Multisystem Processes & Disorders

Rabies: post-exposure prophylaxis decision

Clinical Overview and When to Suspect Rabies Exposure

— Bats account for the majority of US human rabies deaths; bite may be unnoticed (tiny puncture, no pain).

— Small rodents (squirrels, rats, mice, chipmunks, rabbits) and lagomorphs are essentially never rabid — PEP almost never indicated.

— Bite/scratch from a wild carnivore or bat, regardless of provocation

— Bite from a stray or ill-appearing dog/cat/ferret unavailable for observation

— Bat found in room with a sleeping person, unattended child, or intoxicated/cognitively impaired adult — treat as exposure even without visible bite

— Saliva contact with open wound or mucous membrane (rare transmission via organ transplant has occurred)

Board pearl: A patient who wakes up to find a bat in the bedroom and cannot reliably exclude contact is considered exposed — give full PEP even with no visible wound. This is one of the most testable single-line facts in Step 3 emergency medicine. Do not delay PEP awaiting animal testing if the animal is unavailable or high-risk species.

Rabies is a nearly 100% fatal encephalitis caused by a neurotropic lyssavirus (RNA, Rhabdoviridae) transmitted via saliva of infected mammals through bite, scratch, or mucous membrane/non-intact skin contact.

Incubation period: typically 1–3 months (range 5 days to >1 year); longer with bites distal to CNS (hand, foot) vs. shorter with face/neck bites or high inoculum.

In the United States, the dominant reservoirs are bats, raccoons, skunks, and foxes; dogs cause <1% of US human cases (but dominate globally, especially Asia/Africa).

Suspect rabies exposure when:

Once clinical symptoms appear (hydrophobia, aerophobia, agitation, paralysis, autonomic instability), survival is exceptional (<20 documented worldwide). Prevention via timely PEP is the only effective strategy.

Presentation Patterns and Key History

— Animal species (bat, raccoon, skunk, fox, coyote vs. dog/cat/ferret vs. rodent/rabbit)

— Domestic vs. wild, vaccination status of pet, ability to observe or test the animal

— Geography (US vs. travel to canine-rabies-endemic country — India, Philippines, sub-Saharan Africa)

— Provoked vs. unprovoked (unprovoked attack raises concern; provoked dog bite during feeding is lower-risk)

— Exposure type: bite (highest risk), scratch with saliva, mucous membrane/open wound saliva contact, bat in bedroom scenario

— Patient immunization history — previously vaccinated (pre-exposure prophylaxis or prior PEP) vs. naïve

— Prodrome (2–10 days): fever, malaise, paresthesias or pain at bite site (pathognomonic clue)

— Encephalitic ("furious") form (~80%): hydrophobia, aerophobia, pharyngeal spasms with swallowing, hypersalivation, hyperactivity alternating with lucidity, autonomic instability

— Paralytic ("dumb") form (~20%): ascending flaccid paralysis mimicking Guillain-Barré

— Coma and death from respiratory/cardiac failure within 7–14 days of symptom onset

Step 3 management: When the stem gives a bat exposure with uncertain contact, do not ask "was there a bite?" — give PEP. When it gives a healthy vaccinated dog that bit a child, observe the dog 10 days; only initiate PEP if the dog develops signs of illness. These two algorithms drive most exam items.

Most "rabies questions" on Step 3 are actually post-exposure decision stems — the patient is asymptomatic and you must decide whether to give PEP, not diagnose encephalitis.

Critical history elements to extract from the stem:

Symptomatic rabies (rare on exam, but classic):

Physical Exam Findings (and Wound Assessment)

— Location (face/neck/hand bites are higher risk and closer to CNS — shorter incubation expected)

— Depth and number of puncture wounds vs. superficial scratch

— Signs of infection (erythema, purulence, lymphangitis) — bites are polymicrobial; Pasteurella multocida (cats > dogs), Capnocytophaga canimorsus (asplenic patients), anaerobes

— Tendon, joint, nerve, or bone involvement → hand surgery consult

— Hydrophobia: violent pharyngeal/diaphragmatic spasm at sight or attempt to swallow water

— Aerophobia: similar spasm triggered by a puff of air across the face

— Hypersalivation, lacrimation, piloerection (autonomic storm)

— Hyperreflexia, fasciculations, priapism, cardiac arrhythmias

— Paralytic form: areflexia, ascending weakness, bladder dysfunction

CCS pearl: On a CCS case of a dog bite, your opening orders should include: irrigate wound copiously with soap and water (and povidone-iodine), assess tetanus status, document neurovascular exam, photograph wound, and obtain the animal's vaccination and observation status from animal control. Rabies PEP decision flows from these data.

Key distinction: Wound irrigation with soap and water for ≥15 minutes is itself a powerful rabies risk-reduction step — reduces transmission risk substantially even before immunoglobulin/vaccine. Never skip it because you "ordered PEP."

In the asymptomatic exposed patient (the typical Step 3 stem), exam focuses on wound characterization, not neurologic findings.

Wound assessment elements:

Symptomatic rabies exam (low-yield on Step 3 but classic):

Vital sign trajectory in clinical rabies: fever, tachycardia, labile BP, tachypnea progressing to apnea.

Diagnostic Workup — Initial Evaluation

— Direct fluorescent antibody (DFA) testing of brain tissue is the gold standard — sensitive, specific, available through state public health labs within 24–48 hours

— A negative DFA in the biting animal allows discontinuation of PEP already started

— Wild carnivores (bat, raccoon, skunk, fox) caught at the scene → euthanize and test immediately; do not observe

— Healthy dogs, cats, ferrets → 10-day confinement and observation; if animal remains healthy, no PEP needed (or PEP can be stopped)

— Antemortem testing requires multiple specimens: nuchal skin biopsy (immunofluorescence of hair follicle nerves — most sensitive), saliva RT-PCR (serial samples), serum/CSF antibody (positive only late, after BBB breach)

— CSF: lymphocytic pleocytosis, elevated protein, normal glucose (nonspecific encephalitis pattern)

— MRI brain: T2 hyperintensities in brainstem, hippocampus, hypothalamus (late finding)

Board pearl: Do not delay PEP to obtain serology in the exposed patient — PEP is started on exposure history, not testing. Conversely, if the biting dog is healthy and observable, you can defer PEP during the 10-day window. Both decisions are tested.

Step 3 management: Always report animal bites to local animal control / public health — this is the mechanism that enables testing and observation and is a mandatory step in the CCS workflow.

For the exposed but asymptomatic patient, there is no diagnostic test to determine if transmission occurred — decision is made on exposure risk assessment alone.

Animal testing (when animal is available and euthanasia is permissible):

For the symptomatic patient (suspected clinical rabies):

Routine labs in bite victims: CBC, basic chemistries, wound culture if infected, tetanus status review, HIV/hepatitis risk if human bite.

Diagnostic Workup — Advanced or Confirmatory Studies

— Saliva RT-PCR (×3 specimens, ≥3 hours apart) — detects viral RNA

— Nuchal skin biopsy (full thickness with hair follicles) for direct fluorescent antibody and RT-PCR

— Serum rabies antibody — positive only after ~8 days of illness in unvaccinated patient

— CSF rabies antibody — highly specific when positive (indicates intrathecal production)

— MRI may show ill-defined T2/FLAIR hyperintensity in brainstem, thalamus, hippocampus, and spinal cord gray matter; gadolinium enhancement appears only after BBB compromise late in disease

— EEG: nonspecific encephalopathic slowing

— All suspected human rabies cases are reportable to state health departments and CDC

— Specimens shipped to CDC Rabies Laboratory for confirmatory typing (helps identify the viral variant — bat vs. canine vs. raccoon variant — for epidemiologic tracking)

Key distinction: A single negative test does not rule out rabies in a symptomatic patient — sensitivity of each modality is moderate, so serial sampling across multiple tissues is required. In contrast, a single positive test (PCR, DFA, or CSF antibody) is sufficient to confirm.

Board pearl: The Milwaukee protocol (induced coma + antivirals) is not recommended — survival rate is dismal and it has been removed from guideline endorsement. Focus on prevention, not rescue.

In suspected clinical rabies, no single test is sufficient — CDC recommends a combined panel:

Postmortem confirmation: DFA of brain tissue (brainstem and cerebellum) — definitive. Negri bodies on histology are classic but neither sensitive nor specific enough for diagnosis alone.

Imaging:

Public health workflow:

Differential testing in suspected paralytic rabies: GBS workup (LP for albuminocytologic dissociation, NCS/EMG), arboviral encephalitis panel (WNV, EEE), HSV PCR, autoimmune encephalitis antibodies.

Risk Stratification — The Core PEP Decision Algorithm

— Bite with skin penetration: yes

— Scratch, abrasion, or open wound contaminated with saliva: yes

— Mucous membrane contact with saliva/neural tissue: yes

— Bat in bedroom with sleeping/impaired person who cannot exclude contact: yes, treat as exposure

— Petting animal, contact with blood/urine/feces, intact skin contact: not an exposure

— High risk (always give PEP unless animal tests negative): bat, raccoon, skunk, fox, coyote, most wild carnivores, woodchuck

— Observation category: healthy domestic dog, cat, ferret → observe 10 days

— Negligible risk: small rodents (squirrels, rats, mice, hamsters, gerbils), rabbits, hares — PEP almost never indicated; consult public health if unusual

— Livestock, large rodents (woodchucks/groundhogs): case-by-case, often PEP

— Wild high-risk animal captured → euthanize and test; if negative, no/stop PEP

— Wild high-risk animal escaped → assume rabid, give PEP

— Domestic dog/cat/ferret healthy and observable → withhold PEP pending 10-day observation

— Domestic animal sick, behaving abnormally, or unavailable → start PEP, test if possible

Step 3 management: Memorize the 10-day rule for dogs/cats/ferrets and the "all bats get PEP" rule. These two heuristics correctly answer the majority of Step 3 rabies questions. When in doubt, call the state health department — this is an accepted answer choice.

Decision rests on three variables: animal species, animal availability/health status, and exposure type.

Step 1 — Was there a true exposure?

Step 2 — What is the animal?

Step 3 — Is the animal available?

Pharmacotherapy — PEP Regimen in the Unvaccinated Patient

— Dose: 20 IU/kg, given once on day 0

— Administration: infiltrate as much as anatomically feasible into and around the wound(s); any remaining volume given IM at a site distant from the vaccine (e.g., gluteal or anterolateral thigh)

— Do not exceed the calculated dose (saturates antibody response to vaccine)

— If HRIG is unavailable on day 0, it may be given up to day 7 after the first vaccine dose; after day 7, do not give (endogenous antibody response active)

— 4-dose IM series in deltoid (anterolateral thigh in young children): days 0, 3, 7, and 14

— Immunocompromised patients receive a 5th dose on day 28 and should have post-series antibody titers checked

— Never inject vaccine in the gluteal region (reduced immunogenicity)

— HRIG and vaccine must go in different anatomic sites with different syringes

— Copious irrigation with soap/water and virucidal agent (povidone-iodine)

— Tetanus prophylaxis per standard wound-management table

— Empiric amoxicillin-clavulanate for high-risk bites (cat bites, hand bites, deep punctures, immunocompromised, asplenic, delayed presentation)

Board pearl: The 4-dose schedule (0, 3, 7, 14) replaced the older 5-dose regimen in 2010 (ACIP) for immunocompetent patients. The classic abdominal injection series is obsolete — pick deltoid IM on the exam.

Standard US PEP for a previously unvaccinated person consists of two components given concurrently on day 0:

1. Human Rabies Immunoglobulin (HRIG) — passive immunity

2. Rabies vaccine (HDCV — human diploid cell vaccine, or PCECV — purified chick embryo cell vaccine) — active immunity

Wound care adjuncts:

Pharmacotherapy — PEP in the Previously Vaccinated Patient and Pre-Exposure Prophylaxis

— Do NOT give HRIG — would blunt anamnestic response and is unnecessary

— Give 2 vaccine doses only: day 0 and day 3 IM in deltoid

— Still perform wound care, tetanus update, antibiotic prophylaxis as indicated

— Indications: veterinarians, animal handlers, wildlife biologists, spelunkers/cavers, rabies laboratory workers, travelers to canine-rabies-endemic regions with limited medical access

— Updated 2022 ACIP schedule: 2-dose IM series on days 0 and 7

— Titer monitoring: routine workers every 2 years; lab workers every 6 months; booster if titer <0.5 IU/mL by RFFIT

— PrEP does not eliminate the need for post-exposure boosters — it simplifies them (2 doses, no HRIG)

— Local pain, erythema, swelling at injection site (most common)

— Mild systemic: headache, nausea, myalgias, low-grade fever

— Rare: serum sickness-like reaction (~6% with booster doses of HDCV), neurologic events extremely rare with modern cell-culture vaccines

— Anaphylaxis is rare — even with prior reaction, PEP is not contraindicated; manage with antihistamines/epinephrine standby and complete the series (rabies is universally fatal)

Key distinction: Vaccinated patient gets 2 doses, no HRIG. Unvaccinated patient gets 4 doses + HRIG. This single distinction is among the highest-yield items on Step 3.

Previously vaccinated patient (completed pre-exposure prophylaxis, prior full PEP, or documented adequate titer) who has a new exposure:

Pre-exposure prophylaxis (PrEP) — for high-risk individuals before any exposure:

Adverse effects of rabies vaccine:

Pregnancy, infancy, immunosuppression, anticoagulation: none are contraindications to PEP. Switch to SC injection in anticoagulated patients if IM bleeding risk is prohibitive.

Special Populations — Elderly and Renal/Hepatic Impairment

— Immunosenescence may blunt vaccine response; consider checking post-series antibody titer (RFFIT ≥0.5 IU/mL is protective) in patients >65 or with comorbidities suggesting immune compromise

— Higher risk of bacterial superinfection of bite wounds — lower threshold for amoxicillin-clavulanate

— Polypharmacy: review for immunosuppressive medications (prednisone ≥20 mg/day, biologics, chemotherapy) that warrant the 5-dose schedule plus titer confirmation

— Use smallest-gauge needle, firm pressure ×5 min, deltoid site

— Do not withhold PEP — rabies is fatal; bleeding risk is manageable

Step 3 management: In an immunocompromised exposure patient (HIV with low CD4, transplant on tacrolimus, chemotherapy), give the 5-dose schedule (days 0, 3, 7, 14, 28) AND check rabies neutralizing antibody titer 1–2 weeks after the last dose. If <0.5 IU/mL by RFFIT, give a booster dose. This is the only common scenario in which titer testing is routinely required after PEP.

Board pearl: There is no upper age limit, weight limit, or organ-function threshold that contraindicates rabies PEP. Universal fatality of clinical disease overrides standard risk-benefit calculus.

Rabies PEP has no dose adjustment for renal or hepatic impairment — both HRIG and vaccine are biologics not cleared by these organs.

Elderly considerations:

Chronic kidney disease, dialysis: standard PEP regimen; monitor injection sites for hematoma if on anticoagulation; SC route acceptable if IM contraindicated

Cirrhosis/hepatic failure: standard regimen; coagulopathy may again favor SC injection with pressure

Anticoagulated patients (warfarin, DOACs):

Asplenic patients with dog/cat bites — start amoxicillin-clavulanate empirically due to Capnocytophaga canimorsus risk (fulminant sepsis), separate from rabies considerations.

Special Populations — Pregnancy and Pediatrics

— Rabies PEP (HRIG + vaccine) is NOT contraindicated at any trimester

— No documented fetal harm from HDCV/PCECV or HRIG

— Withholding PEP in a pregnant exposure patient is a guideline violation — universal fatality of rabies outweighs any theoretical concern

— Pregnancy is not an indication for pre-exposure prophylaxis, but does not preclude it

— Same 4-dose schedule and HRIG dose (20 IU/kg) — pediatric dosing is weight-based for HRIG only

— Vaccine: full 1 mL IM in anterolateral thigh for infants/toddlers; deltoid when muscle mass adequate (typically ≥1 year)

— Bat exposures in children are particularly important: a child unable to provide reliable history of contact with a bat found in living quarters constitutes a presumed exposure → give PEP

— Same applies to mentally incapacitated or intoxicated adults

— Returning travelers from canine-endemic regions with dog/monkey bites: PEP per standard algorithm

— Many international destinations have limited HRIG availability — counsel high-risk travelers about PrEP before departure

CCS pearl: A 4-year-old who was found playing with a dead bat in the yard, with no witnessed bite — order rabies PEP (HRIG 20 IU/kg infiltrated around any wound/site plus IM remainder, plus vaccine days 0, 3, 7, 14), tetanus update, and notify public health. Do not "reassure and observe" — this is a trap answer.

Key distinction: In children, weight-based HRIG can produce a small volume — infiltrate as much as possible at the wound; any remainder IM. Do not dilute HRIG to a larger volume routinely (acceptable only when wound site is small and dilution is needed for adequate infiltration, e.g., fingertips).

Pregnancy:

Pediatrics:

Breastfeeding: PEP is fully compatible — continue nursing.

Travelers and international adoption:

Complications and Adverse Outcomes

— Clinical rabies is virtually 100% fatal once symptoms manifest; mean survival 7–14 days from prodrome

— Encephalitic form: agitation, hydrophobia, autonomic storm, cardiac arrhythmia, respiratory failure

— Paralytic form: ascending paralysis, respiratory muscle failure, bladder/bowel dysfunction

— No effective antiviral; aggressive supportive care does not change outcome

— Local reactions at injection site: pain, erythema, induration (~25%); usually self-limited

— Systemic vaccine reactions: low-grade fever, headache, myalgia, nausea (~5–15%)

— Serum sickness-like reaction: ~6% with booster HDCV; urticaria, arthralgia, fever 2–21 days after dose; treat with antihistamines, NSAIDs, brief corticosteroid course; complete the series

— Anaphylaxis: rare; manage acutely, premedicate with antihistamines and continue series under monitored conditions — do not abandon PEP

— HRIG: pain at infiltration site, low risk of viral transmission (modern HRIG screened/processed)

— Bacterial infection: cellulitis, abscess, septic arthritis, osteomyelitis, tenosynovitis

— Pasteurella multocida (rapid-onset cellulitis after cat/dog bite), Capnocytophaga canimorsus (asplenic sepsis), Eikenella corrodens (human bites), Bartonella henselae (cat scratch)

— Tetanus, tendon/nerve injury, scarring, functional impairment (especially hand)

Board pearl: The most common preventable cause of human rabies death in the US is failure to recognize bat exposure — a sleeping person and a bat in the room is exposure until proven otherwise. The exam will test this exact scenario.

Of the disease itself (when PEP is omitted or delayed):

Of PEP administration:

Of bite wounds themselves:

System-level adverse outcomes: missed exposure (bat in bedroom dismissed), failure to give HRIG, vaccine given in gluteal site, mistakenly using IG dose >20 IU/kg.

When to Escalate Care — Consultation and Reporting

— Severe wound requiring operative debridement, complex repair, or hand surgery

— Established bite-wound infection with systemic signs (sepsis, deep space infection)

— Asplenic patient with cat/dog bite (concern for fulminant Capnocytophaga)

— Anaphylactic reaction to PEP requiring monitored re-challenge

— State or local public health department — for every animal bite; mandatory reporting in most states; assists with animal testing and PEP availability

— Infectious disease — atypical exposures, immunocompromised patients, PEP failure concerns, suspected clinical rabies

— Hand/plastic surgery — hand bites, tendon involvement

— Pediatrics or social work — child bite victim, suspected animal cruelty/neglect

— CDC Rabies Duty Officer (24/7) — complex cases, organ-donor exposure concerns, vaccine shortage

— ICU admission for supportive care, airway protection, sedation

— Strict contact/droplet precautions for staff handling saliva, CSF, respiratory secretions

— Identify and offer PEP to exposed contacts (family, healthcare workers with mucous-membrane or non-intact skin exposure to saliva)

— Notify state health department and CDC immediately; coordinate testing

CCS pearl: Order "Notify public health / animal control" as part of every animal-bite CCS case. This is a graded order item that captures both the legal mandatory-reporting requirement and the practical need to obtain animal observation/testing.

Step 3 management: Healthcare workers caring for a suspected rabies patient receive PEP only if they had mucous-membrane or non-intact skin exposure to saliva/CSF/neural tissue — not from routine patient care contact.

Inpatient admission is rarely required for PEP itself — most exposures are managed in the ED with outpatient completion of the vaccine series.

Admission indications related to the bite:

Consultations to consider:

Suspected clinical rabies (symptomatic patient):

Key Differentials — Within the Encephalitis/Bite-Related Category

— Temporal lobe predilection on MRI, RBC-rich CSF, treat empirically with acyclovir while CSF HSV PCR pending

— Most common cause of sporadic viral encephalitis in the US — must be ruled out before assuming rabies

— Seasonal (summer/fall), mosquito or tick vector

— West Nile may cause flaccid paralysis mimicking paralytic rabies — distinguish by exposure history and serology

— Trismus, opisthotonos, muscle rigidity after wound — can mimic rabies spasms

— Key distinction: tetanus has sustained rigidity between spasms and no encephalopathy/hydrophobia; rabies patients are lucid between agitation episodes early on

— Ascending paralysis mimics paralytic rabies

— CSF: albuminocytologic dissociation (high protein, normal cells)

— No fever, no encephalopathy, no animal exposure history

— Neutrophilic CSF, low glucose; rapid response to empiric antibiotics

— Psychiatric symptoms, seizures, dyskinesias; antibody panels; tumor associations

— Responds to immunotherapy — important not to miss

— Pasteurella multocida (rapid cellulitis after cat bite)

— Capnocytophaga canimorsus (asplenic sepsis after dog bite)

— Bartonella henselae (cat scratch — regional lymphadenopathy)

— Streptobacillus moniliformis (rat-bite fever)

Board pearl: A patient with progressive encephalitis after a bat exposure — empirically start acyclovir to cover HSV while pursuing rabies workup; the two cannot be distinguished clinically early on.

When symptomatic rabies is suspected, the differential includes other infectious encephalitides and post-infectious processes:

Herpes simplex encephalitis

Arboviral encephalitides (West Nile, Eastern Equine, St. Louis, Powassan, La Crosse)

Tetanus

Guillain-Barré syndrome

Bacterial meningoencephalitis (Listeria, Streptococcus, Neisseria)

Autoimmune encephalitis (NMDA-receptor, LGI1)

Wound-related infections in the exposed but asymptomatic patient:

Key Differentials — Other Categories

— Anticholinergic toxicity: agitation, hyperthermia, mydriasis, dry skin — mimics autonomic hyperactivity

— Sympathomimetic intoxication (cocaine, methamphetamine): agitation, tachycardia, hypertension

— Alcohol withdrawal / delirium tremens: tremor, agitation, autonomic storm — but history of EtOH cessation

— Serotonin syndrome / neuroleptic malignant syndrome: drug exposure, hyperreflexia/rigidity, hyperthermia

— Acute psychosis, conversion disorder — but lack the autonomic and progressive trajectory of rabies

— Hepatic encephalopathy, uremic encephalopathy, hyponatremia, hypoglycemia — screen with metabolic panel, ammonia, glucose

— Stroke, brainstem hemorrhage, posterior reversible encephalopathy syndrome — MRI distinguishes

— Healthy domestic dog bite during play → observe dog 10 days, defer PEP

— Pet rabbit / hamster nip → no PEP (negligible-risk species)

— Bat fly-by in open outdoor space, no contact → no PEP

— Touching a roadkill skunk with bare hands, no mucous membrane or wound contact → no PEP, but wash hands; counsel

— Vaccinated indoor cat scratch during play, cat available and healthy → observe cat, defer PEP

Key distinction: The exam may try to trick you with a squirrel bite or mouse bite — these are negligible-risk rodents and PEP is not indicated regardless of provocation status. Reassure, irrigate, update tetanus, and discharge.

Step 3 management: When facing a borderline scenario (woodchuck, ferret outside the 10-day rule, bat that flew through an open window), consult the state health department — this is always an acceptable answer and reflects real practice.

Drug toxicity / withdrawal:

Psychiatric:

Metabolic encephalopathies:

Structural CNS lesions:

Rabies-related decision differentials (when deciding whether to give PEP):

Secondary Prevention / Discharge Plan / Long-Term Considerations

— Provide a written schedule with specific dates and times

— Identify a single site (primary care office, urgent care, or health department) for subsequent doses to avoid scheduling errors

— Document doses in state immunization registry

— Re-evaluate wound at 48–72 hours for signs of infection

— Suture decision: high-risk bites (hand, puncture, cat bite, >12 hours old) are generally left open or loosely approximated; facial bites may be primarily closed after thorough irrigation due to cosmetic priority

— Tetanus booster if last dose >5 years (≥10 years for clean wounds; ≥5 years for dirty/bite wounds); Tdap if not yet received as adult booster

— TIG (tetanus immunoglobulin) only if never vaccinated or unknown status with a high-risk wound

— Cat bites (always)

— Hand, foot, face bites; deep punctures

— Bites near joints/bones

— Immunocompromised, asplenic, cirrhotic patients

— Delayed presentation (>8–12 hours)

— Crush injuries with significant devitalized tissue

Board pearl: Adherence to the full 4-dose vaccine schedule is essential — a single missed or delayed dose does not require restarting the series if completed within a reasonable window; resume as soon as possible and document.

Step 3 management: Schedule the day-3 and day-7 follow-up before discharge — transitions of care are a tested patient-safety point.

After the day-0 ED encounter, the patient must reliably complete the vaccine series on days 3, 7, and 14 (plus day 28 if immunocompromised).

Wound care follow-up:

Antibiotic prophylaxis (amoxicillin-clavulanate 875/125 mg BID × 3–5 days) for high-risk bites:

Pre-exposure prophylaxis counseling post-recovery: for repeated-exposure occupations or travelers, refer to occupational health or travel clinic for 2-dose PrEP series.

Animal control follow-up: confirm 10-day observation outcome on healthy domestic animals; if animal becomes ill or dies, expedite testing and initiate/complete PEP.

Follow-Up, Monitoring Parameters, and Counseling

— Check injection sites for local reactions; cool compresses, acetaminophen/NSAIDs for symptoms

— Document each dose with date, lot number, site, and route

— Assess wound healing at follow-up visits; obtain wound culture if signs of infection

— Immunocompromised patients (HIV with CD4 <200, transplant recipients, chemotherapy, high-dose corticosteroids, biologics)

— Suspected immune response failure

— Goal: RFFIT ≥0.5 IU/mL within 1–2 weeks after the final dose; if subtherapeutic, give a booster dose

— Routine immunocompetent patients do not need post-PEP titers

— Explain that without completing PEP, rabies is universally fatal — strong adherence message

— Explain that completing PEP is essentially 100% protective when started before symptom onset

— Educate on avoiding future exposures: do not handle wildlife (especially bats, raccoons, skunks); seal bat entry points in homes (chimneys, attics); supervise children outdoors; vaccinate pets

— Travel counseling: if traveling to canine-endemic regions (India, Philippines, parts of Africa), consider PrEP prior to departure

CCS pearl: Order "counsel patient on completing vaccine series" and "schedule follow-up appointments" on day 0 — these capture both the adherence and transition-of-care components of high-quality care that CCS rewards.

Key distinction: Routine immunocompetent patients do not need post-PEP titer checks — order titers only for immunocompromised exposure cases.

Monitoring during the PEP series:

Post-series antibody titer — indicated only for:

Counseling content (Step 3 favorite):

Pet vaccination: a key public health message — owners should confirm dog/cat/ferret rabies vaccination is current per state law; reduces both pet illness and human exposure risk

Documentation: maintain a clear record for the patient (vaccine card) and primary care provider; report to public health.

Ethical, Legal, and Patient Safety Considerations

— Animal bites are reportable in nearly every US state to local animal control and/or public health departments

— This is a legal obligation, not optional — supports rabies surveillance and enables animal testing/observation

— Reporting also triggers investigation if the animal is a stray, may have bitten others, or is part of a suspected animal-cruelty situation

— Discuss benefits (near-100% protection if started before symptoms), risks (local reactions, rare serum sickness, exceptionally rare anaphylaxis), and the alternative (near-100% fatality of clinical rabies)

— Patients may refuse — document risk-discussion and counsel strongly; in cases of impaired capacity (intoxication, dementia), engage surrogate decision-maker

— For minors, parental consent is standard; in bat-in-bedroom scenarios where parents minimize the risk, document detailed counseling and consider involving public health

— Patient autonomy is respected for competent adults

— Document understanding of universal fatality; offer second-opinion or ID consultation

— Notify public health regardless — they can follow up

— A full PEP course is expensive (~$3,000–$10,000 in the US) — concerns about cost should not delay or deny treatment in the ED

— Hospital social work and public health departments can assist with payment programs; some states provide free PEP for indigent patients

— EMTALA obligates evaluation/stabilization regardless of insurance

— Provide a written dosing schedule, contact for missed-dose questions, and a single follow-up clinic location

— Confirm patient comprehension (teach-back); use interpreters when needed

— Healthcare worker exposure to a suspected rabies patient's saliva/neural tissue → eligible for occupational PEP; workplace bears cost

— Veterinarians, animal control: required PrEP and titer monitoring per OSHA-equivalent occupational guidelines

Board pearl: Cost, insurance, and immigration status are never acceptable reasons to deny rabies PEP — the disease is fatal and treatment is the standard of care.

Mandatory reporting:

Informed consent for PEP:

Refusal of PEP:

Cost and access:

Transition-of-care safety:

Occupational exposure:

High-Yield Associations and Rapid-Fire Clinical Facts

Step 3 management: When uncertain, call public health is a correct answer; delaying PEP to gather more info is not when the exposure is clear.

"Bat in bedroom" = PEP even without visible bite (sleeping/impaired patient)

All wild carnivores (bat, raccoon, skunk, fox, coyote) → assume rabid; PEP unless animal tests negative

Rodents/rabbits/squirrels → essentially never rabid → no PEP

Healthy dog/cat/ferret → observe 10 days; defer PEP unless animal becomes ill

Unvaccinated patient PEP: HRIG 20 IU/kg (wound infiltration + IM remainder) + vaccine days 0, 3, 7, 14 (5th dose on day 28 if immunocompromised)

Previously vaccinated patient PEP: 2 vaccine doses (days 0 and 3) only, no HRIG

PrEP regimen (2022 ACIP): 2 doses IM, days 0 and 7

Never inject rabies vaccine in the gluteal site — reduced immunogenicity

Never exceed 20 IU/kg HRIG — saturates and blunts active vaccine response

HRIG and vaccine in different anatomic sites with different syringes

No contraindications: pregnancy, infancy, immunocompromise, anticoagulation all receive PEP

Negri bodies on histology = classic but neither sensitive nor specific

DFA of brain tissue = gold standard postmortem diagnosis

Antemortem testing requires combined saliva PCR + nuchal skin biopsy + serum/CSF antibody

Clinical rabies is near 100% fatal — Milwaukee protocol not recommended

Pasteurella multocida = cat bite cellulitis with rapid onset (<24 h)

Capnocytophaga canimorsus = dog bite sepsis in asplenic patients

Eikenella corrodens = human bite (clenched-fist injury)

Amoxicillin-clavulanate = first-line bite prophylaxis/treatment

Tetanus update: dirty wound → Td/Tdap if last dose >5 years

Animal bites are reportable in essentially all US states

Globally, dog bites cause >95% of human rabies; bats dominate US cases

Incubation 1–3 months typically (range 5 days to >1 year)

Symptoms once present: prodrome → hydrophobia/aerophobia → coma → death in 7–14 days

Board Question Stem Patterns

Board pearl: The two most common right answers across these stems are "give full PEP (HRIG + 4-dose vaccine)" and "observe healthy dog/cat/ferret 10 days; defer PEP." Master the discriminators.

The bat-in-bedroom stem: A 35-year-old wakes to find a bat flying in the bedroom; the bat is captured and escapes before testing. No bite seen. → Give full PEP (HRIG + 4-dose vaccine series). Trap answer: "Reassure and observe."

The healthy-dog bite stem: A 7-year-old is bitten by the neighbor's well-vaccinated, observable dog while playing. → Observe dog 10 days; defer PEP. Wound care, tetanus, possible amoxicillin-clavulanate (hand bite or puncture). Trap: starting PEP immediately.

The previously vaccinated traveler: A veterinarian with documented PrEP is scratched by a raccoon. → 2 vaccine doses (days 0 and 3); no HRIG. Trap: full 4-dose series with HRIG.

The squirrel/rodent stem: A child is bitten by a squirrel in the park. → No rabies PEP; wound care, tetanus, reassure. Trap: starting full PEP.

The international traveler: Returning traveler bitten by a stray dog in India 5 days ago. → Start PEP now; canine rabies is endemic. If they did not receive HRIG abroad, give it now (within 7 days of vaccine initiation). Trap: "It's been too long."

The immunocompromised exposure: Renal transplant recipient on tacrolimus and prednisone exposed to a bat. → HRIG + 5-dose vaccine series (days 0, 3, 7, 14, 28) plus post-series titer. Trap: standard 4-dose regimen.

The pregnancy stem: A 28-week-pregnant woman is bitten by a fox. → Full PEP; pregnancy is not a contraindication. Trap: withhold pending delivery.

The wound-management stem: Cat bite to the hand 6 hours ago, deep puncture. → Irrigate, leave open, amoxicillin-clavulanate, tetanus update; rabies PEP per cat availability (observe healthy cat 10 days). Trap: closing wound primarily.

The clinical-rabies stem (rare): Patient presents weeks after a bat bite with agitation, hydrophobia, hypersalivation. → Supportive ICU care, isolate, offer PEP to exposed contacts, notify public health. Trap: "Start Milwaukee protocol."

One-Line Recap

Rabies post-exposure prophylaxis is a decision driven by exposure type, animal species, and animal availability — give HRIG (20 IU/kg, wound-infiltrated) plus a 4-dose vaccine series (days 0, 3, 7, 14) to unvaccinated patients after any high-risk exposure, observe healthy dogs/cats/ferrets for 10 days before deciding, and never withhold PEP based on pregnancy, immunosuppression, cost, or time elapsed.

Board pearl: When the stem makes you hesitate — bat seen, exposure ambiguous, animal unavailable — err toward giving PEP. The cost of overtreatment is local injection-site pain; the cost of undertreatment is death.

Always-PEP triggers: bat in bedroom with sleeping/impaired person, any wild carnivore (bat, raccoon, skunk, fox, coyote) bite or scratch with broken skin, and any bite from a sick or unavailable domestic animal — start HRIG + vaccine on day 0 without waiting for further data.

Never-PEP triggers: small rodent (squirrel, mouse, rat, hamster) or rabbit/lagomorph bites, intact-skin contact with saliva, and bites from a healthy, observable, vaccinated dog/cat/ferret (instead observe 10 days).

Regimen specifics: unvaccinated → HRIG 20 IU/kg (infiltrate wound, IM remainder) + 4 vaccine doses days 0, 3, 7, 14 (add day 28 if immunocompromised, plus titer check); previously vaccinated → 2 vaccine doses days 0 and 3 only, no HRIG; PrEP → 2 doses days 0 and 7.

Adjuncts you must not forget: copious irrigation with soap and water, tetanus update, amoxicillin-clavulanate for high-risk bite wounds (cat bites, hand, deep puncture, immunocompromised, asplenic), mandatory public health reporting, written follow-up schedule for subsequent vaccine doses, and counsel that completing the series is life-saving against an otherwise universally fatal disease.