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SECTION B - Model Answers (2nd Year MBBS Medical Microbiology)

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Question V [10 Marks] - 30-year-old lorry driver with urethral pus discharge, testicular pain, Gram-negative intracellular diplococci

A. Most likely clinical diagnosis and etiological agent [1 Mark]

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B. Pathogenesis [2 Marks]

1. Attachment: N. gonorrhoeae attaches to non-ciliated columnar epithelial cells of the urethra via pili and Opa (opacity-associated) proteins. Pili prevent phagocytosis; Opa proteins mediate firm attachment.
2. Invasion: The organism enters endocervical/urethral columnar cells by endocytosis and multiplies within vacuoles.
3. Local spread: Lipo-oligosaccharide (LOS) and peptidoglycan fragments trigger local inflammation, causing the purulent discharge. Chemotaxis of PMNs leads to characteristic purulent exudate.
4. Dissemination: From the urethra, the organism can spread to the epididymis causing epididymo-orchitis (as in this patient). Bacteremia may cause disseminated gonococcal infection (DGI) with skin pustules and septic arthritis.

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C. Lab diagnosis [2 Marks]

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D. Four complications [2 Marks]

1. Epididymo-orchitis (as in this patient) - unilateral testicular pain and swelling
2. Disseminated Gonococcal Infection (DGI) - septicemia, migratory arthralgia, suppurative arthritis (wrists, knees, ankles), pustular rash on erythematous base
3. Prostatitis and periurethral abscesses - local extension in males
4. Urethral stricture - due to scarring from repeated infections

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E. Two sexually transmitted diseases caused by this organism [2 Marks]

1. Gonorrhea (Urethritis/Cervicitis) - purulent urethral discharge in men; vaginal discharge + dysuria in women; after 2-5 day incubation
2. Ophthalmia Neonatorum - purulent ocular infection acquired by the neonate at birth (passage through infected birth canal); can cause corneal ulceration and blindness if untreated

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F. Drug of choice [1 Mark]

• Ceftriaxone with azithromycin was the previous standard, but rising azithromycin resistance has shifted guidelines to ceftriaxone monotherapy or ceftriaxone + doxycycline.
• Fluoroquinolones and penicillins are no longer reliable due to widespread resistance.

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Question VI - Short Notes [10 Marks]

A. Lab diagnosis of syphilis + 4 sexually transmitted infections [1+2+2+2+1 = Marks per part]

• Dark-field microscopy: Exudate from the painless indurated chancre shows spirochetes with characteristic corkscrew motility - definitive diagnosis
• Direct Fluorescent Antibody (DFA-TP) for T. pallidum

• Secondary syphilis: RPR 99% sensitive; MHA-TP 100% sensitive
• Tertiary syphilis: reactive RPR confirmed by treponemal test + clinical signs

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1. Gonorrhea (Neisseria gonorrhoeae) - purulent urethral/vaginal discharge
2. Syphilis (Treponema pallidum) - painless chancre -> systemic disease
3. Genital Herpes (Herpes Simplex Virus type 2) - painful vesicular ulcers
4. HIV/AIDS (Human Immunodeficiency Virus) - progressive immunodeficiency

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B. Clinical features and lab diagnosis of Influenza [2 Marks]

• Incubation period: 1-4 days (average 2 days)
• Abrupt onset: high fever (38-40°C), chills, severe myalgia, headache
• Dry, non-productive cough within 6-12 hours of onset
• Rhinitis, sore throat, malaise, anorexia
• Acute phase lasts 3-5 days; full recovery in ~1 week
• Lingering fatigue and cough for 2-6 weeks

• Bacterial superinfection pneumonia (S. pneumoniae, H. influenzae, S. aureus)
• Viral pneumonia (especially in elderly, pregnant)
• Reye syndrome in children (fatty liver + cerebral edema) - associated with salicylate use
• Myositis, myocarditis, CNS dysfunction

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C. Urinary Schistosomiasis [2 Marks]

• Cercariae in fresh water penetrate skin -> schistosomulae -> blood circulation -> lungs -> hepatoportal system -> mature into adult worms in vesical (bladder) venous plexus
• Adult females lay eggs in vesical plexus submucosal venules; eggs pass through bladder wall into urine

• Cercarial dermatitis ("swimmer's itch"): Pruritic papular rash at cercarial penetration site
• Acute (Katayama fever): 5-7 weeks after infection - fever, urticaria, eosinophilia, hepatosplenomegaly (immune complex disease)
• Chronic urinary schistosomiasis:
  • Haematuria (painless terminal haematuria - pathognomonic)
  • Dysuria, frequency
  • Bladder wall granulomas -> calcification ("calcified bladder" on X-ray)
  • Ureteric obstruction -> hydronephrosis
  • Squamous cell carcinoma of the bladder (long-term complication)

• Urine microscopy: Characteristic eggs with terminal spine in urine (concentrated by centrifugation); best collected at noon
• Stool microscopy: Also possible if coinfection with S. mansoni
• Rectal/bladder biopsy: Egg identification
• Serology: ELISA for antibodies (useful in travellers)
• Eosinophilia on CBC

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D. MMR Vaccine [2 Marks]

• Measles: Schwartz or Moraten substrain of Edmonton B strain
• Mumps: Jeryl Lynn strain
• Rubella: RA 27/3 strain
• All are live attenuated viruses

• First dose: 12-15 months of age
• Second dose: 4-6 years of age (pre-school booster)
• ACIP (2017) recommended a 3rd dose in crowded/outbreak settings

• Single dose: ~95% seroconversion, lifelong immunity
• Two-dose schedule increases protection; herd immunity requires >95% coverage

• Pregnancy (live vaccine)
• Immunocompromised individuals (HIV with low CD4, on chemotherapy)
• Severe allergy to gelatin or neomycin
• Recent immunoglobulin administration (delay 3 months)

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E. Larva Migrans [1 Mark]

• Caused by: Ancylostoma braziliense (dog/cat hookworm), A. caninum
• Infection: Larvae penetrate skin from contaminated soil/sand
• Features: Intensely pruritic, serpiginous (snake-like), red, raised tracks on skin; advances a few mm daily; usually on feet/buttocks
• Treatment: Albendazole or ivermectin

• Caused by: Toxocara canis (dog roundworm), T. cati
• Infection: Ingestion of embryonated eggs from contaminated soil
• Features: Larvae migrate to liver, lungs, eyes, CNS; hepatomegaly, eosinophilia, fever; Ocular Larva Migrans (OLM) causes retinal granuloma, risk of blindness
• Treatment: Albendazole or mebendazole (with steroids for ocular/CNS disease)

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Question VII - Answer in Brief [25 Marks, 5 marks each]

A. Why is influenza vaccine changed every year? [5 Marks]

• Gradual, cumulative point mutations in the genes encoding hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins
• Caused by the lack of proofreading ability in viral RNA-dependent RNA polymerase (RdRp)
• Mutant strains with altered HA/NA can escape pre-existing antibody immunity from prior vaccination or infection
• Antigenic drift occurs every 1-3 years in influenza A; less frequently in influenza B
• Result: The vaccine strain becomes antigenically mismatched with the circulating strain

• Abrupt, major change in HA or NA antigens due to genetic reassortment between two different influenza A strains infecting the same cell simultaneously
• Produces a novel subtype (e.g., H1N1, H3N2) to which the population has no immunity
• Can result in pandemics (e.g., 1918 Spanish flu H1N1, 2009 swine flu H1N1)
• Only influenza A undergoes antigenic shift (because it infects multiple species - humans, pigs, birds)

• WHO Global Influenza Surveillance Network monitors circulating strains worldwide year-round
• Each year (February for Northern Hemisphere; September for Southern Hemisphere), WHO recommends which strains to include
• Current seasonal vaccines are typically quadrivalent: two influenza A subtypes (H1N1 + H3N2) and two influenza B lineages (Yamagata + Victoria)

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B. Four important predisposing factors for development of opportunistic infections [5 Marks]

• Loss of CD4+ T lymphocytes is the primary predisposing factor
• CD4 <200 cells/μL: Pneumocystis jirovecii pneumonia (PCP), Toxoplasmosis, Cryptococcosis
• CD4 <50 cells/μL: CMV retinitis, Mycobacterium avium complex (MAC), disseminated fungal infections

• Corticosteroids: Suppress cell-mediated and humoral immunity; risk of fungal infections (Aspergillus, Candida, Mucor), reactivation TB
• Chemotherapy/Radiotherapy: Causes neutropenia; risk of bacterial (Gram-negative, S. aureus) and fungal infections
• Transplant recipients (on cyclosporine, tacrolimus): CMV, EBV-associated PTLD, Aspergillus, Cryptosporidium

• Seen in leukemia, aplastic anemia, post-chemotherapy
• Predisposes to: Pseudomonas aeruginosa, Aspergillus, Candida, viridans streptococci

• Hematological malignancies (leukemia, lymphoma, myeloma) impair cell-mediated immunity, antibody production, complement
• Cryptosporidium, Toxoplasma, Herpes viruses (VZV, HSV), CMV

• Diabetes mellitus (Mucormycosis, recurrent UTIs, Candida)
• Extremes of age (neonates, elderly)
• Splenectomy (encapsulated bacteria: S. pneumoniae, H. influenzae, N. meningitidis)
• Burns/trauma (disruption of skin barrier)

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C. Epstein-Barr Virus (EBV) associated malignancies [5 Marks]

• EBV latent membrane protein 1 (LMP1) acts as constitutively active CD40 receptor, driving B-cell proliferation
• EBNA-2 transactivates cellular oncogenes (c-myc via LMP1)
• EBV encodes viral miRNAs that inhibit apoptosis
• In Burkitt lymphoma: c-myc chromosomal translocation t(8;14) provides the additional oncogenic hit

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D. Role of justice as a guiding principle in patient care [5 Marks]

1. Autonomy, 2. Beneficence, 3. Non-maleficence, 4. Justice

1. Distributive Justice: Allocation of scarce resources (ICU beds, organs for transplant, vaccines) should be based on need and clinical urgency, not on social status, wealth, or ethnicity.
2. Procedural Justice: Decision-making processes must be fair, transparent, and consistently applied. All patients should receive equal consideration under the same standards.
3. Individual vs. Collective Justice: Individual patient rights must sometimes be balanced against community/public health interests (e.g., quarantine for communicable diseases, mandatory reporting of notifiable diseases like TB, gonorrhea).
4. Non-discrimination: Healthcare must not discriminate based on race, gender, socioeconomic status, disability, or HIV status.
5. Access to Care: Healthcare providers have an obligation to work toward equitable access to essential medicines and services.

• Treating a patient with HIV/AIDS without stigma or denial of standard care
• Fair triage protocols in emergencies (most urgent need first)
• Reporting notifiable infections (justice to the community)

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E. Two important key features of biological agents used as biological weapons [5 Marks]

• The agent must be capable of infecting humans with a very low infectious dose
• Ideally transmissible via aerosol (inhalation route), which allows widespread dissemination
• Person-to-person transmission (e.g., pneumonic plague - Yersinia pestis, smallpox - Variola virus) greatly amplifies impact
• Example: Anthrax spores (Bacillus anthracis) are highly stable as aerosols and require very few spores for inhalation anthrax (which has 80%+ mortality if untreated)

• Must cause severe disease with high case fatality rate even with medical intervention
• Should have the potential to overwhelm healthcare systems and cause mass panic/social disruption
• Agents that produce toxins (e.g., botulinum toxin - Clostridium botulinum; the most potent known toxin) or cause disfiguring/frightening disease (smallpox) have psychological as well as physical impact
• Stability in the environment: The agent should resist degradation (e.g., anthrax spores survive for decades in soil)
• Lack of widely available vaccine or treatment at time of attack maximizes casualties

• Bacillus anthracis (Anthrax)
• Yersinia pestis (Plague)
• Variola major (Smallpox)
• Francisella tularensis (Tularemia)
• Botulinum toxin (Clostridium botulinum)
• Viral hemorrhagic fever viruses (Ebola, Marburg)

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