Att 5 - Smallpox article

Special Issue

Tara O’Toole
Johns Hopkins School of Public Health, Baltimore, Maryland, USA
Smallpox virus, which is among the most
dangerous organisms that might be used by
bioterrorists, is not widely available. The
international black market trade in weapons of
mass destruction is probably the only means of
acquiring the virus. Thus, only a terrorist
supported by the resources of a rogue state would
be able to procure and deploy smallpox. An
attack using the virus would involve relatively
sophisticated strategies and would deliberately
seek to sow public panic, disrupt and discredit
official institutions, and shake public confidence
in government.
The following scenario is intended to provoke
thought and dialogue that might illuminate the
uncertainties and challenges of bioterrorism and
stimulate review of institutional capacities for
rapid communication and coordinated action in
the wake of an attack.









































































April 1
The vice-president visits Northeast, a city of
2.5 million. His itinerary includes an awards
ceremony, an appearance at a local magnet
school, and a major speech at the local
university. A crowd of 1,000 people, including
students, is gathered in the university auditorium. Hundreds more wait outside, where the
vice-president stops to shake hands and respond
to queries from the media.
The Federal Bureau of Investigation (FBI)
has information suggesting a possible threat
against the vice-president from a terrorist group
with suspected links to a rogue state. The group
is known to have made inquiries about acquiring
biological pathogens, including smallpox, and is
suspected of having procured aerosolization
Address for correspondence: Tara O’Toole, Johns Hopkins
Center for Civilian Biodefense Studies, Candler Building,
Suite 850, 111 Market Place, Baltimore, MD 21202, USA; fax:
410-223-1665; e-mail: [email protected].

Emerging Infectious Diseases

equipment. FBI decides its information is too
vague and too sensitive to pass on to the
Department of Health and Human Services,
local law enforcement authorities, or the state
health department.
April 8
FBI informants report rumors that something happened while the vice-president was in
Northeast.
April 12
A 20-year-old university student goes to the
university hospital emergency room with fever
and severe muscle aches. She is pale, has a
temperature of 103°F, and is slightly leukopenic,
but the physical exam and laboratory results are
otherwise normal. She is presumed to have a
viral infection and is sent home with instructions
to drink fluids and take aspirin or ibuprofen for
muscle aches. Later that day, a 40-year-old
electrician arrives at the emergency room with
severe lower backache, headache, shaking chills,
and vomiting. He appears pale and has a
temperature of 102°F and a pale erythematous
rash on the face. The patient is a native of Puerto
Rico, where he visited 10 days earlier. A
diagnosis of dengue fever is considered, and the
patient is discharged with ibuprofen and
instructions to drink fluids.
April 13
Over the course of the day, four young adults
in their twenties come to the university hospital
emergency room with influenzalike symptoms
and are sent home.
April 14
The female student returns to the emergency
room after collapsing in class. She now has a red,
vesicular rash on the face and arms and appears
acutely ill. Her temperature is 102°F; her blood
pressure is normal. She is admitted to an
isolation room with presumptive diagnosis of

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adult chickenpox. She has had no contact with
others known to have chickenpox.
April 15
The electrician first seen on April 12 returns
to the emergency room by ambulance. He too has
a vesicular rash and appears very ill. He is also
admitted to an isolation room with presumptive
diagnosis of chickenpox.
That evening at 6 p.m. the infectious disease
consultant and the hospital epidemiologist meet
on the elevator. The infectious disease specialist
has just finished examining the student and the
electrician, both of whom have vesicular rash on
the face, arms, hands, and feet. The skin lesions
are evolving in phase. The possibility of smallpox
is raised. The infectious disease specialist takes a
swab specimen from the electrician’s skin
lesions, sends it to the laboratory, and requests
that it be examined by electron microscopy by an
experienced technician. The doctor assures the
technician that he will be vaccinated if the
specimen shows smallpox. At 7:00 p.m., electron
microscopy shows an orthopoxvirus consistent
with variola—the smallpox virus.
At 7:15 p.m. the hospital epidemiologist
declares a contagious disease emergency. The
two patients are moved to negative-pressure
rooms with HEPA filters. Visitors and hospital
staff not already caring for and in contact with
patients are forbidden to enter the floor.
Infection-control nurses begin interviewing staff
to determine who has been in face-to-face contact
with the patients during initial emergency room
visits and admission. The hospital epidemiologist
calls the chair of the department of medicine and
the hospital vice-president for medical affairs.
Within 45 minutes the chair of the
department of medicine and the president of the
hospital are meeting with the infectious disease
physician, the hospital epidemiologist, the
hospital vice-president for public relations, and
the hospital’s general counsel. The city and state
health commissioners join the meeting by phone.
The need to vaccinate and isolate all contacts of
the patients is recognized and discussed. It is
decided to secure the hospital. No one is allowed
to leave until all persons are identified so that
they can be vaccinated as soon as vaccine can be
obtained from the Centers for Disease Control
and Prevention (CDC). The possibility of
identifying and vaccinating other patient
contacts (e.g., family members not now in the

Vol. 5, No. 4, July–August 1999

hospital) is discussed, but no decisions are made
because the hospital’s legal authority for doing
this is unclear.
Half an hour later, the state health
commissioner calls FBI. He also contacts CDC to
request that smallpox vaccine be released for
hospital staff and patient contacts. Because
vaccine supplies are limited, CDC requests that
the diagnosis of smallpox first be confirmed at
CDC. CDC calls FBI and arranges to fly a threeperson Epidemic Intelligence Service team to
Northeast for assistance.
By 9:30 p.m., an FBI special agent arrives at
the hospital, secures biological samples taken
from the patients, and drives them to Andrews
Air Force Base, where a military aircraft flies the
samples to CDC’s Biosafety Level 4 laboratory in
Atlanta, Georgia. FBI requests that city police be
called to help maintain order and ensure that no
patients, staff, or visitors leave the hospital until
all occupants have been identified and their
addresses have been recorded. More FBI agents
and city police arrive on the hospital grounds.
Hospital visitors are confused and angered
by police refusal to allow anyone to leave the
hospital. No explanation is given for the
containment to staff, visitors, or the police.
Ambulances are rerouted to other hospitals. The
rumor that smallpox has broken out rapidly
spreads through the building, as do rumors that
a terrorist wanted by FBI is in the building. A
fight erupts between people trying to leave the
facility and the police. Three people are injured
and sent to the emergency room. More police and
FBI agents arrive and surround the building.
The local television networks report the
scene outside the hospital on the late night news.
The hospital public relations representative
explains that the lock-in is temporary and
intended only to gather names and addresses so
that people can be contacted and treated if a
suspected, but unnamed, contagious disease is
confirmed. CNN arrives and demands access to
the hospital and affected patients. Rumors about
what the contagious disease might be include
Hong Kong flu, meningitis, Ebola virus,
smallpox, and measles.
The mayor and state attorney general’s office
are contacted by the health commissioner. There
is a phone discussion with the hospital’s general
counsel and epidemiologist about the right to
impose quarantine. Visitors, nonessential personnel, and new patients are blocked from

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entering the hospital, but visitors already in the
building are allowed to leave after their names
and addresses are recorded.
FBI, however, is reluctant to allow anyone to
leave the building. This provokes a lengthy
exchange among the FBI agent-in-charge, the
city police chief, and hospital administrators and
attorneys. The dispute is resolved after a series
of phone calls between FBI headquarters and the
state attorney general’s office.














11:30 p.m.
The specimen arrives at CDC. At midnight,
the diagnosis of smallpox is confirmed. A phone
conference with hospital staff, the city police
chief, the state health commissioner, the state
attorney general, the governor, CDC, FBI, an
assistant secretary of the Health and Human
Service (HHS), and staff from the National
Security Council and the White House (32 people
in all) focuses on whether and how to release the
information to the media. The mayor and the
governor will go on television in the morning
with the health commissioner. The FBI director
will also make a statement. The president will
address the country at noon.
CDC makes arrangements to release
smallpox vaccine early the next morning for use
by patient contacts and the health-care teams
caring for hospitalized victims.
April 16
Morning conference calls between CDC, FBI,
HHS, the National Security Council, and state
health authorities are set up. Federal officials
now assume that a bioterrorist attack has
occurred in Northeast. There is concern that
other attacks might also have taken place but not
yet come to light or that further attacks might be
imminent.
A representative from the counterterrorism
office of the National Security Council asks if it is
necessary or desirable to attempt a complete
quarantine of Northeast, including closure of the
city airport and a ban on rail traffic leaving from
or stopping in the city. The group agrees that
such a step is neither feasible nor warranted. A
heated debate follows about the advisability of
vaccinating all hospital staff and visitors at all
facilities where a single case of smallpox is
clinically suspected. The state health commis-

Emerging Infectious Diseases

sioner presses for enough vaccine for the entire
city of Northeast.
FBI and CDC are reluctant to begin mass
vaccination until the dimensions of the outbreak
are better understood. It is decided to vaccinate
all hospital staff and any visitors to the floor
where the patients were located. All direct
contacts of the patients will also be vaccinated.
By the end of the long phone conference, the
decision is made to vaccinate all health-care
personnel, first responders, police, and firefighters
in any city with confirmed cases of smallpox.
CDC Epidemic Intelligence Service officers
arrive in Northeast to assist the state
epidemiologist, who is establishing a statewide
surveillance and case investigation system.
Efforts begin to develop a registry of all face-toface contacts of smallpox patients and to
monitor, daily, all contacts for fever. Anyone who
has fever >101°F is to be isolated, at home if
possible, and be followed for rash.
The state health department activates a
prearranged phone tree to query all hospitals
and walk-in clinics in the state about similar
cases and counsels immediate isolation of all
suspected patients.
An additional eight admissions for fever and
vesicular rash are discovered. All patients are
extremely ill; two are delirious. The university
hospital emergency room records are searched,
and staff attempt to contact all patients who had
fever during the previous week. Three more
probable smallpox cases are discovered. Telephone follow-up reveals that one has been
admitted to another hospital out of state.
CDC and state health officials discuss
possible strategies for managing the epidemic if
there is insufficient vaccine for all patient
contacts, as seems likely. Home isolation of
nonvaccinated patient contacts is considered,
but the legal authorities, practical logistics, and
ethical implications of such a strategy remain
unclear and unresolved.
After discussion among state health authorities and university hospital staff, it is decided
that the university will serve as the city’s
smallpox hospital and will accept transfers of
smallpox patients now hospitalized at other
facilities in the state. Other hospitals will refer
patients to the university hospital or to the state
armory but will not admit patients with
suspected smallpox. Physicians will be urged to
avoid seeking admission for most smallpox

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patients and to care for patients in their homes.
Arrangements are made by the state health
commissioner to activate a state disaster plan,
which establishes the armory as an emergency
hospital for the quarantine of smallpox patients,
in case the number of smallpox patients exceeds
hospital isolation capabilities.


































During the morning interagency phone
conference, Department of Justice representatives raise questions about potential legal
liabilities associated with adverse vaccine
effects. The questions remain unresolved, but
vaccination will proceed.
On the evening of April 16, the president
goes on television to inform the nation of the
bioterrorist attack by unknown terrorists, vows
that the assailants will be identified and brought
to justice, and urges calm and cooperation with
health authorities.
The initial epidemiologic evidence and FBI
information suggest that the smallpox release
likely occurred during the vice-president’s
January speech at the university in Northeast.
Efforts are begun to identify and vaccinate
everyone who attended the speech. Additional
health department personnel are detailed to help
in the epidemiologic investigation. Media reports
say that the government does not know how
many people are sick or how widespread the
outbreak might be.
By evening, 35 more cases are identified in
eight emergency rooms and clinics around the
city; 10 cases are reported in an adjoining state.
CDC alerts all state health departments to be on
alert for possible smallpox; CDC also urges
prompt and strict isolation measures and
instructs states to send specimens from
suspected patients to its headquarters in Atlanta
for definitive laboratory diagnosis.
April 17
In Northeast, 10,000 residents are vaccinated by the city and state health departments
with assistance from volunteer physicians and
nurses. Vaccination of the entire university
student body, faculty, and staff is discussed and
rejected by federal officials for fear that vaccine
supplies will be needed for contacts of confirmed
cases. State health officials continue to press for
a statewide vaccination effort. Unions representing nurses and other health-care workers call for

Vol. 5, No. 4, July–August 1999

vaccination of all employees whose jobs involve
direct patient contact.
April 18
An additional 20,000 residents of Northeast
are vaccinated.
April 19
CDC and the U.S. Army Medical Research
Institute of Infectious Diseases (USAMRIID)
determine that the infecting strain of smallpox
was not bioengineered. The genomic sequence is
entirely typical of known smallpox strains.
The student with the first diagnosed case
dies. Ten more smallpox cases have been
identified, bringing the number of confirmed
cases to 50. The patients are located in four
states, all in the mid-Atlantic area. Suspected
cases are identified in five other states.
April 20
Governors of affected and unaffected states
press, both behind the scenes and publicly, for
emergency vaccine stocks to be distributed to
states so that immediate action can be taken
should an outbreak occur.
At the close of day 4 of the vaccination
campaign, 80,000 have been vaccinated.
April 22-27
No new cases of smallpox with onset after
April 19 have been confirmed, although many
suspected cases with fever and rash due to other
causes are being seen. In the states reporting
confirmed smallpox cases, thousands of people
are seeking medical care because of worrisome
symptoms. CDC and state health authorities
decide to issue a recommendation that patients
with fever who cannot be definitively diagnosed
be strictly quarantined and observed until the
fever subsides. CDC and state health departments are flooded with calls from health-care
providers seeking guidance on isolation procedures.
Some hospitals and health maintenance
organizations (HMOs) complain to HHS that
they cannot afford to isolate the many patients
with fever and rash at their facilities and
demand that the government pay quarantine
costs. State health departments are similarly
worried about the costs of quarantine.
Local media report an outbreak of sick
children with rash in an area elementary school.

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It is unclear whether the illness is chickenpox or
smallpox. Television stations show film of
parents arriving at school in midday to remove
children from classrooms. A college basketball
star is rushed to hospital by ambulance with an
unknown illness. Local television reports that
the athlete has high fever but no rash. Both
stories are covered on the national evening news.
April 28
Smallpox is diagnosed in two young children
in Megalopolis, a large city in another state. FBI
and the National Security Council worry that
these cases might signal another attack since the
children have had no discernible contact with a
smallpox patient or contacts. The possibility that
there has been a new attack is weighed against
the possibility that the children were infected by
a contact of one of the first wave of patients who
was missed in the epidemiologic investigation.
Members of the state congressional delegation demand that the federal government
implement a massive citywide vaccination
program. CDC notes that a Megalopolis-wide
vaccination program would deplete the entire
civilian vaccine supply.
The media report that the president, vicepresident, cabinet representatives, and prominent
members of Congress have been vaccinated, and
the military has already begun to vaccinate the
troops in affected states and Washington, D.C.


























April 29
Over the course of the day, CDC receives
reports of an additional 100 new cases of
potential smallpox. Sixty of these are in the
original state. The others are scattered over
eight states. It is not immediately clear if these
are truly smallpox or mistaken diagnoses. By
evening, laboratory confirmation of smallpox is
obtained at CDC. Two cases in Montreal and one
in London are also reported. CDC and health
agencies now recognize that they are seeing a
second generation of smallpox cases. It is
presumed that the latest victims were infected
by contact with those who attended the vicepresident’s speech, but a second bioterrorism
attack cannot be immediately ruled out. CDC
enlists additional epidemiologists from around
the country to join teams tracking patients and
their contacts.

Emerging Infectious Diseases

Another 200 probable cases are reported
during the day. CDC receives thousands of
requests for vaccine from individual physicians
and announces that vaccine will be distributed
only through state health departments. Governors of a dozen states are calling the White
House, demanding vaccine. One state attorney
general announces a suit against the federal
government to force release of vaccine for a
large-scale vaccination campaign.
The federal government announces that 90%
of available vaccine stocks will be distributed to
affected states, but cautions that the available
quantity of vaccine can cover only 15% of those
states’ populations. Governors are to determine
their own state-specific priorities and mechanisms of vaccine distribution. Federal officials
also announce an accelerated crash vaccineproduction program that will reduce vaccinemanufacturing time to 24 months.
April 30
A well-known college athlete dies of
hemorrhagic smallpox. The rumor is reported
that he was the victim of a new biological attack
using a different organism since he did not
develop the rash associated with classic
smallpox. Television commentators misinterpret
technical statements from a health-care expert;
the commentators report that the athlete died of
hemorrhagic fever, and they read clinical
descriptions of Ebola virus infection on the air.
The White House and CDC receive dozens of
calls from furious governors, mayors, and health
commissioners, demanding to know why they
were not informed of additional bioterrorist
attacks using Ebola. Nurses, doctors, and
hospital-support personnel in health centers
walk off the job. Thousands of people who
attended college basketball games where the
deceased athlete played call the health
department and ask for treatment.
HHS issues a press release explaining that
the athlete did not have Ebola virus. FBI affirms
that there is no reason to believe that an attack
using any hemorrhagic fever virus has occurred,
but FBI refuses to rule out the possibility that
there has been more than a single bioterrorist
attack using smallpox.
April 31
The widely publicized death of the college
basketball star, plus dramatic footage of young

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children covered with pox, drive thousands of
people to emergency rooms and doctors’ offices
with requests for vaccination and evaluation of
fever and other symptoms. This escalation in
requests for evaluation and care hampers the
ability of state health authorities and CDC to
confirm the number of actual new cases.
May 1
The number of smallpox cases continues to
grow. There are now >700 reported cases
worldwide. In Northeast, the capacity of local
hospitals to accommodate patients needing
isolation has long been exceeded. Smallpox cases
and suspected contacts are being isolated in the
local armory and convention center, where
volunteer physicians and nurses are providing
care.
May 5
Epidemiologists are working around the
clock to interview patients, trace the chain of
infection, place contacts under surveillance, and
isolate smallpox victims. The evidence continues
to indicate that the vice-president’s visit to
Northeast was the occasion for the release, but
some authorities remain concerned about
multiple releases.
May 15-29
The third generation of the epidemic begins.
Cases are reported in Northeast, parts of the
country far beyond Northeast, and worldwide.
The death rate remains 30%. Vaccine supplies
are exhausted. Public concern is mounting
rapidly. The president has declared states with
the largest numbers of victims and people in
quarantine to be disaster areas. Congress votes
to release federal funds to pay for costs of
quarantine. Over the next 2 weeks, 7,000 cases
will have been reported.
May 30
The fourth generation of cases begins. By
mid-June, 15,000 cases of smallpox will be
reported in the United States. Twenty states
report cases, as do four foreign countries. More
than 2,000 will have died. The deceased include
two members of the vice-president’s staff and a
secret service agent.
The city of Northeast, which is hardest hit by
the epidemic, has experienced several outbreaks
of civil unrest. The National Guard has been

Vol. 5, No. 4, July–August 1999

called in to help police keep order and to guard
the facilities where smallpox cases and contacts
are isolated. The mayor of Northeast is
hospitalized with a heart attack.
















The rate of development of new smallpox
cases reported worldwide now appears to be
stabilizing and perhaps subsiding. Vaccination
of contacts has undoubtedly been of benefit.
Perhaps more important is the seasonal decrease
in the spread of virus as warmer weather
returns.
Many business conventions scheduled to
convene in Northeast during the early summer
are canceled. Tourist trade, a major source of
state income, is at a standstill. Many small
businesses in the city have failed because
suppliers and customers are reluctant to visit the
area. Attendance at theaters and sports events is
down markedly. In several states, public schools
are dismissed 1 month early, in part because
parents, fearful of contagion, are keeping their
children home, and partly because teachers are
refusing to come to work. Across the country,
people refuse to serve on juries or attend public
meetings for fear of contracting smallpox. In
hospitals and HMOs where staff have not been
vaccinated, health-care personnel have staged
protests, and some have walked off the job.
The exponential increase in cases around the
globe has caused some governments to institute
strict, harshly enforced isolation and quarantine
procedures. Human rights organizations report
numerous cases of smallpox patients being
abandoned to die or of recovering patients being
denied housing and food.
Domestic and international travel is greatly
reduced. Travelers avoid countries known to
have smallpox. Some countries refuse to admit
U.S. citizens without proof of recent smallpox
vaccination. Others have imposed 14-day
quarantines on all persons entering the country
from abroad. A lucrative black market in falsified
vaccination certificates has sprung up.
Congress has begun oversight investigations
into the epidemic. A congressman accuses the
U.S. Food and Drug Administration of deliberately obstructing the development of smallpox
vaccine and vows to hold hearings into the
matter. Congressional investigations of what
FBI knew, when they knew it, and whom they
talked with, are ongoing. Multiple lawsuits have

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been filed on behalf of and against HMOs,
hospitals, and state and federal governments.
Several large HMOs refuse to pay states for costs
associated with caring for patients in isolation
wards and quarantine facilities. The states with
largest numbers of cases have spent millions of
dollars on the epidemic, including establishing
quarantine operations, paying for added public
health personnel, and overtime pay for police.
In the United States, periodic rumors of
miracle treatments, many fueled by the media,
provoke ardent demands on a beleaguered
health-care system. Since vaccine supplies were
depleted, many people seeking protection have
turned to ancient techniques. Some physicians
are practicing arm-to-arm transfer of vaccinia,
with a few attempting immunization with
inoculation of smallpox virus from pustules.

Emerging Infectious Diseases

Smallpox continues to spread in many parts
of the world, echoing its formerly endemic
character. Without vaccine, the only control
method is isolation, which hinders, but cannot
halt, the spread of the disease. By year’s end,
endemic smallpox is reestablished in 14
countries. The World Health Assembly schedules
a debate on reenacting a global smallpox
eradication campaign.
Dr. O’Toole is a senior fellow at the Johns Hopkins
University Center for Civilian Biodefense Studies. The
Center, sponsored by the Hopkins Schools of Public
Health and Medicine, is dedicated to informing policy
decisions and promoting practices that would help prevent the use of biological weapons.

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