Cells that count: philosophy of a diagnostic test for bovine mastitis.

Cells that count: networks of a diagnostic test for bovine mastitis.

Social Epistemology, 2014, in press. 

Can be accessed http://www.tandfonline.com.proxy.library.uu.nl/doi/full/10.1080/02691728.2013.818730#.Uuoa3D3ox8E

Abstract

Somatic cell count (SCC) is a diagnostic test of milk for mastitis in cows. Its specificity and sensitivity are less than 1.0, making test results uncertain. I discuss epistemological problems of the test such as underdetermination, undercalibration and underdiscrimination, in the solution of which biomedical and economic factors may play a role.

Diagnostics of the SCC should be considered as an epistemological network, functioning in a network in which farmers, veterinarians, epidemiologists and milk industry shift their position following biomedical, technological and economic changes, which is described as an actor-network to understand how human and non-human agents in mastitis may be associated.

Introduction

The aim of the paper is to investigate and discuss the epistemology of a diagnostic test and discuss the role of such a diagnostic test in the framing of disease. The background of this investigation is a study I am performing of the history and philosophy of bovine mastitis, a disease or syndrome of lactating cows that has considerable economic consequences but was hardly a problem at all before milk became a modern commercial product at the end of the 19^th century. I use this study of the history of mastitis as an effort to frame the disease in terms of Rosenberg’s definition of framing disease: ‘In some ways disease does not exist until we have agreed that it does, by perceiving, naming, and responding to it’ (Rosenberg  1992). The way mastitis has been framed, and is still reframed continuously, is in my view driven by both biomedical and social (i.e. non-epistemological) factors, such as technology and commercial interests.

The perceiving and naming of a disease is strongly related to its diagnosis and I have argued before that the diagnosis is part of a system of biomedical knowledge of the disease in which it is interconnected to epidemiology, pathogenesis (i.e. the etiology and pathophysiology) and therapy (Nederbragt 2000). This interconnectedness and mutual dependence of the pieces of knowledge from the different biomedical disciplines result in a more or less stable knowledge of the disease as a biomedical entity. Framing a disease reaches beyond the biomedical; it is a process that must be traced back in the past and the frame can only be understood with knowledge of its history. For a diagnosis to point to a disease in this frame at least some agreement must exist of what the disease is; so both disease and its diagnosis must co-evolve. When we assume non-epistemological influences in the framing of the disease we should also assume such influences in the framing of the diagnostic test of the disease. This will be a main theme in this paper.

The framing of a diagnostic test may be seen as an effort to standardize the test, notwithstanding the uncertainties connected to the outcome of the test. I shall discuss these uncertainties in an epistemological approach, making use of more or less traditional concepts. The uncertainty of tests is a common theme in the discipline of epidemiology. Notwithstanding these uncertainties, diagnosis is, according to Rosenberg (2002), ‘central to the definition and management of the social phenomenon that we call disease’. Apparently, it is necessary that the diagnostic test as an epistemological network moves, via the network of the subdisciplines that constitute the disease as a biomedical entity, to the social phenomenon that we call a disease.

I shall proceed as follows. First I will give a description of the most important aspects of bovine mastitis. I will then concentrate on the somatic cell count as a test for subclinical mastitis in milk and discuss three epistemological aspects of this test, ­i.e. underdetermination, undercalibration and underdiscrimination. These three form key factors in establishing the diagnostic test as an epistemic network. In the final paragraph I will sketch the biomedical-statistical network in which diagnosis participates and I will argue that for understanding a patient and her disease we have to weigh the evidence of the diagnostic test against the context of the patient; to be able to do this we have to leave the biomedical-statistical network and enter a social network. The significance of this approach is that we better understand the patient when we make associations between patient, diagnosis, disease and patient-environment. I shall argue that the application of some of the approaches of the actor-network theory may help us to understand how we can associate these actors and that this may clarify the incompatibility of knowledge of disease and knowledge of the patient that I discussed before (Nederbragt 2000).

Nederbragt, H. 2000. The biomedical disciplines and the structure of biomedical and clinical

Rosenberg, C.E. 1992. Framing disease. Illness, society and history. In Framing Disease. Studies in Cultural History, edited by C.E.Rosenberg and J.Golden, pp. xiii –xxvi, New Brunswick: Rutgers University Press.

For the complete paper, see the website of the journal Social Epistemology.

Those who have no access to this journal may send me an e-mail for a copy.

Counting leukocytes to provide a wholesome milk-supply Part 3

Since in milk “good” streptococci cannot be distinguished from “bad” cocci to characterize the quality of the milk as “good” or “bad” for consumption, maybe it is possible to evaluate the quality of the milk by looking at the leukocytes in the milk.  After all, given the assumption that the consumption of milk with mastitis streptococci and sore throats and gastrintestinal disturbances in man are causally related, the determination of inflammation markers in milk may offer an alternative solution for such an evaluation. This raises two problems. First, it has to be established that increased numbers of leukocytes indeed reflect increased numbers of cocci; second, that a threshold value can be determined on which milk can be judged as safe or harmful. This subject constitutes the last part of Harris’ paper. (1)

Harris starts to discuss the use of the word “pus cell” that was common usage in his time. “All milk contains leukocytes” he quotes W.G.Savage, a British public health expert. “When does a leukocyte become a pus cell, and what distinguishes one from the other?” The presence of leukocytes in milk up to a certain point is physiological, but beyond that point is pathological. The literature shows large variations in leukocyte number, among cows and among quarters of one cow. Some authors report proportional relationships between streptococci and leukocytes, others cannot find them.

Next, Harris discusses the attempts to develop practical methods of leukocyte counting. These methods are mostly based on staining cells in known volumes of milk and counting them with a microscope and a hemocytometer; the staining procedures are complicated and time consuming, but Harris consideres them as good.  An alternative method is the use of the tube developed by Trommsdorff, that is filled with 5 ml of milk, centrifuged, and the volume of the sediment read of as a measure of cell number, bur Harris is not very positive about it.

(from a recent catalogue of Gerber Instruments)

One of the authors he mentions had stated that milk containing 500,000 cells per c.c. togther with the presence of fibrin (an inflammation marker, BN) is to be regarded as suspicious, whereas a cell number of one million per c.c. and associated with fibrin “is conclusive of the presence of pus, i.e., evidence of mastitis.

In the next blog I will discuss Harris’ conclusions.

1. N.M.Harris, ‘The relative importance of streptococci and leukocytes in milk’, The Journal of Infectious Diseases, 4 (1907) 50-62.

To provide a wholesome milk-supply: Streptococci and leukocytes.

Part 2

As we have seen in the preceding blogpost, there was discussion about whether  good and bad streptococci are present in the milk, and , since they cannot be distinguished with methods available in 1907, we have to accept two facts, Harris tells us (1):

First that there exists in udders of normal cows a certain species of bacterium, in great numbers, that performs its service to the dairyman; second that streptococci are observed universally in milk. But Harris does not think that the latter fact “is evidence that the cows giving the milk are diseased and that the milk is in consequence unfit for the use of the human subject.” For if it were evidence “then we would be bound to acknowledge that for the greater part milch cows suffer more or less continuously from inflammation of the udder.”

Harris now proceeds with a speculation (his word) based on a view of some colleagues that the normal lactic acid bacteria of the udder are streptococci, which are for the most part non-pathogeneic. The speculation is that he assumes “that after a time the cocci gradually part with their pathogeneic powers, and, undergoing some modification, give themselves over to a saprophytic existence, comparable to that led by bacteria in the mouths and intestines of the human subject.”

Harris is aware that his arguments for a more doubtful significance of streptocci in milk may not be satisfying, but his aim is a careful reinvestigation of the facts, to “arrive, it is to be hoped, at no distant day to a much clearer point of view … regarding the status of the presence of streptococci in milk.”

There remains a second important question in accordance with the title of the publication, that is the presence of the so-callled “pus cells”, or leucocytes in milk.

(to be continued)

1. N.M.Harris, ‘The relative importance of streptococci and leukocytes in milk’, The Journal of Infectious Diseases, 4 (1907) 50-62.

To provide a wholesome milk-supply: Streptococci and leukocytes.

Part 1

Early in the twentieth century the health quality of milk was of considerable importance, but little was known of how to evaluate it.

Streptococci in milk were supposed to be the cause of diseases in man; in England an outbreak of sour throat could be connected to a herd of the suspected dairy in which a cow was affected with acute mastitis. The problem was to establish suitable standards with regard to streptococci and “pus cells”, i.e. leukocytes, in milk supplies. Norman Harris, a bacteriologist in Chicago, gave an overview in 1907 of his own opinions and those of his colleagues about this problem¹.

In general it was believed that two groups of bacteria could be found in milk ducts of a cow: those that produce lactic acid fermentation and those that do nothing. After a long discussion of the literature Harris concludes that souring of milk by lactic acid is caused by Streptococcus lacticus. But then the question must be asked: ”in what light, then, are we to regard the presence of streptococci in milk as being an index of disease in the cows? It cannot be denied that cows suffer from an inflammation of the udder at one time or another during lactation, and that these lesions are largely caused by the ordinary pyogenic cocci … Of the cocci it would seem that a streptococcus is the more prominent factor, … particularly in that form of mastitis known as acute contagious mastitis.”

Thus, in Harris view, streptococci were responsible either for a harmless souring of milk or for an acute mastitis in cows. It would be very helpful if it were possible to distinguish the several “races” of streptococci, because that would give the possibility “to frame standards whereby we might be able to say that a given sample of milk was fit for consumption, whilst another was not, on the ground that each contained harmless and hurtful cocci respectively.”

Next Harris discusses various methods for making this distinction, such as possible differences in the fermentation of substrates, hemolytic properties, agglutination reactions, reactions to sera and pathogenicity to rabbits, mice and guine pigs, but all without good results.

This latter feature of pathogenicity was important in the light of the believe of Harris and colleagues the the pathogenic streptococci “have a virulence all [of] their own toward the human species … and that these cocci thus causing human infection are those giving rise to the acute contagious variety of mastitis or gelber Galt of the Germans.” Mastitis milk was a danger for humans and identification of harmful streptococci might help in recognizing dangerous milk. But unfortunately, no such test was found yet.

(to be continued)

1. N.M.Harris, ‘The relative importance of streptococci and leukocytes in milk’, The Journal of Infectious Diseases, 4 (1907) 50-62.

Dog history

Dogs are not only subjects of veterinary care, they are also subjects of cultural history. An interesting example may be found in an essay about the history of bloodhounds around 1900 by Neil Pemberton.

I copy the summary, and, as an appetizer, the introduction of the article. Pemberton makes extensive use of newspaper articles.

The bloodhound's nose knows? dogs and detection in Anglo-American culture

Neil Pemberton,  Endeavour 37, 196–208

Summary

The figure of the English bloodhound is often portrayed both positively and negatively as an efficient man-hunter. This article traces the cultural, social and forensic functions of the first attempts to use bloodhounds for police investigation, and argues that the analysis of these developments, which took place at the turn of the twentieth century, further our understanding of the diverse practices and cultures of fin de siècle forensics. Arguing that their dogs could trail tracks of human scent, English pedigree bloodhound breeders promoted and imagined novel ways of detecting and thinking forensically, with which they made claims to social authority in matters of crime and detection. Yet, English bloodhounds were unstable carriers of forensic meaning making their use for tracking criminals deeply problematic: for example, the name of the breed itself invoked a long-line of social and cultural associations. In showing this, we can see how the practices of canine forensics had their roots in a complex history, involving genteel leisure, changing cultural understandings of scent, and shifting dog-keeping mores.

Introduction: a murder mystery at Gorse Hall

From the late 1880s onwards stories of the pursuit of criminals with bloodhounds, whether successful or unsuccessful, made dramatic copy for a penny press on both sides of the Atlantic, eager to fill their pages with narratives that thrilled, shocked and horrified readers. One such article was published in the popular illustrated London weekly the Daily Sketch on the 3 November 1909, in which the bloodhound was characterised as possessing an insatiable curiosity – a dog that pursues even the faintest of scent traces with all the zest of a born detective. The day before, a Lancashire mill owner, George Starres, was found dead at his mansion, Gorse Hall near Stalybridge; he had been shot. Unable to find any actionable crime scene evidence or witnesses to the murder, the police investigators called upon the services of the renowned private dog breeder and trainer, Colonel E.H. Richardson.

In the Daily Sketch's coverage of the investigation, Richardson's sleuthing was much applauded: he was praised as a knowledgeable and trustworthy hunter, who practised the art of detection in a fundamentally different way from other police detectives, whose essential approach to crime solving relied on relating physical evidence to oral testimony. Richardson instead solved criminal mysteries through the recovery of invisible traces of a criminal's scent, employing the reputedly sensitive nose of an English bloodhound. Tracing scent by working with a hound enabled him to reconstruct the genus and movements of human quarry through space. After a long drive in the rain from his London residence, Richardson had arrived at Gorse Hall with two of his bloodhounds, who on arrival had been presented with the murder weapon found at the scene of the crime, in the hope that the dogs would detect the culprit's scent and locate a trail.

In this case however Richardson and his bloodhounds failed to find the culprit for the murder at Gorse Hall. Although the dogs picked up a scent trail at the crime scene, they lost the trail on the surrounding moors, due in large part to the rain, which apparently dispersed what had been a traceable trail. As in the Sherlock Holmes story, in which he demonstrates the forensic productivity of being attuned to canine abilities and behaviour, sometimes the most significant thing is that the dog did not bark. Thus, taking my lead from Holmes's acute attentiveness to canine behaviour, this historical account of using dogs to solve crime avoids documenting either the historical successes or the failures or shortcomings in a specific period, thereby resisting a straightforward listing of criminal cases in which canines ‘barked,’ or not.

In search of the cause of mastitis

Although Nocard and Mollereau had demonstrated in 1884 that cocci could be held responsible for mastitis, the nature of the real cause of the disease troubled many for a long time after.

Here is a report, published in 1892 in the Receuil de Médécine Vétérinaire (vol 69 p.494-495)

by a veterinarian, J.Joquan, from Vitré, who thought that he had made a step forward in the knowledge of the cause of mastitis. This text has been published recently in Dutch in Argos, 49, 2013, 324.

“Sur une cause probable de la mammite infectieuse de la vache.”

“About a year ago I was consulted for a case of mastitis of a cow in the municipality of Vitré. Following a painful swelling the udder of this cow had returned to approximately the normal volume, but she kept giving small quantities of milk that was putrid, watery and unfit for consumption. In vain I looked for the cause of this change and I decided to give the following advice, that did not satisfy me at all: ‘The cow is too fat, she should see the butcher and another one should be bought.’ This was done accordingly. After four or five months the new cow was affected in exactly the same way as the first, but this cow lacked the fat condition, and did therefore not allow me to bring this in association with an unfortunate mastitis.This forced me to go deeper into the case and to look elsewhere for the starting-point of the infection of these two cows. After a tour through the stables, a little bit of searching and asking some questions of the cattle-maid I found out  […] that the bedding of the stables had been taken from the straw-mattresses, used by the numerous and various boarders. Probably my enemies must be found here. Therefore I made them give up the use of this straw and made it replaced by more natural bedding, namely fresh straw that had not served anyone. I treated the cow: she recovered.

I should not have published this notice if I had not been supported by the next, third fact; some time ago I was called to a small farm close to town to treat a mastitis of the same nature as the preceding ones. I did not fail to ask of the bedding: that had its origin in the purchase of straw, made by the infantry regiment of the garrison of Vitré, and it had served too for straw-mattresses for the military men. I don’t want to comment on it.

[…]

Until now I have accused all kinds of more or less vague causes, which are known and have been described as coincidental causes. Now I think I can blame one, if not a general, then at least a frequent, cause of this disease: the infectious nature of bedding that has served as the fillings of straw-mattresses.”

It is noteworthy to read how cautious Joquan has formulated the general discussion at the end: it is the infectious nature of the straw, used in the mattresses, that has to be blamed.

Mastitis and epidemiology

Some provocative arguments about epidemiology by Alex Broadbent, a philosopher of epidemiology in Johannesburg (SA), on his epidemiology blog.

“(1) It is hard to use results which one reasonably suspects might soon be found incorrect.”

“(2) Often, epidemiological results are such that a prospective user reasonably suspects that they will soon be found incorrect.”

“(3) Therefore, often, it is hard to use epidemiological results.”

 “I think that (1) does not need supporting: it is obviously true (or obviously enough for these purposes). The weight is on (2), and my argument for (2) is that from the outside, it is simply too hard to tell whether a given issue – for example, the effect of HRT on heart disease, or the effect of acetaminophen (paracetamol) on asthma – is still part of an ongoing debate, or can reasonably be regarded as settled. The problem infects even results that epidemiologists would widely regard as settled: the credibility of the evidence on the effect of smoking on lung cancer is not helped by reversals over HRT, for example, because from the outside, it is not unreasonable to wonder what the relevant difference is between the pronouncements on HRT and the pronouncements on lung cancer and smoking. There is a difference: my point is that epidemiology lacks a clear framework for saying what it is.”

 (Alex Broadbent on his Philosophy of Epidemiology Blog, 2 september 2012) 
ttp://philosepi.wordpress.com/author/philosepi/page/2/

Do these arguments affect the epidemiological results of mastitis investigations?

There were no comments on Broadbent’s blog, and I do not think mine will raise comments either, but feel free if you want.