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PubMed2006

The smallpox vaccine: a multidimensional model of choice.

Following September 11, 2001, the U.S. government increased its efforts to prepare for future attacks, including those using dangerous biological agents such as smallpox. The smallpox vaccination program called for vaccinating military personnel and smallpox response teams, including healthcare workers and other first responders. The program of vaccinating healthcare workers was largely unsuccessful; few individuals volunteered to be vaccinated, highlighting the importance of understanding the factors that influence choice regarding this complex medical decision. This study examined stated choice and how it was associated with risk perceptions, knowledge, psychological distress, and general vaccine beliefs using a five-dimensional choice model. The model used multivariable modeling strategies in a sample of 256 undergraduate, graduate, and medical students. Sixty-three percent of the sample stated that they would elect to receive the smallpox vaccination. Multiple factors were related to stated choice in multivariable models, including perceived risk/worry, general vaccine beliefs, decisional conflict, and gender. However, the models were more successful at predicting acceptance of the vaccination than vaccine refusal. Although support was obtained for a multidimensional model of choice, several questions were raised by our results, including (a) whether refusal of smallpox vaccination can be more effectively characterized, possibly with additional questions; (b) whether the model translates to actual vaccination behavior; and (c) whether the model describes choice in more at-risk samples (e.g., first responders, healthcare workers). A multidimensional modeling approach should facilitate these and other studies of choice.

Adolescent↗
PubMed2005

Association between smallpox vaccination and hepatitis C antibody positive serology in Pakistani volunteers.

GOALS: To determine whether the smallpox vaccination program has significantly contributed to the widespread prevalence of hepatitis C infection in Pakistan. BACKGROUND: Hepatitis C virus has become a worldwide pandemic and has especially devastated developing nations such as Pakistan. There continues to be an increase in fatalities due to hepatitis C-related cirrhosis in Pakistan. STUDY: We studied 523 volunteers in the city of Lahore to determine whether the smallpox vaccination program, which ran from 1964 to 1982 in Pakistan, may be responsible for the national surge in hepatitis C viral infection, perhaps because of repetitive use of vaccination devices without proper sterilization or to contaminated vaccine contents. RESULTS: There was a significantly higher likelihood of hepatitis C antibody seroprevalence in individuals vaccinated for smallpox versus nonvaccinated individuals (21.0% vs. 4.6%, P < 0.001, age-adjusted odds ratio, 3.39; 95% confidence interval, 1.36-8.46). Subjects with positive hepatitis C serology were also more likely to have a history of transfusions (19.2% vs. 9.0%, P = 0.01), but anti-HCV positive serology was not significantly associated with a history of surgery or dental procedures. Following adjustment for age, sex, and history of other conditions, including transfusion, the association between prior smallpox vaccination and hepatitis C antibody seroprevalence remained strong and highly significant (multivariate adjusted odds ratio, 6.11; 95% confidence interval, 2.58-14.51). CONCLUSION: These results suggest that the widespread prevalence of hepatitis C infection in Pakistan may be an unintended consequence of the country's smallpox vaccination program and that blood transfusion is also a significant risk factor.

Adolescent↗
PubMed2005

Pre-event willingness to receive smallpox vaccine among physicians and public safety personnel.

BACKGROUND: Planning for voluntary smallpox vaccination of health and safety officials began in December 2002. MATERIALS AND METHODS: Surveys were conducted among physicians and fire and police department personnel in Atlanta, Georgia. Information on demographics, willingness to receive smallpox vaccine, self-reported knowledge level, and potential vaccine contraindications was analyzed. RESULTS: Forty-one percent of physicians (n = 199) were undecided on vaccination (32% would receive vaccine and 27% would not). Forty-eight percent of firefighters (n = 343) and 41% of police (n = 466) were undecided; 23% and 41% would receive vaccine, whereas 28% and 18% would not (fire and police, respectively). Absence of contraindications was associated with physicians' willingness to be vaccinated (P = 0.006). Many physicians (66%) and most public safety personnel (88%) considered themselves inadequately informed on smallpox vaccine. In a multivariate analysis, inadequately informed respondents were more likely to be undecided (OR = 2.23, CI = 1.39 to 3.56). CONCLUSIONS: Before implementation of the smallpox vaccination program, self-assessed knowledge about smallpox disease and vaccine were poor.

Adult↗
PubMed2005

Persisting humoral antiviral immunity within the Japanese population after the discontinuation in 1976 of routine smallpox vaccinations.

Concerns have arisen recently about the possible use of smallpox for a bioterrorism attack. Routine smallpox vaccination was discontinued in Japan in 1976; however, it is uncertain exactly how long vaccination-induced immunity lasts. We sought to evaluate the seroprevalence and intensity of anti-smallpox immunity among representatives of the present Japanese population. The subjects included 876 individuals who were born between 1937 and 1982. Vaccinia virus-specific immunoglobulin G (IgG) levels were measured by enzyme-linked immunosorbent assay (ELISA), and 152 of 876 samples were also tested for the presence of neutralizing antibodies. Of the subjects who were born before 1962, between 1962 and 1968, and between 1969 and 1975, 98.6, 98.6, and 66.0%, respectively, still retained the vaccinia virus-specific IgG with ELISA values for optical density at 405 nm (OD(405)) of > or = 0.10. The corresponding figures for retained IgGs with OD405 values of > or = 0.30 were 91.0, 90.3, and 58.2%, respectively. Neutralizing antibodies were also maintained. The sera with OD(405) values of > or = 0.30 showed 89% sensitivity and a 93% positive predictive value for detection of neutralizing antibodies (> or = 4). Thus, approximately 80% of persons born before 1969 and 50% of those born between 1969 and 1975 were also found to have maintained neutralizing antibodies against smallpox. A considerable proportion of the previous vaccinated individuals still retain significant levels of antiviral immunity. This long-lasting immunity may provide some protective benefits in the case of reemergence of smallpox, and the disease may not spread as widely and fatally as generally expected.

Adult↗
PubMed1967

Evaluation of the fluorescent antibody technique for the diagnosis of smallpox.

Smears on slides taken from 44 patients suspected of having smallpox were examined for the presence of smallpox antigens and from 15 of them for chickenpox antigens also, by the fluorescent antibody method, using the conventional ;sandwich' and the complement techniques. In seven, very strong non-specific fluorescence made the result unreadable. When staining for smallpox antigen results agreeing with the diagnoses established by other methods were obtained in 36 of 37, and when staining for chickenpox in 12 of 13 specimens examined. One false positive diagnosis of smallpox and one false negative of chickenpox were made. Because of intense non-specific staining no diagnosis could be made from other smears stored for three years. It was not possible to reach a diagnosis by examination of crust suspensions spread on slides. In five fresh specimens examined during the outbreak there was hardly any non-specific fluorescence and results could more easily be read. Morphological features as seen by fluorescence microscopy are described. The value of the method in the diagnosis of smallpox is discussed.

Antigens↗
PubMed1994

[From dreaded epidemic to rare disease - smallpox in Sweden 1750-1900].

Smallpox contributed to the death of 300,000 people in Sweden between 1750 and 1800. It was one of the most feared diseases of the time. Most victims were children under the age of 10 years. It is estimated that one out of every ten children died from smallpox. The mortality rate was between 10% and 20% but those who survived faced severe complications. Most common were the disfiguring pockmarks among those previously infected. It turned out that women who had contracted smallpox married much later in life than the healthy. Also, both female and male fertility was lowered by smallpox infection. By the mid 1750s inoculation was introduced in Sweden. This was a preventive method where a mild infection was given by putting smallpox matter into an incision in the skin. Success was restricted to the wealthy, even if the doctors tried to reach the common people. The main reasons were lack of confidence for doctors, medical and epidemiological risks, costs and an ineffective organization. In 1801 Eberhard Zacharias Munch of Rosenschöld performed the first vaccination with cowpox matter in Sweden. In a few years an extensive practise was stabilized, which made the Swedish population one of the best vaccinated in the world. Moreover, a unique registration was compiled which, together with the parish records, makes the country one of the best documented. The main reasons behind the success was previous experiences of inoculation, international influences, abolition of the physicians monopoly, an effective organization, better opportunities for financing and rewards, and the compulsory law of 1816.

History, 18th Century↗
PubMed2003

Smallpox.

Until the 1970s, smallpox was feared worldwide for the significant morbidity and mortality it caused. Although naturally occurring disease has been eliminated, the virus itself has not been destroyed, and it is assumed that some of the variola stored in the former Soviet Union has been removed. The majority of the world's population is susceptible to smallpox because vaccination ended in 1972 in the United States and in the rest of the world in 1982. A major epidemic could result if there was an intentional release of smallpox. Variola is both durable and highly infective, 2 features that make it an attractive bioweapon. Because of this threat, physicians should be familiar with the clinical features of smallpox and the appropriate isolation and medical response procedures. Although there is a vaccine that can provide pre- and postexposure protection, the vaccination itself is not without risks. There is no effective therapy for smallpox and studies of new treatments are underway.

Bioterrorism↗
PubMed1988

Outbreaks of smallpox due to variolation in China, 1962-1965.

In 1985, previously unknown outbreaks of smallpox were uncovered which had occurred in Shanxi Province and Nei Monggol Autonomous Region in northern China during 1962-1965, several years after smallpox transmission was thought to have been interrupted. During field investigation, the authors learned that most of the cases were known to local health officials but had not been officially reported to national authorities. All were among persons who had been variolated or were their close contacts. Variolation is an ancient method of protection against naturally acquired smallpox that was officially proscribed in the early 1950s but was renewed in remote areas when smallpox vaccination activities were interrupted during the three-year famine of 1959-1962, following the "great leap forward" program of 1958. It was found that the variolators in Shanxi Province and Nei Monggol Autonomous Region inoculated persons with the use of powdered smallpox scabs mixed with human milk, and that they obtained fresh supplies of scabs every 6-12 months by variolating relatives and friends. The health authorities responded by capturing the variolators, confiscating their variolation material and equipment, and vaccinating the population. The last known cases occurred in 1965, and the practice of variolation is now believed to be extinct.

Adolescent↗
PubMed1968

A study of immunity to smallpox in persons who have experienced a previous attack.

Most persons who recover from an attack of smallpox have lifelong immunity to a second attack but some persons lose their immunity more or less quickly and become susceptible to another attack. A study was made in Afghanistan in 1963-64 on 425 persons of all ages and both sexes who had previously suffered an attack of smallpox to determine their immunity to vaccinia virus. In all, 53.9% of those tested reacted positively to vaccination with vaccinia virus and there were no differences in response in males and females. It was demonstrated that the loss of immunity to vaccinia virus depends upon the time that has elapsed since the attack of smallpox and upon the severity of the attack. Loss of immunity to vaccinia virus rarely occurs among persons who have suffered an attack of smallpox less than 5 years previously. The authors point out that in some endemic areas, such as Afghanistan and Nepal, from 2.5% to more than 10% of the population has been affected by smallpox and should not be excluded from mass-vaccination campaigns.

Afghanistan↗
PubMed1982

Surveillance of orthopoxvirus infections, and associated research, in the period after smallpox eradication.

In 1980, the World Health Assembly declared the global eradication of smallpox and recommended the universal discontinuation of smallpox vaccination; nevertheless, it recommended that surveillance and research on orthopoxvirus infections should continue. By early 1982, all except 8 countries in the world had stopped routine vaccination programmes and all except 1 no longer required an international certificate of smallpox vaccination for travellers. Since 1978, as a result of continuing active surveillance, 176 smallpox rumours have been investigated in 60 countries. Two of these concerned the two laboratory-associated cases that occurred in the United Kingdom in 1978; all the others were false alarms. Special surveillance programmes for human monkeypox have been developed in West and Central Africa. The number of laboratories retaining variola virus stocks has been reduced to four. Investigations to determine the identity and origin of the six known isolates of "whitepox" virus have continued. Research on mapping of variola DNA and on monoclonal antibodies against certain orthopoxvirus antigens is continuing. All these measures are aimed at ensuring that the achievement of smallpox eradication is permanent.

DNA, Viral↗
PubMed1975

[The effect of vaccination status on the clinical form and outcome of the disease in smallpox patients (author's transl)].

During the smallpox epidemic in Yugoslavia in 1972, which involved 175 persons altogether, with 35 (=20 per cent) fatal cases, a number of very important aspects emerged, especially at Kosowo (124 cases0: smallpox vaccination gives almost complete protection for 5 years and a relative immunity for about 10 years. Vaccinations carried out on the first 2 days after contact with smallpox patients provide a convincing protection, reduce mortality and result in the appearance of a particular form of smallpox. The highest mortality (52.1 per cent) was seen in persons who had never been vaccinated, with the appearance of the "flat type" (47.8 per cent). Hemorrhagic smallpox was seen in 8 out of 9 persons who were vaccinated too late after contact and had an immunological deficiency.

Adolescent↗
PubMed1962

Smallpox--a retrospect.

Smallpox has been known as a disease of man since the earliest times. However, its severity increased greatly during the eighteenth century, stimulating physicians and others to find methods of protection against it. Variolation (the inoculation of smallpox material into the skin) was tried, and for a while found general approval, although its practice was not without danger. In 1796, Edward Jenner began his investigations into the use of cow-pox material (vaccination) as a prophylactic against smallpox, and later showed that vaccination could confer protection. Although vaccination centres were first set up in Canada early in the nineteenth century, the disease on occasion assumed epidemic proportions, such as occurred in Montreal in 1885. Sporadic outbreaks have occurred since then, including the recent case in Toronto. From the public health point of view, maintenance of a high level of immunity to smallpox throughout the general population is necessary if serious epidemics are to be avoided.

Animals↗
PubMed2004

A rapid detection method for Vaccinia virus, the surrogate for smallpox virus.

Prior to the World Health Organization's announcement of total eradication in 1977 [J. Am. Med. Assoc. 281 (1999) 1735], smallpox was a worldwide pathogen. Vaccinations were ceased in 1980 and now with a largely unprotected world population, smallpox is considered the ideal biowarfare agent [Antiviral Res. 57 (2002) 1]. Infection normally occurs after implantation of the virus on the oropharyngeal or respiratory mucosa [J. Am. Med. Assoc. 281 (1999) 2127]. Smallpox virus can be detected from the throats of exposed individuals prior to onset of illness and prior to the infectious stage of the illness. A rapid, sensitive real-time assay to detect Variola virus (smallpox) has been developed using the Vaccinia virus, a surrogate of smallpox, as a target. Cyanine 5 dye-labeled anti-Vaccinia antibody was used in a sandwich immunoassay to produce a fluorescent signal in the presence of the Vaccinia virus. The signal was detected using the Analyte 2000 biosensor (Research International, Monroe, WA). The Analyte 2000 uses a 635 nm laser diode to provide excitation light that is launched into a polystyrene optical waveguide. Fluorescent molecules within the evanescent wave are excited and a portion of their emission energy recouples into the waveguide. A photodiode quantifies the emission light at wavelengths between 670 and 710 nm. The biosensor was able to detect a minimum of 2.5 x 10(5) pfu/ml of Vaccinia virus in seeded throat culture swab specimens.

Biosensing Techniques↗
PubMed2006

Estimation of the duration of vaccine-induced residual protection against severe and fatal smallpox based on secondary vaccination failure.

BACKGROUND: Understanding the loss of vaccine-induced immunity against smallpox is essential in determining the fraction of those who are still protected in the present population and in constructing effective countermeasures against bioterrorist attacks. METHOD: Three small Australian outbreaks from the 1880s to early 1900s were investigated. Each documented individual age at infection. The case records for Launceston, 1903, further documented the age at vaccination and disease severity, enabling estimates of the duration of protection against severe and fatal smallpox. RESULTS: A significant association between vaccination and death was observed in the outbreak in Sydney, 1881 (odds ratio of death among vaccinated individuals = 0.3; 95% confidence interval (CI): 0.1, 0.8; p = 0.02), where the time since last vaccination was similar for all vaccinated cases. In Launceston, 1903, where the age at vaccination varied widely, the median duration of partial protection against severe and fatal smallpox was estimated to be 31.7 (95% CI: 13.2, 116.2) and 53.9 (95% CI: 25.6, 123.5) years after vaccination, respectively. Whereas those in their 20s are expected to have the highest frequency of vulnerability to smallpox death in the present population, infections among those in their 30s or 40s are expected to be much less fatal. CONCLUSION: Long lasting partial protection was suggested from the outbreak records, the estimated durations of which were roughly consistent with those reported previously. In the event of a bioterrorist attack, those involved in emergency tasks before emergency vaccination practices are re-established should ideally be previously vaccinated individuals in their 30s or 40s.

Australia↗
PubMed2004

Smallpox: vaccine reactions and contraindications.

Concern regarding the use of smallpox for bioterrorism has led to the reintroduction of smallpox vaccination. The historic background leading to protective methods against smallpox disease, the adverse reactions and contraindications associated with vaccination, and the ongoing development of potentially safer smallpox vaccines are reviewed here.

Adolescent↗
PubMed2005

The history of the smallpox vaccine.

Smallpox was a highly virulent, contagious disease. Initial attempts to control the disease by variolation were controversial and dangerous. Variolation was the subject of some of the earliest published clinical trials. Vaccination was discovered by Edward Jenner in 1796. From initial skepticism by the medical community the uptake became so widespread that smallpox vaccination was made compulsory in England and Wales in 1853. Eventually, this led to the eradication of smallpox in 1980. Parallels can be drawn with modern vaccination and the smallpox vaccine especially with the current intense media scrutiny of modern vaccinations.

History, 18th Century↗
PubMed2004

Design and development of oral drugs for the prophylaxis and treatment of smallpox infection.

Smallpox was eradicated by the World Health Organization (WHO) vaccination campaign in the 1970s and the variola virus was restricted to repositories in the United States and Russia. Recently, however, concerns have arisen about the possible existence of variola outside these sites and the potential for using the virus as a weapon of bioterror. The world population now has little residual immunity to smallpox and supplies of the smallpox vaccine are being reconstituted. Large numbers of individuals with various skin diseases or immunosuppression owing to AIDS or organ transplantation medications, or who are pregnant or have heart disease might not be ideal candidates for vaccination with the current live vaccines. It would be useful to have an orally active drug that could be self-administered in case of an outbreak of smallpox.

Acquired Immunodeficiency Syndrome↗
PubMed2006

LC16m8: an attenuated smallpox vaccine.

The frequency of moderate to severe adverse reactions associated with smallpox vaccines currently stockpiled in the US, and the continued threat of bioterrorism have prompted the development of effective vaccines with improved safety profiles. LC16m8, an attenuated, replicating smallpox vaccine derived from the Lister strain of vaccinia, is currently licensed in Japan where it was safely used in over 50,000 children in the 1970s. It has been shown to have markedly less neurotoxicity than unattenuated vaccines in nonclinical studies. LC16m8 is immunogenic after a single dose, and recent studies in two different animal models have demonstrated protective efficacy equivalent to that of the only FDA-licensed smallpox vaccine. This article reviews the history and available scientific literature regarding LC16m8 and provides comparisons to other smallpox vaccines.

Animals↗