Epidemiology of a bubonic plague outbreak in Glasgow, Scotland in 1900

On 3 August 1900, bubonic plague (Yersinia pestis) broke out in Glasgow for the first time during the Third Pandemic. The local sanitary authorities rigorously tracked the spread of the disease and they found that nearly all of the 35 cases could be linked by contact with a previous case. Despite trapping hundreds of rats in the area, there was no evidence of a rat epizootic and the investigators speculated that the outbreak could be due to human-to-human transmission of bubonic plague. Here we use a likelihood-based method to reconstruct transmission trees for the outbreak. From the description of the outbreak and the reconstructed trees, we infer several epidemiological parameters. We found that the estimated mean serial interval was 7.4–9.2 days and the mean effective reproduction number dropped below 1 after implementation of control measures. We also found a high rate of secondary transmissions within households and observations of transmissions from individuals who were not terminally septicaemic. Our results provide important insights into the epidemiology of a bubonic plague outbreak during the Third Pandemic in Europe.

Have you any concerns about statistical analyses in this paper? I do not feel qualified to assess the statistics

Recommendation? Accept with minor revision (please list in comments)
Comments to the Author(s) This paper provides a very interesting analysis of a small scale outbreak of plague during the 3rd pandemic in the city of Glasgow. The use of historical data to explore the likelihood of human-tohuman plague transmission (through a human ectoparasite vector) and the household clustering of plague cases, make this study sufficiently original and novel for publications in "Open Science". Especially since the epidemiology of plague (both 2nd and 3rd pandemic) in Europe remain poorly understood as the authors rightfully indicate.
Since two previous referees have already commented on the analysis of the data and the conclusions derived from this analysis. And since I deem the responses of the authors on the comments made by the previous referees to be sufficiently satisfying, I will instead focus on the contextualization of the paper within the broader historiography of historical plague studies.
Afterwards, I will also include some minor comments that the authors can choose to implement or ignore at their own discretion, as I do not think them vital enough to prevent publication of the paper.

Contextualization
At several points in the paper, the authors indicate that their findings "provide important insights into the epidemiology of bubonic plague outbreaks in pre-antibiotic Europe". Although I agree that the paper provides important insights, I would ask that the authors to reflect more critically on the representativeness of findings for the 3rd pandemic as indicative for all bubonic plague outbreaks in "pre-antibiotic Europe". Just as we cannot assume that pre-industrial epidemiological experiences necessarily mirror modern ones, findings for 19th century plague outbreaks might not be so easily transposed to late medieval and early modern plague outbreaks. This may, at first, seem like a trivial point, but the disparsities between the 2nd-and 3rd plague epidemics have lead some historical plague experts, such as Samuel Cohn, to claim that , "the Black Death in Europe, 1347-52, and its successive waves to the eighteenth century was any disease other than the rat-based bubonic plague, whose bacillus was discovered in 1894". Even though Cohn wrote these words before laboratory testing could conclusively prove that plague was the causative agent of the 2nd pandemic, the underlying factors that led to his provacative statement remain. Plagues of the 2nd and 3rd pandemic differed noticeably in several key epidemiological characteristics, on the issue of severity alone the present paper illustrates that very fact.

Minor comments (non-compulsory)
To gain further insight in the historical data and provide more information, I would ask the authors to take into account the following elements.
1. What was the geographical occurrence of plague within the city of Glasgow? Were cases clustered in one specific section of the city? Or were they spread out over various parts? 2. What was the total population of Glasgow in 1900. This will help understand how small a percentage of inhabitants died from plague during this outbreak (again see differences between 2nd and 3rd pandemics).
3. Page 3. For literature reference 1, an additional publication might be the book by Myron Echenberg "Plague ports: The global urban impact of bubonic plague, 1894-1901". This study also refers to the 1900 and 1901 plague outbreaks in Glasgow. Alternatively ther is also the article by Echenberg: Pestis Redux, in the journal of World History, which provides some historical background information on the 1900 Glasgow outbreak. 4. Page 3. The sentence "In general, the epidemiology of plague outbreaks in Europe is poorly understood", can be linked (for the 2nd pandemic) to a recent article by Guido Alfani and Tommy Murphy (2017) "Plague and lethal epidemics in the pre-industrial world" p. 318.
5. Page 5. The authors mention several counter-measures implemented by the authorities to mitigate the impact of plague in Glasgow. Some of these 1, 2 and 4 were also widely used in the late medieval and early modern period. Given the limited number of plague cases, would the authors be willing to formulate a hypothesis regarding the effectiveness of the remaining counter-measures as decisive for the limited spread of plague? 6. Page 9. The authors mention that 60% of patients were female and that the overall case-fatality rate was 42.8%. What percentage of overall deaths were female? This also links up with page 11. In describing the epidemiological characteristics of the Glasgow outbreak, the authors reflect on several factors (case fatality rate, symptomatic period), despite the limited sample-size. Would the authors also be willing to describe female over-mortality (if this is the case) and link it up to contemporary findings of female mortality being skewed towards women in certain African cases (e.g. Tanzania)?

19-Nov-2018
Dear Ms Dean On behalf of the Editors, I am pleased to inform you that your Manuscript RSOS-181695 entitled "Epidemiology of a bubonic plague outbreak in Glasgow, Scotland in 1900" has been accepted for publication in Royal Society Open Science subject to minor revision in accordance with the referee suggestions. Please find the referees' comments at the end of this email.
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Once again, thank you for submitting your manuscript to Royal Society Open Science and I look forward to receiving your revision. If you have any questions at all, please do not hesitate to get in touch. Comments to the Author(s) This is an important paper that should be published. It is significant because (a) we still know very little about the mechanisms of historical plague transmission, and (b) it is rare we have such detailed documentary information on the dynamics of the spread and transmission process -i.e. something tangible to support abstract modelling. Some minor adaptations: 1. Bottom p.3/top p. 4. Make clear that better understanding of epidemiological characteristics in the 3rd pandemic does not mean that these characteristics can be simply assumed to be applicable to the 2nd Pandemic. That would have to be demonstrated. 2. Next paragraph down -no evidence for rat epizootics. This is surprising to me. I want to know how unusual this is? How frequently were rat epizootics found in other late 19th-and early 20th century plagues? Basically -is Glasgow a 'special case' or representative of many other Third Pandemic cases. 3. Top of p. 12 -rather than 'historical plague outbreaks' I would explicitly note that these studies find clustering in 2nd pandemic outbreaks from the 14th to the 18th century. on that note -is there really no evidence of household clustering for 3rd pandemics elsewhere? that surprises me. 4. I would like a broader conclusion that notes that you are not dismissing the importance of the rat as a general feature of plague transmission during the 3rd pandemic, but simply suggesting here that the rat-flea-human model is not applicable for every outbreak, and other transmission models (for the bubonic version) can apply in different historical contexts.
Other outstanding problems were already suggested by the previous referees, and well addressed by the authors. Name free to go forward: Dr. Daniel R. Curtis, Leiden University Reviewer: 2 Comments to the Author(s) This paper provides a very interesting analysis of a small scale outbreak of plague during the 3rd pandemic in the city of Glasgow. The use of historical data to explore the likelihood of human-tohuman plague transmission (through a human ectoparasite vector) and the household clustering of plague cases, make this study sufficiently original and novel for publications in "Open Science". Especially since the epidemiology of plague (both 2nd and 3rd pandemic) in Europe remain poorly understood as the authors rightfully indicate.
Since two previous referees have already commented on the analysis of the data and the conclusions derived from this analysis. And since I deem the responses of the authors on the comments made by the previous referees to be sufficiently satisfying, I will instead focus on the contextualization of the paper within the broader historiography of historical plague studies.
Afterwards, I will also include some minor comments that the authors can choose to implement or ignore at their own discretion, as I do not think them vital enough to prevent publication of the paper.

Contextualization
At several points in the paper, the authors indicate that their findings "provide important insights into the epidemiology of bubonic plague outbreaks in pre-antibiotic Europe". Although I agree that the paper provides important insights, I would ask that the authors to reflect more critically on the representativeness of findings for the 3rd pandemic as indicative for all bubonic plague outbreaks in "pre-antibiotic Europe". Just as we cannot assume that pre-industrial epidemiological experiences necessarily mirror modern ones, findings for 19th century plague outbreaks might not be so easily transposed to late medieval and early modern plague outbreaks. This may, at first, seem like a trivial point, but the disparsities between the 2nd-and 3rd plague epidemics have lead some historical plague experts, such as Samuel Cohn, to claim that , "the Black Death in Europe, 1347-52, and its successive waves to the eighteenth century was any disease other than the rat-based bubonic plague, whose bacillus was discovered in 1894". Even though Cohn wrote these words before laboratory testing could conclusively prove that plague was the causative agent of the 2nd pandemic, the underlying factors that led to his provacative statement remain. Plagues of the 2nd and 3rd pandemic differed noticeably in several key epidemiological characteristics, on the issue of severity alone the present paper illustrates that very fact.

Minor comments (non-compulsory)
To gain further insight in the historical data and provide more information, I would ask the authors to take into account the following elements.
1. What was the geographical occurrence of plague within the city of Glasgow? Were cases clustered in one specific section of the city? Or were they spread out over various parts? 2. What was the total population of Glasgow in 1900. This will help understand how small a percentage of inhabitants died from plague during this outbreak (again see differences between 2nd and 3rd pandemics).
3. Page 3. For literature reference 1, an additional publication might be the book by Myron Echenberg "Plague ports: The global urban impact of bubonic plague, 1894-1901". This study also refers to the 1900 and 1901 plague outbreaks in Glasgow. Alternatively ther is also the article by Echenberg: Pestis Redux, in the journal of World History, which provides some historical background information on the 1900 Glasgow outbreak. 4. Page 3. The sentence "In general, the epidemiology of plague outbreaks in Europe is poorly understood", can be linked (for the 2nd pandemic) to a recent article by Guido Alfani and Tommy Murphy (2017) "Plague and lethal epidemics in the pre-industrial world" p. 318.
5. Page 5. The authors mention several counter-measures implemented by the authorities to mitigate the impact of plague in Glasgow. Some of these 1, 2 and 4 were also widely used in the late medieval and early modern period. Given the limited number of plague cases, would the authors be willing to formulate a hypothesis regarding the effectiveness of the remaining counter-measures as decisive for the limited spread of plague? 6. Page 9. The authors mention that 60% of patients were female and that the overall case-fatality rate was 42.8%. What percentage of overall deaths were female? This also links up with page 11. In describing the epidemiological characteristics of the Glasgow outbreak, the authors reflect on several factors (case fatality rate, symptomatic period), despite the limited sample-size. Would the authors also be willing to describe female over-mortality (if this is the case) and link it up to contemporary findings of female mortality being skewed towards women in certain African cases (e.g. Tanzania)?

26-Nov-2018
Dear Ms Dean, I am pleased to inform you that your manuscript entitled "Epidemiology of a bubonic plague outbreak in Glasgow, Scotland in 1900" is now accepted for publication in Royal Society Open Science.
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