Much media coverage of Mycoplasma bovis has focused on dairying, but calf-rearing is where the pathogen causes most problems overseas, as Andrew Swallow found out when he talked to one of the world’s leading experts.

Large herds and communal calf-rearing systems are where Mycoplasma bovis causes most problems overseas, a United Kingdom expert on the pathogen Dr Robin Nicholas says.

Nicholas is on the Ministry for Primary Industries’ (MPI) technical advisory group (TAG) dealing with the incursion and while that prevented him from answering many questions, he detailed how M. bovis has gone from novel organism in 1961 to a growing global gremlin of feedlots and large-scale dairying.

“The disease is worse in feedlot systems where calves are kept in high concentrations and in poorly ventilated housing. Most of Europe is affected, in particular UK, Italy, Hungary, and Germany; also the United States and Canada where feedlots exceed several thousand cattle,” he says.

‘In the feedlots/veal farms of many European countries it is the most important bovine respiratory disease.’

M bovis is now the main causative agent in a quarter to a third of calf pneumonia cases in Europe and 30-40% of UK calf pneumonias involve it too, though Nicholas says reliable data is limited.

“My belief for a long time is that this is a very important but under-reported disease in the UK… I have been on farms where there is 20-30% calf mortality and there is no cure as antibiotics used frequently for control are no longer effective because of antibiotic resistance. In the feedlots/veal farms of many European countries it is the most important bovine respiratory disease.”

In dairy herds the extent of the disease, typically manifesting as mastitis and/or arthritis, is directly related to herd size: the larger the herd, particularly over 500-head, the more prevalent the disease.

“The main problems are in the western USA.”

A 2012 report by Fox in Food Animal Practice put M. bovis prevalence at more than 3% of bulk milk tanks in the northeast and Midwest US but at 9.4% in the large herds of the west, Nicholas noted in a 2016 Veterinary Journal paper.

Mastitic samples from 100 farms in Britain found only one case of M. bovis, a similar prevalence to reports from France, almost certainly because of small herd sizes, though dairy prevalence “may be somewhat higher in other European countries,” he says.

Interestingly, given the frequently reported comment in New Zealand media that Norway is Mycoplasma-free, Nicholas’ 2016 paper refers to his observation, albeit unpublished, of a case there in 2014.

The Irish experience

In Ireland, where dairy systems are increasingly similar to NZ, albeit on a smaller scale, M. bovis was first reported in 1994. University College Dublin’s Catherine Carty, part of UCD’s herd health group, wrote a review article on M. bovis for the Veterinary Ireland Journal in 2017 and says it now appears endemic.

“Anecdotally we have seen an increase in herd outbreaks in the past few years which has coincided with the rapid expansion of the dairy herd post-abolition of milk quota here in Ireland. This is only an observation, and perhaps more vets are just referring these cases: we do not have national prevalence data.”

She says M. bovis is generally assumed to have a short survival time outside the host, hence reducing imports of stock and contact with other herds are the main preventions used. However, transfer of the pathogen into the herd via visiting people or equipment should not be ruled out.

“Very few [Irish] farmers would have specific protocols in place for preventing M. bovis entering the herd but probably have general biosecurity measures in place.”

How to manage a herd if it becomes infected depends on how M. bovis presents as disease, if at all.

“In the outbreaks we see, it seems to be most often combinations of mastitis – typically rapid between quarter transmission and multiple quarters affected – and/or polyarthritis.”

There may also be calf involvement, but that’s not a given, and there are herds that only seem to suffer with calves – where the adult herd appears to have no symptoms.

“In calves, presentations include polyarthritis; inner ear infections causing neurological deficits resulting in drooping ears and head tilts – in severe cases we have seen these tracking all the way into the brain – and pneumonia.”

When high numbers of calves are affected often it’s associated with feeding whole milk or waste milk from the adult herd, which appears to be an efficient means of transmission.

In all cases response to treatment is poor, she says.

“Some of the outbreaks we have dealt with have been quite explosive with large proportions of the herd – up to 50% of the adult herd – affected.”

How outbreaks are tackled depends on the symptoms. Presumed infected cows, based on clinical signs, should be kept separate, with strict milking shed hygiene to prevent intramammary spread. Mastitis cases may be culled.

“We also use PCR to test all animals in the milking herd, first by pooled samples then testing any positive pools as some animals may have no clinical signs and be shedding via milk.”

Regular bulk milk tests are used to monitor clean and ‘infected’ groups regularly until an outbreak is under control in such situations.

In calf cases, any whole milk feeding is stopped immediately, and replaced with powder; clinical animals are separated then treated, although treatment is often unrewarding.

“The other issue we will look at is any concurrent stressor or immunosuppressor,” Carty says.

“In most of the outbreaks we have investigated, we have identified either the pathogen introduced into a naïve herd, and/or the presence of significant stressors on animals – overstocking, feed restriction, negative energy balance etc.”

Whether outbreaks are in fact in a naïve herd, or are the result of some form of immunosuppression in a herd that was carrying M. bovis without showing symptoms, is a regular discussion point.

“Both are probably occurring.”

In a 2011 Veterinary Record paper Nicholas noted the role of immunosuppression in disease developing, either from M. bovis itself or because of M. bovis having a modulatory effect, predisposing the respiratory tract to invasion by other bacterial pathogens, in particular Mannheimia haemolytica.

“The association between M. bovis and viruses is less clear, but the immune deficiency caused by bovine viral diarrhoea (BVD) virus is suspected as an underlying cause of M. bovis-associated disease.”

As for Carty’s point about not ruling out visiting personnel or equipment, while that’s correct, he has never seen any evidence of such transmission in the field.

“Semen and waste milk are the only other real risk factors, besides stock movements.”

Antibiotic and vaccine options limited

It’s been widely reported Mycoplasma bovis doesn’t respond to antibiotics and there’s no vaccine, but as with many things to do with this disease, that’s an over-simplification. It all depends what you use, where the organism sits in the animal, and what strain of M. bovis you have.

That said, none of the drugs or vaccines work well, hence the focus on prevention, not just here but globally.

Some of the most widely used veterinary antibiotics, such as the sulphonamides, ß-lactams and polymixins, have never worked on mycoplasmas, in the latter’s case because they act on bacterial cell walls, and mycoplasmas don’t have one. Some tetracyclines, macrolides, triamilides and quinolones do have, or at least did have, some efficacy. The problem is getting them to the site of infection in the animal in sufficient concentration to be effective, and the ability of mycoplasmas to develop resistance.

UK-based M. bovis specialist, Dr Robin Nicholas, says minimum inhibitory concentrations (MICs) of most tetracyclines, macrolides such as tylosin, tilmicosin, and tulathromycin, and the phenicols, chlorphenicol and florfenicol for control of M. bovis, are now high.

“This has changed in the last 20 years; MICs have increased significantly over this time. The only ones that have remained the same are the fluoroquinolones, though there have been some alarming results from Turkey,” he says.

However, use of fluoroquinolones is discouraged in Europe because they are “the last line of defence [against antimicrobial resistance] for humans,” he says.

Overseas, Zoetis (formerly Pfizer) promotes use of Draxxin (active ingredient tulathromycin) as an M. bovis control, in some cases prophylactically. Nicholas notes that’s despite a high MIC, Zoetis arguing it works by stimulating the immune system so the animal itself is better able to combat the infection.

Meanwhile, tetracyclines have some anti-inflammatory action which may help them work against M. bovis, or at least alleviate symptoms and disease in the animal, if not eliminating the causative agent.

Similarly, some antibiotics which are ineffective against mycoplasmas are still beneficial in a pneumonia/bovine respiratory disease (BRD) outbreak where M. bovis is present because they combat other pathogens such as pasteurella and mannheimia leaving just M. bovis for the animal’s immune system to deal with.

Using combinations of antimicrobials against M. bovis “may help, but probably not for long,” Nicholas says, due to the ability of mycoplasmas to develop resistance, which stems from a naturally high mutation rate and ability to protect themselves with a biofilm.

Antimicrobials also have little effect on mycoplasmal mastitis, due to the drugs being inherently ineffective or resistance having developed, and the infection persisting in other parts of the animal.

“Most investigators have concluded that, based on their field therapy experience, antibiotic therapy of mycoplasma mastitis is not an economically viable control strategy,” Nicholas wrote in a 2016 Veterinary Journal paper on the disease.

There’s some literature on using autogenous vaccines – a herd-specific vaccine created using extracts of a pathogen already present in some animals in a herd – to combat M. bovis but there are no off-the-shelf M. bovis vaccines available internationally, despite considerable research effort.

“No one has found the right one yet,” Nicholas says.

Zoetis says Draxxin is available in NZ, but not widely used as bovine respiratory disease (BRD) is relatively rare here.

However, elsewhere in the world BRD is “massive” and M. bovis is one of the key pathogens in the complex, Zoetis NZ’s technical development manager Wayne Clough says.

“We also don’t have some of the other contributing factors,” he says, referring to outdoor systems and low pathogenicity of the IBR herpes strain present in NZ, another contributor to BRD.

“The fact we don’t see a lot of pneumonia in calves is testament that our conventional rearing facilities are pretty good. We see the odd sporadic case, but it’s not really BRD.”

If M. bovis established itself in NZ, that could change, he believes, but even then the BRD might not be as bad as in other countries due to the environmental differences.

“As long as we’re going for eradication it [treatment] is a moot point really. Everything gets slaughtered and treatment isn’t an option.”

NZ’s place in M bovis history

Mycoplasma bovis was first isolated in 1961 in the United States from a case of severe mastitis in cattle.

“It then appears to have spread, often silently, via animal movements worldwide to many countries, including Israel (1964), Spain (1967), Australia (1970), France (1974), Britain (1974), Czechoslovakia (1975), Germany (1977), Denmark (1981), Switzerland (1983), Morocco (1988), South Korea (1989), Brazil (1989), Northern Ireland (1993), Republic of Ireland (1994), Chile (2000), South Africa (2005), the Czech Republic (2007) and mostly recently China (2008),” UK expert Robin Nicholas wrote in an April 2011 edition of Vet Record.

“There are few countries, with the exception of Norway and New Zealand, which are free of M. bovis today.”

However, that had changed by 2016.

“Outbreaks of mycoplasma mastitis have been reported in… Norway, which, until 2014, had been M. bovis-free (R. Nicholas, unpublished observations),” he wrote in a 2016 Veterinary Journal paper.

At that time, he said NZ was probably free of M. bovis, given McDonald et al’s 2009 NZ Veterinary Journal report of a bulk milk survey.