Gas Gangrene Urinary Tract Infection (UTI) 3-Star Topics Pyogenic Meningitis / Meningococcal Meningitis Pulmonary Tuberculosis Syphilis and Spirochetes Streptococcus pyogenes (Non-suppurative sequelae) Lower Respiratory Tract Infection (LRTI) 2-Star Topics Dermatophytes / Dermatophytosis Chlamydia trachomatis Rabies / Rhabdoviruses Influenza Viruses Cryptococcal Meningitis Answer them in microbiology mbbs muhs ut paper

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Here are complete MUHS UT-style microbiology answers for all topics. Each answer is structured the way MUHS examiners expect - heading, organism, morphology, pathogenesis, clinical features, lab diagnosis, and treatment.

MICROBIOLOGY - MUHS UT ANSWERS

⭐⭐⭐⭐ 4-STAR TOPICS

1. GAS GANGRENE (Clostridial Myonecrosis)

Definition

Gas gangrene is a rapidly spreading, life-threatening infection of muscle characterized by gas production and tissue necrosis. It is also called clostridial myonecrosis.

Causative Organism

Clostridium perfringens (most common, ~80% of cases) - Gram-positive, spore-forming, anaerobic bacillus
Other species: C. novyi, C. septicum, C. histolyticum, C. bifermentans

Morphology

Gram-positive, large, rectangular rods
Non-motile (C. perfringens), capsulated
Central to subterminal oval spores (spores rarely seen in tissue)
Obligate anaerobe

Cultural Characteristics

Blood agar: Double zone of hemolysis (inner complete beta + outer incomplete alpha) - "target hemolysis"
Nagler reaction: Lecithinase (alpha toxin) produces opalescence on egg yolk agar, inhibited by specific antitoxin

Toxins / Virulence Factors

Toxin	Action
Alpha toxin (lecithinase C)	Most important - hydrolyzes cell membrane phospholipids, causes massive hemolysis, tissue necrosis
Theta toxin (perfringolysin)	Cholesterol-dependent cytolysin
Kappa toxin	Collagenase - aids spread
Mu toxin	Hyaluronidase
Nu toxin	DNase
Enterotoxin	Food poisoning

Pathogenesis

Spores enter wound (war wounds, trauma, surgery) → anaerobic conditions (devitalized tissue, low O2 tension) → spores germinate → vegetative forms release toxins → alpha toxin destroys cell membranes → muscle necrosis → gas (CO2, H2, H2S) accumulates → rapid spread

Clinical Features

Incubation: 6 hours to 3 days
Severe pain out of proportion to wound appearance (EARLIEST symptom)
Edema, tense brawny skin with bronze/brown discoloration
Gas in tissue - crepitus on palpation
Characteristic foul-smelling, serosanguinous discharge ("dirty dishwater" fluid)
Wound shows absence of true pus (no neutrophils due to toxin killing them)
Rapid systemic toxemia: fever, tachycardia, hypotension, shock
Death within hours if untreated

Lab Diagnosis

Direct Smear (Gram stain):

Large Gram-positive rods with ABSENCE of pus cells (pathognomonic)
No spores typically seen in smears

Culture:

Robertson's cooked meat medium, thioglycollate broth
Blood agar: Target hemolysis
Nagler plate: Lecithinase reaction
Stormy fermentation of milk (Litmus milk medium)

Biochemical tests:

Glucose, maltose, lactose fermented (acid + gas)
H2S produced

Animal inoculation:

Mice develop gas gangrene within hours

Treatment

Surgical debridement (most important) - wide excision/amputation
Benzylpenicillin (high dose IV) - drug of choice
Metronidazole - alternative
Hyperbaric oxygen therapy - inhibits anaerobic growth, limits toxin production
Polyvalent gas gangrene antitoxin - supportive

Prevention

Proper wound debridement
Penicillin prophylaxis for contaminated wounds
Avoid ischemic conditions

2. URINARY TRACT INFECTION (UTI)

Definition

UTI is microbial colonization of the urine with invasion and inflammation of the urinary tract, from the urethra to the kidneys.

Classification

Type	Location
Cystitis	Bladder
Urethritis	Urethra
Pyelonephritis	Kidney and renal pelvis
Prostatitis	Prostate
Asymptomatic bacteriuria	>10^5 CFU/mL without symptoms

Common Causative Organisms

Community-acquired UTI:

Escherichia coli (most common, ~80%)
Staphylococcus saprophyticus (young sexually active women - 2nd most common)
Klebsiella pneumoniae
Proteus mirabilis (associated with struvite stones - urease producer)
Enterococcus faecalis

Hospital-acquired (nosocomial) UTI:

Pseudomonas aeruginosa, Klebsiella, E. coli, Candida species

Virulence Factors of E. coli

Type 1 fimbriae (mannose-sensitive) - attach to uroepithelium
Type P fimbriae / Pili (mannose-resistant, Pap pili) - bind to P blood group antigens on urothelium → main factor in pyelonephritis
Hemolysin - lyses RBCs, releases iron
Aerobactin - siderophore for iron acquisition
K antigen (capsule) - anti-phagocytic
Urease - Proteus; alkalinizes urine → struvite stones

Pathogenesis

Ascending route (most common): Periurethral colonization → urethra → bladder → ureters → kidney

Risk factors:

Female sex (short urethra, close to anus)
Sexual activity, pregnancy
Urinary catheter (most common risk for nosocomial UTI)
Urinary obstruction, calculi
Diabetes mellitus, immunosuppression

Clinical Features

Lower UTI (Cystitis):

Dysuria, frequency, urgency
Suprapubic pain/tenderness
Cloudy, malodorous urine
Hematuria

Upper UTI (Pyelonephritis):

Fever, chills, rigors
Loin/flank pain, costovertebral angle tenderness
Nausea, vomiting
Features of lower UTI + systemic toxicity

Lab Diagnosis

Urine collection: Midstream clean catch (MSU)

Macroscopic examination:

Turbid/cloudy urine, foul smell

Microscopy:

Pus cells (pyuria) - >5 WBC/HPF or >10 WBC/mL
RBCs, bacteria
Casts (in pyelonephritis)

Significant Bacteriuria (Kass criterion):

≥10^5 CFU/mL in MSU - significant
≥10^3 CFU/mL in symptomatic women
≥10^2 CFU/mL in catheter specimen

Dipstick tests:

Nitrite test: positive (gram-negative bacteria convert nitrate → nitrite)
Leukocyte esterase: positive (pyuria)

Culture: CLED agar (Cystine Lactose Electrolyte Deficient) - prevents swarming of Proteus

Screening tests: Griess nitrite test, catalase test

Treatment

UTI Type	Drug of Choice
Uncomplicated lower UTI	Nitrofurantoin, Trimethoprim-sulfamethoxazole, Fosfomycin
Upper UTI/pyelonephritis	Fluoroquinolones (ciprofloxacin), IV cephalosporins
Hospital-acquired/catheter UTI	Based on culture sensitivity
Recurrent UTI	Low-dose prophylaxis, cranberry products
UTI in pregnancy	Amoxicillin, nitrofurantoin (avoid near term)

⭐⭐⭐ 3-STAR TOPICS

3. PYOGENIC MENINGITIS / MENINGOCOCCAL MENINGITIS

Definition

Pyogenic (bacterial) meningitis is acute inflammation of the meninges (pia mater and arachnoid) caused by pyogenic bacteria.

Common Causative Organisms by Age Group

Age Group	Common Organisms
Neonates (0-3 months)	E. coli (K1 antigen), Group B Streptococcus, Listeria monocytogenes
Infants (1-23 months)	Streptococcus pneumoniae, Neisseria meningitidis, H. influenzae
Children/Young adults (2-50 yrs)	Neisseria meningitidis (most common), S. pneumoniae
Adults >50 yrs	S. pneumoniae, Listeria monocytogenes

NEISSERIA MENINGITIDIS (Meningococcus)

Morphology:

Gram-negative diplococcus (kidney/coffee-bean shaped, arranged with flat surfaces together)
Non-motile, non-sporing
Capsulated (polysaccharide capsule - main virulence factor)
Oxidase positive

Serogroups: A, B, C, W135, X, Y

Group A: Epidemic meningitis in Africa (meningitis belt)
Group B: Sporadic cases in developed countries
Group C: Outbreak-related

Virulence Factors:

Capsule - antiphagocytic, determines serogroup
Pili - adhesion to nasopharyngeal epithelium
IgA protease - cleaves secretory IgA
Outer membrane proteins (OMPs) - adhesins
LPS (lipooligosaccharide) - endotoxin → septic shock, DIC

Cultural Characteristics:

Growth: 37°C, 5-10% CO2 (capnophilic)
Chocolate agar (preferred), Blood agar
Sensitive to cold, drying, bile
Maltose fermenter (distinguishes from N. gonorrhoeae which does NOT ferment maltose)

Pathogenesis

Droplet inhalation → nasopharyngeal colonization → bloodstream invasion (bacteremia/meningococcemia) → seeding of meninges → intense neutrophilic inflammation → meningitis

Clinical Features

Meningitis triad:

Fever
Headache (severe)
Neck stiffness (meningism)

Additional features:

Photophobia, phonophobia
Vomiting
Positive Kernig's sign (inability to extend knee with hip flexed to 90°)
Positive Brudzinski's sign (neck flexion causes involuntary hip flexion)
Altered consciousness, seizures

Meningococcemia (Waterhouse-Friderichsen Syndrome):

Massive bacteremia → DIC → bilateral adrenal hemorrhage
Petechial/purpuric non-blanching rash (classic)
Fulminant septicemia with shock
Very high mortality

Lab Diagnosis

CSF examination (most important):

Parameter	Normal	Pyogenic Meningitis
Appearance	Clear	Turbid/purulent
Pressure	Normal	Raised
Cells	0-5 lymphocytes	200-2000+ neutrophils (PMN)
Protein	15-45 mg/dL	Raised >100 mg/dL
Glucose	50-80 mg/dL	Low (<45 mg/dL), <2/3 blood glucose
Gram stain	-	Gram-negative diplococci

Investigations:

Gram stain + culture of CSF
Blood cultures (positive in 50-60%)
Latex agglutination/immunochromatography - rapid antigen detection
PCR of CSF - most sensitive
Throat swab culture

Treatment

Ceftriaxone (drug of choice, IV 2g BD) or Cefotaxime
Penicillin G - if organism sensitive
Dexamethasone (adjunctive - reduces inflammation)
Contacts: Rifampicin prophylaxis (or ciprofloxacin single dose)

Vaccines

Meningococcal conjugate vaccines: MenACWY
MenB vaccine: Bexsero, Trumenba

4. PULMONARY TUBERCULOSIS

Causative Organism

Mycobacterium tuberculosis (Koch's bacillus)

Also: M. bovis (bovine TB, zoonosis)

Morphology

Slender, straight/slightly curved bacilli
Acid-fast bacillus (AFB) - Ziehl-Neelsen (ZN) stain: bright red bacilli on blue background
Non-motile, non-sporing, non-capsulated
Obligate aerobe (explains predilection for apex of lung - high O2)
Cell wall rich in mycolic acids (responsible for acid fastness and drug resistance)
Beaded appearance on staining; may appear as cords (serpentine cording - virulence feature)

Cultural Characteristics

Slow grower (generation time 14-20 hours)
Grows in 6-8 weeks
Colonies: Dry, buff-coloured, granular, irregular ("breadcrumb" or "cauliflower" colonies)
Lowenstein-Jensen (LJ) medium - gold standard culture medium
BACTEC MGIT system (liquid medium) - faster (10-14 days)
Niacin production positive (differentiates M. tuberculosis from other mycobacteria)
Nitrate reduction positive
Cord factor (trehalose dimycolate) - grows in cords - virulence marker

Pathogenesis

Primary TB (Ghon complex):

Inhalation of 1-5 bacilli → alveolar macrophages engulf bacteria
Bacteria survive intracellularly (inhibit phagolysosome fusion)
Granuloma formation (Ghon focus) with Langhans giant cells
Lymph node involvement → Ghon complex (Ghon focus + lymph nodes) = Primary complex
Usually self-limiting → fibrosis and calcification

Post-Primary (Secondary) TB:

Reactivation of dormant bacilli OR reinfection
Occurs at apices (Simon's focus) due to high O2 tension
Caseous necrosis, cavitation
Spread via bronchi → dissemination

Mantoux/Tuberculin reaction:

Type IV (delayed-type) hypersensitivity mediated by sensitized T lymphocytes
Read at 48-72 hrs
≥10 mm induration = positive (in healthy individuals)
≥5 mm in HIV, immunosuppressed
≥15 mm in low-risk individuals

Clinical Features

Pulmonary TB symptoms:

Chronic cough >2-3 weeks
Hemoptysis (blood in sputum - IMPORTANT symptom)
Low-grade evening fever
Night sweats
Weight loss (constitutional symptoms)
Anorexia, malaise, fatigue
Dyspnea (in advanced disease)

Lab Diagnosis

Sputum examination:

Collect early morning sputum x 3 specimens
ZN stain (direct smear): AFB seen as red rods on blue background
Fluorescent stain: Auramine O / Auramine-rhodamine (more sensitive, examined under fluorescent microscope)
Grading: Scanty, 1+, 2+, 3+

Culture:

LJ medium (6-8 weeks) or MGIT (10-14 days)
Biochemical tests: niacin, nitrate reduction

Molecular tests:

CBNAAT (GeneXpert MTB/RIF) - rapid, detects MTB and rifampicin resistance within 2 hrs
Line probe assay (LPA) - detects MDR-TB

Tuberculin test (Mantoux):

0.1 mL of 5 TU PPD intradermally, read at 48-72 hrs

Other:

Chest X-ray: Consolidation, cavitation at apex, hilar lymphadenopathy
IGRA (interferon gamma release assay): QuantiFERON-TB Gold, T-SPOT.TB

Treatment (DOTS - Directly Observed Treatment Short course)

Category I (New cases):

Intensive phase: 2 months - HRZE (Isoniazid + Rifampicin + Pyrazinamide + Ethambutol)
Continuation phase: 4 months - HR (Isoniazid + Rifampicin)
Total: 6 months

MDR-TB: Bedaquiline, Linezolid, Fluoroquinolones (longer regimen)

5. SYPHILIS AND SPIROCHETES

Causative Organism

Treponema pallidum subspecies pallidum

Morphology (Spirochetes)

Slender, tightly coiled spirochete (8-14 coils)
Length 6-20 µm
Cannot be cultured in artificial media
Visualized by:
- Darkfield microscopy (gold standard for primary syphilis) - corkscrew motility
- Silver impregnation stain (Warthin-Starry, Levaditi stain)
- Immunofluorescence (DFA-TP)
Does not stain with Gram stain or ZN stain

Stages of Syphilis

PRIMARY SYPHILIS (3-4 weeks after infection):

Painless indurated ulcer = CHANCRE (usually on genitals)
Hard, clean-based, with undermined edges
Highly infectious (teeming with spirochetes)
Heals spontaneously in 3-6 weeks
Regional painless lymphadenopathy

SECONDARY SYPHILIS (6-8 weeks after primary):

Systemic dissemination of spirochetes
Generalized maculopapular rash - classically involves palms and soles
Condylomata lata - flat moist warty lesions in moist areas (perianal, vulva)
Mucous patches in mouth
Alopecia (moth-eaten pattern)
Generalized lymphadenopathy
Highly infectious stage

LATENT SYPHILIS:

Early latent (<1 year): May relapse to secondary
Late latent (>1 year): Non-infectious

TERTIARY SYPHILIS (years later):

Gumma - granulomatous lesion in skin, bones, liver (non-infectious)
Cardiovascular syphilis: Aortitis, aortic aneurysm (ascending), aortic regurgitation
Neurosyphilis:
- Meningovascular syphilis
- Tabes dorsalis (posterior column demyelination): Lightning pain, ataxia, Argyll Robertson pupil
- General paresis of insane (GPI)

CONGENITAL SYPHILIS: Early: Snuffles (rhinitis), maculopapular rash, hepatosplenomegaly, condylomata Late: Hutchinson's teeth, interstitial keratitis, 8th nerve deafness (Hutchinson's triad), saddle nose, saber tibia

Lab Diagnosis

Darkfield microscopy: Primary and secondary syphilis (lesion exudate)

Serological tests:

Non-treponemal (screening):

VDRL (Venereal Disease Research Laboratory) - flocculation, detects reagin (anti-cardiolipin antibodies)
RPR (Rapid Plasma Reagin) - more sensitive
False positives: Malaria, SLE, leprosy, pregnancy, viral infections
Used to monitor treatment response (titres fall with treatment)

Treponemal (confirmatory):

TPHA/TPPA (Treponema pallidum haemagglutination/particle agglutination)
FTA-ABS (Fluorescent Treponemal Antibody Absorbed) - most sensitive and specific
ELISA, Chemiluminescent assay (CLIA)
Remain positive for life (cannot monitor treatment)

Prozone phenomenon: Falsely negative VDRL in secondary syphilis due to excess antibodies - resolved by diluting serum

Treatment

Benzathine penicillin G (drug of choice) - single dose 2.4 MU IM for primary and secondary
Tertiary: 3 weekly doses
Penicillin allergy: Doxycycline, Azithromycin
Congenital: Aqueous penicillin G IV
Jarisch-Herxheimer reaction: Fever, chills, rash within hours of first penicillin dose - due to massive lysis of spirochetes

6. STREPTOCOCCUS PYOGENES (Non-Suppurative Sequelae)

Organism

Streptococcus pyogenes (Group A Streptococcus, GAS) - Gram-positive cocci in chains, beta-hemolytic, Lancefield Group A

Suppurative vs Non-Suppurative Sequelae

Suppurative: Pharyngitis, tonsillitis, impetigo, erysipelas, cellulitis, scarlet fever, necrotizing fasciitis, TSS

Non-suppurative (post-streptococcal immunological) sequelae:

Acute Rheumatic Fever (ARF)
Acute Post-Streptococcal Glomerulonephritis (APSGN)
Reactive Arthritis

A. ACUTE RHEUMATIC FEVER (ARF)

Follows: Pharyngeal/throat infection ONLY (not skin infection) Latent period: 2-4 weeks after pharyngitis

Pathogenesis - Molecular Mimicry:

Streptococcal M protein and streptolysins → antibodies formed
These antibodies cross-react with cardiac tissue antigens (molecular mimicry)
Aschoff bodies (pathognomonic) - perivascular granulomas with fibrinoid necrosis
Pancarditis (endo + myo + pericarditis)

Jones Criteria (2015 revised): Major criteria: Carditis, Polyarthritis (migratory), Chorea (Sydenham's), Erythema marginatum, Subcutaneous nodules (Mnemonic: C-P-C-E-S)

Minor criteria: Fever, elevated ESR/CRP, prolonged PR interval, previous RF

Diagnosis: 2 Major OR 1 Major + 2 Minor + evidence of preceding streptococcal infection (throat culture, elevated ASO titre)

ASO (Anti-Streptolysin O) titre:

200 Todd units in adults; >333 Todd units in children - significant
Peaks 3-6 weeks after infection

B. ACUTE POST-STREPTOCOCCAL GLOMERULONEPHRITIS (APSGN)

Follows: Throat OR skin (impetigo) infection Nephritogenic strains: M-types 1, 4, 12 (throat); 49, 55, 57 (skin) Latent period: 1-3 weeks (pharyngitis); 3-6 weeks (skin infection)

Pathogenesis:

Immune complex deposition in glomeruli (Type III hypersensitivity)
Subepithelial "humps" (immune complexes) on electron microscopy
Complement activation → inflammation → glomerulonephritis

Features:

Hematuria (cola/tea-colored urine)
Proteinuria, oliguria
Edema (periorbital, dependent)
Hypertension
Elevated ASO titre
Low complement (C3) levels

Lab: Red cell casts in urine, elevated BUN/creatinine

Prognosis: Usually self-limiting; complete recovery in children; some adults develop chronic renal disease

7. LOWER RESPIRATORY TRACT INFECTION (LRTI)

Classification

Type	Location	Common Organisms
Pneumonia	Lung parenchyma	S. pneumoniae, H. influenzae, S. aureus, Klebsiella
Bronchitis	Bronchi	Viral, H. influenzae, M. catarrhalis
Bronchiolitis	Bronchioles	RSV (in infants)
Lung abscess	Lung cavitation	Anaerobes, S. aureus, Klebsiella

Streptococcus pneumoniae (Pneumococcal Pneumonia)

Most common cause of community-acquired pneumonia (CAP)

Morphology:

Gram-positive, lancet-shaped diplococci
Capsulated (capsule is main virulence factor - anti-phagocytic)
Alpha-hemolytic on blood agar
Bile soluble (autolysis in bile/sodium deoxycholate) - distinguishing test
Optochin (ethylhydrocupreine) sensitive (distinguishes from viridans streptococci)
Quellung reaction (capsular swelling with specific antisera)

Clinical features of pneumococcal pneumonia:

Sudden onset fever, rigors
Productive cough with rusty/blood-stained sputum
Pleuritic chest pain
Lobar consolidation on X-ray

Lab diagnosis:

Sputum Gram stain: Gram-positive lancet-shaped diplococci + PMN leukocytes
Blood culture (positive in bacteremic pneumonia)
Urinary pneumococcal antigen test (rapid)
Widal: negative (rules out enteric fever)

Haemophilus influenzae

Gram-negative coccobacillus
Requires X factor (hemin) and V factor (NAD) for growth
Grows as satellite around Staph on blood agar
Chocolate agar required
Type b (Hib) - causes meningitis, epiglottitis, pneumonia

Klebsiella pneumoniae

Gram-negative rod
Mucoid, encapsulated
Friedlander's bacillus
Red currant jelly sputum (blood-tinged mucoid)
Causes lobar pneumonia in alcoholics, diabetics

Atypical Pneumonia Organisms

Organism	Feature
Mycoplasma pneumoniae	No cell wall, cold agglutinins positive, walking pneumonia
Legionella pneumophila	Legionnaire's disease, water/AC cooling towers, Silver stain, grown on BCYE agar
Chlamydophila pneumoniae	Mimics bacterial pneumonia

Treatment

Condition	Drug
Pneumococcal pneumonia	Amoxicillin / Penicillin G; Azithromycin (atypical)
Klebsiella pneumonia	3rd gen cephalosporins + aminoglycoside
Atypical pneumonia	Macrolides (Azithromycin), Doxycycline
H. influenzae	Amoxicillin-clavulanate, Cephalosporins

⭐⭐ 2-STAR TOPICS

8. DERMATOPHYTES / DERMATOPHYTOSIS

Definition

Superficial fungal infections of keratinized tissues (skin, hair, nails) caused by dermatophytes (keratinophilic fungi).

Classification of Dermatophytes (3 genera)

Trichophyton - skin, hair, AND nails (most common cause of nail infections)
Microsporum - skin AND hair only (not nails)
Epidermophyton - skin AND nails only (NOT hair)

Mnemonic: Trichophyton - Three (skin+hair+nails), Microsporum - Missing nails, Epidermophyton - Excluding hair

Ecological Classification

Anthropophilic - humans (cause chronic, low inflammatory infection): T. rubrum, T. tonsurans, E. floccosum
Zoophilic - animals → humans (cause acute, inflammatory): M. canis, T. verrucosum
Geophilic - soil → humans (cause acute, inflammatory): M. gypseum

Clinical Types (Tineas)

Tinea	Site	Common Organism
Tinea capitis	Scalp and hair	Microsporum, T. tonsurans
Tinea corporis	Body (trunk)	T. rubrum, M. canis
Tinea cruris	Groin ("jock itch")	T. rubrum, E. floccosum
Tinea pedis	Foot ("athlete's foot")	T. rubrum, T. interdigitale
Tinea unguium (Onychomycosis)	Nails	T. rubrum
Tinea versicolor	(Not dermatophyte - Malassezia furfur)

Pathogenesis

Dermatophytes secrete keratinases and proteases that digest keratin → invasion of stratum corneum, hair, nails

Clinical Features (General)

Ring-shaped (annular) lesion with central clearing, advancing scaly border
Itching (pruritus)
Peripheral spread
Chronic in immunocompromised

Tinea capitis features:

Patchy alopecia
Gray patch type (endothrix/ectothrix)
Kerion (acute inflammatory, boggy, pustular - zoophilic)
Favus (T. schoenleinii) - scutula, mouse odor

Lab Diagnosis

KOH (Potassium hydroxide) preparation - MOST IMPORTANT:

Dissolves keratin, reveals fungal elements
Branching septate hyphae + arthrospores in skin and nail
Ectothrix: Spores outside hair shaft (Microsporum)
Endothrix: Spores inside hair shaft (Trichophyton)

Wood's lamp (UV light):

Microsporum species: bright green fluorescence
T. schoenleinii: dull green
Trichophyton: no fluorescence (negative)

Culture:

Sabouraud's Dextrose Agar (SDA) + Cycloheximide + Chloramphenicol
Trichophyton: Urease test, nutritional requirements distinguish species
Macroconidia and microconidia morphology identifies genus

Treatment

Condition	Drug
Tinea capitis	Oral Griseofulvin (drug of choice), or Terbinafine
Tinea corporis, cruris, pedis	Topical azoles (clotrimazole, miconazole), Terbinafine cream
Onychomycosis	Oral Terbinafine (1st choice), Itraconazole
Recurrent/severe	Oral Itraconazole, Fluconazole

9. CHLAMYDIA TRACHOMATIS

Classification

Chlamydia trachomatis - obligate intracellular pathogen

Serovars and diseases:

Serovars	Disease
A, B, Ba, C	Trachoma (hyperendemic blinding)
D - K	Genital tract infection (urethritis, cervicitis, PID)
D - K	Neonatal ophthalmia, neonatal pneumonia
L1, L2, L2a, L3	Lymphogranuloma venereum (LGV)

Morphology and Unique Properties

Gram-negative (thin peptidoglycan but no muramic acid)
Obligate intracellular parasite (cannot synthesize ATP - "energy parasite")
Two forms:
- Elementary body (EB): Infectious, metabolically inactive, extracellular, resistant
- Reticulate body (RB): Non-infectious, metabolically active, replicates intracellularly
Inclusion bodies: Iodine-staining glycogen inclusions (unlike C. psittaci)
Contains DNA, RNA, ribosomes (unlike viruses)

Life Cycle

EB attaches to host cell → endocytosis → EB → RB (reorganization, 8 hrs) → RB multiplies by binary fission → RB → EB (condensation, 24-48 hrs) → cell lyses → release of EBs → new cycle

Diseases

A. TRACHOMA (serovars A, B, Ba, C):

Chronic keratoconjunctivitis
Leading infectious cause of blindness worldwide
MacCallan stages: I (follicular hyperplasia), II (trachomatous inflammation), III (cicatricial), IV (healed)
Arlt's line - scar at limbus
Pannus formation (vascular invasion of cornea)
Entropion → trichiasis → corneal ulceration → blindness
Treatment: Azithromycin (single dose) or Tetracycline

B. GENITAL INFECTIONS (serovars D-K):

Most common bacterial sexually transmitted infection (STI)
Men: Non-gonococcal urethritis (NGU), epididymitis
Women: Mucopurulent cervicitis, PID (Pelvic Inflammatory Disease), infertility, ectopic pregnancy
Reiter's syndrome (urethritis + arthritis + uveitis) - reactive arthritis
Treatment: Azithromycin 1g single dose OR Doxycycline 100mg BD x 7 days

C. LYMPHOGRANULOMA VENEREUM - LGV (serovars L1, L2, L3):

STI predominantly in tropical regions
Primary stage: Small painless papule/ulcer on genitals (transient)
Secondary stage: Inguinal bubo - painful inguinal lymphadenopathy, groove sign (enlargement above and below inguinal ligament), femoral lymph nodes = pathognomonic
Tertiary stage: Esthiomene (genital elephantiasis), rectal strictures
Treatment: Doxycycline 100mg BD x 21 days

D. NEONATAL INFECTIONS:

Transmitted during birth through infected birth canal
Ophthalmia neonatorum (within 5-12 days of birth)
Neonatal pneumonia (afebrile, staccato cough, 3-12 weeks of age)

Lab Diagnosis

Giemsa stain / Iodine stain: Intracytoplasmic inclusion bodies
Cell culture (McCoy cells, HeLa 229) - gold standard
NAAT (PCR) - most sensitive and specific (current gold standard)
Direct fluorescent antibody (DFA)
Micro-IF test: Gold standard serology for LGV
ELISA: Antigen detection

Frei test (historical)

Intradermal test for LGV using Frei antigen - obsolete now

10. RABIES / RHABDOVIRUSES

Causative Organism

Rabies virus - Family Rhabdoviridae, Genus Lyssavirus

Morphology

Bullet-shaped (bacilliform) virus - characteristic
Size: 75 x 180 nm
Enveloped, single-stranded, negative-sense RNA virus
Helical nucleocapsid
Surface: G protein (glycoprotein) spikes - responsible for viral attachment to host cell (nicotinic acetylcholine receptors and neuronal cell adhesion molecule) - main neutralizing antigen, used in vaccines
N protein (nucleoprotein) - complement fixation antigen, used for diagnosis

Transmission

Bite of rabid animal (dogs - most common worldwide, bats in Americas)
Licks on abraded skin/mucosa
Rare: aerosol in bat caves, organ transplant

Pathogenesis

Virus inoculation at bite site → binds to neuromuscular junction → retrograde axonal transport along peripheral nerves to CNS → replication in brain (limbic system, cerebellum, hippocampus) → centrifugal spread to salivary glands, skin, cornea → clinical disease

Incubation period:

10 days to 12 months (average 1-3 months)
Shorter with head/face bites
Longer with foot/leg bites (longer nerve pathway)

Clinical Features

1. Prodrome (2-10 days):

Pain, paresthesia, itching at bite site (PATHOGNOMONIC early feature)
Fever, malaise, headache

2. Acute Neurological Phase:

Furious (encephalitic) rabies (80%):

Hydrophobia - fear of water, pharyngeal spasms on attempting to swallow
Aerophobia - spasms on seeing/feeling air
Hypersalivation, lacrimation
Anxiety, agitation, hallucinations
Autonomic instability

Dumb (paralytic) rabies (20%):

Ascending paralysis (like Guillain-Barre)
No hydrophobia
Less dramatic presentation

3. Coma and Death:

Invariably fatal once clinical symptoms appear
Death within 7-14 days

Lab Diagnosis

Pathognomonic finding:

Negri bodies - intracytoplasmic eosinophilic inclusions in neurons (especially hippocampal pyramidal cells - Sommer's sector, and cerebellar Purkinje cells)
Stain with Mann's or Seller's stain (magenta pink inclusions with blue-black granules)

Antemortem diagnosis:

Nuchal skin biopsy (hair follicle nerve endings): Immunofluorescence (FAT)
Corneal impression smears: FAT
Saliva: RT-PCR
CSF: RT-PCR

Postmortem:

Brain tissue (hippocampus/cerebellum): Seller's stain for Negri bodies
FAT (Fluorescent Antibody Test) - most sensitive and specific, gold standard
Mouse inoculation

Treatment / Prophylaxis

Post-Exposure Prophylaxis (PEP): Step 1 - Wound washing: Wash with soap and water for 15 min → povidone iodine

Step 2 - Rabies Immunoglobulin (RIG):

Human RIG (HRIG): 20 IU/kg; infiltrate at wound site; give on Day 0
Equine RIG (ERIG): 40 IU/kg (if HRIG not available)

Step 3 - Rabies vaccine:

Cell culture vaccines (CCVs): Purified Chick Embryo Cell (PCECV), Human Diploid Cell Vaccine (HDCV), Vero cell vaccine
Schedule:
- Intramuscular: Days 0, 3, 7, 14, 28 (Essen regimen) OR Days 0, 7, 21 (Zagreb regimen)
- Intradermal: Days 0, 3, 7, 28 (TRC-ID regimen) - cost-effective

Pre-Exposure Prophylaxis (PrEP): For veterinarians, lab workers - Day 0, 7, 21/28

WHO wound categorization:

Category I: Touch/lick - no PEP
Category II: Scratches without bleeding - vaccine only
Category III: Penetrating bites/licks on mucosa - vaccine + RIG

11. INFLUENZA VIRUSES

Classification

Family: Orthomyxoviridae Types: Influenza A, B, C (A is most important clinically)

Morphology

Enveloped, negative-sense, segmented ssRNA (8 segments in types A and B - 7 in C)
Pleomorphic (spherical or filamentous)
Two surface glycoproteins (most important):
- Hemagglutinin (H/HA): 18 subtypes - mediates viral attachment to sialic acid receptors on host cells; fusion with endosome membrane; main target for neutralizing antibodies; used in vaccines
- Neuraminidase (N/NA): 11 subtypes - cleaves sialic acid to release new virions; target for antiviral drugs (oseltamivir, zanamivir)
M2 protein: Ion channel, target for amantadine

Antigenic Variation (IMPORTANT)

Antigenic Drift:

Point mutations in HA and NA genes
Responsible for seasonal epidemics
Gradual, continuous change
Requires annual reformulation of vaccine

Antigenic Shift:

Reassortment of RNA segments between animal (avian/swine) and human influenza strains
New HA and/or NA subtypes emerge
Only in Influenza A (segmented genome)
Responsible for pandemics
Pandemics: 1918 (H1N1 - Spanish flu), 1957 (H2N2 - Asian flu), 1968 (H3N2 - Hong Kong flu), 2009 (H1N1 - Swine flu)

Influenza A Subtypes

H1N1 (Seasonal, Swine flu 2009)
H3N2 (Seasonal)
H5N1 (Avian flu - highly pathogenic, zoonotic, high mortality ~60%)

Clinical Features

Uncomplicated influenza:

Abrupt onset fever (38-40°C)
Myalgia, headache (severe)
Dry cough
Rhinorrhea, nasal congestion
Sore throat
Malaise, prostration
Duration: 3-7 days; cough/fatigue may persist weeks

Complications:

Primary viral pneumonia
Secondary bacterial pneumonia (S. pneumoniae, S. aureus, H. influenzae)
Reye's syndrome (aspirin use in children - hepatic encephalopathy)
Myocarditis, encephalitis
Exacerbation of COPD/asthma

Lab Diagnosis

Nasopharyngeal swab (NPS) - collect within 72 hrs of onset
RT-PCR (gold standard) - detects viral RNA, differentiates A from B, identifies subtypes
Rapid Influenza Diagnostic Tests (RIDTs) - antigen detection (less sensitive, quick)
Viral culture: MDCK cells (Madin-Darby canine kidney)
Hemagglutination inhibition (HI) test - serology (4-fold rise in titre diagnostic)
Complement fixation (CF) test

Treatment

Drug	Mechanism	Indication
Oseltamivir (Tamiflu)	Neuraminidase inhibitor	Treatment and prophylaxis; within 48 hrs of symptoms
Zanamivir	Neuraminidase inhibitor	Inhaled; treatment
Baloxavir marboxil	Cap-dependent endonuclease inhibitor	Single oral dose; new drug
Amantadine/Rimantadine	M2 ion channel blocker	Influenza A only; resistance common

Vaccine

Trivalent/Quadrivalent inactivated influenza vaccine (IIV)
Annual administration (due to antigenic drift)
Composition updated every year based on WHO surveillance
LAIV (Live attenuated intranasal) - for healthy 2-49 year olds
High-priority groups: Elderly, pregnant women, healthcare workers, immunocompromised

12. CRYPTOCOCCAL MENINGITIS

Causative Organism

Cryptococcus neoformans (most common)

C. gattii - immunocompetent individuals, less common

Morphology

Encapsulated yeast (large polysaccharide capsule - MOST IMPORTANT virulence factor)
Round to oval, 4-20 µm
Reproduces by narrow-based budding (distinguishes from Blastomyces which has broad-based budding)
Capsule seen as clear halo ("soap bubble" appearance) on India ink preparation
Stains with mucicarmine (capsule stains red) and Alcian blue

Virulence Factors

Polysaccharide capsule: Anti-phagocytic, anti-inflammatory, inhibits leukocyte migration, inhibits complement
Melanin production (laccase enzyme): Protects from oxidative killing, found in brain (melanin from CNS catecholamines); lung tissue
Urease production
Growth at 37°C (thermotolerance)
Mannitol production

Epidemiology

Saprophytic fungus, found in pigeon droppings (avian guano) - high nitrogen content
Also in eucalyptus trees (C. gattii)
Inhalation of basidiospores → primary pulmonary infection → hematogenous dissemination to CNS
Major opportunistic infection in HIV/AIDS (CD4 <100 cells/µL)

Clinical Features

Subacute/chronic meningitis:

Headache (most common, gradual onset)
Fever (low grade)
Nausea, vomiting
Altered mental status
Raised intracranial pressure (ICP) - papilledema, CN palsy
Neck stiffness (meningism)
May have cryptococcoma (CNS mass lesion)
Minimal or absent photophobia compared to bacterial meningitis

Pulmonary cryptococcosis:

Asymptomatic nodule or pneumonia

CSF Findings

Parameter	Value
Appearance	Clear / slightly turbid
Cells	Lymphocytes (10-200/µL)
Protein	Mildly elevated
Glucose	Low to normal
Opening pressure	Usually elevated (>25 cmH2O)
India ink	Encapsulated yeasts with halos

Lab Diagnosis

India ink preparation:

CSF + India ink: Encapsulated yeasts appear as clear halos against black background
Sensitivity ~50-80% in HIV patients

Cryptococcal Antigen (CrAg) test (MOST SENSITIVE):

Latex agglutination (LA) or Lateral flow assay (LFA)
Detects polysaccharide capsular antigen in CSF and serum
Sensitivity >95% in HIV patients
Used for screening (serum CrAg screen in HIV patients with CD4 <100)

Culture:

Sabouraud's Dextrose Agar (SDA) at 37°C
Colonies: Mucoid, cream-colored (due to capsule)
Birdseed agar (Niger seed agar/Staib agar): Brown/black colonies due to melanin production - differentiates C. neoformans from other Cryptococcus
Urease positive

Histopathology:

Mucicarmine stain: Red capsule
PAS stain, Gomori methenamine silver (GMS)
"Soap bubble" lesions in brain on autopsy

Treatment

Induction phase (2 weeks):

Amphotericin B (liposomal) + Flucytosine (5-FC)
Flucytosine acts synergistically with amphotericin B

Consolidation phase (8 weeks):

Fluconazole 400 mg/day

Maintenance/suppressive phase:

Fluconazole 200 mg/day (until CD4 >200 on ART for >3 months)

Management of raised ICP:

Therapeutic lumbar puncture (serial LP) - opens ICP, critical for outcome
Acetazolamide/mannitol - limited role

Prevention in HIV:

Fluconazole prophylaxis when CD4 <100 (in high-prevalence settings)
Serum CrAg screening

QUICK REVISION TABLE

Topic	Key Organism	Diagnostic Test	Drug of Choice
Gas Gangrene	C. perfringens	Nagler reaction, Gram stain (no pus cells)	Penicillin G + debridement
UTI	E. coli	MSU culture (≥10^5 CFU/mL), CLED agar	Nitrofurantoin (lower UTI)
Pyogenic Meningitis	N. meningitidis	CSF - turbid, PMN pleocytosis, low glucose	Ceftriaxone
Pulmonary TB	M. tuberculosis	ZN stain (AFB), LJ medium culture, GeneXpert	HRZE x 2 months + HR x 4 months
Syphilis	T. pallidum	Darkfield microscopy, VDRL (screening), FTA-ABS (confirmatory)	Benzathine penicillin G
Strep pyogenes sequelae	S. pyogenes	ASO titre, Throat culture, C3 levels	Penicillin G (prevention)
LRTI/Pneumonia	S. pneumoniae	Gram stain sputum, Blood culture	Amoxicillin / Penicillin
Dermatophytosis	Trichophyton/Microsporum	KOH preparation, Wood's lamp	Griseofulvin (scalp), Terbinafine
Chlamydia	C. trachomatis	NAAT/PCR (gold standard)	Azithromycin 1g (single dose)
Rabies	Rabies virus (Lyssavirus)	Negri bodies (Seller's stain), FAT	PEP: RIG + cell culture vaccine
Influenza	Influenza A/B	RT-PCR (gold standard), RIDT	Oseltamivir (within 48 hrs)
Cryptococcal Meningitis	C. neoformans	India ink, CrAg test, Mucicarmine stain	Amphotericin B + Flucytosine → Fluconazole

Sources: Bailey & Love's Surgery 28th Ed, Harrison's Principles of Internal Medicine 22E (2025), Goldman-Cecil Medicine, Sherris & Ryan's Medical Microbiology 8th Ed, Medical Microbiology 9e, Robbins Pathologic Basis of Disease

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