Chapter 128. Pneumococcal Infections (Part 10) ppsx

Chapter 128. Pneumococcal Infections
(Part 10)

Prevention
Capsular Polysaccharide Vaccine
The pneumococcal capsular polysaccharide vaccine administered to adults
since the early 1980s contains 25 µg per dose of capsular polysaccharide from
each of the 23 most prevalent serotypes of S. pneumoniae. Vaccination stimulates
antibody to most serotypes in most recipients. One case-control study showed a
protection rate of 85% lasting ≥5 years in adults <55 years old (Table 128-7). The
level and duration of protection decreased with advancing age. Other studies have
suggested an overall protection rate in the adult population of 50–70%. In high-
risk subgroups (e.g., debilitated elderly persons and individuals with severe
chronic lung disease), vaccine has not been shown conclusively to be effective.
Persons who most need the vaccine because of poor IgG responses (e.g., those
with lymphoma or AIDS) are likely not to respond at all. Nevertheless, the
Advisory Committee on Immunization Practices of the Centers for Disease
Control and Prevention has broadened its recommendations for pneumococcal
vaccination to include all persons >2 years of age who are at substantially
increased risk of developing pneumococcal infection and/or having a serious
complication of such an infection. Perhaps most in need of vaccination are persons
with anatomic or functional asplenia, who are at risk for overwhelming, life-
threatening infections. Others who might fall within these recommendations are
persons who (1) are over the age of 65; (2) have a CSF leak, diabetes mellitus,
alcoholism, cirrhosis, chronic renal insufficiency, chronic pulmonary disease, or
advanced cardiovascular disease; (3) have an immunocompromising condition
associated with increased risk of pneumococcal disease (e.g., multiple myeloma,
lymphoma, Hodgkin's disease, HIV infection, organ transplantation, or chronic
glucocorticoid use); (4) are genetically at increased risk (e.g., Native Americans
and Native Alaskans); or (5) live in environments where outbreaks are particularly
likely to occur (e.g., nursing homes).

Table 128-
7 Protective Efficacy of Polyvalent Pneumococcal
Polysaccharide Vaccine
a



Years since Last
Vaccination
Age,
Years
No. of Subject
Pairs
<3 3–5 >5
<55 125 93 89 85
55–64 149 88 82 75
65–74 213 80 71 58
75–84 188 67 53 32
≥85 133 46 22 –13


a
Results of a case-
control study involving all cases of invasive
pneumococcal disease in Connecticut during 7 years (1984–
1990). Vaccinated
subjects were matched with controls, and the rate of invasive pne
umococcal
disease was related to age and time since vaccination. The data, showing
protective efficacy, suggest that, within 5 years of vaccination, protection rates

decline with age—
i.e., from ~90% in persons <65 years of age to <50% in persons
≥85 years
old. Protection also declines with increasing time from vaccination to
infection, and this decline is more prominent in older patients.
Source:
Data adapted from ED Shapiro et al: N Engl J Med 325:1453,
1991; with permission.
Recommendations regarding revaccination seem somewhat inconsistent. A
single revaccination is advocated for persons over the age of 65 if >5 years have
elapsed since the first vaccination. Since antibody levels decline and there is no
anamnestic response, it seems more reasonable simply to recommend
revaccination at 5-year intervals, especially in persons over the age of 65, who
tend to have almost no adverse reaction to vaccination, and in splenectomized
patients, who are most in need.
Protein-Conjugate Pneumococcal Vaccine
Pneumococcal polysaccharide vaccine is not useful in children <2 years of
age, whose immune system does not respond well to polysaccharide antigens.
Conjugating the polysaccharide to a protein yields an immunogen that is effective
in infants and young children. Initial studies of a protein-conjugate pneumococcal
vaccine consisting of capsular material from the seven serotypes most likely to
cause disease in children (Prevnar) showed a 98% reduction in rates of bacteremia
and meningitis and a 67% reduction in rates of otitis media due to vaccine
serotypes. Since it was marketed in 2000, widespread use of this vaccine has
caused a dramatic decline in the incidence of invasive pneumococcal disease
among infants and children (Fig. 128-4). Colonization rates have also greatly
decreased. In an Alaskan village, rates of carriage of vaccine strains decreased in
children from 55% to 10% and in adults from 15% to 5%. Studies of protein
conjugate vaccines that contain antigen from more than seven common infecting
serotypes are nearing completion, with favorable results.

Figure 128-4


The rate of invasive pneumococcal disease per 100,000 population

(vertical axis) is presented for each year since 2000 (bars
) for different age groups
(horizontal axis). Invasive pneumococcal di
sease is more common at the extremes
of age. The incidence in all age groups has fallen steadily during the past 5 years.
The observed reductions reflect direct effects and indirect ("herd") effects of
widespread use of the 7-valent pneumococcal protein-co
njugate vaccine (PCV7;
see text).
(Adapted from Centers for Disease Control and Prevention, MMWR
54:893, 2005.)
The incidence of invasive pneumococcal disease has also declined among
unvaccinated children and among adults, to whom this vaccine is not even
offered
(Fig. 128-4). This decrease illustrates the "herd effect"—
i.e., the impact of
widespread vaccination on unvaccinated members of the population—
and is
probably attributable to the effects of the conjugate vaccine on nasopharyngeal
carriage of vaccin
e serotypes. Another effect of the widespread use of this vaccine
is the decreasing proportion of all pneumococcal disease that is due to antibiotic-
resistant isolates, a trend that reflects the targeting of antibiotic-
resistant strains by
the vaccine. An

unwanted effect of vaccination has been an increase in infections
caused by serotypes that are not included in the vaccine (replacement serotypes
),
which, in fact, are increasingly expressing antibiotic resistance. Still, as noted
above, the overall incide
nce of pneumococcal disease in all segments of the
population has steadily declined. For further information, the reader is referred to
the American Academy of Pediatrics Red Book Online

().

Further Readings
American Academy of Pediatrics and American Academy of Family
Physicians Clinical Practice Guideline: Diagnosis and management of acute otitis
media. Pediatrics 113:1451, 2004
Centers for Disease Control and Prevention: Direct and indirect effects of
routine vaccination of children with 7-
valent conjugate vaccine on incidence of
invasive pneumococcal disease—United States 1998-2003. MMWR 54:893, 2005

Fedson DS, Musher DM: Pneumococcal vaccine, in Vaccines,
4th ed, SA
Plotkin, EA Mortimer Jr (eds). Philadelphia, Saunders, 2003
Karlowsky JA et al: Factors associated with relative rates of antimicrobial
resistance among Streptococcus pneumoniae in the
United States: Results from the
TRUST Surveillance Program (1998-
2002). Clin Infect Dis 36:963, 2003 [PMID:
12684907]
Lexau CA et al: Changing epidemiology of invasive pneumococcal disease

among older adults in the era of pediatric pneumococcal conjugate
vaccine. JAMA
294:2043, 2005 [PMID: 16249418]
Mandell LA et al: Update of practice guidelines for the management of
community-
acquired pneumonia in immunocompetent adults. Clin Infect Dis
37:1405, 2003 [PMID: 14614663]
Musher DM: Pneumococcal vaccine—
direct and indirect ("herd") effects
(editorial). N Engl J Med 354:1522, 2006 [PMID: 16598050]
———: Streptococcus pneumoniae, in
Principles and Practice of
Infectious Diseases,
6th ed, GL Mandell et al (eds). New York, Churchill
Livingstone, 2004
——— e
t al: A fresh look at the definition of susceptibility of
Streptococcus pneumoniae to beta-
lactam antibiotics. Arch Intern Med 161:2538,
2001
Tuomanen EI et al (eds): The Pneumococcus
. Washington, DC, ASM Press,
2004
Bibliography
Gwaltney JM et al: Acute community-
acquired bacterial sinusitis: The
value of antimicrobial treatment and the natural history. Clin Infect Dis 38:227,
2004 [PMID: 14699455]
Heffron R:
Pneumonia: With Special Reference to Pneumococcus Lobar

Pneumonia. A Commonwealth Fund Book,
© 1939. Reprinted by Harvard
University Press, Cambridge, MA, 1979
Musher DM et al: Diagnostic value of microscopic examination of Gram-
stained sputum and sputum culture in patients with bacteremic pneumococcal
pneumonia. Clin Infect Dis 39:165, 2004 [PMID: 15307023]
——— et al: Bacteremic and nonbacteremic pneumococcal
pneumonia: A
prospective study. Medicine 79:210, 2000
Rahav G et al: Invasive pneumococcal infections: A comparison between
adults and children. Medicine 76:295, 1997 [PMID: 9279335]
Scheld WM et al: Pathophysiology of bacterial meningitis: Mechanism(s
)
of neuronal injury. J Infect Dis 186(Suppl 2):S225, 2002
Shapiro ED et al: The protective efficacy of polyvalent pneumococcal
polysaccharide vaccine. N Engl J Med 325:1453, 1991 [PMID: 1944423]
Sinus and Allergy Health Partnership: Antimicrobial trea
tment guidelines
for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg 130(Suppl):1,
2004
Watanakunakorn Cet al: Adult bacteremic pneumococcal pneumonia in a
community teaching hospital, 1992–
1996. A detailed analysis of 108 cases. Arch
Intern Med 157:1965, 1997 [PMID: 9308508]
Thornsberry C et al: Regional trends in antimicrobial resistance among
clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae
, and
Moraxella catarrhalis
in the United States: Results from the TRUST Surveil
lance

Program, 1999–2000. Clin Infect Dis 34(Suppl 1):S4, 2002
Whitney CG et al: Decline in invasive pneumococcal disease after the
introduction of protein-
polysaccharide conjugate vaccine. N Engl J Med 348:1737,
2003 [PMID: 12724479]