John Snow, Asiatic Cholera and the inductive-deductive method - republished
Lecture 3: Incubation period and defining a case and numerator
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Snow continues his description of hundreds of cases of cholera which affect communities. Snow remarks that cholera is transmitted from the healthy to the sick over and over again. He corresponded with scores of physicians up and down the country who reported the same set of signs and symptoms: feeling unwell, followed by the excretion of copious amounts of watery faeces (“rice water”), vomiting and anuria (not passing any urine), followed by death by what we would now call hypovolemic shock.
The post-mortem findings were also typical, with congestion of small bowel mucosa and dryness of tissues. Snow also describes the density of blood, comparing those from the sick with those from the healthy. The acute loss of fluids was the unifying characteristic of all fatal cases, although sometimes of variable severity - from floods to none at all (so-called dry cholera). In the latter rare event, fluids were lost inside the body, which appeared bloated at post-mortem examination.
However, the incubation period drew Snow’s attention (pages 15-16).
Cholera is a specific disease, not a syndrome, with a variety of signs and symptoms that could be due to any one or multiple causes but are not specifically characteristic or indicative of a particular disease or condition (pathognomonic). Rice water diarrhoea and general collapse are the pathognomonic clinical signs of cholera. If untreated with intensive rehydration, it can be lethal. There was no such treatment in Snow’s time.
CONTEMPORARY THEMES
As we will see further on, florid cholera did not need testing for someone with experience in the clinical aspects of the disease. It is a disease with pathognomonic symptoms and instantly recognisable signs. Typical signs and symptoms do not exist for acute respiratory infections, which are fleeting and sometimes life-threatening. If you really want to know if any agent is present when respiratory symptoms manifest themselves, you have to use a laboratory test.
Viral culture takes time but is the gold standard, so we take refuge in antibody testing (even more time-consuming if repeated at two-week intervals to check the rise compared with baseline) or Polymerase Chain Reaction (PCR). The limits of PCR, especially if used in the inappropriate way it was used in 2020-2021, have been glossed over. It is a sophisticated test capable of identifying active cases, i.e. those who can transmit the disease, if used correctly. But it cannot do so in the insane way it was used in the early stages of the pandemic: sucking in resources and distorting perceptions of threat. The inappropriate use was a major driver in the scare tactics used to try to control the populace.
The incubation period is the number of days between becoming infected and experiencing symptoms.
For example, the Imperial College Report 9, which had such an impact on pandemic policy for lockdowns,”assumed an incubation period of 5.1 days Infectiousness is assumed to occur from 12 hours prior to the onset of symptoms for those that are symptomatic and from 4.6 days after infection in those that are asymptomatic with an infectiousness profile over time that results in a 6.5-day mean generation time.”
Two papers from China were used to estimate these timings.
Epidemiological characteristics of novel coronavirus infection: A statistical analysis of publicly available case data. medRxiv 2020;2020.01.26.20018754.
Early Transmission Dynamics in Wuhan, China, of Novel CoronavirusInfected Pneumonia. N Engl J Med 2020;
Questions.
How generalizable are the results of these two papers to the Western world?
What impact does the incubation period have on the spread of infection?
No such problems encumbered Victorian physicians who knew a case of cholera when they saw it. In other words, they had a relatively stable and credible numerator, unlike their modern counterparts who use a bewildering number of definitions of cases and misuse and misinterpret PCR results.
Diagnosing cholera
Currently, the gold standard for the laboratory diagnosis of cholera is isolating and identifying Vibrio cholerae serogroup O1 or O139 by culture of a stool specimen.
A gold standard is a method, procedure or measurement widely accepted as the best available to test for a disease. Usually, the diagnostic test is the best available under reasonable conditions.
The WHO has published a suggested outbreak case definition
A suspected case:
In areas where a cholera outbreak has not been declared: any person aged two years and older presenting with acute watery diarrhoea (AWD)1 and severe dehydration or dying from AWD;
Once a cholera outbreak has been declared, any person presenting with or dying from AWD.
A confirmed case:
a suspected case with Vibrio cholerae O1 or O139 infection confirmed by culture or polymerase chain reaction (PCR), and in countries where cholera is not present or has been eliminated, the Vibrio cholerae 01 or 0139 strain is demonstrated to be toxigenic.
Based on results from an Analysis of Laboratory-Based Surveillance Data from Haiti, 2012–2013, the sensitivity of the WHO case definition for cholera in an epidemic setting was 91%.
That means of 100 people with cholera, 91 will meet the WHO criteria.
However, the specificity is 43% in those without cholera. Therefore, a high number (57) will still meet the criteria but not have cholera. The WHO’s case definition is good for ruling out the disease but not so good at ruling it in, as some people in affected areas will still have watery diarrhoea caused by other reasons (e.g., children could have viral gastroenteritis). This explains why culture or PCR is required with the presence of symptoms to confirm the diagnosis.
Readings
Viral Cultures for Coronavirus Disease 2019 Infectivity Assessment: A Systematic Review, Clinical Infectious Diseases, Volume 73, Issue 11, 1 December 2021, Pages e3884–e3899, https://doi.org/10.1093/cid/ciaa1764
How misuse and poor management of a sensitive molecular test led to mass psychosis and uncertain case numbers: The Long Read
Report 9: Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand
Identifying the most sensitive and specific sign and symptom combinations for cholera: results from an analysis of laboratory-based surveillance data from Haiti, 2012-2013. Am J Trop Med Hyg. 2015 Apr;92(4):758-764. doi: 10.4269/ajtmh.14-0429.
If Snow had practiced in 2020 he would not have been able to do post-mortem examinations. Let's call it medical progress...
thanks for taking us through these things; nice to have the madness of PCR testing woven into what some recognise as more standard methods; and more measured ways; deep in the WHO of the past, must have been some sense and tradition; before they were bought out by big money;
so much education for us here: sensitivity and specificity; though we have heard them many times, good to go back and remind ourselves how they are defined; and the things that lead from them: the sort of puzzles folks set; the incidence of a disease is .. z%; sensitivity is x%; specificity is y%; if the test comes back positive, what is the chance the person truly has the disease? .. that sort of brain teaser ..... could almost just be a short but very educative post ....... best wishes as always for allowing us the privilege of being part of such an wonderfully immersive and endlessly educational and refreshing experience; best wishes again