42 CFR 102.31 - Medical benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.31 Medical benefits. (a) Smallpox vaccine recipients and vaccinia... estate of a deceased smallpox vaccine recipient or vaccinia contact as long as such benefits were accrued...

42 CFR 102.31 - Medical benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.31 Medical benefits. (a) Smallpox vaccine recipients and vaccinia... estate of a deceased smallpox vaccine recipient or vaccinia contact as long as such benefits were accrued...

42 CFR 102.31 - Medical benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.31 Medical benefits. (a) Smallpox vaccine recipients and vaccinia... estate of a deceased smallpox vaccine recipient or vaccinia contact as long as such benefits were accrued...

42 CFR 102.31 - Medical benefits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.31 Medical benefits. (a) Smallpox vaccine recipients and vaccinia... estate of a deceased smallpox vaccine recipient or vaccinia contact as long as such benefits were accrued...

42 CFR 102.31 - Medical benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.31 Medical benefits. (a) Smallpox vaccine recipients and vaccinia... estate of a deceased smallpox vaccine recipient or vaccinia contact as long as such benefits were accrued...

42 CFR 102.51 - Documentation a smallpox vaccine recipient must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Documentation a smallpox vaccine recipient must..., DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.51 Documentation a smallpox vaccine recipient must submit to be deemed eligible by...

42 CFR 102.51 - Documentation a smallpox vaccine recipient must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Documentation a smallpox vaccine recipient must..., DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.51 Documentation a smallpox vaccine recipient must submit to be deemed eligible by...

42 CFR 102.51 - Documentation a smallpox vaccine recipient must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Documentation a smallpox vaccine recipient must..., DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.51 Documentation a smallpox vaccine recipient must submit to be deemed eligible by...

42 CFR 102.51 - Documentation a smallpox vaccine recipient must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Documentation a smallpox vaccine recipient must..., DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.51 Documentation a smallpox vaccine recipient must submit to be deemed eligible by...

42 CFR 102.51 - Documentation a smallpox vaccine recipient must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Documentation a smallpox vaccine recipient must..., DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.51 Documentation a smallpox vaccine recipient must submit to be deemed eligible by...

42 CFR 102.81 - Calculation of benefits for lost employment income.

Code of Federal Regulations, 2011 CFR

2011-10-01

... VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.81 Calculation of benefits... of work lost as a result of a covered injury or its health complications if the smallpox vaccine... based on the smallpox vaccine recipient or vaccinia contact's gross employment income, which includes...

42 CFR 102.81 - Calculation of benefits for lost employment income.

Code of Federal Regulations, 2013 CFR

2013-10-01

... VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.81 Calculation of benefits... of work lost as a result of a covered injury or its health complications if the smallpox vaccine... based on the smallpox vaccine recipient or vaccinia contact's gross employment income, which includes...

42 CFR 102.62 - Documentation an eligible requester seeking a death benefit must submit.

Code of Federal Regulations, 2013 CFR

2013-10-01

... HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To... smallpox vaccine recipient or vaccinia contact. If such a benefit(s) was provided, the requester must... documentation submitted under subpart F, the following: (1) Documentation showing that the deceased smallpox...

42 CFR 102.81 - Calculation of benefits for lost employment income.

Code of Federal Regulations, 2014 CFR

2014-10-01

... VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.81 Calculation of benefits... of work lost as a result of a covered injury or its health complications if the smallpox vaccine... based on the smallpox vaccine recipient or vaccinia contact's gross employment income, which includes...

42 CFR 102.62 - Documentation an eligible requester seeking a death benefit must submit.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To... smallpox vaccine recipient or vaccinia contact. If such a benefit(s) was provided, the requester must... documentation submitted under subpart F, the following: (1) Documentation showing that the deceased smallpox...

42 CFR 102.62 - Documentation an eligible requester seeking a death benefit must submit.

Code of Federal Regulations, 2014 CFR

2014-10-01

... HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To... smallpox vaccine recipient or vaccinia contact. If such a benefit(s) was provided, the requester must... documentation submitted under subpart F, the following: (1) Documentation showing that the deceased smallpox...

42 CFR 102.81 - Calculation of benefits for lost employment income.

Code of Federal Regulations, 2012 CFR

2012-10-01

... VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.81 Calculation of benefits... of work lost as a result of a covered injury or its health complications if the smallpox vaccine... based on the smallpox vaccine recipient or vaccinia contact's gross employment income, which includes...

42 CFR 102.62 - Documentation an eligible requester seeking a death benefit must submit.

Code of Federal Regulations, 2012 CFR

2012-10-01

... HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To... smallpox vaccine recipient or vaccinia contact. If such a benefit(s) was provided, the requester must... documentation submitted under subpart F, the following: (1) Documentation showing that the deceased smallpox...

42 CFR 102.81 - Calculation of benefits for lost employment income.

Code of Federal Regulations, 2010 CFR

2010-10-01

... VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.81 Calculation of benefits... of work lost as a result of a covered injury or its health complications if the smallpox vaccine... based on the smallpox vaccine recipient or vaccinia contact's gross employment income, which includes...

42 CFR 102.50 - Medical records necessary to establish that a covered injury was sustained.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed... to establish that a smallpox vaccine recipient or vaccinia contact sustained a covered injury, a... the smallpox vaccine) or vaccinia contracted through accidental vaccinia inoculation. (c) If certain...

42 CFR 102.41 - How to file a Request Package.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Compensation Program Office, Healthcare Systems Bureau, Health Resources and Services Administration, Parklawn... Smallpox Vaccine Injury Compensation Program Office, Healthcare Systems Bureau, Health Resources and...

42 CFR 102.41 - How to file a Request Package.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Compensation Program Office, Healthcare Systems Bureau, Health Resources and Services Administration, Parklawn... Smallpox Vaccine Injury Compensation Program Office, Healthcare Systems Bureau, Health Resources and...

42 CFR 102.41 - How to file a Request Package.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Compensation Program Office, Healthcare Systems Bureau, Health Resources and Services Administration, Parklawn... Smallpox Vaccine Injury Compensation Program Office, Healthcare Systems Bureau, Health Resources and...

42 CFR 102.41 - How to file a Request Package.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Compensation Program Office, Healthcare Systems Bureau, Health Resources and Services Administration, Parklawn... Smallpox Vaccine Injury Compensation Program Office, Healthcare Systems Bureau, Health Resources and...

42 CFR 102.41 - How to file a Request Package.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Compensation Program Office, Healthcare Systems Bureau, Health Resources and Services Administration, Parklawn... Smallpox Vaccine Injury Compensation Program Office, Healthcare Systems Bureau, Health Resources and...

42 CFR 102.33 - Death benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... under this Program if the Secretary determines that an otherwise eligible deceased smallpox vaccine... vaccine recipient or vaccinia contact during his or her lifetime and to his or her estate after death. (c...

42 CFR 102.33 - Death benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... under this Program if the Secretary determines that an otherwise eligible deceased smallpox vaccine... vaccine recipient or vaccinia contact during his or her lifetime and to his or her estate after death. (c...

42 CFR 102.33 - Death benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... under this Program if the Secretary determines that an otherwise eligible deceased smallpox vaccine... vaccine recipient or vaccinia contact during his or her lifetime and to his or her estate after death. (c...

42 CFR 102.33 - Death benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... under this Program if the Secretary determines that an otherwise eligible deceased smallpox vaccine... vaccine recipient or vaccinia contact during his or her lifetime and to his or her estate after death. (c...

42 CFR 102.53 - Documentation a survivor must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2012 CFR

2012-10-01

... AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible... documentation required in: (1) Section 102.51(a)(2)-(4) (documentation requirements for smallpox vaccine recipients), in the case of a deceased smallpox vaccine recipient. The survivor requester may submit a...

42 CFR 102.53 - Documentation a survivor must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2014 CFR

2014-10-01

... AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible... documentation required in: (1) Section 102.51(a)(2)-(4) (documentation requirements for smallpox vaccine recipients), in the case of a deceased smallpox vaccine recipient. The survivor requester may submit a...

42 CFR 102.53 - Documentation a survivor must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2013 CFR

2013-10-01

... AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible... documentation required in: (1) Section 102.51(a)(2)-(4) (documentation requirements for smallpox vaccine recipients), in the case of a deceased smallpox vaccine recipient. The survivor requester may submit a...

42 CFR 102.53 - Documentation a survivor must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2011 CFR

2011-10-01

... AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible... documentation required in: (1) Section 102.51(a)(2)-(4) (documentation requirements for smallpox vaccine recipients), in the case of a deceased smallpox vaccine recipient. The survivor requester may submit a...

42 CFR 102.53 - Documentation a survivor must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2010 CFR

2010-10-01

... AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible... documentation required in: (1) Section 102.51(a)(2)-(4) (documentation requirements for smallpox vaccine recipients), in the case of a deceased smallpox vaccine recipient. The survivor requester may submit a...

42 CFR 102.61 - Documentation an eligible requester seeking benefits for lost employment income must submit.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for... smallpox vaccine recipient or vaccinia contact as a result of the covered injury or its health... had not used paid leave); (b) The smallpox vaccine recipient or vaccinia contact's gross employment...

42 CFR 102.30 - Benefits available to different categories of requesters under this program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.30 Benefits... vaccine recipients and vaccinia contacts. A requester who is an eligible smallpox vaccine recipient or... vaccine recipient or vaccinia contact may be entitled to receive a death benefit. (c) Benefits available...

42 CFR 102.30 - Benefits available to different categories of requesters under this program.

Code of Federal Regulations, 2013 CFR

2013-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.30 Benefits... vaccine recipients and vaccinia contacts. A requester who is an eligible smallpox vaccine recipient or... vaccine recipient or vaccinia contact may be entitled to receive a death benefit. (c) Benefits available...

42 CFR 102.30 - Benefits available to different categories of requesters under this program.

Code of Federal Regulations, 2012 CFR

2012-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.30 Benefits... vaccine recipients and vaccinia contacts. A requester who is an eligible smallpox vaccine recipient or... vaccine recipient or vaccinia contact may be entitled to receive a death benefit. (c) Benefits available...

42 CFR 102.30 - Benefits available to different categories of requesters under this program.

Code of Federal Regulations, 2014 CFR

2014-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.30 Benefits... vaccine recipients and vaccinia contacts. A requester who is an eligible smallpox vaccine recipient or... vaccine recipient or vaccinia contact may be entitled to receive a death benefit. (c) Benefits available...

42 CFR 102.30 - Benefits available to different categories of requesters under this program.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.30 Benefits... vaccine recipients and vaccinia contacts. A requester who is an eligible smallpox vaccine recipient or... vaccine recipient or vaccinia contact may be entitled to receive a death benefit. (c) Benefits available...

42 CFR 102.52 - Documentation a vaccinia contact must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2010 CFR

2010-10-01

... OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be... in § 102.3(x)(1)-(3) (a person meeting the definition of a smallpox vaccine recipient, except for the... individual described in § 102.3(x)(1)-(3) (a person meeting the definition of a smallpox vaccine recipient...

76 FR 62306 - Countermeasures Injury Compensation Program (CICP): Administrative Implementation, Final Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

... respirators, Respiratory support devices, Ventilators, Anthrax, Smallpox, Botulism, Acute radiation syndrome...] and Relenza[supreg] when used for pandemic purposes; (5) smallpox countermeasures; (6) acute radiation syndrome countermeasures; (7) pandemic influenza diagnostics, personal respiratory devices, and respiratory...

42 CFR 102.62 - Documentation an eligible requester seeking a death benefit must submit.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To... smallpox vaccine recipient or vaccinia contact. If such a benefit(s) was provided, the requester must... vaccine recipient or vaccinia contact is survived by one or more dependents younger than the age of 18...

42 CFR 102.84 - The Secretary's right to recover benefits paid under this program from third-party payors.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false The Secretary's right to recover benefits paid under this program from third-party payors. 102.84 Section 102.84 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of...

42 CFR 102.84 - The Secretary's right to recover benefits paid under this program from third-party payors.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false The Secretary's right to recover benefits paid under this program from third-party payors. 102.84 Section 102.84 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of...

42 CFR 102.84 - The Secretary's right to recover benefits paid under this program from third-party payors.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false The Secretary's right to recover benefits paid under this program from third-party payors. 102.84 Section 102.84 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of...

42 CFR 102.84 - The Secretary's right to recover benefits paid under this program from third-party payors.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false The Secretary's right to recover benefits paid under this program from third-party payors. 102.84 Section 102.84 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of...

42 CFR 102.84 - The Secretary's right to recover benefits paid under this program from third-party payors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false The Secretary's right to recover benefits paid under this program from third-party payors. 102.84 Section 102.84 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of...

42 CFR 102.91 - Secretary's review authority.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Secretary's review authority. 102.91 Section 102.91 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's Determinations § 102.91 Secretary's review authority...

42 CFR 102.91 - Secretary's review authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Secretary's review authority. 102.91 Section 102.91 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's Determinations § 102.91 Secretary's review authority...

42 CFR 102.91 - Secretary's review authority.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Secretary's review authority. 102.91 Section 102.91 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's Determinations § 102.91 Secretary's review authority...

42 CFR 102.91 - Secretary's review authority.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Secretary's review authority. 102.91 Section 102.91 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's Determinations § 102.91 Secretary's review authority...

42 CFR 102.91 - Secretary's review authority.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Secretary's review authority. 102.91 Section 102.91 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's Determinations § 102.91 Secretary's review authority...

42 CFR 102.74 - Disapproval of benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Disapproval of benefits. 102.74 Section 102.74 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.74 Disapproval of benefits. (a) If the Secretary...

42 CFR 102.22-102.29 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false [Reserved] 102.22-102.29 Section 102.22-102.29 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Covered Injuries §§ 102.22-102.29 [Reserved] ...

42 CFR 102.74 - Disapproval of benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Disapproval of benefits. 102.74 Section 102.74 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.74 Disapproval of benefits. (a) If the Secretary...

42 CFR 102.74 - Disapproval of benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Disapproval of benefits. 102.74 Section 102.74 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.74 Disapproval of benefits. (a) If the Secretary...

42 CFR 102.22-102.29 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false [Reserved] 102.22-102.29 Section 102.22-102.29 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Covered Injuries §§ 102.22-102.29 [Reserved] ...

42 CFR 102.74 - Disapproval of benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Disapproval of benefits. 102.74 Section 102.74 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.74 Disapproval of benefits. (a) If the Secretary...

42 CFR 102.22-102.29 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false [Reserved] 102.22-102.29 Section 102.22-102.29 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Covered Injuries §§ 102.22-102.29 [Reserved] ...

42 CFR 102.22-102.29 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false [Reserved] 102.22-102.29 Section 102.22-102.29 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Covered Injuries §§ 102.22-102.29 [Reserved] ...

42 CFR 102.22-102.29 - [Reserved

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false [Reserved] 102.22-102.29 Section 102.22-102.29 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Covered Injuries §§ 102.22-102.29 [Reserved] ...

42 CFR 102.74 - Disapproval of benefits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Disapproval of benefits. 102.74 Section 102.74 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.74 Disapproval of benefits. (a) If the Secretary...

42 CFR 102.43 - Deadlines for submitting documentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Deadlines for submitting documentation. 102.43 Section 102.43 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.43 Deadlines for submitting...

42 CFR 102.44 - Representatives of requesters.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

42 CFR 102.71 - Insufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Insufficient documentation for eligibility and benefits determinations. 102.71 Section 102.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.71...

42 CFR 102.44 - Representatives of requesters.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

42 CFR 102.73 - Approval of benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Approval of benefits. 102.73 Section 102.73 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that...

42 CFR 102.44 - Representatives of requesters.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

42 CFR 102.73 - Approval of benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Approval of benefits. 102.73 Section 102.73 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that...

42 CFR 102.73 - Approval of benefits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Approval of benefits. 102.73 Section 102.73 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that...

42 CFR 102.44 - Representatives of requesters.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

42 CFR 102.43 - Deadlines for submitting documentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Deadlines for submitting documentation. 102.43 Section 102.43 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.43 Deadlines for submitting...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.73 - Approval of benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Approval of benefits. 102.73 Section 102.73 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.71 - Insufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Insufficient documentation for eligibility and benefits determinations. 102.71 Section 102.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.71...

42 CFR 102.71 - Insufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Insufficient documentation for eligibility and benefits determinations. 102.71 Section 102.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.71...

42 CFR 102.43 - Deadlines for submitting documentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Deadlines for submitting documentation. 102.43 Section 102.43 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.43 Deadlines for submitting...

42 CFR 102.44 - Representatives of requesters.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

42 CFR 102.71 - Insufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Insufficient documentation for eligibility and benefits determinations. 102.71 Section 102.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.71...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.43 - Deadlines for submitting documentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Deadlines for submitting documentation. 102.43 Section 102.43 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.43 Deadlines for submitting...

42 CFR 102.43 - Deadlines for submitting documentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Deadlines for submitting documentation. 102.43 Section 102.43 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.43 Deadlines for submitting...

42 CFR 102.71 - Insufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Insufficient documentation for eligibility and benefits determinations. 102.71 Section 102.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.71...

42 CFR 102.73 - Approval of benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Approval of benefits. 102.73 Section 102.73 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that...

42 CFR 102.83 - Payment of all benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Payment of all benefits. 102.83 Section 102.83 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.83 Payment of all benefits. (a) The Secretary...

42 CFR 102.83 - Payment of all benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Payment of all benefits. 102.83 Section 102.83 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.83 Payment of all benefits. (a) The Secretary...

42 CFR 102.60 - Documentation an eligible requester seeking medical benefits must submit.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Documentation an eligible requester seeking medical benefits must submit. 102.60 Section 102.60 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To...

42 CFR 102.83 - Payment of all benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Payment of all benefits. 102.83 Section 102.83 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.83 Payment of all benefits. (a) The Secretary...

42 CFR 102.60 - Documentation an eligible requester seeking medical benefits must submit.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Documentation an eligible requester seeking medical benefits must submit. 102.60 Section 102.60 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To...

42 CFR 102.60 - Documentation an eligible requester seeking medical benefits must submit.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Documentation an eligible requester seeking medical benefits must submit. 102.60 Section 102.60 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To...

42 CFR 102.83 - Payment of all benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Payment of all benefits. 102.83 Section 102.83 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.83 Payment of all benefits. (a) The Secretary...

42 CFR 102.60 - Documentation an eligible requester seeking medical benefits must submit.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Documentation an eligible requester seeking medical benefits must submit. 102.60 Section 102.60 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To...

42 CFR 102.60 - Documentation an eligible requester seeking medical benefits must submit.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Documentation an eligible requester seeking medical benefits must submit. 102.60 Section 102.60 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To...

42 CFR 102.92 - No additional judicial or administrative review of determinations made under this part.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false No additional judicial or administrative review of determinations made under this part. 102.92 Section 102.92 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's...

42 CFR 102.92 - No additional judicial or administrative review of determinations made under this part.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false No additional judicial or administrative review of determinations made under this part. 102.92 Section 102.92 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's...

42 CFR 102.92 - No additional judicial or administrative review of determinations made under this part.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false No additional judicial or administrative review of determinations made under this part. 102.92 Section 102.92 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's...

42 CFR 102.92 - No additional judicial or administrative review of determinations made under this part.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false No additional judicial or administrative review of determinations made under this part. 102.92 Section 102.92 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's...

42 CFR 102.92 - No additional judicial or administrative review of determinations made under this part.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false No additional judicial or administrative review of determinations made under this part. 102.92 Section 102.92 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's...

42 CFR 102.70 - Determinations the Secretary must make before benefits can be paid.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Determinations the Secretary must make before benefits can be paid. 102.70 Section 102.70 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.70 Determinations...

42 CFR 102.70 - Determinations the Secretary must make before benefits can be paid.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Determinations the Secretary must make before benefits can be paid. 102.70 Section 102.70 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.70 Determinations...

42 CFR 102.70 - Determinations the Secretary must make before benefits can be paid.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Determinations the Secretary must make before benefits can be paid. 102.70 Section 102.70 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.70 Determinations...

42 CFR 102.70 - Determinations the Secretary must make before benefits can be paid.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Determinations the Secretary must make before benefits can be paid. 102.70 Section 102.70 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.70 Determinations...

42 CFR 102.70 - Determinations the Secretary must make before benefits can be paid.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Determinations the Secretary must make before benefits can be paid. 102.70 Section 102.70 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.70 Determinations...

42 CFR 102.45 - Multiple survivors.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Multiple survivors. 102.45 Section 102.45 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... smallpox vaccine recipient or vaccinia contact may file Request Forms separately or together. Multiple...

42 CFR 102.45 - Multiple survivors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Multiple survivors. 102.45 Section 102.45 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... smallpox vaccine recipient or vaccinia contact may file Request Forms separately or together. Multiple...

42 CFR 102.45 - Multiple survivors.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Multiple survivors. 102.45 Section 102.45 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... smallpox vaccine recipient or vaccinia contact may file Request Forms separately or together. Multiple...

42 CFR 102.45 - Multiple survivors.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Multiple survivors. 102.45 Section 102.45 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... smallpox vaccine recipient or vaccinia contact may file Request Forms separately or together. Multiple...

42 CFR 102.45 - Multiple survivors.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Multiple survivors. 102.45 Section 102.45 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... smallpox vaccine recipient or vaccinia contact may file Request Forms separately or together. Multiple...

42 CFR 102.42 - Deadlines for filing request forms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 102.42 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) General. Filing deadlines vary depending on whether the injured individual is a smallpox vaccine recipient... this Program. (c) Smallpox vaccine recipients. All Request Forms filed by, or on behalf of, a smallpox...

42 CFR 102.42 - Deadlines for filing request forms.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 102.42 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) General. Filing deadlines vary depending on whether the injured individual is a smallpox vaccine recipient... this Program. (c) Smallpox vaccine recipients. All Request Forms filed by, or on behalf of, a smallpox...

42 CFR 102.42 - Deadlines for filing request forms.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 102.42 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) General. Filing deadlines vary depending on whether the injured individual is a smallpox vaccine recipient... this Program. (c) Smallpox vaccine recipients. All Request Forms filed by, or on behalf of, a smallpox...

42 CFR 102.42 - Deadlines for filing request forms.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 102.42 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) General. Filing deadlines vary depending on whether the injured individual is a smallpox vaccine recipient... this Program. (c) Smallpox vaccine recipients. All Request Forms filed by, or on behalf of, a smallpox...

42 CFR 102.42 - Deadlines for filing request forms.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 102.42 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) General. Filing deadlines vary depending on whether the injured individual is a smallpox vaccine recipient... this Program. (c) Smallpox vaccine recipients. All Request Forms filed by, or on behalf of, a smallpox...

[A study on the 1946 smallpox epidemic in Japan and measures taken against it].

PubMed

Tanaka, Seiji; Sugita, Satoru; Marui, Eiji

2014-09-01

In early 1946, immediately after World War II, there was a smallpox epidemic in Japan. In this paper we investigated trends in the occurrence of smallpox by week and region using official documents of the General Headquarters, Supreme Commander for the Allied Powers (GHQ/SCAP), which are stored in the National Diet Library Modern Japanese Political History Materials Room, and summarized the measures taken against this epidemic. The following two points were clarified: 1) The 1946 smallpox epidemic peaked in Week 13 (March 24-30; 1,405 new patients), and the highest morbidity during this epidemic was seen in Hyogo Prefecture, followed by Osaka Prefecture, Aichi Prefecture, Tokyo Prefecture, and Hokkaido Prefecture. 2) Measures taken against this epidemic were classified into the following three stages: 1. "Vaccine shortage/Manufacture acceleration stage," 2. "Vaccine sufficiency/Smallpox vaccination program implementation stage," and 3. "Detection of defects in vaccination technique/Reimplementation of the smallpox vaccination program stage".

SWOT analysis: strengths, weaknesses, opportunities and threats of the Israeli Smallpox Revaccination Program.

PubMed

Huerta, Michael; Balicer, Ran D; Leventhal, Alex

2003-01-01

During September 2002, Israel began its current revaccination program against smallpox, targeting previously vaccinated "first responders" among medical and emergency workers. In order to identify the potential strengths and weaknesses of this program and the conditions under which critical decisions were reached, we conducted a SWOT analysis of the current Israeli revaccination program, designed to identify its intrinsic strengths and weaknesses, as well as opportunities for its success and threats against it. SWOT analysis--a practical tool for the study of public health policy decisions and the social and political contexts in which they are reached--revealed clear and substantial strengths and weaknesses of the current smallpox revaccination program, intrinsic to the vaccine itself. A number of threats were identified that may jeopardize the success of the current program, chief among them the appearance of severe complications of vaccination. Our finding of a lack of a generation of knowledge on smallpox vaccination highlights the need for improved physician education and dissipation of misconceptions that are prevalent in the public today.

Unraveling the structure of the variola topoisomerase IB-DNA complex: a possible new twist on smallpox therapy.

PubMed

Osheroff, Neil

2006-10-01

Smallpox is a serious and highly contagious disease that is caused by the variola virus. It is one of the most severe infectious human diseases known, with mortality rates as high as 30%. A successful worldwide vaccination program led to the eradication of smallpox in 1980. However, the high transmission rate of variola virus, coupled with the deadly nature of smallpox, makes this virus a potentially devastating weapon for bioterrorism. Currently, there is no specific treatment for smallpox. However, a recent article on the structure of a variola topoisomerase IB-DNA complex provides an intriguing starting point for the rational design of drugs with potential activity against smallpox.

Lessons for Implementation from the World's Most Successful Programme: The Global Eradication of Smallpox.

ERIC Educational Resources Information Center

Pratt, David

1999-01-01

Focuses on lessons educators might learn from the Intensified Campaign for the Global Eradication of Smallpox. Outlines the history of smallpox eradication. Discusses the eradication effort's obstacles, campaign, and costs and benefits. Considers five factors relevant to the successful implementation of educational programs. (CMK)

Emergency physicians' perspectives on smallpox vaccination.

PubMed

Kwon, Nancy; Raven, Maria C; Chiang, William K; Moran, Gregory J; Jui, Jon; Carter, Richard A; Goldfrank, Lewis

2003-06-01

To evaluate emergency physician (EP) attitudes toward smallpox vaccination, the treatment of patients with suspected smallpox, and the threat of a bioterrorist attack. This was a prospective study utilizing a standardized survey instrument that was distributed on November 16, 2002, and collected by February 1, 2003. EPs from a sample of 50 accredited emergency medicine programs were surveyed regarding their perspectives on smallpox vaccination. A total of 989 surveys were collected from 42 emergency medicine programs. Of the respondents, 43.4% would currently volunteer for smallpox vaccination. EPs previously vaccinated against smallpox were 1.46 times more likely to volunteer for vaccination (95% CI = 1.14 to 1.93). EPs who believed they were at risk for complications were less than half as likely to volunteer for vaccination. EPs who perceived a significant risk of a bioterrorist attack were 2.7 times more likely to volunteer for the vaccine compared with those who thought the risk was minimal (95% CI = 2.06 to 3.47). Of the respondents, 34.4% believed the risks of the vaccination outweighed the benefits, 33% did not, and 32.6% were unsure. Currently, fewer than half of EPs surveyed would volunteer for smallpox vaccination. Factors associated with a willingness to be vaccinated include previous smallpox vaccination and the perceived threat of a bioterrorist attack. The variation in EP attitudes toward smallpox vaccination may be due to uncertain risk-to-benefit ratio. The opinions and actions of EPs may be influential on current and future government policy and public opinion.

[The history of smallpox vaccination in the Imperial Moscow foster house].

PubMed

Sher, S A

2011-01-01

The article deals with the history of vaccination against natural smallpox which is directly connected to the Imperial Moscow foster house which became one of smallpox vaccination centers in Russia of XIX century. In 1801, when variolations were substituted by more safe cowpox vaccinations, in Russia the first vaccination using the method of Jenner was made exactly in in the Imperial Moscow foster house. From 1805, the smallpox vaccination received the status of force of law, the Imperial Moscow foster house began to produce and to distribute the smallpox vaccine all over the country and apply the smallpox vaccination not only to its foster children but to all turned to and, besides that, to train the smallpox vaccination. In 1857, the Imperial Moscow foster house became the first establishment in Russia where the revaccination was applied. In 1980, the WHO proclaimed that the implementation of the global program of smallpox irradiation resulted in the natural smallpox elimination on Earth. The smallpox became the first communicable disease defeated due to mass vaccination. One third of Earth population was vaccinated by the Soviet vaccine, which originated mainly because of the activities of physicians of the Imperial Moscow foster house.

Smallpox: clinical features, prevention, and management.

PubMed

Guharoy, Roy; Panzik, Robert; Noviasky, John A; Krenzelok, Edward P; Blair, Donald C

2004-03-01

To describe a general overview of smallpox, clinical presentation, diagnosis, adverse events, and management of both pre- and postexposure vaccination. Literature was identified by search of MEDLINE (1966-June 2003) and International Pharmaceutical Abstracts (1966-May 2003) databases using the key terms smallpox, bioterrorism, biological warfare, and smallpox vaccine. Articles identified from data sources were evaluated, and relevant information was included in this review. Smallpox is spread by human-to-human contact with an infected host and therefore can be contagious. The mortality rate for smallpox is approximately 30%. 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. This concern, combined with the reality of current smallpox vaccination programs in the military and selected civilian populations, mandates a clear understanding of vaccination-related adverse events and contraindications by all healthcare professionals. The vaccine may cause moderate to severe adverse events such as eczema vaccinatum, progressive vaccinia, and generalized vaccinia. The balance between the risks and benefits of mass vaccination in prevention of an epidemic is not clear. The Centers for Disease Control and Prevention has established a guideline for appropriate use of smallpox vaccine in the civilian population.

Smallpox and live-virus vaccination in transplant recipients.

PubMed

Fishman, Jay A

2003-07-01

Recent bioterrorism raises the specter of reemergence of smallpox as a clinical entity. The mortality of variola major infection ('typical smallpox') was approximately 30% in past outbreaks. Programs for smallpox immunization for healthcare workers have been proposed. Atypical forms of smallpox presenting with flat or hemorrhagic skin lesions are most common in individuals with immune deficits with historic mortality approaching 100%. Smallpox vaccination, even after exposure, is highly effective. Smallpox vaccine contains a highly immunogenic live virus, vaccinia. Few data exist for the impact of variola or safety of vaccinia in immunocompromised hosts. Both disseminated infection by vaccinia and person-to-person spread after vaccination are uncommon. When it occurs, secondary vaccinia has usually affected individuals with pre-existing skin conditions (atopic dermatitis or eczema) or with other underlying immune deficits. Historically, disseminated vaccinia infection was uncommon but often fatal even in the absence of the most severe form of disease, "progressive vaccinia". Some responded to vaccinia immune globulin. Smallpox exposure would be likely to cause significant mortality among immunocompromised hosts. In the absence of documented smallpox exposures, immunocompromised hosts should not be vaccinated against smallpox. Planning for bioterrorist events must include consideration of uniquely susceptible hosts.

Can smallpox response teams use the experience of disease management programs?

PubMed

Kozma, Chris M

2003-02-01

Any attempt to widely disperse smallpox vaccinations will necessitate educating people about the risks and benefits of vaccination. Most disease management programs have extensive experience in distributing educational materials and programs to health care workers and patients as well as in tracking response to interventions. Can this experience lend a hand in the event of widespread vaccination?

42 CFR 102.10 - Eligible requesters.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... vaccine recipients, as described in § 102.3(x); (2) Vaccinia contacts, as described in § 102.3(bb); or (3... vaccine recipients or vaccinia contacts (i.e., individuals authorized to act on behalf of the deceased...

42 CFR 102.10 - Eligible requesters.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... vaccine recipients, as described in § 102.3(x); (2) Vaccinia contacts, as described in § 102.3(bb); or (3... vaccine recipients or vaccinia contacts (i.e., individuals authorized to act on behalf of the deceased...

42 CFR 102.10 - Eligible requesters.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... vaccine recipients, as described in § 102.3(x); (2) Vaccinia contacts, as described in § 102.3(bb); or (3... vaccine recipients or vaccinia contacts (i.e., individuals authorized to act on behalf of the deceased...

42 CFR 102.10 - Eligible requesters.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... vaccine recipients, as described in § 102.3(x); (2) Vaccinia contacts, as described in § 102.3(bb); or (3... vaccine recipients or vaccinia contacts (i.e., individuals authorized to act on behalf of the deceased...

42 CFR 102.10 - Eligible requesters.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... vaccine recipients, as described in § 102.3(x); (2) Vaccinia contacts, as described in § 102.3(bb); or (3... vaccine recipients or vaccinia contacts (i.e., individuals authorized to act on behalf of the deceased...

76 FR 28991 - Privacy Act of 1974; Report of a New System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-19

... pandemic 2009 H1N1 influenza vaccines, antiviral medications (e.g., Tamiflu), anthrax vaccines, and smallpox vaccines. The PREP Act directs the Secretary to establish administrative procedures to compensate... resulting from pandemic, epidemic, or security countermeasures such as vaccines identified in declarations...

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

PubMed

Thorne, Craig D; Hirshon, Jon Mark; Himes, Carrie D; McDiarmid, Melissa A

2003-11-01

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.

Tecovirimat, a p37 envelope protein inhibitor for the treatment of smallpox infection.

PubMed

Duraffour, Sophie; Andrei, Graciela; Snoeck, Robert

2010-03-01

Since the eradication of naturally occurring smallpox in 1980, the fear that variola virus could be used as a biological weapon has become real. Over the last 10 years, emergency preparedness programs have been launched to protect populations against a smallpox outbreak or the possible emergence in humans of other orthopoxvirus infections, such as monkeypox. Vaccination against smallpox was responsible for its eradication, but was linked with high rates of adverse events and contraindications. In this context, intensive research in the poxvirus field has led to the development of safer vaccines and to an increase in the number of anti-poxvirus agents in the pipeline. SIGA Technologies Inc, under license from ViroPharma Inc, is developing tecovirimat (ST-246). Tecovirimat is a novel antiviral that inhibits the egress of orthopoxviruses by targeting viral p37 protein orthologs. The development of tecovirimat during the last 5 years for the treatment of smallpox and for its potential use as adjunct to smallpox vaccine is reviewed here.

Control, containment and health education in the smallpox-vaccination campaigns in Mexico in the 1940s.

PubMed

Agostoni, Claudia

2015-01-01

This article examines some of the changes that the Mexican vaccination programs underwent starting in 1943, the year when the National Smallpox Campaign (Campaña Nacional contra la Viruela) was established. It analyzes why a uniform and coordinated vaccination method was adopted to counter the outbreaks of this endemic disease, especially in central Mexico; the actions of its numerous and heterogeneous staff; and the reasons why smallpox vaccination was considered critical to establish a culture of prevention. In summary, the article examines why selective vaccination was chosen and the expansion of the health-education programs, topics that have been seldom addressed in historical research.

A brief history of smallpox eradication in Iran.

PubMed

Azizi, Mohammad Hossein

2010-01-01

Smallpox, which currently is only of historical interest, was once one of the most terrible illnesses with high mortality and morbidity. In the late 18th century, the English physician and naturalist, Edward Jenner (1749 - 1823), discovered an efficient preventive technique against smallpox which he termed "vaccination". Afterwards, the practice of vaccination gradually became widespread when finally in 1979, the World Health Organization formally declared the global eradication of this fatal disease.Presented here is a brief account of smallpox eradication in Iran which started on a limited scale in the 19th century by the order of Abbas Mirza (1789 - 1833), the Crown Prince of Fath Ali Shah Qajar (reign from 1797 - 1834), and reinforced in 1848 by Mirza Taghi Khan Amir Kabir (1807 - 1852) the Prime Minster of Naser ad-Din Shah, and became more popular after the establishment of the Pasteur Institute in Tehran in 1921, where considerable doses of smallpox vaccine were produced. In addition, in subsequent years, a law that mandated public smallpox vaccination was passed by the Iranian parliament (Majles) in 1953 and eventually, the mass vaccination program led to the complete eradication of smallpox in Iran in 1978.

Rethinking smallpox.

PubMed

Weiss, Martin M; Weiss, Peter D; Mathisen, Glenn; Guze, Phyllis

2004-12-01

The potential consequences of a competently executed smallpox attack have not been adequately considered by policy makers. The possibility of release of an aerosolized and/or bioengineered virus must be anticipated and planned for. The transmission and infectivity of variola virus are examined. Arguments for and against pre-event vaccination are offered. The likely morbidity and mortality that would ensue from implementation of a mass pre-event vaccination program, within reasonable boundaries, are known. The extent of contagion that could result from an aerosolized release of virus is unknown and may have been underestimated. Pre-event vaccination of first responders is urged, and voluntary vaccination programs should be offered to the public. Two defenses against a vaccine-resistant, engineered variola virus are proposed for consideration. Methisazone, an overlooked drug, is reported to be effective for prophylaxis only. The extent of reduction in the incidence of smallpox with use of this agent is uncertain. It is useless for treatment of clinical smallpox. N-100 respirators (face masks) worn by uninfected members of the public may prevent transmission of the virus.

Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy.

PubMed

Wittek, Riccardo

2006-05-01

In 1980 the World Health Organization declared that smallpox was eradicated from the world, and routine smallpox vaccination was discontinued. Nevertheless, samples of the smallpox virus (variola virus) were retained for research purposes, not least because of fears that terrorist groups or rogue states might also have kept samples in order to develop a bioweapon. Variola virus represents an effective bioweapon because it is associated with high morbidity and mortality and is highly contagious. Since September 11, 2001, countries around the world have begun to develop policies and preparedness programs to deal with a bioterror attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be associated with a number of serious adverse events, which can often be managed with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in patients for whom pre-exposure smallpox vaccine is contraindicated (such as those with eczema or pregnant women), although it is currently not licensed in these cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have been licensed by the FDA for the management of patients with progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body surface involvement or periocular implantation following inadvertent inoculation.

[The real philanthropic expedition of the smallpox vaccine: monarchy and modernity in 1803].

PubMed

Rigau-Pérez, José G

2004-09-01

Smallpox resulted in the death of 30 % of those who acquired it, so the preventive method discovered by Edward Jenner (London, 1798) spread very quickly. At the request in 1803 of Carlos IV, king of Spain, his government evaluated offers to carry smallpox vaccine to the colonies. The selected proposal, by doctor Francisco Xavier de Balmis, sought to take the lymph to America and Asia in a chain of arm to arm vaccination of foundlings. The Expedition set sail from Corunna on November 30, 1803, stopped in the Canary Isles, Puerto Rico, and Venezuela and after Caracas (1804) split in two groups. Balmis led some members of the Expedition to Cuba and Mexico. For the trip to the Philippines, in 1805, parents lent their children in exchange for economic compensation and the promise that the boys would be returned home. The Expedition returned to Mexico in August, 1807, but Balmis separately took vaccine to China and returned to Spain. Another contingent of the Expedition, under vice-director José Salvany, took vaccine to what we know as Colombia, Ecuador, Peru and Bolivia. His assistant Manuel Grajales reached the Chilean Patagonia in 1811. This article also comments on three principal themes - the institutional management of the scientific project, the conflicts that characterized its course, and the children's experience. The Vaccine Expedition was a brave and humanitarian endeavor, but also an extraordinary sanitary and administrative success. It was not until the twentieth century that a global eradication campaign eliminated smallpox in the world.

Smallpox eradication in West and Central Africa.

PubMed

Foege, W H; Millar, J D; Henderson, D A

1975-01-01

The history of smallpox eradication in the 20 countries of West and Central Africa from Mauritania to Zaire is recounted, including background, evolution of strategy, assessment, maintenance, costs, and significance of the campaign. Smallpox was endemic in these countries, peaking each year at the end of the spring dry season, usually occurring in isolated villages only periodically. The average case fatality was 14.5%, but twice as high in infants and older adults. Clinical exams showed that those with actual vaccination scars rarely got smallpox. The campaign was made feasible because of lyophilized heat-stable vaccine and bifurcated needles or jet injectors. The initial strategy called for mass vaccination and assessment of achieved vaccination. Between 1967 and 1969 100 million persons were vaccinated at collecting points; by 1972, 28 million more children had been protected. In 1966 an outbreak of 34 cases in Nigeria was blocked within 3 weeks of initiation of surveillance and containment. This effort also demonstrated that actual smallpox transmission was slow and relatively ineffective, and further that vaccination of contacts even after exposure was effective. The strategy was replaced by surveillance-containment begun in the seasonal low. The results were that smallpox disappeared within 5 months in an area of 12 million, and within 1 year in 19 of the 20 countries. Maintenance vaccination to prevent importation of the virus is continuing. The cost of the program was $15 million to the U.S. sponsors, or 1/10 the yearly price of smallpox control in the U.S.

[Confronting bioterrorism: Epidemiologic, clinical, and preventive aspects of smallpox].

PubMed

Franco-Paredes, Carlos; del Río, Carlos; Nava-Frías, Margarita; Rangel-Frausto, Sigfrido; Téllez, Ildefonso; Santos-Preciado, José Ignacio

2003-01-01

The worldwide eradication of smallpox, a major achievement in public health, is currently threatened by the risk of bioterrorism. The debate on the destruction of the Variola virus in the two reference laboratories of the World Health Organization has dramatically switched to the preservation of the remaining virus after the September 2001 terrorist events in the U.S. along with the intentional release of Bacillus anthracis in the U.S. The risk of intentional release of Variola virus constitutes a minimal, yet possible risk. A smallpox epidemic could have a devastating impact due to its elevated morbidity and mortality that would inflict in non-immune human population, in addition to the ensuing panic and social unrest. Therefore, the development of national preparedness and response plans along with the availability of smallpox vaccine to be used in the post-exposure phase represent a fundamental part of the preventive efforts to cope with bioterrorism. Reestablishing a preventive vaccination program was recently recommended by the Advisory Committee on Immunization Practices (ACIP). However, the vaccine currently available has historically been associated with serious adverse reactions, even death. Thus, this recommendation has not been universally accepted. To counter an epidemic of smallpox, medical personnel in the frontline need to be prepared with updated smallpox information to identify, diagnose, isolate, and treat cases if a bioterrorist attack should occur. Herein we present an indepth review for health care personnel with relevant epidemiologic, clinical, and preventive information on smallpox.

Reflections on New York City's 1947 Smallpox Vaccination Program and Its 1976 Swine Influenza Immunization Program.

PubMed

Imperato, Pascal James

2015-06-01

In 1947, a smallpox outbreak occurred in New York City with a total of twelve cases and two deaths. In order to contain this outbreak, the New York City Department of Health launched a mass immunization campaign that over a period of some 60 days vaccinated 6.35 million people. This article examines in detail the epidemiology of this outbreak and the measures employed to contain it. In 1976, a swine influenza strain was isolated among a few recruits at a US Army training camp at Fort Dix, New Jersey. It was concluded at the time that this virus possibly represented a re-appearance of the 1918 influenza pandemic influenza strain. As a result, a mass national immunization program was launched by the federal government. From its inception, the program encountered a myriad of challenges ranging from doubts that it was even necessary to the development of Guillain-Barré paralysis among some vaccine recipients. This paper examines the planning for and implementation of the swine flu immunization program in New York City. It also compares it to the smallpox vaccination program of 1947. Despite equivalent financial and personnel resources, leadership and organizational skills, the 1976 program only immunized approximately a tenth of the number of New York City residents vaccinated in 1947. The reasons for these marked differences in outcomes are discussed in detail.

The eradication of smallpox: organizational learning and innovation in international health administration.

PubMed

Hopkins, J W

1988-04-01

The WHO smallpox eradication campaign represents perhaps the best example of a successful international health administration. In the 1st year of the campaign (1967), the guiding strategy was to vaccinate people en masse over a 2-3 year period in countries where smallpox was epidemic thereby conquering the disease. In Western Nigeria where 90% of the population had been vaccinated, a smallpox outbreak occurred in a religious sect resisting vaccinations and a delay in delivery of supplies forced a change in strategy. Campaign staff learned to rapidly isolate infected persons and swiftly vaccinate the uninfected in an outbreak area in order to break the transmission of smallpox, even where 1/2 the population had been vaccinated. Technological advancements also contributed to the campaign's success. For example, the jet injector vaccinated 1000 people/hour with efficient, reliable, mass produced potent, stable freeze dried vaccines (often produced in target countries) or the less costly and virtually maintenance free bifurcated needle was used. The most significant contribution to the success of the campaign, however, was the flexible mode of management adopted by the campaign staff at WHO which provided an appropriate environment for organizational learning and innovation. Although management was open and flexible, the campaign did depend on careful planning and setting of goals, continual assessment, and rapid response to field requests for assistance or advice. Trends in the incidence of smallpox was chosen as the indicator of success as opposed to the number of vaccinations. The campaign demonstrated the need for cultural adaptations as it operated in each country and region. This evaluation of the success of the smallpox campaign presents conclusions that serve as guidelines to the organization and administration of international programs designed to solve other health problems.

Biological Warfare Improved Response Program (BW-IRP) CDC/DoD Smallpox Workshop

DTIC Science & Technology

2005-01-01

national surveillance effort. Awareness of unique symptoms will need to be raised by training clinicians. For example, adults presenting with chicken pox ...no case definitions but rather visual recognition cards. Presently, the chicken pox definition has been modified to create a smallpox definition. The...the last 2 weeks • Pharmaceuticals prescribed or issued for chicken pox • A number of suspected cases of chicken pox • Reports of rashes, especially a

What is Smallpox?

MedlinePlus

... Smallpox Website NIH Smallpox Research CDC Poxvirus and Rabies Branch Poxvirus Diseases What is Smallpox? Recommend on ... Smallpox Website NIH Smallpox Research CDC Poxvirus and Rabies Branch Poxvirus Diseases File Formats Help: How do ...

The decline of adult smallpox in eighteenth-century London.

PubMed

Davenport, Romola; Schwarz, Leonard; Boulton, Jeremy

2011-01-01

Smallpox was probably the single most lethal disease in eighteenth-century Britain, but was a minor cause of death by the mid-nineteenth century. Although vaccination was crucial to the decline of smallpox, especially in urban areas, from the beginning of the nineteenth century, it remains disputed the extent to which smallpox mortality declined before vaccination. Analysis of age-specific changes in smallpox burials within the large west London parish of St Martin-in-the-Fields revealed a precipitous reduction in adult smallpox risk from the 1770s, and this pattern was duplicated in the east London parish of St Dunstan's. Most adult smallpox victims were rural migrants, and such a drop in their susceptibility is consistent with a sudden increase in exposure to smallpox in rural areas. We investigated whether this was due to the spread of inoculation, or an increase in smallpox transmission, using changes in the age patterns of child smallpox burials. Smallpox mortality rose among infants, and smallpox burials became concentrated at the youngest ages, suggesting a sudden increase in infectiousness of the smallpox virus. Such a change intensified the process of smallpox endemicization in the English population, but also made cities substantially safer for young adult migrants.

Smallpox and smallpox vaccine: ocular and systemic risks and ethical uncertainties.

PubMed

Chous, A Paul; Hom, Gregory G

2003-09-01

The threat of bioterrorism and use of biological weapons has drawn renewed attention to smallpox, and smallpox vaccinations have been resumed in the United States. Both smallpox and smallpox vaccine carry risk of potentially debilitating or fatal adverse effects. The optometrist must be familiar with the signs and symptoms of smallpox disease and complications of smallpox vaccine for proper management and preservation of vision. The literature on the ocular and systemic effects of smallpox and smallpox vaccination is reviewed to provide the practicing optometrist with an overview of the issues involved in case management. Recent guidelines have placed additional ocular-related contraindications to receiving the smallpox vaccine. Risk factors for complications arising from smallpox vaccination are discussed. A discussion of the ethical implications is also presented. Knowledge of the signs and symptoms of smallpox infection, and of adverse effects caused by smallpox vaccination, can provide the necessary background to help eye care providers make appropriate diagnoses and referrals. Understanding ethical and legal/Constitutional questions surrounding the risk of outbreak and various vaccination containment strategies will help optometrists make informed decisions as health care professionals, patient advocates, and concerned citizens, as well as weigh the risks and benefits of vaccination, if it is offered to them.

Prediction of Steps in the Evolution of Variola Virus Host Range

PubMed Central

Smithson, Chad; Purdy, Alex; Verster, Adrian J.; Upton, Chris

2014-01-01

Variola virus, the agent of smallpox, has a severely restricted host range (humans) but a devastatingly high mortality rate. Although smallpox has been eradicated by a World Health Organization vaccination program, knowledge of the evolutionary processes by which human super-pathogens such as variola virus arise is important. By analyzing the evolution of variola and other closely related poxviruses at the level of single nucleotide polymorphisms we detected a hotspot of genome variation within the smallpox ortholog of the vaccinia virus O1L gene, which is known to be necessary for efficient replication of vaccinia virus in human cells. These mutations in the variola virus ortholog and the subsequent loss of the functional gene from camelpox virus and taterapox virus, the two closest relatives of variola virus, strongly suggest that changes within this region of the genome may have played a key role in the switch to humans as a host for the ancestral virus and the subsequent host-range restriction that must have occurred to create the phenotype exhibited by smallpox. PMID:24626337

Prediction of steps in the evolution of variola virus host range.

PubMed

Smithson, Chad; Purdy, Alex; Verster, Adrian J; Upton, Chris

2014-01-01

Variola virus, the agent of smallpox, has a severely restricted host range (humans) but a devastatingly high mortality rate. Although smallpox has been eradicated by a World Health Organization vaccination program, knowledge of the evolutionary processes by which human super-pathogens such as variola virus arise is important. By analyzing the evolution of variola and other closely related poxviruses at the level of single nucleotide polymorphisms we detected a hotspot of genome variation within the smallpox ortholog of the vaccinia virus O1L gene, which is known to be necessary for efficient replication of vaccinia virus in human cells. These mutations in the variola virus ortholog and the subsequent loss of the functional gene from camelpox virus and taterapox virus, the two closest relatives of variola virus, strongly suggest that changes within this region of the genome may have played a key role in the switch to humans as a host for the ancestral virus and the subsequent host-range restriction that must have occurred to create the phenotype exhibited by smallpox.

Vaccine Basics (Smallpox)

MedlinePlus

... Smallpox Website NIH Smallpox Research CDC Poxvirus and Rabies Branch Poxvirus Diseases Vaccine Basics Recommend on Facebook ... Smallpox Website NIH Smallpox Research CDC Poxvirus and Rabies Branch Poxvirus Diseases File Formats Help: How do ...

Signs and Symptoms (Smallpox)

MedlinePlus

... Smallpox Website NIH Smallpox Research CDC Poxvirus and Rabies Branch Poxvirus Diseases Signs and Symptoms Recommend on ... Smallpox Website NIH Smallpox Research CDC Poxvirus and Rabies Branch Poxvirus Diseases File Formats Help: How do ...

The Emergency campaign for smallpox eradication from Somalia (1977-1979)--revisited.

PubMed

Deria, Abdullahi

2011-12-30

The historical significance of smallpox eradication from Somalia lies in the fact that the country was the last to record the last endemic smallpox case in the world. Before 1977 the programme was mismanaged. In the mid-1970s, the programme was plagued with concealment. Confirmation of smallpox outbreak in Mogadishu in September 1976 delayed global smallpox eradication. The Government maintained that there was no ongoing smallpox transmission in the country after the Mogadishu outbreak and frustrated independent attempts to verify its claim. In February 1977 the Government allowed World Health Organization (WHO) epidemiologists to search, unhindered, for smallpox outside Mogadishu. Soon widespread smallpox transmission was detected. The Government appealed for international support. The strategy to stop the smallpox transmission was based on surveillance and containment. The WHO took the leading role of the campaign which, in spite of the Somalia/Ethiopia war of 1977/78, culminated in the eradication of smallpox from the country. Somalia was certified smallpox-free on 19 October 1979. Copyright © 2011 Elsevier Ltd. All rights reserved.

What Is Smallpox?

MedlinePlus

... Safe Videos for Educators Search English Español What Is Smallpox? KidsHealth / For Kids / What Is Smallpox? Print en español ¿Qué es la viruela? What Is Smallpox? Smallpox is a very serious illness caused ...

Determination of the appropriate quarantine period following smallpox exposure: an objective approach using the incubation period distribution.

PubMed

Nishiura, Hiroshi

2009-01-01

Determination of the most appropriate quarantine period for those exposed to smallpox is crucial to the construction of an effective preparedness program against a potential bioterrorist attack. This study reanalyzed data on the incubation period distribution of smallpox to allow the optimal quarantine period to be objectively calculated. In total, 131 cases of smallpox were examined; incubation periods were extracted from four different sets of historical data and only cases arising from exposure for a single day were considered. The mean (median and standard deviation (SD)) incubation period was 12.5 (12.0, 2.2) days. Assuming lognormal and gamma distributions for the incubation period, maximum likelihood estimates (and corresponding 95% confidence interval (CI)) of the 95th percentile were 16.4 (95% CI: 15.6, 17.9) and 16.2 (95% CI: 15.5, 17.4) days, respectively. Using a non-parametric method, the 95th percentile point was estimated as 16 (95% CI: 15, 17) days. The upper 95% CIs of the incubation periods at the 90th, 95th and 99th percentiles were shorter than 17, 18 and 23 days, respectively, using both parametric and non-parametric methods. These results suggest that quarantine measures can ensure non-infection among those exposed to smallpox with probabilities higher than 95-99%, if the exposed individuals are quarantined for 18-23 days after the date of contact tracing.

Urban inoculation and the decline of smallpox mortality in eighteenth‐century cities—a reply to Razzell†

PubMed Central

Boulton, Jeremy; Schwarz, Leonard

2015-01-01

Smallpox was probably the single most lethal disease in eighteenth‐century Britain but was reduced to a minor cause of death by the mid‐nineteenth century due to vaccination programmes post‐1798. While the success of vaccination is unquestionable, it remains disputed to what extent the prophylactic precursor of vaccination, inoculation, reduced smallpox mortality in the eighteenth century. Smallpox was most lethal in urban populations, but most researchers have judged inoculation to have been unpopular in large towns. Recently, however, Razzell argued that inoculation significantly reduced smallpox mortality of adults and older children in London in the last third of the eighteenth century. This article uses demographic evidence from London and Manchester to confirm previous findings of a sudden fall in adult smallpox mortality and a rise in the importance of smallpox in early childhood c. 1770. The nature of these changes is consistent with an increase in smallpox transmission in London and Manchester after 1770 and indicates that smallpox inoculation was insufficient to reduce smallpox mortality in large towns. It remains unclear whether inoculation could have operated to enhance smallpox transmission or whether changes in the properties of the smallpox virus drove the intensification of smallpox mortality among young children post‐1770. PMID:26900169

Urban inoculation and the decline of smallpox mortality in eighteenth-century cities-a reply to Razzell.

PubMed

Davenport, Romola J; Boulton, Jeremy; Schwarz, Leonard

2016-02-01

Smallpox was probably the single most lethal disease in eighteenth-century Britain but was reduced to a minor cause of death by the mid-nineteenth century due to vaccination programmes post-1798. While the success of vaccination is unquestionable, it remains disputed to what extent the prophylactic precursor of vaccination, inoculation, reduced smallpox mortality in the eighteenth century. Smallpox was most lethal in urban populations, but most researchers have judged inoculation to have been unpopular in large towns. Recently, however, Razzell argued that inoculation significantly reduced smallpox mortality of adults and older children in London in the last third of the eighteenth century. This article uses demographic evidence from London and Manchester to confirm previous findings of a sudden fall in adult smallpox mortality and a rise in the importance of smallpox in early childhood c . 1770. The nature of these changes is consistent with an increase in smallpox transmission in London and Manchester after 1770 and indicates that smallpox inoculation was insufficient to reduce smallpox mortality in large towns. It remains unclear whether inoculation could have operated to enhance smallpox transmission or whether changes in the properties of the smallpox virus drove the intensification of smallpox mortality among young children post-1770.

Smallpox and American Indians revisited.

PubMed

Riley, James C

2010-10-01

Smallpox ravaged the people of Europe and the Americas in the early modern era. Why it was a catastrophic cause of death for American Indians that helped lead to severe depopulation, but a manageable cause among Europeans that allowed continued population growth, has puzzled scholars. Research on variola continued after smallpox eradication in 1977, prompted in part by the fear that aerosolized smallpox might be used in bioterrorism. That research updates factors that may have aggravated smallpox lethality in American Indians, giving new information about infectivity, the proportion of people who may have contracted smallpox, the burden on infants of mothers who had not had smallpox, and the toll for pregnant women. This essay reviews old and new hypotheses about why so many in the New World died from smallpox using recent smallpox research and older sources.

Smallpox Eradication in Bangladesh, 1972–19761

PubMed Central

Foster, Stanley O.; Hughes, Kenneth; Tarantola, Daniel; Glasser, John W.

2017-01-01

Rahima Bano, the world’s last endemic case of severe smallpox, Variola Major, developed rash on October 16, 1975 on Bhola Island, Bangladesh. Achieving eradication in a country destroyed by war challenged the achievement of smallpox eradication. Between January 1, 1972 and December 31, 1975, 225,000 smallpox cases and 45,000 smallpox deaths occurred. Adapting the global smallpox eradication strategies of surveillance, the detection of smallpox cases, and containment, the interruption of smallpox transmission, utilized progress toward three objectives to monitor performance: 1) Surveillance – the percent smallpox infected villages detected within 14 days of the first case of rash, 2) Knowledge of the Reward – public knowledge of the current amount of the reward for reporting smallpox, and 3) Containment – the percent of infected villages interrupting smallpox transmission within 14 days of detection. Failures to achieve these objectives led to identification and implementation of improved strategies that eventually achieved eradication. Essential to this success was a tripartite partnership of the citizens of Bangladesh, the Bangladesh Ministry of Health and its field staff, and personnel and resources mobilized by the World Health Organization. PMID:22188934

Smallpox eradication in Bangladesh, 1972-1976.

PubMed

Foster, Stanley O; Hughes, Kenneth; Tarantola, Daniel; Glasser, John W

2011-12-30

Rahima Banu, the world's last endemic case of severe smallpox, Variola Major, developed rash on October 16, 1975 on Bhola Island, Bangladesh. Achieving eradication in a country destroyed by war challenged the achievement of smallpox eradication. Between January 1, 1972 and December 31, 1975, 225,000 smallpox cases and 45,000 smallpox deaths occurred. Adapting the global smallpox eradication strategies of surveillance, the detection of smallpox cases, and containment, the interruption of smallpox transmission, utilized progress toward three objectives to monitor performance: (1) surveillance - the percent of smallpox infected villages detected within 14 days of the first case of rash, (2) knowledge of the reward - public knowledge of the current amount of the reward for reporting smallpox, and (3) containment - the percent of infected villages interrupting smallpox transmission within 14 days of detection. Failures to achieve these objectives led to the identification and implementation of improved strategies that eventually achieved eradication. Essential to this success was a tripartite partnership of the citizens of Bangladesh, the Bangladesh Ministry of Health, its field staff, and staff and resources mobilized by the World Health Organization. Copyright © 2011. Published by Elsevier Ltd.

Smallpox: vaccine reactions and contraindications.

PubMed

Tom, Wynnis L; Kenner, Julie R; Friedlander, Sheila F

2004-07-01

Concern regarding the use of smallpox for bioterrorism has led to the reintroduction of smallpox vaccination. The historic background leading to protective methods against smallpox disease, the adverse reactions and contraindications associated with vaccination, and the ongoing development of potentially safer smallpox vaccines are reviewed here.

Smallpox vaccines for biodefense: need and feasibility.

PubMed

Artenstein, Andrew W; Grabenstein, John D

2008-10-01

Smallpox, eradicated as a cause of natural disease through an intensive global effort in the later part of the 20th Century, has resurfaced as a possible agent of bioterrorism. For this reason, there is renewed interest in smallpox vaccines. Live vaccinia virus, an orthopoxvirus related to smallpox, has a long and successful clinical track record as an effective smallpox vaccine; however, its use is associated with uncommon yet serious adverse events. This has led to a surge of recent research into newer-generation smallpox vaccines with improved safety profiles and retained efficacy. This article will review the history of smallpox vaccines, assess the status of newer-generation vaccines and examine the overall risk-versus-benefit profile of smallpox vaccination.

[Smallpox--in the past or not?].

PubMed

Kuljić-Kapulica, Nada

2004-01-01

Smallpox is a potentially deadly illness caused by the variola virus, an orthopoxvirus. Severe illness followed by blister-like body rash is the sign of smallpox. Smallpox symptoms develop about 12 days after exposure. V. variole can spread very readily by aerosol, which may lead to explosive epidemics. For centuries, smallpox has been a worldwide cause of death, killing about 30% of the infected people. In 1972, the epidemic of smallpox in ex-Yugoslavia was the largest postwar smallpox epidemic in Europe. The total number of the affected was 175, out of whom 35 with fatal outcome, accounting for 20% of mortality. However, after a decade-long vaccination effort, the last natural case of smallpox occurred in 1977. The only way to prevent smallpox epidemic is by vaccination and patients' isolation. The possibility of future bioterrorism attacks, which may cause a new outbreak of smallpox and return variola, is very serious. World population is not immune, because of lack of vaccination. In 1980, the World Health Organization (WHO) declared the disease fully eradicated.

Bioterrorism preparedness--Part II. Smallpox vaccination in a hospital setting.

PubMed

Jacobs, Lenworth M; Emanuelsen, Kathy; McKay, Charles; Burns, Karyl

2004-01-01

The threat of using smallpox as an agent for bioterrorism resulted in a directive for the creation of smallpox response teams. In Connecticut, The Commissioner of the Department of Public Health convened public health and hospital leadership to plan for the vaccination of these teams. The purpose of this paper is to provide a description of the vaccination program at Hartford Hospital, a Center of Excellence for Bioterrorism Preparedness, and to report the results of a survey of the vaccinees regarding the vaccination experience. Ninety persons were vaccinated. Six individuals experienced low-grade fever and 10 had axillary node swelling. One individual experienced significant fatigue. A total of six persons lost time from work. Four lost one day and two persons lost between four to five days of work. There was no autoinoculation, transfer inoculation, vaccinia or any other significant complication. Survey results indicate that most vaccinees felt positive about the experience.

Smallpox: what every otolaryngologist should know.

PubMed

Tennyson, Heath C; Mair, Eric A

2004-03-01

In light of recent terrorist events and the potential threat of smallpox as a biological agent, we present information concerning smallpox to better inform the otolaryngologist concerning this disease and its prevention. We performed a review of the smallpox and smallpox vaccination literature over the past 200 years using MEDLINE, PREMEDLINE, Centers for Disease Control and Prevention Internet site, World Health Organization Internet site, and references found in previous publications not found in MEDLINE or PREMEDLINE. Our search focused on the pathogenesis, clinical presentation, course, unique manifestations in the head and neck, diagnosis, and treatment of smallpox, as well as the method of smallpox vaccination, vaccination contraindications, and complications. Smallpox is a viral disease with a high mortality rate. Its clinical course, manifestations, and methods of prevention are carefully analyzed in light of otolaryngology practice. Smallpox manifestations in the head and neck often presented as acute airway obstruction and also as long-term sequelae such as ectropion, nasal vestibular stenosis, conductive hearing loss, and blindness. Most chronic sequelae involve the head and neck. Smallpox vaccination is effective but not without potential serious risks.

From smallpox eradication to contemporary global health initiatives: enhancing human capacity towards a global public health goal.

PubMed

Tarantola, Daniel; Foster, Stanley O

2011-12-30

The eradication of smallpox owes its success first and foremost to the thousands of lay health workers and community members who, throughout the campaign and across continents, took on the roles of advocates, educators, vaccinators, care providers and contributors to epidemic surveillance and containment. Bangladesh provides a good example where smallpox eradication and the capacity enhancement needed to achieve this goal resulted in a two-way mutually beneficial process. Smallpox-dedicated staff provided community members with information guidance, support and tools. In turn, communities not only created the enabling environment for smallpox program staff to perform their work but acquired the capacity to perform essential eradication tasks. Contemporary global health programmes can learn much from these core lessons including: the pivotal importance of supporting community aspirations, capacity and resilience; the critical need to enhance commitment, capacity and accountability across the workforce; and the high value of attentive human resources management and support. We owe to subsequent global disease control, elimination and eradication ventures recognition of the need for social and behavioural science to inform public health strategies; the essential roles that civil society organizations and public-private partnerships can play in public health discourse and action; the overall necessity of investing in broad-based health system strengthening; and the utility of applying human rights principles, norms and standards to public health policy and practice. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Smallpox: the basics.

PubMed

Slifka, Mark K; Hanifin, Jon M

2004-07-01

Variola major is the causative agent of smallpox, a severe disease that was arguably one of the most serious human pathogens in recorded history. Humans are the only known reservoir of variola major; no known animal or insect reservoirs have been identified. Thus, after eradication of smallpox through a global immunization effort, this incredibly lethal scourge was eliminated from all corners of the globe. Despite the total eradication of naturally occurring smallpox, there are still stockpiles of smallpox virus maintained in the United States and the former Soviet Union. Unfortunately, it is impossible to know if all smallpox stocks have been accounted for or whether unknown or unreported stocks of smallpox may still exist. In the age of genetic engineering, these viruses could theoretically be modified to increase their virulence to the levels associated with smallpox itself.

Defending Against Smallpox: a Focus on Vaccines

PubMed Central

Voigt, Emily A.; Kennedy, Richard B.; Poland, Gregory A.

2016-01-01

Smallpox has shaped human history, from the earliest human civilizations well into the 20th century. With high mortality rates, rapid transmission, and serious long-term effects on survivors, smallpox was a much-feared disease. The eradication of smallpox represents an unprecedented medical victory for the lasting benefit of human health and prosperity. Concerns remain, however, about the development and use of the smallpox virus as a biological weapon, which necessitates the need for continued vaccine development. Smallpox vaccine development is thus a much-reviewed topic of high interest. This review focuses on the current state of smallpox vaccines and their context in biodefense efforts. PMID:27049653

Defending against smallpox: a focus on vaccines.

PubMed

Voigt, Emily A; Kennedy, Richard B; Poland, Gregory A

2016-09-01

Smallpox has shaped human history, from the earliest human civilizations well into the 20th century. With high mortality rates, rapid transmission, and serious long-term effects on survivors, smallpox was a much-feared disease. The eradication of smallpox represents an unprecedented medical victory for the lasting benefit of human health and prosperity. Concerns remain, however, about the development and use of the smallpox virus as a biological weapon, which necessitates the need for continued vaccine development. Smallpox vaccine development is thus a much-reviewed topic of high interest. This review focuses on the current state of smallpox vaccines and their context in biodefense efforts.

GeneChip Resequencing of the Smallpox Virus Genome Can Identify Novel Strains: a Biodefense Application▿

PubMed Central

Sulaiman, Irshad M.; Tang, Kevin; Osborne, John; Sammons, Scott; Wohlhueter, Robert M.

2007-01-01

We developed a set of seven resequencing GeneChips, based on the complete genome sequences of 24 strains of smallpox virus (variola virus), for rapid characterization of this human-pathogenic virus. Each GeneChip was designed to analyze a divergent segment of approximately 30,000 bases of the smallpox virus genome. This study includes the hybridization results of 14 smallpox virus strains. Of the 14 smallpox virus strains hybridized, only 7 had sequence information included in the design of the smallpox virus resequencing GeneChips; similar information for the remaining strains was not tiled as a reference in these GeneChips. By use of variola virus-specific primers and long-range PCR, 22 overlapping amplicons were amplified to cover nearly the complete genome and hybridized with the smallpox virus resequencing GeneChip set. These GeneChips were successful in generating nucleotide sequences for all 14 of the smallpox virus strains hybridized. Analysis of the data indicated that the GeneChip resequencing by hybridization was fast and reproducible and that the smallpox virus resequencing GeneChips could differentiate the 14 smallpox virus strains characterized. This study also suggests that high-density resequencing GeneChips have potential biodefense applications and may be used as an alternate tool for rapid identification of smallpox virus in the future. PMID:17182757

Antiviral immunity following smallpox virus infection: a case-control study.

PubMed

Hammarlund, Erika; Lewis, Matthew W; Hanifin, Jon M; Mori, Motomi; Koudelka, Caroline W; Slifka, Mark K

2010-12-01

Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4(+) and CD8(+) T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases.

Antiviral Immunity following Smallpox Virus Infection: a Case-Control Study▿

PubMed Central

Hammarlund, Erika; Lewis, Matthew W.; Hanifin, Jon M.; Mori, Motomi; Koudelka, Caroline W.; Slifka, Mark K.

2010-01-01

Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4+ and CD8+ T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases. PMID:20926574

The South Asian Origins of the Global Network to Eradicate Blindness: WHO, NGOs, and Decentralization.

PubMed

Williams, Logan D A

2018-03-01

The global network to eradicate blindness emerged out of the work of Western and South Asian professionals to eradicate smallpox which was endemic in South Asia. The history of the emergence of the global network to eradicate blindness demonstrates a shift from vertical command and control public health programs directed by the WHO, to the decentralized public health services originating in non-profit, non-governmental organizations and coordinated by the WHO. The WHO constitution started with a federal regionalist structure that encouraged collaboration and coordination with NGOs. In South Asia in particular, epidemiologists and general medical practitioners moved from eradicating smallpox through the WHO to creating their own domestic and international NGOs based in various countries with a mission to control blindness in South Asia and Africa. In 1975, pushed by the WHO Director General, these new NGOs in turn joined with individual ophthalmologists and existing blind member associations to form the International Agency for the Prevention of Blindness. Thus, the WHO was shaped by, and shaping, international NGOs such as the IAPB. The IAPB pushed for the formation of the WHO Prevention of Blindness program. This was the earliest example of how the IAPB facilitates bottom-up agenda-setting in the WHO. In 1980, when the WHO officially closed the smallpox program, the Prevention of Blindness program first received independent funding. Presently, the IAPB acts as a decentralized arm of the WHO. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immunogenicity and protection efficacy of subunit-based smallpox vaccines using variola major antigens.

PubMed

Sakhatskyy, Pavlo; Wang, Shixia; Zhang, Chuanyou; Chou, Te-Hui; Kishko, Michael; Lu, Shan

2008-02-05

The viral strain responsible for smallpox infection is variola major (VARV). 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. This lack of immunity is a concern due to the potential for use of smallpox as a biological weapon. Considerable progress has been made in the development of subunit-based smallpox vaccines resulting from the identification of VACV protective antigens. It also offers the possibility of using antigens from VARV to formulate the next generation subunit-based smallpox vaccines. Here, we show that codon-optimized DNA vaccines expressing three VARV antigens (A30, B7 and F8) and their recombinant protein counterparts elicited high-titer, cross-reactive, VACV neutralizing antibody responses in mice. Vaccinated mice were protected from intraperitoneal and intranasal challenges with VACV. These results suggest the feasibility of a subunit smallpox vaccine based on VARV antigen sequences to induce immunity against poxvirus infection.

Bichat guidelines for the clinical management of smallpox and bioterrorism-related smallpox.

PubMed

Bossi, Philippe; Tegnell, Anders; Baka, Agoritsa; Van Loock, Frank; Hendriks, J; Werner, Albrecht; Maidhof, Heinrich; Gouvras, Georgios

2004-12-15

Smallpox is a viral infection caused by the variola virus. It was declared eradicated worldwide by the Word Health Organization in 1980 following a smallpox eradication campaign. Smallpox is seen as one of the viruses most likely to be used as a biological weapon. The variola virus exists legitimately in only two laboratories in the world. Any new case of smallpox would have to be the result of human accidental or deliberate release. The aerosol infectivity, high mortality, and stability of the variola virus make it a potential and dangerous threat in biological warfare. Early detection and diagnosis are important to limit the spread of the disease. Patients with smallpox must be isolated and managed, if possible, in a negative-pressure room until death or until all scabs have been shed. There is no established antiviral treatment for smallpox. The most effective prevention is vaccination before exposure.

Bichat guidelines for the clinical management of smallpox and bioterrorism-related smallpox.

PubMed

Bossi, P; Tegnell, A; Baka, A; van Loock, F; Werner, A; Hendriks, J; Maidhof, H; Gouvras, G

2004-12-01

Smallpox is a viral infection caused by the variola virus. It was declared eradicated worldwide by the Word Health Organization in 1980 following a smallpox eradication campaign. Smallpox is seen as one of the viruses most likely to be used as a biological weapon. The variola virus exists legitimately in only two laboratories in the world. Any new case of smallpox would have to be the result of human accidental or deliberate release. The aerosol infectivity, high mortality, and stability of the variola virus make it a potential and dangerous threat in biological warfare. Early detection and diagnosis are important to limit the spread of the disease. Patients with smallpox must be isolated and managed, if possible, in a negative-pressure room until death or until all scabs have been shed. There is no established antiviral treatment for smallpox. The most effective prevention is vaccination before exposure.

Remaining questions about clinical variola major.

PubMed

Lane, J Michael

2011-04-01

After the recent summary of World Health Organization-authorized research on smallpox, several clinical issues remain. This policy review addresses whether early hemorrhagic smallpox is disseminated intravascular coagulation and speculates about the cause of the high mortality rate among pregnant women and whether ocular smallpox is partly the result of trachoma or vitamin A deficiency. The joint destruction common in children with smallpox might be prevented by antiviral drugs, but intraarticular infusion of antiviral drugs is unprecedented. Development of highly effective antiviral drugs against smallpox raises the issue of whether postexposure vaccination can be performed without interference by an antiviral drug. Clinicians should consider whether patients with smallpox should be admitted to general hospitals. Although an adequate supply of second-generation smallpox vaccine exists in the United States, its use is unclear. Finally, political and ethical forces suggest that destruction of the remaining stocks of live smallpox virus is now appropriate.

A population survey of smallpox knowledge, perceptions, and healthcare-seeking behavior surrounding the Iraq invasion--Connecticut 2002-03.

PubMed

Marshall, Katherine M; Begier, Elizabeth M; Griffith, Kevin S; Adams, Mary L; Hadler, James L

2005-01-01

Knowledge and perceptions about smallpox would probably influence public behavior following an intentional smallpox release. We assessed public knowledge, perceptions, and related healthcare-seeking behavior in Connecticut during the period of heightened interest in smallpox preparedness surrounding the Iraq invasion. Smallpox-related questions were added to Connecticut's Behavioral Risk Factor Surveillance System survey, an ongoing statewide adult population-based survey during December 2002-July 2003 and November-December 2003. Among 4,074 respondents, when asked about a hypothetical febrile illness, 72% would first contact their primary care provider (PCP) on weekdays. During nights and weekends, respondents would depend nearly equally on PCPs and emergency departments (37% versus 36%). Most knew smallpox is transmissible from person to person (72%) but not that the majority infected with smallpox survive (38%) or that smallpox is most contagious after the appearance of rash (11%). Knowledge regarding transmissibility and mortality improved during the study period (p < 0.001). Only 31% recognized that vaccinia vaccine is riskier than routine vaccines; 41% would choose vaccination if available. Concern about smallpox's potential use as a weapon was high but decreased after President Bush declared "mission accomplished" in Iraq in May 2003 (p < 0.001). Despite national coverage of smallpox by the media, most respondents lacked basic knowledge regarding the disease. Incorrect perceptions regarding vaccinia vaccine's risks could increase inappropriate vaccine demand among nonexposed people with vaccine contraindications during a mass vaccination campaign. Current perceptions should inform future smallpox preparedness planning. In addition, both PCPs and emergency medicine clinicians should be targeted for education regarding smallpox diagnosis.

Immunogenicity and Protection Efficacy of Subunit-based Smallpox Vaccines Using Variola Major Antigens

PubMed Central

Sakhatskyy, Pavlo; Wang, Shixia; Zhang, Chuanyou; Chou, Te-Hui; Kishko, Michael; Lu, Shan

2008-01-01

The viral strain responsible for smallpox infection is variola major (VARV). 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. This lack of immunity is a concern due to the potential for use of smallpox as a biological weapon. Considerable progress has been made in the development of subunit-based smallpox vaccines resulting from the identification of VACV protective antigens. It also offers the possibility of using antigens from VARV to formulate the next generation subunit-based smallpox vaccines. Here, we show that codon-optimized DNA vaccines expressing three VARV antigens (A30, B7 and F8) and their recombinant protein counterparts elicited high-titer, cross-reactive, VACV neutralizing antibody responses in mice. Vaccinated mice were protected from intraperitoneal and intranasal challenges with VACV. These results suggest the feasibility of a subunit smallpox vaccine based on the VARV antigen sequences to induce immunity against poxvirus infection. PMID:17950773

A Case Series of Smallpox Vaccination-Associated Myopericarditis: Effects on Safety and Readiness of the Active Duty Soldier.

PubMed

Sarkisian, Simon A; Hand, Gregory; Rivera, Vanessa M; Smith, Meghan; Miller, Joel A

2018-06-27

Myopericarditis following smallpox vaccination is a documented side effect with increasing incidence since reestablishing mandatory vaccination for deploying military personnel. After the ACAM2000 smallpox vaccine replaced the Dryvax smallpox vaccine, the rate of myopericarditis increased 50-fold.We describe six case reports of active duty soldiers who presented to the emergency department complaining of chest pain shortly after receiving routine pre-deployment vaccinations to include smallpox. All were hospitalized and became non-deployable after developing smallpox vaccination-associated myopericarditis.Some cases of smallpox vaccination-associated myopericarditis are diagnosed in soldiers in austere environments, which have led to the soldier being removed from the mission for months at a time. This can be avoided by having all soldiers who receive the smallpox vaccine screened for clinical evidence of myopericarditis at 30 days after receiving the vaccine. Contributing to the increasing rate of myopericarditis as well as the negative impact on soldier medical readiness, the continued use of the current ACAM2000 smallpox vaccine should be monitored.

Interwoven support: an historical survey of US federal programs enabling immunization.

PubMed

Dalrymple, Dack W; Grabenstein, John D

2014-11-28

The US Government (USG) can date its involvement with immunization to military and civilian efforts in 1777 and 1813 to prevent smallpox. USG involvement began accelerating with federal licensing of vaccine and antibody manufacturers in 1903. In addition to ongoing regulation of manufacturing and product quality, military and civilian arms of the USG have led research efforts into new or improved vaccines. These efforts have included diseases endemic in the United States, as well as medical countermeasures targeted against biological weapons, influenza pandemics, and emerging infectious diseases. Especially since the 1950s, the USG has provided increasing levels of funding to purchase vaccines and conduct vaccination programs. These programs have focused largely on children, although vaccination programs for adults have been expanded somewhat in recent years. Multiple agencies of the USG have convened various panels of accomplished external experts who have generated widely regarded recommendations on vaccine safety and efficacy and optimal immunization practices. USG programs for safety assessment, injury compensation, liability protection, and disease surveillance have been developed to assess needs, evaluate safety questions, ensure vaccine supply, and foster confidence in vaccination efforts. Debates on the extent of government involvement date back to the 1890 s and continue today. Several pivotal expansions of government involvement followed disease outbreaks or manufacturing accidents. This historical survey describes each of the major US federal programs in these categories, including references to applicable law. Copyright © 2014 Elsevier Ltd. All rights reserved.

42 CFR 102.20 - How to establish a covered injury.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 102.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... injuries. Minor injuries include expected and routine responses to the smallpox vaccine, other covered... smallpox vaccine recipient or vaccinia contact sustained an injury listed on the Smallpox (Vaccinia...

42 CFR 102.20 - How to establish a covered injury.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 102.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... injuries. Minor injuries include expected and routine responses to the smallpox vaccine, other covered... smallpox vaccine recipient or vaccinia contact sustained an injury listed on the Smallpox (Vaccinia...

42 CFR 102.20 - How to establish a covered injury.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 102.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... injuries. Minor injuries include expected and routine responses to the smallpox vaccine, other covered... smallpox vaccine recipient or vaccinia contact sustained an injury listed on the Smallpox (Vaccinia...

42 CFR 102.20 - How to establish a covered injury.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 102.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... injuries. Minor injuries include expected and routine responses to the smallpox vaccine, other covered... smallpox vaccine recipient or vaccinia contact sustained an injury listed on the Smallpox (Vaccinia...

42 CFR 102.20 - How to establish a covered injury.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 102.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... injuries. Minor injuries include expected and routine responses to the smallpox vaccine, other covered... smallpox vaccine recipient or vaccinia contact sustained an injury listed on the Smallpox (Vaccinia...

Smallpox.

PubMed

Nafziger, Sarah D

2005-10-01

Smallpox is a highly infectious disease, which, in 1980, was declared eradicated by the World Health Organization as a result of successful vaccination campaigns. Because of its highly infectious nature and historical 30% mortality rate, the disease has possibly been developed as a biological weapon. Variola, the virus that causes smallpox, is readily transmissible from person to person during the incubation period, before infected individuals show signs of illness. When a victim develops the characteristic rash and viral syndrome associated with smallpox infection, the disease requires complex isolation and possibly quarantine. Diagnosis can be confirmed in a high-containment laboratory. The only effective treatment for smallpox is rapid administration of smallpox vaccine.

[Smallpox, bioterrorism agent].

PubMed

Bossi, Philippe; Bricaire, François

2002-11-30

A CONSIDERABLE RISK: Among the infectious agents that might be used as terrorist weapons, the smallpox virus represents a sufficiently high risk, which is difficult to manage and must be seriously taken into account. Two viral strains of the smallpox virus, which belong to the Poxviridae and orthopoxvirus-type families, are known. They are associated with various clinical presentations of smallpox, i.e., variola major and variola minor or "alastrim". Five clinical forms of varying prognosis are described. Common smallpox, haemorrhagic smallpox (the most severe form of the disease), mild smallpox (predominantly observed in vaccinated patients), flat-type smallpox (defined by coalescent and slowly progressive lesions) and so-called "sine eruptione" smallpox. This form is not as severe as variola major and the mortality rate is lesser. Smallpox must be systematically evoked on clinical elements and confirmed by electronic microscopy of a sample of liquid from a vesicle or pustule or a scab. The strains can be characterised by PCR (Polymerase Chain Reaction). It is symptomatic. Early vaccination, within 4 days following exposure to the virus, permits the reduction in mortality by 50%. The only efficient prevention is vaccination prior to any exposure to the virus. In the case of a bioterrorist attack, the United States and most of the EC countries propose to vaccinate only the health professionnals most exposed to the virus and those having contacted identified cases.

The Future of Smallpox Vaccination: is MVA the key?

PubMed Central

Slifka, Mark K

2005-01-01

Eradication of the smallpox virus through extensive global vaccination efforts has resulted in one of the most important breakthroughs in medical history, saving countless lives from the severe morbidity and mortality that is associated with this disease. Although smallpox is now extinct in nature, laboratory stocks of this virus still remain and the subject of smallpox vaccination has gained renewed attention due to the potential risk that smallpox may be used as a biological weapon by terrorists or rogue states. Despite having the longest history of any modern vaccine, there is still much to be learned about smallpox vaccination and the correlates of protection remain to be formally defined. This Commentary will discuss the strengths and weaknesses of traditional smallpox vaccination in comparison with immunization using modified vaccinia virus Ankura (MVA), a non-replicating virus with a strong safety record but weakened immunogenicity. PMID:15740619

Development of the small-molecule antiviral ST-246® as a smallpox therapeutic

PubMed Central

Grosenbach, Douglas W; Jordan, Robert; Hruby, Dennis E

2011-01-01

Naturally occurring smallpox has been eradicated, yet it remains as one of the highest priority pathogens due to its potential as a biological weapon. The majority of the US population would be vulnerable in a smallpox outbreak. SIGA Technologies, Inc. has responded to the call of the US government to develop and supply to the Strategic National Stockpile a smallpox antiviral to be deployed in the event of a smallpox outbreak. ST-246® (tecovirimat) was initially identified via a high-throughput screen in 2002, and in the ensuing years, our drug-development activities have spanned in vitro analysis, preclinical safety, pharmacokinetics and efficacy testing (all according to the ‘animal rule’). Additionally, SIGA has conducted Phase I and II clinical trials to evaluate the safety, tolerability and pharmacokinetics of ST-246, bringing us to our current late stage of clinical development. This article reviews the need for a smallpox therapeutic and our experience in developing ST-246, and provides perspective on the role of a smallpox antiviral during a smallpox public health emergency. PMID:21837250

Smallpox: a review of clinical disease and vaccination.

PubMed

Lofquist, Jennifer M; Weimert, Nicole A; Hayney, Mary S

2003-04-15

The clinical course of smallpox infection and the current and future roles of vaccination and strategies for controlling smallpox outbreaks are reviewed. Close personal contact is required for transmission of variola, the DNA virus that causes smallpox. Following an incubation period, infected persons have prodromal symptoms that include high fever, back pain, malaise, and prostration. The eruptive stage is characterized by maculopapular rash that progresses to papules, then vesicles, and then pustules and scab lesions. The mortality rate for smallpox is approximately 30%. Patients having a fever and rash may be confused with having chickenpox. The most effective method for preventing smallpox epidemic progression is vaccination. Until recently, only 15 million doses of smallpox vaccine--manufactured 20 years ago--were available in the United States. The vaccine is a live vaccinia virus preparation administered by scarification with a bifurcated needle. The immune response is protective against orthopoxviruses, including variola. Vaccination is associated with moderate to severe complications, such as generalized vaccinia, eczema vaccinatum, progressive vaccinia, and postvaccinial encephalitis. Efforts for vaccine production are now focused on a live cell-culture-derived vaccinia virus vaccine. Although smallpox was eradicated in 1980, it remains a potential agent for bioterrorism. As a category A biological weapon, its potential to devastate populations causes concern among those in the public health community who have been actively developing plants to deal with smallpox and other potential agents of biological warfare. The only proven effective strategy against smallpox is vaccination.

Anticipating smallpox and monkeypox outbreaks: complications of the smallpox vaccine.

PubMed

Abrahams, Brian C; Kaufman, David M

2004-09-01

The recent outbreak in the Midwest of monkeypox, as well as the continued fears of a terrorist-induced epidemic of smallpox, prompted the authors' review of the literature regarding past and current experiences with smallpox vaccination. 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. However, vaccinees would be at risk for several vaccine-related neurologic complications. According to prior reports, neurologic complications have occurred in 2.5 per million US individuals, with the most common being postvaccinal encephalomyelitis (PVEM). In older children and adults, PVEM causes stupor and coma, seizures, paraparesis, and other neurologic and mental abnormalities, and, in 16% of cases, permanent neurologic sequelae. The overall mortality rate of neurologic complications is approximately 1.5 per million vaccinees. Risk factors for PVEM were age younger than 1 year and no previous smallpox vaccination, but not a prior episode of PVEM or other preexisting neurologic illnesses. Neither the current smallpox vaccination campaigns in Israel nor the one in the United States has had comparable complications, but the US campaign has been associated with myocarditis and myopericarditis. Although the potential neurologic complications of the smallpox vaccine must be weighed against the threat of monkeypox and smallpox, current experience with vaccination suggests it carries a very low risk of neurologic complications and does not lead to exacerbations of chronic neurologic illnesses.

Standardized emergency management system and response to a smallpox emergency.

PubMed

Kim-Farley, Robert J; Celentano, John T; Gunter, Carol; Jones, Jessica W; Stone, Rogelio A; Aller, Raymond D; Mascola, Laurene; Grigsby, Sharon F; Fielding, Jonathan E

2003-01-01

The smallpox virus is a high-priority, Category-A agent that poses a global, terrorism security risk because it: (1) easily can be disseminated and transmitted from person to person; (2) results in high mortality rates and has the potential for a major public health impact; (3) might cause public panic and social disruption; and (4) requires special action for public health preparedness. In recognition of this risk, the Los Angeles County Department of Health Services (LAC-DHS) developed the Smallpox Preparedness, Response, and Recovery Plan for LAC to prepare for the possibility of an outbreak of smallpox. A unique feature of the LAC-DHS plan is its explicit use of the Standardized Emergency Management System (SEMS) framework for detailing the functions needed to respond to a smallpox emergency. The SEMS includes the Incident Command System (ICS) structure (management, operations, planning/intelligence, logistics, and finance/administration), the mutual-aid system, and the multi/interagency coordination required during a smallpox emergency. Management for incident command includes setting objectives and priorities, information (risk communications), safety, and liaison. Operations includes control and containment of a smallpox outbreak including ring vaccination, mass vaccination, adverse events monitoring and assessment, management of confirmed and suspected smallpox cases, contact tracing, active surveillance teams and enhanced hospital-based surveillance, and decontamination. Planning/intelligence functions include developing the incident action plan, epidemiological investigation and analysis of smallpox cases, and epidemiological assessment of the vaccination coverage status of populations at risk. Logistics functions include receiving, handling, inventorying, and distributing smallpox vaccine and vaccination clinic supplies; personnel; transportation; communications; and health care of personnel. Finally, finance/administration functions include monitoring costs related to the smallpox emergency, procurement, and administrative aspects that are not handled by other functional divisions of incident command systems. The plan was developed and is under frequent review by the LAC-DHS Smallpox Planning Working Group, and is reviewed periodically by the LAC Bioterrorism Advisory Committee, and draws upon the Smallpox Response Plan and Guidelines of the Centers for Disease Control and Prevention (CDC) and recommendations of the Advisory Committee on Immunization Practices (ACIP). The Smallpox Preparedness, Response, and Recovery Plan, with its SEMS framework and ICS structure, now is serving as a model for the development of LAC-DHS plans for responses to other terrorist or natural-outbreak responses.

The Migration of Smallpox and Its Indelible Footprint on Latin American History. Junior Division Winner.

ERIC Educational Resources Information Center

Thomson, Mark

1998-01-01

Addresses the migration of smallpox into the New World where it caused the extinction of entire indigenous civilizations and altered the survivors' cultures. Discusses the historical origins of smallpox and highlights the migration and consequences of smallpox in Central and South America. Includes an annotated bibliography, research description,…

[Spread of Chinese variolation art to the western world and its influence].

PubMed

Xie, S; Zhang, D

2000-07-01

Smallpox inoculation or variolation is a great invention of medicine in ancient China. In this paper, we introduced the process of spread of smallpox inoculation technique from China to western world (mainly to England), and reviewed the royal experiment of smallpox inoculation on human being and its influence on the prevention of smallpox in western countries. The spread and practice of smallpox inoculation in western world was an important event in the history of intercommunication between eastern and western medicines, which is worth emphasizing and further studying.

[Smallpox virus as biological weapon].

PubMed

Kondrusik, Maciej; Hermanowska-Szpakowicz, Teresa

2003-02-01

Smallpox, because of its high case-fatality rate, easy transmission from human to human, lack of specific treatment represents nowadays one of the main threats in bioterrorist attacks. Over the centuries, naturally occurring smallpox with its case-fatality over 30 percent and its ability to spread in any climate and season has been treated as the most dangerous infectious disease. But it is now, 25 years after the last documented case of smallpox and cessation of routine vaccination in present mobile and susceptible population, smallpox virus spread might be rapid and devastating.

Smallpox vaccination and all-cause infectious disease hospitalization: a Danish register-based cohort study.

PubMed

Sørup, Signe; Villumsen, Marie; Ravn, Henrik; Benn, Christine Stabell; Sørensen, Thorkild I A; Aaby, Peter; Jess, Tine; Roth, Adam

2011-08-01

There is growing evidence from observational studies and randomized trials in low-income countries that vaccinations have non-specific effects. Administration of live vaccines reduces overall child morbidity and mortality, presumably due to protection against non-targeted infections. In Denmark, the live vaccine against smallpox was phased out in the 1970s due to the eradication of smallpox. We used the phasing-out period to investigate the effect of smallpox vaccination on the risk of hospitalization for infections. From the Copenhagen School Health Records Register, a cohort of 4048 individuals was sampled, of whom 3559 had information about receiving or not receiving smallpox vaccination. Infectious disease hospitalizations were identified in the Danish National Patient Register. During 87,228 person-years of follow-up, 1440 infectious disease hospitalizations occurred. Smallpox-vaccinated individuals had a reduced risk of all-cause infectious disease hospitalization compared with smallpox-unvaccinated individuals [hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.72-0.98]. The reduced risk of hospitalizations was seen for most subgroups of infectious diseases. The effect may have been most pronounced after early smallpox vaccination (vaccination age <3.5 years: HR 0.81; 95% CI 0.69-0.95; vaccination age ≥ 3.5 years: HR 0.91 95% CI 0.76-1.10). Among the smallpox-vaccinated, the risk of infectious disease hospitalization increased 6% with each 1-year increase in vaccination age (HR 1.06; 95% CI 1.02-1.10). Smallpox vaccination is associated with a reduced risk of infectious disease hospitalization in a high-income setting.

The efficacy and pharmacokinetics of brincidofovir for the treatment of lethal rabbitpox virus infection: a model of smallpox disease.

PubMed

Trost, Lawrence C; Rose, Michelle L; Khouri, Jody; Keilholz, Laurie; Long, James; Godin, Stephen J; Foster, Scott A

2015-05-01

Brincidofovir (BCV) has broad-spectrum in vitro activity against dsDNA viruses, including smallpox, and is being developed as a treatment for smallpox as well as infections caused by other dsDNA viruses. BCV has previously been shown to be active in multiple animal models of smallpox. Here we present the results of a randomized, blinded, placebo-controlled study of the efficacy and pharmacokinetics of a novel, "humanized" regimen of BCV for treatment of New Zealand White rabbits infected with a highly lethal inoculum of rabbitpox virus, a well characterized model of smallpox. Compared with placebo, a dose-dependent increase in survival was observed in all BCV-treatment groups. 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. CDV-PP exposure in PBMCs from rabbits given BCV scaled to human exposures at the dose proposed for treatment of smallpox, which is also currently under evaluation for other indications. The results of this study demonstrate the activity of BCV in the rabbitpox model of smallpox and the feasibility of scaling doses efficacious in the model to a proposed human dose and regimen for treatment of smallpox. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Smallpox

MedlinePlus

Smallpox is a disease caused by the Variola major virus. Some experts say that over the centuries ... diseases combined. Worldwide immunization stopped the spread of smallpox three decades ago. The last case was reported ...

Influence of Population Immunosuppression and Past Vaccination on Smallpox Reemergence

PubMed Central

MacIntyre, C. Raina; Chen, Xin; Segelov, Eva; Chughtai, Abrar Ahmad; Kelleher, Anthony; Kunasekaran, Mohana; Lane, John Michael

2018-01-01

We built a SEIR (susceptible, exposed, infected, recovered) model of smallpox transmission for New York, New York, USA, and Sydney, New South Wales, Australia, that accounted for age-specific population immunosuppression and residual vaccine immunity and conducted sensitivity analyses to estimate the effect these parameters might have on smallpox reemergence. At least 19% of New York’s and 17% of Sydney’s population are immunosuppressed. The highest smallpox infection rates were in persons 0–19 years of age, but the highest death rates were in those >45 years of age. Because of the low level of residual vaccine immunity, immunosuppression was more influential than vaccination on death and infection rates in our model. Despite widespread smallpox vaccination until 1980 in New York, smallpox outbreak severity appeared worse in New York than in Sydney. Immunosuppression is highly prevalent and should be considered in future smallpox outbreak models because excluding this factor probably underestimates death and infection rates. PMID:29553311

Countermeasures and vaccination against terrorism using smallpox: pre-event and post-event smallpox vaccination and its contraindications.

PubMed

Sato, Hajime

2011-09-01

Smallpox, when used as a biological weapon, presents a serious threat to civilian populations. Core components of the public health management of a terrorism attack using smallpox are: vaccination (ring vaccination and mass vaccination), adverse event monitoring, confirmed and suspected smallpox case management, contact management, identifying, tracing, monitoring contacts, and quarantine. Above all, pre-event and post-event vaccination is an indispensable part of the strategies. Since smallpox patients are most infectious from onset of the rash through the first 7-10 days of the rash, vaccination should be administered promptly within a limited time frame. However, vaccination can accompany complications, such as postvaccinial encephalitis, progressive vaccinia, eczema vaccinatum, and generalized vaccinia. Therefore, vaccination is not recommended for certain groups. Public health professionals, as well as physicians and government officials, should also be well equipped with all information necessary for appropriate and effective smallpox management in the face of such a bioterrorism attack.

Smallpox Vaccines for Biodefense

PubMed Central

Kennedy, Richard B.; Ovsyannikova, Inna; Poland, Gregory A.

2009-01-01

Few diseases can match the enormous impact that smallpox has had on mankind. Its influence can be seen in the earliest recorded histories of ancient civilizations in Egypt and Mesopotamia. With fatality rates up to 30%, smallpox left its survivors with extensive scarring and other serious sequelae. It is estimated that smallpox killed 500 million people in the 19th and 20th centuries. Given the ongoing concerns regarding the use of variola as a biological weapon, this review will focus on the licensed vaccines as well as current research into next-generation vaccines to protect against smallpox and other poxviruses. PMID:19837292

Mankind's Magnificent Milestone: Smallpox Eradication.

ERIC Educational Resources Information Center

Small, Parker A., Jr.; Small, Natalie S.

1996-01-01

Illustrates the complex interactions between disease, societal attitudes, and technology by looking at the history of smallpox. Describes one of mankind's most magnificent accomplishments--the eradication of smallpox from the earth. (JRH)

Smallpox vaccines: targets of protective immunity

PubMed Central

Moss, Bernard

2011-01-01

Summary The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second and third generation smallpox vaccines. PMID:21198662

[Development of current smallpox vaccines].

PubMed

Maksiutov, R A; Gavrilova, E V; Shchelkunov, S N

2011-01-01

The review gives data on the history of smallpox vaccination and shows the high topicality of designing the current safe vaccines against orthopoxviruses. Four generations of live smallpox, protein subunit, and DNA vaccines are considered. Analysis of the data published leads to the conclusion that it is promising to use the up-to-date generations of safe smallpox subunit or DNA vaccines for mass primary immunization with possible further revaccination with classical live vaccine.

An open-label, single arm, phase III clinical study to evaluate the efficacy and safety of CJ smallpox vaccine in previously vaccinated healthy adults.

PubMed

Kim, Nak-Hyun; Kang, Yu Min; Kim, Gayeon; Choe, Pyoeng Gyun; Song, Jin Su; Lee, Kwang-Hee; Seong, Baik-Lin; Park, Wan Beom; Kim, Nam Joong; Oh, Myoung-don

2013-10-25

The increased possibility of bioterrorism has led to reinitiation of smallpox vaccination. In Korea, more than 30 years have passed since the last smallpox vaccinations, and even people who were previously vaccinated are not regarded as adequately protected against smallpox. We evaluated the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in healthy adults previously vaccinated against smallpox. We conducted an open label, single arm, phase III clinical trial to evaluate the efficacy and safety of CJ-50300. Healthy volunteers, previously vaccinated against smallpox, born between 1950 and 1978 were enrolled. CJ-50300 was administered with a bifurcated needle over the deltoid muscle according to the recommended method. The rate of the cutaneous take reaction, humoral immunogenicity, and safety of the vaccine was assessed. Of 145 individuals enrolled for vaccination, 139 completed the study. The overall rates of cutaneous take reactions and humoral immunogenicity were 95.0% (132/139) and 88.5% (123/139), respectively. Although 95.9% (139/145) reported adverse events related to vaccination, no serious adverse reactions were observed. CJ-50300 can be used safely and effectively in healthy adults previously vaccinated against smallpox. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lessons from the eradication of smallpox: an interview with D. A. Henderson

PubMed Central

Henderson, D. A.; Klepac, Petra

2013-01-01

It has been more than 35 years since the last naturally occurring case of smallpox. Sufficient time has passed to allow an objective overview of what were the key factors in the success of the eradication effort and what lessons smallpox can offer to other campaigns. Professor D. A. Henderson headed the international effort to eradicate smallpox. Here, we present a summary of D. A. Henderson's perspectives on the eradication of smallpox. This text is based upon the Unither Baruch Blumberg Lecture, delivered by D. A. Henderson at the University of Oxford in November 2012 and upon conversations and correspondence with Professor Henderson. PMID:23798700

Are We Prepared in Case of a Possible Smallpox-Like Disease Emergence?

PubMed Central

Olson, Victoria A.; Shchelkunov, Sergei N.

2017-01-01

Smallpox was the first human disease to be eradicated, through a concerted vaccination campaign led by the World Health Organization. Since its eradication, routine vaccination against smallpox has ceased, leaving the world population susceptible to disease caused by orthopoxviruses. In recent decades, reports of human disease from zoonotic orthopoxviruses have increased. Furthermore, multiple reports of newly identified poxviruses capable of causing human disease have occurred. These facts raise concerns regarding both the opportunity for these zoonotic orthopoxviruses to evolve and become a more severe public health issue, as well as the risk of Variola virus (the causative agent of smallpox) to be utilized as a bioterrorist weapon. The eradication of smallpox occurred prior to the development of the majority of modern virological and molecular biological techniques. Therefore, there is a considerable amount that is not understood regarding how this solely human pathogen interacts with its host. This paper briefly recounts the history and current status of diagnostic tools, vaccines, and anti-viral therapeutics for treatment of smallpox disease. The authors discuss the importance of further research to prepare the global community should a smallpox-like virus emerge.

The Role of Brincidofovir in Preparation for a Potential Smallpox Outbreak.

PubMed

Foster, Scott A; Parker, Scott; Lanier, Randall

2017-10-30

Smallpox (variola) virus is considered a Category A bioterrorism agent due to its ability to spread rapidly and the high morbidity and mortality rates associated with infection. Current recommendations recognize the importance of oral antivirals and call for having at least two smallpox antivirals with different mechanisms of action available in the event of a smallpox outbreak. Multiple antivirals are recommended due in large part to the propensity of viruses to become resistant to antiviral therapy, especially monotherapy. Advances in synthetic biology heighten concerns that a bioterror attack with variola would utilize engineered resistance to antivirals and potentially vaccines. Brincidofovir, an oral antiviral in late stage development, has proven effective against orthopoxviruses in vitro and in vivo, has a different mechanism of action from tecovirimat (the only oral smallpox antiviral currently in the US Strategic National Stockpile), and has a resistance profile that reduces concerns in the scenario of a bioterror attack using genetically engineered smallpox. Given the devastating potential of smallpox as a bioweapon, preparation of a multi-pronged defense that accounts for the most obvious bioengineering possibilities is strategically imperative.

[Smallpox--historical or real threat].

PubMed

Zieliński, Andrzej; Stefanoff, Paweł

2004-01-01

Presently, there is no real possibility of natural re-emergence of smallpox virus, which was eradicated globally more then 25 years ago. During the last decade the possibility of use of smallpox virus as a biological weapon by a criminal organisation was emphasised. The re-emergence of smallpox virus would lead to unprecedented disaster. Theoretical models indicated that only extremely strict and enforced interventions could stop the spread of epidemic, but the assumptions of these models were unrealistic. Presently, there are limited stocks of the first generation smallpox vaccine left in the world. This vaccine, as well as the second-generation vaccine are associated with multiple adverse events, including fatalities and may not be accepted by society. Much safer vaccines are now being developed. Strategic plan of prophylactic vaccinations requires defining the groups to be immunised in the first place and whether immunisation should start before or after a first smallpox case would occur.

Smallpox vaccines: targets of protective immunity.

PubMed

Moss, Bernard

2011-01-01

The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new-generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second- and third-generation smallpox vaccines. Published 2010. This article is a US Government work and is in the public domain in the USA.

Smallpox and pregnancy: from eradicated disease to bioterrorist threat.

PubMed

Suarez, Victor R; Hankins, Gary D V

2002-07-01

Health care personnel must be prepared for the threat of bioterrorism. Our objective is to educate primary care providers, obstetricians in particular, in the prevention, diagnosis, and treatment of smallpox. Smallpox poses a particularly serious threat because of its high case-fatality rate in unvaccinated populations (no one younger than 25 years has been vaccinated, and older persons have little remaining residual immunity). Routine nonemergency smallpox vaccination is restricted to laboratory staff working with smallpox-related viruses. Under these circumstances, contraindications to vaccination are pregnancy, immunodeficiency, exfoliative skin conditions (eczema), and allergy to vaccine components. In case of an intentional release of the smallpox virus, those directly exposed and their close contacts must be vaccinated and isolated. Under such emergency circumstances, pregnant women exposed to the variola virus should be vaccinated because of the lethality of the disease during pregnancy. Currently, there is a limited supply of vaccine available.

Smallpox.

PubMed

Goozé, Lisa L; Hughes, Elizabeth C W

2003-09-01

Until the 1970s, smallpox was feared worldwide for the significant morbidity and mortality it caused. Although naturally occurring disease has been eliminated, the virus itself has not been destroyed, and it is assumed that some of the variola stored in the former Soviet Union has been removed. The majority of the world's population is susceptible to smallpox because vaccination ended in 1972 in the United States and in the rest of the world in 1982. A major epidemic could result if there was an intentional release of smallpox. Variola is both durable and highly infective, 2 features that make it an attractive bioweapon. Because of this threat, physicians should be familiar with the clinical features of smallpox and the appropriate isolation and medical response procedures. Although there is a vaccine that can provide pre- and postexposure protection, the vaccination itself is not without risks. There is no effective therapy for smallpox and studies of new treatments are underway.

[Problem of bioterrorism under modern conditions].

PubMed

Vorob'ev, A A; Boev, B V; Bondarenko, V M; Gintsburg, A L

2002-01-01

It is practically impossible to discuss the problem of bioterrorism (BT) and to develop effective programs of decreasing the losses and expenses suffered by the society from the BT acts without evaluation of the threat and prognosis of consequences based on research and empiric data. Stained international situation following the act of terrorism (attack on the USA) on September 11, 2001, makes the scenarios of the bacterial weapon use (the causative agents of plague, smallpox, anthrax, etc.) by international terrorists most probable. In this connection studies on the analysis and prognostication of the consequences of BT, including mathematical and computer modelling, are necessary. The authors present the results of initiative studies on the analysis and prognostication of the consequences of the hypothetical act of BT with the use of the smallpox causative agent in a city with the population of about 1,000,000 inhabitants. The analytical prognostic studies on the operative analysis and prognostication of the consequences of the BT act with the use of the smallpox causative agent has demonstrated that the mathematical (computer) model of the epidemic outbreak of smallpox is an effective instrument of calculation studies. Prognostic evaluations of the consequences of the act of BT under the conditions of different reaction of public health services (time of detection, interventions) have been obtained with the use of modelling. In addition, the computer model is necessary for training health specialists to react adequately to the acts of BT with the use of different kinds of bacteriological weapons.

Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection.

PubMed

Stittelaar, Koert J; Neyts, Johan; Naesens, Lieve; van Amerongen, Geert; van Lavieren, Rob F; Holý, Antonin; De Clercq, Erik; Niesters, Hubert G M; Fries, Edwin; Maas, Chantal; Mulder, Paul G H; van der Zeijst, Ben A M; Osterhaus, Albert D M E

2006-02-09

There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. Here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called HPMPC or Vistide) or with a related acyclic nucleoside phosphonate analogue (HPMPO-DAPy) after lethal intratracheal infection of cynomolgus monkeys (Macaca fascicularis) with monkeypox virus (MPXV). MPXV causes a disease similar to human smallpox and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines. We show that initiation of antiviral treatment 24 h after lethal intratracheal MPXV infection, using either of the antiviral agents and applying various systemic treatment regimens, resulted in significantly reduced mortality and reduced numbers of cutaneous monkeypox lesions. In contrast, when monkeys were vaccinated 24 h after MPXV infection, using a standard human dose of a currently recommended smallpox vaccine (Elstree-RIVM), no significant reduction in mortality was observed. When antiviral therapy was terminated 13 days after infection, all surviving animals had virus-specific serum antibodies and antiviral T lymphocytes. 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.

Smallpox

MedlinePlus

... of the variola virus that causes smallpox were saved in laboratories. Some people have expressed concern that terrorists could try to ... the virus make the illness less severe in people who do become infected if ... days Can Vaccines Stop a Smallpox Outbreak? After the September 11, ...

Should remaining stockpiles of smallpox virus (variola) be destroyed?

PubMed

Weinstein, Raymond S

2011-04-01

In 2011, the World Health Organization will recommend the fate of existing smallpox stockpiles, but circumstances have changed since the complete destruction of these cultures was first proposed. Recent studies suggest that variola and its experimental surrogate, vaccinia, have a remarkable ability to modify the human immune response through complex mechanisms that scientists are only just beginning to unravel. Further study that might require intact virus is essential. Moreover, modern science now has the capability to recreate smallpox or a smallpox-like organism in the laboratory in addition to the risk of nature re-creating it as it did once before. These factors strongly suggest that relegating smallpox to the autoclave of extinction would be ill advised.

Progression of pathogenic events in cynomolgus macaques infected with variola virus.

PubMed

Wahl-Jensen, Victoria; Cann, Jennifer A; Rubins, Kathleen H; Huggins, John W; Fisher, Robert W; Johnson, Anthony J; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E; Jahrling, Peter B

2011-01-01

Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

Efficacy of CMX001 as a Prophylactic and Presymptomatic Antiviral Agent in New Zealand White Rabbits Infected with Rabbitpox Virus, a Model for Orthopoxvirus Infections of Humans

PubMed Central

Rice, Amanda D.; Adams, Mathew M.; Lampert, Bernhard; Foster, Scott; Lanier, Randall; Robertson, Alice; Painter, George; Moyer, Richard W.

2011-01-01

CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. Although smallpox has been eliminated from the environment, treatments are urgently being sought due to the risk of smallpox being used as a bioterrorism agent and for monkeypox virus, a zoonotic disease of Africa, and adverse reactions to smallpox virus vaccinations. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Here we first review and discuss the rabbitpox virus (RPV) infection of New Zealand White rabbits as a model for smallpox to test the efficacy of CMX001 as a prophylactic and early disease antiviral. Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination. PMID:21369346

Pre-event smallpox vaccination for healthcare workers revisited--the need for a carefully screened multidisciplinary cadre.

PubMed

Malone, John D

2007-03-01

As healthcare institutions are a focus of smallpox transmission early in an epidemic, several mathematical models support pre-event smallpox vaccination of healthcare workers (HCWs). The deciding factor for HCW voluntary vaccination is the risk of disease exposure versus the risk of vaccine adverse events. In a United States military population, with careful screening to exclude atopic dermatitis/eczema and immunosuppression, over 1 million vaccinia (smallpox) vaccinations were delivered with one fatality attributed to vaccination. Among 37901 United States civilian volunteer HCWs vaccinated, 100 serious adverse events were reported including 10 ischemic cardiac episodes and six myocardial infarctions - two were fatal. This older population had a higher rate of adverse events due to age-related coronary artery disease. T-cell mediated inflammatory processes induced by live vaccinia vaccination may have a role in the observed acute coronary artery events. With exclusion of individuals at risk for coronary artery disease, atopic dermatitis/eczema, and immunosuppression, HCWs can be smallpox vaccinated with minimal risk. A carefully screened multidisciplinary cadre (physician, nurse, infection control practitioner, technician), pre-event vaccinated for smallpox, will supply the necessary leadership to alleviate fear and uncertainty while limiting spread and initial mortality of smallpox.

Smallpox vaccine: problems and prospects.

PubMed

Poland, Gregory A; Neff, John M

2003-11-01

Smallpox justifiably is feared because of its morbidity and mortality. Wide-spread population-level susceptibility to smallpox exists, and the only effective tool against the virus is a live, attenuated vaccine that is highly reactogenic and controversial. A significant minority of the population has contraindications that prevent preexposure use of this vaccine. Newer, safer, and equally immunogenic vaccines must be developed and licensed. Several live, attenuated vaccines are in clinical trials. Although these vaccines may prove to be less reactogenic, they still may not be administered safely to a significant portion of the population because they contain live, attenuated viruses. Newer vaccines will be needed if routine preexposure vaccination is to be instituted universally. The idea of a subunit or peptide-based vaccine is appealing, because it obviates potential safety concerns. It may be possible to use a more-attenuated, live vaccine strain for a large segment of the population on a preexposure basis and accept the morbidity and mortality that would result from its use on a postexposure basis, if necessary. The need for widespread population-level protection against variola infection is apparent. The use of the new biology tools to predict or define who might experience serious reactions to the smallpox vaccine and why these reactions occur is an area ripe for additional research. The reason why an individual develops postvaccinal encephalitis remains unknown, and the development is unpredictable and untreatable. In the future, if the mechanism behind such adverse events is defined, it may be possible to screen persons who are likely to experience such events. Although the authors remain proponents for use of the vaccine in alignment with the CDC vaccination program and recommendations, the previous concerns indicate that new knowledge must be gained and shared. Further research on attenuated vaccines and nonliving or peptide vaccines with equal efficacy should remain the goal, as it is apparent that smallpox vaccine once again will become part of the vaccinologist's and public health official's armamentarium in the decades to come.

Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus

PubMed Central

Rubins, Kathleen H.; Huggins, John W.; Fisher, Robert W.; Johnson, Anthony J.; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E.; Jahrling, Peter B.

2011-01-01

Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections – an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions. PMID:21998632

42 CFR 102.46 - Amending a request package.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) Requesters who are survivors. If a smallpox vaccine recipient or vaccinia contact submitted a Request Form...) Requests in which benefits are sought by the estate of a deceased smallpox vaccine recipient or vaccinia...

42 CFR 102.46 - Amending a request package.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) Requesters who are survivors. If a smallpox vaccine recipient or vaccinia contact submitted a Request Form...) Requests in which benefits are sought by the estate of a deceased smallpox vaccine recipient or vaccinia...

42 CFR 102.46 - Amending a request package.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) Requesters who are survivors. If a smallpox vaccine recipient or vaccinia contact submitted a Request Form...) Requests in which benefits are sought by the estate of a deceased smallpox vaccine recipient or vaccinia...

42 CFR 102.46 - Amending a request package.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) Requesters who are survivors. If a smallpox vaccine recipient or vaccinia contact submitted a Request Form...) Requests in which benefits are sought by the estate of a deceased smallpox vaccine recipient or vaccinia...

42 CFR 102.46 - Amending a request package.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) Requesters who are survivors. If a smallpox vaccine recipient or vaccinia contact submitted a Request Form...) Requests in which benefits are sought by the estate of a deceased smallpox vaccine recipient or vaccinia...

Army Medical Department Support to Stability Operations

DTIC Science & Technology

2007-02-28

eliminate bubonic plague , vaccinate against smallpox, and institute measures for a safe water supply.21 Lieutenant General Arthur MacArthur, military...the war.36 Though the many medical assistance programs were plagued with unending challenges, and the overall outcome of the war has yet to be

Mozart and smallpox.

PubMed

Zegers, Richard H C

2007-01-01

In 1767 at 11 years of age, composer Wolfgang Amadeus Mozart contracted smallpox, allegedly causing him temporary blindness. Although now eradicated, smallpox in those days had a high mortality rate, and the history of classical music would have been very different if Mozart had become permanently blind, or died, as a result of the disease.

Smallpox-Related Knowledge and Beliefs among Recent College Graduates

ERIC Educational Resources Information Center

Bungum, Timothy; Day, Charlene

2006-01-01

Recent world events have increased concern and preparations for possible bioterror events. Despite worldwide efforts to limit access to bio-weapons, smallpox is still considered a potential bioterror threat. Americans' understanding of smallpox could prevent panic and enhance the willingness of citizens to receive vaccinations. Objective: The…

42 CFR 102.32 - Benefits for lost employment income.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 102.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipients or vaccinia contacts may be able to receive benefits for loss of employment... may pay benefits for lost employment income to the estate of a deceased smallpox vaccine recipient or...

42 CFR 102.32 - Benefits for lost employment income.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 102.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipients or vaccinia contacts may be able to receive benefits for loss of employment... may pay benefits for lost employment income to the estate of a deceased smallpox vaccine recipient or...

42 CFR 102.32 - Benefits for lost employment income.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 102.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipients or vaccinia contacts may be able to receive benefits for loss of employment... may pay benefits for lost employment income to the estate of a deceased smallpox vaccine recipient or...

42 CFR 102.32 - Benefits for lost employment income.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 102.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipients or vaccinia contacts may be able to receive benefits for loss of employment... may pay benefits for lost employment income to the estate of a deceased smallpox vaccine recipient or...

42 CFR 102.32 - Benefits for lost employment income.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 102.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipients or vaccinia contacts may be able to receive benefits for loss of employment... may pay benefits for lost employment income to the estate of a deceased smallpox vaccine recipient or...

Vaccines and bioterrorism: smallpox and anthrax.

PubMed

Kimmel, Sanford R; Mahoney, Martin C; Zimmerman, Richard K

2003-01-01

Because of the success of vaccination and the ring strategy in eradicating smallpox from the world, smallpox vaccine has not been recommended for the United States civilian populations for decades. Given the low but possible threat of bioterrorism, smallpox vaccination is now recommended for those teams investigating potential smallpox cases and for selected personnel of acute-care hospitals who would be needed to care for victims in the event of a terrorist attack. Treatment and post-exposure prophylaxis for anthrax are ciprofloxacin or doxycycline. Anthrax vaccine alone is not effective for post-exposure prevention of anthrax; vaccination is accompanied by 60 days of antibiotic therapy. In addition to military use, anthrax vaccine is recommended for pre-exposure use in those persons whose work involves repeated exposure to Bacillus anthracis spores.

Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox).

PubMed

Mucker, Eric M; Goff, Arthur J; Shamblin, Joshua D; Grosenbach, Douglas W; Damon, Inger K; Mehal, Jason M; Holman, Robert C; Carroll, Darin; Gallardo, Nadia; Olson, Victoria A; Clemmons, Cody J; Hudson, Paul; Hruby, Dennis E

2013-12-01

Naturally occurring smallpox has been eradicated but remains a considerable threat as a biowarfare/bioterrorist weapon (F. Fleck, Bull. World Health Organ. 81:917-918, 2003). While effective, the smallpox vaccine is currently not recommended for routine use in the general public due to safety concerns (http://www.bt.cdc.gov/agent/smallpox/vaccination). Safe and effective countermeasures, particularly those effective after exposure to smallpox, are needed. Currently, SIGA Technologies is developing the small-molecule oral drug, tecovirimat (previously known as ST-246), as a postexposure therapeutic treatment of orthopoxvirus disease, including smallpox. Tecovirimat has been shown to be efficacious in preventing lethal orthopoxviral disease in numerous animal models (G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, et al., J. Virol. 79:13139-13149, 2005; D. C. Quenelle, R. M. Buller, S. Parker, K. A. Keith, D. E. Hruby, et al., Antimicrob. Agents Chemother., 51:689-695, 2007; E. Sbrana, R. Jordan, D. E. Hruby, R. I. Mateo, S. Y. Xiao, et al., Am. J. Trop. Med. Hyg. 76:768-773, 2007). Furthermore, in clinical trials thus far, the drug appears to be safe, with a good pharmacokinetic profile. 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. Following challenge, 50% of placebo-treated controls succumbed to infection, while all tecovirimat-treated animals survived regardless of whether treatment was started at 2 or 4 days postinfection. In addition, tecovirimat treatment resulted in dramatic reductions in dermal lesion counts, oropharyngeal virus shedding, and viral DNA circulating in the blood. Although clinical disease was evident in tecovirimat-treated animals, it was generally very mild and appeared to resolve earlier than in placebo-treated controls that survived infection. 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.

Efficacy of Tecovirimat (ST-246) in Nonhuman Primates Infected with Variola Virus (Smallpox)

PubMed Central

Mucker, Eric M.; Goff, Arthur J.; Shamblin, Joshua D.; Grosenbach, Douglas W.; Damon, Inger K.; Mehal, Jason M.; Holman, Robert C.; Carroll, Darin; Gallardo, Nadia; Olson, Victoria A.; Clemmons, Cody J.; Hudson, Paul

2013-01-01

Naturally occurring smallpox has been eradicated but remains a considerable threat as a biowarfare/bioterrorist weapon (F. Fleck, Bull. World Health Organ. 81:917–918, 2003). While effective, the smallpox vaccine is currently not recommended for routine use in the general public due to safety concerns (http://www.bt.cdc.gov/agent/smallpox/vaccination). Safe and effective countermeasures, particularly those effective after exposure to smallpox, are needed. Currently, SIGA Technologies is developing the small-molecule oral drug, tecovirimat (previously known as ST-246), as a postexposure therapeutic treatment of orthopoxvirus disease, including smallpox. Tecovirimat has been shown to be efficacious in preventing lethal orthopoxviral disease in numerous animal models (G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, et al., J. Virol. 79:13139–13149, 2005; D. C. Quenelle, R. M. Buller, S. Parker, K. A. Keith, D. E. Hruby, et al., Antimicrob. Agents Chemother., 51:689–695, 2007; E. Sbrana, R. Jordan, D. E. Hruby, R. I. Mateo, S. Y. Xiao, et al., Am. J. Trop. Med. Hyg. 76:768–773, 2007). Furthermore, in clinical trials thus far, the drug appears to be safe, with a good pharmacokinetic profile. In this study, the efficacy of tecovirimat was evaluated in both a prelesional and postlesional setting in nonhuman primates challenged intravenously with 1 × 108 PFU of Variola virus (VARV; the causative agent of smallpox), a model for smallpox disease in humans. Following challenge, 50% of placebo-treated controls succumbed to infection, while all tecovirimat-treated animals survived regardless of whether treatment was started at 2 or 4 days postinfection. In addition, tecovirimat treatment resulted in dramatic reductions in dermal lesion counts, oropharyngeal virus shedding, and viral DNA circulating in the blood. Although clinical disease was evident in tecovirimat-treated animals, it was generally very mild and appeared to resolve earlier than in placebo-treated controls that survived infection. 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. PMID:24100494

Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model.

PubMed

Porco, Travis C; Holbrook, Karen A; Fernyak, Susan E; Portnoy, Diane L; Reiter, Randy; Aragón, Tomás J

2004-08-06

Previous smallpox ring vaccination models based on contact tracing over a network suggest that ring vaccination would be effective, but have not explicitly included response logistics and limited numbers of vaccinators. We developed a continuous-time stochastic simulation of smallpox transmission, including network structure, post-exposure vaccination, vaccination of contacts of contacts, limited response capacity, heterogeneity in symptoms and infectiousness, vaccination prior to the discontinuation of routine vaccination, more rapid diagnosis due to public awareness, surveillance of asymptomatic contacts, and isolation of cases. We found that even in cases of very rapidly spreading smallpox, ring vaccination (when coupled with surveillance) is sufficient in most cases to eliminate smallpox quickly, assuming that 95% of household contacts are traced, 80% of workplace or social contacts are traced, and no casual contacts are traced, and that in most cases the ability to trace 1-5 individuals per day per index case is sufficient. If smallpox is assumed to be transmitted very quickly to contacts, it may at times escape containment by ring vaccination, but could be controlled in these circumstances by mass vaccination. Small introductions of smallpox are likely to be easily contained by ring vaccination, provided contact tracing is feasible. Uncertainties in the nature of bioterrorist smallpox (infectiousness, vaccine efficacy) support continued planning for ring vaccination as well as mass vaccination. If initiated, ring vaccination should be conducted without delays in vaccination, should include contacts of contacts (whenever there is sufficient capacity) and should be accompanied by increased public awareness and surveillance.

[The late media emergency of smallpox vaccine, news coverage of Spanish press (1999-2004)].

PubMed

Martínez-Martínez, Pedro Javier; Tuells, José; Colmenar-Jarillo, Gema

2015-06-01

Discussions on the need for smallpox virus preservation in 1999 focused attention on an eradicated disease 20 years ago. Smallpox was replaced as a potential candidate to be used as a bioterrorist weapon because of the international alarm scenario produced after the 11/9 events in USA. The reactivation of a vaccine which remained forgotten was the direct consequence. The initial target groups were the security forces of America. Spain was also among the countries that were interested in acquiring the smallpox vaccine. The aim of this study is to analyze the considerable media coverage of smallpox obtained in our country. Systematic review of published news in the four largest national daily newspapers (ABC, El Mundo, El País and La Vanguardia) for the period 1999-2004 of the Dow Jones Factiva document database. "Smallpox" were used as a key word. From the obtained data, a qualitative and quantitative analysis was done. 416 reviews were analyzed; the newspaper El Mundo was the most interested in these news (158 citations, 37.98%). Most of the news were published in 2003 (152, 36.5%) The year with more news about smallpox (2003) coincides with the purchase of vaccines in Spain. The type of messages in the news was highly changeable over this six-year period. Those related to "politics and diplomacy", "epidemiological risk", "bioterrorism" and "vaccine" were predominant. The alarm raised around the smallpox vaccination was a media phenomenon due to political strategy issues rather than a real public health problem.

The rediscovery of smallpox.

PubMed

Thèves, C; Biagini, P; Crubézy, E

2014-03-01

Smallpox is an infectious disease that is unique to humans, caused by a poxvirus. It is one of the most lethal of diseases; the virus variant Variola major has a mortality rate of 30%. People surviving this disease have life-long consequences, but also assured immunity. Historically, smallpox was recognized early in human populations. This led to prevention attempts--variolation, quarantine, and the isolation of infected subjects--until Jenner's discovery of the first steps of vaccination in the 18th century. After vaccination campaigns throughout the 19th and 20th centuries, the WHO declared the eradication of smallpox in 1980. With the development of microscopy techniques, the structural characterization of the virus began in the early 20th century. In 1990, the genomes of different smallpox viruses were determined; viruses could be classified in order to investigate their origin, diffusion, and evolution. To study the evolution and possible re-emergence of this viral pathogen, however, researchers can only use viral genomes collected during the 20th century. Cases of smallpox in ancient periods are sometimes well documented, so palaeomicrobiology and, more precisely, the study of ancient smallpox viral strains could be an exceptional opportunity. The analysis of poxvirus fragmented genomes could give new insights into the genetic evolution of the poxvirus. Recently, small fragments of the poxvirus genome were detected. With the genetic information obtained, a new phylogeny of smallpox virus was described. The interest in conducting studies on ancient strains is discussed, in order to explore the natural history of this disease. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

The Smallpox Threat: The School Nurse's Role

ERIC Educational Resources Information Center

Martin, Mary E.; Didion, Judy

2003-01-01

Today, with the threat of bioterrorism and war, there is a new dimension to the traditional role of the school nurse. The smallpox threat to public health will invoke the school nurse's role as an educator, liaison, and consultant in the community. This article discusses smallpox, the vaccination process, adverse effects, and postvaccination care.…

Smallpox: A Review for Health Educators

ERIC Educational Resources Information Center

Bungum, Timothy J.

2003-01-01

Since the declaration of the eradication of smallpox in May of 1980 concern about this virus has ebbed. However, recent world events, including the destabilization of governments, have raised concerns that smallpox could fall into the hands of nefarious individuals or groups who might attempt to use the virus as a weapon. In Centers for Disease…

Smallpox Control in Canada

PubMed Central

Best, E. W. R.; Davies, J. W.

1965-01-01

During the period 1961 to 1963 there were 10 separate importations of smallpox cases by aircraft into England and Wales, Germany, Sweden, Poland and Canada. A feature of the resulting outbreaks was the number of cases and deaths of physicians and other health personnel. With the increasing volume of international air traffic there is a risk of importing incubating cases of smallpox into Canada, as occurred in 1962. Millions of Canadians have been protected against smallpox. Some complications of smallpox vaccination have occurred in Canada; such complications can be minimized by proper attention to contraindications to vaccination. The Food and Drug Directorate, Department of National Health and Welfare, has circularized all physicians in Canada to request their co-operation in reporting adverse reactions to drugs. This includes serious, unusual or unsuspected reactions to immunizing agents (vaccines, toxoids and antitoxins). The latter information will be shared with the Epidemiology Division, Department of National Health and Welfare, and the provincial epidemiologist and manufacturer concerned. The importance of maintaining the smallpox immunity of physicians, nurses and other hospital and health personnel in Canada is emphasized. PMID:14296005

The Knowing Organization as Learning Organization.

ERIC Educational Resources Information Center

Choo, Chun Wei

2001-01-01

In organizational knowledge cycles there is continuous flow of information between sensemaking, knowledge creation, and decision making. The outcome of information use in one provides the context and resources for use in another. The example of the World Health Organization's smallpox eradication program illustrates a continuous cycle of…

The Spanish royal philanthropic expedition to bring smallpox vaccination to the New World and Asia in the 19th century.

PubMed

Franco-Paredes, Carlos; Lammoglia, Lorena; Santos-Preciado, José Ignacio

2005-11-01

The New World was ravaged by smallpox for several centuries after the Spanish conquest. Jenner's discovery of the smallpox vaccine made possible the prevention and control of smallpox epidemics. In response to a large outbreak of smallpox in the Spanish colonies, King Charles IV appointed Francisco Xavier de Balmis to lead an expedition that would introduce Jenner's vaccine to these colonies. During the journey, the vaccine was kept viable by passing it from arm to arm in orphaned children, who were brought along expressly for that purpose and remained under the care of the orphanage's director. This expedition was the first large scale mass vaccination of its kind. The historic legacy of this pioneering event in international health should be revisited in the current era of persistent inequalities in global health.

What was the primary mode of smallpox transmission? Implications for biodefense

PubMed Central

Milton, Donald K.

2012-01-01

The mode of infection transmission has profound implications for effective containment by public health interventions. The mode of smallpox transmission was never conclusively established. Although, “respiratory droplet” transmission was generally regarded as the primary mode of transmission, the relative importance of large ballistic droplets and fine particle aerosols that remain suspended in air for more than a few seconds was never resolved. This review examines evidence from the history of variolation, data on mucosal infection collected in the last decades of smallpox transmission, aerosol measurements, animal models, reports of smallpox lung among healthcare workers, and the epidemiology of smallpox regarding the potential importance of fine particle aerosol mediated transmission. I introduce briefly the term anisotropic infection to describe the behavior of Variola major in which route of infection appears to have altered the severity of disease. PMID:23226686

Smallpox manifestations and survival during the Boston epidemic of 1901 to 1903.

PubMed

Albert, Michael R; Ostheimer, Kristen G; Liewehr, David J; Steinberg, Seth M; Breman, Joel G

2002-12-17

Clinical records of 243 patients with smallpox consecutively admitted to the Southampton Street smallpox hospital in Boston, Massachusetts, during the 1901-1903 epidemic were reviewed. Smallpox was divided into five categories of varying severity; 47% of patients had varioloid, a relatively mild form of the disease usually occurring in previously vaccinated individuals with incomplete immunity. Survival information is available for 206 patients, of whom 36 (17.5%) died. Vaccination status, disease severity, and age were associated with survival, whereas sex, birthplace, and race were not. While full recovery often took weeks, most deaths occurred 7 to 14 days after the onset of symptoms, and all deaths occurred within 18 days of symptom onset. Smallpox was eradicated worldwide in 1977, but knowledge of the disease is essential because its cause, variola virus, is considered a potential biological weapon.

Planning for smallpox outbreaks

NASA Astrophysics Data System (ADS)

Ferguson, Neil M.; Keeling, Matt J.; John Edmunds, W.; Gani, Raymond; Grenfell, Bryan T.; Anderson, Roy M.; Leach, Steve

2003-10-01

Mathematical models of viral transmission and control are important tools for assessing the threat posed by deliberate release of the smallpox virus and the best means of containing an outbreak. Models must balance biological realism against limitations of knowledge, and uncertainties need to be accurately communicated to policy-makers. Smallpox poses the particular challenge that key biological, social and spatial factors affecting disease spread in contemporary populations must be elucidated largely from historical studies undertaken before disease eradication in 1979. We review the use of models in smallpox planning within the broader epidemiological context set by recent outbreaks of both novel and re-emerging pathogens.

Countermeasures to the bioterrorist threat of smallpox.

PubMed

Jahrling, Peter B; Fritz, Elizabeth A; Hensley, Lisa E

2005-12-01

Variola, the agent of smallpox, is a bioterrorist threat, as is monkeypox virus, which also occurs naturally in Africa. Development of countermeasures, in the form of improved vaccines, antiviral drugs, and other therapeutic strategies are a high priority. Recent advances in molecular biology and in animal model development have provided fresh insight into the virulence determinants for smallpox and the pathophysiology of disease. The complex replication cycle for orthopoxviruses, and the pivotal role for viral-specific immunomodulatory proteins which contribute to escape from immunologic surveillance, provide many unique targets for therapeutic intervention. The "toxemia" of smallpox has been elucidated in part by variola-infected primate studies which revealed the central role of apoptosis and the evolution of a cytokine storm leading to hemorrhagic diathesis, resembling fulminent "black" smallpox. This suggests a potential role for therapeutic strategies developed for septic shock, in treatment of smallpox. Drugs licensed for other viruses which share molecular targets with orthopoxviruses (e.g. Cidofovir) or cancer drugs (e.g. Gleevec and other tyrosine kinase inhibitors) have immediate application for treatment of smallpox and monkeypox and provide leads for second generation drugs with higher therapeutic indices. Recent advances in identification of virulence determinants and immune evasion genes facilitate the design of alternative vaccines to replace live vaccinia strains that are unsuitable for a large proportion of individuals in a mass immunization campaign.

Diagnosing smallpox: would you know it if you saw it?

PubMed

Woods, Ryan; McCarthy, Tara; Barry, M Anita; Mahon, Barbara

2004-01-01

The intentional release of anthrax in the United States in 2001 and other recent acts of terrorism have highlighted the possibility of intentional release of smallpox by terrorists. Little is known about physicians' ability to diagnose smallpox, especially in the critical first days, when the potential for rapid control of transmission is greatest. During December 2002 and January 2003, primary care and emergency physicians at a large urban academic medical center were surveyed regarding the diagnosis and management of patients who present with vesicular rash illness. In addition to demographic and training-related questions, the questionnaire included items about perceived comfort in diagnosing and evaluating rashes, knowledge of the key differential diagnostic characteristics of chickenpox and smallpox, and the diagnostic interpretation of color photographs of patients with smallpox or chickenpox. Responses were summarized as a perceived comfort score, a differential diagnosis score, and a picture score. Of 266 eligible physicians, 178 (67%) responded. Of these, 95% thought clinicians need more education about bioterrorism; only 17% reported comfort in diagnosing smallpox. Although most physicians recognized pictures of smallpox and chickenpox, only 36% correctly answered 3 of 4 questions regarding differential diagnosis, an important aspect of identifying cases early. Those who were comfortable diagnosing rash illnesses had higher differential diagnosis scores. Strategies for bioterrorism-related training could take advantage of physicians' awareness of their own knowledge deficits.

The cause of death in smallpox: an examination of the pathology record.

PubMed

Martin, David Barrett

2002-07-01

Because the cause of death in smallpox remains controversial, the human pathology record was examined. The surviving case series of smallpox pathology in humans as well as other review articles from English language journals written during the last 200 years were reviewed. The skin lesions in smallpox developed as a result of viral damage and inflammation. Secondary bacterial infection did not occur until the scabs started shedding. During the papular stage of skin eruption, a secondary viremia caused focal lesions in the pharynx, larynx, tongue, trachea, and esophagus in descending frequency. The virus also caused potentially lethal interstitial pneumonitis as well as tubulointerstitial nephritis. The cytopathic effects of smallpox cause death. The data did not support previously promulgated theories attributing death to a bacterial sepsis syndrome seeded from the pustules or immune complex deposition. In a future outbreak, antibiotic therapy would minimally influence mortality.

Orthopoxvirus variola infection of Cynomys ludovicianus (North American black tailed prairie dog).

PubMed

Carroll, Darin S; Olson, Victoria A; Smith, Scott K; Braden, Zach H; Patel, Nishi; Abel, Jason; Li, Yu; Damon, Inger K; Karem, Kevin L

2013-09-01

Since the eradication of Smallpox, researchers have attempted to study Orthopoxvirus pathogenesis and immunity in animal models in order to correlate results human smallpox. A solely human pathogen, Orthopoxvirus variola fails to produce authentic smallpox illness in any other animal species tested to date. In 2003, an outbreak in the USA of Orthopoxvirus monkeypox, revealed the susceptibility of the North American black-tailed prairie dog (Cynomys ludovicianus) to infection and fulminate disease. Prairie dogs infected with Orthopoxvirus monkeypox present with a clinical scenario similar to ordinary smallpox, including prodrome, rash, and high mortality. This study examines if Black-tailed prairie dogs can become infected with O. variola and serve as a surrogate model for the study of human smallpox disease. Substantive evidence of infection is found in immunological seroconversion of animals to either intranasal or intradermal challenges with O. variola, but in the absence of overt illness. Published by Elsevier Inc.

[Not Available].

PubMed

Kordelas, L; Grond-Ginsbach, C

2000-01-01

Kant's discussion of the ethical implications of smallpox inoculation is presented here. In four fragments Kant analyzes the moral legitimacy of endangering other people in medical practice and especially endangering people who are incapable of giving consent. In addition, we re-evaluate the alleged "success story" of the development of smallpox prevention and review the technical and theoretical difficulties of smallpox inoculation at the time of Kant.

In Vitro Characterization of a Nineteenth-Century Therapy for Smallpox

PubMed Central

Arndt, William; Mitnik, Chandra; Denzler, Karen L.; White, Stacy; Waters, Robert; Jacobs, Bertram L.; Rochon, Yvan; Olson, Victoria A.; Damon, Inger K.; Langland, Jeffrey O.

2012-01-01

In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. With the renewed threat of poxvirus-related infections, our results indicate Sarracenia purpurea may act as another defensive measure against Orthopoxvirus infections. PMID:22427855

In vitro characterization of a nineteenth-century therapy for smallpox.

PubMed

Arndt, William; Mitnik, Chandra; Denzler, Karen L; White, Stacy; Waters, Robert; Jacobs, Bertram L; Rochon, Yvan; Olson, Victoria A; Damon, Inger K; Langland, Jeffrey O

2012-01-01

In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. With the renewed threat of poxvirus-related infections, our results indicate Sarracenia purpurea may act as another defensive measure against Orthopoxvirus infections.

Safety, immunogenicity and protective efficacy in mice of a new cell-cultured Lister smallpox vaccine candidate.

PubMed

Ferrier-Rembert, Audrey; Drillien, Robert; Meignier, Bernard; Garin, Daniel; Crance, Jean-Marc

2007-11-28

It is now difficult to manufacture the first-generation smallpox vaccine, as the process could not comply with current safety and manufacturing regulations. In this study, a candidate non-clonal second-generation smallpox vaccine developed by Sanofi-Pasteur from the Lister strain has been assessed using a cowpox virus challenge in mice. We have observed similar safety, immunogenicity and protection (from disease and death) after a short or long interval following vaccination, as well as similar virus clearance post-challenge, with the second-generation smallpox vaccine candidate as compared to the traditional vaccine used as a benchmark.

Smallpox and biological warfare: the case for abandoning vaccination of military personnel.

PubMed Central

Capps, L; Vermund, S H; Johnsen, C

1986-01-01

Smallpox was officially declared eradicated from the world in 1980. Earlier, in 1972, over 50 nations signed the Biological Weapons Convention renouncing this entire category of weapons. Despite this international agreement, both the United States and the Soviet Union continue to vaccinate their military troops against smallpox, thus implying that each fears the other might still use it in biological warfare. Vaccination is not a harmless procedure, and vaccinia infections continue to be reported in troops and their contacts. Negotiating an end to the vaccination of troops would be a final step in ending the fear of smallpox. PMID:2944401

Ridding London of smallpox: the aerial transmission debate and the evolution of a precautionary approach

PubMed Central

MORTIMER, P. P.

2008-01-01

SUMMARY The efforts of the Metropolitan Asylums Board in Victorian London to isolate cases of smallpox in hospitals, and so limit its spread, set off a controversy about ‘hospital influence’, i.e. alleged escapes of the disease into the neighbourhood. When, in 1870, the Board began to gather cases of smallpox into its new intra-urban isolation hospitals, nearby householders resisted, and in 1881 their fear of aerial transmission was endorsed by a government medical inspector, W. H. Power. Not all agreed with Power, but as a result from 1885 the Board removed almost all known cases of smallpox in London to hospital ships moored in the Thames Estuary. The ships failed to provide adequate and secure accommodation, however, and so Board smallpox hospitals were erected on the adjacent Dartford marshes. After 1903, there being no more smallpox epidemics in Britain, these isolation hospitals and many similar ones outside other towns and cities were little used for their main intended purpose. Their retention for many years thereafter can be seen as an application of the precautionary principle; it bears on current contingency plans in Britain and elsewhere for dealing with serious epidemics. PMID:18325128

Pre-event Smallpox Vaccination for Healthcare Workers Revisited – the Need for a Carefully Screened Multidisciplinary Cadre

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malone, JD D.

2007-03-01

Abstract As healthcare institutions are a focus of smallpox transmission early in an epidemic, several mathematical models support pre-event smallpox vaccination of healthcare workers (HCWs). The deciding factor for HCW voluntary vaccination is the risk of disease exposure versus the risk of vaccine adverse events. In a United States military population, with careful screening to exclude atopic dermatitis/eczema and immunosuppression, over 1 million vaccinia vaccinations were delivered with 1 fatality attributed to vaccination. Among 37,901 U.S. civilian volunteer healthcare workers vaccinated, 100 serious adverse events were reported including 10 ischemic cardiac episodes and six myocardial infarctions – 2 were fatal.more » This older population had a higher rate of adverse events due to age related coronary artery disease. T-cell mediated inflammatory processes, induced by live vaccinia vaccination, may have a role in the observed acute coronary artery events. With exclusion of individuals at risk for coronary artery disease, atopic dermatitis/eczema, and immunosuppression, HCWs can be smallpox vaccinated with minimal risk. A smallpox pre-vaccinated multidisciplinary cadre (physician, nurse, infection control practitioner, technician) will supply leadership to deal with fear and uncertainty while limiting spread and initial mortality of smallpox. Stochastic – from the Greek meaning “skillful in aiming” – is currently interpreted as arising from chance and involving probability. This issue’s article “Containing a large bioterrorist smallpox attack: a computer simulation approach” by Longini et al. is a discrete time, stochastic computer simulation model that offers additional planning guidance for a smallpox (variola virus) outbreak (1). Although interpretation of the model’s information may differ, Longini’s article concludes “Given that surveillance and containment measures are in place, preemptive vaccination of hospital workers would further reduce the number of smallpox cases and deaths, but would require large numbers of prevaccinations” for the greatest effectiveness. In their simulation, the hospital has 686 workers (a relatively small facility compared to many tertiary care institutions) and 133 make close contact with smallpox cases prior to the initiation of isolation measures. Of 828 cases, 50% originated in the hospital and 13% of the contacts were untraceable. Preemptive smallpox (vaccinia virus) vaccination of 10% of the hospital workers, in addition to surveillance and containment, had a small effect on the average number of cases; however, preemptive vaccination of 50% of the hospital workers had a relatively large effect on case reduction. The larger number of preemptive vaccinations required less contact tracing and “ring” containment vaccinations. A delay of one day in fully implementing surveillance and containment resulted in a large epidemic.« less

What Ails Public Health?

ERIC Educational Resources Information Center

Alcabes, Philip

2007-01-01

Public health, once the gem of American social programs, has turned to dross. During the 20th century, the public-health sector wiped smallpox and polio off the U.S. map; virtually eliminated rickets, rubella, and goiter; stopped epidemic typhoid and yellow fever; and brought tuberculosis--once the leading cause of death in U.S. cities--under…

Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

PubMed

Mucker, Eric M; Chapman, Jennifer; Huzella, Louis M; Huggins, John W; Shamblin, Joshua; Robinson, Camenzind G; Hensley, Lisa E

2015-01-01

Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

Revisiting Jenner's mysteries, the role of the Beaugency lymph in the evolutionary path of ancient smallpox vaccines.

PubMed

Damaso, Clarissa R

2018-02-01

In 1796, Edward Jenner developed the smallpox vaccine consisting of pustular material obtained from lesions on cows affected by so-called cow-pox. The disease, caused by cowpox virus, confers crossprotection against smallpox. However, historical evidence suggests that Jenner might have used vaccinia virus or even horsepox virus instead of cowpox virus. Mysteries surrounding the origin and nature of the smallpox vaccine persisted during the 19th century, a period of intense exchange of vaccine strains, including the Beaugency lymph. This lymph was obtained from spontaneous cases of cow-pox in France in 1866 and then distributed worldwide. A detailed Historical Review of the distribution of the Beaugency lymph supports recent genetic analyses of extant vaccine strains, suggesting the lymph was probably a vaccinia strain or a horsepox-like virus. This Review is a historical investigation that revisits the mysteries of the smallpox vaccine and reveals an intricate evolutionary relationship of extant vaccinia strains. Copyright © 2018 Elsevier Ltd. All rights reserved.

Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease

PubMed Central

Mucker, Eric M.; Chapman, Jennifer; Huzella, Louis M.; Huggins, John W.; Shamblin, Joshua; Robinson, Camenzind G.; Hensley, Lisa E.

2015-01-01

Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox. PMID:26147658

The immunology of smallpox vaccines

PubMed Central

Kennedy, Richard B; Ovsyannikova, Inna G; Jacobson, Robert M; Poland, Gregory A

2010-01-01

In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccination dates back to the late 1800s with Edward Jenner, it is only in the past decade that modern immunologic tools have been applied toward deciphering poxvirus immunity. Smallpox vaccines containing vaccinia virus elicit strong humoral and cellular immune responses that confer cross-protective immunity against variola virus for decades after immunization. Recent studies have focused on: establishing the longevity of poxvirus-specific immunity, defining key immune epitopes targeted by T and B cells, developing subunit-based vaccines, and developing genotypic and phenotypic immune response profiles that predict either vaccine response or adverse events following immunization. PMID:19524427

Preparing South Carolina Emergency Departments for Mass Casualties with an Emphasis on the Planning Process

DTIC Science & Technology

2013-03-01

population for patients with symptoms of acute infectious disease, especially smallpox, anthrax, plague, tularemia , and influenza 19 • 50 cases...disease, especially smallpox, anthrax, plague, tularemia , and influenza • 50 cases per million population for patients with symptoms of acute...an additional 1,548–2064 patients with symptoms of acute infectious disease, especially smallpox, anthrax, plague, tularemia , and influenza to be

[Comment on the "medical-legal report of the 1865 smallpox epidemic in Valparaiso" by Doctor Manuel Antonio Carmona].

PubMed

Laval, Enrique

2012-04-01

We transcribe and comment on the report about the smallpox epidemic in Valparaiso in 1865, developed by Dr. Manuel Antonio Carmona. At that time, it was considered as an important contribution to epidemiology and clinical prevention of the disease. It gave rules about the management "of smallpox at home", highlighting mechanisms of transmission of this eruptive infectious disease.

A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

PubMed Central

Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio

2006-01-01

Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912

A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.

PubMed

Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio

2006-04-11

Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II.

PubMed

Bhatnagar, Vibha; Stoto, Michael A; Morton, Sally C; Boer, Rob; Bozzette, Samuel A

2006-05-05

Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications. Two authors reviewed selected papers for smallpox outbreaks. 51 relevant outbreaks were identified from 1,389 publications. The median for the effective first generation reproduction rate (initial R) was 2 (range 0-38). The majority outbreaks were small (less than 5 cases) and contained within one generation. Outbreaks with few hospitalized patients had low initial R values (median of 1) and were prolonged if not initially recognized (median of 3 generations); outbreaks with mostly hospitalized patients had higher initial R values (median 12) and were shorter (median of 3 generations). Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases) and longer (median of 3 generations) compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation). Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks. The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early.

Ability of physicians to diagnose and manage illness due to category A bioterrorism agents.

PubMed

Cosgrove, Sara E; Perl, Trish M; Song, Xiaoyan; Sisson, Stephen D

2005-09-26

Early recognition of a terrorist attack with biologic agents will rely on physician diagnosis. Physicians' ability to diagnose and care for patients presenting after a bioterror event is unknown. The role of online case-based didactics to measure and improve knowledge in the diagnosis and treatment of these patients is unknown. A multicenter online educational intervention was completed by 631 physicians at 30 internal medicine residency programs in 16 states and Washington, DC, between July 1, 2003, and June 10, 2004. Participants completed a pretest, assessing ability to diagnose and manage potential cases of smallpox, anthrax, botulism, and plague. A didactic module reviewing diagnosis and management of these diseases was then completed, followed by a posttest. Pretest performance measured baseline knowledge. Posttest performance compared with pretest performance measured effectiveness of the educational intervention. Results were compared based on year of training and geographic location of the residency program. Correct diagnoses of diseases due to bioterrorism agents were as follows: smallpox, 50.7%; anthrax, 70.5%; botulism, 49.6%; and plague, 16.3% (average, 46.8%). Correct diagnosis averaged 79.0% after completing the didactic module (P<.001). Correct management of smallpox was 14.6%; anthrax, 17.0%; botulism, 60.2%; and plague, 9.7% (average, 25.4%). Correct management averaged 79.1% after completing the didactic module (P<.001). Performance did not differ based on year of training (P = .54) or geographic location (P = .64). Attending physicians performed better than residents (P<.001). Physician diagnosis and management of diseases caused by bioterrorism agents is poor. An online didactic module may improve diagnosis and management of diseases caused by these agents.

THE EFFECT OF GAMMA-RAYS OF Co$sup 60$ ON SMALLPOX VACCINE CONTAMINATING MICROORGANISMS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalenina, E.F.; Abidov, A.Z.

1963-02-01

Liquid smallpox vaccine inactivated by gamma irradiation proved to be fully adequate for studying the effects of gamma irradiation on the viability of microorganism artificially added to it. The complete inactivation of Staphylococcus albus and Bacillus subtilis, which most frequently contaminate smallpox vaccine, occurs by gamma irradiation from Co/sup 60/ ranging from 900,000 to 1.5-million r doses at 47 impulses/second magnitude. (OTS)

[Strategies, actors, promises and fears in the smallpox vaccinations campaigns in Mexico: from the Porfiriato to the Post-revolution (1880-1940)].

PubMed

Agostoni, Claudia

2011-02-01

The article examines some of the strategies employed by the Mexican health authorities that led to the organization of massive and obligatory smallpox vaccination campaigns from the late 1880s to the 1940s, a period of Mexican history that corresponds to the Porfirio Díaz regime (1877-1911), to the armed phase of the Mexican Revolution (1910-1920), and to the first two decades of the Post-revolutionary governments (1920-1940). Attention will be placed of the vaccination programs in the main urban settings, notably in Mexico City, as well as the gradual but decisive organization and regulation of vaccination campaigns in the heterogeneous rural milieu. Furthermore, the importance that hygienic education acquired will be explored, as well as the divergent and contested responses that emerged due to the obligatory vaccination campaigns, responses that included resistance, fear, uncertainty and widespread acceptance.

[Sanitary and epidemiological supply for the Russian Army during the First World War (1914-1918)].

PubMed

gorelova, L E; Loktev, A E

2014-02-01

At the beginning of the First World War the most typical diseases in the Russian Army were typhoid, typhus, diphtheria, cholera, smallpox and other infectious diseases. At the beginning of the First World War the level of infectious morbidity was significantly low, but further increased and pandemic risk arose. Servicemen were mostly ill with typhus, relapsing fever, flux, cholera, smallpox and typhoid. The highest mortality rate was registered in patients with cholera, typhus and typhoid. According the prewar deployment program of the Russian Army anti-epidemiologic facilities were established. By the end of war were established 110 sanitary-and-hygienic and 90 disinfection units. However, organization of anti-epidemiologic security was unsatisfactory. Due to lack of specialists and equipment anti-epidemiologic facilities of units were under strength. Commanders of sanitary units and sanitary service had not enough resources for operational service in the Forces and facilities of rear area.

The French Armed Forces Virology Unit: A Chronological Record of Ongoing Research on Orthopoxvirus

PubMed Central

Delaune, Déborah; Iseni, Frédéric; Ferrier-Rembert, Audrey; Peyrefitte, Christophe N.; Ferraris, Olivier

2017-01-01

Since the official declaration of smallpox eradication in 1980, the general population vaccination has ceased worldwide. Therefore, people under 40 year old are generally not vaccinated against smallpox and have no cross protection against orthopoxvirus infections. This naïve population may be exposed to natural or intentional orthopoxvirus emergences. The virology unit of the Institut de Recherche Biomédicale des Armées (France) has developed research programs on orthopoxviruses since 2000. Its missions were conceived to improve the diagnosis capabilities, to foster vaccine development, and to develop antivirals targeting specific viral proteins. The role of the virology unit was asserted in 2012 when the responsibility of the National Reference Center for the Orthopoxviruses was given to the unit. This article presents the evolution of the unit activity since 2000, and the past and current research focusing on orthopoxviruses. PMID:29295488

Impaired innate, humoral, and cellular immunity despite a take in smallpox vaccine recipients.

PubMed

Kennedy, Richard B; Poland, Gregory A; Ovsyannikova, Inna G; Oberg, Ann L; Asmann, Yan W; Grill, Diane E; Vierkant, Robert A; Jacobson, Robert M

2016-06-14

Smallpox vaccine is highly effective, inducing protective immunity to smallpox and diseases caused by related orthopoxviruses. Smallpox vaccine efficacy was historically defined by the appearance of a lesion or "take" at the vaccine site, which leaves behind a characteristic scar. Both the take and scar are readily recognizable and were used during the eradication effort to indicate successful vaccination and to categorize individuals as "protected." However, the development of a typical vaccine take may not equate to the successful development of a robust, protective immune response. In this report, we examined two large (>1000) cohorts of recipients of either Dryvax(®) or ACAM2000 using a testing and replication study design and identified subgroups of individuals who had documented vaccine takes, but who failed to develop robust neutralizing antibody titers. Examination of these individuals revealed that they had suboptimal cellular immune responses as well. Further testing indicated these low responders had a diminished innate antiviral gene expression pattern (IFNA1, CXCL10, CXCL11, OASL) upon in vitro stimulation with vaccinia virus, perhaps indicative of a dysregulated innate response. Our results suggest that poor activation of innate antiviral pathways may result in suboptimal immune responses to the smallpox vaccine. These genes and pathways may serve as suitable targets for adjuvants in new attenuated smallpox vaccines and/or effective antiviral therapy targets against poxvirus infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impaired Innate, Humoral, and Cellular Immunity Despite a Take in Smallpox Vaccine Recipients

PubMed Central

Kennedy, Richard B.; Poland, Gregory A.; Ovsyannikova, Inna G.; Oberg, Ann L.; Asmann, Yan W.; Grill, Diane E.; Vierkant, Robert A.; Jacobson, Robert M.

2017-01-01

Smallpox vaccine is highly effective, inducing protective immunity to smallpox and diseases caused by related orthopoxviruses. Smallpox vaccine efficacy was historically defined by the appearance of a lesion or “take” at the vaccine site, which leaves behind a characteristic scar. Both the take and scar are readily recognizable and were used during the eradication effort to indicate successful vaccination and to categorize individuals as “protected.” However, the development of a typical vaccine take may not equate to the successful development of a robust, protective immune response. In this report, we examined two large (>1,000) cohorts of recipients of either Dryvax® or ACAM2000 using a testing and replication study design and identified subgroups of individuals who had documented vaccine takes, but who failed to develop robust neutralizing antibody titers. Examination of these individuals revealed that they had suboptimal cellular immune responses as well. Further testing indicated these low responders had a diminished innate antiviral gene expression pattern (IFNA1, CXCL10, CXCL11, OASL) upon in vitro stimulation with vaccinia virus, perhaps indicative of a dysregulated innate response. Our results suggest that poor activation of innate antiviral pathways may result in suboptimal immune responses to the smallpox vaccine. These genes and pathways may serve as suitable targets for adjuvants in new attenuated smallpox vaccines and/or effective antiviral therapy targets against poxvirus infections. PMID:27177944

Prevention

MedlinePlus

... Contagiosum Orf Virus (Sore Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections ... Contagiosum Orf Virus (Sore Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections ...

Treatment

MedlinePlus

... Contagiosum Orf Virus (Sore Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections ... Contagiosum Orf Virus (Sore Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections ...

About Monkeypox

MedlinePlus

... Contagiosum Orf Virus (Sore Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections ... Contagiosum Orf Virus (Sore Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections ...

Signs and Symptoms

MedlinePlus

... Contagiosum Orf Virus (Sore Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections ... Contagiosum Orf Virus (Sore Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections ...

Concurrent smallpox and chickenpox

PubMed Central

Sarkar, J. K.; Mitra, A. C.; Mukherjee, M. K.; Dumbell, K. P.; Almeida, J. D.

1976-01-01

Three patients showing smallpox- and chickenpox-like lesions simultaneously were investigated virologically. Both infections were confirmed in the laboratory and, in one case, by electron microscopy. ImagesFig. 1Fig. 2Fig. 3 PMID:188559

Swimming Pools and Molluscum Contagiosum

MedlinePlus

... Monkeypox Orf Virus (Sore Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections ... Monkeypox Orf Virus (Sore Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections ...

[Lessons learnt from the German smallpox outbreaks after World War II].

PubMed

Sasse, Julia; Gelderblom, Hans R

2015-07-01

Even though smallpox was declared eradicated by WHO in 1980, it cannot be ruled out that the etiological variola virus could be used as a biological weapon. Undestroyed viruses from biowarfare programmes, virus strains left undetected in a freezer or dangerous recombinant poxvirus constructs could cause dangerous outbreaks in a relatively unprotected population. Despite an abundance of studies performed during the eradication of smallpox, epidemiological data for preparedness planning and outbreak control in modern, industrialized countries are scarce. Full-text hand search for the period from 1945 to 1975 in the main German public health journals. After World War II 12 smallpox outbreaks occurred in Germany. They were studied with the focus on the period of contagiousness, the protective effect of vaccination, booster-effect of revaccination and the place of infection. A total of 95 individuals contracted smallpox, including 10 fatalities. Despite having been previously vaccinated, 81 vaccinated persons came down with smallpox, yet 91% of them developed only mild symptoms. These patients presented a high risk for spreading the infection to contact persons due to misinterpretation of symptoms and the continuing social contacts. Basically, the risk of transmission in the first 2 to 3 days after onset of symptoms was low, thus facilitating antiepidemic measures. The importance of hospital preparedness is emphasized by the fact that most infections occurred in hospitals. The data analyzed provide valuable information for today's outbreak response planning and counter bioterrorism preparedness.

Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

PubMed

Slike, Bonnie M; Creegan, Matthew; Marovich, Mary; Ngauy, Viseth

2017-01-01

Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10-20 years post vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112-3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations

PubMed Central

Slike, Bonnie M.; Creegan, Matthew

2017-01-01

Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5–10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10–20 years post vaccination. This contrasted with a comparator group of adults, ages 35–49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112–3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program. PMID:28046039

The prevention and eradication of smallpox: a commentary on Sloane (1755) ‘An account of inoculation’

PubMed Central

Weiss, Robin A.; Esparza, José

2015-01-01

Sir Hans Sloane's account of inoculation as a means to protect against smallpox followed several earlier articles published in Philosophical Transactions on this procedure. Inoculation (also called ‘variolation’) involved the introduction of small amounts of infectious material from smallpox vesicles into the skin of healthy subjects, with the goal of inducing mild symptoms that would result in protection against the more severe naturally acquired disease. It began to be practised in England in 1721 thanks to the efforts of Lady Mary Wortley Montagu who influenced Sloane to promote its use, including the inoculation of the royal family's children. When Edward Jenner's inoculation with the cow pox (‘vaccination’) followed 75 years later as a safer yet equally effective procedure, the scene was set for the eventual control of smallpox epidemics culminating in the worldwide eradication of smallpox in 1977, officially proclaimed by WHO in 1980. Here, we discuss the significance of variolation and vaccination with respect to scientific, public health and ethical controversies concerning these ‘weapons of mass protection’. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society. PMID:25750241

Genetic resistance to smallpox: lessons from mousepox.

PubMed

Karupiah, Gunasegaran; Panchanathan, Vijay; Sakala, Isaac G; Chaudhri, Geeta

2007-01-01

There is increased interest in understanding protective immunity to smallpox for two principal reasons. First, it is the only disease that has been successfully eradicated using a live virus vaccine and, second, there exists a potential threat of intentional or unintentional release of variola virus, the causative agent of smallpox. Although mortality rates associated with smallpox were as high as 40%, a significant subset of those infected recovered. The basis of susceptibility or resistance, and the immune parameters associated with recovery, are still unknown. Animal models of poxvirus infections are being employed to understand what constitutes an effective host response. Ectromelia virus is closely related to variola virus and it causes a disease similar to smallpox in mice. This model is well established, resistant and susceptible strains of mice are defined and four genetic loci associated with resistance have been identified. Susceptibility to infec tion and disease severity is also influenced by virus immune evasion strategies. The outcome of infection is clearly dictated by several factors including host and viral genes, both of which influence the immune response. Here we present data on one virus-encoded immune modifier and its effect on the functions of two host genetic loci associ ated with resistance.

The De Novo Synthesis of Horsepox Virus: Implications for Biosecurity and Recommendations for Preventing the Reemergence of Smallpox.

PubMed

Koblentz, Gregory D

In March 2017, the American biotech company Tonix announced that a Canadian scientist had synthesized horsepox virus as part of a project to develop a safer vaccine against smallpox. The first de novo synthesis of an orthopoxvirus, a closely related group of viruses that includes horsepox and the variola virus that causes smallpox, crosses an important Rubicon in the field of biosecurity. The synthesis of horsepox virus takes the world one step closer to the reemergence of smallpox as a threat to global health security. That threat has been held at bay for the past 40 years by the extreme difficulty of obtaining variola virus and the availability of effective medical countermeasures. The techniques demonstrated by the synthesis of horsepox have the potential to erase both of these barriers. The primary risk posed by this research is that it will open the door to the routine and widespread synthesis of other orthopoxviruses, such as vaccinia, for use in research, public health, and medicine. The normalization and globalization of orthopoxvirus synthesis for these beneficial applications will create a cadre of laboratories and scientists that will also have the capability and expertise to create infectious variola virus from synthetic DNA. Unless the safeguards against the synthesis of variola virus are strengthened, the capability to reintroduce smallpox into the human population will be globally distributed and either loosely or completely unregulated, providing the foundation for a disgruntled or radicalized scientist, sophisticated terrorist group, unscrupulous company, or rogue state to recreate one of humanity's most feared microbial enemies. The reemergence of smallpox-because of a laboratory accident or an intentional release-would be a global health disaster. International organizations, national governments, the DNA synthesis industry, and the synthetic biology community all have a role to play in devising new approaches to preventing the reemergence of smallpox.

75 FR 3244 - Prospective Grant of Exclusive License: Monoclonal Antibodies Against Smallpox/Orthopoxviruses

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

... safe and effective for prevention of smallpox, it is well documented that various adverse reactions in...) prepared from vaccinated humans has historically been used to treat adverse reactions arising from vaccinia...

A shot in the rear, not a shot in the dark: application of a mass clinic framework in a public health emergency.

PubMed

Erwin, Paul Campbell; Sheeler, Lorinda; Lott, John M

2009-01-01

An outbreak of foodborne hepatitis A infection compelled two regional health departments in eastern Tennessee to implement an emergency mass clinic for providing hepatitis immune serum globulin (ISG) to several thousand potentially exposed people. For the mass clinic framework, we utilized the smallpox post-event clinic plans of the Centers for Disease Control and Prevention (CDC), although the plans had only been exercised for smallpox. Following CDC's guidelines for staffing and organizing the mass clinic, we provided 5,038 doses of ISG during a total of 24 hours of clinic operation, using 3,467 person-hours, or 1.45 ISG doses per person-hour-very close to the 1.58 doses per person-hour targeted in CDC's smallpox post-event clinic plans. The mass clinic showed that CDC's smallpox post-event clinic guidelines were feasible, practical, and adaptable to other mass clinic situations.

Modeling potential responses to smallpox as a bioterrorist weapon.

PubMed

Meltzer, M I; Damon, I; LeDuc, J W; Millar, J D

2001-01-01

We constructed a mathematical model to describe the spread of smallpox after a deliberate release of the virus. Assuming 100 persons initially infected and 3 persons infected per infectious person, quarantine alone could stop disease transmission but would require a minimum daily removal rate of 50% of those with overt symptoms. Vaccination would stop the outbreak within 365 days after release only if disease transmission were reduced to <0.85 persons infected per infectious person. A combined vaccination and quarantine campaign could stop an outbreak if a daily quarantine rate of 25% were achieved and vaccination reduced smallpox transmission by > or = 33%. In such a scenario, approximately 4,200 cases would occur and 365 days would be needed to stop the outbreak. Historical data indicate that a median of 2,155 smallpox vaccine doses per case were given to stop outbreaks, implying that a stockpile of 40 million doses should be adequate.

Smallpox virus destruction and the implications of a new vaccine.

PubMed

Henderson, D A

2011-06-01

The World Health Assembly is scheduled to decide in May 2011 whether the 2 known remaining stockpiles of smallpox virus are to be destroyed or retained. In preparation for this, a WHO-appointed committee undertook a comprehensive review of the status of smallpox virus research from 1999 to 2010. It concluded that, considering the nature of the studies already completed with respect to vaccine, drugs, and diagnostics, there was no reason to retain live smallpox virus except to satisfy restrictive regulatory requirements. The committee advised that researchers and regulators define alternative models for testing the vaccines and drugs. Apart from other considerations, the costs of new products are significant and important. These include prospective expenditures required for the development, manufacture, testing, and storage of new products. This commentary provides approximations of these costs and the incremental contribution that a newly developed vaccine might make in terms of public health security.

Comparison of smallpox outbreak control strategies using a spatial metapopulation model.

PubMed

Hall, I M; Egan, J R; Barrass, I; Gani, R; Leach, S

2007-10-01

To determine the potential benefits of regionally targeted mass vaccination as an adjunct to other smallpox control strategies we employed a spatial metapopulation patch model based on the administrative districts of Great Britain. We counted deaths due to smallpox and to vaccination to identify strategies that minimized total deaths. Results confirm that case isolation, and the tracing, vaccination and observation of case contacts can be optimal for control but only for optimistic assumptions concerning, for example, the basic reproduction number for smallpox (R0=3) and smaller numbers of index cases ( approximately 10). For a wider range of scenarios, including larger numbers of index cases and higher reproduction numbers, the addition of mass vaccination targeted only to infected districts provided an appreciable benefit (5-80% fewer deaths depending on where the outbreak started with a trigger value of 1-10 isolated symptomatic individuals within a district).

Abraham Lincoln's Gettysburg illness.

PubMed

Goldman, Armond S; Schmalstieg, Frank C

2007-05-01

When Abraham Lincoln delivered the Gettysburg Address, he was weak and dizzy; his face had a ghastly colour. That evening on the train to Washington, DC, he was febrile and weak, and suffered severe headaches. The symptoms continued; back pains developed. On the fourth day of the illness, a widespread scarlet rash appeared that soon became vesicular. By the tenth day, the lesions itched and peeled. The illness lasted three weeks. The final diagnosis, a touch of varioloid, was an old name for smallpox that was later used in the 20th century to denote mild smallpox in a partially immune individual. It was unclear whether Lincoln had been immunized against smallpox. Indeed, this review suggests that Lincoln had unmodified smallpox and that Lincoln's physicians tried to reassure the public that Lincoln was not seriously ill. Indeed, the successful conclusion of the Civil War and reunification of the country were dependent upon Lincoln's presidency.

Molecular Smallpox Vaccine Delivered by Alphavirus Replicons Elicits Protective Immunity in Mice and Non-human Primates

PubMed Central

Hooper, Jay W.; Ferro, Anthony M.; Golden, Joseph W.; Silvera, Peter; Dudek, Jeanne; Alterson, Kim; Custer, Max; Rivers, Bryan; Morris, John; Owens, Gary; Smith, Jonathan F.; Kamrud, Kurt I.

2009-01-01

Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 70s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRP) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 × 106 PFU of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine. PMID:19833247

Decontamination of Bioaerosols within Engineering Tolerances of Aircraft Materials

DTIC Science & Technology

2012-09-04

sources with intestinal typhoid bacteria. They also released plague infected fleas over several villages in China and Mongolia in 1941. Around the...smallpox, Marburg, Ebola, and Q fever . During their program, the Soviets produced more than 100 tons of anthrax, 20 tons of plague, and 20 tons of...Filoviridae, Bunyaviridae, and Flavividae families, which cause hemorrhagic fevers . The category B viruses include several arboviruses, which cause

Smallpox

MedlinePlus

... is unknown how long past vaccinations stay effective. People who received the vaccine many years ago may no longer be fully ... you have been exposed through bioterrorism. Prevention Many people were vaccinated against smallpox in the past. The vaccine is no longer given to the general public. ...

On the origin of smallpox: correlating variola phylogenics with historical smallpox records.

PubMed

Li, Yu; Carroll, Darin S; Gardner, Shea N; Walsh, Matthew C; Vitalis, Elizabeth A; Damon, Inger K

2007-10-02

Human disease likely attributable to variola virus (VARV), the etiologic agent of smallpox, has been reported in human populations for >2,000 years. VARV is unique among orthopoxviruses in that it is an exclusively human pathogen. Because VARV has a large, slowly evolving DNA genome, we were able to construct a robust phylogeny of VARV by analyzing concatenated single nucleotide polymorphisms (SNPs) from genome sequences of 47 VARV isolates with broad geographic distributions. Our results show two primary VARV clades, which likely diverged from an ancestral African rodent-borne variola-like virus either approximately 16,000 or approximately 68,000 years before present (YBP), depending on which historical records (East Asian or African) are used to calibrate the molecular clock. One primary clade was represented by the Asian VARV major strains, the more clinically severe form of smallpox, which spread from Asia either 400 or 1,600 YBP. Another primary clade included both alastrim minor, a phenotypically mild smallpox described from the American continents, and isolates from West Africa. This clade diverged from an ancestral VARV either 1,400 or 6,300 YBP, and then further diverged into two subclades at least 800 YBP. All of these analyses indicate that the divergence of alastrim and variola major occurred earlier than previously believed.

Inoculating for smallpox.

PubMed

Greene, Jan

2003-04-01

In California, one hospital decided the time was right to inoculate staff volunteers with the smallpox vaccine. Weighing the same pros and cons--civic responsibility, health risk, cost and reluctance of staff--other hospitals opted out of inoculations, at least for now. What led these organizations to such divergent decisions?

Smallpox vaccination: an early start of modern medicine in America.

PubMed

Liebowitz, Dan

2017-01-01

Smallpox was eradicated by the World Health Organization in 1980. Before its eradication thedisease had a mortality rate upwards of 50% and had a significant impact on society. During theAmerican Revolutionary war, smallpox outbreaks were impeding the American war effort until1777 when George Washington carried out a mass inoculation campaign in the ContinentalArmy that reduced the mortality from smallpox to less than 2%. Inoculation was an early formof vaccination that used live virus from active pustules to induce a milder, but still sometimesdeadly, case of disease. Washington has been credited with helping to ease the burden ofsmallpox on the Army which improved the odds of success against the British. When EdwardJenner's vaccine reached America it was more readily accepted by political and medical leadersdue the success of Washington's inoculation campaign. The Founding Fathers argued thatsmallpox vaccination was the greatest discovery in modern medicine and they were likely correctthat it helped to usher in the modern era of vaccinology.

[Treatment and remedies against smallpox outbreaks in Ferrara in the late nineteenth century].

PubMed

Vicentini, Chiara Beatrice; Manfredini, Stefano; Altieri, Lorenzo; Lupi, Silvia; Guidi, Enrica; Contini, Carlo

2013-09-01

Health interventions against smallpox during the two epidemics in the second half of the 19th century are outlined. The 1871 hospital health report and the medical report on smallpox patients treated at the hospital and poorhouse of Ferrara between January 1891 and January 1892, drawn up by Alessandro Bennati, provide both interesting data and insights into the treatments and remedies of the time. The treatment of this illness was - and indeed could be - nothing other than symptomatic, there being no real means to halt the spread of the disease. Rather, other remedies were found by alleviating pain and regaining energy during the various stages of the disease. A close relationship between vaccination and the incidence and gravity of the illness is underlined. When the practice of vaccination started to be widely employed at the end of the century, there were almost no cases of death due to smallpox. The pharmacopoeias of the time, Antonio Campana's Farmacopea ferrarese in particular, proved an essential guide in the analysis of each document.

Why, which, how, who, when? A personal view of smallpox vaccination for the 2000s.

PubMed

Mortimer, P P

2004-06-01

The uncertainty about the extent of proliferation of smallpox virus holdings since the early 1990s, and particularly whether terrorist groups or so-called rogue states might now hold the virus, confronts potential target countries with a continuing dilemma. An increasingly large majority of their populations have never been vaccinated, and those who have been vaccinated may have become susceptible to smallpox again. Yet recent attempts by the United States and other governments to persuade large numbers of key personnel and others to accept vaccination have at least partially failed and a different long-term strategy is needed. This strategy should be based on surveillance of rash illnesses, improved public education, more refined contingency planning and a new approach to smallpox vaccination. The last should if possible be based on cell-grown, less reactogenic vaccines, even though it may be some years before these can become available. Meanwhile this article examines other expedients including the use of existing lymph vaccines.

New insights about host response to smallpox using microarray data.

PubMed

Esteves, Gustavo H; Simoes, Ana C Q; Souza, Estevao; Dias, Rodrigo A; Ospina, Raydonal; Venancio, Thiago M

2007-08-24

Smallpox is a lethal disease that was endemic in many parts of the world until eradicated by massive immunization. Due to its lethality, there are serious concerns about its use as a bioweapon. Here we analyze publicly available microarray data to further understand survival of smallpox infected macaques, using systems biology approaches. Our goal is to improve the knowledge about the progression of this disease. We used KEGG pathways annotations to define groups of genes (or modules), and subsequently compared them to macaque survival times. This technique provided additional insights about the host response to this disease, such as increased expression of the cytokines and ECM receptors in the individuals with higher survival times. These results could indicate that these gene groups could influence an effective response from the host to smallpox. Macaques with higher survival times clearly express some specific pathways previously unidentified using regular gene-by-gene approaches. Our work also shows how third party analysis of public datasets can be important to support new hypotheses to relevant biological problems.

The Effect of Smallpox and Bacillus Calmette-Guérin Vaccination on the Risk of Human Immunodeficiency Virus-1 Infection in Guinea-Bissau and Denmark

PubMed Central

Villumsen, Marie; Jensen, Mette Lundsby; Ravn, Henrik; da Silva, Zacarias J; Sørup, Signe; Baker, Jennifer Lyn; Rodrigues, Amabélia; Benn, Christine Stabell; Roth, Adam E; Aaby, Peter

2017-01-01

Abstract Background The live smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, human immunodeficiency virus (HIV)-1 became an important cause of death after smallpox vaccination was phased out globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and we tested this hypothesis in both Guinea-Bissau and Denmark. Methods We conducted 2 studies: (1) a cross-sectional study of HIV infection and vaccination scars in Guinea-Bissau including 1751 individuals and (2) a case-base study with a background population of 46239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission was almost exclusively sexually transmitted. In Denmark, we excluded intravenous drug users. Data were analyzed using logistic regression. Results Bacillus Calmette-Guérin and/or smallpox vaccination compared with neither of these vaccines was associated with an adjusted odds ratio (aOR) for HIV-1 of 0.62 (95% confidence interval [CI], 0.36–1.07) in Guinea-Bissau and 0.70 (95% CI, 0.43–1.15) in Denmark. We combined the results from both settings in a meta-analysis (aOR = 0.66; 95% CI, 0.46–0.96). Data from Guinea-Bissau indicated a stronger effect of multiple smallpox vaccination scars (aOR = 0.27; 95% CI, 0.10–0.75) as follows: women, aOR = 0.18 (95% CI, 0.05–0.64); men, aOR = 0.52 (95% CI, 0.12–2.33); sex-differential effect, P = .29. Conclusions The studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search for an HIV-1 vaccine. PMID:28852677

Eradicating a Disease: Lessons from Mathematical Epidemiology

ERIC Educational Resources Information Center

Glomski, Matthew; Ohanian, Edward

2012-01-01

Smallpox remains the only human disease ever eradicated. In this paper, we consider the mathematics behind control strategies used in the effort to eradicate smallpox, from the life tables of Daniel Bernoulli, to the more modern susceptible-infected-removed (SIR)-type compartmental models. In addition, we examine the mathematical feasibility of…

42 CFR 102.80 - Calculation of medical benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Calculation of medical benefits. 102.80 Section 102.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... medical items and services that are reasonable and necessary to diagnose or treat a smallpox vaccine...

42 CFR 102.80 - Calculation of medical benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Calculation of medical benefits. 102.80 Section 102.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... medical items and services that are reasonable and necessary to diagnose or treat a smallpox vaccine...

42 CFR 102.80 - Calculation of medical benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Calculation of medical benefits. 102.80 Section 102.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... medical items and services that are reasonable and necessary to diagnose or treat a smallpox vaccine...

42 CFR 102.2 - Summary of available benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Summary of available benefits. 102.2 Section 102.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipient or vaccinia contact was the direct result of a covered injury, as described in...

42 CFR 102.2 - Summary of available benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Summary of available benefits. 102.2 Section 102.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipient or vaccinia contact was the direct result of a covered injury, as described in...

42 CFR 102.2 - Summary of available benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Summary of available benefits. 102.2 Section 102.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipient or vaccinia contact was the direct result of a covered injury, as described in...

42 CFR 102.2 - Summary of available benefits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Summary of available benefits. 102.2 Section 102.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipient or vaccinia contact was the direct result of a covered injury, as described in...

42 CFR 102.2 - Summary of available benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Summary of available benefits. 102.2 Section 102.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipient or vaccinia contact was the direct result of a covered injury, as described in...

Inactivation of Poxviruses by Upper-Room UVC Light in a Simulated Hospital Room Environment

PubMed Central

McDevitt, James J.; Milton, Donald K.; Rudnick, Stephen N.; First, Melvin W.

2008-01-01

In the event of a smallpox outbreak due to bioterrorism, delays in vaccination programs may lead to significant secondary transmission. In the early phases of such an outbreak, transmission of smallpox will take place especially in locations where infected persons may congregate, such as hospital emergency rooms. Air disinfection using upper-room 254 nm (UVC) light can lower the airborne concentrations of infective viruses in the lower part of the room, and thereby control the spread of airborne infections among room occupants without exposing occupants to a significant amount of UVC. Using vaccinia virus aerosols as a surrogate for smallpox we report on the effectiveness of air disinfection, via upper-room UVC light, under simulated real world conditions including the effects of convection, mechanical mixing, temperature and relative humidity. In decay experiments, upper-room UVC fixtures used with mixing by a conventional ceiling fan produced decreases in airborne virus concentrations that would require additional ventilation of more than 87 air changes per hour. Under steady state conditions the effective air changes per hour associated with upper-room UVC ranged from 18 to 1000. The surprisingly high end of the observed range resulted from the extreme susceptibility of vaccinia virus to UVC at low relative humidity and use of 4 UVC fixtures in a small room with efficient air mixing. Increasing the number of UVC fixtures or mechanical ventilation rates resulted in greater fractional reduction in virus aerosol and UVC effectiveness was higher in winter compared to summer for each scenario tested. These data demonstrate that upper-room UVC has the potential to greatly reduce exposure to susceptible viral aerosols. The greater survival at baseline and greater UVC susceptibility of vaccinia under winter conditions suggest that while risk from an aerosol attack with smallpox would be greatest in winter, protective measures using UVC may also be most efficient at this time. These data may also be relevant to influenza, which also has improved aerosol survival at low RH and somewhat similar sensitivity to UVC. PMID:18781204

How long ago did smallpox virus emerge?

PubMed

Shchelkunov, Sergei N

2009-01-01

Unlike vertebrates, for which paleontological data are available, and RNA viruses, which display a high rate of genetic variation, an objective estimate of time parameters for the molecular evolution of DNA viruses, which display a low rate of accumulation of mutations, is a complex problem. Genomic studies of a set of smallpox (variola) virus (VARV) isolates demonstrated the patterns of phylogenetic relationships between geographic variants of this virus. Using archival data on smallpox outbreaks and the results of phylogenetic analyses of poxvirus genomes, different research teams have obtained contradictory data on the possible time point of VARV origin. I discuss the approaches used for dating of VARV evolution and adduce the arguments favoring its historically recent origin.

Overproduction, purification, and biochemical characterization of the dual specificity H1 protein phosphatase encoded by variola major virus.

PubMed

Tropea, Joseph E; Phan, Jason; Waugh, David S

2006-11-01

Smallpox, a highly contagious infectious disease caused by the variola major virus, has an overall mortality rate of about 30%. Because there currently is no specific treatment for smallpox, and the only prevention is vaccination, there is an urgent need for the development of effective antiviral drugs. The dual specificity protein phosphatase encoded by the smallpox virus (H1) is essential for the production of infectious viral particles, making it a promising molecular target for antiviral therapeutics. Here, we report the molecular cloning, overproduction, purification, and initial biochemical characterization of H1 phosphatase, thereby paving the way for the discovery of small molecule inhibitors.

[Smallpox preparedness in Denmark].

PubMed

Heegaard, Erik Deichmann; Fomsgaard, Anders

2005-09-05

Although the likelihood of a deliberate release is considered to be minor, smallpox virus poses a worldwide terrorism security risk because it (1) can easily be disseminated and transmitted from person to person; (2) results in high mortality rates and has the potential to create a major public health impact; (3) might cause public panic and social disruption; and (4) requires special action for public health preparedness. Consequently, Statens Serum Institute and the National Board of Health have developed a Danish smallpox preparedness plan. This article discusses critical aspects of the plan, including risk analysis and a multi-tiered action plan, vaccination, analysis of clinical specimens, the establishment of active surveillance teams and generic contingency elements.

EFFECTS OF X RADIATION ON THE REPRODUCTION OF SMALLPOX VACCINE VIRUS IN TISSUE CULTURE (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamalyan, L.A.; Ter-Pogosyan, R.A.

1963-01-01

Infectious and hemagglutinic properties of smallpox vaccine virus in chick embryo cutaneous-muscular tissue irradiated with 20-kr of x radiation were investigated. It was found that the radiation induced increased virus reproduction. Accumulation of hemagglutinin did not differ in irradiated and nonirradiated cultures. (R.V.J.)

New insights about host response to smallpox using microarray data

PubMed Central

Esteves, Gustavo H; Simoes, Ana CQ; Souza, Estevao; Dias, Rodrigo A; Ospina, Raydonal; Venancio, Thiago M

2007-01-01

Background Smallpox is a lethal disease that was endemic in many parts of the world until eradicated by massive immunization. Due to its lethality, there are serious concerns about its use as a bioweapon. Here we analyze publicly available microarray data to further understand survival of smallpox infected macaques, using systems biology approaches. Our goal is to improve the knowledge about the progression of this disease. Results We used KEGG pathways annotations to define groups of genes (or modules), and subsequently compared them to macaque survival times. This technique provided additional insights about the host response to this disease, such as increased expression of the cytokines and ECM receptors in the individuals with higher survival times. These results could indicate that these gene groups could influence an effective response from the host to smallpox. Conclusion Macaques with higher survival times clearly express some specific pathways previously unidentified using regular gene-by-gene approaches. Our work also shows how third party analysis of public datasets can be important to support new hypotheses to relevant biological problems. PMID:17718913

Analysis of pregnancy and infant health outcomes among women in the National Smallpox Vaccine in Pregnancy Registry who received Anthrax Vaccine Adsorbed.

PubMed

Conlin, Ava Marie S; Bukowinski, Anna T; Gumbs, Gia R

2015-08-26

The National Smallpox Vaccine in Pregnancy Registry (NSVIPR) actively follows women inadvertently vaccinated with smallpox vaccine during or shortly before pregnancy to evaluate their reproductive health outcomes. Approximately 65% of NSVIPR participants also inadvertently received Anthrax Vaccine Adsorbed (AVA) while pregnant, providing a ready opportunity to evaluate pregnancy and infant health outcomes among these women. AVA-exposed pregnancies were ascertained using NSVIPR and electronic healthcare data. Rates of pregnancy loss and infant health outcomes, including major birth defects, were compared between AVA-exposed and AVA-unexposed pregnancies. Analyses included AVA-exposed and AVA-unexposed pregnant women who also received smallpox vaccine 28 days prior to or during pregnancy. Rates of adverse outcomes among the AVA-exposed group were similar to or lower than expected when compared with published reference rates and the AVA-unexposed population. The findings provide reassurance of the safety of AVA when inadvertently received by a relatively young and healthy population during pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Challenges and Achievements in Prevention and Treatment of Smallpox

PubMed Central

Melamed, Sharon; Israely, Tomer; Paran, Nir

2018-01-01

Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV), and the recent synthetic achievements increase the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign, as no other protective measure has been approved to achieve eradication and ensure worldwide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure confers effective protection. The long incubation period, and the uncertainty of the exposure status in the surrounding population, call for the development and evaluation of safe and effective methods enabling extension of the therapeutic window, and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment, or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements, and open questions. PMID:29382130

[The variola virus as a biological weapon].

PubMed

Mlinarić-Galinović, Gordana; Turković, Branko; Brudnjak, Zvonimir; Gjenero-Margan, Ira

2003-01-01

In view of the threat of use of the variola virus as a biological weapon, the interest of medical and other public in this causative agent that was eradicated in the wild at the end of the 1970s has increased. The paper gives an outline of the current knowledge on biological properties of the variola virus, and on the epidemiology, pathogenesis, clinical picture and prophylaxis of the disease caused by this virus. Descriptions of two sudden smallpox epidemics (Germany in 1970 and former Yugoslavia in 1972) could illustrate the potential of the smallpox virus as a biological weapon in bioterrorism and biological warfare. In fact, this virus can spread very readily through aerosol, which may lead to explosive epidemics. Not having been immunised, our population aged less than 25 years totally lacks the immunity. Older individuals are likely to have a low residual specific immunity to the agent. The only way to prevent a smallpox epidemic is by vaccination and patient isolation. A rapid smallpox diagnostics and prompt vaccination of all contacts is of utmost importance in stopping the outbreak.

20 CFR 30.10 - Are all OWCP records relating to claims filed under EEOICPA considered confidential?

Code of Federal Regulations, 2012 CFR

2012-04-01

...' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT...

20 CFR 30.10 - Are all OWCP records relating to claims filed under EEOICPA considered confidential?

Code of Federal Regulations, 2014 CFR

2014-04-01

...' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT...

20 CFR 30.10 - Are all OWCP records relating to claims filed under EEOICPA considered confidential?

Code of Federal Regulations, 2010 CFR

2010-04-01

...' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT...

20 CFR 30.10 - Are all OWCP records relating to claims filed under EEOICPA considered confidential?

Code of Federal Regulations, 2013 CFR

2013-04-01

...' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT...

20 CFR 30.10 - Are all OWCP records relating to claims filed under EEOICPA considered confidential?

Code of Federal Regulations, 2011 CFR

2011-04-01

...' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT...

78 FR 31566 - National Vaccine Injury Compensation Program; List of Petitions Received

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-24

... Vaccine Injury Compensation Program; List of Petitions Received AGENCY: Health Resources and Services... publishing this notice of petitions received under the National Vaccine Injury Compensation Program (``the..., National Vaccine Injury Compensation Program, 5600 Fishers Lane, Room 11C-26, Rockville, MD 20857; (301...

In vitro efficacy of ST246 against smallpox and monkeypox.

PubMed

Smith, Scott K; Olson, Victoria A; Karem, Kevin L; Jordan, Robert; Hruby, Dennis E; Damon, Inger K

2009-03-01

Since the eradication of smallpox and the cessation of routine childhood vaccination for smallpox, the proportion of the world's population susceptible to infection with orthopoxviruses, such as variola virus (the causative agent of smallpox) and monkeypox virus, has grown substantially. In the United States, the only vaccines for smallpox licensed by the Food and Drug Administration (FDA) have been live virus vaccines. Unfortunately, a substantial number of people cannot receive live virus vaccines due to contraindications. Furthermore, no antiviral drugs have been fully approved by the FDA for the prevention or treatment of orthopoxvirus infection. Here, we show the inhibitory effect of one new antiviral compound, ST-246, on the in vitro growth properties of six variola virus strains and seven monkeypox virus strains. We performed multiple assays to monitor the cytopathic effect and to evaluate the reduction of viral progeny production and release in the presence of the compound. ST-246 had 50% effective concentrations of

Immunomodulator-based enhancement of anti smallpox immune responses.

PubMed

Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L; Ríos-Olivares, Eddy; Otero, Miguel

2015-01-01

The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. 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.

Immunomodulator-Based Enhancement of Anti Smallpox Immune Responses

PubMed Central

Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L.; Ríos-Olivares, Eddy; Otero, Miguel

2015-01-01

Background The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. Methods We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. Results The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. Conclusion 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. PMID:25875833

Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial.

PubMed

Overton, Edgar Turner; Stapleton, Jack; Frank, Ian; Hassler, Shawn; Goepfert, Paul A; Barker, David; Wagner, Eva; von Krempelhuber, Alfred; Virgin, Garth; Meyer, Thomas Peter; Müller, Jutta; Bädeker, Nicole; Grünert, Robert; Young, Philip; Rösch, Siegfried; Maclennan, Jane; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

2015-04-01

Background.  First- and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness. The focus of this study was to compare the safety and immunogenicity of a replication-deficient, highly attenuated smallpox vaccine modified vaccinia Ankara (MVA) in HIV-infected and healthy subjects. Methods.  An open-label, controlled Phase II trial was conducted at 36 centers in the United States and Puerto Rico for HIV-infected and healthy subjects. Subjects received 2 doses of MVA administered 4 weeks apart. Safety was evaluated by assessment of adverse events, focused physical exams, electrocardiogram recordings, and safety laboratories. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). Results.  Five hundred seventy-nine subjects were vaccinated at least once and had data available for analysis. Rates of ELISA seropositivity were comparably high in vaccinia-naive healthy and HIV-infected subjects, whereas PRNT seropositivity rates were higher in healthy compared with HIV-infected subjects. Modified vaccinia Ankara was safe and well tolerated with no adverse impact on viral load or CD4 counts. There were no cases of myo-/pericarditis reported. Conclusions.  Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations.

Freeze-dried live attenuated smallpox vaccine prepared in cell culture "LC16-KAKETSUKEN": Post-marketing surveillance study on safety and efficacy compliant with Good Clinical Practice.

PubMed

Nishiyama, Yasumasa; Fujii, Tatsuya; Kanatani, Yasuhiro; Shinmura, Yasuhiko; Yokote, Hiroyuki; Hashizume, So

2015-11-09

In Japan, production of smallpox vaccine LC16m8 (named LC16-KAKETSUKEN) was restarted and was determined to be maintained as a national stockpile in March 2002. To conduct a post-marketing surveillance study of the vaccination of freeze-dried live attenuated smallpox vaccine prepared in cell culture LC16-KAKETSUKEN using attenuated vaccinia strain LC16m8. The study complied with Good Clinical Practice, focusing on a comparison between primary vaccinees and re-vaccinees. 268 personnel (261 males and 7 females) of the Japan Ground Self-Defense Force were inoculated with LC16-KAKETSUKEN and thereafter adverse events and efficacy were evaluated. Among 268 vaccinee participants, the following vaccinees showed adverse events, none serious: 53 of 196 primary vaccinees (without previous smallpox vaccination), 4 of 71 re-vaccinees (with previous smallpox vaccination) and 1 vaccinee with unknown previous vaccination history. A breakdown of adverse events observed in this study (total 268 vaccinees) showed the following minor or mild adverse events: 52 (19.4%) swelling of axillary lymph node, 4 (1.5%) fever, 2 (0.7%) fatigue, 1 (0.4%) of rash, 14 (5.2%) erythema at the inoculation site, 1 (0.4%) swelling at the inoculation site and 1 (0.4%) autoinoculation. The incidence of adverse events for primary vaccinees (53/196; 27.0%) was significantly higher than for re-vaccinees (4/71; 5.6%). However, the proportion of vaccine take was significantly higher for primary vaccinees (185/196; 94.4%) than for re-vaccinees (58/71; 81.7%). Although the proportion of vaccine take of re-vaccinees was significantly lower than for primary vaccinees due to preexisting immunity by previous vaccination, no significant difference was found in neutralizing antibody titers between primary vaccinees and re-vaccinees at 1, 4 and 7 months after LC16-KAKETSUKEN vaccination. The present post-marketing surveillance study compliant with Good Clinical Practice demonstrated the efficacy and safety of the smallpox vaccine LC16-KAKETSUKEN in an adult population. LC16-KAKETSUKEN is the sole currently available licensed smallpox vaccine for both adult and pediatric populations. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

20 CFR 30.303 - What information may OWCP request in connection with a claim under Part E of EEOICPA?

Code of Federal Regulations, 2014 CFR

2014-04-01

...' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT...

20 CFR 30.303 - What information may OWCP request in connection with a claim under Part E of EEOICPA?

Code of Federal Regulations, 2012 CFR

2012-04-01

...' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT...

20 CFR 30.303 - What information may OWCP request in connection with a claim under Part E of EEOICPA?

Code of Federal Regulations, 2010 CFR

2010-04-01

...' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT...

20 CFR 30.303 - What information may OWCP request in connection with a claim under Part E of EEOICPA?

Code of Federal Regulations, 2013 CFR

2013-04-01

...' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT...

20 CFR 30.303 - What information may OWCP request in connection with a claim under Part E of EEOICPA?

Code of Federal Regulations, 2011 CFR

2011-04-01

...' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT...

78 FR 79701 - National Vaccine Injury Compensation Program; List of Petitions Received

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-31

... Vaccine Injury Compensation Program; List of Petitions Received AGENCY: Health Resources and Services... publishing this notice of petitions received under the National Vaccine Injury Compensation Program (the... Vaccine Injury Compensation Program, 5600 Fishers Lane, Room 11C-26, Rockville, MD 20857; (301) 443-6593...

78 FR 72680 - National Vaccine Injury Compensation Program; List of Petitions Received

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-03

... Vaccine Injury Compensation Program; List of Petitions Received AGENCY: Health Resources and Services... publishing this notice of petitions received under the National Vaccine Injury Compensation Program (the... Vaccine Injury Compensation Program, 5600 Fishers Lane, Room 11C-26, Rockville, MD 20857; (301) 443-6593...

Global patterns and trends in human-wildlife conflict compensation.

PubMed

Ravenelle, Jeremy; Nyhus, Philip J

2017-12-01

Human-wildlife conflict is a major conservation challenge, and compensation for wildlife damage is a widely used economic tool to mitigate this conflict. The effectiveness of this management tool is widely debated. The relative importance of factors associated with compensation success is unclear, and little is known about global geographic or taxonomic differences in the application of compensation programs. We reviewed research on wildlife-damage compensation to determine geographic and taxonomic gaps, analyze patterns of positive and negative comments related to compensation, and assess the relative magnitude of global compensation payments. We analyzed 288 publications referencing wildlife compensation and identified 138 unique compensation programs. These publications reported US$222 million (adjusted for inflation) spent on compensation in 50 countries since 1980. Europeans published the most articles, and compensation funding was highest in Europe, where depredation by wolves and bears was the most frequently compensated damage. Authors of the publications we reviewed made twice as many negative comments as positive comments about compensation. Three-quarters of the negative comments related to program administration. Conversely, three-quarters of the positive comments related to program outcomes. The 3 most common suggestions to improve compensation programs included requiring claimants to employ damage-prevention practices, such as improving livestock husbandry or fencing of crops to receive compensation (n = 25, 15%); modifying ex post compensation schemes to some form of outcome-based performance payment (n = 21, 12%); and altering programs to make compensation payments more quickly (n = 14, 8%). We suggest that further understanding of the strengths and weaknesses of compensation as a conflict-mitigation tool will require more systematic evaluation of the factors driving these opinions and that differentiating process and outcomes and understanding linkages between them will result in more fruitful analyses and ultimately more effective conflict mitigation. © 2017 Society for Conservation Biology.

Analysis of variola and vaccinia virus neutralization assays for smallpox vaccines.

PubMed

Hughes, Christine M; Newman, Frances K; Davidson, Whitni B; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Yan, Lihan; Frey, Sharon E; Belshe, Robert B; Karem, Kevin L; Damon, Inger K

2012-07-01

Possible smallpox reemergence drives research for third-generation vaccines that effectively neutralize variola virus. A comparison of neutralization assays using different substrates, variola and vaccinia (Dryvax and modified vaccinia Ankara [MVA]), showed significantly different 90% neutralization titers; Dryvax underestimated while MVA overestimated variola neutralization. Third-generation vaccines may rely upon neutralization as a correlate of protection.

Bioterrorism and Smallpox: Policies, Practices, and Implications for Social Work

ERIC Educational Resources Information Center

Mackelprang, Romel W.; Mackelprang, Romel D.; Thirkill, Ashley D.

2005-01-01

Terrorist acts and the fear of terrorism have become a part of everyday life in the early 21st century. Among the threats most feared is bioterrorism, including the intentional release of smallpox. With the invasion of Iraq and toppling of the Saddam Hussein regime, acute bioterrorism fears have abated; however, an ongoing threat remains. This…

Effects of disability compensation on participation in and outcomes of vocational rehabilitation.

PubMed

Drew, D; Drebing, C E; Van Ormer, A; Losardo, M; Krebs, C; Penk, W; Rosenheck, R A

2001-11-01

The authors sought to determine the relationship between receipt of disability compensation and participants' success in a vocational rehabilitation program. Administrative data for 22,515 individuals who participated in the Veterans Health Administration compensated work therapy program between 1993 and 1998 were analyzed. Six dependent variables were compared between participants who were receiving disability compensation and those who were not: duration of participation in compensated work therapy, number of hours worked per week, mean hourly earnings, total income from compensated work therapy, dropout rate, and competitive employment status at discharge. Regression equations were determined for each dependent variable to assess associations with the degree of disability, the amount of disability compensation, and the type of compensation program. Participants who were receiving disability benefits worked fewer hours in compensated work therapy each week, earned less income, had a higher dropout rate, and were less likely to be competitively employed at discharge. The amount of compensation and the type of program were modestly but significantly associated with participation in compensated work therapy and with outcome. Unintended effects of disability compensation programs discourage full participation in vocational rehabilitation and result in poorer rehabilitation outcomes.

45 CFR 4.6 - Materials related to petitions under the National Vaccine Injury Compensation Program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Vaccine Injury Compensation Program. 4.6 Section 4.6 Public Welfare DEPARTMENT OF HEALTH AND HUMAN... Vaccine Injury Compensation Program. Notwithstanding the provisions of §§ 4.1, 4.2, and 4.3, service of..., shall be served upon the Director, Division of Vaccine Injury Compensation, Office of Special Programs...

45 CFR 4.6 - Materials related to petitions under the National Vaccine Injury Compensation Program.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Vaccine Injury Compensation Program. 4.6 Section 4.6 Public Welfare Department of Health and Human... Vaccine Injury Compensation Program. Notwithstanding the provisions of §§ 4.1, 4.2, and 4.3, service of..., shall be served upon the Director, Division of Vaccine Injury Compensation, Office of Special Programs...

45 CFR 4.6 - Materials related to petitions under the National Vaccine Injury Compensation Program.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Vaccine Injury Compensation Program. 4.6 Section 4.6 Public Welfare DEPARTMENT OF HEALTH AND HUMAN... Vaccine Injury Compensation Program. Notwithstanding the provisions of §§ 4.1, 4.2, and 4.3, service of..., shall be served upon the Director, Division of Vaccine Injury Compensation, Office of Special Programs...

45 CFR 4.6 - Materials related to petitions under the National Vaccine Injury Compensation Program.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Vaccine Injury Compensation Program. 4.6 Section 4.6 Public Welfare DEPARTMENT OF HEALTH AND HUMAN... Vaccine Injury Compensation Program. Notwithstanding the provisions of §§ 4.1, 4.2, and 4.3, service of..., shall be served upon the Director, Division of Vaccine Injury Compensation, Office of Special Programs...

45 CFR 4.6 - Materials related to petitions under the National Vaccine Injury Compensation Program.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Vaccine Injury Compensation Program. 4.6 Section 4.6 Public Welfare DEPARTMENT OF HEALTH AND HUMAN... Vaccine Injury Compensation Program. Notwithstanding the provisions of §§ 4.1, 4.2, and 4.3, service of..., shall be served upon the Director, Division of Vaccine Injury Compensation, Office of Special Programs...

20 CFR 30.220 - What are the criteria for eligibility for benefits relating to chronic silicosis?

Code of Federal Regulations, 2010 CFR

2010-04-01

...' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT... disease that arose as a consequence of the accepted chronic silicosis. ...

Variola virus immune evasion design: expression of a highly efficient inhibitor of human complement.

PubMed

Rosengard, Ariella M; Liu, Yu; Nie, Zhiping; Jimenez, Robert

2002-06-25

Variola virus, the most virulent member of the genus Orthopoxvirus, specifically infects humans and has no other animal reservoir. Variola causes the contagious disease smallpox, which has a 30-40% mortality rate. Conversely, the prototype orthopoxvirus, vaccinia, causes no disease in immunocompetent humans and was used in the global eradication of smallpox, which ended in 1977. However, the threat of smallpox persists because clandestine stockpiles of variola still exist. Although variola and vaccinia share remarkable DNA homology, the strict human tropism of variola suggests that its proteins are better suited than those of vaccinia to overcome the human immune response. Here, we demonstrate the functional advantage of a variola complement regulatory protein over that of its vaccinia homologue. Because authentic variola proteins are not available for study, we molecularly engineered and characterized the smallpox inhibitor of complement enzymes (SPICE), a homologue of a vaccinia virulence factor, vaccinia virus complement control protein (VCP). SPICE is nearly 100-fold more potent than VCP at inactivating human C3b and 6-fold more potent at inactivating C4b. SPICE is also more human complement-specific than is VCP. By inactivating complement components, SPICE serves to inhibit the formation of the C3/C5 convertases necessary for complement-mediated viral clearance. SPICE provides the first evidence that variola proteins are particularly adept at overcoming human immunity, and the decreased function of VCP suggests one reason why the vaccinia virus vaccine was associated with relatively low mortality. Disabling SPICE may be therapeutically useful if smallpox reemerges.

Variola virus immune evasion design: Expression of a highly efficient inhibitor of human complement

PubMed Central

Rosengard, Ariella M.; Liu, Yu; Nie, Zhiping; Jimenez, Robert

2002-01-01

Variola virus, the most virulent member of the genus Orthopoxvirus, specifically infects humans and has no other animal reservoir. Variola causes the contagious disease smallpox, which has a 30–40% mortality rate. Conversely, the prototype orthopoxvirus, vaccinia, causes no disease in immunocompetent humans and was used in the global eradication of smallpox, which ended in 1977. However, the threat of smallpox persists because clandestine stockpiles of variola still exist. Although variola and vaccinia share remarkable DNA homology, the strict human tropism of variola suggests that its proteins are better suited than those of vaccinia to overcome the human immune response. Here, we demonstrate the functional advantage of a variola complement regulatory protein over that of its vaccinia homologue. Because authentic variola proteins are not available for study, we molecularly engineered and characterized the smallpox inhibitor of complement enzymes (SPICE), a homologue of a vaccinia virulence factor, vaccinia virus complement control protein (VCP). SPICE is nearly 100-fold more potent than VCP at inactivating human C3b and 6-fold more potent at inactivating C4b. SPICE is also more human complement-specific than is VCP. By inactivating complement components, SPICE serves to inhibit the formation of the C3/C5 convertases necessary for complement-mediated viral clearance. SPICE provides the first evidence that variola proteins are particularly adept at overcoming human immunity, and the decreased function of VCP suggests one reason why the vaccinia virus vaccine was associated with relatively low mortality. Disabling SPICE may be therapeutically useful if smallpox reemerges. PMID:12034872

Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial

PubMed Central

Overton, Edgar Turner; Stapleton, Jack; Frank, Ian; Hassler, Shawn; Goepfert, Paul A.; Barker, David; Wagner, Eva; von Krempelhuber, Alfred; Virgin, Garth; Meyer, Thomas Peter; Müller, Jutta; Bädeker, Nicole; Grünert, Robert; Young, Philip; Rösch, Siegfried; Maclennan, Jane; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

2015-01-01

Background. First- and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness. The focus of this study was to compare the safety and immunogenicity of a replication-deficient, highly attenuated smallpox vaccine modified vaccinia Ankara (MVA) in HIV-infected and healthy subjects. Methods. An open-label, controlled Phase II trial was conducted at 36 centers in the United States and Puerto Rico for HIV-infected and healthy subjects. Subjects received 2 doses of MVA administered 4 weeks apart. Safety was evaluated by assessment of adverse events, focused physical exams, electrocardiogram recordings, and safety laboratories. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). Results. Five hundred seventy-nine subjects were vaccinated at least once and had data available for analysis. Rates of ELISA seropositivity were comparably high in vaccinia-naive healthy and HIV-infected subjects, whereas PRNT seropositivity rates were higher in healthy compared with HIV-infected subjects. Modified vaccinia Ankara was safe and well tolerated with no adverse impact on viral load or CD4 counts. There were no cases of myo-/pericarditis reported. Conclusions. Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations. PMID:26380340

Problems and Issues for the Classroom: What Works in Generating Class Discussions Using the Method of Shared Inquiry.

ERIC Educational Resources Information Center

Wallace, Robert L.

1997-01-01

Potential extinction of the human smallpox virus lies in the hands of a few scientists and policymakers. Whether this decision should be made can serve as an excellent issue for extended, focused classroom discussion. Outlines the history of smallpox, illustrates the debate, and describes preparation needed before discussing the issue. Also…

Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study.

PubMed

Villumsen, Marie; Sørup, Signe; Jess, Tine; Ravn, Henrik; Relander, Thomas; Baker, Jennifer L; Benn, Christine Stabell; Sørensen, Thorkild I A; Aaby, Peter; Roth, Adam

2009-11-16

Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines. In a background cohort (N=47,622) from the Copenhagen School Health Records Register, cases of leukaemia (N=20) and lymphoma (N=51) were identified through the Danish Cancer Registry. The vaccination status of the cases was compared with the vaccination status of a 5% random sample (N=2073) of the background cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95% CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR=0.81 (0.31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas.

Characterization of Two Historic Smallpox Specimens from a Czech Museum

PubMed Central

Pajer, Petr; Dresler, Jiri; Kabíckova, Hana; Písa, Libor; Aganov, Pavel; Fucik, Karel; Elleder, Daniel; Hron, Tomas; Kuzelka, Vitezslav; Velemínsky, Petr; Klimentova, Jana; Fucikova, Alena; Pejchal, Jaroslav; Hrabakova, Rita; Dundr, Pavel; Stríbrny, Jan; Antwerpen, Markus H.; Meyer, Hermann

2017-01-01

Although smallpox has been known for centuries, the oldest available variola virus strains were isolated in the early 1940s. At that time, large regions of the world were already smallpox-free. Therefore, genetic information of these strains can represent only the very last fraction of a long evolutionary process. Based on the genomes of 48 strains, two clades are differentiated: Clade 1 includes variants of variola major, and clade 2 includes West African and variola minor (Alastrim) strains. Recently, the genome of an almost 400-year-old Lithuanian mummy was determined, which fell basal to all currently sequenced strains of variola virus on phylogenetic trees. Here, we determined two complete variola virus genomes from human tissues kept in a museum in Prague dating back 60 and 160 years, respectively. Moreover, mass spectrometry-based proteomic, chemical, and microscopic examinations were performed. The 60-year-old specimen was most likely an importation from India, a country with endemic smallpox at that time. The genome of the 160-year-old specimen is related to clade 2 West African and variola minor strains. This sequence likely represents a new endemic European variant of variola virus circulating in the midst of the 19th century in Europe. PMID:28749451

Characterization of Two Historic Smallpox Specimens from a Czech Museum.

PubMed

Pajer, Petr; Dresler, Jiri; Kabíckova, Hana; Písa, Libor; Aganov, Pavel; Fucik, Karel; Elleder, Daniel; Hron, Tomas; Kuzelka, Vitezslav; Velemínsky, Petr; Klimentova, Jana; Fucikova, Alena; Pejchal, Jaroslav; Hrabakova, Rita; Benes, Vladimir; Rausch, Tobias; Dundr, Pavel; Pilin, Alexander; Cabala, Radomir; Hubalek, Martin; Stríbrny, Jan; Antwerpen, Markus H; Meyer, Hermann

2017-07-27

Although smallpox has been known for centuries, the oldest available variola virus strains were isolated in the early 1940s. At that time, large regions of the world were already smallpox-free. Therefore, genetic information of these strains can represent only the very last fraction of a long evolutionary process. Based on the genomes of 48 strains, two clades are differentiated: Clade 1 includes variants of variola major, and clade 2 includes West African and variola minor (Alastrim) strains. Recently, the genome of an almost 400-year-old Lithuanian mummy was determined, which fell basal to all currently sequenced strains of variola virus on phylogenetic trees. Here, we determined two complete variola virus genomes from human tissues kept in a museum in Prague dating back 60 and 160 years, respectively. Moreover, mass spectrometry-based proteomic, chemical, and microscopic examinations were performed. The 60-year-old specimen was most likely an importation from India, a country with endemic smallpox at that time. The genome of the 160-year-old specimen is related to clade 2 West African and variola minor strains. This sequence likely represents a new endemic European variant of variola virus circulating in the midst of the 19th century in Europe.

Smallpox infections during pregnancy, lessons on pathogenesis from nonpregnant animal models of infection.

PubMed

Hassett, Daniel E

2003-10-01

Both vaccinated and unvaccinated women during pregnancy who contract variola virus, the causative agent of smallpox, suffer much higher mortality rates than nonpregnants. Furthermore, acute maternal smallpox leads to spontaneous abortion, premature termination of pregnancy and early postnatal infant mortality. The mechanisms governing the abortifacient activity of smallpox, as well as the enhanced susceptibility of gestating women to lethal disease, have remained largely unexamined. Experimental poxvirus infections in nonpregnant small animal models have revealed that T helper type 1 (TH1) cytokines promote efficient resolution of these infections whereas type 2 (TH2) cytokines enhance viral pathogenesis. These data, combined with recent understanding of how the immune system is modulated by pregnancy, may offer important clues as to the increased pathogenesis of variola in pregnant women. The aim of this review is to bring together the current literature on the effects of poxvirus infections in nonpregnant hosts, as well as the effects of pregnancy on the immune system, in order to develop unifying concepts that may provide insight into the pathogenesis of variola during pregnancy and why prior vaccination with vaccinia virus the live anti-variola vaccine offers less protection to pregnant women and their unborn children.

20 CFR 30.11 - Who maintains custody and control of claim records?

Code of Federal Regulations, 2014 CFR

2014-04-01

... LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General... Occupational Illness Compensation Program Act File). This system of records is maintained by and under the...

20 CFR 30.11 - Who maintains custody and control of claim records?

Code of Federal Regulations, 2013 CFR

2013-04-01

... LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General... Occupational Illness Compensation Program Act File). This system of records is maintained by and under the...

20 CFR 30.11 - Who maintains custody and control of claim records?

Code of Federal Regulations, 2011 CFR

2011-04-01

... LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General... Occupational Illness Compensation Program Act File). This system of records is maintained by and under the...

20 CFR 30.11 - Who maintains custody and control of claim records?

Code of Federal Regulations, 2012 CFR

2012-04-01

... LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General... Occupational Illness Compensation Program Act File). This system of records is maintained by and under the...

20 CFR 30.11 - Who maintains custody and control of claim records?

Code of Federal Regulations, 2010 CFR

2010-04-01

... LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General... Occupational Illness Compensation Program Act File). This system of records is maintained by and under the...

Logistics in smallpox: the legacy.

PubMed

Wickett, John; Carrasco, Peter

2011-12-30

Logistics, defined as "the time-related positioning of resources" was critical to the implementation of the smallpox eradication strategy of surveillance and containment. Logistical challenges in the smallpox programme included vaccine delivery, supplies, staffing, vehicle maintenance, and financing. Ensuring mobility was essential as health workers had to travel to outbreaks to contain them. Three examples illustrate a range of logistic challenges which required imagination and innovation. Standard price lists were developed to expedite vehicle maintenance and repair in Bihar, India. Innovative staffing ensured an adequate infrastructure for vehicle maintenance in Bangladesh. The use of disaster relief mechanisms in Somalia provided airlifts, vehicles and funding within 27 days of their initiation. In contrast the Expanded Programme on Immunization (EPI) faces more complex logistical challenges. Copyright © 2011 Elsevier Ltd. All rights reserved.

The new cell culture smallpox vaccine should be offered to the general population.

PubMed

Bicknell, William; James, Kenneth

2003-01-01

A series of major factors must be weighed in deciding whether or not, and to what extent, a particular country should consider pre-exposure vaccination for smallpox. These include the risk of a bioterrorist attack using smallpox, the risk of secondary spread from another country, the risks and benefits of vaccination, the effectivenes s of vaccination pre- and post-exposure, the prevalence of immunocompromised persons, the capacity of the medical care delivery system and the wealth of a nation. We review here the issues and variables relevant for policy making, propose a framework for country-specific decision making and suggest the World Health Organization has a key role to play, particularly with regard to lower-income countries. In doing so, we support the proposition. Copyright 2003 John Wiley & Sons, Ltd.

Eradication: lessons from the past.

PubMed Central

Henderson, D. A.

1998-01-01

The declaration in 1980 that smallpox had been eradicated reawakened interest in disease eradication as a public health strategy. The smallpox programme's success derived, in part, from lessons learned from the preceding costly failure of the malaria eradication campaign. In turn, the smallpox programme offered important lessons with respect to other prospective disease control programmes, and these have been effectively applied in the two current global eradication initiatives, those against poliomyelitis and dracunculiasis. Taking this theme a step further, there are those who would now focus on the development of an inventory of diseases which might, one by one, be targeted either for eradication or elimination. This approach, while interesting, fails to recognize many of the important lessons learned and their broad implications for contemporary disease control programmes worldwide. PMID:10063668

Expanding the histologic findings in smallpox-related post-vaccinial non-viral folliculitis.

PubMed

Bunick, Christopher G; Mariwalla, Kavita; Ibrahim, Omer; Modi, Badri; Imaeda, Suguru; McNiff, Jennifer M

2013-03-01

Post-vaccinial non-viral folliculitis has been recognized in the past decade as a new adverse cutaneous reaction to smallpox vaccination. Contrary to more serious smallpox vaccine reactions, post-vaccinial non-viral folliculitis has a benign course and resolves spontaneously within approximately 7 days. We describe additional histopathologic findings associated with post-vaccinial non-viral folliculitis, which has only been described once previously. New findings include the presence of a neutrophilic or lymphohistiocytic infiltrate that is concentrated around the hair follicles. We compare our findings to the follicular nature of varicella and herpes zoster infections, generating the hypothesis of deposition of vaccinia protein within folliculosebaceous units as a potential pathophysiologic mechanism behind post-vaccinial non-viral folliculitis. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Comparative Pathology of Smallpox and Monkeypox in Man and Macaques

PubMed Central

Cann, J. A.; Jahrling, P. B.; Hensley, L. E.; Wahl-Jensen, V.

2012-01-01

Summary In the three decades since the eradication of smallpox and cessation of routine vaccination, the collective memory of the devastating epidemics caused by this orthopoxvirus has waned, and the human population has become increasingly susceptible to a disease that remains high on the list of possible bioterrorism agents. Research using surrogate orthopoxviruses in their natural hosts, as well as limited variola virus research in animal models, continues worldwide; however, interpretation of findings is often limited by our relative lack of knowledge about the naturally occurring disease. For modern comparative pathologists, many of whom have no first-hand knowledge of naturally occurring smallpox, this work provides a contemporary review of this historical disease, as well as discussion of how it compares with human monkeypox and the corresponding diseases in macaques. PMID:22884034

20 CFR 30.0 - What are the provisions of EEOICPA, in general?

Code of Federal Regulations, 2013 CFR

2013-04-01

... ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General Provisions... Illness Compensation Program Act of 2000, as amended (EEOICPA or Act), 42 U.S.C. 7384 et seq., provides...

20 CFR 30.0 - What are the provisions of EEOICPA, in general?

Code of Federal Regulations, 2012 CFR

2012-04-01

... LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General... Occupational Illness Compensation Program Act of 2000, as amended (EEOICPA or Act), 42 U.S.C. 7384 et seq...

20 CFR 30.0 - What are the provisions of EEOICPA, in general?

Code of Federal Regulations, 2014 CFR

2014-04-01

... ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General Provisions... Illness Compensation Program Act of 2000, as amended (EEOICPA or Act), 42 U.S.C. 7384 et seq., provides...

20 CFR 30.0 - What are the provisions of EEOICPA, in general?

Code of Federal Regulations, 2011 CFR

2011-04-01

... LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General... Occupational Illness Compensation Program Act of 2000, as amended (EEOICPA or Act), 42 U.S.C. 7384 et seq...

20 CFR 30.0 - What are the provisions of EEOICPA, in general?

Code of Federal Regulations, 2010 CFR

2010-04-01

... LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General... Occupational Illness Compensation Program Act of 2000, as amended (EEOICPA or Act), 42 U.S.C. 7384 et seq...

Dual-Probe Real-Time PCR Assay for Detection of Variola or Other Orthopoxviruses with Dried Reagents

DTIC Science & Technology

2008-09-10

can naturally produce disease in humans hat closely resembles smallpox, with up to 15% mortality rates ∗ Corresponding author . Tel.: +1 301 619 2415...GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR (S) Aitichou, M Saleh, S Park, K Huggins, J O’Guinn, M Jahrling, PB Ibrahim, MS 5d. PROJECT...false positivewas btained with dried real-time PCR reagents resulting in 98% speci- city. The false positive was obtained from one of two hantavirus

Self-reported Adverse Health Events Following Smallpox Vaccination in a Large Prospective Study of US Military Service Members

DTIC Science & Technology

2007-08-27

bullous erythema multiforme (Stevens‑Johnson syndrome), eczema vaccinatum, generalized vaccinia, progressive vaccinia, and postvac‑ cinal...reported health outcomes, including mental and physical functioning , cardiovascular diseases, and auto- immune disorders, were found. These findings...words: smallpox vaccine, questionnaires, military medicine , longitudinal studies, chronic disease, quality of life [Human Vaccines 4:2, 127‑133; March

Modified Vaccinia Ankara Virus Vaccination Provides Long-Term Protection against Nasal Rabbitpox Virus Challenge.

PubMed

Jones, Dorothy I; McGee, Charles E; Sample, Christopher J; Sempowski, Gregory D; Pickup, David J; Staats, Herman F

2016-07-01

Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. This study was performed to determine if MVA vaccination provides long-term protection against rabbitpox virus (RPXV) challenge, an animal model of smallpox. Two doses of MVA provided 100% protection against a lethal intranasal RPXV challenge administered 9 months after vaccination. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

20 CFR 30.506 - To whom and in what manner will OWCP pay compensation?

Code of Federal Regulations, 2010 CFR

2010-04-01

... LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED Survivors... Part B of the Act, compensation for any consequential injury, illness, impairment or disease is limited...

The effects of post-exposure smallpox vaccination on clinical disease presentation: addressing the data gaps between historical epidemiology and modern surrogate model data.

PubMed

Keckler, M Shannon; Reynolds, Mary G; Damon, Inger K; Karem, Kevin L

2013-10-25

Decades after public health interventions - including pre- and post-exposure vaccination - were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses. Copyright © 2013 Elsevier Ltd. All rights reserved.

17th Century Variola Virus Reveals the Recent History of Smallpox.

PubMed

Duggan, Ana T; Perdomo, Maria F; Piombino-Mascali, Dario; Marciniak, Stephanie; Poinar, Debi; Emery, Matthew V; Buchmann, Jan P; Duchêne, Sebastian; Jankauskas, Rimantas; Humphreys, Margaret; Golding, G Brian; Southon, John; Devault, Alison; Rouillard, Jean-Marie; Sahl, Jason W; Dutour, Olivier; Hedman, Klaus; Sajantila, Antti; Smith, Geoffrey L; Holmes, Edward C; Poinar, Hendrik N

2016-12-19

Smallpox holds a unique position in the history of medicine. It was the first disease for which a vaccine was developed and remains the only human disease eradicated by vaccination. Although there have been claims of smallpox in Egypt, India, and China dating back millennia [1-4], the timescale of emergence of the causative agent, variola virus (VARV), and how it evolved in the context of increasingly widespread immunization, have proven controversial [4-9]. In particular, some molecular-clock-based studies have suggested that key events in VARV evolution only occurred during the last two centuries [4-6] and hence in apparent conflict with anecdotal historical reports, although it is difficult to distinguish smallpox from other pustular rashes by description alone. To address these issues, we captured, sequenced, and reconstructed a draft genome of an ancient strain of VARV, sampled from a Lithuanian child mummy dating between 1643 and 1665 and close to the time of several documented European epidemics [1, 2, 10]. When compared to vaccinia virus, this archival strain contained the same pattern of gene degradation as 20 th century VARVs, indicating that such loss of gene function had occurred before ca. 1650. Strikingly, the mummy sequence fell basal to all currently sequenced strains of VARV on phylogenetic trees. Molecular-clock analyses revealed a strong clock-like structure and that the timescale of smallpox evolution is more recent than often supposed, with the diversification of major viral lineages only occurring within the 18 th and 19 th centuries, concomitant with the development of modern vaccination. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The effects of post-exposure smallpox vaccination on clinical disease presentation: Addressing the data gaps between historical epidemiology and modern surrogate model data

PubMed Central

Keckler, M. Shannon; Reynolds, Mary G.; Damon, Inger K.; Karem, Kevin L.

2015-01-01

Decades after public health interventions – including pre- and post-exposure vaccination – were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses. PMID:23994378

A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE®

PubMed Central

von Krempelhuber, Alfred; Vollmar, Jens; Pokorny, Rolf; Rapp, Petra; Wulff, Niels; Petzold, Barbara; Handley, Amanda; Mateo, Lyn; Siersbol, Henriette; Kollaritsch, Herwig; Chaplin, Paul

2009-01-01

IMVAMUNE® is a Modified Vaccinia Ankara-based virus that is being developed as a safer 3rd generation smallpox vaccine. In order to determine the optimal dose for further development, a double-blind, randomized Phase II trial was performed testing three different doses of IMVAMUNE® in 164 healthy volunteers. All three IMVAMUNE® doses displayed a favourable safety profile, with local reactions as the most frequent observation. The 1×108 TCID50 IMVAMUNE® dose induced a total antibody response in 94% of the subjects following the first vaccination and the highest peak seroconversion rates by ELISA (100%) and PRNT (71%). This IMVAMUNE® dose was considered to be optimal for the further clinical development of this highly attenuated poxvirus as a safer smallpox vaccine. PMID:19944151

History of Smallpox and Its Spread in Human Populations.

PubMed

Thèves, Catherine; Crubézy, Eric; Biagini, Philippe

2016-08-01

Smallpox is considered among the most devastating of human diseases. Its spread in populations, initiated for thousands of years following a probable transmission from an animal host, was concomitant with movements of people across regions and continents, trade and wars. Literature permitted to retrace the occurrence of epidemics from ancient times to recent human history, smallpox having affected all levels of past society including famous monarchs. The disease was officially declared eradicated in 1979 following intensive vaccination campaigns.Paleomicrobiology dedicated to variola virus is restricted to few studies, most unsuccessful, involving ancient material. Only one recent approach allowed the identification of viral DNA fragments from lung tissue of a 300-year-old body excavated from permafrost in Eastern Siberia; phylogenetic analysis revealed that this ancient strain was distinct from those described during the 20th century.

78 FR 54663 - National Vaccine Injury Compensation Program; List of Petitions Received

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-05

... Vaccine Injury Compensation Program; List of Petitions Received AGENCY: Health Resources and Services... publishing this notice of petitions received under the National Vaccine Injury Compensation Program (the...-6400. For information on HRSA's role in the Program, contact the Director, National Vaccine Injury...

78 FR 66012 - National Vaccine Injury Compensation Program; List of Petitions Received

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-04

... Vaccine Injury Compensation Program; List of Petitions Received AGENCY: Health Resources and Services... publishing this notice of petitions received under the National Vaccine Injury Compensation Program (the...-6400. For information on HRSA's role in the Program, contact the Director, National Vaccine Injury...

78 FR 46354 - National Vaccine Injury Compensation Program; List of Petitions Received

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

... Vaccine Injury Compensation Program; List of Petitions Received AGENCY: Health Resources and Services... publishing this notice of petitions received under the National Vaccine Injury Compensation Program (``the..., (202) 357-6400. For information on HRSA's role in the Program, contact the Director, National Vaccine...

78 FR 38995 - National Vaccine Injury Compensation Program, List of Petitions Received

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-28

... Vaccine Injury Compensation Program, List of Petitions Received AGENCY: Health Resources and Services... publishing this notice of petitions received under the National Vaccine Injury Compensation Program (``the..., (202) 357-6400. For information on HRSA's role in the Program, contact the Director, National Vaccine...

20 CFR 30.16 - What penalties may be imposed in connection with a claim under the Act?

Code of Federal Regulations, 2013 CFR

2013-04-01

... PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS...

20 CFR 30.12 - What process is used by a person who wants to obtain copies of or amend EEOICPA claim records?

Code of Federal Regulations, 2014 CFR

2014-04-01

... WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION...

20 CFR 30.12 - What process is used by a person who wants to obtain copies of or amend EEOICPA claim records?

Code of Federal Regulations, 2013 CFR

2013-04-01

... WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION...

20 CFR 30.12 - What process is used by a person who wants to obtain copies of or amend EEOICPA claim records?

Code of Federal Regulations, 2012 CFR

2012-04-01

... WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION...

20 CFR 30.12 - What process is used by a person who wants to obtain copies of or amend EEOICPA claim records?

Code of Federal Regulations, 2010 CFR

2010-04-01

... WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION...

Medical Readiness of the Reserve Component

DTIC Science & Technology

2012-01-01

once per season) (DoDI 6025.19), whereas others (such as rabies and typhoid ) are service- and/or occupation-specific. 6 For management of risks...gender-specific tests and track only the military protective mask corrective insert. Some requirements, such as for anthrax, smallpox, and yellow fever ...occupational hazards (e.g., rabies, typhoid , hepatitis B) or for a specific planned operation due to the location or threat (e.g., anthrax, smallpox

The Bug Stops Here: Force Protection and Emerging Infectious Diseases

DTIC Science & Technology

2005-11-01

said in 1972 that “the future of infectious diseases will be very dull.” Successful vaccines against smallpox and polio only furthered belief that...probably higher. Mounting evidence implicates microbes in heart disease, rheumatoid arthritis, diabetes, multiple sclerosis, autism , chronic lung diseases...cross protection against smallpox. Louis Pasteur later adopted the word ‘ vaccination ’ for immunization against any disease. 19 “History of Military

Smallpox Vaccination is Not Associated with Infertility in a Healthy Young Adult Population

DTIC Science & Technology

2008-06-01

Naval Health Research Center Smallpox Vaccination is Not Associated with Infertility in A Healthy Young Adult Population I. G. Jacobson G. R...pregnant.34-37 Concerns exist regarding reproductive health , including potential infertility, among young adults with military-related occupational...Gumbs C. J. Sevick T. C. Smith M. A.K. Ryan Report No. 07-27 Approved for public release: distribution is unlimited. Naval Health

[The American Almanac, smallpox in Santiago in 1872 and the isolations hospitals].

PubMed

Laval, Enrique

2015-04-01

Due to the smallpox epidemic in Santiago in 1872, a Commission or Central Board of isolation hospitals was created. These institutions were endowed with the necessary personnel to receive and assist the sick, highlighting the work of medical students, interns at these hospitals. The total number of patients treated in the infirmaries of Santiago reached 6,782, with a fatality rate of 3,073 (45.3%).

The origin of the variola virus.

PubMed

Babkin, Igor V; Babkina, Irina N

2015-03-10

The question of the origin of smallpox, one of the major menaces to humankind, is a constant concern for the scientific community. Smallpox is caused by the agent referred to as the variola virus (VARV), which belongs to the genus Orthopoxvirus. In the last century, smallpox was declared eradicated from the human community; however, the mechanisms responsible for the emergence of new dangerous pathogens have yet to be unraveled. Evolutionary analyses of the molecular biological genomic data of various orthopoxviruses, involving a wide range of epidemiological and historical information about smallpox, have made it possible to date the emergence of VARV. Comparisons of the VARV genome to the genomes of the most closely related orthopoxviruses and the examination of the distribution their natural hosts' ranges suggest that VARV emerged 3000 to 4000 years ago in the east of the African continent. The VARV evolution rate has been estimated to be approximately 2 × 10-6 substitutions/site/year for the central conserved genomic region and 4 × 10-6 substitutions/site/year for the synonymous substitutions in the genome. Presumably, the introduction of camels to Africa and the concurrent changes to the climate were the particular factors that triggered the divergent evolution of a cowpox-like ancestral virus and thereby led to the emergence of VARV.

Effects of behavioral changes in a smallpox attack model.

PubMed

Del Valle, S; Hethcote, H; Hyman, J M; Castillo-Chavez, C

2005-06-01

The impact of individual and community behavioral changes in response to an outbreak of a disease with high mortality is often not appreciated. Response strategies to a smallpox bioterrorist attack have focused on interventions such as isolation of infectives, contact tracing, quarantine of contacts, ring vaccination, and mass vaccination. We formulate and analyze a mathematical model in which some individuals lower their daily contact activity rates once an epidemic has been identified in a community. Transmission parameters are estimated from data and an expression is derived for the effective reproduction number. We use computer simulations to analyze the effects of behavior change alone and in combination with other control measures. We demonstrate that the spread of the disease is highly sensitive to how rapidly people reduce their contact activity rates and to the precautions that the population takes to reduce the transmission of the disease. Even gradual and mild behavioral changes can have a dramatic impact in slowing an epidemic. When behavioral changes are combined with other interventions, the epidemic is shortened and the number of smallpox cases is reduced. We conclude that for simulations of a smallpox outbreak to be useful, they must consider the impact of behavioral changes. This is especially true if the model predictions are being used to guide public health policy.

77 FR 37284 - Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

... DEPARTMENT OF LABOR Office of Workers' Compensation Programs 20 CFR Parts 701, 702, 703, 725, and 726 RIN 1240-AA05 Technical Amendments AGENCY: Office of Workers' Compensation Programs, Labor. ACTION: Final rule. SUMMARY: The Office of Workers' Compensation Programs is making [[Page 37285

The Federal Employees' Compensation Act.

ERIC Educational Resources Information Center

Nordlund, Willis J.

1991-01-01

The 1916 Federal Employees' Compensation Act is still the focal point around which the federal workers compensation program works today. The program has gone through many changes on its way to becoming a modern means of compensating workers for job-related injury, disease, and death. (Author)

20 CFR 30.3 - What do these regulations contain?

Code of Federal Regulations, 2014 CFR

2014-04-01

... EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General Provisions Introduction... criteria for occupational illnesses and covered illnesses compensable under Parts B and E of EEOICPA...

20 CFR 30.3 - What do these regulations contain?

Code of Federal Regulations, 2010 CFR

2010-04-01

... EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General Provisions Introduction... criteria for occupational illnesses and covered illnesses compensable under Parts B and E of EEOICPA...

20 CFR 30.3 - What do these regulations contain?

Code of Federal Regulations, 2013 CFR

2013-04-01

... EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General Provisions Introduction... criteria for occupational illnesses and covered illnesses compensable under Parts B and E of EEOICPA...

20 CFR 30.3 - What do these regulations contain?

Code of Federal Regulations, 2011 CFR

2011-04-01

... EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General Provisions Introduction... criteria for occupational illnesses and covered illnesses compensable under Parts B and E of EEOICPA...

20 CFR 30.3 - What do these regulations contain?

Code of Federal Regulations, 2012 CFR

2012-04-01

... EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED General Provisions Introduction... criteria for occupational illnesses and covered illnesses compensable under Parts B and E of EEOICPA...

A Study of Waste Management within the COL Florence A. Blanchfield Army Community Hospital, Fort Campbell, Kentucky.

DTIC Science & Technology

1981-08-01

besnoiti Borna disease virus Bovine infectious petechial fever virus Camel pox virus Ephemeral fever virus Fowl plague virus Goat pox virus Hog...Varicella virus Vole rickettsia Yellow fever virus, 17D vaccine strain 69 Class 3 Alastrun, smallpox, monkeypox, and whitepox, when used in vitro Arbovirus...animal inoculation experiments Vesicular stomatitis virus Yellow fever virus - wild when used in vitro Class 4 Alastrun, smallpox, monkeypox, and

Designing a Biocontainment Unit to Care for Patients with Serious Communicable Diseases: A Consensus Statement

DTIC Science & Technology

2006-08-29

smallpox), by a global emerging infectious disease (e.g., avian influenza , viral hemorrhagic fevers), or by a laboratory accident. One approach to...of providing care to patients with avian influenza , severe acute respiratory syndrome (SARS), or viral hemorrhagic fever (VHF) while assuring optimal...infected with pathogens introduced by a bioterrorist act (e.g., smallpox), by a global emerging infectious disease (e.g., avian influenza , viral

Public Health and Medicine in the Chinese People’s Republic.

DTIC Science & Technology

1960-10-31

2,5 The fight against smallpox in the Homindan period was very poorly organised^ although the effective method of vaccination h&d been in human...compulsory vaccination of ! " - . ■ ■ ■ ■ - :’the population with the aim of complete elimination of cases of nnallpo?< r- f...the introduction of compulsory free vaccination \\ i nr-toral smallpox has been completely sliadcafced iri all provinces» i ’ | cities and villages

Smallpox as a Bioweapon: Should We Be Concerned?

DTIC Science & Technology

2012-03-01

United Nations U.S. United States of America USAMRIID United States Army Medical Research Institute of Infectious Diseases USFK United States Forces...Union or in the United States of America . There the virus would remain secured, yet available to fulfill future scientific needs.2 The only remaining...smallpox or could be able to manufacture the virus in a laboratory, combined with the fact that the United States of America has a significantly

The Royal Philanthropic Expedition of the Vaccine: a landmark in the history of public health.

PubMed

Soto-Pérez-de-Celis, E

2008-11-01

In 1979, smallpox officially became the first disease ever to be eradicated by mankind. The global efforts to defeat this dreadful pandemic, however, started almost two centuries before. One of the most important, and sometimes forgotten, events in the fight against smallpox was the Royal Philanthropic Expedition of the Vaccine, commissioned by Charles IV of Spain to physicians Francisco Xavier Balmis y Berenguer and Jose Salvany in 1804. The aim of this expedition was to take the smallpox vaccine, discovered by Jenner, to Spain's territories in the Americas and in the Far East. After several years of vaccination in modern day Puerto Rico, Cuba, Venezuela, Ecuador, Peru, Bolivia, Chile, Mexico and the Philippines, the expedition returned to Europe. To this day, the Balmis and Salvany expedition remains a great example of international cooperation, and a landmark in the history of public health.

Therapeutic vaccination to treat chronic infectious diseases

PubMed Central

Boukhebza, Houda; Bellon, Nadine; Limacher, Jean Marc; Inchauspé, Geneviève

2012-01-01

A famous milestone in the vaccine field has been the first successful vaccination against smallpox, in 1798, by Edward Jenner. Using the vaccinia cowpox virus, Jenner was able to protect vaccinees from variola or smallpox. The Modified Virus Ankara (MVA) poxvirus strain has been one of the vaccines subsequently developed to prevent smallpox infection and was selected by the US government in their Biodefense strategy. Progress in molecular biology and immunology associated with MVA infection has led to the development of MVA as vaccine platform, both in the field of preventive and therapeutic vaccines. This later class of therapeutics has witnessed growing interest that has translated into an increasing number of vaccine candidates reaching the clinics. Among those, MVA-based therapeutic vaccines have addressed four major chronic infections including viral hepatitis, AIDS, human papillomavirus-linked pathologies and tuberculosis. Clinical trials encompass phase 1 and 2 and have started to show significant results and promises. PMID:22894957

Preventing the return of smallpox: molecular modeling studies on thymidylate kinase from Variola virus.

PubMed

Guimarães, Ana Paula; Ramalho, Teodorico Castro; França, Tanos Celmar Costa

2014-01-01

Smallpox was one of the most devastating diseases in the human history and still represents a serious menace today due to its potential use by bioterrorists. Considering this threat and the non-existence of effective chemotherapy, we propose the enzyme thymidylate kinase from Variola virus (VarTMPK) as a potential target to the drug design against smallpox. We first built a homology model for VarTMPK and performed molecular docking studies on it in order to investigate the interactions with inhibitors of Vaccinia virus TMPK (VacTMPK). Subsequently, molecular dynamics (MD) simulations of these compounds inside VarTMPK and human TMPK (HssTMPK) were carried out in order to select the most promising and selective compounds as leads for the design of potential VarTMPK inhibitors. Results of the docking and MD simulations corroborated to each other, suggesting selectivity towards VarTMPK and, also, a good correlation with the experimental data.

Insights into human CD8(+) T-cell memory using the yellow fever and smallpox vaccines.

PubMed

Ahmed, Rafi; Akondy, Rama S

2011-03-01

Live virus vaccines provide a unique opportunity to study human CD8(+) T-cell memory in the context of a controlled, primary acute viral infection. Yellow fever virus-17D and Dryvax are two such live-virus vaccines that are highly efficacious, used worldwide and provide long-term immunity against yellow fever and smallpox respectively. In this review, we describe the properties of virus-specific memory CD8(+) T cells generated in smallpox and yellow fever vaccinees. We address fundamental questions regarding magnitude, functional quality and longevity of the CD8(+) T-cell response, which are otherwise challenging to address in humans. These findings provide insights into the attributes of the human immune system as well as provide a benchmark for the optimal quality of a CD8(+) T-cell response that can be used to evaluate novel candidate vaccines.

Cowpox virus infection of cynomolgus macaques as a model of hemorrhagic smallpox.

PubMed

Johnson, Reed F; Yellayi, Srikanth; Cann, Jennifer A; Johnson, Anthony; Smith, Alvin L; Paragas, Jason; Jahrling, Peter B; Blaney, Joseph E

2011-09-30

Hemorrhagic smallpox was a rare but severe manifestation of variola virus infection that resulted in nearly 100% mortality. Here we describe intravenous (IV) inoculation of cowpox virus Brighton Red strain in cynomolgus macaques (Macaca fascicularis) which resulted in disease similar in presentation to hemorrhagic smallpox in humans. IV inoculation of macaques resulted in a uniformly lethal disease within 12 days post-inoculation in two independent experiments. Clinical observations and hematological and histopathological findings support hemorrhagic disease. Cowpox virus replicated to high levels in blood (8.0-9.0 log(10) gene copies/mL) and tissues including lymph nodes, thymus, spleen, bone marrow, and lungs. This unique model of hemorrhagic orthopoxvirus infection provides an accessible means to further study orthopoxvirus pathogenesis and to identify virus-specific and nonspecific therapies. Such studies will serve to complement the existing nonhuman primate models of more classical poxviral disease. Published by Elsevier Inc.

[Epidemics and disease during the Revolution Period in Mexico].

PubMed

Sanfilippo-Borrás, José

2010-01-01

The health condition in Mexico was bad around de beginning of the revolutionary period. The movement of troops led the development of epidemics like yellow fever, typhus, smallpox, and influenza that were enhance with natural disasters and hunger in whole country, from cost to cost and in the north big cities like Monterrey, Guadalajara and Saltillo. Doctor Liceaga conducted a well planned campaign against yellow fever eradicating water stagnant deposits in order to combat the vector transmission, the Aedes aegypti, mosquito with satisfactory results. The first smallpox epidemic in the XX Century in Mexico was in 1916. The Mexican physicians used the smallpox vaccine against this epidemic. An American physician named Howard Taylor Ricketts arrived to Mexico for studying the typhus transmission. Accidentally he had been infected and finally, he died from typhus. Definitively, the epidemics predominate along de revolutionary period in Mexico.

78 FR 11551 - Compensation, Retirement Programs, and Related Benefits

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Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy.

PubMed

Titova, Ksenya A; Sergeev, Alexander A; Zamedyanskaya, Alena S; Galahova, Darya O; Kabanov, Alexey S; Morozova, Anastasia A; Bulychev, Leonid E; Sergeev, Artemiy A; Glotova, Tanyana I; Shishkina, Larisa N; Taranov, Oleg S; Omigov, Vladimir V; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

2015-09-01

The possibility of using immunocompetent ICR mice and immunodeficient SCID mice as model animals for smallpox to assess antiviral drug efficacy was investigated. Clinical signs of the disease did not appear following intranasal (i.n.) challenge of mice with strain Ind-3a of variola virus (VARV), even when using the highest possible dose of the virus (5.2 log10 p.f.u.). The 50 % infective doses (ID50) of VARV, estimated by the virus presence or absence in the lungs 3 and 4 days post-infection, were 2.7 ± 0.4 log10 p.f.u. for ICR mice and 3.5 ± 0.7 log10 p.f.u. for SCID mice. After i.n. challenge of ICR and SCID mice with VARV 30 and 50 ID50, respectively, steady reproduction of the virus occurred only in the respiratory tract (lungs and nose). Pathological inflammatory destructive changes were revealed in the respiratory tract and the primary target cells for VARV (macrophages and epithelial cells) in mice, similar to those in humans and cynomolgus macaques. The use of mice to assess antiviral efficacies of NIOCH-14 and ST-246 demonstrated the compliance of results with those described in scientific literature, which opens up the prospect of their use as an animal model for smallpox to develop anti-smallpox drugs intended for humans.

Identification of SNPs associated with variola virus virulence.

PubMed

Hoen, Anne Gatewood; Gardner, Shea N; Moore, Jason H

2013-02-14

Decades after the eradication of smallpox, its etiological agent, variola virus (VARV), remains a threat as a potential bioweapon. Outbreaks of smallpox around the time of the global eradication effort exhibited variable case fatality rates (CFRs), likely attributable in part to complex viral genetic determinants of smallpox virulence. We aimed to identify genome-wide single nucleotide polymorphisms associated with CFR. We evaluated unadjusted and outbreak geographic location-adjusted models of single SNPs and two- and three-way interactions between SNPs. Using the data mining approach multifactor dimensionality reduction (MDR), we identified five VARV SNPs in models significantly associated with CFR. The top performing unadjusted model and adjusted models both revealed the same two-way gene-gene interaction. We discuss the biological plausibility of the influence of the SNPs identified these and other significant models on the strain-specific virulence of VARV. We have identified genetic loci in the VARV genome that are statistically associated with VARV virulence as measured by CFR. While our ability to infer a causal relationship between the specific SNPs identified in our analysis and VARV virulence is limited, our results suggest that smallpox severity is in part associated with VARV strain variation and that VARV virulence may be determined by multiple genetic loci. This study represents the first application of MDR to the identification of pathogen gene-gene interactions for predicting infectious disease outbreak severity.

Reducing the dose of smallpox vaccine reduces vaccine-associated morbidity without reducing vaccination success rates or immune responses.

PubMed

Couch, Robert B; Winokur, Patricia; Edwards, Kathryn M; Black, Steven; Atmar, Robert L; Stapleton, Jack T; Kissner, Jennifer M; Shinefield, Henry; Denny, Thomas N; Bybel, Michael J; Newman, Frances K; Yan, Lihan

2007-03-15

When the decision was made to prepare for a deliberate release of smallpox, the United States had approximately 15 million doses of Wyeth Dryvax vaccine, which was known to induce significant morbidity when used undiluted; Sanofi Pasteur, Inc., later identified approximately 85 million additional doses in storage. Eleven vaccine-dose groups, each with 30 vaccinia-naive subjects, were given diluted Dryvax vaccine or 1 of 2 lots of Sanofi Pasteur smallpox vaccine and were evaluated for vaccination success rates, morbidity, and immune responses. Estimated doses of 10(6.6)-10(8.2) pfu of virus/mL induced major reactions (or "takes") in 93%-100% of subjects in each dose group. No differences in vaccination take rates, lesion size, erythema, and induration or in serum neutralizing-antibody response were detected between the groups. However, systemic reactogenicity and missed activities were significantly lower for the vaccine groups given doses of 10(6.6)-10(7.2) pfu/mL than for those given doses of 10(7.6)-10(8.2) pfu/mL. These findings support the use of a higher dilution of Wyeth Dryvax vaccine and Sanofi Pasteur smallpox vaccine, given that the resulting morbidity should be significantly lower without loss of vaccine effectiveness. A plan for use of higher dilutions would create an enormous stockpile of vaccine.

Variola minor in coalfield areas of England and Wales, 1921-34: Geographical determinants of a national smallpox epidemic that spread out of effective control.

PubMed

Smallman-Raynor, Matthew R; Rafferty, Sarah; Cliff, Andrew D

2017-05-01

This paper uses techniques of binary logistic regression to identify the spatial determinants of the last national epidemic of smallpox to spread in England and Wales, the variola minor epidemic of 1921-34. Adjusting for age and county-level variations in vaccination coverage in infancy, the analysis identifies a dose-response gradient with increasing odds of elevated smallpox rates in local government areas with (i) medium (odds ratio [OR] = 5.32, 95% Confidence Interval [95% CI] 1.96-14.41) and high (OR = 11.32, 95% CI 4.20-31.59) coal mining occupation rates and (ii) medium (OR = 16.74, 95% CI 2.24-125.21) and high (OR = 63.43, 95% CI 7.82-497.21) levels of residential density. The results imply that the spatial transmission of variola virus was facilitated by the close spatial packing of individuals, with a heightened transmission risk in coal mining areas of the country. A syndemic interaction between common respiratory conditions arising from exposure to coal dust and smallpox virus transmission is postulated to have contributed to the findings. We suggest that further studies of the geographical intersection of coal mining and acute infections that are transmitted via respiratory secretions are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Monkeypox virus and insights into its immunomodulatory proteins

PubMed Central

Weaver, Jessica R.; Isaacs, Stuart N.

2008-01-01

Summary Monkeypox is a disease that is endemic in Central and Western Africa. However, in 2003, there was an outbreak in the US, representing the first documented monkeypox cases in the Western hemisphere. Although monkeypox virus is less fatal and not as transmissible as variola virus, the causative agent of smallpox, there is concern that monkeypox virus could become a more efficient human pathogen. The reason for this may lie in the virus' genetic makeup, ecological changes, changes in host behavior, and the fact that with the eradication of variola virus, routine smallpox vaccination is no longer carried out. In this review, we focus on the viral proteins that are predicted to modulate the host immune response and compare the genome of monkeypox virus with the genomes of variola virus and the vaccinia virus, the orthopoxvirus that represented the smallpox vaccine. There are differences found in several of these immune-modulating genes including genes that express proteins that affect cytokines such as interleukin-1, tumor necrosis factor, and interferon. There are also differences in genes that code for virulence factors and host range proteins. Genetic differences likely also explain the differences in virulence between two strains of monkeypox virus found in two different regions of Africa. In the current setting of limited smallpox vaccination and little orthopoxvirus immunity in parts of the world, monkeypox could become a more efficient human pathogen under the right circumstances. PMID:18837778

Identification of SNPs associated with variola virus virulence

PubMed Central

2013-01-01

Background Decades after the eradication of smallpox, its etiological agent, variola virus (VARV), remains a threat as a potential bioweapon. Outbreaks of smallpox around the time of the global eradication effort exhibited variable case fatality rates (CFRs), likely attributable in part to complex viral genetic determinants of smallpox virulence. We aimed to identify genome-wide single nucleotide polymorphisms associated with CFR. We evaluated unadjusted and outbreak geographic location-adjusted models of single SNPs and two- and three-way interactions between SNPs. Findings Using the data mining approach multifactor dimensionality reduction (MDR), we identified five VARV SNPs in models significantly associated with CFR. The top performing unadjusted model and adjusted models both revealed the same two-way gene-gene interaction. We discuss the biological plausibility of the influence of the SNPs identified these and other significant models on the strain-specific virulence of VARV. Conclusions We have identified genetic loci in the VARV genome that are statistically associated with VARV virulence as measured by CFR. While our ability to infer a causal relationship between the specific SNPs identified in our analysis and VARV virulence is limited, our results suggest that smallpox severity is in part associated with VARV strain variation and that VARV virulence may be determined by multiple genetic loci. This study represents the first application of MDR to the identification of pathogen gene-gene interactions for predicting infectious disease outbreak severity. PMID:23410064

76 FR 8965 - National Vaccine Injury Compensation Program: Revisions to the Vaccine Injury Table

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A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

PubMed

Kramski, Marit; Mätz-Rensing, Kerstin; Stahl-Hennig, Christiane; Kaup, Franz-Josef; Nitsche, Andreas; Pauli, Georg; Ellerbrok, Heinz

2010-04-29

The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus).A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV) outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2) pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50) (minimal monkey infectious dose 50%) of 8.3x10(2) pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection

PubMed Central

Kramski, Marit; Mätz-Rensing, Kerstin; Stahl-Hennig, Christiane; Kaup, Franz-Josef; Nitsche, Andreas; Pauli, Georg; Ellerbrok, Heinz

2010-01-01

The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus). A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV) outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1–3 days after onset of symptoms, even when very low infectious viral doses of 5×102 pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed. We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID50 (minimal monkey infectious dose 50%) of 8.3×102 pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis. PMID:20454688

20 CFR 30.1 - What rules govern the administration of EEOICPA and this chapter?

Code of Federal Regulations, 2013 CFR

2013-04-01

..., DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED...

20 CFR 30.1 - What rules govern the administration of EEOICPA and this chapter?

Code of Federal Regulations, 2014 CFR

2014-04-01

..., DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED...

20 CFR 30.1 - What rules govern the administration of EEOICPA and this chapter?

Code of Federal Regulations, 2012 CFR

2012-04-01

..., DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED...

20 CFR 30.1 - What rules govern the administration of EEOICPA and this chapter?

Code of Federal Regulations, 2011 CFR

2011-04-01

..., DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED...

20 CFR 30.1 - What rules govern the administration of EEOICPA and this chapter?

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED...

20 CFR 1.1 - Under what authority was the Office of Workers' Compensation Programs established?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Under what authority was the Office of Workers' Compensation Programs established? 1.1 Section 1.1 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ORGANIZATION AND PROCEDURES PERFORMANCE OF FUNCTIONS § 1.1 Under...

20 CFR 1.1 - Under what authority was the Office of Workers' Compensation Programs established?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Under what authority was the Office of Workers' Compensation Programs established? 1.1 Section 1.1 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ORGANIZATION AND PROCEDURES PERFORMANCE OF FUNCTIONS § 1.1 Under...

76 FR 30695 - Energy Employees Occupational Illness Compensation Program Act of 2000; Revision to the List of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... DEPARTMENT OF ENERGY Energy Employees Occupational Illness Compensation Program Act of 2000... publishes or revises a list of facilities covered under the Energy Employees Occupational Illness... establishes a program to provide compensation to certain employees who develop illnesses as a result of their...

20 CFR 30.609 - Is a settlement or judgment received as a result of allegations of medical malpractice in...

Code of Federal Regulations, 2010 CFR

2010-04-01

... result of allegations of medical malpractice in treating an illness covered by EEOICPA a recovery that... PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS...

20 CFR 30.609 - Is a settlement or judgment received as a result of allegations of medical malpractice in...

Code of Federal Regulations, 2013 CFR

2013-04-01

... result of allegations of medical malpractice in treating an illness covered by EEOICPA a recovery that... PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS...

20 CFR 30.609 - Is a settlement or judgment received as a result of allegations of medical malpractice in...

Code of Federal Regulations, 2014 CFR

2014-04-01

... result of allegations of medical malpractice in treating an illness covered by EEOICPA a recovery that... PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS...

20 CFR 30.609 - Is a settlement or judgment received as a result of allegations of medical malpractice in...

Code of Federal Regulations, 2012 CFR

2012-04-01

... result of allegations of medical malpractice in treating an illness covered by EEOICPA a recovery that... PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS...

78 FR 9678 - Energy Employees Occupational Illness Compensation Program Act of 2000; Revision to the List of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-11

... DEPARTMENT OF ENERGY Energy Employees Occupational Illness Compensation Program Act of 2000... publishes revisions to its list of facilities covered under the Energy Employees Occupational Illness... establishes a program to provide compensation to certain employees who develop illnesses as a result of their...

20 CFR 30.609 - Is a settlement or judgment received as a result of allegations of medical malpractice in...

Code of Federal Regulations, 2011 CFR

2011-04-01

... result of allegations of medical malpractice in treating an illness covered by EEOICPA a recovery that... PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS...

20 CFR 30.100 - In general, how does an employee file an initial claim for benefits?

Code of Federal Regulations, 2013 CFR

2013-04-01

... PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 CLAIMS FOR COMPENSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS... employee may not want to claim for an occupational illness or a covered illness for which a payment has...

20 CFR 1.1 - Under what authority does the Office of Workers' Compensation Programs operate?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Under what authority does the Office of Workers' Compensation Programs operate? 1.1 Section 1.1 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ORGANIZATION AND PROCEDURES PERFORMANCE OF FUNCTIONS § 1.1 Under...

20 CFR 1.1 - Under what authority does the Office of Workers' Compensation Programs operate?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Under what authority does the Office of Workers' Compensation Programs operate? 1.1 Section 1.1 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ORGANIZATION AND PROCEDURES PERFORMANCE OF FUNCTIONS § 1.1 Under...

20 CFR 1.1 - Under what authority does the Office of Workers' Compensation Programs operate?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Under what authority does the Office of Workers' Compensation Programs operate? 1.1 Section 1.1 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ORGANIZATION AND PROCEDURES PERFORMANCE OF FUNCTIONS § 1.1 Under...

Research Program for Vibration Control in Structures

NASA Technical Reports Server (NTRS)

Mingori, D. L.; Gibson, J. S.

1986-01-01

Purpose of program to apply control theory to large space structures (LSS's) and design practical compensator for suppressing vibration. Program models LSS as distributed system. Control theory applied to produce compensator described by functional gains and transfer functions. Used for comparison of robustness of low- and high-order compensators that control surface vibrations of realistic wrap-rib antenna. Program written in FORTRAN for batch execution.

Triage for Civil Support. Using Military Medical Assets to Respond to Terrorist Attacks

DTIC Science & Technology

2004-01-01

chicken pox , ma- laria, viral syndromes, and meningitis gave way to the suspicion that one or more of the pa- tients may have contracted smallpox. While...awaiting the results of an infectious disease consultation on a patient that appeared to be too ill to have chicken pox (raising the strong suspicion...Whiteman Air Force Base (home to 150 nuclear-armed ICBMs). • (April 2003) A misdiagnosis of chicken pox as smallpox at a major Nashville hospital