Maternal Immunization Efficacy and Safety Saad B. Omer

Transcription

1 Maternal Immunization Efficacy and Safety Saad B. Omer William H. Foege Professor of Global Health Professor of Epidemiology & Pediatrics Emory University, Schools of Public Health & Medicine

2 Pregnancy Pre-partum Birth 6 wks (2 mo) After Birth 10 wks (4 mo) 14 wks (6 mo) Some infections more dangerous in pregnancy (e.g. influenza, Hepatitis E) 5 3 mil. deaths (0-27 days) Mortality data: Liu et al., Lancet; 2012

3 3 Omer, New Eng. J. Med., 2017

4 4 Influenza

5 Pregnancy & infancy as risk factors for severe disease attributable to seasonal influenza Odds ratios for a cardiopulmonary event during influenza season among pregnant women aged years (referent group: postpartum women) Bhat N et al. N Engl J Med Dec 15;353(24): Neuzil KM, Reed GW, Mitchel EF, et al.. Am J Epidemiol.. 5

6 63% reduction in infant influenza after maternal vaccination in pregnancy Shehzad Noorani 17 Zaman et al., New Eng Journal of Medicine, 2008

7 Distribution of the Number of Weeks of Exclusive Breastfeeding 18 Omer, et al., New Eng Journal of Medicine, 2009

8 Synergy between Influenza Virus & S. pneumoniae (pneumococcus) Influenza infection predisposes to pneumococcus Altered immune system particularly innate immune system Most deaths in the 1918 influenza pandemic due to secondary pneumococcal infection 20

9 One-two punch of maternal influenza immunization + infant pneumococcal conjugate vaccine

10 % Efficacy Efficacy of PCV +TIV for Respiratory Illness with Fever Full Study Period Flu Circulation Period Mother PPSV23; Infant Hib Mother PPSV23; Infant PCV7 Mother Control Mother Control Infant Control Infant PCV Mother TIV Infant Control Mother TIV; Infant Hib Mother TIV Infant PCV Mother TIV; Infant PCV7 TIV: Trivalent (inactivated) influenza vaccine; PCV7: 7-valent pneumococcal conjugate vaccine 10 Omer et al., J. Infect. Dis., 2013

11 WHO Strategic Advisory Group of Experts (SAGE) Recommendation: Countries considering the initiation or expansion of seasonal influenza vaccination programmes give the highest priority to pregnant women 24 Wkly Epidemiol Rec., 2012

12 Three Bill & Melinda Gates Foundation Trials Mali Nepal South Africa 25 UN Photo/John Isaac UNFPA/Anna Adhikari UN Photo/P Mugabane

13 Vaccine Efficacy against laboratory confirmed influenza in infants -Data from RCTs 14 Omer, New Eng. J. Med., 2017

14 Vaccine Efficacy against laboratory confirmed influenza in mothers -Data from RCTs 15 Omer, New Eng. J. Med., 2017

15 Birth weight (g) Baseline Mean Birth weight in Trial Countries Nepal 1 Mali 2 South Africa 3 Bangladesh 4 1) Mullany et al., 2007; 2) Teguete et al., 2012; 3) Sabet et al., 2009; 4) UNICEF

16 17 Steinhoff M, IDSA, 2015; Tapia M et al., The Lancet,,2016; Madhi S et al., NEJM, 2014; Steinhoff M et al., Canadian Medical Association Journal, 2012.

17 Steinhoff et al., CMAJ, Distribution of birth weight by vaccine group and circulation period - Bangladesh Mother's Gift Trial

18 Location specific nuances Nepal was the only trial to have low birth weight as a (co-)primary outcome Gestational age at vaccination was lower for the Nepal trial compared to other 3 trials Baseline birth weight was lower in the populations where the Nepal trial was conducted compared to other study sites 32

19 Maternal Influenza Vaccine Evidence of impact on lab confirmed infant influenza Emerging evidence for impact on severe outcomes in infants Appreciating location specific nuances Seasonality Baseline rates of outcomes of interest Evidence-based decision-making

20 22 Pertussis Vaccine

21 Pertussis Burden WHO estimate: 16 million cases/year 95% in developing countries Infants too young to be completely vaccinated at high-risk More severe disease in young infants compared to older children & adults Combined tetanus, diphtheria, and (acellular) pertussis (Tdap) vaccine recommended for pregnant women in multiple countries. (without a phase III clinical trial) 39 WHO, 2011: CDC, 2012

22 40 Kharbanda et al. JAMA. 2014

23 Time Since Prior Tetanus-Containing Vaccine & RR of Tdap Safety Outcomes 2.97 Local Reactions 3.00 Small for Gestational Age 3.00 Preterm Delivery <2 years 2-5 years 0.33 <2 years 2-5 years 0.33 <2 years 2-5 years Reference group: >5 years since prior tetanus-containing vaccine 25 Sukumaran et al., JAMA, 2015

24 26 GBS Vaccine

25 Invasive GBS disease in infants Early-onset GBS (EOGBS) occurs before age 7 days sepsis without a focus (80%-95%) pneumonia (10%-15%) meningitis (5%-10%) Late-onset GBS (LOGBS) occurs in infants aged 7 to 89 days old Meningitis more frequent (21% 35%)» 30% of cases have permanent sequelae (eg, hearing loss, developmental delay). 27 Healy & Baker in Vaccines, 6th Ed.

26 Epidemiology of Group B Streptococcal infection in pregnant women (United States) Universal screening No change in lateonset disease in infants or disease in pregnancy 43 Phares et al. JAMA May 7;299(17):

27 Invasive Group B Streptococcal Infection in Pregnant Women Pregnancy Outcomes Among Women with Invasive GBS Active, population-based surveillance in 10 U.S. states Identified 409 invasive GBS infections in pregnant women 61% 4% 5% SAB or Stillbirth Infant Clinical Infetion Induced Abortion 29 Phares et al. JAMA May 7;299(17):

28 Proportions of Cases of Bacterial Meningitis Caused by Each Pathogen U.S. Emerging Infections Program Thigpen, et al. NEJM, 2011

29 Potential mechanisms of maternal GBS colonization leading to adverse pregnancy outcomes Supportive data Maternal GBS colonization Preliminary data Intra-amniotic, urinary tract, or systemic GBS infection Bacterial virulence factors Subclinical local or systemic inflammation Preterm birth 47

30 Association between Group B Streptococcal colonization and preterm delivery Cross-Sectional Case Control Pooled Cross-Sectional + Case Control Cohort Studies Valkenburg-van den Berg et al. Acta Obstet Gynecol Scand. 2009;88(9):958-67

31 GBS Vaccine Progress Trivalent Type Ia, Ib and III Vaccine to Prevent GBS Infection (Novartis) Purified CPS conjugated to CRM197 Phase I & II trials Further clinical development plans evolving 33

32 34 RSV Vaccine

33 55 Hall et al. NEJM, 2009

34 36 Hall et al. NEJM, 2009

35 Global Neonatal and Infant Deaths in Lozano R et al. Lancet, 2012

36 Estimated case fatality ratio in children <5 years admitted to hospital for RSV-associated severe ALRI <1 year <5 years Industrialised countries 0 7% ( ) 0 3% ( ) Developing countries 2 1% ( ) 2 1% ( ) 38 Nair et al. Lancet, 2010

37 39

38 40

39 41 Ethics

40 legitimacy of a mother s interests in the welfare of her fetus/infant 43

41 Characteristics of an Interests-based Approach Mother s agency front and center Inclusion of women in decision-making Limits options for mandatory maternal immunization Chamberlain et al., Science, 2017

42 Thank 45