1. John Snow’s Investigations of the Cholera Epidemics in London, 1848-1854

2. Source of Information for the John Snow Example
UCLA School of Public Health, Department of Epidemiology
Website:

3. British cholera epidemics:
first modern outbreak in Britain
23,000 deaths
helped to launch the sanitary reform movement :
250,000 cases and 53,000 deaths
prompted Snow (and others) to investigate causes

4. The London Cholera Epidemic of September 1848 – August 1849
Based on his clinical experience and review of epidemiologic characteristics of cholera, Snow formulated a theory of causation and transmission of the disease.

5. The London Cholera Epidemic of September 1848 – August 1849
Snow’s hypotheses concerning cholera:
a gastrointestinal disease, therefore causal agent was likely ingested
diarrhea as most prominent symptom, therefore causal agent likely left the body by this route
if cholera excretions contaminated rivers from which drinking water was taken, then the disease could be widely disseminated

6. The London Cholera Epidemic of September 1848 – August 1849
Causal Hypothesis:
Sewage-contaminated drinking water was a causal agent for the cholera epidemic.

7. The London Cholera Epidemic of 1848-1849
Snow tested this hypothesis by first conducting an “ecologic” study of London districts using:
routine surveillance data on cholera cases
population data at the district level
available information on water companies serving the districts
available data on property values by district

8. The London Cholera Epidemic of 1848-1849
Characteristics of an ecologic study:
unit of analysis is not the individual or case
unit of analysis is a geographical unit such as a district or neighborhood or city or county
useful to initially study a cause-effect relationship when data are easily available and/or an individual level study is not feasible
does not directly link an individual case to an exposure (unless everyone in the geographical unit has a similar exposure)

9. The London Cholera Epidemic of 1848-1849
Snow did not have exact information on the sources of water for the districts.
However, Snow knew that:
the East and South districts were served by water supplies obtained from known polluted parts of the Thames River
the rest of London received drinking water relatively uncontaminated by sewage.

10. Districts of London Population in 1841 Deaths from Cholera
to each 1,000
inhabitants
West
300,711
533
1.77
North
375,971
415
1.10
Central
373,605
920
2.48
East
392,444
1,597
4.06
South
502,548
4,001
7.95
Total
1,948,369
7,466
3.83
Deaths from Cholera in London; Registered from
September 23, 1848 to August 25, 1849

11. The London Cholera Epidemic of 1848-1849
Limitations of ecologic study:
Uncertainties about districts’ water supplies
some residences used water pumps
some districts served by more than one company
Districts may vary by socioeconomic (SES) factors
Don’t know if cholera cases actually drank contaminated water

12. The London Cholera Epidemic of 1848-1849
Most of southern districts were served by two water companies, both using sewage-contaminated water from Thames River.
Southwark and Vauxhall Water Company
Lambeth Water Company

13. In 1852, Lambeth Water Company moved its intake to an uncontaminated part of the Thames River

14. Southwark & Vauxhall and Kent 107 Sourthwark & Vauxhall 94
Cholera death rate in London
according to water company
supplying district of residence
(August 1853 – January 1854)
Water Company
Deaths from cholera in 100,000
Southwark & Vauxhall and Kent
107
Sourthwark & Vauxhall 94
Lambeth and Southwark & Vauxhall 61

16. Water company Population in 1851 Deaths from cholera Deaths in 100,000
Cholera death rate in London
according to water company
supplying sub-district of residence
(August 1853 – January 1854)
Water company
Population in 1851
Deaths from cholera
Deaths in 100,000
Southwark & Vauxhall
12 sub-districts
167,654
192
114
Both companies
16 sub-districts
301,149
182 60
Lambeth
3 sub-districts
14,632

17. Ecologic study of districts and sub-districts could not rule out:
confounding by socio-economic (SES) factors.
Exposure misclassification (e.g., public wells)
Ecologic study could not link cases with exposure. (Cases may not have drunk contaminated water.)

18. The natural experiment: 16 sub-districts served by both water companies, with pipes from both companies going down every street, serving residences in a virtually random fashion.

19. The natural experiment: individual-level study

20. The natural experiment: “shoe-leather epidemiology”
Home of each case was visited to determine source of water to the residence:
next-of-kin recall found to be inadequate
confirmation by water bill receipt or by water sample.
Reports from water companies provided denominator information (# houses supplied in each district)

22. The natural experiment
The preceding table included:
districts served by both companies in an intermingled fashion (i.e., the natural experiment) and
districts served by only one of the companies.
the relative risk = 315/ 37 = 8.5

23. The natural experiment
Because Snow combined both districts with and without intermingled supplies, confounding bias by SES factors was still possible:
the districts served only by Lambeth Co. were wealthier than those served only by Southwark & Vauxhall.
When Snow later focused only on the districts with intermingled supplies, the relative risk fell from 8.5 to 6.9.

24. The Broad Street Pump Outbreak

25. The most terrible outbreak of cholera which ever occurred in this
INSTANCES OF THE COMMUNICATION OF CHOLERA THROUGH THE MEDIUM OF POLLUTED WATER IN THE NEIGHBORHOOD OF BROAD STREET, GOLDEN SQUARE
(August 31 – September 9)
The most terrible outbreak of cholera which ever occurred in this
kingdom, is probably that which took place in Broad Street, Golden Square, and the adjoining streets, a few weeks ago. Within two hundred and fifty yards of the spot where Cambridge Street joins Broad Street, there were upwards of five hundred fatal attacks of cholera in ten days.
Source: Snow J. On the Mode of Communication of Cholera, p 38.

29. The Broad Street Pump Outbreak
Snow began the investigation with:
a hypothesis from his previous work
sewage-contaminated drinking water is a cause of cholera
a working knowledge of the cluster area (he resided nearby).

31. The Broad Street Pump Outbreak
Piped water not contaminated by sewage.
Water samples on 9/3 from pumps near Golden Sq. found that all except the Broad St. pump had visible impurities.
However, local residents reported foul smells from the Broad St. pump water the day before the pump samples were taken.
Days later, small flocculent particles were detected in Broad St. sample.

32. The Broad Street Pump Outbreak: difficulties of exposure assessment
Variability in sampling results over time
sampling a day earlier may have found visible contamination in Broad St pump water
Uncertainties about relevant contaminant
visible particles seen immediately?
flocculent particles seen days later?
High or unknown detection limits
Lack of information on contaminant sources (e.g.,local cesspool near pump)

33. The Broad Street Pump Outbreak: case series evaluation
61 of 73 cases drank water from the Broad St. pump; 6/73 did not; 6/73 unknown.
2 cases living far from the area used water from the Broad St. pump.
No outbreak among those in the outbreak area who did not use Broad St. pump
5 deaths among 535 inmates
0 deaths among 70 brewery workers

34. Cholera outbreak in Golden Square, Broad Street, London 1854

36. Lessons from Snow’s Investigations
Based on review of what was known about cholera, Snow formed a hypothesis:
sewage in drinking water causes cholera
Snow tested hypothesis using available data to conduct an ecologic study comparing cholera rates in districts and subdistricts

37. Lessons from Snow’s Investigations
Snow recognized the limitations of the ecologic study:
could not directly link individual cases to exposure to contaminated drinking water
alternative explanation for findings: confounding by SES factors

38. Lessons from Snow’s Investigations
Snow identified a study area and study population that:
provided an excellent exposure contrast (high vs no exposure)
minimized confounding by SES factors
districts with intermingled supplies of high and low contamination serving homes in a virtual random fashion - a natural experiment

39. Lessons from Snow’s Investigations
shoe-leather epidemiology approach to case verification & exposure assessment:
visiting the homes of the cholera cases
obtaining verification of source of water for each case residence (receipt, water sample)

40. Lessons from Snow’s Investigations
collected denominator data from water companies in order to calculate disease rates among exposed and unexposed.

41. Lessons from Snow’s Investigations
Explored alternative explanations:
focused on districts with intermingled supplies to minimize confounding by SES factors
in the cluster investigation, Snow identified:
brewery workers and inmates unexposed to the contaminated water but worked in cluster area in order to rule out air pathway of exposure
high SES cholera cases living far from the cluster area whose only link to the cluster was drinking from Broad St pump

42. Lessons from Snow’s Investigations
Snow found an association between exposure and disease and used this information for prevention
Snow utilized tables and maps to present a strong case for a causal relationship between sewage-contaminated drinking water and cholera