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United States Department of Agriculture

Agricultural Research Service

Healthy Animals Newsletter

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Issue 15, July 2003
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Researchers Develop Effective Mastitis Treatments

It could be argued that one word should strike fear in the minds of serious connoisseurs of milk, cheese, yogurt, butter, ice cream and other dairy products: mastitis. That's because mastitis, an udder inflamation caused by bacterial infection, leads to lower milk production, wasted milk and a shorter life for infected dairy cows. It's the single most costly dairy cow disease.

Actually, American consumers have nothing to worry about. The United States' dairy production was 169.8 billion pounds in 2002, an increase of 2.6 percent from the previous year. But mastitis is still bad news for cows and dairy producers.

Bacteria invading a cow's mammary gland absorb milk nutrients while secreting poisonous endotoxins that destroy mammary tissue. If these toxins escape the gland and spread throughout the cow's body, they eventually cause organ failure and death.

Annual losses due to mastitis are estimated at more than $2 billion in the United States, and about 3 million dairy cows each year show visible signs of acute infection. Of those 3 million, about 300,000 die from shock induced by the endotoxin or have to be culled. Antibiotics help, but resistant pathogens can make them ineffective. Milk containing antibiotics is not allowed to be sold to consumers, so producers have to wait a few days before selling milk from treated cows.

Mastitis causes an additional $400 million loss to the beef industry, and affects goats, sheep and pigs. The impact in the latter species has not been fully evaluated, particularly as it affects their continued use for breeding and the survival rate of their newborn offspring.

Dairy cow in a pastureNow for the good news: Veterinarians could soon have an effective way to treat and prevent acute endotoxin shock in dairy cows for the first time, thanks to ARS scientists in Beltsville, MD.

Max Paape, a dairy scientist with ARS' Immunology and Disease Resistance Laboratory (IDRL), and colleagues have applied for a patent on the cloned gene that codes for a protein called CD14 naturally suspended in cow's milk and blood plasma, its recombinants, and its application for treating mastitis-infected cows and preventing future cases.

Paape, fellow IDRL scientist Dante Zarlenga and graduate student Yan Wang discovered the protein in cow milk in 1994-95. They knew it was the soluble form of CD14 that increases during coliform infections in humans and laboratory animals. Soluble CD14 is formed when membrane-bound CD14 is shed from the surface of some white blood cells. Coliform bacteria, found throughout dairy barns, account for about 40 to 50 percent of all cases of dairy mastitis in the United States.

CD14 binds and neutralizes endotoxins. When CD14 is injected into the mammary gland during an infection, one end hooks up with a pathogen's endotoxin and the other snags a mammary cell from the cow's mammary system. Then the CD14 complex causes the mammary cell to secrete chemicals that attract specialized white blood cells, called neutrophils, to the infection site to destroy the coliform pathogens. CD14 protects cows from shock and reduces clinical symptoms associated with coliform mastitis. In studies, it was 100 percent effective in preventing mastitis caused by Escherichia coli in lactating dairy cows.

Paape developed procedures to count cells, such as neutrophils, that are present in milk to fight infections, and he coined the term "milk somatic cells" to describe them. Somatic cell counts (SCC) are now used to determine the price dairy farmers receive for milk; the lower the SCC, the better the price. The procedure is used to diagnose infected cows and is an index of milk quality around the world.

Work with CD14 is cutting-edge technology that's also being used in research with humans to increase the killing power of immune cells.

CD14 also sensitizes the lining of a cow's mammary gland to very low levels of endotoxin, which is produced by just a few types of bacteria called gram-negative bacteria. Once the mammary cells are sensitized, they start an attack early enough to prevent the cow from getting sick.

The cloned gene for CD14 can be designed and inserted into a cow's mammary gland so it will secrete the protein only in milk. Paape and colleagues are working on a delivery system for the CD14 protein. They are seeking commercial business partners to license the technology and produce CD14.

Paape and Jai-Wei Lee and Xin Zhao, collaborators at McGill University in Canada, are also interested in the natural causes that lead to an increase of CD14 in cow's milk. They are studying how CD14 concentration is affected by different stages of lactation, somatic cell count, the presence of bacteria and the level of endotoxin secreted by gram-negative bacteria that bind to CD14 receptors.

Transgenic mice expressing recombinant CD14 from cows are being produced by ARS scientist Bob Wall. They will be challenged with E. coli to see if the CD14 prevents mastitis. Eventually, bioengineered cows could be developed with immunity to mastitis.

Another 30 to 40 percent of all clinical dairy mastitis cases are caused by Staphylococcus aureus infections. A retired colleague of Paape's, A. J. Guidry, was part of a team that developed a vaccine to immunize heifers to prevent mastitis caused by all strains of S. aureus. The vaccine was 100 percent effective in protecting heifers from that gram-positive bacterium. The vaccine would prevent mastitis at the very beginning of a cow's productive life. When the vaccine was used with antibiotics, it was 70 percent effective in curing chronic mastitis infections. Testing is under way for both applications in commercial herds around the United States. ARS has applied for a patent and the agency is seeking licensees to produce and market the vaccine.

For more information, contact:

Max Paape, Beltsville, MD

Research Briefs

ARS researchers developed an oil emulsion vaccine of inactivated Salmonella enteritidis, protecting hens exposed to the organism. A patent application has been filed and the vaccine is available for licensing.
Peter Holt
(706) 546-3442

A new software program developed by ARS scientists and cooperators estimates the relative economic value of multiple traits in beef cattle, instead of just one specific trait in each type. This allows producers to rank cattle based on the their potential to produce the most profitable offspring.
Michael D. MacNeil
(406) 232-8213

A hormone-producing gene that may suppress appetite in chickens is being sequenced to find out why broiler birds tend to overeat when given free access to feed. ARS scientists are comparing egg-laying chickens with broilers to see which genetic components govern the differences in feed intake and calorie expenditure in each type.
Mark Richards
(301) 504-8892

Ovulation-inducing techniques that cause cows to have medium-sized follicles at the time of artificial insemination could ensure high pregnancy rates, according to ARS scientists and university collaborators. The procedure also eliminates the need to detect when cows go into heat.
Thomas W. Geary
(406) 232-8215

A new, natural-based algicide is being tested to see if it's safer than current treatments used in catfish ponds to prevent off-flavors. ARS has filed a patent application on the algicide derived from a compound found in ryegrass.
Kevin Schrader
(662) 915-1144

ARS researchers and collaborators are sequencing the chromosomes of bacteria that cause Johne's disease and bovine brucellosis as well as the bacterium that causes leptospirosis. They hope the sequencing could lead to new tests and vaccines for these cattle diseases.
David P. Alt
(515) 663-7645

An important genetic segment of the virus that causes turkey rhinotracheitis, an upper respiratory illness, has been sequenced by ARS scientists. The sequence could be used to develop a diagnostic detection kit.
Bruce Seal and Rene Alvarez
(706) 546-3463

Fish oil containing omega-3 fatty acids helped develop the immune systems of young, weaned pigs. After both groups were challenged with an endotoxin, ARS and university collaborators found that pigs given feed with fish oil ate more and were better prepared to fight the toxin than those given a control diet.
Jeff Carroll
(573) 882-6261

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Last Modified: 2/6/2007
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