---

RESPIRATORY INFECTIONS

---

1. Tuberculosis (Ch. 53) ⭐⭐⭐⭐⭐

• Slender, straight/slightly curved rod; 1-4 µm
• Non-motile, non-sporing, non-capsulated
• Cell wall rich in mycolic acids, arabinogalactan, lipoarabinomannan
• Koch's bacillus; grows slowly (generation time ~20 hrs)
• Culture: Lowenstein-Jensen medium - rough, buff-colored "cauliflower" colonies (3-6 weeks)

• Transmitted by respiratory droplets (Flugge's droplets)
• Primary complex (Ghon's focus = subpleural + hilar LN)
• Tubercle (granuloma): Caseous necrosis, Langhans giant cells, epithelioid cells
• Post-primary TB: reactivation, cavity formation in apices

• Sputum smear: ZN staining - red bacilli on blue background (AFB)
• Fluorochrome stain: Auramine-rhodamine
• Culture: LJ medium; BACTEC radiometric system (rapid)
• Tuberculin (Mantoux) test: 5 TU PPD, read at 48-72 hrs, induration ≥10 mm = positive
• IGRA (Interferon gamma release assay): QuantiFERON-TB Gold
• GeneXpert MTB/RIF: rapid molecular diagnosis, detects rifampicin resistance

• Intensive phase (2 months): HRZE (Isoniazid, Rifampicin, Pyrazinamide, Ethambutol)
• Continuation phase (4 months): HR
• MDR-TB: resistant to H + R; treated with fluoroquinolones + injectable agents
• XDR-TB: MDR + resistant to fluoroquinolones + injectable

---

2. Coronavirus / COVID-19 (Ch. 59) ⭐⭐⭐⭐

• Enveloped virus; largest RNA virus (~30 kb genome)
• Crown-shaped spikes (Spike protein S, M, E, N proteins)
• S protein binds ACE-2 receptor on host cells

• Respiratory droplets, aerosols, fomites
• Incubation: 2-14 days (average 5-6 days)
• S protein → ACE-2 binding → cell entry via TMPRSS2 → cytokine storm → ARDS
• COVID-19 severity: Asymptomatic → Mild → Severe (ARDS) → Critical (multiorgan failure)

• Fever, dry cough, fatigue, dyspnea
• Loss of smell (anosmia) and taste (ageusia) - characteristic
• Complications: ARDS, cytokine storm, thromboembolism, MIS-C (in children)

• RT-PCR (gold standard): nasopharyngeal/oropharyngeal swab; detects N, E, RdRp genes
• Rapid Antigen Test (RAT): less sensitive; used for screening
• Serology (IgM/IgG): not for acute diagnosis; useful for seroprevalence
• CT chest: bilateral ground-glass opacities; "crazy paving" pattern

• Antiviral: Remdesivir (RNA polymerase inhibitor); Molnupiravir, Paxlovid (Nirmatrelvir/Ritonavir)
• Anti-inflammatory: Dexamethasone (severe/critical cases)
• Vaccines: mRNA (Pfizer BNT162b2, Moderna mRNA-1273), Adenoviral vector (AstraZeneca, Covishield), Inactivated (Covaxin - BBV152)

---

3. Streptococcus pneumoniae (Ch. 51) ⭐⭐⭐⭐

• Capsulated (virulence factor); non-motile, non-sporing
• Alpha-hemolytic on blood agar (green zone)
• Optochin sensitive (differentiates from viridans streptococci)
• Bile solubility positive
• Draughtsman/checker-shaped colonies (central depression due to autolysis)

• Polysaccharide capsule: antiphagocytic; basis of serotyping (90+ serotypes)
• Pneumolysin: cytolytic
• IgA protease: cleaves secretory IgA
• Surface protein A (PspA), Neuraminidase

• Lobar pneumonia (commonest cause in adults)
• Meningitis (leading bacterial cause), Otitis media (children), Sinusitis
• Septicemia (especially in asplenic patients)

• Sputum Gram stain: Gram-positive lancet-shaped diplococci
• Culture: Blood agar with CO2; alpha-hemolysis
• Quelling reaction (Neufeld): capsular swelling with type-specific antisera
• Optochin sensitivity test; Bile solubility

---

4. Haemophilus influenzae (Ch. 52) ⭐⭐⭐⭐

• X factor (hemin/hematin) - heat-stable
• V factor (NAD/NADP) - heat-labile
• Both X and V required (distinguishes from H. parainfluenzae - needs V only)
• Chocolate agar: RBCs lysed → releases X & V factors
• Satellite phenomenon: colonies grow near S. aureus streak on blood agar (staphylococci provide NAD)

• Hib: Epiglottitis ("cherry-red epiglottis"), Meningitis (children <5 yrs), Pneumonia, Septicemia, Cellulitis
• Non-typeable (NTHi): Otitis media, sinusitis, COPD exacerbations

• PRP capsule (antiphagocytic); IgA protease; LPS (endotoxin); Pili (adherence)

• Gram stain: Gram-negative coccobacilli (pleomorphic)
• Culture: Chocolate agar / Levinthal's agar
• Satellite phenomenon on blood agar
• Quellung reaction; PCR for Hib

---

5. Diphtheria (Ch. 50) ⭐⭐⭐⭐

• "Chinese letter" / "cuneiform" arrangement (snapping division)
• Metachromatic granules (Babes-Ernst granules / volutin): stain reddish-purple with Loeffler's methylene blue; stain with Albert's stain (blue-green bacilli, dark blue/black granules)
• Culture on Loeffler's serum slope (best for morphology), Tellurite medium (selective - gray-black colonies); blood agar
• Three biotypes: gravis (most virulent), intermedius, mitis

• Diphtheria toxin - encoded by tox gene on bacteriophage (corynephage β)
• Fragment B: binding to host cell
• Fragment A: inhibits protein synthesis by ADP-ribosylation of EF-2 (Elongation Factor 2)
• Elek's gel precipitation test: detects toxin production in vitro

• Faucial diphtheria: pseudo-membrane on tonsils/pharynx (grayish-white, bleeds on removal)
• Toxin spreads → myocarditis (heart block, arrhythmia), neuropathy (palatal palsy, paralysis of accommodation)
• Bull neck appearance (cervical lymphadenopathy)
• Laryngeal diphtheria: "croup" - hoarseness, stridor

• Smear: Albert stain / Loeffler's methylene blue
• Culture: Tellurite medium + Loeffler's slope
• Elek's test (immunodiffusion); PCR for tox gene; ELISA

---

6. Pertussis (Ch. 54) ⭐⭐⭐⭐

• Small, encapsulated, non-motile
• Bordet-Gengou (BG) medium (potato-glycerol-blood agar): "mercury droplet" or "bisected pearl" colonies; narrow zone of hemolysis
• Regan-Lowe medium (alternative transport/culture medium)

• Pertussis toxin (PT): ADP-ribosylates Gi protein → increased cAMP → lymphocytosis promoting factor
• Filamentous Hemagglutinin (FHA): adhesion
• Pertactin, Fimbriae: adhesion
• Adenylate cyclase toxin: impairs phagocyte function
• Tracheal cytotoxin: ciliastasis

1. Catarrhal stage (1-2 weeks): Cold-like symptoms, most infectious
2. Paroxysmal stage (2-6 weeks): Characteristic "whoop" - 5-10 rapid coughs followed by inspiratory whoop; vomiting; post-tussive vomiting; Leukocytosis with absolute lymphocytosis
3. Convalescent stage (weeks-months): Gradual recovery

• Per-nasal swab (best) or nasopharyngeal aspirate
• Culture: Bordet-Gengou agar (within first 2 weeks)
• DFA (direct fluorescent antibody)
• PCR: most sensitive
• Serology: ELISA for anti-PT IgA/IgG (useful in later stages)
• Blood: lymphocytosis (up to 70-80% lymphocytes)

---

CARDIOVASCULAR & BLOODSTREAM

---

7. Infective Endocarditis (Ch. 65) ⭐⭐⭐⭐

• Native valve (subacute): Streptococcus viridans (commonest)
• Native valve (acute): Staphylococcus aureus (commonest overall)
• Prosthetic valve (early, <2 months): S. epidermidis, S. aureus
• Prosthetic valve (late, >2 months): S. viridans
• IVDU: S. aureus (right-sided, tricuspid)
• HACEK organisms: Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella

• Pre-existing valve lesion → platelet-fibrin thrombus → bacteremia → bacterial colonization → vegetation

• Fever, night sweats, weight loss
• New/changing murmur
• Peripheral stigmata: Osler's nodes (painful, fingers/toes), Janeway lesions (painless, palms/soles), Splinter hemorrhages, Roth spots (fundus)
• Splenomegaly; Clubbing

• Major: Positive blood cultures (×2), Echo evidence (vegetation/abscess/new regurgitation)
• Minor: Predisposing condition, Fever ≥38°C, Vascular phenomena, Immunologic phenomena, Microbiological evidence
• Definite IE: 2 major / 1 major + 3 minor / 5 minor

• Blood cultures (gold standard): 3 sets from different sites before antibiotics
• Echo: TTE then TEE (more sensitive for vegetation)
• CBC: anemia, leukocytosis; elevated ESR, CRP; hematuria

• Native valve streptococcal: Penicillin G + Gentamicin × 4-6 weeks
• S. aureus: Nafcillin/Oxacillin; MRSA → Vancomycin
• Surgery for: persistent bacteremia, large vegetation, heart failure, fungal IE

---

8. Enteric Fever / Typhoid (Ch. 70) ⭐⭐⭐⭐⭐

• Gram-negative bacillus, motile (peritrichous flagella), non-capsulated
• Facultative anaerobe; produces H2S on TSI

• Feco-oral route; infective dose ~10^5-10^9 organisms
• Penetrates M cells of Peyer's patches → intracellular survival in macrophages → bacteremia → liver, spleen, bone marrow → secondary bacteremia (symptomatic illness)
• Vi antigen: antiphagocytic capsular polysaccharide

• Week 1: Stepladder fever, headache, relative bradycardia (Faget's sign), rose spots (chest/abdomen, fades on pressure)
• Week 2: High fever, splenomegaly, hepatomegaly, toxemia
• Week 3: Complications - intestinal hemorrhage, perforation, myocarditis
• Week 4: Lysis of fever

• Blood culture (best in 1st week): highest yield (positive ~80%)
• Bone marrow culture: gold standard (positive even after antibiotics); ~95% sensitivity
• Urine culture (3rd week): ~25%
• Stool culture (2nd-3rd week): ~50%
• Widal test: agglutination with somatic (O) and flagellar (H) antigens; significant titre: O ≥1:80, H ≥1:160 (single); rising titre more significant
• ELISA; Typhidot (IgM/IgG anti-OMP); Tubex (IgM anti-O9 antigen)

• Chloramphenicol (historical DOC); now Fluoroquinolones (Ciprofloxacin) or Ceftriaxone (for nalidixic acid-resistant strains)
• MDR typhoid: Azithromycin

• Vi polysaccharide vaccine (single IM dose, >2 yrs)
• Ty21a: live attenuated oral vaccine (3-4 doses)
• Sanitation, clean water, food hygiene

---

9. Rickettsial Infections (Ch. 71) ⭐⭐⭐⭐

• Enter endothelial cells → replicate in cytoplasm (except R. rickettsii - also in nucleus)
• Vasculitis → widespread endothelial damage → rash, hemorrhage, edema

• Triad: Fever + Headache + Rash
• Rash: maculopapular, centrifugal (peripheral → central); RMSF - starts on wrists/ankles
• Scrub typhus: Eschar (painless ulcer with black crust) at bite site → regional lymphadenopathy → rash

• Weil-Felix test: agglutination of Proteus strains (OX-19, OX-2, OX-K)
  • Epidemic typhus, RMSF: OX-19 +++, OX-2 ++
  • Scrub typhus: OX-K +++
  • Q fever: negative (no Weil-Felix reaction)
• Specific: IFA (immunofluorescence assay) - gold standard; ELISA; PCR; Giemsa stain (intracytoplasmic organisms)
• Weil-Felix: non-specific but widely available

---

10. Spirochetal Infections (Ch. 73) - Leptospirosis & Syphilis ⭐⭐⭐

• Organism: Leptospira interrogans - tightly coiled, hook-shaped ends; darkfield microscopy
• Source: Rodents (rats) - urine-contaminated water; Occupational hazard (farmers, sewage workers)
• Transmission: Skin abrasions, mucous membranes
• Clinical (Weil's disease - severe form): Fever, jaundice, renal failure, hemorrhage, uveitis; Conjunctival suffusion (characteristic)
• Leptospiremic phase (1st week): Leptospires in blood/CSF
• Immune phase (2nd week): Antibodies appear, leptospires in urine
• Lab: Darkfield microscopy; ELISA; MAT (Microscopic Agglutination Test - gold standard)
• Treatment: Penicillin G (DOC); Doxycycline (mild disease/prophylaxis)

---

11. Dengue (Ch. 74) ⭐⭐⭐⭐⭐

• First infection: Classical dengue fever (protective immunity to that serotype only)
• Second infection (different serotype): Antibody-Dependent Enhancement (ADE) - non-neutralizing antibodies from 1st infection opsonize virus → increased viral uptake by monocytes → cytokine storm → DHF/DSS
• Thrombocytopenia: virus infects platelets and megakaryocytes; immune complex-mediated destruction

1. Classical Dengue Fever (DF):
   • Abrupt high fever (breakbone fever), severe myalgia/arthralgia
   • Biphasic fever (saddle-back pattern), relative bradycardia
   • Rash: maculopapular, "islands of white in sea of red"
   • Positive tourniquet test (Hess/Rumpel-Leede test)
2. Dengue Hemorrhagic Fever (DHF): Above + hemorrhagic manifestations + thrombocytopenia (≤1 lakh) + plasma leakage (hematocrit rise ≥20%)
3. Dengue Shock Syndrome (DSS): DHF + circulatory failure (narrow pulse pressure <20 mmHg or hypotension)

• Day 1-5 (febrile phase):
  • NS1 antigen (ELISA/RDT) - highly specific, appears early
  • RT-PCR (viral RNA) - gold standard early
• Day 5+ (defervescence):
  • IgM/IgG ELISA (seroconversion)
• CBC: Leukopenia, thrombocytopenia, rising hematocrit

---

BONES, SKIN & SOFT TISSUE

---

12. Staphylococcal Infections (Ch. 107) ⭐⭐⭐⭐⭐

• Golden-yellow pigment colonies on blood agar (beta-hemolysis)
• Catalase positive (differentiates from Streptococci)
• Coagulase positive (tube coagulase - key for S. aureus ID)
• Mannitol salt agar: ferments mannitol (yellow colonies)
• DNase positive; Protein A (binds Fc of IgG)

• Skin: Furuncle, carbuncle, impetigo bullosa, SSSS (Ritter's disease in neonates)
• Respiratory: Pneumonia (post-influenza), Empyema
• Food poisoning: vomiting (2-4 hr incubation), no fever
• Osteomyelitis (hematogenous - most common cause in children)
• Bacteremia, Endocarditis (IVDU)
• TSS: fever, hypotension, diffuse macular rash, multiorgan failure

• Methicillin-resistant S. aureus; mecA gene → altered PBP2a
• Treatment: Vancomycin (DOC); Linezolid, Daptomycin, Teicoplanin

• Gram stain: Gram-positive cocci in clusters
• Culture on blood agar, Mannitol salt agar
• Coagulase test (slide - bound coagulase/clumping factor; tube - free coagulase)
• Antibiotic sensitivity: Oxacillin disc test (MRSA screening)

---

13. Beta-Hemolytic Streptococcal Infections (Ch. 108) ⭐⭐⭐⭐

• Beta-hemolysis (complete hemolysis = clear zone on blood agar)
• Bacitracin sensitive (Group A specific)
• PYR (pyrrolidonyl arylamidase) test: positive
• Group B (S. agalactiae): CAMP test positive; hippurate hydrolysis positive

• Pharyngitis ("strep throat"), Tonsillitis
• Scarlet fever: strawberry tongue, sandpaper rash (spares perioral area - Filatov's sign), Pastia's lines
• Impetigo (non-bullous), Erysipelas, Cellulitis, Necrotizing fasciitis

• Rheumatic Fever (RF): 2-4 weeks after pharyngitis; Jones criteria; involves heart, joints, CNS (Sydenham's chorea)
• Post-Streptococcal Glomerulonephritis (PSGN): Nephritogenic M types (1, 4, 12 - pharyngeal; 49, 55 - skin); immune complex deposition

• Throat swab culture: Blood agar (beta-hemolysis, bacitracin sensitivity)
• ASO titer: raised in RF and PSGN (pharyngeal); not raised in skin infection
• Anti-DNase B: raised in both pharyngeal and skin infections (useful for PSGN)
• Rapid Strep Test (RADT): detects Lancefield A antigen

---

14. Gas Gangrene (Ch. 110) ⭐⭐⭐⭐

• Gram-positive, large, box-car-shaped rods; anaerobic; spore-forming (subterminal, non-bulging)
• Stormy fermentation of milk (Nagler reaction medium)
• Double zone of hemolysis on blood agar

• Type A: Gas gangrene, Food poisoning, Necrotizing enteritis
• Type C: Pig-bel (necrotizing enteritis)

• Follows contaminated wounds (trauma, surgery, ischemia)
• Rapid onset: severe pain, crepitus (gas in tissue - palpable/X-ray), necrosis, bronze-colored skin, foul discharge
• Systemic: Toxemia, shock, renal failure, hemolytic anemia (jaundice)
• Clostridial food poisoning: Ingestion of contaminated meat (>10^8 organisms); incubation 8-24 hrs; watery diarrhea, no vomiting, self-limiting

• Gram stain of wound discharge: Large Gram-positive rods, few/no PMNs
• Culture: Robertson's cooked meat medium (anaerobic); Nagler reaction (egg yolk agar)
• X-ray/CT: gas in tissue

• Surgical debridement + Penicillin G (high dose IV)
• Hyperbaric oxygen (adjunct)
• Polyvalent antitoxin (if available)

---

15. Leprosy (Ch. 111) ⭐⭐⭐⭐⭐

• Grows in armadillos (9-banded) and foot pads of mice
• Obligate intracellular parasite; attacks Schwann cells and macrophages
• Tropism for cool body parts (nose, ears, skin, peripheral nerves, testes)

• Intradermal injection of lepromin
• Early (Fernandez, 48 hr): DTH, not diagnostic
• Late (Mitsuda, 21-28 days): Nodular indurated lesion = positive (indicates host resistance); tuberculoid = positive, lepromatous = negative

• Tuberculoid: Hypopigmented, well-defined patches; loss of sensation, loss of sweating; thickened peripheral nerves (ulnar, radial cutaneous, great auricular); few bacilli
• Lepromatous: Multiple nodular/infiltrated lesions; leonine facies, madarosis (loss of lateral eyebrows), saddle-nose, ear lobe infiltration; glove-and-stocking anesthesia; numerous bacilli (globi)

• Slit-skin smear (slit over ear lobe, nasal septum): ZN staining; Bacteriological Index (BI): log scale 0-6+
• Morphological Index (MI): % of solid-staining (viable) bacilli
• Skin biopsy: Fite-Faraco stain (modified ZN for M. leprae)
• Lepromin test (prognosis, not diagnosis)

• Type 1 (Reversal reaction): Sudden upgrading of immunity; erythema/edema of existing lesions; nerve damage; treat with prednisolone
• Type 2 (Erythema Nodosum Leprosum - ENL): Immune complex-mediated; tender red nodules; treat with Thalidomide/Clofazimine/Prednisolone

• Paucibacillary (TT, BT, BI<2): Dapsone + Rifampicin × 6 months
• Multibacillary (BB, BL, LL, BI≥2): Dapsone + Rifampicin + Clofazimine × 12 months

---

SKIN & VIRAL

---

16. Herpesvirus Infections (Ch. 115) ⭐⭐⭐⭐

• Orolabial herpes (cold sores, fever blisters)
• Primary gingivostomatitis (children), Herpes labialis (recurrent)
• Herpes keratoconjunctivitis (corneal ulcers, dendritic ulcers)
• Herpes encephalitis (temporal lobe) - most common sporadic viral encephalitis
• Whitlow (finger herpes in healthcare workers)

• Genital herpes (primary and recurrent)
• Neonatal herpes (birth canal → disseminated, encephalitis, skin/eyes)

• Tzanck smear: multinucleated giant cells with Cowdry A inclusions (also for VZV)
• Culture: Cytopathic effect (CPE) in cell culture
• PCR (CSF): gold standard for HSV encephalitis
• Serology: ELISA (type-specific)

• Valacyclovir, Famciclovir (better bioavailability)
• Neonatal/Encephalitis: IV Acyclovir

---

17. Varicella-Zoster Virus (Ch. 116) ⭐⭐⭐⭐

• Highly contagious; respiratory droplets + direct contact
• Incubation: 14-21 days
• Prodrome: low fever, malaise (1-2 days)
• Rash: Starts on trunk → spreads centrifugally; hallmark = different stages simultaneously (macule → papule → vesicle → pustule → crust)
• Dew-drop on rose petal appearance of vesicles
• Complications: Secondary bacterial infection, Varicella pneumonia (adults), Reye's syndrome (aspirin use in children), Encephalitis

• Dermatomal distribution (unilateral); extremely painful
• Commonest dermatomes: thoracic (T3-L3), ophthalmic (V1 - Herpes zoster ophthalmicus)
• Ramsay Hunt syndrome: Zoster of geniculate ganglion → facial palsy + vesicles in ear + hearing loss
• Post-herpetic neuralgia: persistent pain after healing

• Chickenpox: Acyclovir (severe cases / immunocompromised); supportive in uncomplicated
• Zoster: Acyclovir/Valacyclovir/Famciclovir (reduces duration); analgesics; Gabapentin for post-herpetic neuralgia

• Live attenuated VZV vaccine (Varivax/Varilrix)
• Zoster vaccine (Zostavax - live; Shingrix - recombinant subunit adjuvanted - preferred in elderly)
• VZIG (Varicella-Zoster Immunoglobulin): post-exposure prophylaxis for immunocompromised

---

18. Measles (Ch. 117) ⭐⭐⭐⭐

• Respiratory epithelium → regional LN → primary viremia → spreads to reticuloendothelial system → secondary viremia → skin, mucosa, CNS
• Transient immunosuppression ("immune amnesia")

• Prodrome (3-4 days): 3 C's - Cough, Coryza, Conjunctivitis + high fever
• Koplik's spots: Pathognomonic - white spots on red base on buccal mucosa opposite lower 2nd molar teeth; appear 1-2 days before rash
• Rash: Maculopapular, brick-red; starts behind ears → face → neck → trunk → extremities (cephalocaudal); lasts 5-7 days; fades with desquamation (branny)
• Rash + fever: Warthin-Finkeldey giant cells (multinucleated) in lymphoid tissue

• Otitis media (common), Pneumonia (giant cell pneumonia - especially immunocompromised - Hecht's pneumonia)
• Encephalitis (1/1000): Post-infectious, fever + seizures
• SSPE (Subacute Sclerosing Panencephalitis): 7-10 years later; defective measles virus; progressive mental deterioration → death; EEG: Radermecker complexes (periodic synchronous discharges)
• Measles keratitis → blindness (especially in Vitamin A deficiency)

• Clinical (Koplik's spots)
• Serology: IgM ELISA (acute), IgG (paired sera)
• RT-PCR; Virus isolation
• CSF (SSPE): very high measles antibody titer

---

19. Dermatophytosis (Ch. 123) ⭐⭐⭐⭐

• Trichophyton - infects skin, hair, nails
• Microsporum - infects skin and hair (not nails)
• Epidermophyton - infects skin and nails (not hair)

• Zoophilic: M. canis (cats/dogs), T. verrucosum (cattle) - more inflammatory
• Geophilic: M. gypseum (soil)
• Anthropophilic: T. rubrum, T. tonsurans - less inflammatory, chronic

• KOH mount (10-20%): Direct microscopy; shows septate hyphae and arthrospores; ecothrix vs endothrix
  • Ectothrix: spores on outside of hair shaft (Wood's lamp: fluorescence) - Microsporum
  • Endothrix: spores inside hair shaft (no fluorescence) - Trichophyton tonsurans, T. violaceum
• Wood's lamp (UV 365 nm): Bright green fluorescence - Microsporum species (M. canis, M. audouinii)
• Culture: Sabouraud's Dextrose Agar (SDA) + cycloheximide + chloramphenicol; identify by colony morphology and microscopy (macroconidia and microconidia)
• Macroconidia: Trichophyton - pencil-shaped, smooth; Microsporum - spindle-shaped, rough (echinulate); Epidermophyton - beaver-tail (club-shaped), smooth

• Topical: Clotrimazole, Miconazole, Terbinafine (for tinea corporis, cruris, pedis)
• Systemic: Terbinafine (DOC for onychomycosis); Griseofulvin (binds keratin precursor cells); Itraconazole, Fluconazole

---

20. Candidiasis (Ch. 127) ⭐⭐⭐⭐

• Yeast form at 37°C; hyphae/pseudohyphae at 25°C
• Germ tube test (Reynolds-Braude phenomenon): Serum incubation at 37°C × 2-3 hrs → germ tubes = C. albicans (also C. dubliniensis)
• Chlamydospores: Thick-walled large spores on cornmeal agar - C. albicans specific

• Immunosuppression (HIV, steroids, cytotoxics), Diabetes mellitus, Prolonged antibiotic use, Pregnancy, Catheters, Neonates

• KOH mount / Gram stain: pseudohyphae + budding yeast cells
• Germ tube test
• Culture: SDA (cream-colored pasty colonies); CHROM agar (color-based species differentiation)
• Biopsy: PAS stain / GMS (Gomori methenamine silver) - stains fungal cell wall
• Serology: Mannan antigen (invasive candidiasis); beta-D-glucan

• Oral/Vaginal/Cutaneous: Topical nystatin, Clotrimazole, Miconazole; Oral fluconazole
• Systemic/Invasive: Fluconazole (DOC for candidemia if not critically ill); Echinocandins (Caspofungin, Micafungin - DOC for critically ill / C. krusei / C. glabrata); Amphotericin B (severe/resistant cases)

---

GENITOURINARY

---

21. Urinary Tract Infection (Ch. 128) ⭐⭐⭐⭐⭐

• Community-acquired: Escherichia coli (80%) - commonest; Staphylococcus saprophyticus (young women); Klebsiella, Proteus, Enterococcus
• Hospital-acquired: E. coli, Klebsiella, Pseudomonas, Enterococcus, Candida

• Ascending route (most common): periurethral flora → urethra → bladder → ureter → kidney
• Virulence: Type 1 fimbriae (mannose-sensitive), P fimbriae/pili (mannose-resistant, Gal-Gal receptor) - E. coli in pyelonephritis
• Women more susceptible: shorter urethra, proximity to anus, lack of prostatic secretions

• Urine microscopy: >10 WBC/HPF (pyuria); bacteria; RBC; casts (pyelonephritis)
• Urine culture (gold standard): ≥10^5 CFU/mL (midstream, clean-catch); catheter specimen ≥10^3
• Dipstick: Nitrite (bacterial nitrate reductase) + Leukocyte esterase
• Cystoscopy, Intravenous pyelogram (IVP), Ultrasound for structural abnormalities

• Uncomplicated cystitis: Nitrofurantoin, TMP-SMX, Fosfomycin (3 days)
• Pyelonephritis: Fluoroquinolones (Ciprofloxacin) 7-14 days; Cephalosporins
• Hospital-acquired/ESBL: Carbapenems
• Prophylaxis: Nitrofurantoin (recurrent UTI)
• In pregnancy: Amoxicillin, Nitrofurantoin, Cephalexin (avoid at term); always treat even asymptomatic bacteriuria

---

22. Syphilis (Ch. 130) ⭐⭐⭐⭐⭐

• Thin, tightly coiled (8-20 coils); 6-20 µm; motile
• Visualized by darkfield microscopy (golden-colored spiral organisms with characteristic corkscrew motility) or Silver stain (Fontana Tribondeau) in tissue

• Chancre: Painless, indurated, clean-based ulcer at site of inoculation (genitalia, perianal, lips)
• Regional painless lymphadenopathy (bilateral, rubbery)
• Darkfield microscopy of chancre exudate (best for diagnosis)

• Dissemination: fever, malaise, generalized lymphadenopathy
• Maculopapular rash - includes palms and soles (characteristic)
• Condylomata lata (moist wart-like perianal/genital lesions - highly infectious)
• Mucous patches (split papules), Alopecia (moth-eaten), Meningitis, Hepatitis

• Early latent (<1 year); Late latent (>1 year)

• Gumma: Granulomatous lesion in skin, bone, viscera (liver - hepar lobatum)
• Cardiovascular: Ascending aortitis → aortic aneurysm (saccular) + aortic regurgitation; Coronary ostial stenosis
• Neurosyphilis: Tabes dorsalis (posterior column demyelination → ataxia, Argyll Robertson pupil, lightning pains), General Paresis of Insane (dementia), Charcot joint

• VDRL (Venereal Disease Research Laboratory): flocculation test; detects antibody to cardiolipin-lecithin-cholesterol
• RPR (Rapid Plasma Reagin): similar principle; easier to perform
• Used for screening and monitoring treatment (titres fall with treatment)
• Biological false positives (BFP): SLE, malaria, pregnancy, leprosy, IV drug use

• TPHA/TPPA (T. pallidum Haemagglutination Assay)
• FTA-ABS (Fluorescent Treponemal Antibody Absorbed): most sensitive, detects early primary
• TPPA, ELISA: confirmatory; remain positive for life (cannot monitor treatment)

• Primary/Secondary/Early latent: Benzathine Penicillin G 2.4 MU IM × single dose
• Late latent/Tertiary: Benzathine Penicillin G 2.4 MU × 3 doses (weekly × 3)
• Neurosyphilis: Aqueous Penicillin G IV × 14 days
• Penicillin allergy: Doxycycline; In pregnancy: Desensitize and give Penicillin
• Jarisch-Herxheimer reaction: Fever, chills 2-8 hrs after first penicillin dose due to sudden release of treponemal antigens

---

23. Chlamydia (Ch. 131) ⭐⭐⭐⭐

• Elementary Body (EB): Extracellular, infectious, metabolically inactive, rigid cell wall, 0.3 µm
• Reticulate Body (RB): Intracellular, non-infectious, metabolically active, replicates by binary fission; 1 µm
• EB → enters cell → RB → multiplies → EB → ruptures cell → infects new cells
• Inclusions: Iodine-staining glycogen inclusions (intracytoplasmic)

• Cell culture (McCoy cells, HeLa cells) - gold standard (not practical)
• NAAT (Nucleic Acid Amplification Test - PCR/SDA): gold standard clinically; first-void urine or genital swab
• Direct fluorescent antibody (DFA)
• ELISA (EIA): antigen detection
• Giemsa stain: intracytoplasmic inclusions (Halberstaedter-Prowazek bodies)
• Frei test: skin test for LGV (historical)

• Uncomplicated genital infection: Azithromycin 1g single dose or Doxycycline 100mg BD × 7 days
• LGV: Doxycycline × 21 days
• Neonatal ophthalmia: Erythromycin eye drops + oral

---

24. STIs (Ch. 129) ⭐⭐⭐⭐

---

CNS INFECTIONS

---

25. Tetanus (Ch. 133) ⭐⭐⭐⭐⭐

• Drumstick/tennis racket appearance - terminal spherical spore (bulging)
• Spores highly resistant (boiling, antiseptics); destroyed by autoclaving
• Ubiquitous in soil, dust, animal feces

• Encoded on plasmid
• Mechanism: Cleaves synaptobrevin (VAMP) → prevents release of inhibitory neurotransmitters (glycine and GABA) from Renshaw cells in spinal cord → unopposed excitation → spastic paralysis
• Spreads via motor nerves (retrograde axonal transport) and blood to CNS
• Tetanolysin: hemolysin (minor role)

• Spores in wound → germinate (anaerobic conditions) → vegetative forms → toxin → retrograde axonal + hematogenous spread to CNS

1. Generalized Tetanus (most common):
   • Trismus (lockjaw) - first symptom (masseter spasm)
   • Risus sardonicus (sardonic smile - facial muscle spasm)
   • Opisthotonos (back arching due to spasm of back muscles)
   • Reflex tetanic spasms triggered by stimuli (noise, touch, light)
   • Autonomic dysfunction: profuse sweating, tachycardia, hypertension, hyperpyrexia
   • Conscious throughout (toxin does not cross BBB to affect cortex)
   • Death from respiratory failure/spasm, aspiration pneumonia
2. Neonatal Tetanus: Infected umbilical stump; generalized tetanus in neonate (day 3-10 of life)
3. Local Tetanus: Spasm confined to affected limb
4. Cephalic Tetanus: Head wounds; facial nerve palsy + cranial nerve involvement

• Human Tetanus Immunoglobulin (HTIG): 3000-6000 IU IM (neutralizes unbound toxin)
• Metronidazole (DOC for organism elimination) or Penicillin G
• Diazepam (control spasms - facilitates GABA)
• Wound debridement (remove necrotic tissue - eliminate anaerobic environment)
• Supportive: airway management, ICU, mechanical ventilation

• Active immunization: TT (tetanus toxoid) - formalin-treated toxoid
• DTP/DTwP: 3 primary doses at 6, 10, 14 weeks; booster at 18 months, 5 years
• Post-exposure prophylaxis: TT + HTIG (if unimmunized/incomplete immunization)
• Maternal TT: 2 doses in pregnancy (prevents neonatal tetanus)

---

26. Rabies (Ch. 135) ⭐⭐⭐⭐⭐

• Single-stranded, negative-sense RNA; 5 structural proteins: N, P, M, G (surface), L

• Bite of infected animal (dog - commonest worldwide); saliva
• Animals: Dog (commonest in India), fox, skunk, bat (reservoir), raccoon
• Incubation: 3 weeks to 3 months (range: 4 days to years); depends on site (shorter for face/head bites)

• Virus enters peripheral nerve endings (nAChR, p75 neurotrophin receptor) → retrograde axonal transport to CNS (travels at ~12-100 mm/day) → brainstem, limbic system → spreads centrifugally to salivary glands, cornea
• Negri bodies: eosinophilic intracytoplasmic inclusion bodies in neurons (especially hippocampal pyramidal cells and Purkinje cells of cerebellum); pathognomonic

1. Prodromal (2-4 days): Fever, headache, paresthesia at bite site (warning sign)
2. Acute Neurologic Phase:
   • Furious (Encephalitic) Rabies (~80%): Hydrophobia (spasm of pharyngeal muscles on attempting to swallow), aerophobia, hypersalivation, agitation, autonomic dysfunction, periods of lucidity alternating with aggression
   • Dumb (Paralytic) Rabies (~20%): Ascending flaccid paralysis (like Guillain-Barré); less agitation; longer course
3. Coma & Death: Virtually 100% fatal once symptoms appear; death within 10-14 days from onset

• Antemortem: Skin biopsy (nape of neck - hair follicle DFA), Corneal smear (DFA), Saliva (RT-PCR), CSF (RT-PCR), Serum/CSF antibodies
• Postmortem: Brain biopsy - Seller's stain (Negri bodies - magenta-pink against blue background); DFA (gold standard for brain); Mice inoculation
• Brain MRI: T2 hyperintensities in brainstem, hippocampus

1. Wound washing: Immediately with soap and water × 15 minutes (most important step); iodine/70% alcohol
2. Rabies Immunoglobulin (RIG): HRIG 20 IU/kg or ERIG 40 IU/kg; infiltrate around wound + remaining IM; give with first vaccine dose
3. Rabies vaccine (cell culture):
   • Essen regimen (WHO): 5 doses on days 0, 3, 7, 14, 28
   • Updated Zagreb regimen: 4 doses (0, 3, 7, 14)
   • Types: HDCV (Human Diploid Cell Vaccine), PCEC (Purified Chick Embryo Cell), PVRV (Purified Vero Cell Rabies Vaccine - Rabipur)
   • Avoid: Brain/nerve tissue vaccines (Semple vaccine - obsolete, causes neuroparalytic complications)

• Category I: Touching, no skin break → Wash only
• Category II: Minor scratches, no bleeding → Wound wash + vaccine
• Category III: Transdermal bite, bleeding, mucous membrane exposure → Wound wash + RIG + vaccine

---

27 & 28. Meningitis / Acute Pyogenic Meningitis (Ch. 140, 141) ⭐⭐⭐⭐⭐

• Bacteremia → choroid plexus → subarachnoid space → meningeal inflammation → increased BBB permeability → cerebral edema → raised ICP
• N. meningitidis: pili adhesion → IgA protease → capsule (antiphagocytic) → LPS (endotoxin) → cytokine cascade

• Classic triad: Fever + Headache + Neck stiffness (Nuchal rigidity)
• Photophobia, Phonophobia, Altered consciousness
• Kernig's sign: Resistance to knee extension with hip flexed at 90°
• Brudzinski's sign: Passive neck flexion causes involuntary hip flexion
• Jolt accentuation: Head turning worsens headache (sensitive early sign)
• N. meningitidis: Petechial/purpuric rash (meningococcemia) - non-blanching; Waterhouse-Friderichsen syndrome (bilateral adrenal hemorrhage → fulminant shock)

• Lumbar puncture (LP): CSF analysis (do CT head first if papilledema/focal neurology to rule out raised ICP)
• Blood culture (before antibiotics)
• Gram stain and culture of CSF
• Latex agglutination / Quellung (rapid antigen detection)
• PCR (CSF): for N. meningitidis, H. influenzae, S. pneumoniae
• India ink stain (CSF): Cryptococcus neoformans (thick capsule)
• Blood: CBC (neutrophilia), CRP, procalcitonin; blood glucose (for comparison)

• Neonate: Ampicillin + Cefotaxime
• Child/Adult: Ceftriaxone (3rd gen cephalosporin) + Dexamethasone (reduces inflammation, deafness)

• 50 yrs/immunocompromised: Add Ampicillin (for Listeria)

• Add Vancomycin if PRSP suspected

• N. meningitidis: Penicillin G IV; Ceftriaxone
• S. pneumoniae: Penicillin G; Ceftriaxone ± Vancomycin
• H. influenzae: Ceftriaxone; Ampicillin
• L. monocytogenes: Ampicillin + Gentamicin

• Rifampicin (600mg BD × 2 days); or Ciprofloxacin single dose; or Ceftriaxone IM (preferred in pregnancy)

• Meningococcal vaccine: MenACWY (quadrivalent conjugate); MenB (serogroup B)
• Hib vaccine; PCV13/PPSV23

---

29. Poliomyelitis (Ch. 134) ⭐⭐⭐⭐

• 3 serotypes (1, 2, 3); Type 1 most common cause of paralysis (Brunhilde strain)
• Stable to acid (survives gastric acid), ether-resistant (non-enveloped)
• Mahoney (type 1), MEF-1 (type 2), Saukett (type 3)

• Oropharynx → tonsils, Peyer's patches → regional LN → viremia → CNS (via blood or neural route)
• Destroys anterior horn cells (lower motor neurons) of spinal cord and motor nuclei of brainstem
• Selective destruction → flaccid paralysis

1. Inapparent infection (95%): No symptoms; seroconversion only
2. Abortive polio (4-8%): Minor illness; fever, sore throat, GI symptoms; self-limiting
3. Non-paralytic (aseptic meningitis, 1-2%): Meningism + CSF pleocytosis; no paralysis; lymphocytic meningitis pattern
4. Paralytic polio (<1%):
   • Spinal polio (most common): Asymmetric flaccid paralysis; lower limb > upper; spares sensation; maximum paralysis within 48-72 hrs; fever at onset
   • Bulbar polio: Involves IX, X, XII cranial nerves → dysphagia, respiratory paralysis; higher mortality
   • Bulbospinal: Combined

• Asymmetric (different muscle groups)
• Flaccid (LMN type): wasting, hypotonia, absent/reduced reflexes
• No sensory loss
• Worse in hot weather, after exercise, after IM injections ("provocation polio")

• Stool culture (most important and best specimen): Collected ≥24 hrs apart; positive up to several weeks
• Throat swab (first week)
• CSF: lymphocytic pleocytosis, slightly elevated protein, normal glucose (aseptic meningitis pattern)
• Serology: 4-fold rise in neutralizing antibody titer
• AFP (Acute Flaccid Paralysis) surveillance: stool for poliovirus culture