In this second part, I will continue the story of cholera and draw some conclusions for the control of emerging infections. The objectives of this part are to define a natural experiment; to define the mode of transmission of cholera as it is now understood; and to discuss the implications of mode of communication for the impact of control measures. At the end of August 1854, following a series of smaller outbreaks in London, a major epidemic of cholera began near Golden Square in Soho, a district in central London with a few thousand residents. Within a few days, more than 100 people had died, residents were fleeing the area, and by the end of the outbreak the death toll was more than 600. Later, Snow would call it, "The most terrible outbreak of cholera which ever occurred in this kingdom." He visited the death registry and obtained the home addresses of the cholera deaths in the area, and then he went around the area door-to-door to identify cases of cholera. The result of his investigation is this famous map of cholera cases. Snow’s suspicions immediately fell on the Broad Street pump, from where local residents drew their drinking water. Snow noted that the cases were clustered around the Broad Street pump, with a few important exceptions. Residents of the brewery were unaffected, and Snow found that they drank their own beer rather than water. More than 500 residents of the workhouse were largely unaffected, and they had their own well. As part of his investigation, Snow determined the walking distance to each nearby pump, and added this line to the map. From any point inside the line, it is quicker to walk to the Broad Street pump than any other pump. Most of the cases fall inside the line, and of those outside, Snow determined that half preferred to visit the Broad Street pump even though it was slightly further than another water source. The evidence that really clinched it for John Snow was when he heard about a case in Hampstead five miles away, in a widow who used to live in Broad Street, and so loved the water that she had the water shipped to her on a weekly basis. Having received a delivery of contaminated water on Thursday, she fell ill on Friday and died on the Saturday. She and her maid were the only two people to die of cholera in Hampstead. On the evening of the 7th of September, John Snow presented his findings to local officials, and convinced them to remove the pump handle, to prevent any new cases. The officials agreed, and the epidemic subsided. A subsequent investigation, not by John Snow, established that the well had probably been contaminated by the cesspit of the house nearest to the pump, in which a baby had been ill with cholera on the 28th of August. John Snow is often credited with controlling the outbreak, through removing the pump handle, which is of course a non-pharmaceutical intervention. However, as Snow noted from the epidemic curve shown here, the epidemic was largely over by the 7th of September. John Snow then proceeded to conduct another, larger study. Snow noted that water was supplied to households in London by a number of different water companies. He obtained, from William Farr, the addresses of the first 334 recorded cholera deaths in a particular area of London that was mainly served by two particular companies, the Southwark and Victoria company, and the Lambeth company, and he visited each household to enquire which company they obtained their water from. He was able to obtain information for 330 of the 334 cases, which is a remarkable effort. Separately, he obtained information on the number of houses in those areas of London whose water was supplied by each of the two companies. He then compared the incidence rates of cholera, and identified a far higher rate among households supplied by the Southwark and Victoria company. Whereas the Lambeth company had recently moved its waterworks upstream, the Southwark and Victoria company drew their water from the Thames in central London, where contamination by fecal matter could have been much greater. This is an example of a natural experiment. In Snow’s own words, "No experiment could have been devised which would more thoroughly test the effect of water supply on the progress of cholera." What distinguishes a natural experiment from a typical scientific experiment is that the interventions are applied by nature, rather than by the investigator. However, the scientific community was not convinced by Snow’s theory that cholera was spread by the fecal-oral route, and communicated through contaminated water. Snow’s report on the water supply companies and the Golden Square outbreak was followed by scathing editorials in The Lancet, continuing to support the miasma theory, and branding Snow as an enemy of sanitary progress. Other commentators also noted that removal of the pump handle did not control the outbreak, and questioned why some people who drank contaminated water failed to fall ill if it was consumption of contaminated water that caused the disease. It was not until 1866, eight years after Snow had died, that his theory was finally accepted. By 1890, Dr John Simon, the first UK Medical Officer of Health, wrote that John Snow’s hypothesis of cholera was “The most important truth yet acquired for the prevention of epidemic disease." Snow's work identifying cholera as a communicable disease is now held up as a textbook example of the arrangement of established facts into chains of inference. While he was not the first to blame contaminated water, Snow is heralded for his elegant analysis of outbreaks, including the one in Golden Square, and the natural experiment with different water supply companies, which provided convincing evidence in support of his theory that the disease was communicated in excretions of cholera victims via contaminated water. So what can we learn from this that is relevant to our topic of non-pharmaceutical interventions? First, John Snow differed from his contemporaries because he was searching for the mode of communication or transmission of cholera between people, rather than the factors that placed people at higher risk of infection. By identifying the mode of communication of cholera, that is the process by which the pathogen spreads between hosts, Snow was able to identify interventions that would be effective. It was not essential to identify the agent, which in the case of Vibrio cholerae was publicized by Robert Koch 30 years later. In the early stages of a contemporary emerging infectious disease epidemic, laboratory scientists will work day and night to identify the pathogen. As a concrete example, we can think of the outbreak of Severe Acute Respiratory Syndrome in 2003. It was a major breakthrough when the SARS coronavirus was identified as the cause of SARS in 2003, but it was more important for public health when scientists realized that SARS was transmitted by respiratory droplets, mostly within hospitals rather than in the community, and that isolation of cases and respiratory protection of healthcare workers was necessary and sufficient to control the outbreak. In other words, the SARS epidemic would not be controlled unless cases were identified, isolated, and front-line staff treating those patients wore protective equipment, and that doing all of these things led to control of the outbreak in a population. Now, SARS transmission did occur outside hospitals, but perhaps not at a high-enough rate to sustain an epidemic. Second, we learn that non-pharmaceutical interventions can be effective in controlling an infectious disease outbreak. The Broad Street epidemic largely subsided because 75% of the residents had left the area within a week of the start of the outbreak, and because exposure was so common that those who were vulnerable to infection were rapidly infected. But if the contaminated pump had been identified sooner, removal of the handle could have prevented hundreds of cholera deaths. In the separate analysis of water supply companies, the decision by the Lambeth company to move its waterworks upstream turned out to save many lives among its clients, and similar actions by other water companies could have prevented more cholera deaths. I will conclude this section by inviting you to read more about the story of John Snow and his pioneering work on cholera.
