New research takes aim at vector-borne illnesses
Interview by Chaunie Brusie
With an increasing US prevalence of vector-borne illnesses such as Lyme disease, which has now been found in all 50 states, there is a pressing need to improve clinical diagnostics, in order to obtain more accurate and earlier detection of resulting diseases. Current diagnostics focus on blood testing, which can be unreliable, especially for diagnosing infections whose symptoms appear slowly, over time.
Left undiagnosed and consequently untreated, vector-borne illnesses cause symptoms that are similar to those of many other diseases—such as joint pain, facial paralysis, sleep disorders, arthritis, neurological conditions, and tingling or numbing of the hands and feet—further hindering their discoverability.
Now, thanks to an expanded partnership among academic and community organizations, the Thought Leadership and Innovation Foundation (TLI; McLean, Va) is turning its attention to the research and development of standard care guidelines for vector-borne diseases. TLI’s research has already made strides in addressing the diagnostic challenges related to chronic illnesses, and uncovered new discoveries relating to bloodborne pathogens.
To find out more about the foundation’s sponsored research, CLP recently spoke to Bill Oldham, TLI founder and chairman of the board, and Marna Ericson, PhD, TLI fellow.
CLP: Why did TLI decide to focus on research for vector-borne diseases?
Bill Oldham: We’ve been interested in vector-borne diseases for a long time, as a result of our work with the military health system as well as some analytics projects in chronic disease. As we became involved with patient communities and researchers, we identified a significant gap in funding and research focused on vector-borne diseases. In light of the limited knowledge in the field, we knew we wanted to be a part of making a difference to close that gap.
CLP: Can you estimate the national healthcare burden of undiagnosed chronic illnesses resulting from vector-borne infections? What are some of the other overarching effects of these diseases?
Oldham: It’s hard to estimate the overall burden, but it is clear that people are living longer with chronic illness. Last month, CDC stated that 6 out of 10 Americans live with at least one chronic illness, and that chronic illness drives 90% of healthcare costs. And while we believe those statistics are dire, we also recognize that they don’t capture the complexity of the underlying causes of chronic illnesses, which may encompass multiple factors, including infections.
CLP: What can you tell us about current diagnostics for vector-borne diseases?
Marna Ericson, PhD: Currently, many providers test the patient’s blood to detect the antibodies that the body makes against an invading pathogen. This procedure can be troublesome, as antibody expression varies over time, often making it difficult to determine whether a high antibody titer indicates past or active infection.
The next type of testing that providers request is polymerase chain reaction (PCR) -based molecular diagnostics of the blood (serum or whole blood). Molecular technologies work okay, but their results are often troubled by false negatives, as the PCR primers may not pick up the particular species of the invading pathogen, the number of copies in the blood may be too low for detection, or the PCR methodology may be suboptimal. Sadly, Bartonella and Borrelia bacteria are notoriously difficult to grow, so detection by tissue culture is truly underdetected.
CLP: How has TLI been involved with chronic disease research in the past?
Oldham: Our work first started about 5 years ago, when we helped a Maryland-based lab of one of our research fellows get started by raising money for equipment. Robert Mozayeni, MD, had been a colleague of ours in some earlier work, and we were pleased to help him get started in Lyme disease research with the equipment he needed.
CLP: What do you hope the foundation’s new research will achieve, and what will be the benefits for patients?
Oldham: Our hope is that the new imaging and analytics work will help to drive improvements in diagnostic capabilities for healthcare professionals. We’re already supporting a much more significant lab analysis capability than was previously available, and we hope to continue that growth and increase accessibility to patients. Our hope is that patients will see faster diagnosis of previously misdiagnosed or unidentified chronic conditions.
CLP: What diagnostics-related benefits do you anticipate resulting from your new research?
Ericson: We are taking a novel, two-pronged approach. First, we use indirect immunofluorescence of blood and thick-tissue biopsies, employing multistaining to look for three or four specific biomarkers, including the antibody to a protein of the bacterial pathogen.1 The tissue sections are 10x thicker than traditional hemotoxylin and eosin sections, so we use laser-scanning microscopy, or single- or multiphoton microscopy, to capture 3-D data sets. This approach reveals where in the skin the bacteria reside, and whether the bacteria are associated with blood vessels, bone, or lymphatic vessels that are important indicators of the biology of infection.2
Second, we use RNA in situ hybridization, employing RNA-specific probes with fluorescent reporters. The beauty of this technique is that the probe is an indicator of active growth of the bacteria in tissue or blood.
CLP: In what specific ways do you anticipate the diagnostics for these types of diseases changing as a result of your research?
Ericson: For Bartonellosis, we are finding that the bacteria often use the dermis of the skin as a primary niche, which may serve as a more reliable indicator of infection status. If we are able to more reliably detect the bacteria in an asymptomatic patient, we can then provide the physician with a more-accurate report of the infectious state of the patient, and monitor the subsequent success or failure of the patient’s treatment.
CLP: How will advanced diagnostics change the way that vector-borne diseases are treated?
Oldham: The major change is that advanced diagnostics will make effective treatment possible. Knowledge about how to judge between treatments, the timing of treatments, and the potential side-effects of underlying conditions are all important pieces of information that have been lacking, but can now be evaluated for increased treatment efficacy. Our biggest challenge now is making the diagnostics well-known and readily available.
CLP: What has your research already uncovered about blood-borne pathogens in blood transfusions?
Ericson: Working with Paulo Velho, MD, in Campinas, Brazil, we were able to induce Bartonellosis in a mouse model by taking blood from a Bartonella-positive mouse and transfusing it into a Bartonella-free mouse. The uninfected transfusion-recipient mouse did indeed develop Bartonellosis.3 Velho also recently found that 3% to 5% of the blood in the Unicamp blood bank carried Bartonella spp. that were viable for 60 days. In the United States, our blood supply is not tested for Bartonella, Borrelia, or many other infectious bacterial and protozoal pathogens.
CLP: What do you hope your research will achieve?
Ericson: Our research can provide an accurate picture of the state of vector-borne infections in the population, and with that information we will have a better idea of the extent of such infections and the role they play in comorbidities. Additionally, treatments can be personalized to the individual, so that the individual host response can be factored into the treatment plan.
CLP: How will the outcomes of this research project benefit patients?
Ericson: Our research will provide more reliable testing for patients. Better testing means better treatment, leading to better outcomes.4 We are also certain that our protocol will provide new information on how these pathogens can affect vessel, nerve, and lymphatic biology and health.
CLP: When do you anticipate the new diagnostics being available for clinical use?
Oldham: The lab research and publications necessary to bring new diagnostics to market are all happening as we speak, but expanding their capacity is really the challenge. Broad-based clinical use will take time. The next phase of our fundraising and development is focused on making the capabilities of our fellows much more accessible.
Chaunie Brusie is associate editor of CLP.
- Ericson M. Imaging tools in discovery and development of phytochemical chemopreventive agents. In: Dong Z, Bode AM, eds. Cancer Prevention: Dietary Factors and Pharmacology. New York City: Springer, 2014:249–264; doi: 10.1007/978-1-4614-9227-6.
- Ericson M, Balakrishnan N, Mozayeni B, et al. Culture, PCR, DNA sequencing and second harmonic generation (SHG) visualization of Bartonella henselae from a surgically excised human femoral head. Clin Rheumatol. 2017;36(7):1669–1675; doi: 10.1007/s10067-016-3524-2.
- Neves da Silva M, Vieira-Damiani G, EricsonM, et al. Bartonella henselae transmission by blood transfusion in mice. Transfusion. 2016;56(6 pt 2):1556–1559; doi: 10.1111/trf.13545.
- Balakrishnan N, Ericson M, Maggi R, Breitschwerdt EB. Vasculitis, cerebral infarction and persistent Bartonella henselae infection in a child. Parasit Vectors. 2016;9(1):254; doi: 10.1186/s13071-016-1547-9.
Featured image: Deer tick photo © KPixMining courtesy Dreamstime (ID 120846422).