Smallpox (Variola)

An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. (Dorland, 28th ed)

Also Known As:

Networked: 1078 relevant articles (95 outcomes, 112 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Vaccinia
2.	Infection
3.	Smallpox (Variola)
4.	Monkeypox
5.	Measles

Experts

1.	Poland, Gregory A: 21 articles (09/2014 - 10/2003)
2.	Damon, Inger K: 19 articles (12/2015 - 06/2004)
3.	Ovsyannikova, Inna G: 15 articles (09/2014 - 11/2008)
4.	Frey, Sharon E: 14 articles (10/2015 - 10/2005)
5.	Kennedy, Richard B: 13 articles (09/2014 - 05/2009)
6.	Hruby, Dennis E: 12 articles (07/2015 - 10/2007)
7.	Moss, Bernard: 12 articles (01/2011 - 08/2003)
8.	Golding, Hana: 11 articles (03/2015 - 08/2003)
9.	Edwards, Kathryn M: 11 articles (02/2015 - 02/2004)
10.	Isaacs, Stuart N: 10 articles (01/2013 - 08/2003)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Smallpox:

1.	VaccinesIBA 12/30/2011 - "Significant changes that have taken place in the last thirty years, since the eradication of smallpox include, among others, (i) post-colonial political changes, with varying commitment to disease eradication initiatives, especially in the parts of the world most burdened by infectious and vaccine preventable diseases, (ii) innovations leading to the development of new and highly effective vaccines, targeted to specific diseases, (iii) the transformation brought about by improvement in education and the new global access to information (cell phones, internet, etc.), leading to an unlimited access to different types of information, subject to either positive or negative use. " 12/01/2009 - "Here, we review the history of smallpox vaccines and recent achievements in the development of highly efficacious and safer vaccines and vaccine applications. " 01/01/2015 - "The authors estimated that i) the likelihood of a smallpox outbreak in Denmark is very low (one event in 200,000 years), ii) the expected efficacy of currently available and new vaccines is 95 and 75 percent, respectively, iii) the expected frequency of serious side effects from vaccination is between 100 and 10,000 fold lower for new than for existing vaccines, depending on modes of action. " 01/01/2013 - "Vaccinia virus protein A33 (A33VACV) plays an important role in protection against orthopoxviruses, and hence is included in experimental multi-subunit smallpox vaccines. " 01/01/2004 - "These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines."
2.	Smallpox VaccineFDA Link 09/01/2004 - "The smallpox vaccine, which is highly effective in preventing the spread of both these orthopoxvirus infectious illnesses, might be administered to numerous health care workers and, in the event of a smallpox attack, millions of other citizens. " 02/05/2008 - "As a result of the successful eradication of smallpox with the vaccinia virus (VACV), the general population is no longer required to receive a smallpox vaccine, and will have no protection against smallpox. " 10/01/2005 - "The only effective treatment for smallpox is rapid administration of smallpox vaccine." 03/01/2004 - "While the disease was completely eradicated by 1980 with successful use of smallpox vaccine, concern has been raised that smallpox may emerge as a tool of bioterrorism. " 01/01/1979 - "However, it took an additional 180 years until the current smallpox vaccine--a modification of Jenner's vaccine--became fully effective, in terms of quality and usage during the global smallpox eradication campaign. "
3.	AntigensIBA 07/01/1968 - "[Can protection against smallpox be achieved with vaccina antigen? " 09/01/1964 - "I. STUDY OF SMALLPOX AND VACCINIA VIRUS SOLUBLE ANTIGENS]." 01/02/2013 - "These data demonstrate that designing vaccine formulation conditions to maximize antigen-adjuvant interactions is a key factor in smallpox subunit-vaccine immunogenicity and protection." 11/01/2012 - "We describe a cohort of four subjects who received smallpox vaccination, and a single subject who received multiple vaccinations, with antibody levels to unrelated antigens monitored for 1-3 years. " 01/01/2011 - "Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. "
4.	cidofovir (Vistide)FDA Link 07/01/2004 - "Proof-of-concept studies suggest that current defences against smallpox could be strengthened by supplementing vaccination with antiviral drug prophylaxis, based on aerosolized or orally available forms of the long-acting medication cidofovir. " 05/01/2015 - "Concentrations of cidofovir diphosphate (CDV-PP), the active antiviral, in rabbit peripheral blood mononuclear cells (PBMCs) were determined for comparison to those produced in humans at the dose proposed for treatment of smallpox. " 12/01/2006 - "Cidofovir (CDV) is an effective drug against viruses of the Orthopoxviridae family and is active in vitro against variola virus, the cause of smallpox. " 02/09/2006 - "These data show that adequate preparedness for a biological threat involving smallpox should include the possibility of treating exposed individuals with antiviral compounds such as cidofovir or other selective anti-poxvirus drugs." 03/23/2002 - "Orally available cidofovir derivative active against smallpox."
5.	AntibodiesIBA 01/01/2013 - "Antibodies to both infectious forms of vaccinia virus, the mature virion (MV) and the enveloped virion (EV), as well as cell-mediated immune response appear to be important for protection against smallpox. " 09/01/1966 - "[Study of the dynamics of hemagglutination-inhibiting antibodies after repeated smallpox vaccination]." 11/01/2005 - "The experiments could reveal the antibodies that bound alastrim strains more effectively that did other VV strains. " 11/01/2005 - "Prevalence of antibodies to Vaccinia virus after smallpox vaccination in Italy." 01/01/2004 - "Furthermore, all selected antibodies were assayed for binding with major alastrim strains of the live variola virus. "
6.	ST-246IBA 12/01/2013 - "Tecovirimat appears to be an effective smallpox therapeutic in nonhuman primates, suggesting that it is reasonably likely to provide therapeutic benefit in smallpox-infected humans. " 01/12/2010 - "These findings suggest that ST-246 may be effective in controlling smallpox or other pathogenic orthopoxviruses in some immunodeficient human populations for whom the vaccine is contraindicated." 12/01/2013 - "In this study, the efficacy of tecovirimat was evaluated in both a prelesional and postlesional setting in nonhuman primates challenged intravenously with 1 × 10(8) PFU of Variola virus (VARV; the causative agent of smallpox), a model for smallpox disease in humans. " 12/01/2013 - "Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox)." 03/01/2013 - "The orally available antiorthopoxvirus drug tecovirimat has recently completed Phase 2 clinical trials and shows promise as a smallpox control agent. "
7.	Proteins (Proteins, Gene)IBA 01/01/2010 - "Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. " 09/01/2003 - "Future studies of additional variola proteins may help illuminate factors associated with its virulence, pathogenesis and strict human tropism. " 03/15/1993 - "The revealed differences between the genes (proteins) of variola and vaccinia viruses under study are discussed." 11/01/2010 - "[Modeling spatial structures of variola and cowpox virus TNF-binding CrmB proteins bound to murine or human TNF]." 11/01/2010 - "While the smallpox homolog of VCP is able to bind VACV A56, the ectromelia virus (ECTV) VCP homolog is only able to bind the ECTV homolog of A56, indicating that these proteins may have coevolved. "
8.	Complement System Proteins (Complement)IBA 03/15/2006 - "Furthermore, targeting and neutralizing these complement regulatory active sites via mAbs is a therapeutic approach that may enhance protection against smallpox." 03/01/2008 - "These findings complement studies that utilize other data sources, such as electronic hospitalization records, and may be reassuring to health care providers and those who receive the smallpox vaccination." 02/01/1904 - "A Clinical and Experimental Study of the Bacteriolytic Complement of the Blood Serum in Variola." 04/01/2008 - "Variola virus, the causative agent of smallpox, encodes a soluble complement regulator named SPICE. " 08/01/2003 - "One of the blocking MAbs recognized SCR 2 while the other two recognized either SCR 4 or the junction between SCRs 3 and 4, indicating that structural elements involved in the interaction of VCP with C3b/C4b are located within SCR domains 2 and 3 and 4. These anti-VCP MAbs may have clinical significance as therapeutic inhibitors of VCP's complement control activity and may also offer a novel approach to managing vaccinia virus vaccine complications that occur from smallpox vaccination."
9.	DNA (Deoxyribonucleic Acid)IBA 07/20/2008 - "Heterogeneity in the A33 protein impacts the cross-protective efficacy of a candidate smallpox DNA vaccine." 10/01/2011 - "In the present study, we have investigated the anatomic distribution in blood and gut mucosal tissues of memory poxvirus-specific CD4 and CD8 T cells in subjects vaccinated with smallpox and compared it with vector (NYVAC)-specific and HIV insert-specific T-cell responses induced by an experimental DNA-C/ NYVAC-C vaccine regimen. " 01/01/2015 - "These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform." 11/12/2012 - "The systems are used to develop OR, AND, and Controlled-AND gates, and the DNA-analyte targets represent two nucleic acid sequences of the smallpox viral genome." 08/01/2011 - "The specificity and sensitivity of the developed method were assessed by analyzing DNA of 29 strains belonging to six orthopoxvirus species as well as the DNA samples isolated from archive clinical specimens of human smallpox cases and experimental specimens isolated from CPXV-infected mice and MPXV-infected marmot."
10.	Neutralizing AntibodiesIBA 02/01/1978 - "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. " 05/26/2009 - "These data indicate that neutralizing antibody titers following primary smallpox vaccination vary by gender." 03/01/2008 - "The detection of neutralizing antibodies against vaccinia virus is a valuable tool for the investigation of previous smallpox vaccination. " 02/19/2007 - "Detectable smallpox-neutralizing antibodies are still present among US adults. " 04/01/2005 - "Thus, approximately 80% of persons born before 1969 and 50% of those born between 1969 and 1975 were also found to have maintained neutralizing antibodies against smallpox. "

Therapies and Procedures

1.	Immunotherapy 09/01/2007 - "These chimpanzee/human anti-A33 MAbs may be useful in the prevention and treatment of vaccinia virus-induced complications of vaccination against smallpox and may also be effective in the immunoprophylaxis and immunotherapy of smallpox and other orthopoxvirus diseases." 02/07/2006 - "These chimpanzee/human anti-B5 mAbs may be useful in the prevention and treatment of vaccinia virus-induced complications of vaccination against smallpox and may also be effective in the immunoprophylaxis and immunotherapy of smallpox." 03/01/2004 - "Vaccinia virus (VV) has been effectively utilized as a live vaccine against smallpox as well as a vector for vaccine development and immunotherapy. " 05/01/2015 - "Vaccinia virus (VACV) continues to be used in immunotherapy for the prevention of infectious diseases and treatment of cancer since its use for the eradication of smallpox. " 10/01/1956 - "[Attempted immunotherapy of smallpox and immunoprevention of typhus fever practiced at Cocard Hospital in 1941]."
2.	Therapeutics 09/01/2010 - "The genetic similarity of ectromelia virus to variola and monkeypox viruses, the common features of the resulting disease, and the convenience of the mouse as a laboratory animal underscores its utility in the study of orthopoxvirus pathogenesis and in the development of therapeutics and prophylactics. " 09/01/2010 - "The absence of herd immunity to orthopoxviruses and the concern that variola or monkeypox viruses could be used for bioterroristic activities has stimulated the development of therapeutics and safer prophylactics. " 05/22/2009 - "The quantities of investigational and licensed therapeutics and diagnostics used were greater than anticipated based on existing smallpox preparedness plans. " 04/01/2015 - "Since the eradication of smallpox in the 1970s with the aid of vaccinia viruses, the vaccinia viruses and other genera of poxviruses have shown various degrees of safety and efficacy in pre-clinical or clinical application for human anti-cancer therapeutics. " 04/01/2006 - "Concerns over the potential use of variola virus as a biological weapon have prompted new interest in the development of small molecule therapeutics to prevent and treat smallpox infection. "
3.	Drug Therapy (Chemotherapy) 03/01/1969 - "Chemoprophylaxis and chemotherapy in variola major. " 03/01/1969 - "Chemoprophylaxis and chemotherapy in variola major. " 05/15/2010 - "In a case-control study, 67 patients with breast cancer who received cytotoxic chemotherapy and who were disease free for at least 1 year were matched with healthy controls according to age, sex, and the number of smallpox vaccinations received. " 05/15/2010 - "Immunity to smallpox is reduced after receipt of chemotherapy for breast cancer. " 01/01/1962 - "The chemotherapy of variola major infection."
4.	Intradermal Injections 12/01/1987 - "Each patient received a smallpox booster injection followed one week later by the first of 13 weekly intradermal injections of 2.0 mg of VMO. " 01/01/1978 - "A notable example is percutaneous smallpox vaccination together with the intradermal injection of BCG. " 01/01/1977 - "The bifurcated needle technique for BCG vaccination was compared with intradermal injection in a mass BCG and smallpox vaccination programme in Afghanistan. " 02/01/1983 - "The most informative and reproducible laboratory methods for evaluating the provisory antigenic and immunogenic potency of smallpox vaccines are the evaluation of the character of lesions developing in rabbits as a result of the intradermal injection of the virus and the determination of the capacity of the virus for multiplication in the skin of a rabbit (reproduction). " 01/01/2009 - "Extensive clinical experience with smallpox, TB, and other vaccines has shown that vaccine delivery into the skin using conventional intradermal injection is generally safe and effective and often elicits the same immune responses at lower doses compared to intramuscular injection. "
5.	Occlusive Dressings (Occlusive Dressing) 05/01/2004 - "The Centers for Disease Control and Prevention recommends a semipermeable occlusive dressing for hospital workers who receive smallpox vaccination. " 02/15/2004 - "After smallpox vaccination, inoculation sites were covered with 2 occlusive dressings. " 02/15/2004 - "The rate of vaccinia recovery outside occlusive bandages covering smallpox vaccination sites was remarkably low, suggesting excellent protection against inadvertent transmission." 11/01/2006 - "Use of an occlusive bandage with a gauze lining is the best choice for coverage of smallpox vaccination sites because of a reduced potential for vaccinia transmission and a lower reactogenicity rate. "