APPENDIX B

Evaluation and Management of Suspected Outbreaks of Meningococcal Disease

As routine vaccination coverage among adolescents with MenACWY increases, the number of serogroup C and Y has declined (CDC, unpublished data, 2012). However, outbreaks might occur in age groups that are not routinely recommended to be vaccinated with MenACWY and deaths caused by meningococcal outbreaks can result in high levels of anxiety in a community (1). Mass vaccination might play a role protecting the population at risk during an outbreak. The decision to implement a mass vaccination campaign to prevent meningococcal disease depends on whether the occurrence of more than one case represents an outbreak or an unusual clustering of endemic disease. Because the number of cases in outbreaks is usually not substantial, this determination often requires evaluation and analysis of the patterns of disease occurrence. Mass vaccination campaigns are expensive, require a massive public health effort, and can create unwarranted concern among the public. However, mass vaccination campaigns might offer an opportunity to increase coverage in otherwise hard-to-reach populations (e.g., adolescents who have dropped out of school).

Population at Risk: Organization- and Community-Based Outbreaks

In addition to close contacts, persons considered to be at increased risk for meningococcal disease compared with historic rates of disease in the same population in the general U.S. population are classified as being at risk. The population at risk is used as the denominator in calculations of the disease attack rate. The population at risk is usually defined on the basis of organizational affiliation or community of residence. In organization-based outbreaks, cases are linked by a common affiliation other than a shared, geographically delineated community; the population at risk is thus usually the group of persons who best represent that affiliation. For example, if the only association between patients is attending the same school or university, the population at risk is all persons attending the school or university. In community-based outbreaks, patients have no common affiliation other than a shared, geographically defined community. The population at risk can be defined as the smallest geographically contiguous population that includes all (or nearly all) patients. This population is usually a neighborhood, town, city, or county whose size is obtained from census data.

Distinguishing whether an outbreak should be classified as organization- or community-based is complicated by the fact that, in certain instances, these types of outbreaks occur simultaneously. Calculation of attack rates for organization-based outbreaks is most useful for large organizations (e.g., universities). However, in the majority of organization-based outbreaks with three or even two cases of disease, the rate will be >10 cases/100,000 population. In such situations, public health officials also might consider vaccination after only two primary cases are identified.

Attack Rate and Decision to Vaccinate

For a primary attack rate to be calculated, all confirmed cases (Box) of the same serogroup should be summed; secondary cases should be excluded and each set of coprimary cases counted as one case. Because attack rates are calculated both to characterize the risk for disease among the general population and to determine whether overall rates have increased, related cases (secondary and coprimary) should not be included.

If three or more cases have occurred in either an organization- or a community-based outbreak during ≤3 months (starting at the time of the first confirmed or probable case), a primary attack rate should be calculated. Rate calculations should not be annualized. The following formula is used to calculate attack rates:

Attack rate per 100,000 = [(number of primary confirmed or probable cases during a 3-month period) / (number of population at risk)] x 100,000.

Vaccination of the population at risk should be considered if the attack rate is >10 cases/100,000 persons. Public health personnel should consider the following factors: 1) completeness of case reporting and number of possible cases of meningococcal disease for which bacteriologic confirmation or serogroup data are not available; 2) occurrence of additional cases of meningococcal disease after recognition of a suspected outbreak (e.g., if the outbreak occurred 2 months previously and if no additional cases have occurred, in which case vaccination might be unlikely to prevent additional cases of meningococcal disease); and 3) logistic and financial considerations. Because available vaccines are not effective against Neisseria meningitidis serogroup B, vaccination should not be considered during serogroup B outbreaks.

Vaccination Group

Those persons designated to be administered vaccine during a vaccination campaign comprise a vaccination group. The vaccination group usually includes either the whole or a subset of the population of risk. Because meningococcal disease outbreak cases occur predominantly among persons aged <30 years (2), the vaccination group usually is that portion of the population at risk aged <30 years.

In the majority of organization-based outbreaks, the vaccination group includes the whole population at risk. In certain organization-based outbreaks, a vaccination group larger than the population at risk might be designated. For example, in a high school in which all outbreak-associated cases occurred among students, authorities might decide to offer vaccine to staff. In community-based outbreaks, the vaccination group usually can be defined as a subset of the population at risk (e.g., persons aged <30 years). In rare situations (e.g., in a town with a limited population) in which multiple cases have occurred among adults aged >29 years, the entire population might be considered for vaccination. For more substantial populations, this decision would be costly in terms of finances and human resources, and restricting the vaccination group to the persons in age groups with the highest attack rates might be more appropriate. Age-specific attack rates can be calculated by using the formula previously provided and by restricting the numerator and denominator to persons within specific age groups (e.g., persons aged <30 years).

Genotyping of N. meningitidis Isolates

Genotyping of N. meningitidis isolates by using such methods as pulsed-field gel electrophoresis or multilocus sequence analysis (MLST) might provide useful information for determining whether a group of cases represents an outbreak (3). Outbreaks of meningococcal disease usually are caused by closely related strains. Genotyping data can allow identification of an outbreak strain and help to better define the extent of the outbreak. If strains from a group of patients are unrelated by genotyping, the group of cases most likely does not represent an outbreak. Because molecular subtyping testing might not be readily available or accessible, initiation of outbreak-control efforts should not be delayed until genotyping results are available.

Other Control Measures

Mass chemoprophylaxis (i.e., administration of antibiotics to substantial populations) is not recommended to control large outbreaks of disease. Disadvantages of mass chemoprophylaxis include cost of the drug and administration, difficulty of ensuring simultaneous administration of drugs to substantial populations, drug side effects, and emergence of resistant organisms. In addition, multiple sources and prolonged risk for exposure make this approach impractical and unlikely to succeed. In the majority of outbreak settings, these disadvantages outweigh the possible benefit in disease prevention. However, in outbreaks involving limited populations (e.g., an outbreak in a single school), administration of chemoprophylaxis might be considered (4), especially in serogroup B outbreaks, for which available vaccines are not effective (5). When making a decision about initiating mass chemoprophylaxis in these settings, public health officials should consider not only the potential for prevention of new cases but also the logistics, cost, and potential for developing antimicrobial resistance (6,7). If mass chemoprophylaxis is undertaken, it should be administered to all targeted persons at the same time. In the United States, measures that have not been recommended for control of meningococcal disease outbreaks include restricting travel to areas with an outbreak, closing schools or universities, or canceling sporting or social events.

Educating communities, physicians, and other health-care personnel about meningococcal disease to promote an early case recognition and early care-seeking behaviors is an important part of managing suspected meningococcal disease outbreaks. Education efforts should be initiated as soon as an outbreak of meningococcal disease is suspected (7). Information about the signs and symptoms of meningococcal disease is available at http://www.cdc.gov/meningococcal/about/symptoms.html.

References

1. Brooks R, Woods CW, Benjamin DK Jr, Rosenstein NE. Increased case-fatality rate associated with outbreaks of Neisseria meningitidis infection, compared with sporadic meningococcal disease, in the United States, 1994–2002. Clin Infect Dis 2006;43:49–54.
2. Jackson LA, Schuchat A, Reeves MW, Wenger JD. Serogroup C meningococcal outbreaks in the United States. An emerging threat. JAMA 1995;273:383–9.
3. Popovic T, Schmink S, Rosenstein NA, et al. Evaluation of pulsed-field gel electrophoresis in epidemiological investigations of meningococcal disease outbreaks caused by Neisseria meningitidis serogroup C. J Clin Microbiol 2001;39:75–85.
4. Zangwill KM, Schuchat A, Riedo FX, et al. School-based clusters of meningococcal disease in the United States. Descriptive epidemiology and a case-control analysis. JAMA 1997;277:389–95.
5. Jackson LA, Alexander ER, DeBolt CA, et al. Evaluation of the use of mass chemoprophylaxis during a school outbreak of enzyme type 5 serogroup B meningococcal disease. Pediatr Infect Dis J 1996;15:992–8.
6. Nelson JD MG. The Pediatr Infect Dis J Newsletter. Pediatr Infect Dis J 1997:16.
7. CDC. Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997;46(No. RR-5):13–21.