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

Brendan Flannery, PhD; Richard T. Heffernan, MPH; Lee H. Harrison, MD; Susan M. Ray, MD; Arthur L. Reingold, MD; James Hadler, MD, MPH; William Schaffner, MD; Ruth Lynfield, MD; Ann R. Thomas, MD, MPH; Jianmin Li, DPE; Michael Campsmith, DDS, MPH; Cynthia G. Whitney, MD, MPH; and Anne Schuchat, MD
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From National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Connecticut Emerging Infections Program, Hartford, Connecticut; Maryland Emerging Infections Program and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Emory University School of Medicine and the Veterans Affairs Medical Center, Atlanta, Georgia; School of Public Health, University of California, Berkeley, California; Vanderbilt Medical Center, Nashville, Tennessee; Minnesota Emerging Infections Program, Minnesota Department of Health, Minneapolis, Minnesota; Oregon Emerging Infections Program, Department of Human Services, Portland, Oregon; and HIV Incidence and Case Surveillance Branch, Division of HIV/AIDS Prevention, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.

Note: This paper was presented in part at the 4th International Symposium on Pneumococci and Pneumococcal Diseases, Helsinki, Finland, 9 to 13 May 2004 (abstract EPI-05), and at the 42nd Annual Meeting of the Infectious Diseases Society of America, Boston, Massachusetts, 30 September to 3 October 2004 (abstract 746).

Acknowledgments: The authors thank the study personnel from the following institutions: Centers for Disease Control and Prevention; the Active Bacterial Core surveillance sites; Minnesota Department of Health; and the University of Texas Health Science Center. They also thank the AIDS surveillance officers.

Grant Support: By the Emerging Infections Program of the Centers for Disease Control and Prevention.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Brendan Flannery, PhD, Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS C-23, Atlanta, GA 30333; e-mail, bflannery@cdc.gov.

Current Author Addresses: Drs. Flannery, Campsmith, Li, Whitney, and Schuchat: Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333.

Mr. Heffernan: Connecticut Emerging Infections Program, 410 Capital Avenue, Hartford, CT 06134.

Dr. Harrison: Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205.

Dr. Ray: Emory University School of Medicine, 69 Jesse Hill Jr. Drive SE, Atlanta, GA 30303.

Dr. Reingold: University of California, Berkeley, 140 Warren, Berkeley, CA 94720-7360.

Dr. Hadler: Connecticut Department of Public Health, 410 Capital Avenue, MS 11 FDS, Hartford, CT 06134-0308.

Dr. Schaffner: Vanderbilt University Medical School, A-1124 MCN, Nashville, TN 37232.

Dr. Lynfield: Minnesota Department of Health, 717 Delaware Street SE, Minneapolis, MN 55414.

Dr. Thomas: Oregon Department of Human Services, 800 NE Oregon Street, Portland, OR 97212.

Author Contributions: Conception and design: B. Flannery, L.H. Harrison, A.L. Reingold, J. Hadler, A.R. Thomas, A. Schuchat.

Analysis and interpretation of the data: B. Flannery, R.T. Heffernan, A.L. Reingold, A.R. Thomas, J. Li, C.G. Whitney, A. Schuchat.

Drafting of the article: B. Flannery, A.L. Reingold, M. Campsmith.

Critical revision of the article for important intellectual content: L.H. Harrison, S.M. Ray, A.L. Reingold, J. Hadler, W. Schaffner, R. Lynfield, A.R. Thomas, J. Li, M. Campsmith, C.G. Whitney, A. Schuchat.

Final approval of the article: B. Flannery, L.H. Harrison, S.M. Ray, A.L. Reingold, J. Hadler, W. Schaffner, R. Lynfield, A.R. Thomas, J. Li, M. Campsmith, C.G. Whitney, A. Schuchat.

Provision of study materials or patients: J. Hadler, W. Schaffner, R. Lynfield.

Statistical expertise: J. Li.

Obtaining of funding: C.G. Whitney, A. Schuchat.

Administrative, technical, or logistic support: A.L. Reingold, W. Schaffner, R. Lynfield, C.G. Whitney.

Collection and assembly of data: R.T. Heffernan, S.M. Ray, J. Hadler, W. Schaffner, A.R. Thomas.

Ann Intern Med. 2006;144(1):1-9. doi:10.7326/0003-4819-144-1-200601030-00004
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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 Minneapolis–St. 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).

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Figure 1.
Surveillance population and comparison groups for cases of invasive pneumococcal disease in persons with and without HIV infection or AIDS.

Population and number of persons living with or without AIDS in the surveillance areas are estimates for 2003. The number of cases of invasive pneumococcal disease and isolates serotyped represents totals during the 6-year surveillance period.

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Figure 2.
Trends in the number of cases of invasive pneumococcal disease (IPD) in adults with HIV infection per 100 000 persons 18 to 64 years of age living with AIDS in 7 Active Bacterial Core surveillance areas.GA

Active Bacterial Core surveillance areas are labeled according to the state in which the surveillance counties are located. Data from the Georgia ( ) surveillance area do not include cases in 1998. The year of conjugate vaccine licensure for use in infants (2000) is indicated by arrows. CA = California; CT = Connecticut; MD = Maryland; MN = Minnesota; OR = Oregon; TN = Tennessee.

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Figure 3.
Trends in the number of cases of invasive pneumococcal disease (IPD) in adults with and without HIV infection per 100 000 persons 18 to 64 years of age with and without AIDS for all pneumococcal serotypes or groups of serotypes.

Data are from Active Bacterial Core surveillance and AIDS surveillance data from 1998 through 2003. Data for 1998 do not include the Georgia surveillance area. The number of adults without AIDS in the surveillance areas was calculated by subtracting the number of persons with AIDS from the population of adults 18 to 64 years of age according to U.S. census data. Bars represent 95% CIs based on serotyping of pneumococcal isolates from 1833 of 2013 cases in adults with HIV infection and 5866 of 6569 cases in adults without HIV infection.

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Figure 4.
Difference in serotype-specific ratio of cases of invasive pneumococcal disease (IPD) among HIV-infected adults per 100 000 persons living with AIDS in 2001, 2002, and 2003 compared with baseline (1998 to 1999 average).

Data are shown for conjugate vaccine serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), the 3 most prevalent vaccine-related serotypes (6A, 19A, and 9N), and a subset of the most prevalent nonvaccine serotypes (3, 11A, 12F, and 22F) or serotypes included in the pneumococcal polysaccharide vaccine (1, 5, 7F, 15B, and 33F).

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Increased Prevalence of Pediatric Pneumococcal
Posted on February 22, 2006
Lawrence A. Cone
Eisenhower Medical Center
Conflict of Interest: None Declared

Increased Prevalence of Pediatric Pneumococcal Serotypes in Elderly Adults:

With the introduction of the 23-valent pneumococcal vaccine in adults and the 7-valent conjugated vaccine in children a significant reduction of pneumococcal disease in the developed world has ensued. The 2 vaccines contain some different serotypes characteristic of each age group's prevalence. Feikin et al (1) recently reported an increased prevalence of pediatric serotypes 6B, 9V, 14, 19F and 23F in elderly adults (>65 years). From 1998-1999 invasive pneumococcal disease described as isolation of Streptococcus pneumoniae from a normally sterile site, such as blood or CSF was studied in 2987 isolates. The data showed that the percentage of adults with pediatric serotypes recently rose from 33% in persons aged 35-64 to 44% in patients 65-74, 47% in those 75-84 and to 51% of patients over 85 years.

Laxau et al (2) described a reduction of invasive pneumococcal disease among adults age 50 years or older and noted that the incidence of disease caused by the 7 conjugate vaccine serotypes declined 55%. Most recently Flannery et al (3) also noted an overall decrease among HIV-infected adults 18 to 64 years of age living with AIDS since the introduction of the pediatric conjugate vaccine.

We have since 1998 serotyped all pneumococci isolated from blood, CNS, sinuses and middle ear of 34 adults over 30 years of age seen in the clinical practice of a single infectious diseases specialist to initially evaluate what percentage of those infected were immunized with 23-valent vaccine. Those data revealed that only a single person with pneumococcal disease had previously been immunized. More recently we have retrospectively examined the serotypes in these same patients and found that 4 were serotype 6B, 2 were serotype 9V, 1 was serotype 14, 6 were 19F, and 8 were 23F. In total, 21 patients of 34 (62%) were infected by these pediatric serotypes, slightly higher than 55% noted by Feiken in the his study. However, in addition to the above we also found serotype 18C in 3 patients but did not isolate serotype 4 in anyone. Thus 6 of 7 pediatric serotypes were isolated in 24 0f 34 patients (70%) in our study group. In the remaining 10 patients, 5 were 11, 2 were 29 and 1 each were 3, 16 and 44. Thus, 3 of 34 (11%) serotypes isolated in our group of patients were not included in either the 23- or 7- valent vaccines.

Twenty six out of 34 patients (76%) were over 65 years and 23 (65%) were over 75 years of age and 9 (30%) were older than 85 years. Seven of 9 patients over the age of 85 (71%) grew out pediatric serotypes, while 16 of 23 (69%) over 75 and 17 of 26 (65%) over 65 years of age revealed pediatric serotypes. Only 2 patients died as a result of pneumococcal infection.

While our numbers are small, and the data reflect a single physician's experience, they confirm Feikin's findings that elderly individuals are more susceptible to pediatric serotypes of Streptococcus pneumoniae. These findings stand in contrast to those of Lexau (2) and Flannery (3) who both showed a decrease of 7 conjugate vaccine serotypes of 55% and 62% respectively in the elderly and those with HIV infection. Both authors note an increase an increase in non- conjugate vaccine containing strains which amounted to only 11% in our series.

Since, only a single patient of 34 in the group received 23-valent pneumococcal vaccine, it would imply that failing natural immunity leads to recurrence of pediatric strains of pneumococci in the elderly and that pediatric conjugate vaccine serotypes continue to be the dominant organisms.


1. Feiken DR, Klugman KP, Facklam RR, Zell ER,Schuchat A, Whitney CG, for the\Active Bacterial Core surveillance/Emerging Infections Program. Increased prevalence of pediatric pneumococcal serotypes in elderly adults. Clin Infect Dis 2005;41:461-7. 2. Lexau CA, Lynfield R, Danila R, et al. Changing epidemiology of invasive pneumococcal disease among older adults in the era of peditaric pneumococcal conjugate vaccine. JAMA 2005;294:2043-51. 3. Flannery B, Hefferman RT, Harrison LH, et al. Changes in invasive pneumococcal disease among HIV- infected adults living in the era of childhood pneumococcal immunization. Ann Intern Med 2006;144:1- 9.

Lawrence A. Cone MD, FACP, 1,2

Ariella E. Morrow 1,2

Radhika Gade-Andavolu, PhD 2

Eisenhower Medical Center, 1

Genetic Research Institute of the Desert 2

Rancho Mirage, CA 92270

Conflict of Interest:

None declared

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