Virology 2

• Serotypes causing epidemics: A and B

• Structure
• Outer proteins:
• Hemagglutinin (HA)
• → virus entry
• Neuraminidase (NA)
• → virus exit/release
• Destroys the cell receptors by hydrolytic cleavage
• M2 ion channel
• assists in virion uncoating inside host cell

Antigenic Variations

• Clinical Features
• Fever, headache, sore throat, cough, myalgia
• Running nose usually absent
• M/c complication → pneumonia

• Laboratory Diagnosis
• Specimen: Nasopharyngeal swab
• Hemagglutination inhibition test (HAI) → positive

Treatment

Case scenario

• An 18-month-old unimmunised girl had fever with rash (as shown in the given picture), cough and coryza.

• There is a history of similar complaints in 2 other children in the neighbourhood.

• The doctor also noticed few red spots with white central parts in the buccal cavity of this child.

• Which vitamin has a role in the management of this child?
ANS
Measles = Vitamin A deficiency

Buzzword: C’s

• Cough → Coryza → Koplik spots → Confluent rash = Measles
• K K sound

Incubation period

• 8-10 days.

• Infective:
• 4 days before to
• 5 days after the onset of rash

• Isolation
• Duration: 7 days after rash onset

• Disease progression:
• day 10 → Fever
• day 12 → Koplik spots near molars
• day 14 → Rash appears
• Starts behind ear/face/neck
• Other symptoms resolve after rash onset

Receptor for measles virus

• CD150 and PVRL4.

Pathognomonic feature

• Presence of multinucleated Warthin Finkeldey giant cells
• Intranuclear + intracytoplasmic inclusion

Measles Rash:

• Confluent maculopapular rash

• Retroauricular in origin

Koplik spot:

• Reddish spots with white centre

• Appears prior to the rash

• Occurs before 48 hours of eruption

• Formed on the buccal mucosa opposite the lower 2nd molar

Measles vaccine

• Strains used:
1. Edmonston Zagreb strain
• most common
2. Schwartz strain.
3. Moraten strain.

Measles vaccination during an outbreak:

• Post exposure Prophylaxis
• Susceptible Contacts with exposure
• Vaccine → within 72 hours of exposure
• Immunoglobulin (IVIG) → upto 6 days following exposure.

Indication	Prophylaxis
>1 yr old/ Immunocompetent/ Non pregnant	Live vaccine:  - Given <72h after exposure  - Effect starts in 11-12 days
<4 yr / Immunocompromised/ Pregnant	Immunoglobulin: • 0.25 ml/kg upto 15 ml • given <3-4 days of exposure  Vaccine only given after 8-10 weeks

• Measles vaccination can be given at 6-9 months age in:
• aka Measles 0 dose (Extra dose).
• During
• Outbreaks
• PEM (Protein-Energy Malnutrition)
• NIS schedule to be continued.
• Gap between NIS & outbreak dosing: >4 weeks.

Vaccine Seroconversion

• Faster than natural incubation

• Antibodies develop in 7–10 days

• NOT CHICKENPOX

WHO Measles Elimination Strategy

• “Catch up, Keep up, Follow up”
• → Again K K sound

Complications:

• Late → SSPE (Subacute Sclerosing Pan Encephalitis)
• Fatal after 7–10 years of infection

Case scenario

• A male child presents to you with swelling below the ear, but no systemic manifestations.

• There have been two other similar cases in the friends of the child in the same village.

• What will you do?

Clinical Features

• 30–40% are subclinical

• Pain and swelling of one or both parotid glands

• Earache on affected side before swelling

• Pain/stiffness in mouth opening before swelling

Features

• Agent:
• RNA virus
• Myxovirus family

• Period of Communicability:
• 4–6 days before rash
• 7 days after rash onset

• Incubation Period (IP):
• 2 – 4 weeks
• very infectious disease

• Mode of Transmission (MOT):
• Droplet

• Symptoms
• M/c → asymptomatic (inapparent)
• M/c symptomatic → bilateral parotitis
• Second M/c → unilateral orchitis

• Secondary Attack Rate (SAR):
• 86%

• Host Factor:
• Age group commonly affected: 5–9 years

• Self-limiting illness and no specific treatment is required.

Complications

• Children:
• Aseptic meningitis

• Adolescents:
• Orchitis (common in males)
• Oophoritis

Vaccine strain

• Jeryl Lynn

• Mild and self-limiting illness that usually improves in 3-5 days.

• Classification: Matonaviridae (previously Togavirus)

Epidemiological & Clinical Features:

• AKA 3 day fever (Very mild illness).

• Mnemonic: Ruby → Threeyy

Age of Incidence:

• Developed countries: 3-10 years.

• Developing countries: >15 years.

Presentation: 

• Shows iceberg phenomenon

• 50-55% cases are subclinical

Incubation period: 

• 2 - 3 weeks.

Period of communicability: 

• 7 days before onset of rash,

• 7 days after.

Prodrome phase

• Low-grade fever, sore throat, malaise, and headache.
• URTI
• Posterior auricular lymphadenopathy (LAP)
• Rash lasting 3 days

• Rash begins on the face and spreads centrifugally - measles-like rash.

• Forsheimer spots on the soft palate and uvula.

Trend of infection: 

• Cyclic (Every 6-9 years).

Prevention:

Routine use:

• Strain: RA 27/3 winstar vaccine.
• Mnemonic: Win star → Vimal → German measles
• Fortunate baby (forchiemer spot)

• Type: Live vaccine.

• Schedule: Single dose after 12 months of age.

• Duration of protection: 14-16 years.

• C/I: Pregnancy.

In outbreaks:

• Strain: RA 27/3.

• Indication:
• Women of reproductive age (Non-pregnant):
• Advice to avoid pregnancy for 6-8 weeks post vaccination.
• Adolescents.
• Infants.

Post Exposure Prophylaxis

• Rubella Immunoglobulin:
• For pregnant females with known exposure to rubella virus.

Rubella Vaccination Strategy

• 1st Priority:
• Women of child-bearing age (15–34 or 15–39 years)
• Prevent Congenital Rubella Syndrome (CRS)

• 2nd Priority:
• All children aged 1–14 years
• Interrupt community transmission

• 3rd Priority:
• Routine immunization of all children under 1 year
• Use combined MR

Initial Presentation

• First wheezing episode in infants.

Epidemiology

• Most common infection in children aged 1–6 months.

• Rare after 2 years of age.

Etiology

• Most common cause: Respiratory Syncytial Virus (RSV).
• Season: Rainy season
• Infants → M/c/c of LRTI
• Adults → causes URTI
• Microscopy: Syncytial (multinuclear) appearance

• Causes inflammation and narrowing of small airways.

Clinical Presentation

• Preceded by respiratory illness in a family member.

• Symptoms:
• Rhinorrhea
• Cough
• Dyspnea
• Sneezing

Radiographic Findings

• Chest X-ray:
• Hyperinflation
• Patchy atelectasis

Treatment Specifics

Oxygenation & Hydration

• Provide oxygen support
• High-flow oxygen via nasal cannula.
• Target SpO₂ > 90%

• Ensure good hydration

Antiviral Therapy in Bronchiolitis

• Nebulized ribavirin:
• Controversial in high-risk cases (Nelson).
• Indicated if co-associated with:
• Congenital heart disease
• Chronic lung disease
• Immune deficiency

Severe Bronchiolitis

• Seen in :
• Premature infants
• Early age of onset
• Presence of comorbidities

Prophylaxis in Bronchiolitis

• I.M. Palivizumab indicated for:
• Act on F protein of RSV
• Children born < 29 weeks gestation
• Significant congenital heart disease
• Chronic lung disease of prematurity
• Immune deficiency
• Neuromuscular disease

 

• Kerala:
• Nipah virus (NiV) 2018 caused outbreak.
• Enveloped Non-segmented RNA Virus
• Paramyxovirus

• Causes encephalitis ± ARDS.

• Route: Human-to-human via secretions.

• Clinical: Encephalitis, fever

• Mortality rate: 60 - 80%

• Infection by:
• Reservoir: Fruit Bat genus → Pteropus.
• primary vector
• Bat urine/saliva/feces contaminates date palm sap
• Contaminated fruit eaten by pig → pig to human/pork exported.
• Pigs = amplifiers
• Virus also in patient secretions

• No treatment exists.

• To diagnose: PCR of CSF for Nipah.

• Causes descending flaccid paralysis

• Phases:
• Alimentary phase
• Lymphatic phase → cervical, mesenteric LN
• Viremic phase → blood
• Neural phase → spinal cord, brain

• 90% infections → asymptomatic/subclinical

Types of Polio Infection & Percentage of All Infections

Carrier Stage

• For 1 infected child
• Approx. 75 adult carriers
• Approx. 1000 child carriers

Clinical features

• Asymmetric involvement

• Most commonly affected muscle: Quadriceps
• Result in Hand knee gait
• D/t Quadriceps weakness

• Most common muscle with complete paralysis: Tibialis anterior

• Most common hand muscle involved: Opponens pollicis

• Neurology
• Pure motor paralysis
• No sensory loss

• Knee deformity (severe cases)
• Triple deformity
• Flexion
• Posterior subluxation
• External rotation

Polio Vaccine strains and adverse effects

OPV vs. IPV

Vaccine-Derived Polio Virus (VDPV) vs.
Vaccine-Associated Paralytic Polio (VAPP)

Timeline in India

Eradication Dates & Locations of Last Cases in India

• 9, 10, 11 → 14, 15, 16

• Note: P1 strain →most epidemics

• Bivalent OPV
• Pink colour liquid stored at -20°C.
• Most heat-sensitive vaccine.

• Animal Inoculation into suckling mice brains

Epidemiology

• Caused by: Lyssa virus (Rhabdoviridae family).



• SSRNA.
• Bullet shaped virus.

• Replication → initial in muscle tissue

• Spread:
• Binds acetylcholine receptors
• Retrograde axonal transport via peripheral nerves
• Reaches dorsal root ganglia → spinal cord → brain (centripetal spread)

• Further spread:
• Centrifugal spread → cornea, salivary glands, other nerves

• Disease progression:
• Axonal spread speed = 3 mm/hr
• Incubation shorter in children, upper limb bites, short stature

Rabies-Free Areas

• States in India:
• Goa
• Andaman & Nicobar Islands
• Lakshadweep Islands

• Countries:
• Australia
• U.K.

Types:

Diagnosis

• Alive Person:
1. Skin biopsy (hair follicles) from nape of neck (Best specimen)
2. Viral antigen detection
• by fluorescent antibody test
• Can also be used for testing dogs

Summary:

Zagreb Regimen

• 4 doses multisite regimen
• Day 0: 2 doses
• One in right deltoid
• One in left deltoid
• Day 7: 1 dose
• Day 21: 1 dose

Rabies Immunoglobulin

• Indication: <7 days of animal bite.

• Dose:
• Equine RIG: 40 IU/Kg.
• Human RIG: 20 IU/Kg.

• Route: 
• maximum infiltrated in/around the wound.
• Remaining given IM at nearest site.

• Not given for re-exposure (Given only once a lifetime).

What is the diagnosis for a 40-year-old woman who experienced fever and joint pain, and subsequently developed a lesion on her nose a few days after taking NSAIDs?

A. Dengue
B. Chikungunya
C. Melasma
D. Fixed drug eruption

ANS

• Chikungunya → Chik sign
• Post-Recovery Sign
• Clinical Features: Fever, migratory arthritis.

• Type: Viral zoonotic disease

Endemic Areas:

• 350 districts
• Uttar Pradesh, Bihar, West Bengal
• North-eastern states (NES)
• South India

• Hosts:
• Ardeid Birds: Maintenance host
• Cow, Cattle, Humans:
• Dead end host
• Pig: Amplifying host

Vectors in India:

• Vector: Culex mosquito

• Global: Culex tritaeniorhynchus (world)

• India: Culex Vishnui (INDIA)

Clinical Features:

• Encephalitis (high grade fever, neurological changes, convulsions)

• Peak age: Children/young adults

• Mnemonic: Japanil Cute (culex) girl with Coca (Kokku → ardeid bird) Cola (Kolar vaccine ) kand oru Pig () vannnu → sex cheyyan (pig - amplify) shremich → freezeril (freeze sensitive) puuti itt → Kill ayi (killed vaccine)

• Important Note:
• Nagayama spots → seen in HHV-6 (sixth disease), not JE

Management:

• Diagnosis: RT-PCR

• Treatment: Symptomatic

• Vaccine, vector control, acute encephalitis surveillance

Vaccines Types

• Live: (S/c)
• SA-14-14-2 strain
• (Earlier used in India)

• Inactivated:
• Nakayama and Beijing P1 strains

• Killed (IM)
• JEEV (SA-14-14-2 strain)
• JENVAC (Kollar strain)

Update 2023: JENVAC

• Killed Kolar Strain (Approved for use in immunization schedule)

• 2 doses: 9 months, 16-24 months

• Route: IM

• Dose: 0.5 mL

• Site: Left thigh

• Unimmunized Child: Immunized till 15 years

• Under open vial policy because not using live vaccine

JE Live Vaccine vs JE Killed Vaccine:

• Note: Adult JE vaccines given in high burden areas.

• Live vaccine is difficult
• Reconstitute
• Put in freezer
• No open vial policy

• Vector: Aedes mosquito

• Seen in household water collection

• Serotypes:
• 4 types (DEN 1-4)
• DEN-2 = most dangerous (M/c)
• DEN-5 found in Bangkok (2013)

• WHO approved vaccines
• Dengvaxia
• Age: 9 - 16 years
• Dose: 3 doses, 6 months apart
• Prerequisite: Must be seropositive
• (Avoid in seronegative as it causes severe primary infection)
• TV003
• Age: 2 - 59
• Live attenuated
• For Seronegative / Seropositive
• Protect against all 4 dengue viruses

Clinical Features:

• ↓↓ platelet count (may need transfusion)

• Haemoconcentration (↑ haematocrit from plasma loss)

• AST/ALT >1000: Danger sign

Danger signs

• Lethargy

• ↑↑ hematocrit with Rapid ↓ Platelet count

• Abdominal pain, tenderness

• Vomiting - persistent

• Fluid accumulation: Ascites, pleural effusion

• Mucosal bleed

• Hepatomegaly >2 cm

Dengue Fever (Bone Break Fever):

• Bimodal fever:
• 2 peaks
• 1st: 2-3 days
• 2nd: 5-7 days

• Retroorbital pain: Characteristic

• Arthralgia, myalgia

Dengue Hemorrhagic Fever:

• Rise in hematocrit rise > 20% of baseline

• Platelets is not in criteria

• Tourniquet Test:
• > 20 petechiae/sq. inch: Positive
• < 10 petechiae/sq. inch: Negative

Dengue Shock Syndrome:

• Systolic BP: < 90 mmHg

• Note: Platelet count is not a criterion

Repeat Infection:

• Increased severity

• no cross immunity

• Cause:
• Occurs in individuals with pre-existing non-neutralizing heterologous dengue antibodies
• From previous infection with a different serotype
• Or passively acquired maternal antibodies in children

• Course:
• Initially resembles classical dengue fever
• Later, condition worsens

Lab Diagnosis:

• < 5 days: NS1 antigen, virus isolation, RT PCR

• > 5 days: IgM (MAC, ELISA)

Indicators for Dengue (Aedes Larval Surveillance):

Treatment in Dengue with Warning Signs

• Primary modality:
• IV fluid (crystalloid)

• Platelet transfusion:
• Indicated only if:
• Severe thrombocytopenia (<10,000)
• Active bleeding present

• FFP & cryoglobulin:
• Not preferred

Criteria for Discharge in Dengue

• Absence of fever for >24 hours without antipyretics

• Platelet count >50,000

• Return of appetite

• Adequate urine output

• Visible clinical improvement

• Minimum 2–3 days after recovery from shock

• No respiratory distress from pleural effusion or ascites

• Breteau index: For Dengue & Chikungunya
• (B → C → D)

• M/c/c of diarrhoea in children

• M/c/c of death by diarrhoea in children < 5 years (29%)

• Most common cause of diarrhea in adults is Norovirus

 

• M/c HIV in India:
• HIV-1 group M subgroup C
• Mnemonic: M C → m/c

• HLA B27/57 → Good prognosis → Controller

• HLA B35 → Poor prognosis → Progressor

• Structural Genes (Mature Virion):
• Env (gp160 → gp120 + gp41)
• Gag → p17 (matrix), p24 (capsid), p7 (nucleocapsid), p6 (budding)
• Pol → p12 (protease), p66/p51 (RT), p32 (integrase)

• Attachment:
• gp120:
• bind CD4 T cells/macrophages
• gp41:
• Transmembrane anchoring protein
• Conformational change & Exposes fusion peptide
• aids cell penetration
• Co-receptors: CXCR4, CCR5
• CCR5 on macrophages (early infection)
• CXCR4 on T cells (late infection)
• CCR5 (delta 32) mutation = Immunity to HIV AIDS
• When the binding is complete the virus enters the cell.

• FRIEBERG CLASSIFICATION

• Disease Course:
• CD4 decreases during acute syndrome
• Clinical latency → 10 years (healthy, but no microbiological latency)
• Later: Opportunistic infections

 

WHO STAGING

• M/c Opportinistic infection:
• TB

• M/c Pneumonia
• Strep > TB

• M/c Ocular feature
• Microangiopathy

• M/c finding in HIV Retinopathy
• Cotton wool spots

• M/c ocular side effect in HAART
• Immune Recovery Uveitis
• Non granulomatous uveitis (anterior > Posterior)
• Usually in CMV Retinitis

Laboratory Diagnosis of HIV: NACO

• Screening in ICTC centers (Integrated Counselling & Testing Centres)
• Mobile ICTC:
• In rural area, ↓ prevalence
• Fixed ICTC:
• In ↑ high prevalence
• Facility integrated ICTC:
• In low burden area
• Standalone ICTC:
• In high burden area

• Method → Community-based screening

 

Screening:

• 4th gen assays → p24 Ag + HIV Ab

• According to NACO → ERS to be performed
• (All 3 to be performed)
1. ELISA: Most sensitive, 1st test
2. Rapid test
3. Dried blood Spot test

• Other screening tests:
• Immunoconcentration
• Particle agglutination

HIV probable +ve

Diagnostic/Conformational tests:

• Adults:
• Western blot >>> qPCR
• Most Diagnostic
• qPCR is only done in adults
• Western Blot (HIV-1) → qPCR
• WHO: 2 envelope proteins (+/- gag/pol)
• Envelope to who
• CDC: Any 2 bands (p24, gp160, gp120, gp41)

• Children:
• HIV TNA/ DNA RT-PCR (IOC)
• TNA: Total nucleic acid
• Also to assess response

• Serology (blood markers):
• Earliest: HIV RNA plasma (used for needle-stick injury)
• Next: HIV-1 p24 antigen

• Others:
• Viral isolation/Viral load estimation

Prognostic test:

• CD4 count (Response to Rx)

All in initiative → Adolescent HIV

Nirantar scheme → To ↑↑ awareness

SUNRISE project → ↑ incidence in North Eastern states

CD4 Count vs Opportunistic Infections

Congenital toxoplasmosis CT

• Eccentric target sign.
• M/c site: basal ganglia

• Retrovirus

• Involves TAX gene.

• Transmission: Blood, body fluids, breast milk

• Diseases:
• Tropical Spastic paralysis
• Causes Adult T-cell Leukemia Lymphoma (ATLL)
• (T-cell leukaemia/lymphomas).

• Microscopy: Clover leaf cells (flower-like nucleus).

• Mnemonic:
• HTLV → Hotel → we give flower (Flower like nucleus) and cards (Clover leaf)
• Hotel should pay tax
• Tax adachillel Paralysis

• Family: Coronaviridae

• Genus: Beta coronavirus

• Morphology:
• Crown-like appearance under EM
• Petal-like peplomers help in attachment

• Structure:
• Spike protein (S1, S2)
• for attachment
• Long petal-shaped
• Nucleocapsid (N)
• Membrane (M)
• Envelope (E)

• Entry Mechanism:
• TMPRSS2 activates spike protein
• Spike attaches to ACE2 receptors

• Incubation Period: 2–14 days (median 5–6 days).

• Most common ocular manifestation of COVID-19 is follicular conjunctivitis

Diagnosis

• Sample:
• Nasopharyngeal swab + oropharyngeal swab
• Both placed in Viral Transport Media (VTM)

• RT-PCR (Real-time Reverse Transcriptase PCR):
• CT Value: lower = more infectivity
• Semi-confirmatory genes: E, N, S genes
• Confirmatory genes: RdRP, ORF1a

• Card test:
• Principle: Immunochromatography (ICT)
• Control line → ensures validity

Histopathology:

• Diffuse alveolar damage.

• Hyaline membrane deposition

Viral vector vaccines / Live vaccines

• Covishield: 
• Using CHAD-OX1 strain with chimpanzee adenovirus.
• Mnemonic: Shield for Chad from Ox and Chimpanzee

• INCOVACC (2022):
• Only nasal vaccine: BBV 154.
• Mnemonic: Cova → BBV
• CC → 154
• X → 152
• Recombinant replication deficient adenovirus, vector vaccine.
• Age: >18 years.
• Mnemonic: Inside Nose Covid Vaccination

• Killed vaccine: 
• Covaxin (BBV-152 strain).
• X → Killed

• Protein subunit vaccine: 
• Corbevax.
• Mnemonic: Corbe → Brotein

• mRNA vaccines.

• Vaccines:
• Pfizer-BioNTech (BNT162b2): 2 doses, 0.3 mL IM, 21 days apart.
• Moderna (mRNA-1273): 2 doses, 0.5 mL IM, 28 days apart.
• AstraZeneca (AZD1222): 2 doses, 0.5 mL IM, 4–12 weeks apart.

M/c HRCT finding:

• Bilateral Multifocal peripheral/ subpleural GGO
• Typical → CORADS 5 (highly suspicious).

• Military (Miliary) people
• get TB
• Laugh (Loeffler’s)
• Heal by eating chicken (healed varicella)
• make History (Histoplasmosis)

• Presentation:
• Usually a female patient
• dry cough, shortness of breath
• associated with connective tissue disorder.

• M/c type
• Idiopathic pulmonary fibrosis

• IOC - HRCT.
• UIP/IPF pattern
• Honeycombing pattern +
• Basal Lower lobe dominance +
• Traction bronchiectasis
• Ni thanna (Nintendanib) Feni done (Pirfenidone) ayi → lung fibrosis ayi (IPF)



• TGF α → KGF α → Menetriers disease
• TGB β → KGF β → drink Feni
• Ninte Dani → PD Girl Friend (PDGF)

Crazy pavement appearance:

• Interlobular septal thickening is seen with ground glass opacity.

• no air filled cavities are seen.

• Seen in Pulmonary alveolar proteinosis >>> COVID 19

• Mnemonic: Crazy Pappu (PAP) in pavement

Cystic Bronchiectasis

• Some of these dilated bronchi contain mucus.

• Bronchi appears as cysts.

• Bunch of grape appearance.