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UNIT 1 - GI & Hepatobiliary

• HBsAg = active infection; Anti-HBs = immunity; HBeAg = high infectivity
• Anti-HBc IgM = acute; IgG = past/chronic
• HBsAg + Anti-HBc + no Anti-HBs = chronic carrier
• Window period = only Anti-HBc IgM is positive
• Hep D needs Hep B to replicate (defective virus)
• Hep E = most dangerous in pregnancy (20-30% mortality)

• Widal: O titre ≥ 1:160 = active; H titre ≥ 1:160 = past infection/vaccine
• Rose spots on abdomen, relative bradycardia, constipation early → diarrhea later
• Best culture: Blood (1st week) → Stool/Urine (2nd-3rd week) → Bone marrow (gold standard anytime)
• Typhidot: IgM = acute; IgG = past

• Comma-shaped gram -ve rod; TCBS agar = yellow colonies (sucrose fermenter)
• El Tor biotype = currently circulating pandemic strain
• Toxin = cAMP ↑ → hypersecretion of Cl⁻/water → rice water stools
• CT-B binds GM1 ganglioside; CT-A activates adenylate cyclase

• Trophozoite has RBCs in cytoplasm (pathognomonic); Cyst has 4 nuclei
• Flask-shaped (anchovy sauce) ulcer in colon
• Liver abscess = chocolate-brown pus, sterile (no trophozoites in pus usually)
• SAT (Serum Amoebic Titre) / ELISA for diagnosis

• Most common after clindamycin/ampicillin/cephalosporins use
• Toxin A = enterotoxin; Toxin B = cytotoxin (more important for diagnosis)
• Pseudomembranous colitis = gray-yellow plaques on colonoscopy
• Dx: Stool ELISA for toxin; Rx: Metronidazole / Vancomycin (oral)

• S. aureus: shortest incubation (1-6 hrs), preformed enterotoxin, vomiting-dominant
• B. cereus: 2 syndromes - emetic (1-6 hrs, fried rice) and diarrheal (6-24 hrs)
• C. perfringens: 8-16 hrs, meat-associated, self-limiting diarrhea
• Botulinum: 12-36 hrs, descending flaccid paralysis, canned food, blocks ACh release

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UNIT 2 - Musculoskeletal, Skin & Soft Tissue

• Tetanospasmin (neurotoxin) = blocks inhibitory interneurons (glycine/GABA) → spastic paralysis
• Trismus (lockjaw) + risus sardonicus + opisthotonus = classic triad
• Clostridium tetani = gram +ve, drumstick spore, anaerobe
• Treatment: Human TIG + wound debridement + Metronidazole + Diazepam

• Coagulase test = differentiates S. aureus (+ve) from CoNS (-ve)
• TSST-1 = Toxic Shock Syndrome (fever, rash, hypotension)
• Exfoliatin (ETA/ETB) = SSS Syndrome (Ritter's disease in neonates) - superficial split at granular layer
• Protein A = virulence factor, binds IgG Fc region

• Tuberculoid (TT): few lesions, AFB -ve, Lepromin +ve, cell-mediated immunity intact
• Lepromatous (LL): many lesions, AFB +++, Lepromin -ve, immune anergy
• Glove-and-stocking anesthesia; Leonine facies in LL
• MDT: PB leprosy = 6 months; MB leprosy = 12 months (Dapsone + Rifampicin ± Clofazimine)

• C. perfringens type A; Lecithinase C (alpha toxin) = main virulence factor
• Nagler's reaction = partial inhibition of lecithinase by antitoxin on egg yolk agar
• Crepitus on palpation; foul-smelling wound; Gram stain = large gram +ve rods, no WBCs
• Treatment: Surgical debridement + Penicillin G + Hyperbaric oxygen

• Three genera: Trichophyton (skin/hair/nails), Microsporum (skin/hair), Epidermophyton (skin/nails only - no hair)
• KOH preparation = see septate hyphae in skin scrapings
• Wood's lamp (UV 365nm): Microsporum = green fluorescence; Trichophyton = NO fluorescence
• Culture: SDA (Sabouraud's Dextrose Agar)

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UNIT 3 - CNS Infections

• N. meningitidis = gram -ve diplococci (kidney-shaped); S. pneumoniae = gram +ve lancet-shaped diplococci; H. influenzae = gram -ve coccobacilli
• Waterhouse-Friderichsen syndrome = bilateral adrenal hemorrhage (meningococcemia)

• Cryptococcus neoformans = encapsulated yeast; pigeon droppings = source
• India ink preparation = negative staining, visualizes capsule as halo
• Mainly in HIV/immunocompromised (CD4 < 100)
• Latex agglutination test for capsular antigen = diagnostic; Rx: Amphotericin B + Flucytosine

• Bullet-shaped (rhabdovirus); Negri bodies = in Purkinje cells of cerebellum and hippocampus (Ammon's horn)
• Ascending paralysis from bite site to brain via retrograde axonal transport
• PEP: Wound wash + RIG (human/equine) local infiltration + Vaccine (Days 0, 3, 7, 14)
• Furious rabies = hydrophobia/aerophobia; Dumb rabies = paralytic form

• P. falciparum ONLY causes cerebral malaria (ring-infected RBCs stick to brain vessels)
• Knobs on RBC surface → cytoadherence to cerebral endothelium
• Thick blood film = best for diagnosis; Rapid Antigen test (HRP-2) for P. falciparum
• Complications: hypoglycemia, blackwater fever (massive hemolysis + hemoglobinuria)

• 3 serotypes (1 = most common, most virulent; 2 = eradicated; 3 = nearly eradicated)
• OPV (Sabin) = live attenuated, oral, used in campaigns; IPV (Salk) = killed, injectable
• VAPP (vaccine-associated paralytic polio) = risk with OPV only
• Destroys anterior horn cells → lower motor neuron lesion → flaccid paralysis

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UNIT 4 - Respiratory Infections

• ZN stain = AFB (acid-fast bacilli, red rods on blue background); requires Lowenstein-Jensen (LJ) medium (growth in 6-8 weeks)
• GeneXpert/CBNAAT = rapid Dx + detects Rifampicin resistance
• Ghon's complex = primary focus + hilar lymph node; Koch's phenomenon = hypersensitivity on 2nd exposure
• Mantoux (Tuberculin test) = ≥10mm induration = positive (≥5mm in HIV/immunocompromised)

• Lancet-shaped gram +ve diplococci in pairs; Alpha-hemolytic on blood agar
• Optochin sensitive (differentiates from Viridans streptococci which are resistant)
• Capsule = main virulence factor; Quellung reaction = capsular swelling with antiserum
• Rust-colored sputum; Lobar pneumonia; Pneumolysin = toxin

• Mycoplasma pneumoniae: no cell wall → penicillin-resistant; Cold agglutinins (IgM) agglutinate O-group RBCs at 4°C
• Legionella pneumophila: BCYE agar (with cysteine + iron); AC units/water towers = source; Pontiac fever (mild form)
• Chlamydia pneumoniae: intracellular; TWAR strain; diagnosed by serology/PCR
• Treatment for all: Macrolides (azithromycin) or Doxycycline (NOT penicillin)

• Antigenic SHIFT = new pandemic strain (exchange of gene segments between human + animal strains)
• Antigenic DRIFT = seasonal epidemic (point mutations in HA/NA)
• HA (Haemagglutinin) = attachment; NA (Neuraminidase) = release of new virions
• Oseltamivir (Tamiflu) = NA inhibitor

• RT-PCR (NAAT) = gold standard; detects viral RNA; nasopharyngeal/oropharyngeal swab
• RAT (Rapid Antigen Test) = fast, less sensitive; useful for symptomatic cases
• Serology (IgM/IgG ELISA) = not for acute diagnosis; used for seroprevalence
• Ct value < 25 = high viral load; > 35 = likely non-infectious

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UNIT 5 - Genitourinary & STI

• E. coli = #1 cause (80%); short urethra in females = predisposing factor
• Significant bacteriuria = ≥10⁵ CFU/mL in midstream clean-catch urine
• CLED agar (no swarming) or MacConkey for culture
• Virulence: P-fimbriae attach to uroepithelium; Hemolysin; Type-1 fimbriae

• Gram -ve intracellular diplococci (kidney-shaped in PMNs); Oxidase +ve
• Thayer-Martin (VCN) medium = selective medium
• Ophthalmia neonatorum = prevented by 1% silver nitrate / erythromycin eye drops at birth
• Complications: PID, infertility, Fitz-Hugh-Curtis syndrome (perihepatitis)

• Primary = painless chancre; Secondary = condylomata lata, mucous patches, diffuse rash (palms/soles)
• VDRL/RPR = non-treponemal (screening, titre falls with treatment, BFP possible)
• TPHA/FTA-ABS = treponemal (confirmatory, remains positive for life)
• BFP (Biological False Positive) VDRL = SLE, malaria, pregnancy, leprosy

• Most common cause = Chlamydia trachomatis (D-K serovars)
• NAAT (PCR) = gold standard for diagnosis; Chlamydia is obligate intracellular
• Reiter's syndrome (reactive arthritis) = urethritis + arthritis + conjunctivitis (triad) - post-chlamydial
• Treatment: Doxycycline 100mg BD × 7 days or Azithromycin 1g single dose

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All 5 units covered. Focus on the Top 10 table from the PDF: UTI > Viral Hepatitis > TB > Bacterial Meningitis > Pneumococcus > Tetanus > Typhoid > Gonorrhoea/Syphilis > Cholera > Rabies/Cryptococcus.

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UNIT 1 - GI & Hepatobiliary

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1. Viral Hepatitis

• HAV/HEV: feco-oral → liver inflammation → cytopathic + immune-mediated hepatocyte injury
• HBV: DNA virus → NOT directly cytopathic → CD8 T-cell mediated hepatocyte destruction
• HCV: RNA virus → chronic infection in 70-80% → cirrhosis → HCC
• HDV: defective virus, needs HBsAg coat → co-infection (acute) or super-infection (worse prognosis)
• HEV: feco-oral → fulminant hepatic failure in pregnant women (3rd trimester)

• Prodrome: fever, malaise, anorexia, nausea, RUQ pain
• Icteric phase: jaundice, dark urine, pale stools, hepatomegaly
• HBV chronic: asymptomatic carrier → cirrhosis → HCC
• HEV in pregnancy: 20-30% mortality (fulminant failure)

• HAV: Anti-HAV IgM = acute; IgG = past/immune
• HBV markers:
  • HBsAg = active infection (acute or chronic)
  • HBeAg = high replication/infectivity
  • Anti-HBs = immunity (vaccine or recovery)
  • Anti-HBc IgM = acute; IgG = past/chronic
  • Window period = only Anti-HBc IgM positive
• HCV: Anti-HCV (ELISA) → confirm with HCV RNA PCR
• HDV: Anti-HDV antibody
• LFT: ALT/AST elevated (ALT > AST in viral hepatitis)

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2. Typhoid / Enteric Fever

• Salmonella typhi ingested → survives gastric acid → invades Peyer's patches (ileum)
• Taken up by macrophages → systemic spread via lymphatics → bacteremia
• Endotoxin (LPS) → fever, toxemia
• 2nd bacteremia → seeding of gallbladder, liver, spleen, bone marrow

• Week 1: Stepladder fever, relative bradycardia, headache, constipation
• Week 2: Rose spots (trunk), splenomegaly, diarrhea
• Week 3-4: Complications - intestinal perforation, hemorrhage, myocarditis

• Blood culture: Gold standard in Week 1 (positive in 80%)
• Bone marrow culture: Gold standard ANY time (positive even after antibiotics)
• Widal test (Week 2 onwards): O titre ≥1:160 = active; H titre ≥1:160 = past/vaccine
• Typhidot: IgM = acute; IgG = past; IgM+IgG = recent

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3. Cholera

• V. cholerae ingested → colonizes small intestine (no invasion)
• Cholera toxin (CT): B subunit binds GM1 ganglioside → A subunit activates adenylate cyclase → cAMP ↑↑
• Massive Cl⁻ + water secretion → profuse watery diarrhea (NO mucosal damage)

• Sudden, profuse "rice water" stools (no blood, no pus)
• Severe dehydration → sunken eyes, loss of skin turgor, washerwoman's hands
• Muscle cramps (electrolyte loss)
• Can lose 10-20 litres/day → shock, death if untreated

• Direct microscopy: "shooting star" motility; Gram stain = gram -ve comma-shaped rods
• Culture: TCBS agar = yellow colonies (V. cholerae) vs blue-green (V. parahaemolyticus)
• Biotype El Tor: Positive Voges-Proskauer test, resistant to Polymyxin B
• String test = positive (organism holds shape in bile salt solution)

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4. Entamoeba histolytica / Amoebic Liver Abscess

• Cysts ingested → excystation in ileum → trophozoites invade colonic mucosa
• Contact-dependent cytolysis via Amoebapore + cysteine proteases
• Flask-shaped ulcer (narrow neck, broad base) in colon
• Portal spread → liver abscess (right lobe, single, chocolate/anchovy sauce pus)

• Intestinal: dysentery (blood + mucus in stool), colicky pain, tenesmus
• Liver abscess: fever, RUQ pain, tender hepatomegaly, diaphragm elevation
• Trophozoites with ingested RBCs = pathognomonic

• Stool microscopy: trophozoite with RBCs inside = E. histolytica (not E. dispar)
• Cyst = 4 nuclei with chromatoid bars
• Liver abscess: Ultrasound → aspiration (chocolate pus, sterile usually)
• Serology: ELISA / SAT (Serum Amoebic Titre) - positive in liver abscess

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5. C. difficile / Pseudomembranous Colitis

• Antibiotics (clindamycin, ampicillin, cephalosporins) → disrupt normal flora → C. difficile overgrowth
• Toxin A (enterotoxin): attracts PMNs, mucosal damage
• Toxin B (cytotoxin): disrupts actin cytoskeleton → cell death (more potent, essential for virulence)
• Pseudomembranes = fibrin + mucus + PMNs on denuded colonic mucosa

• Watery diarrhea (10-15x/day), crampy abdominal pain, fever
• Severe: Pseudomembranous colitis, toxic megacolon, perforation

• Stool ELISA: Toxin A + B detection (most practical)
• GDH (Glutamate dehydrogenase) antigen: sensitive screening test
• Gold standard: Cell cytotoxicity assay (toxin B)
• Colonoscopy: yellow-white pseudomembranes (skip lesions)

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6. Food Poisoning

• S. aureus / B. cereus emetic: vomiting dominant, short duration
• C. perfringens: watery diarrhea, no vomiting, self-limiting
• Botulism: descending flaccid paralysis, diplopia, dysphagia, no fever

• Stool + food culture
• S. aureus: detect enterotoxin in food by ELISA
• Botulism: mouse neutralization test (gold standard); stool/food culture for C. botulinum

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UNIT 2 - Musculoskeletal, Skin & Soft Tissue

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1. Tetanus

• C. tetani spores enter wound → germinate in anaerobic conditions → produce Tetanospasmin
• Toxin travels retrograde axonally to CNS → cleaves VAMP/synaptobrevin
• Blocks release of inhibitory neurotransmitters (glycine + GABA) at Renshaw cells
• Unopposed excitatory activity → spastic paralysis

• Trismus (lockjaw) - earliest sign
• Risus sardonicus (sardonic smile)
• Opisthotonus (arched back)
• Reflex spasms triggered by light/noise
• Neonatal tetanus: inability to suck (trismus) on day 3-7 of life

• CLINICAL diagnosis (no lab test confirms)
• Spatula test: touching posterior pharynx with spatula → reflex bite = positive
• Culture of wound (rarely helpful; spores present in soil everywhere)
• Serum antitoxin level < 0.01 IU/mL = susceptible

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2. Staphylococcal Infections

• Coagulase: converts fibrinogen → fibrin (protects from phagocytosis)
• Protein A: binds IgG Fc region → blocks opsonization
• TSST-1: superantigen → massive T-cell activation → cytokine storm → shock
• Exfoliatin A/B: cleaves desmoglein-1 in granular layer → SSS Syndrome
• PVL (Panton-Valentine Leukocidin): destroys PMNs → necrotizing pneumonia/skin

• SSSS (Ritter's disease): neonates, generalized blistering, Nikolsky sign +ve, perioral crusting
• TSS: fever >38.9°C, diffuse macular rash, hypotension, desquamation (1-2 weeks later)
• Furunculosis, carbuncles, impetigo bullosa, osteomyelitis

• Coagulase test: Slide (bound coagulase/clumping factor) + Tube (free coagulase)
• Culture: golden/yellow colonies on blood agar; beta-hemolysis
• Mannitol Salt Agar (MSA): S. aureus = yellow colonies (ferments mannitol)
• MRSA: oxacillin/cefoxitin disc diffusion; mecA gene PCR

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3. Leprosy

• M. leprae (obligate intracellular; cannot be cultured in vitro) invades Schwann cells + macrophages
• Transmitted via nasal droplets (prolonged contact)
• Disease type depends on host CMI response:
  • Strong CMI → Tuberculoid (TT): granuloma, few bacilli, self-limiting
  • Poor CMI → Lepromatous (LL): foamy macrophages (Virchow cells), millions of bacilli

• TT: single/few hypopigmented anesthetic patches, thickened nerve, AFB -ve
• LL: multiple diffuse lesions, Leonine facies, saddle nose, madarosis (loss of eyebrows), AFB +++
• BT/BB/BL: borderline types
• Lepra reactions: Type 1 (reversal) = immune upgrade; Type 2 (ENL) = immune complex

• Slit skin smear (earlobes, lesion edge): ZN stain for AFB → Bacteriological Index (0-6+)
• Lepromin (Mitsuda) test: TT = strongly positive; LL = negative (not diagnostic, tests immunity)
• Histopathology: TT = epithelioid granulomas; LL = foamy macrophages
• PCR for M. leprae DNA (definitive)

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4. Gas Gangrene

• C. perfringens type A in contaminated wound → anaerobic conditions → rapid multiplication
• Alpha toxin (Lecithinase C): splits lecithin in cell membranes → RBC/muscle/WBC lysis
• Theta toxin (Perfringolysin): cardiotoxic
• Gas production (H₂ + CO₂) → crepitus in tissues
• Nagler's reaction: alpha toxin causes opaque zone on egg yolk agar → inhibited by antitoxin on one half

• Severe pain out of proportion to wound (earliest sign)
• Crepitus on palpation (gas in tissues)
• Bronze/black discoloration of skin, foul-smelling wound
• Fever, tachycardia → toxemia → shock; rapid progression (hours)

• Gram stain of wound: large gram +ve rods, NO inflammatory cells (toxin kills WBCs)
• Culture: anaerobic blood agar → double zone hemolysis (alpha + theta toxin)
• Nagler's reaction: lecithinase activity on egg yolk agar, inhibited by C. perfringens antitoxin
• X-ray: gas in soft tissues

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5. Dermatophytosis

• Trichophyton, Microsporum, Epidermophyton invade only keratinized tissue (hair, skin, nails)
• Produce keratinases → digest keratin → colonize stratum corneum
• Inflammatory response = itching, scaling, ring-shaped lesion
• Ectothrix (spores outside hair shaft) vs Endothrix (spores inside hair shaft)

• Tinea capitis: scalp ringworm; hair loss; broken "black dot" hairs (endothrix)
• Tinea corporis: annular scaly patch with central clearing, raised border
• Tinea pedis: athlete's foot; interdigital maceration
• Tinea unguium (onychomycosis): thickened, brittle, discolored nails
• Tinea cruris: groin; spares scrotum (unlike candidiasis)

• KOH preparation: septate hyphae/arthrospores in skin/nail scraping
• Wood's lamp (UV 365nm): Microsporum = green-yellow fluorescence; Trichophyton = NO fluorescence
• Culture: SDA (Sabouraud's Dextrose Agar) at 25-28°C; macroconidia = species ID
• Trichophyton: pencil-shaped macroconidia; Microsporum: spindle-shaped rough macroconidia; Epidermophyton: club-shaped macroconidia, NO microconidia

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UNIT 3 - CNS Infections

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1. Bacterial Meningitis

• Organisms: N. meningitidis (meningococcus), S. pneumoniae (pneumococcus), H. influenzae type b
• Colonize nasopharynx → bacteremia → cross blood-brain barrier → subarachnoid space
• Capsule resists phagocytosis → massive inflammation → CSF turbid with PMNs
• Cytokines (IL-1, TNF-α) → cerebral edema, ↑ICP → herniation

• Classic triad: fever + severe headache + neck stiffness (nuchal rigidity)
• Kernig's sign (knee cannot extend with hip flexed) + Brudzinski's sign (neck flexion causes hip flexion)
• Meningococcal: petechial/purpuric rash → Waterhouse-Friderichsen syndrome (bilateral adrenal hemorrhage)
• Photophobia, vomiting, altered consciousness, seizures

• Blood culture + CSF culture
• Latex agglutination: rapid antigen detection for S. pneumoniae, N. meningitidis, H. influenzae

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2. Cryptococcal Meningitis

• C. neoformans inhaled from pigeon droppings → lung infection → hematogenous spread to CNS
• Large polysaccharide capsule: blocks phagocytosis + complement
• High affinity for CNS (uses CNS dopamine as nitrogen source)
• In HIV (CD4 <100) → no adequate CMI → uncontrolled growth in CSF

• Subacute meningitis: headache, fever, neck stiffness (may be subtle)
• ↑ICP (high opening pressure on LP) → papilledema, vision changes, cranial nerve palsies
• HIV patients: often presents without classic meningism signs

• India ink preparation: negative staining → capsule seen as clear halo around yeast cell
• Latex agglutination / Lateral flow assay: capsular antigen in CSF/serum (most sensitive, gold standard)
• Culture: Sabouraud's agar → mucoidal colonies (due to capsule)
• Urease positive; Birdseed (Niger seed) agar = brown pigment colonies

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3. Rabies

• Rhabdovirus (bullet-shaped) → enters via bite wound → binds nicotinic ACh receptors
• Travels retrograde axonally at 3mm/hour (explains incubation period based on bite site)
• Reaches CNS → encephalitis → spreads to salivary glands centrifugally
• Inclusion bodies (Negri bodies) = viral replication sites in neurons

• Prodrome: pain/paresthesia at bite site, fever, agitation (2-10 days)
• Furious rabies (80%): hydrophobia (laryngospasm on seeing water), aerophobia, autonomic instability
• Dumb/paralytic rabies (20%): ascending flaccid paralysis (resembles GBS)
• Coma → death (invariably fatal once symptoms appear)

• Antemortem: Skin biopsy (nape of neck) - DFA for viral antigen; Saliva/CSF RT-PCR; Corneal impression smear
• Postmortem: Brain (hippocampus/Ammon's horn + cerebellum) → Negri bodies on Seller's stain (eosinophilic intracytoplasmic inclusions)
• Negri bodies = pathognomonic but absent in 20% cases → DFA is gold standard

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4. Cerebral Malaria (P. falciparum)

• ONLY P. falciparum (no other species) causes cerebral malaria
• Knobs on RBC surface express PfEMP1 → cytoadherence to brain endothelial ICAM-1
• Rosette formation: infected RBCs clump with uninfected RBCs → microvessel occlusion
• Sequestration in brain → hypoxia, ischemia, inflammation → coma

• High fever (48-hour cycle - tertian), headache, vomiting
• Cerebral: impaired consciousness → coma, convulsions, posturing
• Complications: severe anemia, hypoglycemia, blackwater fever (massive hemolysis + hemoglobinuria), pulmonary edema, ARDS

• Peripheral blood smear: THICK film (screening - more sensitive); THIN film (species ID)
• P. falciparum: ring forms only (no mature trophozoites/schizonts in peripheral blood), multiple rings/cell, banana-shaped gametocytes
• Rapid Antigen Test (RDT): HRP-2 antigen = P. falciparum specific
• PCR: most sensitive; used for low parasitemia

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5. Poliomyelitis

• Enterovirus (picornavirus), 3 serotypes (type 1 = most common + virulent)
• Feco-oral route → replicates in oropharynx + intestine → viremia → crosses BBB → anterior horn cells of spinal cord
• Destroys motor neurons → lower motor neuron lesion → flaccid paralysis
• <1% of infections cause paralysis; most are subclinical

• 90-95%: subclinical/inapparent
• Abortive polio: fever, headache, sore throat (no CNS involvement)
• Non-paralytic: aseptic meningitis
• Paralytic: asymmetric, flaccid, areflexic paralysis; no sensory loss; bulbar = cranial nerve involvement

• Stool culture (most reliable; virus shed longest)
• Throat swab culture (positive in early phase)
• CSF: aseptic meningitis pattern (lymphocytes, normal sugar, slightly raised protein)
• Serology: 4-fold rise in neutralizing antibody titre
• VDPV (vaccine-derived poliovirus) differentiation by PCR/sequencing

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UNIT 4 - Respiratory Infections

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1. Tuberculosis

• M. tuberculosis inhaled → droplet nuclei reach alveoli → phagocytosed by alveolar macrophages
• Survives inside macrophage (blocks phagolysosome fusion - cord factor, sulfatides)
• Primary complex (Ghon's complex) = Ghon's focus (lung) + hilar lymph nodes + lymphangitis
• Koch's phenomenon: 2nd exposure → rapid necrosis (hypersensitivity) but also rapid healing (immunity)
• Post-primary TB: reactivation in apex (high O₂) → cavitation

• Constitutional: fever (evening rise), night sweats, weight loss, malaise
• Respiratory: productive cough >3 weeks, hemoptysis, dyspnea, chest pain
• Primary TB: usually asymptomatic or mild; erythema nodosum, pleural effusion
• Miliary TB: hematogenous dissemination → millet-seed lesions on CXR

• ZN (Ziehl-Neelsen) stain: AFB = red rods on blue background (3 acid-fast bacilli/field = positive)
• Fluorescence microscopy (auramine-rhodamine): more sensitive screening
• Culture: LJ medium (8-12 weeks); MGIT liquid system (2-3 weeks) - gold standard
• GeneXpert/CBNAAT: 2 hours, detects M. tuberculosis + rifampicin resistance (rpoB mutation)
• Mantoux test: PPD 5TU intradermal → read at 48-72 hrs; ≥10mm = positive

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2. Pneumococcal Pneumonia

• S. pneumoniae colonizes nasopharynx → aspiration → alveolar infection
• Polysaccharide capsule = MAIN virulence factor (anti-phagocytic)
• Pneumolysin: pore-forming toxin → RBC/PMN lysis
• 4 stages: Congestion → Red hepatization → Grey hepatization → Resolution

• Sudden onset: rigor, high fever, pleuritic chest pain
• Rust-colored (prune juice) sputum = classic
• Lobar pneumonia on CXR
• Herpes labialis may appear on lips
• Complications: empyema, bacteremia, meningitis, pericarditis

• Sputum Gram stain: lancet-shaped gram +ve diplococci (pairs)
• Culture: alpha-hemolysis on blood agar (greenish); optochin sensitivity (inhibited = pneumococcus)
• Quellung (capsular swelling) reaction: capsule swells with type-specific antiserum
• Blood culture: positive in 20-30% of bacteremic cases
• Urine pneumococcal antigen: rapid, sensitive

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3. Atypical Pneumonia

• "Atypical" = does NOT respond to penicillin; no organism on Gram stain; patchy infiltrate (NOT lobar)
• Mycoplasma: no cell wall → walks through mucus → attaches to respiratory epithelium via P1 protein → ciliary destruction
• Legionella: water aerosols inhaled → phagocytosed by macrophages → survives inside (blocks phagolysosome)
• Chlamydia pneumoniae: elementary body (infectious) → reticulate body (replicating) inside cells

• Gradual onset, dry (non-productive) cough, low-grade fever, headache
• "Walking pneumonia" (patient ambulatory despite X-ray changes)
• Legionella: high fever, confusion, diarrhea, hyponatremia, relative bradycardia; Pontiac fever = mild form
• Mycoplasma: bullous myringitis (pathognomonic), extrapulmonary (hemolytic anemia, Stevens-Johnson)

• Mycoplasma: Cold agglutinins (IgM agglutinate O-group RBCs at 4°C) - bedside test; Serology (ELISA) IgM; PCR
• Legionella: Urine Legionella antigen (most practical); BCYE agar with cysteine + iron (will NOT grow on regular blood agar); DFA of sputum
• Chlamydia pneumoniae: Serology (MIF); PCR
• Treatment for all: Azithromycin or Doxycycline (NOT penicillin)

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4. Influenza

• Orthomyxovirus; segmented RNA → allows reassortment
• HA (Haemagglutinin): binds sialic acid on respiratory epithelium → attachment
• NA (Neuraminidase): cleaves sialic acid → releases new virions from cell
• Antigenic DRIFT: point mutations in HA/NA → seasonal epidemics
• Antigenic SHIFT: gene segment reassortment between human + animal strains → NEW subtype → pandemic

• Abrupt onset: high fever, chills, severe myalgia, headache (systemic symptoms dominate)
• Respiratory: dry cough, sore throat, nasal congestion (secondary)
• Complications: primary viral pneumonia, secondary bacterial pneumonia (S. aureus, S. pneumoniae, H. influenzae), Reye's syndrome (aspirin in children), myocarditis

• Rapid Influenza Diagnostic Tests (RIDT): nasopharyngeal swab, quick but low sensitivity
• RT-PCR: gold standard; differentiates A/B/subtypes
• Viral culture: MDCK cells; reference standard
• Direct Fluorescent Antibody (DFA): rapid antigen detection in NPS
• Serology: 4-fold rise in HI (haemagglutination inhibition) titre

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5. COVID-19 Lab Diagnosis

• SARS-CoV-2 spike protein (S protein) binds ACE2 receptor (lungs, heart, gut, kidney)
• Transmembrane serine protease TMPRSS2 primes spike for fusion → cell entry
• Cytokine storm (IL-6, TNF-α, IL-1β) → hyperinflammation → ARDS, multi-organ failure
• D-dimer ↑ → hypercoagulability → thrombosis (DVT, PE, stroke)

• Asymptomatic → mild URTI (most) → severe pneumonia/ARDS (5-10%)
• Cardinal: fever, cough, fatigue; anosmia/ageusia = characteristic
• Severe: dyspnea, SpO₂ <94%, bilateral infiltrates on CXR
• Long COVID: fatigue, brain fog, dyspnea persisting >12 weeks

• RT-PCR (NAAT): gold standard; NPS/OPS swab; Ct value <25 = high viral load
• RAT (Rapid Antigen Test): nucleocapsid antigen; fast (15-30 min); lower sensitivity (use for symptomatic)
• Serology (ELISA): IgM/IgG; NOT for acute diagnosis; used for seroprevalence/epidemiology
• Specimen: NPS preferred; saliva acceptable; BAL for ventilated patients

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UNIT 5 - Genitourinary & STI

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1. UTI

• E. coli #1 (80%) → short urethra in females → ascent from perineum
• Virulence: P-fimbriae (bind uroepithelial Gal-Gal receptor), Type-1 fimbriae, hemolysin, aerobactin
• Uncomplicated: lower UTI (cystitis); complicated: upper UTI (pyelonephritis), structural abnormality, catheter-related
• Nosocomial UTI: Klebsiella, Proteus, Pseudomonas, Enterococcus

• Cystitis: dysuria, frequency, urgency, suprapubic pain, cloudy/foul-smelling urine; NO fever
• Pyelonephritis: high fever, rigors, loin pain (costovertebral angle tenderness), systemic upset
• Asymptomatic bacteriuria: treat only in pregnancy, pre-urological procedure

• Urine microscopy: pyuria (>10 WBC/HPF), bacteriuria, casts (in pyelonephritis)
• Culture: CLED agar (no swarming) or MacConkey; significant bacteriuria = ≥10⁵ CFU/mL (midstream clean-catch)
• Dipstick: nitrite +ve (gram -ve bacteria) + leukocyte esterase = presumptive UTI
• Catheter specimen: ≥10³ CFU/mL = significant

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2. Gonorrhoea

• N. gonorrhoeae (gram -ve intracellular diplococci) attaches to non-ciliated columnar epithelium via pili + Opa proteins
• Endocytosis → submucosa → inflammation; IgA protease destroys mucosal IgA
• LOS (lipooligosaccharide) endotoxin → tissue damage
• Neonatal ophthalmia: infected birth canal → eye inoculation during delivery

• Male: urethral discharge (purulent, yellow-green), dysuria; epididymo-orchitis if untreated
• Female: often asymptomatic; cervicitis, PID (pelvic inflammatory disease), Fitz-Hugh-Curtis (perihepatitis)
• Disseminated: septic arthritis, skin pustules, tenosynovitis
• Neonatal: ophthalmia neonatorum (1-5 days after birth) → corneal ulcer → blindness

• Gram stain of urethral discharge: gram -ve kidney-shaped diplococci inside PMNs (sensitivity 95% males, 50% females)
• Culture: Thayer-Martin (VCN) medium (Vancomycin + Colistin + Nystatin) = selective
• Oxidase +ve; sugar fermentation: glucose only (not maltose/lactose, unlike N. meningitidis which ferments glucose + maltose)
• NAAT (PCR): gold standard for females and pharyngeal/rectal sites

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3. Syphilis

• Treponema pallidum (cannot be cultured in vitro; too thin to see on Gram stain - seen on dark field)
• Enters via mucosal breach → local replication → regional lymph nodes → systemic dissemination
• Endarteritis obliterans (Virchow) = vascular pathology in all stages; perivascular plasma cell infiltrate
• Gumma = granuloma (tertiary syphilis)

• Primary: painless indurated chancre at site of inoculation + painless inguinal lymphadenopathy (heals in 3-6 weeks)
• Secondary (6-8 weeks later): diffuse maculopapular rash (palms + soles = classic), condylomata lata, mucous patches, alopecia, generalized lymphadenopathy
• Latent: asymptomatic (early <2 years; late >2 years)
• Tertiary: Gumma, cardiovascular (aortic regurgitation, aortic aneurysm), neurosyphilis (tabes dorsalis, Argyll Robertson pupil)
• Congenital: Hutchinson's triad (interstitial keratitis + Hutchinson's teeth + VIII nerve deafness), saddle nose, saber shins

• Dark field microscopy: spirochetes in chancre exudate (gold standard for primary)
• Non-treponemal (screening): VDRL / RPR → titre falls with treatment; BFP in SLE, malaria, pregnancy, leprosy
• Treponemal (confirmatory): TPHA, FTA-ABS, TPPA → remains positive for life even after treatment
• CSF VDRL: positive = neurosyphilis (specific but not sensitive)

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4. Non-Gonococcal Urethritis (NGU)

• Chlamydia trachomatis (serovars D-K) = most common cause (40-50%)
• Obligate intracellular parasite: Elementary Body (EB) = infectious, extracellular → enters cell → Reticulate Body (RB) = replicating, intracellular → new EBs released
• Ureaplasma urealyticum = 2nd most common; also Mycoplasma genitalium
• Mucosal inflammation → urethritis; ascending → epididymitis (males), PID (females)

• Males: mucopurulent urethral discharge (less purulent than gonorrhoea), dysuria, urethral discomfort
• Females: often asymptomatic; cervicitis, PID, infertility
• Reiter's syndrome (reactive arthritis): Urethritis + Arthritis + Conjunctivitis ("can't pee, can't see, can't climb a tree")
• Lymphogranuloma Venereum (LGV): serovars L1-L3 → inguinal bubo

• NAAT (PCR): gold standard; urine or urethral swab; detects C. trachomatis + N. gonorrhoeae simultaneously
• Culture: McCoy cells (intracellular inclusions) - gold standard historically, now replaced by PCR
• Urethral smear: ≥5 PMN/HPF without gram -ve diplococci = NGU
• DIF (Direct Immunofluorescence): fluorescent EBs in smear

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Top 5 to drill in last 30 minutes: UTI (long question 2025) → Viral Hepatitis (markers) → TB (ZN stain + GeneXpert) → Bacterial Meningitis (CSF table) → Tetanus (toxin mechanism). All the best!