Virology

• Animal Inoculation into suckling mice brains

Inclusion bodies

Intracytoplasmic Inclusion Bodies:

• Henderson Patterson bodies.
• Positive for: Phloxine tartrate stain.
• Molluscum contagiosum
• Present with: Umbilicated lesions.
• When pressed: Curdy material is extruded.
• Microscopy: Cup-shaped structure.

• Halberstadter Prowazeki bodies:
• Trachoma
• Mnemonic: Trackil odan Horse Power venam

• Levinthal Cole Lillie body:
• C. Psittaci
• Mnemonic: Levinthikkole Lillye sit aaki

• Negri Body:
• Intracytoplasmic eosinophilic inclusion body
• Seen in: Rabies.
• Sellers stain
• Seen after death
• First site: AMMON horn of hippocampus
• Rabies - Hippoptamus
• Sell (Sellers) Nigro (Negri)
• Second site: Cerebellum

Intranuclear Inclusion Bodies:

• Cowdry type A
• Seen in:
• Yellow fever: Torres bodies.
• Herpes Simplex: Lipschultz.
• Mnemonic: Tore Yellow shirt → Kiss Her Lips

• Cowdry type B
• Seen in:
• Adenovirus.
• Poliovirus.
• Mnemonic: Adipoli breast

Both intracytoplasmic + intranuclear forms:

• CMV (Cytomegalovirus)
• Shows: Owl eye appearance.

• Measles
• Shows: Warthin Finkeldey giant cells.
• large grapelike clusters

• Ulcer Characteristics:
• Multiple, painful.
• Vesicles and coalescing erosions (ulcers not typical).

• Incubation: Short (2-7 days)

• Episodes:
• Primary: More painful, severe.
• Recurrent: Less painful, severe, intense.

• Latent in dorsal root ganglion

• Lymphadenopathy: Bilateral painful.

Herpetic Keratitis

• Treatment:
• 3% Acyclovir eye ointment (not drops)
• Steroids are contraindicated.
• Eye drops 1st → Ointment 15 mins later.
• If ointment is applied first:
• It creates a barrier.
• Prevents absorption of the eye drop.

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NOTE

Similar terms	Seen in
Dendritic ulcer	HSV 1 Corneal ulcer
Pseudodendrites	Acanthameba
Pseudodendritic ulcer	Varicella Zoster

Diagnosis of Herpetic Infections:

EEG

• Periodic lateralized epileptiform discharge (PLED)
• Seen in HSV encephalitis
• Mnemonic: His wife → Period late → she seizures

Lab Diagnosis

• Tzanck smear → Lipschultz bodies

• Skin scrapings can be used

• Geimsa staining
• Cytopathic effect = 3M
• Multinucleated
• Molding
• Margination

• Mc coy culture

Tzanck Smear:

• Mnemonic: HSV → His Wife → Has Giant boobs (Multinucleated giant cell) and good lips (Lipschultz) → She wears tank top (Tzank) → She goes to Gym too (Giemsa stain). She becomes a target for others (Target lesions → erythema multiforme)

• For cytology

• Unroof vesicle/bulla or scrape erosion base

• Stain with Giemsa stain

• See: Large multinucleated giant cell (feature of HSV infection)

• Also some acantholytic cells

Gold Standard:

• PCR (differentiates HSV 1 & 2).

Treatment of HSV Infection:

• Treatment available: 
• Acyclovir
• Valacyclovir
• Famciclovir

• Primary infection:

Antiviral	Dosage	Duration	Total/day
Acyclovir	200 mg x five times a day OR 400 mg 3 times/day.	7 to 10 days	1g
Valacyclovir	1 g x twice times a day	7 to 10 days	2g

• Recurrent infection:

Antiviral	Dosage	Duration	Total/day
Acyclovir	400 mg x three times a day	5 days	1.2 g
Valacyclovir	1 g x twice times a day	5 days	3 g

• If > 6 recurrences/year: 
• suppressive treatment (daily)

• If Acyclovir resistant:
• Use Foscarnet and Cidofovir

Hutchinson's

• H → Herpes Zoster Ophthalmicus

• U → subUngual Melanoma (superficial spreading melanoma)
• Hutchinson sign

• T → Triad → congenital syphillis
• Peg shaped teeth
• Interstitial Keratitis (IK + SNHL)
• SNHL

• CH → Chauffeur's Fracture/Backfire Fracture
• Intra articular #

• Son → looking older → Hutchison Gilford
• LMN A gene defect (laminopathy).
• Progeria (onset: Child)

• PUPIL → Hutchinson Pupil
• Herniation of uncus (medial temporal lobe) → compresses ipsilateral CN III → same side pupillary dilatation.
• Kernohan’s notch phenomenon:
• False localizing sign
• Ipsilateral pupil dilatation
• Ipsilateral UMN palsy

• CSF: Monocytes, clefted nuclei (Mollaret cells).

• Variant of aseptic meningitis.

• Virus: HSV-2.
• Causes recurrent aseptic meningitis.

Leading viral encephalitis

• India: Japanese B.

• worldwide: Herpes simplex.

Varicella / Chickenpox:

Smallpox Rash	Chickenpox Rash
Deep seated	Superficial
No area of inflammation around the rash	Area of inflammation around rash
Centrifugal	Centripetal
Palms & Soles not spared	Palms & Soles Spared

Herpes zoster oticus / Ramsay hunt syndrome

• Involves reactivation of herpes zoster virus.

• Virus remains latent in
• Geniculate ganglion, CN 7

• Presents with
• Vesicles in facial nerve distribution (EAM)
• LMN type of facial palsy.
• SNHL due to 8th nerve involvement.
• Otalgia
• Loss of taste in anterior 2/3 tongue

Treatment:

• Antiviral therapy: Acyclovir, Valacyclovir.

• Topical agents and lotions for vesicles.

• Steroids (+/-).

Bell’s palsy

• Idiopathic facial nerve palsy.

• Seen in pregnancy, diabetics.

• Associated with EBV and HSV.

• Clinical features:
• Deviation of angle of mouth.
• Loss of nasolabial fold.
• Sagging of eyebrow.
• Hyperacusis

• If in trigeminal root ganglion

• Hutchinson's Sign: 
• Vesicles along ala of nose
• Means nasociliary nerve involved 
• (branch of ophthalmic division of trigeminal nerve)
• Patient will have ophthalmic manifestations
• ophthalmology referral needed

Treatment of Herpes Zoster:

• Most painful, so highest dose of antivirals

Antiviral	Dosage	Duration	Total/day
Acyclovir	800 mg x five times a day	7 to 10 days	4g
Valacyclovir	1g x three times a day	7 to 10 days	3g

• Need painkillers, B12, etc.

Post-Herpetic Neuralgia (PHN):

• If neural manifestations persist after Herpes Zoster
• Skin subsides, but pain persists

• Duration:
• After one to three months (variable definitions)

• Symptoms: 
• Persistent pain, paraesthesias, tingling, heaviness

• Treatment: 
• Tricylic Antedepressants >>
• Pregabalin or Gabapentin

Hutchinson's

• H → Herpes Zoster Ophthalmicus

• U → subUngual Melanoma (superficial spreading melanoma)
• Hutchinson sign

• T → Triad → congenital syphillis
• Peg shaped teeth
• Interstitial Keratitis (IK + SNHL)
• SNHL

• CH → Chauffeur's Fracture/Backfire Fracture
• Intra articular #

• Son → looking older → Hutchison Gilford
• LMN A gene defect (laminopathy).
• Progeria (onset: Child)

• PUPIL → Hutchinson Pupil
• Herniation of uncus (medial temporal lobe) → compresses ipsilateral CN III → same side pupillary dilatation.
• Kernohan’s notch phenomenon:
• False localizing sign
• Ipsilateral pupil dilatation
• Ipsilateral UMN palsy

 

• Primary disease: Infectious Mononucleosis
• Also called Glandular Fever or Kissing Disease

• Ballerina () + Paul
• Ballerina
• Naughty → NAHT
• says 21 (CD21) yr → actually 18 (8 T cell)
• Kissed → EBV
• Down there → Downey, Duncan
• Hairy → Hairy cell leukemia
• then abdomen (Gastric cancer > Nasopha)
• then neck (Nasopha)

Pathogenesis

• Polyclonal B cell activation

• Entry: via CD21/Cr2 receptor

• Molecules:
• LMP 1
• EBNA 2 (activates SRC proto-oncogenes)
• vIL10 (anti-inflammatory)

Skin manifestation:

• Patients present with fever, lymphadenopathy, sore throat
• misdiagnosed as bacterial
• Given antibiotics (usually Amoxicillin or Ampicillin)

• Develop an exanthem on body called Ampicillin rash

• Mnemonic: Kiss cheythapo hairl ayipoi

Malignancies

• Carcinomas:
• M/c: Gastric carcinoma
• Nasopharyngeal carcinoma

• Lymphomas:
• Hodgkin’s (mixed cellularity)
• Non-Hodgkin: Burkitt’s, DLBCL, Post-transplant lymphoma

• Sarcomas: Leiomyosarcoma

Other conditions

• Duncan Syndrome (lymphoproliferative syndrome)

• Hairy cell / Oral leukoplakia

Lab Diagnosis

• Microscopy:
• Atypical lymphocytes (Downey cells)
• = CD8 T lymphocytes (Cytotoxic T cells)
• "Ballerina skirt appearance"

• Heterophile antibody detection:
• Paul Bunnell Test (older)
• Monospot Test (newer)

• Specific Antibody Tests:
• Viral capsid antigen
• Early antigen
• EBNA

• Most sensitive & specific:
• Nucleic Acid Hybridisation Test

Treatment

• Acyclovir

• Rituximab

• Largest of Herpesviridae

• SRK (salivary, resp, kidney) → Largest → lives in mannat (Monocytes) → big muscle fibre (human fibroblast culture)

• Reservoir: Humans only

• Transmission:
• Common: oral, respiratory, body secretions
• Less common: transplacental, sexual

• Multiplication sites (mnemonic SRK in Mannat):
• Salivary gland
• Respiratory tract
• Kidney

• Latent in: Monocytes

• M/c infection during 1st 4 months of organ transplant

Infections

Features`

• 1st CMV infection — 30%.

• 2nd CMV infection — 1-2% (Developing countries like India).

• Congenital CMV
• 90% of → asymptomatic
• No use of routine screening.
• Most important long-term sequelae in SYMPTOMATIC CMV
• Sensorineural hearing loss.
• Most common non syndromic causes of hearing loss.

Clinical features in Congenital CMV

• Microcephaly
• < 3 SD of HC

• Chorioretinitis.

• Hepatosplenomegaly.

• Jaundice.

• Petechiae.

• Periventricular calcifications.

• Most common cause of vision loss in ocular HIV.

• Mnemonic:
• CMV → Come we have Pizza, scrambled egg and ketch up,
• So brush and come

Features:

• "Pizza pie" appearance.

• "Scrambled egg and ketchup" appearance.

• "Brushfire extension" pattern.

• Causes focal chorioretinitis.

Diagnosis

• Congenital CMV
• Demonstrate replicating virus within the first 3 weeks.
• PCR/Viral culture:
• Best sample - urine sample.
• It can be done using saliva or blood sample.
• CMV IgM:
• ELISA
• Cannot demonstrate replicating virus

• Owl eye inclusion bodies (intra-cytoplasmic + intra-nuclear)

• Virus isolation:
• human fibroblast cell lines (secondary)
• specimen = urine washing

• Detection: PP65 antigen

• PCR

NCCT

Treatment for symptomatic patients

• DOC: Ganciclovir
• Resistance d/t U97 phosphotransferase gene

• Resistance: Foscarnet

• Note:
• UL 57 (DNA Polymerase) causes resistance to Ganciclovir, Foscarnet and cidofovir

1. Kaposi Sarcoma (vascular tumor)

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• Association: Seen in HIV-positive individuals
• Gamma virus
• Most Common Sites:
• First: 
• Seen on legs
• Presents with deep red to bluish papules and nodules
• Second: Lymph node.
• M/c lid malignancy in HIV
• Microscopy:
• Shows spindle cells.
• IHC (Immunohistochemistry): 
• LANA (latency associated nucleic acid) positive.
• Kakkusil pokumbo sing LALA (LANA) and SPIN (Spindle)

2. Primary Effusion Lymphoma
• Effusions (pleural, pericardial)
• CD30 & CD38 +ve

3. CASTLEMAN Disease
• Site: lymph nodes
• Symptoms: B cell symptoms (fever, night sweats, weight loss)
• Histology:
• "Onion skinning of lymphocytes"
• "Lollipop follicles"

A. Angiolymphoma
B. Hodgkin’s lymphoma
C. IgG-4 related disease
D. Castleman disease

ANS

Castleman disease

 

Kaposi Sarcoma

• Cause: Human Herpes Virus 8 (HHV-8).

Note: Causes of AFP

• Poliomyelitis

• Guillain-Barré syndrome

• Traumatic neuritis

• Traumatic myelitis

• Enterovirus A71

• JC () saved 40 () people from Bad Kidney Virus () → Marakkallee (Merkel cell virus)

• Type: Epitheliotrophic.

• Causes warts or verruca

• HPV has 200 subtypes

Histology: 

• Koilocytosis with biopsy indicates CIN 1.

• (Koilocyte is pathognomic for SCC insitu)

Cutaneous involvement:

• HPV 1, 2, 3 → low-risk skin warts
• D: Deep Plantar (HPV 1)
• S: Superficial Plantar (HPV 2)
• P: Plain Warts (HPV 3, 10)

• HPV 5, 8 → high-risk skin warts
• Epidermodysplasia Verruciformis / Tree man syndrome
• chr. 17 defect
• 58 year old tree man with 17 year old girl

• Buschke's Warts

Mucosal involvement:

• HPV 6, 11 → low-risk → mucosal & genital warts (Condyloma Acuminatum)
• Leads to:
• Laryngeal papillomas.
• Genital warts
• Pregnancy → DOC → Trichloracetic Acid
• Mnemonic:
• Pregnant avumbo war (wart) vanna → Ace the war (Trichloroacetic acid)
• 6 ⇔ G (genital warts) ;
• 11 (LL ⇔ Laryngeal papiLLomas)

• HPV 16, 18, 31, 33, 45, 52, 58 → high-risk
• 1618.3133.4552.58
• Cancers caused by HPV:
• Male - penile, oral, anal
• Female - cervix, vagina, vulva
• Cervical cancer
• Most common serotype - HPV 16
• Most malignant serotype - HPV 18
• Most specific serotype - HPV 18
• Most common serotype associated with
• Cervical Squamous cell carcinoma - HPV 16
• Cervical Adenocarcinoma - HPV 18
• Anal cancer
• HPV16
• Oropharyngeal cancer
• HPV16
• Genital cancers / Penile, vulvar, vaginal cancers
• HPV16

 

Structure & Function:

HPV Vaccines

1. Nonavalent (Gardasil 9, in USA):
• Active against HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58.
• Protects against Genital Warts and all Cervical/Anal/Vulvar/Vaginal Cancer (HPV).

2. Quadrivalent (Gardasil/Cervavac):
• Active against HPV types 6, 11, 16, 18.
• Protects against Genital Warts and Cervical Cancer.
• Mnemonic: 4 vaakku parayamo

Cervavac

• India's first vaccine against cervical cancer.
• Developed by Serum Institute of India, Pune.

3. Bivalent (Cervarix):
• Active against HPV types 16, 18.
• Protects against Cervical Cancer.
• Mnemonic: 2 vari padamo



 

Recent update

• Prevent head & neck & Oropharyngeal cancer by HPV

PYQS for HPV Vaccine

• Ideal Age: 11-12 years.

• Age Group (Good): 9-26 years.
• Cervavac can be given only till 26 yrs due to lack of testing

• High Risk Age: 27-45 years.

• C/I: Pregnancy.

• WHO SAGE Recommendation:
• 9 to 20 years old: 1 or 2 doses.
• Over 21 years old: 2 doses.
• HIV positive: 3 doses.

• Common Side Effect: Syncope.

• Vaccines made from: L1 capsid proteins.

HPV Vaccine can be given to:

• HIV Positive Females.

• HIV Positive Males.

• Sexually active females.

• Boys.

• HPV testing before vaccine: Not recommended.

Koilocytes

• Modified keratinocytes

• Have a pyknotic nucleus

• Around nucleus, a clear space (perinuclear halo)

• Features of HPV or Verruca

• Kozhitharam (koilocytes) arnn → HPV vannu → Now no one around him (peri nuclear halo)

• Ellarum veruthu (verucc) →

• Both →
• Plane face (verucca plana → on face) → Black colored (Hyperpigmeted)
• Vulgar body (verucca vulgaris → anywhere in body) → ↑↑↑ skin thickness in body

Inverted Papilloma

• Benign, pre-malignant condition.

• M/c site Middle Meatus

• Arise from pseudostratified columnar epithelium (Schneiderian membrane)

• A/w Human Papilloma virus (HPV).

• Also called:
• Transitional cell papilloma.
• Ringertz tumor.
• Schneiderian papilloma.

• Locally invasive.

• Premalignant
• Associated with malignancy in 5 - 10%.

Clinical features:

• Blood stains in nasal discharge.

• Nasal obstruction.

• Projections from lateral wall of nose.

Histopathology:

• Finger-like projections grow towards stroma.

Treatment:

• Medial Maxillectomy
• via lateral rhinotomy / midfacial degloving approach
• Endoscopic > External approach
• Remove:
• Lateral wall of nose
• Medial wall of maxilla

• Recurrent:
• Cidofovir

• Avoid radiotherapy ⇒ turns malignant

CT Scan