Global incidence of serogroup B invasive meningococcal disease: a systematic review

Summary

Use of recently licensed vaccines against Neisseria meningitidis serogroup B (NmB) will depend partly on disease burden estimates. We systematically reviewed NmB incidence and mortality worldwide between January, 2000, and March, 2015, incorporating data from 37 articles and 12 websites. Most countries had a yearly invasive NmB incidence of less than 2 per 100 000 people. Within these relatively low incidence rates (compared with common causes of invasive bacterial diseases), substantial variation was detected between countries, with a notably higher incidence in Australia, Europe, North America, and South America. China and India had reports only of sporadic cases, and except for South Africa, sub-Saharan Africa showed a near absence of disease. In countries with consistently collected data, NmB incidence has tended to decrease, even as the proportion of invasive meningococcal disease cases caused by serogroup B has increased. With few exceptions, case-fatality ratios were fairly consistent, ranging between 3% and 10%. In high-income countries, incidence rates of NmB were relatively low compared with other vaccine-preventable diseases and might be decreasing. High case-fatality ratios, substantial disease-related morbidity, and the threat of outbreaks could nevertheless make NmB an attractive target for preventive and reactive immunisation programmes. The low availability of data from low-income and middle-income countries suggests the need for improved surveillance before vaccination strategies are designed.

Introduction

Six of 12 Neisseria meningitidis serogroups described (A, B, C, W, X, and Y) cause nearly all cases of invasive meningococcal disease.¹ Licensed vaccines have existed for many years for serogroups A, C, Y, and W, and since 1999 as protein–polysaccharide conjugate vaccines. The first meningococcal conjugate vaccine to be introduced was targeted to the serogroup C in the UK in 1999.² After this, quadrivalent (serogroups A, C, Y, and W) and monovalent (serogroup A) conjugate vaccines were licensed in 2000 and 2010, respectively. Monovalent serogroup A conjugate vaccines were licensed specifically for use in the African meningitis belt.²

Although N meningitidis belonging to serogroup B (NmB) is an important contributor to invasive meningococcal disease, the development of protein–polysaccharide conjugate vaccines against NmB has been impeded by low immunogenicity and potential crossreactivity between the serogroup B polysaccharide capsule and human tissue antigens.³ To overcome this difficulty, vaccines were developed that used non-capsular antigenic components of serogroup B, such as outer membrane vesicles (OMV).⁴ Vaccines based on OMV were used with success to control outbreaks caused by a specific strain. However, they did not offer broad protection against heterologous strains with different porin A (PorA) subtypes, particularly in young children and infants, which restricts the ability of these vaccines to protect against local clonal outbreaks. In January, 2013, Novartis received European Commission approval and subsequently licensure in Canada and Australia, for a multicomponent meningococcal B vaccine (4CMenB) marketed under the brand name Bexsero that contains four main immunogenic components: factor H binding protein, neisserial adhesion A, and neisserial heparin binding protein combined with the New Zealand NZ98/254 strain OMV (NZ OMV) expressing PorA serosubtype P1.4.5, 6

In the USA, two NmB outbreaks took place in 2013 on the campuses of Princeton University (Princeton, NJ, USA) and the University of California, Santa Barbara (Santa Barbara, CA, USA).⁷ Because no NmB vaccine was licensed in the USA at the time, the USA Food and Drug Administration (FDA) provided an Investigational New Drug designation that allowed for the use of nearly 30 000 doses of 4CMenB vaccine.⁸ The FDA subsequently provided full licensure in 2015. In October, 2014, the FDA approved another protein-based serogroup B vaccine—marketed by Pfizer under the brand name Trumenba—containing subfamily A and B factor H binding protein variants.9, 10 Starting in February, 2015, Trumenba was used to control campus outbreaks at Providence College (Providence, RI, USA) and the University of Oregon (Eugene, OR, USA).11, 12

A key question is how and where to use these new vaccines. The two major options are outbreak control and routine use in national immunisation programme schedules. The exact answer will depend partly on the incidence of disease, mortality, and sequelae; age and geographical distribution; coverage of the isolates by these vaccines; ability of the vaccine to provide cross-protection against other serogroups; and incompletely understood issues such as immunity duration and vaccine efficacy against carriage acquisition (and the consequent ability to provide indirect protection). A systematic review in 2010 described the distribution and heterogeneity of hypervirulent serogroup B meningococci causing invasive meningococcal disease.¹³ Although serogroup B dominance in specific countries and the clonal complex distribution of NmB were described in that report, disease incidence was not quantified.¹³ Our Review aims to describe the worldwide NmB disease incidence and case-fatality ratio (CFR).