Cost-Effectiveness of Alternative Uses of Polyvalent
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Original Article Medical Decision Making 2019, Vol. 39(5) 553–567 Ó The Author(s) 2019 Cost-Effectiveness of Alternative Uses Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/0272989X19859899 of Polyvalent Meningococcal Vaccines journals.sagepub.com/home/mdm in Niger: An Agent-Based Transmission Modeling Study S. M. Niaz Arifin, Christoph Zimmer, Caroline Trotter, Anaı¨s Colombini, Fati Sidikou, F. Marc LaForce, Ted Cohen, and Reza Yaesoubi Background. Despite the introduction of an effective serogroup A conjugate vaccine (MenAfriVacä), sporadic epi- demics of other Neisseria meningitidis serogroups remain a concern in Africa. Polyvalent meningococcal conjugate (PMC) vaccines may offer alternatives to current strategies that rely on routine infant vaccination with MenAfriVac plus, in the event of an epidemic, district-specific reactive campaigns using polyvalent meningococcal polysaccharide (PMP) vaccines. Methods. We developed an agent-based transmission model of N. meningitidis in Niger to compare the health effects and costs of current vaccination practice and 3 alternatives. Each alternative replaces MenAfriVac in the infant vaccination series with PMC and either replaces PMP with PMC for reactive campaigns or implements a one-time catch up campaign with PMC for children and young adults. Results. Over a 28-year period, replacement of MenAfriVac with PMC in the infant immunization series and of PMP in reactive campaigns would avert 63% of expected cases (95% prediction interval 49%–75%) if elimination of serogroup A is not followed by serogroup replacement. At a PMC price of $4/dose, this would cost $1412 ($81–$3510) per disability-adjusted life-year (DALY) averted. If serogroup replacement occurs, the cost-effectiveness of this strategy improves to $662 (cost-saving, $2473) per DALY averted. Sensitivity analyses accounting for incomplete laboratory confirmation suggest that a catch-up PMC campaign would also meet standard cost-effectiveness thresholds. Limitations. The assumption that polyvalent vaccines offer similar protection against all serogroups is simplifying. Conclusions. The use of PMC vaccines to replace MenAfriVac in routine infant immunization and in district-specific reactive campaigns would have important health benefits and is likely to be cost-effective in Niger. An additional PMC catch-up campaign would also be cost- effective if we account for incomplete laboratory reporting. Keywords economic evaluation, meningitis, meningococcal, simulation, vaccine Date received: June 29, 2018; accepted: June 4, 2019 The meningitis belt, a region in sub-Saharan Africa with epidemics in this region has relied on reactive vaccination an estimated population of 430 million people, is prone campaigns using polysaccharide vaccines in districts to sporadically occurring meningitis epidemics.1–3 These where the weekly meningitis incidence passes a critical epidemics place a heavy burden on national and local resources,4 resulting in substantial deaths and long-term 5 Corresponding Author disabling sequelae. The largest of these epidemics caused Reza Yaesoubi, Department of Health Policy and Management, Yale an estimated 250,000 cases with more than 25,000 deaths School of Public Health, 60 College Street, New Haven, CT 06510, 6,7 in 1996. For the past 30 years, control of meningitis USA ([email protected]). 554 Medical Decision Making 39(5) incidence threshold of 10/100,000 population.4,8,9 While with PMC vaccine and the addition of this vaccine to this strategy, when deployed early in an epidemic, could EPI (as a replacement for MenAfriVac) will likely be save lives, it has not reduced the frequency and magnitude cost-effective compared with the current World Health of epidemics because 1) polysaccharide vaccines induce Organization (WHO) strategy of reactive vaccination only short-term protection (especially in children)4,10,11 using PMP vaccines.33 Yet the evidence to inform the and 2) the successful implementation of reactive vaccina- best use of these novel polyvalent meningococcal vac- tion campaigns is hampered by significant delays between cines for other countries of the meningitis belt is lacking. outbreak identification and vaccination responses.12,13 Despite similarities in certain characteristics of meningo- The introduction of a Neisseria meningitidis serogroup A coccal epidemics across countries of meningitis belt,10,29 conjugate meningococcal vaccine (PsA-TT, MenAfriVacä) the difference in population sizes and structures, age dis- in the African meningitis belt in 2010 to 2011 has reduced tribution of meningococcal cases, and carriage prevalence meningitis A carriage and cases to an exceptionally low may affect the performance of vaccination strategies level.3,14–17 Despite the early success of MenAfriVac from one setting to another.17 in the prevention of meningitis A epidemics, other In this study, we describe a district-level, agent-based non-A serogroups continue to cause epidemics of menin- model (ABM) of meningococcal transmission in Niger. gitis.9,18–21 Examples include the N. meningitidis ser- While Niger has a similar total population size as ogroup W epidemic in Burkina Faso (2012)22;theN. Burkina Faso, the population density of Niger is consid- meningitidis serogroup X epidemics in Burkina Faso erably lower (with the largest concentrations of individu- (2010), Niger (2006), and Togo (2009)23,24; a recent severe als in southwestern districts), and Niger has experienced epidemic by a novel strain of N. meningitidis serogroup C less severe meningococcal epidemics since 2002. As vacci- (NmC) in Niger (2015)25,26; and the largest ever recorded nation programs may offer relatively smaller health gains epidemic of NmC in Nigeria (2017) with more than in settings with less severe meningococcal epidemics, the 14,000 suspected cases.26,27 evaluation of PMC vaccination strategies in Niger, and To combat the remaining threat from non-A meningo- comparison with previously reported results from coccal serogroups, polyvalent vaccines that target C, Y, W, Burkina Faso, will shed light on how the local epidemiol- and X serogroups (in addition to A) are being considered ogy of disease affects the projected health impact and for use in Africa.12,21,25,28,29 In contrast to the available costs associated with alternative vaccine strategies. polyvalent meningococcal polysaccharide (PMP) vaccines, polyvalent meningococcal conjugate (PMC) vaccines are Methods immunogenic in young children and induce longer-term (10–15 year) protection and, hence, can also be used in reac- An Agent-Based Model of Meningococcal tive and/or mass preventive vaccination campaigns2,30–32 as Transmission in Niger well as in the Expanded Program on Immunization (EPI). Our ABM is a stochastic, and spatially explicit model34–36 A recent cost-effectiveness analysis in Burkina Faso to describe the meningococcal transmission across 44 dis- suggests that a vaccination strategy that involves a catch- tricts of Niger (Figure 1 and Supplementary Figure S2). up nationwide vaccination campaign in young adults Meningitis epidemics in Niger (along with other countries of meningitis belt) occur sporadically and, when they do Department of Epidemiology of Microbial Diseases, Yale School of occur, are of greatly varying severity (Figure 2).21,37,38 Public Health, New Haven, CT, USA (SMNA, CZ, TC); Department This suggests that a stochastic model can best simulate of Veterinary Medicine, University of Cambridge, Cambridge, UK (CT); independent consultant, Madagascar (AC); Centre de Recherche the types of chance events that ultimately lead epidemic Medicale et Sanitaire (CERMES), Niamey, NE, Niger (FS); Serum takeoff or fade out after the appearance of meningitis Institute of India, Pune (FML); and Department of Health Policy and cases within a district. Management, Yale School of Public Health, New Haven, CT, USA Capturing meningococcal epidemics at the district (RY). The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. level is necessary to model reactive vaccination campaigns Financial support for this study was provided by a contract with that are triggered when districts exceed the WHO epi- 4 PATH (https://www.path.org/) and by awards 1K01AI119603 from the demic threshold of 10 per 100,000 population in a week. National Institute of Allergy and Infectious Diseases (https:// We employed a gravity model to approximate the age- www.niaid.nih.gov/), U54GM088558 from the National Institute of specific intensity of contacts among individuals within General Medical Sciences (www.nigms.nih.gov), and a scholarship from the German Research Foundation (DFG; http://www.dfg.de). The and between districts (see the Supplementary Appendix). funding agreement ensured the authors’ independence in designing the Our ABM is based on existing mathematical models study, interpreting the data, writing, and publishing the report. developed for different countries of the meningitis Arifin et al. 555 In our ABM, individuals are assumed to be in 1 of 4 health states at any given time: susceptible, carrier, meningitis, and immune (Figure 1). Susceptible individu- als are at dynamic, age-specific risk of infection with N. meningitidis that is proportional to the prevalence of invasive meningitis and carriage. Infected individuals move to an asymptomatic but infectious state (‘‘carrier’’), where they may develop invasive meningitis disease (‘‘meningitis’’) or lose their carriage