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 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.

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.

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…

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…

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

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.

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.

Can We Capitalize on the Virtues of Vaccines? Insights from the Polio Eradication Initiative

PubMed Central

Aylward, R. Bruce; Heymann, David L.

2005-01-01

Twenty-five years after the eradication of smallpox, the ongoing effort to eradicate poliomyelitis has grown into the largest international health initiative ever undertaken. By 2004, however, the polio eradication effort was threatened by a challenge regularly faced by public health policymakers everywhere—misperception about the benefits and risks of vaccines. The propagation of false rumors about oral poliovirus vaccine safety led to the reinfection of 13 previously polio-free countries and the largest polio epidemic in Africa in recent years. With deft management of such challenges by local, national, and international health authorities, poliomyelitis, a disease that threatened children everywhere just 2 generations ago, could soon be relegated to history like smallpox before it. PMID:15855451

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.

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.

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 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.

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

[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.

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.

Addressing the Challenges and Opportunities of the Polio Endgame: Lessons for the Future.

PubMed

Patel, Manish; Cochi, Stephen

2017-07-01

The Global Commission for the Certification of the Eradication of Poliomyelitis certified the eradication of type 2 poliovirus in September 2015, making type 2 poliovirus the first human pathogen to be eradicated since smallpox. The eradication of type 2 poliovirus, the absence of detection of type 3 poliovirus worldwide since November 2012, and cornering type 1 poliovirus to only a few geographic areas of 3 countries has enabled implementation of the endgame of polio eradication which calls for a phased withdrawal of oral polio vaccine beginning with the type 2 component, introduction of inactivated poliovirus vaccine, strengthening of routine immunization in countries with extensive polio resources, and initiating activities to transition polio resources, program experience, and lessons learned to other global health initiatives. This supplement focuses on efforts by global partners to successfully launch polio endgame activities to permanently secure and sustain the enormous gains of polio eradication forever. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

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.

Eradication of infectious diseases in heterogeneous populations

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

Travis, C.C.; Lenhart, S.M.

1987-04-01

A model is presented of infectious disease in heterogeneous populations, which allows for variable intra- to intergroup contact ratios. The authors give necessary and sufficient conditions for disease eradication by means of vaccination. Smallpox is used as an illustrative example.

[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.

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.

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 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

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

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

[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.

The new ACAM2000 vaccine and other therapies to control orthopoxvirus outbreaks and bioterror attacks.

PubMed

Handley, Lauren; Buller, Robert Mark; Frey, Sharon E; Bellone, Clifford; Parker, Scott

2009-07-01

Quarantine, case tracing and population vaccination facilitated the global eradication, in 1980, of variola virus, the causative agent of smallpox. The vaccines used during the eradication period, including Dryvax, the smallpox vaccine used in the USA, were live vaccinia and cowpoxvirus-based vaccines, which induced long-lasting and cross-protective immunity against variola and other related poxviruses. These vaccine viruses were produced by serial propagation in domesticated animals. The drawbacks to such serially propagated live viral vaccines include the level of postvaccination local and systemic reactions and contraindications to their use in immunocompromised individuals, individuals with certain skin and cardiac diseases, and pregnant women. In the latter stages of the population-based smallpox vaccination campaign, research began with ways to improve safety and modernizing the manufacture of vaccinia vaccines; however, with the eradication of variola this work stopped. Outbreaks of monkeypoxvirus in humans and the bioterrorist threat of monkeypox and variola virus renewed the need for improved vaccinia vaccines. ACAM2000 is one of the new generation of smallpox vaccines. It is produced in cell culture from a clonally purified master seed stock of vaccinia derived from the New York City Board of Health strain of vaccinia. The clonally purified master seed assures a more homogeneous vaccine without the inherent mutations associated with serial propagation and the cell culture limits adventitious and bacterial contamination in vaccine production. In preclinical and clinical trials, ACAM2000 demonstrated an immunogenicity and safety profile similar to that of Dryvax.

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

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.

[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.

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

Generation and Production of Modified Vaccinia Virus Ankara (MVA) as a Vaccine Vector.

PubMed

Pavot, Vincent; Sebastian, Sarah; Turner, Alison V; Matthews, Jake; Gilbert, Sarah C

2017-01-01

The smallpox vaccine based on the vaccinia virus was successfully used to eradicate smallpox, but although very effective, it was a very reactogenic vaccine and responsible for the deaths of one to two people per million vaccinated. Modified Vaccinia virus Ankara (MVA) is an attenuated derivative, also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer. MVA can encode one or more foreign antigens and thus can function as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant properties, and induces humoral and cellular immune responses. Many clinical trials of these new vaccines have been conducted, and the safety of MVA is now well documented. Immunogenicity is influenced by the dose and vaccination regimen, and information on the efficacy of MVA-vectored vaccines is now beginning to accumulate. In this chapter, we provide protocols for generation, isolation, amplification, and purification of recombinant MVA for preclinical and clinical evaluation.

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.

The Florey lecture, 1983. Biological control, as exemplified by smallpox eradication and myxomatosis.

PubMed

Fenner, F

1983-06-22

Biological control is an important method of dealing with plant and insect pests. The control of rabbits by myxomatosis and the eradication of smallpox by vaccination are unusual examples of biological control, in that they involve a vertebrate and a viral pest respectively. Myxomatosis is a benign disease in Sylvilagus rabbits in South America which is transmitted mechanically by mosquitoes. In the European rabbit, Oryctolagus, which is a pest in Australia and England, the virus from Sylvilagus produces a generalized disease that is almost always lethal. Myxomatosis was deliberately introduced into Australia in 1950 and into Europe in 1952. It was at first spectacularly successful in controlling the rabbit pest, but biological adjustments occurred in the virulence of the virus and the genetic resistances of rabbits. After 30 years of interaction, natural selection has resulted in a balance at a fairly high level of viral virulence. Smallpox has been a major scourge of mankind for over 1500 years. It spread from Asia to Europe in the Middle ages and from Europe to Africa and the Americas in the 15th and 16th centuries. Jenner's cowpox vaccine provided a method of control that reduced the severity of the disease during the 19th century but failed to eliminate the disease from many countries before the 1930s. Thereafter it was eradicated from Europe and North America, but remained endemic in South America, Africa and Asia. In 1967 it was still endemic in 33 countries and W.H.O. established a programme for global eradication within 10 years. The goal was achieved in 1977. Problems of the eradication programme and reasons for its success will be described.

Challenges to global measles eradication: is it all in the timing?

PubMed

Davis, Robert; Mbabazi, William Baguma

2017-01-01

The case for global eradication of measles was first made in 1982. Since then, technical aspects of measles eradication have concluded that measles satisfied all criteria required for eradication. To date, only smallpox, among human diseases, has been eradicated, with polio, the next eradication candidate. In all previous eradication programmes, the pattern of slow implementation and missed deadlines is similar. Lessons from these past eradication programs should inform development of a time-limited measles eradication program. Notably, no measles eradication resolution is likely until member states are satisfied that polio eradication is accomplished. However, there is an impetus for measles eradication from the western hemisphere, where governments continue to pay the high costs of keeping their region measles free until global measles eradication is achieved. While previous vaccine preventable diseases eradications have depended on supplemental immunizations (SIAs), measles eradication will have to build both on SIAs and routine immunization systems strengthening. This article reviews non-technical considerations that could facilitate the delivery of a time-limited measles eradication initiative. The issues discussed are categorized as a) specificities of measles disease; b) specifics of measles vaccine/vaccination; c) special considerations for endemic countries and d) organization of international partnerships. The disease and vaccine specific issues are not insurmountable. The introduction of routine measles second dose, in the context of EPI systems strengthening, is paramount to endemic developing countries. In the international partnerships, it should be noted that i) Measles eradication will be easier and cheaper; ii) the return on investment is compelling; iii) leverage is feasible on the experiences of the Measles/Rubella initiative; iv) two disease eradication targets in one initiative are feasible and v) for the first time, an eradication investment case will inform the decisions. However, if previous eradication efforts have been marathons, measles eradication will need to be a sprint.

Challenges to global measles eradication: is it all in the timing?

PubMed Central

Davis, Robert; Mbabazi, William Baguma

2017-01-01

The case for global eradication of measles was first made in 1982. Since then, technical aspects of measles eradication have concluded that measles satisfied all criteria required for eradication. To date, only smallpox, among human diseases, has been eradicated, with polio, the next eradication candidate. In all previous eradication programmes, the pattern of slow implementation and missed deadlines is similar. Lessons from these past eradication programs should inform development of a time-limited measles eradication program. Notably, no measles eradication resolution is likely until member states are satisfied that polio eradication is accomplished. However, there is an impetus for measles eradication from the western hemisphere, where governments continue to pay the high costs of keeping their region measles free until global measles eradication is achieved. While previous vaccine preventable diseases eradications have depended on supplemental immunizations (SIAs), measles eradication will have to build both on SIAs and routine immunization systems strengthening. This article reviews non-technical considerations that could facilitate the delivery of a time-limited measles eradication initiative. The issues discussed are categorized as a) specificities of measles disease; b) specifics of measles vaccine/vaccination; c) special considerations for endemic countries and d) organization of international partnerships. The disease and vaccine specific issues are not insurmountable. The introduction of routine measles second dose, in the context of EPI systems strengthening, is paramount to endemic developing countries. In the international partnerships, it should be noted that i) Measles eradication will be easier and cheaper; ii) the return on investment is compelling; iii) leverage is feasible on the experiences of the Measles/Rubella initiative; iv) two disease eradication targets in one initiative are feasible and v) for the first time, an eradication investment case will inform the decisions. However, if previous eradication efforts have been marathons, measles eradication will need to be a sprint. PMID:29296146

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.

Political epidemiology: strengthening socio-political analysis for mass immunisation - lessons from the smallpox and polio programmes.

PubMed

Taylor, S

2009-01-01

Control and reduction of infectious diseases is a key to attaining the Millennium Development Goals. An important element of this work is the successful immunisation, especially in resource-poor countries. Mass immunisation, most intensively in the case of eradication, depends on a combination of reliable demand (e.g. public willingness to comply with the vaccine protocol) and effective supply (e.g. robust, generally state-led, vaccine delivery). This balance of compliance and enforceability is, quintessentially, socio-political in nature - conditioned by popular perceptions of disease and risk, wider conditions of economic development and poverty, technical aspects of vaccine delivery, and the prevailing international norms regarding power relations between states and peoples. In the past 100 years, three out of six disease eradication programmes have failed. The explanations for failure have focused on biotechnical and managerial or financial issues. Less attention is paid to socio-political aspects. Yet socio-political explanations are key. Eradication is neither inherently prone to failure, nor necessarily doomed in the case of polio. However, eradication, and similar mass immunisation initiatives, which fail to address social and political realities of intervention may be. A comparison of the smallpox and polio eradication programmes illustrates the importance of disease-specific socio-political analysis in programme conceptualisation, design, and management.

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

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.

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

Smallpox: can we still learn from the journey to eradication?

PubMed

Smith, Kendall A

2013-05-01

One of the most celebrated achievements of immunology and modern medicine is the eradication of the dreaded plague smallpox. From the introduction of smallpox vaccination by Edward Jenner, to its popularization by Louis Pasteur, to the eradication effort led by Donald Henderson, this story has many lessons for us today, including the characteristics of the disease and vaccine that permitted its eradication, and the obviousness of the vaccine as a vector for other intractable Infectious diseases. The disease itself, interpreted in the light of modern molecular immunology, is an obvious immunopathological disease, which occurs after a latent interval of 1-2 weeks, and manifests as a systemic cell-mediated delayed type hypersensitivity (DTH) syndrome. The vaccine that slayed this dragon was given the name vaccinia, and was thought to have evolved from cowpox virus, but is now known to be most closely related to a poxvirus isolated from a horse. Of interest is the fact that of the various isolates of orthopox viruses, only variola, vaccinia and monkeypox viruses can infect humans. In contrast to the systemic disease of variola, vaccinia only replicates locally at the site of inoculation, and causes a localized DTH response that usually peaks after 7-10 days. This difference in the pathogenicity of variola vs. vaccinia is thought to be due to the capacity of variola to circumvent innate immunity, which allows it to disseminate widely before the adaptive immune response occurs. Thus, the fact that vaccinia virus is attenuated compared to variola, but is still replication competent, makes for its remarkable efficacy as a vaccine, as the localized infection activates all of the cells and molecules of both innate and adaptive immunity. Accordingly vaccinia itself, and not modified replication incompetent vaccina, is the hope for use as a vector in the eradication of additional pathogenic microbes from the globe.

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.

Genital Autoinoculation with Vaccinia: A Look at Two Cases.

PubMed

Whittington, Julie R; Rollene, Nanette L; Gist, Richard S

2018-05-01

Smallpox, or vaccinia, has been eradicated worldwide as a disease; however, it may be weaponized and is thus a required immunization when military members deploy to certain parts of the world. We report two unusual cases of genital autoinoculation following smallpox vaccination. Both patients' lesions resolved without sequelae within 20 d. We advocate for thorough education on this potential vaccination adverse event. These cases highlight the importance of a broad differential diagnosis when dealing with vulvar lesions, particularly in our military population.

Live attenuated vaccines: Historical successes and current challenges

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

Minor, Philip D., E-mail: Philip.Minor@nibsc.org

Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up inmore » clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues.« less

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.

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 World Health Organization and global smallpox eradication.

PubMed

Bhattacharya, S

2008-10-01

This article examines the multifaceted structures and complex operations of the World Health Organization and its regional offices; it also reassesses the form and the workings of the global smallpox eradication programme with which these bodies were closely linked in the 1960s and 1970s. Using the case study of South Asia, it seeks to highlight the importance of writing nuanced histories of international health campaigns through an assessment of differences between official rhetoric and practice. The article argues that the detailed examination of the implementation of policy in a variety of localities, within and across national borders, allows us to recognise the importance of the agency of field managers and workers. This analytical approach also helps us acknowledge that communities were able to influence the shape and the timing of completion of public health campaigns in myriad ways. This, in turn, can provide useful pointers for the design and management of health programmes in the contemporary world.

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

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.

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

The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon.

PubMed

Fernández de Marco, María del Mar; Alejo, Alí; Hudson, Paul; Damon, Inger K; Alcami, Antonio

2010-05-01

Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.

[International health regulations--evaluation and trends].

PubMed

Vessereau, A

1988-01-01

The current International Health Regulations (IHR) were adopted by the Twenty-second World Health Assembly in 1969 and amended in 1973 and 1981. They are a revised and consolidated version of the International Sanitary Regulations which were adopted by the Fourth World Health Assembly in 1951, themselves based on the previous International Sanitary Conventions. The purpose of the IHR is to ensure maximum security against the international spread of diseases with a minimum interference to world traffic. Over the years the IHR included cholera, yellow fever, plague, smallpox, typhus and relapsing fever, and then dropped the last three as a result of the global eradication of smallpox and the decline of typhus and relapsing fever as international threats. The IHR have played and still play an important part with respect to the diseases for which they were drawn up. The international spread of yellow fever has been contained by the application of a highly effective vaccine to travellers, and of plague by the inspection of ships and aircrafts for rats, and improvements in the design of air and sea cargo carriers to make them increasingly uninhabitable for rats. The role of the IHR was questioned as far as smallpox and cholera are concerned by arguing that smallpox was eradicated by rigorous national local vaccination programmes and cholera must be defeated by improved environmental sanitation. However, one must not lose sight of the fact that an important element of the IHR is the obligation to notify cases of the diseases listed, together with as much epidemiological information as possible, in order to permit other countries to take appropriate action.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

Vaccine refusal and the endgame: walking the last mile first.

PubMed

Saint-Victor, Diane S; Omer, Saad B

2013-08-05

As multiple papers within this special issue illustrate, the dynamics of disease eradication are different from disease control. When it comes to disease eradication, 'the last mile is longest'. For social and ecological reasons such as vaccine refusal, further ending incidence of a disease when it has reached low levels is frequently complex. Issues of non-compliance within a target population often influence the outcome of disease eradication efforts. Past eradication efforts confronted such obstacles towards the tail end of the campaign, when disease incidence was lowest. This article provides a comparison of non-compliance within polio, measles and smallpox campaigns, demonstrating the tendency of vaccine refusal to rise as disease incidence falls. In order to overcome one of the most intractable challenges to eradication, future disease eradication efforts must prioritize vaccine refusal from the start, i.e. 'walk the last mile first'.

Vaccine refusal and the endgame: walking the last mile first

PubMed Central

Saint-Victor, Diane S.; Omer, Saad B.

2013-01-01

As multiple papers within this special issue illustrate, the dynamics of disease eradication are different from disease control. When it comes to disease eradication, ‘the last mile is longest’. For social and ecological reasons such as vaccine refusal, further ending incidence of a disease when it has reached low levels is frequently complex. Issues of non-compliance within a target population often influence the outcome of disease eradication efforts. Past eradication efforts confronted such obstacles towards the tail end of the campaign, when disease incidence was lowest. This article provides a comparison of non-compliance within polio, measles and smallpox campaigns, demonstrating the tendency of vaccine refusal to rise as disease incidence falls. In order to overcome one of the most intractable challenges to eradication, future disease eradication efforts must prioritize vaccine refusal from the start, i.e. ‘walk the last mile first’. PMID:23798696

[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.

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.

The World Health Organization and global smallpox eradication

PubMed Central

Bhattacharya, S

2008-01-01

Background: This article examines the multifaceted structures and complex operations of the World Health Organization and its regional offices; it also reassesses the form and the workings of the global smallpox eradication programme with which these bodies were closely linked in the 1960s and 1970s. Methods: Using the case study of South Asia, it seeks to highlight the importance of writing nuanced histories of international health campaigns through an assessment of differences between official rhetoric and practice. Results and conclusion: The article argues that the detailed examination of the implementation of policy in a variety of localities, within and across national borders, allows us to recognise the importance of the agency of field managers and workers. This analytical approach also helps us acknowledge that communities were able to influence the shape and the timing of completion of public health campaigns in myriad ways. This, in turn, can provide useful pointers for the design and management of health programmes in the contemporary world. PMID:18791049

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

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

[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.

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.

[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.

Adolescent Immunization: Challenges and Opportunities

ERIC Educational Resources Information Center

Grace, Judith A.

2006-01-01

Immunization is one of the greatest public health achievements of the past century. Vaccines are responsible for the worldwide eradication of smallpox, the elimination of polio in the western hemisphere, and most recently the elimination of rubella as a public health threat in the United States. Childhood vaccination rates are at an all-time high,…

Multifaceted contributions: health workers and smallpox eradication in India.

PubMed

Bhattacharya, Sanjoy

2008-01-01

Smallpox eradication in South Asia was a result of the efforts of many grades of health-workers. Working from within the confines of international organisations and government structures, the role of the field officials, who were of various nationalities and also drawn from the cities and rural enclaves of the countries in these regions, was crucial to the development and deployment of policies. However, the role of these personnel is often downplayed in official histories and academic histories, which highlight instead the roles played by a handful of senior officials within the World Health Organization and the federal governments in the sub-continent. This article attempts to provide a more rounded assessment of the complex situation in the field. In this regard, an effort is made to underline the great usefulness of the operational flexibility displayed by field officers, wherein lessons learnt in the field were made an integral part of deploying local campaigns; careful engagement with the communities being targeted, as well as the employment of short term workers from amongst them, was an important feature of this work.

The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon

PubMed Central

Fernández de Marco, María del Mar; Alejo, Alí; Hudson, Paul; Damon, Inger K.; Alcami, Antonio

2010-01-01

Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.—Fernández de Marco, M. M., Alejo, A., Hudson, P., Damon, I. K., Alcami, A. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon. PMID:20019241

[Should the human smallpox virus (variola) be destroyed?].

PubMed

Tryland, Morten

2004-10-21

Smallpox, caused by variola virus, was a terror for civilizations around the world for more than 3000 years. Although the disease is eradicated, hundreds of variola virus isolates are kept in two WHO-collaborating facilities, one in USA and one in Russia. In spite of several agreements on destruction, it is now doubtful that these virus isolates will be destroyed. Variola virus may exist in other places and may be used as a biological weapon in war or for terror. Further research on variola virus is thus essential in order to achieve a better understanding of the pathogenicity of the virus and to develop new anti-variola virus vaccines and antiviral drugs.

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

The XIX century smallpox prevention in Naples and the risk of transmission of human blood-related pathogens.

PubMed

Buonaguro, Franco Maria; Tornesello, Maria Lina; Buonaguro, Luigi

2015-01-27

Vaccines are the most successful strategy developed in Medicine to prevent and even eradicate the most dreadful epidemic infectious diseases. The history of smallpox vaccination in Naples is quite unique. Although Galbiati established the retro-vaccination (1803) and developed the "calf" lymph vaccine, recognized and implemented since 1864 as the optimal smallpox vaccine in the following hundred years, Naples general population was mainly vaccinated with "human" lymph from abandoned children until 1893. Mini-epidemics of syphilis and serum hepatitis were periodically reported as results of arm-to-arm procedure. The risk of transmission of blood-related pathogens was higher in Naples where >80% of abandoned children, used as repository of cowpox virus, were dying in their first year of life. Recent vaccinology standards finally eliminated the risk of adventitious contaminating pathogens. Implementation of hepatitis B vaccination since 1991 eventually contributed to current HBV prevalence in Campania region <1%, within the range of the European Countries.

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

42 CFR 102.11 - Survivors.

Code of Federal Regulations, 2012 CFR

2012-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... direct result of a covered injury. If the Secretary determines that a smallpox vaccine recipient or... is survived under this Program must be a deceased smallpox vaccine recipient or vaccinia contact who...

42 CFR 102.11 - Survivors.

Code of Federal Regulations, 2014 CFR

2014-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... direct result of a covered injury. If the Secretary determines that a smallpox vaccine recipient or... is survived under this Program must be a deceased smallpox vaccine recipient or vaccinia contact who...

42 CFR 102.11 - Survivors.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... direct result of a covered injury. If the Secretary determines that a smallpox vaccine recipient or... is survived under this Program must be a deceased smallpox vaccine recipient or vaccinia contact who...

42 CFR 102.11 - Survivors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... direct result of a covered injury. If the Secretary determines that a smallpox vaccine recipient or... is survived under this Program must be a deceased smallpox vaccine recipient or vaccinia contact who...

42 CFR 102.11 - Survivors.

Code of Federal Regulations, 2013 CFR

2013-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... direct result of a covered injury. If the Secretary determines that a smallpox vaccine recipient or... is survived under this Program must be a deceased smallpox vaccine recipient or vaccinia contact who...

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

Ethical and legal challenges of vaccines and vaccination: Reflections.

PubMed

Jesani, Amar; Johari, Veena

2017-01-01

Vaccines and vaccination have emerged as key medical scientific tools for prevention of certain diseases. Documentation of the history of vaccination shows that the initial popular resistance to universal vaccination was based on false assumptions and eventually gave way to acceptance of vaccines and trust in their ability to save lives. The successes of the global eradication of smallpox, and now of polio, have only strengthened the premier position occupied by vaccines in disease prevention. However, the success of vaccines and public trust in their ability to eradicate disease are now under challenge, as increasing numbers of people refuse vaccination, questioning the effectiveness of vaccines and the need to vaccinate.

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.

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...

Detection and identification of Variola virus in fixed human tissue after prolonged archival storage.

PubMed

Schoepp, Randal J; Morin, Michelle D; Martinez, Mark J; Kulesh, David A; Hensley, Lisa; Geisbert, Thomas W; Brady, Daniel R; Jahrling, Peter B

2004-01-01

Smallpox disease has been eradicated from the human population since 1979, but is again a concern because of its potential use as an agent of bioterrorism or biowarfare. World Health Organization-sanctioned repositories of infectious Variola virus are known to occur in both Russia and the United States, but many believe other undeclared and unregulated sources of the virus could exist. Thus, validation of improved methods for definitive identification of smallpox virus in diagnostic specimens is urgently needed. In this paper, we describe the discovery of suspected Variola infected human tissue, fixed and preserved for decades in largely unknown solutions, and the use of routine histology, electron microscopy, and ultimately DNA extraction and fluorogenic 5' nuclease (TaqMan) assays for its identification and confirmation.

Rapid Viral Diagnosis of Orthopoxviruses by Electron Microscopy: Optional or a Must?

PubMed Central

Gelderblom, Hans R.; Madeley, Dick

2018-01-01

Diagnostic electron microscopy (DEM) was an essential component of viral diagnosis until the development of highly sensitive nucleic acid amplification techniques (NAT). The simple negative staining technique of DEM was applied widely to smallpox diagnosis until the world-wide eradication of the human-specific pathogen in 1980. Since then, the threat of smallpox re-emerging through laboratory escape, molecular manipulation, synthetic biology or bioterrorism has not totally disappeared and would be a major problem in an unvaccinated population. Other animal poxviruses may also emerge as human pathogens. With its rapid results (only a few minutes after arrival of the specimen), no requirement for specific reagents and its “open view”, DEM remains an important component of virus diagnosis, particularly because it can easily and reliably distinguish smallpox virus or any other member of the orthopoxvirus (OPV) genus from parapoxviruses (PPV) and the far more common and less serious herpesviruses (herpes simplex and varicella zoster). Preparation, enrichment, examination, internal standards and suitable organisations are discussed to make clear its continuing value as a diagnostic technique. PMID:29565285

42 CFR 102.54 - Documentation the representative of the estate of a deceased smallpox vaccine recipient or...

Code of Federal Regulations, 2012 CFR

2012-10-01

... deceased smallpox vaccine recipient or vaccinia contact must submit to be deemed eligible by the Secretary... VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.54 Documentation the representative of the estate of a deceased smallpox vaccine recipient or vaccinia contact must...

42 CFR 102.54 - Documentation the representative of the estate of a deceased smallpox vaccine recipient or...

Code of Federal Regulations, 2011 CFR

2011-10-01

... deceased smallpox vaccine recipient or vaccinia contact must submit to be deemed eligible by the Secretary... VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.54 Documentation the representative of the estate of a deceased smallpox vaccine recipient or vaccinia contact must...

42 CFR 102.54 - Documentation the representative of the estate of a deceased smallpox vaccine recipient or...

Code of Federal Regulations, 2013 CFR

2013-10-01

... deceased smallpox vaccine recipient or vaccinia contact must submit to be deemed eligible by the Secretary... VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.54 Documentation the representative of the estate of a deceased smallpox vaccine recipient or vaccinia contact must...

42 CFR 102.54 - Documentation the representative of the estate of a deceased smallpox vaccine recipient or...

Code of Federal Regulations, 2014 CFR

2014-10-01

... deceased smallpox vaccine recipient or vaccinia contact must submit to be deemed eligible by the Secretary... VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.54 Documentation the representative of the estate of a deceased smallpox vaccine recipient or vaccinia contact must...

42 CFR 102.54 - Documentation the representative of the estate of a deceased smallpox vaccine recipient or...

Code of Federal Regulations, 2010 CFR

2010-10-01

... deceased smallpox vaccine recipient or vaccinia contact must submit to be deemed eligible by the Secretary... VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.54 Documentation the representative of the estate of a deceased smallpox vaccine recipient or vaccinia contact must...

Genomic Sequence and Virulence of Clonal Isolates of Vaccinia Virus Tiantan, the Chinese Smallpox Vaccine Strain

PubMed Central

Zhang, Qicheng; Tian, Meijuan; Feng, Yi; Zhao, Kai; Xu, Jing; Liu, Ying; Shao, Yiming

2013-01-01

Despite the worldwide eradication of smallpox in 1979, the potential bioterrorism threat from variola virus and the ongoing use of vaccinia virus (VACV) as a vector for vaccine development argue for continued research on VACV. In China, the VACV Tiantan strain (TT) was used in the smallpox eradication campaign. Its progeny strain is currently being used to develop a human immunodeficiency virus (HIV) vaccine. Here we sequenced the full genomes of five TT clones isolated by plaque purification from the TT (752-1) viral stock. Phylogenetic analysis with other commonly used VACV strains showed that TT (752-1) and its clones clustered and exhibited higher sequence diversity than that found in Dryvax clones. The ∼190 kbp genomes of TT appeared to encode 273 open reading frames (ORFs). ORFs located in the middle of the genome were more conserved than those located at the two termini, where many virulence and immunomodulation associated genes reside. Several patterns of nucleotide changes including point mutations, insertions and deletions were identified. The polymorphisms in seven virulence-associated proteins and six immunomodulation-related proteins were analyzed. We also investigated the neuro- and skin- virulence of TT clones in mice and rabbits, respectively. The TT clones exhibited significantly less virulence than the New York City Board of Health (NYCBH) strain, as evidenced by less extensive weight loss and morbidity in mice as well as produced smaller skin lesions and lower incidence of putrescence in rabbits. The complete genome sequences, ORF annotations, and phenotypic diversity yielded from this study aid our understanding of the Chinese historic TT strain and are useful for HIV vaccine projects employing TT as a vector. PMID:23593246

Genomic sequence and virulence of clonal isolates of vaccinia virus Tiantan, the Chinese smallpox vaccine strain.

PubMed

Zhang, Qicheng; Tian, Meijuan; Feng, Yi; Zhao, Kai; Xu, Jing; Liu, Ying; Shao, Yiming

2013-01-01

Despite the worldwide eradication of smallpox in 1979, the potential bioterrorism threat from variola virus and the ongoing use of vaccinia virus (VACV) as a vector for vaccine development argue for continued research on VACV. In China, the VACV Tiantan strain (TT) was used in the smallpox eradication campaign. Its progeny strain is currently being used to develop a human immunodeficiency virus (HIV) vaccine. Here we sequenced the full genomes of five TT clones isolated by plaque purification from the TT (752-1) viral stock. Phylogenetic analysis with other commonly used VACV strains showed that TT (752-1) and its clones clustered and exhibited higher sequence diversity than that found in Dryvax clones. The ∼190 kbp genomes of TT appeared to encode 273 open reading frames (ORFs). ORFs located in the middle of the genome were more conserved than those located at the two termini, where many virulence and immunomodulation associated genes reside. Several patterns of nucleotide changes including point mutations, insertions and deletions were identified. The polymorphisms in seven virulence-associated proteins and six immunomodulation-related proteins were analyzed. We also investigated the neuro- and skin- virulence of TT clones in mice and rabbits, respectively. The TT clones exhibited significantly less virulence than the New York City Board of Health (NYCBH) strain, as evidenced by less extensive weight loss and morbidity in mice as well as produced smaller skin lesions and lower incidence of putrescence in rabbits. The complete genome sequences, ORF annotations, and phenotypic diversity yielded from this study aid our understanding of the Chinese historic TT strain and are useful for HIV vaccine projects employing TT as a vector.

Vacated niches, competitive release and the community ecology of pathogen eradication

PubMed Central

Lloyd-Smith, James O.

2013-01-01

A recurring theme in the epidemiological literature on disease eradication is that each pathogen occupies an ecological niche, and eradication of one pathogen leaves a vacant niche that favours the emergence of new pathogens to replace it. However, eminent figures have rejected this view unequivocally, stating that there is no basis to fear pathogen replacement and even that pathogen niches do not exist. After exploring the roots of this controversy, I propose resolutions to disputed issues by drawing on broader ecological theory, and advance a new consensus based on robust mechanistic principles. I argue that pathogen eradication (and cessation of vaccination) leads to a ‘vacated niche’, which could be re-invaded by the original pathogen if introduced. Consequences for other pathogens will vary, with the crucial mechanisms being competitive release, whereby the decline of one species allows its competitors to perform better, and evolutionary adaptation. Hence, eradication can cause a quantitative rise in the incidence of another infection, but whether this leads to emergence as an endemic pathogen depends on additional factors. I focus on the case study of human monkeypox and its rise following smallpox eradication, but also survey how these ideas apply to other pathogens and discuss implications for eradication policy. PMID:23798698

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

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 102.1 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM General... the administration of the smallpox vaccine or other covered countermeasure, and to certain individuals... with certain persons vaccinated with the smallpox vaccine or with individuals accidentally inoculated...

42 CFR 102.1 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-10-01

... HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM General... the administration of the smallpox vaccine or other covered countermeasure, and to certain individuals... with certain persons vaccinated with the smallpox vaccine or with individuals accidentally inoculated...

42 CFR 102.1 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-10-01

... HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM General... the administration of the smallpox vaccine or other covered countermeasure, and to certain individuals... with certain persons vaccinated with the smallpox vaccine or with individuals accidentally inoculated...

42 CFR 102.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM General... the administration of the smallpox vaccine or other covered countermeasure, and to certain individuals... with certain persons vaccinated with the smallpox vaccine or with individuals accidentally inoculated...

42 CFR 102.1 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-10-01

... HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM General... the administration of the smallpox vaccine or other covered countermeasure, and to certain individuals... with certain persons vaccinated with the smallpox vaccine or with individuals accidentally inoculated...

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

Outbreak of human monkeypox, Democratic Republic of Congo, 1996 to 1997.

PubMed Central

Hutin, Y. J.; Williams, R. J.; Malfait, P.; Pebody, R.; Loparev, V. N.; Ropp, S. L.; Rodriguez, M.; Knight, J. C.; Tshioko, F. K.; Khan, A. S.; Szczeniowski, M. V.; Esposito, J. J.

2001-01-01

Human monkeypox is a zoonotic smallpox-like disease caused by an orthopoxvirus of interhuman transmissibility too low to sustain spread in susceptible populations. In February 1997, 88 cases of febrile pustular rash were identified for the previous 12 months in 12 villages of the Katako-Kombe Health Zone, Democratic Republic of Congo (attack rate = 22 per 1,000; case-fatality rate = 3.7%). Seven were active cases confirmed by virus isolation. Orthopoxvirus- neutralizing antibodies were detected in 54% of 72 patients who provided serum and 25% of 59 wild-caught animals, mainly squirrels. Hemagglutination-inhibition assays and Western blotting detected antibodies in 68% and 73% of patients, respectively. Vaccinia vaccination, which protects against monkeypox, ceased by 1983 after global smallpox eradication, leading to an increase in the proportion of susceptible people. PMID:11384521

42 CFR 102.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... posthumous child or stepchild of a deceased smallpox vaccine recipient or vaccinia contact who, at the time... vaccinated him/herself. (g) Covered countermeasure means smallpox (vaccinia) vaccines, cidofovir and its...

42 CFR 102.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... posthumous child or stepchild of a deceased smallpox vaccine recipient or vaccinia contact who, at the time... vaccinated him/herself. (g) Covered countermeasure means smallpox (vaccinia) vaccines, cidofovir and its...

42 CFR 102.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... posthumous child or stepchild of a deceased smallpox vaccine recipient or vaccinia contact who, at the time... vaccinated him/herself. (g) Covered countermeasure means smallpox (vaccinia) vaccines, cidofovir and its...

42 CFR 102.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... posthumous child or stepchild of a deceased smallpox vaccine recipient or vaccinia contact who, at the time... vaccinated him/herself. (g) Covered countermeasure means smallpox (vaccinia) vaccines, cidofovir and its...

42 CFR 102.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... posthumous child or stepchild of a deceased smallpox vaccine recipient or vaccinia contact who, at the time... vaccinated him/herself. (g) Covered countermeasure means smallpox (vaccinia) vaccines, cidofovir and its...

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...

Airman Scholar Journal. Volume 17, Fall 2011

DTIC Science & Technology

2011-01-01

and epidemics can wreak on weak governments. Age-old diseases such as cholera , tuberculosis, and malaria, coupled with emerging diseases like...six to three (yellow fever, plague and cholera ) and to mark the global eradication of smallpox.”30 The 2005 revisions to the IHR, which entered...crucial issue for international security are the resur- gence of the some of the human race’s oldest nemeses in the forms of cholera , malaria, and

[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".

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

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.

Identification of vaccinia virus epitope-specific HLA-A*0201-restricted T cells and comparative analysis of smallpox vaccines

PubMed Central

Drexler, Ingo; Staib, Caroline; Kastenmüller, Wolfgang; Stevanović, Stefan; Schmidt, Burkhard; Lemonnier, François A.; Rammensee, Hans-Georg; Busch, Dirk H.; Bernhard, Helga; Erfle, Volker; Sutter, Gerd

2003-01-01

Despite worldwide eradication of naturally occurring variola virus, smallpox remains a potential threat to both civilian and military populations. New, safe smallpox vaccines are being developed, and there is an urgent need for methods to evaluate vaccine efficacy after immunization. Here we report the identification of an immunodominant HLA-A*0201-restricted epitope that is recognized by cytotoxic CD8+ T cells and conserved among Orthopoxvirus species including variola virus. This finding has permitted analysis and monitoring of epitope-specific T cell responses after immunization and demonstration of the identified T cell specificity in an A*0201-positive human donor. Vaccination of transgenic mice allowed us to compare the immunogenicity of several vaccinia viruses including highly attenuated, replication-deficient modified vaccinia virus Ankara (MVA). MVA vaccines elicited levels of CD8+ T cell responses that were comparable to those induced by the replication-competent vaccinia virus strains. Finally, we demonstrate that MVA vaccination is fully protective against a lethal respiratory challenge with virulent vaccinia virus strain Western Reserve. Our data provide a basis to rationally estimate immunogenicity of safe, second-generation poxvirus vaccines and suggest that MVA may be a suitable candidate. PMID:12518065

Live attenuated vaccines: Historical successes and current challenges.

PubMed

Minor, Philip D

2015-05-01

Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Vaccines Through Centuries: Major Cornerstones of Global Health

PubMed Central

Hajj Hussein, Inaya; Chams, Nour; Chams, Sana; El Sayegh, Skye; Badran, Reina; Raad, Mohamad; Gerges-Geagea, Alice; Leone, Angelo; Jurjus, Abdo

2015-01-01

Multiple cornerstones have shaped the history of vaccines, which may contain live-attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response. The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the eighteenth century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on smallpox. The nineteenth century was a major landmark, with the “Germ Theory of disease” of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live-attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for bacille Calmette–Guerin, Polio, DTP, measles, yellow fever, and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010, “The Decade of vaccines” was launched, and on April 1st 2012, the United Nations launched the “shot@Life” campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability, and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated so many life-threatening diseases, despite the vaccination attitudes and waves appearing through history. PMID:26636066

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...

Assessment of vaccination coverage, vaccination scar rates, and smallpox scarring in five areas of West Africa.

PubMed

Henderson, R H; Davis, H; Eddins, D L; Foege, W H

1973-01-01

In 1966, nineteen countries of West and Central Africa began a regional smallpox eradication and measles control programme in cooperation with the World Health Organization. This paper summarizes sample survey data collected to assess the results of the programme in Northern Nigeria (Sokoto and Katsina Provinces), Western Nigeria, Niger, Dahomey, and Togo. These data indicate that the programme, which used mass vaccination campaigns based on a collecting-point strategy, was generally successful in reaching a high proportion of the population. Analysis of vaccination coverage and vaccination scar rates by age underlined the importance to the programme of newborn children who accumulate rapidly following the mass campaign. Of all persons without vaccination scars at the time of the surveys, 34.4% were under 5 years of age; in the absence of a maintenance programme, this figure would rise to 40% after 1 year.

Smallpox virus plaque phenotypes: genetic, geographical and case fatality relationships.

PubMed

Olson, Victoria A; Karem, Kevin L; Smith, Scott K; Hughes, Christine M; Damon, Inger K

2009-04-01

Smallpox (infection with Orthopoxvirus variola) remains a feared illness more than 25 years after its eradication. Historically, case-fatality rates (CFRs) varied between outbreaks (<1 to approximately 40 %), the reasons for which are incompletely understood. The extracellular enveloped virus (EEV) form of orthopoxvirus progeny is hypothesized to disseminate infection. Investigations with the closely related Orthopoxvirus vaccinia have associated increased comet formation (EEV production) with increased mouse mortality (pathogenicity). Other vaccinia virus genetic manipulations which affect EEV production inconsistently support this association. However, antisera against vaccinia virus envelope protect mice from lethal challenge, further supporting a critical role for EEV in pathogenicity. Here, we show that the increased comet formation phenotypes of a diverse collection of variola viruses associate with strain phylogeny and geographical origin, but not with increased outbreak-related CFRs; within clades, there may be an association of plaque size with CFR. The mechanisms for variola virus pathogenicity probably involves multiple host and pathogen factors.

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.

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...

[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 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.

Cutting the Stone: Health Defined in the Era of Value-based Care

PubMed Central

2017-01-01

The immune system contributes to the maintenance of health by preventing and limiting the clinical consequences of infections by pathogenic microorganisms. During the evolution of Homo sapiens, those with the fittest immune system survived. The immune system of Homo sapiens was further improved and adapted by admixture with Neanderthal genes. Nowadays, the human immune system provides adequate protection against the majority of infections. For some 20 infectious diseases, the immune system needs to be improved by vaccination. Vaccination is the number one value-based healthcare intervention and has resulted in global eradication of smallpox. Eradication of poliomyelitis and measles is within reach. A continuous effort will be required for recently emerged pathogens, such as Ebola and HIV, as well as the most difficult - malaria and tuberculosis.   PMID:28348941

Cutting the Stone: Health Defined in the Era of Value-based Care.

PubMed

Rijkers, Ger

2017-02-10

The immune system contributes to the maintenance of health by preventing and limiting the clinical consequences of infections by pathogenic microorganisms. During the evolution of Homo sapiens, those with the fittest immune system survived. The immune system of Homo sapiens was further improved and adapted by admixture with Neanderthal genes. Nowadays, the human immune system provides adequate protection against the majority of infections. For some 20 infectious diseases, the immune system needs to be improved by vaccination. Vaccination is the number one value-based healthcare intervention and has resulted in global eradication of smallpox. Eradication of poliomyelitis and measles is within reach. A continuous effort will be required for recently emerged pathogens, such as Ebola and HIV, as well as the most difficult - malaria and tuberculosis.

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...

PANDEMICS: Recommendations for International Preparedness, Response and Coordination

DTIC Science & Technology

2011-01-01

such as cholera , tuberculosis, and malaria, coupled with emerging diseases like HIV/AIDS, SARS, H5N1 (Avian Flu), and H1N1 (Swine Flu) demonstrate...plague and cholera ) and to mark the global eradication of smallpox.”30 The 2005 revisions to the IHR, which entered into force on 15 June 2007...security are the resur- gence of the some of the human race’s oldest nemeses in the forms of cholera , malaria, and tuberculosis, the ongoing HIV/AIDS

Rapid and High-Throughput pan-Orthopoxvirus Detection and Identification using PCR and Mass Spectrometry

DTIC Science & Technology

2009-07-01

used in this manuscript. Several of the co- authors are or were Ibis employees. * E -mail: meshoo@ibisbio.com Introduction The orthopoxviruses (family...its Eradication. Geneva: World Health Organization. 4. Henderson DA, Inglesby TV, Bartlett JG, Ascher MS, Eitzen E , et al. (1999) Smallpox as a...of Rio de Janeiro: preliminary report. Mem Inst Oswaldo Cruz 95: 625–627. 15. Trindade GS, da Fonseca FG, Marques JT, Diniz S, Leite JA, et al. (2004

Historical aspects of immunization and vaccine safety communication.

PubMed

Helfert, Stephanie M

2015-01-01

It has been a long journey starting from the beginnings of variolation [3] leading up to the greatest success in the history of immunization: the eradication of smallpox [39]. Today, vaccines are an acknowledged important medical advance [40]. Nevertheless, immunization has been the subject of public controversy on several occasions [15, 24, 31]. This article shall provide a short overview of some aspects of the early stages of immunization in Western countries, including some examples of vaccine safety controversies in the past.

Smallpox still haunts scientists: results of a questionnaire-based inquiry on the views of health care and life science experts and students on preserving the remaining variola virus stocks.

PubMed

Srinivasan, Thangavelu; Dedeepiya, Vidyasagar Devaprasad; John, Sudhakar; Senthilkumar, Rajappa; Reena, Helen C; Rajendran, Paramasivam; Balamurugan, Madasamy; Kurosawa, Gene; Iwasaki, Masaru; Preethy, Senthilkumar; Abraham, Samuel J K

2013-01-01

The World Health Organization (WHO) declared eradication of the dreadful disease "smallpox" in 1980. Though the disease has died down, the causative virus "variola" has not, as it has been well preserved in two high security laboratories-one in USA and another in Russia. The debate on whether the remaining stocks of the smallpox virus should be destroyed or not is ongoing, and the World Health Assembly (WHA) in 2011 has decided to postpone the review on this debate to the 67th WHA in 2014. A short questionnaire-based inquiry was organized during a one-day stem cell meeting to explore the views of various health care and life science specialists especially students on this aspect. Among the 200 participants of the meeting, only 66 had answered the questionnaire. 60.6% of participants who responded to the questionnaire were for preserving the virus for future reference, while 36.4% of the participants were for destroying the virus considering the magnitude with which it killed millions. However, 3% of the respondents were not able to decide on any verdict. Therefore, this inquiry expresses the view that "what we cannot create, we do not have the right to destroy."

[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.

A brief history of vaccines & vaccination in India.

PubMed

Lahariya, Chandrakant

2014-04-01

The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.

A brief history of vaccines & vaccination in India

PubMed Central

Lahariya, Chandrakant

2014-01-01

The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts. PMID:24927336

TLR3 and TLR9 agonists improve postexposure vaccination efficacy of live smallpox vaccines.

PubMed

Israely, Tomer; Melamed, Sharon; Achdout, Hagit; Erez, Noam; Politi, Boaz; Waner, Trevor; Lustig, Shlomo; Paran, Nir

2014-01-01

Eradication of smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release. Intranasal infection of mice with ectromelia virus (ECTV), a model for human smallpox, is curable by vaccination with a high vaccine dose given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mice were vaccinated postexposure with Vaccinia-Lister, the conventional smallpox vaccine or Modified Vaccinia Ankara, a highly attenuated vaccine in conjunction with TLR3 or TLR9 agonists. We show that co-administration of the TLR3 agonist poly(I:C) even 5 days postexposure conferred protection, avoiding the need to increase the vaccination dose. Efficacious treatments prevented death, ameliorated disease symptoms, reduced viral load and maintained tissue integrity of target organs. Protection was associated with significant elevation of serum IFNα and anti-vaccinia IgM antibodies, modulation of IFNγ response, and balanced activation of NK and T cells. TLR9 agonists (CpG ODNs) were less protective than the TLR3 agonist poly(I:C). We show that activation of type 1 IFN by poly(I:C) and protection is achievable even without co-vaccination, requiring sufficient amount of the viral antigens of the infective agent or the vaccine. This study demonstrated the therapeutic potential of postexposure immune modulation by TLR activation, allowing to alleviate the disease symptoms and to further extend the protective window of postexposure vaccination.

TLR3 and TLR9 Agonists Improve Postexposure Vaccination Efficacy of Live Smallpox Vaccines

PubMed Central

Israely, Tomer; Erez, Noam; Politi, Boaz; Waner, Trevor; Lustig, Shlomo; Paran, Nir

2014-01-01

Eradication of smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release. Intranasal infection of mice with ectromelia virus (ECTV), a model for human smallpox, is curable by vaccination with a high vaccine dose given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mice were vaccinated postexposure with Vaccinia-Lister, the conventional smallpox vaccine or Modified Vaccinia Ankara, a highly attenuated vaccine in conjunction with TLR3 or TLR9 agonists. We show that co-administration of the TLR3 agonist poly(I:C) even 5 days postexposure conferred protection, avoiding the need to increase the vaccination dose. Efficacious treatments prevented death, ameliorated disease symptoms, reduced viral load and maintained tissue integrity of target organs. Protection was associated with significant elevation of serum IFNα and anti-vaccinia IgM antibodies, modulation of IFNγ response, and balanced activation of NK and T cells. TLR9 agonists (CpG ODNs) were less protective than the TLR3 agonist poly(I:C). We show that activation of type 1 IFN by poly(I:C) and protection is achievable even without co-vaccination, requiring sufficient amount of the viral antigens of the infective agent or the vaccine. This study demonstrated the therapeutic potential of postexposure immune modulation by TLR activation, allowing to alleviate the disease symptoms and to further extend the protective window of postexposure vaccination. PMID:25350003

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...

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?

Pharmacokinetic and pharmacodynamic modeling to determine the dose of ST-246 to protect against smallpox in humans.

PubMed

Leeds, Janet M; Fenneteau, Frederique; Gosselin, Nathalie H; Mouksassi, Mohamad-Samer; Kassir, Nastya; Marier, J F; Chen, Yali; Grosenbach, Doug; Frimm, Annie E; Honeychurch, Kady M; Chinsangaram, Jarasvech; Tyavanagimatt, Shanthakumar R; Hruby, Dennis E; Jordan, Robert

2013-03-01

Although smallpox has been eradicated, the United States government considers it a "material threat" and has funded the discovery and development of potential therapeutic compounds. As reported here, the human efficacious dose for one of these compounds, ST-246, was determined using efficacy studies in nonhuman primates (NHPs), together with pharmacokinetic and pharmacodynamic analysis that predicted the appropriate dose and exposure levels to provide therapeutic benefit in humans. The efficacy analysis combined the data from studies conducted at three separate facilities that evaluated treatment following infection with a closely related virus, monkeypox virus (MPXV), in a total of 96 NHPs. The effect of infection on ST-246 pharmacokinetics in NHPs was applied to humans using population pharmacokinetic models. Exposure at the selected human dose of 600 mg is more than 4-fold higher than the lowest efficacious dose in NHPs and is predicted to provide protection to more than 95% of the population.

The generation of CD8+ T-cell population specific for vaccinia virus epitope involved in the antiviral protection against ectromelia virus challenge.

PubMed

Gierynska, Malgorzata; Szulc-Dabrowska, Lidia; Dzieciatkowski, Tomasz; Golke, Anna; Schollenberger, Ada

2015-12-01

Eradication of smallpox has led to cessation of vaccination programs. This has rendered the human population increasingly susceptible not only to variola virus infection but also to infections with other representatives of Poxviridae family that cause zoonotic variola-like diseases. Thus, new approaches for designing improved vaccine against smallpox are required. Discovering that orthopoxviruses, e.g. variola virus, vaccinia virus, ectromelia virus, share common immunodominant antigen, may result in the development of such a vaccine. In our study, the generation of antigen-specific CD8(+) T cells in mice during the acute and memory phase of the immune response was induced using the vaccinia virus immunodominant TSYKFESV epitope and CpG oligodeoxynucleotides as adjuvants. The role of the generated TSYKFESV-specific CD8(+) T cells was evaluated in mice during ectromelia virus infection using systemic and mucosal model. Moreover, the involvement of dendritic cells subsets in the adaptive immune response stimulation was assessed. Our results indicate that the TSYKFESV epitope/TLR9 agonist approach, delivered systemically or mucosally, generated strong CD8(+) T-cell response when measured 10 days after immunization. Furthermore, the TSYKFESV-specific cell population remained functionally active 2 months post-immunization, and gave cross-protection in virally challenged mice, even though the numbers of detectable antigen-specific T cells decreased. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Vaccines for viral diseases with dermatologic manifestations.

PubMed

Brentjens, Mathijs H; Yeung-Yue, Kimberly A; Lee, Patricia C; Tyring, Stephen K

2003-04-01

Vaccines against infectious diseases have been available since the 1800s, when an immunization strategy against smallpox developed by Jenner gained wide acceptance. Until recently, the only vaccination strategies available involved the use of protein-based, whole killed, and attenuated live virus vaccines. These strategies have led to the development of effective vaccines against a variety of diseases with primary or prominent cutaneous manifestations. Effective and safe vaccines now used worldwide include those directed against measles and rubella (now commonly used together with a mumps vaccine as the trivalent MMR), chickenpox, and hepatitis B. The eradication of naturally occurring smallpox remains one of the greatest successes in the history of modern medicine, but stockpiles of live smallpox exist in the United States and Russia. Renewed interest in the smallpox vaccine reflects concerns about a possible bioterrorist threat using this virus. Yellow fever is a hemorrhagic virus endemic to tropical areas of South America and Africa. An effective vaccine for this virus has existed since 1937, and it is used widely in endemic areas of South America, and to a lesser extent in Africa. This vaccine is recommended once every 10 years for people who are traveling to endemic areas. Advances in immunology have led to a greater understanding of immune system function in viral diseases. Progress in genetics and molecular biology has allowed researchers to design vaccines with novel mechanisms of action (eg, DNA, vector, and VLP vaccines). Vaccines have also been designed to specifically target particular viral components, allowing for stimulation of various arms of the immune system as desired. Ongoing research shows promise in prophylactic and therapeutic vaccination for viral infections with cutaneous manifestations. Further studies are necessary before vaccines for HSV, HPV, and HIV become commercially available.

Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required To Survive a Natural Virus Infection.

PubMed

Kaminsky, Lauren W; Sei, Janet J; Parekh, Nikhil J; Davies, Michael L; Reider, Irene E; Krouse, Tracy E; Norbury, Christopher C

2015-10-01

Viruses that spread systemically from a peripheral site of infection cause morbidity and mortality in the human population. Innate myeloid cells, including monocytes, macrophages, monocyte-derived dendritic cells (mo-DC), and dendritic cells (DC), respond early during viral infection to control viral replication, reducing virus spread from the peripheral site. Ectromelia virus (ECTV), an orthopoxvirus that naturally infects the mouse, spreads systemically from the peripheral site of infection and results in death of susceptible mice. While phagocytic cells have a requisite role in the response to ECTV, the requirement for individual myeloid cell populations during acute immune responses to peripheral viral infection is unclear. In this study, a variety of myeloid-specific depletion methods were used to dissect the roles of individual myeloid cell subsets in the survival of ECTV infection. We showed that DC are the primary producers of type I interferons (T1-IFN), requisite cytokines for survival, following ECTV infection. DC, but not macrophages, monocytes, or granulocytes, were required for control of the virus and survival of mice following ECTV infection. Depletion of either plasmacytoid DC (pDC) alone or the lymphoid-resident DC subset (CD8α(+) DC) alone did not confer lethal susceptibility to ECTV. However, the function of at least one of the pDC or CD8α(+) DC subsets is required for survival of ECTV infection, as mice depleted of both populations were susceptible to ECTV challenge. The presence of at least one of these DC subsets is sufficient for cytokine production that reduces ECTV replication and virus spread, facilitating survival following infection. Prior to the eradication of variola virus, the orthopoxvirus that causes smallpox, one-third of infected people succumbed to the disease. Following successful eradication of smallpox, vaccination rates with the smallpox vaccine have significantly dropped. There is now an increasing incidence of zoonotic orthopoxvirus infections for which there are no effective treatments. Moreover, the safety of the smallpox vaccine is of great concern, as complications may arise, resulting in morbidity. Like many viruses that cause significant human diseases, orthopoxviruses spread from a peripheral site of infection to become systemic. This study elucidates the early requirement for innate immune cells in controlling a peripheral infection with ECTV, the causative agent of mousepox. We report that there is redundancy in the function of two innate immune cell subsets in controlling virus spread early during infection. The viral control mediated by these cell subsets presents a potential target for therapies and rational vaccine design. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The global polio eradication initiative: lessons learned and prospects for success.

PubMed

Aylward, Bruce; Tangermann, Rudolf

2011-12-30

Following the rapid progress towards interrupting indigenous wild poliovirus transmission in the Americas in the early 1980s, the Global Polio Eradication Initiative (GPEI) was launched with a resolution of the World Health Assembly (WHA) in 1988. The GPEI built on many lessons learned from smallpox eradication, including the large-scale deployment of technical assistance, implementing agendas of innovation and research and the use of professionally planned and guided advocacy. By the year 2000, the incidence of polio globally had decreased by 99% compared with the estimated >350,000 cases reported from 125 endemic countries in 1988. By 2002, three WHO Regions (the Americas, Western Pacific and European Regions) had been certified polio-free. By 2005, transmission of indigenous wild poliovirus (WPV) had been interrupted in all but 4 'endemic' countries: India, Nigeria, Pakistan and Afghanistan, where eradication efforts effectively stalled. WPV exported from northern Nigeria and northern India subsequently caused >50 outbreaks and paralysed >1500 children in previously polio-free countries across Asia and Africa. In each of the four remaining polio-endemic countries different challenges, or a combination of factors, prevented to build up sufficient levels of population immunity to stop transmission. Consequently, specific strategies were increasingly tailored to each setting. A new 2010-2012 GPEI Strategic Plan was developed which brought together several approaches to overcome the remaining hurdles to eradication, including the large-scale use of bivalent oral poliovaccine (bOPV) in supplementary immunization activities (SIAs). By the end of 2010, the impact of the new GPEI Strategic Plan 2010-2012 was apparent. Compared to 2009, the number of new polio cases in 2010 fell by 95% in both northern Nigeria and northern India, the world's largest remaining reservoirs of indigenous WPVs. By mid-2011, India had not reported a polio case for more than 5 months, and in Nigeria, endemic transmission appeared to be restricted to the north-east and north-west corners of the country. While polio cases due to WPV type 3 were still being detected in west and central Africa, the overall level of WPV3 transmission globally was at an all-time low. Uncontrolled WPV transmission appeared to be restricted to Chad and Pakistan, which increasingly represented the greatest risks to the GPEI. Although insufficient financing continued to be a major concern, political support for completing polio eradication in polio-infected countries was stronger than ever by mid-2011. While continued transmission in some areas, particularly in Pakistan and Chad, still had to be controlled as a matter of urgency, there were real opportunities to achieve new landmarks in polio eradication, especially in the key WPV reservoirs of India and Nigeria, setting the stage for polio to soon follow smallpox into the history books. Copyright © 2011 Elsevier Ltd. All rights reserved.

Childhood vaccination: achievements and challenges.

PubMed

Ndumbe, P

1996-09-01

As the goal of eradicating smallpox was being met, the World Health Organization created its Expanded Programme on Immunisation (EPI) in 1974 and reached its initial goal of achieving full vaccination of 80% of the world's children by 1990. This effort was aided by the creation of "cold chain" delivery systems and resulted in the annual saving of 3.5 million children in less-developed countries. Current EPI vaccination goals include 1) eradication of poliomyelitis by the year 2000, 2) elimination of neonatal tetanus by the year 1995, 3) control of measles and hepatitis B, and 4) immunization of 90% of the world's children 1 year or younger by the year 2000. Goals of the Children's Vaccine Initiative (formed in 1991) include 1) provision of an adequate supply of affordable, safe, and effective vaccines; 2) production of improved and new vaccines; and 3) simplification of the logistics of vaccine delivery. Future challenges are to sustain high vaccination coverage, reach the unreached, achieve proper storage of vaccines and reduce waste, integrate new vaccines into national programs, and achieve vaccine self-sufficiency. The fact that these challenges will be difficult to achieve is illustrated by the situation in Africa where the high immunization levels achieved in 1990 have dropped dramatically. Those who must act to implement immunization programs are health personnel, families, governments, and development partners. In order to achieve equity in health, every child must be reached, governments must be made accountable for programs, health workers must convince families of the importance of vaccination, delivery systems must be in place to take advantage of the new vaccines being delivered, and a multisectoral approach must be taken to assure sustainability.

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...

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.

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.

Vaccines for the 21st century

PubMed Central

Delany, Isabel; Rappuoli, Rino; De Gregorio, Ennio

2014-01-01

In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2–3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure-based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines. PMID:24803000

The end of the beginning: vaccines for the next 25 years.

PubMed

Oxford, J S

2008-11-18

The first virus vaccines against smallpox and rabies proved their effectiveness even before the ultra microscopic viruses had been identified as a new world of infectious agents. To date most antibacterial and antiviral vaccines have not been designed but rather built step by step. Designer vaccines with T cell epitopes and adjuvants which stimulate innate or acquired immune responses to will are now under serious investigation but have yet to impact on the practical world of infection. The latter is not small, with millions of deaths annually in the world from not uncommon microbes such as enterforms, pneumococci, respiratory and hepatitis viruses and HIV. But can vaccines be used in more social directions to control birth or prevent addiction? Polio should join smallpox this year in the pantheon of eradicated viruses. The infectious disease community can then turn attention to hepatitis B. War has been declared on pandemic influenza but with this zoonotic virus containment is key, with vaccines used alongside antivirals and social distancing. Undoubtedly "we have the guns, and now we can finish the job".

Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution.

PubMed

Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K; Carreño, Leandro J; Riedel, Claudia A; Bueno, Susan M; Genzel, Yvonne; Kalergis, Alexis M

2018-01-01

Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety.

Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution

PubMed Central

Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K.; Carreño, Leandro J.; Riedel, Claudia A.; Bueno, Susan M.; Genzel, Yvonne; Kalergis, Alexis M.

2018-01-01

Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety. PMID:29403503

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...

The personal touch: strategies toward personalized vaccines and predicting immune responses to them

PubMed Central

Kennedy, Richard B.; Ovsyannikova, Inna G.; Lambert, Nathaniel D.; Haralambieva, Iana H.; Poland, Gregory A.

2014-01-01

The impact of vaccines on public health and well-being has been profound. Smallpox has been eradicated, polio is nearing eradication, and multiple diseases have been eliminated from certain areas of the world. Unfortunately, we now face diseases such as: hepatitis C, malaria, or tuberculosis, as well as new and re-emerging pathogens for which lack effective vaccines. Empirical approaches to vaccine development have been successful in the past, but may not be up to the current infectious disease challenges facing us. New, directed approaches to vaccine design, development, and testing need to be developed. Ideally these approaches will capitalize on cutting-edge technologies, advanced analytical and modeling strategies, and up-to-date knowledge of both pathogen and host. These approaches will pay particular attention to the causes of inter-individual variation in vaccine response in order to develop new vaccines tailored to the unique needs of individuals and communities within the population. PMID:24702429

Poxvirus viability and signatures in historical relics.

PubMed

McCollum, Andrea M; Li, Yu; Wilkins, Kimberly; Karem, Kevin L; Davidson, Whitni B; Paddock, Christopher D; Reynolds, Mary G; Damon, Inger K

2014-02-01

Although it has been >30 years since the eradication of smallpox, the unearthing of well-preserved tissue material in which the virus may reside has called into question the viability of variola virus decades or centuries after its original occurrence. Experimental data to address the long-term stability and viability of the virus are limited. There are several instances of well-preserved corpses and tissues that have been examined for poxvirus viability and viral DNA. These historical specimens cause concern for potential exposures, and each situation should be approached cautiously and independently with the available information. Nevertheless, these specimens provide information on the history of a major disease and vaccination against it.

Smallpox Inhibitor of Complement Enzymes (SPICE): Dissecting Functional Sites and Abrogating Activity1

PubMed Central

Liszewski, M. Kathryn; Leung, Marilyn K.; Hauhart, Richard; Fang, Celia J.; Bertram, Paula; Atkinson, John P.

2010-01-01

Although smallpox was eradicated as a global illness more than 30 years ago, variola virus and other related pathogenic poxviruses, such as monkeypox, remain potential bioterrorist weapons or could re-emerge as natural infections. Poxviruses express virulence factors that down-modulate the host’s immune system. We previously compared functional profiles of the poxviral complement inhibitors of smallpox, vaccinia, and monkeypox known as SPICE, VCP (or VICE), and MOPICE, respectively. SPICE was the most potent regulator of human complement and attached to cells via glycosaminoglycans. The major goals of the present study were to further characterize the complement regulatory and heparin binding sites of SPICE and to evaluate a mAb that abrogates its function. Using substitution mutagenesis, we established that (1) elimination of the three heparin binding sites severely decreases but does not eliminate glycosaminoglycan binding, (2) there is a hierarchy of activity for heparin binding among the three sites, and (3) complement regulatory sites overlap with each of the three heparin binding motifs. By creating chimeras with interchanges of SPICE and VCP residues, a combination of two SPICE amino acids (H77 plus K120) enhances VCP activity ~200-fold. Also, SPICE residue L131 is critical for both complement regulatory function and accounts for the electrophoretic differences between SPICE and VCP. An evolutionary history for these structure-function adaptations of SPICE is proposed. Finally, we identified and characterized a mAb that inhibits the complement regulatory activity of SPICE, MOPICE, and VCP and thus could be used as a therapeutic agent. PMID:19667083

Are we there yet? Assessing achievement of vaccine-preventable disease goals in WHO's Western Pacific Region.

PubMed

Hennessey, Karen; Schluter, W William; Wang, Xiaojun; Boualam, Liliane; Jee, Youngmee; Mendoza-Aldana, Jorge; Roesel, Sigrun; Diorditsa, Sergey; Ehrenberg, John

2014-07-23

Accelerated disease control goals have long been appreciated for their role in galvanizing commitment and bringing a sense of urgency for disease prevention. WHO's Western Pacific Region has 14 on-going communicable disease reduction goals including 1 targeting eradication, 10 targeting elimination, and 3 control initiatives. These goals cover mother-to-child transmission of HIV, congenital syphilis, tuberculosis, leprosy, five parasitic diseases and four vaccine-preventable diseases (VPD). The initiatives have distinct objectives, approaches, and means in which to measure achievement of the goals. Given the long history and experience with VPD initiatives in the Western Pacific Region, this manuscript focuses on the Region's following initiatives: (1) smallpox eradication, (2) polio eradication, (3) measles elimination, (4) maternal and neonatal tetanus elimination (MNTE), and (5) hepatitis B control. There is good consistency across the Region's VPD initiatives yet a pattern of more robust and representative data requirements, stricter evaluation criteria, and more formal evaluation bodies are linked to the intensity of the goal - with eradication being the peak. On the other end of this spectrum, the Regional hepatitis B control initiative has established efficient and low-cost approaches for measuring impact and evaluating if the goals have been met. Even within the confines of VPD initiatives there are some deviations in use of terminology and comparisons across other disease control initiatives in the Region are provided. Copyright © 2014 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

The contribution of vaccination to global health: past, present and future.

PubMed

Greenwood, Brian

2014-01-01

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO's Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer's disease.

An inquiry into the causes and effects of the variolae (or Cow-pox. 1798).

PubMed

Jenson, Alfred B; Ghim, Shin-Je; Sundberg, John P

2016-03-01

Few papers have had a greater impact on the health of the human species than the simple, yet elegant, observations and clinical trials of Edward Jenner with what was at the time called the Cow Pox. In fact, this was a naturally attenuated rodent (probably rat) pox that could infect horses and, through farriers and farm hands, dairy cattle. While commonly called the Cow Pox at the time, Jenner's transmission studies between humans used infectious materials from horses. His methods provided protection from the serious effects of smallpox infections. In 1977, smallpox was considered to be eradicated, although people continue to be infected by pox viruses from other mammalian species. We consider this to be our 'favorite historical paper' because it emphasizes careful clinical observation followed by relatively simple clinical testing can have a profound influence on human health, even when almost nothing is known about the underlying molecular mechanisms. Continued follow-up with strict attention to detail resulted in a crude but effective way to deal with an epidemic, methods still used today for containing infectious diseases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vaccinia Virus Vaccines: Past, Present and Future

PubMed Central

Jacobs, Bertram L.; Langland, Jeffrey O.; Kibler, Karen V.; Denzler, Karen L.; White, Stacy D.; Holechek, Susan A.; Wong, Shukmei; Huynh, Trung; Baskin, Carole R.

2009-01-01

Vaccinia virus (VACV) has been used more extensively for human immunization than any other vaccine. For almost two centuries, VACV was employed to provide cross-protection against variola virus, the causative agent of smallpox, until the disease was eradicated in the late 1970s. Since that time, continued research on VACV has produced a number of modified vaccines with improved safety profiles. Attenuation has been achieved through several strategies, including sequential passage in an alternative host, deletion of specific genes or genetic engineering of viral genes encoding immunomodulatory proteins. Some highly attenuated third- and fourth-generation VACV vaccines are now being considered for stockpiling against a possible re-introduction of smallpox through bioterrorism. Researchers have also taken advantage of the ability of the VACV genome to accommodate additional genetic material to produce novel vaccines against a wide variety of infectious agents, including a recombinant VACV encoding the rabies virus glycoprotein that is administered orally to wild animals. This review provides an in-depth examination of these successive generations of VACV vaccines, focusing on how the understanding of poxviral replication and viral gene function permits the deliberate modification of VACV immunogenicity and virulence. PMID:19563829

[On the development of the infectology service in Novi Sad].

PubMed

Canak, Grozdana; Vukadinov, Jovan; Brkić, Snezana; Svarc, Daniela; Ruzić, Maja; Kovacević, Nadica; Fabri, Milotka; Jovanović, Jovana; Klasnja, Biljana; Cvjetković, Dejan; Doder, Radoslava; Sević, Sinisa; Turkulov, Vesna; Stefan-Mikić, Sandra; Knezević, Koviljka; Aleksić-Dordević, Mirjana; Preveden, Tomislav

2007-01-01

Infectious diseases are a part of the history of this region. Devastating epidemics of plague, smallpox, and cholera were frequent during the 18th and the 19th centuries. Other infectious diseases were a serious problem as well: alimentary tract infections, scarlet fever, diphtheria, whooping cough. Geographic position, climate, migrations, as well as the tradition and lack of medical staff and medications, affected the frequency and outcome of infections. Patients with infectious diseases were first treated at home. Later, a hospital in Visarion street was opened as an isolation facility and a hospital for homeless patients. The development of science and the education of medical personnel exerted the greatest influence on the control and later treatment of infectious diseases. These measures resulted in the establishment of the first specialized medical institutions in Novi Sad during the cholera outbreak in 1884. After that, temporary pediatric units were organized for the treatment of scarlet fever, diphtheria and smallpox. A ward for infectious diseases was founded in the The Great City Hospital in the second half of the 19th century (1892). The 20th century was a period of control and eradication of infectious diseases in Vojvodina (smallpox, malaria, diphtheria, polio). Nowdays, major infectious deseases include respiratory, alimentary and parasitic infections. However, new diseases are being registered as well - hemorrhagic fevers, Lyme disease, HIV infection. The Infectologic Service in Novi Sad was developed from an Infectology Departement as part of the Departement of Internal Diseases in the new Provincial Hospital (1909) to the independent Departement for Infectious Diseases (1945). Today, Clinic of lnfectious Diseases is an integral part of the Clinical Center of Vojvodina. The Department of Infectious Diseases of the Faculty of Medicine in Novi Sad was founded in 1960. Undergraduate studies started in 1963/64 for students of medicine and in 1978/79 jor dentistry students. Today. the faculty of the Department takes part in undergraduate studies of medicine, dentistry, health care, as well as in graduate programs. The faculty members are also taking part in specialization programs at the Faculty of Medicine. Infectious disease physicians are involved in the activities of the Infectology Section (founded in 1979) of the Society of Physicians of Vojvodine of the Medical Society of Serbia. The first president of the Infectology Section was Dr. Vera Mudrić, professor, infectologists, whereas Dr. Grozdana Canak, professor, was the vice-president from 2000-2004. The Infectology Section collaborates with various national and international societies for infectious diseases.

Challenges and solutions for a rational vaccine design for TB-endemic regions.

PubMed

Gowthaman, Uthaman; Mushtaq, Khurram; Tan, Amabel C; Rai, Pradeep K; Jackson, David C; Agrewala, Javed N

2015-01-01

Vaccines have been successful for global eradication or control of dreaded diseases such as smallpox, diphtheria, tetanus, yellow fever, whooping cough, polio, and measles. Unfortunately, this success has not been achieved for controlling tuberculosis (TB) worldwide. Bacillus Calmette Guérin (BCG) is the only available vaccine against TB. Paradoxically, BCG has deciphered success in the Western world but has failed in TB-endemic areas. In this article, we highlight and discuss the aspects of immunity responsible for controlling Mycobacterium tuberculosis infection and factors responsible for the failure of BCG in TB-endemic countries. In addition, we also suggest strategies that contribute toward the development of successful vaccine in protecting populations where BCG has failed.

A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus

PubMed Central

Das, Sanchita; Rundell, Mark S.; Mirza, Aashiq H.; Pingle, Maneesh R.; Shigyo, Kristi; Garrison, Aura R.; Paragas, Jason; Smith, Scott K.; Olson, Victoria A.; Larone, Davise H.; Spitzer, Eric D.; Barany, Francis; Golightly, Linnie M.

2015-01-01

CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus). PMID:26381398

A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.

PubMed

Das, Sanchita; Rundell, Mark S; Mirza, Aashiq H; Pingle, Maneesh R; Shigyo, Kristi; Garrison, Aura R; Paragas, Jason; Smith, Scott K; Olson, Victoria A; Larone, Davise H; Spitzer, Eric D; Barany, Francis; Golightly, Linnie M

2015-01-01

CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus).

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.

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...

[Old and new prescriptions for infectious diseases and the newest recipes for biomedical products in plants].

PubMed

Koprowski, Hilary

2002-01-01

The three antiviral vaccines discovered in the 18th century (smallpox), 19th century (rabies), and 20th century (polio) share a common feature: none would ever be licensed today for human vaccination. Yet Jenner's smallpox vaccine led to the eradication of smallpox, Pasteur's rabies vaccine represented the first successful post-exposure treatment of people bitten by rabid animals, and polio vaccine administered since its discovery in 1950 is leading to the eradication of polio (in the years 2004-2005) from the earth. However, in the case of rabies, efforts at complete eradication are unrealistic, despite the availability of a very effective vaccine, since rabies, unlike smallpox and polio, is not limited to humans and can infect all domestic and wild mammalian species. Rabies is probably the oldest known infectious disease, yet knowledge of the virus and the disease is far from complete. For instance, the appearance of 24 cases of "cryptic" rabies in the USA, i.e. cases not associated with any bite or scratch, with an incubation period in humans extending 6-8 years, is a puzzling phenomenon that cannot be readily explained. On the other hand, rabies is one of the few strictly neuronal infections and, as such, is an excellent model for the study of neurotropic virus distribution in the brain. Apoptosis induced by a rabies strain expressing high levels of glycoprotein spreads much more slowly through brain tissue than that induced by strains producing lower glycoprotein levels. Attenuated rabies virus constructed to express twice the normal glycoprotein levels is also an excellent antigen for induction of immune responses in the host. Foreign antigens using this vector may also produce highly immunogenic vaccines. Global approach to immunization. Those monitoring the spread of AIDS in many parts of the world know that cost of treatment is one of the major problems in combating the disease. Vaccines against HIV face the same problem. In general, the price of vaccines and sera is exorbitant for the afflicted population in developing countries. In addition, the dearth of syringes, the unavailability of nurses and doctors to administer multiple vaccine injections, and other factors in these countries require a drastic change in current vaccine production approaches. About 12 years ago, plants became vehicles to produce biomedical reagents. Plants can be exposed directly to a construct containing a foreign gene and Agrobacterium to create a transgenic plant that, over several generations, produces the desired product. Alternatively, plants infected with a plant virus (e.g. alfalfa mosaic virus) fused with a foreign gene can propagate the foreign antigen as the virus multiplies. Extraction of the plant virus followed by purification provides the desired biomedical product. Our use of either of these systems has led to the creation of plants producing vaccines, sera, hormones, and other biological reagents. In two clinical trials at the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznań (Poland), volunteers who ingested lettuce expressing hepatitis B vaccine showed hepatitis B antibodies in their sera. In another trial carried out at the Biotechnology Foundation Laboratories in Philadelphia (USA), volunteers ingesting a spinach-rabies vaccine showed an immunological priming effect, since only one injection of commercially available rabies vaccine significantly raised the level of rabies-specific antibodies. Vaccines against HIV gp120 and Tat have been produced in spinach, and a construct of gp120 with the CD4 receptor is now being adapted to this plant. Two types of antibodies against rabies and against colorectal cancer are being produced in tobacco and in lettuce. The suboptimal quality of the currently available anthrax vaccine prompted our efforts to produce the anthrax protective antigen (PA) in tobacco and lettuce. Quite clearly, plants will play a prominent role in producing a variety of biomedical reagents in the future.

Social contact networks and disease eradicability under voluntary vaccination.

PubMed

Perisic, Ana; Bauch, Chris T

2009-02-01

Certain theories suggest that it should be difficult or impossible to eradicate a vaccine-preventable disease under voluntary vaccination: Herd immunity implies that the individual incentive to vaccinate disappears at high coverage levels. Historically, there have been examples of declining coverage for vaccines, such as MMR vaccine and whole-cell pertussis vaccine, that are consistent with this theory. On the other hand, smallpox was globally eradicated by 1980 despite voluntary vaccination policies in many jurisdictions. Previous modeling studies of the interplay between disease dynamics and individual vaccinating behavior have assumed that infection is transmitted in a homogeneously mixing population. By comparison, here we simulate transmission of a vaccine-preventable SEIR infection through a random, static contact network. Individuals choose whether to vaccinate based on infection risks from neighbors, and based on vaccine risks. When neighborhood size is small, rational vaccinating behavior results in rapid containment of the infection through voluntary ring vaccination. As neighborhood size increases (while the average force of infection is held constant), a threshold is reached beyond which the infection can break through partially vaccinated rings, percolating through the whole population and resulting in considerable epidemic final sizes and a large number vaccinated. The former outcome represents convergence between individually and socially optimal outcomes, whereas the latter represents their divergence, as observed in most models of individual vaccinating behavior that assume homogeneous mixing. Similar effects are observed in an extended model using smallpox-specific natural history and transmissibility assumptions. This work illustrates the significant qualitative differences between behavior-infection dynamics in discrete contact-structured populations versus continuous unstructured populations. This work also shows how disease eradicability in populations where voluntary vaccination is the primary control mechanism may depend partly on whether the disease is transmissible only to a few close social contacts or to a larger subset of the population.

Study of adverse events following immunisation with universal and newer vaccines in the Serampore IMA Child Clinic over a period of 7 years.

PubMed

Das, Pradip Kumar

2013-04-01

Immunisation is an important part of childcare practice. It is one of the most beneficial and cost effective measures for the prevention of diseases. From the previous retrospective studies, it was evident that smallpox has been completely eradicated throughout now-a-days with the wholehearted and sincere efforts of healthcare providers by applying efficient and safe vaccine against smallpox, same is true also to polio which is now close to worldwide eradication and measles and rubella are no longer endemic in certain parts of the world. Not only has that with the introduction of safer and more efficient newer vaccines, the incidence of most other vaccine preventable disease of childhood also reduced considerably. The aim of the present study is to estimate the incidence and clinical presentation of adverse events following immunisation with universal and newer vaccines for a period of seven years using prospective active surveillance. Children under the age of 7 years were taken for universal and newer scheduled vaccinations given in the Serampore IMA Child Clinic under the supervision of the clinicians maintaining strictly the guidelines of Expanded Programme of Immunisation (Government of India). This study of adverse events following immunisation in the Serampore IMA Child Clinic confirms that the adverse events such as fever (0.37%), pain and swelling at the site of injection (0.32%0, urticarial rash (0.02%), anaphylactic shock (0.003%) are negligible. There were only two reports of anaphylaxis following preschool and infant schedule vaccines, including measles, mumps and rubella (MMR), Haemophilus influenzae type B vaccines and typhoid vaccines in approximately 52,000 infants received over a period of 7 years starting from 1st April, 2005 to 31st March, 2012 and there were no deaths or longterm effects reported during the post follow-up period in the Serampore IMA Child Clinic.

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 ...

One More Piece in the VACV Ecological Puzzle: Could Peridomestic Rodents Be the Link between Wildlife and Bovine Vaccinia Outbreaks in Brazil?

PubMed Central

Abrahão, Jônatas S.; Guedes, Maria Isabel M.; Trindade, Giliane S.; Fonseca, Flávio G.; Campos, Rafael K.; Mota, Bruno F.; Lobato, Zélia I. P.; Silva-Fernandes, André T.; Rodrigues, Gisele O. L.; Lima, Larissa S.; Ferreira, Paulo C. P.; Bonjardim, Cláudio A.; Kroon, Erna G.

2009-01-01

Background Despite the fact that smallpox eradication was declared by the World Health Organization (WHO) in 1980, other poxviruses have emerged and re-emerged, with significant public health and economic impacts. Vaccinia virus (VACV), a poxvirus used during the WHO smallpox vaccination campaign, has been involved in zoonotic infections in Brazilian rural areas (Bovine Vaccinia outbreaks – BV), affecting dairy cattle and milkers. Little is known about VACV's natural hosts and its epidemiological and ecological characteristics. Although VACV was isolated and/or serologically detected in Brazilian wild animals, the link between wildlife and farms has not yet been elucidated. Methodology/Principal Findings In this study, we describe for the first time, to our knowledge, the isolation of a VACV (Mariana virus - MARV) from a mouse during a BV outbreak. Genetic data, in association with biological assays, showed that this isolate was the same etiological agent causing exanthematic lesions observed in the cattle and human inhabitants of a particular BV-affected area. Phylogenetic analysis grouped MARV with other VACV isolated during BV outbreaks. Conclusion/Significance These data provide new biological and epidemiological information on VACV and lead to an interesting question: could peridomestic rodents be the link between wildlife and BV outbreaks? PMID:19838293

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.

Infectious diseases - new and ancient threats to world health.

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

Olshansky, S. J.; Carnes, B.; Rogers, R. G.

1997-07-01

When smallpox was eradicated from the globe in the late 1970s, many health experts assumed that infectious and parasitic diseases (IPDs) could at long last be conquered. Death rates from infectious and parasitic diseases had declined during the late 19th century and throughout the 20th century thanks to better public health and sanitation as well as medical advances made possible by economic development. During this period, scientists discovered the germ theory of disease, identified the epidemiology and natural history of many infectious diseases, and created a host of potent antibiotic drugs that helped save millions of lives. Medical researchers learnedmore » to identify and cultivate viruses, which led to vaccines for increasing numbers of diseases.« less

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.

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 niche reduction approach: an opportunity for optimal control of infectious diseases in low-income countries?

PubMed

Roche, Benjamin; Broutin, Hélène; Choisy, Marc; Godreuil, Sylvain; de Magny, Guillaume Constantin; Chevaleyre, Yann; Zucker, Jean-Daniel; Breban, Romulus; Cazelles, Bernard; Simard, Frédéric

2014-07-25

During the last century, WHO led public health interventions that resulted in spectacular achievements such as the worldwide eradication of smallpox and the elimination of malaria from the Western world. However, besides major successes achieved worldwide in infectious diseases control, most elimination/control programs remain frustrating in many tropical countries where specific biological and socio-economical features prevented implementation of disease control over broad spatial and temporal scales. Emblematic examples include malaria, yellow fever, measles and HIV. There is consequently an urgent need to develop affordable and sustainable disease control strategies that can target the core of infectious diseases transmission in highly endemic areas. Meanwhile, although most pathogens appear so difficult to eradicate, it is surprising to realize that human activities are major drivers of the current high rate of extinction among upper organisms through alteration of their ecology and evolution, i.e., their "niche". During the last decades, the accumulation of ecological and evolutionary studies focused on infectious diseases has shown that the niche of a pathogen holds more dimensions than just the immune system targeted by vaccination and treatment. Indeed, it is situated at various intra- and inter- host levels involved on very different spatial and temporal scales. After developing a precise definition of the niche of a pathogen, we detail how major advances in the field of ecology and evolutionary biology of infectious diseases can enlighten the planning and implementation of infectious diseases control in tropical countries with challenging economic constraints. We develop how the approach could translate into applied cases, explore its expected benefits and constraints, and we conclude on the necessity of such approach for pathogen control in low-income countries.

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: 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.

Poliovirus Studies during the Endgame of the Polio Eradication Program.

PubMed

Arita, Minetaro

2017-01-24

Since the beginning of Global Polio Eradication Initiative in 1988, poliomyelitis cases caused by wild poliovirus (PV) have been drastically reduced, with only 74 cases reported in 2 endemic countries in 2015. The current limited PV transmission suggests that we are in the endgame of the polio eradication program. However, specific challenges have emerged in the endgame, including tight budget, switching of the vaccines, and changes in biorisk management of PV. To overcome these challenges, several PV studies have been implemented in the eradication program. Some of the responses to the emerging challenges in the polio endgame might be valuable in other infectious diseases eradication programs. Here, I will review challenges that confront the polio eradication program and current research to address these challenges.

Smallpox Still Haunts Scientists: Results of a Questionnaire-Based Inquiry on the Views of Health Care and Life Science Experts and Students on Preserving the Remaining Variola Virus Stocks

PubMed Central

Srinivasan, Thangavelu; Dedeepiya, Vidyasagar Devaprasad; John, Sudhakar; Senthilkumar, Rajappa; Reena, Helen C.; Rajendran, Paramasivam; Balamurugan, Madasamy; Kurosawa, Gene; Iwasaki, Masaru; Abraham, Samuel J. K.

2013-01-01

The World Health Organization (WHO) declared eradication of the dreadful disease “smallpox” in 1980. Though the disease has died down, the causative virus “variola” has not, as it has been well preserved in two high security laboratories—one in USA and another in Russia. The debate on whether the remaining stocks of the smallpox virus should be destroyed or not is ongoing, and the World Health Assembly (WHA) in 2011 has decided to postpone the review on this debate to the 67th WHA in 2014. A short questionnaire-based inquiry was organized during a one-day stem cell meeting to explore the views of various health care and life science specialists especially students on this aspect. Among the 200 participants of the meeting, only 66 had answered the questionnaire. 60.6% of participants who responded to the questionnaire were for preserving the virus for future reference, while 36.4% of the participants were for destroying the virus considering the magnitude with which it killed millions. However, 3% of the respondents were not able to decide on any verdict. Therefore, this inquiry expresses the view that “what we cannot create, we do not have the right to destroy.” PMID:23970838

Game theory of pre-emptive vaccination before bioterrorism or accidental release of smallpox.

PubMed

Molina, Chai; Earn, David J D

2015-06-06

Smallpox was eradicated in the 1970s, but new outbreaks could be seeded by bioterrorism or accidental release. Substantial vaccine-induced morbidity and mortality make pre-emptive mass vaccination controversial, and if vaccination is voluntary, then there is a conflict between self- and group interests. This conflict can be framed as a tragedy of the commons, in which herd immunity plays the role of the commons, and free-riding (i.e. not vaccinating pre-emptively) is analogous to exploiting the commons. This game has been analysed previously for a particular post-outbreak vaccination scenario. We consider several post-outbreak vaccination scenarios and compare the expected increase in mortality that results from voluntary versus imposed vaccination. Below a threshold level of post-outbreak vaccination effort, expected mortality is independent of the level of response effort. A lag between an outbreak starting and a response being initiated increases the post-outbreak vaccination effort necessary to reduce mortality. For some post-outbreak vaccination scenarios, even modest response lags make it impractical to reduce mortality by increasing post-outbreak vaccination effort. In such situations, if decreasing the response lag is impossible, the only practical way to reduce mortality is to make the vaccine safer (greater post-outbreak vaccination effort leads only to fewer people vaccinating pre-emptively). © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Vaccine herd effect

PubMed Central

Kim, Tae Hyong; Johnstone, Jennie; Loeb, Mark

2011-01-01

Vaccination ideally protects susceptible populations at high risk for complications of the infection. However, vaccines for these subgroups do not always provide sufficient effectiveness. The herd effect or herd immunity is an attractive way to extend vaccine benefits beyond the directly targeted population. It refers to the indirect protection of unvaccinated persons, whereby an increase in the prevalence of immunity by the vaccine prevents circulation of infectious agents in susceptible populations. The herd effect has had a major impact in the eradication of smallpox, has reduced transmission of pertussis, and protects against influenza and pneumococcal disease. A high uptake of vaccines is generally needed for success. In this paper we aim to provide an update review on the herd effect, focusing on the clinical benefit, by reviewing data for specific vaccines. PMID:21604922

Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines.

PubMed

Meseda, Clement A; Atukorale, Vajini; Kuhn, Jordan; Schmeisser, Falko; Weir, Jerry P

2016-01-01

The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited.

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.

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

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.

The Barberry Eradication Program in Minnesota for Stem Rust Control: A Case Study.

PubMed

Peterson, Paul D

2018-06-11

The Barberry Eradication Program was an unprecedented federal and state cooperative plant disease control campaign between 1918 and the late 1970s to remove common barberry (Berberis vulgaris), the alternate host of Puccinia graminis f. sp. tritici, from the major centers of wheat production in the United States. Eradication of barberry has been credited with helping to reduce stem rust of wheat to a minor problem in the United States by the end of the campaign. The Barberry Eradication Program has also been viewed as a model for successful eradication based on its robust leadership, effective publicity and public cooperation, forceful quarantine laws, and adaptive eradication methods and procedures employed in its field operations. The Barberry Eradication Program was particularly successful because of its leaders' ability to adapt to changing internal and external conditions over time. The program lasted nearly a century, extending through two world wars and the Great Depression, with each period producing unique challenges. Because of its central role, barberry eradication in Minnesota offers an excellent case study to examine how the program developed over time and ultimately achieved success. Expected final online publication date for the Annual Review of Phytopathology Volume 56 is August 25, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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.

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.

Viral vaccines and their manufacturing cell substrates: New trends and designs in modern vaccinology.

PubMed

Rodrigues, Ana F; Soares, Hugo R; Guerreiro, Miguel R; Alves, Paula M; Coroadinha, Ana S

2015-09-01

Vaccination is one of the most effective interventions in global health. The worldwide vaccination programs significantly reduced the number of deaths caused by infectious agents. A successful example was the eradication of smallpox in 1979 after two centuries of vaccination campaigns. Since the first variolation administrations until today, the knowledge on immunology has increased substantially. This knowledge combined with the introduction of cell culture and DNA recombinant technologies revolutionized vaccine design. This review will focus on vaccines against human viral pathogens, recent developments on vaccine design and cell substrates used for their manufacture. While the production of attenuated and inactivated vaccines requires the use of the respective permissible cell substrates, the production of recombinant antigens, virus-like particles, vectored vaccines and chimeric vaccines requires the use - and often the development - of specific cell lines. Indeed, the development of novel modern viral vaccine designs combined with, the stringent safety requirements for manufacture, and the better understanding on animal cell metabolism and physiology are increasing the awareness on the importance of cell line development and engineering areas. A new era of modern vaccinology is arriving, offering an extensive toolbox to materialize novel and creative ideas in vaccine design and its manufacture. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular Mechanisms of Bacterial Pathogenicity

NASA Astrophysics Data System (ADS)

Fuchs, Thilo Martin

Cautious optimism has arisen over recent decades with respect to the long struggle against bacteria, viruses, and parasites. This has been offset, however, by a fatal complacency stemming from previous successes such as the development of antimicrobial drugs, the eradication of smallpox, and global immunization programs. Infectious diseases nevertheless remain the world's leading cause of death, killing at least 17 million persons annually [61]. Diarrheal diseases caused by Vibrio cholerae or Shigella dysenteriae kill about 3 million persons every year, most of them young children: Another 4 million die of tuberculosis or tetanus. Outbreaks of diphtheria in Eastern Europe threatens the population with a disease that had previously seemed to be overcome. Efforts to control infectious diseases more comprehensively are undermined not only by socioeconomic conditions but also by the nature of the pathogenic organisms itself; some isolates of Staphylococcus aureus and Enterobacter have become so resistant to drugs by horizontal gene transfer that they are almost untreatable. In addition, the mechanism of genetic variability helps pathogens to evade the human immune system, thus compromising the development of powerful vaccines. Therefore detailed knowledge of the molecular mechanisms of microbial pathogenicity is absolutely necessary to develop new strategies against infectious diseases and thus to lower their impact on human health and social development.

An overview of the development of remote sensing techniques for the screwworm eradication program

NASA Technical Reports Server (NTRS)

Barnes, C. M.; Forsberg, F. C.

1975-01-01

The current status of remote sensing techniques developed for the screwworm eradication program of the Mexican-American Screwworm Eradication Commission was reported. A review of the type of data and equipment used in the program is presented. Future applications of remote sensing techniques are considered.

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...

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family

PubMed Central

2010-01-01

Background Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. Findings De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Conclusions Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein. PMID:20979600

Glycosaminoglycans mediate retention of the poxvirus type I interferon binding protein at the cell surface to locally block interferon antiviral responses

PubMed Central

Montanuy, Imma; Alejo, Ali; Alcami, Antonio

2011-01-01

Eradication of smallpox was accomplished 30 yr ago, but poxviral infections still represent a public health concern due to the potential release of variola virus or the emergence of zoonotic poxviruses, such as monkeypox virus. A critical determinant of poxvirus virulence is the inhibition of interferons (IFNs) by the virus-encoded type I IFN-binding protein (IFNα/βBP). This immunomodulatory protein is secreted and has the unique property of interacting with the cell surface in order to prevent IFN-mediated antiviral responses. However, the mechanism of its attachment to the cell surface remains unknown. Using surface plasmon resonance and cell-binding assays, we report that the IFNα/βBP from vaccinia virus, the smallpox vaccine, interacts with cell surface glycosaminoglycans (GAGs). Analysis of the contribution of different regions of the protein to cell surface binding demonstrated that clusters of basic residues in the first immunoglobulin domain mediate GAG interactions. Furthermore, mutation of the GAG-interaction motifs does not affect its IFN-binding and -blocking capacity. Functional conservation of GAG-binding sites is demonstrated for the IFNα/βBP from variola and monkeypox viruses, extending our understanding of immune modulation by the most virulent human poxviruses. These results are relevant for the design of improved vaccines and intervention strategies.—Montanuy, I., Alejo, A., Alcami, A. Glycosaminoglycans mediate retention of the poxvirus type I interferon binding protein at the cell surface to locally block interferon antiviral responses. PMID:21372110

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family.

PubMed

Antonets, Denis V; Nepomnyashchikh, Tatyana S; Shchelkunov, Sergei N

2010-10-27

Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.

Production of recombinant subunit vaccines: protein immunogens, live delivery systems and nucleic acid vaccines.

PubMed

Liljeqvist, S; Ståhl, S

1999-07-30

The first scientific attempts to control an infectious disease can be attributed to Edward Jenner, who, in 1796 inoculated an 8-year-old boy with cowpox (vaccinia), giving the boy protection against subsequent challenge with virulent smallpox. Thanks to the successful development of vaccines, many major diseases, such as diphtheria, poliomyelitis and measles, are nowadays kept under control, and in the case of smallpox, the dream of eradication has been fulfilled. Yet, there is a growing need for improvements of existing vaccines in terms of increased efficacy and improved safety, besides the development of completely new vaccines. Better technological possibilities, combined with increased knowledge in related fields, such as immunology and molecular biology, allow for new vaccination strategies. Besides the classical whole-cell vaccines, consisting of killed or attenuated pathogens, new vaccines based on the subunit principle, have been developed, e.g. the Hepatitis B surface protein vaccine and the Haemophilus influenzae type b vaccine. Recombinant techniques are now dominating in the strive for an ideal vaccine, being safe and cheap, heat-stable and easy to administer, preferably single-dose, and capable of inducing broad immune response with life-long memory both in adults and in infants. This review will describe different recombinant approaches used in the development of novel subunit vaccines, including design and production of protein immunogens, the development of live delivery systems and the state-of-the-art for nucleic acids vaccines.

[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.

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...

[A comparative study on Koii (public doctor) system and its effect on public health in colonial Taiwan and Korea].

PubMed

Moon, Myungki

2014-08-01

Koii(Public Doctor) System introduced into Taiwan in 1896 for the purpose of filling up medical vacuum of rural area and therefore spreading modern medical system all over Taiwan, was transplanted in 1913 into Colonial Korea for the same purpose. In terms of system itself Koii system in both areas were almost the same, but quite different in practices. First, Koiis in Taiwan was forced to write concrete medical report every month on the medical situation in the area under jurisdiction, whereas to those in Korea writing monthly report was not so compulsory. This difference resulted in some gaps in the quality of medical statistics of the two areas. Second, Unlike their counterparts in Korea, Koiis in Taiwan organized their own associations both locally and nationally and it helped to build up their own networks and share informations on medical situation including informations on infectious diseases. Third, Koiis in Taiwan formed more harmonious relationship between Taiwanese Police than their counterparts in Korea, which helped them to execute various medical activities in more comfortable environment. Taiwanese People went to medical institutions a lot more frequently than Korean People, and this difference was basically derived from the quite different density of Koii assignment in both areas. Korean People had to spend more time and money to utilize modern medical institutions than Taiwanese People did. The different density of Koii assignment also affected the results of prevention and eradication of infectious diseases; in Taiwan plague and small-pox has been successfully controled, whereas Chosun Government general was not so successful in controling infectious diseases including small-pox. Small-pox infected in Korea was about 6 times to Taiwan, and the number of death by small-pox was 9 times to Taiwan. One of the keys to this difference is the different role of Koiis. In Korea, Koiis could do little thing about infectious diseases mainly because of manpower shortage, thus shifting their duties like vaccination onto police officers who was inevitably inferior to doctors in medical terms, whereas vaccination was led by Koiis in Taiwan, with the help of police officers and traditional doctors. The difference between Korea and Taiwan in terms of Koii system and its effect implies that public health network in colonial Taiwan was better organized and more stable than that in colonial Korea, and therefore we should be careful about applying the concept of disciplinary power or modernization theory to colonial medical history of Korea.

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.

Implication of nilgai antelope (Artiodactyla: Bovidae) in reinfestations of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) in South Texas: A review and update

USDA-ARS?s Scientific Manuscript database

The Cattle Fever Tick Eradication Program was the first parasite eradication program of veterinary importance in the United States and is considered to be one of the greatest disease eradication programs of all time. The program’s utilization of pasture vacation of cattle and dipping of cattle in ac...

Immunization update and hot topics in clinical immunology: how does this relate to my practice?

PubMed

Bellanti, Joseph A

2006-01-01

The prevention of infectious diseases by the use of vaccines represents one of medicine's greatest triumphs during the 20th century. This era has witnessed the global eradication of smallpox as a result of Jennerian cowpox vaccination, the elimination of paralytic poliomyelitis from the western hemisphere, and within 5-10 years the anticipated eradication of poliomyelitis worldwide as a result of the poliovirus vaccines. Next slated for worldwide eradication is measles, the great killer of infants and children, which each year extracts a global mortality of one million victims. Throughout the 20th century the percutaneous (i.e., subcutaneous or intramuscular) route has almost exclusively been the preferred way to administer vaccines. However, as a result of several important scientific discoveries made during the 20th century, including new tissue-culturing techniques, the development of recombinant DNA technology, and genetic sequencing, a whole new generation of tailor-made modern vaccines has become available, including DNA vaccines and transgenic plant vaccines. Moreover, it became apparent that alternative routes of administration of vaccines, such as by aerosol immunization might be more appropriate and more effective than immunization via the parenteral route. The overall success in vaccine development, however, has not been without cost. For every new vaccine that has been developed, an adverse effect has been seen. Thus, although modern vaccines are extremely safe and effective, they are neither completely safe nor completely effective. The goal of vaccine development, therefore, is to achieve the highest degree of protection and the lowest rate of adverse effects. This paper describes some of the recent advances in vaccine development and will focus on some hot topics relating to the recent development and use of respiratory aerosolized vaccines.

Suppression of Poxvirus Replication by Resveratrol.

PubMed

Cao, Shuai; Realegeno, Susan; Pant, Anil; Satheshkumar, Panayampalli S; Yang, Zhilong

2017-01-01

Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV), the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.

Identifying and Reducing Remaining Stocks of Rinderpest Virus

PubMed Central

Visser, Dawid; Evans, Brian; Vallat, Bernard

2015-01-01

In 2011, the world was declared free from rinderpest, one of the most feared and devastating infectious diseases of animals. Rinderpest is the second infectious disease, after smallpox, to have been eradicated. However, potentially infectious rinderpest virus material remains widely disseminated among research and diagnostic facilities across the world and poses a risk for disease recurrence should it be released. Member Countries of the World Organisation for Animal Health and the Food and Agricultural Organization of the United Nations are committed to destroying remaining stocks of infectious material or ensuring that it is stored under international supervision in a limited number of approved facilities. To facilitate this commitment and maintain global freedom from rinderpest, World Organisation for Animal Health Member Countries must report annually on rinderpest material held in their countries. The first official surveys, conducted during 2013–2015, revealed that rinderpest material was stored in an unacceptably high number of facilities and countries. PMID:26584400

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.

Boll weevil eradication: a model for sea lamprey control?

USGS Publications Warehouse

Smith, James W.; Swink, William D.

2003-01-01

Invasions of boll weevil (Anthonomus grandis) into the United States and sea lamprey (Petromyzon marinus) into the Great Lakes were similar in many ways. Important species (American cotton, Gossypium hirsutum, and lake trout, Salvelinus namaycush) and the industries they supported were negatively affected. Initial control efforts were unsuccessful until pesticides and application technologies were developed. For boll weevils, controls relying on pesticides evolved into an integrated program that included recommended farming practices and poisoned baits. However, the discovery of a boll weevil sex pheromone in 1964 allowed adoption of an ongoing program of eradication. Despite opposition over concept and cost, insecticides, pheromone traps, poisoned baits, and approved farming practices were used to eradicate boll weevils from Virginia, North Carolina, South Carolina, Georgia, Florida, and Alabama by 1999. Using the working back approach along the path of the original invasion, eradication was nearly completed by 2002 in Mississippi and eradication programs were underway in Arkansas, Tennessee, Oklahoma, Louisiana, and parts of Texas. Insecticide use for cotton production decreased 50 to 90%, and cotton yields and farm income increased an average of 78 kg/ha and $190 U.S./ha in areas where boll weevils were eradicated. For sea lampreys, integrated management uses lampricides, barriers to migration, trapping, and release of sterilized males. Although sea lamprey eradication is not currently feasible, recent research on larval and sex pheromones might provide the tools to make it possible. A successful eradication program for sea lampreys starting in Lake Superior and expanding to the lower Great Lakes would ultimately provide huge ecological and economic benefits by eliminating lampricide applications, removing barriers that block teleost fishes, and facilitating the recovery of lake trout. Should the opportunity arise, the concept of sea lamprey eradication should not be rejected out of hand. The successful boll weevil eradication program shows that sea lamprey eradication might be achievable.

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

[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.

Vaccination with a codon-optimized A27L-containing plasmid decreases virus replication and dissemination after vaccinia virus challenge.

PubMed

Martínez, Osmarie; Bravo Cruz, Ariana; Santos, Saritza; Ramírez, Maite; Miranda, Eric; Shisler, Joanna; Otero, Miguel

2017-10-20

Smallpox is a disease caused by Variola virus (VARV). Although eradicated by WHO in 1980, the threat of using VARV on a bioterror attack has increased. The current smallpox vaccine ACAM2000, which consists of live vaccinia virus (VACV), causes complications in individuals with a compromised immune system or with previously reported skin diseases. Thus, a safer and efficacious vaccine needs to be developed. Previously, we reported that our virus-free DNA vaccine formulation, a pVAX1 plasmid encoding codon-optimized VACV A27L gene (pA27LOPT) with and without Imiquimod adjuvant, stimulates A27L-specific production of IFN-γ and increases humoral immunity 7days post-vaccination. Here, we investigated the immune response of our novel vaccine by measuring the frequency of splenocytes producing IFN-γ by ELISPOT, the TH1 and TH2 cytokine profiles, and humoral immune responses two weeks post-vaccination, when animals were challenged with VACV. In all assays, the A27-based DNA vaccine conferred protective immune responses. Specifically, two weeks after vaccination, mice were challenged intranasally with vaccinia virus, and viral titers in mouse lungs and ovaries were significantly lower in groups immunized with pA27LOPT and pA27LOPT+Imiquimod. These results demonstrate that our vaccine formulation decreases viral replication and dissemination in a virus-free DNA vaccine platform, and provides an alternative towards a safer an efficacious vaccine. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Effect of major epidemics on cultural awareness].

PubMed

Spitzy, K H

1995-01-01

Mankind has been stricken with "major" epidemic diseases throughout its history. The most serious among them immediately threaten man's life e.g. plague, cholera, smallpox, typhus, and dysentery, besides, there are others which take a slower course e.g. lues, leprosy, leishmaniasis, tuberculosis, and malaria. Yet, the "lesser" epidemic diseases like diphtheria, scarlet fever, mumps, pneumococcosis, influenza, and most recently AIDS may also turn into "major" ones. Originally, man exclusively depended on his genetic makeup for protection, and being particularly prone to attacks of disease he was subject to natural selection. Thus, only one human species survived, the homo sapiens. Interbreeding achieved biologic adaptation and created a balanced genetic polymorphism. Advancing in his degree of civilization, man formed groups, developed clothing, fire, houses, and tools, and his increasing cultural awareness allowed him to migrate from the tropical climates to more temperate, and less disease-infested zones. Immigration and wars, and the accompanying infections jeopardized and diminished entire populations and eradicated highly developed cultures like that of the American Indians. The plague, coming from Asia, and lues, from America, as well as cholera, influenza, and smallpox spread around the whole globe. Fear and terror led to irrational conclusions and triggered persecutions. The attitude of accepting disease as a God-sent fate (Hiob), or a God-sent punishment suppressed reasonable measures against disease. The necessary official measures have increasingly restricted liberty, and this patronizing treatment needs to be opposed with a higher sense of responsibility. Medical art has developed from more healing towards prophylactic and predictive medicine, which prognosticates the individual susceptibility to particular infections, and other risk factors.

Effect on time in quarantine of the choice of program for eradication of footrot from 196 sheep flocks in southern New South Wales.

PubMed

Mills, K; McClenaughan, P; Morton, A; Alley, D; Lievaart, J; Windsor, P A; Egerton, J R

2012-01-01

To identify and compare programs for eradicating virulent footrot (VFR) chosen by owners of quarantined sheep flocks in southern New South Wales. Data from 196 sheep flocks in the Wagga Wagga and Young Rural Lands Protection Boards were used to determine the program chosen, the influence of flock size on the program chosen and the effects of the program chosen and the use of contractors on the time in quarantine. The most popular programs in flocks using a single program were: total destocking (61/173; 35.3%) and inspection and culling of affected animals (71/173; 41.0%). Treatment of known infected animals was chosen in 41 flocks and of those, 10 (5.8%) used antibiotics for treatment and 31 (17.9%) used foot-bathing. Combined programs were used in 23 flocks and in 10 flocks a change of program occurred before eradication was achieved. The choice of program was, to some extent, affected by flock size, with owners of small flocks (<500 sheep) more likely to destock. The chosen program strongly influenced the time in quarantine, the shortest time being for destocking (mean 284 days), followed by culling of infected sheep (395 days), treatment with antibiotics (433 days) and finally foot-bathing (502 days). Time in quarantine was significantly shorter when contractors were used. All the options chosen led to the eradication of VFR. However, in this sample both the choice of program and the use of contractors influenced the time taken to achieve eradication and therefore the time in quarantine. Based on time in quarantine, foot-bathing was the least desirable option for the eradication of VFR because of the significantly greater time involved, perpetuation of risk to neighbours and increased cost of inspections. These findings were derived from flocks that were quarantined, but they are relevant to all flock owners considering eradication of VFR. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

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.

Vaccines today, vaccines tomorrow: a perspective.

PubMed

Loucq, Christian

2013-01-01

Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.

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.

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.

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...

The potential impact of immunization campaign budget re-allocation on global eradication of paediatric infectious diseases

PubMed Central

2011-01-01

Background The potential benefits of coordinating infectious disease eradication programs that use campaigns such as supplementary immunization activities (SIAs) should not be over-looked. One example of a coordinated approach is an adaptive "sequential strategy": first, all annual SIA budget is dedicated to the eradication of a single infectious disease; once that disease is eradicated, the annual SIA budget is re-focussed on eradicating a second disease, etc. Herd immunity suggests that a sequential strategy may eradicate several infectious diseases faster than a non-adaptive "simultaneous strategy" of dividing annual budget equally among eradication programs for those diseases. However, mathematical modeling is required to understand the potential extent of this effect. Methods Our objective was to illustrate how budget allocation strategies can interact with the nonlinear nature of disease transmission to determine time to eradication of several infectious diseases under different budget allocation strategies. Using a mathematical transmission model, we analyzed three hypothetical vaccine-preventable infectious diseases in three different countries. A central decision-maker can distribute funding among SIA programs for these three diseases according to either a sequential strategy or a simultaneous strategy. We explored the time to eradication under these two strategies under a range of scenarios. Results For a certain range of annual budgets, all three diseases can be eradicated relatively quickly under the sequential strategy, whereas eradication never occurs under the simultaneous strategy. However, moderate changes to total SIA budget, SIA frequency, order of eradication, or funding disruptions can create disproportionately large differences in the time and budget required for eradication under the sequential strategy. We find that the predicted time to eradication can be very sensitive to small differences in the rate of case importation between the countries. We also find that the time to eradication of all three diseases is not necessarily lowest when the least transmissible disease is targeted first. Conclusions Relatively modest differences in budget allocation strategies in the near-term can result in surprisingly large long-term differences in time required to eradicate, as a result of the amplifying effects of herd immunity and the nonlinearities of disease transmission. More sophisticated versions of such models may be useful to large international donors or other organizations as a planning or portfolio optimization tool, where choices must be made regarding how much funding to dedicate to different infectious disease eradication efforts. PMID:21955853

The potential impact of immunization campaign budget re-allocation on global eradication of paediatric infectious diseases.

PubMed

Fitzpatrick, Tiffany; Bauch, Chris T

2011-09-28

The potential benefits of coordinating infectious disease eradication programs that use campaigns such as supplementary immunization activities (SIAs) should not be over-looked. One example of a coordinated approach is an adaptive "sequential strategy": first, all annual SIA budget is dedicated to the eradication of a single infectious disease; once that disease is eradicated, the annual SIA budget is re-focussed on eradicating a second disease, etc. Herd immunity suggests that a sequential strategy may eradicate several infectious diseases faster than a non-adaptive "simultaneous strategy" of dividing annual budget equally among eradication programs for those diseases. However, mathematical modeling is required to understand the potential extent of this effect. Our objective was to illustrate how budget allocation strategies can interact with the nonlinear nature of disease transmission to determine time to eradication of several infectious diseases under different budget allocation strategies. Using a mathematical transmission model, we analyzed three hypothetical vaccine-preventable infectious diseases in three different countries. A central decision-maker can distribute funding among SIA programs for these three diseases according to either a sequential strategy or a simultaneous strategy. We explored the time to eradication under these two strategies under a range of scenarios. For a certain range of annual budgets, all three diseases can be eradicated relatively quickly under the sequential strategy, whereas eradication never occurs under the simultaneous strategy. However, moderate changes to total SIA budget, SIA frequency, order of eradication, or funding disruptions can create disproportionately large differences in the time and budget required for eradication under the sequential strategy. We find that the predicted time to eradication can be very sensitive to small differences in the rate of case importation between the countries. We also find that the time to eradication of all three diseases is not necessarily lowest when the least transmissible disease is targeted first. Relatively modest differences in budget allocation strategies in the near-term can result in surprisingly large long-term differences in time required to eradicate, as a result of the amplifying effects of herd immunity and the nonlinearities of disease transmission. More sophisticated versions of such models may be useful to large international donors or other organizations as a planning or portfolio optimization tool, where choices must be made regarding how much funding to dedicate to different infectious disease eradication efforts.

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

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...

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...

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 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 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

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...

Lessons Learned and Legacy of the Stop Transmission of Polio Program.

PubMed

Kerr, Yinka; Mailhot, Melinda; Williams, Alford A J; Swezy, Virginia; Quick, Linda; Tangermann, Rudolf H; Ward, Kirsten; Benke, Amalia; Callaghan, Anna; Clark, Kathleen; Emery, Brian; Nix, Jessica; Aydlotte, Eleanor; Newman, Charlotte; Nkowane, Benjamin

2017-07-01

In 1988, the by the World Health Assembly established the Global Polio Eradication Initiative, which consisted of a partnership among the World Health Organization (WHO), Rotary International, the Centers for Disease Control and Prevention (CDC), and the United Nations Children's Fund. By 2016, the annual incidence of polio had decreased by >99.9%, compared with 1988, and at the time of writing, only 3 countries in which wild poliovirus circulation has never been interrupted remain: Afghanistan, Nigeria, and Pakistan. A key strategy for polio eradication has been the development of a skilled and deployable workforce to implement eradication activities across the globe. In 1999, the Stop Transmission of Polio (STOP) program was developed and initiated by the CDC, in collaboration with the WHO, to train and mobilize additional human resources to provide technical assistance to polio-endemic countries. STOP has also informed the development of other public health workforce capacity to support polio eradication efforts, including national STOP programs. In addition, the program has diversified to address measles and rubella elimination, data management and quality, and strengthening routine immunization programs. This article describes the STOP program and how it has contributed to polio eradication by building global public health workforce capacity. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

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

Impact of imitation processes on the effectiveness of ring vaccination.

PubMed

Wells, Chad R; Tchuenche, Jean M; Meyers, Lauren Ancel; Galvani, Alison P; Bauch, Chris T

2011-11-01

Ring vaccination can be a highly effective control strategy for an emerging disease or in the final phase of disease eradication, as witnessed in the eradication of smallpox. However, the impact of behavioural dynamics on the effectiveness of ring vaccination has not been explored in mathematical models. Here, we analyze a series of stochastic models of voluntary ring vaccination. Contacts of an index case base vaccinating decisions on their own individual payoffs to vaccinate or not vaccinate, and they can also imitate the behaviour of other contacts of the index case. We find that including imitation changes the probability of containment through ring vaccination considerably. Imitation can cause a strong majority of contacts to choose vaccination in some cases, or to choose non-vaccination in other cases-even when the equivalent solution under perfectly rational (non-imitative) behaviour yields mixed choices. Moreover, imitation processes can result in very different outcomes in different stochastic realizations sampled from the same parameter distributions, by magnifying moderate tendencies toward one behaviour or the other: in some realizations, imitation causes a strong majority of contacts not to vaccinate, while in others, imitation promotes vaccination and reduces the number of secondary infections. Hence, the effectiveness of ring vaccination can depend significantly and unpredictably on imitation processes. Therefore, our results suggest that risk communication efforts should be initiated early in an outbreak when ring vaccination is to be applied, especially among subpopulations that are heavily influenced by peer opinions.

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.

100 years poliovirus: from discovery to eradication. A meeting report.

PubMed

Skern, Tim

2010-09-01

Just over hundred years ago, Karl Landsteiner and Erwin Popper identified a virus, later termed poliovirus, as the causative agent of poliomyelitis. This groundbreaking discovery simultaneously provided the basis for the measures that today prevent the outbreaks of the terrible epidemics caused by poliovirus. In 1988, the WHO started its eradication program to eliminate the virus from the planet. The symposium celebrated the discovery of poliovirus and discussed our current state of knowledge of poliovirus biology. Prospects for the eradication program were evaluated, with particular emphasis being placed on why certain countries still have not succeeding in interrupting wild-type transmission of poliovirus. Discussion also centred on the role of inactivated poliovirus vaccines in the eradication program and the maintenance of a poliovirus-free world, whenever this goal should be achieved.

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...

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.

Public health measures for prevention and control of AIDS.

PubMed Central

Hopkins, D R

1987-01-01

The grave challenge posed by the recent pandemic of acquired immunodeficiency syndrome is not the first time mankind has faced such a threat. Useful lessons may be drawn from the successful global Smallpox Eradication Program and applied to the current campaign in the areas of surveillance, strategy, operations, and evaluation. The most important epidemiologic characteristic of this new infection is the unprecedented observation that virtually all asymptomatic infected persons are infectious and will remain so indefinitely. In combatting this infection we should concentrate our efforts in the United States on preventing transmission from the estimated 1.5 million persons who are already infected. We must make the best use we can of all the tools we already have: public information, health education, counseling and serologic testing of persons at high risk, treatment and prevention of intravenous drug abuse, and serologic screening of organ and tissue donors. Adequate confidentiality of test results needs to be secured in order to promote voluntary testing as an important means of achieving behavorial change among persons who are most likely to have been exposed to the infections. Persons whose sexual or drug abuse behavior puts them at higher risk of infection are the highest priority target group. They should be sought at every opportunity, whether seen in public clinics or private practice, and advised to be tested. In order to focus on preventing sexual, parenteral, and perinatal transmission of the virus we must avoid numerous potential distractions and irrelevant issues: we don't have time for them. PMID:3116575

[AIDS in Russia. It is still possible to stop the epidemic. Interview with Dr. A.P. Koslov].

PubMed

Bertrand, P

1996-01-01

According to A.P. Koslov, president of the Fourth International Conference on AIDS, Cancer, and Associated Diseases held in Russia in 1996, the conference represents the first high level discussion of AIDS risk management in Russia. Russia has a strong potential for development of a vaccine, having been a key player in the smallpox eradication program in the late 1950s. Conditions are difficult at present, but it is possible that Russia will be able to develop a practical vaccine for distribution in the Third World. Efforts to develop an HIV vaccine underway in different countries have been examined, and a list has been compiled of Russian institutions able to participate in HIV vaccine development. International assistance for vaccine development in Russia would help both the medical establishment in Russia, which has suffered because of the economic and social crisis, and the international community. A meeting is planned for December 1996 in St. Petersburg to organize an AIDS control organization for all of Russia. Mobilization of support for AIDS prevention activities is necessary but very difficult. If nothing is done, the epidemic in Ukraine will soon spread to Russia. But Russia and China are among the few countries where an HIV epidemic could still be prevented or stopped. The association in St. Petersburg cooperates with other former Soviet republics in AIDS control activities, although attendance at international meetings and conferences is frequently curtailed for financial reasons.

Detection of Orthopoxvirus DNA by Real-Time PCR and Identification of Variola Virus DNA by Melting Analysis

PubMed Central

Nitsche, Andreas; Ellerbrok, Heinz; Pauli, Georg

2004-01-01

Although variola virus was eradicated by the World Health Organization vaccination program in the 1970s, the diagnosis of smallpox infection has attracted great interest in the context of a possible deliberate release of variola virus in bioterrorist attacks. Obviously, fast and reliable diagnostic tools are required to detect variola virus and to distinguish it from orthopoxviruses that have identical morphological characteristics, including vaccinia virus. The advent of real-time PCR for the clinical diagnosis of viral infections has facilitated the detection of minute amounts of viral nucleic acids in a fast, safe, and precise manner, including the option to quantify and to genotype the target reliably. In this study a complete set of four hybridization probe-based real-time PCR assays for the specific detection of orthopoxvirus DNA is presented. Melting analysis following PCR enables the identification of variola virus by the PCR product's characteristic melting temperature, permitting the discrimination of variola virus from other orthopoxviruses. In addition, an assay for the specific amplification of variola virus DNA is presented. All assays can be performed simultaneously in the same cycler, and results of a PCR run are obtained in less than 1 h. The application of more than one assay for the same organism significantly contributes to the diagnostic reliability, reducing the risk of false-negative results due to unknown sequence variations. In conclusion, the assays presented will improve the speed and reliability of orthopoxvirus diagnostics and variola virus identification. PMID:15004077

Quantification of dichlorvos released from kill strips used in boll weevil eradication programs

USDA-ARS?s Scientific Manuscript database

Two types of kill strips, Hercon Vaportape II and Plato Insecticide Strip, are used by boll weevil, Anthonomus grandis (Boheman), eradication programs in the U.S. Both types utilize dichlorvos as the killing agent and are marketed to last up to a month in traps. Consequently, programs typically re...

[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.

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

Asian longhorned beetle cooperative eradication program: program accomplishments 2001

Treesearch

Christine Markham

2003-01-01

APHIS spent approximately $3 million to continue ALB eradication activities in New York and Illinois in FY 2001. In New York 6,615 trees were removed, over 4,500 trees replanted, and approximately 121 square miles were under quarantine.

Elimination of Guinea Worm Disease in Ethiopia; Current Status of the Disease's, Eradication Strategies and Challenges to the End Game.

PubMed

Beyene, Habtamu Bedimo; Bekele, Abyot; Shifara, Amanu; Ebstie, Yehenew A; Desalegn, Zelalem; Kebede, Zeyede; Mulugeta, Abate; Deribe, Kebede; Tadesse, Zerihun; Abebe, Tamrat; Kebede, Biruck; Abrha, Getaneh; Jima, Daddi

2017-01-01

Dracunculiasis, also named Guinea Worm Disease (GWD), is one of the Neglected Tropical Diseases (NTDs) caused by a parasitic nematode known as Dracunculus medinensis and has been known since antiquity as 'fiery serpent' from Israelites. It is transmitted to humans via drinking contaminated water containing infective copepods. Given, its feasibility for eradication, the Guinea Worm Eradication Program (GWEP) was launched in 1980 with the aim of eradicating the disease. Since its inception, GWEP has made an extraordinary progress in interrupting transmission. Globally, the number of reported cases reduced from 3.5 million in 20 countries in 1986 to only 22 cases in 2015 from only four countries namely South Sudan, Mali, Chad and Ethiopia. Since Mali has interrupted transmission of GWD in 2016, currently, the disease remains endemic in only three sub-Saharan African countries namely, South Sudan, Chad and Ethiopia. Each endemic country has its own national Guinea Worm Eradication Program. In Ethiopia, the Ethiopian Dracunculiasis Eradication Program (EDEP) which was established in 1993 has made remarkable move towards interruption of disease transmission and now the endgame is fast approaching. The EDEP with support mainly from The Carter Center, WHO, and UNICEF has reduced GWD by more than 99% from 1994 to 2015. In 2015, only 3 indigenous cases in humans and 14 in animals (13 in dogs and 1 in baboon) were reported. In 2016, 3 human cases, 14 dogs and 2 baboon infections were reported.. Refugee influx from the Republic of South Sudan (RSS), increased animal infections with unknown role in transmission of Dracunculiasis, the presence of hard to reach communities and lack of safe water sources in remote non-village areas remain among important challenges at this final stage of GWD eradication in Ethiopia. This paper reviews progress made towards Guinea Worm Eradication with a focus on the experience of the Ethiopian Dracunculiasis Eradication Program (EDEP), and intervention strategies that need further intensification to realize the endgame. Eradication strategies encompassing community education for behavioral change including raising awareness towards cash reward for reporting Guniea Worm Disease (GWD) and animal infection, case containment, surveillance systems, provision of safe water supply, and ABATE chemical application are discussed. It also summarizes challenges the end game faces and recommendations to strengthen the eradication effort.

Elimination of Guinea Worm Disease in Ethiopia; Current Status of the Disease’s, Eradication Strategies and Challenges to the End Game

PubMed Central

Beyene, Habtamu Bedimo; Bekele, Abyot; Shifara, Amanu; Ebstie, Yehenew A.; Desalegn, Zelalem; Kebede, Zeyede; Mulugeta, Abate; Deribe, Kebede; Tadesse, Zerihun; Abebe, Tamrat; Kebede, Biruck; Abrha, Getaneh; Jima, Daddi

2017-01-01

Dracunculiasis, also named Guinea Worm Disease (GWD), is one of the Neglected Tropical Diseases (NTDs) caused by a parasitic nematode known as Dracunculus medinensis and has been known since antiquity as ‘fiery serpent’ from Israelites. It is transmitted to humans via drinking contaminated water containing infective copepods. Given, its feasibility for eradication, the Guinea Worm Eradication Program (GWEP) was launched in 1980 with the aim of eradicating the disease. Since its inception, GWEP has made an extraordinary progress in interrupting transmission. Globally, the number of reported cases reduced from 3.5 million in 20 countries in 1986 to only 22 cases in 2015 from only four countries namely South Sudan, Mali, Chad and Ethiopia. Since Mali has interrupted transmission of GWD in 2016, currently, the disease remains endemic in only three sub-Saharan African countries namely, South Sudan, Chad and Ethiopia. Each endemic country has its own national Guinea Worm Eradication Program. In Ethiopia, the Ethiopian Dracunculiasis Eradication Program (EDEP) which was established in 1993 has made remarkable move towards interruption of disease transmission and now the endgame is fast approaching. The EDEP with support mainly from The Carter Center, WHO, and UNICEF has reduced GWD by more than 99% from 1994 to 2015. In 2015, only 3 indigenous cases in humans and 14 in animals (13 in dogs and 1 in baboon) were reported. In 2016, 3 human cases, 14 dogs and 2 baboon infections were reported.. Refugee influx from the Republic of South Sudan (RSS), increased animal infections with unknown role in transmission of Dracunculiasis, the presence of hard to reach communities and lack of safe water sources in remote non-village areas remain among important challenges at this final stage of GWD eradication in Ethiopia. This paper reviews progress made towards Guinea Worm Eradication with a focus on the experience of the Ethiopian Dracunculiasis Eradication Program (EDEP), and intervention strategies that need further intensification to realize the endgame. Eradication strategies encompassing community education for behavioral change including raising awareness towards cash reward for reporting Guniea Worm Disease (GWD) and animal infection, case containment, surveillance systems, provision of safe water supply, and ABATE chemical application are discussed. It also summarizes challenges the end game faces and recommendations to strengthen the eradication effort. PMID:28878428

Rotary’s PolioPlus Program: Lessons Learned, Transition Planning, and Legacy

PubMed Central

McGovern, Michael; Scott, Robert; Pandak, Carol; Edwards, Amy; Goodstone, David

2017-01-01

Abstract Hundreds of thousands of Rotary volunteers have provided support for polio eradication activities and continue to this day by making financial contributions to the Rotary PolioPlus program, participating in national immunization days, assisting with surveillance, working on local, national, and international advocacy programs for polio eradication, assisting at immunization posts and clinics, and mobilizing their communities for immunization activities (including poliovirus and other vaccines) and other health benefits. Rotary has contributed more than $1.61 billion for the global eradication of polio and has committed to provide an additional $35 million each year until 2018 (all dollar amounts represent US dollars). Its unwavering commitment to eradicate polio has been vital to the success of the program. Rotary is providing additional support for routine immunization and healthcare. When polio is finally gone, we will have the knowledge from the lessons learned with PolioPlus, such as the value of direct involvement by local Rotarians, the program for emergency funding, innovative tactics, and additional approaches for tackling other global issues, even those beyond public health. Rotary has already transitioned its grants program to include 6 areas of focus: disease prevention and treatment, water and sanitation, maternal and child health, basic education and literacy, economic and community development, and peace and conflict prevention/resolution. Funding for these grants in 2015–2016 was $71 million. The legacy of the polio program will be the complete eradication of poliovirus and the elimination of polio for all time. PMID:28838160

Logistics of Guinea Worm Disease Eradication in South Sudan

PubMed Central

Jones, Alexander H.; Becknell, Steven; Withers, P. Craig; Ruiz-Tiben, Ernesto; Hopkins, Donald R.; Stobbelaar, David; Makoy, Samuel Yibi

2014-01-01

From 2006 to 2012, the South Sudan Guinea Worm Eradication Program reduced new Guinea worm disease (dracunculiasis) cases by over 90%, despite substantial programmatic challenges. Program logistics have played a key role in program achievements to date. The program uses disease surveillance and program performance data and integrated technical–logistical staffing to maintain flexible and effective logistical support for active community-based surveillance and intervention delivery in thousands of remote communities. Lessons learned from logistical design and management can resonate across similar complex surveillance and public health intervention delivery programs, such as mass drug administration for the control of neglected tropical diseases and other disease eradication programs. Logistical challenges in various public health scenarios and the pivotal contribution of logistics to Guinea worm case reductions in South Sudan underscore the need for additional inquiry into the role of logistics in public health programming in low-income countries. PMID:24445199

Logistics of Guinea worm disease eradication in South Sudan.

PubMed

Jones, Alexander H; Becknell, Steven; Withers, P Craig; Ruiz-Tiben, Ernesto; Hopkins, Donald R; Stobbelaar, David; Makoy, Samuel Yibi

2014-03-01

From 2006 to 2012, the South Sudan Guinea Worm Eradication Program reduced new Guinea worm disease (dracunculiasis) cases by over 90%, despite substantial programmatic challenges. Program logistics have played a key role in program achievements to date. The program uses disease surveillance and program performance data and integrated technical-logistical staffing to maintain flexible and effective logistical support for active community-based surveillance and intervention delivery in thousands of remote communities. Lessons learned from logistical design and management can resonate across similar complex surveillance and public health intervention delivery programs, such as mass drug administration for the control of neglected tropical diseases and other disease eradication programs. Logistical challenges in various public health scenarios and the pivotal contribution of logistics to Guinea worm case reductions in South Sudan underscore the need for additional inquiry into the role of logistics in public health programming in low-income countries.

A safety rule approach to surveillance and eradication of biological invasions

PubMed Central

Haight, Robert G.; Koch, Frank H.; Venette, Robert; Studens, Kala; Fournier, Ronald E.; Swystun, Tom; Turgeon, Jean J.

2017-01-01

Uncertainty about future spread of invasive organisms hinders planning of effective response measures. We present a two-stage scenario optimization model that accounts for uncertainty about the spread of an invader, and determines survey and eradication strategies that minimize the expected program cost subject to a safety rule for eradication success. The safety rule includes a risk standard for the desired probability of eradication in each invasion scenario. Because the risk standard may not be attainable in every scenario, the safety rule defines a minimum proportion of scenarios with successful eradication. We apply the model to the problem of allocating resources to survey and eradicate the Asian longhorned beetle (ALB, Anoplophora glabripennis) after its discovery in the Greater Toronto Area, Ontario, Canada. We use historical data on ALB spread to generate a set of plausible invasion scenarios that characterizes the uncertainty of the beetle’s extent. We use these scenarios in the model to find survey and tree removal strategies that minimize the expected program cost while satisfying the safety rule. We also identify strategies that reduce the risk of very high program costs. Our results reveal two alternative strategies: (i) delimiting surveys and subsequent tree removal based on the surveys' outcomes, or (ii) preventive host tree removal without referring to delimiting surveys. The second strategy is more likely to meet the stated objectives when the capacity to detect an invader is low or the aspirations to eradicate it are high. Our results provide practical guidelines to identify the best management strategy given aspirational targets for eradication and spending. PMID:28759584

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…

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...

78 FR 50022 - Environmental Impact Statement; Asian Longhorned Beetle Eradication Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... submit comments regarding the environmental impact statement by either of the following methods: Federal..., Environmental Protection Specialist, Environmental and Risk Analysis Services, PPD, APHIS, 4700 River Road Unit...] Environmental Impact Statement; Asian Longhorned Beetle Eradication Program AGENCY: Animal and Plant Health...

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

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.

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.

Determinants of successful arthropod eradication programs

Treesearch

Patrick C. ​Tobin; John M. Kean; David Maxwell Suckling; Deborah G. McCullough; Daniel A. Herms; Lloyd D. Stringer

2014-01-01

Despite substantial increases in public awareness and biosecurity systems, introductions of non-native arthropods remain an unwelcomed consequence of escalating rates of international trade and travel. Detection of an established but unwanted nonnative organism can elicit a range of responses, including implementation of an eradication program. Previous studies have...

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.

Rotary's PolioPlus Program: Lessons Learned, Transition Planning, and Legacy.

PubMed

Sever, John L; McGovern, Michael; Scott, Robert; Pandak, Carol; Edwards, Amy; Goodstone, David

2017-07-01

Hundreds of thousands of Rotary volunteers have provided support for polio eradication activities and continue to this day by making financial contributions to the Rotary PolioPlus program, participating in national immunization days, assisting with surveillance, working on local, national, and international advocacy programs for polio eradication, assisting at immunization posts and clinics, and mobilizing their communities for immunization activities (including poliovirus and other vaccines) and other health benefits. Rotary has contributed more than $1.61 billion for the global eradication of polio and has committed to provide an additional $35 million each year until 2018 (all dollar amounts represent US dollars). Its unwavering commitment to eradicate polio has been vital to the success of the program. Rotary is providing additional support for routine immunization and healthcare. When polio is finally gone, we will have the knowledge from the lessons learned with PolioPlus, such as the value of direct involvement by local Rotarians, the program for emergency funding, innovative tactics, and additional approaches for tackling other global issues, even those beyond public health. Rotary has already transitioned its grants program to include 6 areas of focus: disease prevention and treatment, water and sanitation, maternal and child health, basic education and literacy, economic and community development, and peace and conflict prevention/resolution. Funding for these grants in 2015-2016 was $71 million. The legacy of the polio program will be the complete eradication of poliovirus and the elimination of polio for all time. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

7 CFR 771.7 - Equal opportunity and non-discrimination requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 7 2014-01-01 2014-01-01 false Equal opportunity and non-discrimination requirements... AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS BOLL WEEVIL ERADICATION LOAN PROGRAM § 771.7 Equal opportunity and non-discrimination requirements. No recipient of a boll weevil eradication loan shall directly...

7 CFR 771.7 - Equal opportunity and non-discrimination requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 7 2011-01-01 2011-01-01 false Equal opportunity and non-discrimination requirements... AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS BOLL WEEVIL ERADICATION LOAN PROGRAM § 771.7 Equal opportunity and non-discrimination requirements. No recipient of a boll weevil eradication loan shall directly...

7 CFR 771.7 - Equal opportunity and non-discrimination requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 7 2012-01-01 2012-01-01 false Equal opportunity and non-discrimination requirements... AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS BOLL WEEVIL ERADICATION LOAN PROGRAM § 771.7 Equal opportunity and non-discrimination requirements. No recipient of a boll weevil eradication loan shall directly...

7 CFR 771.7 - Equal opportunity and non-discrimination requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 7 2013-01-01 2013-01-01 false Equal opportunity and non-discrimination requirements... AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS BOLL WEEVIL ERADICATION LOAN PROGRAM § 771.7 Equal opportunity and non-discrimination requirements. No recipient of a boll weevil eradication loan shall directly...

7 CFR 771.7 - Equal opportunity and non-discrimination requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Equal opportunity and non-discrimination requirements... AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS BOLL WEEVIL ERADICATION LOAN PROGRAM § 771.7 Equal opportunity and non-discrimination requirements. No recipient of a boll weevil eradication loan shall directly...

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)

Evaluating human papillomavirus vaccination programs in Canada: should provincial healthcare pay for voluntary adult vaccination?

PubMed

Llamazares, Marco; Smith, Robert J

2008-04-10

Recently, provincial health programs in Canada and elsewhere have begun rolling out vaccination against human papillomavirus for girls aged 9-13. While vaccination is voluntary, the cost of vaccination is waived, to encourage parents to have their daughters vaccinated. Adult women who are eligible for the vaccine may still receive it, but at a cost of approximately CAN$400. Given the high efficacy and immunogenicity of the vaccine, the possibility of eradicating targeted types of the virus may be feasible, assuming the vaccination programs are undertaken strategically. We develop a mathematical model to describe the epidemiology of vaccination against human papillomavirus, accounting for a widespread childhood vaccination program that may be supplemented by voluntary adult vaccination. A stability analysis is performed to determine the stability of the disease-free equilibrium. The critical vaccine efficacy and immunogenicity thresholds are derived, and the minimum level of adult vaccination required for eradication of targeted types is determined. We demonstrate that eradication of targeted types is indeed feasible, although the burden of coverage for a childhood-only vaccination program may be high. However, if a small, but non-negligible, proportion of eligible adults can be vaccinated, then the possibility of eradication of targeted types becomes much more favourable. We provide a threshold for eradication in general communities and illustrate the results with numerical simulations. We also investigate the effects of suboptimal efficacy and immunogenicity and show that there is a critical efficacy below which eradication of targeted types is not possible. If eradication is possible, then there is a critical immunogenicity such that even 100% childhood vaccination will not eradicate the targeted types of the virus and must be supplemented with voluntary adult vaccination. However, the level of adult vaccination coverage required is modest and may be achieved simply by removing the cost burden to vaccination. We recommend that provincial healthcare programs should pay for voluntary adult vaccination for women aged 14-26. However, it should be noted that our model results are preliminary, in that we have made a number of simplifying assumptions, including a lack of age-dependency in sexual partner rates, a lack of sexual activity outside of the vaccine age-range among females and a uniform age of sexual debut; thus, further work is desired to enhance the external generalisability of our results.

Gates, GAVI, the glorious global funds and more: all you ever wanted to know.

PubMed

Nossal, Gustav J V

2003-02-01

Global immunization programmes have achieved some remarkable successes. In 1977, Frank Fenner's Commission declared smallpox to have been eradicated by an 11-year-long intensive campaign. The Expanded Programme on Immunization encompassed six important childhood vaccines and reached over three-quarters of the world's children. Polio eradication has gone remarkably well, with only 10 out of 200 countries reporting residual cases. But amidst all the good news, there is also bad news. Coverage is variable; infrastructure is crumbling; and newer vaccines are not being incorporated in many country programmes. The Bill and Melinda Gates Foundation has introduced a new dynamic here. From their initial gift of $100 million in December 1998, their commitment to date is US$1.5 billion - and rising. At the centre is a Global Children's Vaccine Fund which permitted the launch, in January 2000, of the Global Alliance for Vaccines and Immunization. This is targeted to the 74 poorest countries of the world and is designed to improve vaccination infrastructure, to purchase newer vaccines and to support research and development. Even before we know how successful this programme will be, it has had its imitators. The Global Fund to Fight AIDS, TB and Malaria borrowed many concepts from GAVI. The Global Alliance for Improved Nutrition announced in May 2002 does so as well, and is heavily supported by Gates. Highly effective parasite control programmes antedate all this but will be much strengthened. However, we still face a sizeable budgetary gap both for research and for bringing the best advances to all people who need them.

[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.

Eradication of dracunculiasis from Pakistan.

PubMed

Hopkins, D R; Azam, M; Ruiz-Tiben, E; Kappus, K D

1995-09-02

In 1986 the World Health Organization targeted dracunculiasis (Guinea-worm disease), which seriously impairs socioeconomic development in 16 African countries, India, Pakistan, and Yemen, to be eradicated globally. The target date for eradication by the end of 1995 was established in 1991. Pakistan eradicated dracunculiasis from the country in October, 1993, after a national campaign which began in 1987 with a nationwide village-by-village search for cases. The infection, which is transmitted by drinking water from ponds containing infected water fleas, was eradicated by using health education, cloth filters, and the cyclopsicide, temephos; and in the later stages, by case containment. Methods pioneered in Pakistan's National Guinea Worm Eradication Program are now being applied in remaining endemic countries.

Ecohealth System Dynamic Model as a Planning Tool for the Reduction of Breeding Sites

NASA Astrophysics Data System (ADS)

Respati, T.; Raksanagara, A.; Djuhaeni, H.; Sofyan, A.; Shandriasti, A.

2017-03-01

Dengue is still one of major health problem in Indonesia. Dengue transmission is influenced by dengue prevention and eradication program, community participation, housing environment and climate. The complexity of the disease coupled with limited resources necessitates different approach for prevention methods that include factors contribute to the transmission. One way to prevent the dengue transmission is by reducing the mosquito’s breeding sites. Four factors suspected to influence breeding sites are dengue prevention and eradication program, community participation, housing environment, and weather condition. In order to have an effective program in reducing the breeding site it is needed to have a model which can predict existence of the breeding sites while the four factors under study are controlled. The objective of this study is to develop an Ecohealth model using system dynamic as a planning tool for the reduction of breeding sites to prevent dengue transmission with regard to dengue prevention and eradication program, community participation, housing environment, and weather condition. The methodology is a mixed method study using sequential exploratory design. The study comprised of 3 stages: first a qualitative study to 14 respondents using in-depth interview and 6 respondents for focus group discussion. The results from the first stage was used to develop entomology and household survey questionnaires for second stage conducted in 2036 households across 12 sub districts in Bandung City. Ecohealth system dynamic model was developed using data from first and second stages. Analyses used are thematic analysis for qualitative data; spatial, generalized estimating equation (GEE) and structural equation modeling for quantitative data; also average mean error (AME) and average variance error (AVE) for dynamic system model validation. System dynamic model showed that the most effective approach to eliminate breeding places was by ensuring the availability of basic sanitation for all houses. Weather factors such as precipitation can be compensated with the eradication of breeding sites activities which is conducted as scheduled and at the same time for the whole areas. Conclusion of this study is that dengue prevention and eradication program, community participation, and housing environment contributed to breeding places elimination influenced the existence of the breeding sites. The availability of basic sanitation and breeding places eradication program done timely and collectively are the most effective approach to eradicate breeding sites. Ecohealth dynamic system model can be used as a tool for the planning of breeding sites eradication program to prevent disease transmissions at city level.

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 ...

Leprosy: eradication or cure?

PubMed

Kakar, S

1995-01-01

The National Leprosy Eradication Program (NLEP), launched in 1986, has brought medicine for leprosy to more people than ever before, covering 200 of India's 455 districts. Since 1988, the number of leprosy patients discharged as cured each year has been greater than the number of newly detected, thus moving the country closer to its goal of eradicating leprosy from India. A substantial number of the 3 million people with leprosy in India are likely to come under the coverage of the NLEP. The author, however, argues that the fight against leprosy and the NLEP should be considered in their historical context. Leprosy is therefore used to illustrate how the perhaps interchangeable terms eradication and cure are charged with history and custom. Historically, the focus on eradicating leprosy has had terrible consequences for the patient. In England, perceptions about leprosy are relevant to the situation India, for colonial policy on leprosy was largely derivative. In the 1880s, especially, leprosy excited the public imagination. Asylums adopted segregation and confinement during this period for people with leprosy and the colonial government in India supported that approach from 1882. The author concludes that while the NLEP is laudable, the program must not focus upon eradicating leprosy. It should instead focus upon the leprosy patient, who has for so long been denied and discriminated against. The individual must be placed at the center of any program. Some steps in this direction have been taken.

Combining tactics to exploit allee effects for eradication of alien insect populations

Treesearch

David Maxwell Suckling; Patrick C. Tobin; Deborah G. McCullough; Daniel A. Herms

2012-01-01

Invasive species increasingly threaten ecosystems, food production, and human welfare worldwide. Hundreds of eradication programs have targeted a wide range of nonnative insect species to mitigate the economic and ecological impacts of biological invasions. Many such programs used multiple tactics to achieve this goal, but interactions between tactics have received...

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 ...

Exploring the use of anti-tick vaccine as tool for integrated eradication of the cattle fever tick, Rhipicephalus (Boophilus) annulatus

USDA-ARS?s Scientific Manuscript database

Bovine babesiosis, also known as cattle fever, is a tick-borne protozoal disease foreign to the United States. It was eradicated by eliminating the vector species, Rhipicephalus (Boophilus) annulatus and R. (B.) microplus, through the efforts of the Cattle Fever Tick Eradication Program (CFTEP), wit...

A safety rule approach to surveillance and eradication of biological invasions

Treesearch

Denys Yemshanov; Robert G. Haight; Frank H. Koch; Robert Venette; Kala Studens; Ronald E. Fournier; Tom Swystun; Jean J. Turgeon; Yulin Gao

2017-01-01

Uncertainty about future spread of invasive organisms hinders planning of effective response measures. We present a two-stage scenario optimization model that accounts for uncertainty about the spread of an invader, and determines survey and eradication strategies that minimize the expected program cost subject to a safety rule for eradication success. The safety rule...

Quantifying dispersal of the Asian longhorned beetle (Anoplophora glabripennis, Coleoptera) with incomplete data and behavioral knowledge

Treesearch

R. Talbot Trotter; Helen M. Hull-Sanders

2015-01-01

Eradication programs for invasive species can benefit from tools that delineate infestations and identify patterns of spread to guide eradication priorities and activities. However, identifying these patterns in cryptic organisms such the Asian longhorned beetle can be complicated by the sometimes conflicting needs of rapid eradication and research. Here, we describe...

Monitoring the effectiveness of Phytophthora ramorum eradication treatments in Oregon tanoak forests

Treesearch

Ellen Michaels Goheen; Alan Kanaskie; Everett Hansen; Wendy Sutton; Paul Reeser; Nancy Osterbauer

2013-01-01

Phytophthora ramorum, the cause of sudden oak death, was first discovered in Oregon forests in July 2001. An aggressive eradication treatment program was immediately put into place on all lands where it was found. Eradication treatments have changed over time as we have learned more about pathogen behavior. Treatment prescriptions currently consist...

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 ...

Economic evaluation of the eradication program for bovine viral diarrhea in the Swiss dairy sector.

PubMed

Thomann, B; Tschopp, A; Magouras, I; Meylan, M; Schüpbach-Regula, G; Häsler, B

2017-09-15

Since 2008, the Swiss veterinary service has been running a mandatory eradication program for Bovine Viral Diarrhea (BVD) that is focused on detecting and eliminating persistently infected (PI) animals. Detection was initially based on antigen testing from ear tag samples of the entire cattle population, followed by antigen testing of all newborn calves until 2012. Since then, bulk milk serology (dairy herds) and blood sample serology (beef herds) have been used for the surveillance of disease-free herds. From 2008 to 2012, the proportion of newborn PI calves decreased from 1.4% to less than 0.02%. However, this success was associated with substantial expenditures. The aim of this study was to conduct an economic evaluation of the BVD eradication program in the Swiss dairy sector. The situation before the start of the program (herd-level prevalence: 20%) served as a baseline scenario. Production models for three dairy farm types were used to estimate gross margins as well as net production losses and expenditures caused by BVD. The total economic benefit was estimated as the difference in disease costs between the baseline scenario and the implemented eradication program and was compared to the total eradication costs in a benefit-cost analysis. Data on the impact of BVD virus (BVDV) infection on animal health, fertility and production parameters were obtained empirically in a retrospective epidemiological case-control study in Swiss dairy herds and complemented by literature. Economic and additional production parameters were based on benchmarking data and published agricultural statistics. The eradication costs comprised the cumulative expenses for sampling and diagnostics. The economic model consisted of a stochastic simulation in @Risk for Excel with 20,000 iterations and was conducted for a time period of 14 years (2008-2021). The estimated annual financial losses in BVDV infected herds were CHF 85-89 per dairy cow and CHF 1337-2535 for an average farm, depending on the production type. The median net present value (NPV) was estimated at CHF 44.9 million (90% central range: CHF 13.4 million-69.4 million) and the break-even point to have been reached in 2015. Overall, the outcomes demonstrate that the Swiss BVD eradication program results in a net benefit for the dairy sector. These findings are relevant for planning similar BVD control programs in other countries. Copyright © 2017. Published by Elsevier B.V.

Ebola hemorrhagic Fever and the current state of vaccine development.

PubMed

Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-Il

2014-12-01

Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine.

Mapping monkeypox transmission risk through time and space in the Congo Basin

USGS Publications Warehouse

Nakazawa, Yoshinori J.; Lash, R. Ryan; Carroll, Darin S.; Damon, Inger K.; Karem, Kevin L.; Reynolds, Mary G.; Osorio, Jorge E.; Rocke, Tonie E.; Malekani, Jean; Muyembe, Jean-Jacques; Formenty, Pierre; Peterson, A. Townsend

2013-01-01

Monkeypox is a major public health concern in the Congo Basin area, with changing patterns of human case occurrences reported in recent years. Whether this trend results from better surveillance and detection methods, reduced proportions of vaccinated vs. non-vaccinated human populations, or changing environmental conditions remains unclear. Our objective is to examine potential correlations between environment and transmission of monkeypox events in the Congo Basin. We created ecological niche models based on human cases reported in the Congo Basin by the World Health Organization at the end of the smallpox eradication campaign, in relation to remotely-sensed Normalized Difference Vegetation Index datasets from the same time period. These models predicted independent spatial subsets of monkeypox occurrences with high confidence; models were then projected onto parallel environmental datasets for the 2000s to create present-day monkeypox suitability maps. Recent trends in human monkeypox infection are associated with broad environmental changes across the Congo Basin. Our results demonstrate that ecological niche models provide useful tools for identification of areas suitable for transmission, even for poorly-known diseases like monkeypox.

Use of Internally Controlled Real-Time Genome Amplification for Detection of Variola Virus and Other Orthopoxviruses Infecting Humans▿

PubMed Central

Fedele, C. G.; Negredo, A.; Molero, F.; Sánchez-Seco, M. P.; Tenorio, A.

2006-01-01

Smallpox, once a devastating disease caused by Variola virus, a member of the Orthopoxvirus genus, was eradicated in 1980. However, the importance of variola virus infections has been stressed widely in the last few years, particularly following recent social events in the world. Today, variola virus is considered to be one of the most significant agents with potential use as a biological weapon. In this study we developed an internally controlled real-time PCR assay for rapid detection and simultaneous differentiation of variola virus from other orthopoxviruses. The assay is based on TaqMan 3′-minor groove binder (MGB) chemistry and uses generic primers, designed in highly conserved genomic regions of the crmB gene, and three TaqMan MGB probes designed to identify orthopoxviruses, variola virus, and an internal control. The results obtained suggest that the assay is rapid, sensitive, specific, and suitable for the generic detection of orthopoxviruses and the identification of variola virus and avoids false-negative results in a single reaction tube. PMID:17065259

Use of internally controlled real-time genome amplification for detection of variola virus and other orthopoxviruses infecting humans.

PubMed

Fedele, C G; Negredo, A; Molero, F; Sánchez-Seco, M P; Tenorio, A

2006-12-01

Smallpox, once a devastating disease caused by Variola virus, a member of the Orthopoxvirus genus, was eradicated in 1980. However, the importance of variola virus infections has been stressed widely in the last few years, particularly following recent social events in the world. Today, variola virus is considered to be one of the most significant agents with potential use as a biological weapon. In this study we developed an internally controlled real-time PCR assay for rapid detection and simultaneous differentiation of variola virus from other orthopoxviruses. The assay is based on TaqMan 3'-minor groove binder (MGB) chemistry and uses generic primers, designed in highly conserved genomic regions of the crmB gene, and three TaqMan MGB probes designed to identify orthopoxviruses, variola virus, and an internal control. The results obtained suggest that the assay is rapid, sensitive, specific, and suitable for the generic detection of orthopoxviruses and the identification of variola virus and avoids false-negative results in a single reaction tube.

Ebola virus disease: preparedness in Japan.

PubMed

Ashino, Yugo; Chagan-Yasutan, Haorile; Egawa, Shinichi; Hattori, Toshio

2015-02-01

The current outbreak of Ebola virus disease (EVD) is due to a lack of resources, untrained medical personnel, and the specific contact-mediated type of infection of this virus. In Japan's history, education and mass vaccination of the native Ainu people successfully eradicated epidemics of smallpox. Even though a zoonotic virus is hard to control, appropriate precautions and personal protection, as well as anti-symptomatic treatment, will control the outbreak of EVD. Ebola virus utilizes the antibody-dependent enhancement of infection to seed the cells of various organs. The pathogenesis of EVD is due to the cytokine storm of pro-inflammatory cytokines and the lack of antiviral interferon-α2. Matricellular proteins of galectin-9 and osteopontin might also be involved in the edema and abnormality of the coagulation system in EVD. Anti-fibrinolytic treatment will be effective. In the era of globalization, interviews of travelers with fever within 3 weeks of departure from the affected areas will be necessary. Not only the hospitals designated for specific biohazards but every hospital should be aware of the biology of biohazards and establish measures to protect both patients and the community.

Mapping monkeypox transmission risk through time and space in the Congo Basin.

PubMed

Nakazawa, Yoshinori; Lash, R Ryan; Carroll, Darin S; Damon, Inger K; Karem, Kevin L; Reynolds, Mary G; Osorio, Jorge E; Rocke, Tonie E; Malekani, Jean M; Muyembe, Jean-Jacques; Formenty, Pierre; Peterson, A Townsend

2013-01-01

Monkeypox is a major public health concern in the Congo Basin area, with changing patterns of human case occurrences reported in recent years. Whether this trend results from better surveillance and detection methods, reduced proportions of vaccinated vs. non-vaccinated human populations, or changing environmental conditions remains unclear. Our objective is to examine potential correlations between environment and transmission of monkeypox events in the Congo Basin. We created ecological niche models based on human cases reported in the Congo Basin by the World Health Organization at the end of the smallpox eradication campaign, in relation to remotely-sensed Normalized Difference Vegetation Index datasets from the same time period. These models predicted independent spatial subsets of monkeypox occurrences with high confidence; models were then projected onto parallel environmental datasets for the 2000s to create present-day monkeypox suitability maps. Recent trends in human monkeypox infection are associated with broad environmental changes across the Congo Basin. Our results demonstrate that ecological niche models provide useful tools for identification of areas suitable for transmission, even for poorly-known diseases like monkeypox.

Mapping Monkeypox Transmission Risk through Time and Space in the Congo Basin

PubMed Central

Nakazawa, Yoshinori; Lash, R. Ryan; Carroll, Darin S.; Damon, Inger K.; Karem, Kevin L.; Reynolds, Mary G.; Osorio, Jorge E.; Rocke, Tonie E.; Malekani, Jean M.; Muyembe, Jean-Jacques; Formenty, Pierre; Peterson, A. Townsend

2013-01-01

Monkeypox is a major public health concern in the Congo Basin area, with changing patterns of human case occurrences reported in recent years. Whether this trend results from better surveillance and detection methods, reduced proportions of vaccinated vs. non-vaccinated human populations, or changing environmental conditions remains unclear. Our objective is to examine potential correlations between environment and transmission of monkeypox events in the Congo Basin. We created ecological niche models based on human cases reported in the Congo Basin by the World Health Organization at the end of the smallpox eradication campaign, in relation to remotely-sensed Normalized Difference Vegetation Index datasets from the same time period. These models predicted independent spatial subsets of monkeypox occurrences with high confidence; models were then projected onto parallel environmental datasets for the 2000s to create present-day monkeypox suitability maps. Recent trends in human monkeypox infection are associated with broad environmental changes across the Congo Basin. Our results demonstrate that ecological niche models provide useful tools for identification of areas suitable for transmission, even for poorly-known diseases like monkeypox. PMID:24040344

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 ...

Reserve Component Programs Fiscal Year 1989

DTIC Science & Technology

1990-04-01

interdiction efforts and domestic capability. marijuana eradication since 1983. In state duty status, some states have used The Board recommends...continued National Guard units in support of emphasis on resolving Air Force Air marijuana eradication and drug Liaison Officer shortages and close air...interdiction since 1977. Domestic support communications requirements marijuana eradication has been the for the Army’s reserve components. primary

Eradicating European pine shoot moth on ornamental pines with methyl bromide.

Treesearch

V.M. Carolin; W.H. Klein; R.M. Thompson

1962-01-01

The recent introduction of the European pine shoot moth into this region poses a serious threat to natural pine stands. To combat this threat, quarantines were invoked and eradication programs undertaken. Destruction of infested trees has been used tentatively as an eradication technique. In the meantime, fumigation with methyl bromide was tested over the period of a...

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

Strengthening the partnership between routine immunization and the global polio eradication initiative to achieve eradication and assure sustainability.

PubMed

Abdelwahab, Jalaa; Dietz, Vance; Eggers, Rudolf; Maher, Christopher; Olaniran, Marianne; Sandhu, Hardeep; Vandelaer, Jos

2014-11-01

Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, the number of polio endemic countries has declined from 125 to 3 in 2013. Despite this remarkable achievement, ongoing circulation of wild poliovirus in polio-endemic countries and the increase in the number of circulating vaccine-derived poliovirus cases, especially those caused by type 2, is a cause for concern. The Polio Eradication and Endgame Strategic Plan 2013-2018 (PEESP) was developed and includes 4 objectives: detection and interruption of poliovirus transmission, containment and certification, legacy planning, and a renewed emphasis on strengthening routine immunization (RI) programs. This is critical for the phased withdrawal of oral poliovirus vaccine, beginning with the type 2 component, and the introduction of a single dose of inactivated polio vaccine into RI programs. This objective has inspired renewed consideration of how the GPEI and RI programs can mutually benefit one another, how the infrastructure from the GPEI can be used to strengthen RI, and how a strengthened RI can facilitate polio eradication. The PEESP is the first GPEI strategic plan that places strong and clear emphasis on the necessity of improving RI to achieve and sustain global polio eradication. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

A model for long-distance dispersal of boll weevils (Coleoptera: Curculionidae)

NASA Astrophysics Data System (ADS)

Westbrook, John K.; Eyster, Ritchie S.; Allen, Charles T.

2011-07-01

The boll weevil, Anthonomus grandis (Boheman), has been a major insect pest of cotton production in the US, accounting for yield losses and control costs on the order of several billion US dollars since the introduction of the pest in 1892. Boll weevil eradication programs have eliminated reproducing populations in nearly 94%, and progressed toward eradication within the remaining 6%, of cotton production areas. However, the ability of weevils to disperse and reinfest eradicated zones threatens to undermine the previous investment toward eradication of this pest. In this study, the HYSPLIT atmospheric dispersion model was used to simulate daily wind-aided dispersal of weevils from the Lower Rio Grande Valley (LRGV) of southern Texas and northeastern Mexico. Simulated weevil dispersal was compared with weekly capture of weevils in pheromone traps along highway trap lines between the LRGV and the South Texas / Winter Garden zone of the Texas Boll Weevil Eradication Program. A logistic regression model was fit to the probability of capturing at least one weevil in individual pheromone traps relative to specific values of simulated weevil dispersal, which resulted in 60.4% concordance, 21.3% discordance, and 18.3% ties in estimating captures and non-captures. During the first full year of active eradication with widespread insecticide applications in 2006, the dispersal model accurately estimated 71.8%, erroneously estimated 12.5%, and tied 15.7% of capture and non-capture events. Model simulations provide a temporal risk assessment over large areas of weevil reinfestation resulting from dispersal by prevailing winds. Eradication program managers can use the model risk assessment information to effectively schedule and target enhanced trapping, crop scouting, and insecticide applications.

A model for long-distance dispersal of boll weevils (Coleoptera: Curculionidae).

PubMed

Westbrook, John K; Eyster, Ritchie S; Allen, Charles T

2011-07-01

The boll weevil, Anthonomus grandis (Boheman), has been a major insect pest of cotton production in the US, accounting for yield losses and control costs on the order of several billion US dollars since the introduction of the pest in 1892. Boll weevil eradication programs have eliminated reproducing populations in nearly 94%, and progressed toward eradication within the remaining 6%, of cotton production areas. However, the ability of weevils to disperse and reinfest eradicated zones threatens to undermine the previous investment toward eradication of this pest. In this study, the HYSPLIT atmospheric dispersion model was used to simulate daily wind-aided dispersal of weevils from the Lower Rio Grande Valley (LRGV) of southern Texas and northeastern Mexico. Simulated weevil dispersal was compared with weekly capture of weevils in pheromone traps along highway trap lines between the LRGV and the South Texas/Winter Garden zone of the Texas Boll Weevil Eradication Program. A logistic regression model was fit to the probability of capturing at least one weevil in individual pheromone traps relative to specific values of simulated weevil dispersal, which resulted in 60.4% concordance, 21.3% discordance, and 18.3% ties in estimating captures and non-captures. During the first full year of active eradication with widespread insecticide applications in 2006, the dispersal model accurately estimated 71.8%, erroneously estimated 12.5%, and tied 15.7% of capture and non-capture events. Model simulations provide a temporal risk assessment over large areas of weevil reinfestation resulting from dispersal by prevailing winds. Eradication program managers can use the model risk assessment information to effectively schedule and target enhanced trapping, crop scouting, and insecticide applications.

Vaccinations against smallpox and tuberculosis are associated with better long-term survival: a Danish case-cohort study 1971-2010.

PubMed

Rieckmann, Andreas; Villumsen, Marie; Sørup, Signe; Haugaard, Line Klingen; Ravn, Henrik; Roth, Adam; Baker, Jennifer Lyn; Benn, Christine Stabell; Aaby, Peter

2017-04-01

When vaccinations with vaccinia against smallpox and Bacillus Calmette-Guérin (BCG) against tuberculosis were phased out in some high-income countries around 1980, the impact on overall mortality was not examined. Recent studies from low-income countries have suggested that these vaccines are associated with mortality reductions, not explained by specific disease protection. We examined whether vaccinia and BCG administered in childhood were associated with long-term mortality reductions in a high-income population. In this case-cohort study, we followed 47 622 schoolchildren from Copenhagen, Denmark, born 1965 to 1976, from their first health examination to 2010. This cohort experienced the phase-out of vaccinia and BCG vaccination programmes. A sub-cohort of 5 316 individuals (699 excluded) was followed for 164 450 person-years (0.2% were lost to follow-up), and 401 deaths due to natural causes (841 deaths in total) occurred in the full cohort. Compared with individuals who had not received vaccinia or BCG, those who had received both vaccinia and BCG had an adjusted hazard ratio (aHR) of 0.54 [95% confidence interval (CI): 0.36-0.81] for mortality due to natural causes of death; those who only received BCG had an aHR of 0.58 (95% CI: 0.39-0.85). Vaccinia and BCG were not associated with any protection against deaths by accidents, suicide or murder, the combined aHR being 0.94 (95% CI: 0.62-1.42). Vaccinia and BCG vaccinations were associated with better long-term survival, which was not explained by specific protection. Vaccines with beneficial non-specific effects may reduce overall mortality even after the target diseases are eradicated. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association

Measles and rubella eradication.

PubMed

Hinman, Alan R

2018-01-02

This article discusses concepts of eradication, some issues relating to vertical and horizontal public health programs, some current issues relating to measles and rubella, and what we need to do about them. It concludes that measles and rubella/CRS can and should be eradicated. A target date should be established in 2020 (or before). Eradication can only be accomplished in the context of strengthening ongoing immunization services and strengthening surveillance so it can guide activities. Additional resources will be required to achieve the goal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Research and development of anti-tick vaccines for use in Texas and Puerto Rico Rhipicephalus (Boophilus) microplus control programs

USDA-ARS?s Scientific Manuscript database

This year marks the first time anti-tick vaccination will be used in the United States and Puerto Rico to control, Rhipicephalus (Boophilus) microplus and R. annulatus. The 110-year-old Cattle Fever Tick Eradication Program has eradicated the southern cattle fever tick from the majority of the Unite...

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.

Public-private partnership experience enabling translational research for anti-tick vaccine used in integrated Rhipicephalus (Boophilus) microplus and R. annulatus tick eradication in the United States of America

USDA-ARS?s Scientific Manuscript database

Rhipicephalus (Boophilus) microplus and R. annulatus are invasive tick species and vectors of microbes causing bovine babesiosis and anaplasmosis that were declared eradicated from the United States of America in 1943 through efforts of the Cattle Fever Tick Eradication Program. These tick disease v...

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.

Oversight role of the Independent Monitoring Board of the Global Polio Eradication Initiative.

PubMed

Rutter, Paul D; Donaldson, Liam J

2014-11-01

The Global Polio Eradication Initiative (GPEI) established its Independent Monitoring Board (IMB) in 2010 to monitor and guide its progress toward stopping polio transmission globally. The concept of an IMB is innovative, with no clear analogue in the history of the GPEI or in any other global health program. The IMB meets with senior program officials every 3-6 months. Its reports provide analysis and recommendations about individual polio-affected countries. The IMB also examines issues affecting the global program as a whole. Its areas of focus have included escalating the level of priority afforded to polio eradication (particularly by recommending a World Health Assembly resolution to declare polio eradication a programmatic emergency, which was enacted in May 2012), placing greater emphasis on people factors in the delivery of the program, encouraging innovation, strengthening focus on the small number of so-called sanctuaries where polio persists, and continuous quality improvement to reach every missed child with vaccination. The IMB's true independence from the agencies and countries delivering the program has enabled it to raise difficult issues that others cannot. Other global health programs might benefit from establishing similar independent monitoring mechanisms. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The dichotomy of pathogens and allergens in vaccination approaches

PubMed Central

Baird, Fiona J.; Lopata, Andreas L.

2014-01-01

Traditional prophylactic vaccination to prevent illness is the primary objective of many research activities worldwide. The golden age of vaccination began with an approach called variolation in ancient China and the evolution of vaccines still continues today with modern developments such as the production of GardasilTM against HPV and cervical cancer. The historical aspect of how different forms of vaccination have changed the face of medicine and communities is important as it dictates our future approaches on both a local and global scale. From the eradication of smallpox to the use of an experimental vaccine to save a species, this review will explore these successes in infectious disease vaccination and also discuss a few significant failures which have hampered our efforts to eradicate certain diseases. The second part of the review will explore designing a prophylactic vaccine for the growing global health concern that is allergy. Allergies are an emerging global health burden. Of particular concern is the rise of food allergies in developed countries where 1 in 10 children is currently affected. The formation of an allergic response results from the recognition of a foreign component by our immune system that is usually encountered on a regular basis. This may be a dust-mite or a prawn but this inappropriate immune response can result in a life-time of food avoidance and lifestyle restrictions. These foreign components are very similar to antigens derived from infectious pathogens. The question arises: should the allergy community be focussing on protective measures rather than ongoing therapeutic interventions to deal with these chronic inflammatory conditions? We will explore the difficulties and benefits of prophylactic vaccination against various allergens by means of genetic technology that will dictate how vaccination against allergens could be utilized in the near future. PMID:25076945

"Hep C, where art thou": What are the remaining (fundable) questions in hepatitis C virus research?

PubMed

Rosen, Hugo Ramón

2017-01-01

Hepatitis C virus (HCV) has dominated the field of hepatology for the past 25 years, and its cure in the majority of treated patients is one of the greatest achievements in all of medicine. However, the latter has led to the belief by some that HCV research should be shelved for other, more pressing areas. The mission for HCV eradication is far from accomplished. As a historical reference, we should consider that disease elimination has required vaccination with all previously controlled infections including smallpox and polio and that simple, effective treatment is not sufficient in most infections to lead to substantial control. Syphilis is the best example, for which a single dose of penicillin (which literally costs pennies and that we have had since 1945) is curative in early stages. Not only have we not eradicated syphilis, rates of infection have increased in many places within the United States in recent years. Most HCV-infected subjects are unaware of their infection, remaining at risk for transmission to others and disease progression, including cirrhosis and hepatocellular carcinoma. In the era of highly effective direct-acting antivirals (DAAs), many questions pertaining to HCV remain, but they are more complex and difficult to answer. Here, I provide my perspective on some of these salient issues: the residual risk for disease progression after sustained virologic response, the optimal approach to current DAA failures, the impact of targeting people who inject drugs with DAAs, vaccine prospects, and application of neutralizing HCV glycoprotein antibodies. (Hepatology 2017;65:341-349). © 2016 by the American Association for the Study of Liver Diseases.

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.

Brucellosis

USDA-ARS?s Scientific Manuscript database

Brucella suisis an intracellular pathogen that causes reproductive losses in swine and zoonotic infections in people. Althought an eradication program based on serologic detection and whole-herd depopulation has nearly eradicated the disease in the United States, it is endemic in feral swine. The b...

The polio endgame.

PubMed

Minor, Philip

2014-01-01

Paralytic poliomyelitis is a disease that became a public health issue at the beginning of the twentieth century and was more or less eliminated in developed countries by the early 1970s. The Global Polio Eradication Initiative of WHO has now eradicated endemic polio from all but three countries although re-introductions occur. The progress in polio eradication is striking and has accelerated over the last few years. It is likely that it will be finally eradicated from the world soon, the looming issue will then be how to stop vaccinating or modify immunization programs safely so that poliomyelitis does not re-emerge. This review article discusses the history and pathogenesis of poliomyelitis. The progress made, and challenges in sustaining the eradication of this debilitating infectious disease are considered.

The polio endgame

PubMed Central

Minor, Philip

2014-01-01

Paralytic poliomyelitis is a disease that became a public health issue at the beginning of the twentieth century and was more or less eliminated in developed countries by the early 1970s. The Global Polio Eradication Initiative of WHO has now eradicated endemic polio from all but three countries although re-introductions occur. The progress in polio eradication is striking and has accelerated over the last few years. It is likely that it will be finally eradicated from the world soon, the looming issue will then be how to stop vaccinating or modify immunization programs safely so that poliomyelitis does not re-emerge. This review article discusses the history and pathogenesis of poliomyelitis. The progress made, and challenges in sustaining the eradication of this debilitating infectious disease are considered. PMID:25608050

Length of Barrett's segment predicts failure of eradication in radiofrequency ablation for Barrett's esophagus: a retrospective cohort study.

PubMed

Luckett, Tyler; Allamneni, Chaitanya; Cowley, Kevin; Eick, John; Gullick, Allison; Peter, Shajan

2018-05-21

We aim to investigate factors that may contribute to failure of eradication of dysplastic Barrett's Esophagus among patients undergoing radiofrequency ablation treatment. A retrospective review of patients undergoing radiofrequency ablation for treatment of Barrett's Esophagus was performed. Data analyzed included patient demographics, medical history, length of Barrett's Esophagus, number of radiofrequency ablation sessions, and histopathology. Subsets of patients achieving complete eradication were compared with those not achieving complete eradication. A total of 107 patients underwent radiofrequency ablation for Barrett's Esophagus, the majority white, overweight, and male. Before treatment, 63 patients had low-grade dysplasia, and 44 patients had high-grade dysplasia or carcinoma. Complete eradication was achieved in a majority of patients (57% for metaplasia, and 76.6% for dysplasia). Failure of eradication occurred in 15.7% of patients. The median number of radiofrequency ablation treatments in patients achieving complete eradication was 3 sessions, compared to 4 sessions for failure of eradication (p = 0.06). Barrett's esophagus length of more than 5 cm was predictive of failure of eradication (p < 0.001). Radiofrequency ablation for dysplastic Barrett's Esophagus is a proven and effective treatment modality, associated with a high rate of complete eradication. Our rates of eradication from a center starting an ablation program are comparable to previously published studies. Length of Barrett's segment > 5 cm was found to be predictive of failure of eradication in patients undergoing radiofrequency ablation.

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?

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...

[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.

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

Research Advances in the Screwworm Eradication Program over the Past 25 Years

USDA-ARS?s Scientific Manuscript database

Screwworms, Cochliomyia hominivorax (Coquerel) (Calliphoridae: Chrysomyinae), are devastating pests of warm blooded animals that cause significant economic damage to livestock. The successful campaign to eradicate screwworms from continental North America using the sterile insect technique, led by t...

An Oral DNA Vaccine Encoding Endoglin Eradicates Breast Tumors by Blocking Their Blood Supply

DTIC Science & Technology

2006-05-01

W81XWH-04-1-0489 TITLE: An Oral DNA Vaccine Encoding Endoglin Eradicates Breast Tumors by Blocking Their Blood Supply PRINCIPAL...Encoding Endoglin Eradicates Breast Tumors by Blocking Their Blood Supply 5b. GRANT NUMBER W81XWH-04-1-0489 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...blocking renewal of blood vessel growth in the tumor bed, have been proposed as suitable antitumor strategies. Endoglin (CD105) is a suitable

Trial watch

PubMed Central

Vacchelli, Erika; Martins, Isabelle; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2012-01-01

Prophylactic vaccination constitutes one of the most prominent medical achievements of history. This concept was first demonstrated by the pioneer work of Edward Jenner, dating back to the late 1790s, after which an array of preparations that confer life-long protective immunity against several infectious agents has been developed. The ensuing implementation of nation-wide vaccination programs has de facto abated the incidence of dreadful diseases including rabies, typhoid, cholera and many others. Among all, the most impressive result of vaccination campaigns is surely represented by the eradication of natural smallpox infection, which was definitively certified by the WHO in 1980. The idea of employing vaccines as anticancer interventions was first theorized in the 1890s by Paul Ehrlich and William Coley. However, it soon became clear that while vaccination could be efficiently employed as a preventive measure against infectious agents, anticancer vaccines would have to (1) operate as therapeutic, rather than preventive, interventions (at least in the vast majority of settings), and (2) circumvent the fact that tumor cells often fail to elicit immune responses. During the past 30 y, along with the recognition that the immune system is not irresponsive to tumors (as it was initially thought) and that malignant cells express tumor-associated antigens whereby they can be discriminated from normal cells, considerable efforts have been dedicated to the development of anticancer vaccines. Some of these approaches, encompassing cell-based, DNA-based and purified component-based preparations, have already been shown to exert conspicuous anticancer effects in cohorts of patients affected by both hematological and solid malignancies. In this Trial Watch, we will summarize the results of recent clinical trials that have evaluated/are evaluating purified peptides or full-length proteins as therapeutic interventions against cancer. PMID:23264902

A new role for HERPUD1 and ERAD activation in osteoblast differentiation and mineralization.

PubMed

Américo-Da-Silva, Luan; Diaz, Jheimmy; Bustamante, Mario; Mancilla, Georthan; Oyarzún, Ingrid; Verdejo, Hugo E; Quiroga, Clara

2018-03-23

Bone integrity depends on a finely tuned balance between bone synthesis by osteoblasts and resorption by osteoclasts. The secretion capacity of mature osteoblasts requires strict control of proteostasis. Endoplasmic reticulum-associated degradation (ERAD) prevents the accumulation of unfolded ER proteins via dislocation to the cytosol and degradation by the proteasome. The ER membrane protein, homocysteine-inducible endoplasmic reticulum protein with ubiquitin-like domain 1 (HERPUD1), is a key component of the ERAD multiprotein complex which helps to stabilize the complex and facilitate the efficient degradation of unfolded proteins. HERPUD1 expression is strongly up-regulated by the unfolded protein response and cellular stress. The aim of the current study was to establish whether HERPUD1 and ERAD play roles in osteoblast differentiation and maturation. We evaluated preosteoblastic MC3T3-E1 cell and primary rat osteoblast differentiation by measuring calcium deposit levels, alkaline phosphatase activity, and runt-related transcription factor 2 and osterix expression. We found that ERAD and proteasomal degradation were activated and that HERPUD1 expression was increased as osteoblast differentiation progressed. The absence of HERPUD1 blocked osteoblast mineralization in vitro and significantly reduced alkaline phosphatase activity. In contrast, HERPUD1 overexpression activated the osteoblast differentiation program. Our results demonstrate that HERPUD1 and ERAD are important for the activation of the osteoblast maturation program and may be useful new targets for elucidating bone physiology.-Américo-Da-Silva, L., Diaz, J., Bustamante, M., Mancilla, G., Oyarzún, I., Verdejo, H. E., Quiroga, C. A new role for HERPUD1 and ERAD activation in osteoblast differentiation and mineralization.

Linear Epitopes in Vaccinia Virus A27 Are Targets of Protective Antibodies Induced by Vaccination against Smallpox.

PubMed

Kaever, Thomas; Matho, Michael H; Meng, Xiangzhi; Crickard, Lindsay; Schlossman, Andrew; Xiang, Yan; Crotty, Shane; Peters, Bjoern; Zajonc, Dirk M

2016-05-01

Vaccinia virus (VACV) A27 is a target for viral neutralization and part of the Dryvax smallpox vaccine. A27 is one of the three glycosaminoglycan (GAG) adhesion molecules and binds to heparan sulfate. To understand the function of anti-A27 antibodies, especially their protective capacity and their interaction with A27, we generated and subsequently characterized 7 murine monoclonal antibodies (MAbs), which fell into 4 distinct epitope groups (groups I to IV). The MAbs in three groups (groups I, III, and IV) bound to linear peptides, while the MAbs in group II bound only to VACV lysate and recombinant A27, suggesting that they recognized a conformational and discontinuous epitope. Only group I antibodies neutralized the mature virion in a complement-dependent manner and protected against VACV challenge, while a group II MAb partially protected against VACV challenge but did not neutralize the mature virion. The epitope for group I MAbs was mapped to a region adjacent to the GAG binding site, a finding which suggests that group I MAbs could potentially interfere with the cellular adhesion of A27. We further determined the crystal structure of the neutralizing group I MAb 1G6, as well as the nonneutralizing group IV MAb 8E3, bound to the corresponding linear epitope-containing peptides. Both the light and the heavy chains of the antibodies are important in binding to their antigens. For both antibodies, the L1 loop seems to dominate the overall polar interactions with the antigen, while for MAb 8E3, the light chain generally appears to make more contacts with the antigen. Vaccinia virus is a powerful model to study antibody responses upon vaccination, since its use as the smallpox vaccine led to the eradication of one of the world's greatest killers. The immunodominant antigens that elicit the protective antibodies are known, yet for many of these antigens, little information about their precise interaction with antibodies is available. In an attempt to better understand the interplay between the antibodies and their antigens, we generated and functionally characterized a panel of anti-A27 antibodies and studied their interaction with the epitope using X-ray crystallography. We identified one protective antibody that binds adjacent to the heparan sulfate binding site of A27, likely affecting ligand binding. Analysis of the antibody-antigen interaction supports a model in which antibodies that can interfere with the functional activity of the antigen are more likely to confer protection than those that bind at the extremities of the antigen. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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...