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Smallpox eradication: progress and problems.

In 1958, the Eleventh World Health Assembly, on the proposal of the USSR, approved a resolution for world-wide smallpox eradication. In that year alone the disease occurred in 59 countries, and in addition many other areas experienced imported cases. When the intensified eradication programme began in 1967, there were 33 countries with endemic smallpox and two more countries subsequently became endemic. These 33 countries had a population of over 1,200,000,000 and were located in four of the six WHO regions. The most important endemic area was in Asia, but the disease was also endemic in South America and in Africa, south of the Sahara. The intensified campaign quickly narrowed the endemic area. In April 1971, the last case was reported from Brazil, the stronghold of the disease in the Western Hemisphere. By 1973, with the exception of those in the Horn of Africa, smallpox transmission was interrupted in all African countries. The last case in Asia occurred in Bangladesh where variola major made its last stand. The last known case of smallpox in the world was reported from Somalia on 27 October 1977. If no more cases are discovered it will be possible, in two years from that date, to certify that smallpox has been eradicated from all areas of the world, and Member States of the World Health Organization will be able to celebrate an unprecedented victory for preventive medicine. The complete eradication of smallpox is not only the liberation of the world from one of its most dangerous diseases, but also provides an example of what can be achieved when countries throughout the world join together with a common aim.

Africa↗

Trsmission of smallpox by contact and by aerosol routes in Macaca irus.

Smallpox is believed not to occur naturally in species other than man. However, reports of several epizootics of an exanthematous disease, similar to smallpox, in wild monkeys have raised the question of a simian reservoir. If such a reservoir for smallpox exists, the eradication of this disease from the world would be a difficult or impossible task. Transmission of smallpox in Macaca irus has been studied to determine whether transmission occurs and if infection chains can be maintained by this species.Transmission was consistently accomplished by both contact and aerosol routes. In the contact transmission studies, the smallpox infection was maintained through 6 passages but was lost with the seventh passage. The virulence of the virus did not appear to increase as the virus was serially passed in monkeys. Continuing studies of the possible occurrence of smallpox and of monkeypox in simian populations are warranted.

Aerosols↗

The effect of measles infection and of vaccination with certain live vaccines upon humoral immunity to smallpox.

The results of a study of the effect of measles infection and of vaccination with live measles vaccine (Leningrad-16 strain) on the level of humoral immunity to smallpox in children previously vaccinated against smallpox show that a measles infection markedly depressed the humoral immunity to smallpox, which did not reach its initial level in the 2-3 months of observation that followed clinical recovery. Immunoglobulin administered during the incubation period did not prevent the fall in smallpox antibody titres.It was also found that live measles vaccine, however intense the clinical reaction to the vaccination may be, does not have any marked effect on the smallpox antibody level in children. Similarly, 2 administrations of live trivalent poliomyelitis vaccine had no effect on humoral immunity to smallpox.

Child↗

The Future of Smallpox Vaccination: is MVA the key?

Eradication of the smallpox virus through extensive global vaccination efforts has resulted in one of the most important breakthroughs in medical history, saving countless lives from the severe morbidity and mortality that is associated with this disease. Although smallpox is now extinct in nature, laboratory stocks of this virus still remain and the subject of smallpox vaccination has gained renewed attention due to the potential risk that smallpox may be used as a biological weapon by terrorists or rogue states. Despite having the longest history of any modern vaccine, there is still much to be learned about smallpox vaccination and the correlates of protection remain to be formally defined. This Commentary will discuss the strengths and weaknesses of traditional smallpox vaccination in comparison with immunization using modified vaccinia virus Ankura (MVA), a non-replicating virus with a strong safety record but weakened immunogenicity.

Editorial↗

Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense.

OBJECTIVE: To develop consensus-based recommendations for measures to be taken by medical and public health professionals following the use of smallpox as a biological weapon against a civilian population. PARTICIPANTS: The working group included 21 representatives from staff of major medical centers and research, government, military, public health, and emergency management institutions and agencies. Evidence The first author (D.A.H.) conducted a literature search in conjunction with the preparation of another publication on smallpox as well as this article. The literature identified was reviewed and opinions were sought from experts in the diagnosis and management of smallpox, including members of the working group. CONSENSUS PROCESS: The first draft of the consensus statement was a synthesis of information obtained in the evidence-gathering process. Members of the working group provided formal written comments that were incorporated into the second draft of the statement. The working group reviewed the second draft on October 30, 1998. No significant disagreements existed and comments were incorporated into a third draft. The fourth and final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: Specific recommendations are made regarding smallpox vaccination, therapy, postexposure isolation and infection control, hospital epidemiology and infection control, home care, decontamination of the environment, and additional research needs. In the event of an actual release of smallpox and subsequent epidemic, early detection, isolation of infected individuals, surveillance of contacts, and a focused selective vaccination program will be the essential items of an effective control program.

Biological Warfare↗

The new cell culture smallpox vaccine should not be offered to the general population.

Cell based smallpox vaccines are to be welcomed, but any decision to vaccinate whole populations must await firstly better intelligence about the gravity of the threat from bioterrorists, including their ability to release smallpox in such a way that wide dissemination could take place; secondly evidence that vaccines grown in cell culture are protective and safe; and thirdly that the vaccines would be generally acceptable and their introduction would not compromise the rest of national immunisation programmes. Smallpox vaccination should not be offered to the general population until these uncertainties have been resolved, by which time bioterrorism might possibly have been overcome or the development of antiviral treatment might have made renewed smallpox vaccination unnecessary. Meanwhile, preparations for rapid deployment of the historically well-tried containment measures at the epicentres of any smallpox release should proceed, their effectiveness should be tested, and their adequacy kept under review.

Bioterrorism↗

Mass smallpox immunization program in a deployed military setting.

A prospective, observational study of immunizing over 6,000 active-duty troops against smallpox in a 4-week time period was conducted. It focused on the complications of the vaccine and lost workdays. Comparison is made to the complication rates of earlier smallpox immunization programs. In direct response to elevated bioterrorism concerns, the United States military and civilian first-responders have begun a mass smallpox immunization program. This article reviews the experience with implementing such a program in a forward-deployed location while maintaining military readiness. The objectives were to assess the impact of a mass smallpox immunization program on operations in a forward-deployed military setting and to comment on lessons learned in the screening and immunization process. From January 16, 2003 through February 11, 2003 6,002 members of the United States military were immunized in a forward-deployed location. Information was obtained using data from the Air Force Complete Information Tracking Application (AFCITA) and the Global Expeditionary Medical System (GEMS) we plan to calculate the following Main Outcome Measures data: (1)Percentage of individuals eligible to receive the vaccine, (2) Vaccine take rate by CDC criteria, (3) Number of serious complications, (4) Number of life-threatening complications, and (5) Number of manpower days lost as a complication of the vaccine. A total of 6,739 individuals were screened for vaccination with 6,348 (94%) remaining eligible for the vaccine. The "take" rate for the vaccine was 98.6% as per Centers for Disease Control and Prevention (CDC) criteria. The immunization program produced an additional 156 medical visits (2.6% of patients required one visit). A total of 0.55% of immunized individuals lost one or more work days. In conclusion, a mass smallpox vaccination program can be effectively administered in a forward-deployed military setting despite high tempo military operations with minimal operational impact.

Humans↗

Smallpox containment updated: considerations for the 21st century.

The emergence and re-emergence of infectious diseases since the eradication of smallpox has had a direct impact on preparedness for a deliberately-caused smallpox outbreak, should one occur. The emergence of HIV has placed restrictions on the safe and effective use of smallpox vaccines and made the need for vaccinia immune globulin important for outbreak control. At the same time, the threat of international spread of emerging and re-emerging infections has prompted global investments in surveillance and response mechanisms such as the Global Outbreak Alert and Response Network (GOARN), a mechanism that would enhance the world's collaboration in smallpox containment as it did during the recent outbreak of SARS. Though global preparedness for a deliberately-caused smallpox outbreak has increased with the creation of GOARN, it does not replace the need for increased national public health investment to expand surge capacity for the management of patients and their contacts and to strengthen emergency communication networks to ensure effective response.

Bioterrorism↗

Smallpox and pregnancy: from eradicated disease to bioterrorist threat.

Health care personnel must be prepared for the threat of bioterrorism. Our objective is to educate primary care providers, obstetricians in particular, in the prevention, diagnosis, and treatment of smallpox. Smallpox poses a particularly serious threat because of its high case-fatality rate in unvaccinated populations (no one younger than 25 years has been vaccinated, and older persons have little remaining residual immunity). Routine nonemergency smallpox vaccination is restricted to laboratory staff working with smallpox-related viruses. Under these circumstances, contraindications to vaccination are pregnancy, immunodeficiency, exfoliative skin conditions (eczema), and allergy to vaccine components. In case of an intentional release of the smallpox virus, those directly exposed and their close contacts must be vaccinated and isolated. Under such emergency circumstances, pregnant women exposed to the variola virus should be vaccinated because of the lethality of the disease during pregnancy. Currently, there is a limited supply of vaccine available.

Adult↗

Smallpox vaccine and its stockpile in 2005.

Smallpox vaccine was the most important tool in the successful eradication of smallpox. In 1980, this achievement made it possible for all nations to cease smallpox vaccination. However, the threat of smallpox bioterrorism has made it necessary to reconsider the need for vaccination. Over the past 3 years, many nations have set up action plans for use in the event of such an attack. The setting up of these plans was not simple. Several factors needed to be considered, including the judgement of risk, vaccine complications, conventional vaccines versus new vaccines, optimal stockpile of smallpox vaccine, and its use for different target populations in different emergency situations. Here, I review measures taken by the USA, Japan, and other nations, and discuss likely national and global efforts in 2005 and subsequently, in view of the fact that half of the world's population is now apparently unvaccinated and that this proportion will increase with time.

Europe↗

Can postexposure vaccination against smallpox succeed?

What can be achieved by the vaccination of individuals exposed to smallpox virus after release of the virus by bioterrorists? There exist several past sources of information on postexposure vaccination failures from which it may be inferred that prompt vaccination of contacts (i.e., individuals exposed to smallpox) often prevented smallpox altogether, that revaccination of previously vaccinated individuals at any time during the first week of the incubation period was largely protective, and that revaccination done even as late as the second week of the incubation period attenuated disease and prevented most deaths. Primary vaccination done within 4 days of exposure was also usually protective at least from serious illness. Modern contingency planning against the release of smallpox virus during a bioterrorist attack should therefore include the capacity for prompt tracing and (re)vaccination of all contacts. Because a growing majority of the population has never before been vaccinated against smallpox and, so, may be unreachable within 4 days, anticipatory vaccination of sections of the populations of potential target countries should be considered if the bioterrorist threat intensifies.

Bioterrorism↗

Prediction of residual immunity to smallpox, by means of an intradermal skin test with inactivated vaccinia virus.

BACKGROUND: Intradermal skin testing with inactivated vaccinia virus was evaluated for its prediction of residual immunity to smallpox. METHODS: An intradermal skin test was performed with heat-inactivated Lancy-Vaxina. Two days later, the subjects were vaccinated with Lancy-Vaxina. The skin lesions resulting from this vaccination were used as a surrogate marker of residual immunity to smallpox, and this surrogate marker was compared with the available indicators of susceptibility to smallpox. RESULTS: Of the 83 subjects, 30 (36%) showed the typical primary response after vaccination (i.e., absence of residual immunity), whereas 34 (41%) showed the typical revaccinee's response (i.e., presence of residual immunity); the remaining 19 (23%) had an indeterminate response and were excluded from the final analysis. The sensitivity and specificity of the intradermal skin test (induration size, >or=4 mm) for prediction of residual immunity to smallpox were 85% and 97%, respectively, whereas those of a positive vaccinia-specific interferon- gamma -producing T cell response (>or=9 spot forming cells/10(6) peripheral-blood mononuclear cells) were 32% and 63%, respectively, and those of a positive neutralizing antibody (titer, >or=1 : 8) were 79% and 80%, respectively. CONCLUSION: The intradermal skin test appears to be a simple and reliable method for prediction of residual immunity to smallpox.

Adult↗

Should smallpox vaccine be tested in children?

Following the terrorist attacks on 11 September 2001 there has been increased concern about bioterrorism, much of it focused on smallpox. Routine smallpox vaccination in the USA was discontinued in 1972 and most US citizens are susceptible to smallpox. The last natural case of smallpox occurred in 1978 but the virus has been stocked in freezers. If a terrorist had access to stored smallpox virus a release could produce a chaotic situation. In response the USA has developed a program for vaccinating adults but children have been left out. The only available vaccine has recently been tested in adults but a proposal for testing children was not approved. We need to know if available vaccines are safe for children so children can be safely and effectively vaccinated in an emergency situation.

Adolescent↗

Unraveling the structure of the variola topoisomerase IB-DNA complex: a possible new twist on smallpox therapy.

Smallpox is a serious and highly contagious disease that is caused by the variola virus. It is one of the most severe infectious human diseases known, with mortality rates as high as 30%. A successful worldwide vaccination program led to the eradication of smallpox in 1980. However, the high transmission rate of variola virus, coupled with the deadly nature of smallpox, makes this virus a potentially devastating weapon for bioterrorism. Currently, there is no specific treatment for smallpox. However, a recent article on the structure of a variola topoisomerase IB-DNA complex provides an intriguing starting point for the rational design of drugs with potential activity against smallpox.

Animals↗

Smallpox: an update for nurses.

The global eradication of smallpox in the late 1970s was a major achievement of the 20th century and brought out the best in science and public health. Prior to eradication, smallpox was a devastating disease with an overall mortality rate of approximately 5% to 30% for the most common form of the disease depending on vaccination status and the clinical presentation. The more severe forms of smallpox (i.e., flat and hemorrhagic type) had case fatality rates of approximately 96% to 100%. Currently, there is heightened international concern regarding the potential use of the smallpox virus as an agent for bioterrorism. Therefore, it is imperative that health care workers become familiar with clinical aspects of this disease as part of the national efforts to ensure homeland security. This article reviews the history, disease progression, and adverse events of smallpox; immunization practices; and nursing considerations.

Bioterrorism↗

Safeguarding our nation's children: the diagnosis, management, and containment of smallpox in infants and children.

Smallpox continues to be a major national health concern as it poses the most serious bioterrorist threat to the US population at this time. Due to similarities in clinical presentation, smallpox may easily be confused with varicella (chickenpox) in young children. Management of a large-scale outbreak of smallpox in young children would require an intensive health care response. In addition, the current debate concerning potential revisions to the Centers for Disease Control and Prevention (CDC) interim guidelines for vaccination against smallpox has significant health implications for high-risk children and infants. As such, the diagnosis, management, and containment of smallpox in infants and children deserve special consideration.

Bioterrorism↗

Individual-based computational modeling of smallpox epidemic control strategies.

In response to concerns about possible bioterrorism, the authors developed an individual-based (or "agent-based") computational model of smallpox epidemic transmission and control. The model explicitly represents an "artificial society" of individual human beings, each implemented as a distinct object, or data structure in a computer program. These agents interact locally with one another in code-represented social units such as homes, workplaces, schools, and hospitals. Over many iterations, these microinteractions generate large-scale macroscopic phenomena of fundamental interest such as the course of an epidemic in space and time. Model variables (incubation periods, clinical disease expression, contagiousness, and physical mobility) were assigned following realistic values agreed on by an advisory group of experts on smallpox. Eight response scenarios were evaluated at two epidemic scales, one being an introduction of ten smallpox cases into a 6,000-person town and the other an introduction of 500 smallpox cases into a 50,000-person town. The modeling exercise showed that contact tracing and vaccination of household, workplace, and school contacts, along with prompt reactive vaccination of hospital workers and isolation of diagnosed cases, could contain smallpox at both epidemic scales examined.

Adult↗

Smallpox vaccine: the good, the bad, and the ugly.

Smallpox inarguably shaped the course of human history by killing countless millions in both the Old World and the New World. Dr. Edward Jenner's discovery of vaccination in the late 18th century, and the global eradication of smallpox in the 1970s, rank among the greatest achievements in human history. Amidst recent growing concerns about bioterrorism, smallpox vaccination has resurfaced from the history books to become a topic of major importance. Inoculation with vaccinia virus is highly effective for the prevention of smallpox infection, but it is associated with several known side effects that range from mild and self-limited to severe and life-threatening. As the United States moves forward with plans to vaccinate selected health care workers and the military, and perhaps offer the vaccination to all citizens in the future, it is important to fully understand and appreciate the history, risks, and benefits of smallpox vaccination.

Humans↗