Case 10 - Complete Answers

(1) Most Probable Diagnosis

• 11-year-old boy with step-ladder fever rising over 10 days - the classic presentation
• Anorexia, vague abdominal pain, lethargy - typical prodromal/early symptoms
• Hepatosplenomegaly on examination
• Leukopenia (WBC 3800/cmm) with relative lymphocytosis (70%) - hallmark finding that distinguishes typhoid from bacterial sepsis (most infections raise the WBC, typhoid lowers it)
• Positive Widal test: S. Typhi O (1:240) and H (1:320) - diagnostic titres
• Elevated CRP (32.4 mg/L) and raised ESR (45 mm/hr) - markers of systemic inflammation
• Malarial parasites not detected - rules out malaria as an alternative diagnosis
• Paratyphi A and B negative - confirms S. Typhi specifically

(2) Route of Transmission

(3) Laboratory Diagnosis of the Causative Agent (Salmonella Typhi)

A. Microbiological (Culture) - Gold Standard

• Gram-negative rod (non-lactose fermenter)
• On TSI agar: alkaline slant/acid butt with H2S production, no gas (K/A, H2S, no gas) - unlike other Salmonella spp. which produce gas
• On HE agar: Black colonies due to H2S production with ferric ammonium citrate
• Biochemical: glucose+, lactose-, H2S+, urease-, indole-, motile

B. Serological - Widal Test (Felix-Widal)

• Detects agglutinating antibodies against O (somatic) and H (flagellar) antigens
• O antibodies appear on day 6-8; H antibodies appear on day 10-12
• Diagnostic titres: O antigen >1:160 and H antigen >1:160 in endemic areas; some labs use >1:320 (O) and >1:640 (H)
• In this case: O 1:240 and H 1:320 - both positive and diagnostic
• Limitations: false positives in malaria, typhus, other salmonelloses; false negatives in early disease or after antibiotic use; requires paired sera for definitive confirmation
• Vi antigen titre: high titres indicate chronic carrier state

C. Newer/Rapid Diagnostic Tests

• Typhidot test: Detects specific IgM and IgG against a 50 kDa antigen of S. Typhi; takes ~3 hours
• Typhidot-M: Detects IgM only - useful for acute infection
• TUBEX test: Detects IgM anti-O9 antibodies; results in minutes
• Dipstick test: Detects S. Typhi-specific IgM antibodies using LPS antigen
• PCR / NAATs: Nucleic acid amplification from blood or stool; highly specific but not widely available in resource-limited settings
• Blood counts: Leukopenia with relative lymphocytosis is a supportive finding - Park's Textbook of Preventive and Social Medicine

(4) Complications When Not Treated in Time

Intestinal Complications (Most Feared)

• Intestinal hemorrhage - sudden drop in temperature, signs of shock, dark/fresh blood in stool; occurs in 3rd week
• Intestinal perforation - most likely in the 3rd week; causes peritonitis, requires emergency surgery; involves Peyer's patch necrosis
• Paralytic ileus

Systemic/Extra-intestinal Complications

(5) Prophylaxis (Prevention) of Typhoid Fever

1. Control of Reservoir

• Early diagnosis and treatment of cases
• Isolation of cases until 3 consecutive negative stool and urine cultures
• Identification and management of chronic carriers: carriers must not handle food/water; treat with fluoroquinolones for 4-6 weeks; cholecystectomy if gallstones are present
• Disinfection of stools and urine with 5% cresol for at least 2 hours
• Notification to public health authorities (notifiable disease)

2. Control of Sanitation (Break Transmission)

• Safe water supply: chlorination and purification of drinking water
• Proper sewage disposal: prevent contamination of water sources
• Food hygiene: safe handling, cooking, and storage of food
• Personal hygiene: hand-washing with soap after defecation and before preparing food
• Fly control: flies are important mechanical vectors

3. Immunization (Specific Prophylaxis)

• Typhoid Conjugate Vaccine (TCV - TYPBAR-TCV): Vi polysaccharide conjugated to tetanus toxoid protein carrier; T-cell dependent response; single IM dose; effective from age 6 months; WHO-prequalified; recommended by WHO for endemic areas

• Residents of endemic areas
• Household contacts of confirmed cases
• School children and hospital staff
• Travelers to endemic regions

Sources: Park's Textbook of Preventive and Social Medicine; Jawetz Melnick & Adelbergs Medical Microbiology 28E; Harrison's Principles of Internal Medicine 22E

Case 11 - Complete Answers

(1) Provisional Diagnosis

• Causative agent: Streptococcus pyogenes (Group A Beta-Hemolytic Streptococcus / GABHS)

• 8-year-old child (peak age for streptococcal pharyngitis: 5-15 years)
• Sore throat + fever for 5 days, with recurrent similar episodes in the past
• Peritonsillar abscess on examination - a classic suppurative complication of GABHS pharyngitis
• Throat swab grew beta-hemolytic colonies on blood agar - the image shows opaque white colonies surrounded by a clear zone of complete (beta) hemolysis, exactly as seen with S. pyogenes
• Chest clear - ruling out lower respiratory tract infection

(2) Classification of the Causative Pathogen (Streptococcus pyogenes)

Morphological Classification

• Gram-positive cocci arranged in chains
• Facultatively anaerobic
• Catalase-negative (distinguishes from Staphylococcus)
• Non-spore forming, non-motile

Hemolytic Classification (Brown's classification - by pattern on blood agar)

Lancefield Serological Classification (based on cell wall carbohydrate antigens)

"Using the Lancefield classification, hemolytic streptococci can be classified into types A through G based on acid-extractable carbohydrate antigens of cell wall material. The major pathogenic β-hemolytic streptococci are group A (Streptococcus pyogenes) and group B (Streptococcus agalactiae)." - Goldman-Cecil Medicine

Further Classification of S. pyogenes

• M-protein typing: >150 different M protein serotypes based on the N-terminal variable region of M protein - used for epidemiological typing
• T-antigen typing: Based on trypsin-resistant surface proteins
• Emm gene sequencing: Molecular epidemiological tool

(3) Non-Suppurative Complications of GABHS Infection

1. Acute Rheumatic Fever (ARF)

• Occurs ~2 weeks after acute streptococcal pharyngitis (not skin infection)
• Mechanism: Molecular mimicry - antibodies against streptococcal M protein cross-react with cardiac tissue (particularly cardiac myosin), synovial tissue, and basal ganglia
• Revised Jones Criteria for diagnosis:

• Complications: Rheumatic heart disease (35-70% progress); mitral stenosis/regurgitation is the most common long-term valvular lesion
• Note: ARF does NOT follow skin infection (impetigo)

2. Post-Streptococcal Glomerulonephritis (PSGN)

• Can follow both pharyngitis AND skin infections (impetigo)
• Onset: 1-3 weeks after pharyngitis, or 3-6 weeks after skin infection
• Mechanism: Immune complex deposition (Type III hypersensitivity) in glomeruli
• Features: Hematuria (cola-colored urine), proteinuria, edema, hypertension, oliguria
• Most cases resolve spontaneously; rarely progresses to chronic renal failure
• Important: Treating the streptococcal infection does NOT prevent PSGN (unlike ARF)

3. Post-Streptococcal Reactive Arthritis (PSRA)

• Distinct from the arthritis of ARF
• Does not fulfill Jones criteria for ARF
• Occurs after both pharyngeal and skin infections
• Large and small joints affected
• Less responsive to aspirin/NSAIDs than ARF arthritis
• May have carditis but less severe than ARF

4. Scarlet Fever

• Caused by strains producing pyrogenic exotoxins (erythrogenic toxins A, B, C) acting as superantigens
• Features: Strawberry tongue, sandpaper rash (truncal, sparing face), Pastia's lines, circumoral pallor
• Follows pharyngitis (not skin infection)
• Desquamation occurs during recovery

5. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections)

• OCD, tics, and other neuropsychiatric symptoms triggered by GAS infection
• Mechanism: Antibody cross-reactivity with basal ganglia (similar to Sydenham's chorea)
• Related to but distinct from Sydenham's chorea

Sources: Goldman-Cecil Medicine; Scott-Brown's Otorhinolaryngology Head & Neck Surgery; Kaplan & Sadock's Comprehensive Textbook of Psychiatry

Case 12 - Complete Answers

(1) Causative Agent

• Alpha-hemolytic colonies with greenish discoloration on blood agar - the hallmark of S. pneumoniae (partial hemolysis converts hemoglobin to biliverdin causing the green color)
• The Gram stain image shows lancet-shaped diplococci surrounded by a clear halo (capsule), typical of pneumococci
• Elderly man (60 years) - high-risk age group
• Community-acquired lobar pneumonia with pleuritic chest pain - classic pneumococcal presentation

(2) Provisional Clinical Diagnosis

"The classic presentation of pneumococcal pneumonia consists of a rigor followed by sustained fever, cough, dyspnea, and production of rusty or mucoid sputum... Pleuritic chest pain is common and may be severe. The typical radiographic appearance is a lobar or segmental consolidation." - Murray & Nadel's Textbook of Respiratory Medicine

(3) Morphology of the Organism (from the Gram stain image)

Microscopic Morphology of S. pneumoniae:

• Shape: Oval to lancet-shaped (flame-shaped) cocci
• Arrangement: Diplococci - arranged in pairs, with the broad ends facing each other and the pointed ends facing outward (like a flame or lancet)
• Gram reaction: Gram-positive - stain deep purple/violet
• Capsule: Surrounded by a clear unstained halo (polysaccharide capsule) - visible in the image as a pale zone around the cocci
• Size: ~0.5-1.25 µm in diameter
• In culture: May form short chains
• In the image the large lavender/pink cells are red blood cells and white cells (PMNs) are also visible, typical of a purulent sputum specimen
• The small dark purple paired cocci (diplococci) are the pneumococci

Cultural Morphology (on Blood Agar):

• Alpha (α) hemolysis: Incomplete, greenish zone due to conversion of hemoglobin to biliverdin by hydrogen peroxide produced by the organism
• Colony appearance: Small, dome-shaped, mucoid colonies (due to polysaccharide capsule), later become umbilicated (central depression) due to autolysis by pneumococcal autolysin

(4) Laboratory Tests Available for Diagnosis

A. Direct Microscopy

• Gram stain of sputum: Gram-positive lancet-shaped diplococci surrounded by a clear capsular halo; look for >25 PMNs and <10 squamous epithelial cells per low-power field (a quality sputum sample)
• Capsule staining: India ink / Quellung reaction

B. Culture (Gold Standard)

• Sputum culture on Blood Agar: Alpha-hemolytic (greenish) colonies; quality sample required (Bartlett's criteria)
• Blood culture: Two sets before antibiotics - positive in bacteremia; essential in severe/hospitalized CAP
• Pleural fluid culture: If parapneumonic effusion present

C. Identification Tests for S. pneumoniae

D. Antigen Detection

• Pneumococcal urinary antigen test (BinaxNOW): Detects pneumococcal C-polysaccharide antigen in urine; rapid, high specificity; recommended for severe CAP
• Sputum antigen: Less commonly used

E. Molecular Tests

• PCR: Multiplex respiratory PCR panels (FilmArray) - detect S. pneumoniae directly from respiratory samples; high sensitivity
• 16S rRNA gene sequencing: For identification when culture fails

F. Serology

• Anti-pneumococcal antibody titres: Mostly used for vaccine response assessment, not acute diagnosis

G. Imaging

• Chest X-ray: Lobar/segmental consolidation (confirm pneumonia; define lobe involved)
• CT chest: Better definition of consolidation, identify complications (empyema, abscess)

H. Other Supporting Tests

• CBC: Leukocytosis with neutrophilia
• CRP, procalcitonin: Elevated (procalcitonin useful to guide antibiotic duration)
• LDH, ABG: Assess severity

(5) Two Differences Between Upper Respiratory Tract Infection (URTI) and Lower Respiratory Tract Infection (LRTI)

As in this case: The 60-year-old man has LRTI (pneumonia) - with features typical of lower tract disease: productive cough, pleuritic pain, crepitations in the right mid lobe, consolidation on CXR, and dyspnea. An URTI would have presented with sore throat, runny nose, and nasal congestion without chest findings.

Sources: Murray & Nadel's Textbook of Respiratory Medicine; Red Book 2021 - Report of the Committee on Infectious Diseases; Fishman's Pulmonary Diseases and Disorders