Yellow Fever Vaccination: Doing Away with the Ten Yearly Booster

Transcription

1 Yellow Fever Vaccination: Doing Away with the Ten Yearly Booster Philippe Duclos, WHO CISTM14 Québec, 26 May 2015

2 I have no interest to report Philippe Duclos

3 Outline Background on yellow fever (YF) and WHO's process to develop evidence based recommendations Approach used to review recommendations on use of yellow fever vaccine (YFV) and need for booster doses and related evidence Describe the use and challenges of GRADE 3

4 Background: Yellow Fever (YF) No specific treatment prevention critical Yellow fever vaccine (YFV) used since 1937; >> 600 million doses delivered All YFV are live attenuated vaccines (17D lineage), highly immunogenic and effective YFV recommended for person >= 9 months living in or travelling to areas at risk for YF transmission in South America and Africa 4

5 Background: International Health Regulations (IHR) and Yellow Fever Policies regarding YFV use included in the IHR Under IHR countries can require proof of YFV receipt Validity of certificate initially set to 6 years Since 1965, a single dose of YFV considered to protect against infection starting 6 days following administration and for 10 years only In 2003, review and recommendation of booster every 10 years maintained because of IHR 5

6 Strategic Advisory Group of Experts Principal advisory group to WHO for vaccines and immunization Membership Meetings and operational procedures (GRADE) Working groups Report and communications (SAGE) on Immunization 6

7 SAGE process from evidence to recommendation (1 of 2) 1. Definition of questions to inform recommendations 2. Identification of critical questions for which an in-depth review is needed 3. Systematic review of the literature 4. Reviewing the quality of the evidence through risk of bias 7

8 SAGE process from evidence to recommendation (2 of 2) 5. Rating of the quality of the evidence (GRADE) 6. Development of proposed recommendations (GRADE_DECIDE) 7. Presentation of proposed recommendations to SAGE 8. SAGE discussion, deliberation, and ultimate decision 8

9 9 SAGE Recommendations Usually no formal rating Weak recommendations are of little value to country immunization programs (different from conditional recommendations) Need consistent and clear wording Recommendations for off-license use are acceptable

10 Moving from evidence to recommendations: GRADE_DECIDE guideline process Benefits and harms Resource use and value for money Equity impacts Feasibility Acceptability Values and preferences Other considerations: Potential impact of a differential recommendation for residents of endemic countries and travellers 10

11 Updating of Recommendations In 2013, SAGE asked to review recommendations on the use of YFV Consistent with SAGE processes establishment of a YFV working group (multiple expertise and geographic diversity) Systematic review of published and unpublished evidence and quality assessment using GRADE 11

12 Yellow Fever Working Group Questions addressed Need for doses every 10 years to maintain protection in: YF endemic countries population Travellers Interference between YF and other co-administered vaccines Safety of YFV in special populations Impact of vaccination strategies on YF control 12

13 YFV: immunogenicity & protection Historical perspective No YFV efficacy studies Several observations supported protective effect Reduction in laboratory-acquired infection in vaccinated workers YF only in unvaccinated persons in South America following vaccine introduction Disappearance of cases in outbreaks when campaign conducted Protection of monkeys against virulent virus challenge by neutralizing antibodies Rhesus monkey studies log 10 neutralization index (LNI) of >0.7 correlates with protection 1 Correlates using more common plaque reduction neutralization test (PRNT) not established Mason. Appl Microbiol. 1973; 25: 539.

14 Findings of systematic review on duration of YF antibodies following vaccination Six additional studies published since dose interval last established Year # of subjects Population US military (travelers) Time since YF vaccine Testing Findings years PRNT 90 78% with titers; varied by service (60-97%) Travelers 10 years PRNT % detectable titers Travelers years PRNT 90 75% titer Endemic 5-24 years PRNT 75 68% titer Endemic 10 years PRNT % titer Travelers 1-60 years PRNT 80 93% years; 95% titer 10; 87% 20 years 14 PRNT n = Plaque reduction neutralization testing where the reciprocal of the highest serum dilution at which n% of virus is inhibited

15 Findings of systematic review on YFV failures Since 1930s, only 12 YF cases documented in vaccine recipients Ten cases lacked laboratory confirmation Two cases were in persons vaccinated <2 weeks before disease onset All cases 5 years after YFV administration No secondary vaccine failures* noted 15 *Primary vaccine failure = failure to seroconvert after vaccination; secondary vaccine failure = loss of protection after initial seroconversion.

16 Is there evidence that a booster dose is required in immunocompetent individuals to ensure long-term protection? GRADE: Quality assessment Rating Adjustment to rating No. of studies/starting rating 10/ observational 1 2 Factors decreasing confidence Factors increasing confidence Limitation in study design None Serious 2 0 Inconsistency None serious 0 Indirectness None serious 3 0 Imprecision None Serious 0 Publication bias None serious 0 Large effect Not applicable 0 Dose-response Not applicable 0 Antagonistic bias and confounding Not applicable 0 Final numerical rating of quality of evidence observational studies reported % neutralizing antibody (NTAb) 10years after vaccination. One small study reported 65% (n=13/20) with protective NTAb after 10 years (De Melo et al. 2011). One study (Gomez SY et al. 2008) reported NTAb in >68% in vaccinees after 4years post vaccination. One study (Veit et al.2009) reported 88% NTAb 1-10 years after vaccination and one study reported 73% with NTAb 3-4 years after vaccination (Gibney et al. 2012). 2 Limitations in only 2 of 8 studies/therefore no downgrading: No clear description of method and incomplete medical records of vaccinated (Poland et al. 1981). Non-standardized methods such as mouse-protection test used (Groot et al. 1962). 3 Serological marker as proxy to assess level of clinical protection, yet overall agreement in the assumption that titer>1:10 in plaque reduction neutralization test is associated with protective immunity (Hepburn at al. 2006; Monath et al. 2005), therefore no downgrading. 16

17 Evidence that a booster dose is required in immunocompetent individuals to ensure long-term protection? Systematic review suggests immunity following YF vaccination is life-long and secondary vaccine failures do not occur Observational studies attest vaccine effectiveness No demonstrated need for booster dose every ten years in immunocompetent persons Confidence in estimate of effect on outcome is limited 17

18 Additional Considerations (1 of 2) YF only in unvaccinated persons during outbreaks Data suggest role of innate and cell-mediated immunity in initial and memory immune response Vaccine specific serious adverse events only in primo-vaccinees Some natural boosting likely in endemic areas 18

19 Additional Considerations (2 of 2) Flaws of logic of a repeat dose every 10 years to ensure protection Global supply problem Savings for patients, loss of income for some Equity issue 19

20 Conclusions & Recommendations Based on currently available data, a single dose of YF vaccine appears to confer life-long protective immunity against YF disease A booster dose of YF vaccine is not needed to maintain immunity Further research is needed in certain groups, who may have suboptimal seroconversion rates following a single dose of the vaccine to determine if they may benefit from a single booster dose 20 14

21 Impact of SAGE recommendations WHO position paper updated in 2013 In May 2014 World Health Assembly adopted amendment to Annex 7 of IHR Change duration of validity of certificates Will come legally in force in June 2016 To date 34 countries extended the duration of validity of certificates from 10 years to life 21

22 Challenges of GRADE Cumbersome Too much focus on the GRADE tables Variability in applying judgement need working group with both experts and methodologists Rating of evidence for observational studies Lack of consideration of entire body of evidence and insufficient consideration of consistency of evidence Importance of proper wording of question 22

23 Advantages of GRADE Transparent and systematic process Framework facilitates systematic approach and limits possibly biased expert views International standard and recognition Adds to credibility Evolution 23

24 24 Thank you for your attention

25 To date 34 countries have already extended the duration of validity of certificates from 10 years to life Algeria Angola Bahamas Bahrain Brunei Darussalam Cameroon Congo Costa Rica Ecuador Egypt El Salvador Ghana Guatemala Guyana Honduras Iran (Islamic Republic of) Jamaica Jordan Libyan AJ Madagascar Maldives Myanmar Oman Paraguay Sao Tome Principe Saudi Arabia South Africa Sri Lanka St Kitts and Nevis Sudan Suriname Tanzania (United Republic of) Zambia Zimbawe 25