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Comparison of Meningococcal Disease Surveillance Systems — United States, 2005–2008

Meningococcal disease is a nationally notifiable disease caused by the bacterium Neisseria meningitidis. Rates of the disease have decreased since 2000 and are currently at a historic low (1). The National Notifiable Diseases Surveillance System (NNDSS) and Active Bacterial Core surveillance (ABCs) are the two surveillance systems in the United States that track cases of meningococcal disease (2). Whereas NNDSS (a passive surveillance system) covers all of the United States and records both probable and confirmed cases of meningococcal disease, ABCs (an active surveillance system) covers six states and portions of four other states and records only culture-confirmed cases. However, ABCs surveillance data are more detailed than NNDSS and are more widely used in vaccine policy and development. To determine whether ABCs estimates of the number of cases of meningococcal disease were far lower than NNDSS counts and the contribution of polymerase chain reaction (PCR) to that difference, CDC conducted an analysis to compare the two systems. CDC compared 1) the number of meningococcal disease cases reported by NNDSS in ABCs areas during 2005–2008 with the number reported by both systems and 2) the mean annual number of cases reported by NNDSS nationally during 2005–2008, with the mean projected national number from ABCs. The results of these two calculations indicated that 8.9% or 14.5% of meningococcal disease cases reported by NNDSS, respectively, were not reported by ABCs, most commonly because they were probable cases detected by PCR testing. Because ABCs data do not substantially underestimate the number of cases of meningococcal disease, implementing PCR testing for N. meningitidis in all ABCs reference laboratories likely would not increase estimates of disease greatly.

NNDSS comprises confirmed and probable cases (Table 1) identified through passive reporting in all 50 states, the District of Columbia, and five territories (3). ABCs is an active, laboratory- and population-based surveillance system that is part of CDC's Emerging Infections Program (EIP) network (4,5). ABCs conducts surveillance for N. meningitidis in a catchment area consisting of six states and portions of four other states (Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, and selected counties in California, Colorado, New York, and Tennessee). The area has 41.4 million U.S. residents, approximately 13% of the U.S. population. Confirmed cases reported by ABCs are defined by isolation through culture of N. meningitidis from a normally sterile site in a resident of the ABCs surveillance area. Cases identified in ABCs also should be reported to NNDSS.

Bacterial culture is the criterion standard for diagnostic confirmation of meningococcal disease; however, latex agglutination, Gram stain, specific clinical criteria, and detection of N. meningitidis DNA by PCR all are used for diagnosis. PCR can have greater diagnostic sensitivity than culture, particularly when antibiotics are administered before collection of a specimen for culture (6). PCR for meningococcal disease diagnosis is not standardized or widely available, but is being used by some state public health laboratories. ABCs reports only culture-confirmed meningococcal disease cases, whereas NNDSS reports both culture-confirmed cases and probable cases identified by PCR and other testing methods.

Incidence estimates derived from ABCs surveillance are used to help guide vaccine policy and development because of the system's high specificity, data completeness, and collection of isolates for determination of serogroup and molecular epidemiology. However, ABCs likely underestimates the actual number of cases of meningococcal disease because probable cases diagnosed by PCR and other nonculture diagnostic tests are not reported. To understand the extent to which ABCs might underestimate meningococcal disease incidence, CDC identified the number of cases reported by NNDSS during 2005–2008 that occurred within ABCs surveillance areas but were not reported by ABCs. In addition to comparisons from ABCs surveillance sites only, CDC compared NNDSS and ABCs data on a national scale, projecting case counts from ABCs to the national level. Projected national counts from ABCs are estimated by standardizing ABCs estimates for race and age group (1). Finally, subanalyses were conducted regarding diagnostic practices that produced discrepant cases in selected ABCs sites, and assessment of PCR practices and capacity in all ABCs sites.

ABCs versus NNDSS data from 10 ABCs states only. Cases were categorized as reported in the ABCs database only, reported in the NNDSS database only, or reported by both systems. During 2005–2008, a total of 728 unique meningococcal disease cases were reported by NNDSS and/or ABCs from the ABCs states. Of the 728 cases, 65 (8.9%) were reported by NNDSS only, 23 (3.2%) by ABCs only, and 640 (87.9%) by both databases. The reason 23 were reported by ABCs but not NNDSS is unknown.

NNDSS versus ABCs data projected to national scale. During 2005–2008, the mean annual number of reported meningococcal disease cases (probable and confirmed) from NNDSS overall was 1,172 (range: 1,077–1,245). From ABCs, the projected national mean annual case count (including all serogroups) was 1,002 (range: 914–1,045). Based on these national estimates, ABCs estimated 14.5% fewer annual cases of meningococcal disease than NNDSS.

Subanalysis of five ABCs states by NNDSS diagnostic criteria. Five ABCs states (California, Georgia, Minnesota, Maryland, and Oregon) with more than six cases reported by NNDSS and not by ABCs (n = 56) were asked to provide additional information on the NNDSS diagnostic criteria used for the discrepant cases. Diagnostic criteria included PCR in 24 (42.9%) cases, "unknown" laboratory confirmation in 11 (19.6%), Gram stain in 10 (17.9%), and latex agglutination in seven (12.5%). The diagnosis of meningococcal disease in four (7%) was based on clinical suspicion alone (Table 2).

PCR practices of 10 ABCs states. Of the 10 ABCs states, only California, Georgia, and Minnesota had laboratory capacity to perform PCR for diagnosis of meningococcal disease during the study period. In each of these three states, only one laboratory had PCR capacity for meningococcal testing. The decision protocol for submission of a specimen for PCR testing in the 10 states varied considerably, from absence of guidelines to inconsistent implementation of guidelines across counties. A higher proportion of NNDSS cases from the three states with routine PCR testing (38 of 286, 13.3%) were reported only to NNDSS than from the states without routine PCR testing (26 of 442, 5.9% [p<0.001]). In the three states with routine PCR testing, approximately 8% of NNDSS cases were identified by PCR (nine of 111 cases, 8.1%; six of 82, 7.3%; and eight of 93, 8.6%, respectively).

Reported by

Amanda C. Cohn, MD, Jessica MacNeil, MPH, Thomas A. Clark, MD, Div of Bacterial Diseases, National Center for Immunization and Respiratory Diseases; Sara Tartof, PhD, EIS Officer, CDC. Corresponding contributor: Sara Tartof, startof@cdc.gov, 404-639-3769.

Editorial Note

Because meningococcal disease is nationally notifiable both by NNDSS and ABCs surveillance, the two systems can be compared and the contribution of their different diagnostic criteria can be evaluated. PCR was the most common nonculture diagnostic test used in the three ABCs states that routinely conducted PCR testing for meningococcal disease. These states reported more cases of meningococcal disease under NNDSS definitions than states that did not use PCR testing. However, PCR testing was not performed on all specimens; therefore, estimating the actual proportion of specimens that would test negative by culture but positive by PCR is difficult.

In countries such as the United Kingdom, PCR is a routine diagnostic modality for patients with meningitis; therefore, a large proportion of cases are confirmed by PCR (7,8). In countries that rely on PCR for diagnosis, surveillance that includes cases identified by PCR is important. However, this study suggests that the additional cases identified through nonculture methods are not enough to warrant a change in the use of ABCs to guide vaccine policy and develop U.S. incidence projections and supports continued use of culture-confirmed surveillance. Among the ABCs states, approximately 8% of cases reported to NNDSS were diagnosed by PCR (as probable cases) and might have been missed by ABCs diagnostics (culture-confirmed) alone. If PCR had been used systematically in all suspected cases, this proportion might have been higher, as evidenced by the significantly higher proportion of discrepant cases from states with routine PCR testing, as compared with states without routine PCR testing. Nonetheless, in this study, ABCs culture-based surveillance captured >85% of cases of meningococcal disease.

The findings in this report are subject to at least two limitations. First, ABCs represents only 13% of the U.S. population, and data from the ABCs catchment area might not be generalizable to the rest of the United States. Second, use of PCR testing did not contribute substantially to overall national disease incidence during the study period, and assessing the potential contribution of a standardized system of PCR testing to national meningococcal disease surveillance is difficult. If the use of PCR in meningococcal disease diagnosis increases in coming years, a reassessment of the analyses in this study might be warranted.

Because ABCs has more complete and accurate data on serogroup, underreporting of cases is acceptably low and validates the use of ABCs as an important source of meningococcal disease data. In the United States, PCR can be a useful tool for decision-making regarding treatment or chemoprophylaxis. However, universal implementation of PCR for surveillance purposes does not appear warranted at this time.

Acknowledgments

Shetul Shah, Div of Bacterial Diseases, National Center for Immunization and Respiratory Diseases; CDC. ABCs officers and supervisors.

References

  1. Cohn AC, MacNeil JR, Harrison LH, et al. Changes in Neisseria meningitidis disease epidemiology in the United States, 1998–2007: implications for prevention of meningococcal disease. Clin Infect Dis 2010;50:184–91.
  2. Koo D, Wetterhall SF. History and current status of the National Notifiable Diseases Surveillance System. J Public Health Manag Pract 1996;2:4–10.
  3. CDC. Case definitions for infectious conditions under public health surveillance. MMWR 1997;46(No. RR-10).
  4. CDC. Active Bacterial Core surveillance (ABCs). Atlanta, GA: US Department of Health and Human Services, CDC. Available at http://www.cdc.gov/abcs/index.html. Accessed April 28, 2012.
  5. Schuchat A, Hilger T, Zell E, et al. Active bacterial core surveillance of the emerging infections program network. Emerg Infect Dis 2001;7:92–9.
  6. Nigrovic LE, Malley R, Macias CG, et al. Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis. Pediatrics 2008;122:726–30.
  7. Gray SJ, Trotter CL, Ramsay ME, et al. Epidemiology of meningococcal disease in England and Wales 1993/94 to 2003/04: contribution and experiences of the Meningococcal Reference Unit. J Med Microbiol 2006;55(Pt 7):887–96.
  8. Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010;23:467–92.

What is already known on this topic?

National Notifiable Diseases Surveillance System (NNDSS) and Active Bacterial Core surveillance (ABCs) are the surveillance systems for meningococcal disease in the United States. ABCs detects only culture-confirmed meningococcal disease cases while NNDSS detects probable cases defined by polymerase chain reaction (PCR) and other tests as well as culture-confirmed cases. However, the extent to which ABCs underestimates incidence by missing probable cases was unknown.

What is added by this report?

During 2005–2008, depending on the method of calculation, 8.9% or 14.5% of the total number of reported meningococcal disease cases were reported by NNDSS and not by ABCs, most commonly because they were detected by PCR. Use of PCR is not common or systematic across states. Of the three ABCs states that use PCR routinely for the diagnosis of Neisseria meningitidis infection, approximately 8% of cases were detected by PCR.

What are the implications for public health practice?

Although ABCs only captures confirmed meningococcal disease cases, comparisons with NNDSS indicate that ABCs data do not underestimate the number of cases substantially. A recommendation to implement PCR testing for N. meningitidis in all reference laboratories would not appreciably improve the estimates for meningococcal disease. However, the contribution of PCR testing to meningococcal disease reporting should continue to be monitored.


TABLE 1. Characteristics of surveillance systems for meningococcal disease — United States, 2005–2008

Characteristic

NNDSS

ABCs

Surveillance type

Passive

Active

Population coverage

100%

13%

Confirmed case definition

Neisseria meningitidis cultured from normally sterile anatomic site

N. meningitidis cultured from normally sterile anatomic site

Probable case definition

Detection of polysaccharide antigen by latex agglutination, PCR, or immunohistochemistry in cerebrospinal fluid
OR
Clinically compatible illness with purpura fulminans

Not applicable

Abbreviations: NNDSS = National Notifiable Diseases Surveillance System; ABCs = Active Bacterial Core surveillance; PCR = polymerase chain reaction.


TABLE 2. Number of reported cases of meningococcal disease and criteria used for diagnosis — five ABCs states,* 2005–2008

State

No. of reported meningococcal disease cases overall

(NNDSS and ABCs)

No. of cases reported by NNDSS and not by ABCs

Diagnostic criteria used by NNDSS

PCR

Latex agglutination

Gram stain

Clinical suspicion only

Unknown laboratory confirmation

California (ABCs counties)

111

18

9

1

8

Georgia

82

12

6

2

2

2

Minnesota

93

8

8

Maryland

85

9

1

5

2

1

Oregon

178

9

6

1

2

Total

549

56

24

7

10

4

11

Abbreviations: NNDSS = National Notifiable Diseases Surveillance System; ABCs = Active Bacterial Core surveillance; PCR = polymerase chain reaction.

* The five ABCs states with more than six cases reported by NNDSS but not by ABCs.

PCR performed by CDC.


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