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Maxi-Vac: planning mass smallpox vaccination clinics.

To help emergency response planners prepare for conducting mass smallpox vaccination clinics, the Centers for Disease Control and Prevention researchers developed the Maxi-Vac software (available free from http://www.bt.cdc.gov/agent/smallpox/vaccination/maxi-vac/index.asp); it assists in designing a mass vaccination clinic with up to 9 separate stations. Users select clinic characteristics that best represent their intended setup, and the software displays the optimal placement of staff to vaccinate the maximum number of people possible. For example, for a clinic that will have 3 physicians, 30 nurses, and 10 other staff members available per 12-hour shift, Maxi-Vac shows how these staff members can best be deployed, and it projects the maximum number of persons who can be vaccinated at 8,245 per 24-hour period. Users can alter the number of available staff, which will probably be the greatest limiting factor, to determine the impact on the number of persons vaccinated per 24-hour period.

Bioterrorism↗

The sequence of camelpox virus shows it is most closely related to variola virus, the cause of smallpox.

Camelpox virus (CMPV) and variola virus (VAR) are orthopoxviruses (OPVs) that share several biological features and cause high mortality and morbidity in their single host species. The sequence of a virulent CMPV strain was determined; it is 202182 bp long, with inverted terminal repeats (ITRs) of 6045 bp and has 206 predicted open reading frames (ORFs). As for other poxviruses, the genes are tightly packed with little non-coding sequence. Most genes within 25 kb of each terminus are transcribed outwards towards the terminus, whereas genes within the centre of the genome are transcribed from either DNA strand. The central region of the genome contains genes that are highly conserved in other OPVs and 87 of these are conserved in all sequenced chordopoxviruses. In contrast, genes towards either terminus are more variable and encode proteins involved in host range, virulence or immunomodulation. In some cases, these are broken versions of genes found in other OPVs. The relationship of CMPV to other OPVs was analysed by comparisons of DNA and predicted protein sequences, repeats within the ITRs and arrangement of ORFs within the terminal regions. Each comparison gave the same conclusion: CMPV is the closest known virus to variola virus, the cause of smallpox.

Animals↗

Smallpox vaccination site complications.

The typical resolution of the smallpox vaccination site is a smooth scar, a sequela that is discussed during prevaccination counseling. In addition, other types of lesion may develop at the scar site, including short- or long-term benign and malignant changes, as reviewed below. Although current recommendations do not discuss potential scar complications or scar surveillance, healthcare providers would benefit from an awareness of these potential complications, and should consider periodic scar surveillance as part of a general physical examination.

Cicatrix↗

Genome sequence diversity and clues to the evolution of variola (smallpox) virus.

Comparative genomics of 45 epidemiologically varied variola virus isolates from the past 30 years of the smallpox era indicate low sequence diversity, suggesting that there is probably little difference in the isolates' functional gene content. Phylogenetic clustering inferred three clades coincident with their geographical origin and case-fatality rate; the latter implicated putative proteins that mediate viral virulence differences. Analysis of the viral linear DNA genome suggests that its evolution involved direct descent and DNA end-region recombination events. Knowing the sequences will help understand the viral proteome and improve diagnostic test precision, therapeutics, and systems for their assessment.

DNA, Viral↗

Virus particle content of smallpox vaccines.

Calf lymph smallpox vaccines contain too much extraneous debris for an accurate assessment of their virus particle content. The process of partial purification of the vaccine utilizing enzymatic digestion by chymotrypsin, subtilisin, and collagenase solubilized enough debris to permit electron microscopic virus particle count. Enzyme treatment did not degrade or destroy the virus nor did it reduce the infective titer. Commercial vaccines studied ranged in virus content from 1.89 x 10(9) to 1.09 x 10(11) virus particles/ml. The pocking efficiencies on the chorioallantoic membrane of some of these vaccines varied from 200 to 1,200 virus particles per pock-forming unit.

Agar↗

Experience with electron microscopy in the differential diagnosis of smallpox.

The usefulness of negative-contrast electron microscopy in the rapid differential diagnosis of poxvirus and herpesvirus exanthems is described in this study of 301 specimens from patients with vesicular exanthematous diseases. Specimens from patients with smallpox, various forms of vaccination complications, varicella, zoster (shingles), and herpes simplex are included in this evaluation. Electron microscopy, when applied to the study of lesion material, was found to be more sensitive than the classical techniques of virus isolation in the diagnosis of both poxvirus and herpes/varicella virus infections. However, since specific identification of a virus within a group cannot be made morphologically by electron microscopy, it is recommended that both electron microscopy and virus isolation methods be employed for the routine differential diagnosis of vesicular exanthematous diseases in the reference diagnostic laboratory.

Animals↗

Cell-mediated immune responses to smallpox vaccination.

We report that vaccine dilution (1:1 or 1:10) and previous vaccinia virus vaccination status had no significant effect on cell-mediated immune responses (i.e., the immediate vaccinia virus-specific gamma interferon-producing T-cell response measured by enzyme-linked immunospot assay) 1 month after smallpox vaccination (Lancy-Vaxina; Berna Biotech, Switzerland).

Adult↗

Experiments on terminal disinfection by formaldehyde vapor in the case of smallpox.

The usually recommended terminal disinfection by formaldehyde vapor is unable to completely inactivate vaccinia viruses embedded in scabs. In view of our results, we recommend doubling the concentration of formaldehyde (10 g of formaldehyde per m3 of space) and prolonging the time of exposure to 24 h for terminal disinfection in the case of smallpox. Subsequent disinfection by scrubbing assumes special importance, since no complete inactivation of the scabs occurs.

Animals↗

Laboratory confirmation of generalized vaccinia following smallpox vaccination.

The reinitiation of smallpox vaccination has renewed interest in implementing modern diagnostic methods to assess orthopoxvirus infection and adverse events following vaccination. We report here the laboratory confirmation of vaccinia virus in pustular lesions of a healthy adult vaccinee by use of a two-tier algorithm incorporating TaqMan PCR and electron microscopy.

Adult↗

Clinical and immunological study of percutaneous revaccination in children who originally received smallpox vaccine subcutaneously.

In a large multicenter smallpox vaccination study carried out from 1970 to 1973, it was found that 39% of children who were initially immunized by the subcutaneous route and then challenged percutaneously with a standard vaccination did not have measurable neutralizing antibody upon follow-up. Because of this finding, a percutaneous revaccination study was conducted at the St. Louis study center in 1975 and 1976. There were four study groups, which were composed on the basis of route of primary immunization (subcutaneous or percutaneous) and whether neutralizing antibody was detectable following the original percutaneous challenge immunization. Of 52 children revaccinated, all but four had accelerated reactions. There was no difference in size of lesions or day of maximum erythema among the four study groups. Only 66% of children originally vaccinated subcutaneously who did not have postchallenge neutralizing antibody had measurable neutralizing antibody following revaccination. Transformation studies with vaccinia viral antigen before and after revaccination were performed on lymphocytes from 50 children. There was no appreciable differences in responses either before or after revaccination when the four groups were compared. However, the mean stimulation ratio for the total group increased from 2.4 before revaccination to 4.6 3 weeks later. In primary subcutaneous vaccine recipients without pre-revaccination neutralizing antibody, lymphocyte transformation correlated directly with the neutralizing antibody response.

Antibodies, Viral↗

Averting disaster: the Hudson's Bay Company and smallpox in western Canada during the late eighteenth and early nineteenth centuries.

During the late eighteenth and early nineteenth centuries the Hudson's Bay Company served as a de facto public health agency across western Canada. Among its biggest challenges was combating the smallpox epidemics that periodically threatened the Aboriginal people of the region. Initially, the Company's employees turned to quarantine over variolation in order to prevent the spread of the disease to Hudson Bay in the summer of 1782. Although well thought-out, ultimately this policy proved unsuccessful. Within thirty years the HBC had turned to the newly discovered vaccination, a strategy that was to prove far more effective in fighting the disease. By the late 1830s the Company was able to mount an effective vaccination campaign that covered much of western Canada.

Canada↗

Imagining inoculation: Smallpox, the body, and social relations of healing in the eighteenth century.

People in colonial New York adopted inoculation for smallpox as quickly and as thoroughly as did people anywhere in the British Atlantic world. Such adoption was not dependent upon the authority of formal medicine, but rather upon everyday epistemology. Inoculation became accepted as local knowledge because ordinary New Yorkers integrated it imaginatively into common ideas about the body and disease, reconceptualized its theological meaning, and incorporated it into familiar social relations of healing.

Culture↗

Uncertain benefit: the public policy of approving smallpox vaccine research.

Without an accurate assessment of the prospect of bioterrorist attack, it is especially challenging to evaluate the protocols for testing smallpox vaccines in the pediatric population. Usual regulatory mechanisms cannot shepherd research protocols with benefits that can only be characterized as "uncertain" in the face of more than minimal risk. When a protocol is placed in a government forum for analysis, the public has a unique opportunity to debate the balancing of research risks and benefits on behalf of children who are unable to assent to research themselves, as well as to express views about vaccination policy broadly. This model for review of pediatric research that may be without benefit will be especially important as challenging studies of various vaccines against a range of infectious properties, such as anthrax and severe acute respiratory syndrome (SARS), emerge.

Biomedical Research↗

With demand lacking, smallpox vaccine expiring.

The Bush administration's campaign to vaccinate health care workers against smallpox has proved unpopular, largely because of concerns about the safety of the vaccine and who would pay for any needed medical treatment. State health departments have destroyed about 61,000 doses of expired vaccine--substantially more than the number actually administered.

Humans↗

Negotiating with Dharma Pinnu: towards a social history of smallpox in colonial Orissa.

This paper explores the social complexities associated with the history of smallpox in colonial Orissa in Eastern India. It focuses on tribal communities while taking into account their interactions with non-tribal communities and colonialism. This research grapples with the phenomenon of of the Hinduisation of tribes and the way this implies an acceptance as well as a rejection of the various aspects of non-tribal, Hindu society. Thus, I examine the specific elements of non-tribal groups inoculation, black magic, and subversive cults, demonstrating the close affinities some of these features have with tribal communities.

Colonialism↗

"Lo! The poor Indian!" colonial responses to the 1862-63 smallpox epidemic in British Columbia and Vancouver Island.

The smallpox epidemic that swept through the colonies of Vancouver Island and British Columbia in 1862-63 was particularly devastating to the First Nations of the region. Colonists responded to the developments with a mixture of pity, revulsion, a smug sense of inevitability, and, above all, an overriding concern for their own self-interest. The colonial population may not have consciously attempted to devastate the First Nations populations, but their frequently negative attitudes towards them ensured that actions to prevent this occurrence were sporadic, poorly planned, counterproductive, or simply minimal.

Attitude↗

Smallpox models as policy tools.

Mathematical models can help prepare for and respond to bioterrorism attacks, provided that their strengths and weaknesses are clearly understood. A series of initiatives within the Department of Health and Human Services brought modelers together with biologists and epidemiologists who specialize in smallpox and experts in bioterrorism response and health policy and has led to the parallel development of models with different technical approaches but standardized scenarios, parameter ranges, and outcome measures. Cross-disciplinary interactions throughout the process supported the development of models focused on systematically comparing alternate intervention strategies, determining the most important issues in decision-making, and identifying gaps in current knowledge.

Bioterrorism↗