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Five instances of side-effects after oral smallpox immunisation (out of 2568 persons orally immunised) are reported. Vaccinal lesions on the tongue, gums and (once) nares predominated and had been caused by biting open the vaccine-containing capsule or tablet with release of the virus.
Due to the highly visible nature of the disease, smallpox received a lot of attention from the colonial and independent Indian governments. An assessment of the changing official views about the impact of geographical and environmental factors on modes of variola causation and control presents insights into themes that are generally ignored in the existing historiography. Rather than being synchronised efforts, imposed top-down, provincial level officials in charge of running vaccination programmes were able to retain a great degree of autonomy and shape the nature of local immunisation drive. As a result, vaccination work in the country was often disjointed, marked by official disagreements about the usefulness of certain strategies and technological inputs, with these trends being most noticeable in rural areas. Thus, this study seeks to highlight the importance of recognising--and studying--the fractured nature of medical and public health administration in the South Asian sub-continent.
In the event of a widespread biological attack involving smallpox, it may not only be morally permissible, but morally obligatory, to dispense with the ordinary requirements of informed consent for vaccination. The government should also commit to educating the public about the vaccine, distributing the vaccine efficiently and fairly, and ensuring access to health care to those who experience adverse events as a result of vaccination. In addition, the government should provide a program of financial compensation for any persons who experience permanent disability as a consequence of vaccination and for the families of those who die as a result of vaccination.
Vaccinia virus is reactogenic in a significant number of vaccinees, with the most common adverse events being fever, lymphadenopathy, and rash. Although the inoculation is given in the skin, these adverse events suggest a robust systemic inflammatory response. To elucidate the cytokine response signature of systemic adverse events, we used a protein microarray technique to precisely quantitate 108 serum cytokines and chemokines in vaccine recipients before and 1 week after primary immunization with Aventis Pasteur smallpox vaccine. We studied 74 individuals after vaccination, of whom 22 experienced a systemic adverse event and 52 did not. The soluble factors most associated with adverse events were selected on the basis of voting among a committee of machine-learning methods and statistical procedures, and the selected cytokines were used to build a final decision-tree model. On the basis of changes in protein expression, we identified 6 cytokines that accurately discriminate between individuals on the basis of adverse event status: granulocyte colony-stimulating factor, stem cell factor, monokine induced by interferon-gamma (CXCL9), intercellular adhesion molecule-1, eotaxin, and tissue inhibitor of metalloproteinases-2. This cytokine signature is characteristic of particular inflammatory response pathways and suggests that the secretion of cytokines by fibroblasts plays a central role in systemic adverse events.
Persistence of neutralizing antibodies after revaccination against smallpox was studied. Single serum samples from 140 revaccinated donors were tested for neutralizing antibodies using the plaque reduction assay. The donors, aged 21-49 years at sampling, had been vaccinated in infancy and revaccinated at 8 and 18 years; they formed seven groups of 20 men each, revaccinated about 3, 5, 10, 15, 20, 25, and 30 years before sampling. The differences in mean titer among groups were insignificant (P greater than .01). The titer significantly decreased during the first 3 years after the revaccination but remained stable for at least 30 years thereafter (geometric mean titer, 10.5; 95% confidence interval, 6.8-16.4). The results suggest that there is probably no need for routine revaccinations beyond the primary and two revaccinations; nevertheless, persons at high risk should be revaccinated regardless of their vaccination status.
Realizing that the Spanish colonies were being devastated by epidemics of smallpox resulting in thousands of deaths, Charles IV, King of Spain, sent one of his court's physicians to apply the recently discovered vaccine. Without refrigeration, the vaccine was passed from one child to another (boys taken out of orphanages). Francisco Xavier de Balmis and a team that included three assistants, two surgeons, and three nurses sailed from Spain on November 30. 1803. They vaccinated more than 100,000 people from the Caribbean Islands and South, Central, and North America, reaching up to San Antonio, Texas, and then traveled to the Philippines, Macao, Canton, and Santa Elena Island, landing back in Cadiz on September 7, 1806. During his journey, Balmis instructed local physicians on how to prepare, preserve, and apply the vaccine, while collecting rare biologic specimens. On the 200th anniversary of their sailing, recognition is given to this group for conducting what was the first global vaccination campaign that reached Texas and California.
Decades after smallpox was eradicated and vaccination discontinued, the level of residual immunity in today's population is largely unknown. This study describes an epidemiological assessment in Italians of antibodies against the intracellular mature virus (IMV) and extracellular envelope virus (EEV) forms of Vaccinia virus. Serum samples (n = 642) were taken in 1993 and 2003 from people between 11 and 102 years old. Most citizens >27 years old were positive for antibodies to IMV and EEV. These antibodies were long-lasting and similar titres were present in citizens between 30 and 100 years old. Serum samples from 1993 and 2003 displayed very similar EEV- and IMV-specific antibody titres. By using these data and demographic considerations, it was predicted that, in 2003, 46 % of the Italian population were positive for both IMV and EEV, 42 % were negative for both and 12 % were positive for one antigen.
From the introduction of smallpox vaccination approximately 200 years ago right up to its discontinuation (1980), reports by physicians and scientists about positive side-effects such as healing of chronic skin rashes, reduced susceptibility to various infectious diseases, e.g. measles, scarlet fever and whooping cough, and even the prophylactic use of the vaccination, e.g. against syphilis, were published again and again. Comparison with the period after cessation of vaccination confirms the experiences of the above vaccinators. As early as 1956, targeted research on these observations led to evidence of the 'ring-zone phenomenon', i.e. the production of soluble antiviral substances in infected chicken embryos and cell cultures. With the help of modern immunological and bioengineering methods, it was later possible to demonstrate that these effects are based on the activation of lymphoreticular cells and the regulatory effect of certain cytokines within the context of the non-specific immune system. These findings led to the development of paramunization with paraspecific vaccines from highly attenuated animal pox viruses. During attenuation, deletions in the virus DNA occur. Attenuated animal pox strains are therefore suited for the production of vector vaccines. The fact that these vector vaccines demonstrate an especially high level of paraspecific efficacy and lack harmful effects is likewise the result of the attenuated animal pox viruses. Optimum regulation of the entire immune system leads to increased paramunity already in the first few days after vaccination and to enhanced antigen recognition and thus accelerated commencement of specific immunity.
This study assessed the persistence of humoral (neutralising antibody titre to vaccinia virus) and cellular (immediate vaccinia-specific interferon (IFN)-gamma-producing T-cell) immunities to smallpox in a Korean population. Individuals who were vaccinated 25-60 years previously had higher neutralising antibody titres (geometric mean titre (GMT) 13.7; 95% CI 11.0-17.2) than vaccinia-naive individuals (GMT 6.7; 95% CI 5.5-8.0; p <0.001). However, there was no significant difference in cellular immunity between individuals vaccinated previously and vaccinia-naive individuals, and only 15% of the individuals vaccinated previously displayed an immediate IFN-gamma-producing effector-memory response in ELISPOT assays.
UNLABELLED: Concerns about bioterrorism have prompted a national voluntary smallpox (SP) vaccination program in the United States. Although emergency health care providers are among the first targeted for vaccination, little is known about how these providers view the risks and benefits of SP vaccination. OBJECTIVES: To assess the willingness of emergency health care personnel to receive pre-event SP vaccination prior to the start of the national program. METHODS: The authors conducted a national cross-sectional, anonymous survey of 1,701 emergency physicians, nurses, and mid-level practitioners working full time in 13 adult and pediatric academic emergency departments in large U.S. cities in November and December 2002. The main outcome measure was willingness to be vaccinated against SP. Secondary outcomes included the prevalence of self-reported contraindications, and reasons for and against vaccination. RESULTS: 732 emergency health care providers returned questionnaires (response rate 43%). Overall, 73% (95% CI = 66% to 80%) were willing to receive pre-event SP vaccination. 18% (95% CI = 14% to 23%) reported contraindications to vaccination, and 50% (95% CI = 39% to 61%) of these providers were willing to receive pre-event SP vaccination. Self-protection (72%) was the most common reason cited for desiring vaccination against SP; concern about vaccine-related adverse events (54%) was the most common reason cited for not wanting immunization. CONCLUSIONS: Most emergency health care providers express a willingness to receive pre-event SP immunization; self-protection is a principal motivating reason. A subset of health care providers, however, may place themselves at increased risk by desiring vaccination despite contraindications.
Two hundred years ago--in May 1796--Edward Jenner carried out a pioneering feat in the history of "clinical investigation' which not only paved the way for the eventual elimination of one of the world's most terrifying infections (variola), but also heralded widespread vaccination campaigns and the foundation of the discipline of clinical immunology. Vaccination superseded the formerly used technique of variolation which had been introduced into England by Lady Mary Wortley Montague. Under-recognised is the fact that the first clinical trial(s) of this new development were carried out under the supervision of William Woodville at the St Pancras Smallpox Hospital (situated at Battle Bridge--now King's Cross); this work was crucially important in the 'vaccination saga' and deserves far greater acceptance than is currently the case.
A comparative study of two smallpox vaccines, standard calf lymph vaccine, and an attenuated vaccine, CVI-78, was performed in 95 children. Primary vaccination with CVI-78 resulted in a more attenuated response than primary vaccination with standard vaccine. Sixty-one percent of those vaccinated with CVI-78 and 96 percent of those vaccinated with standard vaccine developed a major dermal reaction; 16 percent of those vaccinated with CVI-78 and 89 percent of those vaccinated with standard vaccine developed post-vaccination neutralizing antibodies. Twenty-seven percent of the children vaccinated with CVI-78 demonstrated neither a dermal nor serologic postvaccination response, whereas only 2 percent of those vaccinated with standard vaccination demonstrated no postvaccination response.
Revaccination with standard calf lymph vaccine was performed on 26 children who had received a primary vaccination with an attenuated smallpox vaccine, CVI-78, and 22 children who had received primary vaccination with standard calf lymph. Revaccination resulted in a vesicular reaction in 96 percent of those who had been vaccinated previously with CVI-78 and 73 percent of those vaccinated previously with standard calf lymph. All children had a positive hemagglutination-inhibition (HI) antibody titer either after primary vaccination or revaccination. Only 65 percent of those initially vaccinated with CVI-78 vaccine had positive neutralizing antibodies after revaccination. All children who received primary vaccination with standard calf lymph had postrevaccination neutralizing antibodies. The children who had neither a dermal nor a serologic response after primary vaccination responded as primary vaccinees on challenge with standard calf lymph.
Despite the underwhelming response to the federal government's initiative to inoculate health care workers against smallpox, the Bush administration has indicated that the program will continue and that it could be expanded to include other health care providers, emergency service workers, and others deemed essential for continuity of government. We discuss the reasons for the program's failure to date, outline recent advisories questioning the extent of the vaccination effort, and suggest suspension of further vaccination efforts until certain questions and issues are resolved.
With the international threat of bioterrorism, smallpox is again a matter of intense debate. The authors review this disease and raise considerations on the exploitation of the etiologic agent as a biological weapon. Also bring to discussion the available efforts to produce and develop vaccines against the disease.
In Imperial Brazil, the Academy of Medicine played an important role in promoting debates and discussions about local medicine. It was a symbol of the movement to try to organize the Brazilian medical body and lend it legitimacy. The article focuses on issue surrounding the Academy's activities regarding the smallpox vaccine and its conceptions and practice, covering the period form the Academy's birth as the Rio de Janeiro Society of Medicine till its transformation into the National Academy of Medicine, when Brazil became a Republic at the close of the nineteenth century. The main source for this study were the Academy's periodicals, which portrayed Brazilian medical thought and practice throughout the nineteenth century and underscored the lack of research and the need for greater reading on the topic so local studies could be conducted. These publications were devoted to disseminating works that had already been published in other countries or to discussion raised by Brazilian physicians. The later at first targeted clinical and hospital cases and statistics and the later, starting in the 1880s, began to incorporate laboratory experiments.
In this article, I describe the complex nature of the final phases of the Indian smallpox eradication program. I examine the unfolding of policies at different levels of administration and the roles played by a wide range of national and international actors. A careful examination of unpublished official correspondence, on which this article is largely based, shows that the program's managers were divided and that this division determined the timing of the achievement of eradication. This material also reveals that Indian health workers and bureaucrats were far more capable of reshaping policies in specific localities, often in response to local infrastructural and political concerns, than has been acknowledged in the historiography.
We present a stochastic model for the spread of smallpox after a small number of index cases are introduced into a susceptible population. The model describes a branching process for the spread of the infection and the effects of intervention measures. We discuss scenarios in which ring vaccination of direct contacts of infected persons is sufficient to contain an epidemic. Ring vaccination can be successful if infectious cases are rapidly diagnosed. However, because of the inherent stochastic nature of epidemic outbreaks, both the size and duration of contained outbreaks are highly variable. Intervention requirements depend on the basic reproduction number (R0), for which different estimates exist. When faced with the decision of whether to rely on ring vaccination, the public health community should be aware that an epidemic might take time to subside even for an eventually successful intervention strategy.