John Snow, Asiatic Cholera and the inductive-deductive method - republished
Lecture 6: Point source outbreaks
Last week, we discussed disseminated source outbreaks. In today’s post, we will discuss point source outbreaks. In a later post, we will learn about the important link between exposure and outcome.
The Snow series is an educational course. We hope you will recognise our efforts by donating to TTE or becoming a paying subscriber, as writing the series took a lot of time and effort.
Snow realised that river contamination could not explain some outbreaks, which seemed to be very localised and clustered, so he added what we now call a point source outbreak to his theory.
Snow’s theory is described on the following page. Towards the end of page 56 of On the Mode of Communication of Cholera 2nd edition (MCC 2), he points out that river-borne poison is far more widely distributed (“extended”) than that from a point source outbreak, i.e. originating from a single point such as a well or a pump.
Whatever the means of transmission, however, Snow repeatedly pointed out the close connection between dirty water (which often gives off an offensive smell if left to settle in a container) and cholera cases.
However, other than collecting information from around the country and the world, how could he test his hypotheses?
Snow kept going despite scepticism and criticism from the establishment. Paneth et al. point out that Snow refined his hypothesis, focused it, and tested it between publishing MCC's first and second versions.
CONTEMPORARY THEMES
In the chaos of mass testing, media noise, politicking and fear induced by ignorance, superstition and vested interests, few scientists considered describing and analysing the mode of spread of SARS-CoV-2. Was it a propagated source epidemic, point source, or both? We doubt the data are good enough to allow any credible retrospective analysis. However, we offer you this original daily overview of the Feb to 24 March 2020 progression of SARS-CoV-2 cases (or at least of those who “tested positive”) in the whole region of Lombardy.
The table is part of a document the Lombardy Italian governments used to make decisions. Look at the trend: do you notice anything? To help you, we suggest you disregard deaths which had unclear attribution rules and ICU admissions which were confounded by the “just in case” approach in a proportion of early cases:
The national lockdown was introduced on 9 March.
Below is the Lombardy cumulative case map as of March 25, 2020. The key colours on the right get progressively darker as the number of cases increases in the area, so the darkest blue means more than 700 cases since the start of the outbreak.
What are we looking at?
If (and it is a big if) the map is remotely accurate, it shows four dark blue clusters with a bit of spread around them. But here we are dealing with viruses, not bacteria. These clusters have yet to be investigated and have not been subjected to the in-depth analysis Snow carried out in 1854. Thus, the appearance is of four-point source outbreaks with a spread around them, but the blank spaces worry us. Are they real, or were the data not reported?
Learning objective: what are point source outbreaks?
An outbreak in which persons are exposed to the same source of infection over a brief period, such as through a single meal or an event. In a point source outbreak, the number of cases increases rapidly to a peak and then falls off more gradually. The majority of cases occur within one incubation period of the disease.
Readings
Paneth N, et al. A rivalry of foulness: official and unofficial investigations of the London cholera epidemic of 1854. Am J Public Health. 1998 Oct;88(10):1545-53. doi: 10.2105/ajph.88.10.1545.
Getting ahead of the curve – what are epidemic curves and why are they important? Public Health Agency, Northern Ireland.
Subscribe to Trust the Evidence
Informing health decisions by separating evidence from opinion
The incidence map of Lombardy is fascinating. You ask if the pale spots might be due to under-reporting or lack of data. That might well be the case, given that rural areas often lack access to doctors and hospitals.
However, there's one thing which intrigues me, something John Snow did not have the means to investigate but which could well be investigated in relation to covid: why were/are so many people not affected or only mildly affected? Perhaps some methods of treatment or even prevention might be discovered?
When this was first published, someone pointed out that the four dark blue areas centre on major bus stations in Lombardy. There is a speculation which explains the map.
All RNA viruses replicate poorly and have to be DNA cloned to be studied. DNA polymerase is literally a million times more true than RNA polymerase fidelity. At ~30kb coronaviruses have more than double the genome size of other RNA viruses. They seem to survive only because non-structural protein nsp14 gives some degree of error correction. Even then electrophoresis shows poor replication fidelity. So if someone cloned a viral genome and transcribed it back to RNA then every viral particle in the bottle would be whole genome, instead of debris. (It is actually the mass of debris which makes you ill.) Now if you released a bottle at 4 bus stations on successive weeks you would get the appearance of the Lombardy map with a big jump in numbers on release but dying off quickly due to the poor replication.