Case Study: Streptococcus pneumoniae

Streptococcus pneumoniae mode of infection and pathogenicity

-Bacteria evade mucociliary system and reach lungs, where capsule prevent macrophages from engulfing the bacteria -Some bacteria will lyse, releasing pneumotoxin as well as damaging host mucosal cells >Impairs the host's ability to clear the bacteria trapped in mucus and facilitates in the colonization of the bacteria in the lungs >Pneumotoxin also initiates a localized inflammatory response in the lung, which attracts more phagocytic cells to the area -Gas exchange mechanisms are impaired and the person becomes cyanotic due to lack of oxygen from lung cell damage -Often follows an upper respiratory tract infection -Fever and chills, chest pain, difficulty breathing, malaise, weakness and a cough yielding sputum -Case-fatality rates of 5-7%, higher in the elderly -In 15-30% of patients with pneumococcal pneumonia, the bacteria enter the bloodstream, where they lyse and the cell wall components trigger a massive cytokine release resulting in fever and septic shock (mortality rate of this bacteremia is 20%, up to 60% in elderly) - 3000-6000 cases/ year of meningitis in the USA >Occurs when bacteria from the bloodstream attach to the membranes that cover the brains and spinal column, with symptoms including headache, lethargy, vomiting, irritability, fever, seizures, and coma.

The capsule of Streptococcus pneumoniae

-Compose of polysaccharide completely enveloping pneumococcal cells. -90 different capsule types of pneumococci have been identified -Polysaccharide is non-toxic and does not induce an inflammatory response --> an antibody-mediated response to the polysaccharide can be induced -Different capsule types can be identified by serological testing >To determine the capsular type, a sample of the bacterial colony is mixed with a specific monoclonal antibody, a positive test indicated by the swelling of the capsule which can be viewed under a phase-contrast microscope: QUELLUNG REACTION (quellung = swelling)

Vaccine and prevention of Streptococcus pneumoniae infections

-Current vaccine: purified capsular polysaccharide antigens of 23 types of the bacteria, cross-reactivity occurs for several of the capsular types -Vaccine is given to high-risk persons: elderly, immunosuppressed, patients with pulmonary disease -Does not elicit a strong response (polysaccharides immunogenicity < proteins), especially in high-risk groups -Conjugate vaccine consisting of polysaccharide antigens covalently bonded to proteins (increased immunogenicity) --> covers 7 capsular types, used primarily for prevention of ear infections -Antibody that is induced results in effective opsonization of the bacteria and contributes to the host's recovery

Evasion of the host defences by Streptococcus pneumoniae

-Encapsulated organisms are pathogenic for humans and experimental animals, whereas mutant derivatives without polysaccharide capsules are not (capsule is an essential determinant of the virulent of the bacteria) -Invades and grows primarily due to the resistance to the host phagocytic response --> capsule can hide bacterial components such as peptidoglycan which can induce the alternate complement pathway and prevents the formation of C3b complex -Capsule ALSO interferes with phagocytosis by preventing C3b opsonization of the bacteria

Diagnosis of Streptococcus pneumoniae infections

-From sputum, blood or cerebrospinal fluid = Gm(+), hemolytic activity and bile sensitivity --> causes alpha hemolysis on blood agar plates in aerobic conditions (reduction of RBC hemoglobin = greening) > in anaerobic conditions, bacteria cause beta hemolysis (complete lysis of the RBCs surrounding the colony -The bacteria can be difficult to grow, so a negative result does not rule out pneumococcal pneumonia. Also, positive cultures from sputum samples may be the result of contamination from bacteria in the mouth of a colonized patient

Streptococcus pneumoniae as an opportunistic pathogen

-It is often present in the normal flora of healthy individuals, but only causes disease in debilitated hosts -Common bacterial complication of influenza and measles infections -Infants and young children are at greater risk due to not fully developed immune systems -Elderly patients are at greater risk due to inefficient immune systems (won't often develop fevers in response to bacterial infections) -Smokers are at increased risk due to damaged mucociliary transport, and a decrease in the coughing reflex -Alcohol abusers are at an increased risk due to the sedative effects and diminished reflexes that trigger coughing and sneezing, as well as interfering with macrophage action

The Bacterium

-Non-motile -Non-sporulating -Gm(+) -Cocci -Often diplococci, sometimes single, sometimes in short chains -Transient member of the normal flora, colonizing the nasopharynx of 40% or healthy people with no adverse effects -Very sensitive to heat, cold, and drying -Transmission via respiratory droplets -Major virulence factors: >anti-phagocytic polysaccharide capsule >several adhesins >pneumolysin (a toxin that binds to cholesterol in the host cell membrane and disrupts them by forming pores) >LTA (lipoteichoic acid)

Treatment of Streptococcus pneumoniae infection

-OLD: penicillin and penicillin-derivatives, now resistance is common -NOW: Erythromycin and tetracycline, resistance on the rise

The Diseases cause by Streptococcus pneumoniae

-Pneumonia (inflammation of the lungs) -Bacteremia (bacteria in the blood) -Meningitis (inflammation of the membranes surrounding the brain and the spinal column) -Otitis media (middle ear infection) --> 6 million cases/ year in USA -70% of all bacterial pneumonias -50% of nosocomial pneumonias -Most vaccine-preventable bacterial disease

Pneumococcal pneumonia

-The most common clinical presentation of disease among adults -Two forms: bronchial pneumonia and lobar pneumonia >Bronchial pneumonia: most prevalent in infants, young children and aged adults and involves the alveoli contiguous to the larger bronchioles of the bronchial tree >Lobar pneumonia: more likely to occur in younger adults and involves all of a single lobe of the lungs (may be more than 1 lobe involved)