Context Rabies postexposure prophylaxis (RPEP) treatments and associated costs
have increased in the United States. The extent to which RPEP use is consistent
with guidelines is not well understood.
Objective To characterize animal contacts and determine the frequency and factors
associated with inappropriate RPEP use.
Design, Setting, and Patients Prospective case series study of patients presenting with an animal
exposure–related complaint from July 1996 to September 1998 at 11 university-affiliated,
urban emergency departments (the Emergency ID Net).
Main Outcome Measures Exposure type, circumstances, and RPEP use (appropriateness defined
by local public health departments).
Results Of 2030 exposures, 1635 (81%) were to dogs; 268 (13%) to cats; 88 (4%)
to rodents/rabbits; 10 (0.5%) to raccoons; 5 (0.2%) to bats; and 24 (1.2%)
to other animals. Among those exposed, 136 (6.7%) received RPEP after dog
(95), cat (21), raccoon (8), bat (4), or other animal (8) exposures. Use of
RPEP varied by site (range, 0%-27.7% of exposures), with most frequent use
reported at sites in the eastern United States. Management was considered
appropriate in 1857 exposures (91.5%). Use of RPEP was considered inappropriate
in 54 cases (40% of those in which it was given), owing to factors including
animal availability for observation and exposure in a low-endemicity area.
Rabies postexposure prophylaxis was considered inappropriately withheld from
119 cases (6.3% of those not receiving RPEP), often because a domestic animal
was unavailable for observation or testing.
Conclusion These results suggest that use of RPEP is often inappropriate. Greater
compliance with current guidelines would increase RPEP use. Physician education,
improved coordination with public health officials, and clarification of RPEP
guidelines could optimize use of this expensive resource.
Although human rabies infection is rare in the United States, animal
bites are a frequently encountered problem in clinical practice. Several million
US residents are victims of animal bites each year. Dog bites alone account
for more than 300,000 emergency department (ED) visits, with total reimbursement
of more than $100 million annually.1 Rabies
is invariably fatal but is preventable with proper treatment, including rabies
postexposure prophylaxis (RPEP) for certain types of animal exposures. Control
of rabies in domestic animal populations and use of RPEP has led to a decline
in annual human rabies cases from more than 100 at the beginning of the 20th
century to 1 to 3 per year at present. Only 32 cases of human rabies were
diagnosed in the United States between 1980 and 1996.2
Since the 1970s, the expanding epizootic of rabies in raccoons in the
eastern United States has caused increased concern about potential transmission
to humans. In 1997, a total of 8509 animal rabies cases were reported in the
United States—an increase of 19.4% from 1996.3
The epizootic of rabies in raccoons appears to be expanding, and reports of
rabies in cats have increased in the same areas.4
Although no documented human rabies cases have occurred with the raccoon rabies
virus variant, the use of RPEP has greatly increased.5
In 1987, it was estimated that 18,000 RPEP treatments were given in the United
States; in 1997, an estimated 39,000 treatments were given.3
Although costs of RPEP can vary greatly, the cost in the United States is
approximately $1500 per treatment course for biologics alone.6
Physician and follow-up clinic charges add even more to the cost of treatment.
General guidelines for proper administration of RPEP have been published
by the Advisory Committee on Immunization Practices (ACIP), and many local
public health agencies publish specific guidelines based on local rabies epidemiology.7 Guidelines indicate that unvaccinated persons potentially
exposed to rabies should be treated with human rabies immune globulin and
begin a 5-dose series of rabies vaccine. Although it is suspected that many
RPEP treatments are not indicated based on guidelines, no prospective studies
have investigated this practice.
Because RPEP is often initiated in the ED, we chose to prospectively
study RPEP use in this setting. The objectives of this study were to characterize
animal exposures of patients who presented to the ED and to determine the
frequency of and factors associated with inappropriate RPEP use. Understanding
the extent of and reasons for inappropriate RPEP use could facilitate development
of strategies to reduce unnecessary RPEP while ensuring that RPEP is given
when appropriate.
The current study was a prospective case series of patients presenting
to a network of 11 geographically diverse, university-affiliated urban EDs
(the Emergency ID Net). The approximate total combined annual visit census
of these EDs is 900,000. A detailed description of the Emergency ID Net, including
administrative structure, data collection methods, and data transfer, has
been published.8 Institutional review board
approval was obtained at all sites.
Patients presenting to these EDs between July 1996 and September 1998
with a primary complaint related to mammalian animal exposure by bite, scratch,
body fluid exposure, handling, or proximity were enrolled in the study. Treating
physicians (primarily emergency medicine residents) collected data prospectively
at the bedside during the ED evaluation using standardized data entry forms.
Data collected included demographic information, animal type, exposure type
and circumstances, and RPEP use. Treatment decisions were left to the individual
physicians. Patients were contacted by telephone approximately 1 month after
enrollment to obtain follow-up data, including results of animal observation
or animal testing for rabies and any subsequent treatment given.
To categorize RPEP treatments as appropriate or inappropriate, a standard
algorithm for RPEP use was developed based on the animal type, exposure type
and circumstances, animal vaccination status, and animal availability for
observation or testing (Figure 1).
The treatment algorithm was based on ACIP guidelines that were current at
the time data were collected.9 Circumstances
that were considered to indicate a provoked exposure included attempting to
feed an animal, trespassing on an animal's territory, breaking up an animal
fight, petting or playing with an animal, handling an animal in a veterinary
office or laboratory, having contact with an injured animal, and walking,
running, or riding past an animal. The treatment given was considered inappropriate
if it deviated from the guideline algorithm.
The algorithm was reviewed with local public health officials at each
of the study sites to ensure that the guidelines were consistent with local
recommendations. Each of the study sites was identified by the local health
department as a low-endemicity or high-endemicity area for wild or domestic
animals, based on local rabies epidemiology. Sites considered to be high-endemicity
areas for both wild and domestic animals were New York, NY; Philadelphia,
Pa; Charlotte, NC; and Orlando, Fla. Sites that were considered high-endemicity
areas for wild animals but low-endemicity areas for domestic animals were
Kansas City, Mo; Atlanta, Ga; Albuquerque, NM; Phoenix, Ariz; Los Angeles,
Calif; and New Orleans, La. The only site that was considered to be of low
endemicity for both wild and domestic animals was Portland, Ore. Some sites
(Atlanta, Kansas City, Albuquerque, and Philadelphia) considered a scratch
from a terrestrial wild carnivore or larger animal (eg, raccoon, skunk, coyote)
to be a potential exposure.
Case-finding audits were conducted by review of ED logs during two 1-month
periods in January 1997 and January 1998 to determine the proportion of missed
cases and to compare their demographic and clinical characteristics with identified
cases. Case-finding sensitivity was defined as the total number of patients
enrolled divided by the total number of patients who met entry criteria. Limited
demographic and clinical data were also abstracted from charts of missed cases
to compare with those of identified cases to evaluate selection biases.
Simple descriptive statistics were used to summarize characteristics
of ED patients with animal exposures and the proportion of patients receiving
RPEP, stratified by site and by animal type. Epi Info Version 6.04b (Centers
for Disease Control and Prevention, Atlanta, Ga) was used to calculate univariate
risk ratios (RRs) for factors related to inappropriate RPEP use. When appropriate,
Mantel-Haenszel stratified analysis was used to adjust the RR estimates for
confounding by other risk factors.
A total of 2030 patients with animal contact were enrolled. Their median
age was 27 years (range, <1-91 years; interquartile range, 11-39 years),
and 59% were male. The racial/ethnic distribution was 43% white non-Hispanic,
30% black, 22% Hispanic, 3.4% other, and 1.6% unknown. The distribution of
animal types and RPEP use at the sites are summarized in Table 1. Bite exposures accounted for 1777 cases (87.5%). Other
exposures included saliva contact with broken skin or mucous membrane (6.5%),
scratch only (3.2%), touching only (3 cases), and proximity only (2 cases).
The majority of exposures occurred in urban or residential areas; only 37
(2.0%) of 1873 exposures for which location information was available occurred
in rural or wilderness areas.
Rabies postexposure prophylaxis was given to 136 (6.7%) of 2030 patients
with animal exposures (Table 2).
Although exposures to bats, raccoons, and other wild carnivores were uncommon,
the majority of these patients received RPEP. Rabies postexposure prophylaxis
was given for only 6.1% of dog and cat exposures, but because most exposures
were to dogs and cats, these accounted for 86% of all RPEP treatments given.
Based on local guidelines, case management was considered inappropriate
in 54 (40%) of 136 patients given RPEP and in 119 (6.3%) of 1894 patients
who were not given RPEP. Overall compliance with guidelines was therefore
1857 (91.5%) of 2030. Inappropriate RPEP use occurred more frequently in low-endemicity
areas (Table 3). Most exposures
for which RPEP was given inappropriately were to dogs or cats (Table 4). The most common reason that RPEP was considered inappropriate
was that the animal was available for observation or testing (28 of 54). Other
reasons included exposure in a low-endemicity area due to a provoked attack
with no unusual circumstances (22 of 54) and lack of bite or body fluid exposure
(4 of 54). Inappropriate failure to give RPEP occurred more frequently in
high-endemicity areas. The most common reason for inappropriate failure to
give RPEP was exposure in a high-endemicity area from an animal unavailable
for observation or testing (70 of 119). Other reasons included exposures in
a low-endemicity area with an unprovoked attack or unusual circumstances for
which the animal was not available (49 of 119).
Follow-up data were available for 985 cases (48.5%), including 69 (51%)
of those who received RPEP and 916 (48%) of those who did not receive RPEP
at the initial ED visit. Of the 69 receiving RPEP at the initial visit, 24
had not continued the full series at the time of follow-up approximately 1
month after the initial visit. In 7 of these cases, the animals had normal
behavior during observation, and 1 was due to a rat exposure. Reasons for
discontinuing treatment were unknown for the remainder. For 25 of the 69 patients
receiving RPEP, the treatment was considered inappropriate, yet 10 (40%) had
continued the full RPEP series at the time of follow-up. Of the 916 follow-up
patients who did not receive RPEP at the initial visit, 45 should have received
it according to local guidelines. For only 1 of these 45 patients, RPEP was
started after the initial visit—a cat exposure in Florida for which
the animal was not available.
No outside consultation for RPEP use was sought for 982 (87.1%) of 1127
cases for which this information was available. Consultation was sought from
the local health department in 4.3% of these cases, from other public resources
(eg, Centers for Disease Control and Prevention, poison center) in 3.2%, from
another source in 4.1%, and from a written protocol in 2.5%. The proportion
of inappropriate RPEP treatments did not appear to be related to whether consultation
was used. Rabies postexposure prophylaxis was considered inappropriate for
16 (27%) of 60 cases for which it was reported that consultation was not obtained
and was inappropriate for 2 (25%) of 8 cases for which the local health department
was consulted.
Among the 1829 patients for whom RPEP was not considered indicated,
there was no association between RPEP use and sex, age, race, insurance status,
bite vs nonbite exposure, anatomic site, time elapsed since exposure, dog
vs cat exposure, or class ification of site as high vs low endemicity. Rabies
postexposure prophylaxis was more likely to be given inappropriately to those
exposed to a wild vs domestic animal (RR, 9.5; 95% confidence interval [CI],
5.0-17.9, adjusted for availability of animal) or to an animal at a low-endemicity
site that was not available for observation/testing (RR, 4.3; 95% CI, 2.7-7.1,
adjusted for wild vs domestic animal).
Among the 201 patients for whom RPEP was considered indicated, there
was no association between nonuse of RPEP and sex, age, race, insurance status,
bite vs nonbite exposure, anatomic site, time elapsed since exposure, dog
vs cat exposure, or animal availability. Rabies postexposure prophylaxis was
more likely to be inappropriately withheld from those exposed to a domestic
vs wild animal (RR, 5.0; 95% CI, 0.8-31.4) and from exposures associated with
abnormal animal behavior occurring at sites classified as low vs high endemicity
for rabies (RR, 1.4; 95% CI, 1.1-1.7).
Case-finding audits revealed that approximately 76% of eligible cases
were enrolled. Compared with entered cases, missed cases were similar in terms
of age (median, 37 years; range, 2-69 years), sex (63% male), race (59% white/Hispanic,
33% black, 17% other), type of animal (79% dog), and bite vs nonbite exposure
(84% bite). Rabies postexposure prophylaxis was not given to any unenrolled
patients reviewed in the audits.
The significant expansion of animal rabies in the United States has
created a health care dilemma. Although RPEP is considered universally effective
to prevent rabies, a disease considered to be invariably fatal, this treatment
is expensive and may be overused based on current rates of human rabies. Past
studies have retrospectively evaluated patients given RPEP and determined
that it was frequently misused.10-12
Consequently, a 50% reduction of RPEP use was a goal in the Healthy People
2000 objectives.13 To the best of our knowledge,
this is the first prospective investigation of RPEP use and nonuse among patients
presenting with an animal exposure. Our study demonstrated that RPEP was prescribed
inappropriately in 40% of cases in which it was given, based on local guidelines.
However, in more cases RPEP was not given when it would be recommended.
Many public health experts believe that improving physician compliance
with guidelines for use of RPEP would reduce health care costs by reducing
unnecessary use of RPEP. If all cases in our series were managed according
to local guidelines, 54 cases in which RPEP should have been withheld would
be offset by 119 cases for which RPEP should have been given, and the total
number of RPEP treatments would actually increase 47% (from 137 to 201). Although
our sites may not accurately reflect RPEP use in the entire United States,
if this were extrapolated to the currently estimated 39,000 RPEP treatments
given in the United States annually, more than 18,000 extra RPEP treatments
would be given. At a cost of $1500 per treatment, this would result in additional
expenditures of more than $27 million.
The sites at which RPEP was given most frequently are located in the
region of the eastern US raccoon rabies epizootic, where the treatment strategies
led to a more liberal use of prophylaxis. The greatest proportion of increased
RPEP use at these sites appeared to be related to the strategy of giving it
for exposures to domestic animals that are not available for observation.
Since RPEP is considered appropriate in this setting, it would appear that
the best way to reduce RPEP would be to increase the proportion of cases in
which the animal is observed or tested. If physicians cannot be assured that
proper animal observation or testing will take place, they may err on the
side of giving RPEP, even for relatively low-risk exposures.
Although RPEP was given to a minority of patients with dog or cat exposures,
these domestic animals accounted for the large majority of RPEP cases (including
85% of the inappropriately treated cases). In recent decades, more than 90%
of animal rabies reported in the United States has occurred in wildlife.3 Because rabies is now rare among domestic animals
in this country, it appears that RPEP use for domestic animal exposures could
be targeted to reduce unnecessary RPEP. Common circumstances that should have
precluded RPEP use for domestic animal exposures in our study included an
animal being available for observation or testing, an exposure in a low-endemicity
area in which the attack was provoked without unusual circumstances, and lack
of exposure to animal saliva or body fluids. It may be useful to emphasize
these common errors in written guidelines and educational programs for physicians.
Eight inappropriate RPEP treatments were for exposures to animals other
than dogs or cats. Five of these exposures were to raccoons. Although some
would recommend RPEP for raccoon exposures in high-risk areas pending results
of brain testing, it is safe to withhold treatment if test results are available
within 48 hours. Only 1 of our sites (Portland, Ore) stated that guidelines
would not recommend treatment for a raccoon exposure if the animal were not
available, yet 2 of 3 persons with raccoon exposures at this site received
RPEP.
Rabies postexposure prophylaxis was given to 4 of 5 patients with bat
exposures in this study. In the single bat exposure for which RPEP was not
given, the bat tested negative for rabies. Bat-associated rabies virus variants
have been identified from 17 (85%) of the 20 cases of human rabies acquired
in the United States between 1980 and 1996.2
Because a definite bite history was not elicited from many of these cases,
the most recent ACIP guidelines emphasize that RPEP should be considered in
all situations in which there is reasonable probability that contact with
a bat may have occurred, unless prompt laboratory testing of the bat has ruled
out rabies infection.7 The small proportion
of bat exposures in our series would indicate that treatment of all bat exposures
presenting to EDs would not significantly increase use of RPEP. However, a
telephone survey in Oregon showed that 1.3% of respondents in the general
population reported potential bat exposures and that treatment of all these
individuals would represent an enormous burden on the US health care system.14
If the proportion of inappropriately withheld RPEP treatments is extrapolated
to all animal exposures in the United States, it appears that a large number
of potentially significant rabies exposures are going untreated. If this were
the case, we would expect occasional cases of rabies among patients who were
evaluated for animal exposures and not given RPEP. This has not been the case
with any human rabies diagnosed in the United States in several decades. Although
this is indirect evidence that RPEP is probably overused rather than underused,
it is not known whether stricter RPEP guidelines could reduce RPEP use without
withholding treatment for true rabies exposures.
Our study identified a large number of cases for which withholding RPEP
was inconsistent with local guidelines, but this does not necessarily mean
that it was an error to withhold RPEP. Good physician judgment in this setting
may prevent the use of RPEP that might be considered indicated by a strict
interpretation of local guidelines. All but 1 of these cases were due to dog
or cat exposures and more than half involved exposures in a high-endemicity
area for which the animal was not available for observation. Some areas that
are currently considered as having high endemicity for rabies actually have
very low reported rates of rabies in dogs and cats. Reclassification of these
areas for domestic animal exposure risk could potentially reduce RPEP use
safely. The other inappropriately untreated dog and cat exposures were due
to unprovoked attacks or abnormally behaving animals that were not available
for observation. Revision of guidelines to include very specific descriptions
of the exposure circumstances that should prompt RPEP could reduce ambiguity.
Although interpretation of animal behavior may be unreliable, perhaps future
research could identify objective observations that are associated with a
very low likelihood of rabies (eg, presence of a collar) such that RPEP could
be safely withheld when the animal is not available for observation.
Several factors may limit the internal and external validity of this
study. Not all patients with animal exposures were enrolled. However, our
audits of all ED animal exposure cases indicated that enrolled cases were
similar to nonenrolled cases. Physician behavior may have been influenced
by the fact that a study of RPEP was being done. However, other than retrospective
chart reviews for which data accuracy is seriously limited, no feasible and
valid alternative study designs exist. We made no attempts to influence RPEP
practices during orientation to the study. Rabies postexposure prophylaxis
guidelines were not discussed, and physicians were instructed to treat patients
as usual. Follow-up data were available on less than half of cases. We do
not know how many patients who started RPEP treatments received the full series.
Likewise, it is possible that we were not aware of some patients not given
RPEP in the ED who received it subsequently. Practice patterns in large, urban,
university-affiliated hospitals may not reflect practices in smaller community
or rural hospitals. Because use of RPEP varies considerably by location, the
proportion of patients with animal contacts who received RPEP in our study
is sensitive to the selection of study sites, and may not be representative
of the entire US ED population. However, we believe the geographic diversity
of the network is adequate to describe RPEP use in US EDs with reasonable
accuracy.
Analysis of the appropriateness of RPEP use is highly dependent on the
algorithm used as the standard. It is possible that the local health department
would agree on a general treatment algorithm but that the actual health department
recommendation for a specific case might not strictly follow general guidelines.
We do not know why physicians did not follow guidelines in individual cases.
It is possible that there were specific details about the exposure circumstances
that could not be adequately described using checklists on a data sheet. Although
attacks were coded as "unprovoked" or specific types of animal behavior (eg,
aggressive, lethargic) were coded as "abnormal," some subtle aspects of these
cases that were not captured by our coding process may have influenced treatment
decisions. Interpretation of subtleties is sometimes used as an argument against
the use of written protocols or flow charts for RPEP. Written guidelines that
are specific enough to address these concerns would seem to be the best way
to achieve consistent and rational treatment of animal exposures based on
the best scientific evidence.
Our data indicate that improved compliance with guidelines will not
necessarily reduce the use of RPEP in the United States. For this to occur,
the guidelines would need to be revised. Because the majority of RPEP use
is for exposure to dogs and cats, and because rabies is now uncommon among
these animals, it would appear that guidelines could be revised to reduce
RPEP use for these exposures without significantly increasing the risk of
human rabies. Health departments may wish to consider whether RPEP is really
necessary for all dog bites for which the dog is not available—rabies
in dogs is rare even in areas of the raccoon rabies epizootic. Perhaps treatments
could be limited only to exposures involving specifically described high-risk
circumstances.
The appropriateness of RPEP use in US EDs might be improved by developing
and facilitating access to site-specific practice guidelines in conjunction
with local public health agencies. Physicians should have a low threshold
for consulting local public health agencies with questions regarding care
and follow-up of persons with possible rabies exposure. Posting of the 24-hour
public health department telephone number in the ED is recommended. Health
departments could also post recommendations on Internet sites in an interactive
algorithm format. Guidelines should be clear and provide examples regarding
features that have been found to be associated with improper use of RPEP such
as animal availability for observation, circumstances of exposure and provocation,
and questionable exposure to animal body fluids. It is important that guidelines
designed to reduce unnecessary RPEP do not lead to failure to give prophylaxis
when truly indicated. As noted in a JAMA article more than 100 years ago,
"With such a disorder prophylaxis is a necessity and any error had better
be on the safe side."15 Future research should
focus on development and evaluation of more specific practice guidelines and
educational programs to reduce the need for and improve the appropriateness
of RPEP use.
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