Biology of Variola Virus.

Variola virus is an anthroponotic agent that belongs to the orthopoxvirus family. It is an etiological agent of smallpox, an ancient disease that caused massive mortality of human populations. Twentieth century has witnessed the death of about 300 million people due to the unavailability of an effective vaccine. Early detection is the primary strategy to prevent an outbreak of smallpox. Variola virus forms the characteristic pus-filled pustules and centrifugal rash distribution in the infected patients while transmission occurs mainly through respiratory droplets during the early stage of infection. No antiviral drugs are approved for variola virus till date. Generation of first-generation vaccines helped in the eradication of smallpox which was declared by the World Health Organization.

Countering the potential re-emergence of a deadly infectious disease-Information warfare, identifying strategic threats, launching countermeasures.

OBJECTIVES: Eradicated infectious diseases like smallpox can re-emerge through accident or the designs of bioterrorists, and cause heavy casualties. Presently, the populace is largely susceptible as only a small percentage is vaccinated, and their immunity is likely to have waned. And when the disease re-emerges, the susceptible individuals may be manipulated by disinformation on Social Media to refuse vaccines. Thus, a combination of countermeasures consisting of antiviral drugs and vaccines and a range of policies for their application need to be investigated. Opinions regarding whether to receive vaccines evolve over time through social exchanges via networks that overlap with but are not identical to the disease propagation networks. These couple the spread of the biological and information contagion and necessitate a joint investigation of the two. METHODS: We develop a computationally tractable metapopulation epidemiological model that captures the joint spatio-temporal evolution of an infectious disease (e.g., smallpox, COVID-19) and opinion dynamics. RESULTS: Considering smallpox, the computations based on the model show that opinion dynamics have a substantial impact on the fatality count. Towards understanding how perpetrators are likely to seed the infection, we identify a) the initial distribution of infected individuals that maximize the overall fatality count; and b) which habitation structures are more vulnerable to outbreaks. We assess the relative efficacy of different countermeasures and conclude that a combination of vaccines and drugs minimize the fatalities, and by itself, drugs reduce fatalities more than the vaccine. Accordingly, we assess the impact of increase in the supply of drugs and identify the most effective among a collection of policies for administering of drugs for various parameter combinations. Many of the observed patterns are stable to variations of a diverse set of parameters. CONCLUSIONS: Our findings provide a quantitative foundation for various important elements of public health discourse that have largely been conducted qualitatively.

Rethinking the History of Smallpox in the Early Twentieth Century: The SS Korea and Uncertainty Surrounding the Diagnosis of Smallpox.

This research explores the case of the 1903 smallpox outbreak on the SS Korea , a transpacific carrier making runs between Southeast Asia, East Asia, Hawaii, and the United States. These regions were connected to a degree that no one had ever imagined through the SS Korea . Honolulu, Hawaii, was one of the most important territories in US maritime history and served as a waypoint between Asia and San Francisco on the mainland. As increasing numbers of people traveled by sea, various microbes were communicated across the Pacific Ocean. International tourists traveling across the ocean to Hawaii and the United States were alerted to infectious diseases, smallpox being one of the most significant of such diseases. The story of the SS Korea serves as an important lens through which to explore the early twentieth century transpacific world connected through Honolulu. Focusing on the spread of smallpox via international travelers, this research studies aspects of the public health system that were developed to contain smallpox infection on international ships and the application of smallpox vaccination as a method for infectious disease control. More importantly, in bringing attention to the uncertainty surrounding the diagnosis of smallpox, this research argues for the necessity of historians to build a more comprehensive medical historical context for disease control systems that includes the limits of medical science in making diagnoses of infectious diseases, the uncertainties arising from a lack of this component, and the implementation of health policies and preventative medical technologies.

[Colleges of royal physicians and isolation hospitals to control public hygiene in Chile from 1879 to 1920]. / Protomedicatos y lazaretos como instituciones de control de la higiene pública en Chile entre 1879 y 1920.

This article investigates the emergence of two institutions for the control of public hygiene in Chile between 1879 and 1920: colleges of royal physicians and isolation hospitals using the case of smallpox in La Araucanía, a region located in the South of Chile. We cover the characteristics and context of these institutions that allowed the State of Chile to address the problems of public hygiene and to prompt health professionals to professionalize the practice of medicine. The liberal positivist state of the late nineteenth century understood that the issue of hygiene was not only a matter of individual responsibility but had a social, public, and environmental dimension. People practiced hygiene alongside the existence of hygienic and anti-hygienic environments. Therefore, hygiene, the royal colleges of physicians, health records, isolation hospitals, doctors, and vaccinators are studied. All of these components of the health care system of the time were in permanent tension with the central government authorities due to the insufficient resources provided by the state for the care of infected patients with smallpox. The study follows a qualitative methodology with a descriptive historiographic design. We used archival primary and secondary sources available in Chile and Germany. The results show that the presence of smallpox appeared ferociously in South-Central Chile in the second half of the 19th century and remained in La Araucanía until the first half of the 20th century. The extent to which smallpox spread, spawning fear and insecurity in people of different social classes, had as one of its leading causes the precarious conditions of health and hygiene of the population.

El presente artículo indaga la aparición de dos instituciones de control de la higiene pública en Chile entre los años 1879 y 1920: los protomedicatos y lazaretos. El objeto de estudio utiliza como caso la presencia de la viruela en La Araucanía. Se abordan las características y contexto que adquirió la instalación de estos dispositivos que permitieron al Estado de Chile operacionalizar el asunto de la higiene pública, lo que interpeló a los profesionales de la salud para avanzar a mayores niveles de perfeccionamiento del ejercicio profesional de la medicina. El Estado liberal positivista de fines de siglo XIX comprendió que el tema de la higiene no era solamente una cuestión de responsabilidad individual, sino que tenía una dimensión social, pública y medio ambiental. No sólo había personas que eran higiénicas, sino también ambientes higiénicos y antihigiénicos. Por tanto, se estudia la higiene, el tribunal del protomedicato, la hoja sanitaria, lazaretos, médicos y vacunadores; quienes estuvieron en permanente tensión con las autoridades del gobierno central debido a los insuficientes recursos proporcionados por el Estado para la atención de los enfermos contagiados con viruela. El estudio se orienta desde una metodología cualitativa con un diseño historiográfico con alcances descriptivos densos. Se han utilizado fuentes primarias y secundarias disponibles en archivos en Chile y Alemania. Los resultados evidencian que la presencia de viruela apareció violentamente en el centro sur de Chile en la segunda mitad del siglo XIX y permaneció en la Araucanía hasta la primera mitad del siglo XX. La violencia con que se desarrolló la viruela generó miedo e incertidumbre afectando a personas de diferentes clases sociales, y tuvo como una de sus causas principales las precarias condiciones de salubridad de la población.

Protomedicatos y lazaretos como instituciones de control de la higiene pública en Chile entre 1879 y 1920 / Colleges of royal physicians and isolation hospitals to control public hygiene in Chile from 1879 to 1920

El presente artículo indaga la aparición de dos instituciones de control de la higiene pública en Chile entre los años 1879 y 1920: los protomedicatos y lazaretos. El objeto de estudio utiliza como caso la presencia de la viruela en La Araucanía. Se abordan las características y contexto que adquirió la instalación de estos dispositivos que permitieron al Estado de Chile operacionalizar el asunto de la higiene pública, lo que interpeló a los profesionales de la salud para avanzar a mayores niveles de perfeccionamiento del ejercicio profesional de la medicina. El Estado liberal positivista de fines de siglo XIX comprendió que el tema de la higiene no era solamente una cuestión de responsabilidad individual, sino que tenía una dimensión social, pública y medio ambiental. No sólo había personas que eran higiénicas, sino también ambientes higiénicos y antihigiénicos. Por tanto, se estudia la higiene, el tribunal del protomedicato, la hoja sanitaria, lazaretos, médicos y vacunadores; quienes estuvieron en permanente tensión con las autoridades del gobierno central debido a los insuficientes recursos proporcionados por el Estado para la atención de los enfermos contagiados con viruela. El estudio se orienta desde una metodología cualitativa con un diseño historiográfico con alcances descriptivos densos. Se han utilizado fuentes primarias y secundarias disponibles en archivos en Chile y Alemania. Los resultados evidencian que la presencia de viruela apareció violentamente en el centro sur de Chile en la segunda mitad del siglo XIX y permaneció en la Araucanía hasta la primera mitad del siglo XX. La violencia con que se desarrolló la viruela generó miedo e incertidumbre afectando a personas de diferentes clases sociales, y tuvo como una de sus causas principales las precarias condiciones de salubridad de la población.

This article investigates the emergence of two institutions for the control of public hygiene in Chile between 1879 and 1920: colleges of royal physicians and isolation hospitals using the case of smallpox in La Araucanía, a region located in the South of Chile. We cover the characteristics and context of these institutions that allowed the State of Chile to address the problems of public hygiene and to prompt health professionals to professionalize the practice of medicine. The liberal positivist state of the late nineteenth century understood that the issue of hygiene was not only a matter of individual responsibility but had a social, public, and environmental dimension. People practiced hygiene alongside the existence of hygienic and anti-hygienic environments. Therefore, hygiene, the royal colleges of physicians, health records, isolation hospitals, doctors, and vaccinators are studied. All of these components of the health care system of the time were in permanent tension with the central government authorities due to the insufficient resources provided by the state for the care of infected patients with smallpox. The study follows a qualitative methodology with a descriptive historiographic design. We used archival primary and secondary sources available in Chile and Germany. The results show that the presence of smallpox appeared ferociously in South-Central Chile in the second half of the 19th century and remained in La Araucanía until the first half of the 20th century. The extent to which smallpox spread, spawning fear and insecurity in people of different social classes, had as one of its leading causes the precarious conditions of health and hygiene of the population.

An Uneasy Pleasure: Representing the Dangers of Skin-to-skin Contact in Eighteenth-century London 'The William Bynum Prize Essay'.

This article considers the social function of contagious disease as moderator of class relationships in England during the first half of the eighteenth century and takes into account the ways in which the 'communicability' of the plague, great pox (syphilis) and smallpox (variola) was used by authors to crystallise social interaction and tension along class lines. The essay begins by examining the representation of the plague, syphilis and smallpox in the medical tradition, before shifting its attention to the practice of maritime quarantine, as laid out by Richard Mead in his Short Discourse Concerning Pestilential Contagion (1720). By foregrounding medical writing on contagion through skin contact, I suggest that pornographic texts such as John Cleland's The Memoirs of a Woman of Pleasure (Fanny Hill) (1748) had an interventionist function. Cleland is often charged with sanitising the true horrors of sex work in this period. This article proposes that if we take the time to appreciate the way infectious cutaneous diseases were believed to operate and spread we can recognise the moments in which he not only alludes to disease but invokes it for structural and thematic purposes. In proposing this, I am challenging the dominant interpretation that the problematic realities of eighteenth-century prostitution, especially disease, are subordinated to the narrative's greater interest in erotic pleasure.

Health system capacity in Sydney, Australia in the event of a biological attack with smallpox.

Planning for a re-emergent epidemic of smallpox requires surge capacity of space, resources and personnel within health systems. There are many uncertainties in such a scenario, including likelihood and size of an attack, speed of response and health system capacity. We used a model for smallpox transmission to determine requirements for hospital beds, contact tracing and health workers (HCWs) in Sydney, Australia, during a modelled epidemic of smallpox. Sensitivity analysis was done on attack size, speed of response and proportion of case isolation and contact tracing. We estimated 100638 clinical HCWs and 14595 public hospital beds in Sydney. Rapid response, case isolation and contact tracing are influential on epidemic size, with case isolation more influential than contact tracing. With 95% of cases isolated, outbreak control can be achieved within 100 days even with only 50% of contacts traced. However, if case isolation and contact tracing both fall to 50%, epidemic control is lost. With a smaller initial attack and a response commencing 20 days after the attack, health system impacts are modest. The requirement for hospital beds will vary from up to 4% to 100% of all available beds in best and worst case scenarios. If the response is delayed, or if the attack infects 10000 people, all available beds will be exceeded within 40 days, with corresponding surge requirements for clinical health care workers (HCWs). We estimated there are 330 public health workers in Sydney with up to 940,350 contacts to be traced. At least 3 million respirators will be needed for the first 100 days. To ensure adequate health system capacity, rapid response, high rates of case isolation, excellent contact tracing and vaccination, and protection of HCWs should be a priority. Surge capacity must be planned. Failures in any of these could cause health system failure, with inadequate beds, quarantine spaces, personnel, PPE and inability to manage other acute health conditions.

[Between vaccines, diseases, and resistances: the impacts of a smallpox epidemic in nineteenth-century Porto Alegre]. / Entre vacinas, doenças e resistências: os impactos de uma epidemia de varíola em Porto Alegre no século XIX.

This article examines a smallpox epidemic which killed 1% of the population of Porto Alegre in 1874. Through extensive documentary research and comparison with data from those who died, we problematize why smallpox manifested as an epidemic in the city. Maps showing vaccination in the years preceding the outbreak reveal that only low levels of the population of Porto Alegre participated in prevention efforts, and the benefits of these efforts were ignored by the different social groups which were interconnected within the city. As sick soldiers arrived from other places, the disease spread rapidly through the city and caused the death of hundreds of people.

Uma epidemia de varíola que vitimou fatalmente 1% da população de Porto Alegre em 1874 é o tema deste artigo. Com base em ampla pesquisa documental e no cruzamento de informações produzidas por ocasião da morte dos indivíduos atingidos durante o evento, buscamos problematizar as razões pelas quais a varíola apresentou-se em formato epidêmico na cidade. De posse dos mapas de vacinados nos anos anteriores à eclosão da epidemia, pudemos constatar a baixa adesão da população de Porto Alegre ao preventivo, cujo benefício poderia ser ignorado pelos distintos grupos sociais que teciam relações dentro da cidade. Com a chegada de soldados doentes, oriundos de outras localidades, a moléstia se espalhou rapidamente pela cidade, causando a morte de centenas de pessoas.

[Human poxvirus infections]. / Infections humaines à poxvirus.

Poxvirus (PXV) infections are a common cause of cutaneous signs. In France, certain forms of poxvirus are frequent and benign (molluscum contagiosum), while others are rare but potentially serious (cowpox virus [CPXV]). Whereas only smallpox and molluscum contagiosum viruses have a human reservoir and are transmitted between humans, most poxvirus infections are zoonoses having only animal reservoirs. Only a small number of poxviruses are responsible for infection in humans, but the increasing number of new pets, some of which are exotic, coupled with the rapid rise in international travel are creating a greater risk of transmission of zoonotic PXV to new vectors and of spread of these diseases to new regions throughout the world. In France, molluscum contagiosum, orf and milkers' nodule give rise to numerous consultations and are well known to dermatologists. However, dermatologists must also be able to identify other parapoxviruses of similar presentation to orf; thus, CPXV and monkeypox are considered potentially emergent viruses with a high risk of epidemic and spread due to increasing international transport and the loss of the maximum protection against smallpox. Finally, despite its declared eradication, smallpox is currently being monitored because of the potential risk of reintroduction, whether accidentally or deliberately through bioterrorism.

Entre vacinas, doenças e resistências: os impactos de uma epidemia de varíola em Porto Alegre no século XIX / Between vaccines, diseases, and resistances: the impacts of a smallpox epidemic in nineteenth-century Porto Alegre

Resumo Uma epidemia de varíola que vitimou fatalmente 1% da população de Porto Alegre em 1874 é o tema deste artigo. Com base em ampla pesquisa documental e no cruzamento de informações produzidas por ocasião da morte dos indivíduos atingidos durante o evento, buscamos problematizar as razões pelas quais a varíola apresentou-se em formato epidêmico na cidade. De posse dos mapas de vacinados nos anos anteriores à eclosão da epidemia, pudemos constatar a baixa adesão da população de Porto Alegre ao preventivo, cujo benefício poderia ser ignorado pelos distintos grupos sociais que teciam relações dentro da cidade. Com a chegada de soldados doentes, oriundos de outras localidades, a moléstia se espalhou rapidamente pela cidade, causando a morte de centenas de pessoas.

Abstract This article examines a smallpox epidemic which killed 1% of the population of Porto Alegre in 1874. Through extensive documentary research and comparison with data from those who died, we problematize why smallpox manifested as an epidemic in the city. Maps showing vaccination in the years preceding the outbreak reveal that only low levels of the population of Porto Alegre participated in prevention efforts, and the benefits of these efforts were ignored by the different social groups which were interconnected within the city. As sick soldiers arrived from other places, the disease spread rapidly through the city and caused the death of hundreds of people.

Evidence of Long-Distance Aerial Convection of Variola Virus and Implications for Disease Control.

Two distinct phenomena of airborne transmission of variola virus (smallpox) were described in the pre-eradication era-direct respiratory transmission, and a unique phenomenon of transmission over greater distances, referred to as "aerial convection". We conducted an analysis of data obtained from a systematic review following the PRISMA criteria, on the long-distance transmission of smallpox. Of 8179 studies screened, 22 studies of 17 outbreaks were identified-12 had conclusive evidence of aerial convection and five had partially conclusive evidence. Aerial convection was first documented in 1881 in England, when smallpox incidence had waned substantially following mass vaccination, making unusual transmissions noticeable. National policy at the time stipulated spatial separation of smallpox hospitals from other buildings and communities. The evidence supports the transmission of smallpox through aerial convection at distances ranging from 0.5 to 1 mile, and one instance of 15 km related to bioweapons testing. Other explanations are also possible, such as missed chains of transmission, fomites or secondary aerosolization from contaminated material such as bedding. The window of observation of aerial convection was within the 100 years prior to eradication. Aerial convection appears unique to the variola virus and is not considered in current hospital infection control protocols. Understanding potential aerial convection of variola should be an important consideration in planning for smallpox treatment facilities and protecting potential contacts and surrounding communities.

Dynamics of Pathological and Virological Findings During Experimental Calpox Virus Infection of Common Marmosets (Callithrix jacchus).

Experimental intranasal infection of marmosets (Callithrix jacchus) with calpox virus results in fatal disease. Route and dose used for viral inoculation of the test animals mimics the natural transmission of smallpox, thus representing a suitable model to study pathogenesis and to evaluate new vaccines against orthopoxvirus infection. However, the pathogenic mechanisms leading to death are still unclear. Therefore, our study aimed at investigating the kinetics of pathological alterations to clarify the pathogenesis in calpox virus infection. Following intranasal inoculation with two different viral doses, common marmosets were sacrificed on days 3, 5, 7, 10 and 12 post inoculation. Collected tissue was screened using histopathology, immunohistochemistry, transmission electron microscopy, and virological assays. Our data suggest that primary replication took place in nasal and bronchial epithelia followed by secondary replication in submandibular lymph nodes and spleen. Parallel to viremia at day 7, virus was detectable in many organs, mainly located in epithelial cells and macrophages, as well as in endothelial cells. Based on the onset of clinical signs, the histological and ultrastructural lesions and the immunohistochemical distribution pattern of the virus, the incubation period was defined to last 11 days, which resembles human smallpox. In conclusion, the data indicate that the calpox model is highly suitable for studying orthopoxvirus-induced disease.

A New Document on Smallpox Vaccination.

Modern medicine owes much to the invaluable heritage of the practices of past generations and their achievements that have now become medical rules. In the case of vaccination, there is evidence that the nomads of Baluchistan (Southeast Iran) demonstrated natural immunization against cowpox, a practice that was later introduced to the medical community by Edward Jenner. Although the discoveries of scientists cannot be ignored, they are certainly based on the traditional and indigenous experiences that have been transferred from generation to generation until reaching us.

History of Smallpox and Its Spread in Human Populations.

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.

Position on reproductive donors and smallpox vaccine: a committee opinion.

Although there is presently no definitive evidence linking vaccinia virus transmission through reproductive cells, the Society for Assisted Reproductive Technology (SART) and the American Society for Reproductive Medicine (ASRM) accordingly recommend that assisted reproductive technology (ART) practitioners consider deferring individuals who are planning on donating gametes for reproductive use (reproductive donors) who have recently received smallpox vaccine or contracted symptomatic vaccinia virus infection through close contact with a vaccine recipient (until after the vaccine or infectious scab has spontaneously separated). Good donor practice further suggests that reproductive donors who are not in good health, including those with recent complications from smallpox vaccine, should be similarly deferred. This document replaces the previous document of the same name last published in 2012 (Fertil Steril 2012;98:e1-e2).

Dynamics of Multi-stage Infections on Networks.

This paper investigates the dynamics of infectious diseases with a non-exponentially distributed infectious period. This is achieved by considering a multi-stage infection model on networks. Using pairwise approximation with a standard closure, a number of important characteristics of disease dynamics are derived analytically, including the final size of an epidemic and a threshold for epidemic outbreaks, and it is shown how these quantities depend on disease characteristics, as well as the number of disease stages. Stochastic simulations of dynamics on networks are performed and compared to output of pairwise models for several realistic examples of infectious diseases to illustrate the role played by the number of stages in the disease dynamics. These results show that a higher number of disease stages results in faster epidemic outbreaks with a higher peak prevalence and a larger final size of the epidemic. The agreement between the pairwise and simulation models is excellent in the cases we consider.

Smallpox Vaccination of Laboratory Workers at US Variola Testing Sites.

To evaluate the need to revaccinate laboratory workers against smallpox, we assessed regular revaccination at the US Laboratory Response Network's variola testing sites by examining barriers to revaccination and the potential for persistence of immunity. Our data do not provide evidence to suggest prolonging the recommended interval for revaccination.

Poxvirus countermeasures during an emergency in the United States.

Although smallpox was eradicated worldwide by 1980, national security experts remain concerned that it could be used in a deliberate attack. The United States and other governments have given priority to developing and stockpiling vaccines and antivirals to protect their populations from the potential reintroduction of this deadly disease. Public health officials are also concerned about the spread of related zoonotic orthopoxviruses such as monkeypox and cowpox, against which smallpox vaccine provides protection. This report analyzes how medical countermeasures available in the US Strategic National Stockpile will be given priority and used in the event of an intentional or accidental release of smallpox in the United States.