Bartonella: Quantifying new risks to veterinarians, patients

National Report— Bartonellosis: It's no longer considered a self-limiting disease, and for some people chronic infection can be as debilitating and hard to diagnose as Lyme disease.

While new human medical and veterinary research is quickly debunking traditional beliefs about these infectious bacteria, expert Dr. Edward Breitschwerdt, of North Carolina State University's College of Veterinary Medicine, wants veterinarians to sit up and take notice. The health risks appear to be very real, and they are heightened by frequent contact with sick animals.

"Going from not knowing a genus of bacteria existed in the 90s to now realizing that cats, dogs, cows, deer, squirrels, voles, moles and kangaroos in Australia are all running around with their own Bartonella species in their blood changes the dynamics of the human-animal bond. And it creates some caution that we didn't have to worry about five years or 10 years ago when we didn't know this information."

Breitschwerdt has spent much of his professional career studying vector-borne infectious diseases. And while cat-scratch disease was recognized nearly 100 years ago, the bacteria that causes this and other Bartonella-related disease manifestations and the routes by which humans become infected needs much more research. What is known is that Bartonella henselae, B. clarridgeiae, B. koehlerae can be transmitted by infected fleas and the inoculation of flea feces. The infected nail beds and saliva of cats are routes of transmission following a bite or scratch," Breitschwerdt says. And persistent intravascular infection in some individuals can result in a cascade of medical conditions like arthritis, endocarditis, encephalitis and others (Tables 1 and 2).

"In the last 2.5 years, we published eight research manuscripts involving human infection. If you spent the time to read all eight, you would be very concerned."

Just last month, a scientific report was published in the Journal of Veterinary Internal Medicine chronicling potential transmission of Bartonella vinsonii subsp. berkhoffii, for which dogs, foxes and coyotes are the reservoir hosts, from an accidental needle stick.

The science challenges two long-standing myths:

> Cat-scratch disease is always self limiting — in other words, the problem (and the infection) just goes away with time.

> And Bartonella causes chronic bacteremia in immunocompromised people but does not cause persistent bacteremia in immunocompetent people.

The science is so new that most physicians aren't aware of the threat to some patients, especially those who handle animals frequently.

In fact, in a paper recently published by Breitschwerdt, et al. titled "PCR amplification of Bartonella koehlerae from human blood and enrichment blood cultures", the study concludes that B. koehlerae bacteremia is more common in immunocompetent people than previously suspected. New studies, the authors suggest, are needed to determine if B. koehlerae is a cause or cofactor in the development of arthritis, peripheral neuropathies or tacyarrhythmias in patients."

So how serious is the threat? No one really knows.

In the past 20 years, researchers have identified 26 species of this bacteria. Some pose health concerns to people, dogs and, increasingly recognized, cats. While evolution has helped cats deal with Bartonella and "they can carry those organisms for years without becoming outwardly sick," they can develop disease.

"What we do know is that there has been a microbiological revolution in the discovery of numerous species in the genus Bartonella. These bacteria reside in the blood of healthy and sick animals that are seen by veterinarians every day. The problem for veterinarians, other animal-health professionals and for individuals with intimate animal contact or frequent arthropod exposure is that our understanding of the transmission of these bacteria is very incomplete," he says.

The recognition of this safety risk has spurred more study on these vector-transmitted diseases.

In fact, Breitschwerdt's team at NCSU started testing people to determine if they could find Bartonella in human blood samples after newly developed techniques improved the detection in cat and dog blood samples. "Although unintentionally biased, the study population became people who were attending national, local, regional and international meetings where Breitschwerdt lectured – thus, they were veterinarians, technicians, a veterinarian's wife or husband who might have been holding the animal that had been hit by a car at night. Someone might receive a bite or scratch while holding this painful and fractious animal, while another person was trying to get a catheter in and sedate the animal.

"What became rapidly clear, as we tested sick veterinarians, was the fact that a rather high percentage of people — up to 50 percent depending on the population that we looked at — were actually infected with one or more Bartonella species." The researchers also tested 30 healthy individuals who did not have extensive animal contact or arthropod exposure, and they never found Bartonella in the blood.

"The only thing we can definitively say at this point is ... veterinarians or others who do have extensive animal contact and arthropod exposure are more likely to have these bacteria in their blood."

Treatment with antibiotics is generally effective. The problem, Breitschwerdt says, it's just not on the radar of most physicians or veterinarians as a cause of disease in people or pets.

"This is one of the areas where a lot of work needs to be done. We need to better understand what types of disease Bartonella might be able to cause and determine how Bartonella causes disease."

Case in point? Dr. Michael Lappin's laboratory at Colorado State University and others from around the world have PCR amplified DNA of various Bartonella species from saliva. "We don't know for sure whether saliva is infectious at this point in time... but I do think that contact with saliva should be limited until we have a better understanding of the transmission dynamics," he adds.

Problem list keeps getting longer

It is known that dogs and people develop very similar pathology (Tables 1 and 2), and the list keeps growing: thrombocytopenia, immune-mediated hemolytic anemia, encephalitis and arthritis.

The best characterized examples of disease in dogs or humans is endocarditis. In fact, it's the number one cause of blood-culture negative endocarditis. Immunocompromised people or those on immunosuppressive drugs can develop an unusual vasoproliferative lesion, called bacillary angiomatosis. This rare pathological entity has been reported in the literature in a dog that was immunosuprressed and was later confirmed to be infected with B. vinsonii subsp. berkhoffi.

"One thing I have said in lectures is that the dog is a wonderful naturally occurring model to help us understand human bartonellosis. And the human is a wonderful naturally occurring model to better understand canine bartonellosis." Bartonellosis is an excellent example of the importance of "One Medicine and One Health," he adds.

And while Breitschwerdt's affiliation with a testing service called Galaxy Diagnostics hopes to improve data on the numbers of confirmed cases of animal and human infections throughout the United States, the problem, Breitschwerdt says, is the lack of funding for Bartonella research. Currently, the National Institutes of Health has only two funded Bartonella research grants throughout the United States.

"I think both the bacteria and the diseases that these bacteria cause are very much under-appreciated. During the past few years, I certainly have invested a fair amount of my life trying to convince people that there is a problem. I also realize that it takes a lot of medically relevant information from a lot of laboratories and research centers before our medical infrastructure sits up and takes notice of a potentially important cause of chronic disease."

But, Breitschwerdt wants veterinarians and team members to have a clear understanding of the risks associated with these bacteria to help with an early diagnosis and needed advancements in treatment strategies.