Uncovering a Stealth Pathogen, Bartonellosis

Bartonella henselae bacilli in cardiac valve of a patient with blood culture-negative endocarditis. The bacilli appear as black granulations. (Photo by Warthin Starry, CDC, Wikimedia)

Bartonella henselae bacilli in cardiac valve of a patient with blood culture-negative endocarditis. The bacilli appear as black granulations. (Photo by Warthin Starry, CDC, Wikimedia)

I interviewed in October veterinarian and infectious disease researcher Ed Breitschwerdt of North Carolina State University about his studies of infections by bacteria in the genus Bartonella–the most familiar of which is cat scratch fever. Over his career, Breitschwerdt and his colleagues have discovered many new species of the bacteria and new hosts to the infections, including humans. Readers here may be interested that the number of bacterial species (sometimes acting as opportunistic pathogens), hosts, and reservoirs make this a very interesting, if complicated, disease ecology system. As Breitschwerdt said:

“We went from not knowing that Bartonella species existed in animals or humans in North America in 1990 to now finding Bartonellas in almost every animal that someone has taken the time to investigate.”

The most interesting part of the interview came toward the end, when he talked about the challenges this group of bacteria posed as he worked on parsing out where they are and how they affect hosts:

“…Disease causation is a complicated issue. The complication comes from the fact that we have a highly adapted bacteria that has figured out a way to live in the bloodstream of numerous mammalian species throughout the planet without being highly pathogenic and inducing disease. When a reservoir-adapted Bartonella, essentially a Bartonella that you might find in a cat or a squirrel or a cow, is transmitted to a non-reservoir host, such as a human, then, it appears that developing disease is much more likely…. All microbiologists and physician infectious disease researchers understand that trying to sort out causation in extremely chronic infections is epidemiologically challenging and can be clinically challenging as well.”

When Breitschwerdt set out, Bartonellas were difficult to culture, and his lab made a novel breakthrough in their culturing methods:

“Because Bartonellas could be transmitted by so many different insect vectors, we elected to see whether they would grow better in an insect biochemical composition growth media as compared to a mammalian growth media. Importantly, whether we’re discussing animal health or human health, or veterinary microbiology or human microbiology, microbiologists have used mammalian growth media to grow organisms from mammalian patients. And so, our idea to try an insect growth media was absolutely novel. Most folks using these media to support the growth of insect cells did not want bacterial contamination of their cell culture systems. And yet, when we in the laboratory took seven different Bartonella species and did growth curves, we could get better growth curves, we could get better growth curves in an insect growth media, which we subsequently went on to optimize further than we could in any mammalian growth media. That work’s been repeated by Volker Kempf’s group in Germany with the Max Planck Institute, that work has been repeated by Michael Kosoy at the CDC, and I think one thing that we have now accomplished in addition to providing researchers and diagnosticians with a new tool is an agreement among researchers that these are highly fastidious bacteria, they’re extremely hard to find in patient samples, and that’s the reason they were missed. As a result of that, we started testing people that had arthritic disease or neurologic disease. And, at lease based on case reports and response to therapy, there are a substantial number of people with Bartonella in their blood, documented by techniques that we developed, that have chronic arthritic or neurologic manifestations of the disease.”

He then spoke about the resistance from the medical community that he has come up against as he has worked with this group of organisms:

“For a number of years, I hoped that Bartonella would reach what they refer to as the tipping point, the tipping point where there was more general acceptance that this genus of bacteria might be an important cause of illness in animals and human patients. We’ve still not reached the tipping point for the genus of Bartonella, where there is acceptance that this bacteria deserves more attention from researchers and funding agencies than has occurred historically. However, if you were to graph the publications in PubMed, you will see that Bartonella over the last couple of years is on a direct vertical course; the manuscripts are being generated by numerous laboratories now around the world, and I think, particularly, I’d credit my very small and very hardworking research group at NC State with the development and use of the BAPGM enrichment blood culture platform for putting enough case reports, enough case series, and at least two large patient series in collaboration with Dr. Robert Mozayeni, a rheumatologist in Maryland, into the literature, that our results cannot be ignored. And either researchers are going to have to prove–as has been suggested by some reviewers of scientific manuscripts that we’ve submitted–that our results are inaccurate and a reflection of contamination in the laboratory, or that our results are accurate, they’re real, and we actually do have a real problem that needs to be addressed in patients.”

The future research on Bartonellosis will be very interesting to watch play out, especially as new techniques open up new possibilities for studying this group of bacteria. I’ll be staying tuned. In the meantime, listen to the full podcast of my interview with Breitschwerdt here.

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