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Chapter 17 : Immunodeficiency and Invasive Pneumococcal Disease

Authors: Edward N. Janoff1, Jeffrey B. Rubins2
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Affiliations: 1: Mucosal and Vaccine Research Center and Infectious Disease Section, Veterans Affairs Medical Center, University of Minnesota School of Medicine, Minneapolis, MN 55417; 2: Mucosal and Vaccine Research Center and Pulmonary Section, Veterans Affairs Medical Center, University of Minnesota School of Medicine, Minneapolis, MN 55417
Content Type: Monograph
Publication Year: 2004

Category: Bacterial Pathogenesis; Clinical Microbiology

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Abstract:

This chapter focuses on the rates and clinical manifestations of invasive pneumococcal disease in patients at high risk, on proposed mechanisms of impaired defense, as well as on strategies for prevention of invasive pneumococcal disease in these groups. It describes how individual host defects may each contribute independently to the increased risk of invasive disease, and observes that the potential number of immunological risk factors is greatest and rates of invasive pneumococcal disease are highest among HIV type 1 (HIV-1). The extremely high rates of invasive pneumococcal disease in apparently otherwise healthy children suggest the presence of specific defects related to this class of organisms. HIV-1-associated immunodeficiency, rather than behavioral (e.g., smoking), medical (e.g., splenectomy, liver disease), environmental (e.g., seasonality), or bacteriological features (serotypes or colonization), appears to underlie the remarkable rates of disease in this population. Despite the many fold-increased rates of pneumonia and, particularly, invasive pneumococcal disease during HIV-1 infection, no specific overriding risk or target for intervention has been confirmed. The protection provided by both the 23-valent polysaccharide vaccine in adults and the 7-valent conjugate vaccine in children is most apparent and consistent against invasive pneumococcal disease. Specific immune defects can be identified for particular groups at higher risk of invasive pneumococcal infection, whereas more generalized deficiencies in immune and nonimmune defenses underlie bacteremia in others. The development of newer vaccines which are more universally immunogenic and which combat mucosal disease more effectively is an important goal in preventing pneumococcal disease in the immunocompromised host.

Citation: Janoff E, Rubins J. 2004. Immunodeficiency and Invasive Pneumococcal Disease, p 252-280. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch17

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Immunodeficiency and Invasive Pneumococcal Disease
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Citation: Janoff E, Rubins J. 2004. Immunodeficiency and Invasive Pneumococcal Disease, p 252-280. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch17
/content/10.1128/9781555816537.chap17.fig17-1
FIGURE 1

Rates of invasive pneumococcal disease by risk group and age (all ages versus those in children <2 years of age [yo]). Some rates are approximated from several studies.

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10.1128/9781555816537/fig17-1.gif
Image of FIGURE 1
FIGURE 1

Rates of invasive pneumococcal disease by risk group and age (all ages versus those in children <2 years of age [yo]). Some rates are approximated from several studies.

Citation: Janoff E, Rubins J. 2004. Immunodeficiency and Invasive Pneumococcal Disease, p 252-280. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch17
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FIGURE 2

Association of case-fatality rates among 15,860 patients (ages 2 to 104 years) with invasive pneumococcal disease by age with and without U.S. Advisory Committee of Immunization Practices indications for pneumococcal vaccine in nine areas of the United States, 1995 to 1998. Overall case-fatality rates were 11.7% among those with indications (“Yes”) and 4.0% among those without indications (“No”) ( ).

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10.1128/9781555816537/fig17-2.gif
Image of FIGURE 2
FIGURE 2

Association of case-fatality rates among 15,860 patients (ages 2 to 104 years) with invasive pneumococcal disease by age with and without U.S. Advisory Committee of Immunization Practices indications for pneumococcal vaccine in nine areas of the United States, 1995 to 1998. Overall case-fatality rates were 11.7% among those with indications (“Yes”) and 4.0% among those without indications (“No”) ( ).

Citation: Janoff E, Rubins J. 2004. Immunodeficiency and Invasive Pneumococcal Disease, p 252-280. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch17
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FIGURE 3

Relative risk of death from invasive pneumococcal disease among 3,049 hospitalized patients with bacteremic pneumococcal pneumonia and specific underlying illnesses in nine cities in the United States and Canada. Overall case-fatality rates were 12% (range, 6 to 27%) ( ). Heme., hematologic; immunosupp., immunosuppressive; CHF, congestive heart failure.

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10.1128/9781555816537/fig17-3.gif
Image of FIGURE 3
FIGURE 3

Relative risk of death from invasive pneumococcal disease among 3,049 hospitalized patients with bacteremic pneumococcal pneumonia and specific underlying illnesses in nine cities in the United States and Canada. Overall case-fatality rates were 12% (range, 6 to 27%) ( ). Heme., hematologic; immunosupp., immunosuppressive; CHF, congestive heart failure.

Citation: Janoff E, Rubins J. 2004. Immunodeficiency and Invasive Pneumococcal Disease, p 252-280. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch17
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FIGURE 4

Mechanisms which may impair killing of

10.1128/9781555816537/fig17-4_thmb.gif
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Image of FIGURE 4
FIGURE 4

Mechanisms which may impair killing of

Citation: Janoff E, Rubins J. 2004. Immunodeficiency and Invasive Pneumococcal Disease, p 252-280. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch17
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FIGURE 5

Effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in adults >65 years of age (Seattle, Wash.) in a retrospective cohort study monitoring 127,180 patient years (84,203 after immunization), including 61 cases of invasive disease. Compromised patients (those with cancer, immunosuppressive therapy, chronic renal failure, and liver failure) comprised 19% of subjects and 26% of patients with invasive disease. Values for immunocompetent patients with chronic lung disease were unadjusted for influenza virus vaccine and other factors. #0.06 for protection compared with unimmunized adults in the same group ( ). COPD, chronic obstructive pulmonary disease.

10.1128/9781555816537/fig17-5_thmb.gif
10.1128/9781555816537/fig17-5.gif
Image of FIGURE 5
FIGURE 5

Effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in adults >65 years of age (Seattle, Wash.) in a retrospective cohort study monitoring 127,180 patient years (84,203 after immunization), including 61 cases of invasive disease. Compromised patients (those with cancer, immunosuppressive therapy, chronic renal failure, and liver failure) comprised 19% of subjects and 26% of patients with invasive disease. Values for immunocompetent patients with chronic lung disease were unadjusted for influenza virus vaccine and other factors. #0.06 for protection compared with unimmunized adults in the same group ( ). COPD, chronic obstructive pulmonary disease.

Citation: Janoff E, Rubins J. 2004. Immunodeficiency and Invasive Pneumococcal Disease, p 252-280. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch17
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Tables

Immunodeficiency and Invasive Pneumococcal Disease
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Citation: Janoff E, Rubins J. 2004. Immunodeficiency and Invasive Pneumococcal Disease, p 252-280. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch17
/content/10.1128/9781555816537.chap17.tab17-1
TABLE 1

Factors which may be associated with increased rates or severity of invasive infection in the compromised host

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10.1128/9781555816537/tab17-1.gif
Generic image for table
TABLE 1

Factors which may be associated with increased rates or severity of invasive infection in the compromised host

Citation: Janoff E, Rubins J. 2004. Immunodeficiency and Invasive Pneumococcal Disease, p 252-280. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch17
/content/10.1128/9781555816537.chap17.tab17-2
TABLE 2

Immunocompromised persons for whom pneumococcal vaccine is recommended

10.1128/9781555816537/tab17-2_thmb.gif
10.1128/9781555816537/tab17-2.gif
Generic image for table
TABLE 2

Immunocompromised persons for whom pneumococcal vaccine is recommended

Citation: Janoff E, Rubins J. 2004. Immunodeficiency and Invasive Pneumococcal Disease, p 252-280. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch17