Viral infections

How viruses are classified

• DNA viruses (mostly double-stranded, replicate in the nucleus): herpesviruses, adenovirus, papillomavirus, polyomavirus, hepadnavirus (HBV, partly double-stranded; it copies itself through an RNA intermediate but is still a DNA virus), parvovirus (single-stranded, smallest) and poxvirus (largest; replicates in the cytoplasm).
• RNA viruses (mostly single-stranded, replicate in the cytoplasm): picornaviruses (polio, coxsackie, hepatitis A, rhinovirus), flaviviruses (dengue, hepatitis C, yellow fever), orthomyxovirus (influenza), paramyxoviruses (measles, mumps, RSV, parainfluenza), togavirus (rubella), rhabdovirus (rabies), retroviruses (HIV, HTLV-1), reovirus (rotavirus, double-stranded), coronaviruses, hepatitis E.
• Enveloped viruses are killed by detergents, drying and bile. Non-enveloped viruses (enteroviruses, hepatitis A and E, rotavirus, norovirus, adenovirus) survive the gut and the environment, so they spread faecal–orally.
• Prions (Creutzfeldt–Jakob disease) are misfolded proteins with no nucleic acid. They resist ordinary autoclaving, so instruments used on brain, spinal cord or posterior eye of a suspected case are discarded or given extended high-temperature cycles with sodium hydroxide.

Oncogenic viruses

• HPV protein E6 degrades p53 and E7 inactivates Rb, removing two brakes on the cell cycle. Infected squamous cells on a smear are koilocytes: a clear perinuclear halo around an enlarged, wrinkled (raisin-like) nucleus. The HPV vaccine is given to adolescents before sexual debut mainly to prevent cervical cancer.
• Burkitt lymphoma (endemic form: jaw mass in an African child, EBV-linked) shows a starry-sky pattern and the t(8;14) translocation that drives MYC.

HIV

• Retrovirus (lentivirus) with two copies of single-stranded RNA. It is an RNA virus, not a "DNA retrovirus". Reverse transcriptase makes DNA, integrase inserts it into the host genome and protease cuts viral proteins into mature form.
• Entry: gp120 binds CD4, then co-receptor CCR5 (early, macrophage-tropic) or CXCR4 (later, T-cell-tropic); gp41 fuses the membranes. CCR5-Δ32 homozygotes resist infection.
• Transmission: sexual (commonest), blood and needles, mother to child (pregnancy, delivery, breastfeeding).
• Course: seroconversion illness at 2–4 weeks, then years of clinical latency (one of the longest incubation periods of any infection) while CD4 cells fall. AIDS is a CD4 count below 200 cells/µL or an AIDS-defining illness.
• Tests: fourth-generation antibody plus p24 antigen immunoassay for screening, confirmed by a second, different assay (Western blot was the classic confirmatory test). Viral load is measured by reverse transcription PCR, because the RNA must first be copied into DNA. Infants of positive mothers need PCR, since maternal IgG persists for up to 18 months.
• Treatment: start combination ART as soon as possible after diagnosis (same day if ready), for life; a common first line is two NRTIs (tenofovir with lamivudine or emtricitabine) plus dolutegravir. Other classes: NNRTIs (efavirenz, nevirapine), boosted protease inhibitors, maraviroc (blocks CCR5).
• Mother-to-child prevention: ART for the mother throughout pregnancy and breastfeeding, and prophylaxis for the baby (zidovudine or nevirapine). Zidovudine was the first drug proven to cut vertical transmission.
• Post-exposure prophylaxis after a needlestick from a viraemic source: start as soon as possible, ideally within hours and no later than 72 hours, and continue for 28 days. First aid: let the wound bleed, wash with soap and water, do not scrub or suck.

Opportunistic infections by CD4 count

• Oesophageal candida (painful swallowing, white plaques, budding yeast and pseudohyphae) signals T-cell immunosuppression. AIDS cancers: Kaposi sarcoma, non-Hodgkin and primary CNS lymphoma (EBV), invasive cervical cancer.

Rabies

• Rhabdovirus: bullet-shaped, enveloped, single-stranded RNA. Spread by the bite, scratch or lick on broken skin of an infected animal; in Pakistan mostly dogs.
• It multiplies in muscle at the bite, enters nerve endings and climbs to the CNS by retrograde axonal transport, not the blood, then travels out to the salivary glands. Incubation is usually 1–3 months; bites on the face, head and hands are shorter (nearer the brain, richly innervated).
• Furious rabies: agitation, hydrophobia (painful throat spasm at the sight of water), aerophobia, hypersalivation. Paralytic rabies: ascending flaccid paralysis.
• Pathology: encephalitis with Negri bodies (eosinophilic cytoplasmic inclusions), especially in the hippocampus and Purkinje cells. Once symptoms begin it is almost always fatal, so prevention is everything.
• Post-exposure prophylaxis: wash the wound with soap and running water for about 15 minutes, apply antiseptic, delay suturing; give cell-culture rabies vaccine; for category III exposure (bites or scratches breaking the skin, licks on broken skin or mucosa, any bat contact) also infiltrate rabies immunoglobulin into and around the wound.
• Why both? The vaccine needs 7–14 days to make antibody (active immunity). Immunoglobulin is ready-made antibody (passive immunity) that neutralises virus at the wound at once and needs no helper T cells; it bridges the gap. It is not given more than 7 days after the first vaccine dose.

Herpesviruses: where they hide and what they cause

• Herpes cells on a Tzanck smear are multinucleated giant cells with intranuclear inclusions. Aciclovir is activated by viral thymidine kinase, so it works only in infected cells.
• HSV encephalitis: fever, confusion, focal seizures, temporal lobe oedema and haemorrhage on MRI, lymphocytes and red cells in CSF. Start IV aciclovir immediately, before results.
• HSV keratitis: topical aciclovir or ganciclovir gel; never steroid drops until herpes is excluded.
• Herpetic whitlow (painful vesicles on a fingertip of a dental or medical worker): oral aciclovir, and do not incise, which spreads the virus and achieves nothing. Gloves prevent it.
• Shingles: oral valaciclovir (or aciclovir) within 72 hours of the rash in older adults speeds healing and reduces pain. Ophthalmic zoster with vesicles on the tip of the nose (Hutchinson sign, nasociliary nerve) predicts eye involvement and needs urgent eye review.

Influenza and other respiratory viruses

• Orthomyxovirus: enveloped, segmented RNA (8 segments) with haemagglutinin (binds sialic acid) and neuraminidase (releases new virions).
• Antigenic drift: point mutations in H and N cause seasonal epidemics, so the vaccine changes every year. Antigenic shift: reassortment of whole segments between human and animal strains creates a new subtype and a pandemic; only influenza A shifts. H1N1 (swine flu) is a subtype of influenza A.
• Secondary bacterial pneumonia, classically Staphylococcus aureus (cavitating), follows because the virus destroys ciliated epithelium and the mucociliary escalator. Aspirin in children risks Reye's syndrome.
• Drugs: oseltamivir or zanamivir (neuraminidase inhibitors, best within 48 hours). Amantadine blocked the M2 ion channel and so uncoating; it acts on influenza A only and is now abandoned for resistance. Prevention: annual inactivated vaccine for the elderly, pregnant women, health workers and chronic disease.
• RSV causes bronchiolitis in infants (coryza, then wheeze, crackles, poor feeding): treatment is supportive (oxygen, feeding support); bronchodilators, steroids and antibiotics do not help. Parainfluenza causes croup (barking cough, stridor). Stridor with toxicity and drooling in an unvaccinated child suggests epiglottitis from *Haemophilus influenzae* type b.

Measles, mumps, rubella and dengue

• Measles: Koplik spots, cough, coryza, conjunctivitis; pneumonia, encephalitis and late SSPE. Vitamin A reduces complications and deaths, because measles depletes it and deficiency damages epithelium and immunity.
• Mumps: parotitis; after puberty the commonest complication is orchitis (subfertility, rarely sterility). A raised amylase may come from the salivary glands rather than pancreatitis.
• Rubella: maternal infection in the first trimester carries a high risk of congenital rubella (sensorineural deafness, the commonest single feature; cataract; patent ductus arteriosus). The baby is confirmed by rubella IgM, because only IgG crosses the placenta. Early confirmed infection needs counselling about the high fetal risk and the option of termination; MMR is a live vaccine and is never given in pregnancy.
• Dengue (flavivirus, *Aedes* mosquito, monsoon): fever, severe myalgia, retro-orbital pain. The critical phase comes around day 3–7 as the fever settles: plasma leakage with rising haematocrit (20% or more), falling platelets, abdominal pain, cold extremities and restlessness. Give careful IV fluids, then reduce them in recovery to avoid pulmonary oedema. No routine platelet transfusion without significant bleeding, however low the count; avoid NSAIDs and IM injections.
• Orf (parapoxvirus) from sheep and goats, common after Eid-ul-Adha: a red-violet weeping finger nodule that heals by itself in about six weeks; do not excise.

Hepatitis viruses and HBV serology

• Hepatitis A and E spread faecal–orally (school or water-borne outbreaks) and do not become chronic; acute hepatitis A is confirmed by IgM anti-HAV. Hepatitis E in the third trimester can cause fulminant hepatic failure. HBV, HCV and HDV are blood-borne; HCV becomes chronic most often.

• HDV is defective and needs HBsAg. Co-infection with HBV usually clears; superinfection of a chronic carrier causes severe acute hepatitis (anti-HDV IgM) and often chronic disease.

Chlamydial and fungal infections in surgical practice

• *Chlamydia trachomatis*: obligate intracellular; the infectious elementary body enters the cell and becomes a replicating reticulate body. It cannot grow on agar, so diagnosis is by NAAT. It is the commonest cause of non-gonococcal urethritis (pus cells but no organisms on Gram stain) and of silent PID causing tubal infertility. Fitz-Hugh–Curtis syndrome is perihepatitis with "violin-string" adhesions and usually normal liver tests. Serovars L1–L3 cause lymphogranuloma venereum (groove sign); aspirate fluctuant buboes, do not incise.

• *Candida*: oesophagitis in immunosuppression; the commonest fungal infection in burns and after long broad-spectrum antibiotics. Candidaemia is never a contaminant: give an echinocandin (caspofungin, micafungin) and remove the central line. *Candida auris* resists fluconazole, is misidentified by routine tests, persists on surfaces and spreads in ICUs.
• *Aspergillus*: aspergilloma (fungal ball) in an old TB cavity with an air crescent and haemoptysis; otomycosis with white debris and black specks (*A. niger*); stop antibiotic drops, clean and use topical antifungal.
• Mucormycosis in diabetic ketoacidosis: black nasal eschar, proptosis; broad, ribbon-like, non-septate hyphae branching at right angles (*Aspergillus* has narrow septate hyphae at acute angles). Treat with urgent debridement plus liposomal amphotericin; voriconazole is ineffective.
• Mycetoma in barefoot farmers: black grains mean fungal eumycetoma (itraconazole for months, then wide excision); pale grains with fine filaments mean actinomycetoma (antibiotics).
• *Histoplasma*: bird or bat droppings; small yeasts inside macrophages. Kerion: boggy inflammatory tinea capitis; treat with oral antifungal, never incise. Toe-web tinea is the portal for recurrent leg cellulitis and must be treated.
• Azoles inhibit lanosterol 14α-demethylase, blocking ergosterol synthesis; they also inhibit human cytochrome P450, raising the INR on warfarin and tacrolimus levels.

Remember Rabies climbs nerves, herpes hides in ganglia, HIV hides in the genome, and influenza A swaps segments.

Exam trap Rabies reaches the CNS by retrograde axonal transport; immunoglobulin is added because the vaccine takes 1–2 weeks to work.

Exam trap Dengue becomes dangerous as the fever falls; a low platelet count alone is not an indication for transfusion.

How FCPS asks about this

• HIV entry and viral load: gp120 binds CD4 with CCR5 or CXCR4; viral load by reverse transcription PCR; infants tested by PCR, not antibody.
• HIV needlestick: PEP as soon as possible, within 72 hours, for 28 days; PCP below CD4 200 is prevented with co-trimoxazole.
• Latency sites: HSV-1 trigeminal ganglion, VZV sensory ganglia, EBV B cells; Hutchinson sign predicts eye involvement.
• Rabies: Negri bodies in hippocampus and Purkinje cells; wash, vaccine and immunoglobulin for category III bites.
• Influenza: shift (influenza A only) causes pandemics; amantadine blocks M2 uncoating; post-flu *S. aureus* pneumonia.
• Oncogenic viruses: HPV 16/18 cervical and penile cancer, HPV 6/11 warts and laryngeal papillomas; HTLV-1 and HCV are the RNA ones.
• Congenital infections: CMV commonest (deafness, owl's-eye inclusions); rubella confirmed by IgM, deafness and PDA.