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PubMed2005

Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge.

It is unknown whether smallpox vaccination would protect human immunodeficiency virus type 1 (HIV-1)-infected individuals, because helper CD4(+) cells, the targets of HIV-1 infection, are necessary for the induction of both adaptive CD8(+) cell and B cell responses. We have addressed this question in macaques and have demonstrated that, although smallpox vaccination is safe in immunodeficient macaques when it is preceded by immunization with highly attenuated vaccinia strains, the macaques were not protected against lethal monkeypox virus challenge if their CD4(+) cell count was <300 cells/mm(3). The lack of protection appeared to be associated with a defect in vaccinia-specific immunoglobulin (Ig) switching from IgM to IgG. Thus, vaccination strategies that bypass CD4(+) cell help are needed to elicit IgG antibodies with high affinity and adequate tissue distribution and to restore protection against smallpox in severely immunocompromised individuals.

Animals↗
PubMed2005

Hospital decision-making regarding the smallpox pre-event vaccination program.

OBJECTIVES: To understand the factors underlying the decision by U.S. hospitals to participate or not in the U.S. Smallpox Pre-Event Vaccination Program (SPVP). METHODS: We conducted semistructured telephone interviews with a convenience sample of 123 hospital decision-makers in nine states between June and November 2003. RESULTS: Within our sample, 88 hospitals (72%) decided to participate in the SPVP and 35 (28%) decided against doing so. Nearly all hospital decision-makers considered the risk of a smallpox outbreak, risks associated with vaccination, hospital costs, and the reaction of hospital stakeholders. However, these factors often were weighed differently by hospitals that decided to participate compared to those that did not. Fewer than half of all hospitals reported that public health officials played an important role in their decision-making process, but those that did felt the influence of public health officials was positive. CONCLUSIONS: Strengthening the linkage between the public and private health sectors may help to address some of the barriers to broader participation by hospitals in the SPVP and foster the success of smallpox outbreak response preparedness efforts in the future.

Community-Institutional Relations↗
PubMed2003

Transmission potential of smallpox: estimates based on detailed data from an outbreak.

Recent discussions on the use of variola virus by bioterrorists have rekindled interest in the parameters that govern the transmissibility of smallpox. Here, the authors estimate by maximum likelihood the parameters of the spread of smallpox from historical data on an epidemic in 1967 in the town of Abakaliki, Nigeria, afflicting a religious group that refused vaccination. According to the authors' estimates, 79.9% (95% confidence interval (CI): 63.6, 87.9) of the infectious contacts occurred within the compounds of the cases and 93.3% (95% CI: 80.6, 98.8) among compound members and other close contacts. Each case had 0.164 (95% CI: 0, 1.31) sufficiently close contacts on average during the fever period that preceded the rash and 6.87 (95% CI: 4.52, 10.1) sufficiently close contacts during the whole course of infectivity. These results support the widely held belief that smallpox spreads slowly, mainly among close contacts, and that infectivity before the onset of rash was negligible.

Adolescent↗
PubMed2003

Case isolation and contact tracing can prevent the spread of smallpox.

Fears that terrorist groups may have gained access to variola virus have led to widespread discussions on how to prevent the reintroduction of smallpox by vaccination and on the availability of sufficiently large amounts of vaccine. In this paper, the author examines how the spread of smallpox is affected by isolating overt cases and taking their contacts under close surveillance for up to 3 weeks. The author assumes that case detection gradually improves from initially 7 days to 3 days. This intervention should be accompanied by vaccination, but its outcome does not depend on the vaccine's efficacy. It may, therefore, be especially important in controlling outbreaks caused by pathogens whose immunologic properties have been modified by genetic engineering. Using stochastic computer simulations, the author demonstrates that contact tracing and case isolation can extinguish smallpox outbreaks in highly susceptible populations within less than half a year without causing totals of more than 550 secondary cases per 100 index cases. The author also derives simple approximate expressions that allow prognostication on how efficiently an outbreak can be controlled by the described measures alone and prediction of the expected number of cases in an outbreak and the number of people that must be taken under surveillance.

Biological Warfare↗
PubMed1977

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary subcutaneous vaccination.

Six months after subcutaneous vaccination with one of four smallpox vaccines, 655 children were challenged with a standard percutaneous smallpox vaccine. Response to reimmunization was characterized by a significant acceleration and diminution of skin response, but not to the degree seen in an equivalent group who had received their primary immunization percutaneously. Fever after revaccination was absent if there had been a "take" with primary subcutaneous vaccination. The overall incidence of minor vaccine-related complications with revaccination was 2-1/2%. The neutralizing antibody response to revaccination was markedly reduced, as compared to that of children who received either one or two successful percutaneous vaccinations. Subcutaneous vaccination followed by percutaneous vaccination is not recommended as a schedule for smallpox immunization, because complications are not avoided, and the incidence and mean titer of resultant neutralizing antibody are low.

Antibody Formation↗
PubMed1998

Vaccination policy against smallpox, 1835-1914: a comparison of England with Prussia and Imperial Germany.

There are three identifiable phases in comparing vaccination policy in England, Prussia and Imperial Germany. (1) Prior to the 1870's the tradition of medical police in Prussia resulted in the vaccination of the population being treated as a State responsibility earlier than in England and provided an appropriate administrative framework. The administrative pressure that could be exerted persuaded the Prussian authorities that legislation to make vaccination compulsory was unnecessary. In contrast, England and Wales lacked both the tradition and administrative structures of a medical police. Legislation (1840, 1853) for free and universal infant vaccination was followed by radical ideological and administrative innovation. (2) From 1875 to 1889 both countries provided free and compulsory vaccination for all. In England this was limited to infants; in Germany including Prussia, it included the re-vaccination of children. (3) After 1889 England and Germany began to diverge more sharply. In England vaccination rates fell and after 1898 conscientious objectors were excused from having to have their children vaccinated. Germany retained compulsory vaccination and rates in the two countries increasingly diverged. England came to rely on the local public health administration for the surveillance and containment of smallpox, including selective vaccination of contacts. Despite these differences smallpox mortality dropped sharply in both countries, although in Germany somewhat earlier. The English reliance on surveillance and containment prefigures that of the WHO in the eradication of smallpox in the Third World. It suggests that the emphasis on the importance of high levels of mass vaccination in the German literature should perhaps be revised.

Germany↗
PubMed2000

Slavery, smallpox, and revolution: 1792 in Ile de France (Mauritius).

In 1792 a slave-ship arrived on the french Indian Ocean island of Ile de France (Mauritius) from South India, bringing with it smallpox. As the epidemic spread, a heated debate ensued over the practice of inoculation. The island was in the throes of revolutionary politics and the community of French colonists were acutely aware of their new rights as 'citizens'. In the course of the smallpox epidemic, many of the political tenisons of the period came to focus on the question of inoculation, and were played out on the bodies of slaves. Whilst some citizens asserted their right, as property owners, to inoculate their slaves, others, equally vehemently, objected to the practice and asserted their right to protect their slaves from infection. Eighteenth-century colonial medicine was largely geared to keeping the bodies of slaves and workers productive and useful, but formal medicine never had a monopoly. Slaves on Ile de France brought with them a rich array of medical beliefs and practices from Africa, India, and Madagascar. We have little direct historical evidence for these, but we do know that many slaves came from areas in which forces of smallpox inoculation were known and practised.

Colonialism↗
PubMed1996

Should smallpox virus be destroyed? The relevance of the origins of vaccinia virus.

The fate of surviving stocks of smallpox virus is still uncertain, and it is important that arguments in favour of retention or destruction should present balanced evidence. This article balances the view, probably incorrect and possibly alarmist presented earlier in this Journal by Peter Razzell, that vaccinia and cowpox viruses were derived from smallpox virus. The generally accepted alternative view that all three viruses are independent species and that smallpox virus could not emerge through simple mutation of the other two is presented, together with appropriate literature citations.

Cowpox↗
PubMed2006

Immunity and immunological memory following smallpox vaccination.

The smallpox vaccine consists of live vaccinia virus and is generally considered the gold standard of vaccines, since it is the only one that has led to the complete eradication of an infectious disease from the human population. Renewed fears that smallpox might be deliberately released in an act of bioterrorism have led to resurgence in the study of immunity and immunological memory to vaccinia virus and other poxviruses. Here we review our current understanding of memory T-cell, memory B-cell, and antibody responses to vaccinia and related poxviruses, both in animal models and human subjects. Of particular interest are recent advances in understanding protective immunity to poxviruses, quantifying immunological memory to the smallpox vaccine in humans, and identifying major vaccinia-specific T-cell and B-cell epitopes. In addition, potential mechanisms for maintenance of immunological memory are discussed.

Animals↗
PubMed2004

Reasons physicians accepted or declined smallpox vaccine, February through April, 2003.

From February to April 2003, we performed an e-mail-based survey to assess responses of physicians at Yale University to being offered smallpox vaccine. Of 58 respondents, 3 (5%) had been or intended to be vaccinated. Reasons cited for declining vaccination included: belief that benefits did not outweigh risks (55%), belief that the vaccination program was unnecessary (18%), desire to wait and see what side effects occurred in vaccinees (11%), and worries about compensation or liability (7%). Most (94%) considered risks to themselves, family, or patients in their decision. Only 3% thought a smallpox attack in the next 5 years was likely or very likely. Physicians did not accept the smallpox vaccine because they did not believe the potential benefits were sufficient.

Attitude of Health Personnel↗
PubMed2005

Severe headaches following smallpox vaccination.

Headaches are common following smallpox vaccination; the re-introduction of civilian vaccination necessitates better understanding of the clinical features and outcome of postvaccination headache. We identified patients reporting headache following vaccination from among those reported to the U.S. Vaccine Adverse Events Reporting System to characterize demographic and clinical features. One-hundred and eight reports were obtained from among 627 smallpox vaccine-related reports, including 15 hospitalized persons. None had neurologic dysfunction or acute laboratory abnormalities; headache resolved in all except 2 hospitalized patients within 3 months. Severe headache following smallpox vaccination is generally transient, but debilitating headache may occur and further characterization is needed.

Adult↗
PubMed1999

The cost of disease eradication. Smallpox and bovine tuberculosis.

Although eradication is the ideal approach to reduce the economic and human health costs of disease, there may be both short- and long-term consequences. A $300 million effort succeeded in completely eradicating smallpox in less than ten years. The campaign was effective because variola virus produced acute illness, had no carrier stage or non-human reservoirs, and had an effective vaccine that was used in combination with international surveillance and public education. Bovine tuberculosis was completely eradicated in many U.S. herds at a cost of $450 million over 50 years using a "test and slaughter" program combined with meat inspection. Mycobacterium bovis often does not produce acute disease, persists in the carrier stage, has multiple non-human reservoirs, and easily crosses species. No effective vaccine or centralized global surveillance or eradication programs currently exist. Control measures result in significant economic losses. Smallpox eradication had limited economic consequences but has left much of world's population highly susceptible to zoonotic orthopoxviruses and to the use of smallpox as a biologic weapon. The primary threat of M. bovis exists in wildlife that share watering holes or pasture land with domestic stock. In the developed world, surveillance can minimize risks, but one-third of the world's population lacks effective agricultural and food safety programs, leaving them at substantial risk for zoonotic infection by M. bovis.

Animals↗
PubMed1975

Detection by radioimmunoassay of antibodies in human smallpox patients and vaccinees.

A radioimmunoassay procedure was developed for determining smallpox and vaccinia antibodies in human sera. The test detected and measured both primary and secondary immune responses in persons infected with variola virus or vaccinia virus. The antibody titers obtained by complement fixation, hemagglutination inhibition, plaque reduction neutralization, and radioimmunoassay methods were compared. In sequential serum specimens, the radioimmunoassay test indicated fourfold or greater increases in all of the smallpox patients and in six of eight vaccinated persons. Both the complement fixation and the hemagglutination inhibition tests were less effective. In persons who had been vaccinated, radioimmunoassay and plaque reduction neutralization tests appeared to measure the same immune response. However, in smallpox patients the immune response was readily detected by radioimmunoassay, whereas an immune response was not detected by the plaque reduction neutralization test when vaccinia virus was the antigen in the test system. Radioimmunoassay is an operationally simple procedure which provides objective and quantitative end-point titers in serological determinations.

Antibodies, Viral↗
PubMed2004

Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox.

Two decades after a worldwide vaccination campaign was used to successfully eradicate naturally occurring smallpox, the threat of bioterrorism has led to renewed vaccination programs. In addition, sporadic outbreaks of human monkeypox in Africa and a recent outbreak of human monkeypox in the U.S. have made it clear that naturally occurring zoonotic orthopoxvirus diseases remain a public health concern. Much of the threat posed by orthopoxviruses could be eliminated by vaccination; however, because the smallpox vaccine is a live orthopoxvirus vaccine (vaccinia virus) administered to the skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting of four vaccinia virus genes (L1R, A27L, A33R, and B5R) were protected from severe disease after an otherwise lethal challenge with monkeypox virus. Animals vaccinated with a single gene (L1R) which encodes a target of neutralizing antibodies developed severe disease but survived. This is the first demonstration that a subunit vaccine approach to smallpox-monkeypox immunization is feasible.

Animals↗
PubMed1994

Case report: pulmonary calcification in smallpox handler's lung.

Smallpox handler's lung was first described by Morris Evans and Foreman in 1963. During the South Wales smallpox outbreak of 1962 several nurses were noted to develop a "flu-like" illness following an exposure to smallpox patients. The late development of pulmonary calcification in one of these nurses, who is now 74 years old, is described.

Calcinosis↗
PubMed2004

[Seeds against smallpox: Joaquim Vás and the scientific translation of bananeira brava seeds in Goa, India (1894-1930)].

In 1914, in the former Portuguese colony of Goa, India, the physician António Joaquim Vás announced the discovery of a wonderful treatment for smallpox, entailing clinical application of seeds from the bananeira brava (Heliconia biabi Sw.m.), a plant remedy allegedly derived from Indian medical practices. The present article explores the circumstances surrounding the successes and failures of this discovery. The concept of scientific translation is used to interpret the transformation of bananeira brava seeds into an early twentieth-century remedy for smallpox. This transfer from indigenous use to scientific therapeutic constitutes the creation of a quasi-medicine, that is, a case of 'medium translation'. Although these seeds occupy a problematic place within the program of scientific translation, they enjoyed active circulation within science and remained a part of medical practices for combating smallpox.

Heliconiaceae↗
PubMed2003

Cutting edge: long-term B cell memory in humans after smallpox vaccination.

Memory B cells are a central component of humoral immunity, and yet little is known about their longevity in humans. Immune memory after smallpox vaccination (DryVax) is a valuable benchmark for understanding the longevity of B cell memory in the absence of re-exposure to Ag. In this study, we demonstrate that smallpox vaccine-specific memory B cells last for >50 years in immunized individuals. Virus-specific memory B cells initially declined postimmunization, but then reached a plateau approximately 10-fold lower than peak and were stably maintained for >50 years after vaccination at a frequency of approximately 0.1% of total circulating IgG(+) B cells. These persisting memory B cells were functional and able to mount a robust anamnestic Ab response upon revaccination. Additionally, virus-specific CD4(+) T cells were detected decades after vaccination. These data show that immunological memory to DryVax vaccine is long-lived and may contribute to protection against smallpox.

Adolescent↗
PubMed1976

After smallpox eradication: yaws?

The WHO-coordinated Smallpox Eradication Program (SEP) has reduced the number of smallpox-endemic countries from 30 to 1, and now expects to complete the eradication of smallpox after a 10-year campaign. Campaigns to eradicate yaws were begun in the early 1950's with WHO and UNICEF support, and have greatly reduced the prevalence of that disease. Yaws has not yet been eradicated from any large geographic area, however, and is already resurgent in some countries. Some of the differences between the two diseases and available control measures are discussed. The thesis of this paper is that yaws programs have been deficient in failing to aggressively seek and contain yaws cases and contacts after mass treatment campaigns reduced yaws prevalence to low levels. It is further suggested that by using a modified SEP-type strategy to focus investigation and control efforts on infections yaws cases and their contacts, and by taking advantage of new methods to obtain more accurate diagnosis of yaws cases in the field, it should be possible to control yaws more effectively and efficiently, and perhaps to eradicate it. Outstanding barriers to yaws eradication are also discussed.

Adolescent↗