Modelling the impact of 4CMenB and MenACWY meningococcal combined vaccination strategies including potential 4CMenB cross-protection: An application to England

Beck, Ekkehard; Klint, Johan; Garcia, Stephanie; Abbing, Victoria; Abitbol, Véronique; Åkerborg, Örjan; Argante, Lorenzo; Bekkat-Berkani, Rafik; Hogea, Cosmina; Neine, M.; Vadivelu, Kumaran; Whelan, Jane; Meszaros, Kinga

doi:10.1016/j.vaccine.2020.08.007

Cited by 16 publications

(15 citation statements)

References 29 publications

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“…This would involve direct protection of infants, the age group with the highest IMD incidence, and older age groups by the administration of a catch-up or additional vaccination in adolescents. A modeling study assuming dynamic transmission, with separate variables for meningococcal carriage and IMD for MenB, MenACWY and 'Other' mostly nonpathogenic serogroups showed that combined strategies with infant/adolescent 4CMenB and adolescent or toddler/adolescent MenACWY vaccination would result in the largest decrease in IMD cases [68].…”

Section: Discussionmentioning

confidence: 99%

Evolving strategies for meningococcal vaccination in Europe: Overview and key determinants for current and future considerations

Martinón-Torres

Taha

Knuf³

et al. 2021

Pathogens and Global Health

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Invasive meningococcal disease (IMD) is a life-threatening, unpredictable condition. Vaccines are available against 5 of the 6 meningococcal serogroups (Men) accounting for nearly all IMD cases worldwide; conjugate monovalent MenC, quadrivalent MenACWY, and protein-based MenB vaccines are commonly used. We provide a comprehensive overview of the evolution of meningococcal vaccination strategies employed in national immunization programmes (NIPs) and their impact on IMD incidence in Europe. A more in-depth description is given for several countries: the United Kingdom (UK), the Netherlands, Greece, Italy, and Ireland. We searched European health authorities' websites and PubMed. Various vaccines and immunization schedules are used in 21 NIPs. Most countries implement MenC vaccination in infants, MenACWY in adolescents, and a growing number, MenB in infants. Only Malta has introduced MenACWY vaccination in infants, and several countries reimburse immunization of toddlers. The UK, Italy, Ireland, Malta, Andorra, and San Marino recommend MenB vaccination in infants and MenACWY vaccination in adolescents, targeting the most prevalent serogroups in the most impacted age groups. Main factors determining new vaccination strategies are fluctuating IMD epidemiology, ease of vaccine implementation, ability to induce herd protection, favorable benefit-risk balance, and acceptable cost-effectiveness. Since 1999, when the UK introduced MenC vaccination, the reduction in IMD incidence has been gradually enhanced as other countries adopted routine meningococcal vaccinations. Meningococcal vaccination strategies in each country are continually adapted to regional epidemiology and national healthcare priorities. Future strategies may include broader coverage vaccines when available (e.g., MenABCWY, MenACWY), depending on prevailing epidemiology.

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Section: Discussionmentioning

confidence: 99%

Evolving strategies for meningococcal vaccination in Europe: Overview and key determinants for current and future considerations

Martinón-Torres

Taha

Knuf³

et al. 2021

Pathogens and Global Health

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“…Precise and accurate estimates of 4CMenB effectiveness are essential to appropriately inform costeffectiveness analyses that support public health decision making. 21,22 Provided the availability of strain typing data 23,24 on the same disease cases used for this re-assessment, the higher precision of our approach will allow to further stratify data and to assess 4CMenB effectiveness against different strain types. Such estimates, combined with strain typing data from other countries, 25 would allow even more robust predictions of 4CMenB effects in different geographies, improving costeffectiveness evaluations.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study in Australia failed to detect any effect on carriage, that could lead to indirect effects of vaccination, particularly in 10 adolescents. 28,29 The approach employed here, if expanded with a dynamic model of meningococcal asymptomatic transmission and invasive disease 20,22,30 as done previously for evaluating a serogroup C immunization program, 20 could detect indirect effects using IMD surveillance data, without or before running further meningococcal carriage studies.…”

Section: Discussionmentioning

confidence: 99%

A Re-assessment of 4CMenB Vaccine Effectiveness Against Serogroup B Invasive Meningococcal Disease in England based on an Incidence Model

Argante¹,

Abbing‐Karahagopian²,

Vadivelu³

et al. 2021

Preprint

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Background: The four-component serogroup B meningococcal 4CMenB vaccine (Bexsero, GSK) has been routinely given to all infants in the United Kingdom at 2, 4 and 12 months of age since September 2015. After three years, Public Health England (PHE) reported a 75% [95% confidence interval: 64%; 81%] reduction in the incidence of serogroup B invasive meningococcal disease (IMD) in age groups eligible to be fully vaccinated. In contrast, vaccine effectiveness (VE) evaluated in the same immunization program applying the screening method was not statistically significant. We re-analyzed the data using an incidence model and obtained more precise VE estimates. Methods: Aggregate data stratified by age, year and doses received were provided by PHE: serogroup B IMD case counts for the entire population of England (years 2011-2018) and 4CMenB vaccine uptake in infants. We combined uptake with national population estimates to obtain counts of vaccinated and unvaccinated person-time by age and time. We re-estimated VE comparing incidence rates in vaccinated and non-vaccinated using a Bayesian Poisson model for case counts with person-time data as an offset. The model was adjusted for age, time and number of doses received. Results: The incidence model showed that cases decreased until 2013-2014, followed by an increasing trend that continued in the non-vaccinated population during the immunization program. VE in fully vaccinated (three doses) was 80.1% [95% Bayesian credible interval (BCI): 70.3%; 86.7%]. After a single dose, VE was 33.5% [12.4%; 49.7%]95%BCI, and, after two doses, 78.7% [71.5%; 84.5%]95%BCI. We estimated that vaccination has averted 312 cases [252; 368]95%BCI between 2015 and 2018. VE was in line with the previously reported incidence reduction. Conclusions: Our estimates of VE had higher precision than previous estimates based on the screening method, that were not statistically significant. When disease incidence is low and vaccine uptake is high, the screening method applied to cases exclusively from the population eligible to vaccination may not be enough precise and produce misleading point-estimates. Precise and accurate VE estimates are fundamental for informing public health decision making. VE assessment can be enhanced using models that leverage data on subjects not eligible for vaccination.

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“…A dynamic transmission-based cost-effectiveness model was developed consisting of a dynamic transmission model (DTM) to simulate the transmission of meningococcal carriage and occurrence of IMD cases 47 and an economic decision tree model attributing costs and health outcomes to the simulated IMD cases (see Appendix Figure 1 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2020.09.004).…”

Section: Model Description and Structurementioning

confidence: 99%

“…The new structure (see Appendix Figure 2 in Supplemental Materials found at https:// doi.org/10.1016/j.jval.2020.09.004) also allows for a more detailed evaluation of cross-protection of 4CMenB against non-MenB IMD serogroups C, W, and Y in addition to its potential impact on carriage. 47 The structure of the economic decision tree model represents the disease pathway (i.e., acute phase of disease, death in acute phase due to IMD, occurrence of long-term sequelae for survivors, and premature IMD-related death for survivors due to long-term sequelae) with probabilities of events and associated costs and utilities (see Appendix Figure 3 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2020.09.004). The 5 disease burden categories were reflected in the model structure to allow for a comprehensive analysis: a decision-tree structure for sequelae allowed for the occurrence of multiple types of sequelae independently of each other; multipliers for adjusting QALY losses in patients in the acute phase, death and survival to account for health spillover effects; considering broad-ranging costs related to the acute phase (e.g.…”

Section: Model Description and Structurementioning

confidence: 99%

Cost-Effectiveness of 4CMenB Infant Vaccination in England: A Comprehensive Valuation Considering the Broad Impact of Serogroup B Invasive Meningococcal Disease

Beck

Klint²,

Neine

et al. 2021

Value in Health

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This cost-effectiveness analysis (CEA) of 4CMenB infant vaccination in England comprehensively considers the broad burden of serogroup B invasive meningococcal disease (MenB IMD), which has not been considered, or was only partially considered in previous CEAs.Methods: A review of previous MenB vaccination CEAs was conducted to identify aspects considered in the evaluation of costs and health outcomes of the disease burden of MenB IMD. To inform the model structure and comprehensive analysis, the aspects were grouped into 5 categories. A stepwise analysis was conducted to analyze the impact of each category, and the more comprehensive consideration of disease burden, on the incremental cost-effectiveness ratio (ICER).Results: MenB IMD incidence decreased by 46.0% in infants and children 0-4 years old within 5 years after introduction of the program. Stepwise inclusion of the 5 disease burden categories to a conventional narrow CEA setting reduced the ICER from £360 595 to £18 645-that is, considering the impact of all 5 categories, 4CMenB infant vaccination is cost-effective at a threshold of £20 000 per QALY gained.Conclusions: When considering comprehensively the MenB IMD burden, 4CMenB infant vaccination can be cost-effective, a finding contrary to previous CEAs. This analysis allows policy decision-makers globally to infer the impact of current disease burden considerations on the cost-effectiveness and the comprehensive assessment necessary for MenB IMD. Although this comprehensive CEA can help inform decision making today, it may be limited in capturing the full disease burden and complex interactions of health and economics of MenB IMD.

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Modelling the impact of 4CMenB and MenACWY meningococcal combined vaccination strategies including potential 4CMenB cross-protection: An application to England

Cited by 16 publications

References 29 publications

Evolving strategies for meningococcal vaccination in Europe: Overview and key determinants for current and future considerations

Evolving strategies for meningococcal vaccination in Europe: Overview and key determinants for current and future considerations

A Re-assessment of 4CMenB Vaccine Effectiveness Against Serogroup B Invasive Meningococcal Disease in England based on an Incidence Model

Cost-Effectiveness of 4CMenB Infant Vaccination in England: A Comprehensive Valuation Considering the Broad Impact of Serogroup B Invasive Meningococcal Disease

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