Why We Give Acyclovir in Chickenpox

Mechanism of Action (How It Works)

1. VZV-encoded thymidine kinase phosphorylates acyclovir into acyclovir monophosphate.
2. Host cell enzymes convert it to acyclovir triphosphate.
3. This competes with deoxyguanosine triphosphate and inhibits viral DNA polymerase, halting viral DNA chain elongation.
4. Because the phosphorylation depends on viral (not human) kinase, acyclovir is selectively toxic to virus-infected cells - minimal toxicity to normal host cells.

What Acyclovir Does in Chickenpox

• Decreases the number of new lesions
• Shortens the duration of the illness (reduces symptoms by ~50%)
• Reduces viral shedding by ~90%
• Reduces the risk of visceral complications (pneumonia, encephalitis, hepatitis) especially in immunocompromised patients

Who Gets Acyclovir? (Indications)

Dosing

• Oral (adults/adolescents): Acyclovir 800 mg 5 times daily for 5-7 days
• Oral (children <12 years, if indicated): 20 mg/kg every 6 hours
• IV (severe/immunocompromised): High-dose IV acyclovir

Why NOT in Healthy Young Children?

• The disease is usually mild and self-limiting
• The benefit (modest reduction in lesion count/duration) does not outweigh routine antiviral use
• Supportive care (antipruritic lotions, hygiene, nail trimming to prevent secondary bacterial infection) is sufficient
• Aspirin is contraindicated in children with chickenpox due to risk of Reye syndrome - but this is not a reason to give acyclovir, just an important co-point

Summary

The Meningoencephalitis Cocktail (Empirical Treatment)

Core Drugs

Add-ons Based on Risk Groups

Why Each Drug Is Given

• Together these cover both susceptible and drug-resistant S. pneumoniae - the most dangerous bacterial cause
• Ceftriaxone alone may miss penicillin-resistant strains, hence vancomycin is always added empirically

• HSV encephalitis is rapidly fatal if untreated (mortality up to 70% untreated vs ~20% treated)
• It cannot be excluded clinically from bacterial meningitis at presentation
• Given empirically to ALL patients unless HSV can be confidently excluded
• Ensure adequate IV fluids alongside acyclovir - risk of renal tubular precipitation increases in hypovolemic patients

• Reduces CSF inflammation and cytokine surge
• Proven to reduce mortality in pneumococcal meningitis in adults
• Reduces hearing loss and neurological sequelae in children
• Must be given before or simultaneously with the first antibiotic dose - giving it after antibiotics reduces its benefit
• Dose: 10 mg IV every 6 hours for 4 days (adults)

• Listeria is inherently resistant to all cephalosporins
• Added empirically in age >50 years, immunosuppressed, pregnant, and alcoholic patients who are disproportionately affected

Timing is Everything

Never delay antibiotics for CT scan or lumbar puncture. Blood cultures take 5 minutes to draw. Get them, then give the cocktail immediately. Even if LP is delayed, antibiotics should not be.

Quick Summary Mnemonic: "CVAD ± A"

• C - Ceftriaxone
• V - Vancomycin
• A - Acyclovir
• D - Dexamethasone
• ± A - Ampicillin (if Listeria risk present)

CSF Findings: Bacterial vs Viral Meningitis

Master Comparison Table

Key Points to Remember

1. Cell Count and Type

• Bacterial: WBC typically >1000/µL with neutrophilic (PMN) dominance - this is the hallmark
• Viral: WBC typically <500/µL with lymphocytic dominance
• Important exception: In early viral meningitis (first 24-48 hours), PMNs can predominate (especially in echovirus 9, West Nile virus, EEE virus, mumps). Repeat LP after 8-12 hours typically shows shift to lymphocytes
• About 10% of bacterial meningitis cases can show lymphocyte predominance - do not be misled

2. Glucose

• Bacterial: Glucose <40 mg/dL or CSF:serum ratio ≤0.3 - bacteria consume glucose and cause inflammation that disrupts transport
• Viral: Glucose is normal in most cases
• Low CSF glucose with lymphocytic pleocytosis should raise suspicion for TB, fungal, or Listeria meningitis (not typical viral)
• Mumps and LCMV (lymphocytic choriomeningitis virus) are exceptions - they can lower CSF glucose in 10-30% of viral cases

3. Protein

• Bacterial: Often markedly elevated (100-500 mg/dL or more) due to blood-brain barrier disruption and cellular breakdown
• Viral: Normal or mildly elevated (usually <100 mg/dL, normal <45 mg/dL)

4. Opening Pressure

• Bacterial: Elevated (often >200 mmH2O)
• Viral: Usually normal (100-350 mmH2O range)

Practical Diagnostic Tip

Low glucose + neutrophilic pleocytosis = bacterial until proven otherwise → treat immediately

Normal glucose + lymphocytic pleocytosis = viral likely, but consider TB/fungal if glucose is low

What Partially Treated Bacterial Meningitis Looks Like

• Glucose remains low
• Protein remains elevated
• Neutrophil predominance persists

Purified Vero Cell Rabies Vaccine (PVRV)

What Is It?

Why Vero Cells?

Composition

• Contains inactivated rabies virus (Wistar PM/WI 38 1503-3M strain)
• Propagated on Vero cells
• Purified by zonal centrifugation and ultrafiltration
• Inactivated with beta-propiolactone
• No preservatives (e.g., no thimerosal) in WHO-prequalified formulations
• Potency: ≥2.5 IU per single IM dose
• Available as lyophilized powder - must be reconstituted with the supplied diluent
• Use immediately after reconstitution, or within 6-8 hours if refrigerated
• Storage: +2°C to +8°C, protected from sunlight; shelf life ≥3 years

WHO Exposure Categories (When to Use)

Post-Exposure Prophylaxis (PEP) Schedules

Intramuscular Route (IM)

• Days 0, 3, 7, 14, 28 - one IM dose each day
• Used for immunocompromised patients (mandatory)

• Day 0: 2 doses (one in each deltoid simultaneously)
• Day 7: 1 dose
• Day 21: 1 dose

• Days 0, 3, 7, 14 - one IM dose each day
• For healthy, fully immunocompetent persons who also receive wound care + RIG

Intradermal Route (ID) - cost-saving option

• 2-site ID regimen: 0.1 ml at 2 sites (both deltoids) on days 0, 3, 7, 28
• Dose = 1/5th of the IM dose
• Requires trained staff; endorsed by WHO but must be nationally approved

Rabies Immunoglobulin (RIG) - for Category III

• Give only once, on day 0, before or with the first vaccine dose
• Infiltrate as much as possible into and around the wound
• Remaining volume given IM at a site distant from vaccine injection
• Never inject in the same syringe or site as vaccine - they neutralize each other
• If RIG not given on day 0, it can still be given up to day 7 after starting vaccine
• After day 7, RIG is NOT given (active immunity already developing)

Pre-Exposure Prophylaxis (PrEP)

• 3 doses IM or ID on days 0, 7, and 21 or 28
• Booster every 2 years for those at continuous risk (check antibody titre)

Previously Vaccinated Persons (Re-exposure)

• Only 2 doses on days 0 and 3
• No RIG needed (anamnestic immune response occurs)
• Applies to those who completed a full PEP or PrEP with a cell-culture vaccine and have documented antibody titres

Special Populations

Key Points to Remember

1. PVRV is the most widely used modern rabies vaccine in developing countries
2. No nerve tissue vaccines (brain-derived) should be used - they cause severe neuroparalytic reactions
3. Wound washing with soap and water for 15 minutes is the single most effective first step - it reduces viral load dramatically
4. Never delay vaccine and RIG out of fear of side effects - untreated rabies is 100% fatal once symptoms appear
5. Potency must be ≥2.5 IU/dose per WHO standard
6. Gluteal injection is prohibited - poor deltoid muscle mass leads to fat deposition, reducing immunogenicity