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bacteria, vet sees key to human ills Sarah Avery, Staff Writer
A notion struck Betsy Sigmon on the way to the hospital to tend to her 13-year-old son Jason.
The youngster, who was admitted after suffering weeks of excruciating headaches, had been bitten by a tick days before he grew sick. While blood tests showed no hint of a tick-borne infection, the idea nagged at her.
So Sigmon called Dr. Ed Breitschwerdt, a veterinary researcher at N.C. State University. Sigmon, herself a vet, knew Breitschwerdt studied tick-borne diseases.
"Do you know of any kind of infectious agent that might be causing Jason's symptoms?" Sigmon recalls asking Breitschwerdt.
In reaching out to Breitschwerdt, Sigmon turned to a man who may know a hidden cause behind many chronic human ailments that often aren't recognized as infections transmitted by animals and insects.
With the right diagnosis using a process he patented, Breitschwerdt says, many could be easily cured with antibiotics.
Medical doctors have been slow to listen to a veterinarian about how to treat humans, but promising results are helping Breitschwerdt's views gain acceptance. Antibiotic treatment has cured people of pain and weakness doctors originally attributed to migraines, chronic fatigue and even multiple sclerosis.
At the heart of Breitschwerdt's research is a pathogen carried by insects -- a bacteria known as Bartonella. Spread by biting pests such as fleas, lice, sandflies and possibly ticks, Bartonella are difficult to detect in human blood. As a result, Breitschwerdt thinks the bacteria are taking an unacknowledged toll on human health.
"I believe it's a silent epidemic," says Breitschwerdt, who is also an adjunct professor in infectious diseases at Duke University Medical School.
His belief is based on his own patients -- the cats, dogs, rabbits, cows and other animals that harbor Bartonella in their blood. With so many insects spreading the bacteria to so many animals, he contends, the bugs are certain to readily infect humans.
Breitschwerdt suspected a Bartonella infection was behind Jason Sigmon's headaches. He urged Betsy Sigmon to ask the hospital staff at WakeMed to draw an extra vial of the youngster's blood for him to test. Using a technique he patented and special equipment in his lab at N.C. State, Breitschwerdt went on the hunt for Bartonella.
Understanding evolves
As bugs go, Bartonella species are fairly recent entries on the list of known infectious germs. Bartonella was first noted as the culprit behind a severe fever illness that explorers picked up in Peru from sandfly bites. Then in World War I, a strain was identified as the cause of trench fever, which sickened thousands of soldiers who caught it from body lice that spread in the cramped, filthy conditions of war.
Thereafter, doctors figured Bartonella was a pathogen isolated by geography or limited to decrepit conditions.
That began to change in the early 1990s, however, when scientists determined that a Bartonella infection caused skin lesions on AIDS patients and among homeless people in the United States.
About the same time, another species of the bacteria was identified as the source of cat scratch disease. The illness, which afflicts about 22,000 people a year in the United States, had previously been attributed to another pathogen.
Marked by swollen lymph nodes, fever and general malaise, the disease occurs after contact with a Bartonella-infected cat. And those are legion. About half of cats in flea-prone regions harbor the bacteria at some point in their lives, spreading it through their saliva and in fleas. In fact, it gets on cats' claws because they scratch at the fleas, raking up the germ from the fleas' feces.
Talk of the newly identified pathogen was everywhere in veterinary circles. Breitschwerdt, who had been studying tick-borne bacteria, including the one that causes Rocky Mountain spotted fever, was intrigued.
"These aren't new bacteria -- they've been around for millions of years," Breitschwerdt says. "What is new is our knowledge of their presence, not only on the planet, but in animals."
His lab at N.C. State soon began studying Bartonella and, by the mid-1990s, had isolated a species of the bacteria in dogs -- demonstrating that it was far more prevalent in the animal world than originally thought. Other findings followed. There was strong evidence that the bug was carried by ticks as well as fleas. It had a large family of closely related but distinct species -- at least 22 and counting. Strains were found in the blood of a variety of mammals -- even dolphins and whales.
It wasn't always a benign invader. In dogs, it could cause heart valve infections, neurological disorders -- even sudden death.
Tracking the bacteria
The more Breitschwerdt studied Bartonella, the more convinced he became that the bacteria played a larger role in human illness than commonly thought. But finding proof was difficult. Most blood tests didn't catch it, because they detect evidence of infection only if a patient's immune system has mounted a response.
A more sensitive test, called polymerase chain reaction, or PCR, could pick up molecular evidence of the actual bacteria in blood. This was a better approach, but even PCR proved ineffective in diagnosing Bartonella.
"It was easy to isolate from cats," Breitschwerdt says. "There was one bacteria to each normal blood cell in a cat. But when it jumped to a human or a dog, the situation was a little different." Instead of a one-to-one ratio of bacteria to blood, the ratio in dogs and humans was more like one bacteria to 10 million blood cells.
So Breitschwerdt and a colleague, Ricardo Maggi, developed a way to cultivate the bacteria. The process, which Breitschwerdt patented, uses a special growth medium his lab concocted that basically re-creates the environment of an insect's belly, where the bacteria flourish. By adding the growth factor to the blood, once undetectable levels of bacteria multiply into a population large enough to be seen by PCR analysis.
Breitschwerdt tried it first on dogs. Animals that had shown signs of illness but had tested negative for Bartonella were, in fact, infected.
Now the question was whether the same was true in people.
Vets had symptoms
A weird thing started to happen when Breitschwerdt talked about Bartonella infections in dogs at veterinary meetings around the country. His colleagues, most of them working vets, said they had the same symptoms he described in the pets -- arthritis, fatigue, neurological problems. One man's symptoms worsened until he could no longer jog and his hands grew numb; he had been diagnosed with multiple sclerosis.
It seemed that they had been exposed to the bacteria, either from animal bites and scratches or from bug bites.
In 2005, the board at NCSU that oversees scientific studies approved Breitschwerdt's request to test human blood. Of 50 people in the initial group he tested using his culture process and PCR, half were infected with Bartonella. Many had chronic conditions that stubbornly defied traditional treatments.
"[Infection is] an occupational risk for vets," Breitschwerdt says.
But getting the medical community to consider Bartonella has been difficult -- especially for veterinary researchers such as Breitschwerdt. It's a frustration shared by other Bartonella hunters.
"There's a lack of attention, and certainly a lack of funding," says Dr. Bruno Chomel, a researcher at the University of California, Davis. He says even Lyme disease, another tick-borne illness that has met skepticism among doctors over its geographic range and treatment requirements, enjoys more acceptance.
Reading the clues
Betsy Sigmon called one August afternoon three years ago, desperate for help.
Jason Sigmon had not been able to start middle school because of excruciating, unrelenting migraines. The pain was so bad he often threw up.
"It was unlike anything I had ever experienced," Jason says. "It was awful."
Brain scans showed nothing. Heavy-duty pain pills made no dent. Knowing Jason had been bitten by a tick earlier that month while helping his father trim hedges, Betsy Sigmon suggested that doctors run blood tests. The blood work even screened for Bartonella antibodies, but no tick diseases showed up.
Finally, Jason's neurologist recommended the teen be hospitalized and treated with intravenous drugs to help break the migraine cycle.
Betsy Sigmon wasn't convinced that Jason suffered migraines -- a diagnosis that could have kept him out of school for a year if treatments didn't work.
"One thing we as veterinarians recognize is there are a lot of correlations of diseases between animals and humans," she says. "Our patients can't talk to us, so we have to go by seeing signs and symptoms, and we have to be critical thinkers and keep in touch with what's going on with infectious diseases. So I was thinking, who could I call?"
Betsy Sigmon thought of Breitschwerdt. She and her husband had helped fund his work with donations to his lab, and she knew he was a leading researcher in tick diseases.
When Breitschwerdt asked Betsy Sigmon for the extra vial of blood, Jason's doctor happily obliged.
Twenty-four hours later, Breitschwerdt had results. Even without growing the bacteria using his process, Breitschwerdt detected Bartonella under PCR analysis. Later tests confirmed the findings.
A hunch is confirmed
The next day, after a round of antibiotics, Jason finally felt better.
"It was the first relief I had had," he says.
After three days of treatments he was almost back to normal. Subsequent blood tests show no signs of the bacteria.
In a paper published last month, Breitschwerdt detailed Jason Sigmon's case along with five others. All had Bartonella infections that caused chronic, untreatable illnesses. Jason and two others, including the vet who had been diagnosed with multiple sclerosis, were cured with antibiotic treatment. One continues on antibiotics and has shown improvement, while two did not respond to treatment.
Breitschwerdt says the findings demonstrate that Bartonella should be considered when otherwise healthy people develop sudden, chronic illnesses. He says many diagnoses in people could be attributed to Bartonella if better testing were more widely available.
But it remains a hard sell.
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J Clin Microbiol. 2008 Sep;46(9):2856-61. Epub 2008 Jul 16. Links Bartonella sp. bacteremia in patients with neurological and neurocognitive dysfunction.Breitschwerdt EB, Maggi RG, Nicholson WL, Cherry NA, Woods CW. College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough St, Raleigh, NC 27606, USA. [email protected]
We detected infection with a Bartonella species (B. henselae or B. vinsonii subsp. berkhoffii) in blood samples from six immunocompetent patients who presented with a chronic neurological or neurocognitive syndrome including seizures, ataxia, memory loss, and/or tremors. Each of these patients had substantial animal contact or recent arthropod exposure as a potential risk factor for Bartonella infection. Additional studies should be performed to clarify the potential role of Bartonella spp. as a cause of chronic neurological and neurocognitive dysfunction.
PMID: 18632903 [PubMed - in process]
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