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Smallpox vaccination immunity in relation to number of insertions.

The influence of the number of insertions of vaccine on smallpox vaccination immunity has been the subject of considerable controversy. In this study the problem was investigated in children of comparable age, sex, and smallpox vaccination history. The incidence of post-vaccinal fever and the antibody response of subjects given single and double insertions were compared. While single insertions caused fewer febrile reactions than double insertions, the difference was not significant. Successful vaccination invariably elicited a marked neutralizing antibody response. However, subjects who received two insertions developed significantly higher antibody titres than subjects with a single insertion. In the revaccinated group the difference in titre was still demonstrable 16 months after vaccination. It is concluded that the number of insertions may play a role in the duration of vaccination immunity.

Antibody Formation↗

Smallpox vaccination by intradermal jet injection. 3. Evaluation in a well-vaccinated population.

Smallpox vaccinations were performed in a well-vaccinated prison population by multiple-pressure technique and by intradermal jet injection using serial dilutions of vaccine. A total of 140 subjects were divided into groups, and each group was vaccinated by the multiple-pressure technique or by jet injection using 1 of 3 vaccine dilutions with the following calculated titres: ID-Jet 1 = 10(7.0) TCID(50)/ml, ID-Jet 1a = 10(6.3) TCID(50)/ml, ID-Jet 2 = 10(6.0) TCID(50)/ml. Clinical observations were made at intervals during the first week after vaccination. Prevaccination and post-vaccination serum samples were obtained immediately before and 30 days after the vaccination. Results based on clinical and serological evaluations indicated that smallpox vaccination by jet injection with the ID-Jet 1 vaccine was at least as efficacious as vaccination by the standard multiple-pressure technique.

Adult↗

Smallpox eradication in Brazil, 1967-69.

The Campanha de Erradicacão da Varéola (CEV) was established in 1966 by the Brazilian Ministry of Health to eradicate smallpox. By October 1970 more than 75 million people had been vaccinated through this programme of systematic vaccination. In the 12 states where the attack phase had been completed by June 1969, there was an 80% decrease in reported cases in 1969 compared with the previous year. This decline in incidence contrasts sharply with the 99% increase in cases recorded in the other 15 states due to the increased level of surveillance.In 1969, 74% of cases occurred in persons under 15 years of age, while almost 93% of the persons infected were less than 30 years of age. The annual case-fatality rate, which has varied from 0.5% to 3.3% since 1956, indicates the disease to be variola minor. This has been confirmed by laboratory study.Careful investigation of reported cases has shown that in past years case reporting has been at a very low level, about 2.5% of the actual incidence.Data from epidemiological investigations of 22 outbreaks comprising more than 2000 cases and contacts indicate that the efficacy of smallpox vaccination was approximately 94%.

Adolescent↗

[Smallpox vaccination (author's transl)].

The Author examines the reasons that have led to the discontinuance of the routine vaccination against smallpox in Italy. The epidemiology of smallpox and deaths from vaccination complications observed in Italy during the period 1952-1972 are examined.

Encephalitis↗

The mechanism of group differences in the character of the vaccinal process in immunization against natural smallpox.

The effect of antigenic polymorphism of the ABO-system blood groups on the character of the vaccinal process after immunization against natural smallpox was investigated. The increased susceptibility of persons possessing A antigen to the harmful effect of smallpox vaccine virus is due to hereditary rather than to acquired factors. The leukocytes of peripheral blood of these persons showed a poorer binding capacity with respect to the smallpoxvaccine virus; they also exhibited a high rate of chromosomal aberration after vaccination, resulting to some extent from increased proliferative ability of the cells.

ABO Blood-Group System↗

[Characteristics of cellular immune reactions in animals vaccinated with smallpox and ADPT vaccines].

Immunization with absorbed DPT vaccine in 1 or 3 subcutaneous injections, as well as the intradermal or intracardiac immunization of guinea pigs with smallpox vaccine resulted in the accumulation of 0-positive lymphoyctes, determined by the cytotoxic test, in the lymph nodes. On the 7th day after the intracardiac injection of smallpox vaccine in massive doses a sharp decrease in the content of 0-positive lymphocytes was observed. The number of small lymphocytes with surface immunoglobulin receptors detected by immunofluorescence remains unchanged in the animals of all groups at any period of the experiment.

Animals↗

Occupationally-acquired smallpox in an IgM-deficient health worker.

A 21-year-old Indian who worked as a vaccinator in the smallpox programme developed an atypical case of variola major despite several previous, successful vaccinations. The clinical course of the disease was unusual, as there were two distinctly separate "crops" of smallpox. The disease began less than one month after a successful vaccination, which therefore gave the briefest period of protection recorded for this reliable immunization. The patient was found to have a virtually complete IgM deficiency with normal levels of circulating antibody against orthopox virus.

Adult↗

[Experimental basis for associated subcutaneous jet injection immunization against plague and smallpox].

Experiments in guinea-pigs have indicated that combined immunization with the mixture of live plague and smallpox vaccines introduced subcutaneously by means of a jet injector are safe and faintly reactogenic. Highly intense immunity, as revealed by serological shifts and by the degree of protection of the vaccinated animals challenge with the virulent cultures of the corresponding infective agents, allows the recommendation that combined subcutaneous immunization against plague and smallpox by means of a jet injector be further studied on humans.

Animals↗

[MVA-vaccine in primovaccination against smallpox after the age of three (author's transl)].

These are the results of 417 primary vaccinations against smallpox with MVA, an attenuated vaccine. All of the patients were over three years old. In Europe, this group has an increased risk of postvaccinal encephalitis. The intracutaneous inoculation produced a light local infiltration and only 11.7% showed a light generalized reaction. In order to attain a reliable immunity, a second inoculation was performed one week later, epicutaneously with Elstree-vaccine. The local reaction was in general that of a normal revaccination, and 79.4% of our patients had neither fever nor general symptoms. Among the others no one became seriously ill. We did not observe any complications specific for a smallpox vaccination. In comparison to the other vaccination methods currently used, the MVA "Two-step"-vaccination is probably the safest. Its risk of a postvaccinal encephalitis is supposed to be lower according to animal experiments and theoretical considerations. This hypothesis has been confirmed meanwhile by the results of several thousand vaccinations in the already mentioned age-group.

Adult↗

The influence of modifications in the potency of smallpox vaccines on the immunological reactivity of the organism.

The possible influence of shipment and storage conditions upon the potency of smallpox vaccines was investigated by testing the direct effect of vaccine potency on the type of cutaneous reaction and on the level of serum antibodies. Vaccine no. 1--freshly prepared, shipped and stored at +4 degrees C--proved to be more potent than vaccine no. 2, at the limit of its efficiency, shipped and maintained under usual conditions. To maintain the initial potency of smallpox vaccines it is recommended either to improve the shipment and storage conditions, or to use a lyophilized vaccine.

Adult↗

Comparison of military and civilian reporting rates for smallpox vaccine adverse events.

INTRODUCTION: US smallpox vaccination (SMA) started most recently in December 2002. Military and civilian personnel report adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS), a surveillance system that relies on spontaneous reports. Although reported rates of probable myo/pericarditis after SMA in the literature are similar between military personnel and civilian healthcare workers, some civilian AE reporting rates after SMA appeared higher than those in the military. OBJECTIVE: Determine if SMA-associated reporting rates are different in civilians than in the military, considering age, sex, seriousness, and expectedness of the AE, as well as self-reporting. METHODS: Numerators were SMA reports in VAERS from 12/12/02 to 3/1/04. Limitations of VAERS include underreporting and lack of diagnostic confirmation. Denominators were number of military and civilian vaccinees. RESULTS: Reporting rates stratified by age and sex of serious and non-serious AEs were significantly higher in civilian than military personnel ages <55 years (rate ratios 4-27). These rate ratios decreased with increasing age. CONCLUSIONS: Reporting rates in VAERS differed significantly and substantially in civilians compared to military personnel <55 years of age. Differences in stimulated passive surveillance systems, and AE reporting practices, including the 'threshold' for reporting most likely explain these findings. These results suggest that in the case of smallpox vaccine AEs, there may be systematic differences in reporting completeness between the civilian and military sectors, and that passive surveillance data should be interpreted with caution.

Adult↗

Topography of variola smallpox virus inverted terminal repeats.

We examined the nucleotide sequences of the inverted terminal repeat (ITR) regions adjacent to the covalently closed hairpin end sequences of three variola major and four minor strains from smallpox outbreaks in Europe, Asia, Africa, and South America. The ITR regions ranged in size from 581 to 1051 base pairs (bp) and contained no apparent open reading frames. Two nonrepetitive sequence elements, NR1 and NR2, were conserved and resembled nonrepetitive elements in the ITRs of other orthopoxviruses. Depending on strain, the terminally positioned NR1 and the more internal NR2 flanked a direct repeat region containing from none to four copies of a 69-bp sequence and one copy of a 54-bp related sequence partial repeat. A distinctive pattern of ITR topography of NR1 and NR2 flanking a single copy of the 69-bp unit characterized each of three examined alastrim variola minor strains. A nonalastrim African minor strain from the last natural case of smallpox in Somalia in 1977 showed the largest ITR region of the examined viruses because of a second direct repeat cluster following NR2.

Africa↗

The effect of social mixing controls on the spread of smallpox--a two-level model.

Responding to a possible bioterror attack of Smallpox has become a major concern to governments, local public officials and health authorities. This concern has been reflected in numerous studies that model and evaluate possible response strategies. Many of these studies consider only vaccination policies and assume homogeneous mixing, where all instances of contacts in the population are equally likely. Such a mixing pattern is rather unlikely to represent population interaction in a modern urban setting, which typically is separated into households on the one hand, and into daily meeting sites such as schools and offices, on the other hand. In this paper we develop a two-level social interaction model where an individual moves back and forth between home and a daily meeting site, possibly passing through a general meeting site such as mass transit system or other crowded areas. Based on the model, we evaluate the effect of social mixing controls, situational awareness of the public health system and mass vaccination on the spread of smallpox. It is shown that mixing controls and alertness of the response system may have a significant impact on the spread of the epidemic. Some policy recommendations are discussed.

Bioterrorism↗

Ocular vaccinia following exposure to a smallpox vaccinee.

PURPOSE: To describe the presentation and management of the first identified case of ocular vaccinia infection associated with the current smallpox vaccination program. DESIGN: Case report. METHODS: Vaccinia virus was isolated by cell culture of a conjunctival swab. Direct staining with fluorescein isothiocyanate-labeled vaccinia antibody and polymerase chain reaction testing confirmed the diagnosis. RESULTS: In February 2003, a 26-year-old woman developed right preseptal cellulitis and blepharoconjunctivitis following contact with a vaccinated member of the military. The preseptal cellulitis resolved with antibacterial therapy, and the conjunctival infection was treated successfully with a 14-day course of topical trifluridine and a single dose of intravenous vaccinia immune globulin. CONCLUSIONS: To facilitate rapid diagnosis and appropriate treatment, clinicians must maintain a high index of suspicion for ocular smallpox vaccine-associated adverse reactions in vaccine recipients and their close contacts.

Adult↗

Comparison of clinical presentation of acute myocarditis following smallpox vaccination to acute coronary syndromes in patients <40 years of age.

Smallpox vaccine-associated myopericarditis may have a similar presentation to acute coronary syndrome (ACS). The clinical records of 78 young patients (<40 years of age) presenting with ACS (n = 16) or myocarditis after smallpox vaccination (n = 62) were reviewed. Comparisons were made among clinical presentation, cardiac enzymes, echocardiographic findings, and electrocardiographic changes. The presence of cardiac risk factors or focal wall motion abnormalities on echocardiography were associated with a diagnosis of ACS. There was a trend toward earlier elevation of troponin-I and creatine kinase in patients with myocarditis compared with ACS.

Acute Disease↗

Society for assisted reproductive technology position statement on donor suitability of recipients of smallpox vaccine (vaccinia virus).

Although there is presently no definitive evidence linking vaccinia virus transmission through reproductive cells, SART/ASRM accordingly recommends that assisted reproductive technology (ART) practitioners consider deferring donors who have recently received smallpox vaccine or contracted symptomatic vaccinia virus infection through close contact with a vaccine recipient (until after the vaccine or infectious scab has spontaneously separated). Good donor practice further suggests that donors who are not in good health, including those with recent complications from smallpox vaccine, should be similarly deferred.

Humans↗

Multiple branch retinal arteriolar occlusions associated with smallpox vaccination.

We describe a rare combination of multiple multiple branch retinal arteriolar occlusions (BRAO) and encephalopathy, which developed in an adult male 10 days after smallpox vaccination. A 53-year-old physician presented with sudden temporal visual field loss in the left eye. Ten days earlier he had received a smallpox vaccination. Hyperbaric oxygen was administered because of suspected BRAO. Examination on day 3 revealed a decrease in visual acuity and loss of visual field. Fundoscopy of the left eye disclosed a retinal infarct in the inferior macula and multiple cotton wool spots over the entire posterior pole. Fluorescein angiography showed delayed arterial filling and multiple non-perfused areas. Magnetic resonance imaging of the brain disclosed white matter focal lesions. Neurological examination was normal. Audiological examination revealed mild hearing loss caused by an old phonic trauma. A combination of intravenous methylprednisolone and immunoglobulins, recommended for the treatment of Susac syndrome, was administered. At the follow-up visit 3 months later, visual acuity in the left eye improved, fundoscopy showed resolution of the cotton wool spots and temporal disc pallor, and the visual field was substantially restored.

Anti-Inflammatory Agents↗

An integral equation model for the control of a smallpox outbreak.

An integral equation model of a smallpox epidemic is proposed. The model structures the incidence of infection among the household, the workplace, the wider community and a health-care facility; and incorporates a finite incubation period and plausible infectivity functions. Linearisation of the model is appropriate for small epidemics, and enables analytic expressions to be derived for the basic reproduction number and the size of the epidemic. The effects of control interventions (vaccination, isolation, quarantine and public education) are explored for a smallpox epidemic following an imported case. It is found that the rapid identification and isolation of cases, the quarantine of affected households and a public education campaign to reduce contact would be capable of bringing an epidemic under control. This could be used in conjunction with the vaccination of healthcare workers and contacts. Our results suggest that prior mass vaccination would be an inefficient method of containing an outbreak.

Algorithms↗