Download Autopsies in outbreak situations

Autopsies in outbreak
situations
Jeannette Guarner, MD
Department of Pathology and Laboratory
Medicine
Emory University
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Conflicts: none
Disclosures:
 Paid
by The Emory Clinic
 Worked at CDC 1997-2007, now guest researcher
 Brought up in Mexico, thus funny accent
 Husband, at Emory University, Chair of Global Health

Images, own and from CDC:
 http://phil.cdc.gov/phil/home.asp
 http://dpd.cdc.gov/dpdx/HTML/Image_Library.htm
In the past 12 months, I have not had a significant financial interest or other
relationship with the manufacturer(s) of the product(s) or provider(s) of the
service(s) that will be discussed in my presentation.
This presentation will include discussion of diagnostic devices that have been
approved by the FDA.
Objectives
When is an autopsy important for
epidemiologic purposes?
 What are the tissues that need to be
obtained?
 Who does these autopsies?
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Diseases that need to be reported
immediately
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Animal or human
cases of:
 Anthrax
 Plague
 Viral
hemorrhagic
fevers: Ebola,
Marburg, Lassa,
Congo-Crimean
Diseases that need to be reported
immediately
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Human cases of:
 Botulism
 Melioidosis
 Smallpox
 Tularemia
 Novel
influenza
viruses
Other reportable diseases
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STDs: (HIV, chancroid,
gonococcal infections, syphilis)
Encephalitis & meningitis
(prions, viral, bacterial, fungal or
parasitic)
Diarrheal bacterial diseases:
Salmonella, E. coli 0157, Shigella,
Vibrio, Campylobacter, Yersinia
Tuberculosis, leprosy
Invasive disease by: streptococci,
meningococci, H. influenzae, S.
aureus
Miscellaneous:
 Rickettsia, Anaplasma,
Ehrlichia, Coxiella, C. psittaci,
C. trachomatis,
 Listeria, Brucella, Leptospira,
Bordetella, Borrelia, Legionella
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Fungal: coccidioidomycosis
GI parasites: giardiasis,
amebiasis, cryptosporidiosis,
cyclosporiasis
Blood parasites: malaria,
babesia
Viral diseases of childhood:
mumps, measles, rubella,
chickenpox—hospitalizations &
deaths)
Hepatitis (A through E)
Miscellaneous: dengue, yellow
fever, rabies, polio
Food poisoning related
(ciguatera, scombroid, paralytic
shellfish poisoning)
Other reportable diseases
Occurrence of any unusual disease
 Outbreaks of any disease
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Who usually
does the
reporting?
Recipient
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17 years old male.
Use of allogenic tendon tissue
to repair of anterior cruciate ligament.
Admitted one week later for fever, chills, and
pain and erythema around the knee incision.
Taken to surgery for debridement of necrotic
tissue (muscle and allograft).
Streptococcus pyogenes was cultured from
blood and surgical wound.
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During the hospitalization
the patient had persistent
fever and fluid in the knee.
The patient was treated with
antibiotics.
The case is reported to
CDC for investigation of
transplant associated
infection:
 Was there
contamination?
(donor, tissue collection,
tissue bank, surgery...)
Retrospective review of donor
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33 years old male with history of surgery to
cervical vertebrae one month before death.
Seen by physician because of pain in back at
the level of the chest, nausea, and vomiting.
Treated with tramadol and cyclobenzaprin.
Diagnosis: allergic reaction.
Sent to hospital for treatment but expires in
transit.
Autopsy had been performed by the ME
He donates soft tissues and bone.
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Autopsy of the donor:
 Severe coronary
atherosclerosis.
 Focal
bronchopneumonia.
Drug toxicity is considered
the cause of death..
As part of the CDC
investigation, autopsy
material (paraffin blocks)
are obtained from the
donor for testing.
lung
liver
Lee EH, et al. Invasive group-A streptococcal infection in an allograft
recipient. A case report. J Bone Joint Surg Am. 2007;89:2044-7.
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In May 2004, 3
patients that had
received
transplants die of
encephalitis.
Autopsies
performed in
academic center.
Negative IHC tests for: enteroviruses,
arenaviruses, Chagas, toxoplasmosis,
herpes, flaviviruses…
Retrospective review of charts:
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Common donor hospitalized for nausea,
vomiting, fever, and altered mental status.
Cocaine is found in urine. CT shows
subarachnoid hemorrhage.
All patients receiving organs (kidney and liver)
developed encephalitis that ended in coma and
death 3 weeks later.
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A 4th patient that received a liver from another
donor also dies with rabies encephalitis.
Epidemiologic investigation showed that rabies
transmission to the 4th patient was through an
iliac artery fragment obtained from the donor
that had transmitted rabies to the other
recipients.
Tacrolimus
Mycophenolate I&D of liver
mofetil Prednisone abscess
Hepatic
artery
revision
Agitation
Seizures
Hemodynamic
Delirium Fever
instability
X
Iliac Artery
Vent
Tacrolimus
Mycophenolate
mofetil Prednisone
Fever Vent
Diffuse tremors
Hemodynamic
sleepiness
instability
Home
Liver
X
X
Donor
Agitation
seizures
Abdominal
- flank pain
Fever
Mild
rejection
Cyclosporin A
Sirolimus
Prednisone
Kidney
Home
X
Home
Vent
Appendectomy
Confusion
Agitation Fever
Myoclonus Vent
Tacrolimus
Mycophenolate
mofetil Prednisone
Kidney
Transplant
nephrectomy
X
Home
April - June, 2004
6-22
6-19
6-16
6-13
6-10
6-7
6-4
6-1
5-29
5-26
5-23
5-20
5-17
5-14
5-11
5-8
5-5
5-2
4-29
Hemodynamic
instability
Srinivasan A, et al. Transmission of Rabies Virus from an Organ Donor
to Four Transplant Recipients. N Engl J Med 2005;352:1103-1111.
October 2003
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Report of deaths in children due to respiratory
disease in November and December.
Tested positive for H3N2 influenza A virus.
Surveillance is increased and included cases
from late September, 2003 to May, 2004.
 153 deaths from 40 states of patients < 18
years old
Pathology of upper respiratory tract
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Guarner J, et al Histopathologic
and immunohistochemical
features of influenza virus
infections in children during the
2003-04 season. Clin Infect Dis
2006;43:132-140
Congestion 45/48 cases (94%)
Mononuclear inflammation in
submucosa 33 (69%)
Hemorrhage 25 (52%)
Epithelial necrosis 22 (46%)
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Interstitial inflammation 36/55
cases (65%)
Intraalveolar edema 36 (65%)
Intraalveolar hemorrhage 31
(56%)
Diffuse alveolar damage 38
(69%)
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Location:
 Bronchoepithelial cells
staining in 25 cases
 Glandular cells staining in 8
 Staining of cells in alveoli in
6
Amount:
 15 (55%) significant
 12 (44%) rare (2 to 3 cells)
San Diego, March 2009
10 year old presents with
fever, cough and vomiting.
 Mother and brother had
had a similar respiratory
disease.
 A specimen is obtained
since the clinic is testing a
new diagnostic technique.
 Patient is treated
symptomatically.
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9 year old presents
with fever and
cough.
 Brother and cousin
had has similar
symptoms.
 A specimen is
obtained since they
are performing an
epidemiologic study.
 Patient is treated
symptomatically.
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Initial tests in patient 1 demonstrate
influenza A virus but could not be defined
if the patient had H1N1, H3N2, or H5N1.
 The San Diego Health Laboratory received
the specimens of both patients and could
not define the type of influenza virus.
 Specimens are sent to CDC arriving April
13 and 17.
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Mexico, April 2009
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12th WHO is notified of an increase in the number of
cases with atypical pneumonia.
17th Increase surveillance and initiation of epidemiologic
investigation.
23rd Canadian Reference Laboratory confirms that the
virus in these cases is a novel H1N1. The PHO is
notified.
24th Mexican Ministry of Health implements public
measures in airports and vaccinates all healthcare
professionals for seasonal influenza.
25th Presidential decree allowing sick people that do not
require hospitalization to stay at home.
26th Mexico starts performing PCR for novel H1N1.
27th Schools are closed.
MMWR. May 8, 2009 / 58:453-458
Denison AM et al. Diagnosis of
influenza from respiratory autopsy
tissues: detection of virus by real-time
reverse transcription-PCR in 222
cases. J Mol Diagn 2011;13:123-8.
Munster VJ et al. Science 2009;325:481
Predictions were not fulfilled
Avian influenza,
Porcine
 In Asia, in
America
 In the winter, in
the summer
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Index case
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October 3, 2001: A local hospital calls the
Florida State Health Department as Bacillus
anthracis has been isolated from CSF of a
photographer that worked for a newspaper.
Presence of B. anthracis is confirmed and a BT
investigation was started by CDC and other local
and federal FBI authorities.
Patient had 2 days of fever, fatigue, sweats, and
altered mental status.
Case definition
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Patient with clinical disease compatible
with cutaneous, gastrointestinal or
inhalational anthrax with
 B.
anthracis isolated from the affected site, or
 2 other tests positive for B. anthracis
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PCR, serology, or immunohistochemistry.
Patient died October 5
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Reasons to do the
autopsy:
 Route
of infection
 Potential homicide
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People involved in
process
Autopsy measures
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Measures needed to perform the autopsy:
 Universal
precautions (sharps)
 DO NOT use electrical saw to open skull
 Clean the autopsy room with 0.5% HCl and
autoclave instruments used.
 DO NOT embalm, recommend incineration
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Once tissues are formalin fixed they are
non-infectious
Concomitant second case, also in
Florida
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A mailroom worker from the same newspaper
was being treated with antibiotics because of a
pneumonia.
This patient had persistent bilateral pleural
effusions.
Cultures in clinic were negative.
Later, evidence of anthrax by IHC and PCR on
pleural fluid cell block and pleural fluid.
Third case, in New York City
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Secretary working at TV station
developed cutaneous lesion, onset
September 25.
Received antibiotics without obtaining
culture lesion samples.
October 12, 2001: biopsy obtained
Culture and PCR: negative for B.
anthracis.
Evidence anthrax by IHC on biopsy
and positive serology.
Summary of cases related with the
2001 bioterrorism attack
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Inhalational anthrax: 11 cases all confirmed, 5
deaths.
Cutaneous anthrax: 10 cases 8 confirmed, no
deaths.
Jernigan JA, et al. Bioterrorism-related inhalational anthrax: the first 10
cases reported in the United States. Emerg Infect Dis 7: 933-944, 2001.
Jernigan DB, et al. Investigation of bioterrorism-related anthrax, United
States, epidemiologic findings. Emerg Infect Dis 2002;8: 1019-28.
Guarner J, et al. Pathology and pathogenesis of bioterrorism-related
inhalational anthrax . Am J Pathol 2003;163:701-709.
Shieh WJ, et al. The critical role of pathology in the investigation of
bioterrorism-related cutaneous anthrax. Am J Pathol 2003;163(5): 1901-10.
NEJM 1999;
341: 815- 826
Pathogenesis of
inhalational anthrax
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With IHC, large amounts of bacilli and
antigens are found in mediastinal lymph
nodes and pleura. Hypothesis:
 Pleural
effusions could be attributed to
direct bacterial damage.
 It is possible that some macrophages with
spores go directly to the pleura where bacilli
germinate and cause damage.
 The persistent effusions could be due to
persistence of antigens in the pleura.
Pathogenesis of inhalational
anthrax
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Presence of vasculitis:
 Previous reports describe vasculitis and
capillaritis.
 The cases related with the bioterrorism
attack appear to have less vasculitis.
Hypothesis:
 Early diagnosis and treatment with new
antibiotic and better medical support care.
 Differences may be due to the dose or the
type of aerosol.
Case
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A 22-year-old man presented with fever and
hemoptysis.
His chest X ray showed no effusions or
infiltrates.
He had attended the funeral of his sister the
previous week in a rural community in Ecuador.
Several family members were also sick,
including his father who had died suddenly also
of a febrile disease and hemoptysis.
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Blood culture was obtained and grew:
Non motile, catalase positive, but
negative for oxidase, urease, and indole
Gabastou JM et al. An outbreak of plague including cases with
probable pneumonic infection, Ecuador 1998.
Trans R Soc Trop Med Hyg 2000;94:387-91.
Autopsies in 2 cases helped in reconstruction of plague
transmission, Ecuador 1998
Bubo
Secondary pneumonic plague
Septicemia
Second host with
primary
pneumonic plague
Infected guinea pig
Objectives
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When is an autopsy important for epidemiologic
purposes? All the time as you never know which ones
will and which will not be useful for epidemiologic
purposes. There are only a handful that you know in
advance.
What are the tissues that need to be obtained? Depends
on the pathogenesis of the possible infectious disease. If
you suspect an infectious diseases but no agent has
been implicated you will need to take an array of tissues
and keep some frozen for PCR and culture.
Who does these autopsies? Every pathologists that
performs autopsies.