirus detection rate (95%CI) Number of diarrhoea related deaths Number of deaths attributed to rotavirus 49% (34-64) <1 000 <1 000 Low child mortality 40% (36-44) Asia 1 42% (35-48) Americas 1 42% (37-47) Africa 1 33% (28-38) Total High and medium mortality countries. Rotavirus accounts for 37% of all diarrhoea related death; and 5% of all-cause deaths in children under-5. 95% of rotavirus deaths occur in 72 GAVI eligible countries Tate JE, et al. Lancet Infect Dis; 2012; 12: (adapted)

35 Point estimates of Rotarix* and RotaTeq vaccine Efficacy in Relation to Country GDP Possible reasons for lower efficacy in developing countries High maternal antibody titres Breastfeeding at vaccination Micronutrient deficiencies Interfering microorganisms HIV and malaria Nelson EAS & Glass RI, Lancet 2010; 367: 568-9

36 Effectiveness of rotavirus vaccination in children younger than 5 years Patel MM et al. Lancet Infect Dis 2012; 12: (Adapted)

37 Number of diarrhea-related deaths among children aged <59 months in Mexico by age group; July 2002 to May %; 95%CI 36 to 47 29%; 95%CI 17 to 39 Richardson V et al. N Eng J Med 2010; 362;

38 Proportion of countries, by income-group, that have introduced rotavirus vaccine into immunization programs Source: UNICEF. Pneumonia and Diarrhoea. June Available: Increasing vaccination against rotavirus to levels of DTP3 coverage in low-income countries estimated to potentially prevent under-5 deaths annually. Tate JE, et al. Lancet Infect Dis; 2012; 12: (adapted)

39 Countries in Which Rotavirus Vaccine Has Been Introduced. Source: IVAC VIMS Report. Dec 2013

40 Rotavirus Vaccine Introduction Into GAVI Eligible Countries (2013) 2013: Eighty percent of worlds infants (103 million) unlikely to receive rotavirus vaccine Seventy-percent of world s infants live in countries where RV has not been introduced Source: IVAC VIMS Report. Dec 2013

41 Overview Trends in Global under-5 childhood mortality. Recent contribution of childhood vaccines in reducing under-5 mortality. Potential of new childhood vaccines in reducing under-5 mortality. New horizons in reducing childhood morbidity and mortality by vaccination.

42 Regional Causes of Death In Children under-5 Years Age: Western Pacific Liu L et al. Lancet 2012; 379:

43 Cause-specific mortality rates in Western Pacific Children aged 0-27 days, 2000 to 2010 Liu L et al. Lancet 2012; 379:

44

45 Neonatal Tetanus Global Annual Reported Cases and TT2plus coverage,

46 Maternal vaccination for reducing neonatal morbidity and mortality: Influenza vaccination. Acellular pertussis vaccine. GBS vaccination. RSV vaccine.

47 Reduced Influenza-confirmed Illness in Young Infants Whose Mothers received TIV vs. PPV. Enrollment Historic Influenza Season 63% (95%CI: 5 to 85) reduction in influenza confirmed illness in infants of TIV vaccinated mothers. 29% (95%CI: 7 to 46) reduction in febrile respiratory illness. 36% (95%CI: 4 to 57) reduction in maternal respiratory illness with fever. Zaman K et al. NEJM 2008; 359:

48 Vaccine Efficacy of Influenza Vaccination of Pregnant HIV- Women against PCR-confirmed Influenza Illness up Until 24 weeks Post-partum. AR: 3.6% AR: 1.8% VE (ITT): 50.4% (95%CI: 14.5; 71.2) VE (PP): 54.4% (95%CI: 19.5; 74.2) HIV- unpublished data (Madhi SA et al. ISID, Apr 2012, Cape Town, South Africa)

49 Vaccination of HIV- Pregnant Women in Preventing Influenza-Confirmed illness in their Infants up until 24 Weeks of age. AR: 3.6% AR:1.9% VE (ITT): 48.8% (95%CI: 11.5; 70.3) VE (PP): 45.6% (95%CI: 2.4; 69.7) HIV- unpublished data (Madhi SA et al. ISID, Apr 2012, Cape Town, South Africa)

50 Da Vinci

51 Fetal Outcomes of the 1918 Influenza Pandemic Bloom-Fesbach K et al. J Infect Dis 2011; 204:

52 Prevented Fraction of Prematurity in Georgia, USA by Influenza Activity Period Omer S PlosMed 2011:8 e100041

53 Newborn and Fetal Effects of Maternal Influenza Vaccination or Illness Steinhoff M et al; Am J Obs Gynec. 2012

54 Guidelines for Vaccinating Pregnant Women, USA

55 Conclusions Vaccines have potential toward reducing under-5 childhood mortality. Significant advances made since 1990 in reduction of mortality from polio, measles and neonatal tetanus over relative short periods because of vaccination. Newly licensed vaccine against major pathogens causing diarrhoea (rotavirus) and pneumonia (pneumococcus) have potential of preventing approximately thousand childhood deaths annually. Also, promise of other soon-to-be licensed vaccines against other major infectious causes of under-5 mortality. Next frontier is targeting vaccination of pregnant women for reducing death from neonatal vaccine-preventable diseases.

56 Challenge: Sustaining, secured supply of live-saving vaccines at affordable prices to low and low-middle income countries, particularly to most economically marginalized sectors of communities.