Risks and benefits of preexposure and postexposure smallpox vaccination. (1).This article presents a model and decision criteria for evaluating a person's risk of pre- or postexposure smallpox smallpox, acute, highly contagious disease causing a high fever and successive stages of severe skin eruptions. The disease dates from the time of ancient Egypt or before. vaccination vaccination, means of producing immunity against pathogens, such as viruses and bacteria, by the introduction of live, killed, or altered antigens that stimulate the body to produce antibodies against more dangerous forms. in light of serious vaccine-related adverse events (death, postvaccine encephalitis encephalitis (ĕnsĕf'əlī`təs), general term used to describe a diffuse inflammation of the brain and spinal cord, usually of viral origin, often transmitted by mosquitoes, in contrast to a bacterial infection of the meninges and progressive vaccinia progressive vaccinia
A severe or even fatal form of vaccinia occurring as a complication of smallpox vaccination chiefly in persons with an immunologic deficiency or dyscrasia, characterized by progressive enlargement of the initial and secondary ). Even at a 1-in-10 risk of 1,000 initial smallpox cases, a person in a population of 280 million has a greater risk for serious vaccine-related adverse events than a risk for smallpox. For a healthcare worker to accept preexposure vaccination, the risk for contact with an infectious smallpox case-patient must be >1 in 100, and the probability of 1,000 initial cases must be >1 in 1,000. A member of an investigation team would accept preexposure vaccination if his or her anticipated risk of contact is 1 in 2.5 and the risk of attack is assumed to be >1 in 16,000. The only circumstances in which postexposure vaccination would not be accepted are the following: if vaccine efficacy Vaccine efficacy is defined as the reduction in the incidence of a disease among people who have received a vaccine compared to the incidence in unvaccinated people. The efficacy of a new vaccine is measured in phase III clinical trials by giving one group of people a vaccine and were <1%, the risk of transmission were <1%, and (simultaneously) the risk for serious vaccine-related adverse events were >1 in 5,000.
Smallpox has been identified as a weapon that may be used by a bioterrorist (2,3). Terrorist groups and even nations may have acquired stocks of smallpox produced in the former Soviet Union (4). As a response to this threat, the U.S. federal government has begun to produce and stockpile stock·pile
A supply stored for future use, usually carefully accrued and maintained.
tr.v. stock·piled, stock·pil·ing, stock·piles
To accumulate and maintain a supply of for future use. approximately 300 million doses of smallpox vaccine smallpox vaccine
A vaccine containing vaccinia virus suspensions that is inoculated subcutaneously to immunize against smallpox. (2). Properly administered as a preexposure prophylactic prophylactic /pro·phy·lac·tic/ (pro?-fi-lak´tik)
1. tending to ward off disease; pertaining to prophylaxis.
2. an agent that tends to ward off disease.
n. , the vaccine is approximately 95%-98% effective. However, smallpox vaccine contains a live virus (vaccinia vac·cin·i·a
1. See cowpox.
2. An infection induced in humans by inoculation with the vaccinia virus in order to confer resistance to smallpox; it is usually limited to the site of inoculation. ), and a risk for serious, vaccine-related adverse events exists (5,6). How the stockpile of smallpox vaccine should be used is much debated. Some mathematical models
Others have called for a large-scale, voluntary preexposure vaccination campaign open to the entire U.S. population (10,11). Some concur CONCUR - ["CONCUR, A Language for Continuous Concurrent Processes", R.M. Salter et al, Comp Langs 5(3):163-189 (1981)]. with such a position in part because they are skeptical that a postattack vaccination-based response will be adequate (12). A telephone survey of the U.S. population, conducted during October to December 2002, found that 61% of the respondents In the context of marketing research, a representative sample drawn from a larger population of people from whom information is collected and used to develop or confirm marketing strategy. would accept smallpox vaccination if ".... offered as a precaution against terrorist attacks" (13). However, despite this trepidation trepidation /trep·i·da·tion/ (trep?i-da´shun)
2. nervous anxiety and fear.trep´idant
1. An involuntary trembling or quivering. about smallpox, the U.S. federal government's program to vaccinate vac·ci·nate
To inoculate with a vaccine in order to produce immunity to an infectious disease such as diphtheria or typhus.
vac up to 500,000 healthcare workers and first responders first responder First response personnel Emergency medicine A person employed in the public sector–EMT, fire fighter, police, volunteer EMS–whose duties include provision of immediate medical care in the event of an emergency; FRs have basic emergency has found that concerns about vaccine-associated risks has caused many to question the need for preexposure vaccination (14-17). Part of this hesitancy hes·i·tan·cy
An involuntary delay or inability in starting the urinary stream. includes questions regarding compensation for vaccine-related adverse events (17-19).
This article presents a risk-benefit model of pre- and postexposure smallpox vaccination, which will help public health officials better understand the public's risk-benefit appraisal. Other papers have examined pre- and postsmallpox attack responses from a societal so·ci·e·tal
Of or relating to the structure, organization, or functioning of society.
Adj. perspective (3,7). The model presented quantifies the perspective of an individual person. The model can be applied to other situations involving pre- and postexposure prophylaxis Postexposure prophylaxis (PEP)
Any treatment given after exposure to a disease to try to prevent the disease from occurring. In the case of rabies, PEP involves a series of vaccines given to an individual who has been bitten by an unknown animal or one that is for infectious diseases infectious diseases: see communicable diseases. (e.g., other vaccines).
I constructed a risk-benefit model (using a standard computer-based spreadsheet; see online Appendix at URL URL
in full Uniform Resource Locator
Address of a resource on the Internet. The resource can be any type of file stored on a server, such as a Web page, a text file, a graphics file, or an application program. : http://www.cdc.gov/ncidod/EID/vol9no11/03-0369_spreadsht.xls), which balances the risks for smallpox disease against vaccine-related adverse events (vaccine-related "disease"). The general model is formulated as follows:
Net risk of disease = (risk from smallpox without preexposure vaccination)--(risk of smallpox due to vaccine failure A vaccine failure is when an organism develops a disease in spite of being vaccinated against it. Primary vaccine failure occurs when an organism's immune system does not produce enough antibodies when first vaccinated. + risk for vaccine-related adverse events from preexposure vaccination) and the precise formula is the following:
Net risk for disease =
The symbols and the value for each variable are defined in the Table.
The term "disease" refers to case-patients with clinical symptoms caused by either smallpox or serious vaccine-related adverse events. The phrase "serious vaccine-related adverse events" includes death, postvaccinial encephalitis, and progressive vaccinia. Each serious side-effect requires medical care, such as vaccinia immunoglobulin immunoglobulin: see antibody; immunity; immunology.
Any of the glycoproteins in the blood serum that are induced in response to invasion by foreign antigens and that protect the host by eradicating pathogens. , hospitalization hospitalization /hos·pi·tal·iza·tion/ (hos?pi-t'l-i-za´shun)
1. the placing of a patient in a hospital for treatment.
2. the term of confinement in a hospital. , or a number of visits to a physician's office. In 1968, the rate of postvaccinial encephalitis and progressive vaccinia among first time vaccinees ranged from approximately 0.3 to 1.2 in 100,000 for those aged 1-19 years, 0.7 to 4 in 100,000 for those <1 year of age, and 0 to 1.4 in 100,000 for those >20 years of age (20,21). As most preevent vaccinees are likely to adults, I used a rate of 1/100,000 vaccinees ([P.sub.SideEffect], Table). Vaccine-related adverse events such as eczema vaccinatum eczema vac·ci·na·tum
A form of generalized vaccinia supervening upon an existing atopic dermatitis and accompanied by a high fever, malaise, and enlargement of the lymph nodes. , soreness or redness at site of vaccination, headache, and mild and temporary nausea nausea, sensation of discomfort, or queasiness, in the stomach. It may be caused by irritation of the stomach by food or drugs, unpleasant odors, overeating, fright, or psychological stress. It is usually relieved by vomiting. are not considered to be serious vaccine-related adverse events in the model. A risk for eczema vaccinatum occurs in about 1 in 100,000 primary vaccinations (20), which can result in serious consequences requiring intensive medical care, and even (rarely) death (6). I thus underestimate the risk for vaccine-related adverse events, biasing the model toward acceptance of vaccination.
If net risk for disease is >0, then the risk for disease from smallpox is greater than the risk for serious vaccine related adverse events, and a person would chose preexposure vaccination, If the net risk for disease is <0, then the risk for serious vaccine-related adverse events is greater than the risk for smallpox, and an individual person would chose no preexposure vaccination.
I use the model to evaluate the net risk for disease faced by a person who is a member of one of the following three groups: 1) The general population. The model compares the risk of being a smallpox patient before an attack is detected to the risk for serious vaccine-related adverse events from preexposure vaccination. The risk of being an actual smallpox patient is modeled by setting the risk for transmission at 1 (Table). Two populations "at risk" are modeled: a population of 9 million, representing a metropolitan area assumed to be the sole target, and the entire U.S. population of approximately 280 million. 2) The healthcare community. For a healthcare worker (HCW HCW Health care worker, see there ) who faces potential exposure to smallpox as a result of caring for a person with smallpox, the risk of contracting smallpox from the patient is compared with the risk for serious vaccine-related adverse events attributable to preexposure vaccination. 3) A smallpox investigation team. For a person who is trained to be deployed to investigate potential patients or attacks (i.e., deliberately seek out potential smallpox patients and material that may be contaminated contaminated,
v 1. made radioactive by the addition of small quantities of radioactive material.
2. made contaminated by adding infective or radiographic materials.
3. an infective surface or object. by smallpox), the risk for contracting smallpox from the patient or other source of smallpox (e.g., aerosol aerosol (âr`əsōl,–sŏl): see colloid.
System of tiny liquid or solid particles evenly distributed in a finely divided state through a gas, usually air. , container) is compared with the risk for serious vaccine-related adverse events from preexposure vaccination. Investigation team members will take precautions precautions Infectious disease The constellation of activities intended to minimize exposure to an infectious agent; precautions imply that the isolation of an infected Pt is optional, but not mandatory. to reduce risk for transmission (e.g., wear gloves, face masks Face mask
The simplest way of delivering a high level of oxygen to patients with ARDS or other low-oxygen conditions.
Mentioned in: Adult Respiratory Distress Syndrome , and gowns), reducing risk for transmission to an assumed 0.4 (no data exist regarding the actual reduction in risk attributable to using such barrier precautions barrier precautions Infection control A general term referring to any method or device used to ↓ contact with potentially infectious body fluids, including facial masks, doubled gloves and fluid-resistant gowns. See Isolation, Reverse isolation, Universal precautions. ).
For all scenarios, after an attack is detected, I assume that appropriate responses will be taken, including effective isolation of patients (2) and vaccination of susceptible contacts. Thus, the results only apply up to the point of discovery of the bioterrorist event.
In the model, I assume that persons considering preexposure vaccination value equally the risk for disease from either smallpox or from serious vaccine-related adverse events. In reality, a person may be more worried about contacting a clinical case of smallpox than of experiencing serious vaccine-related adverse events. The risk of dying from smallpox vaccine is approximately 1:1,000,000 vaccinees (20,21), while the death rate due to smallpox may be as high as 30% of all unvaccinated clinical cases (23,24). Using the relative risk of death, I set a comparative value of I case of smallpox = 35 cases of serious vaccine-related adverse events ([P.sub.Valuation] = 1/35 = 0.02857). (2) Other sensitivity analyses include increasing the number of cases of smallpox before detection of the attack from 1,000 to 100,000 (Table), and setting the risk for serious vaccine-related adverse events to either 1 in 10,000 or 1 in 1,000,000. The former represents the risk of experiencing probable vaccine-related myocarditis Myocarditis Definition
Myocarditis is an inflammatory disease of the heart muscle (myocardium) that can result from a variety of causes. While most cases are produced by a viral infection, an inflammation of the heart muscle may also be instigated by or pericarditis Pericarditis Definition
Pericarditis is an inflammation of the two layers of the thin, sac-like membrane that surrounds the heart. This membrane is called the pericardium, so the term pericarditis means inflammation of the pericardium. , as measured during the current smallpox vaccination program among civilians (25). The latter is the risk, measured in the 1960s, of serious vaccine-related adverse events (e.g., postvaccinial encephalitis and progressive vaccinia) among revaccinees (20,21).
Risk-Benefit Analysis risk-benefit analysis,
n the consideration as to whether a medical or surgical procedure, particuarly a radical approach, is worth the risk to the patient compared with the possible benefits if the procedure is successful. of Postexposure Vaccination
The model can used to evaluate a person's perspective of the risks and benefits of receiving a smallpox postexposure vaccination. I considered a person who has been exposed to somebody who may or may not have smallpox. To model such uncertainty, I set [P.sub.R] = 1, and let PE range from 1 in 10 to 1 in 100,000. I then assumed either a postexposure vaccine efficacy of 10% ([P.sub.VEpost], Sensitivity analyses, Table) and a risk for transmission of 70% ([P.sub.T], Sensitivity analyses, Table), or a postexposure vaccine efficacy of 60% and a risk for transmission of 35%. Additional sensitivity analyses can further vary the values for transmission and efficacy of postexposure vaccination.
I also considered the case in which a person has been exposed to a definite smallpox case (i.e., [P.sub.R] = 1, [P.sub.E] = 1). I examined the risk-benefit of postexposure vaccination using a range of risks for vaccine-related adverse events, from 1 in 500 vaccinees to 1 in 100,000 vaccinees. This range encompasses the risks for serious vaccine-related adverse events faced by those without any contraindications for receiving the vaccine, as well as those who would have contraindications for receiving preexposure vaccination (e.g., pregnant women, those with auto-immune diseases, HIV-positive persons). I modeled a "worst case" approach and assumed that postexposure vaccine efficacy would only be 1% (representing, for example, a delay of several days between exposure and being offered the vaccine). The risk for transmission was set at either 1% or 30%, representing possible scenarios, for example, the person considering postexposure vaccination was appropriately wearing gloves, gown gown
A robe or smock worn in operating rooms and other parts of hospitals as a guard against contamination.
n , and mask in the presence of the infected in·fect
tr.v. in·fect·ed, in·fect·ing, in·fects
1. To contaminate with a pathogenic microorganism or agent.
2. To communicate a pathogen or disease to.
3. To invade and produce infection in. person or only had a very brief contact.
Time and the Need for Revaccinations
No data exist that record the percentage of persons in a cohort cohort /co·hort/ (ko´hort)
1. in epidemiology, a group of individuals sharing a common characteristic and observed over time in the group.
2. who remain free from smallpox over time (in years) after immunization immunization: see immunity; vaccination. against smallpox. (3) Data from relatively small studies describe levels (titers) of vaccine-induced neutralizing antibodies neu·tral·iz·ing antibody
An antibody that reacts with an infectious agent, usually a virus, and destroys or inhibits its infectiveness and virulence. for up to 50 years after vaccination or revaccination re·vac·ci·na·tion
Vaccination of a person previously vaccinated. (28,29). No data correlate antibody titers antibody titer The amount of a specific antibody present in the serum, usually as a result of an acquired infection; titers for IgM usually rise abruptly at the time of infection–acute phase and fall slowly; during the 'convalescent' phase, IgG ↑ and is to immunity from disease. Without data describing the duration of protection afforded by a single vaccination, the current model does not consider the need for additional revaccinations over time. Thus, the results for this model only apply to the primary vaccinations. The model does not discount risk over-time, although some evidence exists that persons have a high discount rate for personal health issues (30).
When these decision criteria are used for a person in a general population of 280 million, the risk for serious vaccine-related adverse events is greater than the risk for smallpox (Figure 1a). This is true even if the risk for a smallpox attack is 1 in 10. An individual person would therefore decline preexposure vaccination. Only when the population at risk is limited to 9 million and the risk for attack approaches 1 in 10, does the risk for smallpox outweigh out·weigh
tr.v. out·weighed, out·weigh·ing, out·weighs
1. To weigh more than.
2. To be more significant than; exceed in value or importance: The benefits outweigh the risks. the risk for serious vaccine-related adverse events, indicating that the person would accept vaccination (Figure la). For a HCW to accept preexposure vaccination, the risk for contact with an infectious case of smallpox must be [greater than or equal to] 1 in 100 and the probability of an attack causing 1,000 cases must be >1 in 1,000 (Figure lb). If the risk for contact drops to I in 1,000, then the risk for attack must be >1 in 100 to accept vaccination (Figure 1b). For a member of an investigation team, if the anticipated risk for contact is 1 in 2.5 and the risk for attack is [greater than or equal to] 1 in 16,000, then a team member would accept preexposure vaccination (Figure 1c). If the risk for contact drops to 1 in 5, then the risk for attack must increase to [greater than or equal to] 1 in 8,000 for the person to accept preexposure vaccination (Figure 1c).
[FIGURE 1 OMITTED]
If a member of the general population of 280 million were to equate e·quate
v. e·quat·ed, e·quat·ing, e·quates
1. To make equal or equivalent.
2. To reduce to a standard or an average; equalize.
3. 1 case of smallpox to 35 cases of serious vaccine-related adverse events, they would accept preexposure vaccination only if the risk for a smallpox attack approached 1 in 10 (Figure 2a). However, if the risk for attack is assumed to be 1 in 100, then the person would have to equate 1 case of smallpox to 290 cases of serious vaccine-related adverse events to accept preexposure vaccination (data not shown). If a person assumes both that the initial attack would cause 100,000 cases before detection and that 1 case of smallpox is equivalent to 35 cases of serious vaccine-related adverse events, then the risk for attack would have to be >1 in 1,000 to accept preexposure vaccination (Figure 2b).
[FIGURE 2 OMITTED]
Assuming a risk for serious vaccine-related adverse events of 1 in 10,000 (25) and the same values used to produce Figure 1a, a person in a population of 9 million would not accept vaccination even if the risk for attack were 1 in (2) When the same risk for adverse events is used in considering the scenarios evaluated in Figure 2b (100,000 cases before detection, valuation of 1 case smallpox = 35 cases of vaccine-related adverse events), the risk for attack would have to be >8 in 1,000 before accepting vaccination (results not shown).
For a person in a population of 280 million who is considering preexposure revaccination with a risk for serious vaccine-related adverse events of 1 in 1,000,000, even at a 1 in 10 risk for smallpox attack, the net risk is <0, and the decision criteria would indicate not accepting revaccination (scenario assumed 1,000 smallpox cases before discovery of the attack, and setting [P.sub.Valuation] = 1:1). In the same scenario, if [P.sub.Valuation] = 1:35, then the risk for a smallpox attack would have to be >1 in 125 for a person to accept revaccination. For a Hew to accept preexpsoure vaccination, the risk for attack would have to be >1 in 700 (risk for contact = 1-in-1,000; [P.sub.Valuation] = 1:1; revaccination [P.sub.SideEffect] = 1-in-l,000,000). If the Hew assumed that the risk for contact increased to 1 in 100, then the risk for attack would have to be >1 in 7,000 in order to accept revaccination.
After uncertain exposure to smallpox (e.g., contact with a person who may or may not be infectious with smallpox), the decision criteria would indicate acceptance of postexposure vaccination if the risk for exposure is thought to be [greater than or equal to] 1 in 21,000; the risk for transmission is assumed to be 35%, and efficacy of postexposure vaccine is 60% (Figure 3a). If the risk for transmission is assumed to be 70%, but postexposure vaccine efficacy only 10% (e.g., postexposure vaccination offered several days after potential exposure), vaccination would be accepted only if the risk for exposure is assumed to be [greater than or equal to] 1 in 8,000 (Figure 3a). If postexposure vaccine efficacy were set at 98%, and risk for transmission at 70%, then risk for actual exposure to smallpox would have to be [greater than or equal to] 1 in 69,000 in order to accept postexposure (data not shown).
[FIGURE 3 OMITTED]
For persons who have had a definite exposure to smallpox, the only time that postexposure vaccination would not be accepted is if vaccine efficacy was [less than or equal to] 1%, risk of transmission was [less than or equal to] 1%, and the risk for serious vaccine-related adverse events were [greater than or equal to] 1 in 5,000 (Figure 3b). In the same scenario, if the risk for transmission were 30%, postexposure vaccination would accepted even if risk for serious vaccine-related adverse events were 1 in 500 (Figure 3b).
Figures 1 and 2 show that the single most influential variable impacting the net risk for disease, and therefore the decision to accept preexposure vaccination, was the probability of attack of smallpox. For persons in the general population, the second most important variable is the valuation of one case of smallpox relative to cases of serious vaccine-related adverse events ([P.sub.Valuation]). For a HCW or a member of an investigation team, the second most important variable was the risk for contact with a smallpox patient or infectious material.
The model suggests that most persons in the general population would not accept preexposure smallpox vaccination. Increasing the risk for vaccine-related adverse events (e.g., including the risk for eczema vaccinatum and vaccine-related myocarditis orpericarditis) moves all the graph lines in Figures 1 and 2 downward. This supposition increases the likelihood of not accepting preexposure vaccination. These results and conclusions are not unique. In 1971, some argued that the risks for routine childhood smallpox vaccination in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. outweighed the risks of contracting a case of smallpox (4,31,32). These arguments influenced the 1971 recommendation to stop routine childhood immunization childhood immunization Children's vaccination, childhood vaccination In the US, it is recommended that all children receive vaccination against Diphtheria, tetanus, pertussis, HBV, H influenzae against smallpox in the United States (33). The studies and arguments influencing the decision took an implicit societal perspective, while this study considers the perspective of the individual person.
For an individual healthcare worker, the decision to accept preexposure vaccination hinges Hinges may refer to:
See Middle Atlantic States.
Noun 1. Mid-Atlantic states - a region of the eastern United States comprising New York and New Jersey and Pennsylvania and Delaware and Maryland
U.S.A. of New Jersey, New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of , Pennsylvania (New Jersey, New York, and Pennsylvania), approximately 440 general hospitals exist; 83% operate an emergency room (34). These hospitals are staffed by approximately 18,000 full-time equivalents Full-time equivalent (FTE) is a way to measure a worker's involvement in a project, or a student's enrollment at an educational institution. An FTE of 1.0 means that the person is equivalent to a full-time worker, while an FTE of 0.5 signals that the worker is only half-time. (FTEs) physicians and dentists Dentists can refer to one of the following:
FTE Full-Time Employee
FTE Full-Time Equivalency
FTE Full Time Employment
FTE Foundation for Teaching Economics
FTE Full Time Enrollment
FTE For the Enterprise (SQL)
FTE Fund for Theological Education = 1.13 persons), 24,144 trainees and approximately 430,000 "other salaried" staff, for a total stall stall, small division of a larger space, sometimes partly partitioned. The term is used for a booth for display and selling at an exhibition, for a compartment in a stable or kennel, or, in England, for the forward seats in a theater orchestra. " of approximately 650,000 (34,35). If one assumes that 10% work in the emergency rooms, 65,000 hospital staff in New Jersey, New York, and Pennsylvania are vulnerable to infection before a smallpox attack is detected. Further assume that an attack causes 1,000 smallpox cases confined con·fine
v. con·fined, con·fin·ing, con·fines
1. To keep within bounds; restrict: Please confine your remarks to the issues at hand. See Synonyms at limit. to the New Jersey, New York, Pennsylvania area. By days 7-8 postinfection, <20% of those will proceed to the prodrome prodrome /pro·drome/ (pro´drom) a premonitory symptom; a symptom indicating the onset of a disease.prodro´malprodro´mic
n. pl. and rash stages (1,2), perhaps causing medical care to be sought. Blendon et al. (13) reported that 52% of survey respondents stated that they would go to their own family doctor if they thought they had smallpox, with 42% stating that they would go to a hospital emergency room. Thus, approximately 100 patients (1,000 x 20% early cases x 50% to hospital) might seek medical care at a hospital in the first 7-9 days after infection.
The healthcare workers in emergency rooms therefore face a risk for exposure to an infectious smallpox patient of change to <1 in 600 (65,000/100). If one assumes a risk for transmission of 70%, the risk of contracting smallpox is almost I in 1,000. The many part-time and temporary workers in a hospital further reduces this risk ratio. Even if one patient can potentially infect infect /in·fect/ (in-fekt´)
1. to invade and produce infection in.
2. to transmit a pathogen or disease to.
1. up to 10 healthcare workers in a hospital setting (36), the risk is still 1 in 65. Note that the risk for exposure is not confined to medical doctors or nurses. Many members of a hospital staff, such as those working in housekeeping A set of instructions that are executed at the beginning of a program. It sets all counters and flags to their starting values and generally readies the program for execution. and maintenance, are at risk of coming into contact with an infectious patient.
Figure 3a may suggest to some that almost any exposure to a possible case of smallpox, such as coming into contact with a person with an unexplained unexplained
strange or unclear because the reason for it is not known
Adj. 1. unexplained - not explained; "accomplished by some unexplained process" rash, would warrant immediate postexposure vaccination (e.g., before laboratory confirmation that patient with unknown rash actually had smallpox). However, postexposure vaccination given within 7 days after exposure reduces the risk of a clinical case of smallpox developing to approximately 2% compared with 79% among those never vaccinated (37). If vaccination is delayed up to 10 days postexposure, then the risk for smallpox may be reduced just 22% (from 96% among those never vaccinated to 75% among those vaccinated within 10 days postexposure) (38). (4) A more compelling conclusion from Figure 3a is that if, by day 6 postexposure, the type of exposure cannot be accurately determined and a person could have been exposed to smallpox (i.e., risk for exposure is [greater than or equal to] 1 in 21,000), then the person would use the decision criteria to accept postexposure vaccination.
The biggest problem in interpreting the results from the model is understanding how a person will actually value risks and events. Valuing risks depends on understanding probabilities, which are often difficult to explain (41). Even the type of visual aid used to explain risk can make a difference in valuation (42). Merely stating a number (e.g., 1 in 10,000) is often not sufficient. A person's valuation of the risks and benefits of vaccination may include factors not explicitly defined in the model. A person may accept preexposure vaccination, for example, as an attempt to reduce potential risk for smallpox to family and friends and even out of a sense of duty to society in general. The valuation of a case of smallpox relative to a case of serious vaccine-related adverse events is a proxy for valuing a person's contribution to family, friends, and society.
Public health planners and medical care providers should appreciate the extent that an individual acceptance or rejection of smallpox vaccination depends on valuation of risk and benefits. A person's risk aversion risk aversion
The tendency of investors to avoid risky investments. Thus, if two investments offer the same expected yield but have different risk characteristics, investors will choose the one with the lowest variability in returns. is not completely explained by numerical analyses (43,44). A person's valuation of risk depends on a variety of factors, including a sense of control, degree of trust of the source providing the data, the newness of the risk, and even the passage of time (41,45). Note that time and information may not alter the actual risk faced, but a factor such as new information (e.g., reported cases of vaccine-related adverse events) could alter the perception and valuation of risk. Accurately predicting the direction and extent of a change in valuation attributable to, for example, new information may not be possible. Public health officials, however, must always be prepared to explain how the new information alters the risks involved. Explaining a given risk, and how a new development may impact that risk, will likely require more than just a single numerical statement.
Table. Model input variables and values used Variable Symbol Probability of attack [P.sub.R] No. of cases before [X.sub.CASE] detection of attack General population [X.sub.POP] "at risk" (a) No. of susceptible [X.sub.HCW] HCW (b) Probability of [P.sub.E] exposure to smallpox, for an Individual member of general populace (c) Individual HCW contacting infectious person (d) Individual member of investigation team (e) Probability of [P.sub.T] transmission of smallpox, for an Individual member of general populace (f) Individual HCW contacting infectious person (g) Individual member of investigation team (h) Probability of [P.sub.Vepre] vaccine effectiveness, preexposure Probability of [P.sub.SideEffect] serious vaccine-related adverse events (i) Probability of [P.sub.VEpost] vaccine effectiveness, postexposure Relative individual [P.sub.Valuation] valuation; case of smallpox Case(s) of serious vaccine related adverse events (k) Values Variable Base cases Sensitivity analyses Probability of attack 1:10-1:100,000 No. of cases before 1,000 100,000 detection of attack General population 9 million or 280 "at risk" (a) million No. of susceptible 100,000 or 1,000,000 HCW (b) Probability of exposure to smallpox, for an Individual member 1:9,000 or 1:280,000 1:1 (j) of general populace (c) Individual HCW 1:100 or 1;100,000 1:1 (j) contacting infectious person (d) Individual member 1:2.5 or 1:5 1:1 (j) of investigation team (e) Probability of transmission of smallpox, for an Individual member 1.0 0.01-0.70 (j) of general populace (f) Individual HCW 0.70 0.01-0.70 (j) contacting infectious person (g) Individual member 0.40 0.01-0.70 (j) of investigation team (h) Probability of 0.98 (l) vaccine effectiveness, preexposure Probability of 1:100,000 1:500-1:1,000,000 (j) serious vaccine-related adverse events (i) Probability of 0.01-0.60 (j) vaccine effectiveness, postexposure Relative individual 1:1 1:35 valuation; case of smallpox Case(s) of serious vaccine related adverse events (k) (a) Two populations "at risk" are modeled: a population of 19 million, representing a metropolitan area assumed to be the sole target of a smallpox attack and the entire U.S. population of approximately 280 million. Exactly how a given metropolitan area would be defined as the single target at risk is a matter of speculation. (b) HCW, healthcare worker. (c) Risk for exposure for member of the general populace is defined as the risk of contracting, and subsequently developing, a clinical case of smallpox before detection of the event (for individual person in general populace, [P.sub.E] = [X.sub.CASE]/[X.sub.POP]. See text further details (d) Risk of a HCW's becoming exposed is a function of the number of cases divided by number of susceptible HCWs (for HCW, [P.sub.E] = [X.sub.CASE]/[X.sub.HCW]). (e) Probability of a member of an investigation team being exposed to smallpox includes the probability of being sent to a site where smallpox may be present, such as in a container. There are no data that can be used to accurately define such a risk, and the data used here are assumed. (f) Probability of transmission of smallpox = 1 indicates that the model only considers those members from the general populace in whom a clinical case of smallpox develops. See text for further details. (g) Probability of transmission represents when HCWs are not using any effective barrier-type protection (e.g., gloves, gowns, masks). The rate of transmission used, 0.70. is equivalent to the upper estimates of the rates of transmission to unvaccinated household members living with a smallpox patient (Appendix 1 in ref. 2). (h) Probability of transmission for investigation teams represents a risk after barrier-type protection is used. There are no data representing the actual reduction in risk, and the value of 0.40 is assumed. (i) Serious vaccine-related adverse events are defined as those adverse events which require "notable" amounts of medical care, such as vaccinia immunoglobulin, hospitalization, or a number of visits to a physician's office. The rate of 1:100,000 is derived from the number of "serious" adverse events (e.g.. death, postvaccine encephalitis, progressive vaccinia) measured in 1968 among first-time adult smallpox vaccinees (19,20) (j) These values are used to examine the risk-benefit of an individual person's accepting smallpox vaccination, including those being revaccinated, for preexposure and postexposure scenarios. See text for further details. (k) In the base case, it was assumed that a person would value 1 case of smallpox equal to 1 case of case of serious vaccine-related adverse events. However, a person may be more worried about contracting a clinical smallpox than experiencing vaccine-related adverse events. Thus, in the sensitivity analyses, the valuation was altered to reflect a higher valuation of a case of smallpox relative to a case of serious vaccine-related adverse events (see text for further details). (l) Fenner et al. (22) reviewed five separate studies and reported vaccine efficacy to range from approximately 91% to 97%
(a) Two populations "at risk" are modeled: a population of 9 million, representing a metropolitan area assumed to be the sole target of a smallpox attack and the entire U.S. population of approximately 280 million. Exactly how a given metropolitan area would be defined as the single target at risk is a muller Mul·ler , Hermann Joseph 1890-1967.
American geneticist. He won a 1946 Nobel Prize for the study of the hereditary effect of x-rays on genes.
Mül·ler , Johannes Peter 1801-1858. of speculation.
(b) HCW, healthcare worker.
(c) Risk for exposure for member of the general populace is defined as the risk of contracting, and subsequently developing, a clinical case of smallpox before detection of the event (for individual person in general populace, [P.sub.E] = [X.sub.CASE]/[X.sub.POP]). See text for further details.
(d) Risk of a HCW's becoming exposed is a function of the number of cases divided by number of susceptible HCWs (for HCW, [P.sub.E]--[X.sub.CASE]/[X.sub.HCW]).
(e) Probability of a member of an investigation team being exposed to smallpox includes the probability of being sent to a site where smallpox may be present, such as in a container. There are no data that can be used to accurately define such a risk, and the data used here are assumed.
(f) Probability of transmission of smallpox = 1 indicates that the model only considers those members from the general populace in whom a clinical case of smallpox develops. See text for further details.
(g) Probability of transmission represents when HCWs are not using any effective barrier-type protection (e.g., gloves, gowns, masks). The rate of transmission used, 0.70, is equivalent to the upper estimates of the rates of transmission to unvaccinated household members living with a smallpox patient (Appendix 1 in ref. 2).
(h) Probability of transmission lot investigation teams represents a risk after barrier-type protection is used. There are no data representing the actual reduction in risk, and the value of 0.40 is assumed.
(i) Serious vaccine related adverse events are defined as those adverse events which require "notable" amounts of medical care, such as vaccinia immunoglobulin, hospitalization, or a number of visits to a physician's office. The rate of 1:100,000 is derived from the number of "serious" adverse events (e.g., death, postvaccine encephalitis, progressive vaccinia) measured in 1968 among first-time adult smallpox vaccinees (19,20)
(j) These values are used to examine the risk-benefit of an individual person's accepting smallpox vaccination, including those being revaccinated, for preexposure and postexposure scenarios. See text for further details.
(k) In the base case, it was assumed that a person would value 1 case of smallpox equal to I case of serious vaccine-related adverse events. However, a person may be more worried about contracting a clinical case of smallpox than experiencing vaccine-related adverse events. Thus, in the sensitivity analyses, the valuation was altered to reflect a higher valuation of a case of smallpox relative to a case of serious vaccine-related adverse events (see text for further details).
(l) Fenner et al. (22) reviewed five separate studies and reported vaccine efficacy to range from approximately 91% to 97%.
(1) This article presents further methodologic details and results of a study presented at a workshop entitled en·ti·tle
tr.v. en·ti·tled, en·ti·tling, en·ti·tles
1. To give a name or title to.
2. To furnish with a right or claim to something: "Scientific and Policy Considerations in Developing Smallpox Vaccination Options," Institute of Medicine, Washington, DC, 2002 (1).
(2) Assume that only a single metropolitan population of 9 million is at risk from an initial attack, and the initial attack results in 1,000 cases before discovery. For a person in that population, the risk for death from smallpox is approximately 33 times greater than the risk for death from the smallpox vaccine [smallpox risk for death/vaccine-related risk for death = (1,000 cases/ 9 million x 0.3)/0.000001]. For a person in a population of 280 million, the risk of dying from smallpox in the initial 1,000 cases is approximately equal to the risk for death from the vaccine.
(3) In data reported by Rao from Madras Madras.
1 State and former province, India: see Tamil Nadu.
2 City, India: see Chennai. , India (Figures 17/1 and 17/3 ), among the unvaccinated, approximately 80% of all cases of smallpox occurred in children <10 years of age. A distinct shift in age of the case-patients occurred among the vaccinated, with <10% of cases occurring in children <10 years of age, 19% of cases occurring in children 10-19 years, and 46% of cases occurring in persons 20-30 years of age. Rao did not report at what age most of those vaccinated received vaccine (a likely hypothesis would be before 2 years of age). Further complicating com·pli·cate
tr. & intr.v. com·pli·cat·ed, com·pli·cat·ing, com·pli·cates
1. To make or become complex or perplexing.
2. To twist or become twisted together.
1. the analysis of such data is the fact that many persons in Madras received more than one smallpox vaccination (Figure 17/5, ). A similar age-shift in occurrence of cases among the vaccinated can be discerned from the data reported by Hanna (24) from Liverpool, England, in 1902-03. The data from both Rao (23) and Hanna (26) further indicate that even a 20-year-old vaccination may reduce the severity of disease. The risk for death is markedly reduced 20-30 years postvaccination (23,26,27).
(4) In addition to the estimates quoted in the main text, Rao et al. (39) found that successful postexposure vaccination reduced, on average, the rate of smallpox among contacts by approximately 38% (from 48% among unvaccinated to 30% among postexposure vaccinees). Dixon (40) reported that in a group of 59 contacts under 5 years of age "... approximately half of those who had a successful vaccination after contact developed disease." The wide variations in reports of the degree of protection afforded by postexposure vaccination are probably due to a number of reasons, including small sample sizes and difficulty in determining when exposure and potential transmission actually took place.
Dr. Meltzer is senior health economist in the Office of Surveillance, National Center for Infectious Diseases, Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. . His research interests include studying the economics of interventions to control and prevent infectious diseases and providing economic data to aid the planning for catastrophic infectious disease Infectious disease
A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions. events.
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v. in·flect·ed, in·flect·ing, in·flects
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2. Grammar To alter (a word) by inflection.
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extermination of an infectious agent so that no further cases of the related disease can occur.
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Address for correspondence: Martin I. Meltzer, Centers for Disease Control and Prevention, Mailstop D59, 1600 Clifton Rd., Atlanta, GA 30345, USA; tax: 404-371-5445; email: email@example.com
Martin I. Meltzer *
* Centers for Disease Control and Prevention, Atlanta, Georgia, USA