PNEUMOCOCCAL PNEUMONIA
1. INTRODUCTION – see text pp. 553-563
a. Definitions:
1. Pneumonia – inflammation of the lungs with consolidation.
FOUR TYPES OF PNEUMONIA (see text p. 560-561)
a. Lobar pneumonia – a homogeneous involvement of a distinct segment of the lung such as a lobe or a segment of a lobe. Alveoli are usually involved, not the bronchioles or interstitium. The alveoli become consolidated with an infiltrate of inflammatory cells (neutrophils and macrophages). Consolidation – the process of becoming or the condition of being solid, as when the lung becomes firm as air spaces are filled with exudate in pneumonia. e.g. pneumococcus, H. influenzae, and Legionella
b. Bronchopneumonia- inflammation of the lungs which begins in the terminal bronchioles and can extend to nearby areas of the lung. The process is more patchy than lobar pneumonia, often occurring in more than onearea of the lung at the same time. M. pneumoniae and respiratory viruses
c. Interstitial pneumonia – involvement of the lung interstitium - pertaining to or situated between parts or in the interspaces of a tissue
e.g.: Influenza viruses, cytomegalovirus, P. carinii pneumonia in AIDS patients
d. Lung Abscess – one or more areas of the lung are replaced by cavities filled with debris generated by the infectious process. e.g.anaerobic bacteria
2. Infections of the Lungs May Spread Into the:
a. Pleural space - causing pleurisy or empyema. Pleura - the lining of the lungs
Visceral pleura – the layer of the pleura lining the lungs which cannot be separated from the lungs. Parietal pleura – the portion of the pleura lining the walls of the thoracic cavity. Pleural space (pleural cavity)– the space between the two pleural layers. It is empty except for a thin film of fluid that separates the two layers and allows the lungs to move within their sac without friction.
Pleurisy - inflammation of the pleura, with exudation into its cavity and upon its surface.
Empyema – accumulation of pus in the pleural space
b. Pericardium (rare) – the sac that surrounds the heart
c. Bloodstream (via the lymphatic drainage and the thoracic duct) causing bacteremia or septicemia. (common)
d. Meningitis – spread across the blood-brain barrier causing inflammation of the meninges (the membranes that envelop the brain and spinal cord).
2. Classification of Pneumonia Syndromes (Table 59.4, p. 554 in Text)
a. Acute
(1) Community Acquired-
a. Person–to-Person – S. pneumoniae, Mycoplasma
pneumoniae, H. influenzae
b. Animal/Environmental Exposure – Legionella
pneumophila, Yersinia pestis, Bacillus anthracis
2. Nosocomial - Enterobacteriaceae, Pseudomonas aeruginosa
b. Chronic - Mycobacterium tuberculosis
c. Pneumonia in the immunocompromised patient – Pneumocystis carinii, and others
2. MICROBIOLOGY (The Organism)
Streptococcus pneumoniae “The Pneumococcus” – the most frequent cause of acute, community acquired bacterial pneumonia. Causes 500,000 cases of pneumonia in the U.S. with 50,000 deaths. (About 60-80% of all pneumonias)
Morphology and Cell Surface Structures–
a. Gram positive coccus (usually seen as diplococci with a distinctive “lancet shape”. Belongs to the alpha hemolytic "viridans” streptococci.
b. Cell surface structures:
(1) Peptidoglycan cell wall – stimulates inflammatory response
(2) C substance – teichoic acid in the cell wall – reacts with the C reactive protein in serum, activating the complement cascade via the alternative pathway
(3) Main virulence factor– polysaccharide capsule that protects it from phagocytosis and is highly antigenic. There are more than 80 capsular serotypes (each reacting with specific typing serum), but most cases of pneumococcal pneumonia are caused by 23 serotypes. The presence of the capsule can be visualized under the light microscope using the Quellung test.
3. EPIDEMIOLOGY
a. Reservoir – Exclusively a human pathogen; no animal or environmental reservoir. Carried in the nasopharynx of 40-70% of humans without
symptoms. (Highest carriage by children – see Table 13.1 in text)
b. Transmission: person to person from a sick person or a carrier is via the aerosol route. Epidemics can occur in institutional settings such as nursing homes or in the close quarters of the military barracks. While pneumococcal pneumonia can be acquired from another infected person, it is usually caused endogenously from one's own S. pneumoniae carried in the nasopharynx. (Strains vary in virulence, and disease outcome is determined by the virulence of the strain and the host's defenses.
Disease is associated with predisposing factors:
a. Age (highest incidence under 5 yrs. or over 50 yrs.)
b. Damage to the ciliated epithelium
c. Alcohol and drug intoxication (depresses phagocytic activity, depresses the cough reflex).
d. Splenectomy or splenic dysfuntion (sickle cell anemia) – more prone to bacteremia and death.
e. Trauma to the head that causes leakage of spinal fluid through the nose – predisposes to meningitis.
4. CLINICAL FEATURES
a. Upper respiratory tract infections – otitis media and sinusitis.
b. Pneumococcal Pneumonia – “the classical symptoms” – sudden chill, fever, cough, and pleuritic pain. Sputum is red or brown “rusty color”.
c. Complications:
(1) Pleural effusions – serous fluid in the pleural space
(2) Empyema – pneumococci enter the pleural space
(3) Bacteremia (15-50% of patients)
(4) Meningitis -from the bloodstream, bacteria can cross the blood- brain barrier and infect the meninges. Damage to the brain can lead to hearing loss, blindness, learning disabilities, paralysis and death.
5. PATHOGENESIS
a. Entry into the body via aerosols, and colonization of the nasopharynx.
Virulence factors associated with colonization:
1. protein adhesin
2. sIgA protease
TWO PATHWAYS - LEADING TO UPPER RESPIRATORY OR LOWER RESPIRATORY INFECTIONS:
1. Upper Respiratory Infections: they gain access through the eustachian tube to the middle ear causing otitis media, or into the sinuses causing sinusitis
OR
2. Lower Repiratory Infections: Respiratory secretions containing pneumococci are aspirated into the lower respiratory tract.
Virulence factors that help them reach the lungs:
1. sIgA protease
2. Pneumolysin -cytotoxin binds to cholesterol in host cell membranes and disrupts them by forming pores. Also activates complement.
Production of pneumonia in the lungs- primary virulence factor – the antiphagocytic capsule:
1. The pneumococci that reach the lungs escape phagocytosis by the alveolar macrophages and the neutrophils (that arrive later as part of the inflammatory response) because of their antiphagocytic capsule.
2. The bacteria multiplying in the alveoli of the lungs release cell wall components (teichoic acid and peptidoglycan) which activate complement, trigger cytokine release and cause a local inflammatory response. THE HOST'S INFLAMMATORY RESPONSE TO THE PNEUMOCOCCI CAUSES THE SYMPTOMS OF THE DISEASE!
See text Fig. 13.3 for the four zones or stages of lung involvement.
1. Lung Alveoli fill with Serous Fluid – containing pneumococci, but few inflammatory cells. This tremendous outpouring of serous edema fluid facilitates the growth and spread of the pneumococci to adjacent alveoli and interferes with gas exchange.
2. Early Consolidation – alveoli are infiltrated by red blood cells (because of capillary fragility) and professional phagocytes which are unsuccessful at killing the bacteria. (Neutrophils are drawn in by strong chemotactic signals produced by the pneumococci, and by the products of the alternative complement pathway.)
The pneumococci resist phagocytosis because of their capsules. (However, if they are phagocytosed, they are killed – a classic example of an extracellular pathogen. Phagocytosis is enhanced by opsonization with (1) antibody from a previous infection, (2) by C3b from activation of the alternative complement pathway, or (3) by interaction of the pneumococcal C-substance with the C-reactive protein of serum).
(3) Late Consolidation
By the 4th or 5th day, neutrophils predominate in the consolidated alveoli. Damage to the lung can disrupt gas exchange so severely, that the patient becomes cyanotic and literally suffocates.
Complications:
a. Pleural effesion and/or empyema
b. Bacteria enter the blood (bacteremia) via the lymphatic system, or because of damage to lung endothelial cells. This occurs in 25% of cases of pneumococcal pneumonia (need for blood cultures)
(Secondary sites may be infected – heart valves, joints, peritoneal cavity) Importance of the RES system demonstrated by those without spleens – overwhelming bacteremia.
c. Bacteria breach the blood-brain barrier and enter the cerebrospinal fluid – meningitis
(4) Resolution of the lung infection- neutrophils are replaced with scavenging macrophages which clear the debris from the inflammatory response. Architecture of the lungs is eventually restored to normal. No necrosis or fibrous scar formation.
SUMMARY OF VIRULENCE FACTORS USED BY PNEUMOCOCCI ONCE THEY REACH THE LUNGS:
1. Survival of pneumococci in the lungs is the result of the antiphagocytic capsule. (Mutants without capsules are not virulent and anticapsular antibody protects against the disease.)
2. Damage to the lungs has been attributed to a variety of other virulence factors including:
a. Cell wall components – peptidoglycan and teichoic acid which elicit the powerful inflammatory response.
b. Pneumolysin – cytotoxin that kills ciliated epithelial cells and damages lung tissue; it activates complement and contributes to the inflammatory response.
c. Hydrogen peroxide, produced by the bacteria contribute to lung damage.
6. The Host's Specific Immune Response
Specific antibody to the capsule develops in humans as a result of asymptomatic infection or clinical disease, or administration of vaccine. Capsular polysaccharide elicits primarily a B cell (i.e. T cell independent) immune response. Capsular antibody opsonizes the organism, facilitates phagocytosis, and promotes resistance to the disease.
7. Laboratory Diagnosis
a. Direct examination of specimens to give a presumptive i.d.:
Sputum- Gram stain smear showing Gram + lancet shaped diplococci with many neutrophils (and few squamous cells)
2. Spinal Fluid- Gram stain smear of cerebral spinal fluid (CSF) a presumptive i.d.
b. Culture of sputum, blood, and CSF followed by identification based on
based on phenotypic characteristics – routine i.d.
1. alpha hemolytic on blood agar plate (usually mucoid colonies
because of capsule).
Distinquish from other alpha hemolytic viridans strep phenotypically. Pneumococci are:
2. sensitive to optochin
3. bile-soluble – lysed by bile
c. Serology – definitive identification
Demonstrate the pneumococcal capsule in sputum, spinal fluid, or from organisms growing on blood agar plates using the Quellung test.
The opsonized capsule absorbs water, becomes increasingly refractile, and is visible under the light microscope.
8. Treatment: Antibiotics
9. Vaccine
A vaccine against pneumococcal pneumonia is currently available which contains the 23 most common capsular serotypes, so it protects against most of the commonly encountered strains.
Problems with the vaccine include:
1. The other 57 serotypes not included in the vaccine
2. Because it is a polysaccharide vaccine, it is not effective in infants (who do not respond to T cell-independent antigens) and it works poorly in the elderly (whose ability to mount an antibody response is lessened.) These two groups are at highest risk of serious pneumoccal disease.
Despite the vaccine's shortcomings, levels of protection as high as 60% have been reported for elderly populations, and protection levels in youger adults are higher. A protection rate of 60% is high enough to reduce the incidence of infection in the population and thus provide some herd immunity for people in the population who do not mount an antibody response to the vaccine. For this reason, the balance of medical opinion favors continued use of the vaccine.