An Observational Study to Assess the Effectiveness of 4CMenB against Meningococcal Disease and Carriage and Gonorrhea in Adolescents in the Northern Territory, Australia-Study Protocol

Helen S Marshall, Prabha H Andraweera, James Ward, John Kaldor, Ross Andrews, Kristine Macartney, Peter Richmond, Vicki Krause, Ann Koehler, David Whiley, Lynne Giles, Rosalind Webby, Heather D'Antoine, Jonathan Karnon, Rob Baird, Andrew Lawrence, Helen Petousis-Harris, Philippe De Wals, Belinda Greenwood-Smith, Michael Binks, Lisa Whop, Helen S Marshall, Prabha H Andraweera, James Ward, John Kaldor, Ross Andrews, Kristine Macartney, Peter Richmond, Vicki Krause, Ann Koehler, David Whiley, Lynne Giles, Rosalind Webby, Heather D'Antoine, Jonathan Karnon, Rob Baird, Andrew Lawrence, Helen Petousis-Harris, Philippe De Wals, Belinda Greenwood-Smith, Michael Binks, Lisa Whop

Abstract

Invasive meningococcal disease (IMD) causes significant morbidity and mortality worldwide with serogroup B being the predominant serogroup in Australia and other countries for the past few decades. The licensed 4CMenB vaccine is effective in preventing meningococcal B disease. Emerging evidence suggests that although 4CMenB impact on carriage is limited, it may be effective against gonorrhoea due to genetic similarities between Neisseria meningitidis and Neisseria gonorrhoeae. This study protocol describes an observational study that will assess the effect of the 4CMenB vaccine against meningococcal carriage, IMD and gonorrhoea among adolescents in the Northern Territory (NT). All 14-19-year-olds residing in the NT with no contraindication for 4CMenB vaccine will be eligible to participate in this cohort study. Following consent, two doses of 4CMenB vaccine will be administered two months apart. An oropharyngeal swab will be collected at baseline and 12 months to detect pharyngeal carriage of Neisseria meningitidis by PCR. The main methodological approaches to assess the effect of 4CMenB involve a nested case control analysis and screening method to assess vaccine effectiveness and an Interrupted Time Series regression analysis to assess vaccine impact. Research ethics approvals have been obtained from Menzies and Central Australian Human Research Ethics Committees and the Western Australian Aboriginal Health Ethics Committee. Results will be provided in culturally appropriate formats for NT remote and regional communities and published in international peer reviewed journals. ClinicalTrials.gov Identifier: NCT04398849.

Keywords: 4CMenB; gonorrhoea; meningitis; meningococcal disease; vaccination; vaccine.

Conflict of interest statement

H.S.M. is an investigator on clinical trials of investigational vaccines sponsored by Industry. H.S.M.’s, institution receives funding from Industry (GSK, Pfizer, Sanofi-Pasteur, Novavax) for Investigator led research and for sponsored studies. H.S.M. receives no personal payments from Industry. P.R. has served on scientific advisory boards for meningococcal vaccines for GlaxoSmithKline and Pfizer on behalf of the University of Western Australia. His Institution has received funding for investigator grants outside the submitted work from GlaxoSmithKline. His institution has received funding for industry sponsored multicentre studies for GlaxoSmithKline, Pfizer outside the submitted work. He has not received personal remuneration for this work. Other authors report no conflict of interest.

Figures

Figure 1
Figure 1
Study design.

References

    1. Chang Q., Tzeng Y., Stephens D. Meningococcal disease: Changes in epidemiology and prevention. Clin. Epidemiol. 2012;4:237–245. doi: 10.2147/clep.s28410.
    1. Jafri R.Z., Ali A., Messonnier N.E., Tevi-Benissan C., Durrheim D., Eskola J., Fermon F., Klugman K.P., Ramsay M., Sow S., et al. Global epidemiology of invasive meningococcal disease. Popul. Health Metr. 2013;11:17. doi: 10.1186/1478-7954-11-17.
    1. Wang B., Santoreneos R., Giles L., Haji Ali Afzali H., Marshall H. Case fatality rates of invasive meningococcal disease by serogroup and age: A systematic review and meta-analysis. Vaccine. 2019;37:2768–2782. doi: 10.1016/j.vaccine.2019.04.020.
    1. Borrow R., Alarcon P., Carlos J., Caugant D.A., Christensen H., Debbag R., De Wals P., Echaniz-Aviles G., Findlow J., Head C., et al. The Global Meningococcal Initiative: Global epidemiology, the impact of vaccines on meningococcal disease and the importance of herd protection. Expert Rev. Vaccines. 2017;16:313–328. doi: 10.1080/14760584.2017.1258308.
    1. Caugant D.A., Tzanakaki G., Kriz P. Lessons from meningococcal carriage studies. FEMS Microbiol. Rev. 2007;31:52–63. doi: 10.1111/j.1574-6976.2006.00052.x.
    1. Christensen H., May M., Bowen L., Hickman M., Trotter C.L. Meningococcal carriage by age: A systematic review and meta-analysis. Lancet Infect. Dis. 2010;10:853–861. doi: 10.1016/S1473-3099(10)70251-6.
    1. Ladhani S.N., Andrews N., Parikh S.R., Campbell H., White J., Edelstein M., Bai X., Lucidarme J., Borrow R., Ramsay M.E. Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England. N. Engl. J. Med. 2020;382:309–317. doi: 10.1056/NEJMoa1901229.
    1. Marshall H.S., McMillan M., Koehler A.P., Lawrence A., Sullivan T.R., MacLennan J.M., Maiden M.C.J., Ladhani S.N., Ramsay M.E., Trotter C., et al. Meningococcal B Vaccine and Meningococcal Carriage in Adolescents in Australia. N. Engl. J. Med. 2020;382:318–327. doi: 10.1056/NEJMoa1900236.
    1. World Health Organization . Global Incidence and Prevalenceof Selected Curable Sexually Transmitted Infections–2008. World Health Organization; Geneva, Switzerland: 2012.
    1. Ochoa-Azze R.F. Cross-protection induced by VA-MENGOC-BC(R) vaccine. Hum. Vaccines Immunother. 2018;14:1064–1068. doi: 10.1080/21645515.2018.1438028.
    1. Pérez O., del Campo J., Cuello M., González E., Nuñez N., Cabrera O., Llanes R., Acevedo R., Zayas C., Balboa J. Mucosal approaches in Neisseria vaccinology. VacciMonitor. 2009;18:53–55.
    1. Petousis-Harris H., Paynter J., Morgan J., Saxton P., McArdle B., Goodyear-Smith F., Black S. Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: A retrospective case-control study. Lancet. 2017;390:1603–1610. doi: 10.1016/S0140-6736(17)31449-6.
    1. Lahra M.M., Enriquez R.P., George C.R.R. Australian Gonococcal Surveillance Programme Annual Report, 2018. Commun. Dis. Intell. 2020;44 doi: 10.33321/cdi.2020.44.4.
    1. Kirby Institute . HIV, Viral Hepatitis and Sexually Transmissible Infections in Australia: Annual Surveillance Report 2018. Kirby Institute, UNSW Sydney; Sydney, Australia: 2018.
    1. Birrell J.M., Gunathilake M., Singleton S., Williams S., Krause V. Characteristics and Impact of Disseminated Gonococcal Infection in the "Top End" of Australia. Am. J. Trop. Med. Hyg. 2019;101:753–760. doi: 10.4269/ajtmh.19-0288.
    1. Longtin J., Dion R., Simard M., Betala Belinga J.F., Longtin Y., Lefebvre B., Labbé A.C., Deceuninck G. Possible impacts of wide-scale vaccination against serogroup B Neisseria meningitidis on gonorrhoea incidence rates in one region of Quebec, Canada; Proceedings of the Advancing Science, Improving Care; San Diego, CA, USA. 4–8 October 2017.
    1. Whittles L.K., White P.J., Didelot X. Assessment of the Potential of Vaccination to Combat Antibiotic Resistance in Gonorrhea: A Modeling Analysis to Determine Preferred Product Characteristics. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2020;71:1912–1919. doi: 10.1093/cid/ciz1241.
    1. The Australian Government Department of Health Invasive Meningococcal Disease National Surviellance Report. 1 January to 30 June 2019. [(accessed on 15 June 2021)]; Available online: .
    1. Australian Bureau of Statistics Estimates of Aboriginal and Torres Strait Islander Australians June 2016 (Table 3) [(accessed on 15 June 2021)]; Available online: .
    1. Thors V., Morales-Aza B., Pidwill G., Vipond I., Muir P., Finn A. Population density profiles of nasopharyngeal carriage of 5 bacterial species in pre-school children measured using quantitative PCR offer potential insights into the dynamics of transmission. Hum. Vaccines Immunother. 2016;12:375–382. doi: 10.1080/21645515.2015.1090069.
    1. McMillan M., Walters L., Mark T., Lawrence A., Leong L.E.X., Sullivan T., Rogers G.B., Andrews R.M., Marshall H.S. B Part of It study: A longitudinal study to assess carriage of Neisseria meningitidis in first year university students in South Australia. Hum. Vaccines Immunother. 2019;15:987–994. doi: 10.1080/21645515.2018.1551672.
    1. Buckley C., Forde B.M., Trembizki E., Lahra M.M., Beatson S.A., Whiley D.M. Use of whole genome sequencing to investigate an increase in Neisseria gonorrhoeae infection among women in urban areas of Australia. Sci. Rep. 2018;8:1503. doi: 10.1038/s41598-018-20015-x.
    1. Lawlor D.A., Tilling K., Davey Smith G. Triangulation in aetiological epidemiology. Int. J. Epidemiol. 2016;45:1866–1886. doi: 10.1093/ije/dyw314.
    1. Grimes D.A., Schulz K.F. Compared to what? Finding controls for case-control studies. Lancet. 2005;365:1429–1433. doi: 10.1016/S0140-6736(05)66379-9.
    1. Verani J.R., Baqui A.H., Broome C.V., Cherian T., Cohen C., Farrar J.L., Feikin D.R., Groome M.J., Hajjeh R.A., Johnson H.L., et al. Case-control vaccine effectiveness studies: Preparation, design, and enrollment of cases and controls. Vaccine. 2017;35:3295–3302. doi: 10.1016/j.vaccine.2017.04.037.
    1. Quinn H.E., Gidding H.F., Marshall H.S., Booy R., Elliott E.J., Richmond P., Crawford N., McIntyre P.B., Macartney K.K. Varicella vaccine effectiveness over 10 years in Australia; moderate protection from 1-dose program. J. Infect. 2019;78:220–225. doi: 10.1016/j.jinf.2018.11.009.
    1. Farrington C.P. Estimation of vaccine effectiveness using the screening method. Int. J. Epidemiol. 1993;22:742–746. doi: 10.1093/ije/22.4.742.
    1. Marshall H.S., Andraweera P.H., Wang B., McMillan M., Koehler A.P., Lally N., Almond S., Denehy E., A’Houre M., Giles L.C., et al. Evaluating the effectiveness of the 4CMenB vaccine against invasive meningococcal disease and gonorrhoea in an infant, child and adolescent program: Protocol. Hum. Vaccines Immunother. 2021;17:1450–1454. doi: 10.1080/21645515.2020.1827614.
    1. Wang B., Santoreneos R., Afzali H., Giles L., Marshall H. Costs of invasive meningococcal disease: A global systematic review. PharmacoEconomics. 2018;36:1201–1222. doi: 10.1007/s40273-018-0679-5.
    1. Drummond M.F., Sculpher M.J., Claxton K., Stoddart G.L., Torrance G.W. Methods for the Economic Evaluation of Health Care Programmes. Oxford University Press; Oxford, UK: 2015. pp. 245–250.
    1. Pharmaceutical Benefits Advisory Committee Guidelines for Preparing Submissions to the Pharmaceutical Benefits Advisory Committee (version 5.0) [(accessed on 15 June 2021)]; Available online:
    1. van den Hout W.B. The value of productivity: Human-capital versus friction-cost method. Ann. Rheum. Dis. 2010;69((Suppl. 1)):i89–i91. doi: 10.1136/ard.2009.117150.
    1. Koopmanschap M.A., Rutten F.F., van Ineveld B.M., van Roijen L. The friction cost method for measuring indirect costs of disease. J. Health Econ. 1995;14:171–189. doi: 10.1016/0167-6296(94)00044-5.
    1. Kigozi J., Jowett S., Lewis M., Barton P., Coast J. Estimating productivity costs using the friction cost approach in practice: A systematic review. Eur. J. Health Econ. 2016;17:31–44. doi: 10.1007/s10198-014-0652-y.
    1. Tinsley C.R., Nassif X. Analysis of the genetic differences between Neisseria meningitidis and Neisseria gonorrhoeae: Two closely related bacteria expressing two different pathogenicities. Proc. Natl. Acad. Sci. USA. 1996;93:11109–11114. doi: 10.1073/pnas.93.20.11109.
    1. Semchenko E., Tan A., Borrow R., Seib K. The serogroup B meningococcal vaccine Bexsero elicits antibodies to Neisseria gonorrhoeae; Proceedings of the 21st International Pathogenic Neisseria Conference; Asilomar, CA, USA. 4–8 October 2018.
    1. Ruiz García Y., Sohn W.Y., Seib K.L., Taha M.K., Vázquez J.A., de Lemos A.P.S., Vadivelu K., Pizza M., Rappuoli R., Bekkat-Berkani R. Looking beyond meningococcal B with the 4CMenB vaccine: The Neisseria effect. NPJ Vaccines. 2021;6:130. doi: 10.1038/s41541-021-00388-3.
    1. Wang B., Giles L., Andraweera P., McMillan M., Almond S., Beazley R., Mitchell J., Lally N., A’Houre M., Denehy E., et al. Evaluating the effectiveness of the 4CMenB vaccine against invasive meningococcal B disease and gonorrhoea in an infant, child and adolescent program. Lancet Infect. Dis. 2022. in press .

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner