Haemophilus influenzae Invasive Disease Among Children Aged less than 5 Years -- California, 1990-1996

Haemophilus influenzae (Hi) causes a variety of severe clinical illnesses including meningitis, pneumonia, epiglottitis, and septic arthritis (1). In the prevaccine era (i.e., before 1988), Haemophilus influenzae type b (Hib) caused approximately 95% of the Hi invasive disease among children aged less than 5 years (1). In 1988, Hib conjugate vaccines were introduced for use among children aged 18 months-5 years; they were subsequently recommended for routine use in infants by the Advisory Committee on Immunization Practices (ACIP) in 1990 (2). During 1989-1995, Hib invasive disease among children aged less than 5 years declined 95% nationally (3). To document the decline of Hib invasive disease and to examine the epidemiology of reported nontype b Hi invasive disease among children aged less than 5 years, CDC, in collaboration with the California Department of Health Services, analyzed reported cases in California from 1990 to 1996. This report summarizes the results of the analysis and documents the decline of Hib without an increase of nontype b Hi invasive disease among children aged less than 5 years.

Hi invasive disease has been a reportable disease in California since 1989, and cases were collected passively from laboratories, clinics, and hospitals. In Los Angeles County, which accounts for 30% of the population in the state aged less than 5 years, active surveillance for Hi invasive disease was conducted during 1986-1992 (4) and 1995-1996 through monthly telephone calls to all local laboratories and periodic laboratory audits. In 1989, three counties in the San Francisco Bay area (Alameda, Contra Costa, and San Francisco), which account for 7% of the population aged less than 5 years, initiated active, laboratory-based surveillance. Laboratorians and infection-control practitioners were contacted biweekly, and laboratory audits were performed once in 1991, 1993, and 1994, and twice in 1995 and 1996. Cases were reported to CDC.

Data from these surveillance systems were combined (n=1090), and the 65 duplicate cases (i.e., cases with identical date of birth, onset, county of residence, and demographic data) and 11 reports that did not include age were eliminated. California census information for 1990 to 1996 was used to calculate race/ethnicity-, sex-, and county-specific incidence rates; county-specific incidence rates were mapped using the Atlas GIS mapping program. Census data from 1993 was used to calculate the average annual incidence of nontype b Hi invasive disease by race/ethnicity.

During 1990-1996 in California, 1014 cases of invasive Hi disease were reported among children aged less than 5 years: 591 (58%) cases of Hib, 160 (16%) cases of nontype b Hi, and 263 (26%) cases of unknown serotype; 71 (27%) of the 263 isolates with unknown serotype were from the three Bay area counties or Los Angeles County. From 1990 to 1996, the number of reported Hib cases decreased 99% (from 346 {13.9 per 100,000} to four {0.1 per 100,000}) (Table_1), and the number of reported Hi cases attributable to unknown serotype declined 93% (from 134 to 10). The proportion of isolates with unknown serotype (approximately 30%) remained relatively constant. During 1990-1996, the incidence of nontype b invasive disease remained stable; the average annual incidence was 0.9 per 100,000 children aged less than 5 years.

During 1990-1996, most (51% {82 of 160}) nontype b Hi invasive disease cases among children aged less than 5 years were reported from Los Angeles County, where the average annual incidence was 1.5 per 100,000 children aged less than 5 years (Table_2). In the three Bay area counties, the number of nontype b Hi cases ranged from one to four per year (1.5 per 100,000 children aged less than 5 years). Overall, 20 (35%) of 58 counties in California reported at least one case of nontype b Hi invasive disease. The average annual incidence rates were higher for both the Bay area counties (1.5 per 100,000 children aged less than 5 years) and Los Angeles County (1.5), compared with the rate for all of California (0.9). The two counties with nontype b incidence rates of greater than or equal to 3 per 100,000 children aged less than 5 years had populations of less than 20,000 children in this age group.

The average annual incidence rates of nontype b Hi invasive disease among non-Hispanic black children were higher than for other racial/ethnic groups (Table_3). The average annual incidence rates of nontype b Hi invasive disease for each racial/ethnic group was higher in the active surveillance sites (the three Bay area counties and in Los Angeles County) than in the remainder of California. The proportion of case-patients aged less than 1 year was similar among nontype b Hi cases (59%) and Hib cases (61%). The average annual incidence of nontype b was similar for males (0.9) and females (0.8).

Reported by: G Rothrock, MPH, A Reingold, MD, California Emerging Infections Program, Oakland; N Alexopoulos, MPH, Los Angeles County Dept of Health Svcs, Los Angeles; C O'Malley, PhD, NJ Smith, MD, SH Waterman, MD, State Epidemiologist, California Dept of Health Svcs. Meningitis and Special Pathogens Br, and Respiratory Diseases Br, Div of Bacterial and Mycotic Diseases, National Center for Infectious Diseases; Child Vaccine-Preventable Diseases Br, Epidemiology and Surveillance Div, National Immunization Program, CDC.

Editorial Note

Editorial Note: The decline of reported Hib invasive disease cases among children aged less than 5 years from 1990 to 1996 in California reflects the decline in Hib invasive disease cases reported nationally associated with the widespread use of Hib vaccine in children (3). The parallel decline in the number of Hi invasive disease cases attributable to unknown serotypes in California suggests that a large number of cases with unknown serotype had been serotype b. In California, the proportion of Hi isolates with unknown serotype information (26%) was lower than for national data in 1994 and 1995 (44%) (3), suggesting more complete ascertainment of serotype information by the active surveillance sites and the California Department of Health Services.

The decline of Hib invasive disease raised concerns about an increase of Hi invasive disease caused by other serotypes (5,6). However, the rate of nontype b invasive disease has remained stable. The low number of reported nontype b Hi invasive disease cases in 1994 may be due to random variation in incidence. By year and by racial/ethnic groups, the rate of nontype b invasive disease was higher in the two regions of California with active surveillance compared with passive reporting from the remainder of California, a trend consistent with other analyses of reporting practices (7). The differences in disease incidence among racial/ethnic groups may be a marker for other risk factors, such as low socioeconomic status (3).

Surveillance for all Hi invasive disease needs to be strengthened to document the remaining disease burden and to monitor vaccination program effectiveness (8). Because the clinical presentation of Hi invasive disease may not vary by serotype (a, b, c, d, e, f, and nontypeable strains), laboratory testing is necessary to identify an isolate's serotype. The identification of serotype b is needed because only Hib invasive disease can be prevented with vaccination. State health departments should identify laboratories that can perform serotyping on Hi isolates from children aged less than 15 years with invasive disease; if serotyping is not available, state health departments can contact CDC.

The incidence rate of nontype b Hi invasive disease is under evaluation by CDC as a tool to help jurisdictions assess whether their surveillance system is sensitive enough to detect a Hib case. If a standard rate can be identified, and if it is relatively stable over time and by geographic regions, it may serve as an external standard for monitoring the quality of reporting of Hib invasive disease (8). Additional studies are needed to establish a baseline rate of nontype b Hi invasive disease that could be used as a surveillance evaluation tool throughout the United States.

References

1. Ward J, Lieberman JM, Cochi SL. Haemophilus influenzae vaccines. In: Plotkin SA, Mortimer EA, eds. Vaccines. 2nd ed. Philadelphia, Pennsylvania: WB Saunders Co., 1994;337-86.

2. CDC. Recommendations for the use of Haemophilus b conjugate vaccines and a combined diphtheria, pertussis, and Haemophilus type b vaccine: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1993;42(no. RR-13):1-15.

3. Bisgard KM, Kao A, Leake J, Strebel PM, Perkins BA, Wharton M. Haemophilus influenzae invasive disease in the United States, 1994-1995: near disappearance of a child vaccine preventable disease. Emerg Infect Dis 1998;4:229-37.

4. Vadheim CM, Greenberg DP, Eriksen E, et al. Eradication of Haemophilus influenzae type b disease in southern California. Arch Pediatr Adolesc Med 1994;148:51-6.

5. Wenger JD, Pierce R, Deaver K, et al. Invasive Haemophilus influenzae disease: a population-based evaluation of the role of capsular polysaccharide serotype. J Infect Dis 1992;165:S34-S35.

6. Urwin G, Krohn JA, Deaver-Robinson K, et al. Invasive disease due to Haemophilus influenzae serotype f: clinical and epidemiologic characteristics in the H. influenzae serotype b vaccine era. Clin Infect Dis 1996;22:1069-76.

7. Standaert SM, Lefkowitz LB, Horan JM, et al. The reporting of communicable disease: a controlled study of Neisseria meningitidis and Haemophilus influenzae infections. Clin Infect Dis 1995;20:30-6.

8. CDC. Manual for surveillance of vaccine-preventable diseases. Atlanta, Georgia: US Department of Health and Human Services, Public Health Service, CDC, 1997.

TABLE 1. Number and rate* of Haemophilus influenzae  type b invasive disease cases among children aged <5 years, by year and
serotype -- California, 1990-1996
===============================================================================================================================
                  1990             1991           1992            1993           1994            1995            1996
              --------------  --------------  ------------    ------------   --------------  --------------   ------------
Serotype       No.     Rate    No.     Rate    No.    Rate     No.    Rate    No.     Rate    No.     Rate    No.    Rate
-------------------------------------------------------------------------------------------------------------------------------
Type b         346   (13.9)    148    (5.8)     55   (2.1)      17   (0.6)     14    (0.5)      7    (0.3)      4   (0.1)
Nontype b+      30    (1.2)     28    (1.1)     28   (1.1)      20   (0.8)      7    (0.3)     21    (0.8)     26   (1.0)
Unknown        134    (5.4)     52    (2.0)     30   (1.2)      13   (0.5)     14    (0.5)     10    (0.4)     10   (0.4)
-------------------------------------------------------------------------------------------------------------------------------
* Per 100,000 children.
+ Includes serotypes a, c, d, e, f, and nontypeable Hi.
===============================================================================================================================

TABLE 2. Number and rate* of nontype b Haemophilus influenzae  invasive disease cases among children aged <5 years, by year and region -- California,
1990-1996
==========================================================================================================================================================
                          1990            1991           1992            1993               1994               1995            1996            Total+
                      -------------   -------------  -------------   -------------   ---------------------  ------------    ------------    --------------
Region                 No.    Rate     No.    Rate    No.     Rate    No.    Rate     No.           Rate    No.     Rate    No.    Rate      No.     Rate
----------------------------------------------------------------------------------------------------------------------------------------------------------
Bay Area                 4   (2.1)       4   (2.0)      3    (1.5)      3   (1.4)       1          (0.5)      4    (2.0)      3   (1.5)       22    (1.5)
Los Angeles Co.         11   (1.4)      12   (1.5)     19    (2.4)      7   (0.9)       6          (0.8)     10    (1.3)     17   (2.1)       82    (1.5)
Remainder of state      15   (0.6)      12   (0.5)      6    (0.2)     10   (0.4)       0            (0)      7    (0.3)      6   (0.2)       56    (0.3)
----------------------------------------------------------------------------------------------------------------------------------------------------------
* Per 100,000 children.
+ Average annual incidence. 
& Alameda, Contra Costa, and San Francisco counties.
==========================================================================================================================================================

TABLE 3. Number* and rate+ of nontype b Haemophilus influenzae  invasive disease cases& among children aged <5 years,
by region and race/ethnicity -- California, 1990-1996
======================================================================================================================
                          Hispanic                 Non-Hispanic Black           Non-Hispanic White      Other @
                      ----------------             -------------------         --------------------  ------------
Region                  No.      Rate                   No.    Rate                  No.     Rate    No.     Rate
Bay Area**               4      (1.3)                     6   (2.4)                   10    (1.5)     2     (0.8)
Los Angeles Co.         44      (1.3)                    14   (2.1)                   10    (0.7)     3     (0.6)
Remainder of state      24      (0.6)                     0   (0.0)                   24    (0.4)     2     (0.2)
----------------------------------------------------------------------------------------------------------------------
*  Number of cases during the 7-year period.
+  Per 100,000 children.
&  Race/ethnicity data were not reported for 17 cases.
@  Numbers for other racial/ethnic groups were too small for meaningful analysis.
** Alameda, Contra Costa, and San Francisco counties.
======================================================================================================================

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