An Unwanted but Long-Known Company: Post-Viral Symptoms in the Context of Past Pandemics in Switzerland (and Beyond).

Objectives: Some people do not fully recover from an acute viral infection and experience persistent symptoms or incomplete recovery for months or even years. This is not unique to the SARS-CoV-2 virus and history shows that post-viral conditions like post COVID-19 condition, also referred to as Long Covid, are not new. In particular, during and after pandemics caused by respiratory viruses in which large parts of the population were infected or exposed, professional and public attention was increased, not least because of the large number of people affected. Methods: Given the current relevance of the topic, this article aims to narratively review and summarize the literature on post-viral symptoms during past pandemics and to supplement and illustrate it with Swiss examples from the pandemics of 1890, 1918-1920 and later. Results: Post-viral diseases were an increasingly emphasised health topic during and after past pandemics triggered by respiratory infections over the last 150 years. Conclusion: In the next pandemic, it should not be surprising that post-viral conditions will again play a role, and pandemic plans should reflect this.

The 1919-21 influenza pandemic in Greenland.

In Alaska, the 1918-20 influenza pandemic was devastating, with mortality rates up to 90% of the population, while in other arctic regions in northern Sweden and Norway mortality was considerably lower. We investigated the timing and age-patterns in excess mortality in Greenland during the period 1918-21 and compare these to other epidemics and the 1889-92 pandemic. We accessed the Greenlandic National Archives and transcribed all deaths from 1880 to 1921 by age, geography, and cause of death. We estimated monthly excess mortality and studied the spatial-temporal patterns of the pandemics and compared them to other mortality crises in the 40-year period. The 1918-21 influenza pandemic arrived in Greenland in the summer of 1919, one year delayed due to ship traffic interruptions during the winter months. We found that 5.2% of the Greenland population died of the pandemic with substantial variability between counties (range, 0.1% to 11%). We did not see the typical pandemic age-pattern of high young-adult mortality, possibly due to high baseline mortality in this age-group or remoteness. However, despite substantial mortality, the mortality impact was not standing out relative to other mortality crises, or of similar devastation reported in Alaskan populations.

Regional differences in historical diphtheria and scarlet fever notification rates in The Netherlands, 1905-1925: a spatial-temporal analysis.

BACKGROUND: We describe how rates of two frequently occurring notifiable diseases-diphtheria and scarlet fever-varied between regions of The Netherlands in the early twentieth century, and identify potential factors underlying this variation. METHODS: Digitized weekly mandatory notification data for 1905-1925, municipality level, were aggregated into 27 'spatial units' defined by unique combinations of province and population density category (high: more than 4500; mid : 1250-4500; low: less than 1250 inhabitants km-2). Generalized additive regression models were fitted to estimate the associations between notification rates and population density, infant mortality rate and household income, while adjusting for temporal trends per spatial unit. RESULTS: Annual per capita notification rates for both diphtheria and scarlet fever tended to rise from the beginning of the period 1905-1925 until peaking around 1918/1919. Adjusted diphtheria notification rates were higher for high- and mid- compared with low-density municipalities (by 71.6 cases per 100 000, 95% confidence interval (CI) : 52.7-90.5; 39.0/100 k, 95% CI : 24.7-53.3, respectively). Scarlet fever showed similar associations with population density (35.7 cases per 100 000, 95% CI : 9.4-62.0; 21.4/100 k, 95% CI: 1.5-41.3). CONCLUSIONS: There was considerable spatial variation in notification rates for both diseases in early twentieth century Netherlands, which could partly be explained by factors capturing variation in living conditions and socio-economic circumstances. These findings aid understanding of contemporary respiratory infection transmission.

Historical epidemics of scrub typhus in Queensland and Papua New Guinea.

Undifferentiated febrile diseases (e.g., Mossman fever) from northern Queensland were eventually partially attributed to mite-transmitted rickettsial infections known as scrub typhus or tsutsugamushi fever. Scrub typhus became a major medical threat to military operations in Papua New Guinea during the Second World War and killed more Australian soldiers than malaria in the pre-antibiotic era. Further investigations showed scrub typhus to be an occupational disease of rural workers in north Queensland especially around Cairns and Innisfail. Occasional small epidemics of scrub typhus still occur during military exercises in Queensland, but as scrub typhus is not a reportable disease, its presence in the civilian community is largely unknown. Increased use of serological testing in patients with fever and rash illnesses after exposure in northern Queensland is likely to show that scrub typhus is a modern infection that remains treatable with antibiotics once it is identified.

It Was Not the Perfect Storm: The Social History of the HIV-2 Virus in Guinea-Bissau.

The perfect storm model that was elaborated for the HIV-1M pandemic has also been used to explain the emergence of HIV-2, a second human immunodeficiency virus-acquired immunodeficiency syndrome (HIV-AIDS) that became an epidemic in Guinea-Bissau, West Africa. The use of this model creates epidemiological generalizations, ecological oversimplifications and historical misunderstandings as its assumptions-an urban center with explosive population growth, a high level of commercial sex and a surge in STDs, a network of mechanical transport and country-wide, en masse mobile campaigns-are absent from the historical record. This model fails to explain how the HIV-2 epidemic actually came about. This is the first study to conduct an exhaustive examination of sociohistorical contextual developments and align them with environmental, virological and epidemiological data. The interdisciplinary dialogue indicates that the emergence of the HIV-2 epidemic piggybacked on local sociopolitical transformations. The war's indirect effects on ecological relations, mobility and sociability were acute in rural areas and are a key to the HIV-2 epidemic. This setting had the natural host of the virus, the population numbers, the mobility trends and the use of technology on a scale needed to foster viral adaptation and amplification. The present analysis suggests new reflections on the processes of zoonotic spillovers and disease emergence.

Spatial and Temporal Analyses of the Event of Death for 1480 in Milan Using the Data Contained in the Sforza's Registers of the Dead.

Historical death registration was conducted primarily to assess the presence of plague. The Liber Mortuorum of Milan was one of Europe's first registers with many socio-demographical details. In this work, we consider 1480 to make spatial and temporal analyses of the event of death to find possible explanations about the events' distribution and the events' trend over time. The spatial analyses involved Moran's I, the LISA, and the heatmaps; the temporal analysis applied the Durbin-Watson test. All the analyses were conducted separately on all subjects (1813), children (765), and adults (1046). Contrade (districts) were considered for spatial analysis. Moran's I and the Durbin Watson test were significant on all subjects and children's analyses, and the LISA showed the same results for those groups. Children may significantly impact the distribution of death and the trend over time. At least half of the children were 0 years old, and survival in the very first childhood period was closely linked to the family, so that it could be a proxy of the conditions of an area.

Secular trends of suicide risk for residents in mainland China (2004 to 2019): An updated age-period-cohort analysis.

BACKGROUND: The overall suicide rate in China has dropped substantially since the 1990s, but a slowdown in the decrease and even a reversing trend was observed in specific groups in recent years. This study aims to investigate the latest suicide risk in mainland China by using the age-period-cohort (APC) analysis. METHOD: This population-based multiyear cross-sectional study included Chinese ages 10 to 84 years using data from the China Health Statistical Yearbook (2005-2020). Data were analyzed by the APC analysis and intrinsic estimator (IE) technique. RESULTS: The data satisfactorily fit the constructed APC models. The cohort effect indicated a high risk of suicide among people birth in 1920-1944 and a sharp decline in the 1945-1979 cohort. The lowest risk occurred in the 1980-1994 cohort before a sharp increase in generation Z (birth years in 1995-2009). The period effect showed a declining trend since 2004. The age effect indicated that the suicide risk increased over time, except for a gradual decline from age 35 to 49. The suicide risk increased greatly in adolescents and reached the highest among the elderly. LIMITATIONS: The aggregated population-level data and the non-identifiability of the APC model could result in bias in the accuracy of results in this study. CONCLUSIONS: This study successfully updated the Chinese suicide risk from the age, period and cohort perspective using the latest available data (2004-2019). The findings enhance the understanding of suicide epidemiology and provide evidence supporting policies and strategies at the macro-level for suicide prevention and management. Immediate action is needed to focus on a national suicide prevention strategy that targets generation Z, adolescents and the elderly which will require a collaborative effort by government officials, public/community health planners and health care agencies.

Mapping the plague through natural language processing.

Pandemic diseases such as plague have produced a vast amount of literature providing information about the spatiotemporal extent, transmission, or countermeasures. However, the manual extraction of such information from running text is a tedious process, and much of this information remains locked into a narrative format. Natural Language processing (NLP) is a promising tool for the automated extraction of epidemiological data, and can facilitate the establishment of datasets. In this paper, we explore the utility of NLP to assist in the creation of a plague outbreak dataset. We produced a gold standard list of toponyms by manual annotation of a German plague treatise published by Sticker in 1908. We investigated the performance of five pre-trained NLP libraries (Google, Stanford CoreNLP, spaCy, germaNER and Geoparser) for the automated extraction of location data compared to the gold standard. Of all tested algorithms, spaCy performed best (sensitivity 0.92, F1 score 0.83), followed closely by Stanford CoreNLP (sensitivity 0.81, F1 score 0.87). Google NLP had a slightly lower performance (F1 score 0.72, sensitivity 0.78). Geoparser and germaNER had a poor sensitivity (0.41 and 0.61). We then evaluated how well automated geocoding services such as Google geocoding, Geonames and Geoparser located these outbreaks correctly. All geocoding services performed poorly - particularly for historical regions - and returned the correct GIS information only in 60.4%, 52.7% and 33.8% of all cases. Finally, we compared our newly digitized plague dataset to a re-digitized version of the plague treatise by Biraben and provide an update of the spatio-temporal extent of the second pandemic plague outbreaks. We conclude that NLP tools have their limitations, but they are potentially useful to accelerate the collection of data and the generation of a global plague outbreak database.

Emergency typhoid immunisation after the fall of Singapore 1942.

Singapore surrendered to the Japanese invasion in February 1942 after its water supply collapsed. At the suggestion of the colonial medical authorities, an emergency typhoid immunisation campaign was then begun using locally manufactured vaccine from extemporary materials; within 3 months, >600 000 had been immunised. Comparison with prewar statistics suggests that a postsurrender typhoid fever epidemic was prevented despite an increase in other enteric infections. Public health crises with disrupted supply chains may make locally manufactured vaccines of increasing importance in the future.

Testing the waters: Syndemic gastrointestinal distress in Lambaréné, Gabon, 1926-1932.

This paper argues that a cluster of pathogens, hazardous labor conditions, and environmental constraints rendered chronic gastrointestinal distress fatal for African laborers living near Lambaréné, Gabon during the 1920s. Application of syndemic theory and epidemiological methods on patient records at Hospital Schweitzer, the central hospital of the region, explain how a seemingly simple diagnosis of chronic gastrointestinal distress belied a complex web of worsening biological and social outcomes for laborers in the tropical forests of central Gabon. An analysis of the syndemic suffering of GI patients reveals how the dysentery pathogen became tied to the peaks and valleys of the colonial economy, and in particular, the colonial extraction of tropical hardwoods. These processes culminated in the summer of 1929 when the highest number of timber exports coincided with the deadliest months of dysentery outbreak for the patient population at Hospital Schweitzer. This case study proposes syndemics as an effective theoretical framework to research historical precedents of the entanglement of people, pathogens, and illness.

Archiving time series sewage samples as biological records of built environments.

This commentary encourages the regular archiving of nucleic-acid-stabilized serial samples of wastewaters and/or sewage. Stabilized samples would facilitate retrospective reconstitution of built environments' biological fluids. Biological time capsules would allow retrospective searches for nucleic acids from viruses such as SARS-CoV-2. Current resources for testing need not be diverted if samples are saved in case they become important in the future. Systematic storage would facilitate investigation into the origin and prevalence of viruses and other agents. Comparison of prevalence data from individual and clinical samplings with community wastewater would allow valuable comparison, contrast and correlation among different testing modalities. Current interest is focused on SARS-CoV-2, but archived samples could become valuable in many contexts including surveys for other infectious and chemical agents whose identity is not currently known. Archived time series of wastewater will take their place alongside other biological repositories and records including those from medical facilities, museums, eDNA, living cell and tissue collections. Together these will prove invaluable records of the evolving Anthropocene.

Understanding what shapes disease control: An historical analysis of foot-and-mouth disease in Kenya.

Interpreting the interplay between politics, social demographics and epidemiology is essential for understanding how a disease's occurrence and control evolve over time. Foot-and-mouth disease (FMD) virus was first detected in Kenya in 1915 and serotyped in 1932. This review aims to describe and appraise initiatives to control FMD in Kenya since its independence from British rule in 1964, using information from the scientific literature. We describe the historical dynamics of FMD epidemiology in the country and determine socio-political factors that have shaped the control strategies used. PubMed, Scopus, CAB abstracts, Science Direct, Web of Science and Google Scholar were used to search and retrieve papers, using predetermined search criteria encompassing FMD, Kenya and disease control programme descriptors. In total 1234 papers were identified and screened for relevance using the World Health Organization's guidelines for rapid review. Ultimately 69 references from this search were included, and information extracted and consolidated. These papers highlight that following independence, there was a structured effort to control FMD consisting of a compulsory subsidised vaccination programme in the Rift Valley with movement controls and quarantine when outbreaks occurred. This programme led to an initial decrease in recorded FMD outbreaks. However, endemic circulation continued and this programme was discontinued due to multiple factors, including political deprioritisation and changes in the structure of veterinary services. Only low levels of active surveillance have been applied since 1964; most surveillance is passive and relies on outbreak reports. Currently control focuses on outbreak management and a mixture of public- and privately-funded vaccination. This review highlights critical drivers influencing disease control programme implementation including veterinary service structure, the active participation of stakeholders with farming systems and availability of affordable and matched FMD vaccine. Additionally, it appraises the availability of historical information and draws attention to gaps in the historical record.

Introducing activities of the Archives of Infectious Diseases History (AIDH) project: Historical epidemiology.

The AIDH is a project as a historical epidemiology. The AIDH aims to collect, maintain, and manage past epidemiological materials and to offer these materials to persons who are interested in the history and in the fields of tropical medicine and global health. In this paper, we introduce our purpose and activities and show a hypothesis about lymphatic filariasis with Brugia malayi in Japan as a case of historical epidemiology. We hope to build fruitful ties between historians and scholars of tropical medicine and global health workers through an interdisciplinary approach to the history of control of infectious diseases.

Historical trends in breast Cancer among women in China from age-period-cohort modeling of the 1990-2015 breast Cancer mortality data.

BACKGROUND: Evidence on historical trends extracted embedded in recent data can advance our understanding of the epidemiology of breast cancer for Chinese women. China is a country with significant political, socioeconomic, and cultural events since the 1900s; however, no such studies are reported in the literature. METHODS: Age-specific mortality rates of breast cancer during 1990-2015 in China were analyzed using APC modeling (age-period-cohort modeling) method. Net effect from birth cohort was derived to measure cancer mortality risk during 1906-1990 when no mortality data were collected, and net effect from time period was derived to measure cancer mortality risk during 1990-2015 when data were collected. Model parameters were estimated using intrinsic estimator, a novel method to handle collinearity. The estimated effects were numerical differentiated to enhance presentations of time/age trend. RESULTS: Breast cancer mortality rate per 100,000 women increased from 6.83 in 1990 to 12.07 in 2015. After controlling for age and period, the risk of breast cancer mortality declined from 0.626 in 1906-10 to - 1.752 in 1991-95 (RR = 0.09). The decline consisted of 3 phases, a gradual phase during 1906-1940, a moderate phase with some fluctuations during 1941-1970, and a rapid phase with large fluctuations during 1971-1995. After controlling for age and cohort, the risk of breast cancer mortality increased from - 0.141 in 1990 to 0.258 in 2015 (RR = 1.49) with an acceleration after 2005. The time trends revealed by both the cohort effect and the period effect were in consistency with the significant political and socioeconomic events in China since the 1900s. CONCLUSIONS: With recent mortality data in 1990-2015, we detected the risk of breast cancer mortality for Chinese women over a long period from 1906 to 2015. The risk declined more than 90% from the highest level in 1906-10 to the lowest in 1990-95, followed by an increase of 49% from 1990 to 2015. Findings of this study connected historical evidence with recent data, supporting further research to exam the relationship between development and risk of breast cancer for medical and health decision-making at the population level and prevention and treatment at the individual level.

Análisis histórico epidemiológico de la pandemia de gripa de 1918-1919 en Boyacá, un siglo después / Historical and Epidemiological Analysis of the Pandemic Flu of 1918-1919 in Boyaca a Century Later / Análise histórica epidemiológica da pandemia de gripe de 1918-1919 em Boyacá, um século depois

Resumen Introducción : la gripa que ocurrió entre 1918-1919 causó la mayor mortalidad en la historia de las pandemias, se estima que 50 millones de personas fallecieron. Se realizó un estudio histórico-epidemiológico a partir de fuentes documentales contrastadas con un análisis estadístico de 142963 registros de defunción consignados en los libros parroquiales de 94 municipios de Boyacá y los censos de los años 1912, 1918 y 1928. Desarrollo : a partir de las fuentes primarias obtenidas, se reconstruye la realidad socio-sanitaria de Boyacá y el desarrollo cronológico de la pandemia en el departamento. La gripa era conocida en Boyacá antes de la pandemia. Durante el periodo pandémico (1918-1919) se encontraron 20102 decesos en los libros parroquiales, 3305 registrados como gripa, de los cuales el 80.9 % ocurrieron en los últimos 3 meses de 1918, siendo los menores de 4 años el grupo poblacional más afectado. Conclusiones : después de la pandemia, la gripa se hace endémica en Boyacá. En el periodo pandémico, la tasa promedio de mortalidad en los municipios ubicados sobre los 2000 msnm es tres veces mayor a aquellos que se encuentran por debajo de esta altura. Las condiciones de pobreza y hacinamiento acentuaron la letalidad de la pandemia, por lo que fueron ineficientes las acciones de las direcciones de higiene para enfrentarla. Las juntas de socorros y la Junta Patriótica de Sanidad son las únicas que realizaron acciones efectivas.

Abstract Introduction : The flu of 1918-1919 caused the highest mortality in the history of pandemics; there is an estimate that 50 million people died. We conducted a historical-epidemiological study from documentary sources, contrasted with a statistical analysis of 142,963 deaths recorded in the church books of 94 municipalities of Boyaca and the census of the years 1912, 1918 and 1928. Development : From the historical records consulted, we reconstructed the social health reality of Boyaca, as well as the chronological development of the pandemic. Boyaca knew the flu before the pandemic (1918-1919). During it, the church books recorded 20,102 deaths; the flu was responsible for 3,305. Of those cases, 80.9 % occurred in the last three months of 1918; the most affected population were children of less than four years of age. Conclusions : After the pandemic, the flu became endemic in Boyaca. In the pandemic period, the average mortality rate in municipalities located above 2000 MASL was three times higher than those below this height. The conditions of poverty and overcrowding accentuated the lethality of the pandemic; the hygiene directives to face them were inefficient. The relief and the Patriotic Health Board were the only ones that carried out effective actions.

Resumo Introdução : a gripe de 1918-1919 causou a maior mortalidade na história das pandemias, estima-se que 50 milhões de pessoas faleceram. Se realizou um estudo histórico-epidemiológico a partir de fontes documentais contrastadas com uma análise estatística de 142.963 atestados de óbito consignados nos livros paroquiais de 94 municípios de Boyacá e os censos dos anos 1912, 1918 e 1928. Desenvolvimento : a partir das fontes primárias obtidas, se reconstrói a realidade socio sanitária de Boyacá e o desenvolvimento cronológico da pandemia no departamento. A gripe era conhecida em Boyacá antes da pandemia. Durante o período pandémico (1918-1919) se encontraram 20 102 decessos nos livros paroquiais, 3.305 registrados como gripe, dos quais o 80. 9% ocorreram nos últimos 3 meses de 1918, sendo os menores de 4 anos, o grupo populacional mais afetado. Conclusões : depois da pandemia, a gripe se faz endémica em Boyacá. No período pandémico a taxa média de mortalidade nos municípios localizados sobre os 2000 msnm, é três vezes maior àqueles que se encontram por debaixo desta altura. As condições de pobreza e amontoamento acentuaram a letalidade da pandemia, sendo ineficientes as ações das direções de higiene para enfrenta-la. As juntas de socorros e a Junta Patriótica de Sanidade, são as únicas que realizam ações efetivas.

Tuberculosis as a Risk Factor for 1918 Influenza Pandemic Outcomes.

Tuberculosis (TB) mortality declined after the 1918 pandemic, suggesting that influenza killed those who would have died from TB. Few studies have analyzed TB as a direct risk factor for 1918 influenza morbidity and mortality by age and sex. We study the impacts of TB on influenza-like illness (% of population sick) and case fatality (% of cases dying) by age and sex through case-control comparisons of patients (N = 201) and employees (N = 97) from two Norwegian sanatoriums. Female patients, patients at Landeskogen sanatorium, and patients aged 10-39 years had significantly lower morbidity than the controls. None of the 62 sick employees died, while 15 of 84 sick patients did. The case-control difference in case fatality by sex was only significant for females at Lyster sanatorium and females at both sanatoriums combined. Non-significant case-control differences in case fatality for males were likely due to small samples. Patients 20-29 years for both sexes combined at Lyster sanatorium and at both sanatoriums combined, as well as females 20-29 years for both sanatoriums combined, had significantly higher case fatality. We conclude that TB was associated with higher case fatality, but morbidity was lower for patients than for employees. The results add to the study of interactions between bacterial and viral diseases and are relevant in preparing for pandemics in TB endemic areas.

Historical trends in suicide risk for the residents of mainland China: APC modeling of the archived national suicide mortality rates during 1987-2012.

PURPOSE: Distinctive and dramatic changes in the history of China with a rapid suicide decline in recent years present an opportunity to investigate the risk of suicide. In this study, we investigated suicide risk with a historical perspective with archived data to inform suicide research and prevention policies and strategies. METHOD: Documented age-specific suicide mortality rates in 1987-2012 were decomposed into age, period, and cohort effect using APC-modeling method and intrinsic estimator (IE) technique. The estimated effects were further analyzed by numerical differentiation. RESULTS: The data satisfactorily fit the constructed APC models. Cohort effect indicated that suicide risk in China fluctuated at very high levels during 1903-1967, followed by a sharp decline during 1968-1977, and reached the lowest level in 1983-1987 before increased again. Period effect confirmed the declining trend since 1987. Three sunny cohorts with reduced suicide risk and four cloudy cohorts with increased risk were, respectively, associated with significant cultural, social, political, and economic events in China since the 1900s. CONCLUSIONS: The mega trends in the suicide risk at the population level are closely related to significant historical events in China. Suicide is anticipated to increase because of the growing risk for the young cohorts (particularly young females) as the country further develops. Study findings suggest the significance of national strategies for suicide prevention and control, including maintenance of social harmony and stability, provision of more opportunities for development, enhancement of social integration, and restriction of suicide facilitating factors.

At the intersection of medical geography and disease ecology: Mirko Grmek, Jacques May and the concept of pathocenosis.

Environmental historians are not sufficiently aware of the extent to which mid twentieth-century thinkers turned to medical geography-originally a nineteenth-century area of study-in order to think through ideas of ecology, environment, and historical reasoning. This article outlines how the French-Croatian Mirko D. Grmek (Krapina, 1924-Paris, 2000), a major thinker of his generation in the history of medicine, used those ideas in his studies of historical epidemiology. During the 1960s, Grmek attempted to provide, in the context of the Annales School's research program under the leadership of Fernand Braudel, a new theoretical framework for a world history of disease. Its development was inspired by several sources, most notably the French-American Jacques M. May (Paris 1896-Tunisia, 1975), who was then pioneering an opening up of medical geography and movement towards the concept of disease ecology. The cornerstone of Grmek's "synthetic approach" to the field was the notion of "pathocenosis". The diverse uses of this notion in the course of time-from his early agenda focused on a longue durée history of diseases in Western Antiquity to his last, relating to the new epidemiological threat of (re)emerging infectious diseases, specifically HIV/aids-enables us firstly, to note how concepts of ecology sat uneasily alongside those of medical geography; secondly, to assess the reach and limits of his theoretical contribution to historical epidemiology; and thirdly, to understand better the uneven fortunes of his concept of pathocenosis at the end of the twentieth and beginning of the twenty-first centuries.

The geography of smallpox in England before vaccination: A conundrum resolved.

Smallpox is regarded as an ancient and lethal disease of humans, however very little is known about the prevalence and impact of smallpox before the advent of vaccination (c.1800). Here we use evidence from English burial records covering the period 1650-1799 to confirm a striking geography to smallpox patterns. Smallpox apparently circulated as a childhood disease in northern England and Sweden, even where population densities were low and settlement patterns dispersed. However, smallpox was a relatively rare epidemic disease in southern England outside the largest cities, despite its commercialised economy and the growing spatial interconnectedness of its settlements. We investigated a number of factors hypothesised to influence the regional circulation of smallpox, including exposure to naturally occurring orthopox viruses, settlement patterns, and deliberate preventative measures. We concluded that transmission was controlled in southern England by local practices of avoidance and mass inoculation that arose in the seventeenth and eighteenth centuries. Avoidance measures included isolation of victims in pest houses and private homes, as well as cancellation of markets and other public gatherings, and pre-dated the widespread use of inoculation. The historical pattern of smallpox in England supports phylogenetic evidence for a relatively recent origin of the variola strains that circulated in the twentieth century, and provides evidence for the efficacy of preventative strategies complementary to immunisation.