TARGETED SMALLPOX VACCINATIONS
COULD BE EFFECTIVE INTERVENTION AGAINST DELIBERATE ATTACK
Emory Biostatistics Model Shows That Existing Immunity Plus First-Responder
and Voluntary Vaccination Would Increase Benefits of Targeted Vaccine
Strategy
ATLANTA -- Targeted vaccination
of the close contacts of infected individuals following a smallpox outbreak
could rival the effectiveness of mass vaccination, given a sufficiently
high level of immunity within the population, according to a new study
by biostatisticians at Emory University. The research is published in
the Nov. 15 issue of Science. Since targeted vaccinations would
lead to fewer adverse vaccine reactions and would prevent more cases
of smallpox per dose of vaccine, a targeted strategy would be desirable
given an equally effective outcome, say the investigators. The existing
immunity could be a combination of residual immunity from smallpox vaccinations
received prior to 1972, new vaccinations of first responders, and voluntary
vaccinations of other individuals, they suggest.
M. Elizabeth Halloran, M.D.,
D.Sc., and Ira M. Longini, Jr., Ph.D., professors of biostatistics at
Emory University’s Rollins School of Public Health, along with colleagues
Azhar Nizam and Yang Yang, constructed a model that simulated the spread
of smallpox deliberately introduced by infected individuals moving through
a community. The model is based on the investigators’ previous experience
with modeling flu epidemics. It assumes that people interact primarily
within known contact groups, including their own household, schools
or daycare centers, their neighborhood and their community. The model
differs from other recent models of smallpox epidemics that assume random
mixing of individuals within a large, homogeneous population, with the
conclusion that mass vaccination is the only way to sufficiently control
an outbreak.
The Emory model simulated
a range of scenarios for smallpox epidemics, based on different probabilities
of how smallpox might spread, whether or not there was residual immunity
from prior vaccinations, at what stage individuals might stay home during
different stages of their disease, and the effectiveness of smallpox
vaccines in different age groups.
The investigators conducted
200 simulations for each proposed intervention within their model, using
a statistical community of 2000 people based on the age distribution
and approximate household sizes reported in the U.S. Census 2000. Each
simulated community consisted of four neighborhoods, one high school,
one middle school, two elementary schools, small play groups, and day
care centers. Households had between one and seven people, and 33% of
households consisted of single adults. The model assumed that in a deliberate
smallpox attack, either one or five individuals already infected with
smallpox would circulate through the community at the beginning of the
infectious stage of their disease.
Drs. Halloran and Longini
believe their model is more realistic than "deterministic" models that
assume all individuals within a large, homogenous population interact
randomly with others, concluding that an epidemic always follows the
same course. The Emory study considered many different variables, including
where transmission was likely to be highest (first within households,
then schools, then neighborhoods, and lastly the community at large)
and which individuals were likely to have residual immunity. For individuals
vaccinated prior to 1972, the investigators assumed different levels
of immunity ranging from zero to half the immunity level induced by
a fresh vaccination. They also considered the three different stages
of smallpox incubation (10 to 14 days); prodromal phase, (flu-like
symptoms); and pox phase and the likelihood of interaction and transmission
within a community each day following infection. Based on historical
data, they assumed that smallpox is more likely to be transmitted through
close contact than through casual contact on the streets or in a subway.
The model investigated two
different scenarios of mass vaccination, either before an introduction
of smallpox, with vaccine coverage levels of 30, 50, or 80%, or after
an epidemic begins, with 80% coverage within 10 days.
In the targeted vaccination
scenario, people in close contact with either 80% or 100% of identified
cases were vaccinated. Targeted vaccination included all household members,
all day care and play group contacts, 80-100% of children in the same
school, and 1.5% of neighborhood contacts. Vaccinations began either
with the first known case or after the 15th or 25th case to account
for possible delays in vaccination. In simulations of both mass and
targeted vaccinations, a rapid response to identified smallpox cases
made a significant difference in the ability to prevent or contain an
epidemic.
"Our study demonstrates the
importance of modeling the details of likely contact patterns when developing
strategies to prevent or contain a deliberately planned smallpox epidemic,"
says Dr. Halloran. "We found, as have other investigators, that a rapidly
implemented mass vaccination strategy following a smallpox outbreak
would be more effective than targeted vaccination if there is no pre-existing
immunity. However, our model found a much smaller difference in effectiveness
between the two strategies than did previous models that assumed homogeneous
mixing within a large population. And, taking into account possible
pre-existing immunity, the potential for increasing that pre-existing
immunity, and the desirability of decreasing harmful vaccine reactions,
we believe it is important to continue a serious exploration of the
benefits of targeted vaccination. We will continue to refine our simulation
to better reflect the variations and conditions within a large U.S.
population. It also will be very important to include new information,
as it becomes available, about the immune protection offered by prior
immunizations."
"The daily contacts that
people make within their communities could have a significant impact
on the speed of smallpox spread and the reach of an epidemic," Dr. Longini
adds. "In future models, we will explore additional possibilities, such
as the interconnectedness of different communities, the possibility
of the original infected individuals moving among more than one community,
and different methods of how smallpox might be introduced. We also will
explore whether targeted vaccination could be focused on areas where
epidemics occur, rather than mass vaccination throughout the country."
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