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Viral Respiratory
Infections in the
Morbidity and Mortality
of Airway Diseases and
Immunocompromised
States
Acute and Chronic Bronchitis,
COPD, Asthma, Cystic Fibrosis,
and Immunocompromised
Cancer Patients
Frequency, Seasonality,
and Characteristics of
Viral Respiratory
Infections (VRIs)
Impact of VRIs
• Recognized for the last century as the most
common infectious illness in humans
• Terminology has varied
– Common respiratory infection
– Common cold
– Rhinosinusitis
• Rhinoviruses (RVs) cause a majority of these
infections
Monto AS et al. Clin Ther. 2001;1615.
Economic and Societal Burden
of VRIs
• Adults average ~2 to 4 colds1,2 and children average 3 to 8
colds3 per year
• In 1996, colds were associated with ~148 million days
restricted activity, 20 million days missed work, 22 million
days missed school, 45 million days bedridden4
• In 1998, 25 million office visits to primary care providers for
upper respiratory infections (URIs)5
• Costs associated with VRIs estimated at ~$25 billion
annually6
1. Turner RB. Pediatr Ann. 1998;27:790.
2. Monto AS et al. Clin Ther. 2001;23:1615.
3. Rosenstein N et al. Pediatrics. 1998;101:181
4. Adams PF et al. Vital Health Stat. 1999;10 (200).
5. Gonzales R et al. Clin Infect Dis. 2001;33:757.
6. Fendrick AM et al. Value in Health. 2001;4:412.
Mean Annual Incidence of Respiratory
Illnesses per Person-Year, Tecumseh,
Michigan, 1965–1971
7
Females
Mean annual
illness incidence
6
Males
5
4
3
2
1
0
1
1–2
3–4
5–9
10–14
15–19 20–24
Age group (yr)
Reprinted from Monto AS, Ullman BM. JAMA. 1974;227:164.
25–29
30–39
40–49 50–59
60
Seasonality of Respiratory Agents: Proportion
Isolated in Each Calendar Month During
6 Years of Tecumseh, Michigan, Study
30
RV
Parainfluenza viruses
Respiratory syncytial virus (RSV)
Influenza virus
Percent
25
20
15
10
5
0
30
Percent
25
20
15
10
5
0
Jan Apr Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jan Apr Sep Oct Nov Dec Jan Feb Mar Apr May Jun
Reprinted from Br J Prev Soc Med, 1977;31:101-108, with permission from the BMJ Publishing Group.
Transmission of Respiratory
Viruses
• Transmission of viruses differs
• Influenza
– Airborne transmission1
– Widespread outbreaks
• RVs
– Closer contact required
– Aerosol and direct2,3
– Households and schools are sites of transmission4
1. Goldman DA. Pediatr Infect Dis J. 2000;19(10 suppl):S97.
2. Gwaltney JM Jr, Hendley JO. Am J Epidemiol. 1982;116:828.
3. Dick EC et al. J Infect Dis. 1987;156:442.
4. Gwaltney JM Jr. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases.
5th ed. Philadelphia: Churchill Livingstone; 2000:1940.
Characteristics of VRIs of
Known Etiology
Coryza
Sore throat
Headache
100
Cough
Activity restriction
Lower respiratory symptoms
Percent
80
60
40
20
0
RV
RSV
Parainfluenza
virus
Hemolytic
streptococci
Influenza A
Influenza B
Reprinted from Br J Prev Soc Med, 1977;31:101-108, with permission from the BMJ Publishing Group.
Characteristics of RV-Associated
Illnesses
Illness with indicated syndrome (%)
Percent with
Median
duration Activity
Age group No. of
Lower
Upper
LaryngoPhysician
(years) isolates respiratory respiratory pharyngeal Other (days) restriction consultation
0–4
61
14.8
83.6
1.6
—
12
0
16.4
5–19
39
5.1
74.4
15.4
5.1
7
56.4
15.4
20–39
59
33.9
59.3
6.8
—
13
11.9
15.3
40
17
64.7
29.4
5.9
—
20
35.3
35.3
176
23.8
68.2
6.8
1.2
12
19.9
17.6
Total
Reprinted with permission from Monto AS et al. J Infect Dis. 1987;156:43.
©1987 by The University of Chicago. All rights reserved.
Clinical Features and Duration of
Illness in Adults with RV Colds
(n=276, RV confirmed by PCR or culture)
Clinical feature
RV %
positive
First symptom (% of subjects)
Sore throat
Stuffy nose
Runny nose
Sneezing
39
17
17
8
Most bothersome symptom (% of subjects)
Runny nose
Stuffy nose
Sore throat
Malaise
36
20
19
10
Median duration of symptoms (days)
Cold episode
Sleep disturbance
Interference with daily activities
11
4
7
Adapted with permission from Arruda E et al. J Clin Microbiol. 1997;35:2864.
Detection of Viruses by RT-PCR in Middle
Ear Fluid and Nasopharyngeal Aspirates
from 92 Children with Acute Otitis Media
Middle ear
fluid, *No. (%)
Nasopharyngeal
aspirate, †No. (%)
Infected
children, No. (%)
RV
22 (24%)
28 (30%)
32 (35%)
RSV
17 (18%)
21 (23%)
26 (28%)
HCV
7 (8%)
14 (15%)
16 (17%)
44 (48%)
57 (62%)
69 (75%)
Virus
Total positive
*2 samples had both HRV and RSV RNA; †2 aspirates had both HRV and RSV RNA,
and 1 had both RSV and HCV RNA.
RV=rhinovirus; RSV=respiratory syncytial virus; HCV=human coronavirus.
Reproduced with permission from Pediatrics, Vol. 102, Pages 291-295, Table 2. Copyright 1998.
RV in Acute Sinusitis
• Sinusitis is an extremely common part of the
common cold syndrome
• RV has been detected in 50% of adult patients
with sinusitis by RT-PCR of maxillary sinus
brushings or nasal swabs1
• Frequency of association of RV infection with
sinusitis suggests the common cold could be
considered a rhinosinusitis2
1. Pitkäranta A et al. J Clin Microbial. 1997;35:1791.
2. Gwaltney JM Jr. Clin Infect Dis. 1996;23:1209.
VRIs and Acute Bronchitis
• Respiratory viruses are common pathogens in acute
bronchitis1
• Respiratory virus infection associated with cough1
–
–
–
–
Influenza virus: 75%–93% of cases
Adenovirus: 45%–90%
RVs: 32%–60%
Coronavirus: 10%–50%
• 40% of nonasthmatic patients with acute
bronchitis had FEV1 80% of predicted2
• Bronchial reactivity remained increased up to
5 weeks after episode of acute bronchitis2,3
1. Gwaltney JM Jr. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases.
5th ed. Philadelphia: Churchill Livingstone; 2000:703.
2. Williamson HA Jr. J Fam Pract. 1987;25:251.
3. Hallett JS, Jacobs RL. Ann Allergy. 1985;55:568.
RV Infection in the Elderly
• In persons 60–90 years of age with RV
infection, median duration of illness was
16 days
• 19% were confined to bed; 26% had
restriction of daily activities
• 63% had lower respiratory tract symptoms;
43% consulted their physician
• Burden of RV infection in the elderly appears
to exceed that of influenza
Nicholson KG et al. BMJ. 1996;313:1119.
Symptoms of RV Infection in
35 Culture-Documented Illnesses
in a Long-Term Care Facility
Symptom
Upper respiratory
Cough
Coryza
Nasal or sinus congestion
Sore throat
Total
Lower respiratory
Productive cough
Dyspnea
Hoarseness
Total
Gastrointestinal
Anorexia
Nausea, vomiting, or diarrhea
Total
Systemic
Malaise or fatigue
Myalgia
Sweating or chills
Total
Reprinted from Wald TG et al. Ann Intern Med. 1995;123:588.
No. of patients (%)
34 (97)
31 (89)
21 (60)
18 (51)
35 (100)
19 (54)
8 (23)
5 (14)
23 (66)
11 (31)
4 (11)
12 (34)
23 (66)
8 (23)
5 (14)
25 (71)
Summary
• VRIs are the most common infectious diseases
worldwide
• RVs are predominant cause of VRIs in all
age groups
• Transmission requires relatively close contact
• Family and school major sites of transmission
• RV infections peak in autumn, with minor spring
peaks
• RVs cause AOM, sinusitis, and bronchitis in
otherwise healthy people
Role of VRIs in Asthma
Exacerbations
Causes of Asthma Exacerbations
• Poor underlying control
• Environmental factors
–
–
–
–
–
–
–
VRIs
Allergen exposure
Air pollution
Bacterial infections
Stress
Exercise/cold air
Occupational exposure
Viruses Detected During Asthma
Exacerbations in Children
Method of detection
Virus
PCR
Culture
Picornaviruses
146
47
17
14
Coronavirus
Influenza viruses
Immunofluorescence
Antibody rise
by ELISA
Total
147 *
21
38
14
10
20
21
Parainfluenza
viruses 1, 2, and 3
6
6
18
21
RSV
6
6
12
12
Other
2
1
2
3
*84 identified as RV on further testing.
ELISA=enzyme-linked immunosorbent assay.
Reprinted from BMJ. 1995;310:1225-1229, with permission from the BMJ Publishing Group.
VRIs and Hospitalizations
for Asthma
Hospital admissions for asthma correlate with virus
isolation peaks and school terms.
URIs
20
Total pediatric and
adult hospitalizations
15
School holidays
10
5
0
Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar
Adapted with permission from Johnston SL et al. Am J Respir Crit Care Med. 1996;154:654. Official Journal
of the American Thoracic Society. ©American Lung Association.
Children with Wheezing
Presenting to the ER
• Comparison of wheezing and nonwheezing (control)
children
– Age, atopic status, eosinophil markers
• In wheezing children <2 years old
– Respiratory viruses detected in 82% (18/22)
– RSV predominant, 68% (15/22)
• In wheezing children 2 years old
– Respiratory viruses detected in 83% (40/48)
– RV predominant, 71% (34/48)
– +PCR for RV and nasal eosinophilia or elevated nasal ECP,
48% (23/48)
Rakes GP et al. Am J Respir Crit Care Med. 1999;159:785.
Viruses Detected in 229
Symptomatic Asthma Episodes
in Adults
Pathogen
RV
HCV OC43
HCV 229E
Influenza B
Parainfluenza
RSV
Chlamydia psittaci
Dual infection
Number
Percent of
all episodes
76
21
15
2
5
2
3
5
33.2
9.2
6.6
0.9
2.2
0.9
1.3
2.2
RV=rhinovirus; HCV=human coronavirus; RSV=respiratory syncytial virus.
Nicholson KG et al. BMJ. 1993;307:982.
Viruses Detected in Adult Patients
Hospitalized with Asthma
3%
Influenza A
Influenza B
RV
Adenovirus
RSV
Herpes
3%
6.1%
27.3%
54.5%
6.1%
33 organisms isolated; 5 subjects had >1 virus detected and some viruses were
detected by >1 test.
Data from Teichtahl H et al. Chest. 1997;112:591.
Respiratory Infections in
Infancy May Protect Against
Development of Asthma
• 2 episodes of “common cold” before
age 1 yr decrease risk of asthma by age 7
by ~50%
• Other viral infections—eg, herpes, varicella,
measles—also protective
• Reported LRI with wheeze in the first 3 years
of life increases risk of asthma
Illi S et al. BMJ. 2001;322:390.
Effect of Day Care in Infancy and
Number of Older Siblings on
Asthma Risk
Children who had 2 older siblings or attended day care
during first 6 mo of life had increased risk of wheeze early
in life but decreased risk later.
Adjusted relative risk
of frequent wheezing
2.7
P=0.01
P=0.03
1.0
P=0.001
P<0.001
P<0.001
0.4
0.1
1
2
3
4
5
6
7
8
Age (yr)
9
10
11
12
Reprinted with permission from Ball TM et al. N Engl J Med. 2000;343:538. Copyright ©2000
Massachusetts Medical Society. All rights reserved.
13
14
Immunologic Mechanisms of VRIInduced Asthma Exacerbations
• Viral infections (esp.
RV) frequently cause
exacerbations of
asthma
• Possible mechanisms
– Extension into the lower
airway1-3
– Inflammation2,3
1. Gern JE et al. Am J Respir Crit Care Med. 1997;155:1159.
2. Gern JE, Busse WW. J Allergy Clin Immunol. 2000;106:201.
3. Fraenkel DJ et al. Am J Respir Crit Care Med. 1995;151:879.
RV-Induced Airway Inflammation
Plasma
leakage
Inflammatory
cell recruitment
and activation
Mucus
hypersecretion
Virus-infected
epithelium
Airway
Hyperresponsiveness
Neural activation
Adapted from Gern JE, Busse WW. J Allergy Clin Immunol. 2000;106:201.
What Is Different About VRIs in
Asthma?
• VRIs (especially RV infections in children >2 yr old)
and atopy synergistically enhance the risk of
wheezing1
– Antigen-specific IgE
– Eosinophilic inflammation
• Cytokine production pattern is related to outcomes
of experimental infection2
• High IFN-/IL-5 ratio=Th1-type (antiviral) response2
• Low IFN-/IL-5 ratio=Th2-type (allergic) response2
1. Rakes GP et al. Am J Respir Crit Care Med. 1999;159:785.
2. Gern JE et al. Am J Respir Crit Care Med. 2000;162:2226.
Immunologic Risk Factors for
More Severe VRIs
• PBMC IFN- secretion
• Sputum IFN-/IL-5
mRNA ratio correlates
with
– Lower symptom
scores
– More rapid viral
clearance
IFN/IL-5 ratio (units)
– Reduced peak viral
shedding
104
Th1
103
102
101
100
Th2
No
Yes
Virus detected at 14 days?
Parry DE et al. J Allergy Clin Immunol. 2000;105:692.
Reprinted from Gern JE et al. Am J Respir Crit Care Med. 2000;162:2226.
Summary
• Viruses cause asthma exacerbations in adults
and children
• RVs cause ~60% of virus-induced exacerbations
of asthma
• RVs directly infect the bronchial airways
• The response to viral infection is shaped by the
host’s antiviral response
• VRIs in early childhood may protect against the
development of asthma
Role of VRI and RV in
Acute Exacerbations of
Chronic Bronchitis
Cost of Acute Exacerbations of
Chronic Bronchitis (AECB)
• Hospitalization (500,000 episodes)
– Total cost, $1.6 billion
– Mean LOS, 6 days
– Mean cost, $5500/patient
• Outpatient office visits
– 65 yr: 331,000, cost $24.9 million
– <65 yr: 237,000, cost $15.1 million
• Indirect costs
– Days lost from work
– Lost productivity
.
Niederman MS et al. Clin Ther. 1999;21:576-591
AECB: Etiology
• Infectious, 80%
– Bacterial pathogens, 40%–50%
– Viruses, 30%–40%
– Atypical bacteria, 5%–10%
• Noninfectious, 20%
– Environmental factors
– Noncompliance with medical therapy
Sethi S. Chest. 2000;117(suppl):380S.
Viral AECB: Pathogens
35
Control
% of total identified
30
FEV1 50%
25
FEV1 <50%
20
15
10
5
0
Picornaviruses
Parainfluenza
viruses
Coronaviruses
Influenza
viruses
Data from Greenberg SB et al. Am J Respir Crit Care Med. 2000;162:167.
RSV
Adenoviruses
Virus-Associated Illness in
Controls and COPD Patients
Controls
FEV1 50%
FEV1 <50%
No. patients
55
30
32
No. respiratory
illnesses/yr
1.4
1.8
3
No. VRIs/yr
0.54
0.38
0.52
% LRT
symptoms
alone
0
0
26
LRT = lower respiratory tract.
Data from Greenberg SB et al. Am J Respir Crit Care Med. 2000;162:167.
Viral AECB: Medical Resource
Utilization
100
• FEV1<50%
predicted
80
70
60
% VRI
– 52 hospitalizations
in 12 patients
– 82% acute
exacerbations,
22% pneumonia
– 5 of 6 deaths were
COPD related
Control
FEV1 50% predicted
FEV1 <50% predicted
50
40
30
20
10
0
Office
ER=emergency room.
Data from Greenberg SB et al. Am J Respir Crit Care Med. 2000;162:167.
ER
Hospital
Viral AECB: Clinical Presentation
• AECB manifestations
– Increased dyspnea, 76%
– Increased sputum volume, 62%
– Increased sputum purulence, 39%
• Anthonisen type
– Type 1 (all 3 of above symptoms), 20%
– Type 2 (2 of above symptoms), 46%
– Type 3 (1 of above symptoms), 34%
• 64% of AECB associated with prior cold (18 days)
Seemungal T et al. Am J Respir Crit Care Med. 2001;164:1618.
AECB: Viral Detection and
Symptoms
25
% of reported exacerbations
• 39.2% of AECB
associated with
viral infection
• Cold, increased
dyspnea with cold,
and sore throat
associated with
viral isolation
20
15
10
5
0
RV
Corona Infl A
Data from Seemungal T et al. Am J Respir Crit Care Med. 2001;164:1618.
Infl B Parainfl Adeno RSV
Summary
• AECB are associated with considerable
morbidity, mortality, and health care costs
• VRIs are an important cause of AECB
• RVs are frequently detected in the airway
secretions of patients with AECB
VRIs in Patients with
Cystic Fibrosis
Cystic Fibrosis (CF): Respiratory
Viruses
• Cause exacerbations and LRIs
• Contribute to long-term pulmonary
deterioration, morbidity, mortality
• Strongly associated with every measure of
CF disease progression1
• Contribute to initial bacterial colonization2
1. Wang EEL et al. N Engl J Med. 1984;311:1653.
2. Armstrong et al. Pediatr Pulmonol. 1998;26:371.
CF: Proposed Mechanisms of
Virus-Induced Exacerbation
• Infection of epithelial cells
– Release of proinflammatory mediators
– Attraction and activation of inflammatory cells
– Neutrophil release of prostaglandins and oxygen
radicals
•
•
•
•
Altered endothelial permeability
Promotion of edema, enhanced cell recruitment
Stimulation of mucus secretion
Airway smooth muscle contraction
Prober CG. Clin Rev Allergy. 1991;9:87.
Summary
• VRIs are associated with clinical
exacerbations of CF with disease
progression
• Inflammatory response most likely
mechanism by which VRIs exacerbate CF
• Viruses predispose to bacterial colonization
and infection
VRIs in
Immunosuppressed
Cancer Patients
Impairments in Viral Immunity
in BMT Recipients with Cancer
• B lymphocytes
–
–
–
Reduced response to stimulatory cytokines (IL-4)
Reduced serum immunoglobulins
Depressed primary and secondary responses to antigens
• T lymphocytes
–
–
–
–
–
Reduced CD4 lymphocyte numbers
Reduced helper cell activity
Increased suppressor cell activity
Reduced proliferative responses
Reduced CD8 lymphocyte cytotoxic function
• Mucositis
• Reduced IgA secretion
Couch RB et al. Am J Med. 1997;102(suppl 3A):2.
Risk Factors Associated with
Serious Morbidity from VRIs in
BMT Recipients
• Allogeneic transplant
• Hematologic malignancy
• Graft-vs-host disease
• Corticosteroid therapy
• ? Conditioning regimen
• Lymphopenia (<200/mL)
• Age >65 years
• <100 days post-transplant
Sable CA, Donowitz GR. Clin Infect Dis. 1994;18:273.
Important Features of VRIs in
Immunocompromised Patients
• High potential for nosocomial acquisition1
• Prolonged shedding of virus, even with
treatment2
• High frequency of pneumonia and death1
• Viral pneumonia often associated with other
infections1
• Outbreaks can occur in absence of
community epidemic1
1. Couch RB et al. Am J Med. 1997;102(suppl 3A):2.
2. Bodey GP. Am J Med. 1997;102(suppl 3A):77.
Progression of VRIs in
Leukemia and BMT
No. of infections
leading to pneumonia
Pneumonia
(% of infections)
Death
(% of those
with pneumonia)*
22
33
59
61
32
36
Leukemia
BMT
27
20
78
70
33
25
Parainfluenza
Leukemia
BMT
9
45
67
58
44
22
22
32
100
RSV1
Leukemia
BMT
Influenza
RV2
BMT
*Other pulmonary infections often present.
1. Data from Couch RB et al. Am J Med. 1997;102(suppl 3A):2.
2. Data from Ghosh et al. Clin Infect Dis. 1999;29:528.
Summary
• VRIs are an important cause of morbidity
and mortality in immunosuppressed cancer
patients
• Underlying disease and immunosuppressive
therapy contribute to the high mortality rate
in BMT patients with VRIs
Acute Respiratory
Infections and Antibiotic
Use: A Primary Care and
Health Services
Research Perspective
Acute Respiratory Infections (ARIs):
Primary Care Office Visits, Antibiotic Use,
and Bacterial Prevalence in US, 1998
100
25,000
Office visits (1000)
Antibiotic prescription
20,000
80
Bacterial prevalence
60
15,000
62%
76%
10,000
30%
40
59%
70%
20
5000
0
0
URI
Otitis media Sinusitis
Pharyngitis Bronchitis
Reprinted from Gonzales R et al. Clin Infect Dis. 2001;33:757.
Antibiotic Rx and estimated
bacterial prevalence (% of visits)
Office visits
Estimated Annual Cost of Antibiotic
Use for ARIs in US, 1998
ARI diagnosis
Otitis media
Pharyngitis
URI
Sinusitis
Bronchitis
Total
No. of
prescriptions
(millions)
9.6
8.7
7.4
7.9
7.8
41.4
Cost estimate
(millions)
$280
$215
$227
$310
$289
$1322
Estimated 55% of prescriptions (22.6 million) for ARIs are
unnecessary, at a cost of $726 million.
Adapted from Gonzales R et al. Clin Infect Dis. 2001;33:757.
Emergency Department Visits and
Antibiotic Use for ARIs in US, 1996
Condition
URIs, all
Visits (millions)
Antibiotic use
2.0
26%
URIs only*
1.6
24%
Bronchitis, all
2.1
42%
1.2
42%
Otitis media
2.7
55%
Pharyngitis
1.5
52%
Total ARIs
8.1
44.5%
Bronchitis only*
*Excludes patients with additional diagnoses of asthma, COPD, chronic bronchitis,
pneumonia, otitis, pharyngitis, sinusitis, HIV.
Adapted from Stone S et al. Ann Emerg Med. 2000;36:320.
Use of Antibiotics: Patient
Expectations, Physician Perceptions,
Public Beliefs
• Patients who expect antibiotics receive them more often1-3
• Strongest predictor of receipt of antibiotics for ARI is
MD perception of patient expectation1,3
• Patient satisfaction more closely related to quality of
communication (explanations, contingency plans) than receipt of
antibiotics1,3,4
• Public beliefs about antibiotic effectiveness5
– Useful for VRI: 55%
– Useful for bacterial but not viral illness: 21%
1. Hamm RM et al. J Fam Pract. 1996;43:56.
2. Bauchner H et al. Pediatrics. 1999;103:395.
3. Mangione-Smith R et al. Pediatrics. 1999;103:711.
4. Mangione-Smith R et al. Arch Pediatr Adolesc Med. 2001;155:800.
5. Wilson AA et al. J Gen Intern Med. 1999;14:658.
Decreasing Antibiotic Overuse
Is Hard But Possible
• Pre-, post-intervention trial to decrease antibiotic
use in acute, uncomplicated bronchitis in HMO sites
• Full intervention: household and office-based
patient-education materials; clinician education,
profiling, and academic detailing
• Limited intervention: office-based patient education
materials
• Antibiotic use declined from 74% to 48% only at site
with full intervention
• No differences in revisits, other prescriptions, other
diagnoses
Gonzales R et al. JAMA. 1999;281:1512.
Summary
• “Just Say No” to unnecessary antibiotics
for ARI
– Community and patient education
– Office-based interventions
– Clinician-oriented interventions
• Better technology for rapid diagnostic testing
to identify bacterial vs viral illness
• Possible development of antiviral
medications
Program Summary
• VRIs are an important cause of morbidity and increased
health care costs
• RVs are the most common cause of VRIs
• RVs are also an important cause of morbidity in patients
with asthma, COPD, and CF, and in
immunocompromised patients
• In immunocompromised cancer patients, VRIs increase
mortality and morbidity from pneumonia
• The mechanism of exacerbation of asthma, chronic
bronchitis, and CF is related to the host inflammatory
response
• Patients with VRIs are often prescribed antibiotics
Contributors
Homer A. Boushey, Jr., MD, Editor
University of California
San Francisco
Gerald P. Bodey, Sr., MD
The University of Texas
M. D. Anderson Cancer Center
Houston
Sebastian L. Johnston, MD
Imperial College of Science, Technology
and Medicine
London, UK
James E. Gern, MD
University of Wisconsin
Madison
Arnold S. Monto, MD
University of Michigan School of Public Health
Ann Arbor
Ethan A. Halm, MD, MPH
Mount Sinai School of Medicine
New York
Harley A. Rotbart, MD
University of Colorado Health Sciences Center
Denver
Sanjay Sethi, MD
State University of New York
Buffalo