Human rabies in the US (technical, but perhaps of interest)

RABIES, HUMAN - USA 1990-2004
*****************************
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Date: Thu 11 Aug 2005
From: ProMED-mail
Source: Morbidity and Mortality Weekly Report, Fri 12 Aug 2005
/54(31);767-769
[edited]
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5431a2.htm


USA: Human Rabies -- Florida, 2004 (ex Haiti)
- ---------------------------------------------
Rabies is a viral infection of the central nervous system, usually
contracted
from the bite of an infected animal, and nearly always fatal without
postexposure prophylaxis (1). In February 2004, a man aged 41 years died
after
a 4-day hospitalization in Broward County, Florida. A diagnosis of
rabies was
considered on the day before the patient's death; however, no antemortem
samples were obtained for testing. In March 2004, postmortem samples of
fixed
brain material were sent to CDC, where laboratory testing confirmed a
diagnosis of rabies, the 47th case of human rabies reported in the
United
States since 1990 (CDC, unpublished data, 2005). This report summarizes
results of the subsequent investigation led by the Broward County Health
Department and laboratory testing at CDC, which determined that the
rabies
virus was a canine variant present in Haiti, where the man had traveled
and
reportedly been bitten by a dog. Rabies should be considered in persons
after
a dog bite, especially if the bite occurs in a country where canine
rabies is
enzootic.

The man arrived at the hospital emergency department with a 2-day
history of
dysphagia accompanied by hyperventilation and agitation when he
attempted to
swallow liquids. The problem had worsened by the time of admission; he
was
noted as "almost phobic" to liquids. The patient reported having a brief
period of mild fever. He was able to swallow soft, solid food and did
not
complain of throat pain or discomfort. Upon physical examination of his
mouth
and throat, the patient became agitated and experienced
hyperventilation. He
was admitted for further observation and diagnostic evaluation. On the
day of
admission, a neurology consultant concluded that the dysphagia etiology
was
unknown and recommended infectious disease, gastrointestinal, and
pulmonary
consultations. Examination results by a gastrointestinal consultant on
the
same day were unremarkable, except for dysphagia and phobia to liquids.

The patient reported a history of malaria and ureteral stricture and
surgery.
Magnetic resonance imaging study results were unremarkable. Results of
examinations of the patient's ear, nose, and throat, including a swallow
test
(i.e., cervical esophagram), and radiographs of neck and soft tissue
were
normal. Because examination elicited substantial agitation and
hyperventilation in the patient, anti-anxiety medical management was
instituted, and the patient was referred for psychiatric evaluation On
his 3rd
day of hospitalization, the patient had a consistent fever of 103 F
(39.4 C)
and an elevated white blood cell count of 14.5/microL (normal: 3.6 to
11.0/microL). An infectious disease consultant recommended a lumbar
puncture
and testing for viral illness, especially rabies. The patient's wife
reported
that her husband had been bitten on the fingertip by a dog 8 months
earlier
while he was visiting Haiti. The wife reported that the dog was still
alive;
however, that could not be confirmed by investigators. She said her
husband
had not traveled back to Haiti during the interim. Anti-malarial
treatment of
the patient also was empirically initiated pending the results of
malaria
testing.

On the 4th day of hospitalization, the patient experienced diplopia and
was
decreasingly responsive. He went into cardiopulmonary arrest and died.
Antemortem rabies testing was under consideration, but the patient died
before
samples were collected. On histopathologic examination of the cerebral
cortex,
pons, hippocampus, and spinal cord, the medical examiner described
cytoplasmic
inclusions consistent with Negri bodies. Unstained slides of
formalin-fixed
samples of brain material were sent to CDC for diagnosis and typing.
Rabies
virus antigen was detected by a modification of the direct fluorescent
antibody test (2). A reverse transcription-polymerase chain reaction
assay
produced an amplicon sequence that was compatible with a canine rabies
virus
variant present in Haiti. This variant has not been documented among
domestic
or wild animal reservoirs in the United States. One close family member
underwent postexposure prophylaxis for exposure to the patient's
secretions.

MMWR Editorial note
- -------------------
Of the 47 cases of human rabies reported in the United States since
1990, 4
occurred in organ transplant recipients and were associated with an
undetected
case of rabies in a single organ donor (3); the remainder apparently
were
acquired from contact with animals with rabies virus infections. 38 (81
percent) of the infections were acquired in the United States. Among the
9
infections acquired elsewhere, 2 were acquired in Haiti (the 2004 case
described in this report and a 1994 case), 2 in Mexico (1993 and 1994),
and
one each in India (1992), Southeast Asia (1996), Ghana (2000), the
Philippines
(2001), and El Salvador (2004).

The greatest risk for naturally acquired rabies in the United States is
from
encounters with and bites from insectivorous bats (4). In particular, a
rabies-
virus variant associated with 2 small-bodied bats, the eastern
pipistrelle bat
(_Pipistrellus subflavus_) and silver-haired bat (_Lasionycteris
noctivagans_)
was identified in 20 (69 percent) of 29 persons with samples tested.

Human rabies is preventable if the exposure is recognized and the
patient
receives appropriate wound care and postexposure prophylaxis before
clinical
signs of rabies are evident. Postexposure prophylaxis consists of rabies
immune globulin infiltrated at the site of the exposure and 1 dose of
rabies
vaccine administered in the deltoid (or anterolateral thigh of infants
and
small children) on days 0, 3, 7, 14, and 28 (1). When applied
appropriately,
this combination has been effective in preventing death after an
exposure.

However, the continued availability of rabies vaccine currently relies
upon
only one licensed manufacturer in the United States; a 2nd manufacturer
suspended and has not resumed production after a voluntary recall of its
rabies vaccine in March 2004 (5).

In the United States, mandatory vaccination and stray-dog control
programs
have virtually eliminated circulation of any canine rabies virus variant
among
dogs (6). In comparison, occurrence of rabies in dogs remains a problem
in
Haiti and other developing countries (7). Because of the risk for rabies
exposure in these countries, travelers are advised to avoid contact with
dogs
and other animals, and rabies pre-exposure prophylaxis (consisting of 3
intramuscular doses of rabies vaccine on days 0, 7, and 21 or 28) is
recommended for persons planning to stay longer than 30 days in remote
areas
without access to medical facilities (1). The patient described in this
investigation reportedly was bitten by a dog in Haiti 8 months before
clinical
signs of rabies became evident. This was the longest incubation period
among
12 U.S. rabies cases with exposure history reported since 1997 (median:
39
days; range: 21 to 240 days); however, longer incubation periods of 11
months
to 6 years were suggested by findings in 3 cases previously described
(8).

Although human rabies is rare in the United States, it should be
considered in
the postmortem differential diagnosis of fatal viral encephalitis cases
with
short morbidity periods if no cause of disease has been established.
Hospitalized patients with encephalitis of unknown etiology should be on
contact precautions, and rabies should be part of antemortem
differential
diagnosis in these patients. Both antemortem and postmortem testing for
rabies
are available at CDC and can be arranged through state health
departments.
Antemortem diagnostic samples consist of a full-thickness skin biopsy (4
to 6
mm in diameter) from the nape of the neck, fresh saliva, serum, and
cerebrospinal fluid. Although postmortem rabies diagnosis can be
performed on
formalin-fixed brain material, fresh brain material provides the optimal
sample for maximum sensitivity, specificity, and time efficiency.

With the recent report from Wisconsin of a survivor of clinical rabies
(9),
rapid diagnosis of rabies is even more critical to managing a patient's
clinical course, despite a poor prognosis. In addition to enabling
consideration of novel interventions, advantages of early diagnosis
include
prompt implementation of appropriate infection-control measures, thereby
limiting the number of persons exposed or potentially exposed who
require
postexposure prophylaxis. Retrospective detection of 4
transplant-associated
rabies cases (3) and retrospective identification of an additional case
in
California in an immigrant from El Salvador, brought the total number of
2004
cases in the United States to eight, the highest number of human rabies
cases
reported since 1956, when 10 cases were reported.

References
- -----------
(1) CDC. Human rabies prevention--United States, 1999: recommendations
of the
Immunization Practices Advisory Committee (ACIP). MMWR 1999;44(No. RR-1).

(2) Warner CK, Zaki SR, Shieh WJ, et al. Laboratory investigation of
human
deaths from vampire bat rabies in Peru. Am J Trop Med Hyg 1999;60:502--7.

(3) CDC. Update: investigation of rabies infections in organ donor and
transplant recipients--Alabama, Arkansas, Oklahoma, and Texas, 2004.
MMWR
2004;53:615--6.

(4) CDC. Human death associated with bat rabies--California, 2003. MMWR
2004;53:33--5.

(5) CDC. Manufacturer's recall of human rabies vaccine--April 2, 2004.
MMWR
2004;53:287--9.

(6) Krebs JW, Mandel EJ, Swerdlow DL, Rupprecht CE. Rabies surveillance
in the
United States during 2003. J Am Vet Med Assoc 2004;225:1837--49.

(7) World Health Organization. Rabnet. Geneva, Switzerland: World Health
Organization; 2005. Available at
http://gamapserver.who.int/globalatlas/home.asp.

(8) Smith JS, Fishbein DB, Rupprecht CE, Clark K. Unexplained rabies in
three
immigrants in the United States: a virologic investigation. N Engl J Med
1991;324:205--11.

(9) CDC. Recovery of a patient from clinical rabies--Wisconsin, 2004.
MMWR
2004;53:1171--3.

(10) Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after
treatment
of rabies with induction of coma. N Engl J Med 2005;352: 2508--14.

- --
ProMED-mail


[This report provides an excellent review of rabies virus infection in
the USA
in recent years. The continuing lack of awareness of the hazard and the
failure of travellers to rabies-endemic areas to take adequate
precautions for
their own protection are matters of concern -- as is the decline in
vaccine
production. - Mod.CP]

[ProMED has posted 36 reports of rabies in humans in the USA since 1995.
Those interested should search the ProMED website, www.promedmail.org,
using
the search words rabies, USA & human in the Title. - Mod.JW]

[Elsevier reference:
C. Sriaroon et al. 2005. Common dilemmas in managing rabies exposed
subjects.
Travel Medicine & Infectious Disease 3(1)1-7.
http://dx.doi.org/10.1016/j.tmaid.2004.05.003]