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Treating patients with smallpox in the operating room.

Recent events around the world have emphasized the need for health care facilities to prepare to deal with biological threats, including smallpox. At Walter Reed Army Medical Center, Washington, DC, administrators recognized the need for a policy on handling patients with smallpox in the OR and asked a group of students to create a template policy for care of patients with smallpox in need of surgery. This article provides a brief history of smallpox, concerns surrounding smallpox today, and smallpox characteristics with which perioperative personnel should be familiar, as well as a guideline for treating patients in the OR who have smallpox.

Disaster Planning↗

Eosinophilic-lymphocytic myocarditis after smallpox vaccination.

Smallpox is an eradicated viral disease that has re-emerged as a potential bioterrorism threat. Smallpox vaccination was historically the most effective defence measure against wild smallpox virus. The risk of myopericarditis after vaccination might limit this option. We report a case of biopsy-proven eosinophilic-lymphocytic myocarditis diagnosed in vivo with histological evidence for eosinophil-mediated cardiac myocyte necrosis shortly after smallpox vaccination. Furthermore, we report a beneficial haemodynamic response to high-dose corticosteroids. A better understanding of the aberrant immune mechanism of myocyte injury after smallpox vaccination might improve the risk/benefit assessment for people considering smallpox vaccination and better smallpox vaccines in the future.

Adult↗

Smallpox vaccination and risk of allergy and asthma.

BACKGROUND: It has been proposed that childhood vaccinations may influence the development of allergy. Atopy and allergic diseases have increased after routine smallpox vaccination was stopped in the 1970s. OBJECTIVE: We examined whether administration of smallpox vaccination during childhood was associated with a decreased risk of atopy, allergic rhinitis, and asthma. METHODS: The occurrence of atopy, allergic rhinitis, and asthma was studied in nearly 2000 women participating in a national birth cohort study. Detailed information on smallpox vaccination was available from school health records. Atopic status was assessed serologically by a specific response to 11 common inhalant allergens by using serum samples obtained from the women during the period 1997 to 2001. Information on allergic rhinitis and asthma was available from telephone interviews. RESULTS: We found no association between having been vaccinated against smallpox in childhood and risk of atopy or allergic rhinitis. Smallpox vaccination was associated with a slightly decreased risk of asthma. There was no association between age at smallpox vaccination and risk of atopy, allergic rhinitis, or asthma. Adjusting for birth cohort, sibship size, age of the woman's mother at birth, and social class in childhood did not change these results. CONCLUSION: Our findings do not suggest that childhood vaccination against smallpox, even if given early in life, influences the development of atopy or allergic rhinitis. The association with asthma should be interpreted with caution and needs further study.

Adolescent↗

[Development and trial of a new system of active search for the intensive suppression of smallpox outbreaks in India].

In carrying out emergency smallpox control campaign in Uttar Pradesh State of India in the spring of 1973 the authors developed and first tried in a large-scale field work a new system of smallpox control consisting in repeated weekly search of cases in the entire territory of the affected district followed by intensive suppression of the discovered foci of the disease by vaccination. This new strategy for smallpox eradication was officially adopted since October, 1973, in the smallpox eradication programme in India. The new system was widely used for smallpox control in the last smallpox-endemic countries of the Hindustan peninsula which significantly speeded up smallpox eradication.

Disease Outbreaks↗

Superinfection following smallpox vaccination (Vaccinia), United States: surveillance January 2003 through January 2004.

BACKGROUND: Superinfection is an adverse event following smallpox vaccination. The clinical presentation is similar to that of a large normal vaccine reaction or "robust take," and the frequency is unknown. METHODS: We retrospectively reviewed all reported severe local reactions consistent with superinfection among United States civilian smallpox vaccinees from January 2003 through January 2004. We applied a standard case definition and estimated the frequency of superinfection following smallpox vaccination. RESULTS: We identified 48 reported cases for further review among 39,350 [corrected] smallpox vaccinees. Two (4%) of the 48 reported cases met the case definition for superinfection; neither of the patients had a pathogenic organism isolated from their infection site. Both were treated with antibiotics and resolved their infection. Of the 46 cases determined not to be superinfection, 41 (89%) were temporally consistent with a large normal vaccine reaction. Thirty (75%) of 40 reported case patients for whom data were available received antibiotic therapy. CONCLUSIONS: Superinfection following smallpox vaccination is rare. Most of the reported superinfection cases were probably large normal smallpox vaccine reactions. Educating providers about the normal response to smallpox vaccine may decrease the overdiagnosis of superinfection and the unnecessary use of antimicrobials.

Adult↗

Myopericarditis following smallpox vaccination among vaccinia-naive US military personnel.

CONTEXT: In the United States, the annual incidence of myocarditis is estimated at 1 to 10 per 100,000 population. As many as 1% to 5% of patients with acute viral infections involve the myocardium. Although many viruses have been reported to cause myopericarditis, it has been a rare or unrecognized event after vaccination with the currently used strain of vaccinia virus (New York City Board of Health). OBJECTIVE: To describe a series of probable cases of myopericarditis following smallpox vaccination among US military service members reported since the reintroduction of vaccinia vaccine. DESIGN, SETTING, PARTICIPANTS: Surveillance case definitions are presented. The cases were identified either through sentinel reporting to US military headquarters surveillance using the Defense Medical Surveillance System or reports to the Vaccine Adverse Event Reporting System using International Classification of Diseases, Ninth Revision. The cases occurred among individuals vaccinated from mid-December 2002 to March 14, 2003. MAIN OUTCOME MEASURE: Elevated serum levels of creatine kinase (MB isoenzyme), troponin I, and troponin T, usually in the presence of ST-segment elevation on electrocardiogram and wall motion abnormalities on echocardiogram. RESULTS: Among 230,734 primary vaccinees, 18 cases of probable myopericarditis after smallpox vaccination were reported (an incidence of 7.8 per 100,000 over 30 days). No cases of myopericarditis following smallpox vaccination were reported among 95,622 vaccinees who were previously vaccinated. All cases were white men aged 21 years to 33 years (mean age, 26.5 years), who presented with acute myopericarditis 7 to 19 days following vaccination. A causal relationship is supported by the close temporal clustering (7-19 days; mean, 10.5 days following vaccination), wide geographic and temporal distribution, occurrence in only primary vaccinees, and lack of evidence for alternative etiologies or other diseases associated with myopericarditis. Additional supporting evidence is the observation that the observed rate of myopericarditis among primary vaccinees is 3.6-fold (95% confidence interval, 3.33-4.11) higher than the expected rate among personnel who were not vaccinated. The background incidence of myopericarditis did not show statistical significance when stratified by age (20-34 years: 2.18 expected cases per 100,000; 95% confidence interval [CI], 1.90-2.34), race (whites: 1.82 per 100,000; 95% CI, 1.50-2.01), and sex (males: 2.28 per 100,000; 95% CI, 2.04-2.54). CONCLUSION: Among US military personnel vaccinated against smallpox, myopericarditis occurred at a rate of 1 per 12 819 primary vaccinees. Myopericarditis should be considered an expected adverse event associated with smallpox vaccination. Clinicians should consider myopericarditis in the differential diagnosis of patients presenting with chest pain 4 to 30 days following smallpox vaccination and be aware of the implications as well as the need to report this potential adverse advent.

Adult↗

Healthcare workers who elected not to receive smallpox vaccination.

BACKGROUND: The goal of the National Smallpox Vaccination Program was to vaccinate a cadre of healthcare workers and first responders who could care for smallpox patients in the event of an attack. METHODS: Using a convenience sample of health departments (n=49) and hospitals (n=60) in five states, we conducted a telephone interview between July 2003 and April 2004 of healthcare workers and first responders who chose not to receive smallpox vaccination. (Data were analyzed in 2004 and 2005.) RESULTS: The response rate was 63%. Of 1895 respondents, 723 (38.2%) reported having a contraindication, 280 (14.8%) reported being contraindicated because of a household member's condition, and 892 (47.0%) reported having no contraindication to smallpox vaccination. Among respondents with no contraindication, the leading reasons for nonvaccination were concerns about side effects (20.6%) and not feeling that the risk of outbreak was high enough (19.5%). More than half (54.8%) were somewhat or very concerned about having an adverse reaction to the vaccine; Hispanics, blacks, and Asians were significantly more likely than whites to be somewhat or very concerned about side effects. Less than one fifth (17.9%) reported that there was a policy to financially compensate employees who developed side effects from vaccination, and 40.7% reported that there was a policy to provide liability coverage to employees who transmitted vaccinia to a patient. CONCLUSIONS: Many people who chose not to receive smallpox vaccine perceived their personal risk-benefit balance as not favoring vaccination. The success of future smallpox vaccination efforts or vaccination against other bioterrorist health threats depends on addressing potential barriers to participation including compensation and liability issues, in addition to clearly communicating risks and benefits.

Adolescent↗

The myth of the medical breakthrough: smallpox, vaccination, and Jenner reconsidered.

A discussion of the particulars leading to the eradication of smallpox is pertinent to both investigators and the public as the clamor for more "breakthroughs" intensifies. The rational allocation of biomedical research funds is increasingly threatened by disease-advocacy groups and congressional earmarking. An overly simplistic view of how advances truly occur promises only to stunt the growth of researchers and research areas not capable of immediate great breakthroughs. The authors review the contributions of Jenner and his countless predecessors to give a more accurate account of how "overnight medical breakthroughs" truly occur-through years of work conducted by many people, often across several continents. In the public eye, few achievements are regarded with such excitement and awe as the medical breakthrough. Developments such as the discovery of penicillin and the eradication of polio and smallpox have each become a great story built around a singular hero. Edward Jenner, for example, is credited with discovering a means of safely conferring immunity to smallpox. The success of vaccination and subsequent eradication of this disease elevated Jenner to a status in medical history that is rivaled by few. However, the story of the eradication of smallpox does not start or end with the work of Jenner. Men such as Benjamin Jesty and Reverend Cotton Mather as well as unnamed physicians from tenth century China to eighteenth century Turkey also made critical contributions to the crowning achievement. Inoculation to prevent smallpox was commonplace in Europe for generations prior to Jenner's work. Jenner himself was inoculated as a child. In fact, vaccination with cowpox matter was documented in England over 20 years prior to Jenner's work. The authors' review of primary and secondary sources indicates that although Jenner's contribution was significant, it was only one of many. It is extremely rare that a single individual or experiment generates a quantum leap in understanding; this "lone genius" paradigm is potentially injurious to the research process. Wildly unrealistic expectations can only yield unsuccessful scientific investigation, but small steps by investigators supported by an informed public can build toward a giant leap, as the story of smallpox eradication clearly demonstrates.

History, 16th Century↗

[The threat of smallpox].

Smallpox is a highly contagious disease mainly transmitted by aerosols with a high case-fatality. The smallpox virus has evolved from a long adaptation to humans during Evolution, explaining that the virus is highly specific for humans and nonpathogenic for animals. Smallpox was eradicated in 1977 and vaccination was abandoned in the 1980's. This virus is a dreadful potential biological weapon since the reemergence of smallpox on the planet might be expected to be devastating, due to its high 'contagiosity', which would rapidly spread in naive populations, especially those living in urban areas, and worldwide through air travels. There is no anti-viral treatment and vaccine is active in the first four days post-exposure. Today, the stocks of smallpox virus constitute one of the most dangerous threats for humanity. There is a need for improving the safety of the vaccine and to reconsider the preventive strategy to face a possible attack by smallpox virus.

Bioterrorism↗

Smallpox vaccination and patients with human immunodeficiency virus infection or acquired immunodeficiency syndrome.

Smallpox vaccination strategies are evolving rapidly and have important implications for human immunodeficiency virus (HIV)-infected persons. Cell-mediated immunity is important for controlling both smallpox and vaccinia. For smallpox, the concern is a substantial increase in the associated mortality rate, which is 30% among healthy persons. For smallpox vaccination, the concern is progressive vaccinia, which is usually lethal but relatively uncommon. The risks associated with both smallpox and vaccinia viruses probably correlate with CD4 cell count, and, as a corollary, the best protection against infection with each is presumably immune reconstitution. It appears that all vaccinations will be voluntary, with 2 recommendations: (1) HIV-infected persons will be advised to decline preemptive vaccination, and (2) in the event of a bioterrorism attack involving smallpox, HIV-infected patients with exposures will be advised to receive vaccine.

Acquired Immunodeficiency Syndrome↗

Smallpox revisited?

This article reviews the history of smallpox and ethical issues that arise with its threat as a biological weapon. Smallpox killed more people than any infectious disease in history--and perhaps three times more people in the 20th Century than were killed by all the wars of that period. Following a WHO-sponsored global vaccination campaign, smallpox was officially declared eradicated in 1980. It has since been revealed that the Soviet Union, until its fall in the early 1990s, manufactured tens of tons of smallpox for military purposes. A worry is that some of this may have fallen into the hands of "rogue" nations or terrorists. Current U.S. debate questions whether smallpox vaccine should therefore be made available to the American public, which--like the rest of the world--now lacks immunity. Because the vaccine is considerably dangerous, public dialogue cannot resolve this matter if evidence material to the likelihood of attack is classified (i.e. secret). I conclude by recommending numerous future areas for ethics research related to the weaponization of smallpox.

Biological Warfare↗

Oncology nursing implications related to smallpox bioterrorism preparations.

Although smallpox was globally eradicated in 1977, the current threat of smallpox as a bioterrorism agent is unknown. Based on intelligence reports, the U.S. government and public health sectors have recommended smallpox vaccination for very select individuals. Patients with cancer are at particular risk for complications from the smallpox vaccine because of potential immunosuppression. Vaccinated nurses caring for these patients also need to take special precautions because of the possibility of secondary transmission of this live vaccine to patients. This article reviews background information on bioterrorism, the presentation and clinical features of smallpox, contraindications to the smallpox vaccine, and implications for oncology nurses.

Bioterrorism↗

Countermeasures to the bioterrorist threat of smallpox.

Variola, the agent of smallpox, is a bioterrorist threat, as is monkeypox virus, which also occurs naturally in Africa. Development of countermeasures, in the form of improved vaccines, antiviral drugs, and other therapeutic strategies are a high priority. Recent advances in molecular biology and in animal model development have provided fresh insight into the virulence determinants for smallpox and the pathophysiology of disease. The complex replication cycle for orthopoxviruses, and the pivotal role for viral-specific immunomodulatory proteins which contribute to escape from immunologic surveillance, provide many unique targets for therapeutic intervention. The "toxemia" of smallpox has been elucidated in part by variola-infected primate studies which revealed the central role of apoptosis and the evolution of a cytokine storm leading to hemorrhagic diathesis, resembling fulminent "black" smallpox. This suggests a potential role for therapeutic strategies developed for septic shock, in treatment of smallpox. Drugs licensed for other viruses which share molecular targets with orthopoxviruses (e.g. Cidofovir) or cancer drugs (e.g. Gleevec and other tyrosine kinase inhibitors) have immediate application for treatment of smallpox and monkeypox and provide leads for second generation drugs with higher therapeutic indices. Recent advances in identification of virulence determinants and immune evasion genes facilitate the design of alternative vaccines to replace live vaccinia strains that are unsuitable for a large proportion of individuals in a mass immunization campaign.

Animals↗

Expected adverse events in a mass smallpox vaccination campaign.

CONTEXT: Recent anthrax attacks in the United States have raised concern about the nation's vulnerability to a smallpox attack. Many strategies have been suggested to minimize the impact of such an attack, ranging from quarantine and vaccination of case contacts to resumption of routine vaccination. Before the latter strategy is adopted, an understanding of the likely consequences of mass vaccination is essential. COUNT: Number of adverse events resulting from two vaccination campaigns: vaccinating persons 1 to 29 years of age and vaccinating those 1 to 65 years of age. CALCULATION: Number of adverse events = incidence rate of adverse events x number vaccinated. We assumed 75% vaccine uptake in the target group (i.e., we estimated that about 25% of potential vaccine recipients would be excluded because they are, or have close contact with, individuals who have eczema or are immunocompromised). DATA SOURCE: Historical data on the incidence of adverse events from smallpox vaccination were identified by a literature search. Number vaccinated was drawn from the January 2000 U.S. Census estimate. RESULTS: Fever (<1 case per 5 vaccine recipients) and rash (<1 case per 100 vaccine recipients) would be the most common adverse events. Serious adverse events, including encephalitis (<3 cases per million) and death (<2 cases per million), although rare, would be more common than with other currently recommended vaccines. After excluding high-risk individuals and their contacts, we estimate that a vaccination strategy directed at people aged 1 to 29 years would result in approximately 1600 serious adverse events and 190 deaths. Vaccinating people aged 1 to 65 years would result in approximately 4600 serious adverse events and 285 deaths. LIMITATIONS: While advances in health care over the past three decades could mitigate vaccine complications, the increased number of unimmunized high-risk individuals (e.g., those with eczema or immune suppression) could increase complication rates. CONCLUSIONS: The decision to resume smallpox vaccination depends on weighing the likelihood of a smallpox attack and its anticipated mortality against expected harm from a mass immunization program. Smallpox vaccine has a higher complication rate than any other vaccine currently being used. Careful prevaccination exclusion of high-risk individuals and their close contacts would be essential to minimize complications of a mass vaccination campaign, although such exclusions necessarily mean that some proportion of the population will remain susceptible to smallpox.

Adolescent↗

[Confronting bioterrorism: Epidemiologic, clinical, and preventive aspects of smallpox].

The worldwide eradication of smallpox, a major achievement in public health, is currently threatened by the risk of bioterrorism. The debate on the destruction of the Variola virus in the two reference laboratories of the World Health Organization has dramatically switched to the preservation of the remaining virus after the September 2001 terrorist events in the U.S. along with the intentional release of Bacillus anthracis in the U.S. The risk of intentional release of Variola virus constitutes a minimal, yet possible risk. A smallpox epidemic could have a devastating impact due to its elevated morbidity and mortality that would inflict in non-immune human population, in addition to the ensuing panic and social unrest. Therefore, the development of national preparedness and response plans along with the availability of smallpox vaccine to be used in the post-exposure phase represent a fundamental part of the preventive efforts to cope with bioterrorism. Reestablishing a preventive vaccination program was recently recommended by the Advisory Committee on Immunization Practices (ACIP). However, the vaccine currently available has historically been associated with serious adverse reactions, even death. Thus, this recommendation has not been universally accepted. To counter an epidemic of smallpox, medical personnel in the frontline need to be prepared with updated smallpox information to identify, diagnose, isolate, and treat cases if a bioterrorist attack should occur. Herein we present an indepth review for health care personnel with relevant epidemiologic, clinical, and preventive information on smallpox.

Bioterrorism↗

Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions.

CDC and the U.S. Food and Drug Administration rely on state and local health departments, health-care providers, and the public to report the occurrence of adverse events after vaccination to the Vaccine Adverse Event Reporting System. With such data, trends can be accurately monitored, unusual occurrences of adverse events can be detected, and the safety of vaccination intervention activities can be evaluated. On January 24, 2003, the U.S. Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and local volunteers who might be first responders during a biologic terrorism event. As part of the DHHS Smallpox Preparedness and Response Program, CDC in consultation with experts, established surveillance case definitions for adverse events after smallpox vaccination. Adverse reactions after smallpox vaccination identified during the 1960s surveillance activities were classified on the basis of clinical description and included eczema vaccinatum; fetal vaccinia; generalized vaccinia; accidental autoinoculation, nonocular; ocular vaccinia; progressive vaccinia; erythema multiforme major; postvaccinial encephalitis or encephalomyelitis; and pyogenic infection of the vaccination site. This report provides uniform criteria used for the surveillance case definition and classification for these previously recognized adverse reactions used during the DHHS Smallpox Preparedness and Response Program. Inadvertent inoculation was changed to more precisely describe this event as inadvertent autoinoculation and contact transmission, nonocular and ocular vaccinia. Pyogenic infection also was renamed superinfection of the vaccination site or regional lymph nodes. Finally, case definitions were developed for a new cardiac adverse reaction (myo/pericarditis) and for a cardiac adverse event (dilated cardiomyopathy) and are included in this report. The smallpox vaccine surveillance case definitions presented in the report can be used in future vaccination programs to ensure uniform reporting guidelines and case classification.

Adverse Drug Reaction Reporting Systems↗

[The topicality of return to smallpox vaccination: problems and prospects].

Nowadays there are certain facts which evidence the necessity of return to smallpox vaccination in Russia, especially concerning people who will be engaged in the liquidation of the nidi of this infection, should such appear. Smallpox virus is kept in laboratories of some countries; there is a real threat of biological terrorism; population immunity to smallpox infection is virtually absent. Considering the present situation in development and production of smallpox vaccines and remedies against vaccine-related complications, the tactics of population vaccination in Russia may vary. The main problems concerning return to smallpox vaccination in Russia are the following: there are no modern schemes (schedules) of smallpox immunization; there are no currently available and safe vaccines for primary immunization of adults; there are no preparations for prevention and treatment of vaccine-related complications. Thus, the priority areas are: development of effective and safe oral adult vaccines for primary immunization; production of human and heterologous immune globulins and their storage.

Administration, Topical↗

Farewell to smallpox vaccination.

Man's first attempt to immunize susceptibles against smallpox infection was by variolation, a practice which could be traced back several thousand years. The attempt obviously failed to control the disease until Jenner discovered the effectiveness of cowpox vaccine during the late 18th century. However, it took an additional 180 years until the current smallpox vaccine--a modification of Jenner's vaccine--became fully effective, in terms of quality and usage during the global smallpox eradication campaign. The campaign appears to be on the threshold of success, which could well mean extinction of one of the most dangerous pathogens from the natural environment. If this is verified, we may say farewell to routine smallpox vaccination. The paper discusses different measures taken to ensure the quality and the use of smallpox vaccine in the best possible manner during the eradication campaign and, on its completion, the fate of smallpox vaccination.

Adolescent↗