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Hello. Hello and welcome back to Current Vet. This is the podcast that makes veterinary medicine simple. I'm Dr. Lottie, and today we are going to be talking about bovine tuberculosis or bovine tb.
This is a disease that sits right in the middle of farm practice, public health and policy. It is a massive, ongoing global challenge, and you'll hear about it in farm practice, in government work, and in one health discussions. So let's try and make sense of it from the case you might see in clinical practice all the way to science prognosis and how to control it.
So let's start with our case. You are called out to a dairy farm in late spring. Farmer John looks uneasy as you pull into the yard. Three days ago you were there to carry out the herd's, routine tuberculin skin test, injecting both bovine and avian purified protein derivatives or PPDs into the necks of his 150 Holstein cows.
Now it's day three and you are back to check on the reactions. As you work down the race, most of the cows have no visible swelling until you reach one in mid lactation whose bovine site looks notably raised and firm compared to the avian injection site. Farmer John leans over the gate and says that she's been fine eating and milking well, but he's just got a really bad feeling about her.
You finish the recordings, record the measurements, and confirm what farmer John suspected. She is an inconclusive reactor. You explain that she'll need retesting in 60 days, and in the meantime her movement is restricted and she must be isolated from the rest of the herd.
So to really understand what we're dealing with, in this case, let's discuss what causes TB and how it affects cows like our inconclusive reactor.
Bovine tuberculosis is caused by Mycobacterium Bovis, which is a slow growing acid fast bacterium. It's part of the microbacterium tuberculosis complex, which is a group of closely related mycobacteria that caused TB in various different species, including humans. M. Bovis primarily affects cows, but it can also infect many other species, including badgers, deer, goats, pigs, dogs, cats, and even humans, which is why it remains such a big one health issue.
So the bacterium is transmitted mainly through aerosol droplets from infected animals, for example, when they cough or sneeze. And it can also spread via contaminated feed or water. And this is especially in areas where wildlife reservoirs are involved, as they may contact a cow's feed or water source, contaminate it, and then that infection spreads into the herd.
So while aerosolisation is the primary root of transmission, it can also be spread in any body secretions. So the faeces, urine, semen, saliva, and milk. The milk one means that calves of infected cows quickly become infected themselves. So once these bacteria have been inhaled, they are engulfed by macrophages in the lungs, but they are not destroyed.
Instead, they survive and replicate inside the macrophages, which leads to the formation of granulomas, also known as tubercles, which are firm caseous nodules most commonly found in, of course, the lungs, but they can also be in lymph nodes and sometimes other organs depending on where these infected macrophages spread.
The disease process is really slow and chronic, so in many cows it remains subclinical for months or even years. However, even if infection is asymptomatic, these animals can still shed bacteria and spread disease within the herd. Bovine TB is endemic in most of the world, and most countries. For example, the UK, Ireland and New Zealand have national eradication programs to try and control the disease.
What clinical signs are we going to be seeing in practice? So I think it's important to say that we're not. Uh, not commonly going to see a textbook case of bovine TB in live cows, especially if you're practicing in an area where TB testing is routine, because the tests are going to pick up infected animals long before the clinical signs start to be seen.
So a lot of these animals that we're diagnosing with TB will in fact be asymptomatic. However, when clinical signs are present, or if these cows aren't caught early on in the disease process, the clinical signs are usually chronic and pretty non-specific. So we might see progressive weight loss despite a good appetite, reduced milk yield, a chronic moist cough which may be more noticeable or flare up after exercise or excitement, enlarged lymph nodes, so superficial nodes like the cervical or retropharyngeal nodes may be palpable. And in advanced disease we might see dyspnea, respiratory distress because of these pulmonary tubercles.
On postmortem, you might find the classic caseous calcified nodules in the lungs as well as in the bronchial and mediastinal lymph nodes. And occasionally, like we said, the other organs, so maybe the udder liver or spleen, depending on where these macrophages are spreading and where granulomas form.
Let's go back to your dairy farm and the inconclusive reactor. What tests do we have available to actually diagnose bovine tb? So the mainstay of diagnosis is the single intradermal comparative cervical tuberculin test, or SICCT It's a bit of a mouthful, but it's also known as the comparative skin test.
So this is something I really struggled to understand in vet school, but it's actually quite straightforward. So essentially two sites on the neck are injected Intradermally, one with the M Bovis, purified protein derivative, or PPD, and the other one with the M Avium PPD. Skin thickness at the site is measured before and 72 hours after injection.
So some of you're probably wondering why the hell are we injecting avian PPDs as well as bovine? Well, the avian protein is used as a comparison site. If the reaction to the avian protein is similar to or significantly larger than the bovine site, the animal has likely only been exposed to environmental mycobacteria or avian strains.
And the slight swelling at the bovine site is not a concern. This comparison is essential for assessing whether swelling at the bovine site is due to a true infection with M. bovis. So there are three possible results once the thin skin, once the skin thickness at each site has been measured. If the bovine site swells significantly more than the avian site, the animal is considered a reactor.
If the result is borderline, it's classed as inconclusive and retested at 60 days like our cow was in our case. And if there is no significant swelling at the bovine site, the cow is a non-reactive.
Why are we looking at swelling? What does it mean? So swelling indicates that there has been a significant immune response and inflammation to the protein injected. Previous sensitization to a pathogen initiates a rapid immune response. So previous sensitization could mean that the animal has been infected before, is currently infected or has been vaccinated with a killed or inactive strain, and that indicates that they are a risk for the rest of the herd and could be a source of infection.
Any reactor cows must be reported to the health authorities because bovine TB is a notifiable disease and the cow has to go for compulsory slaughter. Inconclusive reactors, like the cow on our farm, must be isolated from the rest of the herd and retested in 60 days. In the UK, farms lose their official TB free status and all milk in the bulk tank must be dumped. TB free status can then only be regained if the farm has two consecutive tests with no reactors or inconclusive reactors on the farm. This test has a high specificity of about 99.9%, so really, really low false positive rate, but it only has a moderate sensitivity, so around 80%, which means it has a reasonable chance of getting a false negative.
This means it's good for herd level control, but it's not perfect at detecting every infected animal. The really low false positive rate means that we aren't culling huge numbers of uninfected cows and therefore are limiting the financial cost of bovine tb. But the higher false negative rate means that some infected cows are slipping through our fingers and not giving positive results, and these cows might be spreading the disease further through the herd.
Next up we have the Gamma Interferon assay test, or IFN gamma test.
This blood test detects cell mediated immune responses to M. bovis antigens. It is more sensitive than the skin test and can pick up early infections, but it is also more prone to false positives. So it's usually used as a supplementary test in high risk herds. But a few benefits to the Interferon gamma test over the Tuberculin skin test are that it can detect infection earlier, has a lower false negative rate, it's lab-based, so it's an objective test and there is no degree of interpretation when it comes to results . And it doesn't interfere with any subsequent testing because with the Tuberculin skin test, when we inject those purified protein derivatives, that can then actually sensitize the cow to those proteins, so the next time we perform a skin test, they may react more anyway, even if they haven't been infected. So we are actually causing that sensitization with the purified protein injection. This isn't a huge cause for concern, but it is just something to think about.
However, the interferon gamma test has a higher false positive rate, the test itself is more expensive to do, and there are the difficulties of getting blood samples to a lab in a good condition to give accurate test results.
The third diagnostic option we have is postmortem and culture. This is a little bit less practical. Definitive diagnosis can be obtained through culture or PCR from lesions, but this is typically done with lymph node or lung samples collected at slaughter. However, M. Bovis is extremely slow growing, so these cultures can take up to 12 weeks to grow.
It is very costly and really not practical at all if we're trying to contain a disease in a real life situation. In endemic regions, molecular tools like PCR based typing or whole genome sequencing can be used, but these are more a research based tool and not commonly used for diagnosis in practice. So in practice, the majority of diagnosis is done with the tuberculin skin test and interferon gamma tests.
So your role as the vet is to interpret these tests, relay results to the farmer and authorities if there are any reactors, and help them come up with a herd plan to navigate the next steps. The restrictions and financial implications of TB for farmers can make this a really stressful time for them, so it's always something to keep in mind when approaching these cases.
We need to tread carefully.
Okay, let's move on and talk about how we now are going to treat these cases. The short answer is that we are not, there is no practical or legal treatment for bovine TB in cows. So even though antibiotics like and rifampicin are effective against M. Tuberculosis in humans, they are not permitted in cows for three main reasons.
One is that they don't fully eliminate the infection, so they're not actually completely effective in the first place. Two, they risk creating carriers that appear healthy, they appear that they recovered once you've treated them, but because the infection isn't fully eliminated, they actually remain infectious and can continue spreading the disease.
And thirdly, it can promote antibiotic resistance that is then gonna jeopardize human TB treatment. So in practice, all reactor animals must be culled. There are compensation schemes for farms, but these vary by country. So for example, the UK government pays farmers based on the animal's market value if they have to be slaughtered because they test positive for tb.
This is one of the hardest aspects of bovine TB control, and it's difficult emotionally and financially for farmers. So vets play a key role in communication and support while herd breakdowns are going on.
While we can't treat tb, we can try and prevent infection occurring in the first place. Because there's no treatment, it makes prevention absolutely critical. There are two main aspects to consider for prevention.
First, we're gonna think about how to prevent the disease coming onto the farm from outside, and then how to prevent spread from within the farm. So in order to control both of these, we can consider strategies like testing to identify infected animals early and then cull the reactors to remove them from the herd, restrict animal movements during breakdowns to prevent any further spread.
Preventing contact between cows and potential wildlife reservoirs, so badgers, deer, possums. So we could do things like fencing off feed stores, securing any water sources and reducing shared grazing pasteurization of all milk coming from herds with reactors or inconclusive reactors is essential. Milk pasteurization virtually eliminated human TB in developed countries and is so, so important for public health. And finally, one of the most important aspects of surveillance that people forget about is in the abattoirs. They play a huge role in picking up subclinical cases when carcasses and organs are inspected at slaughter.
So using abattoir reports is crucial to see how well farms are doing at controlling infection and preventing spread.
Let's Talk about vaccination. So there is a BCG vaccine available, which can be used in cows, which achieves partial protection, but it is not routinely used at all and is in fact not recommended. So the reason being is that the vaccination complicates diagnosis because vaccinated animals have been intentionally sensitized to the mycobacterium and then are likely to react to the skin test. To overcome this, DIVA tests, which stands for differentiate infected from vaccinated animals, are being developed to distinguish true infection from vaccinated responses and large scale field trials are currently going on in the UK for this vaccine. And if successful BCG vaccine could become a valuable tool in the next decade, but as of now, it is not recommended because of the difficulties it causes when we are trying to diagnose bovine tb.
Before we finish up, I'm gonna talk about the public health and one health aspects of both on tb. So BTB like we said is zoonotic. So this means that humans can become infected usually through unpasteurized milk or more rarely direct contact with infected animals. In humans, M. bovis causes a form of tuberculosis that looks almost identical to mycobacteria tuberculosis infection, but is often resistant to pyrazinamide, which is one of the standard human TB antibiotics used. Modern pasteurization of milk and meat inspection have drastically reduced human cases in developed countries.
But zoonotic TB remains a concern in regions with unpasteurized dairy or limited veterinary control.
This is why bovine TB control isn't just about protecting herds. It is a one health issue and links animal health, human health, and environmental health.
A couple of resources that I think are really great if you wanna stay up to date on bovine tb are the WOAH so the World organization for Animal Health has global disease status updates. The APHA Science Blog and the TB Hub are great resources for UK vets. If you are in the US, the USDA has a really great page on bovine TB that you should read.
And for a couple of nice overviews of bovine TB and the ongoing vaccine research, check out the links in the show notes to a couple of articles in science and pathogens journals.
So let's finish off with our key points to remember about bovine tb. Bovine TB is caused by microbacterium bovis. It is spread primarily through aerosolization and infects macrophages in the lungs leading to the formation of granulomas in lungs and lymph nodes.
Many infections are subclinical and only detected by testing or at slaughter. Diagnosis relies on the tuberculin skin test and gamma interferon assays, but definitive diagnosis can be done with culture or PCR from lesions. There is no legal treatment, so prevention is key, and control relies on testing and slaughtering movement restrictions and really strict biosecurity.
Bovine TB is a zoonotic disease, but pasteurization and meat inspection protect human health. There is a BCG vaccination, and it's showing promise, but is not yet recommended or in general use.
And that is bovine tuberculosis. It is a quite complex chronic disease that every large animal vet will encounter in some form.
It's quite frustrating and controversial, but it's also quite interesting and a really great example of how veterinary medicine plays such a huge role in public health. If you found this episode helpful, please take a second to follow or subscribe wherever you get your podcasts. It really helps our podcast to grow.
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Thanks for listening, and we'll see you next time.