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There's no doubt that dairy cattle are a very profitable part of the country's ag economy, but transition cows are fragile animals. Getting them through the transition period without disease is going to be more profitable for producers during that lactation. However, if a transition cow experiences postpartum disease, it becomes an economic burden if she survives. 

So what disease challenges do transition cows face, why and what can be done about it is what Marcus Kehrli, DVM, USDA National Animal Disease Center director talked about in the September Hoard's Dairyman webinar, Bolstering Transition Cow Immunity

A large study in the 1980s indicated cows showed the greatest rate of new infections in the mammary glands in the first two weeks after dry off and the first two weeks before calving. 

"Those are a concern," said Kehrli. "If a cow maintains an infection at that point of calving, a very high percentage of those cows will develop clinical mastitis in the first month after calving." 

With these new infection rate two to six times greater than at any other point in the dry period, as well as in lactation, it's important to know why these cows are getting these infections, Kehrli said. 

Data from countries around the world have shown a lot of new infections occurring right after dry off, another period of new infections just before calving and after the cow calves there is a very high rate of clinical cases. This holds true even on well-managed dairies. 

"This begs the question, are transition cows immune suppressed," said Kehrli. 

Immunity suppression

Since most pathogens responsible for mastitis in dairy cows "don't really have a whole lot of ability to cause disease if the immune system is working well," evidence points to  immune suppression converting subclinical infections into clinical disease like mastitis and retained placenta, Kehrli explained. 

"Immunosuppression has many causes," said Kehrli. "Many physiological transitions such as calving, shipping, transport, weaning, are all factors that will stress a cow’s immune system or a calf’s immune system."

Vaccinating against the many pathogens that could cause mastitis is impractical. However, phagocytic cells, which are part of the animal's innate immunity, are known to respond very quickly to try and kill pathogens. One type of phagocytic cell, neutrophils, are "essential for udder healthy — critical for preventing or resolving many postpartum diseases including mastitis and retained placenta," said Kehrli. 

A number of studies show a pattern of decline of immune capability which Kehrli and colleagues determined "have very critical importance for development of disease in cows.

Kehrli showed video of neutrophils rolling through the bloodstream surveilling for inflammation and moving out of the blood and into tissue to combat infection. Any delay in that inflammatory response "was a very poor prognosis for the cow."

"It's important to understand that this immune impairment begins and exists well before calving time," Kehrli stressed. 

Bolstering immunity

Kehrli and colleagues wondered if they could use biotherapeutics to increase the circulating pool of neutrophils important for mastitis resistance.

They settled on a molecule called granulocyte colony stimulatory factor (G-CSF), a natural molecule of the immune system of all animals.

"It's primary role is to increase production of neutrophils from the bone marrow where they are normally made," said Kehrli. "It activates a critical adhesion molecule that would predict faster response but more efficient surveillance and also enhances a range of neutrophil functions."

The first study done on G-CSF in the 1980s showed a profound effect on the immune system. Cows were given daily injections about two weeks before calving. It took about 10 days for cows to reach their peak response. Then they were challenged with different mastitis pathogens.

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In one study, G-CSF reduced mastitis by nearly 47 percent, Kehrli reported. In another, cows cleared the infection by six hours compared to control cows that were culture positive for seven days. Control cows had fever and abnormal milk for five days, while those that received G-CSF were no longer running a fever after 12 hours and their milk was normal in appearance within 24 hours. Both studies were done on mid-lactation cows. 

In a study on early lactation cows, with a lower dose of G-CSF treated for five days in a row starting three days after calving, there was a 50 percent reduction in the number of new infections, faster bacterial clearance rates, reduced severity scores, and improved milk production and feed consumption. 

In 2016, the Federal Drug Administration (FDA) approved a form of G-CSF called pegbovigrastim (PEG-gCSF) for use in transition cows with the first dose to be given about seven days before calving and a second dose within 24 hours of calving. 

The FDA conducted work with PEG-gCSF in four U. S. dairies, treating 320 cows, which showed a 35 percent reduction in clinical mastitis even though cows were treated seven days before calving and within 24 hours of calving. Kehrli said the work also showed a "lingering effect to reduce clinical mastitis within the first 30 days of milk," and it also "reduced the failure to return to estrus as measured over the first 80 days of milk."

The product was also evaluated after it was launched in Mexico on more than 5,000 cows in 17 Mexican dairies, which had a fairly low incident of mastitis naturally during the course of the study. The incidence of mastitis was still reduced by 25 percent, there was a reduction in the number of treatments, less discarded milk, a reduction in retained placenta and it improved the odds of cows being inseminated during the first 100 days in milk, according to Kehrli

"With G-CSF there is no milk discard requirement, so any time you can reduce antibiotic usage, you’re reducing the amount of milk you have to discard," Kehrli said. 

Since there is a FDA approved immune restorative available that "targets the most important immune cell, the neutrophil, for the protection of the udder," Kehrli said it is important for farmers to focus on transition cow management.

"Any dairy farmers that follows their cows closely, they understand that it is a very immune suppressive event to give birth," said Kehrli. "It’s also well recognized that if you have a case of mastitis before the peak of lactation, you will blunt the entire lactation curve, so preventing mastitis has a profound financial impact on a dairy farmer’s bottom line."  

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