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PubMed1984

Historical epidemiology of smallpox in Aland, Finland: 1751-1890.

We analyze a 140-year series of smallpox deaths in the Aland Islands, Finland. Vaccination, introduced in 1805, dramatically reduced the annual number of smallpox deaths. It also influenced the age distribution of smallpox deaths, changing smallpox from a childhood disease before 1805 to one which affected both adults and children after 1805. This appears to be due to the fact that Alanders were usually vaccinated only once during childhood and often lost their immunity during adulthood. Spectral analysis of the prevaccination time series of smallpox deaths demonstrates a strong seven-year periodicity, reflecting the amount of time necessary to build up a cohort of nonimmune individuals. After the introduction of vaccination, the periodicity changes to eight years. The probability that a parish in Aland was affected by a smallpox epidemic is shown to be highly correlated with migration patterns and parish population sizes.

Finland↗
PubMed1981

The eradication of smallpox in Shanghai, China, October 1950-July 1951.

Smallpox (variola major) was endemic in China for thousands of years until it was finally eradicated from the country in the early 1960s. The strategy and tactics of the eradication campaign in Shanghai, the largest city and major communications centre in China, were typical of those employed throughout China, but had some additional features of interest.The decision to eradicate smallpox was made in 1950 and three preparatory steps were taken immediately: supplies of potent (liquid) vaccine were assured; popular support was enlisted by intensive propaganda; and teams of vaccinators were trained. In Shanghai, the mass vaccination campaign began in October 1950, at a time when a smallpox epidemic was raging in the city. The last case of smallpox in the city was recorded in July 1951. A special feature of the campaign in Shanghai was the introduction of a national vaccination certificate to prevent export of smallpox from the city by the 2 800 000 persons who moved in and out of Shanghai each week by rail, bus, or boat.Eradication was followed up by a programme of vaccination of all infants, with revaccination at 6, 12, and 18 years of age, and mass vaccination campaigns in 1963, 1968, 1972, and 1978. The number of adverse reactions to vaccination was small and fell progressively from an overall figure of 8.4 per 100 000 in 1963 to 2.5 per 100 000 in 1978. Vaccination requirements were relaxed in 1978, but smallpox vaccination is still offered to children as part of the immunization programme.

Adolescent↗
PubMed1965

SMALLPOX CONTROL IN CANADA.

During the period 1961 to 1963 there were 10 separate importations of smallpox cases by aircraft into England and Wales, Germany, Sweden, Poland and Canada. A feature of the resulting outbreaks was the number of cases and deaths of physicians and other health personnel. With the increasing volume of international air traffic there is a risk of importing incubating cases of smallpox into Canada, as occurred in 1962. Millions of Canadians have been protected against smallpox. Some complications of smallpox vaccination have occurred in Canada; such complications can be minimized by proper attention to contraindications to vaccination. The Food and Drug Directorate, Department of National Health and Welfare, has circularized all physicians in Canada to request their co-operation in reporting adverse reactions to drugs. This includes serious, unusual or unsuspected reactions to immunizing agents (vaccines, toxoids and antitoxins). The latter information will be shared with the Epidemiology Division, Department of National Health and Welfare, and the provincial epidemiologist and manufacturer concerned. The importance of maintaining the smallpox immunity of physicians, nurses and other hospital and health personnel in Canada is emphasized.

Biometry↗
PubMedDate not supplied

The history of smallpox.

The history of smallpox, from its probable origin 3000 to 6000 years ago to its worldwide eradication in 1978, is a fascinating story. A feared infection, even today, smallpox has caused the deaths of millions of people and disfigured many. This article describes the possible origin of the infection and traces its progress throughout the world. The introduction of inoculation with material from smallpox lesions and vaccination using cowpox virus is described. The World Health Organization's successful smallpox eradication program in the 1960s and 1970s is described. Personal experience of this program in Bangladesh in 1973 is outlined, as is the laboratory escape of the major smallpox virus in Birmingham in 1978. The possible use of the smallpox virus as a biological weapon is discussed.

History, 15th Century↗
PubMed2006

Containing a large bioterrorist smallpox attack: a computer simulation approach.

BACKGROUND: A bioterrorist release of smallpox is a constant threat to the population of the USA and other countries. DESIGN: A stochastic simulation model of the spread of smallpox due to a large bioterrorist attack in a structured population was constructed. Disease natural history parameter estimates, time lines of behavioral activities, and control scenarios were based on the literature and on the consensus opinion of a panel of smallpox experts. RESULTS: The authors found that surveillance and containment, i.e., isolation of known cases and vaccination of their close contacts, would be sufficient to effectively contain a large intentional smallpox release. Given that surveillance and containment measures are in place, preemptive vaccination of hospital workers would further reduce the number of smallpox cases and deaths but would require large numbers of prevaccinations. High levels of reactive mass vaccination after the outbreak begins would further reduce smallpox cases and deaths to a minimum, but would require even larger numbers of vaccinations. Reactive closure of schools would have a minimal effect. CONCLUSION: A rapid and well-organized response to a bioterrorist attack would be necessary for effective surveillance and containment to control spread. Preemptive vaccination of hospital workers and reactive vaccination of the target population would further limit spread, but at a cost of many more vaccinated. This cost in resources and potential harm due to vaccination will have to be weighed against the potential benefits should an attack occur. Prevaccination of the general population is not necessary.

Bioterrorism↗
PubMed2004

The scarring mechanism of smallpox.

BACKGROUND: Smallpox is notorious for leaving its survivors with disfiguring scars, but it is unclear how these scars are produced. Modern dermatopathology textbooks report that smallpox produced epidermal lesions, yet the process of scarring requires dermal involvement. OBJECTIVES: Our goal was to uncover past theories on the mechanism of smallpox scarring. METHODS: We conducted a comprehensive review of English-language textbooks and English-translations of textbooks in general medicine, dermatology, pathology, and dermatopathology from the past 150 years as well as relevant journal publications for the same time period. RESULTS: We identified five different theories to explain the scarring of smallpox. The five proposals are that scarring resulted from: the extension of suppuration into the dermis; the extension of suppuration into the dermis along with inappropriate treatment and scratching; secondary bacterial ecthyma; the destruction of elastic fibers; or the destruction of sebaceous glands. CONCLUSION: The theory that best fits clinical and histological observations is that smallpox caused scars through the destruction of sebaceous glands, first proposed by Gerrit Bras in 1952. Although this explanation is not found in any dermatopathology text, it is supported by today's leading authorities on smallpox. However, since variola virions have never actually been identified in sebaceous glands, or even in the dermis, further study of preserved tissue is warranted. Until then, the mechanism of scar formation remains speculative.

Cicatrix↗
PubMed2004

Ocular complications in the Department of Defense Smallpox Vaccination Program.

OBJECTIVE: The purpose of this case series was to present an overview of the nature and frequency of ocular complications in the Department of Defense (DoD) Smallpox Vaccination Program. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: The authors retrospectively evaluated data collected on individuals with an ophthalmologic complaint after receiving smallpox vaccination or after contact with a recently immunized individual. The vaccinee and contact cases occurred secondary to inoculations given between December 13, 2002 and May 28, 2003 as part of the DoD Smallpox Vaccination Program. METHODS: Data were collected primarily from reports to military headquarters or to the Vaccine Adverse Event Reporting System and individual medical records. MAIN OUTCOME MEASURES: The incidence, types, and timing of ocular complications were evaluated. Diagnostic and treatment considerations also were reviewed. RESULTS: Between December 13, 2002 and May 28, 2003, 450,293 smallpox vaccinations were given. We identified 16 confirmed or probable cases of ocular vaccinia, with an incidence of 3.6 per 100,000 inoculations. Of these cases, 12 (75%) were seen in the vaccinees, and 4 (25%) in close contacts. Of the 12 self-inoculation cases, 7 (58.3%) were seen in individuals receiving the vaccine for the first time (primary vaccination), and 3 (25.0%) were seen in individuals previously vaccinated (revaccination); the vaccination status in 2 cases was unknown. Clinical manifestations included lid pustules, blepharitis, periorbital cellulitis, conjunctivitis, conjunctival ulcers, conjunctival membranes, limbal pustules, corneal infiltrates, and iritis, with onset of symptoms 3 to 24 days after inoculation or contact. Five of 9 tested cases were culture or polymerase chain reaction positive for vaccinia. Treatment for most cases was topical trifluridine 1% (Viroptic; King Pharmaceuticals, Inc., Bristol, TN). Vaccinia immune globulin was used in 1 case. In all patients, recovery occurred without significant visual sequelae. CONCLUSIONS: When compared with historical data on the ocular complications of smallpox vaccination, the incidence of ocular complications during the DoD Smallpox Vaccination program has been low. In addition, the severity of disease seems to be less than during other vaccination periods. These findings perhaps are the result of improved screening of vaccinees, prevaccination counseling, postvaccination wound care, and the suggested efficacy of trifluridine in the treatment of ocular vaccinia.

Acyclovir↗
PubMed2002

Primary induction of human CD8+ cytotoxic T lymphocytes and interferon-gamma-producing T cells after smallpox vaccination.

This study measured the ability of a standard smallpox vaccine, given by scarification (by bifurcated needle), to induce primary human vaccinia virus-specific cytotoxic and interferon (IFN)-gamma-producing T lymphocyte responses. Because protection against smallpox may be mediated in part by T cell memory responses induced by vaccination, an analysis of the induction of primary human cytotoxic T lymphocytes (CTL) and IFN-gamma-producing T cell responses was performed. Although smallpox is no longer an epidemic threat under natural conditions, vaccination is still recommended for persons working with vaccinia viruses in the laboratory and for those who may be at risk from the potential use of smallpox virus as a bioterrorism agent. The results demonstrate that smallpox vaccine given by bifurcated needle induces strong vaccinia virus-specific CD8(+) CTL and IFN-gamma-producing T cell responses and provide baseline information useful for planning the immunologic assessment of future smallpox vaccines.

Adult↗
PubMed2004

Diagnosing smallpox: would you know it if you saw it?

The intentional release of anthrax in the United States in 2001 and other recent acts of terrorism have highlighted the possibility of intentional release of smallpox by terrorists. Little is known about physicians' ability to diagnose smallpox, especially in the critical first days, when the potential for rapid control of transmission is greatest. During December 2002 and January 2003, primary care and emergency physicians at a large urban academic medical center were surveyed regarding the diagnosis and management of patients who present with vesicular rash illness. In addition to demographic and training-related questions, the questionnaire included items about perceived comfort in diagnosing and evaluating rashes, knowledge of the key differential diagnostic characteristics of chickenpox and smallpox, and the diagnostic interpretation of color photographs of patients with smallpox or chickenpox. Responses were summarized as a perceived comfort score, a differential diagnosis score, and a picture score. Of 266 eligible physicians, 178 (67%) responded. Of these, 95% thought clinicians need more education about bioterrorism; only 17% reported comfort in diagnosing smallpox. Although most physicians recognized pictures of smallpox and chickenpox, only 36% correctly answered 3 of 4 questions regarding differential diagnosis, an important aspect of identifying cases early. Those who were comfortable diagnosing rash illnesses had higher differential diagnosis scores. Strategies for bioterrorism-related training could take advantage of physicians' awareness of their own knowledge deficits.

Attitude of Health Personnel↗
PubMed2005

Use of an electronic monitoring system for self-reporting smallpox vaccine reactions.

OBJECTIVES: Tracking vaccine reactions and adverse events during a large-scale vaccination program such as the recent smallpox program or a pandemic flu outbreak will be a challenge. We report on vaccine reaction data collected using a novel telephone- and web-based electronic reporting system. The system was used to monitor vaccinees during the U.S. Army's smallpox vaccination campaign, which was part of the national program to prepare against biological attack. In addition, we report on the time course of events after smallpox vaccination based on the self-reported data and evaluate the validity and reliability of self-reported take information after smallpox vaccination. METHODS: A prospective cohort of subjects receiving the smallpox vaccination volunteered to use an electronic monitoring system to track and report their vaccination reactions. RESULTS: Users made 6.8 +/- 6.2 (mean +/- SD) reports using the electronic monitoring system. The sensitivity and positive predictive value of self-reported takes were high, 98.8% and 99.6%, respectively. The vaccination-site reactions progressed faster for revaccinees than first-time vaccinees. CONCLUSIONS: Simple-to-use telephone/Internet-based technology allowed detailed self-recording of response to smallpox vaccination among outpatients. Self-reports on site appearance were sufficient to determine vaccine takes in most vaccinees. During a mass vaccination event, an electronic monitoring system could facilitate tracking of vaccine reactions, including providing an early warning system for adverse events, and might reduce the burden associated with follow-up visits with healthcare professionals.

Adult↗
PubMed2005

Laser resurfacing of smallpox scars.

BACKGROUND: At the beginning of the twentieth century, smallpox affected every continent and country in the world, but over the first half of the twentieth century this disease was eliminated in most countries, including Korea, thanks to the World Health Organization's eradication program. Most survivors of smallpox have facial scars with a distinct cobblestone appearance. Though most smallpox scar patients want smooth skin, it is difficult to achieve good results with dermabrasion or chemical peeling. Recently, with advances in laser technology, laser resurfacing has become more effective and safer than conventional methods because of its depth control precision. METHODS: Between September of 1996 and August of 2001, 76 patients with significant smallpox scars were treated with a high-powered carbon dioxide laser at Korea University's Anam Medical Center. Different resurfacing methods, such as even-depth resurfacing, the shoulder technique, and the laser punch-out method, were applied according to the depth and pattern of the scars. RESULTS: The authors found that 54 patients (71 percent) had excellent or good results. The sharply demarcated margins of the smallpox scars faded out, and the depth and width of the depressed scars improved in most patients. Only seven patients sustained hypertrophic scarring after laser resurfacing, but this was resolved by intradermal triamcinolone injections. Prolonged erythema occurred in six patients (7.9 percent) and hyperpigmentation occurred in 15 (19.7 percent), but the erythema disappeared spontaneously and the hyperpigmentation could be readily managed with postoperative skin care. CONCLUSION: Laser resurfacing was found to be a useful treatment method for smallpox scarring.

Aged↗
PubMed1968

Comparison of titrations on the chorioallantoic membrane of chick embryos with the rabbit scarification technique for the potency assay of smallpox vaccines.

The potency of the U.S. Reference Smallpox Vaccine, Lot 2, the International Reference Preparation of Smallpox Vaccine, and commercial smallpox vaccines was determined by the chorioallantoic membrane (CAM) and rabbit scarification (RS) potency assay methods. The mean titer of the U.S. Reference (based on 107 ampoules) was 10(8.1) pock-forming units (PFU) per ml and that of the International Reference (based on 3 ampoules) was 10(7.8) PFU/ml. A statistical analysis of the CAM data for the U.S. Reference resulted in the establishment of a table of limits of acceptance for smallpox vaccines. Of the commercial smallpox vaccines tested by the CAM and RS methods, 89% demonstrated potencies comparable to the U.S. Reference. Our results show that the CAM test method has application in the control testing of smallpox vaccines produced by U.S. licensed manufacturers provided it is used within the limits discussed.

Animals↗
PubMed2006

Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II.

BACKGROUND: Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. METHODS: A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications. Two authors reviewed selected papers for smallpox outbreaks. RESULTS: 51 relevant outbreaks were identified from 1,389 publications. The median for the effective first generation reproduction rate (initial R) was 2 (range 0-38). The majority outbreaks were small (less than 5 cases) and contained within one generation. Outbreaks with few hospitalized patients had low initial R values (median of 1) and were prolonged if not initially recognized (median of 3 generations); outbreaks with mostly hospitalized patients had higher initial R values (median 12) and were shorter (median of 3 generations). Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases) and longer (median of 3 generations) compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation). CONCLUSION: Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks. The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early.

Communicable Disease Control↗
PubMedDate not supplied

Smallpox-related knowledge and beliefs among recent college graduates.

UNLABELLED: Recent world events have increased concern and preparations for possible bioterror events. Despite worldwide efforts to limit access to bio-weapons, smallpox is still considered a potential bioterror threat. Americans' understanding of smallpox could prevent panic and enhance the willingness of citizens to receive vaccinations. OBJECTIVE: The authors' purpose in this study was to describe graduating college students' levels of smallpox-related knowledge. METHOD SUMMARY: Participants at a graduation ceremony--mostly female, with a mean age of 28.4+/-8.1 years--were handed a 35-item questionnaire that assessed smallpox knowledge and whether respondents would submit to vaccination under hypothetical circumstances. RESULTS: The convenience sample was ignorant of numerous facts about smallpox and unaware of government efforts to prepare for an attack, answering an average of 3.8 out of 10 items correctly. CONCLUSION: These findings raise concern because, in a smallpox event, prompt responses to directives of public health officials will be necessary to maximize the effectiveness of response plans.

Adolescent↗
PubMed1977

Smallpox in the Republic of Guinea, West Africa. II. Eradication using mobile teams.

Smallpox transmission was interrupted in the Republic of Guinea in January 1969, 13 months after the beginning of the National Smallpox Eradication Program, and after approximately 60% of the population had been mass vaccinated. The eradication strategy was founded on the recent epidemiology of smallpox in Guinea and surrounding countries. Tactics were based on use of mobile teams specifically trained for mass vaccination, assessment, surveillance, and epidemic investigation. Guinea was one of 15 West African countries officially certified by the World Health Organization in 1976 as having eradicated smallpox. Continued vigilance to detect any possible importation is needed and would best be part of a program to improve quarantinable disease surveillance. An acceptable immunity level to smallpox should be maintained in priority groups until worldwide smallpox eradication is achieved.

Adolescent↗
PubMed2003

Smallpox Vaccine Injury Compensation Program: administrative implementation. Interim final rule.

The Smallpox Emergency Personnel Protection Act of 2003 (SEPPA), authorizes the Secretary of Health and Human Services (the Secretary), to establish the Smallpox Vaccine Injury Compensation Program ("the Program"). This program is designed to provide benefits and/or compensation to certain persons harmed as a direct result of receiving smallpox covered countermeasures, including the smallpox vaccine, or as a direct result of contracting vaccinia through certain accidental exposures. In addition, the Secretary may provide death benefits to certain survivors of individuals who died as the direct result of these injuries. On August 27, 2003, the Secretary published an interim final rule that set out a Smallpox (Vaccinia) Vaccine Injury Table ("the Table"). The table includes adverse effects (including injuries, disabilities, conditions, and deaths) within specific time periods that shall be presumed to result from the receipt of, or exposure to, the smallpox vaccine. The Secretary will use this table, as well as the procedures set out in this regulation, in deciding whether persons are eligible to receive benefits under the program. In this interim final rule, the Secretary is setting out the administrative policies, procedures, and requirements governing the program, as authorized by the SEPPA. The Secretary is seeking public comment on this interim final rule.

Bioterrorism↗
PubMed2005

Folliculitis after smallpox vaccination: a report of two cases.

Rashes are frequent and potentially serious adverse consequences of smallpox vaccination. Life-threatening rashes must be differentiated from benign, self-limiting ones. Generalized vaccinia, erythema multiforme, and folliculitis are distinct self-limiting entities but may be difficult to differentiate from one another. Two cases of folliculitis after smallpox vaccination are described. Both patients received anthrax vaccination within 2 weeks before smallpox vaccination. Both presented with a papulopustular rash 9 days after smallpox vaccination. Although the rashes were initially diagnosed as erythema multiforme, the clinical features were more consistent with folliculitis. Self-limiting rashes after smallpox vaccination are common and may be difficult to distinguish from each other. These rashes are clinically distinct, with characteristic features. Improvement in diagnosis may help classify the frequency and risk of rashes after smallpox vaccination. The association of vaccine-associated folliculitis, anthrax vaccine, and other potential antigenic triggers should be further explored.

Adult↗
PubMedDate not supplied

[Verification of the safety, inoculability, reactogenicity and antigenic properties of a live recombinant smallpox-hepatitis B vaccine in an experiment in volunteers].

Trials of the first Soviet live recombinant smallpox-hepatitis B vaccine (SHBV) in volunteers (20 men aged 18-20 years) showed its safety, good "take"-rate, and lower reactogenicity as compared with the standard smallpox vaccine (LIVP strain). Smallpox virus-neutralizing antibodies in response to SHBV were produced as well as in response to the smallpox vaccine. Revaccination of human subjects with smallpox vaccine and SHBV 45 days after the previous vaccination resulted in antibody booster to vaccinia virus. After two inoculations of SHBV at an interval of 45 days no anti-HBsAg antibodies were found for 3 months after the last vaccination. However, even a single vaccination with SHBV induced priming to HBsAg. This could be demonstrated after inoculation of the subjects vaccinated with SHBV with one dose of plasma hepatitis vaccine. In the subjects vaccinated with SHBV antibody in response to the plasma vaccine formed more frequently and in higher titres than in those prevaccinated with smallpox vaccine or placebo.

Adolescent↗