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Last week, we discussed Snow’s investigation of local outbreaks in South London.  In today’s post, we will discuss the contemporary objections to Snow’s theory and how he dealt with them. On Thursday, we will start on the famous Broad Street outbreak.

Towards the end of On the Mode of Communication of Cholera. 2nd edition (MCC2) Snow tackles some objections to his waterborne theory.

First, some of Snow’s critics remarked that there were several fatal cases of people coming from the country into London. These cases could not be reconciled with contaminated water exposure in London. Snow investigated these cases and found that upon arriving in the Southern Districts, these fatalities had been exposed to water from the Southwark and Vauxhall Company. He mentioned that all these cases manifested symptoms of cholera all within a short space of each other after exposure (48 hours), as did the sailors in the Baltic fleet. This is incompatible with the action of water as a mediating or predisposing factor and incompatible with the clustering of cases around a contaminated water source. So, the contingent contagionism theory was not supported by these facts. It is incompatible as a mediating factor because miasma theory proposed a reaction/fermentation between “cholerine” or the cholera poison, which took some time to activate (see Lecture 4). 

Snow also made an analogy with other diseases transmitted through bad hygiene:

Then he discussed the “challenge” cases when, involuntarily or voluntarily, several people swallowed cholera faeces.

He goes on: “the large quantity of the evacuation taken might even prevent its action”.

Remarkably for someone who could not visualise or identify the agent, he continues: “It must be remembered that the effects of a morbid poison are never due to what first enters the system but from the crop or progeny produced from this during the period or reproduction.” 

The great hygienist and contingent contagionist Max Von Pettenkofer is perhaps the most famous example of such a purposeful self-experiment (see also Lecture 4). On October 9, 1892, he ingested a broth of cholera to disprove Koch’s postulates, having first neutralised his gastric acids by ingesting bicarbonate. Von Pettenkofer argued that vibrios (identified and causally linked to cholera by then) on their own were insufficient to cause disease but had to be modified by contact with soil to activate it.

Snow’s observation based on the length of the incubation period also introduces the concept of infectious dose.

A further objection raised by Dr Thiersch “is that the cholera evacuations are not at first capable of generating the disease; but that a decomposition takes place in them, and that in from six to nine days they become in a state to induce cholera. He founds this opinion on experiments which he performed by giving small quantities of the cholera evacuations to white mice. Although it is not contrary to all analogy that some change or development should take place in the cholera poison in the interval between its leaving one person and entering another, it is most probable that the fatal bowel complaint produced in white mice by Dr Thiersch was not a specific disease, but the ordinary effect of putrefying ingesta. Many of the best attested instances of the communication of cholera are those, such as were related at the commencement of this work, where the patient is attacked in from twenty-four to forty-eight hours after first being near another patient, and although an interval of a week or so, often elapses between one case of the disease and those which follow, it is extremely probable that, in these instances, the evacuations remain the greater part of this time in a dry state on the soiled linen, without undergoing any change.“

In response, Snow argues the objection, repeating the idea of contact transmission and clustering of the disease in its acute phase. His great experiment in South London had already disproved the miasma hypothesis.

Readers can appreciate how Snow again turns the objections into a logical explanation of facts which fit his theory.

CONTEMPORARY THEMES

The issue of the ecology of the agents will be discussed again in the context of lecture 13 when we introduce the concept of Farr’s Law of Epidemics (see also Lecture 6).

Here, we will discuss the issue of interaction and complexity. Based on Koch’s initial formulation of his postulates, the idea that simplicity can prove transmission and infection is easy to refute. “One bug, causing one disease” is not what happens, as the ecology of the agents is complex. Von Pettenkofer’s original and everlasting contribution to epidemiology is the introduction of the issues of interaction between agent, host and environment (see also Lecture 4).

This understudied aspect of epidemiology explains why sometimes exposure and host susceptibility are not sufficient to explain the insurgence of the disease.   

This can be seen in contemporary challenge studies in which immunologically naive people volunteer to have live agents (usually respiratory viruses) squirted up their noses, i.e. their bodies and immunity are challenged. Not everyone is infected; in the SARS-CoV-2 challenge study, 47% of volunteers did not develop symptoms. In the MRC Common Cold Unit, Sir Christopher Andrewes, one of the discoverers of the human influenza virus, got even worse results due to his puzzlement. So, “simple” is not likely to exist in the transmission of viral agents or microbes, and embracing uncertainty is the only rational way to study viral agents with an open mind.

Readings

Epidemiologic interactions, complexity, and the lonesome death of Max von Pettenkofer. Am J Epidemiol. 2007 Dec 1;166(11):1233-8. doi: 10.1093/aje/kwm279. 

Morabia Responds to “The Context and Challenge of von Pettenkofer's Contributions to Epidemiology”, American Journal of Epidemiology, Volume 166, Issue 11, 1 December 2007, Pages 1242–1243, doi: 10.1093/aje/kwm285

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.

Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults. Nat Med. 2022 May;28(5):1031-1041. doi: 10.1038/s41591-022-01780-9. Epub 2022 Mar 31.

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