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PubMed1983

The Florey lecture, 1983. Biological control, as exemplified by smallpox eradication and myxomatosis.

Biological control is an important method of dealing with plant and insect pests. The control of rabbits by myxomatosis and the eradication of smallpox by vaccination are unusual examples of biological control, in that they involve a vertebrate and a viral pest respectively. Myxomatosis is a benign disease in Sylvilagus rabbits in South America which is transmitted mechanically by mosquitoes. In the European rabbit, Oryctolagus, which is a pest in Australia and England, the virus from Sylvilagus produces a generalized disease that is almost always lethal. Myxomatosis was deliberately introduced into Australia in 1950 and into Europe in 1952. It was at first spectacularly successful in controlling the rabbit pest, but biological adjustments occurred in the virulence of the virus and the genetic resistances of rabbits. After 30 years of interaction, natural selection has resulted in a balance at a fairly high level of viral virulence. Smallpox has been a major scourge of mankind for over 1500 years. It spread from Asia to Europe in the Middle ages and from Europe to Africa and the Americas in the 15th and 16th centuries. Jenner's cowpox vaccine provided a method of control that reduced the severity of the disease during the 19th century but failed to eliminate the disease from many countries before the 1930s. Thereafter it was eradicated from Europe and North America, but remained endemic in South America, Africa and Asia. In 1967 it was still endemic in 33 countries and W.H.O. established a programme for global eradication within 10 years. The goal was achieved in 1977. Problems of the eradication programme and reasons for its success will be described.

Animals↗
PubMed1977

Undernutrition and immunity: smallpox vaccination in chronically starved, undernourished subjects and its immunologic evaluation.

This study illustrates the specific immune response of chronically starved, undernourished adults after inoculation of live smallpox vaccine. It produced no adverse effect, and major vaccinial reaction was observed in all. 63% of undernourished individuals showed a fourfold or greater rise of the neutralizing antibody titre. In contrast, only 9% of normal healthy subjects could show similar response. However, the prevaccination titre was much lower in the undernourished group than in the control group, and the postvaccination titre also remained persistently lower in the former than in the latter group. Furthermore, whereas the specific humoral antibody response in the undernourished subjects was partially adequate, the development of specific cellular immunity against vaccinia was remarkably poor, indicating that smallpox vaccination in these subjects might be less effective against variola infection. This observed profound effect of chronic starvation and severe undernutrition on the immune apparatus was possibly multifactorial, protein depletion being the most important factor, as proved by the significantly low serum albumin level. The significantly low peripheral blood lymphocyte count and spectacular unresponsiveness to many antigens in these individuals suggested profound depression of the thymolymphatic system. Further, the significantly low level of neutralizing antibody in the malnourished subjects suggested that the formation of this protective antibody might necessitate the cooperation of T lymphocytes.

Adult↗
PubMed2004

Differential willingness to undergo smallpox vaccination among African-American and white individuals.

OBJECTIVE: To examine potential disparities in willingness to be vaccinated against smallpox among different U.S. racial/ethnic groups. DESIGN: Cross-sectional survey using an experimental design to assess willingness to be vaccinated among African Americans compared to whites according to 2 strategies: a post-exposure "ring vaccination" method and a pre-exposure national vaccination program. SETTING: Philadelphia County district courthouse. PARTICIPANTS: Individuals awaiting jury duty. MEASUREMENTS: We included 2 scenarios representing these strategies in 2 otherwise identical questionnaires and randomly assigned them to participants. We compared responses by African Americans and whites. MAIN RESULTS: In the pre-exposure scenario, 66% of 190 participants were willing to get vaccinated against smallpox. In contrast, 84% of 200 participants were willing to get vaccinated in the post-exposure scenario (P =.0001). African Americans were less willing than whites to get vaccinated in the pre-exposure scenario (54% vs 77%; P =.004), but not in the post-exposure scenario (84% vs 88%; P =.56). In multivariate analyses, overall willingness to undergo vaccination was associated with vaccination strategy (odds ratio, 3.29; 95% confidence interval, 1.8 to 6.1). CONCLUSIONS: Racial disparity in willingness to get vaccinated varies by the characteristics of the vaccination program. Overall willingness was highest in the context of a post-exposure scenario. These results highlight the importance of considering social issues when constructing bioterror attack response plans that adequately address the needs of all of society's members.

Adult↗
PubMed1979

Continuing mortality and morbidity from smallpox vaccination.

Three cases of cross-infection after smallpox vaccination are described, in two of which the outcome was fatal. Probably all occurred because simple precautions were not observed at the time of vaccination--for example, exclusion of contraindications and warnings about risks. If those countries still requiring evidence of vaccination for entry were to abolish this rule, however, the risk of cross-infection could be eliminated. Vaccinating a person with contraindications is justified only when exposure to smallpox has occurred.

Adult↗
PubMed2004

Bioterrorism and smallpox planning: information and voluntary vaccination.

Although smallpox was declared eradicated in 1980, there are fears that stocks of the virus manufactured for military purposes by the Soviet Union may have fallen into the hands of "rogue nations" or terrorists. Worries about bioterrorism have thus sparked debate about whether or not the smallpox vaccine, which can be dangerous, should be offered to the general public. Meaningful public debate on this issue requires expert information about the likelihood that the virus will in fact be used as a weapon. Informed voluntary individual decision making, about whether to get vaccinated if vaccine is made available to the public, would similarly require appreciation of the likelihood of attack. Public deliberation and private deliberation thus both require briefing by the intelligence community.

Bioterrorism↗
PubMed1997

Edward Jenner and the eradication of smallpox.

Edward Jenner's careful investigations into the usefulness of cowpox vaccination for the prevention of smallpox during the late 1790s, and his enthusiastic and continued advocation of vaccination despite the scepticism of critics, laid the foundations for the growth of understanding about the nature of infectious disease and the development of immunity during the 19th century. He began the long process which resulted in the successful eradication of the smallpox virus in 1980. His life story remains an inspiration to physicians facing an uncertain future as viruses and bacteria not yet eradicated adapt to the antibiotic age.

England↗
PubMed2003

The smallpox threat: the school nurse's role.

Today, with the threat of bioterrorism and war, there is a new dimension to the traditional role of the school nurse. The smallpox threat to public health will invoke the school nurse's role as an educator, liaison, and consultant in the community. This article discusses smallpox, the vaccination process, adverse effects, and postvaccination care. In addition to the role of educator, the school nurse has the role of a liaison between the school and the local health department. The school nurse also plays a vital role in school health policy development and implementation. Being prepared and educated makes our nation less vulnerable to these threats and will assist in keeping our children and communities safe.

Bioterrorism↗
PubMed2004

Between persuasion and compulsion: Smallpox control in Brooklyn and New York, 1894-1902.

Two major outbreaks of smallpox occurred in Brooklyn and New York around the turn of the twentieth century. Health officials moved aggressively to contain the disease, conducting mass vaccinations from house to house and in workplaces. Although these programs were ostensibly voluntary, the manner in which they were conducted was often coercive, giving many people the impression they had no choice but to submit. Officials portrayed their programs as voluntary because they lacked a clear legal basis for their actions and because they believed this was the most effective strategy for gaining public cooperation. This essay examines the events that surrounded a series of legal cases challenging the use of coercive measures to enforce vaccination during and after the smallpox epidemic of 1894, and the repercussions that this litigation had on disease-control efforts and popular attitudes toward vaccination and other measures. The cases described here were part of an extensive body of nineteenth-century jurisprudence on vaccination that was crucial for the evolution of public health police powers in general, and of vaccination policy in particular.

Coercion↗
PubMed2006

Smallpox antiviral drug development: satisfying the animal efficacy rule.

Concerns over the potential use of variola virus as a biological weapon have prompted new interest in the development of small molecule therapeutics to prevent and treat smallpox infection. Since smallpox is no longer endemic, human clinical trials designed to link antiviral efficacy to clinical outcome have been supplanted by antiviral efficacy evaluations in animal models of orthopoxvirus disease. This poses a unique challenge for drug development; how can animal efficacy data with a surrogate virus be used to establish clinical correlates predictive of human disease outcome? This review will examine the properties of selected animal models that are being used to evaluate poxvirus antiviral drug candidates, and discuss how data from these models can be used to link drug efficacy to clinical correlates of human disease.

Animals↗
PubMedDate not supplied

[Smallpox, an old foe].

Smallpox has accompanied mankind for centuries, causing deaths and permanent lesions. Used in the past as a biological weapon during wars, it has come into focus again precisely because of this renewed possibility, although the disease has been eradicated in the Americas since 1971 and worldwide since 1977. Data gathered during the eradication campaigns show that the disease spread relatively slowly through close contacts between patients and susceptibles. Sub-clinical infection in non-vaccinated individuals was a rare event, and blockade vaccination surrounding new cases (as long as these cases were confirmed early) was able to prevent the disease from spreading in the community. Even with only one dose, vaccinated individuals rarely developed a serious case of the disease upon reinfection. The use of smallpox as a biological weapon should be considered a real possibility, although according to the available data, highly virulent viral suspensions spread very close to the target population would be necessary to infect a large number of persons.

Biological Warfare↗
PubMed2004

Modeling for a smallpox-vaccination policy against possible bioterrorism in Japan: the impact of long-lasting vaccinal immunity.

BACKGROUND: There has been concern that variola virus might be held clandestinely elsewhere. Through constructing mathematical model based on the detailed epidemiologic data, we focused on simulating the various possible scenarios arising from a bioterrorist attack whereby smallpox virus was introduced into Japan, and sought to develop the most effective way of nationwide vaccination policy based on the theory of residual immunity. METHOD: The analysis is based on a deterministic mathematical model which predicted the epidemiologic outcome while simultaneously evaluating the effect of any specified control strategy of the smallpox epidemic. To clarify the required amount of vaccines, we performed mathematical analysis for hypothetical population to acquire herd immunity based on long-lasting vaccinal immunity. RESULTS: It is demonstrated that the crude size of the potential epidemic could be greatly affected by possible level of residual immunity. The results also suggest the possibility to develop optimal distribution of nationwide vaccination according to the immune status. The prevalence at 50th day among population without immunity in our simulation would be approximately 405 times greater than expected population with residual immunity, and required amount of vaccines for equal distribution would be 3.13 times more than optimal distribution. CONCLUSION: The mathematical model formulated could determine the vaccination priority based on the real status of immunity which required much less amount of vaccinations than would be calculated using an equal distribution program. It is therefore crucial to determine the real immunity status of the population via epidemiologic studies.

Bioterrorism↗
PubMed2003

Flow cytometry and T-cell response monitoring after smallpox vaccination.

Orthopoxvirus zoonosis or smallpox as result of bioterrorism or biological warfare represents a risk for epidemic spread. By monitoring T-cell responses by flow cytometry, we observed a recall response after recent vaccination against smallpox. When the high similarity between the orthopoxviruses is considered, this rapid assay that uses vaccinia antigens could identify recently exposures.

Antigens, Viral↗
PubMed2005

Beveled needle technique is not associated with low "take" rates in Israeli smallpox revaccination campaign.

BACKGROUND: In its first large-scale smallpox vaccination campaign in the 20(th) century, Israel has experienced an exceptionally high rate of failure to achieve clinical take following vaccination. It was hypothesized that this failure rates might be attributed to the unique vaccination technique adopted in Israel, of using beveled needles rather than bifurcated needles. MATERIALS AND METHODS: We retrospectively identified two cohorts vaccinated in the defined dates during the Israeli revaccination campaign, in which beveled needles and bifurcated needles were used alternately, and studied the impact of different covariates on clinical vaccination outcome measures. RESULTS: Of 116 subjects that were vaccinated within the defined dates, 46 were vaccinated using bifurcated needles, and 70 by beveled needles. 'Take' rates in subjects vaccinated up to 20 years earlier was 77.5%, compared with 97.2% among those vaccinated in the more distant past (p = 0.001). In multivariate analyses, vaccination 'take' was independently associated with a shorter time from previous vaccination (p = 0.013), but not with gender, birth country, vaccinator or the vaccination technique used. CONCLUSIONS: The low take rates observed in the Israeli smallpox revaccination campaign could not be attributed to the unique local vaccination technique, and was most likely induced by a higher rate of residual immunity among vaccinees, compared with the US, as well as by the lower vaccine concentrations used in Israel. In countries and circumstances when bifurcated needles are not sufficiently available, the beveled needle technique may be considered an appropriate alternative.

Adult↗
PubMedDate not supplied

Modeling dimensions of choice in accepting the smallpox vaccine.

OBJECTIVE: To model the dimensionality of understanding refusal to be vaccinated against smallpox. METHOD: The Smallpox Vaccination Choice Questionnaire was administered to a convenience sample of students. Through a series of factor analyses, responses were subjected to a statistical evaluation of the underlying factor structure of potential influences on choice. RESULTS: The analyses suggest 5 dimensions: knowledge, perceptions of risk and worry, psychological distress, general beliefs about vaccines, and age. CONCLUSION: This model will be used to help identify targets of intervention to increase acceptance of the vaccine and satisfaction with choice.

Adolescent↗
PubMed2006

Factors that influence the decision of military dependents to decline smallpox vaccination during an outbreak.

OBJECTIVE: To examine factors that influence the decision of military dependents to decline smallpox vaccination in the event of an outbreak. METHODS: A total of 373 military dependents, 18 to 65 years of age, were surveyed in December 2003, at Fort Hood, Texas, and Fort Sill, Oklahoma, concerning smallpox vaccine knowledge, adverse reactions, and willingness to receive the vaccine. RESULTS: A total of 89% of respondents were willing to receive the vaccine. Respondents were less willing if the vaccine was unsafe during pregnancy or caused blood clots and heart attacks. African American and Hispanic respondents were less willing to be vaccinated than were Caucasian respondents (p < 0.0079), as were respondents with lower vaccine knowledge scores (p < 0.0029). CONCLUSIONS: The majority of military dependents would want to receive the vaccine in the event of an outbreak. Vaccine safety in pregnancy and an unproven link to blood clots and heart attacks may influence vaccine refusal. African American respondents, Hispanic respondents, and respondents with lower vaccine knowledge scores were less willing to receive the vaccine.

Adolescent↗
PubMedDate not supplied

Investigations on allergic and serological reactions following inoculation of inactivated smallpox vaccines by cutaneous scarification.

A number of 154 young adults were given a smallpox vaccine inactivated by UV (103 subjects) or by 4degrees/00 formol (51 subjects). Inoculation induced an early cutaneous reaction in 75.4% of the revaccinated subjects. The incidence of positive HAI reactions in this group increased from 30.2% before vaccination to 63.8% after inoculation, while the geometric mean titer increased from 2.88 to 10.73. This would prove the early reactions to be allergic responses of organisms sensitized against smallpox vaccine, capable of stimulating antibody formation. No cutaneous reaction was recorded in the 7 persons vaccinated for the first time (without pre-existent cutaneous scars). These subjects developed neither cutaneous nor humoral response to the killed virus, as there was no previous sensitization to the respective antigen.

Adult↗
PubMed2000

[Eradication of smallpox, already 20 years ago].

Smallpox, an infectious disease that has killed and maimed hundreds of thousands of people through the ages and across all continents, has disappeared. Its eradication has been the result of an enormous and intense collective effort carried out over several years. Furthermore, it made possible the elimination of many of the risks associated with vaccination against smallpox, which had rare but very real side effects. The 20th anniversary of this momentous event will take place on 8th May 2000.

France↗
PubMed2002

[Smallpox--eradicated disease and a potential terrorist weapon].

Smallpox is a disease that followed humanity for thousands of years up until thirty years ago. It was possible to eradicate, since an effective live vaccine from crossreacting vaccinia could be developed. Twenty years passed since vaccinations stopped and very few people are protected against the disease today. Variola today has become an object of discussion due to the possibility that it can be used as a bioweapon. Due to the number of complications that can be expected a general vaccination is probably not possible. Research is ongoing to develop new vaccines. Many countries are improving their capabilities to respond to a renewed threat of a smallpox epidemic.

Asia↗