Here are your comprehensive university exam notes for all three topics, sourced from Medical Microbiology 9e and Sherris & Ryan's Medical Microbiology 8e.
🦠 MICROBIOLOGY EXAM NOTES
1. VARICELLA-ZOSTER VIRUS (VZV)
Classification
- Family: Herpesviridae, Subfamily: Alphaherpesvirinae
- HHV-3 (Human Herpesvirus 3)
- Smallest genome of all human herpesviruses (HHVs)
Key Trigger Words (Exam Clue)
Chickenpox, shingles, dermatome, DRG latency, alphaherpesvirus, Oka strain vaccine
Structure & Replication
- Enveloped, dsDNA virus
- Replicates slower and in fewer cell types than HSV
- Productive replication in: human diploid fibroblasts (in vitro), activated T cells, epithelial cells, epidermal cells (in vivo)
- VZV is sequestered into lysosomes and degraded in most cells (via mannose-6-phosphate receptor binding); only terminally differentiated skin cells (lacking this receptor) release infectious virus
- Spreads within the body via cell-to-cell contact
Pathogenesis
Primary Infection (Varicella / Chickenpox):
- Acquired by inhalation - replication begins in tonsils and respiratory mucosa
- Virus spreads via bloodstream and lymphatics to reticuloendothelial system
- Secondary viremia spreads virus to skin - forms vesicular rash in successive crops
- VZV infects T cells which home to skin and transfer virus to keratinocytes
- Overcomes IFN-α, produces dermal vesiculopustular rash
CPE: Cowdry type A intranuclear inclusions + syncytia formation
Latency:
- Establishes latency in dorsal root ganglia (DRG), cranial nerve ganglia, and other ganglia
- Unlike HSV: viral RNAs AND specific viral proteins can be detected in latently infected cells
Reactivation (Herpes Zoster / Shingles):
- Occurs when cell-mediated immunity wanes (elderly, immunocompromised)
- Virus travels along neuron to skin → vesicular rash in single dermatome
- Typical sites: thoracic dermatome, head (ophthalmic branch of CN V)
- Postherpetic neuralgia (PHN): chronic pain lasting months-years; occurs in ~30%
Immunity
- Cell-mediated immunity is the key control mechanism
- VZV encodes thymidine kinase (like HSV) - basis of antiviral susceptibility
- Immunocompromised patients: risk of dissemination to lungs, brain, liver (potentially fatal)
- Neonates at risk for severe progressive disease
Laboratory Diagnosis
| Test | Notes |
|---|
| PCR / genome detection | Method of choice (VZV labile in transport) |
| Direct fluorescent antibody to membrane antigen (FAMA) | Skin scraping/biopsy |
| Serology (IFA, ELISA) | Screens immunity; antibody levels normally low |
| Culture | NOT routinely done - virus is labile |
Treatment, Prevention, Control
| Drug | Use |
|---|
| Acyclovir (ACV) | Approved for VZV; requires higher doses than for HSV (VZV TK less sensitive) |
| Famciclovir | Better pharmacodynamics |
| Valacyclovir | Better pharmacodynamics |
| VZIg (Varicella-Zoster Immune Globulin) | Post-exposure prophylaxis in high-risk/immunocompromised; NOT effective as therapy for active disease |
Vaccines:
- Varivax: Live attenuated Oka strain - administered after 1 year of age; induces antibody AND cell-mediated immunity
- Shingrix: Adjuvanted subunit vaccine for zoster prevention in adults ≥50
- Medical Microbiology 9e
2. SYPHILIS (Treponema pallidum)
Classification
- Organism: Treponema pallidum subspecies pallidum
- Family: Spirochaetaceae
- Gram negative (does not stain well - outer membrane is antigen-poor)
- Exclusively human pathogen under natural conditions
Key Trigger Words
Chancre, condylomata lata, tabes dorsalis, VDRL/RPR, FTA-ABS, gumma, penicillin G
Transmission & Epidemiology
- Direct sexual contact with active primary/secondary lesion (>50% transmission when lesion present)
- Transplacental (congenital syphilis) - after 4th month of gestation
- Non-genital contact, needle sharing (IDU)
- Late disease is NOT infectious (no blood transmission via modern screening)
- ~6 million new cases annually worldwide; HIV co-infection synergy (syphilitic lesions = portal for HIV)
Pathogenesis
- Spirochete enters via microscopic skin breaks or mucosal passage
- Adheres via adhesin binding to fibronectin and extracellular matrix components
- Multiplies slowly, minimal initial tissue reaction (paucity of outer membrane antigens)
- Basic pathologic lesion: endarteritis - swelling and proliferation of endothelial cells of arterioles
- Endarteritis reduces blood supply → necrotic ulceration of primary lesion
Stages of Disease
PRIMARY SYPHILIS
- Incubation: median 3 weeks (range 3-90 days)
- Chancre: painless, indurated ulcer with firm base and raised margins at site of inoculation (usually genitalia, cervix, anal, or oral area)
- Firm, nonsuppurative, painless regional lymphadenopathy within 1 week
- Heals spontaneously in 4-6 weeks
SECONDARY SYPHILIS
- Appears 2-8 weeks after chancre (primary lesion may still be present)
- Symmetric maculopapular rash - distributed on trunk, extremities, PALMS and SOLES (key exam feature), face
- Generalized nontender lymphadenopathy + fever + malaise
- Condylomata lata: painless mucosal warty erosions in warm moist areas (genitals, perineum)
- All lesions teeming with spirochetes - HIGHLY infectious
- Resolves spontaneously; 1/3 of patients resolve, 2/3 enter latent stage
LATENT SYPHILIS
- No clinical manifestations; positive serology only
- Early latency: relapses of secondary syphilis possible
- Late latency (>4 years): relapses cease; resistance to reinfection develops
- Mothers can still transmit to fetus throughout latency
TERTIARY SYPHILIS (appears 5-20 years later)
- Occurs in ~1/3 of untreated secondary cases
| Type | Manifestations |
|---|
| Neurosyphilis | Chronic meningitis, cortical degeneration (psychosis, hallucinations), tabes dorsalis (demyelination of posterior columns/dorsal roots - ataxia, wide-based gait, loss of sensation), paresis |
| Cardiovascular syphilis | Arteritis of vasa vasorum → medial necrosis of aorta → aortic aneurysm (ascending/transverse aorta), aortic valve incompetence |
| Gummatous syphilis | Localized granulomatous lesion (gumma) in skin, bone, joints, other organs |
Mnemonic for Paresis: P-A-R-E-S-I-S = Personality, Affect, Reflexes, Eyes, Sensorium, Intellect, Speech
CONGENITAL SYPHILIS
- Susceptibility after 4th month of gestation
- Analogous to secondary syphilis in adult
- Manifestations: rhinitis (snuffles), maculopapular rash, bone changes
- Routine serologic screening in early pregnancy (repeat in 3rd trimester in high-risk women)
Diagnosis
| Test | Category | Notes |
|---|
| VDRL / RPR | Non-treponemal (screening) | May be false positive (SLE, pregnancy, mono); titer correlates with disease activity |
| FTA-ABS / TPPA | Treponemal (confirmatory) | Specific; remains positive for life |
| Dark-field microscopy | Direct visualization | Requires fresh specimen from lesion |
Treatment
- Penicillin G remains drug of choice at ALL stages
- Primary/secondary/early latent: Benzathine penicillin G IM single dose
- Late latent/tertiary: Benzathine penicillin G IM x 3 doses
- Neurosyphilis: IV aqueous penicillin G
- Penicillin allergy (non-pregnant): doxycycline
- Congenital syphilis / neurosyphilis / pregnancy: penicillin G - NO substitute
- Sherris & Ryan's Medical Microbiology 8e
3. TUBERCULOSIS (Mycobacterium tuberculosis)
Classification
- Family: Mycobacteriaceae
- Weakly gram-positive, strongly acid-fast aerobic rods
- Lipid-rich cell wall (mycolic acids) = resistant to stains, disinfectants, detergents, many antibiotics, and host immune response
Key Trigger Words
Acid-fast, caseating granuloma, Ghon complex, Langhans giant cells, PPD/TST, IGRA, INH + rifampin + PZA + EMB, BCG vaccine, intracellular macrophage survival
Biology & Virulence
- Obligate intracellular pathogen (alveolar macrophages)
- Strictly pathogenic (unlike NTM)
- Humans are the only natural reservoir
- Spread: person-to-person via infectious aerosols (droplet nuclei <5 µm)
Pathogenesis & Immunity
Step 1 - Entry:
- Inhaled droplet nuclei reach alveoli
- Phagocytized by alveolar macrophages
Step 2 - Macrophage Survival (KEY):
- M. tuberculosis prevents phagosome-lysosome fusion by blocking EEA1 (early endosomal autoantigen 1)
- Phagosome can still fuse with other vesicles - organism accesses nutrients
- Result: intracellular survival and replication
Step 3 - Immune Response:
- T cell activation triggers IFN-γ release
- Activated macrophages form granulomas (tubercles)
- Granuloma = epithelioid macrophages + Langhans giant cells + lymphocytic cuff + central caseous necrosis
Disease States:
| State | Description |
|---|
| Primary TB | Initial infection; Ghon focus (lower/mid lung) + hilar lymphadenopathy = Ghon complex; usually self-limited |
| Latent TB | Infection contained; TST/IGRA positive, no symptoms, non-infectious |
| Secondary (Reactivation) TB | Upper lobe cavitary disease; occurs when immunity wanes |
| Miliary TB | Hematogenous dissemination; millet-seed lesions on CXR; common in immunocompromised |
Epidemiology
- ~1/4 of world population infected (latent)
- ~10.4 million new active cases/year; ~1.6 million deaths/year
- Highest burden: India, Pakistan, sub-Saharan Africa, South Africa, China, Eastern Europe
- At-risk groups: foreign-born, HIV+ patients, immunocompromised, homeless, drug/alcohol abusers, those in close contact with active TB
Laboratory Diagnosis
Microscopy (Acid-Fast Staining):
| Stain | Method |
|---|
| Ziehl-Neelsen | Hot acid-fast stain (carbolfuchsin) |
| Kinyoun | Cold acid-fast stain |
| Truant fluorochrome | Auramine-rhodamine fluorescent dye (most sensitive) |
Culture:
- Löwenstein-Jensen (egg-based) or Middlebrook (agar-based): 4+ weeks
- Broth cultures: 2 weeks faster
- Specimens decontaminated with 2% NaOH before culture (kills normal flora, mycobacteria survive brief alkali)
Immunologic Tests:
- TST (Tuberculin Skin Test / Mantoux / PPD): intradermal injection; induration read at 48-72h; sensitive marker for exposure (not disease)
- IGRA (Interferon-γ Release Assays): QuantiFERON-TB Gold, T-SPOT.TB; in vitro; not affected by BCG vaccination
Nucleic Acid Tests:
- NAAT (nucleic acid amplification tests): important where culture unavailable or microscopy inaccurate
Identification Methods:
- Species-specific molecular probes, nucleic acid sequencing, mass spectrometry (MALDI-TOF), biochemical tests (slow, being replaced)
Treatment
| Phase | Drugs | Duration |
|---|
| Intensive phase | Isoniazid (INH) + Rifampin (RIF) + Pyrazinamide (PZA) + Ethambutol (EMB) | 2 months |
| Continuation phase | INH + Rifampin | 4-6 months |
| Total | | 6-9 months |
Mnemonic: RIPE = Rifampin, Isoniazid (INH), Pyrazinamide, Ethambutol
Prophylaxis (Latent TB):
- INH monotherapy for 6-9 months
- OR daily rifampin for 4 months
- Drug-resistant exposure: pyrazinamide + ethambutol or levofloxacin x 6-12 months
Why multiple drugs? Prevent emergence of drug-resistant strains (MDR-TB, XDR-TB)
Prevention
- BCG vaccine (Bacillus Calmette-Guérin): live attenuated M. bovis; used in endemic countries; protects children from severe disseminated disease but does NOT reliably prevent pulmonary TB in adults; makes TST positive
- Active surveillance, contact tracing, case monitoring
- Medical Microbiology 9e; Sherris & Ryan's Medical Microbiology 8e
QUICK COMPARISON TABLE
| Feature | VZV | Syphilis | TB |
|---|
| Organism | Herpesvirus (dsDNA) | T. pallidum (spirochete) | M. tuberculosis (acid-fast rod) |
| Transmission | Respiratory (aerosol) | Sexual/transplacental | Respiratory aerosol |
| Key lesion | Dermatome vesicles | Chancre → maculopapular rash → gumma | Caseating granuloma |
| Latency site | Dorsal root ganglia | Serology positive, no symptoms | Alveolar macrophages |
| Immunity | Cell-mediated | Humoral + cellular | Cell-mediated (T cells, IFN-γ) |
| Key test | PCR / FAMA | VDRL screen; FTA-ABS confirm | TST/IGRA; AFB smear; culture |
| Drug of choice | Acyclovir/valacyclovir | Penicillin G | RIPE regimen |
| Vaccine | Varivax (live), Shingrix (subunit) | None | BCG |
Good luck on your exam! These notes cover the key exam targets: classification, pathogenesis, clinical stages, diagnosis, and treatment for all three organisms.
