Smallpox and BioterrorismWhy the Plan to Protect the Nation Is Stalled

and What to Doby William J. Bicknell, M.D., and Kenneth D. Bloem

William J. Bicknell, M.D., MPH, is a former commissioner of public health in Massachusetts and professor of internationalhealth at Boston University School of Public Health. Kenneth D. Bloem, former CEO of Stanford University Hospital andGeorgetown University Medical Center, participated in the smallpox eradication program in the Congo and Bangladesh.

No. 85

The Iraq war is over, no weapons of mass destruc-tion (WMD) have yet been found, and the presi-dent’s smallpox plan, though sound, is running outof steam. Instead of being well on the way to pro-tecting the nation’s civilian population by vaccinat-ing up to 10 million health, emergency, and publicsafety workers, we are stalled at 37,971 vaccinatedcivilians while the military has successfully and safe-ly vaccinated more than 450,000 people. Moreover,whether or not WMD are found in Iraq, it is onlyone of a number of nations on the list of suspects.

Of all biological weapons, smallpox has the great-est potential for doing widespread harm. Given thatthe risk of death or serious harm to anyone from anyform of terrorism is very low, we should live our dailylives normally, not in fear. However, to do that we needto be sure that our government is taking effective stepsto reduce the chances of terrorism and, when it occurs,to minimize its consequences. Even though there is

enough vaccine for everyone, we are ill prepared torapidly contain smallpox after a bioterrorist release.

Although Centers for Disease Control andPrevention (CDC) guidelines have recentlyimproved, they continue to overstate the risk of sideeffects of the vaccine and erroneously suggest that,after an attack, the techniques used decades ago toeradicate smallpox will work well today.

Medicine and public health are very risk-averseprofessions in our risk-averse culture. We have notyet realized the complexity and difficulty of vaccinat-ing millions of Americans rapidly after an attack.Nor have we come to grips with the need to makerapid, possibly draconian, post-attack decisionsbased on limited data of uncertain quality. That typeof decisionmaking runs counter to the culture ofpublic health.

The Bush administration needs to revitalize ourpreparations for a smallpox bioterrorist event.

September 5, 2003

The President’s Plan

The September 11, 2001, terrorist attacks,followed by several anthrax mailings in the fallof 2001, forced many Americans to recognizetheir vulnerability to various bioterroristthreats. Smallpox, in particular, had a longhistory as a devastating disease before its erad-ication in the 1970s. Recently, it has capturedthe attention of homeland security planners,who view it as one of the most likely and dead-liest agents for bioterrorism. Federal govern-ment officials initially considered a programof modest pre-exposure vaccination to protectagainst deliberate release of the smallpox virusby bioterrorists.1 That approach was superced-ed when the White House announced a moreambitious plan on December 13, 2002.

Phase I of the president’s plan called for thevoluntary vaccination of approximately 500,000health workers, 18 years old and older, by mid-January 2003.

Phase II called for the voluntary vaccina-tion of up to 10,000,000 health and emer-gency workers in the following 90 days.

Phase III, to begin in mid-2003, wouldmake the vaccine available to, but not recom-mended for, the general adult population.

The plan also called for the immediate vac-cination of up to 500,000 members of thearmed forces.2 As of June 25, 2003, the militaryhad vaccinated more than 450,000 individuals;the civilian program had vaccinated only37,971 people by July 18. Some states had sus-pended their programs while awaiting guid-ance from the Centers for Disease Control andPrevention (CDC) on how to screen for cardiacconditions. In the District of Columbia, 105people have been vaccinated, in Chicago 70,and in Massachusetts 120.3 The civilian num-bers are not reassuring.

What Are the Specific Objectives of Pre-Exposure Vaccination?

We have not found the specific objectivesclearly articulated in any one place. From var-ious White House, Department of Health andHuman Services, and CDC announcements,we glean these probable objectives:

Phase I• Vaccinate sufficient vaccinators so that,

if there is an attack using smallpox, theentire country can be vaccinated within10 days.

• Vaccinate sufficient first responders toidentify, pick up, and transport patientswith suspected smallpox to hospitals.

• Vaccinate enough hospital workers inacute care hospitals so that, if a hospitalreceives a smallpox patient, it will be ableto use staff personnel who are immuneto smallpox to treat that patient.

Phase II• Vaccinate as many additional acute care

workers as possible to decrease the trans-mission of smallpox in hospitals and toensure that essential emergency medical,police, and fire services can continuewithout emergency workers being eitherat risk of smallpox or at risk of transmit-ting smallpox. Once Phase II is complet-ed, whether the event is small and ineptor major and multifocal, the nation willbe well prepared to rapidly respond toand stop an outbreak of smallpox.

Phase III• In mid-2003, after Phase II is completed,

permit, but do not recommend, vaccina-tion of any healthy adult. This approachboth allows informed adults to maketheir own risk/benefit decision andincreases population immunity.

When Phases I and II are completed, whetherthe event is small and inept or major and multi-focal, the nation will be well prepared to rapidlyrespond to and stop an outbreak of smallpox. Ifand as the general adult public opts for volun-tary vaccination in Phase III, post-exposure con-trol becomes even easier and faster. There will befewer people to vaccinate, and, as the number ofpeople susceptible to smallpox will be reduced,disease transmission will be slowed.

Does the President’s Plan Make Sense?The answer is yes. Why is the plan sensible?

2

The civilian program had

vaccinated only37,971 people by

July 18. The civilian numbers

are not reassuring.

First, it is phased and selective. Limiting vacci-nation to healthy adults dramatically reducesthe risk of serious vaccine side effects. Second,by starting with 500,000 military personneland a similar number of civilians, we developcurrent data about the risks of vaccinationand can easily modify the plan if actual risksexceed those expected. Third, when Phase II iscomplete, there will be enough people vacci-nated to vaccinate the balance of the popula-tion on a voluntary basis within 10 days fromthe time the first case is identified. Finally, andof great importance, hospitals and emergencyservices will be able to continue to operatewhile intensive mass vaccination is takingplace. After an outbreak is recognized, the vastmajority of people are highly likely to acceptvoluntary vaccination. At that point there willprobably be no need for mandatory vaccina-tion and its attendant problems.4

The pre-attack plan is correctly limited tohealthy adults, as the risk of serious complica-tions and death from vaccination is substan-tially higher in children. However, the age forvaccination could safely be dropped to 10years, as the overwhelming majority of deathsand severe complications from vaccinationoccur in children 9 years of age or younger.5 Ifwe are prepared to vaccinate rapidly after anattack, children can be isolated at home for afew days until they can be vaccinated. Thisapproach avoids a number of serious andsome fatal complications of vaccination inchildren that would likely occur if done pre-attack, while minimizing smallpox cases anddeaths post-attack.

Why Is the Plan Stalled?

The problems are not exclusive to any onegroup or agency. The administration, as we dis-cuss in more detail below, has never providedclear objectives or the rationale underlying theplan. Once announced, the plan was perceivedby many people as not being a high priority forthe administration. That perception washeightened when liability and compensationissues were addressed too late and little atten-

tion was paid to concerns about funding hos-pitals and health departments for costs relatedto vaccination. In addition, many medical andpublic health professionals continue to makethree mutually reinforcing errors:

• Not distinguishing between the risk of vac-cination in healthy, well-screened adults andthe risk to children and high-risk adults.

• Not adequately recognizing the differencebetween naturally occurring disease anddisease introduced by bioterrorism. Forexample, no one has epidemic-controlexperience with smallpox in a nonim-mune, highly mobile population whereexposure will be malicious rather thanbenign. The relevance of lessons from theeradication experience (characterized byvery different circumstances) is limited.

• Not sufficiently appreciating that thedecision to undertake pre-exposure vac-cination is far more than a medical deci-sion about the risks of vaccination. Ofequal or greater importance, it involvessocial, economic, and national securityconsiderations, as shown schematicallyin Figure 1.

It is important to emphasize that assessingthe risk of attack is a national intelligence esti-mate, not a medical or public health estimate.

Before addressing in greater depth the rea-sons why the plan is stalled, it is necessary toreview the nature of the threat and some factsabout the risks of vaccination.

The Threat

Smallpox (variola major) is a deadly scourgewith, at present, no known treatment. It has anoverall mortality rate in the unvaccinated of 30percent and leaves 60 percent to 80 percent ofall survivors permanently disfigured. Smallpoxhas death rates in the very young and the elder-ly approaching 50 percent. An effective livevirus vaccine is available that rarely results indeath but somewhat less rarely causes severecomplications.

3

The decision toundertake pre-exposure vaccination is farmore than a medical decisionabout the risks ofvaccination. Itinvolves social,economic, andnational securityconsiderations.

The last naturally occurring case of small-pox was identified in 1977 in Somalia, andthe last case, a laboratory accident, occurredin England in 1978.6 The United States andBritain already had stopped routine child-hood vaccination in the early 1970s. Theworld was declared free of smallpox in 1980by the World Health Organization.7

Smallpox had been weaponized by theSoviet Union.8 Weaponized virus may havebeen taken from the former Soviet Union,and stocks of virus may not have beendestroyed by some countries, as called for byWHO in the late 1970s.9 The former WHOdirector of smallpox eradication, Dr. D. A.Henderson, summarized the threat in 1999:“One can only speculate on the probablerapidity of spread of the smallpox virus in apopulation where no one younger than 25years of age has ever been vaccinated andolder persons have little remaining residualimmunity.”10 The former deputy director ofthe Soviet Biological Weapons Program con-siders it certain that North Korea possessesthe smallpox virus and probable that Iraqdoes, too.11 Vaccination of North Korean andIraqi troops has also been reported.12

Bioterrorism, particularly with smallpox,became a pressing U.S. and international issueafter September 11, 2001. The call for pre-expo-sure vaccination came quickly. The head ofRussia’s Vektor Institute, which has functionssimilar to those of the CDC, urged widespreadimmunization against smallpox.13 The Britishgovernment bought enough vaccine for 50 per-cent of the population. Germany purchased 6million doses, and Israel vaccinated approxi-mately 18,000 first responders and medicalworkers. The U.S. government considered thethreat sufficient to purchase vaccine and vac-cinia immune globulin (VIG) for all Americansin preparation for a possible smallpox attack.By late 2002 the United States had sufficientsmallpox vaccine to immunize and VIG tomanage the complications of vaccination forthe entire population.14

It is tempting to think that, with theSaddam Hussein regime gone, the risk of abioterrorism attack by any agent is substan-tially reduced. That may be the case. However,it is also plausible that the escaping Iraqiregime took away small but sufficientamounts of smallpox virus for bioterrorismpurposes and has long since sequestered them

4

Bioterrorism, particularly with

smallpox, becamea pressing U.S.

and internationalissue after

September 11,2001.

Figure 1The Weight of the Evidence

in jurisdictions far from Iraq. Furthermore,the smallpox risk has never been thought to belimited to the Hussein regime. In any case, aswas true before the Iraq war, the decisionregarding post-Iraq smallpox as a nationalsecurity risk is for the intelligence communityto assess, not for medical and public healthpersonnel. Those personnel need to considerother types of risks.

The Risks of Vaccination

What Is the Real Risk of VaccinatingHealthy Adults?

There are three particularly relevant histor-ical data sources. The 1963 and 1968 U.S.national vaccination surveys include the num-ber of persons vaccinated by age, vaccinationstatus, and type of complication.15 The reviewby Lane et al. of vaccine deaths in the UnitedStates from 1959 to 1966 and 1968 details vac-cine complications, but, as the data were notavailable for all years studied, it does not spec-ify the total number of persons vaccinated.16

Considering all adults and children, both first-time and repeat vaccinees, 14,014,000 peoplewere vaccinated in 1963 with seven deaths,and, in 1968, 14,168,000 with nine deaths. Asvaccination was being done routinely, there isno reason to think that either more or fewerpeople were vaccinated in years other than1963 and 1968. Lane found 68 deaths or anaverage of 7.5 deaths a year for the nine yearshe studied. It seems reasonable to concludethat the historical risk of death (adult andchild) is closer to 1 death per 2 million thanthe 1 or 2 deaths per million that CDC con-tinues to report.17

As the current national plan is limited tovoluntary vaccination of healthy adults 18 andolder, it is particularly appropriate to look atthe probability of deaths and complications inthis age group. Lane found two primary vacci-nees in the 10-to-19-year age group who died ofpostvaccinial encephalitis (PVE). One of thosewas 14 and is reported in the 1963 data. Theother death did not occur in either 1963 or1968, and the age cannot be determined. To be

conservative, we assume this person was in the15-to-19-year age group. Lane also found tworevaccinated adults who died of PVE (a 33-year-old woman and a 64-year-old man), both with-out underlying disease. As previously noted,vaccination was routine and ongoing for thenine years Lane studied. Therefore, we assumeroughly the same number of persons were vac-cinated in each of the years studied.Extrapolating from the numbers reported in1963 and 1968 for ages 15–19 and for ages 20and older, 10,405,000 individuals were vacci-nated, for an average of 5,202,500 per year, or atotal of just over 46,000,000 for nine years.18 Tobe conservative, we round down to 45,000,000,giving an estimated risk of PVE in adults of 3per 45,000,000 or about 1 per 15,000,000. Thisis an exceedingly low risk. Even if this estimateis too low by half, the risk is still extremelysmall.

What about other vaccine-related deathsin primary vaccinees and revaccinees in the15-and-over age group? There were a total offive other deaths, all of revaccinees, for thenine-year study period: three had leukemia,one had Hodgkin’s disease, and one had aconnective tissue disease (scleroderma) andwas on steroids. Today, because of our appre-ciation of their increased risk and the atten-dant careful screening, people with those andsimilar diseases should be screened out asineligible for vaccination.

What about serious complications withlong-term effects other than death? A carefulreview of historical and current data sup-ports the conclusion that when healthyadults are vaccinated, persistent, serious sideeffects are extremely rare.

In summary, in a nine-year period, eightadults died (three of PVE with no underlyingdisease, five others with underlying disease).The death rate in healthy adults may be as lowas 1 in 15,000,000 vaccinees. It is quite possi-ble, and would not be surprising, that whenPhase II of the national plan is completed, wewill have no deaths of persons voluntarily vac-cinated, and it is likely we will have fewer thanfive deaths. The current U.S. military experi-ence with 454,856 vaccinated personnel as of

5

When healthyadults are vaccinated, persistent, serious sideeffects areextremely rare.

June 11, 2003, (71 percent were primary vacci-nees and 29 percent were revaccinees) with nodeaths and no long-lasting complicationsstrongly supports the conclusion that vaccina-tion of healthy adults is safe.

Accidental Vaccination of Patients,Family Members, and Other Contacts

Accidental vaccination may occur when arecently vaccinated person (whose vaccina-tion scab has not yet fallen off) comes intophysical contact with an unvaccinated personand transfers vaccinia virus from the vaccina-tion site to the unvaccinated person. That canhappen when the site on a recently vaccinatedperson rubs against another person or arecently vaccinated person touches the siteand then touches a susceptible person. Theclassic situation is two children playingtogether in a sandbox and rubbing up againsteach other.

Accidental vaccination is a particular con-cern today, because we have a far higher num-ber of persons whom we would deliberatelynot vaccinate pre-outbreak (for example,transplant recipients, as well as many patientson cancer chemotherapy, on systemic steroids,or infected with HIV/AIDS). Further, it isbelieved that eczema19 is substantially morecommon in the general population todaythan it was 30 or 40 years ago. Individuals suf-fering from eczema are more likely to get acci-dentally infected with vaccinia virus by closecontact with a recently vaccinated familymember, friend, or caregiver.20 The conse-quences could be very serious, even fatal.

How big is this risk? The 1963 and 1968data show that there were 200 reported casesof accidental infections of other persons as aconsequence of vaccinating 28,182,000 per-sons. Only 25 cases, or 12.5 percent, occurredin adults, with no deaths. Historically, wellover 90 percent of accidental vaccination ofothers occurs either from child to child orfrom child to caregiver or vice versa.21 Lanereports one case of a recently vaccinated nursecaring for a child with severe eczema and oneof a recently vaccinated adult woman whoslept with and infected a man. Both the child

and the man acquired vaccinia.22 Today thenurse would use a double semipermeablemembrane dressing (described in the nextparagraph), wear long sleeves, and not beworking on a unit with such a child until thevaccination scab had fallen off, by which timethe nurse would no longer be shedding virus.The other case would be harder to prevent, butthe semipermeable dressing would reduce therisk of transmission by 95 percent. Under theBush plan, health care professionals are notvaccinating children today, and they are urg-ing people with children who have eczema athome either not to get vaccinated or to avoidclose contact with the children until their vac-cination scabs fall off.

The already low risk of accidental vaccina-tion of another person can be reduced furtherby careful screening and the use of the inex-pensive and readily available semipermeablemembrane dressing. Because there is appropri-ate concern about accidental transmission toothers, particularly the immunocompromised,reducing the shedding of virus from the vacci-nation site into the environment to the lowestpossible levels makes sense. Shedding of virusafter vaccination can occur until the scab driesand falls off the vaccination site (about 21days). The semipermeable membrane dressing,available commercially as “Tegaderm+Pad”from 3M and “OpSite” from Smith & Nephew,significantly reduces the shedding of virus.Those products combine a gauze pad with amembrane that allows the passage of air butnot the vaccinia virus. Shedding is reduced by95 percent and can be further reduced to 99percent or more if a second layer of membranewith no gauze is applied over the first ban-dage.23 CDC advises that “only persons work-ing in healthcare settings should use semiper-meable dressings”; members of public healthresponse teams not involved in patient care cankeep their vaccination sites covered with aporous dressing (e.g., gauze).24

Since the semipermeable membrane dress-ing is simple to use, relatively inexpensive, andgreatly reduces the already low risk of trans-mission to others, why not reduce the risk ofaccidental transmission everywhere to the

6

The already lowrisk of accidental

vaccination ofanother personcan be reduced

further by carefulscreening and the

use of the inexpensive andreadily available

semipermeablemembrane

dressing.

lowest possible levels? CDC might furtherreduce the risk of accidental vaccination byrecommending that everyone who is vaccinat-ed pre-exposure, whether in Phase I, II, or III,should use this dressing, wear long sleeves,and pay careful attention to hand washing,particularly after touching the dressing ortouching anywhere near the vaccination site.25

We have not yet specifically considered theimmunocompromised, burn, dermatitis,chemotherapy, and similar patients who arein the category of persons at greatest risk. Inthe New England Journal of Medicine, KentSepkowitz recently reviewed worldwide casereports of vaccinia spreading to others inhome and hospital settings from 1907 until1975. He found 12 instances of spread inhospitals, with the last death in 1952 inFrance. Sepkowitz makes the point thattoday the number of patients at risk in hos-pitals is considerably greater than in the firsttwo-thirds of the 20th century. He also notes,“The current plan for an occlusive dressing atthe vaccination site and other now-routineinfection-control procedures, includinghand hygiene and isolation for any patientwith unexplained fever and rash, shouldeffectively limit potential spread.”26 The U.S.military operates multiple major hospitalswith wards containing burn patients andneonates in intensive care, as well as trans-plant and chemotherapy patients. All are at ahigher than usual risk for accidental vaccina-tion. The military approach has been to usethe semipermeable membrane dressing forpersonnel with patient care responsibilities,to encourage long sleeves over the dressing,and, where possible, to rotate workers offhigh-risk units until they are no longer shed-ding virus. Between mid-December 2002 andmid-June 2003, the military vaccinated morethan 12,000 hospital workers and accumu-lated 27,700 worker-months of clinical con-tact time with no transmission from healthworkers to patients.27 That is reassuring.However, there is no doubt that hospitalsshould carefully think through staff assign-ments and infection control procedures astheir workers are vaccinated.28

Assuming Phase II of the national plan isfully completed and 10 million healthy adultsare vaccinated, we estimate the number of peo-ple who may die because of accidental vacci-nation by exposure to a recently vaccinatedperson at less than one. Stated somewhat dif-ferently, most likely, no one will die. As thereare an increased number of immunocompro-mised persons at risk of death from accidentaltransmission today, it is necessary to correctand increase this estimate. However, the esti-mate must be increased by more than a factor of20 to reach one death. (See Table 2, note 1, fora detailed explanation of this estimate of risk.)

Two things have changed since vaccinationstopped in the 1970s. There are more peopleat risk of vaccine complications, and infectioncontrol techniques have also improved. Weconsider both, but in the estimate above wehave given more weight to increased risk thanto improved infection control.

The bottom line: Voluntarily vaccinatinghealthy, well-screened adults, using the semi-permeable membrane dressing for all who getvaccinated—not just health care workers—andurging all vaccinees to wear long sleeves untiltheir vaccination scab falls off makes thenational plan safe for everyone.

What about Recent Reports of HeartComplications?

Two different types of vaccine complica-tions involving the heart (heart attack orischemic heart disease) and inflammation oftissues around the heart (myocarditis) havebeen widely reported in the recent news.

One member of the military and four civil-ians had heart attacks within 5 to 17 days ofbeing vaccinated. Three died. The patientswere all older (ages 54, 55 [two cases], 57, and64), with known preexisting heart disease.29

Heart attacks are expected to occur in this agegroup. The question is whether vaccinationincreases the risk of heart attack. If the num-ber of heart attacks expected from historicaldata is unchanged after vaccination, then it isreasonable to conclude there is no causal rela-tionship between vaccination and heartattack. The military data strongly support

7

It is reasonable toconclude there isno causal relationshipbetween vaccination andheart attack.

this conclusion. Historically, on an annualbasis, the military would expect several heartattacks per week, and that rate has notchanged since the smallpox vaccination pro-gram began.30 The evidence to date supportsthe conclusion that older people, who nor-mally have more heart attacks, are continuingto have them at the same rate since we begansmallpox vaccination. However, CDC and theU.S. military are being cautious and have tem-porarily advised that people with a history ofheart disease postpone getting vaccinateduntil the data have been further studied.31 Asthe aims of both the military and the civilianvaccination programs can be met withoutvaccinating persons with a history of heartand certain other diseases, this caution posesno threat to the integrity of the overall vacci-nation program.

Myocarditis is different. Historically, therehave been very occasional reports of myocardi-tis after smallpox vaccination. Those caseswere mostly mild with full recovery.32

However, a total of four deaths reported fromFinland, the United States, Australia, and

Great Britain since 1947 can reasonably beattributed to myocarditis secondary to vacci-nation.33 The most relevant experienceinvolved 126 Finnish military recruits withmyocarditis admitted to the central militaryhospital and carefully studied between 1976and 1981.34 Ten percent (12 cases) were con-sidered caused by smallpox vaccination, andthe remaining 90 percent were attributed tovarious other viruses and bacteria. All recov-ered uneventfully. This is the case to date withthe 42 probable and 1 confirmed cases in theU.S. military and the 10 U.S. civilian cases (asof June 11).35 The Finns found a myocarditisrate of 1 per 10,000 in their recruits, and theU.S. military rate is very similar.36 The strain ofvaccinia used to make the Finnish smallpoxvaccine is different from the U.S. strain. It isrelated to the Lister strain, which has moreside effects than the strain used in the UnitedStates (New York Board of Health strain).37 Wecan continue to expect occasional cases ofmyocarditis with uneventful recoveries. Somewill be due to vaccination and some to othercauses. Deaths, if they occur, will be rare.

Table 1Smallpox Vaccination: Risk of Death of Healthy Adults

Estimated TotalRisk Group Persons at Risk Deaths Death Risk

Recalculated historical risk of death 126,000,000 68 .5/1,000,000for all age groups1 or

1/2,000,000

Recalculated risk of death for 45,000,000 8 .2/1,000,000people 15 and older with historical orscreening1 1/5,000,000

Recalculated historical risk of death 45,000,000 3 .07/1,000,000for people 15 and older with orimproved screening1, 2 1/15,000,000

1Recalculated risk based on nine years of data (see text).2This calculation excludes 5 deaths (3 leukemia, 1 Hodgkin's disease, 1 scleroderma). The 45,000,000 figure does notchange because the number of people in the historical denominator with scleroderma, Hodgkin's disease, aplastic ane-mia, and chronic lymphocytic leukemia was small and the denominator has already been rounded down by 1,800,000.Further adjustments are not needed and would also suggest a greater degree of precision than is the case.

8

We can continueto expect

occasional casesof myocarditis

with uneventfulrecoveries. Some

will be due to vaccination and

some to othercauses. Deaths, if

they occur, will berare.

Comparing Everyday Risksand Vaccine Risks

Tables 1 and 2 summarize the vaccine risksdiscussed above. Table 3 compares vaccinerisk to the risk of dying on a scheduled com-mercial U.S. airline flight or the risk of anadult in the United States dying from an acci-dent of any type in the next 10 years. Giventhat vaccination is no more than a once-in-10-years event, the comparison with the riskof accidental death from all causes in 10 yearsis reasonable.

We would not expect adults to get revacci-nated more frequently than once in 10 yearssince the protection lasts about that long. Overthe same 10-year time period, the risk of deathfrom an accident of any type for an adult inAmerica is 3/1000 or 3,000/1,000,000.38 Thus, a

healthy adult is 42,000 times more likely to diefrom an accident in the next 10 years than froma smallpox vaccination! The risk of death on ascheduled domestic major airline is between 1in 8 million and 1 in 10 million.39 A healthyadult has less risk of death from a smallpox vac-cination than from flying from Denver toWashington, D.C. And, as flying is far safer thandriving, when most of us drive to work, to themovies, or to a vacation destination voluntarily,we expose ourselves and our companions to farmore risk than a smallpox vaccination does.

The bottom line: vaccination of healthyadults is safe. In our judgment, the best policyguidance that the CDC can offer is: if you are ahealthy adult who does not worry about driv-ing to work, you should not worry about get-ting vaccinated or accidentally vaccinatinganother person.40

9

A healthy adult is42,000 timesmore likely to diefrom an accidentin the next 10years than from asmallpox vaccination.

Table 2Smallpox Vaccination: Risk of Death of Persons Accidentally Vaccinated

Risk of Death for anUnvaccinated

Healthy Person/1,000,000Adults Vaccinated Healthy

Risk Group Vaccinated Deaths Adults

Projected deaths from accidental 10,000,0002 < 1 .09/1,000,000transmission to account for orincreased number of 1/11,000,000immunocompromised, etc.1

1Based on 200 cases of accidental transmission and 3 deaths from 28,000,000 vaccinations in 1963 and 1968. As we arenot vaccinating children, reduce accidental infection by 70 percent to 60 cases and, as we can use the semipermeable mem-brane, reduce by another 95 percent to 3 cases of accidental transmission. When accidental transmission occurred, thedeath rate in accidentally vaccinated persons was 3 deaths per 200 cases or 1.5 percent. Therefore the number of deathsexpected from accidental transmission today would be less than one (3 cases x 1.5 percent = .045 deaths). In 1963 and1968, 10,400,000 persons aged 15 and older were vaccinated. This is close to the target number for the end of Phase II of10,000,000. The estimated 0.045 deaths per 10,000,000 also can be expressed as 0.0045 deaths of an accidentally vacci-nated person per million healthy adult vaccinees or 1 death of an accidentally vaccinated person per 222,000,000 healthyadult vaccinees. As this estimate does not take into account the increased number of persons at risk of death from acci-dental transmission, we increase the estimate by a factor of 20 and are still at just under 1 projected death of accidentallyvaccinated persons after vaccinating 10,000,000 healthy adults.

Using the same assumptions, but stating the case somewhat differently, a 20-fold increase in susceptibles would leadto 4,000 cases (200 x 12). Eliminating children reduces this by 70 percent to 60 cases, and using the semipermeable mem-brane dressing reduces the number by another 95 percent with the same result—less than 1 projected death of accidental-ly vaccinated persons after vaccinating 10,000,000 healthy adults.2If 10,000,000 people are vaccinated in Phase II, then, with proper precautions, the number of deaths from accidental vac-cination could be as low as zero and is unlikely to exceed five.

An In-Depth Look at Whythe Plan Is Stalled

Determining the reasons why the currentnational plan to vaccinate healthy adults isstalled involves not just correcting misper-ceptions of the risks of vaccination. Itrequires analysis of both immediate or obvi-ous contributing factors and the subtler butperhaps more important underlying factorsthat must be understood if there is to be atimely, effective, and enduring fix.

First, medical and public health practi-tioners and the general public have receivedinadequate and confusing informationabout the risk of smallpox vaccination tohealthy adults. Because healthy adults are theonly group targeted in the national plan, thisis a serious omission. CDC has never ade-quately distinguished between healthy adultswho are at low risk of complications fromvaccination and sick adults and all children,sick or well, who are at far greater risk of vac-cine complications. Nor has CDC promoted

the wide use of the semipermeable mem-brane dressing, which greatly decreases therisk of accidental vaccination of others.Finally, the ease of control after an event, par-ticularly the value of vaccinating after expo-sure to smallpox, has been both overstatedand misstated.41

Result: The perception of vaccine risk bymany medical and public health practition-ers, as well as by the public, is far greater thanthe actual risk. Misperceptions remain aboutthe spread and control of smallpox after abioterrorism event.

Second, the executive branch has been slowin proposing or putting in place sufficient cov-erage for liability and compensation for any-one who suffers a serious complication ordeath, including persons who may becomeaccidentally vaccinated by close contact with avaccinated person as well as the institutionsand providers who do the vaccinating. Thisbarrier has now fallen, and on April 30 the pres-ident signed into law the Smallpox EmergencyPersonnel Protection Act of 2003.42

Table 3Smallpox Vaccination: Risks of Everyday Living Compared to Risks of Vaccination

Deaths per Risk Group Million Comparative Risk

Healthy adults vaccinated once 0.07/1,000,000 One death per 15 millionevery 10 years healthy adults

Projected deaths from accidental 0.09/1,000,000 One unintended death of transmission to account for an unvaccinated person per increased number of 11 million vaccinated healthyimmunocompromised, etc. adults

Risk of death from flying once on a 0.1/1,000,000 Flying once has a 1.4 timescommercial airline greater risk of death than

getting vaccinated, or1 in 10 million

Risk of death in 10 years from any 3,000/1,000,000 The risks of everyday living accident for an adult are 42,000 times greater

than the risk of dyingfrom vaccination,or 1 per 333

Note: See text and the notes to Table 1 and Table 2 for an explanation of the numbers in Table 3.

10

The perception ofvaccine risk bymany medical

and public healthpractitioners, as

well as by thepublic, is far

greater than theactual risk.

Result: Widespread hesitation to vaccinateor accept vaccination due to fears of absent orinadequate compensation for care of vaccine-related complications that may result in workloss, severe illness, and even death. (It is still toosoon to determine the degree to which SEPPAwill help solve this problem.)

Third, a surprising silence on the part ofleaders in the administration from just afterthe president’s announcement of his plan onDecember 13 until the week of March 10,when CDC director Dr. Julie Gerberding, Dr.D. A. Henderson, and the surgeon generalwere very publicly vaccinated (President Bushwas vaccinated previously, on December 21).43

But there still has been no good, easily under-stood, widely available explanation of thenational plan.

Result: A perception that the national planis neither well designed nor a high priority.

When those three factors are combined,far too many people reasonably and under-standably, but erroneously, are prone to con-clude that vaccination before an attack is toodangerous, its complications may not be paidfor, and it probably isn’t very important any-way. After adding to the mix the natural andappropriate caution of physicians makingrecommendations to patients, it is little won-der that not many people are getting vacci-nated. But deeper and more subtle factorsstand in the way of the national plan.

Root Causes of Delay

The threat of bioterrorism extends beyondsmallpox. Many other agents such as anthrax,botulinum toxin, and plague, to name just a few,are on the list of potential threats.44 The rootcauses of delay that we present below, althoughrelevant to the smallpox program, are not limit-ed to smallpox. Thus, some of the lessons welearn from smallpox should be relevant to ouroverall approach to planning for and managingbioterrorism events by any agent.

Malicious dissemination, whether ofsmallpox or other bioterrorism agents, is dif-ferent from naturally occurring disease.

Though obvious, this distinction is vital.What we know from naturally occurring dis-ease may help in bioterrorism planning, but itis insufficient and, in some cases, misleading.For example, what worked during the finalyears of smallpox eradication when popula-tion immunity was high, population mobilitywas much lower, and there was no maliciousintent to disseminate is not likely to worktoday with bioterrorism. In today’s communi-cation environment, public awareness of asingle case of smallpox will be worldwidewithin minutes, and demands for swift actionwill run ahead of response capacity.

We emphasize that many members of thepublic health, medical, and nursing profes-sions are participating actively and workingwith diligence to prepare the nation for abioterrorism attack, whether it involvessmallpox or another agent. Further, we arenot conspiracy theorists and do not believeany one person, group, or agency is conspir-ing to undermine the president’s plan.Rather, a variety of interacting and mutuallyreinforcing factors best explains the delay.

Risk and Public HealthOurs is a risk-averse culture. Physicians and

public health personnel are particularly riskaverse and, for the most part, appropriately so.However, the increasing threat of bioterrorismdemands a new paradigm for balancingunknown but real risks against the variouscosts and benefits of preparedness. This type ofassessment is particularly difficult for physi-cians who often feel they are violating an ethi-cal canon if they endorse a certain risk today,however small, to obviate an uncertain andunknown risk tomorrow. The justification forthis attitude is the oft-quoted primum nonnocere, or “first do no harm.” This belief struc-ture and cultural attitude facilitate focusing onthe potential risks of vaccination, without con-sidering the magnitude or societal conse-quences of those risks, ways to mitigate them,or any benefits that might offset the risks.

The CDC Advisory Committee for Immu-nization Practices and the CDC NationalImmunization Program seem uncomfortable

11

The increasingthreat of bioterrorismdemands a newparadigm for balancingunknown but realrisks against thevarious costs andbenefits of preparedness.

with the thesis that an unquantifiable andprobably low risk of attack nevertheless poses aserious risk to the population. Such a stanceimpedes consideration of the following impor-tant question: If there were to be pre-event vac-cination, what are the risks to different subsetsof the population? This determination fallsfully within the expertise of ACIP and NIP.However, neither body has any special expertisein assessing national security risk (i.e., the riskof attack) or the social and economic conse-quences of a bioterrorism attack. They alsohave no special expertise in determining anappropriate plan for either pre- or post-eventcontrol.

Further, there seems to be a belief amongsome health professionals that assessing risk ofattack and risk of vaccination is just too muchfor the average American, let alone health careearly responders, to handle and that suchassessment must be kept in the hands ofexperts. That assumption is well illustrated bya passage from an article by Lane andGoldstein published in March of this year:

We might allow citizens to make indi-vidual choices about obtaining vacci-nation after they have been given infor-mation about the risks associated withvaccination and potential threat ofsmallpox. Public health authoritieswould thus cede decisions on a policywith considerable technical ramifica-tions to persons with widely varyingabilities to comprehend and weigh therisks and benefits. The media and themedical profession would have tocommunicate an accurate portrayal ofthe data and options. In the absence ofa known threat of smallpox exposure,this option would be dangerous tomany potential vaccinees, their con-tacts, and the public health initiative. Itwould subject the population to aknown risk for severe adverse events.The publicity about such complica-tions might subsequently keep somepersons from accepting vaccination ifthe need actually arises. 45

Every day, patients are asked to compre-hend extremely complex risks and make judg-ments about them as they consider medicaland surgical choices much more difficult andwith far greater risks to themselves and othersthan vaccination. There is neither any basisnor any right for anyone in the public healthand medical professions to assume that thepublic is not competent to make such deci-sions. It is essential to remember that the prin-ciple of individuals making their own deci-sions lies at the heart of our social fabric andsystem of government.

In the words of Thomas Jefferson,

I know of no safe depository of the ulti-mate powers of the society but the peo-ple themselves; and if we think themnot enlightened enough to exercisetheir control with a wholesome discre-tion, the remedy is not to take it fromthem but to inform their discretion.46

Contributing to the confusion betweennational security risk and vaccination risk is thebelief held by some that no one in his right mindwould ever use smallpox as a weapon. After all, itwould spread all over the world and would comeback to bite those who released it. Yet we needonly remember that Soviet premier MikhailGorbachev in the late 1980s ordered smallpoxwarheads to be put on Russian missiles toreplace some nuclear warheads.47 It is foolishand naive to assume our logic and values are thelogic and values of others, let alone terrorists.48

The fact that few observers would have believed,before it happened, that a terrorist attack on thescale and scope of the 9/11 attack was plausibledid not keep it from occurring.

Turf IssuesThe initial vaccination plan proposed by

CDC in late 2001 and early 2002 was viewed bythe administration as inadequate. Respon- sibili-ty for development of what became the presi-dent’s plan was removed from ACIP and CDC byHHS and the White House. Now the same orga-nization and many of the same people whoseadvice was rejected have been asked to imple-

12

Every day,patients are asked

to comprehendextremely

complex risks andmake judgments

about them asthey consider

medical and surgical choices

much more difficult and with

far greater risksto themselves and

others than vaccination.

ment a plan they did not develop. That unusualhistory may help to explain some of the delayand hesitation shown by CDC.

There have recently been clear signs of positivechange. Information from CDC is improving,but it is not yet fully correct or adequate. TheCDC website, a primary source of informationfor the several thousand state and local healthagencies in the United States and worldwide, ismuch improved but still hard to navigate. OnMarch 7 HHS, CDC, and the American Collegeof Preventive Medicine sponsored a “ClinicianCommunication Briefing Summary” with HHSsecretary Tommy Thompson, CDC director JulieGerberding, and Acting Assistant Secretary forPublic Health Preparedness Jerome Hauer asspeakers under the headline of “Need toAccelerate the Smallpox Vaccination Program.”49

The briefing confirmed the following:

• Terrorists have demonstrated the intentto inflict mass casualties on the UnitedStates, and they more than likely haveaccess to smallpox.

• The administration is concerned thatwe are not yet prepared to ward off asmallpox attack and that we will not beable to respond if there is an attack.

• Smallpox preparedness, including the vac-cination of health care and public healthpersonnel who would serve on responseteams, is a national security issue.

• HHS and CDC remain committed to con-ducting the smallpox vaccination pro-gram as safely as possible but stress theneed to scale it up and speed it up in thecurrent context of the situation in theMiddle East and the rest of the world.

• HHS and CDC are asking clinician lead-ers to support the smallpox vaccinationprogram and to assist other clinicians inhealth care facilities in making informeddecisions about their willingness to vol-unteer for the smallpox vaccination pro-gram.

Those and similar developments are encour-aging. However, much more is needed, and theday-to-day actions and behavior of professional

staff within CDC must become far more con-gruent with the direction set by the director ofCDC and the secretary of HHS (see the discus-sion of problems with CDC guidance below).

This neither suggests nor requires mind-less obeying of orders. Rather, it requires thatthe professional staff raise and argue differentviewpoints and, when a decision is made,either agree and support the decision, ask forreassignment, or resign. As decisions of thistype are argued internally, the different opin-ions should be shared with the public. Suchopenness builds public confidence in thedecision finally taken.

Spillover ConcernsOther Immunization Programs May Be Set

Back. Many professionals in the NIP and onthe ACIP have devoted their lives to gettingparents to immunize their children against awide range of childhood diseases as well asgetting adults to accept immunizations suchas the influenza vaccine. They are under-standably concerned that adverse reactionsto smallpox vaccinations will spill over andresult in the public avoiding other types ofvaccinations that have fewer side effects.Thus, they may fear that real risks of diseasesthat we know are present and can be prevent-ed will be increased as a consequence of thepublic’s reaction to adverse events that maybe associated with vaccinating for a diseasethat has yet to reappear. Paradoxically, CDC,by its alarmist attitude toward smallpox vac-cination, may be inadvertently fanning irra-tional fears of all vaccinations.

Smallpox and Bioterrorism Initiatives UndercutFar More Important Public Health Efforts. Somepublic health professionals feel that the entirebioterrorism initiative, and its smallpox focusin particular, take away from other far moreneeded public health programs and, withoutmore specific additional funding for smallpoxand bioterrorism, the fabric of public health isat risk. Certainly more funding dedicated forbioterrorism would be welcome, but theseconcerns are exaggerated. One of us (WB) is aformer state commissioner of public health,who knows what it takes and is taking to

13

Paradoxically,CDC, by itsalarmist attitudetoward smallpoxvaccination, maybe inadvertentlyfanning irra-tional fears of all vaccinations.

respond to bioterrorism and smallpox. Forexample, it is frequently said that “everyone isworking on smallpox.” That is a substantialexaggeration. The chronic cries of bureaucratsneed to be dramatically discounted.

Budget cuts in public health funding,sometimes very severe, have occurred in manystates. However, it does not follow that federalbioterrorism funds are or could be fungibleand available for general support of publichealth at the state and local levels. Although anumber of reports have observed that the unitcost of administering vaccine pre-event is highand possibly prohibitive, that is partly due tothe inaccurate information about vaccine safe-ty that keeps clinics operating at very low vol-umes. If clinic volumes were higher and inte-grated into routine immunization and othermedical care activities, unit costs would bemuch lower.

Smallpox and bioterrorism are often seenas an opportunity to get new money.However, when public health officials makethe unsubstantiated assertion that, for bioter-rorism initiatives to succeed, it is necessary tostrengthen the rather vaguely defined “publichealth system,” the argument is weak. What isthe exact logic that links the “public healthsystem” to effective response to bioterrorism?Further, what exactly is the “public health sys-tem,” and which parts of it are essential to aneffective bioterrorism control program? Untilthose questions are answered convincinglyand with precision, substantial new money isunlikely to flow to public health agencies.

There actually are some convincing answers.We strongly support enhanced public healthlaboratory capacity at the state level; enhanceddisease surveillance and early warning systems;and strengthened, proactive, epidemiologicintelligence capacity at the state and local levels.Investing in those public health activities makessense for an effective bioterrorism response,and it is a good example of a dual-use invest-ment. For example, investment of this typecould help with SARS and monkeypox today aswell as in the identification and management ofother diseases totally unrelated to bioterrorismbut of public health importance.

Problems with CDC Guidance Although we believe the burden of bioter-

rorism on state and local health agencies hasbeen overstated, it is true that state and localefforts have been greater than needed becauseguidance from CDC has been confusing,needlessly complex, and sometimes wrong.One example will suffice. Because of seriouserrors in content, long known to CDC, theentire national post-event federal planningguideline for state and local health agencieswas removed from the CDC website onJanuary 27.50 Then, for one additional month,the nation was without any national post-event guidance. On February 27 new guidancewas posted without either explanation or anyclear statement about what was new and howthe guidance to state and local health agencieshad changed. It is unfortunate that all post-event state plans were developed within theframework of CDC guidance to the states thatwas known to be flawed.

Since February 27, 2003, CDC guidancehas substantially improved.51 However, aserroneous information was posted for over ayear and widely disseminated in the media,public and professional awareness of changesremains limited. Therefore, major changesneed to be highlighted and brought to theattention of professionals and the lay publicthrough the media. In clearing up continu-ing misperceptions, the following points areof particular importance:

1. Transmission of smallpox is very possi-ble and should be assumed before theappearance of any visible rash.

2. In a bioterrorism outbreak states shouldplan to move to local mass vaccinationas they also identify and vaccinate easilyidentified contacts of the first case orcases.

3.Vaccination after exposure, particularlywithin three to five days, is likely to preventdeath but is unlikely to prevent disease andfurther spread of smallpox. Therefore,though valuable for individuals, it has lim-ited value in planning for post-event con-trol in the general population.

14

Guidance fromCDC has been

confusing, needlessly

complex, andsometimes wrong.

4. Fast and effective post-event control iscritically dependant upon completingsubstantial pre-event vaccination as calledfor in Phase II of the president’s plan.

Points 1 and 2 are now clearly and consis-tently expressed in current guidance. Point 3,as previously noted, remains flawed,52 and cur-rent CDC guidelines, though modified, stilluse the words “will prevent” in guidance tostate and local agencies and to the general pub-lic.53 As yet, Point 4 does not appear to beacknowledged.

Silence of Most State and Local HealthOfficials

State and local health officials, with somenotable exceptions, have been silent about theinadequacies of CDC plans and information.Yet many of those professionals have perceivedthe plans as confusing and not feasible. Whyhave they been silent? Smallpox is a new areafor most state and local agencies, while CDChas people who have seen and worked withsmallpox. Thus, it is reasonable to give CDCthe benefit of the doubt. Further, CDC pro-vides money to state and local agencies.Speaking out is perceived as putting funding atrisk and degrading otherwise good and colle-gial professional relationships. Finally, stateand local officials are part and parcel of a risk-averse culture that discourages making wavesand rocking the boat. Given that the constitu-tional authority for protecting the public’sheath remains at the state, not the federal, level,this is particularly troubling.54

Political ConcernsThe smallpox threat was seen by some as a

Bush administration ploy to gain support forthe war against Iraq. Therefore, any supportof vaccination was seen as an endorsement ofwar. Variants of this theme include concernssuch as, “If I support vaccination I am sup-porting the president’s social policies andlegislative program, which undermine publichealth.” It is not necessary here to debate thepros and cons of the administration’s posi-tions on other issues. It is only necessary to

realize that individual political opinions ontopics that really are not related to the small-pox threat are shaping the judgments andrecommendations of some public health andmedical practitioners.

Systems Thinking and theCulture of Public HealthTo fully understand why the president’s

smallpox vaccination plan has been delayed,we must dig even deeper and consider howpublic heath professionals think and theextent to which the culture of public health isrelevant or antithetical to national prepared-ness for bioterrorism.

Smallpox expert Dr. D. A. Hendersonwarned as early as 1999 that malicious dis-semination of smallpox by bioterrorists couldbe disastrous.55 There is much to support hisopinion, and it is not unreasonable to con-clude that this risk is the primary rationalebehind the president’s plan.56 However, thereare powerful voices that still say smallpox isdifficult to transmit and maintain that thelessons of control from the eradication yearsare valid today.57

It is essential to recognize that eradicationtook place over a period of more than 10 yearswhen the level of population immunity wasgrowing, populations were far less mobilethan today, and there was no malicious intentto disseminate smallpox.58 The persistentinability of many public health professionalsto grasp the importance of these points sug-gests that systems thinking—seeing how thepieces fit and interact—is not sufficient in theprofession. Consider the CDC director’s state-ment that the true measure of the president’spre-event vaccination plan is whether theentire nation could be vaccinated within 10days of an attack. Juxtapose that with thewords of others in CDC: “It would be a suc-cess if no one receives the vaccine, but weoffered this opportunity to all the right peo-ple.”59 Because the speed of post-event vacci-nation is directly dependent on the numberof vaccinators willing to expose themselves to

15

Eradication tookplace over a period of morethan 10 yearswhen the level ofpopulationimmunity wasgrowing, populations werefar less mobilethan today, andthere was nomalicious intentto disseminatesmallpox.

the risk of smallpox, the smaller the numberof immunized vaccinators, the faster small-pox would spread across the country. Further,if neither health care workers nor the generalpopulation are immunized, our hospitals andmedical care system will be at grave risk ofbeing swamped and losing significant capaci-ty after a smallpox attack. That is exactly whatthe president’s plan was designed to prevent.It is difficult to comprehend how no pre-event vaccination can be called a success.

The above is but one example of inade-quate systems thinking in moving from themacro level—the overall approach to pre- andpost-event smallpox planning—to the microlevel of how clinics will work and determiningwhat exactly must take place to avoid bottle-necks in the distribution and administrationof vaccine. For example, having prepositionedat the state level vaccine supplies that are suf-ficient to begin substantial vaccination assoon as a case is identified would speed upinitiating a control program by at least 12 to24 hours. As demonstrated by Kaplan, Craft,and Wein, many public health officials fail torealize the importance of response logistics indetermining the outcome of a bioterrorismevent.60 That misunderstanding is emblemat-ic of the widespread but dangerous devalua-tion of the benefits of applying sophisticatedyet pragmatic systems approaches to small-pox and bioterrorism planning.

Inadequate systems thinking about small-pox lies within a larger construct. Public health,by its very nature, prefers to deal with eventsonce full data are available. It eschews makingproactive decisions when nothing has yet hap-pened, as is the case with the threat of smallpoxwhen there is no attack and no illness.

However, in emergencies with lethal poten-tial, far-reaching decisions may have to bemade on the basis of very limited data.61 Thattype of emergency situation requires thinkingthat is completely contrary to the usual think-ing of public health professionals. Typically, agood public health professional

collects good and complete data,analyzes with care,

plans and involves concerned constituencies,prepares within the framework of the plan,acts if needed, andevaluates and revises.

That is a time-consuming and risk-mini-mizing approach for the public and for theprofessional. It is consistent with the risk-averse culture that permeates public healthand medicine. It works well for much of pub-lic health decisionmaking, but it is not cor-rect for decisionmaking with regard tobioterrorism, whether it involves smallpox oranother agent, where decisions may need tobe made with little data and less time.

Sweeping decisions based on limited datarun counter to the culture of public health.Opting for pre-event national vaccination isjust such a sweeping decision. Post-eventdecisions will also have to be made on thebasis of fragmentary, inadequate data andwill require fast, even draconian, action with-out the certain knowledge that the actionwill, in hindsight, be correct. This too is anti-thetical to the culture of public health. Weposit that such will be the case whether weare dealing with smallpox, anthrax, or otheragents.

Once you take your pick of several under-lying forces and mix them with more imme-diate causes for delay, it becomes easy tounderstand why the national pre-event vacci-nation plan is stalled. Is the situation serious?Yes. Is it catastrophic? No. We have enoughvaccine to vaccinate the entire country in caseof an attack. But instead of vaccinating rapid-ly within 10 days, with our current level ofpreparedness, we could easily take one to twomonths, with needless spread of disease,avoidable deaths, and much suffering andeconomic loss. We can muddle through. Butmuddling through at the expense of hun-dreds, perhaps thousands, of lives is not goodenough.

We are focusing only on the limitations ofpublic health with regard to bioterrorism andare not making a sweeping indictment of pub-lic health. However, we submit that much ofwhat is good about public health may stand in

16

The smaller thenumber of

immunized vaccinators, thefaster smallpox

would spreadacross the

country.

the way of effectively planning for and respond-ing to bioterrorism. Rather than ask a work-horse to be a racehorse or vice versa, let’s debatethe desirability of creating a structure thatdraws only on those elements of public healththat can contribute to an effective response toall bioterrorism agents. We are concerned aboutefforts to make the public health apparatusinto something it isn’t and shouldn’t be. This isexemplified by the recent letter to the directorof CDC from the Institute of Medicine'sCommittee on Smallpox Vaccination ProgramImplementation.62

The Institute of Medicine Committee letter,though containing some useful recommenda-tions, is flawed. Equating smallpox prepared-ness with chronic disease and obesity and sug-gesting that responses to such diverse threatsto health should be integrated strains creduli-ty. The statement that “ . . . a high level of pre-paredness may well be possible without vacci-nating any personnel pre-event” is wrong, irre-sponsible, and dangerous. In another part oftheir letter, the committee suggests that indi-vidual states may have goals of vaccinatingtheir populations in 2 to 10 days. The impossi-bility of achieving either with no pre-event vac-cination is not mentioned. Later, the commit-tee says, “It is unclear . . . how numbers of vac-cinated personnel relate to the ability torespond effectively to a smallpox attack.”These and other inconsistencies and contradic-tions are obvious yet not addressed by the com-mittee. In yet another place the committee sug-gests that in a post-event situation it may notbe possible to immediately vaccinate everyone,so plans should be made for “prioritizing cate-gories of vaccinees . . . pre-event” or rationingaccess. We can only speculate about the prob-lems of crowd control when access to vaccine isneedlessly denied in the face of a disease with a30 percent fatality rate. Although the commit-tee mentioned the military have vaccinatedover 450,000 people, they failed to commenton the fundamental finding from the militaryexperience that smallpox is a safe vaccine whenadministered with care to healthy adults. Inbrief, the IOM letter illustrates poor risk assess-ment and inadequate systems thinking that

neither serve good public health nor supportsound national preparation for a possible ter-rorist release of smallpox.

What to Do?

Short TermThe CDC needs to clearly articulate the

rationale for the president’s three-phase planand, within that rationale, specifically includethe basis for the number and categories of peo-ple to be vaccinated pre-event. It must developand publicize a fair, understandable, well-doc-umented assessment of vaccination risk that isupdated as new information becomes avail-able. Since CDC has, so far, been unable toaccomplish either objective, it is likely that rig-orous oversight by HHS and Congress will berequired to make this happen.

Another important short-term measureinvolves reducing the risk of accidental vaccina-tion of others by recommending the use of thesemipermeable membrane dressing for every-one who is vaccinated, not just hospital workers.

CDC and other health policy officials inthe Bush administration should explainclearly to the public the key details of recent-ly approved vaccine compensation coverageand how it is linked to workers’ compensa-tion and other disability income insurance. Itshould be emphasized that very few peoplewill have events that trigger the need for com-pensation.

The secretary of homeland security and theWhite House should reaffirm the importanceof the National Smallpox Vaccination Pro-gram and meet with leaders of medical, hospi-tal, and nursing associations and relevantunions, to stress that this is a national securityissue, the risk to healthy adults is minimal,there is a good approach in place for liabilityand compensation, and the nation needs theirhelp.

Medium TermTo ensure that bioterrorism response plans

are adequate, President Bush should requireCDC and HHS to jointly empanel an advisory

17

The CDC needsto clearly articulate therationale for thepresident’s three-phase planand specificallyinclude the basisfor the numberand categories ofpeople to be vaccinated pre-event.

group that has expertise in systems analysis andoperations research, public administration,public health and behavioral science, hospitaland medical care administration, law, epidemi-ology, and clinical medicine, including infec-tious diseases. The panel should have militaryrepresentation as well. Most of the membersshould be fresh faces, not people drawn fromexisting committees and agency workinggroups. The charge to the panel and its staffwould be to critically examine and test all bioter-rorism plans—not just those for smallpox—toidentify weaknesses, propose changes, and ulti-mately ensure their adequacy. The underlyingquestion should be: Are the plans adequate for aworst-case scenario? That requires analysis ofpre- and post-event plans as well as of the inter-action between federal and state plans. It cannotbe limited to federal plans alone.

Though bioterrorism is a public healthissue, the primary impact of bioterrorism willfall on the acute care system, particularly hos-pitals. That is where people go when they aresick or think they are sick. We must recognizethat our hospitals, especially their emergencyrooms, are a critical first line of defense againstbioterrorism. But after two decades of reim-bursement policies driven by managed carecompetition in the private sector and adminis-tered pricing for public-sector programs, hos-pitals are operated on a “just-in-time, just-what’s-required” basis. For an adequate hospi-tal-sector level of preparedness, critical issuesof surge capacity and shortages (staff, equip-ment, and facilities) and the need for adequategovernment funding for bioterrorism pre-paredness and response must be addressed.

What can be learned from our approach tosmallpox? What must be done to ensure thatwe are adequately prepared, not just for small-pox, but for all bioterrorism hazards? Whatcan we learn from the recent military experi-ence with vaccination? Are there ways to capi-talize on the strengths of CDC and state andlocal public health agencies while addressingweaknesses in systems thinking and commu-nication? Is the culture of public health suffi-ciently malleable to allow, even to foster, rapiddecisionmaking with vast consequences based

on very limited data? As the best possiblepreparation for and protection against bioter-rorism is in all our interests, those questionsand more merit public discussion and debate.

A Note on SARS,Monkeypox, and Public

HealthThe onset and spread of Severe Acute

Respiratory Syndrome and monkeypox havedominated public health headlines in recentmonths. SARS, although infectious and com-municable and thus akin to smallpox, hasbeen appropriately addressed by the applica-tion of classic public health epidemiologic andlaboratory methods. SARS is less infectiousthan smallpox and has a lower mortality rate.Its impact develops far more slowly than thatof anthrax and botulinum toxin. An under-standing of SARS, what it is, and how to con-trol it can be determined only by rapid, but notprecipitous, epidemiologic and laboratoryinvestigation that pays exquisite attention toall possibly relevant details. SARS differs sub-tly but significantly from bioterrorism, and itexemplifies where classic public health canshine. In the case of bioterrorism, thoroughinvestigation and retrospective analysis priorto taking fast and sweeping action is morelikely to ensure failure than lead to success.SARS does dramatically demonstrate thathospital workers may be particularly vulnera-ble and hospitals can serve as epidemiologicpumps contributing to the spread of diseaseas they struggle to control the same disease.Most notably, the economic and social conse-quences of even a small epidemic like SARSalready have been vast.

Monkeypox reminds us that we must expectthe first case of smallpox to be identified slowly.Initiating civilian vaccination at our current stateof preparedness will be neither easy nor fast.

Finally, SARS and monkeypox demonstratethe ease with which infections can be transmit-ted in our era of easy, worldwide air travel andthe impact of rapid, global communication onhow citizens and governments respond.

18

In the case ofbioterrorism,

thorough investigation and

retrospectiveanalysis prior to

taking fast andsweeping action is

more likely toensure failure

than lead to success.

Conclusion

With sufficient vaccine and VIG, the nationnow has the material, but not the human,capacity to rapidly control a bioterrorist small-pox outbreak. Pre-event vaccination of10,000,000 medical, public health, and emer-gency workers is central and essential for rapidpost-event control. However, few health andemergency workers have opted for voluntaryvaccination. The overt reasons are

• inadequate and misleading vaccine riskinformation provided by CDC,

• delay in passing liability and compensa-tion legislation, and

• insufficient education about and sup-port for vaccination by key leaders in theadministration directed to the publicand key professional groups.

Further, a variety of subtle but powerfulunderlying reasons is delaying vaccination andweakening post-event planning. Perhaps themost important are deficient systems thinkingin public health and a public health culture thatprefers to be reactive rather than proactive.

In the near term, far better informationabout the risk of vaccination along with a clearrationale for the president’s plan are needed.With the passage of compensation legislation,the administration now needs to reemphasizethat vaccination is safe and that our nation’ssecurity requires the timely completion of thenational pre-event plan. Those actions will effec-tively neutralize the weapons potential of small-pox. The only reason for less preparation wouldbe that the national intelligence assessment sup-ported a conclusion that the threat of dissemi-nation is significantly reduced or absent.

In the medium term, the adequacy of ourpre- and post-event response plans for allbioterrorism agents should be subjected tocritical, multidisciplinary analysis. Those ofus in the health professions need to considerif and how public heath expertise can bemade more relevant to planning for andmanaging bioterrorism events. However we

organize to combat bioterrorism, furtherquestioning of premises and conventionalwisdom is likely to illuminate weaknessesand suggest more robust approaches.

NotesThe authors wish to thank Julie Adelson, JimBentley, Col. John Grabenstein, Jane Hale,Kristian Heggenhougen, Dr. Ken James, EdwardKaplan, Ken Mirvis, and Dr. James Plorde fortheir many helpful suggestions.

1. William J. Bicknell, “The Case for VoluntarySmallpox Vaccination,” New England Journal ofMedicine 346 (2002): 1323–25. In November 2001the federal government awarded a $428 millioncontract to a private joint venture between twopharmaceutical manufacturers, Acambis andBaxter International, to produce 155 million dosesof smallpox vaccine to be delivered by the end of2002. The new purchase would be added to the 15million older doses of smallpox vaccine that thegovernment already had stockpiled and the 40 mil-lion newer doses previously ordered in 2000 by theCenters for Disease Control and Prevention. Inaddition, about 85 million doses of older smallpoxvaccine were discovered in storage by vaccine makerAventis Pasteur and donated to the federal govern-ment on March 29, 2002. See Veronique de Rugyand Charles V. Peña, “Responding to the Threat ofSmallpox Bioterrorism: An Ounce of Prevention IsBest Approach,” Cato Institute Policy Analysis no.434, April 18, 2002, p. 5; and Ceci Connolly,“Aventis to Donate Smallpox Vaccine,” WashingtonPost, March 30, 2002, p. A2.

2. Centers for Disease Control and Prevention(CDC), “Protecting Americans: SmallpoxVaccination Program,” December 13, 2002, www.bt.cdc.gov/agent/smallpox/vaccination/vaccination-program-statement.asp; White House, “FrequentlyAsked Questions: Smallpox Response Teams,”December 13, 2002, www.whitehouse.gov/news/releases/2002/12/20021213-3.html; and CDC,“CDC Telebriefing Transcript: HHS Teleconferenceon Smallpox Policy,” December 14, 2002, www.cdc.gov/od/oc/media/transcripts/t021214. htm.

3. Personal Communication with Col. JohnGrabenstein, deputy director, military vaccines,U.S. Army Medical Command; CDC, Office ofCommunication, “Smallpox Vaccination ProgramStatus by State,” www.cdc.gov/od/oc/media/spvaccin.htm (accessed July 25, 2003); and U.S.Department of Defense, “Smallpox VaccinationProgram Safety Summary, as of June 15, 2003,”www.smallpox.army.mil/event/SPSafetySum.asp.

19

In the near term,far better informationabout the risk ofvaccination alongwith a clear rationale for thepresident’s planare needed.

4. International Communications Research, Studyno. Q946, Medis, Pa., November 2001; and JosephBarbera et al., “Large-Scale Quarantine FollowingBiological Terrorism in the United States: ScientificExamination, Logistic and Legal Limits, andPossible Consequences,” Journal of the AmericanMedical Association 286 (2001): 2711–17.

5. J. Michael Lane et al., “Complications ofSmallpox, National Surveillance in the UnitedStates 1968,” New England Journal of Medicine 281(1969): 1201–8; John M. Neff et al., “Complicationsof Smallpox Vaccination, National Survey in theUnited States, 1963,” New England Journal of Medicine276 (1967): 125–31; and John M. Neff et al. “Risk ofTransmission of Vaccinia Virus to Contacts,” Journalof the American Medical Association 288 (2002): 1901–4.

6. Frank Fenner et al., Smallpox and Its Eradication(Geneva: World Health Organization, 1988), www.who.int/emc/diseases/smallpox/Smallpoxeradication.html.

7. Fenner et al.

8. Ken Alibek, Biohazard (New York: RandomHouse, 1999).

9. Ken Alibek, Testimony before a Special U.S.Congressional Hearing, “Combating Terrorism:Assessing the Threat of a Biological Weapons Attack,”October 22, 2001, www.newsmax.com/archives/arti-cles/2001/10/21/204923.shtml; and Andre Picard,“Experts Raise Smallpox Alert: Global VaccinationCampaign Urged by Scientists Fearing BioterrorThreat,” Globe and Mail, November 6, 2001, p. 1.

10. Donald A. Henderson, “Smallpox: Clinicaland Epidemiologic Features,” Emerging InfectiousDiseases 5 (1999): 537–39.

11. Alibek, Testimony.

12. Personal communication with Dr JonathanTucker, director of the chemical and biologicalweapons nonproliferation program of the MontereyInstitute, Washington, D.C., June 4, 2002. He statedthat declassified Defense Intelligence Agency docu-ments noted evidence of recent vaccination of NorthKorean troops and vaccination of Iraqi troops at anunspecified time.

13. Picard.

14. William J. Bicknell and Kenneth James, “TheNew Cell Culture Vaccine Should Be Offered tothe General Population,” Reviews in MedicalVirology 13 (January 2003): 5–15; and John G.Bartlett et al., “Smallpox Vaccination in 2003: KeyInformation for Clinicians,” Clinical InfectiousDiseases 36 (2003): 883–902. VIG is a blood prod-

uct derived from the plasma of humans who haverecently been vaccinated, and it is an antidote tosome of the vaccine’s side effects. For a full andcurrent discussion of the use of VIG, see ibid.

15. Lane et al., “Complications of Smallpox,National Surveillance in the United States 1968”;and Neff et al., “Complications of SmallpoxVaccination, National Survey in the United States,1963.”

16. J. Michael Lane et al., “Deaths Attributable toSmallpox Vaccination, 1959 to 1966 and 1968,”Journal of the American Medical Association 212 (1970):441–44.

17. CDC, “Vaccine Overview,” March 31, 2003, www.bt.cdc.gov/agent/smallpox/vaccination/facts.asp.

18. The data for 1963 and 1968 are aggregated forthe 15-to-19-year age group and cannot be brokenout. Therefore, the age group starts at 15 eventhough the national plan begins at 18. However,because vaccine risk increases with decreasing age,if this introduces error, it will be conservative andshow increased risk.

19. Eczema or atopic dermatitis is a skin condi-tion that tends to wax and wane. It occurs morecommonly in children than adults, and, whetherit is active or not, it is thought to place the personat higher risk of a vaccine complication. If the der-matitis is active in an unvaccinated person, thatperson is at higher risk of being accidentallyinfected by coming into close contact with arecently vaccinated person.

20. Bartlett et al.

21. Neff et al., “Risk of Transmission of VacciniaVirus to Contacts.”

22. Ibid.

23. Robert B. Belshe, Presentation at CDC, May 8,2002, reporting no detectable viral sheddingwhen a double-thickness semipermeable mem-brane was used over a folded gauze pad.

24. Melinda Wharton et al, “Recommendations forUsing Smallpox Vaccine in a Pre-Event VaccinationProgram,” Morbidity and Mortality Weekly Report(CDC), February 26, 2003, www.cdc.gov/mmwr/preview/mmwrhtml/m2d226.htm.

25. Hand washing, a cornerstone of good infec-tion control, is very important until the scab atthe vaccination site falls off, often around 21 daysafter vaccination. It should be done after chang-ing the dressing covering the vaccination site orwhenever the vaccination site is touched. The

20

dressing is typically changed every 2 to 4 days.

26. Kent A. Sepkowitz, “Current Concepts: HowContagious Is Vaccinia?” New England Journal ofMedicine 348, no. 5 (January 30, 2003): 439–46.

27. Personal Communication with Col. JohnGrabenstein.

28. For details of the military experience, see U.S.Department of Defense, “Smallpox VaccinationProgram Safety Summary, as of May 16, 2003.”

29. “Update: Adverse Events Following SmallpoxVaccination—United States 2003,” Morbidity andMortality Weekly Report, April 4, 2003, pp. 278–81;and www.smallpox.army.mil/event/SPSafetySum.asp, as of March 31, 2003.

30. Personal Communication with Col. JohnGrabenstein.

31. CDC, “Interim Smallpox Fact Sheet, SmallpoxVaccine and Heart Problems,” www.bt.cdc.gov/agent/smallpox/vaccination/heartproblems.asp(acessed June 8,2003); U.S. Department of Defense,“Smallpox Vaccination Program, ResourcesRegarding Cardiac Adverse Events,” www.smallpox.army.mil/event/cardiac.asp (accessed June8,2003); and U.S. Department of Defense,“Smallpox Vaccination Program Safety Summaryas of March 31, 2003.”

32. Jouko Karjalainen et al., “Etiology of MildAcute Infectious Myocarditis,” Acta MedicaScandinavia 213 (1983): 65–73; and Brian J. Feery,“Adverse Reactions after Smallpox Vaccination,”Medical Journal of Australia 2 (1977): 180–83.

33. L. R. Finlay-Jones, “Fatal Myocarditis afterVaccination against Smallpox: Report of a Case,”New England Journal of Medicine 270 (1964): 41–42

34. Karjalainen et al.

35. “Cardiac Adverse Events Following SmallpoxVaccination—United States 2003,” Morbidity andMortality Weekly Report, March 28, 2003, pp.248–50; www.smallpox.army.mil/event/SPSafetySum.asp, as of March 31, 2003; and personal com-munication with Col. John Grabenstein

36. Ibid.

37. Morbidity and Mortality Weekly Report, March28, 2003.

38. “Risk of Death: Assigning Numbers to HealthRisks,” New York Times, July 7, 2002.

39. Arnold Barnett and Alexander Wang, “Are SomeAirlines Safer Than the Others?” http://web.mit.edu

/-msey/www/are some airlines safer.html; see also“Flying? No Point in Trying to Beat the Odds,” WallStreet Journal, September 9, 1998.

40. This assumes that everyone vaccinated usesthe semipermeable membrane dressing andhealth workers who have contact with patients forthe 21 days during which they may accidentallyinfect another person have their work assign-ments modified so that they are not working inpatient care areas with high-risk patients(immunocompromised, burns, etc.).

41. Cyril W. Dixon, “Smallpox in Tripolitania,1946: An Epidemiological and Clinical Study of500 Cases, Including Trials of PenicillinTreatment,” Journal of Hygiene 46 (1948): 351–77(see particularly Table 6, p. 369); Philip P.Mortimer, “Can Postexposure Vaccination againstSmallpox Succeed?” Clinical Infectious Diseases 36(2003): 622–29; and William Bicknell and KennethJames, “Smallpox Vaccination after a Bioterrorism-Based Exposure,” Letter to the editor, ClinicalInfectious Diseases, August 2003, p. 467.

42. CDC, “Smallpox Emergency PersonnelProtection Act: Benefits and Compensation forSmallpox Vaccine Injuries,” June 6, 2003, www.bt.cdc.gov/agent/smallpox/vaccination/bene-comp.asp. The law established a no-fault program toprovide benefits and/or compensation to certainindividuals, including health care workers and emer-gency responders, who are injured as the result ofadministration of smallpox countermeasures. Theprogram will also provide benefits and/or compen-sation to certain individuals who are injured as aresult of accidental vaccinia inoculation throughcontact. The Homeland Security Act of 2002 alreadyhad protected physicians and other health careworkers from lawsuits by those they vaccinate. Itdeemed entities and individuals involved in themanufacture, distribution, and administration ofthe smallpox vaccine to be “employees” of the PublicHealth Service for tort liability purposes. That legis-lation effectively transferred liability to the federalgovernment under the Federal Tort Claims Act(which limits remedies for those seeking redress). SeeRobin J. Strongin and Eileen Salinsky, “Who WillPay for the Adverse Events Resulting from SmallpoxVaccination? Liability and Compensation Issues,”National Health Policy Forum Issue Brief no. 788,March 12, 2003, p. 5. However, Strongin andSalinsky observed that section 304 of the HomelandSecurity Act did not appear to provide liability pro-tection for hospitals or other health care organiza-tions that ask their employees to volunteer for thevaccine but are not directly responsible for adminis-tering the vaccine. The liability status of health careworkers who are vaccinated and may inadvertentlypass the vaccinia virus to an unvaccinated personalso remained unclear, at best. In addition, the 2002

21

legislation did not establish a clear avenue of com-pensation for individuals who incur injuries causedby administration of the vaccine. Ibid, pp. 6–7; seealso “Smallpox Vaccine: Easing Fears onInoculations,” American Medical News, May 12, 2003,www.ama-assn.org/sci-pubs/amnews/amn_03/edsa0512.htm.

43. CNN.com/Health, “Surgeon General Vaccinatedagainst Smallpox,” March 11, 2003, www5.cnn.com/2003/HEALTH/03/11/smallpox.surgeon.gen.ap.

44. Alibek, Biohazard.

45. J. Michael Lane and Joel Goldstein, “Evaluationof 21st-Century Risks of Smallpox Vaccination andPolicy Options,” Annals of Internal Medicine 138(2003): 492. See also de Rugy and Peña; and Bicknell.

46. Quoted by Dr. Gregory Saathoff speaking atthe King’s College conference on “Communicatingthe War on Terror,” London, June 5, 2003.

47. Alibek, Biohazard.

48. To the extent that smallpox is in the hands ofnations other than Russia and the United States,there is always the chance of accidental release with-out malicious intent. Moreover, we should notassume that everyone who possesses samples of thevirus will be as diligent or capable as designatedWHO repositories in storing and handling the virus.An exposure of this type would be easily confusedwith bioterrorism but, we hope, easier to control.

49. American College of Preventive Medicine,“Clinician Communication Briefing 6 Summary,Special Smallpox Preparedness Program UpdateTelephone Briefing,” March 7, 2003, www.acpm.org/hhs_smallpox.htm.

50. Personal communication with Dr. LarryAnderson, CDC, January 26, 2003.

51. CDC, “Smallpox Response Plan and Guidelines(Version 3.0).” See particularly Draft Guide A—Smallpox Surveillance and Case Reporting; ContactIdentification, Tracing, Vaccination, and Surveillance;and Epidemiologic Investigation (May 21, 2003) andGuide B—Vaccination Guidelines for State and LocalHealth Agencies (February 27, 2003), www.bt.cdc.gov/agent/smallpox/response-plan/index.asp.

52. Dixon; Mortimer; and Bicknell and James,“Smallpox Vaccination after a Bioterrorism-BasedExposure.”

53. CDC, “Smallpox Fact Sheet: Vaccine Overview,”www.bt.cdc.gov/agent/smallpox/vaccination/facts.a

sp (accessed August 3, 2003).

54. To give the reader a sense of the power of peerpressure, as we write these words both authors areuncomfortable, not with the truth of the facts setforth in this article, but with the knowledge thatwhat we are writing may seem like airing dirtylinen in public.

55. Henderson.

56. Bicknell; and Edward H. Kaplan, David L. Craft,and Lawrence M. Wein, “Emergency Response to aSmallpox Attack: The Case for Mass Vaccination,”Proceedings of the National Academy of Science 99(2002): 10935–40, published online before print as10.1073/pnas.162282799.

57. Thomas Mack, “A Different View of Smallpoxand Vaccination,” New England Journal of Medicine348 (January 30, 2003): 5; Lane and Goldstein; andwww.bt.cdc.gov/agent/smallpox/response-plan/index.asp.

58. Edward H. Kaplan and Lawrence M. Wein,“Smallpox Eradication in West and Central Africa:Surveillance—Containment or Herd Immunity?”Epidemiology 14 (2003): 1–4; and Bicknell and James,“The New Cell Culture Vaccine Should Be Offeredto the General Population.”

59. Ceci Connolly, “Bush Smallpox InoculationPlan Near Standstill: Medical Professionals CitePossible Side Effects, Uncertainty of Threat,”Washington Post, February 24, 2003, p. A6; and DavidMcGlinchey, “Smallpox: CDC Says It Never Aimedfor 500,000 in First Phase,” Global Security Newswire,February 26, 2003, www.nti.org/d_newswire/issues/newswires/2003_2_26.html#4.

60. Kaplan, Craft, and Wein; and Lawrence M.Wein, David L. Craft, and Edward H. Kaplan,“Emergency Response to an Anthrax Attack,”Proceedings of the National Academy of Science 100(2003): 4346–51, published online before print as10.1073/pnas.06 36861100.

61. William Bicknell and Daniel C. Walsh, “The First‘Red Tide’ in Recorded Massachusetts History:Managing an Acute and Unexpected Public HealthEmergency,” in Proceedings of the First InternationalConference on Toxic Dinoflagellate Bloom (Boston:Massachusetts Science and Technology Foundation,1975), pp. 337–45.

62. Institute of Medicine, "Review of the Centers forDisease Control and Prevention's SmallpoxVaccination Program Implementation," LetterReport #4, August 12, 2003.

22