1 2. The Genus Streptococcus.

2 2.1. Definition. Classification

3 Streptococci are Gram-positive spherical cocci that form pairs or chains during the cell di-
4 vision. They are widespread in nature. Some are part of the normal human flora; others are
5 associated with significant human conditions due partly to streptococcal infection and partly
6 to the immune response of the host. There is not yet a perfect system for classifying all species
7 of streptococci. Some of the many species have medical significance (in human pathology)
8 and among them are: Streptococcus pyogenes (group A), S. agalactiae (group B), S. viridans (be-
9 longing to the normal flora), S. pneumoniae (pneumococcal), etc. Streptococci are immobile,
10 non-spore-forming and may have capsule or not.
11 Streptococcus faecalis was described in 1906 and in 1919, Streptococcus faecium. Together
12 with a third species, S. durans (very similar to S. faecium), in 1937 the group of enterocococci,
13 included in the D group of the genus Streptococcus, was defined. Since 1984, it has been decided
14 on the basis of molecular hybridization studies that these species form part of a separate genus,
15 the genus Enterococcus (see paragraph 28.9). Enterococococci may be isolated from normal
16 enteric flora. They are nonhemolytic (occasionally α-haemolytic); they have a positive reaction
17 to bile-esculin test. Tolerates NaCl at a concentration of 6,5 %. They are resistant to many
18 classes of antibiotics and chemotherapeutic agents. Treatment of infections with enterocci can
19 be a very serious problem.
20 1. Classification systems For a period of time, the classification of streptococci was based
21 on a number of observations concerning:
22 a) colony morphology and hemolysis produced on blood agar;
23 b) antigenic specificity of group (Lancefield Classification) and type specific substances;
24 c) biochemical reactions;
25 d) resistance to physical and chemical factors;
26 e) various ecological characteristics.
27 After 1980 additional biochemical tests and molecular genetic studies were introduced.
28 The Lancefield Classification divides streptococci into serological groups (A-H and K-U),
29 depending on the polysaccharides in the wall composition, while the M protein subdi-
30 vides the group A streptococci into serological types. The antigenic specificity of capsular
31 polysaccharides is used to classify S. pneumoniae in more than 90 types and for group B
32 streptococci typing (S. agalactiae).
33 2. Medically important streptococci
34 a) S. pyogenes - most of the streptococci possessing the group A antigen are pyogenic
35 streptococci. They are beta-haemolytic (typically, they produce large areas of clear
36 haemolysis around small colonies). S. pyogenes is the main microbe associated with
37 local or systemic invasion and post-streptococcal immune reaction. Generally, pyo-
38 genic streptococci are susceptible to bacitracin.
39 b) S. agalactiae - is a normal component of the vaginal microbiota of women and can
40 be an important cause of sepsis and neonatal meningitis; they are beta-haemolytic
41 and produce haemolysis areas that are only slightly wider than colonies (1-2 mm in
42 diameter). Group B streptococci hydrolyzate sodium hypopurate and give a positive
43 reaction in CAMP test (using -staphylococcal toxine impregnated disks)
 14 The Genus Streptococcus.

1 c) Groups C and G streptococci - these streptococci are sometimes isolated from na-
2 sopharynx and may cause sinusitis, bacteremia or endocarditis. They often form
3 colonies similar to those of pyogenic streptococcus and are beta-haemolytic. They
4 are identified by reactions with antiserum specific to C or G groups.
5 d) S. bovis - it is part of group D streptococci and is a normal component of the flora.
6 Occasionally, it produces endocarditis or bacteremia in patients with colorectal car-
7 cinoma. It doesn’t produce hemolysis and gives a positive reaction to bile esculin
8 test.
9 e) S. pneumonia - pneumocococci are α-haemolytic; their growth is inhibited by op-
10 tochin and colonies are destroyed by bile and bile salts.
11 f) S. viridans - part of the normal flora of the upper respiratory tract. They are typi-
12 cally alpha-haemolytic, but they can be non-hemolytic. Their growth is not inhib-
13 ited by optochin. As a result of a trauma, they can reach the blood torrent, con-
14 stituting an important cause of endocarditis that occurs in patients with valvular
15 pathology. Some viridans streptococci (example S. mutans) possess the capacity to
16 produce polysaccharides involved in dental caries development.
17 g) Peptostreptococcus - they grow only under anaerobic or microaerophile conditions
18 and produce hemolizins in varying ways. They are part of the normal oral flora, the
19 flora of the upper respiratory tract, the intestinal tract and the female genital tract.
20 Often in association with other bacterial species, they cause ploymicrobial anaero-
21 bic infections on different levels of human body - abdominal, pelvic, pulmonary or
22 cerebral.

23 2.2. Streptococcus pyogenes

24 1. General characteristics
25 a) Habitat
26 Pyogenic streptococci can be found in the upper human respiratory tract. In some
27 specific conditions, they should be removed. Some streptococci species only col-
28 onize the dental surface (they become detectable only after dental eruption). For
29 other species, the habitat data have been presented above.
30 b) Morphotinctorial characteristics
31 Pyogenic streptococci are Gram-positive, spherical or ovoid cocci (diameter of about
32 1 µm). They divide in one plane, perpendicular to their long axis and are arranged
33 in chains (up to 50 bacterial elements). Chain length varies and is subject to envi-
34 ronmental factors.
35 Some streptococci possess a polysaccharidic capsule comparable to the pneumoccal
36 one. Most group A, B and C species produce the capsule of hyaluronic acid. The
37 capsule can protect bacteria from phagocytosis; it is more clearly seen in young
38 bacteria cultures. Streptococcus pyogenes pili are covered by lipopeichoic acid; they
39 play a major role in adhesion to host cells.
40 c) Culture characteristics
41 Most streptococci grow on solid media and form discoid, S type colonies (diam-
42 eter of about 1-2 mm). The beta-hemolytic group A pyogenic streptococcus pro-
43 duces pinpoint colonies. Often, mucoide colonies (M type) present capsule. Most
44 streptococci are aerobic, optional anaerobic bacteria; peptostreptococci are strictly
45 anaerobic.
46 Nutritional needs vary widely depending on the species. Streptococci involved in
47 human pathology are generally fastidious organisms, requiring a variety of growth
48 factors. A useful culture media (both selective and differential media) is the blood-
 Streptococcus pyogenes 15

1 agar media. On this, streptococci can be differentiated according to the ability to

2 produce hemolysis. The complete destruction of erythrocytes with the release of
3 hemoglobin is called beta-haemolysis and is useful in the identification of pyogenic
4 streptococci (small S-type colonies surrounded by a clear haemolysis area with a
5 diameter bigger than the colony diameter); the incomplete lysis of erythrocytes
6 generating a green pigment is called alpha-hemolysis (or viridans hemolysis). In-
7 complete hemolysis without a greenish shade is called alpha-prime (α‘) hemolysis.
8 If streptococci don’t produce hemolysis, they are classified as γ streptococci.
9 Depending on the producing of hemolysis, more frecquently involved in human
10 pathology are beta-hemolysis streptococci, of which the group A beta-haemolytic
11 streptococci. Group A beta-haemolytic pyogenic streptococci produces two types
12 of hemolysines:
13 – streptolysin O - an antigenic protein (60.000 Da molecular weight); hemolytic
14 active only in a reversibly reduced state (available SH- groups);
15 – streptolysin S - not antigenic protein.
16 d) Biochemical characteristics
17 One of the major biochemical characteristics is the production of hemolysis it-
18 self. Pyogenic streptococci are fastidious organisms requiring, for a proper develop-
19 ment, the addition of vitamins, amino acids, glucose or at least the use of blood-agar
20 or nutritional broth as media culture. The glycolic path is the main route to degrade
21 glucose. A large proportion of species can also ferment other sugars and sugar al-
22 cohols by using some inductive enzymes (synthesized only in the presence of that
23 carbohydrates and in the absence of glucose). Usually, the pyogenic streptococci
24 are susceptible to bacitracin.
25 e) Resistance to physical and chemical factors
26 The pyogenic streptococci are destroyed in 30 minutes at 56 °C, but can survive in
27 dry secretions at room temperature and in the dark for several weeks. Since it is not
28 sensitive to the action of three-phenyl-methane colorants, the violet crystal may be
29 used in selective culture media.
30 f) Antigenic structure
31 The haemolytic streptococci can be divided into serological groups (more than 18
32 serological groups noted with the uppercase letters of the alphabet, A-U), based
33 on carbohydrate C, present in the wall structure of many streptococci (Lancefield
34 groups). The serological specificity of the group-specific carbohydrates is deter-
35 mined by an amino sugar:
36 – for group A streptococci: rhamnose-N-acetyl-glucosamine;
37 – for group B streptococci: rhamnose-glucosamine-polysaharid, etc.
38 The most important are groups A, B, C, F and G (include beta-hemolytic strepto-
39 cocci).
40 Group A beta-haemolytic streptococci possess a parietal M protein, the most impor-
41 tant pathogenicity factor for this group of streptococci. M type-specific antibodies
42 confer type-specific immunity. Since there are more than 100 types of M protein
43 (but not all of them possess phagocytosis prevention properties), a person can de-
44 velop repeated infections with a group A S. pygenes of different types. Protein M
45 has also been identified in group G streptococci.
46 Other antigenic structures are represented by:
47 – M protein associated protein (MAP);
48 – T-substance which allows to differentiate certain types of streptococci by ag-
49 glutination with specific antiserum;
50 – C5A peptidase (the C5a fragment cleavage of the complement system);
 16 The Genus Streptococcus.

1 – R protein, a surface antigen;

2 – F protein, an adhesine;
3 – nucleoproteins (P-substances) which are likely to form the major part of the
4 streptococcic structure;
5 – various toxins and enzymes:
6 ◦ streptokinase (fibrinolysin) – converts the plasminogen to plasmin; can
7 be useful in intravenous treatment in pulmonary embolism, arterial and
8 venous thrombosis and acute myocardial infarction; an antigen structure;
9 ◦ streptodornase (deoxyribonuclease) - causes hydrolysis of DNA; Anti-DN-
10 ase antibodies appear after streptococcal infections, especially after skin
11 infections;
12 ◦ hyaluronidase – able to degrade the hyaluronic acid, an important compo-
13 nent of the basic substance in connective tissue;
14 ◦ soluble erythrogenic toxin - destroyed by boiling in one hour; it causes the
15 rash (characteristic eruption) which occurs in scarlatine; the erythrogenic
16 toxin is produced only by the lysogenized streptococci; there is only one
17 type of erythrogenic toxin;
18 ◦ diphosphopyridine nucleotidase - an enzyme developed and released into
19 the environment by some streptococci;
20 ◦ haemolysins mentioned above.
21 2. Immune system response
22 Resistance to streptococcic infections is a type-specific resistance. The immunity to group
23 A streptococci infection is linked to the presence of specific anti-M-protein antibodies.
24 Because there are more than 80 types of M protein, a person can develop repeated infec-
25 tions caused by different types of group A S. pyogenes. The structure and function of the
26 M protein have been extensively studied. The molecule has a helical structure that sepa-
27 rtes functional domains, thus allowing a large number of sequences to be changed while
28 the function is maintained. Two major classes (I and II) of- protein have been identified;
29 antibodies against M protein can be serologically identified.
30 Since there is only one type of erythrogenic toxin, in the case of streptococcal infection
31 leading to scarlatin, immunity after the disease is long-lasting, possibly even life-long.
32 Anti-streptococcal antibodies appear in the course of streptococcal infection; they can
33 be identified by serological tests (i.e. the ASLO test). Antibody titers may be useful in
34 the diagnosis of streptococcal and poststreptococcal infections.
35 3. Pathogenicity characteristics
36 Protein F - by linking to the fibronectin of host cells, it has a role of adhesine; also, has a
37 role in invasion.
38 Protein M - is the most important antigenic and pathogenicity factor for A group beta-
39 hemolytic streptococci. Protein M appears as an outgrowth in cell wall. Protein M forms
40 fibrillary structures which can e/xtend 50/-60 nm outside the bacterial cell; with the other
41 side, they are in the cytoplasmic membrane.
42 Experimentally, it has been proven that, when protein M is present, streptococci are
43 virulent. In the absence of specific antibody against M protein, streptococci are capable
44 to withstanding the phagocytosis. Protein M is also involved in adhesion process to the
45 host’s epithelial cells. A group streptococci lacking in M protein is avirulent.
46 Protein M and possibly other streptococcal antigens seem to play an important role in the
47 pathogenesis of “rheumatic fever” (acute articular rheumatism). Preserved antigen do-
48 mains of class M proteins (especially class I) cross-react with human cardiac muscle struc-
49 tures. Other M protein types share similarities with myosin, keratin or -tropomyosin.
50 Some strains of S. pyogenes form a capsular structure composed of hyaluronic acid; they
 Streptococcus pyogenes 17

1 develop mucoid colonies on blood-agar (the capsular material isn’t immunogenic); it may
2 be part of the virulence of certain strains.
3 Hialuronidase facilitates the spread of infected microorganisms.
4 Diphosphopyridine nucleotidase is an enzyme developed and released into media culture
5 by some streptococci; this substance allows the microorganism to destroy leucocytes.
6 All pyogenic streptococci produce C5a-peptidase, a serine-protease involved in the cleav-
7 age of the C5a component. C5a is one of the main factors to attract PMN to the site of
8 the infectious process.
9 Erythrogenic toxin, produced only by the beta-hemolytic group A streptococci, is in-
10 volved in the pathogenicity of rash in scarlet fever.
11 4. Specific pathogenicity and pathology.
12 Streptococci are potentially involved in a wide variety of diseases. Their pathogenicity is
13 mainly due to multiplication and invasiveness. The biological properties of the infected
14 microorganisms, the nature of the host immune response and the site of bacterial entry
15 have a high influence on the clinical picture. Streptococcal infections could be grouped
16 as follows:
17 a) Invasive diseases caused by pyogenic streptococci
18 The clinical picture is determined by the entry site. In each case, there may be rapid
19 and diffuse expansion of the infection along the lymphatic routes, accompanied by
20 minimal pus. Infection can be spread in the circulatory system. This category may
21 include;
22 – erysipelas - occurs when the entry site is tegument;
23 – puerperal fever - developing in the case of intrauterine streptococcal infection;
24 – streptococcal sepsis.
25 b) Localized diseases
26 This group includes:
27 – streptococcal pharyngitis which is the most common infection due to beta-
28 haemolytic streptococci. Virulent group A streptococci has the capacity to ad-
29 here to the pharyngeal epithelium through lipoteichoic acid. The glycopro-
30 tein fibronectin of epithelial cells is likely to serve as a ligand for lipoteichoic
31 acid. The expansion at the tonsil level and possibly at the level of other struc-
32 tures is called “streptococcal angina”. The disease manifests itself with pain in
33 the throat, rhinopharyngitis, “red” and purulent tonsils, increased and painful
34 cervical lymph nodes, fever (39-40 °C). There is a tendency (especially in young
35 children) to extend the infection to the middle ear, the mastoid and meninges. It
36 should be noted that about 10-20% of infections can be asymptomatic;
37 – when streptococci are lysogenized (infected with a specific bacteriophagus),
38 they produce erythrogenic toxin. Characteristic eruption and scarlet fever oc-
39 cur if the patient doesn’t have an antitoxic immunity. The antitoxins in relation
40 to the erythrogenic toxin prevent the rash occurrence, but don’t interfere with
41 streptococcal infection;
42 – pneumonia can be rapidly progressive and severe; usually occurs as a compli-
43 cation, after a viral infection (e.g. influenza, measles, etc.; infection with the
44 respiratory syncytial virus in the infants can also be followed by streptococcal
45 pneumonia);
46 – impetigo is an infection localized at the surface layers of the skin, especially
47 in children.
48 c) Infective endocarditis
49 Infective endocarditis clinically presents with either an acute or subacute course.
50 In the case of acute endocarditis, during bacteremia, streptococci can settle a nor-
 18 The Genus Streptococcus.

1 mal or a damaged heart valve. In the absence of proper antibiotic treatment and
2 sometimes, valve prosthesis, it goes to rapid destruction of valves and frequently
3 more than that, toward fatal outcome in days or weeks.
4 Subacute endocarditis frequently involves abnormal heart valves – congenital ab-
5 normalities, rheumatic heart disease or atherosclerosis.
6 d) Post-streptococcal diseases
7 Post-streptococcal diseases include rheumatoid arthritis (RA), rheumatic carditis
8 and acute post-streptococcal glomerulonephritis (AGN). After an acute infection
9 episode by group A beta-haemolytic streptococci, there is a latency period (about
10 1-4 weeks); after that period post-streptococcal diseases can develop. The latency
11 period suggests that post-streptococcal disease isn’t due to the direct effect of the
12 bacterial release, but represents a response in a hypersensitivity state following
13 repeated, untreated or mistreated infections with pyogenic group A beta-hemolytic
14 streptococci.
15 i. Acute post-streptococcal acute glomerulonephritis (AGN)
16 AGN can occur about 3 weeks after streptococcal infection (often the entry site
17 is the tegument), especially determined by types 12, 4, 2, 49, 59-61. Glomeru-
18 lonephritis is due to a type III hypersensitivity mechanism by producing exces-
19 sive antigen-antibody immune complexes, which circulate and deposit at the
20 level of the glomerular basal membrane. In acute nephritis, hematuria, pro-
21 teinuria, face edema (i.e. periorbital), arterial hypertension, urea retention can
22 occur; serum complement level is low.
23 ii. Rheumatoid arthritis
24 ARA is the most serious sequel of streptococcal infection, as it affects heart
25 valves and cardiac muscle. Certain types of group A streptococci possess anti-
26 gens that cross-react with human cardiac tissue structures or base ganglia
27 structures.
28 The RA is preceded by a streptococcal infection. All types of hypersensitivity
29 are included in RA pathogenicity, especially those of type II (cytotoxic) and
30 type IV (cellular/delayed mechanism), but also autoimmune phenomena. Spe-
31 cific signs and symptoms in the RA include fever, migratory polyarthritis and
32 signs related to inflammation at heart structures – rheumatic carditis.
33 5. Treatment
34 Treatment of streptococcal pharyngitis - penicillin for 10 days at the appropriate doses
35 (calculated in IU/kg body weight in the case of children). In the case of a subject with
36 penicillin allergy (reactivity to penicillin should be investigated, anamnestic and various
37 tests); erythromycin can be used, or antibiotic susceptibility test may be necessary.
38 6. Epidemiology
39 Group A streptococci frequently colonize the throat of asymptomatic persons and may
40 also colonize the skin, rectum, and vagina.
41 Streptococcal disease is ordinarily spread by direct person-to-person contact. In cases
42 of pharyngitis and respiratory infections, droplet nuclei of saliva or nasal secretions are
43 the mode of spread. Crowding such as occurs in schools or military barracks favors
44 interpersonal spread of the organism in community outbreaks. Fomites can also be a
45 source of streptococcal transmission.
46 A variety of clinical presentations may occur, including pharyngitis, otitis media, quinsy
47 (peritonsillar abscess), skin and soft tissue infections (pyoderma, impetigo, erysipelas,
48 and scarlet fever), pneumonia, and puerperal fever.
49 CDC estimates approximately 11,000 to 24,000 cases of invasive group A strep disease
50 occur each year in the United States. Each year between 1,200 and 1,900 people die due
 Streptococcus pneumoniae (pneumococcus) 19

1 to invasive group A strep disease. Invasive group A strep disease can include:
2 – cellulitis with blood infection
3 – necrotizing fasciitis
4 – pneumonia
5 – streptococcal toxic shock syndrome
6 In contrast, experts estimate that several million cases of non-invasive group A strep ill-
7 nesses occur each year. Non-invasive group A strep diseases include strep throat and im-
8 petigo. Complications of these group A streptococcal infections, like post-streptococcal
9 glomerulonephritis and acute rheumatic fever, are rare.
10 Globally, the burden from group A streptococcal infections is even greater. For example,
11 the WHO estimates:
12 – 111 million children in the developing world have impetigo;
13 – 470.000 new cases of acute rheumatic fever occur each year;
14 – 282.000 new cases of rheumatic heart diseases occur each year;
15 – 15,6 million people have rheumatic heart.
16 7. Prophylaxis
17 In order to prevent accidents mainly related to contamination and streptococcal infec-
18 tions from surgical interventions on the respiratory, gastrointestinal and urinary tract
19 leading to the emergence of a bacteria, antibiotics could be administrated for preventive
20 purpose to known heart disease patients.
21 The control procedures for streptococcal infections are primarily addressed to the human
22 source, consisting of:
23 – early antimicrobial identification and therapy of respiratory and skin infections
24 with group A pyogenic streptococci; it is necessary to maintain appropriate levels
25 of penicillin in tissues for 10 days; erythromycin can be an alternative;
26 – prophylaxis with antistreptococcal antibiotics in persons suffering from a RA at-
27 tack;
28 – eradication of group A streptococci to carriers. The option is particularly important
29 when they work in places at risk, such as delivery and operating rooms, classrooms
30 or medical cabinets.

31 2.3. Streptococcus pneumoniae (pneumococcus)

32 1. Definition. Classification.
33 Streptococcus pneumoniae are Gram-positive, elongated, lancet-shaped cocci, usually found
34 in pairs (diplococci) aligned on their long axis. They are encapsulated, non-spore-forming
35 and immobile. The pneumococci are aerobe and facultative anaerobe bacteria. On blood
36 agar it causes α-hemolysis, as does Streptococcus viridans. An atmosphere of 5% CO2 at a
37 temperature of 37 °C is favorable for its growth. Streptococcus pneumniae one of the main
38 causes of otitis media and other respiratory infections, including pneumonia. Pneumo-
39 coccal meningitis is, however, a redoubtable nosological entity.
40 One of the major therapeutic problems arising from the development of antibiotic re-
41 sistance is the emergence of penicillin-resistant pneumococci and other antimicrobial
42 drugs. The severity of this situation results from the increased incidence of pneumococ-
43 cal pneumonia (40 – 50% of community acquired pneumonia etiology) and the extremely
44 alarming incidence of penicillin-resistant pneumococci (20-40% of isolated strains in
45 Western Europe or North America), that are sometimes multidrug resistant.
46 2. General characteristics
47 a) Habitat
48 The pneumococci can be isolated from healthy people, pertaining to the normal
 20 The Genus Streptococcus.

1 flora of the upper respiratory tract (especially mouth, nasal and pharyngeal). Al-
2 though the frequency of oropharyngeal carriers is estimated at 30-70%, in a recent
3 study on voluntarily participating students at the end of the 2nd year (unpublished
4 data, 2007), we did not identify any Streptococcus pneumoniae carrier.
5 b) Microscopic characteristics
6 They are Gram-positive, elongated, lancet-shaped, generally found in pairs (diplo-
7 cocci), encapsulated (pairs found within a common capsule), immobile, non-spore-
8 forming. After methylene blue staining, the capsule can be seen as a halo around
9 the pneumococci. Using anti-capsular antibodies, rapid identification (including di-
10 rectly on the specimen – i.e. sputum) can be achieved by the capsular swelling
11 reaction.
12 c) Culture characteristics
13 Pneumococci are fastidious aerobic and facultative anaerobic germs, which do not
14 grow on simple media. On blood agar, they form type S or type M colonies, sur-
15 rounded by an area of α-hemolysis (like Streptococcus viridans). Multiplication is
16 favorable in a 5% CO2 atmosphere at a temperature of 37 °C. Glucose is the main en-
17 ergy source for pneumococci. They synthesize glycolytic, proteolytic and lipolytic
18 enzymes.
19 Due to pneumococcal growth, the liquid culture media get a cloudy homogeneous
20 appearance.
21 d) Biochemical characteristics
22 Glucose is the main energy source for pneumococci. They develop glycolytic, pro-
23 teolytic and lipolytic enzymes. The fermentation of inulin (a type of sugar) is an
24 important biochemical characteristic, as it is useful to differentiate pneumococci
25 from S. viridans (both streptococci produce α-hemolysis on blood agar).
26 They produce autolytic enzymes. The autolysis is induced and accelerated by bile,
27 bile salts, bile acids; the test is useful for pneumococci identification (bilolysis test,
28 Neufeld test).
29 They are sensitive to optochin (ethylhydrocupreine), this also being useful for iden-
30 tification and differentiation from Streptococcus viridans.
31 e) Resistance to physical and chemical factors
32 Pneumococci can survive several months in dry sputum, in a dark environment.
33 The resistance is low in the external environment. Over time, the germs become
34 Gram-negative and have the tendency to spontaneously autolyze. The autolysis of
35 pneumococci is intensified by surfactants.
36 f) Antigenic structure
37 A group-specific polysaccharide, common to all pneumococci can be found in the
38 cell wall. The pneumococcal C polysaccharide includes teichoic acid (covalently
39 linked to the peptidoglycan).
40 The most important antigenic and pathogenic determinant is the polysaccharide
41 capsule (K antigen), which protects the pneumococcus against phagocytosis and
42 allows invasiveness. The structure of the capsular polysaccharide is specific to each
43 serotype. To this date, over 90 different capsular serotypes have been identified, as
44 well as the structure of most of these serotypes. There are two different systems
45 that are used to classify capsular types. The American system numbered the capsu-
46 lar types in the order of their discovery. The Danish system groups several related
47 antigenic types. For example, group 19 of the Statens Serum Institute classifica-
48 tion which utilises the notations 19A-C and 19F types, are, in the American clas-
49 sification system, numbered as 19, 57, 58 and 59 respectively. Specific polyvalent
50 and monovalent anti-capsule serums were produced and are useful for identifying
 Streptococcus pneumoniae (pneumococcus) 21

1 pneumococci with the help of the capsular swelling reaction.

2 Lipoteichoic acid also called F antigen (Forsman) was also described; the anti-F
3 antigen antibodies cross-react with the C polysaccharide of pyogenic streptococci.
4 Phosphocholine (PC) is found in both lipoteichoic acid and parietal teichoic acid.
5 The presence of PC residues is necessary for division, autolysis and for genetic
6 process of transformation. PC also acts as an adhesin (it binds to “choline-binding
7 proteins” on the surface of the host cells).
8 All pneumococci secrete IgA1 protease (one of the Zn-proteinases produced by S.
9 pneumoniae).
10 g) Immune response
11 Immunity to pneumococcal infection is type specific and depends on both the an-
12 tibodies that appear against the capsular polysaccharide and on the function of
13 phagocytes. Vaccination induces the production of antibodies against the capsular
14 polysaccharide.
15 h) Pathogenicity characteristics
16 S. pneumoniae is a conditionally pathogenic germ that, when involved in human
17 pathology, manifests itself through multiplication and invasiveness. The virulence
18 of pneumococci depends on the capsule, which confers resistance to phagocyto-
19 sis. A serum that contains antibodies against type-specific polysaccharides protects
20 against infection. If such a serum is absorbed with type-specific polysaccharides it
21 loses its protective power.
22 Other pathogenicity factors:
23 – IgA1 proteases;
24 – intracellular hemolysin (pneumolysin), released through autolysis (inhibits PMN
25 chemotactism, inhibits lymphocyte proliferation and antibody synthesis);
26 – surface proteins (PspA) that are similar to M protein of S. pyogenes ;
27 – neuraminidases (NanA and NanB) and hyaluronidase.
28 Since about 30-70% of people can be pneumococcal carriers at a certain point in
29 their lives, the normal respiratory mucosa has a significant level of natural resis-
30 tance to these microorganisms. Among the factors that predispose to infection, it
31 would be important to mention:
32 – constitutional or acquired abnormalities of the respiratory tract (viral infec-
33 tions, local allergies, bronchial obstructions, respiratory tract disorders due to
34 irritant substances, etc.);
35 – alcohol or drug poisoning, which inhibits phagocytic activity and cough reflex;
36 – tobacco consumption (smoking);
37 – malnutrition, hyposplenism or complement system deficiencies.
38 3. Pathogenesis and specific pathology. In most pneumococcal infections there is an
39 initial bacteremic phase, during which the microorganism can be isolated from blood cul-
40 tures. The pneumococcus is pathogenic through multiplication and invasiveness, leading
41 to various infections of the upper and lower respiratory tract, middle ear, sinuses, but also
42 other infections caused by hematogenous dissemination (e.g. meningitis, endocarditis,
43 which can be very serious).
44 Pneumococcal pneumonia is accompanied by the presence of alveolar edema and fibri-
45 nous exudate, followed by the appearance of red blood cells and leukocytes. Numerous
46 pneumococci can be found in the exudate. The onset of pneumonia is often sudden, with
47 high fever, chills, chest pain. The characteristic sputum is “rusty” (pathognomonic sign).
48 The radiological aspect is characteristic when a single lobe is affected and consists of a
49 triangular-shaped opacity, with the base towards the periphery and the apex towards the
50 mediastinum (lobar pneumonia).
 22 The Genus Streptococcus.

1 4. Laboratory diagnosis of Streptococcus pneumoniae infections Please see the cor-

2 responding LP.
3 5. Treatment
4 Streptococcus pneumoniae had very good susceptibility to penicillin about 20-25 years
5 ago. Changes in enzyme structures (especially in PBPs) have led to decreased penicillin
6 affinity for them and to the emergence of resistance. Penicillin-resistant strains may also
7 exhibit resistance to other antibiotics, including cephalosporins, chloramphenicol, clin-
8 damycin, tetracycline, erythromycin, etc. This type of resistance was discovered about
9 30 years ago; subsequently there was a spread of resistant strains, which are currently
10 involved in a significant proportion of cases of otitis media, a very common condition in
11 children. Antibiotic susceptibility testing is nowadays strictly necessary in pneumococ-
12 cal infections.
13 6. Epidemiology
14 In adults, types 1-8 are responsible for about 75% of pneumococcal pneumonia cases and
15 for more than half of the fatal cases following pneumococcal bacteremia; in children,
16 types 6, 14, 19 and 23 are most commonly involved.
17 As mentioned above, there is a significant number of pneumococcal carriers, and the
18 transmission is airborne.
19 Between 2004 and 2006, in Romania, there were more cases of pneumococcal pneumonia,
20 compared to previous years, i.e. 4904 cases in 2005 (incidence 22.7 o/oooo ) and 3079 cases in
21 2006, the incidence was 14 3 o/oooo (compared to 1,695 cases reported in 2000, for example).
22 In the US, pneumococcal pneumonia is not a disease that is reported nationally; however,
23 the number of cases of invasive strains of Streptococcus pneumoniae resistant to antibi-
24 otics and chemotherapeutic agents is reported and recorded (2.966 cases in 2005, with an
25 incidence of 1.42 o/oooo ; of these cases, there were 1495 cases in children less than 5 years
26 old).
27 7. Prophylaxis
28 It is currently possible to immunize with specific capsular polysaccharides, vaccines that
29 can provide about 90% protection against bacterial pneumonia. Initially, the vaccines
30 contained 12 polysaccharide types, and after 1983 a polyvalent vaccine with 23 types
31 was developed in the USA. This vaccine is indicated for the immunization of children,
32 the elderly, and immunocompromised patients. Pneumococcal vaccines have a low im-
33 munogenicity in children under 2 years old and in patients with Hodgkin’s lymphoma.
34 Since 1998, a vaccine has been developed in which the capsular polysaccharides are cou-
35 pled with a protein (diphtheria anatoxin), proving good efficacy in the prevention of otitis
36 and pneumococcal meningitis in children.
37 In addition, avoiding predisposing factors as well as prompt diagnosis and early estab-
38 lishment of correct antibiotic therapy for the isolated and identified strain are desired.