Category Archives: Influenza


Opening the Plague Files

Book Citation: A.P. Cook & N.D. Cook.  The Plague Files: Crisis Management in Sixteenth-Century Seville.  Louisiana State University Press, 2009. 296 pp. ISBN: 978-0-8071-4360-5.

Public Health Crisis Management

Time and Place:
Seville, Spanish Empire, 1579-1581.


Those interested in history, crisis management, public health, and political science; written for a general audience.


The Plague Files is an intensive history of the daily challenges and crises dealt with by the royal governor and city council of Seville from 1579 to 1582.  As its title implies, this book is about crisis management and it stays true to this focus. Seville was faced with two very different pandemics, influenza and plague, within the same year compounded by food shortages, economic pressures, response funding difficulties, response fatigue, and the potential of civil unrest. If you ever wondered what it would be like for plague and an influenza pandemic to go (sequentially) head to head in the same population, Seville in 1579-1580 is your ideal test population.  The challenges and limitations of both quarantine and a cordon sanitaire are highlighted throughout the book.

I was impressed by their case investigation and surveillance system.Workers were contracted and paid based on their service, so detailed reports were filed to justify their pay from the plague commission. Using these reports, the authors were able to trace the detailed steps of case investigators as they tracked exposed people and textiles that they viewed as contagious. Dispatched surveillance officers also had to file detailed reports of their efforts and findings to draw their pay. The Count of Villar, the royal governor, handed out penalties including jail time for officials and others who were deemed negligent in their duties.

It was fascinating to see how their concepts of contagion played into their public health response. Textiles were the gravest concern for controlling plague contagion inside the city walls. The trail of dead owners of some clothing or bedding seems to justify their concern. Yet, there is no evidence of personal protective equipment/behavior or concern over grain storage. On the other hand, the city was on the verge of starvation much of the time so they couldn’t be very choosy about grain shipment or storage. Physicians were advisers to the Plague Council but not central to the decision-making process. Most were hired to work for the duration of the plague, often one per hospital or outlying village. The Plague Council was primarily concerned with controlling movements of people, and  providing and paying for the poor and destitute who they knew were kindling for an explosive outbreak. Diagnosis was the physicians most useful duty to the plague council. Plague diagnoses were complicated by concurrent outbreaks of influenza, typhus, other ‘common fevers’ (possibly malaria), and malnutrition. There is no doubt that the plague with all its classic symptoms was the primary pathogen.

One of my take home lessons from The Plague Files is how long and relentless a plague outbreak could be. Response fatigue was a critical problem for everyone. People just get tired of the restrictions and become conditioned to the steadiness of death. Unlike the short, sharp influenza mortality, plague deaths often trickled in at less than ten per week for months punctuated by spikes of death.

Historical  & Scientific Content:

This microhistory draws almost entirely  from a cache of primary source documents in Seville’s Municipal Archive. Surprisingly, quotes from these documents are very short. The focus on Seville is so intense context is often lacking.

The science is anecdotal and kept at the level of sixteenth century understanding. They don’t apply modern understanding of plague or influenza.  Medical treatment is discussed vaguely; few specific treatments are detailed. For example, the council paid for apothecaries to stock and provide plague medicines but the authors didn’t discuss what they stocked or if they had difficulty obtaining medicines. It appears that there was no standard treatment or medication used in the region. They don’t make an effort to accumulate data or do any standard epidemiological analysis. By the end of the book I was craving some data. The volume of anecdotal evidence does provide plenty of evidence that diagnosis was not very secure for many individuals complicating data classification.  Historical epidemiologists will have to cope with other concurrent diseases, significant for plague outbreaks that last months to over a year. Ironically in the case of Seville, I suspect a standard epidemiological chart of total deaths vs time would have highlighted the difference between influenza and plague.

References, Illustrations, and Usability

It has a full bibliography but minimal footnotes, mostly to primary sources. I suspect that it would be fairly difficult to look for more information based on their footnotes and access to the primary sources.  They appear to have made minimal use of the secondary sources, or at least there are very minimal footnotes to them. It does have a glossary for Spanish terms; all quotes are translated. The illustrations were okay. It could have used a few more local maps fit into the text where appropriate.

I recommend this book primarily for biosecurity and crisis managers. Its usefulness to the sciences and humanities is primarily for anecdotal information.

Top 11 in 2011

As the year comes to a close, I thought I would share the top 11 posts here at Contagions for this past year. I’m excluding round-ups and the educational chain of infection posts. These chain of infection posts account for over a third of all page views on this blog over the year and all time! So without further ado, here are the top 11 regular posts based on page view stats as of December 29, 2011.

  1. Pandemic Influenza: 1510-2010
  2. Beyond Pelusium
  3. Did India and China Escape the Black Death?
  4. Vampire Prevention in Eighth Century Ireland
  5. Rinderpest, Measles and Medieval Emerging Infectious Diseases
  6. The Vampire in the Plague Pit
  7. Hunting Pathogens in the Siberian Permafrost
  8. Plague in 18th century Egypt
  9. DNA of the Black Death at East Smithfield, London
  10. Plague DNA from Late Antique Bavaria
  11. Epidemiology of the Russian Flu, 1889-1890

Happy New Year!!

Insights into the pathogenesis of the Spanish Flu

ResearchBlogging.orgThis post was chosen as an Editor's Selection for

One of the enduring mysteries of influenza is why the 1918 H1N1 influenza, better known as the Spanish Flu, was so unusually deadly. The 2009 H1N1 influenza was certainly capable of creating a pandemic but was not nearly as deadly. Granted most of the fatalities in 1918 had bacterial pneumonia that could probably have been cured today. However, the incidence of fatal viral pneumonia appears to have been much higher in 1918. This viral pneumonia was reported to cause “massive acute pulmonary hemorrhage or pulmonary edema”.

New techniques in reverse genetics have allowed two groups, one from the CDC and the other from Japan, to recreate the 1918 virus. This allows either the whole 1918 virus or specific genes or genetic segments to be directly tested on animals.

Contemporary H1N1 influenza viruses infect the upper airways only. The reconstructed 1918 H1N1 virus creates an intense infection in the lungs of non-human primates that culminated in acute respiratory failure and death. Necropsy results have shown extensive pulmonary edema and hemorrhages not found in animals infected with contemporary H1N1 viruses. Microarray analysis showed that the 1918 virus infected animals mounted a strong but atypical innate immune response.

So what is it about the 1918 H1N1 influenza virus that increases its virulence and triggers such a strong but atypical immune response?

Its been known for some time that the hemagglutinin (HA) gene –responsible for host cell selection and membrane fusion — is critical for the high virulence of the avian viruses. The 1918 H1N1 virus lacks the specific motif identified on the avian HA gene that has been attributed to its virulence. When the 1918 HA gene is added to an otherwise contemporary H1N1 virus, it produced a high lung titer causing severe lung damage in mice with infiltration by neutrophils and alveolar macrophages. The results were similar to the whole reconstructed 1918 H1N1 virus. The exact portion of the HA gene that is critical for its virulence is yet to be determined. It is not very surprising that a viral spike responsible for host cell binding and fusion is involved in expanding the target tissue to the lungs.

The role of the 1918 viral RNA polymerase complex in viral repication. (click to enlarge, from Watanabe & Kawaoka, 2011)

The viral RNA polymerase complex has also been implicated in the high  virulence of the 1918 virus. Unlike contemporary influenza viruses, the 1918 virus replicates in the nasal cavity but also along the trachea and within the lungs. As you can see in the figure to the left, the hybrid virus containing the 1918 RNA polymerase complex and NP gene  (PA, PB1, PB2, and NP genes) and the remainder from a contemporary H1N1 virus replicated in the same tissues as the complete 1918 virus. The contemporary H1N1 virus replicated only in the upper respiratory system. Here we have replication of the hybrid virus without the 1918 HA gene replicating in the lungs. Clearly more research is required to reconcile the HA and RNA polymerase complex results.

Other genes have been implicated in increasing the effectiveness of the 1918 virus but the results are more vague.  The availability to reconstruct all or part of the 1918 H1N1 virus along with the 2009 H1N1 pandemic virus and contemporary drifted H1N1 viruses should mean that we will be able to eventually unravel some of the mysteries of influenza but there is still a long road ahead.


Watanabe, T., & Kawaoka, Y. (2011). Pathogenesis of the 1918 Pandemic Influenza Virus PLoS Pathogens, 7 (1) DOI: 10.1371/journal.ppat.1001218

This review paper is freely available here.