POST-MORTEM FINDINGS
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A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
Date: Fri 9 Apr 2010
Source: MMWR Weekly, 59(13);393-396 [abbr. and edited]
Human Rabies -- Kentucky/Indiana, 2009
--------------------------------------
On 19 Oct 2009, clinicians from Kentucky contacted the CDC [Centers
for Disease Control and Prevention] regarding a suspected case of
rabies in a man from Indiana aged 43 years. This report summarizes
the patient's clinical presentation and course, the subsequent
epidemiologic investigation, and, for the 1st time, provides
infection control recommendations for personnel performing autopsies
on decedents with confirmed or suspected rabies infection.
Before the patient's death on 20 Oct 2009, a diagnosis of rabies was
suspected based on the history of acute, progressive encephalitis
with unknown etiology [recorded in the ProMED-mail post archived as:
"Rabies, bat, human - USA: (IN) 20091028.3733". - Mod.CP].
Preliminary serology results on antemortem serum samples detected
rabies virus-specific antibodies. Because local pathologists were
concerned about the biosafety risk posed by infectious aerosols at
autopsy and potential contamination of autopsy facilities, the
Kentucky Department for Public Health (KDPH) asked CDC staff members
to travel to Kentucky and perform an autopsy to confirm the diagnosis
and assist with the epidemiologic investigation.
Testing of autopsy samples was conducted at the CDC and detected
rabies virus antigens in brainstem and cerebellum. Rabies viral RNA
was isolated and typed as a variant common to the tricolored bat
(_Perimyotis subflavus_). Although rabies virus transmission from
organ or tissue transplant has been documented rarely (1,2),
transmission of rabies virus to persons performing autopsies has not
been reported. Autopsies can be performed safely on decedents with
confirmed or suspected rabies using careful dissection techniques,
personal protective equipment, and other recommended precautions.
Case Report
-----------
On 5 Oct 2009, a previously healthy man from Indiana aged 43 years
visited an employee health clinic with fever and cough. His vital
signs and physical examination were unremarkable except for coarse
rales on lung auscultation. The clinician made a diagnosis of
bronchitis, prescribed antibiotics, and asked the patient to return
the following day. At this follow-up appointment, the patient
reported worsening fever and chills, as well as new chest pain and
left arm numbness; he also exhibited decreased grip strength of the
left hand. An electrocardiogram showed no evidence of cardiac
ischemia. Later that day, an evaluation at a local emergency
department (ED) was similarly unrevealing, and the patient was given
narcotics and muscle relaxants for presumed musculoskeletal pain and
discharged home.
On 7 Oct 2009, the patient returned to the same ED, where he was
noted to have akathisia and motor restlessness thought to be side
effects from the muscle relaxant. The ED physician advised admission
to the hospital, but the patient returned home. Upon follow-up the
next day with a primary-care physician, the patient had prominent
muscle fasciculations, fever, tachycardia, and hypotension. Given
these signs, the physician was concerned about the possibility of
sepsis and admitted him to the hospital.
After admission, the patient's mental status deteriorated rapidly,
and he underwent endotracheal intubation for airway protection. On 9
Oct 2009, he was transferred to a referral hospital in the
neighboring state of Kentucky. A lumbar puncture yielded
cerebrospinal fluid (CSF) with glucose of 72 mg/dL (normal: 40--70
mg/dL), protein 140 mg/dL (normal: 15--45 mg/dL), 3 red blood
cells/mm3 (normal: 0--2 cells/ mm3), and 38 white blood cells /mm3
(normal: 0--5 cells/mm3); differential showed 99 percent lymphocytes
and 1 percent monocytes. During 9-19 Oct 2010, no etiology for the
patient's disease was identified, and his hospital course became
complicated by bradycardia, hypotension, rhabdomyolysis, and renal
failure requiring hemodialysis. Results of a magnetic resonance image
of the brain and a brain perfusion study were normal. Bacterial and
fungal cultures of CSF, in addition to laboratory tests for West Nile
virus, herpes simplex virus, influenza, and human immunodeficiency
virus, were negative.
On 19 Oct 2009, diagnostic testing for rabies was requested, and
samples of the patient's serum, saliva, and a nuchal skin biopsy were
sent to CDC for analysis. However, on 20 Oct 2009, while these tests
were pending, the patient's physical examination,
electroencephalogram, and apnea testing all indicated brain death.
Ventilatory support was withdrawn, and the patient died on 20 Oct 2010.
Postmortem Findings
-------------------
On 22 Oct 2009, testing at the CDC indicated rabies specific
immunoglobulin G (1:2,048) and immunoglobulin M (1:512) antibodies in
serum by the indirect fluorescent-antibody (IFA) assay. Subsequent
testing detected rabies virus neutralizing antibodies (0.44 IU/mL) in
serum by rapid fluorescent focus inhibition test (RFFIT). The
formalin-fixed nuchal skin biopsy specimen tested negative for viral
antigens by immunohistochemistry (IHC). On 27 Oct 2009, a CSF sample
collected on 11 Oct 2009 and located postmortem was sent to the CDC
and also tested negative for rabies antibodies by IFA and RFFIT. The
family requested an autopsy, but pathologists at the referral
hospital were concerned about the biosafety risk posed by infectious
aerosols at autopsy and potential contamination of autopsy
facilities. In response to a request for assistance from KDPH, CDC
staff members traveled to Kentucky and performed an autopsy limited
to the head to collect tissue specimens for diagnostic evaluation.
At autopsy, the brain weighed 1610 g (normal: 1300--1400 g) and
showed markedly congested and hemorrhagic leptomeninges.
Histopathologic examination revealed encephalomyelitis and abundant
neuronal cytoplasmic inclusions (Negri bodies). Rabies virus antigens
were detected in multiple samples of fresh central nervous system
(CNS) tissue by direct fluorescent antibody (DFA) testing and in
formalin-fixed CNS tissues by IHC. Viral RNA was detected in the
patient's saliva collected antemortem and CNS tissues collected at
autopsy by reverse transcription--polymerase chain reaction and was
typed as a variant common to the tricolored bat (_Perimyotis subflavus_).
Public Health Investigation [abbreviated]
-----------------------------------------
An investigation identified no specific source of rabies virus
exposure. However, the patient, who worked as a mechanic and lived in
a farming community in southern Indiana, had mentioned to his friends
that he had seen a bat in late July after removing a tarpaulin from a
tractor adjacent to his residence. He had not mentioned a bite or a
non-bite exposure associated with this or any other incident.
MMWR Editorial Note
-------------------
The case described in this report represents the 1st rabies death in
an Indiana resident since 2006 and only the 2nd such death since
1959. Including this case, a total of 31 cases of human rabies have
been reported in the United States since 2000. Of these, 14 (45
percent) were diagnosed postmortem, reinforcing the need to consider
rabies in all cases of acute progressive encephalitis of unknown
etiology. Human rabies cases in the United States might be
underreported because of lack of recognition and lack of
confirmation by diagnostic testing. When rabies is suspected,
antemortem diagnosis requires testing of serum, saliva, CSF, and a
nuchal skin biopsy.
The postmortem diagnosis of rabies is made by examination of tissue
from the brain (e.g., medulla, cerebellum, and hippocampus).
Autopsies fulfill an important function by diagnosing cases of rabies
and furthering understanding of the disease. By providing a diagnosis
for deceased patients with suspected but unconfirmed rabies, or for
patients in whom the disease was never suspected clinically,
autopsies can 1) aid the public health investigation; 2) help raise
public awareness of rabies associated with specific exposures; 3)
emphasize the importance of seeking medical evaluation after such an
exposure occurs; and 4) add to knowledge about current human rabies
incidence. In patients with confirmed rabies, autopsies provide
information about pathogenesis that might be relevant to
investigations of treatment.
Although contact with decedents with confirmed or suspected rabies
can cause anxiety, no confirmed case of rabies has ever been reported
among persons performing postmortem examinations of humans or
animals. Even from living patients with rabies, human-to-human
transmission has been documented only rarely, in cases of organ or
tissue transplantation (1,2). Aerosol transmission of rabies virus
has never been well documented outside of a research laboratory
setting (5). Both the CDC and the World Health Organization (WHO)
have stated that the infection risk to health-care personnel from
human rabies patients is no greater than from patients with other
viral or bacterial infections. In addition, rabies post-exposure
prophylaxis (PEP) is available for exposed personnel. Nevertheless,
because of the nearly universal fatal outcome from rabies, both the
CDC and the WHO recommend that all personnel working with rabies
patients or decedents adhere to recommended precautions (3,6).
Even the minimal risk for rabies virus transmission at autopsy can be
reduced by using careful dissection techniques and appropriate
personal protective equipment, including an N95 or higher respirator,
full face shield, goggles, gloves, complete body coverage by
protective wear, and heavy or chain mail gloves to help prevent cuts
or sticks from sharp instruments or bone fragments. Aerosols should
be minimized by using a handsaw rather than an oscillating saw, and
by avoiding contact of the saw blade with brain tissue while removing
the calvarium. Ample use of a 10 percent solution of sodium
hypochlorite for disinfection is recommended both during and after
the procedure to ensure decontamination of all exposed surfaces and equipment.
Participation in the autopsy should be limited to persons directly
involved in the procedure and collection of specimens. Previous
vaccination against rabies is not required for persons performing
such autopsies. PEP of autopsy personnel is recommended only if
contamination of a wound or mucous membrane with patient saliva or
other potentially infectious material (e.g., neural tissue) occurs
during the procedure (3,7,8). The case described in this report
highlights the need to educate pathologists and other hospital
personnel about appropriate rabies infection control procedures so
that autopsies can be performed safely in cases of confirmed or
suspected human rabies.
References
----------
(1) Helmick CG, Tauxe RV, Vernon AA. Is there a risk to contacts of
patients with rabies? Rev Infect Dis 1987;9:511--8.
(2) CDC. Investigation of rabies infections in organ donor and
transplant recipients---Alabama, Arkansas, Oklahoma, and Texas, 2004.
MMWR 2004;53:586--9.
(3) CDC. Human rabies prevention---United States, 2008:
recommendations of the Advisory Committee on Immunization Practices.
MMWR 2008;57(No. RR-3).
(4) CDC. Use of a reduced (4-dose) vaccine schedule for postexposure
prophylaxis to prevent human rabies: recommendations of the Advisory
Committee on Immunization Practices. MMWR 2010;59(No. RR-2).
(5) Gibbons RV. Cryptogenic rabies, bats, and the question of aerosol
transmission. Ann Emerg Med 2002;39:528--36.
(6) World Health Organization. WHO expert committee on rabies. World
Health Organ Tech Rep Ser 2005;931:1--121.
(7) CDC. Human rabies---California, 1987. MMWR 1988;37:305--8.
(8) CDC. Human rabies---Miami, 1994. MMWR 1994;43:773--5.
--
Communicated by:
ProMED-mail
[There is the need to consider rabies in all cases of acute
progressive encephalitis of unknown etiology. Human rabies cases in
the United States might be underreported because of lack of
recognition and lack of confirmation by diagnostic testing. For the
1st time, this document provides infection control recommendations
for personnel performing autopsies on decedents with confirmed or
suspected rabies infection.
Interested readers should access the original text to view images of
the decedent's brain at autopsy and the histopathology. - Mod.CP]
[see also:
Rabies, bat, human - USA: (IN) 20091028.3733]
..................cp/ejp/mpp
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