Invasive Meningococcal Disease Outbreak Management

Invasive meningococcal disease (IMD) is a major global health challenge with high rates of morbidity and mortality. Disproportionately, the highest burden of disease occurs in children. Although vaccines have been effective in preventing meningococcal disease, occurrence of outbreaks continue. Lack of access to vaccines, socially disadvantaged populations and behavioral and environmental determinants may increase the risk of nasopharyngeal colonization and disease transmission in this vulnerable pediatric population. This review examines the response and management of invasive meningococcal disease outbreaks, drawing on the literature and available guidelines. MENINGOCOCCAL DISEASE EPIDEMIOLOGY IMD caused by the bacterium Neisseria meningitidis (N. meningitidis), a gram-negative diplococcus, colonizes the upper respiratory tract. Pharyngeal carriage of N. meningitidis has an overall population prevalence of around 10%1 and presents asymptomatically. The bacteria can spread to the bloodstream and sterile sites, causing invasive disease and manifest as meningitis or septicemia. Although an uncommon disease, sequelae in children can be severe, leading to lifelong disability involving hearing loss, loss of limbs and neurological impairment.2 Compared with other age groups, IMD incidence is highest in infants >1 year of age and children under 4 years, followed by a second peak in adolescents aged 15–19 years. Asymptomatic N. meningitidis carriage is considered higher in adolescents, with carriage prevalence of up to 24% in adolescents compared with 4.5% in infants.3 Although the incidence of IMD is higher in infants, the case-fatality rate is greatest in adolescents.4 Adolescents are important transmitters of the disease, given higher carriage rates and engagement in social and behavioral risk factors, including smoking/vaping, attending pubs/clubs and mouth kissing.5 Lower education and family income levels have been linked to higher IMD incidence among adolescents in the United States.6 Immature immune system, household overcrowding, close contact with a carrier/case and exposure to cigarette smoke increase the risk of infection for infants and young children.2 Based on the immunochemistry and genetic composition of the N. meningitidis capsular polysaccharides, 12 serogroups have been identified, of which 6—A, B, C, W, X and Y—are associated with causing invasive disease.7 IMD incidence varies across age, geographical location and by serogroup. In high-resource countries such as the United Kingdom and Australia, meningococcal serogroup B accounts for the majority of IMD cases, particularly among infants, younger children and adolescents. The spatial distribution and potential for these serotypes to cause outbreaks vary, given IMD epidemiology is dynamic with evolving hypervirulent strains.8 MENINGOCOCCAL DISEASE PREVENTION AND CONTROL Vaccination Vaccination is the most effective method in preventing IMD. Monovalent vaccines protect against serogroups A and C; quadrivalent meningococcal conjugate vaccines against serogroups A, C, W and Y (MenACWY); meningococcal B (MenB) vaccine for serogroup B protection.9 Availability of meningococcal vaccination programs for children and adolescents varies by country and is influenced by local epidemiology and serogroup prevalence. Not all countries recommend MenACWY and MenB to both infants/children and adolescents, and it appears that many countries do not offer MenB to adolescents despite this group being at increased risk of IMD and carriage acquisition.9 The World Health Organization (WHO) is striving to eliminate bacterial meningitis by 203010 with a focus on developing new affordable vaccines, such as the current licensed pentavalent meningococcal conjugate vaccine (serogroups A, C, Y, W and X) offering broader protection against serogroups.11 Increasing meningococcal vaccination programs to achieve high immunization coverage is aimed at reducing global disease incidence and frequency and magnitude and duration of outbreaks.10 Clearance Antibiotics for Close Contacts Identifying close contacts of IMD cases through contact tracing is essential for preventing onward transmission of infection and controlling subsequent meningococcal outbreaks. Clearance antibiotics are recommended for close contacts to eliminate nasopharyngeal carriage (and thus transmission) of what could be a potentially hypervirulent serogroup circulating within the close contact network.12 There are varying definitions of a close contact described in IMD management guidelines. Generally, a close contact is defined as prolonged close contact with the case, before the case's onset of illness, usually in the 7 days prior, and until the case has received 24 hours of appropriate antibiotics. However, there is no universally accepted close contact definition, or what approximates a prolonged length of time, potentially leading to an inconsistent response in the management of close contacts across jurisdictions and in outbreak settings. Household contacts, which include living or sleeping within a household setting (eg, dormitory style), appear to be consistently defined as close contacts across jurisdictions. Evidence from a systematic review showed that clearance antibiotics given to household contacts reduced the risk in preventing further cases by 89%.13 Other close contacts including sexual contacts, child-care (if the degree of contact with the case is the same as a household contact), passengers seated adjacent to the case during long travel and health care workers (if directly exposed to droplets or secretions from the respiratory tract of a case) are similarly characterized across international guidelines.14–18 UK meningococcal guidelines refer only to household close contacts, with the caveat that other close contacts are based on prolonged duration.19 In addition, if the case's serogroup is vaccine preventable, unvaccinated close contacts are recommended for vaccination to reduce the risk of disease and to reduce pharyngeal carriage and transmission.1 Provision of information on meningococcal disease should be made available to all contacts, so that persons can act promptly if compatible clinical symptoms occur. Meningococcal Outbreaks Outbreaks vary in scale, frequency, severity and duration.10 There is no clear definition of a meningococcal outbreak. Typically, an infectious disease outbreak is defined as an increase in cases more than what is expected for a specific location and time.20 Thresholds may be used in declaring a meningococcal outbreak and, depending on the outbreak type, are characterized by the number of cases required within a specified time. For example, in countries with low IMD incidence, the number of cases required to declare an organization-based outbreak (common connection, eg, child-care) can be 2–3, or more cases occurring within 1–3 months, and a community outbreak (shared geographically defined community) is 3 or more cases within 3 months.14,15,17,19 In regions with higher IMD incidence, such as the African meningitis belt, the WHO refers to >10 suspected cases per 100,000 population per week.21 Local IMD epidemiology may guide an acceptable outbreak definition and set outbreak thresholds if appropriate. Among children and adolescents, a high burden of disease is reported in indigenous populations. Outbreaks have occurred in socially disadvantaged populations such as the Māori and Pacific children in New Zealand22 and the Aboriginal and Torres Strait Islander children in Australia.23 Environmental determinants, including dry and dusty climatic conditions, may be associated with increased seasonal incidence of outbreaks in the African meningitis belt.24 IMD outbreaks in children and adolescents occur in different settings, with the risk increasing in crowded conditions. Outbreaks have occurred in organization-based settings such as universities, schools, sports clubs and child-care,12 while community outbreaks occur within geographically defined communities such as towns, villages or social networks.25 Outbreak Management The goal of IMD outbreak management is to interrupt transmission and prevent further cases. Once an outbreak is recognized, or on suspicion, an immediate, coordinated public health response should occur. Meningococcal outbreaks are usually coordinated and managed by public health/health authorities, with actions largely determined by guidelines developed for meningococcal disease management. Not all jurisdictions will have access to public health teams or guidelines; however, the response to IMD outbreaks described is generally consistent with available meningococcal public health guidelines used in this review. A response to an outbreak considers the population at risk, setting, source of exposure, available resources (public health staff) and access to pharmaceutical interventions.25 Expanded Clearance Antibiotics Independent of the outbreak setting, close contacts (defined by local health authorities) of meningococcal cases should be given clearance antibiotics as soon as possible, ideally within 24 hours of the index case (first case identified in the outbreak) (Table, Supplemental Digital Content 1, https://links.lww.com/INF/G316). Administration of mass clearance antibiotics may be used in outbreak control together with vaccination, or as an interim measure if vaccination is not feasible to implement, or appropriate to interrupt transmission on a broader scale. Implementation of mass clearance antibiotics may be used in some organization-based outbreaks with a defined cohort, such as in residential or correctional facilities.17 However, there is limited evidence on the benefit of administering mass clearance antibiotics as an outbreak control measure. A review found that mass antibiotic chemoprophylaxis implemented in military, child-care and school outbreaks, and community outbreaks targeting children, may have offered temporary protection, but the impact was difficult to assess in the absence of the intervention.26 Identifying the appropriate target population, administrative logistics including cost, risk of adverse events and development of antibiotic resistance must be considered.26 With no clear guidance or demonstrated value for the use of mass chemoprophylaxis in an outbreak, particularly in community outbreaks, the benefits and risks must be carefully balanced. Vaccination for Populations at Risk Vaccination programs for controlling IMD outbreaks due to vaccine-preventable serogroups (A, C, W, Y and B) have been implemented in organization-based and community outbreaks for at-risk populations (Table, Supplemental Digital Content 2, https://links.lww.com/INF/G317). Mass vaccination programs have been used to control outbreaks in schools. For example, a mass vaccination program with monovalent C vaccine was used to control a school outbreak, followed by a nationwide vaccination program for all 1- to 19-year-old persons in Fiji.27 Following 2 school clusters of MenB in Brittany, France, more than 10,000 11- to 19-year-old children and adolescents were vaccinated.28 Community outbreaks in remote South Australia29 and New Zealand22 were controlled through vaccination programs targeting children within a defined population cohort, achieving high vaccination coverage. Mass vaccination programs also face implementation challenges due to timing of vaccination following cases, defining the population and delivery logistics and cost, particularly if the target cohort is large.17 Availability of standard operating procedures for control measures in the remote South Australian community outbreak was seen as an important requirement that would have assisted with some of the logistical challenges.29 IMD prevention through childhood vaccination programs is more effective and efficient compared with vaccination programs implemented in response to outbreaks. Role of the Pediatric Doctor The pediatrician's role in early recognition of IMD cases is crucial, as this initiates the first response in meningococcal disease investigation. IMD cases, confirmed or suspected, result in initiating a diagnosis, case treatment and setting up necessary infection control procedures such as isolating the case, droplet precautions and use of appropriate personal protective equipment to minimize the risk of transmission. All cases of suspected or confirmed IMD require immediate notification by the pediatrician to the jurisdictional health agency or organization responsible for meningococcal disease follow-up. Public health response usually begins with interviewing IMD cases to identify contacts, which are risk-assessed to determine the degree of contact with the case. Additional control measures described earlier will be initiated in the event of an outbreak. Pediatricians play a crucial role in advocating for vaccination against meningococcal disease by identifying children at increased risk, ensuring appropriate vaccination coverage for children and raising awareness about the importance of vaccination. Meningococcal Outbreak Challenges Limited available evidence and lack of current evidence published in meningococcal disease public health guidelines challenge best practice in managing meningococcal outbreaks. WHO's roadmap to eliminate meningitis calls for evidence-based policies and interventions to prevent and respond to meningococcal outbreaks, robust and efficient surveillance systems to support timely outbreak responses, rapid diagnostic tests for identification of outbreaks and national guidelines for outbreak response and management with consideration given to different populations.10 Whole-genomic sequencing is becoming increasingly important in identifying meningococcal outbreaks, and is used to characterize the genetic variability and identify emerging clonal complexes, and may become part of routine investigation in countries with whole-genomic sequencing capability30.