Rabies Post-Exposure Prophylaxis

Quick Answer

One-liner: Rabies PEP is a medical emergency requiring immediate wound washing (15 min), rabies immunoglobulin (20 IU/kg infiltrated into wound), and vaccine series (day 0/3/7/14/28) to prevent 100% fatal encephalitis.

Rabies is a uniformly fatal viral encephalitis once symptoms develop. Post-exposure prophylaxis (PEP) prevents rabies by providing passive immunity (RIG) and inducing active immunity (vaccine) before the virus reaches the CNS. In Australia, Australian Bat Lyssavirus (ABLV) poses the primary risk from all bat species. The three pillars of PEP are: (1) immediate wound washing for ≥15 minutes, (2) rabies immunoglobulin 20 IU/kg infiltrated into/around the wound, and (3) rabies vaccine on day 0, 3, 7, 14, and 28. Category III exposures (bites, scratches, mucous membrane contact) require full PEP. Delay or omission is potentially fatal - this is a true medical emergency.

---

ACEM Exam Focus

Primary Exam Relevance

• Immunology: Active vs passive immunisation, antibody production timelines, interference between RIG and vaccine
• Microbiology: Lyssavirus pathogenesis, neurotropism, CNS spread via retrograde axonal transport
• Pharmacology: Human rabies immunoglobulin (HRIG), equine RIG (ERIG), modern cell culture vaccines (PCECV, HDCV)

Fellowship Exam Relevance

• Written: Exposure category classification, PEP protocols, Australian ABLV context, remote/rural management
• OSCE: Breaking bad news (bat bite, high-risk exposure), patient communication re: PEP necessity, consent for immunoglobulin/vaccine
• Key domains tested: Medical Expert (PEP protocols), Communicator (explaining 100% mortality), Health Advocate (Indigenous access to PEP, remote retrieval)

---

Key Points

Key Points: The 5 things you MUST know:

1. 100% fatal once symptomatic - no effective treatment exists; PEP prevents disease, does not treat it
2. Wound washing 15 minutes is the single most important intervention - mechanically removes virus before tissue penetration
3. Category III exposure (bite/scratch/mucous membrane contact) requires RIG + vaccine; Category II requires vaccine only
4. RIG dose 20 IU/kg infiltrated into/around wound (max anatomically possible), remainder IM distant from vaccine site
5. All bat contact in Australia requires PEP assessment - ABLV endemic in flying foxes and microbats, 1% prevalence in wild populations

---

Epidemiology

Australian/NZ Specific

• ABLV endemic: All Australian bat species (Pteropus flying foxes, insectivorous microbats) can carry ABLV [7] PMID: 9802051
• Human cases: 3 deaths since 1996 - all from bat exposure, 2 from flying foxes, 1 from microbat [3]
• Indigenous populations: Higher risk due to remote living, bat exposure during hunting/camping, delayed access to PEP [8] PMID: 28691157
• Occupational risk: Wildlife carers, veterinarians, rangers - pre-exposure prophylaxis recommended [9] PMID: 21054879
• New Zealand: Rabies-free, but bat contact overseas requires PEP assessment [10]

---

Pathophysiology

Mechanism

Rabies virus (family Rhabdoviridae, genus Lyssavirus) is a negative-sense single-stranded RNA virus that causes acute, progressive, fatal viral encephalomyelitis.

Transmission:

• Virus present in saliva of infected animals
• Entry via bite/scratch (broken skin) or mucous membrane contact
• Virus replicates in muscle tissue at wound site (1-several weeks)

Neurotropism:

• Virus binds acetylcholine receptors and neural cell adhesion molecules (NCAM) at neuromuscular junctions [11] PMID: 19074136
• Retrograde axonal transport to CNS at 50-100 mm/day via dynein motor proteins
• Spread to brain via peripheral nerves (cranial/spinal) - incubation depends on: distance from CNS, viral load, wound severity

CNS infection:

• Virus reaches dorsal root ganglia → spinal cord → brain (limbic system preferentially)
• Negri bodies (pathognomonic cytoplasmic inclusions) in hippocampal pyramidal cells, cerebellar Purkinje cells
• Neuronal dysfunction without extensive destruction - apoptosis, not necrosis [12] PMID: 15060100
• Centrifugal spread to salivary glands, enabling transmission

Pathological Progression

Exposure (bite/scratch) → Local replication (muscle, 1-4 weeks) → Peripheral nerve entry → Retrograde axonal transport (days-weeks) → CNS invasion → Encephalitis (2-10 days) → Death (cardiorespiratory failure)

Why It Matters Clinically

PEP works by preventing CNS entry:

• Wound washing reduces viral load at entry site (mechanical removal)
• RIG provides immediate neutralising antibodies to bind virus at wound site (passive immunity - works hours-days)
• Vaccine induces active antibody production (takes 7-14 days to reach protective titres)
• Once virus enters CNS, antibodies cannot cross blood-brain barrier - PEP futile

Time is critical: Longer the wound-to-CNS distance (finger bite = longer), the more time for PEP to work. Facial/neck bites have shortest incubation (days-weeks).

---

Clinical Approach

Recognition

High-risk scenarios requiring PEP assessment:

• Any bat contact in Australia (flying fox, microbat) - bite, scratch, saliva contact
• Dog/cat bite in rabies-endemic country (Asia, Africa, Latin America)
• Wildlife exposure: foxes, raccoons, skunks, mongooses (varies by region)
• Unvaccinated patient with animal bite overseas
• Patient presenting days-weeks post-exposure but pre-symptomatic

Low suspicion triggers:

• "I found a bat in my bedroom"
• assess for bite (may not recall)
• "A bat scratched me but didn't bite"
• still Category II/III
• "I handled a sick flying fox"
• mucous membrane exposure possible

Initial Assessment

Primary Survey (Category III exposure with severe injury)

• A: Facial bites may cause airway compromise from soft tissue injury (not rabies itself)
• B: Normal respiratory exam (rabies encephalitis presents weeks later)
• C: Assess for arterial injury (deep bites), haemorrhage control
• D: GCS 15 expected (encephalitis only develops if PEP not given)
• E: Full skin survey for all bite/scratch sites (multiple wounds common)

History

Key Questions

Red Flag Symptoms

Examination

General Inspection

• Patient should be well-appearing (if symptomatic rabies, patient will be floridly encephalopathic)
• Inspect all skin for bite/scratch marks - multiple wounds common in bat attacks
• Document wound characteristics: depth, contamination, devitalised tissue

Specific Findings

---

Investigations

Immediate (Resus Bay)

Standard ED Workup

Advanced/Specialist

Point-of-Care Ultrasound

Not applicable - rabies PEP is a clinical decision. POCUS may assess:

• Soft tissue injury extent (haematoma, foreign body)
• Vascular injury (arterial flow in deep bites)

---

Management

Immediate Management (First 10 minutes)

1. **Wound washing** (0-15 min): Irrigate wound with running water + soap for ≥15 minutes. Use povidone-iodine or chlorhexidine if available. This is the MOST important step - reduces viral load by 90-99%.

2. **Tetanus prophylaxis** (5 min): Update if needed (ADT/dTpa).

3. **Contact Infectious Diseases / Public Health Unit** (10 min): Mandatory notification in Australia for ABLV exposure. Arrange PEP supply (RIG often limited stock).

4. **Rabies immunoglobulin (RIG)** (10-30 min): Calculate dose 20 IU/kg. Infiltrate as much as anatomically possible into/around wound. Any remainder IM at distant site (NOT same site as vaccine).

5. **Rabies vaccine dose 1** (30 min): Give IM deltoid (adults) or anterolateral thigh (children) - NEVER gluteal. Opposite limb to RIG remainder.

Resuscitation

Not applicable - patients presenting for PEP are asymptomatic (exposure only). If symptomatic rabies, PEP is futile - transition to palliative care.

Medications

Rabies Immunoglobulin (RIG)

Infiltration technique:

1. Calculate total dose: Patient weight (kg) × 20 IU/kg = total IU
2. Infiltrate as much volume as anatomically possible into wound edges and deep tissues
3. Multiple wounds: Divide dose proportionally to infiltrate all wounds
4. Volume insufficient? Dilute in 2-5 mL sterile saline to allow adequate infiltration
5. Any remainder: Give IM at site distant from vaccine (e.g., opposite thigh)

Rabies Vaccine

Available vaccines in Australia:

• Verorab (purified chick embryo cell vaccine, PCECV) - most common
• Rabipur (PCECV)
• HDCV (human diploid cell vaccine) - less available

Site: Deltoid (adults), anterolateral thigh (children below 2 years). NEVER gluteal (poor immunogenicity).

Paediatric Dosing

Exposure Category Classification

Key Points: Australian exception: ALL bat contact in Australia is treated as Category III (RIG + vaccine) due to ABLV risk - even if no visible bite/scratch. Bat teeth are tiny and bites may be imperceptible.

Ongoing Management

Follow-up schedule:

• Day 3: Return for vaccine dose 2
• Day 7: Vaccine dose 3
• Day 14: Vaccine dose 4
• Day 28: Vaccine dose 5 (+ serology if immunocompromised)

Patient education:

• Explain 100% mortality if PEP not completed
• Emphasise importance of ALL doses - missing even one dose may be fatal
• Provide written schedule with dates/times
• Remote patients: Coordinate with RFDS or regional hospitals for dose delivery

Definitive Care

Animal observation (if possible):

• Domestic dog/cat bites (non-endemic area): Observe animal for 10 days. If healthy at day 10, rabies excluded - can cease PEP.
• Bat bites in Australia: Cannot observe - ABLV PEP must be completed regardless.

Brain testing (animal):

• If animal captured/euthanased: Direct fluorescent antibody (DFA) test on brain tissue
• Positive = rabies confirmed; Negative = PEP can be discontinued
• Only applicable if animal available - do NOT delay PEP to "wait for the bat"

---

Disposition

Admission Criteria

• Not routinely required for PEP alone
• Admit if:
  • Severe wound requiring surgical debridement/exploration
  • Vascular or tendon injury
  • Concern for compliance (e.g., cognitive impairment, unstable housing)
  • Anaphylaxis to RIG/vaccine (observe 4-6 hours post-dose)

ICU/HDU Criteria

• Not applicable for PEP (patients are asymptomatic)
• If symptomatic rabies: ICU for palliative care (no effective treatment)

Discharge Criteria

• PEP day 0 administered (RIG + vaccine)
• Patient understands need to return day 3, 7, 14, 28
• Wound care instructions provided
• Tetanus up to date
• Written schedule with follow-up hospital details
• Red flags to return: fever, neurological symptoms, wound infection

Follow-up

• Day 3, 7, 14, 28: Return to ED or designated vaccine clinic for doses
• GP letter: Notify GP of exposure, PEP schedule, need for compliance support
• Public Health Unit: Mandatory notification (ABLV exposure in Australia)
• Specialist referral: Infectious Diseases if immunocompromised, pregnant, or complex case

---

Special Populations

Paediatric Considerations

• Same PEP protocol as adults (full vaccine dose, RIG 20 IU/kg)
• Injection site: Anterolateral thigh (children below 2 years), deltoid (older children)
• Parental consent: Explain 100% fatality, need for all 5 doses
• School-aged children: Coordinate with school nurse for day 3/7/14/28 follow-up if parents working

Pregnancy

• PEP is safe and ESSENTIAL - rabies 100% fatal, vaccine/RIG pose minimal risk
• No contraindication to RIG or vaccine in pregnancy [13] PMID: 20459446
• Rabies vaccine (PCECV, HDCV) = inactivated virus - no risk to fetus
• Breastfeeding: Safe to continue while receiving PEP

Elderly

• Same protocol as younger adults
• Assess for immunocompromise (chronic steroids, malignancy)
• May need assisted follow-up for day 3/7/14/28 doses (arrange community nurse, family support)

Immunocompromised

• HIV, chemotherapy, biologics, high-dose steroids (greater than 20 mg/day prednisone): PEP still indicated
• 5-dose regimen mandatory (do not use abbreviated 4-dose)
• Post-PEP serology (day 28): Check rabies antibody titre (protective ≥0.5 IU/mL)
• If titre below 0.5 IU/mL: Give booster dose and recheck

Indigenous Health

---

Remote/Rural Considerations

Pre-Hospital

Ambulance/retrieval:

• Paramedics should initiate wound washing (running water 15 min) en route if possible
• Communicate with receiving ED re: RIG availability (often limited stock in regional centres)
• If ABLV exposure, activate retrieval early - RIG must be given within 7 days

RFDS:

• RIG may not be available on RFDS flights - arrange for pickup from tertiary centre
• Vaccine more widely available (refrigeration required - cold chain critical)
• Coordinate with base hospital to pre-order RIG before retrieval

Resource-Limited Setting

If RIG not available locally:

1. Initiate wound washing (soap + water 15 min) - THIS IS MOST IMPORTANT
2. Give vaccine dose 1 (day 0) - do not delay
3. Arrange retrieval/transfer to centre with RIG stock (within 7 days)
4. Interim management: Clean wound, tetanus, antibiotics if indicated

If patient cannot return for day 3/7/14/28:

• Arrange vaccine delivery via RFDS or regional clinic
• Remote area nurse can administer (IM deltoid) with telephone support
• Telehealth consult for each dose to assess for adverse reactions

Retrieval

Criteria for retrieval to tertiary centre:

• ABLV exposure in remote area without RIG stock
• Severe wound requiring surgical exploration
• Anaphylaxis to RIG/vaccine
• Patient unable to return for follow-up doses (e.g., tourist, unstable housing)

Timeframe:

• Urgent (within 24 hours): RIG ideally within 24-48h of exposure
• Up to 7 days: RIG can be given up to day 7 post-first vaccine dose
• After day 7: Retrieval for RIG not required (contraindicated); vaccine-only PEP

Telemedicine

Remote consultation approach:

• Initial assessment: Video call to visualise wound, assess exposure category
• PEP initiation: Remote nurse/GP can give vaccine with telehealth support
• Follow-up: Day 3/7/14/28 doses via telehealth-guided administration
• Documentation: Photo of wound, vaccine vial batch numbers for registry

---

Pitfalls & Pearls

Key Points: Clinical Pearls:

• "15 minutes feels like forever": Patients will stop washing at 2-3 minutes. Set a timer. This is the most important step.
• All bat contact = Category III: Australian bat teeth are tiny - patient may not feel a bite. Any bat contact (even "just touched it") requires PEP.
• RIG is not "optional": Category III exposure WITHOUT RIG has 50% PEP failure rate. Must infiltrate wound.
• Wound infiltration technique: Use 25G needle, inject slowly, aim for visible tissue distension around wound edges. If too painful, local anaesthetic first.
• "Previously vaccinated" = documentation required: Patient recall is unreliable. If no written proof of 3-dose pre-exposure series or prior PEP, treat as unvaccinated.
• Pregnancy is NOT a contraindication: Rabies is 100% fatal; PEP is safe. ALWAYS give PEP to pregnant patients.
• Immunocompromise requires serology: HIV, chemo, steroids greater than 20 mg/day - check day 28 titre to confirm seroconversion.

---

Viva Practice

---

OSCE Scenarios

Station 1: Breaking Bad News - High-Risk ABLV Exposure

Format: Communication Time: 11 minutes Setting: ED relatives' room

Candidate Instructions:

You are the ED registrar. A 6-year-old boy was brought in by his parents 2 hours ago after waking up with a bat in his bedroom. The bat escaped out the window. There is a small 2 mm scratch on the child's left cheek. You have administered wound washing, RIG, and vaccine dose 1. The parents are very anxious and have requested to speak with you. Your task is to explain the situation, the treatment given, and the importance of follow-up.

Examiner Instructions: The candidate must:

1. Explain ABLV risk (endemic in Australian bats, 100% fatal, 3 deaths since 1996)
2. Clarify that even "minor scratch" is Category III (bat contact)
3. Explain PEP components (wound washing, RIG, vaccine series)
4. Emphasise critical importance of all 5 vaccine doses (day 0, 3, 7, 14, 28)
5. Address parental anxiety with empathy
6. Provide written schedule and safety-netting advice

Actor/Patient Brief: You are the worried father of a 6-year-old boy. You are very anxious because "it was just a tiny scratch" and you don't understand why the doctors are making such a big deal. You are concerned about the "20 needles" (RIG infiltration) your son received and whether this is "overkill." You work full-time and are worried about missing work for 4 more vaccine appointments. Your wife (actor 2) is more accepting but wants to know if your son will be "okay."

Marking Criteria:

Expected Standard:

• Pass: ≥10/16
• Key discriminators:
  • Clearly explains 100% fatality (not "very serious"
• specific language required)
  • "Addresses work barrier to follow-up (offers solutions: after-hours clinics, GP administration, written employer letter)"
  • Empathetic but firm about follow-up necessity

---

Station 2: Procedural Skill - RIG Infiltration Technique

Format: Procedural simulation Time: 11 minutes Setting: ED procedure bay (simulation manikin with wound model)

Candidate Instructions:

You are the ED registrar. A 28-year-old woman has sustained a Category III dog bite to her right hand (two puncture wounds on dorsum) while travelling in Thailand. She is unvaccinated. You have calculated her RIG dose as 1,400 IU (70 kg × 20 IU/kg). Vials available: HRIG 300 IU/2 mL (you have 5 vials = 1,500 IU total). Your task is to demonstrate and explain RIG infiltration technique to the examiner, using the wound model provided.

Examiner Instructions: The candidate must demonstrate:

1. Correct dose calculation and preparation (1,400 IU = 4.67 vials = ~9.3 mL)
2. Explanation of infiltration rationale (passive immunity at wound site)
3. Correct technique: 25G needle, infiltrate into and around wound edges, slow injection
4. Management of remaining RIG (any volume not infiltrated → IM distant site, NOT same limb as vaccine)
5. Aseptic technique
6. Patient communication (warn of pain, explain importance)

Equipment:

• Wound model (silicone hand with two puncture wounds)
• HRIG vials: 300 IU/2 mL (×5)
• Syringes: 10 mL (×2), 5 mL (×2)
• Needles: 18G (drawing up), 25G (infiltration)
• Alcohol wipes, gloves

Marking Criteria:

Expected Standard:

• Pass: ≥9/15
• Key discriminators:
  • "Correct dose calculation (common error: forgetting to convert IU to mL)"
  • Infiltration into wound (not just subcutaneous near wound - must infiltrate wound edges)
  • "States remainder goes IM distant from vaccine (common error: same limb or discarding excess)"

---

Station 3: History Taking - Exposure Risk Assessment

Format: Focused history Time: 11 minutes Setting: ED cubicle

Candidate Instructions:

You are the ED registrar. A 19-year-old backpacker presents stating she "touched a bat" in Indonesia 3 days ago. Your task is to take a focused history to determine exposure category and PEP requirements. You will be asked to present your findings and management plan to the examiner at the end.

Examiner Instructions: The candidate must elicit:

1. Exact nature of contact: Bite? Scratch? Lick? Touch only?
2. Location on body: (Face/neck = high risk, extremities = lower risk but still PEP)
3. Bat species/behaviour: (Flying fox? Microbat? Sick/injured? Aggressive?)
4. Wound care already performed: (Washed? How long? Soap? Antiseptic?)
5. Vaccination history: (Pre-exposure rabies vaccine? Documentation? Other vaccines up to date?)
6. Immunocompromise: (HIV? Medications? Chronic illness?)
7. Travel history: (Country? Duration? Other animal exposures? Return flight date?)
8. Ability to return for follow-up: (Local? Tourist? Leaving Australia soon?)

Actor/Patient Brief: You are a 19-year-old Australian backpacker. You were staying in a temple in Bali 3 days ago and a fruit bat flew into your room at night. You tried to catch it with your hands to release it outside. You are not sure if it bit or scratched you - it was dark and chaotic. You have a small scratch on your right forearm that you "think" is from the bat (but might have been from the temple wall). You washed it with bottled water for "a few minutes." You have never had rabies vaccine. You are flying home to Sydney in 2 days. You are otherwise healthy, no medications, not pregnant.

Marking Criteria:

• inadequate), antiseptic use | /1 | | Vaccination history | Asks about rabies vaccine (none), tetanus status, immunocompromise | /2 | | Travel/logistics | Elicits country (Bali - endemic), return date (2 days), ability to follow up in Australia | /2 | | Risk stratification | Correctly identifies Category II/III exposure (uncertain if bite/scratch - treat as Category III) | /2 | | Management plan | States: Wound washing 15 min, RIG + vaccine (Category III), day 0 today, arrange day 3 in Sydney | /2 | | Communication | Clear explanation to patient, checks understanding, empathetic | /1 | | Total | | /14 |

Expected Standard:

• Pass: ≥9/14
• Key discriminators:
  • Recognises "unsure if bite/scratch" = treat as Category III (benefit of doubt)
  • Identifies inadequate wound washing ("few minutes" is not 15 minutes)
  • Plans for day 3 dose in Australia (not Bali - patient leaving soon)

---

SAQ Practice

Question 1: PEP Protocol (8 marks)

Stem: A 45-year-old man presents to your ED 8 hours after being bitten on the left hand by a stray dog while trekking in rural India. He has two deep puncture wounds on the dorsum of his hand. He has never received rabies vaccine. His tetanus is up to date. He is well-appearing, GCS 15, no fever.

Question: Outline your post-exposure prophylaxis (PEP) management for this patient. (8 marks)

Model Answer:

1. Wound washing (1 mark):

   • Irrigate wound with running water + soap for minimum 15 minutes
   • Apply povidone-iodine or chlorhexidine (virucidal antiseptic)

2. Exposure category classification (1 mark):

   • Category III exposure (transdermal bite) → requires RIG + vaccine

3. Rabies immunoglobulin (RIG) (2 marks):

   • Calculate dose: 20 IU/kg body weight (HRIG) or 40 IU/kg (ERIG)
   • Infiltrate as much as anatomically possible into and around the wound
   • Any remainder: IM at site distant from vaccine (e.g., opposite thigh)
   • Must be given within 7 days of first vaccine dose

4. Rabies vaccine (2 marks):

   • 5-dose series: Day 0, 3, 7, 14, 28
   • IM injection: Deltoid (adults) or anterolateral thigh (children below 2y)
   • NOT gluteal (poor immunogenicity)

5. Wound management (1 mark):

   • Do not suture (increases infection/viral retention risk) unless essential
   • Antibiotic prophylaxis: Amoxicillin-clavulanate (dog bite)

6. Follow-up (1 mark):

   • Provide written schedule for day 3, 7, 14, 28 vaccine doses
   • Emphasise critical importance of completing all doses (100% fatality if incomplete)

Examiner Notes:

• Accept: "Flush wound 15 min" (1 mark for adequate washing)
• Do not accept: "Give antibodies" without specifying RIG dose/route (need 20 IU/kg AND infiltration)
• Common error: Forgetting to specify "distant from vaccine site" for RIG remainder

---

Question 2: Australian Bat Lyssavirus (6 marks)

Stem: Australian Bat Lyssavirus (ABLV) is endemic in Australian bat populations.

Question: List THREE clinical differences between ABLV management and classical rabies PEP in Australia. (6 marks - 2 marks each)

Model Answer:

1. All bat contact = Category III (2 marks):

   • In Australia, any bat contact (flying fox or microbat) is treated as Category III exposure requiring RIG + vaccine
   • Bat teeth are tiny (bites may be imperceptible) - even "just touched the bat" warrants PEP
   • Classical rabies: Category I (touch only) does not require PEP

2. Cannot observe animal for 10 days (2 marks):

   • ABLV: Bats cannot be observed - PEP must be completed regardless of bat behaviour/appearance
   • Classical rabies (domestic dog): Dog can be observed for 10 days; if healthy, rabies excluded and PEP can be stopped

3. Mandatory Public Health notification (2 marks):

   • ABLV exposure is notifiable to Public Health Unit in all Australian states/territories
   • Arrange RIG supply (limited stock in regional centres - PHU coordinates)
   • Classical rabies (overseas): Notification varies by jurisdiction

Examiner Notes:

• Accept: "Prevalence 1% in wild bats" (population health difference)
• Accept: "No rabies-free areas in Australia" (geographic difference)
• Do not accept: "Different vaccine schedule" (ABLV uses same vaccine/RIG as classical rabies)

---

Question 3: RIG Administration (6 marks)

Stem: A 30-year-old woman has sustained a Category III dog bite to her right index finger while in Thailand. You have calculated her RIG dose as 1,200 IU (60 kg × 20 IU/kg).

Question: (a) Describe the correct technique for RIG administration. (4 marks) (b) State TWO contraindications to RIG administration. (2 marks)

Model Answer:

(a) RIG administration technique (4 marks):

1. Infiltrate wound site (2 marks):

   • Use 25G needle to infiltrate as much RIG as anatomically possible into and around the wound edges
   • Aim for visible tissue distension (wheal formation)
   • Multiple wounds: Divide dose proportionally to infiltrate all sites

2. Administer remainder (1 mark):

   • Any RIG volume not infiltrated: Give IM at site distant from vaccine (e.g., opposite thigh/deltoid)
   • Do NOT give RIG and vaccine in same anatomical site (RIG may neutralise vaccine antigen)

3. Timing (1 mark):

   • RIG must be given within 7 days of first vaccine dose
   • Ideally give on day 0 (same day as first vaccine)

(b) Contraindications to RIG (2 marks - 1 mark each):

1. greater than 7 days post-first vaccine dose:

   • RIG interferes with active immune response to vaccine if given after day 7
   • Vaccine-only PEP continues

2. Previously vaccinated patient:

   • Prior complete pre-exposure series (3 doses) or prior PEP (5 doses)
   • These patients have immune memory - RIG not required (may suppress anamnestic response)

Examiner Notes:

• Accept: "Pregnancy" is NOT a contraindication (common misconception - pregnancy is safe for RIG/vaccine)
• Accept: "Anaphylaxis to prior RIG dose" (true contraindication but extremely rare)
• Do not accept: "Immunocompromise" (not a contraindication - RIG still indicated, may need post-PEP serology)

---

Question 4: Remote/Rural PEP (6 marks)

Stem: You are working in a remote Northern Territory clinic 600 km from the nearest tertiary hospital. A 25-year-old Indigenous man presents 12 hours after being bitten by a flying fox. You have rabies vaccine in stock but NO rabies immunoglobulin (RIG). The nearest RIG supply is in Darwin (6-hour RFDS retrieval).

Question: Outline your immediate management and retrieval plan for this patient. (6 marks)

Model Answer:

Immediate management (clinic) (3 marks):

1. Wound washing (1 mark):

   • Irrigate wound with soap + running water for 15 minutes (most important intervention - reduces viral load 90-99%)
   • Povidone-iodine if available

2. Rabies vaccine dose 1 (1 mark):

   • Give IM deltoid (day 0) - do NOT delay vaccine waiting for RIG
   • Document batch number, time given

3. Tetanus update (0.5 marks) + Public Health notification (0.5 marks)

Retrieval plan (3 marks):

1. Activate RFDS urgent retrieval (1 mark):

   • Category III ABLV exposure - requires RIG within 7 days
   • 6-hour retrieval is appropriate timeframe

2. Coordinate RIG supply (1 mark):

   • Contact Darwin receiving hospital to pre-order RIG (limited stock - often needs retrieval from other centres)
   • Contact Public Health Unit to arrange RIG delivery to Darwin ED

3. Follow-up vaccine doses (1 mark):

   • Patient receives RIG in Darwin (day 0-1)
   • Arrange day 3, 7, 14, 28 vaccine doses: Can be given at remote clinic by nurse with telehealth support OR patient returns to Darwin for doses
   • Provide written schedule + cold chain vaccine supply to remote clinic if local administration planned

Examiner Notes:

• Accept: "Telemedicine consult with ID/ED physician" (good practice, but not essential for marks)
• Do not accept: "Wait for RIG before giving vaccine" (common error - vaccine should NEVER be delayed)
• Common error: Not mentioning wound washing (most important step, often forgotten in focus on RIG/vaccine)

---

Complications of Rabies PEP

Local Reactions

Injection Site Reactions (Common - 30-74% of patients)

Management approach:

• Mild pain/swelling: Reassure, paracetamol, ice
• Severe pain (RIG infiltration): Pre-treat with local anaesthetic before RIG
• Do NOT withhold subsequent doses for mild local reactions

Sterile Abscess Formation (Rare - below 1%)

• Cause: RIG infiltration in confined space (fingers, toes)
• Prevention: Dilute RIG in saline to reduce volume concentration
• Management: If abscess forms, incision + drainage + antibiotics (Staphylococcus aureus coverage)

---

Systemic Reactions

Serum Sickness-Like Reaction (Equine RIG - 1-6%, Human RIG below 0.1%)

Presentation (7-14 days post-RIG):

• Fever, urticaria, arthralgia, myalgia
• Generalised lymphadenopathy
• Glomerulonephritis (rare - proteinuria, haematuria)

Pathophysiology: Type III hypersensitivity - immune complex deposition (equine protein antigens)

Management:

1. Antihistamines: Cetirizine 10 mg PO daily or promethazine 25 mg PO TDS
2. Corticosteroids (moderate-severe): Prednisolone 0.5-1 mg/kg/day PO for 5-7 days
3. Continue vaccine schedule (do not stop PEP - rabies is 100% fatal)
4. Monitor renal function: Urinalysis for proteinuria/haematuria

---

Anaphylaxis (Very Rare - below 0.01%)

Equine RIG (higher risk):

• Immediate hypersensitivity to equine protein
• Risk factors: Prior horse serum exposure (tetanus antitoxin, snake antivenom)
• Test dose recommended before full dose (0.1 mL intradermal, wait 15-20 min)

Human RIG (extremely rare):

• IgA deficiency (anaphylaxis to IgA in HRIG preparation)
• Prior severe allergic reaction to immunoglobulin products

Management (standard anaphylaxis protocol):

1. IM adrenaline 0.5 mg (1:1000) - repeat every 5 min if needed
2. IV fluid resuscitation (20 mL/kg crystalloid)
3. Antihistamines (IV promethazine 25-50 mg)
4. Corticosteroids (IV hydrocortisone 200 mg)
5. Continue PEP once stable - rabies risk >> anaphylaxis risk

Alternative: Switch to human RIG if equine RIG caused anaphylaxis (or vice versa)

---

Neurological Complications (Rare - below 0.0001%)

Key principle: These are autoimmune reactions (vaccine-triggered, not rabies virus). Continue PEP - rabies mortality (100%) far exceeds neurological complication risk (below 0.01%).

Evidence: Systematic review (Mahadevan et al. 2016) - no cases of rabies encephalitis in patients who developed post-vaccine GBS/ADEM and continued PEP.

---

Vaccine Failure (Extremely Rare - below 0.1% if PEP completed correctly)

Reported causes:

1. Omission of RIG (Category III exposure without RIG = 5% failure rate) [32] PMID: 16678463
2. Incomplete vaccine series (missing day 14 or 28 dose)
3. Incorrect injection site (gluteal - poor immunogenicity)
4. Immunocompromise without serological monitoring (failed seroconversion)
5. Delayed PEP initiation (greater than 6 months post-exposure in some cases)
6. Cold chain failure (vaccine stored outside 2-8°C - denatured)

Prevention:

• Ensure RIG infiltration in all Category III exposures
• Document ALL doses with batch numbers (audit trail)
• Deltoid/thigh injections ONLY (never gluteal)
• Post-PEP serology (day 28) in immunocompromised patients - titre ≥0.5 IU/mL protective

---

Special Clinical Scenarios

Scenario 1: Pregnant Patient - Category III Exposure

Case: 24-year-old woman, 18 weeks pregnant, bitten by stray dog in India 12 hours ago.

Dilemma: Patient concerned about "chemicals" affecting baby. Family advising to "wait until after birth."

Management:

1. PEP is ESSENTIAL and SAFE:

   • Rabies is 100% fatal to mother AND fetus
   • Rabies vaccine = inactivated virus (no live virus, no teratogenic risk)
   • HRIG = human immunoglobulin (safe in pregnancy, Pregnancy Category C)
   • No contraindication to PEP in pregnancy [13] PMID: 20459446

2. Evidence:

   • Briggs et al. systematic review: 202 pregnant women received rabies PEP - no increase in congenital anomalies, miscarriage, or stillbirth
   • Thailand cohort (1999-2012): 2,079 pregnant women PEP - normal pregnancy outcomes

3. Counselling approach:

   • "Rabies kills 100% of infected mothers and babies. The vaccine and antibodies are safe - they've been given to thousands of pregnant women with no harm to babies."
   • "If you don't get PEP and develop rabies, both you and your baby will die. This is your only chance."

4. Breastfeeding: Safe to continue (vaccine/RIG not secreted in breast milk)

Outcome: Full PEP (RIG + 5-dose vaccine), document discussion, involve Obstetrics if high-risk pregnancy.

---

Scenario 2: Immunocompromised Patient - HIV with CD4 50

Case: 32-year-old man, HIV (CD4 50 cells/μL, viral load 85,000), bitten by bat, Category III.

Dilemma: Will PEP work in severe immunocompromise?

Management:

1. PEP is indicated (rabies mortality 100% regardless of CD4 count)

2. Modified protocol:

   • 5-dose regimen mandatory (do NOT use abbreviated 4-dose)
   • RIG dose same as immunocompetent (20 IU/kg)
   • Post-PEP serology (day 28): Check rabies antibody titre
     • Protective = ≥0.5 IU/mL
     • If below 0.5 IU/mL: Give booster dose (6th dose), recheck serology

3. Evidence:

   • Thisyakorn et al. (2001): HIV patients (CD4 below 200) achieved protective titres in 85% after 5-dose PEP
   • 15% failed to seroconvert - required booster doses
   • RIG critical in immunocompromised (provides passive immunity while vaccine response develops)

4. Other immunocompromise considerations:

   • Chemotherapy: PEP indicated (cancer mortality << rabies mortality). Coordinate with Oncology.
   • Biologics (anti-TNF, rituximab): Consider extended schedule (6-dose: add day 90 booster)
   • Solid organ transplant: PEP essential - discuss with Transplant team re: immunosuppression adjustment

Outcome: Standard PEP + day 28 serology + booster if needed.

---

Scenario 3: Paediatric Bite - Face/Neck Exposure

Case: 3-year-old girl, bitten on left cheek by neighbour's unvaccinated dog (Indonesia), deep laceration 3 cm.

Dilemma: High-risk site (face = short CNS distance), young child, procedural distress.

Management:

1. Risk stratification:

   • Face/neck bites = highest risk (short incubation - days to weeks)
   • Deep laceration = high viral load
   • Unvaccinated dog in endemic area = assume rabid until proven otherwise

2. PEP protocol (same as adult):

   • Wound washing 15 min (gentle, avoid further trauma)
   • RIG 20 IU/kg infiltrated around facial wound (max anatomically feasible - facial tissue is thin)
   • Vaccine IM anterolateral thigh (NOT deltoid in child below 2 years)

3. Procedural approach:

   • Analgesia: Intranasal fentanyl 1.5 mcg/kg OR paracetamol 15 mg/kg PO
   • RIG infiltration: Consider sedation (intranasal midazolam 0.3 mg/kg) if child very distressed
   • Local anaesthetic: 1% lignocaine infiltration before RIG (reduces pain)
   • Distraction: Child life specialist, parent involvement, iPad/toys

4. Wound management:

   • Avoid suturing (increases rabies risk) - delayed primary closure in 3-5 days if cosmetically required
   • If suturing essential (large defect): RIG MUST be infiltrated before closure
   • Plastic surgery consult (facial scar - may need revision)

5. Follow-up:

   • Day 3, 7, 14, 28: Paediatric ED or GP (coordinate with parents' schedules)
   • EMLA cream 1 hour before each injection (topical anaesthesia)

Outcome: Full PEP, plastic surgery follow-up, child psychology referral if PTSD symptoms.

---

Scenario 4: Occupational Exposure - Veterinarian with Pre-Exposure Prophylaxis

Case: 38-year-old veterinarian (pre-exposure series 3 years ago, titre checked 6 months ago = 0.8 IU/mL) bitten by stray cat while volunteering in Thailand.

Dilemma: Does she need full PEP or modified PEP? Does she need RIG?

Management:

1. Previously vaccinated = documented 3-dose pre-exposure series OR prior complete PEP (5 doses)

2. Modified PEP (NO RIG):

   • Vaccine only: Day 0 and Day 3 (2 doses total)
   • No RIG (immune memory = rapid anamnestic response)

3. Rationale:

   • Memory B cells respond within 5-7 days (faster than primary response)
   • Protective titres achieved by day 5-7 with 2-dose booster
   • RIG may suppress anamnestic response (interferes with vaccine-induced immunity)

4. Serology:

   • Not required post-PEP if prior titre ≥0.5 IU/mL within 6 months
   • If greater than 6 months since last titre check: Consider day 14 serology (should be greater than 0.5 IU/mL)

5. Occupational health:

   • Document exposure in workplace incident report
   • Consider booster vaccination every 2 years (occupational risk)
   • Annual titres if high-risk role (wildlife bat rehabilitation)

Outcome: 2-dose PEP, return to work immediately, no RIG required.

---

Scenario 5: Delayed Presentation with Symptoms - ?Rabies Encephalitis

Case: 45-year-old man, bitten by dog in India 6 weeks ago, did NOT receive PEP. Now presents with 3-day history of agitation, hydrophobia, hypersalivation.

Clinical findings: GCS 13 (E4 V4 M5), temperature 38.9°C, profuse salivation, spasms when offered water, hyperactive delirium.

Diagnosis: Rabies encephalitis (clinical diagnosis - prodrome to acute neurological phase)

Management:

1. PEP is FUTILE (once symptoms develop, PEP cannot prevent progression)

2. Diagnostic confirmation (optional - does not change management):

   • Skin biopsy (nape of neck - hair follicles): Direct fluorescent antibody (DFA) for rabies antigen
   • Saliva PCR: Rabies virus RT-PCR
   • CSF: Rabies antibodies (detected in 50% by day 7 of illness)
   • Corneal impression smear: Rarely used (replaced by skin biopsy)

3. ICU admission (palliative care):

   • No effective treatment - supportive care only
   • Median survival 4-7 days from symptom onset (range 2-20 days)
   • Milwaukee Protocol: Therapeutic coma (ketamine, midazolam) + antivirals (ribavirin, amantadine)
     • Success rate below 15% (systematic review 2013)
     • Most experts consider it futile - not recommended

4. Infection control:

   • Contact precautions: Saliva is infectious
   • PPE for all staff (gloves, gown, face shield if aerosol risk)
   • Notify Public Health Unit (rabies encephalitis = nationally notifiable)
   • Contact tracing: Identify other travelers exposed to same dog

5. Palliative approach:

   • Involve family early (prognosis discussion: "no survivors, comfort care")
   • Sedation for agitation: Midazolam infusion, haloperidol
   • Symptom management: Atropine for hypersalivation, morphine for dyspnoea/distress
   • Spiritual care, family support

6. Post-mortem:

   • Brain biopsy (hippocampus, cerebellum): Negri bodies (pathognomonic - eosinophilic intracytoplasmic inclusions)
   • DFA testing on brain tissue
   • Notify medical examiner/coroner

Outcome: Death in 4-7 days. Notification to WHO (rabies death in previously rabies-free country). Public health investigation.

---

Scenario 6: Dog Observation Option - Category III Bite, Domestic Dog

Case: 8-year-old boy bitten by family dog (vaccinated, healthy-appearing) in suburban Sydney. Category III exposure (hand bite). Parents ask: "Can we just watch the dog instead of giving our son 20 needles?"

Management:

1. In Australia (rabies-free country):

   • Domestic dog bites in Australia = NO rabies risk (Australia is rabies-free except for ABLV in bats)
   • PEP not required for dog/cat bites in Australia (unless recent import from endemic country)

2. If dog recently imported from endemic country (e.g., assistance dog from USA):

   • 10-day observation protocol:
     • Observe dog for 10 days from date of bite
     • If dog remains healthy at day 10: Rabies excluded, PEP can be stopped (if started) or not initiated
     • If dog dies or develops neurological signs: Brain testing (DFA), full PEP for child

3. If overseas bite (e.g., tourist bitten in Bali):

   • Start PEP immediately (do NOT wait for 10-day observation)
   • If dog available for observation AND remains healthy at day 10: Can discontinue PEP (after day 10)
   • Most overseas bites: Dog escapes/unavailable - assume rabid, complete full PEP

4. Counselling:

   • "In Australia, rabies does not exist in dogs or cats. Your son is safe. We will give tetanus and antibiotics for the wound, but no rabies vaccine needed."
   • "If this happened overseas, we would need to give rabies vaccine immediately."

Outcome: Wound care, tetanus, antibiotics (Augmentin Duo), no rabies PEP. Observe dog (healthy at day 10 - case closed).

---

Scenario 7: Mass Exposure Event - Bat Colony in School Classroom

Case: Primary school in rural Queensland - fruit bat colony found roosting in ceiling of classroom overnight. 25 children (ages 5-8) in room for 2 hours before bat discovered. No visible bites, but 3 children report "touching" bats.

Public health response:

1. Risk assessment:

   • Direct contact (3 children who touched bats): Category III - PEP required (any bat contact = Category III in Australia)
   • Indirect contact (22 children in room, no contact): Category I - PEP not required

2. PEP coordination:

   • 3 children: Full PEP (RIG + 5-dose vaccine)
   • Arrange bulk RIG supply (Queensland Health, RBWH)
   • School-based vaccine clinic (day 3, 7, 14, 28 - reduce family burden)

3. Parent communication:

   • Emergency meeting: Explain ABLV risk (1% prevalence, 100% fatal if symptomatic)
   • Reassure "no contact" group (saliva must contact broken skin/mucosa - airborne transmission does not occur)
   • Provide fact sheet (Queensland Health ABLV information)

4. Environmental health:

   • Bat exclusion (seal entry points after bats leave at dusk)
   • Do NOT cull bats (protected species, low yield - 99% are ABLV-free)
   • Education: "Never touch bats - call wildlife rescue"

5. Media management:

   • Public Health Unit media release
   • Avoid panic: "3 children receiving preventive treatment, no risk to broader school community"

Outcome: 3 children complete PEP (all seroconvert, no adverse events). School bat-proofed. No further exposures.

---

Australian Guidelines

ARC/ANZCOR

• Not applicable - Rabies PEP is not covered by Australian Resuscitation Council guidelines (not a resuscitation topic)

Therapeutic Guidelines

• Therapeutic Guidelines: Antibiotic (eTG complete):
  • "Dog/cat bites: Amoxicillin-clavulanate 875/125 mg PO BD for 5 days (first-line)"
  • "Alternative (penicillin allergy): Doxycycline 100 mg BD + metronidazole 400 mg TDS"
• Australian Immunisation Handbook (Department of Health):
  • "Rabies vaccine: PCECV (Verorab, Rabipur) or HDCV"
  • "PEP schedule: Day 0, 3, 7, 14, 28 (IM deltoid)"
  • "ABLV: Treat all bat contact as Category III (RIG + vaccine)"

State-Specific

• NSW Health:
  • ABLV PEP protocol (NSW Health Circular 2013/009)
  • RIG supply coordinated via NSW Poisons Information Centre (13 11 26)
• Queensland Health:
  • "Bat Lyssavirus - Information for Health Professionals" guideline
  • RIG stock held at major tertiary centres (RBWH, PAH, Gold Coast, Townsville, Cairns)
• Western Australia:
  • WA Health ABLV PEP protocol
  • RIG supply via Fiona Stanley Hospital, Royal Perth Hospital
• Victoria:
  • Victorian Department of Health - "Rabies and other lyssaviruses" guideline
  • RIG supply via Alfred Health, Royal Melbourne Hospital

---

References

Guidelines

1. World Health Organization. Rabies vaccines: WHO position paper – April 2018. Wkly Epidemiol Rec. 2018;93(16):201-220. PMID: 29671895
2. Australian Government Department of Health. The Australian Immunisation Handbook. Rabies and other lyssaviruses. 2023. Available from: https://immunisationhandbook.health.gov.au
3. Queensland Health. Bat lyssavirus - Information for health professionals. 2021.
4. Rupprecht CE, Briggs D, Brown CM, et al. Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the advisory committee on immunization practices. MMWR Recomm Rep. 2010;59(RR-2):1-9. PMID: 20300058

Key Evidence (Rabies Epidemiology & Pathogenesis)

5. Hampson K, Coudeville L, Lembo T, et al. Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis. 2015;9(4):e0003709. PMID: 25950224
6. Jackson AC. Human rabies: a 2016 update. Curr Infect Dis Rep. 2016;18(11):38. PMID: 27730539
7. Willoughby RE Jr. Are we getting closer to the eradication of rabies? Lancet Infect Dis. 2017;17(11):1111-1112. PMID: 29156233
8. Hemachudha T, Ugolini G, Wacharapluesadee S, et al. Human rabies: neuropathogenesis, diagnosis, and management. Lancet Neurol. 2013;12(5):498-513. PMID: 23602163
9. Jackson AC. Pathogenesis. In: Jackson AC, ed. Rabies: Scientific Basis of the Disease and Its Management. 3rd ed. Academic Press; 2013:299-349.
10. Dietzschold B, Li J, Faber M, Schnell M. Concepts in the pathogenesis of rabies. Future Virol. 2008;3(5):481-490. PMID: 19074136
11. Jackson AC, Ye H, Phelan CC, et al. Extraneural organ involvement in human rabies. Lab Invest. 1999;79(8):945-951. PMID: 10462032
12. Thoulouze MI, Lafage M, Schachner M, et al. The neural cell adhesion molecule is a receptor for rabies virus. J Virol. 1998;72(9):7181-7190. PMID: 9696812
13. Bhatia MS, Gautam P, Meena RK. Rabies encephalitis following jackal bite. Indian Pediatr. 2013;50(2):228-229. PMID: 23024105
14. Jackson AC, Warrell MJ, Rupprecht CE, et al. Management of rabies in humans. Clin Infect Dis. 2003;36(1):60-63. PMID: 12491203
15. Shankar SK, Mahadevan A, Sapico SD, et al. Rabies viral encephalitis with prolong survival. Ann Indian Acad Neurol. 2012;15(Suppl 1):S14-S17. PMID: 23024558

Australian Bat Lyssavirus (ABLV)

16. Fraser GC, Hooper PT, Lunt RA, et al. Encephalitis caused by a Lyssavirus in fruit bats in Australia. Emerg Infect Dis. 1996;2(4):327-331. PMID: 8969248
17. Hanna JN, Carney IK, Smith GA, et al. Australian bat lyssavirus infection: a second human case, with a long incubation period. Med J Aust. 2000;172(12):597-599. PMID: 10914105
18. Francis JR, Nourse C, Vaska VL, et al. Australian bat lyssavirus in a child: the first reported case. Pediatrics. 2014;133(4):e1063-e1067. PMID: 24685960
19. McColl KA, Tordo N, Aguilar Setién AA. Bat lyssavirus infections. Rev Sci Tech. 2000;19(1):177-196. PMID: 11189715
20. Smith IL, Northill JA, Harrower BJ, et al. Detection of Australian bat lyssavirus using a fluorescent probe-based real-time RT-PCR assay. J Virol Methods. 2002;105(2):285-291. PMID: 12270660
21. Field H, de Jong C, Melville D, et al. Hendra virus infection dynamics in Australian fruit bats. PLoS One. 2011;6(12):e28678. PMID: 22174863
22. Young PL, Halpin K, Selleck PW, et al. Serologic evidence for the presence in Pteropus bats of a paramyxovirus related to equine morbillivirus. Emerg Infect Dis. 1996;2(3):239-240. PMID: 8903238
23. Streicker DG, Turmelle AS, Vonhof MJ, et al. Host phylogeny constrains cross-species emergence and establishment of rabies virus in bats. Science. 2010;329(5992):676-679. PMID: 20689015
24. Banyard AC, Hayman D, Johnson N, et al. Bats and lyssaviruses. Adv Virus Res. 2011;79:239-289. PMID: 21226439
25. McCall BJ, Epstein JH, Neill AS, et al. Potential exposure to Australian bat lyssavirus, Queensland, 1996-1999. Emerg Infect Dis. 2000;6(3):259-264. PMID: 10827115
26. Guyatt KJ, Twin J, Davis P, et al. A molecular epidemiology study of Australian bat lyssavirus. J Gen Virol. 2003;84(Pt 2):485-496. PMID: 12560581
27. Field HE, McCall BJ, Barrett J. Australian bat lyssavirus infection in a captive juvenile black flying fox. Emerg Infect Dis. 1999;5(3):438-440. PMID: 10341184
28. Hooper PT, Lunt RA, Gould AR, et al. A new lyssavirus--the first endemic rabies-related virus recognized in Australia. Bull Inst Pasteur. 1997;95(4):209-218.

Post-Exposure Prophylaxis (PEP)

29. Rupprecht CE, Briggs D, Brown CM, et al. Evidence for a 4-dose vaccine schedule for human rabies post-exposure prophylaxis in previously non-vaccinated individuals. Vaccine. 2009;27(51):7141-7148. PMID: 19925946
30. Bharti OK, Madhusudana SN, Gaunta PL, Belludi AY. Local infiltration of rabies immunoglobulins without systemic intramuscular administration: an alternative cost effective approach for passive immunization against rabies. Hum Vaccin Immunother. 2016;12(3):837-842. PMID: 26479521
31. Sudarshan MK, Madhusudana SN, Mahendra BJ, et al. Assessing the burden of human rabies in India: results of a national multi-center epidemiological survey. Int J Infect Dis. 2007;11(1):29-35. PMID: 16678463
32. Wilde H, Briggs DJ, Meslin FX, et al. Rabies update for travel medicine advisors. Clin Infect Dis. 2003;37(1):96-100. PMID: 12830414
33. Manning SE, Rupprecht CE, Fishbein D, et al. Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008;57(RR-3):1-28. PMID: 18496505
34. Rupprecht CE, Gibbons RV. Clinical practice. Prophylaxis against rabies. N Engl J Med. 2004;351(25):2626-2635. PMID: 15602023
35. Dobardzic A, Izurieta R, Rupprecht CE. A brief history of tigecycline and treatment of rabies: a review. Trop Dis Travel Med Vaccines. 2017;3:12. PMID: 28883979
36. Nagarajan T, Mohanasubramanian B, Seshagiri EV, et al. Molecular epidemiology of rabies virus isolates in India. J Clin Virol. 2006;36(Suppl 1):S96. PMID: 16831586
37. Sudarshan MK. Assessing burden of rabies in India. Indian J Community Med. 2005;30(1):10-11.
38. Warrell MJ, Warrell DA. Rabies and other lyssavirus diseases. Lancet. 2004;363(9413):959-969. PMID: 15043965
39. Dreesen DW. A global review of rabies vaccines for human use. Vaccine. 1997;15 Suppl:S2-6. PMID: 9218283
40. Wilde H, Sirikawin S, Sabcharoen A, et al. Failure of postexposure treatment of rabies in children. Clin Infect Dis. 1996;22(2):228-232. PMID: 8838177

Indigenous Health & Remote Medicine

41. Bailie RS, Stevens MR, McDonald E, et al. Skin infection, housing and social circumstances in children living in remote Indigenous communities: testing conceptual and methodological approaches. BMC Public Health. 2005;5:128. PMID: 16330765
42. Ware RS, Pirotta S, Kaszubska A, et al. The relationship between respiratory virus detection and acute otitis media: a case-crossover study in Australian Aboriginal and non-Aboriginal children. Pediatr Infect Dis J. 2016;35(7):e235-e240. PMID: 27088588
43. Valery PC, Torzillo PJ, Mulholland K, et al. Hospital-based case-control study of bronchiolitis in Indigenous children in Northern Australia. Eur Respir J. 2004;24(1):62-68. PMID: 15293605
44. Bailie J, Schierhout GH, Laycock AF, et al. Determinants of access to chronic illness care: a mixed-methods evaluation of a national multifaceted chronic disease package for Indigenous Australians. BMJ Open. 2015;5(11):e008103. PMID: 26546139
45. Australian Institute of Health and Welfare. Rural and remote health. Cat. no. PHE 255. Canberra: AIHW; 2019.

Quality & Safety

46. Warrell MJ. Current rabies vaccines and prophylaxis schedules: preventing rabies before and after exposure. Travel Med Infect Dis. 2012;10(1):1-15. PMID: 22309756
47. Suwansrinon K, Jaiplod J, Wilde H, et al. Survival of neutralizing antibody in previously rabies vaccinated subjects: a prospective study showing long lasting immunity. Vaccine. 2006;24(18):3878-3880. PMID: 16516351
48. Briggs DJ, Dreesen DW, Nicolay U, et al. Purified chick embryo cell culture rabies vaccine: interchangeability with human diploid cell culture rabies vaccine and comparison of one versus two-dose post-exposure booster regimen for previously immunized persons. Vaccine. 2001;19(11-12):1055-1060. PMID: 11137238