Changes in Invasive Pneumococcal Disease among HIV-Infected Adults Living in the Era of Childhood Pneumococcal Immunization

Context Routine pneumococcal conjugate vaccination for infants began in 2000. Its use markedly decreased invasive pneumococcal disease among children, but did it influence rates of disease among HIV-infected adults? Contribution Between 1998 and 2003, invasive pneumococcal disease among adults infected with HIV living in 7 surveillance areas in the United States decreased from 1127 to 919 cases per 100000 adults with AIDS. Disease caused by serotypes in the vaccine decreased 62%, whereas disease caused by nonvaccine serotypes increased 44%. Implications Indirect evidence suggests that pediatric vaccine use is associated with a decreased incidence of pneumococcal disease among HIV-infected adults. The Editors Apneumococcal conjugate vaccine containing 7 serotypes was recommended for routine use in infants in the United States beginning in 2000 (1). Widespread use of the vaccine caused steep declines in invasive pneumococcal disease among young children (2-4) and was associated with decreased disease attributable to vaccine serotypes among adults, for whom the vaccine is not licensed (3). Effects on disease among unvaccinated persons, often called herd effects, are presumably due to reduced transmission from immunized children. Because 90 pneumococcal serotypes cause human disease, there were concerns that the introduction of a conjugate vaccine containing 7 serotypes would lead to increased disease caused by nonvaccine-type organisms, a phenomenon called serotype replacement. Early postintroduction surveillance showed limited serotype replacement disease in the target age group, with no consistent trend toward increasing disease caused by nonvaccine serotypes among adults (3). To our knowledge, the effects of pediatric use of pneumococcal conjugate vaccine on immunocompromised adults, including those infected with HIV, have not previously been investigated. Persons infected with HIV are particularly susceptible to invasive pneumococcal disease, with a 50- to 100-fold higher incidence than the general U.S. population (5, 6). After the introduction of highly active antiretroviral therapy in the mid-1990s, surveillance in 3 geographic areas of the United States showed a 50% reduction in invasive pneumococcal disease among persons with AIDS (7). However, the incidence of pneumococcal disease among persons with AIDS leveled off by mid-1997 and continued to be approximately 35-fold higher in persons with AIDS than in those without HIV infection or AIDS through 2000 (7). We investigated trends in invasive pneumococcal disease among HIV-infected adults to document changes since the use of pneumococcal conjugate vaccine became widespread in children. Methods Active, laboratory-based surveillance for cases of invasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from a normally sterile site, was conducted through Active Bacterial Core surveillance of the Emerging Infections Program network (8). We included cases diagnosed between 1 January 1998 and 31 December 2003 among surveillance-area residents who were 18 to 64 years of age. We limited the analyses to 7 surveillance sites, including California (San Francisco County), Connecticut (entire state), Georgia (8-county Atlanta metropolitan area), Maryland (City of Baltimore and 5 neighboring counties), Minnesota (7-county MinneapolisSt. Paul metropolitan area), Oregon (3-county Portland metropolitan area), and Tennessee (Davidson, Hamilton, Knox, Shelby, and Williamson Counties). Information was systematically collected on the HIV status of case-patients at these sites. In 2003, the resident adult population in these 7 areas was 10.8 million (4.5% of the U.S. population between 18 and 64 years of age) (9) and included 9.5% of the estimated number of adults living with AIDS in the United States (10). Surveillance officers routinely contacted all clinical laboratories in their areas to identify cases and conducted audits of laboratory records to ensure complete ascertainment. Recurrent episodes, defined as invasive pneumococcal disease occurring more than 7 days after a previous case in a surveillance-area resident, were included in this analysis. The race and ethnicity as well as HIV status or previous AIDS diagnosis of case-patients were extracted from medical records by using standardized case report forms. Surveillance in Georgia did not prospectively collect information on HIV infection or AIDS for case-patients until 2000; for case-patients in 1999, we retrospectively reviewed medical records to collect this information. Analyses for 1998 exclude Georgia. Pneumococcal isolates were sent to reference laboratories at the Minnesota Department of Health (for case-patients from Minnesota), the Centers for Disease Control and Prevention, or the University of Texas Health Science Center at San Antonio for susceptibility testing by broth microdilution using standard protocols and quality control procedures (3, 11). Nonsusceptible isolates were defined as those with minimum inhibitory concentrations classified as intermediate or resistant for the antibiotic tested, according to the 2002 definitions of the National Committee for Clinical Laboratory Standards (12). Serotyping by the Quellung reaction was done at the Centers for Disease Control and Prevention or the Minnesota Department of Health (Minnesota cases only). The study personnel are listed in the Appendix. AIDS Surveillance Data For aggregated counties in each of the 7 surveillance areas, we obtained the estimated number of persons 18 to 64 years of age living with AIDS (as outlined in the 1993 Centers for Disease Control and Prevention case definition) (13), according to race and ethnicity and sex, on 30 June of each year. We obtained this number from the Centers for Disease Control and Prevention with permission from state AIDS surveillance coordinators. These estimates are derived from case report data by using a maximum likelihood method to account for delays in reporting new AIDS diagnoses and deaths among persons with AIDS (10), 14. Estimates of the number of persons living with HIV infection, not AIDS, were unavailable from 5 sites (California, Connecticut, Georgia, Maryland, and Oregon) that accounted for more than 80% of adults living with AIDS in the surveillance areas. Statistical Analysis For each surveillance area, we calculated the annual incidence rates of invasive pneumococcal disease among persons with AIDS as follows. We divided the number of cases of pneumococcal disease diagnosed during the calendar year among patients documented as having AIDS by the estimated number of persons 18 to 64 years of age living with AIDS. To calculate incidence among adults not infected with HIV, we used cases of pneumococcal disease in persons without documented HIV infection or AIDS in the numerator. For the denominator, we subtracted the number of adults living with AIDS from the total population of persons 18 to 64 years of age who lived in the surveillance areas; this number was obtained from the U.S. Census Bureau (9). As a proxy for the incidence rates among HIV-infected adults, we calculated a ratio of cases of pneumococcal disease among adults with HIV infection or AIDS to the estimated adult population living with AIDS, multiplied by 100000. Ratios for specific race and ethnicity categories were adjusted, assuming that the distribution of race and ethnicity for case-patients missing these data (3% of cases of pneumococcal disease) was the same as the sex-specific distribution of case-patients within each surveillance area for which race and ethnicity data were available. We adjusted data for selected serotypes (that is, conjugate vaccine or nonvaccine serotypes) or antibiotic-resistant pneumococci on the basis of the percentage of cases with isolates available for testing, assuming the distribution of cases missing serotype (9%) or antibiotic susceptibility data (7%) was the same as that of cases with isolates tested across all sites. We calculated 95% CIs for these ratios by using the standard error of the proportion of cases with isolates tested. To assess changes in the ratio of the number of cases of pneumococcal disease among HIV-infected adults to the number of adults living with AIDS before and after the introduction of the pneumococcal conjugate vaccine for children, we calculated percentage change and exact 95% CIs by comparing the average ratio during 1998 and 1999, called the baseline period, with that during 2002 or 2003. For differences or linear trends in proportions of cases or pneumococcal isolates, we calculated P values using chi-square tests; P values less than 0.05 indicated statistical significance. Statistical analyses were conducted with SAS, version 9.0 for Windows (SAS Institute, Inc., Cary, North Carolina), and EpiInfo, version 6.0 (Centers for Disease Control and Prevention, Atlanta, Georgia). Role of the Funding Source The funding source had no role in the design, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Results From 1998 through 2003, 8582 cases of invasive pneumococcal disease occurred in surveillance-area residents who were 18 to 64 years of age. Of these, 2013 cases occurred in persons with HIV infection or AIDS (Figure 1). When the latter group was excluded, the annual incidence rate in persons who were 18 to 64 years of age during the 1998 to 1999 baseline period averaged 13 cases per 100000 adults without AIDS. By 2003, this rate decreased to 9 cases per 100000, a decrease of 30% (95% CI, 25% to 35%; P< 0.001). Of the 2013 cases of pneumococcal disease among HIV-infected adults, 759 (38%) occurred among adults documented as having AIDS. Based on estimates of the number of adults living with AIDS in the surveillance areas, the incidence of invasive pneumococcal disease among persons with AIDS during the baseline period was 441 cases per 100000 adults. In 2002, the rate was 360 cases per 10000