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The world's last endemic case of smallpox: surveillance and containment measures.

On 31 October 1977, the world's last known case of endemic smallpox was discovered in Merca, Somalia. The source of infection was quickly identified; 19 days previously, the male patient had been in contact with two other cases for not more than 15 minutes, but the surveillance activities surrounding these cases did not identify him as a contact. The patient was isolated and containment and surveillance activities and a vaccination campaign were rapidly instituted; 161 contacts were identified, 41 of whom had not been vaccinated within the last three years. The patient recovered and fortunately no other cases occurred.

Adult↗

[Comparative assessment of the means and methods of immunizing humans against smallpox].

Serological efficacy of oral smallpox vaccination was studied in comparison with the scarification and jet methods (1677 persons were vaccinated orally, 148 by scarification, and 1864 by the jet method). In all the three groups percentage of persons with increase of antibodies in comparison with the initial level proved to be statistically equal, constituting about 80% the first 5 months, and falling to 39-61% in 12 months. After revaccination by the scarification and jet methods the mean geometrical antibody titres increased 11--14-fold, and after oral revaccination--5-fold. However, not in a single case they were below 1:25 (observation time--up to 5 months). Vaccination teams consisting of 2--3 persons were capable of vaccinating by the oral method 1456 persons, by the jet method 891 persons, and by scarfication 27 persons per hour.

Administration, Oral↗

[Autistic syndrome (Kanner) and vaccination against smallpox (author's transl)].

3-4 weeks following an otherwise uncomplicated first vaccination against smallpox a boy, then aged 15 months and last seen at the age of 5 1/2 years, gradually developed a complete Kanner syndrome. The question whether vaccination and early infantile autism might be connected is being discussed. A causal relationship is considered extremely unlikely. But vaccination is recognized as having a starter function for the onset of autism.

Autistic Disorder↗

[World-wide eradication of smallpox].

A short history of the disease and its vaccination is described. The role of WHO and its country members is underlined, in this unique triumph of the history of medicine. The success of the implementation of the programme and its monitoring of the epidemiological situation of the disease to the final declaration of the WHO 1980, of smallpox eradication, are analyzed.

Health Planning Technical Assistance↗

Encephalitis complicating smallpox vaccination.

A smallpox vaccination program has been initiated. The vaccine is a live virus that was used in the last century. Postvaccinal encephalitis is a complication of this vaccine. The clinical presentation, course, neuroimaging findings, and spinal fluid abnormalities are similar to a disorder that physicians are familiar with, acute disseminated encephalomyelitis. This complication can be prevented with the administration of antivaccinia gamma globulin at the time of vaccination. Antivaccinia gamma globulin is not efficacious once this complication occurs. Intravenous methylprednisolone is the recommended therapy, although intravenous immunoglobulin and plasmapheresis should be investigated in the treatment of postvaccinal encephalitis.

Animals↗

The African connection. Cotton Mather and the Boston smallpox epidemic of 1721-1722.

The contributions of black Americans to early American culture have still not been fully explored or given the attention deserved. A case in point is the significant contributions African slaves made to 18th-century American folk medicine. A review of the events incident to the smallpox epidemic in Boston in 1721 will illustrate the degree to which some reputable men of science depended on the testimony and experience of Africans in dealing with a particularly dread disease.

Africa↗

Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975.

We analyzed the 186,102 base pairs (bp) that constitute the entire DNA genome of a highly virulent variola virus isolated from Bangladesh in 1975. The linear, double-stranded molecule has relatively small (725 bp) inverted terminal repeat (ITR) sequences containing three 69-bp direct repeat elements, a 54-bp partial repeat element, and a 105-base telomeric end-loop that can be maximally base-paired to contain 17 mismatches. Proximal to the right-end ITR sequences are another seven 69-bp elements and a 53- and a 27-bp partial element. Sequence analysis showed 187 closely spaced open reading frames specifying putative major proteins containing > or = 65 amino acids. Most of the virus proteins correspond to proteins in current databases, including 150 proteins that have > 90% identity to major gene products encoded by vaccinia virus, the smallpox vaccine. Variola virus has a group of proteins that are truncated compared with vaccinia virus counterparts and a smaller group of proteins that are elongated. The terminal regions encode several novel proteins and variants of other poxvirus proteins that potentially augment variola virus transmissibility and virulence for its only natural host, humans.

Animals↗

An emergent poxvirus from humans and cattle in Rio de Janeiro State: Cantagalo virus may derive from Brazilian smallpox vaccine.

The biological properties of poxvirus isolates from skin lesions on dairy cows and milkers during recent exanthem episodes in Cantagalo County, Rio de Janeiro State, Brazil, were more like vaccinia virus (VV) than cowpox virus. PCR amplification of the hemagglutinin (HA) gene substantiated the isolate classification as an Old World orthopoxvirus, and alignment of the HA sequences with those of other orthopoxviruses indicated that all the isolates represented a single strain of VV, which we have designated Cantagalo virus (CTGV). HA sequences of the Brazilian smallpox vaccine strain (VV-IOC), used over 20 years ago, and CTGV showed 98.2% identity; phylogeny inference of CTGV, VV-IOC, and 12 VV strains placed VV-IOC and CTGV together in a distinct clade. Viral DNA restriction patterns and protein profiles showed a few differences between VV-IOC and CTGV. Together, the data suggested that CTGV may have derived from VV-IOC by persisting in an indigenous animal(s), accumulating polymorphisms, and now emerging in cattle and milkers as CTGV. CTGV may represent the first case of long-term persistence of vaccinia in the New World.

Amino Acid Sequence↗

Chromosomal aberrations and SCE in lymphocytes of children revaccinated against smallpox.

Chromosomal changes were analysed in the peripheral lymphocytes of 14 twelve-year-old children before and 3 months and 10 months after smallpox revaccination (group A), and in peripheral lymphocytes of 8 children of the same age before and 1.5 and 8 months after revaccination (group B). A significantly increased number of aberrant cells was found after 1.5 and 3 months. In the blood samples collected 8 and 10 months after revaccination there was a decrease in the number of aberrant cells which, however, did not reach the control level. Sister chromatid exchanges (SCE) were counted in 5 children 1.5 and 8 months after revaccination, and their numbers did not differ from controls.

Child↗

The age-dependent risk of postvaccination complications in vaccinees with smallpox vaccine.

The use of vaccinia virus in recombinant systems may result in the occurrence of complications observed following smallpox vaccination. The results are presented of a large survey carried out in the USSR between 1968 and 1979. High complication rates are reported, particularly in older primary vaccinees; for example, there were 312.5 cases of neurological complications per million in those aged greater than or equal to 5 years. The author concludes that this factor will limit the use of vaccinia virus in recombinant technology.

Age Factors↗

Indications for smallpox vaccination: policies still differ.

The need for vaccination of those handling vaccinia and other related orthopoxviruses is still uncertain, with UK and US authorities adopting different policies. The former revised an earlier decision and now no longer recommend vaccination; the latter confirmed earlier decisions to recommend vaccination. These policies are reviewed in the light of evidence on the safety and efficacy of smallpox vaccine.

Contraindications↗

25 years since the eradication of smallpox: why poxvirus research is still relevant.

The World Health Organization (WHO) announced the eradication of smallpox twenty-five years ago this month. This conquest of an infectious disease, which has been the bane of humankind for centuries, still stands as the WHO's greatest achievement. The anniversary of such a scientific and medical landmark provides an appropriate occasion to reflect on this feat and to assess the significance and necessity of the poxvirus research that has followed this.

Animals↗

Comparative efficacy of replicating smallpox vaccine strains in a murine challenge model.

There is currently considerable concern about the vulnerability of human populations to biowarfare or bioterrorist attacks with variola virus (VARV). Traditional smallpox vaccines were manufactured using the lymph of ruminants infected with the vaccinia virus (VACV). However, these production methods do not meet current standards for vaccines, especially since the emergence of transmissable spongiform encephalopathies in domesticated ruminants. This study has examined the protective efficacy of the Lister (Elstree) vaccine strain from various sources in a murine lethal challenge model. Considerable variation in efficacy is observed between the Lister material obtained from the American Type Culture Collection (ATCC) and the same strain obtained from vaccine stockpiles. A new, tissue-culture derived Lister vaccine is assessed against a bench-mark of multiple lots from a historical stockpile of the traditional vaccine. Apparent qualitative differences are observed between historical and new vaccines. Statistically significant differences are observed between different batches of the traditional vaccine, and the efficacy of the tissue-culture produced vaccine falls within this range.

Administration, Intranasal↗

Clinical and immunological responses to undiluted and diluted smallpox vaccine with vaccinia virus of Lister strain.

The potential to increase the supply of vaccine by diluting the vaccinia virus of Lister strain to face possible bioterrorism with smallpox was evaluated. Vaccinia-naïve subjects (n=97) were randomized to receive either undiluted or diluted (1:5, 1:10) vaccine, and previously vaccinated subjects (n=122) were randomized to receive either undiluted or diluted (1:10, 1:30) vaccine. Except two subjects who received 1:30 diluted vaccine, the vaccination of all subjects was successful clinically. All subjects had significant vaccinia-specific T cell and antibody responses. The diluted vaccine was not associated with decreased local or systemic reactions, lower T cell responses, or higher antibody titers when compared with undiluted vaccine. Here we show the diluted vaccine of Lister strain can be used in vaccinia-naïve subjects and previously vaccinated subjects if viral titer > or =10(8) and 10(7.5) pfu/mL after dilution, respectively. The reactogenicity of vaccinia virus may not be a dose-dependent response.

Adult↗

Efficacy of novel plasmid DNA encoding vaccinia antigens in improving current smallpox vaccination strategy.

We tested a DNA vaccine strategy in order to improve the efficacy and safety of the current live smallpox vaccine involving priming with DNA vaccines and boosting with live vaccinia virus (VacV). We generated DNA plasmids encoding the A4L, A27L and H5R VacV genes. A considerable increase in antigen-specific IFN-gamma responses, high proliferative and humoral antigen-specific responses were detected in experimental primed Balb/C mice compared to controls after VacV boost. The VacV-DNA plasmids elicited IFN-gamma production in HLA-A2.1 transgenic mice in response to predicted HLA-A2.1 restricted peptide epitopes, providing valuable data for further vaccine development.

Animals↗

Emergency medicine tools to manage smallpox (vaccinia) vaccination complications: clinical practice guideline and policies and procedures.

In December 2002, the federal government began a program to immunize approximately 500000 civilian public health and health care workers with smallpox (vaccinia) vaccine as a part of our pre-event defense against bioterrorism. First responders will likely follow, and the general US population might be offered vaccination in the next 1 to 2 years. Recent reports that suggest the possible association of the vaccine to adverse cardiac events (including deaths), liability concerns for hospitals, and the availability of compensation for workers with vaccine complications have significantly reduced voluntary participation. Vaccinees might experience robust primary takes or serious adverse events, including viral or even bacterial cellulitides, encephalitis, progressive skin destruction, and other life-threatening complications. With the increasing prevalence of immune suppression from both diseases and immunosuppressive medications, complications might be seen in higher frequency than previously reported. Emergency medicine providers and staff must become familiar with clinical presentations and management of vaccine complications. In addition, policies and procedures must be developed to prevent unimmunized providers from inadvertently contacting the active vaccination sites of their patients and, if the providers themselves have active vaccination sites, to protect their patients and their own families.

Antiviral Agents↗

Smallpox vaccination techniques. 2. Accessories and aftercare.

The various accessories used for smallpox vaccination are surveyed. These included modified vaccination instruments and various other items which facilitated the procedure, containers for preservation and transport of vaccine, sterilising equipment, aids to interpretation and recording, and a variety of skin preparations and dressings. Three phases can be discerned in the development and use of such items and procedures. Initially, in the pre-bacteriological era, there was little need for accessory equipment apart from the means of preserving and transporting vaccine. Later, particularly by the end of the 19th century, the importance of aseptic and antiseptic procedures was realised, use was made of more traumatic vaccination techniques and glass capillaries became the standard method for preservation and transport. All this led to the increasing availability of a wide range of accessories, particularly of skin preparations and dressings. Finally, from about 1930, it was appreciated that skin preparation and dressings were often unnecessary, and could be counter-productive. So, although accessories for this were still available their use was very much reduced. In some respects the use of accessories during this last phase, based on scientific analysis was a return to the earliest, 'pre-scientific', era.

Aftercare↗