Streptococci
Important Properties
Streptococci are spherical gram-positive cocci arranged in chains or pairs (Figure
1). All streptococci are catalase-negative, whereas staphylococci are catalase-
positive.
FIGURE 1 Streptococcus pyogenes—Gram stain. Arrow points to a long chain of gram-positive cocci
- One of the most important characteristics for identification of streptococci is
the type of hemolysis (Figure 2):
(1) α-Hemolytic streptococci form a green zone around their colonies as a result of
incomplete lysis of red blood cells in the agar. The green color is formed when
hydrogen peroxide produced by the bacteria oxidizes hemoglobin (red color) to
biliverdin (green color).
(2) β-Hemolytic streptococci form a clear zone around their colonies because
complete lysis of the red cells occurs. β-Hemolysis is due to the production of
enzymes (hemolysins) called streptolysin O and streptolysin S
(3) Some streptococci are nonhemolytic (γ-hemolysis).
FIGURE 2 : α-Hemolysis and β-hemolysis on blood agar—Short arrow points to an α-hemolytic colony,
probably a viridans group streptococcus. Long arrow points to a β-hemolytic colony, probably
Streptococcus pyogenes. The specimen was a throat swab taken from a person with a sore throat
There are two important antigens of β-hemolytic streptococci:
(1) C carbohydrate determines the group of β-hemolytic streptococci. It is located
in the cell wall, and its specificity is determined by an amino sugar.
(2) M protein is the most important virulence factor and determines the type of
group A β-hemolytic streptococci. It protrudes from the outer surface of the cell
and interferes with ingestion by phagocytes (i.e., it is antiphagocytic). Antibody to
M protein provides type-specific immunity. There are approximately 80 serotypes
based on the M protein, which explains why multiple infections with S. pyogenes
can occur. Strains of S. pyogenes that produce certain M protein types are
rheumatogenic (i.e., cause primarily rheumatic fever), whereas strains of S.
pyogenes that produce other M protein types are nephritogenic (i.e., cause
primarily acute glomerulonephritis). Although M protein is the main
antiphagocytic component of S. pyogenes, the organism also has a polysaccharide
capsule that plays a role in retarding phagocytosis.
Classification of Streptococci
A- β-Hemolytic Streptococci
These are arranged into groups A–U (known as Lancefield groups) on the basis of
antigenic differences in C carbohydrate. In the clinical laboratory, the group is
determined by precipitin tests with specific antisera or by immunofluorescence.
1- Group A streptococci (S. pyogenes) are one of the most important
human pathogens. They are the most frequent bacterial cause of
pharyngitis and a very common cause of skin infections. They adhere to
pharyngeal epithelium via pili composed of lipoteichoic acid and M
protein. Many strains have a hyaluronic acid capsule that is
antiphagocytic. The growth of S. pyogenes on agar plates in the
laboratory is inhibited by the antibiotic bacitracin, an important
diagnostic criterion (figure 3)
FIGURE 3: Bacitracin test—Arrow points to zone of inhibition of growth of group A streptococci
(Streptococcus pyogenes) caused by bacitracin that has diffused from the disk labeled A. Upper half of
blood agar plate shows β-hemolysis caused by group A streptococci, except in the region around the
bacitracin disk. Lower half of blood agar plate shows β-hemolysis caused by group B streptococci
(Streptococcus agalactiae), and there is no zone of inhibition around the bacitracin disk.
2- Group B streptococci (S. agalactiae) colonize the genital tract of some
women and can cause neonatal meningitis and sepsis. They are usually
bacitracin-resistant. They hydrolyze (break down) hippurate, an
important diagnostic criterion.
3- Group D streptococci include enterococci (e.g., E. faecalis and
Enterococcus faecium) and nonenterococci (e.g., S. bovis).
· Enterococci are members of the normal flora of the colon and are
noted for their ability to cause urinary, biliary, and cardiovascular
infections. They are very hardy organisms; they can grow in
hypertonic (6.5%) saline or in bile and are not killed by penicillin G.
As a result, a synergistic combination of penicillin and an
aminoglycoside (e.g., gentamicin) is required to kill enterococci.
Vancomycin can also be used, but vancomycin-resistant enterococci
(VRE) have emerged and become an important and much feared
cause of life-threatening nosocomial infections. More strains of E.
faecium are vancomycin resistant than are strains of E. faecalis.
· Nonenterococcal group D streptococci, such as S. bovis, can cause
similar infections but are much less hardy organisms (e.g., they are
inhibited by 6.5% NaCl and killed by penicillin G). Note that the
hemolytic reaction of group D streptococci is variable: most are α-
hemolytic, but some are β-hemolytic, and others are nonhemolytic.
Groups C, E, F, G, H, and K–U streptococci infrequently cause
human disease.
B- Non–β-Hemolytic Streptococci
Some streptococci produce no hemolysis; others produce α-hemolysis. The
principal α-hemolytic organisms are
· S. pneumoniae (pneumococci)
· Viridans group of streptococci (e.g., Streptococcus mitis, Streptococcus
sanguinis, and Streptococcus mutans).
Pneumococci and viridans streptococci are distinguished in the clinical laboratory
by two main criteria:
(1) the growth of pneumococci is inhibited by optochin, whereas the growth of
viridans streptococci is not inhibited; and
(2) colonies of pneumococci dissolve when exposed to bile (bile-soluble), whereas
colonies of viridans streptococci do not dissolve.
Viridans streptococci are part of the normal flora of the human pharynx and
intermittently reach the bloodstream to cause infective endocarditis. S. mutans
synthesizes polysaccharides (dextrans) that are found in dental plaque and lead to
dental caries. Streptococcus intermedius and Streptococcus anginosus (also known
as the S. anginosus-milleri group) are usually α-hemolytic or nonhemolytic, but
some isolates are β-hemolytic. They are found primarily in the mouth and colon.
Peptostreptococci
These grow under anaerobic or microaerophilic conditions and produce variable
hemolysis. Peptostreptococci are members of the normal flora of the gut, mouth,
and female genital tract and participate in mixed anaerobic infections. The term
mixed anaerobic infections refers to the fact that these infections are caused by
multiple bacteria, some of which are anaerobes and others are facultatives. For
example, peptostreptococci and viridans streptococci, both members of the oral
flora, are often found in brain abscesses following dental surgery.
Peptostreptococcus magnus and Peptostreptococcus anaerobius are the species
frequently isolated from clinical specimens.
Transmission
Most streptococci are part of the normal flora of the human throat, skin, and
intestines but produce disease when they gain access to tissues or blood.
Viridans streptococci and S. pneumoniae are found chiefly in the oropharynx; S.
pyogenes is found on the skin and in the oropharynx in small numbers; S.
agalactiae occurs in the vagina and colon; and both the enterococci and anaerobic
streptococci are located in the colon.
Pathogenesis
Group A streptococci (S. pyogenes) cause disease by three mechanisms:
(1) pyogenic inflammation, which is induced locally at the site of the
organisms in tissue;
(2) exotoxin production, which can cause widespread systemic
symptoms in areas of the body where there are no organisms; and
(3) immunologic, which occurs when antibody against a component
of the organism cross-reacts with normal tissue or forms immune
complexes that damage normal tissue . The immunologic reactions
cause inflammation (e.g., the inflamed joints of rheumatic fever),
but there are no organisms in the lesions.
The M protein of S. pyogenes is its most important antiphagocytic factor, but its
capsule, composed of hyaluronic acid, is also antiphagocytic. Antibodies are not
formed against the capsule because hyaluronic acid is a normal component of the
body and humans are tolerant to it.
Group A streptococci produce three important inflammation-related enzymes:
(1) Hyaluronidase degrades hyaluronic acid, which is the ground substance of
subcutaneous tissue. Hyaluronidase is known as spreading factor because it
facilitates the rapid spread of S. pyogenes in skin infections (cellulitis).
(2) Streptokinase (fibrinolysin) activates plasminogen to form plasmin, which
dissolves fibrin in clots, thrombi, and emboli. It can be used to lyse thrombi in the
coronary arteries of heart attack patients.
(3) DNase (streptodornase) degrades DNA in exudates or necrotic tissue.
Antibody to DNase B develops during pyoderma; this can be used for diagnostic
purposes. Streptokinase–streptodornase mixtures applied as a skin test give a
positive reaction in most adults, indicating normal cell-mediated immunity.
In addition, group A streptococci produce five important toxins and
hemolysins:
(1) Erythrogenic toxin causes the rash of scarlet fever. Its mechanism of action is
similar to that of the TSST of S. aureus (i.e., it acts as a superantigen;). It is
produced only by certain strains of S. pyogenes lysogenized by a bacteriophage
carrying the gene for the toxin. The injection of a skin test dose of erythrogenic
toxin (Dick test) gives a positive result in persons lacking antitoxin (i.e.,
susceptible persons).
(2) Streptolysin O is a hemolysin that is inactivated by oxidation (oxygenlabile). It
causes β-hemolysis only when colonies grow under the surface of a blood agar
plate. It is antigenic, and antibody to it (ASO) develops after group A streptococcal
infections. The titer of ASO antibody can be important in the diagnosis of
rheumatic fever.
(3) Streptolysin S is a hemolysin that is not inactivated by oxygen (oxygenstable).
It is not antigenic but is responsible for β-hemolysis when colonies grow on the
surface of a blood agar plate.
(4) Pyrogenic exotoxin A is the toxin responsible for most cases of streptococcal
toxic shock syndrome. It has the same mode of action as does staphylococcal
TSST (i.e., it is a superantigen that causes the release of large amounts of cytokines
from helper T cells and macrophages).
(5) Exotoxin B is a protease that rapidly destroys tissue and is produced in large
amounts by the strains of S. pyogenes, the so-called ―flesh-eating‖ streptococci that
cause necrotizing fasciitis.
Pathogenesis by group B streptococci (S. agalactiae) is based on the ability of the
organism to induce an inflammatory response. However, unlike S. pyogenes, no
cytotoxic enzymes or exotoxins have been described, and there is no evidence for
any immunologically induced disease. Group B streptococci have a polysaccharide
capsule that is antiphagocytic, and anticapsular antibody is protective.
Pathogenesis by S. pneumoniae and the viridans streptococci is uncertain, as
no exotoxins or tissue-destructive enzymes have been demonstrated. The main
virulence factor of S. pneumoniae is its antiphagocytic polysaccharide capsule.
Many of the strains of viridans streptococci that cause endocarditis produce a
glycocalyx that enables the organism to adhere to the heart valve.
Clinical features: see Table 1.
Table 1: Clinical diseases caused by streptococci.
Laboratory Diagnosis
A- Microbiologic
Gram-stained smears are useless in streptococcal pharyngitis because viridans
streptococci are members of the normal flora and cannot be visually distinguished
from the pathogenic S. pyogenes. However, stained smears from skin lesions or
wounds that reveal streptococci are diagnostic. Cultures of swabs from the pharynx
or lesion on blood agar plates show small, translucent β-hemolytic colonies in 18
to 48 hours. If inhibited by bacitracin disk, they are likely to be group A
streptococci .
Group B streptococci are characterized by their ability to hydrolyze hippurate and
by the production of a protein that causes enhanced hemolysis on sheep blood agar
when combined with β-hemolysin of S. aureus (CAMP test). Group D streptococci
hydrolyze esculin in the presence of bile (i.e., they produce a black pigment on
bile-esculin agar). The group D organisms are further subdivided: the enterococci
grow in hypertonic (6.5%) NaCl, whereas the nonenterococci do not.
Although cultures remain the gold standard for the diagnosis of streptococcal
pharyngitis, a problem exists because the results of culturing are not available for
at least 18 hours, and it is beneficial to know while the patient is in the office
whether antibiotics should be prescribed. For this reason, rapid tests that provide a
diagnosis in approximately 10 minutes were developed. The rapid test detects
bacterial antigens in a throat swab specimen. In the test, specific antigens from
the group A streptococci are extracted from the throat swab with certain enzymes
and are reacted with antibody to these antigens bound to latex particles.
Agglutination of the colored latex particles occurs if group A streptococci are
present in the throat swab. The specificity of these tests is high, but the sensitivity
is low (i.e., false-negative results can occur). If the test result is negative but the
clinical suspicion of streptococcal pharyngitis is high, a culture should be done.
A rapid test is also available for the detection of group B streptococci in vaginal
and rectal samples. It detects the DNA of the organism, and results can be obtained
in approximately 1 hour. Viridans group streptococci form α-hemolytic colonies on
blood agar and must be distinguished from S. pneumoniae (pneumococci), which is
also α-hemolytic. Viridans group streptococci are resistant to lysis by bile and will
grow in the presence of optochin, whereas pneumococci will not. The various
viridans group streptococci are classified into species by using a variety of
biochemical tests
B- Serologic
Anti-Streptolysin O (ASO) titers are high soon after group A streptococcal
infections. In patients suspected of having rheumatic fever, an elevated ASO titer
is typically used as evidence of previous infection because throat culture results are
often negative at the time the patient presents with rheumatic fever. Titers of anti-
DNase B are high in group A streptococcal skin infections and serve as an
indicator of previous streptococcal infection in patients suspected of having Acute
GlomeruloNephritis (AGN).
Treatment
Group A streptococcal infections can be treated with either penicillin G or
amoxicillin, but neither rheumatic fever nor AGN patients benefit from penicillin
treatment after the onset of the two diseases. In mild group A streptococcal
infections, oral penicillin V can be used. In penicillin-allergic patients,
erythromycin or one of its long-acting derivatives (e.g., azithromycin) can be used.
However, erythromycin-resistant strains of S. pyogenes have emerged that may
limit the effectiveness of the macrolide class of drugs in the treatment of
streptococcal pharyngitis. Clindamycin can also be used in penicillin-allergic
patients. S. pyogenes is not resistant to penicillins.
Endocarditis caused by most viridans streptococci is curable by prolonged
penicillin treatment. However, enterococcal endocarditis can be eradicated only by
a penicillin or vancomycin combined with an aminoglycoside.
Enterococci resistant to multiple drugs (e.g., penicillins, aminoglycosides, and
vancomycin) have emerged. Resistance to vancomycin in enterococci is mediated
by a cassette of genes that encode the enzymes that substitute D-lactate for D-
alanine in the peptidoglycan. The same set of genes encodes vancomycin
resistance in S. aureus.
VREs are now an important cause of nosocomial infections; there is no reliable
antibiotic therapy for these organisms. At present, two drugs are being used to treat
infections caused by VRE: linezolid (Zyvox) and daptomycin (Cubicin).
Nonenterococcal group D streptococci (e.g., S. bovis) are not highly resistant and
can be treated with penicillin G. The drug of choice for group B streptococcal
infections is either penicillin G or ampicillin. Some strains may require higher
doses of penicillin G or a combination of penicillin G and an aminoglycoside to
eradicate the organism. Peptostreptococci can be treated with penicillin G.
Prevention
Rheumatic fever can be prevented by prompt treatment of group A streptococcal
pharyngitis with penicillin. Prevention of streptococcal infections (usually with
benzathine penicillin once each month for several years) in persons who have had
rheumatic fever is important to prevent recurrence of the disease. There is no
evidence that patients who have had AGN require similar penicillin prophylaxis.
In patients with damaged heart valves who undergo invasive dental procedures,
endocarditis caused by viridans streptococci can be prevented by using amoxicillin
perioperatively. To avoid unnecessary use of antibiotics, it is recommended to give
amoxicillin prophylaxis only to those patients who have the highest risk of severe
consequences from endocarditis (e.g., those with prosthetic heart valves or with
previous infective endocarditis) and who are undergoing high-risk dental
procedures, such as manipulation of gingival tissue. It is no longer recommended
that patients undergoing gastrointestinal or genitourinary tract procedures receive
prophylaxis.
The incidence of neonatal sepsis caused by group B streptococci can be reduced by
a two-pronged approach: (1) All pregnant women at 35 to 37 weeks’ gestation
should be screened by doing vaginal and rectal cultures. If cultures are positive,
then penicillin G (or ampicillin) should be administered intravenously at the time
of delivery. (2) If the patient has not had cultures done, then penicillin G (or
ampicillin) should be administered intravenously at the time of delivery to women
who experience prolonged (longer than 18 hours) rupture of membranes, whose
labor begins before 37 weeks’ gestation, or who have a fever at the time of labor. If
the patient is allergic to penicillin, either cefazolin or vancomycin can be used.
Oral ampicillin given to women who are vaginal carriers of group B streptococci
does not eradicate the organism. Rapid screening tests for group B streptococcal
antigens in vaginal specimens can be insensitive, and neonates born of antigen-
negative women have, nevertheless, had neonatal sepsis. Note, however, that as
group B streptococcal infections have declined as a result of these prophylactic
measures, neonatal infections caused by E. coli have increased. There are no
vaccines available against any of the streptococci except S. pneumoniae (see next
section).
STREPTOCOCCUS PNEUMONIAE
Diseases
Streptococcus pneumoniae causes pneumonia, bacteremia, meningitis, and
infections of the upper respiratory tract such as otitis media, mastoiditis, and
sinusitis. Pneumococci are the most common cause of community-acquired
pneumonia, meningitis, sepsis in splenectomized individuals, otitis media, and
sinusitis. They are a common cause of conjunctivitis, especially in children.
Note : S. pneumoniae is also known as the pneumococcus (plural, pneumococci).
Important Properties
Pneumococci are gram-positive lancet-shaped cocci arranged in pairs (diplococci)
or short chains (Figure 4). (The term lancet-shaped means that the diplococci are
oval with somewhat pointed ends rather than being round.)
On blood agar, they produce α-hemolysis. In contrast to viridans streptococci, they
are lysed by bile or deoxycholate, and their growth is inhibited by optochin (Figure
5).
FIGURE 4: Streptococcus pneumoniae—Gram stain. Arrows point to typical gram-positive diplococci.
Note that the clear area around the organism is the capsule
FIGURE 5: Optochin test—Arrow points to zone of inhibition of growth of Streptococcus pneumoniae
caused by optochin that has diffused from the disk labeled P. In the lower half of the blood agar plate,
there is α-hemolysis caused by S. pneumoniae, except in the region around the optochin disk. The arrow
points to the outer limit of the zone of inhibition. Upper half of blood agar plate shows αhemolysis caused
by a viridans streptococcus, and there is no zone of inhibition around the optochin disk.
Pneumococci possess polysaccharide capsules of more than 85 antigenically
distinct types. With type-specific antiserum, capsules swell (quellung reaction),
and this can be used to identify the type. Capsules are virulence factors (i.e., they
interfere with phagocytosis and favor invasiveness). Specific antibody to the
capsule opsonizes the organism, facilitates phagocytosis, and promotes resistance.
Such antibody develops in humans as a result either of infection (asymptomatic or
clinical) or of administration of polysaccharide vaccine. Capsular polysaccharide
elicits primarily a B-cell (i.e., T-independent) response. Another important surface
component of S. pneumoniae is a teichoic acid in the cell wall called C-substance
(also known as C-polysaccharide). It is medically important not for itself, but
because it reacts with a normal serum protein made by the liver called C-reactive
protein (CRP). CRP is an ―acute-phase‖ protein that is elevated as much as 1000-
fold in acute inflammation. CRP is not an antibody (which are γ-globulins) but
rather a β-globulin. (Plasma contains α-, β-, and γ-globulins.)
CRP is a nonspecific indicator of inflammation and is elevated in response to the
presence of many organisms, not just S. pneumoniae. Clinically, CRP in human
serum is measured in the laboratory by its reaction with the carbohydrate of S.
pneumoniae. The medical importance of CRP is that an elevated CRP appears to
be a better predictor of heart attack risk than an elevated cholesterol level.
Transmission
Humans are the natural hosts for pneumococci; there is no animal reservoir.
Because a proportion (5%–50%) of the healthy population harbors virulent
organisms in the oropharynx, pneumococcal infections are not considered to be
communicable. Resistance is high in healthy young people, and disease results
most often when predisposing factors (see below) are present.
Pathogenesis
The most important virulence factor is the capsular polysaccharide, and
anticapsular antibody is protective.
Lipoteichoic acid, which activates complement and induces inflammatory cytokine
production, contributes to the inflammatory response and to the septic shock
syndrome that occurs in some immunocompromised patients.
Pneumolysin, the hemolysin that causes α-hemolysis, may also contribute to
pathogenesis.
Pneumococci produce IgA protease that enhances the organism’s ability to
colonize the mucosa of the upper respiratory tract. Pneumococci multiply in tissues
and cause inflammation. When they reach alveoli, there is outpouring of fluid and
red and white blood cells, resulting in consolidation of the lung. During recovery,
pneumococci are phagocytized, mononuclear cells ingest debris, and the
consolidation resolves.
Factors that lower resistance and predispose persons to pneumococcal infection
include:
(1) alcohol or drug intoxication or other cerebral impairment that can depress the
cough reflex and increase aspiration of secretions;
(2) abnormality of the respiratory tract (e.g., viral infections), pooling of mucus,
bronchial obstruction, and respiratory tract injury caused by irritants (which disturb
the integrity and movement of the mucociliary blanket);
(3) abnormal circulatory dynamics (e.g., pulmonary congestion and heart failure);
(4) splenectomy; and
(5) certain chronic diseases such as sickle cell anemia and nephrosis. Patients with
sickle cell anemia autoinfarct their spleen, become functionally asplenic, and are
predisposed to pneumococcal sepsis. Trauma to the head that causes leakage of
spinal fluid through the nose predisposes to pneumococcal meningitis.
Laboratory Diagnosis
1- In sputum,
· pneumococci are seen as lancet-shaped gram-positive diplococci in
Gram-stained smears (Figure 4).
· They can also be detected by using the quellung reaction with
multitype antiserum. When pneumococci of a certain type are mixed
with specific antipolysaccharide serum of the same type—or with
polyvalent antiserum—on a microscope slide, the capsule swells
markedly, and the organisms agglutinate by crosslinking of the
antibodies (see Figure6 ). This reaction is useful for rapid
identification and for typing of the organisms, either in sputum or in
cultures. The polyvalent antiserum, which contains antibody to all of
the types (―omniserum‖), is a good reagent for rapid microscopic
determination of whether or not pneumococci are present in fresh
sputum.
· On blood agar, pneumococci form small α-hemolytic colonies. The
colonies are bile-soluble (i.e., are lysed by bile), and growth is
inhibited by optochin (Figure 5).
Figure 6: S. pneumoniae quellung reaction: a small amount of growth is mixed with saline, antisera
against the capsule polysaccharide, and methylene blue stain. After incubation at room temperature for 1
hour, the reaction is observed under the microscope. The organisms are outlined in light blue. A positive
reaction shows clumping because of cross-linking of the antibodies and pneumococci.
2- Blood cultures are positive in 15% to 25% of pneumococcal infections.
3- Culture of cerebrospinal fluid is usually positive in meningitis. Rapid diagnosis
of pneumococcal meningitis can be made by detecting its capsular polysaccharide
in spinal fluid using the latex agglutination test.
4- A rapid test that detects urinary antigen is also available for the diagnosis of
pneumococcal pneumonia and bacteremia. The urinary antigen is the C
polysaccharide (also known as the C substance), not the capsular polysaccharide.
Because of the increasing numbers of strains resistant to penicillin, antibiotic
sensitivity tests must be done on organisms isolated from serious infections.
Treatment
Most pneumococci are susceptible to penicillins and erythromycin, although
significant resistance to penicillins has emerged (see next paragraph). In severe
pneumococcal infections, penicillin G is the drug of choice, whereas in mild
pneumococcal infections, oral penicillin V can be used. A fluoroquinolone with
good antipneumococcal activity, such as levofloxacin, can also be used. In
penicillin-allergic patients, erythromycin or one of its long-acting derivatives (e.g.,
azithromycin) can be used. In the. Vancomycin is the drug of choice for the
penicillin-resistant pneumococci, especially for severely ill patients. Ceftriaxone or
levofloxacin can be used for less severely ill patients. However, strains of
pneumococci tolerant to vancomycin have emerged. Strains of pneumococci
resistant to multiple drugs have also emerged.
Prevention
Despite the efficacy of antimicrobial drug treatment, the mortality rate of
pneumococcal infections is high in immunocompromised (especially
splenectomized) patients and children under the age of 5 years. Such persons
should be immunized with the 13-valent pneumococcal conjugate vaccine (Prevnar
13). The immunogen in this vaccine is the pneumococcal polysaccharide of the 13
most prevalent serotypes conjugated (coupled) to a carrier protein (diphtheria
toxoid).The unconjugated 23-valent pneumococcal vaccine (Pneumovax 23)
should be given to healthy individuals age 50 years or older.
These vaccines are safe and effective and provide long-lasting (at least 5 years)
protection. Immunization of children reduces the incidence of pneumococcal
disease in adults because children are the main source of the organism for adults
and immunization reduces the carrier rate in children.
A booster dose is recommended for (1) people older than 65 years who received
the vaccine more than 5 years ago and who were younger than 65 years when they
received the vaccine, and (2) people between the ages of 2 and 64 years who are
asplenic, infected with human immunodeficiency virus (HIV), receiving cancer
chemotherapy, or receiving immunosuppressive drugs to prevent transplant
rejection.
A potential problem regarding the use of the pneumococcal vaccine is that of
serotype replacement. Will the vaccine reduce the incidence of disease caused by
the serotypes in the vaccine but not the overall incidence of pneumococcal disease
because other serotypes that are not in the vaccine will now cause disease? In fact,
an increase in invasive pneumococcal disease caused by serotype 19A, which was
not in the previously used 7-valent vaccine, occurred. This led to the production of
the current conjugate vaccine containing 13 serotypes, including 19A.
