A 46 year old febrile man was admitted to the hospital. He had been coughing with yellowish expectoration. Physical examination revealed high fever (38°C), tachycardia, tachypnea and appeared confused. He also complained of chest pain. Breath sound appear crackled. Chest X-ray suggested dense left lower lobe consolidation. Hematological examination revealed leucocytosis and CRP was elevated.

What is your diagnosis?
It is a case of acute lower respiratory tract infection, probably lobar pneumonia. Differential diagnosis must include viral or fungal pneumonia, bronchitis, COPD, lung abscess etc.

Which are the bacterial etiological agents of pneumonia?
Pneumonia can be caused by bacteria such as Streptococcus pneumoniae (pneumococcus), Hemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus. Other rarer pathogenic bacteria include Legionella pneumophila and Pseudomonas aeruginosa. People with poor oral hygiene, altered swallowing reflexes, or impaired consciousness are predisposed to infection by anaerobes due to aspiration of oral fluids. Mycoplasma pneumoniae is known to cause primary atypical pneumonia.

What are the specimens collected?
Patient is asked to expectorate sputum into a sterile container. In a severely ill patient specimen such as bronchial washing specimen or transtracheal aspirate may be taken. Blood may be collected for blood culture, CRP & routine blood examination. Urine may also be collected for demonstration of pneumococcal antigens.

How is the sputum specimen processed?
A gram stained smear should be made from the thick part of the sputum and observed for pus cells and bacteria. A good specimen must have less than 10 squamous epithelial cells and more than 25 pus cells per low-power field. The sputum should also be inoculated on to Blood agar or chocolate agar and incubated at 37^oC in 5-10% CO₂, preferably in a candle jar.

What are your observations?
Gram smear of sputum showed plenty of pus cells along with gram positive lanceolate shaped cocci in pairs. Small, circular, smooth, draughtsman-type colonies with alpha hemolysis were seen on blood/chocolate agar.

How do you identify the growth?
Gram stained smear of the colonies revealed gram positive lanceolate shaped cocci in pairs suggestive of pneumococci. These colonies were catalase negative. Bile solubility, inulin fermentation, optochin susceptibility, quellung reaction and mouse intraperitoneal inoculation may be done to differentiate pneumococci from viridans streptococci. Pneumococci are positive for bile solubility, inulin fermentation, quellung reaction, are susceptible to optochin and are pathogenic to mouse. The capsular antgien may be detected by latex agglutination or co-agglutination.

What is quellung reaction?
The Neufeld's quellung reaction is also known as "capsule swelling" reaction. When a suspension of pneumococcal colonies are treated with a loop of serum containing anitbodies to capsular polysaccharide and observed under microscope, the capsule appears swollen. The binding of antibodies to capsular antigen brings about a change in its refractive index, making it appear swollen. A drop of methylene blue may also be added to the suspension to provide contrast. The serum used may be monovalent or polyvalent (omniserum).

What is optochin susceptibility?
Optochin is ethyl hydrocuprein hydrochloride, a disc 5 µg of strength is placed on the lawn culture of pneumococci and incubated. A wide zone of inhibition (at least 10-13 mm diameter) around the disc indicates susceptibility.

What is bile solubility test?
Pneumococci have amidase enzymes that result in autolysis. These enzymes can be activated by surface active agents such as bile salts. Bile solubility test can be done in test tube or in culture plates. To a turbid, 1ml overnight broth culture of pneumococci, addition of few drops of 10% sodium deoxycholate results in clearance of the broth in 15 minutes. Colonies suspected to be of pneumococci are marked and a loopful of 2% sodium deoxycholate is placed on them and incubated at 37^oC for 30 minutes. The disappearance of colonies leaving behind an area of alpha hemolysis indicates positive test.

What is the pathogenesis of pneumococcal pneumonia?
Pneumonia is defined as inflammation and consolidation of the lung tissue due to an infectious agent. Streptococcus pneumoniae reach the lungs after first colonizing the oropharynx. S pneumoniae generally resides in the nasopharynx and is carried asymptomatically in approximately 50% of healthy individuals. Viral infections increase pneumococcal attachment to the receptors on activated respiratory epithelium. Presence of capsule is a major virulence factor as it helps the bacterium to evade phagocytosis. The pneumonic lesion progresses as pneumococci multiply in the alveolus and invade alveolar epithelium. Pneumococci spread from alveolus to alveolus, thereby producing inflammation and consolidation along lobar compartments. A patchy bronchopneumonic pattern involving the lower lobes is seen in the elderly. Since S. pneumoniae infection has a tendency to involve the pleura, pleural effusion is often seen.

Which are the other infections produced by pneumococci?
Pneumococci is known to cause sinusitis, otitis media, bronchitis, lung abscess, septic arthritis, septicemia, meningitis, peritonitis and endocarditis.

Which are the antibiotics used in the treatment of this condition?
Penicillin used to be the drug of choice but large number of strains are now developing resistance due to alteration in the penicillin binding proteins.  Alternate choices include macrolides (erythromycin, roxithromycin, clindamycin), quinolones (ciprofloxacin, levofloxacin) , cephalosporins (cefuroxime, cefpodoxime, cefotaxime). Many of the penicillin-resistant strains are also resistant to erythromycin, cotrimoxazole, tetracycline, and chloramphenicol. The choice of suitable antibiotic must be made after antibiotic susceptibility testing only.

Which conditions can predispose to pneumococcal infections?
Chronic alcoholism, splenectomy, previous viral respiratory illness, malnutrition, chronic smoking, cirrhosis of liver, coronary artery disease etc.

Are any vaccines available against pneumococcal disease?
A 23-valent polysaccharide vaccine against 23 common serotypes has been in use in some countries. 23-valent pneumococcal polysaccharide vaccines has been recommended for use among children aged ≥2 years who have high rates of disease, including those with sickle cell disease (SCD), chronic underlying diseases, human immunodeficiency virus (HIV) infection, or others who are immunocompromised. 23-valent pneumococcal polysaccharide vaccines are effective in preventing invasive pneumococcal disease among older children and adults, these vaccines do not protect children aged <2 years. A 7-valent pneumococcal polysaccharide-protein conjugate vaccine was licensed for use among infants and young children as it decreases colonization and prevents pneumococcal disease among children aged ≤2 years.