Mass vaccination unnecessary in the event of a large bioterrorist US smallpox attack

Instead, the current U.S. government policy of post-release surveillance, prompt containment of victims and vaccination of hospital workers and close contacts would be sufficient to thwart an epidemic, according to lead author Ira M. Longini Jr., Ph.D., a world leader in using mathematical and statistical methods to study the natural course of infectious diseases.

"We found that a well-prepared response of surveillance and containment, if done quickly, within a day or two of detecting the first smallpox case, would contain a large attack if up to 500 people were infected," said Longini, a member of the Public Health Sciences Division at the Hutchinson Center and a professor of biostatistics at the University of Washington School of Public Health and Community Medicine. These results apply to scenarios involving even the most virulent, fatal forms of the virus.

However, Longini emphasizes, failure to quickly isolate known smallpox cases and vaccinate their close contacts could thwart the containment of an epidemic.

These findings emerge from a committee of smallpox experts – including infectious-disease modelers, epidemiologists, statisticians and clinicians – who were commissioned by former Secretary of Health and Human Services Tommy Thompson to evaluate a variety of intervention strategies to determine whether the United States could contain a large-scale smallpox bioterrorist attack and, if so, how.

Specifically, the researchers were charged with determining whether surveillance and containment – isolation of detected smallpox cases and vaccination of their close contacts – would be sufficient to contain a large attack. They also wanted to find out whether other interventions, such as mass pre-vaccination of the general public, pre-vaccination of hospital personnel, vaccination of the target community and closure of schools after a smallpox release would help contain the spread of the disease.

Thompson's senior science adviser, Donald Ainslie (D.A.) Henderson, the physician and epidemiologist who oversaw the World Health Organization's successful campaign to eradicate smallpox from the world in the late 1970s, served as a consultant to the committee, known as the Smallpox Modeling Working Group. The group was convened by the Secretary's Advisory Council on Public Health Preparedness, a branch of the U.S. Department of Health and Human Services.

"Earlier studies recommended mass pre-vaccination of the general population to protect against a smallpox attack. None of us on the committee believed this was necessary, including D.A. Henderson, who intimately understands the natural history of the virus," Longini said. "The secretary of Health and Human Services wanted to settle such issues regarding smallpox containment once and for all, and this was our charge."

While the researchers did find that mass vaccination would slightly reduce the number of deaths from smallpox, they also found that the rate of severe illness and death caused by the vaccine itself would cancel out any benefit from mass vaccination. One person in 10,000 will have a severe reaction and one in a million will die from the vaccine, Longini said.

"Precautionary vaccination of hospital personnel and post-release vaccination of the target population would further contain the spread of smallpox, but at a cost of many more people being vaccinated," said co-author and Hutchinson Center biostatistician M. Elizabeth (Betz) Halloran, M.D., D.Sc. "The financial cost and potential illness and death related to vaccination must be weighed against the potential benefits in the event of an attack. In our opinion, pre-vaccination of the population at large is unnecessary," she said. Longini, Halloran and colleagues also found that closure of schools after a smallpox attack would have a minimal effect in preventing transmission of the disease, and that any delay in quarantining infected individuals would take a much greater toll on the community than failing to pre-vaccinate potential cases.

To conduct the study, Longini and colleagues created a computer model that calculated the spread of smallpox via aerosol dissemination – the most likely choice of terrorists – within a community of 50,000. Members of this virtual community interacted the way people normally do: within households, neighborhoods, preschool groups, schools, a community hospital and the community at large. The age distribution and household sizes were based on the U.S. census for 2000.

Predicting the spread of an infectious disease such as smallpox requires much more than simply connecting dots on a map. Instead Longini and colleagues rely on a tool called stochastic modeling to take into account real-world unpredictability, as well as many factors about the disease and the affected population. In constructing these models, Longini and colleagues begin with assumptions about how people interact and how the virus spreads. They also introduce and evaluate the effectiveness of various intervention strategies.

The study represents the first attempt to integrate what science knows about the natural history of smallpox – how various forms of the disease manifest over time – with human patterns of behavior to construct the most-comprehensive model of a smallpox epidemic to date.

"If smallpox appeared in Seattle tomorrow, which it could do, I'm absolutely confident that we could contain it if our recommendations for surveillance and containment were put into practice. I rest easier now that we've done this study," Longini said. "The process was kind of like unveiling the enemy to the point where we really understood it. This research has helped us demystify the threat a bit."

Although smallpox has been eliminated as a naturally-occurring disease, the virus still exists in two approved laboratories in the United States and Russia. The Centers for Disease Control and Prevention classifies it as a "Category A" agent, presenting the greatest potential threat for harming public health if developed and used as a bioterrorist agent.

Smallpox is caused by the variola virus, which emerged thousands of years ago. Variola major, the most common form of the virus, is divided into four subcategories: ordinary (which accounts for about 90 percent of cases and has a fatality rate of about 30 percent), modified (which occurs in people who have been vaccinated and has a death rate of about 10 percent), and flat and hemorrhagic (both very rare and uniformly fatal).

According to the CDC, exposure to the variola virus is followed by an incubation period of seven to 17 days, during which people are not contagious and feel fine. The first symptoms emerge during what is called the prodrome phase, and they include head and body aches, fatigue, a high fever and, sometimes, vomiting. This phase lasts two to four days and at this point people may or may not be contagious. Then a rash emerges all over the body and grows increasingly severe over the next 20 or so days, eventually forming scabs; during this period people are contagious, particularly during the first seven to 10 days of the rash. The disease eventually resolves and contagion ends after all of the scabs have fallen off. People who survive are then considered to be immune from smallpox.

A person can become infected by prolonged, face-to-face exposure with someone who is contagious, direct contact with infected bodily fluids or a contaminated object, such as bedding or clothing, and exposure to an aerosol release.

Routine smallpox vaccination ended in 1972, which leaves at least 43 percent of the U.S. population unvaccinated, Longini said. Research suggests that those previously vaccinated may still have substantial residual immunity although, if infected, they could still transmit the virus to others. Those most vulnerable to the virus are the very young and those whose immune systems are compromised due to HIV/AIDS, cancer or some other medical condition. An estimated 50 million Americans fall into this category, Longini said.

Source: Fred Hutchinson Cancer Research Center

Effective health messages may yield vaccine compliance among ER workers
Emergency room workers will be the first line of defense in the event of a disease pandemic and will be forced to deal with the chaos that inevitably comes with treating thousands of sick and dying. In order to protect themselves and allow them to care for the public, these first responders need to be fully prepared by getting available vaccines now.
Most people believe smallpox not an extinct disease
The vast majority of Scottish people interviewed in the streets of Edinburgh are unaware of one of the greatest achievements of medical science – the eradication of smallpox from the world over 40 years ago. A poll sponsored by the Society for General Microbiology (SGM), in conjunction with the Edinburgh International Science Festival, has revealed that 87% of 200 individuals questioned did not know that the horrendous, killer disease is now extinct.
Smallpox vaccine alternative identified
University of California, Irvine infectious disease researchers have shown the effectiveness of a potential alternative to the existing smallpox vaccine that can replace the current biodefense stockpile for this lethal virus.
Poxvirus' ability to hide from the immune system may aid vaccine design
The cowpox virus, a much milder cousin of the deadly smallpox virus, can keep infected host cells from warning the immune system that they have been compromised, researchers at Washington University School of Medicine in St. Louis have found. The scientists also showed that more virulent poxviruses, such as the strains of monkeypox prevalent in Central Africa, likely have the same ability.
Research suggests America may over-vaccinate
A new study published in the New England Journal of Medicine this week by Oregon Health & Science University researchers suggests that timelines for vaccinating and revaccinating Americans against disease should possibly be reevaluated and adjusted. The study shows that in many cases, the established duration of protective immunity for many vaccines is greatly underestimated. This means that people are getting booster shots when their immunity levels most likely do not require it. The results are published in the November 8 edition of the journal.
Fever after smallpox vaccination tied to individual genetic variations
St. Louis researchers have identified common DNA variations that underlie susceptibility to fever after smallpox vaccination. Their finding is the first to link individual differences written into the genetic code with a vaccine-related complication – albeit a mild one.
Genetic factors are linked to fever following smallpox vaccination
New evidence supports the link between genetic factors and certain adverse events related to smallpox vaccination. The study, published in the July 15th issue of The Journal of Infectious Diseases, now available online, may have implications for predicting adverse events from other live vaccines.
Herpes infection may be symbiotic, help beat back some bacteria
Mice with chronic herpes virus infections can better resist the bacterium that causes plague and a bacterium that causes one kind of food poisoning, researchers report in this week's Nature.

Mass vaccination unnecessary in the event of a large bioterrorist US smallpox attack

Related stories:

News discussion: