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[Historical review of smallpox, the eradication of smallpox and the attenuated smallpox MVA vaccine].

After the WHO had declared smallpox to be eradicated in 1980, smallpox vaccination ceased to be carried out in humans all over the world. The cutaneous inoculations carried out with live vaccines based on the vaccinia virus from 1798 onwards protected both the global population and, indirectly, the animals living with humans against orthopox infections in general. A large percentage of humans and animals no longer enjoy this protection. Idiopathic orthopox in animals (reservoir possibly rats and mice) are thus experiencing a renaissance, posing a threat to humans and animals. The paper provides an historical retrospective of smallpox epidemics in humankind, their course of development and methods employed to combat this disease, commencing long before the birth of Christ with primitive attempts in China and India and from the end of the 18th century with increasingly enhanced methods, most recently with worldwide smallpox vaccination programmes using live vaccinia vaccines. Smallpox vaccination was always accompanied by a variety of complications, especially postvaccinal encephalitis. The MVA strain was developed to reduce or prevent such adverse effects. MVA has meanwhile proved its worth both as a parenteral vaccine against orthopox infections in humans and animals and as a vector for insertion of foreign genes. The history of smallpox, the fight against this disease and the development of MVA are documented with the help of figures and tables.

Animals↗

The ocular complications of smallpox and smallpox immunization.

Although smallpox was eradicated worldwide, concerns have been raised about the use of smallpox as a biological weapon. Plans are being considered for smallpox immunization in the United States. Variola virus, the cause of smallpox, and vaccinia virus, used in smallpox immunization, are both orthopoxviruses that are associated with serious ocular complications, including eyelid and conjunctival infection, corneal ulceration, disciform keratitis, iritis, optic neuritis, and blindness. About 5% to 9% of patients with smallpox develop ocular complications, and case-fatality rates reach 20% to 35% among unvaccinated individuals. About 10 to 20 patients develop ocular complications per 1 million smallpox immunizations, usually through autoinoculation, in which the patient transfers vaccinia from the immunization site to the eye. The risk of ocular vaccinia infection may be reduced by instructing patients and individuals in close contact with the vaccinee to wash their hands often and avoid touching the immunization site and their eyes. Topical antiviral therapy, topical steroids, and topical and oral antibiotics have been used to reduce the ocular complications of smallpox immunization. In contrast, there has been little experience with the use of these therapies for the ocular complications of smallpox.

Biological Warfare↗

Women with smallpox vaccine exposure during pregnancy reported to the National Smallpox Vaccine in Pregnancy Registry--United States, 2003.

In the absence of circulating smallpox, pregnant women should not be exposed to live vaccinia virus contained in the smallpox vaccine. The smallpox vaccine should not be administered to women who are pregnant or might become pregnant within 4 weeks after vaccination because of the risk for fetal vaccinia, a rare but serious infection of the fetus. In addition, persons who have close contact (e.g., household contact or sexual contact) with pregnant women are advised to forego vaccination. To prevent inadvertent exposure of pregnant women to vaccinia virus, screening for pregnancy is a component of pre-event smallpox vaccination programs. To monitor outcomes of pregnancy in women exposed to smallpox vaccines, CDC, in collaboration with the Department of Defense (DoD) and the Food and Drug Administration (FDA), has established the National Smallpox Vaccine in Pregnancy Registry. This report summarizes data from the registry about these exposures. CDC and the Advisory Committee on Immunization Practices (ACIP) recommendations to screen for pregnancy as a contraindication to smallpox vaccination appear to be effective at preventing inadvertent exposures.

Adult↗

[Abolition of compulsory vaccination against smallpox. Increased danger to humans from animal smallpox? (author's transl)].

After the world-wide eradication of human smallpox, compulsory vaccination against smallpox will no longer be applicable in future in most countries. Although the human smallpox virus (variola virus) appears to have no animal reservoir, humanity is increasingly endangered in future by animal smallpox viruses pathogenic in man against which he has been so far protected by the general smallpox vaccination. This is a virus type of the Genus Orthopox virus. The risk from animal pox viruses, which are not related to the Orthopox virus, remains unchanged. Of the animal Orthopox viruses the monkey pox viruses deserve special attention; possibly rodents also play a decisive role in transmission of smallpox.

Animals↗

Smallpox Vaccine Injury Compensation Program: Smallpox (Vaccinia) Vaccine Injury Table. Interim final rule.

The Smallpox Emergency Personnel Protection Act of 2003 (SEPPA), Public Law 108-20, 117 Stat. 638, authorized the Secretary of Health and Human Services (the Secretary), through the establishment of the Smallpox Vaccine Injury Compensation Program (the Program), to provide benefits and/or compensation to certain persons who have sustained injuries as a result of the administration of smallpox covered countermeasures (including the smallpox vaccine) or as a result of vaccinia contracted through accidental vaccinia inoculations. The SEPPA directed the Secretary to establish, by interim final rule, a table identifying adverse effects (including injuries, disabilities, conditions, and deaths) that shall be presumed to result from the administration of or exposure to the smallpox vaccine, and the time interval in which the first symptom or manifestation of each listed injury must manifest in order for such presumption to apply. As mandated by law, the Secretary is establishing such a Smallpox (Vaccinia) Vaccine Injury Table (the Table) through this interim final rule. The Secretary is also establishing a set of Table Definitions and Requirements, which define the terms and conditions included on the Table and are to be read in conjunction with the Table. The Secretary is seeking public comment on the Table established through this interim final rule. At a later date, the Secretary will publish a companion final rule setting forth the administrative implementation of the Program. The public will then be afforded an additional opportunity to comment on the procedures set forth therein.

Compensation and Redress↗

[Results of examining wild monkeys for the presence of smallpox antibodies and smallpox group viruses].

The results of examinations of sera, blood and organs of different species of monkeys from some Asian and African countries for the presence of antibody to smallpox and viruses of the smallpox group. Significant titers of smallpox antibodies (antihemagglutinins virus-neutralizing and, in some cases, precipitating antibody) were found in a considerable number of monkeys shot near foci with human cases (Equatorial province of Zair Republic). In the same monkeys kidney tissues yielded 3 isolates of smallpox virus group two of which were indistinguishable in the laboratory tests from variola virus. On the basis of these data it is concluded that smallpox viruses circulate among wildlife monkeys in some areas of Equatorial Africa. Further studies along these lines are necessary.

Africa↗

[Smallpox and smallpox virus--200 years since the first vaccination in Norway].

In December 1801, the first vaccination against smallpox in Norway took place. Vaccine material came from Denmark, England, Ireland, and other countries; it was also obtained from a few local cowpox cases. What mattered was the effect, not the origin. Several reports indicate that variola virus itself, the cause of smallpox, was also used for human vaccination after passages through cows and horses. A vaccine institute for production of vaccine in calves was established in Kristiania in 1891. Cowpox was once a rare disease in cattle, but a total of 70,985 bovine cases were reported between 1889 and 1928. The source of infection was thought to be humans vaccinated against smallpox. Pox-like diseases were also registered in horses, pigs, sheep, goats and dogs at that time. Compulsory vaccination continued in Norway until 1976; smallpox is now eradicated. During the last decades, however, cowpox virus infections have re-emerged among zoo animals, domestic cats and humans in Western Europe, with small wild rodents and shrews as wildlife reservoirs. Vaccinia virus is also met with new interest as a vector in recombinant vaccines. Given the fact that the human population no longer has immunity against orthopoxviruses and the new possible exposure through pets and wildlife, it may be appropriate to reflect on poxvirus history in Norway in the light of the present situation.

Animals↗

Duration of immunity after smallpox vaccination: a study on vaccination policy against smallpox bioterrorism in Japan.

The success of global smallpox eradication in 1980 led all the nations of the world to discontinue smallpox vaccination. To date, however, the threat of deliberate release of smallpox virus has led health authorities to reconsider smallpox vaccination and at the same time, to urge to evaluate duration of the immunity of the population vaccinated before 1980. Although available data is scarce and incomplete, the study suggests that protective immunity lasts longer in a good percentage of vaccinees, although the real percentage and duration are not known. Accordingly, how to establish a national vaccination policy for preparedness in Japan and elsewhere was discussed. The study is intended to cause interest and debate among the medical and public health community.

Bioterrorism↗

[Persistant danger of smallpox and necessity of continuing mandatory smallpox vaccination in France].

The WHO stated a short time ago that the total eradication of smallpox would occur shortly. This announcement has been contradicted by an epidemic of smallpox in Somaila which in spite of the energetic measures taken, remained in the capital from August 1976 to January 1977 then extended to 10 regions out of 16 with from January 1977 to 18 June 1977, 1 567 cases of smallpox. This is only a provisional estimation as it is increasing every week. In view of the ease and rapidity of airline communication, it is very possible that infected subjects or products arrive in France, it is necessary for doctors to be warned and counteract the present tendancy to neglect the legal requirement for smallpox vaccination.

Animals↗

Smallpox surveillance in Bangladesh: II - Smallpox facial scar survey assessment of surveillance effectiveness.

A smallpox facial scar survey of 465 892 persons aged 0-19 years was carried out in Bangladesh in 1976, covering approximately 1% of the 0-19 year old population. Of the 4 306 persons found with facial scarring consistent with previous smallpox infection, none had a history of smallpox with onset after the last reported case on October 16, 1975. Histories taken from persons with facial scars allowed smallpox incidence to be estimated for each year from 1972 to 1975. These estimates indicate that completeness of reporting increased steadily from 11.8% in 1972 to 83.0% in 1975, reflecting the increasing effectiveness of surveillance.

Adolescent↗

Smallpox Vaccine Adverse Events Monitoring and Response System for the first stage of the smallpox vaccination program.

Smallpox vaccination of civilian volunteer health-care workers began on January 24, 2003. As of February 4, a total of 37 states and counties have received shipments of smallpox vaccine, and 18 states and counties have begun smallpox vaccination; no serious adverse events have been reported. To monitor the occurrence of adverse events associated with vaccination, both those expected on the basis of previous experience and possible new unexpected adverse events, CDC and state health departments have established the Smallpox Vaccine Adverse Events Monitoring and Response System. The system also will be used to monitor the effectiveness of contraindication screening, identify new contraindications, and coordinate the distribution of vaccinia immune globulin (VIG) and cidofovir to the civilian population. This notice describes the components of the system, delineates roles and responsibilities, and explains how data from the system will be compiled and communicated.

Adverse Drug Reaction Reporting Systems↗

The recovery of smallpox virus from patients and their environment in a smallpox hospital.

Attempts had been made in 1961 to recover smallpox virus by air sampling in smallpox wards and close to the mouths of smallpox patients, but these had been largely unsuccessful, possibly owing to the air sampling method used. Further attempts were therefore made in 1963, with a fluid impinger for air sampling and with Petri dishes placed below the orifice of the impinger to collect large droplets or particulate matter that the impinger might miss.Air samples from near the patients' mouths yielded little virus, this being more readily recovered from the settling-plates. Patients' bedclothes sampled with the impinger yielded rather more virus, but again even more was obtained from the Petri dishes.The results suggest that contamination of the air in the vicinity of smallpox patients is due to relatively large particles of infected dust from the patients' bedclothes rather than from fine droplets or droplet nuclei coming from the upper respiratory tract. Secretions from the mouth and upper respiratory tract appear to be responsible for the early contamination of pillows and bedclothes.

Female↗

Smallpox and smallpox vaccination: neurological implications.

Compulsory vaccination was discontinued in the U.S. in 1972; the world was declared free of smallpox infection in 1980. Since that time, no new smallpox infections have been recognized, and only limited numbers of military and laboratory personnel have been vaccinated. As a result, the majority of the U.S. and the world population have no or diminished immunity to smallpox. Widespread vaccination, beginning with the military and health care workers, is now being undertaken. Public health strategies for immunizing the general population include preexposure voluntary vaccination, case surveillance with ring vaccination, and mass vaccination at the time of attack. Cutaneous complications of vaccination occur in immunosuppressed subjects and in those with atopic dermatitis. Among the most serious complications is postvaccinal encephalomyelitis (PVEM). A related condition, postvaccinial encephalopathy (PVE), may be seen in children less than two years of age. There are no markers to predict who will develop PVEM. In the past, mortality was high, ranging from 10 to 50%. The neuropathology of PVEM suggested an immune-mediated attack on the CNS, but the target of the immune response is unknown. Comprehensive programs are needed for surveillance and confirming case definitions for neurologic complications. Multi-institutional controlled trials of antiviral and immune modulating therapy of PVEM should be considered. Neurologists should be actively involved in the planning process for vaccination programs and in the treatment of neurologic complications.

Adult↗

[Global program of smallpox eradication. 1. Smallpox in the world before acceptance of the program of its eradication by the World Health Organization].

Despite a considerable success in control smallpox in a number of countries reached as a result of vaccination the problem of eradication of this infection could not be solved without uniting the efforts of all the countries in the world. Guided by humanity principles the delegation of the USSR suggested in 1958 a program of smallpox eradication in the whole world. World smallpox morbidity is analyzed in this work.

Africa↗

Ten years of freedom from smallpox: lessons and experiences. Dedicated to the tenth anniversary of worldwide freedom from smallpox.

Many lessons and experiences were learned during the global programme of smallpox eradication, the most important being those which could be generalized and applied to other health programmes. This does not mean imitating or implementing smallpox eradication techniques to other diseases, since each infection requires its own strategy. It is difficult to dissect out the single key element or to equate the various factors responsible for the success, as these always worked together, in combination, depending one on others. For global eradication, the element of essential importance was international cooperation and close coordination of activities between nations. This would be impossible without proper mechanisms dedicated to international cooperation in the field of health, provided by the World Health Organization, which also assured mobilization of world resources for national programmes and application of appropriate techniques across international borders. The established specific, practical and measurable goals, objectives and targets made every programme worker clearly understand what was to be accomplished and to find his own role in achieving these objectives. Operational techniques had to be flexible, modified appropriately from country to country to make them suitable to present epidemiological situations, local administrative and health structures as well as to demographic and geographic patterns. It was the effective system of surveillance and outbreak-containment that ultimately proved to have been the key to eradication. However, application of skillful management, sound epidemiological principles, advanced technology and adequate logistic support contributed significantly to the achievement of the final goal.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

[Use of the passive hemaglutination reactions for the determination of anti-smallpox antibodies in primary vaccination and revaccination against smallpox].

The authors present the results of studying the PHAT sensitivity in comparison with the neutralization test and the hemagglutination inhibition test in examination of 254 sera of revaccinated and 95 sera of primarily vaccinated children. It appeared that PHAT was characterized by a sufficiently high sensitivity, and reproducibility, in case the same batch of erythrocytic diagnostic agent was used; at the same time the test was simple, accessible, economic, and gave rapid results. This test can be used for assessment of the immunological efficacy of smallpox revaccination.

Antibodies, Viral↗

[Comparative study of smallpox vaccines from strains B-51, EM-63 and L-IVP in a controlled epidemiologic trial. I. Reactogenic characteristics of the smallpox vaccines].

A comparative study of smallpox vaccines prepared from the l-ivp zm-63 and b-51 strains was carried out under conditions of controlled epidemiological trial. Children subject to planned vaccination were scarified with commercial batches of the preparations under study (with the same infectious activity). As a result of investigations it was found that in the group of those scarified with the vaccine from zm-63 strain strong local and catarrhal reactions and some disturbances of general condition were more frequent than in those scarified with preparations from the l-ivp and b-51 strain. Along with this, the temperature elevation of various intensity showed no statistically significant difference in the groups a vaccinated with the vaccines compared. Integral analysis of signs characterising different manifestations of reactigenic properties of the vaccines compared led to the conclusion that preparations made of zm-6 strain had greater reactogenic properties.

Child↗