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Laboratory-Based Surveillance for Meningococcal Disease in Selected Areas, United States, 1989-1991

Lisa A. Jackson, M.D. Jay D. Wenger, M.D. Meningitis and Special Pathogens Branch Division of Bacterial and Mycotic Diseases National Center for Infectious Diseases and the Meningococcal Disease Study Group * Abstract

Problem/Condition: Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia in the United States. Accurate surveillance for meningococcal disease is required to detect trends in patient characteristics, antibiotic resistance, and serogroup-specific incidence of disease.

Reporting Period Covered: January 1989 through December 1991. Description of System: A case of meningococcal disease was defined by the isolation of N. meningitidis from a normally sterile site, such as blood or cerebrospinal fluid, in a resident of a surveillance area. Cases were reported by personnel in each hospital laboratory in the surveillance areas. The surveillance areas consisted of three counties in the San Francisco metropolitan area, eight counties in the Atlanta metropolitan area, four counties in Tennessee, and the entire state of Oklahoma.

Results: Age- and race-adjusted projections of the U.S. population suggest that approximately 2,600 cases of meningococcal disease occurred annually in the United States. The case-fatality rate was 12%. Incidence declined from 1.3/100,000 in 1989 to 0.9/100,000 in 1991. Seasonal variation occurred, with the highest attack rates in February and March and the lowest in September. The highest rates of disease were among infants, with 46% of cases affecting those less than or equal to 2 years of age. Males accounted for 55% of total cases, with an incidence of 1.2/100,000, compared with 1.0/100,000 among females (relative risk (RR) = 1.3, 95% confidence interval (CI) 1.0-1.6). The incidence was significantly higher among blacks (1.5/100,000) than whites (1.1/100,000) (RR = 1.4 {95% CI 1.1-1.8}). Serogroup B caused 46% of cases and serogroup C, 45%. Thirty-eight percent of isolates were reported to be resistant to sulfa; none were reported to be resistant to rifampin.

Interpretation: The decline in incidence of meningococcal disease from 1989 through 1991 cannot be explained by any change in public health control measures; this trend should be monitored by continued surveillance. The age, sex, and race distribution and seasonality of cases are consistent with previous reports. The proportion of N. meningitidis isolates resistant to sulfa continues to be substantial. A relatively small proportion of cases is potentially preventable by the use of the currently available polysaccharide vaccine, which induces protection against serogroups A, C, Y, and W135 and is effective only for persons greater than 2 years of age.

Actions Taken: Current recommendations against the use of sulfa drugs for treatment or prophylaxis of meningococcal disease unless the organism is known to be sensitive to sulfa should be continued. Since resistance to rifampin is rarely reported, it continues to be the drug of choice for prophylaxis. The development of vaccines effective for infants and vaccines inducing protection against serogroup B would be expected to have a substantial impact on disease. INTRODUCTION

Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia in the United States (1). Although epidemic meningococcal disease continues to be a major public health problem in sub-Saharan Africa and other parts of the developing world, most disease in the United States is sporadic. Approximately half the cases in the United States are caused by serogroup B, with the highest attack rates in children less than 2 years of age (2). Efforts to control disease have been limited because the currently available quadrivalent meningococcal polysaccharide vaccine is effective only against serogroups A, C, Y, and W135 and is poorly immunogenic in children less than 2 years of age (3). Accurate surveillance for meningococcal disease is required to detect trends in a) patient characteristics, which may allow groups at higher risk of disease to be identified; b) antibiotic resistance, which influences the choice of antimicrobial agents for treatment and prophylaxis; and c) serogroup-specific incidence of disease, which influences the potential applications of the quadrivalent meningococcal polysaccharide vaccine. This report summarizes information from a laboratory-based surveillance system for invasive meningococcal disease conducted in a large U.S. population from January 1989 through December 1991. METHODS

Laboratory-based surveillance, using methods previously described (1,2), was conducted in an aggregate population of 10.3 million persons (4.1% of the U.S. population), consisting of residents of three counties in the San Francisco metropolitan area, eight counties in the Atlanta metropolitan area, four counties in Tennessee, and the entire state of Oklahoma. Seventy-one percent of residents in the surveillance areas were white and 18% were black, compared with 80% and 12%, respectively, of the U.S. population. Surveillance was initiated in November 1988 and is ongoing; however, only cases reported from January 1, 1989, through December 31, 1991, are included in this report.

A case of meningococcal disease was defined by the isolation of Neisseria meningitidis from a normally sterile site, such as blood or cerebrospinal fluid (CSF), in a resident of a surveillance area. Cases were reported to surveillance workers by contacts in each hospital laboratory in the surveillance areas. A case report form with information about age, sex, race, outcome, and clinical syndrome of the patient, as well as the site of isolation, serogroup, and antibiotic sensitivities of the organism, was completed for each identified case. Hospital laboratory directors were asked to send N. meningitidis isolates to CDC for serogrouping; 65% of case isolates were received at CDC. To evaluate the sensitivity of reporting, hospitals were periodically audited by review of microbiology records. The audit completed in January 1990 identified 91 N. meningitidis cultures from sterile sites. Eighty-eight had been reported through the surveillance system, for a sensitivity of 96%.

Because race is a likely risk marker for meningococcal disease, data were analyzed by race, and the projected national incidence and annual number of cases based on incidence among surveillance area residents were adjusted for race. Races other than white or black were designated in less than 5% of records; therefore, only results of stratification by white and black race are reported.

Rates of disease were calculated by using 1990 population data from the U.S. Bureau of the Census. Fisher's exact test was used to assess statistical significance. RESULTS

In the years 1989 through 1991 in the four surveillance areas, 332 cases of meningococcal disease were detected, for an average incidence of 1.1/100,000 population during this period. Based on this rate, when the data were adjusted for differences in racial distribution between the surveillance area population and the U.S. population, an estimated 2,600 cases of meningococcal disease occurred annually in the United States. The incidence was 1.3/100,000 in 1989, 1.0/100,000 in 1990, and 0.9/100,000 in 1991; this trend toward decreasing incidence with time was statistically significant (chi-square for linear trend, p = 0.019). Seasonal variation occurred, with the highest attack rates in February and March and the lowest in September (Figure 1). Of the 314 cases for which outcome information was available, 36 persons died, for a case-fatality rate of 12%. The case-fatality rate did not vary by sex, race, age, clinical syndrome, serogroup, or site of isolation of the organism.

The highest rates of disease occurred in infants less than 1 year of age, with a peak incidence of 26.4/100,000 population in infants less than 4 months of age (Figure 2). Twenty-nine percent of cases were in infants less than 1 year of age, 46% in children less than or equal to 2 years of age, and 25% in persons greater than or equal to 30 years of age. The age distribution of cases did not vary by sex or race. Males accounted for 55% of total cases, with an incidence among males of 1.2/100,000, compared with 1.0/100,000 among females (RR = 1.3; 95% CI, 1.0-1.6). The incidence was significantly higher among blacks (1.5/100,000) than whites (1.1/100,000; RR = 1.4; 95% CI, 1.1-1.8).

The average annual incidence of disease for the period 1989 through 1991 varied among the surveillance areas, with a peak of 1.3/100,000 in the San Francisco metropolitan area and a low of 0.6/100,000 in Oklahoma (p less than 0.001). The incidence was higher among blacks than whites in all surveillance areas except Tennessee (Figure 3). The highest annual incidence, 1.9/100,000, occurred in San Francisco in 1989. An increased rate of disease in the less than 2-year-old age group accounted for most of the increase in overall rate in this area during 1989. The attack rate in the less than 2-year-old age group in the San Francisco surveillance area was 23.0/100,000 in 1989, compared with 5.1/100,000 in 1990 and 10.2/100,000 in 1991. The cases among children less than or equal to 2 years old were not temporally clustered, and the serogroup distribution was similar to that reported for this age group in 1990 and 1991.

Meningitis, defined as N. meningitidis isolated from CSF and/or meningitis reported as the clinical syndrome on the case report form, accounted for 58% of cases, with an incidence of 0.6/100,000 population. The case-fatality rate for meningitic disease was 13% (25/192), which does not differ significantly from the case-fatality rate of 9% (13/140) for disease not meeting the above case definition for meningitic disease. The incidence of meningitic disease did not vary significantly by race; however, meningitis represented a higher proportion of total disease among whites (61%) than blacks (47%) (p less than 0.05). The incidence of nonmeningitic disease declined after 12 months of age until age 20, when a secondary increase in incidence was seen that continued through the greater than or equal to 60 age group (Figure 4). Nonmeningitic disease accounted for 63% of total disease in persons greater than or equal to 30 years.

Meningitis was reported as the clinical syndrome on the case report form in 57% of cases and primary bacteremia in 49%. Other syndromes were much less common, with pneumonia reported in 4% of cases, otitis media in 2%, cellulitis in 0.6%, and arthritis in 0.3%. N. meningitidis was isolated from blood in 66% of cases, CSF in 51%, joint fluid in 1%, and pleural and peritoneal fluid in 0.3% each. More than one clinical syndrome or site of isolation was reported for some cases. The case-fatality rate when the organism was isolated from blood (regardless of whether it was also isolated from another site) was 11.5% (25/218); the case-fatality rate when the organism was isolated only from CSF was 9.3% (10/110).

A total of 217 isolates were serogrouped at CDC; serogroup information was collected locally and recorded on the case report form for 179. Serogroup data were available from either or both sources for 261 (79%) of cases. For 132 isolates, serogroup information was reported from both sources; the sources agreed in 118 (89%) cases. When a discrepancy occurred, the CDC results were used. The proportion of cases with serogroup information did not differ by race.

Serogroup B organisms accounted for 46% and serogroup C organisms for 45% of isolates for which serogroup information was available. W135, Y, and nontypeable serogroups accounted for 3%, 2%, and 2% of isolates, respectively. One isolate was reported to be serogroup A, and two others were reported as "other" serogroup; these isolates were not submitted to CDC for serogrouping. The estimated serogroup-specific incidences were 0.5/100,000 population for both serogroups B and C. Serogroup B disease accounted for 51% of disease among whites but for only 27% among blacks (p less than 0.01). A significantly higher incidence of group C disease (1.0/100,000 vs. 0.4/100,000 {p less than 0.01}) and a similar (not significantly different) incidence of group B disease (0.4/100,000 vs. 0.6/100,000; p = 0.4) occurred among blacks compared with whites.

A significantly higher proportion of group C disease occurred in older age groups, with 69% of group C disease, compared with 37% of group B disease, in persons greater than 2 years of age (p less than 0.001) (Table 1). The incidence of group C disease varied by surveillance area, with rates of 0.4/100,000 and 0.2/100,000 in Tennessee and Oklahoma, compared with a rate of 0.7/100,000 both in Atlanta and San Francisco. Rates of group B disease varied less by surveillance area (Figure 5).

The proportion of meningitic and nonmeningitic disease caused by serogroups B and C was similar. Serogroups other than B and C accounted for four (44%) of nine pneumonia cases, compared with only 19 (6%) of 323 cases of all other syndromes (p=0.002). Twenty-eight (38%) of the 73 isolates for which sulfa sensitivity was reported were reported to be resistant. Sulfa resistance did not vary by serogroup. None of the 42 isolates for which rifampin sensitivity was reported were found to be resistant. DISCUSSION

The average annual rate of disease, 1.1/100,000 population, detected by this laboratory-based surveillance system in an aggregate population of 10 million persons from 1989 through 1991 was slightly lower than the rate of 1.3/100,000 population detected by a similar surveillance system in an aggregate population of 34 million in 1986 (2). The incidence declined substantially, from 1.3/100,000 in 1989 to 0.93/100,000 in 1991.

This decrease in the rate of disease cannot be attributed to public health control measures adopted during this period. The decline in incidence therefore could represent a natural fluctuation in disease incidence or could indicate a change in the occurrence of disease, possibly due to factors such as changes in the population's susceptibility to disease or in the organism's prevalence or virulence. The rate of meningococcal disease in the United States, as reported by CDC through the National Notifiable Diseases Surveillance System, also declined over a similar period, suggesting that the decrease was not limited to the geographic areas included in the laboratory-based surveillance system. The rate of meningococcal disease reported by CDC decreased from 1.2/100,000 population in 1988 to 1.1/100,000 population in 1989, 1.0/100,000 population in 1990, and 0.8/100,000 population in 1991 (chi-square test for linear trend, p less than 0.001) (4). Continued surveillance for meningococcal disease is needed to determine the importance of this trend.

The age, sex, and race distribution and seasonality of cases reported by this laboratory-based surveillance system are consistent with previous reports. The higher attack rate among males, who accounted for 55% of total cases, was not found in 1986; however, higher rates of meningococcal meningitis in males have been reported previously (5,6). The 1986 laboratory-based surveillance system detected a higher rate of invasive meningococcal disease among blacks (2), and a report of bacterial meningitis passive surveillance data from 1978 through 1981 also noted higher rates of meningococcal meningitis among blacks compared with whites (5). Previous studies have reported a higher incidence of meningococcal disease among blacks than whites (2,5). Reasons for this difference are unclear; however, race is likely a risk marker rather than a risk factor for meningococcal disease. The race-specific variation in disease rates may reflect differences in factors such as household crowding, urban residence, or exposure to tobacco smoke. Risk markers may be useful for identifying groups to target with prevention efforts and may also suggest potential risk factors to investigate in future studies.

Serogroups B and C accounted for approximately equal proportions of disease; however, only 30% of cases in the less than or equal to 2-year-old age group were due to serogroup C. Although serogroup C represented a higher proportion of total cases in older age groups, the incidence of disease in these age groups was lower; thus, the total estimated number of cases of group C disease in the greater than 2-year-old age group is relatively small. Even if vaccination were 100% effective against group C disease and all persons greater than 2 years of age were routinely vaccinated with the polysaccharide vaccine, only 33% of meningococcal disease would be prevented. At current rates of disease, routine vaccination is unlikely to be a cost-effective preventive measure. However, vaccination of populations with clusters of disease (with high incident rates) is warranted, and further evaluation of the potential role of immunization for group C disease is under way. Development of vaccines that protect against serogroup B disease and are immunogenic in the age groups at highest risk of disease might improve the effectiveness of vaccination for meningococcal disease.

In 1986, a reported 61% of isolates were resistant to sulfa, with a significantly higher rate of resistance among group C compared with group B isolates (2). In contrast, in the present study the rate of resistant to sulfa was 37%; no difference was detected in resistance patterns by serogroup. Variation in reported sulfa resistance was also identified in data received through the CDC passive surveillance system from 1970 through 1980; the reported proportion of sulfa resistance varied from 12% to 67%, although it did not exceed 16% after 1974 and varied only from 11% to 16% from 1974 through 1980 (7). The prevalence of sulfa-resistant N. meningitidis is consistently high enough to warrant continuation of current recommendations against the use of sulfa drugs for treatment or prophylaxis of meningococcal disease unless the organism is known to be sensitive to sulfa. Since resistance to rifampin is rarely reported, it continues to be the drug of choice for prophylaxis.

The highest rates of both meningitic and nonmeningitic meningococcal disease occurred in infants less than 1 year of age. A secondary peak was noted in nonmeningitic disease only after age 20, with an increase in rate that continued through persons greater than or equal to 60 years of age (Figure 5). This secondary peak in incidence of nonmeningitic meningococcal disease was noted previously in a report of a laboratory-based surveillance system for invasive disease due to N. meningitidis (1). This report differed from the present study in noting a significantly higher case-fatality rate for nonmeningitic, compared with meningitic, meningococcal disease (17% vs. 12%).

Efforts to develop a serogroup B vaccine and protein conjugate C vaccines that would be immunogenic in infants are ongoing (8-10). Such vaccines, if incorporated into routine childhood vaccination schedules, would be expected to have a substantial impact on meningococcal disease, which remains an important cause of morbidity and mortality (an estimated 2,600 cases per year, 12% of which are fatal) in the United States.

References

  1. Wenger JD, Hightower AW, Facklam RR, Gaventa S, Broome CV, the

Bacterial Meningitis Study Group. Bacterial meningitis in the United States, 1986: report of a multistate surveillance study. J Infect Dis 1990;162:1316-23.

2. Pinner RW, Gellin BG, Bibb WF, et al. Meningococcal disease in the United States -- 1986. J Infect Dis 1991;164:368-74.

3. CDC. Meningococcal vaccines. MMWR 1985;34:255-9. 4. CDC. Summary of notifiable diseases, United States, 1991. MMWR 1992;40:58.

5. Schlech WF, Ward JI, Band JD, Hightower A, Fraser DW, Broome CV. Bacterial meningitis in the United States, 1978 through 1981. JAMA 1985;253:1749-54.

6. Fraser DW, Geil CC, Feldman RA. Bacterial meningitis in Bernalillo County, New Mexico: a comparison with three other American populations. Am J Epidemiol 1974;100:29-34.

7. Band JD, Chamberland ME, Platt T, Weaver RE, Thornsberry C, Fraser DW. Trends in meningococcal disease in the United States, 1975-1980. J Infect Dis 1983;148:754-8.

8. Frasch CE. Vaccines for prevention of meningococcal disease. Clin Microbiol Rev 1989;2(Suppl):S134-8.

9. Bjune F, Hoiby EA, Gronnesby JK, et al. Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet 1991;338:1093-6. 10. de Moraes JC, Perkins BA, Camargo MC, et al. Protective efficacy of a serogroup B meningococcal vaccine in Sao Paulo, Brazil. Lancet 1992; 340:1074-8.

  • Members of the Meningococcal Disease Study Group are Katherine A. Deaver, Richard Pierce, M.P.H., and Robert Weaver, M.D., Ph.D., CDC; Gretchen Anderson, M.P.H., Pam Daily, M.P.H., Kevin Kraus, Bharat Pattni, M.D., M.P.H., Elizabeth Stone, M.P.H., and Arthur L. Reingold, M.D., San Francisco (California) Department of Health; Margaret Rados, Jo Taylor, R.N., Louis Lefkowitz, M.D., Department of Preventive Medicine, Vanderbilt Medical Center, Nashville, TN; Pam Archer, M.P.H., Laura M. K. Smithee, M.S., Jane Strack, Gregory R. Istre, M.D., Oklahoma State Department of Health, Oklahoma City, OK; Christopher Harvey, M.P.H., Tina Stull, M.D., Monica Farley, M.D., and David Stephens, M.D., Emory University Department of Medicine, Atlanta, GA.



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