Treatment
Human Rabies Immune Globulin (HRIG)
Although rabies among humans is rare in the US, every year approximately 100,000 persons receive postexposure prophylaxis. In order to manage potential human exposures to rabies appropriately, the risk of infection must be accurately assessed. Administration of rabies postexposure prophylaxis is usually a medical urgency, not a medical emergency (facial and neck wounds are the exception), BUT EVALUATIONS AND DECISIONS MUST NOT BE DELAYED.
Systemic prophylactic treatments occasionally are complicated by adverse reactions, but these reactions are rarely severe. Data on the safety, immunogenicity, and efficacy of active and passive rabies immunization have come from both human and animal studies. Although controlled human trials have not been performed, extensive field experience from many areas of the world indicates that postexposure prophylaxis combining aggressive local wound care, passive immunization (HRIG), and vaccination, is uniformly effective when appropriately applied timely in patients with healthy immune systems. Failures have been rare.
Rabies Vaccine (for Human Use) = Killed vaccine
RabAvert® (chicken embryo cell culture)/Imovax (human diploid cell culture)
Rabies is a viral infection transmitted via the saliva of infected mammals. The virus enters the central nervous system of the host (victim), causing an encephalomyelitis (brain/spinal cord infection) that is almost invariably fatal. The incubation period from contact to onset of illness varies between 5 days and several years, but is usually 45 days + 15 .
Clinical rabies presents either in a “furious” or in a “paralytic” form. Clinical illness most often starts with prodromal complaints of malaise, poor appetite, fatigue, headache, and fever, followed by pain or paresthesia (odd sensations) at the bodily site of animal contact. Anxiety, agitation, and irritability may be prominent during this period, followed by hyperactivity, disorientation, seizures, aero- and hydrophobia, hypersalivation, and eventually paralysis, coma and death.
Modern day prophylaxis (preventive treatment) has proven nearly 100% successful; most human fatalities now occur in people who fail to seek medical treatment, usually because they do not recognize a risk in the animal contact leading to the infection or were unaware of any contact. Inappropriate postexposure prophylaxis may also result in clinical rabies. Survival after clinical rabies is extremely rare, and would probably be associated with severe brain damage and permanent disability.
Rabies vaccine, in combination with passive immunization with Human Rabies Immune Globulin (HRIG) and aggressive local wound treatment in postexposure treatment against rabies has been shown to protect patients of all age groups from rabies, when the vaccine was administered according to the CDC’s Advisory Committee on Immunization Practices (ACIP) or World Health Organization (WHO) guidelines and as soon as possible after rabid animal contact. Anti-rabies antibody titers after immunization have been shown to reach levels well above the minimum antibody titer accepted as seroconversion (protective blood antibody level) within 14 days after initiating the postexposure treatment series.
Postexposure Treatment
No postexposure vaccine failures have occurred in the United States since cell culture vaccines have been routinely used. Failures have occurred abroad, almost always after deviation from the recommended postexposure treatment protocol.
The sooner treatment is begun after exposure, the better. However, there have been instances in which the decision to begin treatment was made as late as 6 months or longer after exposure due to delay in recognition that an exposure had occurred. Postexposure antirabies treatment should always include administration of both passive antibody (HRIG) and rabies vaccination series, with the exception of persons who have previously received complete immunization regimens (preexposure or postexposure) with a cell culture vaccine, or persons who have been immunized with other types of vaccines and have had documented rabies antibody titers. Persons who have previously received rabies immunization should receive 2 intramuscular doses of vaccine: 1 on day 0 and another on day 3. They SHOULD NOT BE GIVEN HRIG (unless possibly if they are immune-compromised) as this may blunt their immune system rapid memory response to rabies vaccine antigen (and so impair vaccine efficacy).
Serum rabies antibody can be measured 2-4 weeks (physician decision) after the last vaccine dose.
Contraindications
In view of the almost invariably fatal outcome of rabies, there is no contraindication to postexposure prophylaxis, including pregnancy, where there has been legitimate exposure. If there had been prior anaphylactic allergic reaction to HRIG or the vaccine, that would be managed by expert consultation with an Allergy / Immunology specialist, but the rabies preventive treatment is still indicated as soon as possible.
Altered Immune Status
Individuals with diseases which impair or weaken their immune systems (HIV, blood and blood-forming malignancies, lymphomas, etc.) or who have recently received or are on immune-compromising treatments (steroids; cancer chemotherapy; radiotherapy; autoimmune disease biologicals, like Remicaid, Humira, Embrel, etc.) may have suboptimal responses to any vaccine. Such cases must be evaluated individually by an expert to decide if the usual vaccination schedule will be sufficient to provide protection and when post-vaccination protective rabies antibody should be measured to assure the vaccine worked. Immune-suppressant medications may need to be held during rabies immunization and not resumed until an expert has approved it.
Frequent Rabies Questions / Issues
1. Bats don’t “carry” rabies. Like other mammals, they must be infected (ill) to be shedding rabies virus, and so are a risk to give it to other animals/humans.
About 0.2-1.0% of bats are rabid. If a bat is flying around during daytime, enters a house, has contact with humans, or is found lying on a surface, it is more than likely to have rabies.
2. Only several people die yearly in the U.S. from rabies. A person living in the U.S. is more likely to catch polio, leprosy, or plague.
Worldwide, over 100,000 die each year – 99% from unvaccinated, rabid dogs and cats.
3. People can have had bat contact without knowing it and without apparent bite or scratch marks. A person who has been intellectually incompetent (dementia, small kids) or mentally unaware (sleeping, demented, medicated, or intoxicated) for any amount of time in a closed air-space where a bat is found MUST receive full rabies preventive care unless the bat’s brain can be confirmed as rabies negative by testing by public health authorities.
4. You cannot catch rabies by just being near a bat (unless physical trauma to the bat produces aerosolized bat saliva that lands on human mucous membranes in the eyes, nose, or mouth, or rarely by aerosol exposure in bat caves.) Otherwise, there must be direct physical contact.
5. There is no evidence that bats transmit rabies to other kinds of wildlife or domestic pets. Numerous carnivores gather to feed on the 20 million Mexican free-tailed bats at Bracken Cave, TX, and there have been no known rabies outbreaks in those animals.
6. Large urban bat colonies (such as at the famous Congress Avenue Bridge in Austin, TX) have not been linked to increased human rabies cases.
7. Bat rabies has been implicated in most U.S. human rabies cases the past 25 years.
8. Media, health agencies, and inexpert physicians who do not regularly deal with rabies exposure, diagnosis, and treatment may give misinformation and inappropriate recommendations. With rabies, you must see an expert for proper advice and care.
9. Rabies exposure can be avoided by vaccinating domestic pets; avoiding stray/wild animals; not “taking in” sick animals (without Animal Control/Public Health advice); not directly handling stray/wild animals (especially bats) or touching carcasses without impermeable hand covering. Any animal bite or contact with a wild/stray animal should be discussed with a physician rabies expert or local Animal Control. This includes raccoons and feral cats.
10. Post-exposure rabies treatment is not extremely painful as in the past. Shots are no longer given in the abdomen. They are given in the thigh or upper arm and the patient experience is the same as with a flu shot.
FURTHER DETAIL ON RABIES
MYTH: Rabies IS NO LONGER A U.S. threat
FACT: There are 1.4 MILLION legitimate exposures in the U.S. yearly
CDC just reported in 9/2025 6 DEATHS in the past 6 months from multiple sites around the U.S. (avg has been 2-3/yr in past decades).
Between 5/5/25-7/27/25, 200 people were exposed to in-house bats at a WYOMING Travel Lodge.
Because of accessible preventive treatment the U.S. deaths are minimal (20,000-30,000/yr each in China and India); 60,000-100,000 deaths/yr., worldwide.
WHAT is RABIES?
Some interesting FACTS,
- A ZOONOTIC, viral disease of the Central Nervous System (CNS), with certain death, untreated.
- HIGHEST CASE-FATALITY rate of any disease
- From SALIVA by bite, scratch, lick from MAMMALS, including livestock
- NOT CURABLE once in NERVOUS SYSTEM
- RECORDED back 4,000 YEARS
- “RABIES from LATIN: RABERE= To RAVE
- 60K-100K Deaths/ Yr.
- FATAL BITES: Dogs= 99%(WORLDWIDE)
Bats= U.S.
- Wound CAUTERIZATION: THE TREATMENT from the 1st Century A.D- Mid 20th Century
- 1885: Attenuated Vaccine- PASTEUR
- Early 19th Century: U.S. EPIZOOTIC- imported dogs/foxes
- 1958: Fluorescent ANTIBODY TEST (First Dx Test)
FROM Bite to Brain
- As stated, SALIVA SOURCE (not blood) to skin break or mucous membrane.
- Deposited in MYOCYTE and MACROPHAGE CELLS
- Eventually ENTERS NEURONS (treatment will NO LONGER WORK); to CNS by AXONAL transport.
- MAJOR CNS DYSFUNCTION; virus then spreads to ALL NERVES
- Little APOPTOSIS (CNS cell death)
- NITROUS OXIDE (excitotoxic) extreme CNS levels
- DYSAUTONOMIA
- MYOCARDITIS / CEREBRAL EDEMA
· No reported transmission to healthcare workers or household contacts
Incubation: 5 days to 2 years, or more
Average= 45 days + 15
Prodrome: Fever
Poor appetite
Nausea/vomiting
Headache
Malaise
Lethargy
Pain/abnormal sensations at bite siteAcute Neurological Illness: 2-7 Days*
Hyperventilation
Hypoxia
Aphasia
Lack of coordination
CNS signs (weakness, paralysis, etc)
Pharyngeal spasms (5-15 seconds)
Confusion
Hydrophobia
Delirium
Hallucinations
Marked hyperactivity
Anxiety
Agitation
Depression
· See Sir William Gower’s clinical depiction of rabiesComa: 5-14 Days
Respiratory failure
Circulatory collapse
Cardiac arrhythmias/arrestDeath
RABIES PREVALENCE
- EVERY CONTINENT, EXCEPT ANTARCTICA
- WORLDWIDE:160 deaths/day
60K-100K/yr
4/10= kids < 15 y.o.
- U.S.: 100,000 Post-Exposure Prophylaxis (PEP) Treatments each year
No Rabies: Antarctica
New Zealand
Taiwan
Japan
Norway
Sweden
Spain
Hawaii
Several Islands
104 U.S. rabies deaths 1980-2025 (45yrs); 2-3/yr, avg.
U.S. WILDLIFE RESERVOIRS
ALL MAMMALS (warm-blooded) are susceptible (not rodents or oppossums, though)- ?die too soon (to carry rabies) from larger animal bite trauma because they are small?
2022 CDC Survey (animals with rabies)
- Skunks (22%)
- Foxes (16.5%)
- Raccoons (9.6%)
- Bats (5.2%)
- Domestic animals (0.8%)
- Cats, dogs, cattle
- Mongoose (Puerto Rico)
MYTH: BATS MOST COMMON rabies EXPOSURE in U.S.
FACT: - NO! Bats most common RABIES DISEASE source
U.S. Rabies EXPOSURES
- 94% = PETS/ DOMESTIC
- 81% DOGS
- 13% CATS
- 0.2% Bats
2030 U.S. Exposures: 1600 dogs, 5 bats
RABIES THREAT
- Threat to KIDS: HUGE
- Kids more likely to APPROACH ANIMAL
- Kids CLOSER TO GROUND
- Kids Less able to DEFEND themselves
- So: Multiple, severe bites to HIGHLY INNERVATED, High-Risk body areas – HEAD, FACE, NECK, HANDS
KIDS/ Pediatric WOUNDS
- Bites- 80% HEAD/ NECK
- 44,000 Facial injuries/yr
- Facial Wounds: 33% Severe and Kids < 10
POST-EXPOSURE PROPHYLAXIS (PEP) TREATMENT PROTOCOL
1. Cleanse Wounds IMMEDIATE, THOROUGH, SOAP & H20 x 15min, VIRUCIDAL AGENT (I2)s
2. HUMAN RABIES IMMUNOGLOBULIN (HRIG), if previously UNVACCINATED
- PASSIVE/ Virus Neutralizing Antibody
3. VACCINE: Produces protective antibodies in 7-10 D
CDC- ACIP Detailed GUIDELINES
HRIG: 20 Units/Kg
- FULL DOSE in wounds
- DISTANT from Vaccine injection site
- NO MORE HRIG THAN,
1) Recommended Dose
2) 7 days after FIRST VACCINE Dose
VACCINE:
- HDCV (Human Diploid Cell Vaccine)
- CHICK EMBRYO Cell Vaccine
MYTH: HRIG ADMINISTRATION
- ½ into WOUND/ rest IM
FACT: NO!!!
- AS MUCH AS POSSIBLE INTO WOUNDS
NOTE: Greatest Reason for Guidelines NON-ADHERENCE= FAILURE to infiltrate ALL Wounds
PEP Failure/ IMPROPER HRIG OFTEN the CAUSE of FAILURE
Reasons:
1)INADEQUATE INFILTRATION of wounds
2) HRIG ONLY given as intramuscular injection, remote from bite wounds
3)HRIG VOLUME NOT SUFFICENT TO COVER ALL WOUNDS
Study 1- Hwang et al.
INADEQUATE WOUND INFILTRATION
- 246 Patients were studied for ADHERENCE to CDC/ACIP Guidelines
1) 44% No HRIG into/ around wounds
2)17% into buttocks incorrectly
3)10% HRIG + vaccine = SAME SITE
4)9% NO HRIG (with POS INDICATION)
80%
Study 2 – Whitehouse et al. (Lancet ID)
BREAKTHROUGH INFECTIONS (1980-2022)
- Medical Literature review
- 122 cases of treatment failure (deaths)
Results:
1)36% HRIG intramuscularly only (not into wounds)
2)Inadequate wound cleansing
3)Inappropriate Vaccine admin (>50%)
HRIG covers the 7-10 days UNPROTECTED by onset of vaccine effect (until vaccine neutralizing antibody starts) – TO STOP nerve cell entry by virus.
RABIES RESOURCES
CDC
WHO
GARC (Global Alliance for Rabies Control)
Rabiesdoc.com (International Medicine Center, Houston, TX, USA)