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Infections without borders 2011 ASCP Annual Meeting Jeannette Guarner, MD Department of Pathology and Laboratory Medicine Emory University
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Page 1: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

Infections without borders

2011 ASCP Annual Meeting

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

2011 ASCP Annual Meeting

� Husband, at Emory University, Chair of Global Health

� Images, own and from CDC: � http://phil.cdc.gov/phil/home.asp

� http://www.terrorismcentral.com/Library/WMD/Bio/plague/LabProtocols.html

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Objectives

� Identify the epidemiology, clinical and pathologic presentation and microbiologic aspects of anthrax, plague, mycobacteria, SARS coronavirus, and 2009 H1N1 influenza virus.

�Recognize these diseases and consult with the appropriate health care entities.

2011 ASCP Annual Meeting

appropriate health care entities.

�Assess if their area/ hospital preparedness plan includes these infectious agents.

�Structure:� Scenarios/ cases

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QUESTION: A CSF sent from the Emergency Department

shows the following on the Gram stain. What is the best

description for the structures present inside the red circle?

1. Gram-positive cocci

2. Gram-negative bacilli

3. Gram-positive bacilli

4. Gram-negative cocci

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

4. Gram-negative cocci

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Gram stain

Crystal violet

Fixation

Iodine

(mordant)

Alcohol

(decolorization)

Safranin

(counterstain)

2011 ASCP Annual Meeting

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QUESTION: What organisms should be considered in the

differential diagnosis of this case based on the Gram stain?

1. Streptococcus

pneumoniae,

Staphylococcus aureus

2. Bacillus spp., Listeria

monocytogenes, and

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

monocytogenes, and

Corynebacterium spp.

3. Neisseria meningitidis,

Haemophilus influenzae

4. Pseudomonas spp.,

Escherichia coli., and

Salmonella spp.

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Chart review

�The specimen belongs to a 63 year old man that

presented with fever, vomiting and confusion.

�Past medical history: 4 days of fever, myalgias, and

malaise. He had not had a sore throat or any other

upper respiratory symptoms.

2011 ASCP Annual Meeting

upper respiratory symptoms.

�He had been trekking in the North Carolina

mountains the week before his symptoms started.

�Physical exam: No nuchal rigidity. Chest

examination revealed bibasilar ronchi.

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�The chest X-Ray

showed a widened

mediastinum

2011 ASCP Annual Meeting

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QUESTION: In this patient with the gram-positive bacillus in

his CSF, what is the most likely cause of a widened

mediastinum?

1. Ruptured esophagus

2. Metastases to mediastinal

lymph nodes

3. Inhalational anthrax

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0% 0%0%0%

3. Inhalational anthrax

4. Aortic aneurysm

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Bacillus anthracis in the laboratory

� Bacillus anthracis should grow within six to eight hours.

� Colonies show a “medusa head” appearance or have comma shaped projections

� Colonies are sticky when picked up

2011 ASCP Annual Meeting

� Colonies are sticky when picked up

� The organisms are gram-positive, spore forming, catalase positive and non-motile.

� The capsule can be highlighted using India ink

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QUESTION: To which one of the following agencies does the

hospital where the patient is being treated needs to

immediately report that there is a suspect anthrax case?

1. State Public Health

Department

2. Local Federal Bureau of

Investigation (FBI)

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

Investigation (FBI)

3. Department of Homeland

Security

4. Centers for Disease Control

and Prevention (CDC)

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Hospital course

�The patient was empirically treated with intravenous

cefotaxime and vancomycin.

�Within hours after admission, the patient had a

generalized grand mal seizure and was intubated

and high dose steroids were added.

2011 ASCP Annual Meeting

and high dose steroids were added.

�On the second hospital day, hypotension and acute

renal failure developed. He continued to be

unconscious during the hospitalization.

�On the third hospital day, he developed refractory

hypotension, had a cardiac arrest and died.

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QUESTION: Should an autopsy be performed?

1. Yes, because the cause

of death is unknown.

2. Yes, because this death

was a possible homicide.

3. No, because the cause

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0% 0%0%0%

3. No, because the cause

of death is known.

4. No, because an autopsy

would expose other

individuals to the

infectious agent.

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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

2011 ASCP Annual Meeting

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.

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QUESTION: A Laboratory technologist brings to your attention

a Giemsa stained blood smear that shows “very funny

bacteria”. How would you describe the organisms that you see

in this image?

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

1. Gram-positive rod-shaped

bacteria containing spores

2. Bipolar staining bacteria

3. Gram-positive, rod-shaped

bipolar bacteria

4. Rod-shaped bacteria in chains

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QUESTION: What organisms should be included in the

differential diagnosis based on this Giemsa stain?

1. Burkholderia

pseudomallei, Yersinia

pestis

2. Clostridium perfringens,

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

Clostridium perfringens,

Listeria monocytogenes

3. Staphylococcus aureus,

Streptoccous

pneumoniae

4. Legionella spp.,

Chlamydiophila

pneumoniae

Page 17: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

Case:

�53 year old diabetic man from New Mexico

vacationing in New York.

�On admission, he complained of fatigue and had

diaphoresis, rigors, tender left inguinal adenopathy

with overlying edema, and lower extremity necrosis.

2011 ASCP Annual Meeting

with overlying edema, and lower extremity necrosis.

�Temperature 40.2°C, blood pressure 78/50 mm Hg.

�WBC 24,700/µl, platelets 72,000/µl.

�He was admitted to the ICU with the diagnosis of

septic shock. Guarner J, et al. Persistent Yersinia pestis antigens in ischemic tissues of a patient

with septicemic plague. Hum Pathol 2005;36:850-853.

Page 18: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

QUESTION: 48 hours later the following plate and Gram

stain are available from microbiology. What is the possible

diagnosis?

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

1. Burkholderia pseudomallei

2. Francisella tularensis

3. Yersinia pestis

4. Salmonella typhi

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Pathology of pneumonic plaguePrimary Secondary

Guarner J,et al.

2011 ASCP Annual Meeting

Guarner J,et al.

Immunohistochemi

cal detection of

Yersinia pestis in

formalin-fixed,

paraffin-embedded

tissue. Am J Clin

Pathol 2002;117:

205-209.

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QUESTION: Why is it important to distinguish between

primary and secondary plague pneumonia?

1. Treatment is different

2. Possible bioterrorism

3. Worse prognosis

4. Chest X-ray interpretation

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

4. Chest X-ray interpretation

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QUESTION: What term is used to describe an illness

acquired by a traveler in one area who becomes ill in

another area where the illness is not endemic?

1. Peripatetic

2. Endemic

3. Dislocated

Autochthonous

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

4. Autochthonous

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QUESTION: What is the vector for transmission of plague?

1. Fleas

2. Mosquitoes

3. Ticks

4. Tsetse flies

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

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2011 ASCP Annual Meeting

Page 24: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

Clinical history

�A 35 years old a farm worker originally from

Central America presented with fever and was

found to have a lung nodule in a Chest X ray. A

PPD was placed.

�His first sputum AFB smears shows:

2011 ASCP Annual Meeting

�His first sputum AFB smears shows:

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QUESTION: How many AFB organisms need to be present

in 1 µL of sputum so as to have a positive smear?

1. 100

2. 1,000

3. 10,000

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

4. 100,000

Siddiqi K et al. Clinical diagnosis of

smear-negative pulmonary tuberculosis in

low-income countries: the current

evidence. Lancet Infect Dise 2003;3:288

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QUESTION: The sputum culture exposed to light grew the

following colonies within 1 week, how would you classify this

mycobacteria?

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

1. Rapid grower

2. A photochromogen

3. A scotochromogen

4. Not in the Runyon

classification

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Runyon classification

2011 ASCP Annual Meeting

Not in the classification:

M. tuberculosis, M. bovis

Page 28: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

End of case

�The patient took his treatment which included

isoniazid, ethambutol, rifampin, pyrazinamide, and

vitamin B6, but did not go for his monthly follow ups.

�At 2 months he started feeling weak and having

nausea. He went to a physician and his liver

2011 ASCP Annual Meeting

nausea. He went to a physician and his liver

function tests were markedly elevated.

�Even though isoniazid was discontinued the patient

went into liver failure and he has been placed in the

waiting list for a liver transplant.

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2011 ASCP Annual Meeting

GERMANY - CIRCA 2005: Robert Koch

http://www.shutterstock.com/gallery-166210p1.html

USA - CIRCA 1975: Emily P. Bissell -

http://www.shutterstock.com/gallery-89286p1.html ?

MALI - CIRCA 1975: ambulance car and lungs

http://www.shutterstock.com/gallery-376564p1.html

POLAND - CIRCA 1982: Odo Bujwid (1857-1942),

bacteriologist,

http://www.shutterstock.com/cat.mhtml

wheel=1#id=67821679

SPAIN - CIRCA 1953: charity to fight tuberculosis,

http://www.shutterstock.com/gallery-472024p1.html

Page 30: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

� In January of 2003, an American businessman that

had been travelling in China and Vietnam presented

with a severe influenza-like illness to a Hanoi

hospital.

The patient rapidly went into respiratory failure

Case

2011 ASCP Annual Meeting

�The patient rapidly went into respiratory failure

requiring intubation.

�Hospital officials suspected avian influenza.

�However, Dr Carlo Urbani contacted WHO for

assistance since he thought the disease was not

avian influenza.

Page 31: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

QUESTION: Hospital officials were thinking the patient had

avian influenza (H5N1). Why?

1. Severe respiratory disease

is frequently caused by

influenza viruses

2. Avian influenza viruses are

easily transmissible from

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

easily transmissible from

human to human

3. This patient had eaten

chicken and other birds

while traveling

4. Influenza pandemics always

start in Asia

Page 32: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

QUESTION: What test is used for avian influenza viruses

(H5N1)?

1. Using commercially

available fluorescent

antibodies

2. Culturing nasopharyngeal

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

2. Culturing nasopharyngeal

specimens

3. Testing for IgM antibodies

against avian influenza

viruses

4. All of the above

Page 33: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

Detection of influenza viruses

Direct fluorescent Assays

(DFA)

Viral cultures

2011 ASCP Annual Meeting

Page 34: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

QUESTION: What test is used in your institution to diagnose

seasonal influenza viruses?

1. Viral cultures/ R-mix

2. PCR for respiratory

viruses

3. Direct fluorescent

2011 ASCP Annual Meeting1 2 3 4 5

0% 0% 0%0%0%

3. Direct fluorescent

antibody testing from

primary specimen

4. Rapid antigen testing

5. Other

Page 35: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

Sensitivity and specificity of influenza tests during the

2009 H1N1 pandemic

Rapid

antigen

DFA R-mix PCR

Luminex

Sensitivity 17.8 46.7 88.9 97.8

Specificity 93.6 94.5 100 100

2011 ASCP Annual Meeting

Specificity 93.6 94.5 100 100

PPV 77.4 91.3 100 100

NPV 47.9 58.9 87.9 97.3

Ginocchio CC et al. Evaluation of multiple test methods for the detection of the novel 2009

influenza A (H1N1) during the New York City outbreak. J Clin Virol. 2009;45:191-5.

Page 36: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

QUESTION: When people talk about influenza viruses they

mention H (number) and N (number) to refer to them. What

do H and N stand for?

1. Hydroxylysine and

neuraminidase

2. Hemagglutinin and

nalidixic acid

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

nalidixic acid

3. Hemolysin and nucleotide

4. Hemagglutinin and

neuraminidase

Page 37: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

QUESTION: What is the best way to protect yourself from

getting influenza?

1. Wash hands frequently

2. Avoid contact with sick

individuals

3. Avoid having wet

2011 ASCP Annual Meeting1 2 3 4 5

0% 0% 0%0%0%

3. Avoid having wet

hair/clothing while in cold

environments

4. Vaccination

5. Avoid contact with

children

Page 38: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

�Dr. Carlo Urbani, saw the patient in Hanoi and 2

weeks later, while attending a conference in

Thailand, became sick.

�He had respiratory failure and persistent fevers.

In a matter of weeks, Dr. Urbani and five other

Back to our case

2011 ASCP Annual Meeting

� In a matter of weeks, Dr. Urbani and five other

health care professionals that took care of the

patient died.

� Influenza testing was negative.

�Specimens obtained from Dr. Urbani were sent

to the CDC for study. Ksiazek TG, el al. A novel coronavirus associated

with severe acute respiratory syndrome. N Engl J

Med 2003; 348: 1953-1966.

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QUESTION: Electron microscopy of the viral culture showed

the following virus, which family does it belong to:

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

1. Togavirus

2. Flavivirus

3. Coronovirus

4. Rhabdovirus

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RabiesHerpes

Adenovirus SARS coronavirus

2011 ASCP Annual Meeting

Influenza Ebola

Pox

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�During the 2003 SARS

outbreak, symptoms

included:

� Fever

� Non-productive cough

� Muscle aches

2011 ASCP Annual Meeting

� Muscle aches

� Difficulty breathing

� Chills and shivering

Page 42: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

QUESTION: During the 2003 outbreak, what was the

method used for diagnosing a patient with SARS?

1. Reverse-transcriptase

Polymerase Chain

Reaction (RT-PCR)

2. Electron microscopy

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

3. Culture

4. Differential white blood

cell count

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Usual appearance of Ag & Ab

2011 ASCP Annual Meeting

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QUESTION: What was the use of serology during the outbreak?

1. Diagnose exposure

2. Diagnosis for isolation of

the patient

3. Screening of subjects

2011 ASCP Annual Meeting1 2 3 4

0% 0%0%0%

3. Screening of subjects

4. 1 and 3 are correct

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�Quarantine all patients with symptoms

�Ensure that healthcare staff are protected

appropriately and come to work healthy

�Enforce personal hygiene (hand washing)

Measures that hospitals used to decrease the

spread of SARS included:

2011 ASCP Annual Meeting

�Enforce personal hygiene (hand washing)

�Constant and active communication with staff as

well as with state and national health

departments

�Ensure that uninfected patients and their family

members are not exposed

Page 46: Infections without bordersdn3g20un7godm.cloudfront.net/2011/AM11SA/152.pdf · 2011-11-16 · bioterrorism-related anthrax, United States, epidemiologic findings. Emerg Infect Dis

QUESTION: Which of the following could potentially be the

next deadly global outbreak that necessitates strategies to

evaluate and respond to the infection?

1. Another form of SARS

2. Influenza H5N1

3. Influenza H1N1

2011 ASCP Annual Meeting1 2 3 4 5

0% 0% 0%0%0%

3. Influenza H1N1

4. A novel microbial

pathogen

5. All of the above

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�Hospitals need to produce a preparedness plan for outbreaks and pandemics so that they can take care of patients and staff.

2011 ASCP Annual Meeting