"M. bovis was once a major cause of tuberculosis (TB) in the United States and other industrialized nations... Although human-to-human transmission of disease has become less common, HIV infection and continued immigration from countries with endemic disease, including Mexico, contribute to the persistence of M. bovis in the United States[6]" - from the Book "Tuberculosis & non-tuberculous mycobacterial infections, 5th Edition" Ed. Schlossberg, David

[6] link is - Dankner WM, Waecker NS, Essey MA, et al. Mycobacterium bovis infections in San Diego: A Clinicoepidemiologic study of 73 patients and a historical review of a forgotten pathogen. Medicine. 1993;72:11–37

Hope this will help

Thanks a lot!

I have been looking for a long time off and on without success for evidence that humans catch TB from cow's milk, either nowadays or in the past.  I am beginning to seriously doubt that this ever happened.

Thanks Dr. Anthony

It's interesting

"Thanks Dr. Anthony. It's interesting"

But not interesting or important enough, apparently, for anyone to quote direct evidence for TB from milk.

Actually, all you need to do is run a simple pubmed search on tuberculosis and milk, to turn up more than 200 articles on the subject, including a recent one with molecular typing from some of my colleagues showing the incidence of human/cattle transmission in Ethiopia. There are also recent articles from Tanzania discussing the data. Most of the work these days is involved in tracking the prevalence of TB in infected milk and meat, because the health issues regarding it are well established.

The bulk of the key studies, however are mostly beyond the reach of Pubmed, being performed in the US and in Europe in the 19th and early 20th centuries. You'll need to hit the library and look in the old journal stacks if you want to find those. Pasteur and Roux are probably the authors to seek out first. If that's a problem you can get a good overview from Atkins PJ. The pasteurization of milk in England: the science, culture and health implications of milk processing, 1900-1950. In: Smith D, Phillips J, eds. Food, Science, Policy and Regulation In The 20th Century. London: Routledge, 2000: 37-51.

The basic key points are that M. bovis was isolated in a substantial number of cases from humans in the 19th and early 20th centuries and M. tuberculosis was also found in cattle - and in their meat and milk. That transmission could ocur via this route was formally proven by animal experiments (feeding infected meat and milk led to disease in exposed animals) and indicated by proximity or linkage studies like the one I cited above (humans in contact with infected animals and those eating their products had higher relative rates of TB). The current TB outbreak in lions in Kruger national park is a recent example of this, where, the TB strains decimating the lions are the same as those found to be spreading in one of their prey animals: water buffalo. Ironicaly, the buffalo appear to have contracted it from infected domestic cattle which were often (illegally) pastured inside the park.

Correlation is not causation of course, but for most clinicians the link between TB transmission and milk was validated by the fact that the pasteurisation of milk was rapidly followed by a decline in tuberculosis incidence in humans, and in particular with the near disappearance of what was called "abdominal tuberculosis" which had been historically associated with infected milk. If you want a more recent example, you can research the outbreak of M. bovis in humans in San Diego in the 1980s: this was linked to unpasteurised fresh cheeses from infected mexican herds, which were shown to be contaminated with the same strains driving the outbreak. There was also an outbreak in New York, in 2001, also linked to unpastuerised cheese from Mexico.

There really is no reason to doubt the link between consuming mycobacteria-contaminated food and disease: it's stood the test of a century and a half of investigation and although now rare in most developed countries, still occurs from time to time. In countries where TB control has been less rigorous (Romania and Russia are two examples with recent studies), simply consuming unpasteurised milk is a significant extra risk factor for TB (and M. bovis infection).

As far as human to human transmission of M. bovis goes, I would not state that it does not happen: rather, I don't know of any cases where it has been proven to occur, which is not quite the same thing. All the M. bovis cases I know of are linked instead to contact with cattle, or with unpasteurised dairy products.

Thanks Dr. Doherty

It will be very useful.

It's been useful to me, as well. Based on the idea that you should always check things that you think you know, I did a few searches for human-to-human transmission and turned up several recent studies which very strongly indicate human to human transmission of M. bovis, for example:

PMID:15455603

PMID: 17434402

PMID: 21430093

There are older studies suggesting the same thing, but those were pre-DNA fingerprinting so there was alway some doubt as to whether they really represented clusters. The same is not true of these studies, so I have to say that now there really is good evidence of human-to-human transmission of M. bovis, albeit at a much lower level than with M. tuberculosis.

As an amusing side note, I also turned up some recent studies documenting animal-to-human-to-animal transmission of M. bovis, indicating that the circle is complete: humans can get TB from cows, and then give it back to other cows.

Dr. Doherty

Thanks for your suggests.

I guess this one it's interesting too.

Evans et al.

Cluster of human tuberculosis caused by Mycobacterium

bovis: evidence for person-to-person transmission in the UK

Lancet 2007; 369: 1270–76

"The basic key points are that M. bovis was isolated in a substantial number of cases from humans in the 19th and early 20th centuries and M. tuberculosis was also found in cattle - and in their meat and milk. That transmission could ocur via this route was formally proven by animal experiments"

Every time I check this old animal literature I come away more confused than ever. This study seems, however, to be quite clear (Practitioner 1901;67:498).   Doctor Lund fed his own child "for a year after birth exclusively on milk drawn from a tuberculous cow.  The child appears to have suffered no injury to its health".   I have not read the original account (in Hospitalstidende 1867), but it would seem that this must have been done to prove a point, that infants do not get TB from infected milk.  So, is there any direct evidence in humans that TB in infants is caught by drinking infected milk?

Yes. There is direct evidence, as cited above.

It's always dangerous to work only from studies with negative results - and this goes double for TB, where 90% of infections are latent, and may not become symptomatic for decades. It's even worse to work from a case report with one subject. Just because one child exposed to tuberculosis-contaminated milk did not become ill, you can't assume that nobody will - in fact, even if infected, the odds are 9 to 1 that the child would not show symptoms. And of course the majority of cows with tuberculous lesions may not actually secrete M. bovis in their milk: it depends very much on the localisation of the pathology.

So here we have a study with one child who may have been exposed and may have been infected, but did not develop disease. That's all.

As an analogy, I got shot in the head as a child. Despite requiring emergency surgery to remove a bullet from my brain (!) I survived with no apparent harm. Does this mean it's perfectly harmless to get shot in the head? I don't think so, but the evidence is just as strong as for this case report. A sample size of one tells you absolutely nothing (except that in this case the doctor in question behaved unethically and possibly unlawfully - even by the standards of 1901 - in knowingly exposing a child to possible TB).

 If you look at the modern outbreak studies I commented on, we have direct evidence: unpastuerised dairy products were shown to be contaminated with M. bovis. Some - not all, by a large margin, but some - people who consumed those products later developed M. bovis tuberculosis. No other risk factors were identified and in the few cases where spoligotyping was done, the bacteria were the same strain as that isolated from contaminated dairy products.

See, for example:

Winter, A., Driver, C., Macaraig, M., Clark, C., Munsiff, S.S., Pichardo, C., Jereb, J., LoBue, P., Lynch, M., 2005. Tuberculosis Cases caused by Mycobacterium bovis Infections, New York City, 2001–2004. MMWR 54, 605–608.

Wayne M. Dankner and Charles E. Davis. Mycobacterium bovis as a Significant Cause of Tuberculosis in Children Residing Along the United States-Mexico Border in the Baja California Region. Pediatrics.  2000;105;79.

Harris NB et al. Recovery of Mycobacterium bovis from soft fresh cheese originating in Mexico. Appl Environ Microbiol. 2007 Feb;73(3):1025-8. Epub 2006 Dec 1.

You can't really ask for stronger evidence than that, and we have data from not one, but several recent outbreaks, plus of course a huge amount of less-detailed data from the last century and half which all points in the same direction.

The epidemiological data is also very solid. For example, in Australia (Tuberculosis due to Mycobacterium bovis in the Australian population: cases recorded during 1970–1994 Cousins, D. V.; Dawson, D. J. The International Journal of Tuberculosis and Lung Disease, Volume 3, Number 8, August 1999, pp. 715-721(7)) the overwhelming majority of Australians developing M. bovis- related TB worked with livestock. They had no other identifiable risk factors. We see this pattern all the time, in many countries.

There really is no reason to doubt this vast volume of data. And to be honest, I can't see anything about the animal data that is confusing: if you feed animals meat or milk infected with M. bovis, a small percentage of them become infected and some of those go on to develop TB-like pathology. It's about as straightforward as can be.

"Winter, A., Driver, C., Macaraig, M., Clark, C., Munsiff, S.S., Pichardo, C., Jereb, J., LoBue, P., Lynch, M., 2005. Tuberculosis Cases caused by Mycobacterium bovis Infections, New York City, 2001–2004. MMWR 54, 605–608."

Here is the abstract from this paper.  This boy may have been infected from contaminated cheese, which I am not disputing.  I am asking for cases due to consumption of infected milk.  This is not a pedantic academic exercise, as there are people who attribute the dramatic decline in infant mortality from the start of last century to improvement in the public milk supply.

Abstract

In March 2004, a U.S.-born boy aged 15 months in New York City (NYC) died of peritoneal tuberculosis (TB) caused by Mycobacterium bovis infection. M. bovis, a bacterial species of the M. tuberculosis complex, is a pathogen that primarily infects cattle. However, humans also can become infected, most commonly through consumption of unpasteurized milk products from infected cows. In industrialized nations, human TB caused by M. bovis is rare because of milk pasteurization and culling of infected cattle herds. This report summarizes an ongoing, multiagency investigation that has identified 35 cases of human M. bovis infection in NYC. Preliminary findings indicate that fresh cheese (e.g., queso fresco) brought to NYC from Mexico was a likely source of infection. No evidence of human-to-human transmission has been found. Products from unpasteurized cow's milk have been associated with certain infectious diseases and carry the risk of transmitting M. bovis if imported from countries where the bacterium is common in cattle. All persons should avoid consuming products from unpasteurized cow's milk.

"Wayne M. Dankner and Charles E. Davis. Mycobacterium bovis as a Significant Cause of Tuberculosis in Children Residing Along the United States-Mexico Border in the Baja California Region. Pediatrics.  2000;105;79."

This paper contains no data on the food intake of these cases, nor any reference to a previous study in a peer-reviewed journal relating TB in children to drinking raw or infected milk. 

"the overwhelming majority of Australians developing M. bovis- related TB worked with livestock"

I will need a lot of convincing, from unambiguous epidemiological investigations, that this is not due to aerial spread, as with M. tuberculosis.

"Correlation is not causation of course, but for most clinicians the link between TB transmission and milk was validated by the fact that the pasteurisation of milk was rapidly followed by a decline in tuberculosis incidence in humans, and in particular with the near disappearance of what was called "abdominal tuberculosis" which had been historically associated with infected milk"

Olmstead AL & Rhode PW Arresting Contagion, Harvard Univ Press 2015, have a relevant chapter reviewing Bovine Tuberculosis and the Milk Problem:

"There remains considerable uncertainty about the incidence of bovine tuberculosis in humans and the number of deaths it caused...

Bovine-type infections were far more common in non-pulmonary cases and in children, expecially infants, because of the consumption of untreated milk...  M. bovis infections were most lethal for infants.."

Comment: In the USA and UK, infant mortality started to drop rapidly from the start of the 20th C, before milk pasteurization had begun (Fig 10.2).  In the smallest US cities, still only 60% of the milk was being treated by 1936.  The larger cities, where IM was greatest, had had full coverage by 1920.

In 1900, TB was the leading cause of death in the USA.  "As of 1908, epidemiologists had positively linked about 500 U.S. epidemics of typhoid fever, diphtheria, and scarlet fever to the milk supply.."  So why could not O & R find a single epidemiological study linking TB to milk?   And why did Koch in his 1905 Nobel address say "bovine tuberculosis is not transmissible to man."

" (humans in contact with infected animals and those eating their products had higher relative rates of TB)."

For bovine TB, according to O & R (2015) above: "The most thorough research was conducted in Denmark, where about 60 per cent of all tuberculosis of the lungs in the farm population who had been incontact with heavily infected cattle was of the bovine type".  They referenced a Lancet leading article summarising this work (1947,1:756-7): "The general conclusion reached from these results is that in Denmark pulmonary tuberculosis of bovine origin is mainly due to close contact with tuberculous cattle, and that infection is contracted by inhalation rather than ingestion [by young children]".

 "zoonotic tuberculosis (M. bovis) is not transmitted among immunocompetent humans."

J Sigurdsson (1945) Studies on the risk of infection with bovine tuberculosis to the rural population has a chapter on Bovine Infection from Man to Man.

He concludes his literature review "Most of the cases here are very strongly suggestive of a bovine infection from man to man, and there can no longer be any doubt that bovine tuberculosis may be transmitted from one person to another...

All these things together suggest very strongly that in the present material the way of infection has chiefly been the same in the bovine and in the human pulmonary tuberculosis, namely: preponderantly aerogenous.  Additional studies show that the bovine infection in patients of the present material may conceivably be due to transmission from man to man but in a slight degree. On the other hand, the great majority of the patients have had an abundant opportunity in the cow-stables to inhale virulent bovine tubercle bacilli.."   

"You can't really ask for stronger evidence than that, and we have data from not one, but several recent outbreaks, plus of course a huge amount of less-detailed data from the last century and half which all points in the same direction."

With respect to milk, I am certainly asking for stronger evidence, in particular, that infants got TB from drinking milk.  I have not checked all the literature, but this study is relevant (Howarth WJ The Method of Feeding in Relation to Infant Mortality Public Health 1907;20:203-5):

These data are based on systematic visits by women inspectors to 13274 infants.  The death rate from abdominal TB was 1.5 per 1000 in the breast-fed, 4.3 in the mixed-fed, 10.0 in the hand-fed.  So, the more exposure to potentially tuberculous milk, the more TB in infants.  But this a good example where correlation does not prove causation, since

I don't think that scrounging around in papers from the very dawn of microbiology - over a century ago - while ignoring the very solid evidence from the last decade (or indeed, the 11 decades intervening) makes a very convincing case.

For example, you note that Koch stated in 1905 that M. bovius was a minor health risk in humans. This is true -  in fact, he made the same statement even earlier, at the British Congress on Tuberculosis in 1901. However it's  a little dishonest to repeat this claim without noting that Robert Koch is on the record already in 1908 stating that he had been wrong earlier, and that M. bovis was indeed a significant health risk to humans.

I do understand that it can be useful to question orthodoxy when it comes to a specific question, but research does not consist of hunting around for a few articles that might support your position: a real researcher looks at the total literature. Every single article has potential weaknesses: it's the body of assembled literaure that gives an accurate picture of what we know - and equally importamtly why we think we know it.

So in citing only the oldest articles, not only do you ignore what came after (as with Koch) but you you also seem to be repeating the errors of the old work. For example, that pulmonary disease results from aerosol inhalation and that abdominal disease results from consumption of infected milk. That intuitively seems to make sense, was widely believed by physicians a century ago, and like many intuitively obvious things in biology has turned out to be untrue on investigation.

M. bovis infection in the naive host leads to systemic infection (it's been shown many times in animal studies and in fact, I've done this myself many times) and can lead to disease in multiple sites. So you can get pulmonary disease from oral infection (indeed, this is a relatively common outcome, regardless of the site of infection) or you can get intestinal lesions (abdominal TB) from a respiratory infection (though this is far less common). Ancient studies using the presentation of disease as in indicator of route of infection are therefore - at best - quite unreliable.

Now, there's no question at all that M. bovis can be transmitted by the consumption of infected, unpasteurised dairy products. Animal studies since the 1880's have consistently shown that giving M. bovis-contaminated milk to other animals to consume can transfer infection and disease - whether by inoculating milk or using naturally-contaminated milk from animals with M. bovis mastitis. This is true, not just in cattle, but in a variety of species. So yes, we know with certainty that contaminated dairy products can transfer M. bovis infection to other mammalian species.

There is no reason, given the proven infectivity of this pathogen in humans to suspect that the same is untrue of humans (and every reason to believe that in fact it is transferred the same way in humans). The two reports from the last decade already cited from San Deigo and New York that tied consumption of infected dairy products to M. bovis outbreaks in children, even though these children had no exposure to cattle or other risk factors apart from consumption of contaminated dairy products strongly suports this. There is also good evidence that it can spread in humans via the respiratory and blood contact routes - the high rates of M. bovis infection among slaughterhouse workers and the recent report on proven transfer of M. bovis from the meat of infected white-tailed deer to hunters in Michigan show that. 

So at this point I'd turn it around - you seem to believe that M. bovis infection cannot occur in humans via drinking infected milk, although it has been proven that 1) humans are susceptible to infection and develop a disease very similar to that seem in other mammals and 2) in all mammalian  species where it has been tested directly, M. bovis infected milk can lead to infection and disease.

What special mechanism do you propose protects humans from infection via the oral route (but not by other routes) that does not operate in other mammalian species?

Edit: I should also note that if one really wanted to use the very old literature in this case, then you can easily find reports of human infection with M. bovis attributed to consumption of milk. The article "Reports on bovine tuberculosis and public health. Salmon, D. E. USDA, 1904." lists well over a dozen cases of infection, including some oddball ones such as use of cream (from milk from a cow with tuberculous mastitis) to treat eczema, leading to percutaneous tuberculosis infection, as well as more conventional infections derived from drinking milk from a cow with tuberculous mastitis - including one where 12 girls at a boarding school contracted abdominal tuberculosis (5 of whom died). On investigation of that case, it was found that the cow supplying milk for the girls had tuberculous mastitis. The girls had no other known risk factors and were not in contact with the animal directly, leaving the milk as the only known source of infection.  You can find this report in fascimile online, and there are literally hundreds of similar reports from the first quarter of the 20th century.

The trouble with using these ancient reports indicating infection is exactly the same as with the ancient reports you referred to above: the science was still evolving and back in the early 20th century they were still investigating questions about host range, transmission and susceptibility that were conclusively settled decades ago. The scientists of the time were smart enough to know how limited their knowledge was. Salmon wrote of the case reports of infection via milk:

"These are examples of clinical evidence which might be greatly extended, but all are, of course, open to the objection that we do not know absolutely that the disease was caused by the bovine bacillus. However, the occurrence of abdominal tuberculosis soon after the use of milk from tuberculous cows is a coincidence which justifies us in accepting the cases as strong circumstantial evidence, not of themselves demonstrating the communicability of bovine tuberculosis, but, taken with other evidence, making a case which it is difficult to contest."

 In the 21st century, however, we have no such problems and the recent outbreaks in the US already cited not only were proven by typing to be M. bovis, but were linked to the same strains in contaminated unpasteurised dairy products and the strains themselves proven by spoligotyping to overwhelmingly be those circulating in cattle not in the local region (where M bovis infection is rare), but in Mexico (see, for example, Rodwell et al. Tracing the origins of Mycobacterium bovis tuberculosis in humans in the USA to cattle in Mexico using spoligotyping. IJID.  2010, 14: e129–e135. In this case, transmission by direct contact with cattle can be clearly ruled out and a direct line of infection via contaminated dairy produce remains the most likely route of infection (indeed, the only plausible route, in many cases).

Given the clear evidence available from recent outbreak investigations, why would one resort to musty, century-old studies with weaknesses acknowledged even at the time?

Is there really such a big difference between M.Bovis and M.Tuberculosis? The only obvious difference is that one was first isolated from Bovis and another from human. It could be vice versa, and their names would be changed. Maybe lungs are the preferred target of TB only because TB needs oxygen to be active?

As for children, 90% of adults are already infected and the rest 10% (and their children) will never be infected due to their (human) genetics. Those 90% can transfer their infection to infants even without milk, but unpasteurized milk is the most important possible threat to infants. It's all about probabilities. 

It would be very interesting to know how often TB found in milk is M.Bovis and how often M.Tuberculosis. Does anyone have references to such studies?

"I should also note that if one really wanted to use the very old literature in this case, then you can easily find reports of human infection with M. bovis attributed to consumption of milk."

I have put up a separate question on RG on this point.   When I put it up, I thought there were such cases, but the more I read about it, the less likely this now seems. 

"It would be very interesting to know how often TB found in milk is M.Bovis and how often M.Tuberculosis. Does anyone have references to such studies?"

I doubt you will find much in the modern literature, but I am sure there is plenty in the very old literature.

Old literature bases on (not very reliable) morphological differences of strains, now sequencing gives much better results.

What do people think about this article?

http://drbroxmeyer.netfirms.com/MadCow.htm

The idea is brilliant, Mad Cow disease just a M.Bovis meningitis...

"Old literature bases on (not very reliable) morphological differences of strains, now sequencing gives much better results."

I can see that modern sequencing methods give better results, but are you saying that older studies are completely unreliable, or worse than useless?

Maybe my statement is too strong, but there is a variety of M.Tuberculosis and a variety of M.Bovis and these varieties change it time and from region to region. I am not aware of any one definite morphological feature of either bacteria that allows to distinguish it from the other. Differentiation is based on several weak criteria. What I know is that there is a strain called M.Bovis was initially isolated from kettle and is infectious to humans and a strain called M.Tuberculosis that came to bacterial collections from humans and is infectious to kettle. Maybe M.Tuberculosis and M.Bovis are just two samples from the ocean of intermediate strains?   

Really people in the past did a very good job concerning TB, many of works are well-forgotten or just ignored. Medicine is very conservative. We just should not expect reliable differential diagnostics between M.Bovis and M.Tuberculosis in the past, as e.g. in the case of isolation of micobacteria from cattle it is very natural to identify it as M.Bovis:) just because it's a cow. I would not rely on differentiation of TB in past studies, but would easily accept most of other aspects of the studies.