mpact of MenZB on the incidence of gonorrhoea and potential future implications for cost effectiveness of teenage meningococcal vaccination https://www.meningitis.org/mrf-conference-2017

1. IMPACT OF MENZB ON THE
INCIDENCE OF GONORRHOEA AND
POTENTIAL FUTURE IMPLICATIONS
FOR COST EFFECTIVENESS OF
TEENAGE MENINGOCOCCAL
VACCINATION
JANINE PAYNTER, HELEN PETOUSIS-HARRIS,
JANE MORGAN, FELICITY GOODYEAR-SMITH,
PETER SAXTON, STEVEN BLACK

2. DISCLOSURES
THIS RESEARCH HAS BEEN FUNDED BY NOVARTIS VACCINES &
DIAGNOSTICS AG (NOW A MEMBER OF THE GSK GROUP OF
COMPANIES, DUE TO THE ACQUISITION BY GSK GROUP OF
COMPANIES OF THE NON-INFLUENZA NOVARTIS’ VACCINES
DIVISION) AND SPONSORED BY AUCKLAND UNISERVICES LTD.

3. THE STORY BEGINS WITH THE
MENINGOCOCCAL VACCINATION
PROGRAMME…
• EPIDEMIC CAUSED BY MENINGOCOCCAL GROUP B
BACTERIA
• VACCINE DEVELOPED USING A NEW ZEALAND PORA
STRAIN OF THE NEISSERIA MENINGITIDES GROUP B
• VACCINATION PROGRAMME 2004-2008 WITH EVERYONE
UNDER 20 YEARS OLD ELIGIBLE FROM 2004-2006.
• OVER 300 CASES IN 2001 TO LESS THAN 30 CASES
IN 2010. (MINISTRY OF HEALTH WEBSITE)

4. AN EXCELLENT SCIENTIST WONDERED
SOMETHING AFTER READING
SOMETHING ABOUT THE
MENINGOCOCCAL B VACCINE
PROGRAMME EVALUATION…
• PROFESSOR STEVEN BLACK
• CONSIDERED? MENZB™
EFFECTIVENESS AGAINST
INVASIVE PNEUMOCOCCAL
DISEASE
• IMPACT ON A NEISSERIA????
RELATIVE

5. THERE WAS A STRANGE ANOMALY IN
INCIDENCE OF GONORRHOEA
COMPARED TO ANOTHER SIMILAR STI
IN NEW ZEALAND AFTER THE MENZB
PROGRAMME…
Health Intelligence Team, Institute of
Environmental Science and Research
Limited

6. WE CONDUCTED A CASE –
CONTROL STUDY…
• USED MINISTRY OF HEALTH DATA – THE NATIONAL
IMMUNISATION REGISTER AND NHI DATA
• VACCINATION STATUS, ETHNICITY, DEPRIVATION, SEX AND
AGE
• SEXUAL HEALTH CLINICS FROM AROUND NEW ZEALAND
PROVIDED DATA ON GONORRHOEA AND CHLAMYDIA
DIAGNOSIS AND CONFIRMATION
• VACCINE EFFECTIVENESS ESTIMATE
OF 31% (95% CI 21–39).

7. WANTED TO DO SOMETHING
MORE ROBUST – A COHORT
STUDY
• COHORT STUDY FOLLOWS A GROUP OF
PEOPLE SOME WHO HAVE BEEN
VACCINATED SOME WHO HAVEN’T
THEN SEES WHAT HAPPENS TO THEM –
DID LESS VACCINATED YOUNG ADULTS
GET GONORRHOEA?
• EXCEPT MANY YOUNG PEOPLE LIKE TO
TRAVEL
• NOT KNOWING WHO HAS STAYED AND
WHO HAS TRAVELLED FOR A
SUBSTANTIAL PERIOD OF TIME IS A
PROBLEM HOWEVER…..

9. DATA USED FROM THE
INTEGRATED DATA
INFRASTRUCTURE
• NATIONAL HEALTH INDEX POPULATION DEMOGRAPHICS
TABLE
• CUSTOMS NZ JOURNEY DATA TABLE
• NATIONAL MINIMUM DATASET (HOSPITAL DISCHARGES)
• NATIONAL IMMUNISATION REGISTER
• EDUCATION AND TAX DATASETS (BASIC TABLE OF
WHETHER OR NOT A PERSON HAS FILED A TAX RETURN) AS
EXTRA CHECKS FOR PRESENCE IN NEW ZEALAND

10. Disclaimer:
Access to the data presented was managed by Statistics New
Zealand under strict micro-data access protocols and in
accordance with the security and confidentiality provisions of
the Statistic Act 1975. Our findings are not Official Statistics.
The opinions, findings, recommendations, and conclusions
expressed are those of the author(s)/researchers, not
Statistics NZ.

11. PRIMARY OUTCOME –
GONORRHOEA CONSIDERED
REASON FOR HOSPITALISATION
27/11/2017 11
ICD-10
Code Text description
A54.0
Gonococcal infection including cervicitis, cystitis,
urethritis, vulvovaginitis
A54.2
Gonococcal pelviperitonitis including epididymitis,
female pelvic inflammatory disease, orchitis,
prostatitis
A54.3 Gonococcal conjunctivitis
A54.4 Gonococcal infection of musculoskeletal system
A54.8
Other gonococcal infections including meningitis,
septicaemia
A54.9 Gonococcal infection, unspecified

12. Flow chart describing selection of participants
from the Integrated Data Infrastructure for the
cohort study

13. Associations between co-variates and vaccination status
(N = 1,108,602)
Vaccination status
Covariate Partial Unvaccinated Vaccinated
Sex n (%) n (%) n (%) Chi-square P
Female 18,258 (3.4) 210,738 (40.5) 310,134 (57.5) <0.0001
Male 20,460 (3.6) 229,698 (41.9) 319,131 (56.1)
missing 0 (0.0) 138 (79.3) 36 (20.7)
Ethnicity
European, Asian & Other 18,063 (2.7) 275,790 (41.9) 382,722 (56.6) <0.0001
Māori 16,188 (5.3) 101,244 (35.1) 187,488 (61.5)
Pacific Peoples 4,323 (3.9) 47,640 (44.9) 58,545 (53.0)
missing 144 (0.9) 15,903 (96.7) 546 (3.3)
Deprivation
Low 7,506 (2.8) 94,032 (36.5) 163,758 (61.7) <0.0001
Medium 13,299 (3.3) 148,359 (38.6) 235,875 (59.3)
High 17,067 (4.5) 144,624 (39.6) 221,040 (57.8)
missing 852 (1.4) 53,562 (86.1) 8,631 (13.7)
Age Group (Birth years)
Oldest (1984-1988) 15,471 (4.6) 225,000 (69.6) 98,334 (29.0) <0.0001
Middle (1989-1993) 13,449 (3.7) 109,830 (31.3) 241,359 (66.2)
Youngest (1994-1999) 9,801 (2.4) 105,753 (26.7) 289,608 (71.5)

14. VACCINE EFFECTIVENESS BASED ON
PROPORTIONAL HAZARDS – MEDIAN AGE AT
START - 18 (IQR 17-19)
Vaccination status Nevents/N
Univariate Hazard
ratio (95% CI)
Adjusted Hazard Ratio
(95% CI)*
Vaccine
effectiveness
(95% CI)
Older - Vaccination status
Partial (1 or 2 doses) 15/14,544 2.07 (1.14-3.74) 1.59 (0.88-2.88) -59% (-188-12%)
Vaccinated 18/102,042 0.62 (0.36-1.05) 0.69 (0.41-1.17) 31% (-17-59%)
Unvaccinated 87/222,072 Ref Ref
Sex
Male 0.23 (0.15-0.37)
Female Ref
Ethnicity
Māori 5.16 (3.24-8.24)
Pacific Peoples 1.92 (0.91-4.02)
NZ European, Asian & Other Ref
Deprivation
High 2.52 (1.33-4.79)
Medium 0.96 (0.47-1.95)
Low Ref

15. VACCINE EFFECTIVENESS BASED ON
PROPORTIONAL HAZARDS – MEDIAN AGE AT
START - 13 (IQR 12-14)
Nevents/N
Univariate Hazard
ratio (95% CI)
Adjusted Hazard
Ratio (95% CI)*
Vaccine
effectiveness (95%
CI)
Middle-Vaccination status
Partial (1 or 2 doses) S/12,147 S S S
Vaccinated 60/245,553 0.58 (0.37-0.91) 0.53 (0.34-0.82) 47% (18-66%)
Unvaccinated 30/106,845 Ref Ref
Sex
Male 0.20 (0.12-0.34)
Female Ref
Ethnicity
Māori 9.44 (5.09-17.51)
Pacific Peoples 2.96 (1.21-7.25)
NZ European, Asian & Other Ref
Deprivation
High 3.60 (1.48-8.77)
Medium 2.00 (0.79-5.09)
Low Ref

16. VACCINE EFFECTIVENESS BASED ON
PROPORTIONAL HAZARDS – MEDIAN AGE AT
START - 8 (IQR 6-9)
Nevents/N
Univariate Hazard ratio
estimate (95% CI)
Adjusted Hazard Ratio
estimate (95% CI)*
Vaccine
effectiveness (95%
CI)
Youngest -Vaccination status
Partial (1 or 2 doses) S/9,237 S S S
Vaccinated 27/293,433 2.44 (0.64-9.25) 1.82 (0.48-6.87) -82% (-587-52%)
Unvaccinated 0/102,480 Ref Ref
Sex
Male 0.13 (0.04-0.39)
Female Ref
Ethnicity
Māori 5.33 (1.98-14.35)
Pacific Peoples 1.81 (0.38-8.68)
NZ European, Asian &
Other Ref
Deprivation
High 3.15 (0.78-12.67)
Medium 1.68 (0.38-7.33)
Low Ref

17. LIMITATIONS
• HOSPITALISATION DUE TO GONORRHOEA IS A RARE EVENT –
CAN BIAS THE ESTIMATE – WE APPLIED A CORRECTION (FIRTH
CORRECTION FOR RARE EVENTS)
• WIDE RANGE IN AGES AT THE START OF THE STUDY
• VACCINATION STATUS FOR ALL AT BEGINNING OF STUDY WAS
UNVACCINATED BUT MOST VACCINATED BY 2006
• YOUNGEST AGE GROUP NOT AT RISK OF GONORRHOEA UNTIL
LATER IN FOLLOW-UP PERIOD
• NO SPECIFIC DATA ON WHEN SEXUAL ACTIVITY BEGINS FOR
EACH INDIVIDUAL AND THEREFORE WHEN AT RISK JUST USE
AGE AS A PROXY

18. STRENGTHS
• LARGE LINKABLE DATA SOURCES
• HIGH QUALITY VACCINATION RECORDS
• SUPPORT I GET FROM MY TEAM WHICH HAS EXPERTISE IN
VACCINOLOGY, CLINICAL EXPERTISE IN SEXUAL HEALTH
CARE AND PRIMARY CARE AND EPIDEMIOLOGY


19. CONCLUSION
• RESULTS FROM THE COHORT STUDY ARE CONSISTENT
WITH THE CASE-CONTROL STUDY
• THE MENINGOCOCCAL B OMV VACCINE APPEARS TO HAVE
SOME EFFECTIVENESS AGAINST GONORRHOEA.
• POTENTIALLY 20% TO ABOUT HALF OF HOSPITALISATIONS
FOR GONORRHOEA PREVENTED AND 30% OVERALL.
THANK YOU