Autopsies in outbreak

situations

Jeannette Guarner, MD

Department of Pathology and Laboratory Medicine

Emory University

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?

Diseases that need to be reported

immediately

Animal or human

cases of:

Anthrax

Plague

Viral hemorrhagic

fevers: Ebola,

Marburg, Lassa,

Congo-Crimean

Diseases that need to be reported

immediately

Human cases of:

Botulism

Melioidosis

Smallpox

Tularemia

Novel influenza

viruses

Other reportable diseases 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

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

Who usually

does the

reporting?

Recipient

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.

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

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.

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.

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:

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.

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.

Kidney Home

Confusion

Agitation

Myoclonus

Donor

X

April - June, 2004

Liver Home

4-2

9

5-2

5-5

5-8

5-1

1

5-1

4

5-1

7

5-2

0

5-2

3

5-2

6

5-2

9

6-1

6-4

6-7

6-1

0

6-1

3

6-1

6

6-1

9

6-2

2

Kidney Home X

X

Home

X

X

Fever

Vent

Hemodynamic

instability

Transplant

nephrectomy

Mild

rejection Abdominal

- flank pain

Appendectomy

Agitation

seizures

Vent

Diffuse tremors

sleepiness

I&D of liver

abscess

Hepatic

artery

revision

Agitation

Seizures

Fever Delirium

Vent

Hemodynamic

instability

Fever

Fever

Vent

Hemodynamic

instability

Iliac Artery

Cyclosporin A

Sirolimus

Prednisone

Tacrolimus

Mycophenolate

mofetil Prednisone

Tacrolimus

Mycophenolate

mofetil Prednisone

Tacrolimus

Mycophenolate

mofetil Prednisone

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

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

Congestion 45/48 cases (94%)

Mononuclear inflammation in

submucosa 33 (69%)

Hemorrhage 25 (52%)

Epithelial necrosis 22 (46%)

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

Interstitial inflammation 36/55 cases (65%)

Intraalveolar edema 36 (65%)

Intraalveolar hemorrhage 31 (56%)

Diffuse alveolar damage 38 (69%)

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.

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.

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.

Mexico, April 2009 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

Index case

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

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

PCR, serology, or immunohistochemistry.

Patient died October 5

Reasons to do the

autopsy:

Route of infection

Potential homicide

People involved in

process

Autopsy measures

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

Once tissues are formalin fixed they are

non-infectious

Concomitant second case, also in

Florida

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

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

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 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 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

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.

Blood culture was obtained and grew:

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.

Non motile, catalase positive, but

negative for oxidase, urease, and indole

Autopsies in 2 cases helped in reconstruction of plague

transmission, Ecuador 1998

Infected guinea pig

Bubo

Septicemia

Secondary pneumonic plague

Second host with

primary

pneumonic plague

Objectives

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.