Technician Ami Frank studies images of Leptospira in silver-stained experimental tissues while veterinary medical officer David Alt observes.

Looking for Ways to Control Leptospirosis

It's not often you hear much about leptospirosis, which is a rare and severe disease that affects humans and animals. One reason may be because symptoms can be mistaken for those of other diseases.

Leptospirosis is a contagious disease caused by Leptospira bacteria. It's transmitted naturally from infected domestic animals and wildlife to humans through urine-contaminated water, food or soil. The disease can cause a severe infection in humans. Symptoms include headaches, fever, vomiting, diarrhea and chills. Without treatment, people infected with the disease can suffer from kidney damage, meningitis, liver failure and respiratory distress.

"Leptospirosis occurs on a periodic basis in endemic areas like Brazil," says Richard Zuerner, a retired microbiologist who worked at the Agricultural Research Service (ARS) National Animal Disease Center (NADC) in Ames, Iowa. "Some of the people infected will experience pulmonary hemorrhage, which can lead to a very rapid and painful death."

In livestock such as cattle, leptospirosis can cause abortions, stillbirths, lower fertility and reduced milk production, Zuerner says. It can also result in uveitis, a potential cause of blindness in horses.

Zuerner and his colleagues at NADC looked at the spread of leptospirosis in sea lions, tested vaccines for cattle, and examined the hamster as a model to better understand the disease.

Source for sick sea lions
The latest incident in 2011 of sick and dying sea lions washing ashore along the West Coast is the kind of driving force that keeps scientists searching for answers as to how Leptospira got into California sea lion populations. This has been a mystery since the disease was first discovered in these mammals in the 1970s.

Studying leptospirosis in sea lions could provide more information about the disease in wildlife and reduce the potential risk to public health. Infected mammals stranded along beaches pose a threat to people who come to their rescue, risking exposure to the disease.

Zuerner and David Alt, a veterinary medical officer in NADC's Infectious Bacterial Diseases Research Unit, teamed with scientists at the Marine Mammal Center in Sausalito, Calif., to identify the disease strain that causes infection in sea lions. They looked at urine and kidney samples of infected mammals and determined that the responsible strain was L. interrogans serovar Pomona, which also affects cattle and other species.

California sea lions periodically undergo acute infection outbreaks, Zuerner says. However, research indicates that they are becoming maintenance hosts.

"Maintenance hosts normally carry the bacteria and show few outward signs of infection," Zuerner says, "whereas accidental hosts, like humans, often come down with a severe infection."

Scientists have set up a surveillance network, with the help of marine and wildlife agencies, along the Pacific coast to locate marine mammals that have leptospirosis. They have discovered that the spread of the diseases coincides with the northern seasonal migration of male marine mammals. The outbreaks first occurred in southern California, and by the end of the year, disease-infected sea lions were found in Washington and Canada.

A vaccine for cattle
Scientists are constantly looking for effective vaccines that reduce the spread of leptospirosis in cattle. They recently evaluated a commercial vaccine for its ability to provide short- and long-term protection against experimental infection with L. borgpetersenii serovar Hardjo, the main cause of bovine leptospirosis.

In the study, cattle were vaccinated twice with the commercial vaccine, a standard vaccine, or a control vaccine. Animals were challenged with serovar Hardjo a year after the second vaccination. To test the vaccine's ability to induce short-term immunity to infection, cattle were challenged three months after a second vaccination.

"The commercial vaccine induced greater immunologic responses than the standard vaccine and greater protection against shedding after challenge," Alt says. "However, it did not provide complete protection from shedding."

With the commercial vaccine, scientists were not able to detect any bacteria in either the urine or the kidney at the end of the short-term study. Cattle vaccinated and then challenged with the live bacteria cleared the bacterial infection of the kidney more efficiently, Zuerner says. Results of the year-long study indicated that only one animal had bacteria in the kidney.

Results showed that the immune system of vaccinated animals was exhibiting a recall response and naturally eliciting an appropriate reaction against the bacteria, he says.
Despite the success with the commercial vaccine, it's not always easy to find the right vaccine. It all depends on the infecting serovar, Alt says. More than 200 serovars can cause leptospirosis, and it's difficult to identify differences within the genus.

A valid model
To determine the effects of leptospirosis and evaluate potential vaccines, scientists need a reliable model. In the past, the hamster, which is widely used, presented challenges in demonstrating lethal infection with Hardjo.

One reason is because in earlier studies it was unknown that serovar Hardjo occurred in two species — L. interrogans serovar Hardjo and L. borgpetersenii serovar Hardjo.
"There was no way to differentiate clearly or genetically which particular Hardjo was used to induce a lethal infection in hamsters," Alt says.

Scientists used the hamster model to evaluate two closely related L. borgpetersenii serovar Hardjo strains. Hamsters were challenged with a strain that produced an acute, potentially lethal infection and another strain that produced a chronic infection.

Results of the chronic strain experiment revealed large numbers of bacteria in the kidney of hamsters. The infection closely mimicked the type of infection observed in cattle.

Scientists are now examining the use of the hamster model to learn more about leptospirosis and to identify the differences between infections induced by the lethal strain versus the chronic strain. A small animal model may also help in evaluating the effectiveness of future vaccines.

For more information about animal disease research, contact Cyril Gay, or Eileen Thacker, co-leaders of the ARS National Program #103, Animal Health.

Editor's Note: This article most recently appeared in the April 2012 USDA ARS newsletter Healthy Animals.

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