Epidemiology and Prevention of Meningococcal Disease

A Critical Appraisal of Vaccine Policies

Marco AP Sáfadi; E David G McIntosh

Disclosures

Expert Rev Vaccines. 2011;10(12):1717-1730. 

In This Article

Abstract and Introduction

Abstract

Meningococcal disease is characterized by a marked variation in incidence and serogroup distribution by region and over time. In several European countries, Canada and Australia, immunization programs, including universal vaccination of infants or toddlers with catch-up campaigns in children and adolescents, aimed at controlling disease caused by meningococcal serogroup C have been successful in reducing disease incidence through direct and indirect protection. More recently, meningococcal conjugate vaccines targeting disease caused by serogroups A, C, W-135 and Y have been licensed and are being used in adolescent programs in the USA and Canada while a mass immunization campaign against serogroup A disease has been implemented in Africa. Positive results from clinical trials using vaccines against serogroup B disease in various age groups suggest the possibility of providing broader protection against serogroup B disease than is provided by the currently used outer membrane vesicle vaccines. The purpose of our review of meningococcal epidemiology and assessment of existing policies is to set the stage for future policy decisions. Vaccination policies to prevent meningococcal disease in different regions of the world should be based on quality information from enhanced surveillance systems.

Introduction

Neisseria meningitidis has become a leading cause of bacterial meningitis and sepsis in infants, children, adolescents and young adults. This has become more noticeable after the introduction of Haemophilus influenzae type b and pneumococcal conjugate routine vaccination in many countries, which has resulted in significant reductions in those infections. Globally, up to 500,000 cases of invasive meningococcal disease occur annually, resulting in an estimated 50,000 deaths.[1] Invasive meningococcal disease is often sudden in onset, rapidly progressive and potentially fatal in outcome.[2] The increasing use of PCR for diagnosis has increased case detection by up to 30%.[3] Survivors are liable to have long-term consequences such as cognitive impairment, deafness and the need for amputation.[4]

Serogroups A, B, C, W-135, Y and X are responsible for virtually all cases of invasive meningococcal disease. Meningococci have been shown to have the potential capacity to exchange the genetic material responsible for capsular production and to switch capsular phenotype. Antigenic variations of capsular and surface proteins resulting from these genetic mechanisms enhance the ability of meningococci to evade immune responses. This partly explains the organism's capability of causing outbreaks of meningococcal disease. The epidemiology of meningococcal disease varies markedly by region. In Europe and in the Americas, the disease is mostly endemic, with average incidence rates ranging from less than 0.5 to 8.9 cases per 100,000 total population.[5,101,102]

After the introduction of meningococcal C conjugate vaccines into the routine immunization programs of several countries in Europe, serogroup C disease has declined dramatically, an occurance unlikely to be due to natural variation – leaving these countries with a predominance of serogroup B disease.[6] In the USA, serogroups B, C and Y each cause approximately a third of cases.[7] Serogroups B and C are responsible for the majority of cases in Latin America, although there are increasing reports of serogroup W-135 (including in Florida, USA, which has a large Latin American population) and serogroup Y disease.[5,8]

The 'meningitis belt' in Africa reports the highest incidence rates of disease in the world and is primarily affected by serogroup A,[9,10] although other serogroups such as W-135 in Burkina Faso[11,12] and X in western Kenya,[13,14] Burkina Faso, Togo[15] and Niger[16] are emerging in this region. By contrast to disease in the developed world, which is commonly sporadic, there is seasonality of disease in this region with recurrent epidemics.[9]

Surveillance data on meningococcal disease epidemiology in Asia and the Middle East are scant and limited, with low incidence rates of disease reported and infrequent outbreaks or epidemics.[17] For example, one survey performed in the city of Hefei in China reported an annual incidence of between 1.19 and 2.86 per 100,000 total population between 2003 and 2007.[18] There was an upwards shift in age distribution over this period towards those aged 12–17 years, with an incidence of 6.57 per 100,000 inhabitants. All isolates that were serogrouped were found to be serogroup C. There are Chinese reports of outbreak control using plain polysaccharide vaccine. Serogroup A is common in many parts of Asia, but cases of serogroups B and C disease are increasingly reported in the region.[17] A serogroup A outbreak occurred in and around New Delhi in 2005–2006, during which there was effective use of not only isolation, antibiotic chemotherapy and chemoprophylaxis, but also of immunization.[19,20] Outbreaks of meningococcal disease caused by the W-135 serogroup have been reported among nomadic Muslims in Saudi Arabia. Vaccination using the serogroup A vaccine has been successful in decreasing infection associated with the Hajj.[21]

The introduction of meningococcal C conjugate vaccines into national immunization programs in several European countries, Canada and Australia resulted in a dramatic and immediate reduction in the incidence of meningococcal disease caused by serogroup C. Three monovalent serogroup C conjugate vaccines are currently licensed. Two vaccines are based on oligosaccharides derived from serogroup C capsular polysaccharide conjugated to the nontoxic CRM197 mutant diphtheria toxin (Menjugate® by Novartis Vaccines and Diagnostics, Siena, Italy, and Meningitec® by Wyeth [now Pfizer] Vaccines, NY, USA). The other vaccine is based on a de-O-acetylated oligosaccharide conjugated to tetanus toxoid (Neisvac-C® by Baxter Vaccines, Beltsville, MD, USA). There is no evidence to favor one vaccine over another in the routine clinical setting. A striking feature of these meningococcal C conjugate vaccination programs, which included catch-up of children and adolescents using different immunization schedules, has been the additional decrease in disease incidence in unvaccinated individuals as a result of herd protection.[6] Immunization of adolescents and young adults (the age groups that have the highest rates of colonization) in these catch-up campaigns reduced the carriage rates of meningococcal serogroup C and may have prevented transmission of the organism and acquisition by other individuals.

One of the key lessons learned with the meningococcal serogroup C vaccination programs was the importance of herd protection to their success. However, the duration of individual immunity and of herd protection is as yet unknown, and surveillance of disease is crucial to address all of these issues. There is a focus on the pros and cons of infant versus single-dose toddler routine schedules after mass immunization programs.[22] After a successful mass immunization campaign, the institution of a single-dose toddler schedule has merits and 'clears' the infant schedule in readiness for new vaccines. However, in countries with a high burden of disease in infants, this cost-effective approach has yet to prove its feasibility. In the UK there is discussion about removing one of the infant doses. Recent data showing waning immunity after meningococcal C conjugate vaccination suggest the need for a booster dose during adolescence to maintain sustained population immunity against the disease.[23–25]

In health systems where meningococcal C conjugate vaccines have been extensively deployed (Table 1),[26–35,103] there is now increasing interest in the control of other serogroups, such as, serogroups A, B, W-135 and Y. The introduction of multivalent vaccines such as the conjugate vaccine against serogroups A, C, W-135 and Y has the potential to reduce further the incidence of infection.[36–38] Most countries where meningococcal conjugate vaccines are licensed have a policy for vaccinating at-risk individuals.

The global incidence of serogroup B infection is estimated to be between 20,000 and 80,000 cases per year, with a 10% fatality rate.[104] There is a need for a vaccine against serogroup B disease, the licensing and deployment of which has the potential to address this elusive serogroup.[8]

In countries with meningococcal vaccination policies, establishment of enhanced surveillance systems is crucial in order to monitor the impact of meningococcal vaccination programs on the epidemiology of meningococcal disease. Given the potential impact of meningococcal disease on individuals and communities, a critical appraisal of the different policies used by various countries is insightful, and such an appraisal is the purpose of this article.

In order to do this, our starting point was to describe the policies used in countries with universal indications for meningococcal serogroup C conjugate and quadrivalent vaccines, to move to policies for outbreak control and travel, and then to give a short country/regional overview. It is sometimes necessary to deduce policy decisions from how meningococcal vaccines are used in different situations. Underlying this approach was a description of epidemiology and changing epidemiology.

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